Volume 2: Appendices - Avoidable Mortality in the European Union

Transcription

EU Public Health Program 2007106
AMIEHS
Avoidable mortality in the European Union:
Towards better indicators for the effectiveness of health systems
Volume 2: Appendices
August 2011
This report arises from the project AMIEHS which has received funding from the European Union, in the
framework of the Public Health Program
Iris Plug, Rasmus Hoffmann and Johan Mackenbach (eds.)
Table of contents
A. Tables
Table 1 (Chapter 1)……………………………………………………………………………………….. ……..
5
Table 2 (Chapter 1)……………………………………………………………………………………….. ……… 22
Table 3 (Chapter 2)……………………………………………………………………………………….. ………
23
Table 4-20 (Chapter 2)……………………………………………………………………………………………
27
Table 21 (Chapter 7)………………………………………………………………………………………………
73
B. Questionnaire to obtain information on the timing of the introduction of innovations…………
75
C. Standardized cause-specific all-age mortality trends for the age range 0-74 yrs, ……………… 87
by gender and by country with the lines for the mortality trend, and (below) lines
for the periods of expected mortality decline (on top of each graph there is the cause
of death, gender (M or F) and the innovation)
D. Standardized mortality trends (all ages), Percent Annual Chance (PAC) for each period……..
(with confidence intervals), by gender (M/F) and by country (alphabetical order)
104
HIV………………………………………………………………………………………………………………….. 105
Malignant colorectal neoplasm………………………………………………………………………………….. 113
Malignant neoplasm of breast……………………………………………………………………………………. 121
Malignant neoplasm of cervix uteri……………………………………………………………………………… 125
Malignant neoplasm of testes……………………………………………………………………………………. 129
Hodgkin’s disease…………………………………………………………………………………………………. 133
Leukaemia…………………………………………………………………………………………………………. 140
Rheumatic heart disease………………………………………………………………………………………… 148
Hypertension………………………………………………………………………………………………………
156
Ischaemic heart disease…………………………………………………………………………………………. 164
Heart failure……………………………………………………………………………………………………….
172
Cerebrovascular disease………………………………………………………………………………………..
179
Peptic ulcer………………………………………………………………………………………………………..
187
Renal failure……………………………………………………………………………………………………….. 195
2
E: Standardized mortality trends (ages 0-74), Percent Annual Chance (PAC) for each period (with confidence
intervals), by gender (M/F) and by country (alphabetical order)
HIV………………………………………………………………………………………………………………….. 203
Malignant colorectal neoplasm………………………………………………………………………………….. 211
Malignant neoplasm of breast……………………………………………………………………………………. 219
Malignant neoplasm of cervix uteri……………………………………………………………………………… 223
Malignant neoplasm of testes……………………………………………………………………………………. 227
Hodgkin’s disease…………………………………………………………………………………………………. 231
Leukaemia…………………………………………………………………………………………………………. 238
Rheumatic heart disease………………………………………………………………………………………… 246
Hypertension………………………………………………………………………………………………………
254
Ischaemic heart disease…………………………………………………………………………………………. 262
Heart failure……………………………………………………………………………………………………….
270
Cerebrovascular disease………………………………………………………………………………………..
277
Peptic ulcer………………………………………………………………………………………………………..
285
Renal failure……………………………………………………………………………………………………….. 293
F. Vignettes send out for Delphi exercise…………………………………………………………………..
300
G. Country specific reports in alphabetical order
The country specific reports present the insight of country experts on the mortality trends and the value of the association
analyses. These reports have been written by the participants of the AMIEHS study.
Country specific report on mortality trends in Estonia………………………………………………………..
370
Country specific report on mortality trends in France…………………………………………………………
378
Country specific report on mortality trends in Germany………………………………………………………
384
Country specific report on mortality trends in the Netherlands………………………………………………
389
Country specific report on mortality trends in Spain…………………………………………………………..
397
Country specific report on mortality trends in Sweden………………………………………………………..
408
Country specific report on mortality trends in the UK…………………………………………………………
418
H. Evaluation report …………………………………………………………………………………..
430
3
Appendix A. Tables
4
Table 1 (Chapter 1): Change in age standardised deaths rates (per 100,000) and absolute number of deaths in 1979
and 2000 (beginning and end of ICD-9 period) in England and Wales. Causes of death potentially included if ≥ 100
deaths in 2000 and decline in mortality ≥ 30%
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
Neonatal death
0.000
6.414
0
2
Typhoid and paratyphoid fevers
0.005
0.000
100%
2
0
NO
3
Other salmonella infections
0.041
0.017
60%
22
9
NO
4
Shigellosis
0.007
0.000
100%
4
0
NO
5
Other food poisoning (bacterial)
0.009
0.000
100%
5
0
NO
6
Amoebiasis
0.005
0.002
63%
2
1
NO
8
Intestinal infections due to other organisms
0.057
0.087
-52%
23
50
NO
9
Ill-defined intestinal infections
0.210
0.123
42%
85
48
NO
11
Pulmonary tuberculosis
0.634
0.247
61%
330
134
YES
12
13
Other respiratory tuberculosis
Tuberculosis of meninges and central
nervous system
Tuberculosis of intestines, peritoneum and
mesenteric glands
0.002
0.005
-193%
1
3
NO
0.034
0.011
67%
17
6
NO
0.014
0.006
56%
7
3
NO
15
Tuberculosis of bones and joints
0.023
0.033
-45%
11
18
NO
16
Tuberculosis of genitourinary system
0.022
0.000
100%
11
0
NO
17
Tuberculosis of other organs
0.015
0.011
24%
7
6
NO
18
Miliary tuberculosis
0.077
0.039
50%
39
20
NO
27
Other zoonotic bacterial diseases
0.016
0.009
42%
8
5
NO
33
Whooping cough
0.019
0.005
71%
7
2
NO
34
Streptococcal sore throat and scarlatina
0.014
0.002
83%
6
1
NO
36
Meningococcal infection
0.231
0.423
-83%
95
188
NO
37
Tetanus
0.005
0.000
100%
2
0
NO
38
Septicaemia
0.341
1.083
-218%
171
572
NO
39
Actinomycotic infections
0.008
0.008
8%
5
4
NO
40
41
Other bacterial diseases
Bacterial infection in conditions classified
elsewhere and of unspecified site
0.014
0.014
0%
7
7
NO
0.035
0.096
-174%
15
50
NO
46
Slow virus infection of central nervous system
0.060
0.130
-117%
32
66
NO
47
48
Meningitis due to enterovirus
Other enterovirus diseases of central nervous
system
Other non-arthropod-borne viral diseases of
central nervous system
0.016
0.009
45%
7
4
NO
0.006
0.004
25%
3
2
NO
0.095
0.023
76%
43
12
NO
52
Chickenpox
0.041
0.032
21%
19
16
NO
53
Herpes zoster
0.021
0.004
79%
12
2
NO
54
Herpes simplex
0.064
0.025
61%
27
12
NO
55
Measles
0.045
0.002
95%
17
1
NO
56
Rubella
0.005
0.000
100%
2
0
NO
70
Viral hepatitis
0.194
0.346
-78%
88
175
NO
73
Ornithosis
0.005
0.006
-25%
2
3
NO
74
Specific diseases due to Coxsackie virus
0.011
0.000
100%
5
0
NO
49
5
2335
Potentially
included
0
14
0
N
Deaths
2000
NO
ICD-9
75
78
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
Infectious mononucleosis
Other diseases due to viruses and
chlamydiae
Viral infection in conditions classified
elsewhere and of unspecified site
0.009
0.002
74%
4
1
NO
0.010
0.034
-236%
4
15
NO
0.058
0.036
37%
23
17
NO
83
Other rickettsioses
0.002
0.000
100%
1
0
NO
84
Malaria
0.012
0.034
-190%
6
17
NO
85
Leishmaniasis
0.002
0.004
-94%
1
2
NO
90
Congenital syphilis
0.006
0.000
100%
3
0
NO
93
Cardiovascular syphilis
0.032
0.000
100%
18
0
NO
94
Neurosyphilis
0.032
0.000
100%
17
0
NO
97
Other and unspecified syphilis
0.006
0.000
100%
3
0
NO
98
Gonococcal infections
0.004
0.002
44%
2
1
NO
100
Leptospirosis
0.006
0.007
-17%
3
4
NO
112
Candidiasis
0.008
0.042
-416%
4
20
NO
117
Other mycoses
0.051
0.112
-118%
25
57
NO
122
Echinococcosis
0.014
0.000
100%
6
0
NO
127
Other intestinal helminthiases
0.002
0.000
100%
1
0
NO
135
136
Sarcoidosis
Other and unspecified infectious and parasitic
diseases
0.157
0.142
9%
75
74
NO
0.050
0.083
-67%
20
42
NO
137
Late effects of tuberculosis
0.462
0.034
93%
238
20
NO
138
139
Late effects of acute poliomyelitis
Late effects of other infectious and parasitic
diseases
0.034
0.020
41%
17
11
NO
0.019
0.000
100%
10
0
NO
140
Malignant neoplasm of lip
0.041
0.008
80%
23
4
NO
141
Malignant neoplasm of tongue
0.457
0.480
-5%
234
252
NO
142
Malignant neoplasm of major salivary glands
0.193
0.137
29%
101
74
NO
143
Malignant neoplasm of gum
0.133
0.107
20%
72
57
NO
144
145
Malignant neoplasm of floor of mouth
Malignant neoplasm of other and unspecified
parts of mouth
0.133
0.086
36%
68
44
NO
0.212
0.285
-35%
114
150
NO
146
Malignant neoplasm of oropharynx
0.230
0.302
-31%
118
153
NO
147
Malignant neoplasm of nasopharynx
0.230
0.177
23%
116
92
NO
148
149
Malignant neoplasm of hypopharynx
Malignant neoplasm of other and ill-defined
sites within the lip, oral cavity a
0.337
0.184
45%
175
99
NO
0.167
0.255
-52%
88
130
NO
150
Malignant neoplasm of oesophagus
4.319
5.845
-35%
2315
3166
NO
151
152
Malignant neoplasm of stomach
Malignant neoplasm of small intestine,
including duodenum
12.412
4.788
61%
6816
2673
YES
0.310
0.293
6%
162
159
NO
Malignant neoplasm of colon
Malignant neoplasm of rectum, rectosigmoid
junction and anus
Malignant neoplasm of liver and intrahepatic
bile ducts
Malignant neoplasm of gallbladder and
extrahepatic bile ducts
10.785
8.062
25%
5798
4435
NO
6.908
4.120
40%
3715
2244
YES
1.279
2.194
-72%
658
1194
NO
1.157
0.453
61%
637
248
YES
Malignant neoplasm of pancreas
Malignant neoplasm of retroperitoneum and
peritoneum
6.930
5.919
15%
3726
3220
NO
0.311
0.241
22%
159
131
NO
79
153
154
155
156
157
158
6
ICD-9
160
161
162
163
164
165
170
171
Condition
Malignant neoplasm of nasal cavities, middle
ear and accessory sinuses
Malignant neoplasm of larynx
Malignant neoplasm of trachea, bronchus and
lung
Malignant neoplasm of pleura
Malignant neoplasm of thymus, heart and
mediastinum
sites within the respiratory system
Malignant neoplasm of bone and articular
cartilage
Malignant neoplasm of connective and other
soft tissue
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
0.272
0.146
46%
138
76
NO
1.097
0.794
28%
579
422
NO
47.882
29.891
38%
25777
16484
YES
0.395
0.647
-64%
201
353
NO
0.108
0.104
3%
52
53
NO
0.002
0.028
-1600%
1
15
NO
0.490
0.325
34%
252
159
YES
0.667
0.916
-37%
332
473
NO
172
Malignant melanoma of skin
1.427
2.112
-48%
672
1096
NO
173
Other malignant neoplasm of skin
0.316
0.209
34%
174
116
YES
174
Malignant neoplasm of female breast
17.457
12.694
27%
8604
6607
NO
175
179
Malignant neoplasm of male breast
Malignant neoplasm of uterus, part
unspecified
0.125
0.065
48%
63
35
NO
0.369
0.433
-17%
195
230
NO
180
Malignant neoplasm of cervix uteri
3.421
1.474
57%
1662
764
YES
181
Malignant neoplasm of placenta
0.013
0.006
53%
6
3
NO
182
183
Malignant neoplasm of body of uterus
Malignant neoplasm of ovary and other
uterine adnexa
female genital organs
1.383
0.767
45%
751
417
YES
5.760
4.684
19%
2863
2475
NO
0.486
0.286
41%
264
157
YES
185
Malignant neoplasm of prostate
3.756
4.431
-18%
2222
2573
NO
186
187
Malignant neoplasm of testis
Malignant neoplasm of penis and other male
genital organs
0.397
0.128
68%
186
64
NO
0.141
0.096
32%
78
51
NO
Malignant neoplasm of bladder
Malignant neoplasm of kidney and other and
unspecified urinary organs
4.266
3.027
29%
2393
1713
NO
2.622
3.064
-17%
1340
1640
NO
190
Malignant neoplasm of eye
0.199
0.084
58%
102
44
NO
191
192
Malignant neoplasm of brain
parts of nervous system
4.444
4.414
1%
2129
2278
NO
0.105
0.065
38%
51
34
NO
193
194
Malignant neoplasm of thyroid gland
Malignant neoplasm of other endocrine
glands and related structures
sites
Malignant neoplasm without specification of
site
0.448
0.230
49%
242
127
YES
0.207
0.286
-38%
95
141
NO
0.393
0.341
13%
213
187
NO
6.989
11.042
-58%
3784
6070
NO
200
Lymphosarcoma and reticulosarcoma
1.138
0.122
89%
589
62
NO
201
202
Hodgkin’s disease
Other malignant neoplasm of lymphoid and
histiocytic tissue
Multiple myeloma and immunoproliferative
neoplasms
1.054
0.373
65%
512
194
YES
1.924
4.115
-114%
972
2205
NO
1.996
1.891
5%
1085
1043
NO
204
Lymphoid leukaemia
1.288
1.028
20%
672
537
NO
205
Myeloid leukaemia
2.709
2.287
16%
1358
1222
NO
206
Monocytic leukaemia
0.097
0.020
80%
50
11
NO
207
Other and unspecified leukaemia
0.069
0.017
76%
38
9
NO
184
188
189
195
199
203
7
ICD-9
210
Condition
Benign neoplasm of lip, oral cavity and
pharynx
Benign neoplasm of other parts of digestive
system
Benign neoplasm of respiratory and
intrathoracic organs
Benign neoplasm of bone and articular
cartilage
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
0.008
0.000
100%
5
0
NO
0.040
0.028
29%
22
15
NO
0.028
0.027
2%
14
13
NO
0.004
0.002
55%
2
1
NO
Lipoma
Other benign neoplasm of connective and
other soft tissue
0.006
0.004
39%
3
2
NO
0.006
0.015
-133%
3
7
NO
216
Benign neoplasm of skin
0.003
0.006
-127%
1
3
NO
217
Benign neoplasm of breast
0.002
0.000
100%
1
0
NO
218
Uterine leiomyoma
0.040
0.011
73%
18
6
NO
220
221
Benign neoplasm of ovary
Benign neoplasm of other female genital
organs
Benign neoplasm of kidney and other urinary
organs
Benign neoplasm of brain and other parts of
nervous system
Benign neoplasm of other endocrine glands
and related structures
0.025
0.007
70%
14
4
NO
0.002
0.000
100%
1
0
NO
0.003
0.000
100%
2
0
NO
0.304
0.180
41%
155
98
NO
0.119
0.035
71%
57
18
NO
Haemangioma and lymphangioma, any site
Benign neoplasm of other and unspecified
sites
0.066
0.013
80%
31
6
NO
0.006
0.030
-438%
2
14
NO
Carcinoma in situ of digestive organs
Carcinoma in situ of breast and genitourinary
system
Carcinoma in situ of other and unspecified
sites
Neoplasm of uncertain behaviour of digestive
and respiratory systems
Neoplasm of uncertain behaviour of
genitourinary organs
Neoplasm of uncertain behaviour of
endocrine glands and nervous system
Neoplasm of uncertain behaviour of other and
unspecified sites and tissues
0.002
0.000
100%
1
0
NO
0.007
0.000
100%
3
0
NO
0.002
0.000
100%
1
0
NO
0.046
0.043
7%
24
24
NO
0.015
0.000
100%
8
0
NO
0.125
0.051
59%
59
26
NO
211
212
213
214
215
223
225
227
228
229
230
233
234
235
236
237
238
0.255
0.197
23%
140
108
NO
239
Neoplasm of unspecified nature
0.939
1.012
-8%
477
548
NO
240
Simple and unspecified goitre
0.010
0.002
83%
5
1
NO
241
Nontoxic nodular goitre
0.005
0.005
9%
3
3
NO
242
Thyrotoxicosis with or without goitre
0.175
0.040
77%
93
22
NO
244
Acquired hypothyroidism
0.210
0.031
85%
121
18
NO
245
Thyroiditis
0.010
0.002
81%
5
1
NO
246
Other disorders of thyroid
0.002
0.004
-83%
1
2
NO
250
251
Diabetes mellitus
Other disorders of pancreatic internal
secretion
4.637
3.859
17%
2567
2143
NO
0.032
0.030
6%
15
16
NO
Disorders of parathyroid gland
Disorders of the pituitary gland and its
hypothalamic control
0.020
0.006
70%
10
3
NO
0.042
0.025
41%
21
13
NO
254
Diseases of thymus gland
0.003
0.000
100%
1
0
NO
255
Disorders of adrenal glands
0.126
0.033
74%
63
17
NO
256
Ovarian dysfunction
0.003
0.000
100%
1
0
NO
252
253
8
ICD-9
261
263
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
Nutritional marasmus
Other and unspecified protein-calorie
malnutrition
0.006
0.003
47%
3
2
NO
0.031
0.012
59%
16
7
NO
265
Thiamine and niacin deficiency states
0.008
0.000
100%
4
0
NO
266
Deficiency of B-complex components
0.003
0.000
100%
2
0
NO
268
270
Vitamin D deficiency
Disorders of amino-acid transport and
metabolism
Disorders of carbohydrate transport and
metabolism
0.009
0.002
83%
6
1
NO
0.038
0.013
66%
16
6
NO
0.029
0.015
48%
11
6
NO
272
Disorders of lipoid metabolism
0.145
0.189
-30%
65
96
NO
273
Disorders of plasma protein metabolism
0.057
0.071
-25%
32
41
NO
274
Gout
0.014
0.000
100%
8
0
NO
275
276
Disorders of mineral metabolism
Disorders of fluid, electrolyte and acid-base
balance
Other and unspecified disorders of
metabolism
0.079
0.060
24%
40
31
NO
0.078
0.088
-13%
42
46
NO
0.581
0.549
5%
270
269
NO
278
Obesity and other hyperalimentation
0.220
0.277
-26%
110
143
NO
279
Disorders involving the immune mechanism
0.042
0.055
-31%
19
28
NO
280
Iron deficiency anaemias
0.073
0.000
100%
43
0
NO
281
Other deficiency anaemias
0.150
0.004
97%
86
2
NO
282
Hereditary haemolytic anaemias
0.065
0.056
14%
31
28
NO
283
Acquired haemolytic anaemias
0.060
0.040
33%
29
21
NO
284
Aplastic anaemia
0.250
0.123
51%
131
64
NO
285
Other and unspecified anaemias
0.166
0.039
77%
98
22
NO
286
Coagulation defects
0.138
0.113
18%
70
55
NO
287
Purpura and other haemorrhagic conditions
0.111
0.042
63%
56
21
NO
288
289
Diseases of white blood cells
Other diseases of blood and blood-forming
organs
Senile and presenile organic psychotic
conditions
0.033
0.071
-116%
16
38
NO
0.279
0.494
-77%
149
278
NO
0.792
0.709
11%
480
431
NO
291
Alcoholic psychoses
0.003
0.032
-1149%
1
16
NO
294
Other organic psychotic conditions (chronic)
0.011
0.025
-129%
6
14
NO
295
Schizophrenic psychoses
0.034
0.028
18%
16
16
NO
296
Affective psychoses
0.025
0.007
73%
14
4
NO
297
Paranoid states
0.003
0.000
100%
2
0
NO
298
Other nonorganic psychoses
0.060
0.340
-466%
35
206
NO
300
Neurotic disorders
0.015
0.006
59%
7
3
NO
303
Alcohol dependence syndrome
0.227
0.584
-158%
98
290
NO
304
Drug dependence
0.228
0.855
-275%
109
428
NO
305
306
Nondependent abuse of drugs
Physiological malfunction arising from mental
factors
Special symptoms or syndromes not
elsewhere classified
Specific nonpsychotic mental disorders
following organic brain damage
0.233
1.222
-424%
104
607
NO
0.002
0.000
100%
1
0
NO
0.043
0.044
-3%
20
22
NO
0.006
0.000
100%
3
0
NO
Depressive disorder, not elsewhere classified
0.025
0.019
22%
14
11
NO
271
277
290
307
310
311
9
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
318
Other specified mental retardation
0.023
0.002
92%
10
1
NO
319
Other specified mental retardation
0.034
0.025
28%
16
13
NO
320
Bacterial meningitis
0.407
0.189
54%
178
91
NO
322
Meningitis of unspecified cause
0.150
0.143
5%
65
70
NO
323
Encephalitis, myelitis and encephalomyelitis
0.126
0.066
48%
54
34
NO
324
325
Intracranial and intraspinal abscess
Phlebitis and thrombophlebitis of intracranial
venous sinuses
Late effects of intracranial abscess or
pyogenic infection
Cerebral degenerations usually manifest in
childhood
0.062
0.047
25%
30
23
NO
0.022
0.028
-28%
10
14
NO
0.067
0.000
100%
32
0
NO
0.058
0.126
-119%
26
53
NO
331
Other cerebral degenerations
0.385
0.775
-102%
193
436
NO
332
333
Parkinson’s disease
Other extrapyramidal disease and abnormal
movement disorders
1.006
0.653
35%
618
394
YES
0.259
0.294
-14%
124
150
NO
334
Spinocerebellar disease
0.080
0.108
-35%
38
56
NO
335
Anterior horn cell disease
1.456
1.533
-5%
738
815
NO
336
Other diseases of spinal cord
0.056
0.063
-11%
29
34
NO
337
Disorders of the autonomic nervous system
0.001
0.004
-147%
1
2
NO
340
341
Multiple sclerosis
Other demyelinating diseases of central
nervous system
1.607
1.158
28%
756
585
NO
0.022
0.013
39%
10
7
NO
342
Hemiplegia
0.544
0.037
93%
329
21
NO
343
Infantile cerebral palsy
0.154
0.337
-119%
71
155
NO
344
Other paralytic syndromes
0.132
0.095
28%
67
50
NO
345
Epilepsy
1.274
1.459
-14%
583
728
NO
347
Cataplexy and narcolepsy
0.001
0.000
100%
1
0
NO
348
349
Other conditions of brain
Other and unspecified disorders of the
nervous system
0.163
0.229
-41%
75
114
NO
0.024
0.064
-169%
11
31
NO
Trigeminal nerve disorders
Mononeuritis of upper limb and mononeuritis
multiplex
0.003
0.000
100%
1
0
NO
0.001
0.000
100%
1
0
NO
Mononeuritis of lower limb
Hereditary and idiopathic peripheral
neuropathy
0.004
0.021
-408%
2
10
NO
0.040
0.105
-162%
22
60
NO
357
Inflammatory and toxic neuropathy
0.055
0.035
36%
25
19
NO
358
Myoneural disorders
0.054
0.039
27%
27
19
NO
359
363
Muscular dystrophies and other myopathies
Chorioretinal inflammations and scars and
other disorders of choroid
0.319
0.376
-18%
156
177
NO
0.001
0.000
100%
1
0
NO
Disorders of the orbit
Strabismus and other disorders of binocular
eye movements
Nonsuppurative otitis media and Eustachian
tube disorders
0.003
0.000
100%
2
0
NO
0.003
0.000
100%
2
0
NO
0.003
0.000
100%
1
0
NO
382
Suppurative and unspecified otitis media
0.081
0.012
86%
36
6
NO
383
Mastoiditis and related conditions
0.004
0.000
100%
2
0
NO
385
Other disorders of middle ear and mastoid
0.006
0.004
34%
3
2
NO
326
330
350
354
355
356
376
378
381
10
ICD-9
390
Condition
Rheumatic fever without mention of heart
involvement
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
0.003
0.000
100%
1
0
NO
391
Rheumatic fever with heart involvement
0.003
0.031
-1093%
1
17
NO
393
Chronic rheumatic pericarditis
0.012
0.004
68%
7
2
NO
394
Diseases of mitral valve
2.584
0.684
74%
1334
379
YES
395
Diseases of aortic valve
0.280
0.016
94%
142
9
NO
396
Diseases of mitral and aortic valves
0.706
0.185
74%
362
102
YES
397
Diseases of other endocardial structures
0.268
0.083
69%
138
47
NO
398
Other rheumatic heart disease
0.848
0.074
91%
436
42
NO
401
Essential hypertension
0.521
0.103
80%
288
58
NO
402
Hypertensive heart disease
4.209
1.568
63%
2342
854
YES
403
Hypertensive renal disease
0.694
0.191
72%
366
112
YES
404
Hypertensive heart and renal disease
410
411
Acute myocardial infarction
Other acute and subacute forms of ischaemic
heart disease
413
414
Angina pectoris
Other forms of chronic ischaemic heart
disease
0.218
0.074
66%
117
41
NO
118.991
34.684
71%
64375
19316
YES
2.316
0.090
96%
1223
49
NO
0.081
0.037
54%
46
21
NO
38.104
34.807
9%
20923
19376
NO
415
Acute pulmonary heart disease
2.957
3.632
-23%
1631
1999
NO
416
Chronic pulmonary heart disease
1.203
0.399
67%
658
208
YES
417
Other diseases of pulmonary circulation
0.009
0.011
-20%
5
5
NO
420
Acute pericarditis
0.085
0.034
60%
45
19
NO
421
Acute and subacute endocarditis
0.288
0.275
5%
143
147
NO
422
Acute myocarditis
0.167
0.103
38%
78
51
NO
423
Other diseases of pericardium
0.181
0.131
28%
94
70
NO
424
Other diseases of endocardium
3.051
1.554
49%
1685
878
YES
425
Cardiomyopathy
1.535
2.182
-42%
734
1116
NO
426
Conduction disorders
0.072
0.050
31%
43
26
NO
427
Cardiac dysrhythmias
1.098
0.870
21%
625
492
NO
428
429
Heart failure
Ill-defined descriptions and complications of
heart disease
4.784
1.974
59%
2814
1144
YES
3.171
0.885
72%
1859
469
YES
430
Subarachnoid haemorrhage
6.306
3.647
42%
3054
1880
YES
431
432
Intracerebral haemorrhage
Other and unspecified intracranial
haemorrhage
Occlusion and stenosis of precerebral
arteries
9.273
3.739
60%
5075
2018
YES
0.201
0.391
-94%
100
211
NO
0.502
0.146
71%
262
80
NO
434
Occlusion of cerebral arteries
8.967
1.911
79%
5319
1081
YES
435
Transient cerebral ischaemia
0.020
0.019
5%
11
11
NO
436
Acute but ill-defined cerebrovascular disease
20.203
8.827
56%
11849
5199
YES
437
Other and ill-defined cerebrovascular disease
2.475
1.347
46%
1490
797
YES
438
Late effects of cerebrovascular disease
0.032
0.109
-241%
19
63
NO
440
Atherosclerosis
1.981
0.246
88%
1213
146
YES
441
Aortic aneurysm
5.745
5.346
7%
3296
3103
NO
442
Other aneurysm
0.154
0.168
-9%
83
94
NO
433
11
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
444
Arterial embolism and thrombosis
0.412
0.106
74%
228
58
NO
446
Polyarteritis nodosa and allied conditions
0.292
0.175
40%
140
93
NO
447
Other disorders of arteries and arterioles
0.217
0.308
-42%
117
169
NO
448
Diseases of capillaries
0.017
0.002
88%
10
1
NO
451
Phlebitis and thrombophlebitis
1.365
1.181
13%
748
648
NO
452
Portal vein thrombosis
0.034
0.041
-22%
17
23
NO
453
Other venous embolism and thrombosis
2.571
0.181
93%
1416
98
NO
454
Varicose veins of lower extremities
0.107
0.043
60%
59
23
NO
455
Haemorrhoids
0.004
0.006
-66%
2
3
NO
456
Varicose veins of other sites
0.059
0.059
0%
31
29
NO
457
Noninfective disorders of lymphatic channels
0.005
0.019
-261%
2
11
NO
458
Hypotension
0.027
0.024
12%
17
13
NO
459
Other disorders of circulatory system
0.095
0.079
17%
50
43
NO
462
Acute pharyngitis
0.004
0.004
-14%
2
2
NO
463
Acute tonsillitis
0.014
0.007
52%
7
3
NO
464
465
Acute laryngitis and tracheitis
Acute upper respiratory infections of multiple
or unspecified site
0.135
0.021
84%
52
10
NO
0.063
0.006
91%
24
3
NO
466
Acute bronchitis and bronchiolitis
1.382
0.304
78%
618
156
YES
473
Chronic sinusitis
0.015
0.020
-37%
8
10
NO
474
Chronic disease of tonsils and adenoids
0.005
0.000
100%
2
0
NO
475
Peritonsillar abscess
0.008
0.000
100%
4
0
NO
478
Other diseases of upper respiratory tract
0.051
0.031
39%
25
16
NO
480
Viral pneumonia
0.533
0.080
85%
232
38
NO
481
Pneumococcal pneumonia
2.271
1.079
53%
1214
588
YES
482
Other bacterial pneumonia
0.198
0.169
15%
90
88
NO
483
Pneumonia due to other specified organism
0.019
0.049
-161%
9
26
NO
485
Bronchopneumonia, organism unspecified
19.646
9.842
50%
11354
5624
YES
486
Pneumonia, organism unspecified
1.271
3.891
-206%
625
2169
NO
487
Influenza
0.488
0.151
69%
262
82
NO
490
Bronchitis, not specified as acute or chronic
0.375
0.103
72%
196
55
NO
491
Chronic bronchitis
16.841
0.852
95%
9653
483
YES
492
Emphysema
1.620
1.236
24%
901
696
NO
493
Asthma
2.216
1.391
37%
1109
726
YES
494
Bronchiectasis
0.791
0.618
22%
407
339
NO
495
496
Extrinsic allergic alveolitis
Chronic airways obstruction, not elsewhere
classified
0.023
0.022
8%
13
12
NO
2.846
12.079
-324%
1609
7002
NO
500
Coalworkers’ pneumoconiosis
0.189
0.070
63%
115
43
NO
501
502
Asbestosis
Pneumoconiosis due to other silica or
silicates
0.041
0.054
-31%
22
32
NO
0.040
0.013
67%
24
8
NO
503
Pneumoconiosis due to other inorganic dust
0.002
0.004
-115%
1
2
NO
504
Pneumopathy due to inhalation of other dust
0.028
0.000
100%
15
0
NO
505
Pneumoconiosis, unspecified
0.070
0.005
93%
39
3
NO
12
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
510
Empyema
0.093
0.171
-84%
48
93
NO
511
Pleurisy
0.056
0.048
14%
29
27
NO
512
Pneumothorax
0.051
0.026
49%
27
13
NO
513
Abscess of lung and mediastinum
0.161
0.091
43%
85
49
NO
514
Pulmonary congestion and hypostasis
0.050
0.056
-12%
30
31
NO
515
516
Postinflammatory pulmonary fibrosis
Other alveolar and parietoalveolar
pneumopathy
0.444
0.625
-41%
239
352
NO
0.494
1.100
-122%
254
610
NO
518
Other diseases of lung
0.153
0.299
-95%
78
146
NO
519
Other diseases of respiratory system
0.540
1.059
-96%
250
604
NO
522
524
Diseases of pulp and periapical tissues
Dentofacial anomalies, including
malocclusion
Diseases of the oral soft tissues, excluding
lesions specific for gingiva and tongue
0.002
0.004
-157%
1
2
NO
0.003
0.000
100%
1
0
NO
0.003
0.004
-20%
2
2
NO
530
Diseases of oesophagus
0.315
0.370
-17%
174
192
NO
531
Gastric ulcer
1.523
0.700
54%
834
387
YES
532
Duodenal ulcer
1.878
1.329
29%
1020
744
YES
533
Peptic ulcer, site unspecified
0.205
0.199
3%
117
113
NO
534
Gastrojejunal ulcer
0.025
0.006
78%
14
3
NO
535
Gastritis and duodenitis
0.042
0.141
-232%
22
73
NO
536
Disorders of function of stomach
0.026
0.017
35%
12
9
NO
537
Other disorders of stomach and duodenum
0.127
0.050
61%
69
29
NO
540
Acute appendicitis
0.178
0.098
45%
95
53
NO
541
Appendicitis, unqualified
0.043
0.016
64%
22
8
NO
542
Other appendicitis
0.003
0.000
100%
2
0
NO
543
Other diseases of appendix
0.003
0.000
100%
2
0
NO
550
551
Inguinal hernia
Other hernia of abdominal cavity, with
gangrene
Other hernia of abdominal cavity with
obstruction, without mention of gangrene
Other hernia of abdominal cavity without
mention of obstruction or gangrene
0.148
0.075
50%
84
41
NO
0.002
0.036
-1712%
1
19
NO
0.258
0.124
52%
150
68
NO
0.258
0.085
67%
127
48
NO
140
94
NO
528
552
553
555
Regional enteritis
0.278
0.179
36%
556
Idiopathic proctocolitis
0.306
0.126
59%
160
69
NO
557
Vascular insuffiency of intestine
1.107
1.072
3%
616
598
NO
558
560
Other noninfective gastroenteritis and colitis
Intestinal obstruction without mention of
hernia
0.200
0.211
-5%
101
117
NO
0.816
0.593
27%
437
333
NO
562
564
Diverticula of intestine
Functional digestive disorders, not elsewhere
classified
0.925
0.763
18%
523
438
NO
0.068
0.044
35%
35
24
NO
566
Abscess of anal and rectal regions
0.020
0.020
0%
10
11
NO
567
Peritonitis
0.148
0.302
-104%
79
168
NO
568
Other disorders of peritoneum
0.041
0.068
-65%
24
37
NO
569
Other disorders of intestine
0.246
0.503
-104%
134
280
NO
570
Acute and subacute necrosis of liver
0.131
0.061
53%
62
31
NO
571
Chronic liver disease and cirrhosis
3.832
8.317
-117%
1861
4196
NO
13
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
573
Other disorders of liver
0.119
0.144
-21%
58
72
NO
574
Cholelithiasis
0.375
0.219
42%
208
121
YES
575
Other disorders of gallbladder
0.201
0.170
16%
113
96
NO
576
Other disorders of biliary tract
0.147
0.151
-3%
82
81
NO
577
Diseases of pancreas
1.010
0.950
6%
511
506
NO
578
Gastrointestinal haemorrhage
0.222
0.469
-111%
118
268
NO
579
Intestinal malabsorption
0.048
0.025
49%
25
13
NO
580
Acute glomerulonephritis
0.032
0.015
53%
16
8
NO
581
Nephrotic syndrome
0.092
0.027
71%
46
13
NO
582
583
Chronic glomerulonephritis
Nephritis and nephropathy, not specified as
acute or chronic
0.536
0.041
92%
274
22
NO
0.169
0.087
49%
85
48
NO
584
Acute renal failure
0.339
0.188
44%
189
109
YES
585
Chronic renal failure
1.468
0.419
71%
821
237
YES
586
Renal failure, unspecified
0.610
0.438
28%
340
242
NO
587
588
Renal sclerosis, unspecified
Disorders resulting from impaired renal
function
0.014
0.020
-43%
8
11
NO
0.006
0.004
34%
3
2
NO
589
Small kidney of unknown cause
0.002
0.007
-349%
1
4
NO
590
Infections of kidney
1.024
0.282
72%
559
156
YES
591
Hydronephrosis
0.062
0.023
63%
34
12
NO
592
Calculus of kidney and ureter
0.165
0.085
48%
94
47
NO
593
Other disorders of kidney and ureter
0.206
0.196
5%
101
106
NO
594
Calculus of lower urinary tract
0.015
0.000
100%
8
0
NO
595
Cystitis
0.036
0.019
48%
20
10
NO
596
597
Other disorders of bladder
Urethritis, not sexually transmitted, and
urethral syndrome
0.049
0.037
25%
28
20
NO
0.001
0.000
100%
1
0
NO
598
Urethral stricture
0.015
0.000
100%
9
0
NO
599
Other disorders of urethra and urinary tract
0.198
0.620
-214%
113
361
NO
600
Hyperplasia of prostate
0.385
0.040
90%
237
24
NO
601
Inflammatory diseases of prostate
0.006
0.004
41%
4
2
NO
602
Other disorders of prostate
0.006
0.003
45%
3
2
NO
604
Orchitis and epididymitis
0.009
0.004
56%
4
2
NO
608
Other disorders of male genital organs
0.006
0.030
-383%
4
15
NO
611
614
Other disorders of breast
Inflammatory disease of ovary, fallopian tube,
pelvic cellular tissue and perit
Inflammatory diseases of uterus, except
cervix
0.006
0.002
72%
3
1
NO
0.046
0.023
50%
23
12
NO
0.014
0.015
-11%
8
8
NO
618
Genital prolapse
0.019
0.004
80%
11
2
NO
619
620
Fistulae involving female genital tract
Noninflammatory disorders of ovary, fallopian
tube and broad ligament
0.010
0.007
34%
5
4
NO
0.032
0.031
4%
16
16
NO
621
Disorders of uterus, not elsewhere classified
0.025
0.012
54%
12
6
NO
627
Menopausal and postmenopausal disorders
0.003
0.000
100%
1
0
NO
633
Ectopic pregnancy
0.006
0.010
-62%
3
5
NO
615
14
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
635
Legally induced abortion
0.005
0.002
56%
2
1
NO
637
639
Unspecified abortion
Complications following abortion and ectopic
and molar pregnancies
Antepartum haemorrhage, abruptio
placentae, and placenta praevia
Hypertension complicating pregnancy,
childbirth and the puerperium
Other complications of pregnancy, not
Infective and parasitic conditions in the
mother classifiable elsewhere but com
Other current conditions in the mother
classifiable elsewhere but complicating
Abnormality of organs and soft tissues of
pelvis
Other fetal and placental problems affecting
management of mother
Other problems associated with amniotic
cavity and membranes
0.004
0.000
100%
2
0
NO
0.002
0.000
100%
1
0
NO
0.013
0.002
86%
6
1
NO
0.027
0.013
51%
13
7
NO
0.006
0.000
100%
3
0
NO
0.002
0.000
100%
1
0
NO
0.013
0.009
26%
6
5
NO
0.002
0.000
100%
1
0
NO
0.007
0.002
73%
3
1
NO
0.002
0.000
100%
1
0
NO
660
Obstructed labour
0.002
0.000
100%
1
0
NO
665
Other obstetrical trauma
0.002
0.000
100%
1
0
NO
666
668
Postpartum haemorrhage
Complications of the administration of
anaesthetic or other sedation in labour
Other complications of labour and delivery,
not elsewhere classified
0.004
0.000
100%
2
0
NO
0.006
0.000
100%
3
0
NO
0.006
0.002
72%
3
1
NO
670
671
Major puerperal infection
Venous complications in pregnancy and the
puerperium
0.002
0.004
-81%
1
2
NO
0.016
0.004
78%
7
2
NO
673
674
Obstetrical pulmonary embolism
Other and unspecified complications of the
puerperium, not elsewhere classified
0.015
0.012
22%
7
6
NO
0.013
0.011
13%
6
6
NO
680
Carbuncle and furuncle
0.001
0.000
100%
1
0
NO
682
Other cellulitis and abscess
0.062
0.236
-282%
33
130
NO
685
686
Pilonidal cyst
Other local infections of skin and
subcutaneous tissue
0.002
0.004
-111%
1
2
NO
0.017
0.022
-28%
8
12
NO
693
Dermatitis due to substances taken internally
0.003
0.006
-111%
1
3
NO
694
Bullous dermatoses
0.010
0.007
35%
6
4
NO
695
Erythematous conditions
0.025
0.035
-37%
15
19
NO
696
Psoriasis and similar disorders
0.020
0.013
35%
10
7
NO
707
709
Chronic ulcer of skin
Other disorders of skin and subcutaneous
tissue
0.097
0.137
-42%
57
80
NO
0.008
0.002
79%
4
1
NO
710
Diffuse diseases of connective tissue
0.528
0.333
37%
257
176
YES
711
714
Arthropathy associated with infections
Rheumatoid arthritis and other inflammatory
polyarthropathies
0.036
0.055
-54%
21
31
NO
0.928
0.430
54%
514
246
YES
715
Osteoarthrosis and allied disorders
0.146
0.039
73%
87
23
NO
716
Other and unspecified arthropathies
0.054
0.014
73%
31
8
NO
718
Other derangement of joint
0.006
0.002
68%
4
1
NO
719
720
Other and unspecified disorder of joint
Ankylosing spondylitis and other inflammatory
spondylopathies
0.029
0.120
-321%
16
68
NO
0.039
0.012
69%
21
6
NO
641
642
646
647
648
654
656
658
669
15
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
722
Intervertebral disc disorders
0.015
0.014
6%
8
8
NO
723
Other disorders of cervical region
0.001
0.002
-1%
1
1
NO
724
Other and unspecified disorders of back
0.012
0.010
16%
6
5
NO
725
726
Polymyalgia rheumatica
Peripheral enthesopathies and allied
syndromes
0.008
0.002
81%
5
1
NO
0.006
0.004
35%
3
2
NO
728
730
Disorders of muscle, ligament and fascia
Osteomyelitis, periostitis and other infections
involving bone
Osteitis deformans and osteopathies
associated with other disorders classified
0.012
0.036
-198%
6
21
NO
0.040
0.069
-71%
21
38
NO
0.030
0.003
90%
18
2
NO
733
Other disorders of bone and cartilage
0.159
0.147
8%
96
86
NO
736
Other acquired deformities of limbs
0.001
0.000
100%
1
0
NO
737
Curvature of spine
0.063
0.097
-54%
34
51
NO
738
Other acquired deformity
0.006
0.002
66%
3
1
NO
740
Anencephalus and similar anomalies
0.189
0.000
100%
70
0
NO
741
742
Spina bifida
Other congenital anomalies of nervous
system
1.252
0.080
94%
481
39
NO
0.585
0.177
70%
232
74
NO
743
Congenital anomalies of eye
0.004
0.000
100%
2
0
NO
744
745
Congenital anomalies of ear, face and neck
Bulbus cordis anomalies and anomalies of
cardiac septal closure
0.003
0.000
100%
1
0
NO
1.535
0.381
75%
621
174
YES
746
747
Other congenital anomalies of heart
Other congenital anomalies of circulatory
system
1.436
0.553
61%
587
249
YES
0.640
0.225
65%
260
101
YES
748
Congenital anomalies of respiratory system
0.314
0.049
85%
118
18
NO
749
750
Cleft palate and cleft lip
Other congenital anomalies of upper
alimentary tract
Other congenital anomalies of digestive
system
0.016
0.003
83%
6
1
NO
0.113
0.016
86%
45
6
NO
0.300
0.053
82%
118
23
NO
752
Congenital anomalies of genital organs
0.005
0.002
57%
2
1
NO
753
754
Congenital anomalies of urinary system
Certain congenital musculoskeletal
deformities
0.597
0.099
83%
260
51
NO
0.009
0.004
52%
4
2
NO
755
Other congenital anomalies of limbs
0.022
0.004
81%
9
2
NO
756
Other congenital musculoskeletal anomalies
0.367
0.064
83%
141
27
NO
757
Congenital anomalies of the integument
0.031
0.026
16%
13
11
NO
758
Chromosomal anomalies
0.350
0.255
27%
137
114
NO
759
760
Other and unspecified congenital anomalies
Fetus or newborn affected by maternal
conditions which may be unrelated to pres
Fetus or newborn affected by maternal
complications of pregnancy
Fetus or newborn affected by complications
of placenta cord and membranes
Fetus or newborn affected by other
complications of labour and delivery
0.682
0.172
75%
268
73
NO
0.073
0.003
96%
27
1
NO
0.405
0.005
99%
150
2
NO
0.292
0.003
99%
108
1
NO
0.140
0.000
100%
52
0
NO
0.022
0.003
87%
8
1
NO
1.639
0.016
99%
607
6
NO
731
751
761
762
763
764
765
Slow fetal growth and fetal malnutrition
Disorders relating to short gestation and
unspecified low birthweight
16
ICD-9
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
767
Birth trauma
0.516
0.000
100%
191
0
NO
768
Intrauterine hypoxia and birth asphyxia
0.942
0.011
99%
349
4
NO
769
770
Respiratory distress syndrome
Other respiratory conditions of fetus and
newborn
2.254
0.047
98%
835
17
NO
1.474
0.088
94%
546
32
NO
771
Infections specific to the perinatal period
0.253
0.011
96%
95
4
NO
772
773
Fetal and neonatal haemorrhage
Haemolytic disease of fetus or newborn, due
to isoimmunization
0.524
0.003
99%
194
1
NO
0.100
0.000
100%
37
0
NO
Other perinatal jaundice
Endocrine and metabolic disturbances
specific to the fetus and newborn
Haematological disorders of fetus and
newborn
0.008
0.003
66%
3
1
NO
0.027
0.003
90%
10
1
NO
0.073
0.000
100%
27
0
NO
Perinatal disorders of digestive system
Conditions involving the integument and
temperature regulation of fetus and new
Other and ill-defined conditions originating in
the perinatal period
0.197
0.025
87%
73
9
NO
0.046
0.003
94%
17
1
NO
0.254
0.005
98%
94
2
NO
General symptoms
Symptoms concerning nutrition, metabolism
and development
0.025
0.023
7%
12
12
NO
0.001
0.000
100%
1
0
NO
784
Symptoms involving head and neck
0.014
0.000
100%
6
0
NO
785
786
Symptoms involving cardiovascular system
Symptoms involving respiratory system and
other chest symptoms
0.011
0.012
-6%
6
6
NO
0.012
0.018
-51%
6
9
NO
790
Nonspecific findings on examination of blood
0.011
0.003
76%
4
1
NO
791
Nonspecific findings on examination of urine
0.005
0.000
100%
2
0
NO
797
Senility without mention of psychosis
0.033
0.068
-104%
22
45
NO
798
799
Sudden death, cause unknown
Other ill-defined and unknown causes of
morbidity and mortality
Railway accident involving collision with
rolling stock
2.591
0.567
78%
982
214
YES
0.196
1.426
-628%
93
695
NO
0.010
0.000
100%
4
0
NO
804
Fall in, on or from railway train
0.041
0.004
89%
19
2
NO
805
Hit by rolling stock
0.169
0.081
52%
79
39
NO
806
Other specified railway accident
0.009
0.000
100%
4
0
NO
807
810
Railway accident of unspecified nature
Motor vehicle traffic accident involving
collision with train
Motor vehicle traffic accident involving reentrant collision with another motor vehicle
Other motor vehicle traffic accident involving
collision with another motor vehicle
collision with other vehicle
collision with pedestrian
Other motor vehicle traffic accident involving
collision on the highway
Motor vehicle traffic accident due to loss of
control, without collision on the
Noncollision motor vehicle traffic accident
while boarding or alighting
Other noncollision motor vehicle traffic
accident
0.007
0.004
33%
3
2
NO
0.014
0.002
83%
6
1
NO
0.113
0.000
100%
51
0
NO
4.181
2.009
52%
2028
990
YES
0.519
0.172
67%
265
82
NO
2.980
1.024
66%
1481
510
YES
1.541
0.606
61%
757
290
YES
0.786
0.623
21%
379
299
NO
0.027
0.006
78%
14
3
NO
0.123
0.054
56%
60
27
NO
774
775
776
777
778
779
780
783
800
811
812
813
814
815
816
817
818
17
ICD-9
821
822
823
824
825
Condition
Nontraffic accident involving other off-road
motor vehicle
Other motor vehicle nontraffic accident
involving collision with moving object
Other motor vehicle nontraffic accident
involving collision with stationary object
Other motor vehicle nontraffic accident while
boarding and alighting
Other motor vehicle nontraffic accident of
other and unspecified nature
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
0.019
0.037
-95%
8
17
NO
0.052
0.020
61%
24
9
NO
0.019
0.008
55%
9
4
NO
0.008
0.002
69%
4
1
NO
0.021
0.027
-30%
10
13
NO
826
Pedal cycle accident
0.079
0.055
30%
40
27
NO
827
Animal-drawn vehicle accident
0.002
0.004
-101%
1
2
NO
828
Accident involving animal being ridden
0.040
0.028
30%
19
14
NO
830
Accident to watercraft causing submersion
0.101
0.020
80%
46
10
NO
831
832
Accident to watercraft causing other injury
Other accidental submersion or drowning in
water transport accident
Other fall from one level to another in water
transport
0.009
0.000
100%
4
0
NO
0.042
0.005
88%
20
3
NO
0.014
0.002
85%
6
1
NO
835
Other and unspecified fall in water transport
0.007
0.002
75%
3
1
NO
836
Machinery accident in water transport
0.002
0.002
2%
1
1
NO
837
838
Explosion, fire or burning in watercraft
Other and unspecified water transport
accident
Accident to powered aircraft at takeoff or
landing
Accident to powered aircraft, other and
unspecified
0.006
0.000
100%
3
0
NO
0.011
0.006
50%
5
3
NO
0.010
0.006
35%
4
3
NO
0.059
0.032
45%
27
16
NO
842
Accident to unpowered aircraft
0.024
0.008
65%
11
4
NO
844
846
Other specified air transport accidents
Accidents involving powered vehicles used
solely in an industrial or commercial
Accidental poisoning by analgesics,
antipyretics, antirheumatics
0.011
0.004
67%
5
2
NO
0.029
0.000
100%
13
0
NO
0.260
0.962
-270%
120
481
NO
Accidental poisoning by barbiturates
Accidental poisoning by other sedatives and
hypnotics
0.196
0.004
98%
92
2
NO
0.090
0.034
62%
41
17
NO
Accidental poisoning by tranquillizers
Accidental poisoning by other psychotropic
agents
Accidental poisoning by other drugs acting on
central and autonomic nervous sys
0.080
0.043
47%
37
21
NO
0.076
0.136
-78%
34
67
NO
0.016
0.034
-116%
7
17
NO
856
Accidental poisoning by antibiotics
0.003
0.000
100%
1
0
NO
858
860
Accidental poisoning by other drugs
Accidental poisoning by alcohol, not
Accidental poisoning by cleansing and
polishing agents, disinfectants, paints a
Accidental poisoning by petroleum products,
other solvents and their vapours, n
Accidental poisoning by agricultural and
horticultural chemical and pharmaceuti
Accidental poisoning by corrosives and
caustics, not elsewhere classified
Accidental poisoning by other and
unspecified solid and liquid substances
Accidental poisoning by gas distributed by
pipeline
0.150
0.421
-180%
70
211
NO
0.186
0.320
-72%
83
160
NO
0.006
0.002
72%
3
1
NO
0.023
0.006
74%
11
3
NO
0.006
0.000
100%
3
0
NO
0.005
0.002
66%
3
1
NO
0.007
0.000
100%
3
0
NO
0.149
0.015
90%
74
7
NO
834
840
841
850
851
852
853
854
855
861
862
863
864
866
867
18
ICD-9
869
Condition
Accidental poisoning by other gases and
vapours
Accidental cut, puncture, perforation or
haemorrhage during medical care
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
0.011
0.004
67%
6
2
NO
0.063
0.084
-34%
33
46
NO
Failure in dosage
Mechanical failure of instrument or apparatus
during procedure
Other and unspecified misadventures during
medical care
Surgical operation and other surgical
procedures as the cause of abnormal react
Other procedures, without mention of
misadventure at the time of procedure, as
0.002
0.000
100%
1
0
NO
0.009
0.004
59%
4
2
NO
0.019
0.008
60%
9
4
NO
0.139
0.186
-34%
69
101
NO
0.003
0.035
-908%
2
19
NO
880
Fall on or from stairs or steps
0.755
0.645
15%
379
339
NO
881
Fall on or from ladders or scaffolding
0.222
0.122
45%
104
64
NO
882
Fall from or out of building or other structure
0.288
0.199
31%
134
98
NO
883
Fall into hole or other opening in surface
0.030
0.008
72%
14
4
NO
884
885
Other fall from one level to another
Fall on same level from slipping, tripping or
stumbling
Fall on same level from collision, pushing or
shoving, by or with other person
0.278
0.137
51%
137
70
NO
0.199
0.071
65%
108
39
NO
0.006
0.006
0%
3
3
NO
887
Fracture, cause unspecified
0.139
0.185
-34%
77
109
NO
888
Other and unspecified fall
0.991
0.703
29%
543
374
YES
890
891
Conflagration in private dwelling
Conflagration in other and unspecified
building or structure
0.535
0.191
64%
245
96
NO
0.041
0.015
64%
22
7
NO
892
Conflagration not in building or structure
0.010
0.006
40%
4
3
NO
893
Accident caused by ignition of clothing
0.090
0.021
77%
45
11
NO
894
895
Ignition of highly inflammable material
Accident caused by controlled fire in private
dwelling
Accident caused by controlled fire not in
building or structure
Accident caused by other specified fire and
flames
0.065
0.054
16%
31
26
NO
0.043
0.008
82%
23
4
NO
0.002
0.000
100%
1
0
NO
0.207
0.129
38%
103
65
NO
899
Accident caused by unspecified fire
0.023
0.027
-18%
12
14
NO
900
Excessive heat
0.004
0.000
100%
2
0
NO
901
Excessive cold
0.349
0.098
72%
177
53
NO
904
905
Hunger, thirst, exposure and neglect
Venomous animals and plants as the cause
of poisoning and toxic reactions
0.092
0.013
86%
42
7
NO
0.016
0.004
74%
7
2
NO
906
Other injury caused by animals
0.013
0.016
-26%
5
8
NO
907
908
Lightning
Cataclysmic storms, and floods resulting from
storms
0.004
0.000
100%
2
0
NO
0.007
0.000
100%
3
0
NO
Accidental drowning and submersion
Inhalation and ingestion of food causing
obstruction of respiratory tract or su
Inhalation and ingestion of other object
causing respiratory tract obstruction
0.688
0.376
45%
317
177
YES
0.981
0.265
73%
438
131
YES
0.032
0.032
0%
15
15
NO
Accidental mechanical suffocation
Foreign body accidentally entering eye and
adnexa
0.337
0.290
14%
150
133
NO
0.002
0.000
100%
1
0
NO
870
873
874
876
878
879
886
897
898
910
911
912
913
914
19
ICD-9
916
917
Condition
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
Struck accidentally by falling object
Striking against or struck accidentally by
objects or persons
0.232
0.109
53%
105
53
NO
0.064
0.020
68%
29
10
NO
918
Caught accidentally in or between objects
0.018
0.010
42%
8
5
NO
919
920
Accidents caused by machinery
Accidents caused by cutting and piercing
instruments or objects
Accident caused by explosion of pressure
vessel
0.364
0.104
72%
167
52
NO
0.041
0.022
47%
19
12
NO
0.002
0.000
100%
1
0
NO
922
Accident caused by firearm missile
0.028
0.022
20%
13
11
NO
923
924
Accident caused by explosive material
Accident caused by hot substance or object,
caustic or corrosive material and s
0.058
0.008
86%
26
4
NO
0.054
0.012
78%
27
5
NO
925
Accident caused by electric current
0.160
0.082
49%
72
39
NO
927
928
Overexertion and strenuous movements
Other and unspecified environmental and
accidental causes
0.006
0.000
100%
3
0
NO
0.113
0.408
-262%
57
213
NO
929
Late effects of accidental injury
0.161
0.123
23%
77
61
NO
935
Analgesics, antipyretics and antirheumatics
0.004
0.000
100%
2
0
NO
938
Other central nervous system depressants
0.003
0.002
21%
1
1
NO
939
Psychotropic agents
0.004
0.002
63%
2
1
NO
949
950
Other vaccines and biological substances
Suicide and self inflicted poisoning by solid or
liquid substances
Suicide and self inflicted poisoning by gases
in domestic use
Suicide and self inflicted poisoning by other
gases and vapours
Suicide and self inflicted injury by hanging,
strangulation and suffocation
Suicide and self inflicted injury by submersion
[drowning]
Suicide and self inflicted injury by firearms
and explosives
Suicide and self inflicted injury by cutting and
piercing instruments
Suicide and self inflicted injuries by jumping
from high place
Suicide and self inflicted injury by other and
unspecified means
0.002
0.000
100%
1
0
NO
3.158
1.233
61%
1471
620
YES
0.019
0.000
100%
9
0
NO
1.040
0.704
32%
463
355
YES
1.883
3.160
-68%
881
1581
NO
0.522
0.137
74%
254
70
NO
0.359
0.194
46%
168
97
NO
0.224
0.136
39%
106
68
NO
0.390
0.180
54%
180
90
NO
0.604
0.600
1%
278
297
NO
921
951
952
953
954
955
956
957
958
959
Late effects of self inflicted injury
0.002
0.002
-2%
1
1
NO
960
Fight, brawl, rape
0.051
0.002
97%
23
1
NO
962
Assault by poisoning
0.021
0.040
-87%
10
18
NO
963
Assault by hanging and strangulation
0.172
0.199
-16%
79
97
NO
964
Assault by submersion [drowning]
0.025
0.009
63%
10
4
NO
965
Assault by firearms and explosives
0.086
0.054
37%
38
26
NO
966
Assault by cutting and piercing instrument
0.382
0.201
47%
175
99
NO
967
Child battering and other maltreatment
0.055
0.013
77%
20
5
NO
968
969
Assault by other and unspecified means
Late effects of injury purposely inflicted by
other person
0.317
0.228
28%
141
109
NO
0.004
0.002
51%
2
1
NO
970
Injury due to legal intervention by firearms
Poisoning by solid or liquid substances,
undetermined whether accidentally or p
0.004
0.000
100%
2
0
NO
1.175
1.103
6%
545
551
NO
980
20
ICD-9
982
983
984
985
986
987
988
994
999
Condition
Poisoning by other gases, undetermined
whether accidentally or purposely inflicted
Hanging, strangulation or suffocation,
undetermined whether accidentally or
purposely inflicted
Submersion (drowning), undetermined
whether accidentally or purposely inflicted
Injury by firearms and explosives,
undetermined whether accidentally or
purpose
Injury by cutting and piercing instruments,
undetermined whether accidentally o
Falling from high place, undetermined
whether accidentally or purposely inflict
Injury by other or unspecified means,
undetermined whether accidentally or purp
Injury due to war operations by destruction of
aircraft
Late effects of injury due to war operations
ASDR
1979
ASDR
2000
Percentage
decline in
ASDR
N deaths
1979
N
Deaths
2000
Potentially
included
0.092
0.063
31%
42
32
NO
0.114
0.566
-398%
55
278
NO
0.722
0.296
59%
348
149
YES
0.059
0.028
53%
27
14
NO
0.010
0.038
-271%
5
19
NO
0.206
0.114
44%
98
56
NO
0.627
1.289
-106%
282
623
NO
0.004
0.000
100%
2
0
NO
0.012
0.000
100%
6
0
NO
21
Table 2 (Chapter 1):Temporal changes in population-based overall 5-year relative survival rates (%) of patients of
12-27
28
29
various cancer types in Europe (EUROCAREII
, III &IV )
#
Cancer Type
19781980
%
19811983
%
19841986
%
19871989
%
Testicular
Haematological malignancies
• Acute lymphoblastic
leukaemia
• Acute myeloblastic
leukaemia
• Chronic lymphocytic
leukaemia
• Chronic myelocytic
leukaemia
• Non-Hodgkin’s lymphoma
• Hodgkin’s disease
• Multiple myeloma
79
85
86
92
20
18
29
28
95
42
22
6
9
11
12
53
59
63
32
23
43
Cancer of the kidney
(hypernephroma)
Colorectal
• Colon
• Rectal
Gynaecological tumours
• Cervix uteri
• Corpus uteri
• Ovary
Prostate
Breast
Melanoma (<75 years of age)
†
Change
in 5 year
survival
%
20
Reduction
in 5 year
fatality
%
76
10
3
17
183
12
66
69
30
34
33
34
38
19
9
46
46
50
56
30
23
66
27
69
27
73
30
73
27
82
32
24
19
47
7
44
46
47
50
32
25
-
40
38
42
40
48
42
48
46
58
54
52
49
30
29
20
18
-
61
75
30
56
66
67
60
73
33
55
68
69
63
75
35
55
71
73
64
75
33
59
72
76
64
79
41
79
81
82
82
5
5
37
41
23
22
55
70
5
17
3
4
11
64
75
7
18
4
3
10
63
74
8
21
3
4
12
66
76
9
21
6
4
14
8
16
16
52
44
45
-
‡
Thyroid
• Male
• Female
19881999
%
25
47
10
9
200%
6
4
0
0
16
45
6
14
Lung
• Men
27
28
29
29
• Female
26
25
26
28
42
Nasopharyngeal
*NR
*NR
*NR
*NR
19
Primary malignant brain tumour
18
18
18
21
6
1
56
Soft tissue
55
55
60
59
2
2
58
Bone
40
39
55
53
45
30
‡Denmark, Finland, Sweden, Scotland, England and Italy; †data not reported in time periods; #Data from EUROCARE III
&
IV;
*Data
reported
collectively
for
1978-1989
divided
by
age
ranges
Head and Neck
Oesophageal
Gastric
Primary liver
Pancreatic
Biliary
22
Table 3 (Chapter 2) The criteria for defining the time period for the expected favourable shift in
mortality trend.
Starting year of the
time period for the
expected effect on
mortality
Pharmaceuticals
Criteria with priority
number
1) The year when clinical
trials started* (or if data
on the start is not
available three years
before the publication
year) if there are
indications on continued
diffusion of the method
2) The year when 15 %1 of
maximum sales level was
reached in the specific
country or when there
are indications of a 15 %
coverage rate for the
target population of the
medication if there are
3) Five year before the
year when there are
indications of a 50 %
target population (that
year included)
4) Five years before the
national guidelines were
published (publication
year included)
5) If specific data was not
available the year of
registration with the
specific indication
6) Information of
introduction year from
personal communication
with national expert
Screening programs
23
1) The year when clinical
trials started* (or if data
on the start is not
before the publication
year) if there are
2) when there are
screening if there are
year when there are
target population (that
year included)
4) If specific data of the
start of implementation
was not available the
year of the national
decision
5) Information of
introduction year from
personal communication
with national expert
Other interventions
1) The year when
clinical trials
started* (or if data
on the start is not
before the
publication year) if
there are indications
on continued
diffusion of the
method
2) When there are
coverage rate for
the target
population of the
method if there are
indications on
continued diffusion
of the method
year when there are
coverage rate for
24
the target
population (that
year included)
4) If specific data was
not available five
years before the
national guidelines
were published
(publication year
included)
5) Information of
introduction year
from personal
communication with
national expert
Last year of the time
period for the
expected effect on
mortality
General criteria
All innovations
a) Both a time period for
implementation and a
time period for the
expected medical effect
was added to the start
year according to
criteria below
b) The length of the
implementation period
was limited to a
maximum of five years
(unless national yearly
statistics indicates a
slower diffusion)
c)
The last year of
the
implementation
period
Pharmaceuticals
The length of the total
time period was
specified to be between
5-10 Years4
1) the year when 50% of the
maximum sales level was
reached in the specific
country or when there
are indications of a 50 %
medication
available five years after
the starting year
(starting year included)
Screening programs
25
1) The year when there are
target population
the starting year
(starting year included)
Other interventions
3) The year when there are
target population
4) two years after the
national guidelines was
published
the starting year
(starting year included).
The time period
for medical effect
added to the last
year of
implementation
Primary prevention
A time period up to a total of 10
years (implementation period
included)
Other interventions
Five years (the last two years of
implementation included)
26
Table 4 (Chapter 3) Expected time period for a favourable shift in mortality trend for AIDS
influenced by the introduction of treatment of HIV with antiretroviral drugs
Treatment of
HIV with the
anti-retroviral
drugs
(Azidothymidine
or Zidovudine)
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
19891996
1987-1994
19881995
19891996
19932000
19952004
19881996
1
United Kingdom: Registration 1987 For Zidovudine in the UK, in 1999 the number of prescription
2
3 4
items dispensed was 0,3 thousand . Clinical trials in the 1990s with the first complete starting year
5
1989. Guidelines in 1997 .
6
7
8
The Netherlands: Registration 1987 . Clinical trials starting in 1987 and 1988 . Maximum sales level
for Zidovudine (1997-2007) was in 1997 (442 300 DDD).
9
10
Germany: Registration 1987 . Multicenter clinical trial started in 1988 . Clinical studies reported in
11
12
13
1991 .Guidelines in 2004 . Maximum sales level for Zidovudine (1999-2008) was in 1999 .
14
France: Registration 1987 . In France, maximum sales level (2002-2007) of Zidovudine was reached
15
in 2002 (22370 reimbursements). Clinical trial with the complete starting year 1989 and a multicenter
16
European trial with the starting year 1993 .
17
16
Spain: Registration 1987 . Participation in a European multicenter clinical trial starting in 1993 .
18
19
Publication of a clinical study in 1993 . Recommendations in 2000 . Maximum sales level for
Zidovudine (2000-2007) was in 2000.
20
Estonia: Registration 1995 . For Zidovudine in Estonia, Maximum sales level (1999-2008) was
reached in 2006 (0,052 DDD/1000 inhabitants and year). Half of maximum level was reached in 2004
21
.
22
23
Sweden: Registration 1987 . Clinical trial starting in 1988 . For Zidovudine in Sweden, Maximum
sales level (1987-2008) was reached in 1997 (0.09 DDD/1000 inhabitants per year). Half of maximum
24
25
level was reached in 1993 . An evaluation study including long-term follow up of a cohort in 1999 .
26
Consensus recommendations were defined in 2005 .
27
References
1. British National Formulary. http://www.bnf.org/bnf/
http://emc.medicines.org.uk/medicine/10629/SPC/Cimetidine+200mg+5ml+Oral+Solution+
+(Rosemont+Pharmaceuticals+Ltd)/#AUTHDATE
2. http://www.ic.nhs.uk/statistics-and-data-collections/primary-care/prescriptions
3. Cohen J.Early AZT takes a pounding in French-British 'Concorde' trial. Science 1993;260:157.
4. White IR, Walker S, Babiker AG, Darbyshire JH.Impact of treatment changes on the interpretation
of the Concorde trial. AIDS 1997;11:999-1006.
5. Brettle RP, Burns SB, Povey S, Leen CL, Welsby PD.British HIV Association guidelines for
antiretroviral treatment of HIV seropositive individuals. Lancet 1997;349:1837-8.
6. http://www.cbg-meb.nl/CBG/nl/humanegeneesmiddelen/geneesmiddeleninformatiebank/default.htm
7. Perenboom R, Reiss P, Danner SA, van 't Wout JW. Zidovudine therapy in 141 patients with
symptoms of HIV infection; a multicenter study. (In Dutch). Ned Tijdschr Geneeskd
1990;134:120-4.
8. Mulder JW, Cooper DA, Mathiesen L, Sandström E, Clumeck N, Gatell JM, French M, Donovan B,
Gray F, Yeo JM, et al.Zidovudine twice daily in asymptomatic subjects with HIV infection
and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study.
The European-Australian Collaborative Group (Study 017). AIDS 1994;8:313-21.
9. Data base: AMIS, DIMDI Köln. http://www.dimdi.de/static/de/db/index.htm
10. Survival of patients receiving zidovudine before or after AIDS diagnosis: results of a German
multicenter study. German AIDS Study Group. Clin Investig 1994;72:111-6.
11. Rübsamen-Waigmann H, Schröder B, Biesert L, Bauermeister CD, von Briesen H, Suhartono H,
Zimmermann F, Brede HD, Regeniter A, Gerte S, et al.Markers for HIV-disease progression in
untreated patients and patients receiving AZT: evaluation of viral activity, AZT resistance,
serum cholesterol, beta 2-microglobulin, CD4+ cell counts, and HIV antigen.
1991;Infection:Suppl 2:S77-82.
12. Salzberger B, Marcus U, Vielhaber B, Arasteh K, Gölz J, Brockmeyer NH, Rockstroh J.GermanAustrian recommendations for the antiretroviral therapy of HIV-infection (status May 2004).
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13. Arzneiverordnungs-Report 2000 bis 2009. Daten: GKV-Arzneimittelindex Im Wissenschaftlichen
Institut der AOK (WIdO) (In German).
14. Agence Française de Sécurité Sanitaire et des Produits de Santé
15. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred
zidovudine in symptom-free HIV infection. Concorde Coordinating Committee. Lancet
1994;343:871-81.
16. Katlama C, Ingrand D, Loveday C, Clumeck N, Mallolas J, Staszewski S, Johnson M, Hill AM,
Pearce G, McDade H.Safety and efficacy of lamivudine-zidovudine combination therapy in
antiretroviral-naive patients. A randomized controlled comparison with zidovudine
monotherapy. Lamivudine European HIV Working Group. JAMA 1996;276:118-25.
17. Ministry of Health. AGENCIA ESPAÑOLA DEL MEDICAMENTO Y PRODUCTOS SANITARIOS (AEMPS)
18. Podzamczer D, Bolao F, Clotet B, García P, Casanova A, Pagerols X, Gudiol F.Low-dose
interferon alpha combined with zidovudine in patients with AIDS-associated Kaposi's
sarcoma. Intern Med;233:247-53.
19. Miró JM, Antela A, Arrizabalaga J, Clotet B, Gatell JM, Guerra L, Iribarren JA, Laguna F, Moreno
S, Parras F, Rubio R, Santamaría JM, Viciana P.Recommendation of GESIDA (AIDS Study
Group)/National Plan on AIDS with respect to the anti-retroviral treatment in adult patients
infected with the human immunodeficiency virus in the year 2000 (I). (In Spanish). Enferm
Infecc Microbiol Clin 2000;18:329-51.
20. State Agency of Medicines,Estonia.
http://193.40.10.165/register/register.php?keel=eng&inim_vet=inim.
21. State Agency of Medicines, wholesalers reports. Estonia.
22. http://www.lakemedelsverket.se/.
23. Double blind dose-response study of zidovudine in AIDS and advanced HIV infection. Nordic
Medical Research Councils' HIV Therapy Group. BMJ. 1992 1992;304:13-7.
24. Sales statistics. Apoteket AB, Stockholm
25. Lindbäck S, Vizzard J, Cooper DA, Gaines H.Long-term prognosis following zidovudine
monotherapy in primary human immunodeficiency virus type 1 infection. J Infect Dis
1999;179:1549-52.
28
26. Gisslén M, Ahlqvist-Rastad J, Albert J, Blaxhult A, Hamberg AK, Lindbäck S, Sandström E, Uhnoo
I; Swedish Consensus Group.Antiretroviral treatment of HIV infection: Swedish
recommendations 2005. Scand J Infect Dis 2006;38:86-103.
29
Table 5 (Chapter 3) Expected time period for a favourable shift in mortality trend
for colorectal cancer influenced by the introduction of treatment with Oxaliplatin
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1995-2002
1999-2005
2001-2005
1988-1995
1994-2003
1999-2005
1999-2005
1
2
United Kingdom: Involvement in multicenter clinical trials starting in 1995 . Registration in 1999 .
3
Guidelines from 2002 in which Oxaliplatin was recommended for patients where inoperable liver
4
metastases can potentially be made operable with chemotherapy .
5
The Netherlands: Registration in 1999 . No further data available.
6
7
Germany: Registration in 2001 . In the year 2000 a consensus for treatment of colon cancer was
presented in which Oxaliplatin was mentioned as a promising new drug but not yet generally
8
recommended. Maximum sales level (1999-2008) in 2001 .
8
9
France: There are clinical trials starting in 1988 and 1990 and involvement in multicenter clinical
10
1
11
trials starting in 1994 and 1995 . Registration in 1996 .
12
Spain: There is a paper from 1998 reporting a clinical trial starting in 1994 . Involvement in
1
13
multicenter clinical trials starting in 1995 . Registration in 1999 . Maximum sales level (2000-2008) in
2006. Half of maximum sales level reached in 2003.
14
Estonia: Registration in 1999 . For Oxaliplatin in Estonia, maximum sales level (2000-2008) was
15
reached in 2008 (323 g/year).Half maximum level was reached in 2007 . No further information.
16
Sweden: Country reports on registration in 1999 . For Oxaliplatin in Sweden, Maximum sales level
(1977-2008) was reached in 2008 (20076 packages/ year). Half of maximum level was reached in
17
18
2004.
Oxaliplatin recommended as one alternative in a SBU review from 2001 .
30
References:
1. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H,
Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson
C, Morvan F, Bonetti A.Leucovorin and fluorouracil with or without oxaliplatin as first-line
treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938-47.
2. British National Formulary. http://www.bnf.org/bnf/
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5.http://www.cbg-meb.nl/CBG/nl/humanegeneesmiddelen/geneesmiddeleninformatiebank/default.htm
7. Graeven U, Schmiegel W.Colon carcinoma. Consensus of therapeutic strategies. (In German).
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Institut der AOK (WIdO) (In German).
9. Levi F, Perpoint B, Garufi C, Focan C, Chollet P, Depres-Brummer P, Zidani R, Brienza S, Itzhaki
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study of 5-day continuous venous infusion at circadian rhythm modulated rate. Eur J Cancer
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10.Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF,
Letourneau Y, Coudert B, Bertheaut-Cvitkovic F, Larregain-Fournier D, Le Rol A, Walter S,
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chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal
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11. Agence Française de Sécurité Sanitaire et des Produits de Santé
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31
Table 6 (Chapter 3) Expected time period for a favourable shift in mortality trend for colorectal
cancer influenced by the introduction of systematically used diagnostic examination with
colonoscopy/sigmoidoscopy
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1988-1995
1985-1992
19781985
1990-1997
1987-1994
N.d
19811988
N.d.: No data
United Kingdom: Large clinical evaluation study with sigmoidoscopy of screening of symptomatic
1
2
patients starting in 1988 . There is also a population-based clinical trial published in 1998 in favour
of using sigmoidoscopy for screening. Manual of improving outcomes in colorectal cancer published
3
by the Department of Health in 1997, updated in 2004 . Guidelines published 2000, updated in 2007.
4
Generally implemented in the UK in 2006 . Following successful pilots, a national bowel screening
program was initiated in summer 2006 and is being rolled out progressively. It is based on FOB
5-11
screening with follow up using endoscopy where indicated
. The colonoscopy services in the UK
12
was evaluated in 1999 showing that half of the centres had full capacity
13
The Netherlands: Colonoscopy for diagnostics of colorectal cancer mentioned in literature in 1985 .
14-16
Clinical trial for a limited number of familiar cancer in late 1980s and first part of 1990s
, starting in
15
1985 and including also an international comparative clinical study starting in 1990 . The practice for
17
using colonoscopy in follow-up of colorectal cancer patients was evaluated in 1995 showing that
colonoscopy for local recurrence were used by 90% of the hospitals. The participation in a screening
18
19
program was evaluated in 2000 in which 45% of the invited people participated. Guidelines 2008 .
Germany: Clinical study of postoperative endoscopic surveillance program starting in 1978
20
21
published in 1994 . There is also a clinical study starting in 1983 published in 1988 . Guidelines
22
from 2002 .
23 24 25
. A paper from 1996 reported that 24
France: Guidelines from conferences in 1994 and 1997
% of individuals attending a centre for periodic health examination and with a family history of
26
colorectal cancer have had an examination with colonoscopy . Colonoscopy was also found in
25
general use in a survey to gastroenterologists in 1999 .
27
Spain: The effectiveness of post-operative surveillance with colonoscopy was evaluated in 1998
28
29
based on a cohort starting in 1987. Guidelines from 1995 . Evaluation study also in 2001
Estonia: No data available.
Sweden: There is a clinical study of post-operative surveillance with colonoscopy of patients 198130
1990 published in 1992 and clinical trial of post-operative surveillance starting in 1983 published in
31
32
1995 . Guidelines for hereditary colon cancer from 2000 . In 1979-2005 only about 8 % of cancers in
33
a county were reported detected by colonoscopy . This proportion increased in the 1990s and
reached 15 % in 1993.
32
References:
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colorectal cancer: a study of 22 kindreds in The Netherlands. Am J Med 1989;86:278-81.
15. Vasen HF, Mecklin JP, Watson P, Utsunomiya J, Bertario L, Lynch P, Svendsen LB, Cristofaro G,
Müller H, Khan PM, et al.Surveillance in hereditary nonpolyposis colorectal cancer: an
international cooperative study of 165 families. The International Collaborative Group on
HNPCC. Dis Colon Rectum 1993;36:1-4.
16. Vasen HF, Taal BG, Nagengast FM, Griffioen G, Menko FH, Kleibeuker JH, Offerhaus GJ, Meera
Khan P.Hereditary nonpolyposis colorectal cancer: results of long-term surveillance in 50
families. Eur J Cancer 1995;31A:1145-8.
17. Bruinvels DJ, Stiggelbout AM, Klaassen MP, Kievit J, Dik J, Habbema F, Van de Velde CJ.Followup after colorectal cancer: current practice in The Netherlands. Eur J Surg
1995;161:827-31.
18. Kremers SP, Mesters I, Pladdet IE, van den Borne B, Stockbrügger RW.Participation in a
sigmoidoscopic colorectal cancer screening program: a pilot study. Cancer Epidemiol
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19. Guideline Coloncarcinoom. www.oncoline.nl
20. Eckardt VF, Stamm H, Kanzler G, Bernhard G. Improved survival after colorectal cancer in
patients complying with a postoperative endoscopic surveillance program. Endoscopy
1994;26:523-7.
21. Mennigen R, Kusche J, Barkun J, Schreckenberger C, Troidl H. Usefulness and limitations of
colonoscopy in a proctological clinic. Surg Endosc 1998;2:84-7.
22. Krebsfrüherkennungs-Richtlinien (Koloskopie) Bundesanzeiger 2002, Nr. 186.
23. National Consensus Conference in France 1994.
24. Conférence de Consensus. Prévention, dépistage et prise en charge des cancers du côlon
ANAES, Paris 1998.
25. Greff M.Colorectal cancer screening in France: guidelines and professional reality. Endoscopy
1999;3:471.
26. Eisinger F, Giordanella JP, Didelot R, Julian-Reynier C, Moatti JP, Sobol H, Seitz JF. Screening
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(In French). Gastroenterol Clin Biol 1996:627-32.
33
27. Castells A, Bessa X, Daniels M, Ascaso C, Lacy AM, García-Valdecasas JC, Gargallo L, Novell F,
Astudillo E, Filella X, Piqué JM.Value of postoperative surveillance after radical surgery for
colorectal cancer: results of a cohort study. Dis Colon Rectum. 1998;41:714-23
(discussion 23-4).
28. PLAN DE SALUD 1995 Ministerio de Sanidad. Centro de Publicaciones. Madrid 1995.
29. Cuquerella J, Ortí E, Canelles P, Martínez M, Quiles F, Sempere J, Bixquert M, Medina E.
Colonoscopic follow-up of patients undergoing curative resection of colorectal cancer. (In
Spanish) Gastroenterol Hepatol 2001;24:415-20.
30. Granqvist S, Karlsson T.Postoperative follow-up of patients with colorectal carcinoma by
colonoscopy. Eur J Surg 1992;158:307-12.
31. Ohlsson B, Breland U, Ekberg H, Graffner H, Tranberg KG.Follow-up after curative surgery for
colorectal carcinoma. Randomized comparison with no follow-up. Dis Colon Rectum
1995;38:619-26.
32. Presymtomatisk diagnostik av ärftlig kolorektal cancer (In Swedish;Presymtomatic diagnosis of
hereditary colorectal cancer). Stockholm: SBU, 2000.
33. Dafnis G, Blomqvist P, Granath F, Påhlman L, Ekbom A.Colorectal cancer detection by
colonoscopy in a Swedish county, 1979-95. Scand J Gastroenterol. 2003 Oct;38(10):1059-67
2003;38:1059-67.
34
Table 7(Chapter 3) Expected time period for a favourable shift in mortality trend for breast cancer
influenced by the introduction of treatment with Tamoxifen
Treatment of breast
cancer with
Tamoxifen
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1976-1983
1981-1988
19811988
19811988
19881995
19922001
19761985
1
2
3
United Kingdom: Registration 1973 . Clinical trials published in 1977 and starting in 1976 and
4
1978 , respectively. For Tamoxifen in the UK, in 1999 the number of items dispensed was 1045
5-7
thousand . Since 2005 tamoxifen has also been registered for anovulatory infertility.
8
9
The Netherlands: Registration 1975 . Clinical trial starting in 1981 .
10
11 12
Germany: Registration 1983 . Clinical trials starting in 1981
13
and 1984 , respectively.
71 14
15
16
France: Registration 1977
. Clinical trials reported from a single centre starting in1981 , 1984
17
and from a national study group starting in 1986 .
18
19
Spain: Registration 1977 . Clinical trial was published in 1991
20
Estonia: Registration 1992 . For Tamoxifen in Estonia, maximum sales level (1999-2008) was
reached in 2003 (1,098 DDD/1000 inhabitants and year). Half of maximum level was reached in 1999.
21
22
23 24
. For Tamoxifen in Sweden,
Sweden: Registration 1976 . Also cilinical trials starting in 1976
maximum sales level (1977-2008) was reached in 1996 (2.23 DDD/1000 inhabitants per year). Half of
25
the maximum level was reached in 1984.
35
References:
1. Jordan VC. Tamoxifen: a most unlikely pioneering medicine. Nature Reviews 2003;2:205-13.
2. Priestman T, Baum M, Jones V, Forbes J.Comparative trial of endocrine versus cytotoxic
treatment in advanced breast cancer. Br Med J. 1977;1(6071)(May 14):1248-50.
3. Ribeiro G, Swindell R.The Christie Hospital adjuvant tamoxifen trial. Natl Cancer Inst Monogr
1992;11:121-5.
4. Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial. Report
from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh.
Lancet. 1987 1987;2(8552)(Jul 25):171-5.
5. http://www.dh.gov.uk/en/Publicationsandstatistics/Statistics/StatisticalWorkAreas/Statisticalh
althcare/DH_4086488
6. http://www.ic.nhs.uk/statistics-and-data-collections/primary-care/prescriptions/prescriptionsdispensed-in-the-community-statistics-for-1998-to-2008:-england
7. http://www.dh.gov.uk/en/Publicationsandstatistics/Statistics/StatisticalWorkAreas/Statistical
althcare/DH_4086488#_4
8. http://www.cbg-meb.nl/CBG/nl/humanegeneesmiddelen/geneesmiddeleninformatiebank/default.htm
9. Beex L, Burghouts J, van Turnhout J, Breed W, Hillen H, Holdrinet A, Boetius G, Hoogendoorn G,
Doesburg W, Verhulst M, et al.Oral versus im administration of high-dose
medroxyprogesterone acetate in pretreated patients with advanced breast cancer. Cancer
Treat Rep 1987;71(12):151-6.
11. Kaufmann M.Current trials of the German Adjuvant Breast Cancer Group (GABG). Recent Results
Cancer Res 1998;152:471-8.
12. Kaufmann M, Jonat W, Abel U, Hilfrich J, Caffier H, Kreienberg R, Trams G, Brunnert K,
Schermann J, Kleine W, et alAdjuvant randomized trials of Doxorubicin/cyclophosphamide
versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen
in women with node-positive breast cancer. J Clin Oncol. 1993;11(3):454-60.
13. Schumacher M, Bastert G, Bojar H, Hübner K, Olschewski M, Sauerbrei W, Schmoor C, Beyerle C,
Neumann RL, Rauschecker HF. Randomized 2 x 2 trial evaluating hormonal treatment and
the duration of chemotherapy in node-positive breast cancer patients. German Breast
Cancer Study Group. J Clin Oncol. 1994;Oct;12(10)::2086-93.
14. http://documents.irevues.inist.fr/bitstream/2042/373/1/sfspm_308_316.pdf.
15. Mauriac L, Durand M, Chauvergne J, Bonichon F, Avril A, Mage P, Dilhuydy MH, Le Treut A,
Wafflart J, Marée D, et al. Adjuvant trial for stage II receptor-positive breast cancer: CMF
vs. CMF + tamoxifen in a single centre. Breast Cancer Res Treat. 1988;May;11(2):179-86.
16. Bonneterre J, Mauriac L, Weber B, Roche H, Fargeot P, Tubiana-Hulin M, Sevin M, Chollet P,
Cappelaere P. Tamoxifen plus bromocriptine versus tamoxifen plus placebo in advanced
breast cancer: results of a double blind multicentre clinical trial. Eur J Cancer Clin Oncol.
1988;24(12):1851-3.
17. Gérard JP, Héry M, Gedouin D, Monnier A, Goudier MJ, Jacquin JP, Plat F, Cabarrot E, Serin D,
Namer M, et al.Postmenopausal patients with node-positive resectable breast cancer.
Tamoxifen vs FEC 50 (6 cycles) vs FEC 50 (6 cycles) plus tamoxifen vs control--preliminary
results of a 4-arm randomised trial. The French Adjuvant Study Group. Drugs 1993;45 Suppl
2::60-7.
19. Bellmunt J, Solé L.European early phase II dose-finding study of droloxifene in advanced breast
cancer. Am J Clin Oncol. 1991;14 (Suppl 2:S):36-9.
23. Rutqvist LE, Cedermark B, Glas U, Johansson H, Nordenskjöld B, Skoog L, Somell A, Theve T,
Friberg S, Askergren J.The Stockholm trial on adjuvant tamoxifen in early breast cancer.
Correlation between estrogen receptor level and treatment effect. Breast Cancer Res
Treat. 1987 . 1987;Dec;10(3):255-66.
24. Rutqvist LE, Cedermark B, Fornander T, Glas U, Johansson H, Nordenskjöld B, Rotstein S, Skoog
L, Somell A, Theve T, et al.The relationship between hormone receptor content and the
effect of adjuvant tamoxifen in operable breast cancer. J Clin Oncol 1989;Oct;7(10:147484.
25. Sales statistics. Apoteket AB, Stockholm.
36
Table 8 (Chapter 3) Expected time period for a favourable shift in mortality trend for breast cancer
influenced by the introduction of screening with mammography
Screening for breast
cancer with
mammography
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1979-1986
1975-1982
20012005
19891996
19921999
20052005
19761983
12
3
United Kingdom: Clinical trials starting between 1979 and 1981 . National program 1988 .
4-7
National coverage was achieved in the UK by mid 1990s and generally implemented in 2008 .
89
The Netherlands: Clinical studies starting at the end of 1974 and 1975 . Consensus on policy for
10 11
12
screening strategies in 1983
. National program in 1989 .
Germany:.In 2001 it was reported that opportunistic screening with mammography covered about
13
40% of all women between 40 to 70 years, despite a lack of organized program . National program
14
15
in 2003 . Guidelines published in 2004 .
France: Since 1989 several district mammography screening programs have been carried out and
16
17
18
avaluated and a national programme was implemented in 1994 . National decision 1998 .
19 20
Mammography also generally implemented in France in 1998
.
21
22
Spain: National program 1995 . Clinical trial reported starting in two districts in 1992 . Från ett
23
district rapporterades 1996 att 9-13% av populationen deltog I mammografi screening . Another
24
evaluation study from several districts performed in 1994 showed mean coverage rates of 55 % .
25
Estonia: National program 2005 .
26 27 28
29
Sweden: Clinical trials reported starting in 1976-1978,respectively
. National decision1986 .
The time period for introduction of screening with mammography in different health administrative
30
areas varies between 1974 and 1997 .
37
References:
1. Roberts MM, Alexander FE, Anderson TJ, Forrest AP, Hepburn W, Huggins A, Kirkpatrick AE, Lamb
J, Lutz W, Muir BB.The Edinburgh randomised trial of screening for breast cancer:
description of method. Br J Cancer 1984;50(1):1-6.
2. First results on mortality reduction in the UK Trial of Early Detection of Breast Cancer. UK Trial of
Early Detection of Breast Cancer Group. Lancet 1988;2(8608):411-6.
3. http://www.cancerscreening.nhs.uk/breastscreen/publications/forrest-report.pdf.
4. http://www.cancerscreening.nhs.uk/breastscreen/publications/nhsbsp-annualreview2008.pdf
5. http://info.cancerresearchuk.org/cancerstats/types/breast/screening/history/.
6. http://www.cancerscreening.nhs.uk/breastscreen/publications/nhsbsp61.pdf.
7. Quinn M, Babb P, Jones J, Allen E. Effect of screening on incidence of and mortality from cancer
of cervix in England: evaluation based on routinely collected statistics. BMJ
1999;318:904.http://www.bmj.com/cgi/content/full/318/7188/904/DC1.
8. Verbeek AL, Hendriks JH, Holland R, Mravunac M, Sturmans F, Day NE Reduction of breast cancer
mortality through mass screening with modern mammography. First results of the Nijmegen
project, 1975-1981. Lancet 1984;1(8388):1222-4.
9. Collette HJ, Day NE, Rombach JJ, de Waard F. Evaluation of screening for breast cancer in a
non-randomised study (the DOM project) by means of a case-control study. Lancet
1984;1(8388):1224-6.
10. Klazinga NS, Casparie AF, van Everdingen JJE.Contribution of medical decision-making to
consensus development conferences. Health Policy 1987;8:339-46.
11. Zwaveling A. Consensus "Mammography Policy 1983". (In Dutch). Ned Tijdschr Geneeskd.
1984;128(30):1424-25.
12. Personal communication: RIVM,CVZ.
13. Perleth M, Busse R, Gibis B, Brand A. Evaluation of preventive technologies in Germany: case
studies of mammography, prostate cancer screening, and fetal ultrasound. Int J Technol
Assess Health Care. 2001;17(3):329-37.
14. Richtlinie des Gemeinsamen Bundesausschusses über die Früherkennung von Krebserkrankungen.
(Krebsfrüherkennungs-Richtlinie, vom 18 06.2009) (Neufassung), Kap. B-III. http://www.gba.de/informationen/beschluesse/841/
15. Albert US, Schulz KD; German Association of the Scientific Medical Societies (AWMF), German
Agency for Quality in Medicine (AeZQ).Short version of the Guideline: Early Detection of
Breast Cancer in Germany. An evidence-, consensus-, and outcome-based guideline
according to the German Association of the Scientific Medical Societies (AWMF) and the
German Agency for Quality in Medicine (AeZQ). J Cancer Res Clin Oncol. 2004;130(9):52736.
16. Mamelle N, Lacour A, Anes A, Bazin B, Chaperon J, Duru G, Piette C, San Marco JL, Schaffer P,
Arnold F, et al. Experience in mass screening of breast cancer with mammography in
France. (In French)Rev Epidemiol Sante Publique. 1994;42(1):34-49.
17. Séradour B, Allemand H, Schaffer P. French screening program of breast cancer. Results from 5
districts (1989-1994).(In French) Bull Cancer 1997;84(8):822-8.
18. Loi 98-11-94 du 23 décembre 1998 (décision de la généralisation du dépistage organisé du
cancer du sein à tout le territoire)
19. BEH n° 04-2003, 21 january 2003, numéro thématique: dépistage organisé du cancer du sein.
20. Dilhuydy MH. .Le dépistage organisé des cancers du sein: particularités du système français. J
Gynecol Obstet Biol Reprod 2004;33:683-91.
22. Turabián JL, Ruiz R.. Program of early detection of breast cancer in Castilla-la-Mancha.
Preliminary data of the first 5 months of performance. Regional Group on the Evaluation of
the Program of Early Detection of Breast Cancer. (In Spanish). Rev Sanid Hig Publica
1994;68(3):377-83.
23. Bonfill Cosp X, Marzo Castillejo M, Sentís Crivillé M, Rossell Mir R, Gallardo Cistaré X, Florensa
Masip R, Rivero Ferrer E, Moreno Quiroga C. Evaluation of the regular practice of breast
cancer screening in a health area. Int J Technol Assess Health Care 1996;12(2):388-94.
24. Luengo S, Lázaro P, Azcona B, Madero R, Fitch K. Use of mammography among women residing
in Spanish provinces with breast cancer screening programmes. Eur J Cancer Prev
1999;8(6):517-24.
25.http://veeb.haigekassa.ee/files/est_raviasutusele_ravijuhendid_andmebaas_tunnustatud/Rinnav
ahk.pdf.
26. Tabàr L, Gad A.Screening for breast cancer: the Swedish trial. Radiology. 1981;138(1):219-22.
38
27. Tabár L, Fagerberg CJ, Gad A, Baldetorp L, Holmberg LH, Gröntoft O, Ljungquist U, Lundström
B, Månson JC, Eklund G, et al.Reduction in mortality from breast cancer after mass
screening with mammography. Randomised trial from the Breast Cancer Screening Working
Group of the Swedish National Board of Health and Welfare. Lancet. 1985;1(8433)(Apr
13):829-32.
28. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjöld B, Rutqvist LE. Long-term effects of
mammography screening: updated overview of the Swedish randomised trials. Lancet
2002;359:909-19.
29. Screening with mammography. SOSFS 1986:3. National Board of Health and Welfare
Stockholm 1986.
30. Cancer care in Sweden. Quality, structure and present challenges National Board of Health and
Welfare Stockholm 2007.
39
Table 9 (Chapter 3) Expected time period for a favourable shift in mortality trend for cancer of
cervix uteri influenced by the introduction of cervical screening
Screening
for cervix
cancer
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1985-1992
1980-1987
1971-1978
N.h.d.
N.h.d
2003-2005
1970-1977
N.h.d.: No hypothesis defined
Comments:
United Kingdom: As reported by Patnick, cervical screening began in a rather hap-hazard manner in
1
2 3
the 1960s but without any desirable impact on mortality . There was a national programme in 1988
14
to ensure that screening took place at an equitable level across the country. In 1989 half of the
5
district health authorities reported in a survey that they called women for cervical screening . In
1
6
1997/98 the coverage rate has been reported to be 85 % or 61-76 % . In 1998, 72 of the 100 health
authorities in England had a coverage of more than 85% and only 13 had a coverage of less than
7
80% .
The Netherlands: Regional population screening programmes has been reported for the period
8
1970-84 . Van Ballegooijen reported that since the introduction around 1970, there has been a
combination of local and regional invitational programs and opportunistic screening. the
9
implementation rate for cervical screening was reported to be 24% in the late 1970's, early 1980's .A
3
4
National program from 1980 has been reported as well as a national program from 1996 , i.e. in
1996 the previous national 3-yearly screening policy between ages 35 and 53 years was changed into
a 5-yearly policy between the ages 3 and 60 years. The implementation rate was 24% in the late
1970’s, early 1980’s. The coverage rate in 1997 was 77 %, analysed with data from a nationwide
6
register including all smears in the country. Also in 2003 the coverage rate was reported to be 75-80
3
10
%. . In 2004, a mean proportion of 74 % attended cervical screening.
Germany: There are several references reporting that cervical screening was initiated in 1971 in West
Germany, extended to the East in 1991 (where it had been encouraged through county
3 4 11
recommendations since the beginning of the 1970s)
. Also in 1976, screening programmes was
12
described in Germany . In the early 1990s the annual uptake rate increased from one third to
11
around 50% . For 1996 the attendance rate is reported as 50% in West Germany and 47% in East
11
6
Germany . In 1997, the coverage rate was more than 80 % .
France: In two recent documents dating from 2007, it is stated that no organized national screening
13 14
program is implemented in France yet
. Regional organised cervical screening started in four
3 4 15
regions in France in 1990-1994 (Isére, Doubs, Bas-Rhin and Martinique)
covering about 5 % of
6
the French population . Otherwise, in 1997 it was reported that screening in France was opportunistic
6 15
. In 1990 there was a consensus conference in Lille giving recommendations to screen all women
in the age group 25-65 years every 3 years. An association was created following this conference and
16
in 1993 guidelines on the evaluation on the quality of cervical smears was established . In 1997 and
6 15
2000, it was estimated that 60 % of the 20-69 year age group had a cervical smear
. The decrease
in incidence rate of invasive carcinomas has, at least in part, been attributed to the opportunistic
15
cervical screening in France .
Spain: Organised screening implemented only in some areas. In Spain, a screening programme with
Pap smear was started by the National Health Service in the mid-1970s and offered by family planning
clinics. This programme did not reach an proportion considered important, (between 30% and 46%), of
17
sexually active women until the mid-1980s . Also, women attending a first screening often did not
continue in the programme. Any positive effect of this programme has been considered unlikely to be
appreciated before 1990. Other sources comment mainly on regional programmes, such as
40
346
programmes in Castilla Y León and Catalonia
. The programme in Castilla Y Ledin started in 1986
and was incorporated into the European Nerwork of Cervical Cancer Screening Programmes in 1994
18
18
. In 1995 the coverage rate of the programme was 41 % and in 1998 89 % . The program in
19
20
Catalonia started in 1993 . There was also a national recommendations in 1995 . The AFRODITA
Study with data from 2005 showed that in Spain, at the national preventive gynecological
examinations are well established but oppurtunistic; most examinations occur on an annual (64.1%) or
21
biannual (21.8%) basis In general, a Pap smear is taken at every visit.
22
Estonia: A national cervical screening was preceded by a pilot program in 2003-2005 . In the year
23
2006, nationwide organized cervical cancer screening was started in Estonia . The late start is
supported by a paper from year 2000 stating that at that time there was no mass-screening
24
programme for cervix cancer in Estonia .
Sweden: Organized cervical screening was first implemented in the mid-1960s (implemented in
34
different counties 1967-73) and has been considered to be nationwide in the beginning of the 1970s .
25 26
However, the national decision was established first in 1985
. Already in 1985 a decline in
27
mortality in the 1970s was interpreted to be due to increased screening . In 1997 the coverage rate
6
was reported to be around 80 % .
41
References:
1. Patnick J. Cervical cancer screening in England. European Journal of Cancer 2000;36:2205-08.
2. http://info.cancerresearchuk.org/cancerstats/types/cervix/screening/briefhistory/#source2.
3. Anttila A, Ronco G, Clifford G, Bray F, Hakama M, Arbyn M, Weiderpass E.Cervical cancer
screening programmes and policies in 18 European countries Br J Cancer 2004;91:935-41.
4. Linos A, Riza E. Comparisons of cervical cancer screening programmes in the European Union.
European Journal of Cancer 2000:2260-65.
5. Elkind A, Eardley A, Thompson R, Smith A. How district health authorities organise cervical
screening. BMJ 1990;301:915-8.
6. van Ballegooijen M, van den Akker-van Marle E, Patnick J, Lynge E, Arbyn M, Anttila A, Ronco G,
Dik J, Habbema F.Overview of important cervical cancer screening process values in
European Union (EU) countries, and tentative predictions of the corresponding effectiveness
and cost-effectiveness. European Journal of Cancer 2000(36):2177-88.
7. Cervical screening programme, England 1997-98, . In: Health. Do, editor. London: Crown
Copyright 1999.
8. Population screening for cervical cancer in the Netherlands. A report by the Evaluation
Committee. Int J Epidemiol 1989:775-81.
9. van Ballegooijen M, Effects and costs of Cervical cancer screening. [(Thesis)], 1998.
10. Braspenning JCC, Schellevis FG, Grol RPTM(redactie). Tweede Nationale Studie naar ziekten en
verrichtingen in de huisartspraktijk. Kwaliteit huisartsenzorg belicht Utrecht/Nijmegen:
NIVEL/WOK, 2004.
11. Schenck U, von Karsa L. Cervical cancer screening in Germany. European Journal of Cancer
2000;36:2221-26.
12. http://www.g-ba.de/informationen/richtlinien/historie/zur-richtlinie/17/
13. http://www.invs.sante.fr/publications/2007/cancer_col_uterus%20evaluation/col_uterus.pdf.
14. https://www.e-cancer.fr/component/docman/doc_download/2298-rapportcoluterus07pdf
15. Schaffer P, Sancho-Garnier H, Fender M, Dellenbach P, Carbillet JP, Monnet E, Gauthier GP,
Garnier A.Cervical screening in France European Journal of Cancer 2000;36:2215-20.
16. Marsan C, Cochand-Priollet B. Quality evaluation in cervicovaginal cytology. National program
Arch Anat Cytol Pathol 1993;41:185-6.
17. Llorca J, Dolores Prieto M, Delgado-Rodríguez M,Increase in cervical cancer mortality in
Spain,1951–1991. J Epidemiol Community Health 1999;53:408-11.
18. Fernández Calvo MT, Hernández Rubio A, Rosell Aguilar I. Cervical screening in Spain. European
Journal of Cancer 2000;36:2250-54.
19. Bray F, Loos AH, McCarron P, Weiderpass E, Arbyn M, Møller H, Hakama M, Parkin DM.Trends in
Cervical Squamous Cell Carcinoma Incidence in 13 European Countries: Changing Risk and
the Effects of Screening. Cancer epidemiology, biomarkers and prevention. 2005;14:677-86.
21. Puig-Tintoré LM, Torné A, Alonso I. Current techniques in screening for cervical cancer in Spain:
Updated recommendations. Gynecologic Oncology 2008;10: S8-S10.
22. Raud T, Klaar U. Pilot project of cervical cancer in Estonia. (In Estonian). Eesti Arst
2006;85:834-8.
23. http://www.cancer.ee/?op=body&id=123
24. Lehtinen M, Kibur M, Luostarinen T, Anttila A, Pukkala E. Prospects for phase III-IV vaccination
trials in the Nordic countries and in Estonia. J Clin Virol 2000(19):113-22.
25. Dillner J. Cervical cancer screening in Sweden. European Journal of Cancer 2000:2255-59.
27. Wall S, Rosén M, Nyström L. The Swedish mortality pattern: a basis for health planning ? Int J
Epidemiol 1985(14):285-92.
42
Table10 (Chapter 3) Expected time period for a favourable shift in mortality trend testicular
cancer influenced by the introduction of treatment with Cisplatin
Treatment of
testicular
cancer with
Cisplatin
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
19761983
1976-1983
19731980
19771984
19811988
19952003
19811988
1
2
United Kingdom: Multicenter study starting in 1976 . Registration in 1981 , also for metastatic
3
ovarian tumours, also cervical tumours, lung carcinoma and bladder cancer . The UK Children's
45
have followed patients with testicular cancer in a protocol for 1979-1988,
Cancer Study Group
during which period cisplatin was only given to about 7% of paediatric testicular cancer patients. There
6
is also a clinical study from Scotland for the period 1981-1985 .
The Netherlands: Registration in 1982. The first clinical trial was a clinical study starting in 1976 and
7
8
published in 1979 . A ten-year follow-up study was published in 1989 . Cisplatin was reported in use in
9
10
a follow-up study of patients from the time period 1969-82 . Follow-up study for patients 1979-83 and
11
from 1978-83 have been published. There is a paper in Dutch from the 1970’s has also been
12
evaluated in a paper showing no general use of cisplatin 1970-78 .
13
14
15
Germany: Registration in 1979 . Clinical trials were published in 1976 and 1983 .
16
France: There is a clinical study for patients treated in 1977-82
17
dose cisplatin starting in 1985 .
and a small clinical trial with high
18
Spain: Registration in 1981 .
19
Estonia: Registration in 1995 . For Cisplatin in Estonia, Maximum sales level (2000-2008) was
20
reached in 2005 (359 g/year).Half maximum level was reached in 2000 . Registered also for ovarian
or bladder carcinoma, lung cancer head and neck squamous-cell carcinoma.
21
Sweden: A Swedish-Norwegian clinical trial from 1981-1986 has been published . Registration in
22
1983 . For Cisplatin in Sweden, Maximum sales level (1980-2008) was reached in 1984 (13331
23
packages/year) . Registered also for cancer of the ovarium, lung and skin. A nutritional project for
24
patients with cisplatin treatment was reported on in 1988 .
43
References:
1. Prognostic factors in advanced non-seminomatour germ-cell testicular tumours: results of a
multicentre study. The Lancet 1985;325:8-11.
2. BritishNationalFormulary.http://www.bnf.org/bnf/
3. http://emc.medicines.org.uk/medicine/623/SPC/Cisplatin_1_mg/ml_Sterile_Concentrate/
4. Mann JR, Pearson D, Barrett A, Raafat F, Barnes JM, Wallendszus KR.Results of the United
Kingdom Children's Cancer Study Group's malignant germ cell tumor studies. Cancer
1989;63:1657-67.
5. Huddart SN, Mann JR, Gornall P, Pearson D, Barrett A, Raafat F, Barnes JM, Wallendsus KR.The
UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J
Pediatr Surg 1990;25:406-10.
6. Graham J, Harding M, Mill L, Kerr DJ, Rankin E, Calman KC, Kaye SB.Results of treatment of non
seminomatous germ cell tumours; 122 consecutive cases in the West of Scotland, 1981-1985.
Br J Cancer 1988;57:182-5.
7. Stoter G, Sleijfer DT, Vendrik CP, Schraffordt Koops H, Struyvenberg A, Van Oosterom AT,
Brouwers TM, Pinedo HM. Combination chemotherapy with cis-diammine-dichloro-platinum,
vinblastine, and bleomycin in advanced testicular non-seminoma. Lancet 1979;313:941-5.
8. Stoter G, Koopman A, Vendrik CP, Struyvenberg A, Sleyfer DT, Willemse PH, Schraffordt Koops H,
van Oosterom AT, ten Bokkel Huinink WW, Pinedo HM.Ten-year survival and late sequelae in
testicular cancer patients treated with cisplatin, vinblastine, and bleomycin. Clin Oncol
1989:1099-104.
9. Nijman JM, Schraffordt Koops H, Oldhoff J, Kremer J, Jager S.Sexual function after bilateral
retroperitoneal lymph node dissection for nonseminomatous testicular cancer. Arch Androl
1987;18:255-67.
10. Jansen RL, Sylvester R, Sleyfer DT, ten Bokkel Huinink WW, Kaye SB, Jones WG, Keizer J, van
Oosterom AT, Meyer S, Vendrik CP, et al.Long-term follow-up of non-seminomatous
testicular cancer patients with mature teratoma or carcinoma at postchemotherapy surgery.
EORTC Genitourinary Tract Cancer Cooperative Group (EORTC GU Group). Eur J Cancer
1991;27:695-8.
11. Gelderman WA, Schraffordt Koops H, Sleijfer DT, Oosterhuis JW, Van der Heide JN, Mulder NH,
Marrink J, De Bruyn HW, Oldhoff J.Results of adjuvant surgery in patients with stage III and
IV nonseminomatous testicular tumors after cisplatin-vinblastine-bleomycin chemotherapy.
J Surg Oncol 1988;38:227-32.
12. Zwaveling A, Soebhag R.Testicular tumors in the Netherlands. Cancer 1985(1):1612-7.
14. Osieka R, Bruntsch U, Gallmeier WM, Seeber S, Schmidt CG. Cis-Diamino-dichloro-platinum (II) in
the treatment of otherwise treatment-resistant malignant testicular teratoma. (In German).
Dtsch Med Wochenschr 1976;101:191-5, 99.
15. Haas RJ, Brämswig J, Göbel U, Harms D, Janka G, Weissbach L.Malignant testicular tumors in
children and adolescents concept of the MAHO 82 cooperative therapeutic study of the
Society for Pediatric Oncology. (In German). Klin Padiatr 1983;195:196-200.
16. Flamant F, Schwartz L, Delons E, Caillaud JM, Hartmann O, Lemerle J.Nonseminomatous
malignant germ cell tumors in children. Multidrug therapy in Stages III and IV. Cancer
1984:1687-91.
17. Ghosn M, Droz JP, Theodore C, Pico JL, Baume D, Spielmann M, Ostronoff M, Moran A, Salloum
E, Kramar A, et al. Salvage chemotherapy in refractory germ cell tumors with etoposide
(VP-16) plus ifosfamide plus high-dose cisplatin. A VIhP regimen. Cancer 1988:24-7.
21. Aass N, Klepp O, Cavallin-Stahl E, Dahl O, Wicklund H, Unsgaard B, Baldetorp L, Ahlstrom S,
Fossa SD. Prognostic factors in unselected patients with nonseminomatous metastatic
testicular cancer: a multicenter experience. Journal of Clinical Oncology 1991;9:818-26.
24. Drott C, Unsgaard B, Scherstén T, Lundholm K.Total parenteral nutrition as an adjuvant to
patients undergoing chemotherapy for testicular carcinoma: protection of body
composition--a randomized, prospective study. Surgery 1988;103:499-506.
44
Table 11(Chapter 3) Expected time period for a favourable shift in mortality trend for Hodgkin’s
disease influenced by the introduction of high dose therapy and peripheral blood stem cell
transplantation.
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1999-2005
1994-2001
1988-1995
1992-1999
1992-1999
N.h.d.
1985-1992
N.h.d: No hypothesis defined
United Kingdom:
There seems to have been a professional debate about the method in the 1990s. Smaller clinical
1
study from 1992-1997 showed promising results . Smaller clinical trials from beginning of the 1990s
2
on high-dose therapy has also been described arguing for the method . Involvement in an
international clinical trial starting in 1993 showed no favourable results compared to conventional
3
chemotherapy , and a regional clinical trial starting in 1988-2000 showed similar results. Guidelines
4
for high dose therapy of Hodgkin’s disease from 2003 . Also illustrated by guidelines on the provision
5
of facilities for the cure of adult patients with haematological malignancies . UK was also involved in
6
an European group for blood and marrow transplantation which reported their results in 1997 . For the
whole of Europe, a European committee has surveilled the trends in hematopoetic stem cell
transplantation showing a considerable increase for Hodgkin’s disease in the 1990s, mainly in the first
7
part of the 1990s . The papers showed for all indications a low rate of stem cell transplantation in an
European comparison.
The Netherlands: Papers from a clinical trial of peripheral blood stem cell transplantation starting in
89
10
1994 . Guidelines from 2006 and 2001. For the whole of Europe, an European committee has
surveilled the trends in hematopoietic stem cell transplantation showing a considerable increase for
7
Hodgkin’s disease in the 1990s, mainly in the first part of the 1990s .
Germany: An evaluation of patients in the time period 1988-1998 showed that a third was treated
11
with high-dose therapy and stem cell transplantation . In 1989 15 % in the database of the German
11
Hodgkin Lymhome study group were treated with high-dose therapy . There is a paper from clinical
12
trials starting in 1990s. In 1994 the proportion was 47 %. For the whole of Europe, a European
committee has surveilled the trends in hematopoietic stem cell transplantation showing a considerable
7
increase for Hodgkin’s disease in the 1990s, mainly in the first part of the 1990’s .
France: A French data-base of patients treated with autologous stem-cell transplantation started in
1982 but the rate of patients was low in the 1980s and the main part of patients 1982-1995 was
13
14
treated in 1992 or later . Reports from small-scale clinical study in 1993 starting in 1988 and a long
15
16
term follow-up was published in 1998 . A consensus conference in 1993 stated that there was a
need for more clinical trials and did not recommend the method unless included in clinical trials. In
1999 a case-control study was published based on data from the French register concluding that
autologous stem-cell transplantation represents the best therapeutic option currently available for
17
patients with primary induction failure . For the whole of Europe, an European committee has
surveilled the trends in hematopoietic stem cell transplantation showing a considerable increase for
7
Hodgkin’s disease in the 1990s, mainly in the first part of the 1990s .
Spain: Clinical results from 494 patients connected to a Spanish cooperation group starting in 1984
18
(main part from 1992) was reported in 2001 showing more complete chemotherapy-based regimens
and improved outcome from 1992. For the whole of Europe, an European committee has surveilled
the trends in hematopoetic stem cell transplantation showing a considerable increase for Hodgkin’s
7
disease in the 1990s, mainly in the first part of the 1990s . Personal communication from the involved
19
department states that the introduction was in the middle of the 1990s
Estonia: Only a few events per year. Original data from 1993 received from the European committee
which has surveilled the trends in hematopoietic stem cell transplantation from the first part of the
7
1990s .
45
20
Sweden: A national program in 1985 in which recommendations concerning
high-dose therapy followed by autologous bone marrow transplantation as a second line treatment
were given. Stem cell transplantation in combination with high dose therapy was reported in a clinical
21
trial from 2000 . In 2001 an expert group from Swedish Council of Technology Assessment in Health
Care stated that High dose chemotherapy with stem cell support is presently often used in patients
who are chemotherapy induction failures, who relapse after a short initial remission or after a longer
initial remission and treated initially with seven or eight drugs, or who have had multiple relapses.
However, this use is based on data from uncontrolled or small controlled studies, not being fully
22
convincing with respect to effect on survival . For the whole of Europe, an European committee has
surveilled the trends in hematopoetic stem cell transplantation showing a considerable increase in the
7
1990s, mainly in the first part of the 1990s .
46
References
1. Jackson GH, Angus B, Carey PJ, Finney RD, Galloway MJ, Goff DK, Haynes A, Lennard AL, Leonard
RC, McQuaker IG, Proctor SJ, Russell N, Windebank K, Taylor PR; Scotland and Newcastle
Lymphoma Group. High dose ifosfamide in combination with etoposide and epirubicin
followed by autologous stem cell transplantation in the treatment of relapsed/refractory
Hodgkin's disease: a report on toxicity and efficacy.Leuk Lymphoma 2000;37:561-70.
2. Zekri JM, Mouncey P, Hancock BW.Trials in advanced Hodgkin's disease: more than 30 years
experience of the British National Lymphoma Investigation. Clin Lymphoma 2004:174-83.
3. Federico M, Bellei M, Brice P, Brugiatelli M, Nagler A, Gisselbrecht C, Moretti L, Colombat P,
Luminari S, Fabbiano F, Di Renzo N, Goldstone A, Carella AM (for the
EBMT/GISL/ANZLG/SFGM/GELA Intergroup HD01 Trial). High-Dose Therapy and Autologous
Stem-Cell Transplantation Versus Conventional Therapy for Patients With Advanced
Hodgkin’s Lymphoma Responding to Front-Line Therapy Journal of Clinical Oncology
2003;21:2320-25.
4. http://www.nice.org.uk/nicemedia/pdf/NICE_HAEMATOLOGICAL_CSG.pdf
5. www.bcshguidelines.com/pdf/CLH3.pdf <http://www.bcshguidelines.com/pdf/CLH3.pdf.
6. Majolino I, Pearce R, Taghipour G, Goldstone AH.Peripheral-blood stem-cell transplantation
versus autologous bone marrow transplantation in Hodgkin's and non-Hodgkin's lymphomas: a
new matched-pair analysis of the European Group for Blood and Marrow Transplantation
Registry Data. Lymphoma Working Party of the European Group for Blood and Marrow
Transplantation. J Clin Oncol 1997;15:509-17.
7. Gratwohl A, Baldomero H, Horisberger B, Schmid C, Passweg J, Urbano-Ispizua A ( for the
Accreditation Committee of the European Group for Blood and Marrow Transplantation
(EBMT) ).Current trends in hematopoietic stem cell transplantation in Europe Blood
2002;100:2374-86.
8. Vellenga E, van Agthoven M, Croockewit AJ, Verdonck LF, Wijermans PJ, van Oers MH, Volkers
CP, van Imhoff GW, Kingma T, Uyl-de Groot CA, Fibbe WE.Autologous peripheral blood stem
cell transplantation in patients with relapsed lymphoma results in accelerated
haematopoietic reconstitution, improved quality of life and cost reduction compared with
bone marrow transplantation: the Hovon 22 study. Br J Haematol 2001;114:319-26.
9. van Agthoven M, Vellenga E, Fibbe WE, Kingma T, Uyl-de Groot CA.Cost analysis and quality of
life assessment comparing patients undergoing autologous peripheral blood stem cell
transplantation or autologous bone marrow transplantation for refractory or relapsed nonHodgkin's lymphoma or Hodgkin's disease. a prospective randomised trial. Eur J Cancer
2001;37:1781-9.
10. Guideline: Maligne lymfomen (ziekte van Hodgkin en non-Hodgkin lymfomen). www.oncoline.nl
11. Josting A, Rueffer U, Franklin J, Sieber M, Diehl V, Engert A.Prognostic factors and treatment
outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin
Lymphoma Study Group. Blood. 2000 2000;96:1280-6.
12. Kleiner S, Kirsch A, Schwaner I, Kingreen D, Schwella N, Huhn D, Siegert W.High-dose
chemotherapy with carboplatin, etoposide and ifosfamide followed by autologous stem cell
rescue in patients with relapsed or refractory malignant lymphomas: a phase I/II study.
Bone Marrow Transplant 1997:953-9.
13. André M, Henry-Amar M, Blaise D, Colombat P, Fleury J, Milpied N, Cahn JY, Pico JL, Bastion Y,
Kuentz M, Nedellec G, Attal M, Fermé C, Gisselbrecht C.Treatment-related deaths and
second cancer risk after autologous stem-cell transplantation for Hodgkin's disease. Blood
1998;92:1933-40.
14. Moreau P, Milpied N, Mechinaud-Lacroix F, Mahe B, Rapp MJ, Le Tortorec S, Bourdin S, Dupas B,
Harousseau JL.Early intensive therapy with autotransplantation for high-risk Hodgkin's
disease Leuk Lymphoma 1993;12:51-8.
15. Moreau P, Milpied N, Rapp MJ, Moreau A, Bourdin S, Mahe MA, Dupas B, Le Tortorec S, Hamidou
M, Maisoneuve H, Mahe B, Bulabois CE, Morineau N, Jardel H, Harousseau JL.Early intensive
therapy with autologous stem cell transplantation in high-risk Hodgkin's disease: long-term
follow-up in 35 cases. Leuk Lymphoma 1998:313-24.
16. Coiffier B, Philip T, Burnett AK, Symann ML.Consensus conference on intensive chemotherapy
plus hematopoietic stem cell transplantation in malignancies, Lyon, June 4-6, 1993. Ann
Oncol 1994;5:19-23.
17. André M, Henry-Amar M, Pico JL, Brice P, Blaise D, Kuentz M, Coiffier B, Colombat P, Cahn JY,
Attal M, Fleury J, Milpied N, Nedellec G, Biron P, Tilly H, Jouet JP, Gisselbrecht
C.Comparison of high-dose therapy and autologous stem-cell transplantation with
47
conventional therapy for Hodgkin's disease induction failure: a case-control study. Société
Francaise de Greffe de Moelle. J Clin Oncol 1999;17:222-9.
18. Sureda A, Arranz R, Iriondo A, Carreras E, Lahuerta JJ, García-Conde J, Jarque I, Caballero MD,
Ferrà C, López A, García-Laraña J, Cabrera R, Carrera D, Ruiz-Romero MD, León A, Rifón J,
Díaz-Mediavilla J, Mataix R, Morey M, Moraleda JM, Altés A, López-Guil. Autologous stemcell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients
from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish
Cooperative Group J Clin Oncol 2001(19):1395-404.
19. Personal communication. The Spanish Transplant Office (ONT) .
20. Glimelius B, Enblad G, Kälkner M, Gustavsson A, Jakobsson M, Branehög I, Lenner P, Björkholm
M.Treatment of Hodgkin's disease: The Swedish national care programme experiences.
Leukemia and Lymphoma 1996;21:71-78.
21. Andersson PO, Brune M, Ekman T.Remission inversion and no transplant-related mortality--a
single centre experience of autologous stem cell transplantation in malignant lymphoma.
Acta Oncol 2000(39):849-56.
22. Brandt L, Kimby E, Nygren P, Glimelius B; SBU-group. Swedish Council of Technology Assessment
in Health Care.A systematic overview of chemotherapy effects in Hodgkin's disease. Acta
Oncol 2001;40:185-97.
48
Table 12 (Chapter 3) Expected time period for a favourable shift in mortality trend for rheumatic
heart disease influenced by the introduction of treatment with artificial valve replacement.
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
N.h.d.
N.d.
N.d.
1970-1977
1974-1981
1980-1987
N.h.d
N.h.d.: No hypothesis defined; N.d.: No data
1
United Kingdom: Reported in use in the 1970s referring also to papers before 1970. In 1985, the
UK Department of Health (then the Department of Health & Social Security) and representatives of the
UK Society of Cardiothoracic Surgeons agreed on a national registry for all artificial heart valves
2
implanted through the National Health Service (NHS) hospitals within the UK.
The Netherlands: No data
Germany: No data
3
France: Reported in use in the first part of the 1970s . Multicenter follow-up study of patients with
4
5
operations starting in 1984 has been published . Guidelines 2008 . Implementation rate 2007 was
approximately 100-150 mechanical circulatory assistance on 600-1800 subjects that are susceptible to
5
have it .
6
7
Spain: There are clinical studies of patients operated in the time period 1974-1986 and 1981-1986 .
8
Estonia: 15 % coverage rate was reported achieved about 1980 .
9
Sweden: Reported in use before the study period .
49
References:
1. Oakley C, Doherty P.Pregnancy in patients after valve replacement. Br Heart J
1976;38:140-8.
2. http://www.scts.org/doc/918.
3. Acar J, Michel PL, Dorent R, Luxereau P, Vahanian A, Cormier B, Veron P. Etiologic course of
heart valve diseases surgically treated during 20 years in France (In French). Arch Mal Coeur
Vaiss 1992;85:411-5.
4. Marchand M, Aupart M, Norton R, Goldsmith IR, Pelletier C, Pellerin M, Dubiel T, Daenen W,
Casselman F, Holden M, David TE, Ryba EA. Twelve-year experience with CarpentierEdwards PERIMOUNT pericardial valve in the mitral position: a multicenter study. . J Heart
Valve Dis 1998;7:292-98.
5.<http://www.hassante.fr/portail/upload/docs/application/pdf/synthese_assistance_ventriculaire
.pdf>
6. Duran CG.Reconstructive techniques for rheumatic aortic valve disease. J Card Surg 1988;3:23-8.
7. Vallejo JL, Gonzalez-Santos JM, Albertos J, Riesgo MJ, Bastida ME, Rico MJ, Gonzalez-Diego F,
Arcas R Eight years' experience with the Medtronic-Hall valve prosthesis. Ann Thorac Surg
1990;50:429-36.
8. Personal communication. Dr Sirje Kõvask, , on behalf of the Department of Cardiac Surgery,
Tartu University Clinics.
9. Hedstrand H, Cullhed I.Pregnancy in patients with prosthetic heart valves (Starr-Edwards). Scand
J Thorac Cardiovasc Surg 1968;2:196-9.
50
Table 13 (Chapter 3) Expected time period for a favourable shift in mortality trend for
hypertension influenced by increased number of patients treated for hypertension
Increase in
the number
of patients
treated for
hypertension
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1977-1984
1979-1986
1978-1985
19751982
19801987
N.h.d.
19731980
N.h.d: No hypothesis defined
Comments:
United Kingdom: In the UK, an increase in the prevalence in treatment of hypertension in general
1
practice has been reported 1994-98 . Small-scale clinical trials have been reported in the second part
23
of the 1970s . Larger clinical trials on new generation of anti-hypertensives were published in the
45
1980s starting in 1977. In 1997 it was reported that there were British Hypertension Society (BHS)
6
guidelines for antihypertensive treatment of patients aged 70-79 years .
The Netherlands: The Netherlands participated in an European clinical trial introducing
7
antihypertensive treatment in the elderly starting by the end of the 1970s . There was also a small8
9
scale clinical trial in the 1980s . There was a consensus meeting in 1990 and an official consensus
report in 2001.
Germany: Guidelines from 1986, which are a revision of guidelines from 1982, has been commented
10
11
on in the literature . There was also a clinical trial reported from the first part of the 1980s .
France: There were multicenter clinical trials in the 1970s
12
13
and early 1980s .
14
Spain: An increased use of antihypertensives was reported in 1980-1983 . There are evaluation
15
16
studies of hypertension programs in 1984 and 1989 . A survey from 1987 showed wide
17
prescription of antyhypertensives while a study from one area showed only 30 % acceptable
18
19-22
medication . In 1990 and 1991 there were reports from (a) consensus conference(s)
. Sales
statistics showing maximum sales level (2000-2008; hospital data not included) of antihypertensive
drugs was reached in 2000.
Estonia: In Estonia there was increasing use of antihypertensive medications in 1999-2008 according
23
to sales statistics from this period . ( Increasing from 17,2-25,5 % of adult population aged 20+
24
between 2001 and 2008) . No data available before that time period.
25 26
Sweden: There are reports from clinical trials in the 1970s published in 1976
and a program
27
28
implemented in a county in 1977 . There was a national programme in 1979 . An evaluation report
29
indicates that antihypertensives were in use in the first part of the 1970s .
51
References:
1. http://www.statistics.gov.uk/StatBase/xsdataset.asp?vlnk=2337&Pos=&ColRank=1&Rank=272
2. Forrest WA. Oxprenolol in hypertension: a report on 2,770 patients in general practice originally
treated with methyldopa.Scott Med J 1976 21:28-30.
3. Forrest WA. A multicentre evaluation of sustained release oxprenolol in the management of
hypertension in hospital out-patient practice.. J Int Med Res 1978;6:136-40.
4. Coronary heart disease in the Medical Research Council trial of treatment of mild hypertension.
Medical Research Council Working Party on Mild Hypertension.. Br Heart J. 1988 59:364-78.
5. MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working
Party. Br Med J (Clin Res Ed) 1985;291:97-104.
6. Coppola WG, Whincup PH, Walker M, Ebrahim S. Identification and management of stroke risk in
older people: a national survey of current practice in primary care..J Hum Hypertension
1997(11):185-91.
7. Fletcher A, Amery A, Birkenhäger W, Bulpitt C, Clement D, de Leeuw P, Deruyterre ML, de
Schaepdryver A, Dollery C, Fagard R, et al.Risks and benefits in the trial of the European
Working Party on High Blood Pressure in the Elderly. J Hypertens 1991(Mar;9(3)):225-30.
8. van der Veur E, ten Berge BS, Donker AJ, May JF, Schuurman FH, Wesseling H. Comparison of
hydrochlorothiazide and atenolol as initial treatment in uncomplicated hypertension
Eur J Clin Pharmacol 1984;26:157-62.
9. Struyvenberg A. Hypertension consensus in The Netherlands (In Dutch) Ned Tijdschr Geneeskd
1990 134:2086-93.
10. 1986 guidelines for the treatment of mild hypertension: memorandum from a WHO/ISH meeting.
J Hypertens 1986 4:383-6.
11. Haimerl F, Lehmann K, Köpcke W. Treatment of essential hypertension with a potassium-sparing
diuretic combination. Results of a German multicenter study with Moduretic (In German)
Fortschr Med 1985 12:812-6.
12. Jouve A, Goldet L, Mathieu M.Results of a national therapeutic trial conducted in 10,000
hypertensive patients by 2000 general practitioners. Clin Sci Mol Med
1978(Suppl.Dec;4):353s-54s.
13. Mimran A, Zambrowski JJ, Coppolani T. The antihypertensive action of indapamide: results of a
French multicentre study of 2,184 ambulant patients. Postgrad Med J 1981;57:Suppl 2: 60-3.
14. Pardell H. Epidemiología de la hipertensión Barcelona: Ediciones DOYMA, 1999.
15. Martínez-Amenós A, Caralps Riera A, Carreras Berges L, Font Andreu I, Rama Andrade H, Sarrias
Lorenz X, Alsina Rocasalbas J. Arterial hypertension in the hospital. The experience of the
Hypertension Section of the Bellvitge-Princeps d'Espanya Hospital. (In Spanish) ed Clin
(Barc). 1984;82:698-701.
16. Abat X, Albiol M, González de la Rubia C, Meléndez C, Perelló N, Sala C, Travería M. Evaluation
of arterial hypertension program in a primary care center (In Spanish) ten Primaria. 1989
6:448, 50-2, 54.
17. Pardell H, Tresserras R, Armario P, Salto E. Detection, treatment and control of hypertension in
Spain.J Hum Hypertens 1990 4:297-9.
18. Beltrán Brotons JL, López Gallardo EJ, Gervas Camacho JJ. Drug prescription in primary care.
Pharmacoepidemiologic study in the Albacete area. (In Spanish). Rev Sanid Hig Publica
(Madr) 1990 64:673-92.
19. Balaguer Vintro I. Consensus for the control of cholesterolemia and hypertension and the
prevention of cardiovascular diseases in Spain. (In Spanish). Rev Sanid Hig Publica (Madr)
1990 64:343-6.
20. Consensus for the control of arterial hypertension in Spain. (In Spanish). Rev Sanid Hig Publica
(Madr) 1990 64:439-77.
21. Consensus on control of arterial hypertension in Spain. Ministry of Health and Consumption
([Article in Spanish). Rev Esp Cardiol 1991 44:76-94.
22. Consensus for the Control of Arterial Hypertension in Spain. Madrid, 1989. Aten Primaria 1991
276:282-4.
24. Data from Statistics Estonia (www.stat.ee).
25. Hansson L, Karlberg BE, Aberg H, Westerlund A, Jameson S, Henningsen NC. Long-term
hypotensive effect of atenolol (ICI 66.082), a new beta-adrenergic blocking agent. Acta Med
Scand 1976;199:257-61.
26. Berglund G, Isacsson SO, Rydén L.The Skaraborg project--a controlled trial regarding the effect
of structured hypertension care. Acta Med Scand Suppl 1979;626:64-8.
52
27. Eckerlund I, Jonsson E, Rydén L, Råstam L, Berglund G, Isacsson SO. Economic evaluation of a
Swedish medical care program for hypertension. Health Policy 1985;5:299-306.
28. Underlag till vårdprogram för högt blodtryck (In Swedish:A program foundation for hypertension
care). Stockholm: Socialstyrelsens vårdprogramnämnd. National Board of Health and
Welfare, 1979.
29. Boethius G.The treatment of hypertension--an analysis of drug prescription data. Acta Med
Scand Suppl 1976;602:120-3.
53
Table 14 (Chapter 3) Expected time period for a favourable shift in mortality trend for myocardial
infarction influenced by the introduction of coronary care units
Coronary care
units for acute
management of
myocardial
infarction
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
N.h.d.
1977-1984
N.d.
19952002
19911998
19801987
1975-1982
N.h.d.: No hypothesis defined , N.d: No data available
Comments coronary care units:
United Kingdom: No hypothesis defined due to early introduction before the study period and slow
diffusion. Coronary care units were introduced in the UK in the 1960s but their expansion was initially
1
2 3
slow . Writing in 1987, Julian stated that 25% of hospitals still did not have cardiologists . National
4
guidelines were established in 1996 . The information about the slow introduction was supported by
an evaluation from a district general hospital in 1994 by Wong stating that only a small proportion of
5
patients were admitted to coronary care units . However, there is an example of a medical centre
6
giving recommendations for coronary care units in the early 1990 .
7 8
The Netherlands: Coronary care units were reported in use in 1977 . This is supported by an
evaluation study by Bots 1996 in which the decline in coronary heart disease mortality in the
Netherlands from 1978 to 1985 in which coronary care units were considered to have contributed
9
significantly to the mortality decline in that time period .
Germany: No data available.
10
France: There are national recommendations from 1999 . Around 1990, the acute coronary care was
evaluated showing a large proportion of acute patients primarily seeking private practitioners and
mobile emergency care units instead of hospital care, which may indicate that coronary care units
11 12
were not the main type of care in that time period
. For instance, only 3.5% of patients were
11
reported to go directly to hospital in the 'Bas-Rhin' department in 1986-87 .
Spain: A multicenter-register of coronary care in 119 hospitals showed a 60 % admission rate in
13
1995-2001 . In a population register study from 1996-98 89% of MI patients in ages 25-74 years were
14
15
admitted to Coronary care units . There is also a consensus document from 1999 .
Estonia: Became widespread (almost standard) in early 1980-s according to personal communication
with prof Margus Viigimaa, leading cardiologist.
16
17
18
Sweden: Reported in use in 1975 in twelve Swedish hospitals . Widely implemented in 1994 .
19
Consensus on intensive care in 1995
Total pattern: It may not be implausible that the Netherlands and Estonia (late 1970s and early 1980s)
were early adapters of the Coronary care units, while the main pattern for the majority of countries was
that it was generally implemented in the 1990s. Differences may for instance be due to differences in
the level of geographical concentration of the country and to medical care system.
54
References:
1. Julian DC. The evolution of the coronary care unit. Cardiovascular Research 2001;51:621-24.
2. http://heart.bmj.com/cgi/reprint/57/6/497.pdf
3. Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KA, Julian D, Lengyel M, Neumann
FJ, Ruzyllo W, Thygesen C, Underwood SR, Vahanian A, Verheugt FW, Wijns W. Management
of acute myocardial infarction in patients presenting with ST-segment elevation. The Task
Force on the Management of Acute Myocardial Infarction of the European Society of
CardiologyEurHeartJ2003Jan;24(1):2866.
http://eurheartj.oxfordjournals.org/cgi/reprint/24/1/28.
4. http://www.nice.org.uk/nicemedia/pdf/CG48FullGuideline.pdf.
5. Wong W jA, Goodwin TJ. Audit on myocardial infarction in a district general hospital: is there
room for improvement in diagnostic accuracy ? J R Soc Med 1994;87:571.
6. Hampton JR MA. Purchasing care for patients with acute myocardial infarction. Quality in health
care 1992;1:68-73.
7. Vroom RJAF. Hartbewaking in streekziekenhuis. Amsterdam Universiteit van Amsterdam, 1977.
Proefschrift.
8. Leidraad cardiologie from 2002.
http://www.nhj.nl/cardiologie.nl/2/pagecontent/main_protocollen/leidraadcardiologie200
2.pdf
9. Bots ML GD. Decline of coronary heart disease mortality in the Netherlands from 1978 to 1985:
contribution of medical care and changes over time in presence of major cardiovascular risk
factors. Journal of Cardiovascular Risk 1996;3:271-76.
10. Recommandations de la société française de cardiologie pour la prise en charge des urgences
cardiologiques Archives des maladies du coeur et des vaisseaux 1999;92:337-45.
11. Arveiler D, Cambou JP, Nuttens MC, Bingham A, Hedelin G, Ruidavets JB, Richard JL, Salomez
JL, Sacrez A, Schaffer P.Acute coronary care and treatment of myocardial infarction in the
three French MONICA registers.
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VDocSum&ordinalpos=21. Rev Epidemiol Sante Publique.1990;38:429-34.
12. Arveiler D, Bingham A, Escudero I, Fender M, Gonzales M, Hedelin G, Richard JL, Schaffer P,
Zaffra F. Evaluation of the status of access to emergency care of subjects with myocardial
infarction Rev Epidemiol Sante Publique 1988;36:350-9.
13. Ruiz-Bailén M, Aguayo de Hoyos E, Ramos-Cuadra JA, Díaz-Castellanos MA, Issa-Khozouz Z,
Reina-Toral A, López-Martínez A, Calatrava-López J, Laynez-Bretones F, Castillo-Parra JC,
De La Torre-Prados MV; ARIAM Group. Influence of age on clinical course, management and
mortality of acute myocardial infarction in the Spanish population. Int J Cardiol.
2002;85:285-96.
14. Alvarez-León EE, Elosua R, Zamora A, Aldasoro E, Galcerá J, Vanaclocha H, Segura A, Fiol M,
Turumbay J, Pérez G, Arteagoitia JM, Tormo MJ, Cabadés A, Vega G, Ayestarán JI, García V,
Hurtado-de-Saracho I, Navarro C, Zurriaga O, Muñiz J, Sala J, Marrugat J; IBERICA
Study.Hospital resources and myocardial infarction case fatality. The IBERICA study. (In
Spanish). Rev Esp Cardiol. 2004;57:514-23.
15. Arós F, Loma-Osorio A, Alonso A, Alonso JJ, Cabadés A, Coma-Canella I, García-Castrillo L,
García E, López de Sá E, Pabón P, San José JM, Vera A, Worner F.The clinical management
guidelines of the Sociedad Española de Cardiología in acute myocardial infarct. (In Spanish).
Rev Esp Cardiol. 1999;52:919-56.
16. Nordlander R, Nyquist O.Patients treated in a coronary care unit without acute myocardial
infarction: identification of high risk subgroup for subsequent myocardial infarction and/or
cardiovascular death. Br Heart J 1979;41:647-53.
17. Henning R, Lundman T. Swedish Co-operative CCU Study. A study of 2008 patients with acute
myocardial infarction from 12 Swedish hospitals with coronary care unit. Part I. A
description of the early stage. Part II. The short-term prognosis. . Acta Med Scand Suppl.
1975;586:1-64.
18. Swedish working group on early heart attack care. A survey of treatment routines and
educational level of health care providers in the initial phase of suspected acute myocardial
infarction in Sweden in 1994. Swedish Working Group on Early Heart Attack Care. . Eur J
Emerg Med 1996;3:149-56.
55
19. Wilhelmsen L, Asserhed G, Bjurman A, Britton M, Baeckström P, Ekström L, Haverdahl A,
Nordlander R, Olsson B, Rosén M, Schlyter M, Sjögren A, Skoglund C, Sonnhag C, Swedberg
K, Waagstein L. A consensus statement. Heart attack--acute or threatening myocardial
infarction (In Swedish). Läkartidningen 1995;92:2329-35.
56
Table 15 (Chapter 3) Expected time period for a favourable shift in mortality trend for myocardial
infarction influenced by the introduction of medication for secondary prevention with betablockers.
Medication
for
secondary
prevention
of
myocardial
infarction
with betablockers.
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1978-1985
1985-1992
1979-1986
19871994
19821989
19801987
19761983
12
United Kingdom: There are reports on involvement in clinical trials from the first part of the 1980s ,
6
starting in 1978 . The diffusion was further facilitated by the publication of a multicenter study (ISIS-1)
3
in 1986 . An audit from 1998 showed that Blood pressure was managed according to current
4
567
guidelines for 82% of the patients . Guidelines in 2001
.
8
9
The Netherlands: There are country reports about registration in 1985 and guidelines from 2006 .
Secondary prevention with beta-blocker has been suggested that it may have had an impact on the
10
mortality decline also in the period before 1985 . In 1995 about 60 % of CHD-patients were reported
11
to have therapeutic control of blood pressure .
Germany: There was an European multicenter study mainly performed in Germany starting in 1979
12
and reported in 1984 . In 1995 about 60 % of CHD-patients were reported to have therapeutic control
11
of blood pressure and about 40% used beta-blockers . Metoprolol was registered for this indication
13
in 2001 .
14
France: There are reports about involvement in clinical trials starting in 1987 and published in 1990
15
16
. In 1995, 64% of MI-patients were reported using beta-blockers . Beta-blockers were registered in
17
France for secondary prevention after myocardial infarction in 2009. . However, generally
18
19 20
implemented (82%) in 2006 . Guidelines were published in 2007
.
Spain: In the literature, the prescription of beta-blockers for MI patients increased from 20% to 30-35
21
22
% between 1982 and 1988 . In 1989 the proportion had raised to 62 % . . Guidelines were
23
24
published in 1995 . Registration for cardiac arrhythmias was in 1966 .
Estonia: Country reports on registration in 1993
27
Estonia since early 1980s .
25
26
and guidelines in 2004
but widespread use in
Sweden: There are reports in the literature on involvement in large clinical trials from the beginning of
28-30
31
32
the 1980s
, starting in 1976 . Guidelines were published in 1998 .
57
References:
1. Dollery C.Diuretic agents and beta-blockers in the treatment of hypertension.
Hypertension 1989(13 (may)):Suppl 162-5.
2. Julian DG, Jackson FS, Szekely P, Prescott RJ.A controlled trial of sotalol for 1 year after
myocardial infarction. Circulation. 1983 1983;67(6 Pt 2)::I61-2.
3. http://www.pharmj.com/pdf/articles/pj_20071110_landmarkdrugs02.pdf.
4. Campbell NC, Thain J, Deans HG, Ritchie LD, Rawles JM.Secondary prevention in coronary heart
disease: baseline survey of provision in general practice BMJ 1998;316:1430-4.
5. http://www.nice.org.uk/nicemedia/pdf/Full_HF_Guideline.pdf.
6. http://www.nice.org.uk/nicemedia/pdf/CG68FullGuideline.pdf
7. http://www.cks.nhs.uk/mi_secondary_prevention/management/prescribing_information
8. http://www.cbg-meb.nl/CBG/nl/humanegeneesmiddelen/ geneesmiddeleninformatiebank/
default.htm
9. Multidisciplinar guideline: Cardiovasculair risicomanagement. www.nvvc.nl
10. Bots ML, Grobbee DE.Decline of coronary heart disease mortality in The Netherlands from 1978
to 1985: contribution of medical care and changes over time in presence of major
cardiovascular risk factors J Cardiovasc Risk 1996(3):271-6.
11. EUROASPIRE I and II Group; European Action on Secondary Prevention by Intervention to Reduce
Events. Clinical reality of coronary prevention guidelines: a comparison of EUROASPIRE I and
II in nine countries. EUROASPIRE I and II Group. European Action on Secondary Prevention by
Intervention to Reduce Events. Lancet 2001(357):995-1001.
12. European Infarction Study (E.I.S.) A secondary prevention study with slow release oxprenolol
after myocardial infarction: morbidity and mortality. Eur Heart J 1984;5:189-202.
14. Boissel JP, Leizorovicz A, Picolet H, Peyrieux JC.Secondary prevention after high-risk acute
myocardial infarction with low-dose acebutolol. Am J Cardiol 1990;66:251-60.
15. Boissel JP, Leizorovicz A, Picolet H, Ducruet T. Efficacy of acebutolol after acute myocardial
infarction (the APSI trial). The APSI Investigators. Am J Cardiol 1990;66:24C-31C.
16. Danchin N, Hanania G, Grenier O, Vaur L, Amelineau E, Guéret P, Blanchard D, Ferrières J,
Genès N, Lablanche JM, Cantet C, Cambou JP. Trends in discharge prescriptions for patients
hospitalized for acute coronary syndromes in France from 1995 to 2000. Data from the Usik
1995, Prevenir 1, Prevenir 2 and Usic 2000 surveys. (In French) Ann Cardiol Angeiol (Paris)
2003;52:1-6.
17. Indicateurs de pratique clinique - Infarctus du myocarde HAS (Haute autorité en santé :
www.has-sante.fr). Avril 2009.
18. Tuppin P, Neuman A, Danchin N & alii. Combined secondary prevention after hospitalization for
myocardial infarction in France : Analysis from a large administrative datebase Archives of
cardiovascular disease 2009;102:279-92.
19. Guideline : “ALD n° 13 : Guide médecin sur la maladie coronarienne”. www.has-sante.fr.
20. Syndromes coronariens aigus, infarctus du myocarde : modalités de prise en charge. www.hassante.fr.
21. Agustí A, Arnau JM, Laporte JR.Clinical trials versus clinical practice in the secondary prevention
of myocardial infarction. Eur J Clin Pharmacol 1994;46:95-9.
22. Martínez M, Agustí A, Arnau JM, Vidal X, Laporte JR.Trends of prescribing patterns for the
secondary prevention of myocardial infarction over a 13-year period. Eur J Clin Pharmacol
1998;54:203-8.
23 . PLAN DE SALUD 1995 Ministerio de Sanidad. Centro de Publicaciones. Madrid 1995.
26. Soopõld Ü, Marandi T, Ainla T, Viigimaa M jt. . ST-elavation Acute MI Guideline
Estonian Physician 2004
27. Personal communication, prof Margus Viigimaa, leading cardiologist in Estonia.
28. Hjalmarson Å, Herlitz J, Málek I, Rydén L,Vedin A, Waldenström A, Wedel H, Elmfeldt D,
Holmberg S, Nyberg G, Swedberg K, Waagstein F, Waldenström J, Wilhelmsen L,
Wilhelmsson C.Effect on mortality of Metoprolol in acute myocardial infarction. The Lancet
1981;318:823-27.
29. Werkö L. Mortality in the Stockholm heart disease secondary prevention study. J Intern Med
1989;225:427-8.
58
30. Olsson G, Levin LA, Rehnqvist N.Economic consequences of postinfarction prophylaxis with beta
blockers: cost effectiveness of metoprolol. BMJ (Clin Res Ed) 1987;294:339-42.
31. Herlitz J, Waagstein F, Lindqvist J, Swedberg K, Hjalmarson A. Effect of metoprolol on the
prognosis for patients with suspected acute myocardial infarction and indirect signs of
congestive heart failure (a subgroup analysis of the Göteborg Metoprolol Trial).erg K,
Hjalmarson A. Am J Cardiol 1997:40J-44J.
32. Nationella riktlinjer för kranskärlssjukvård (National guidelines for coronary care). Stockholm:
National Board of Health and Welfare, 1998.
59
Table 16 (Chapter 3) Expected time period for a favourable shift in mortality trend influenced by
treatment of heart failure with ACE-inhibitors.
Treatment
of heart
failure with
ACEinhibitors4
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1991-1998
1990-1997
1991-1998
19881995
19911998
19942001
19851992
Comments:
1
United Kingdom: ACE-inhibitors were reported registered in (Captopril) 1981 and (Enalapril) in
2-4
1985. In literature, first reports on involvement in clinical trials in 1991-1992 . Reports of the
5
5
6
implementation rates showed 17 % and 57 % use, respectively, in 1994, 40 % use in 1998 and
7
8
9
2003 , 54 % in 2004 and about 70 % in 2005 . In 2003, NICE guidelines on heart failure were
10
published recommending ACE-inhibitors . Before that the National Service Framework (NSF) for
Coronary Heart Disease (CHD) (in 2000) set similar national standards for the management of people
9
with heart failure in England .
11
The Netherlands: Captopril was available in the Netherlands in 1979 and Enalapril in 1984 . For
12
treatment of heart failure, a small-scale clinical study was published in 1990 . There are guidelines on
13
treatment of heart failure (CBO and NHB) from 1994 and 1995 recommending ACE-inhibitors. ACE14
inhibitors were registered for heart failure in (Captopril) 1997 and (Enalapril) 1999 . In 1998, it was
15
reported that only 50 % of heart failure patients were treated with ACE-inhibitors .
16
Germany: ACE-inhibitors were reported registered (Enalapril and Capropril) in 1984 . Involvement in
2 4
clinical trials starting in 1991 . There are guidelines on the treatment of heart failure from 1998
(Medical Commission of the physician associations (AkdA) and the German Society of
13
17
Cardiology,DGK) . In 1999-2000 the level of use was reported to be 61% .
France: First reimbursement of ACE-inhibitors were reported in 1988. Involvement in clinical trials
18
19
published in 1989 . A report from one hospital showed only 15 % use in 1998 . Other reports in 2000
20
showed 75% use , but 38% took lower-than-recommended doses, and 48% in ages > 75 years
21
versus 63% in ages < 75 years) . According to sales statistics in France, maximum sales levels
(2002-2007) of ACE-inhibitors were reached in 2007.
22
Spain: ACE-inhibitors was reported registered in 1981 , but maximum sales level (20002008;hospital data not included) of ACE-inhibitors were reached in 2008. Involvement in clinical trials
2 4 23
started in 1991
. There are guidelines on the treatment of heart failure from 1999 (the Working
13
Group for HF of the Spanish Soc. of Cardiology) . In the beginning of the 2000s more than 80 % of
24
patients at heart failure centres used ACE-inhibitors .
25
Estonia: Registration for heart failure in 1994-1996 .
Sweden: For ACE-inhibitors (total group) in Sweden, Involvement in clinical trials for congestive
2 26 27
28
heart failure starting in 1985
and for chronic heart failure in the 1990s . Registration for the
29
indication of heart failure in 1994 . In the late 1990s there was a report on underuse of ACE-inhibitors
30
in heart failure patients . There are guidelines on the treatment of heart failure from 1998 (National
13
Board of Health and Welfare) . In 2002, 50 % of heart failure patients at a primary care centre were
31
reported to have optimal treatment with ACE-inhibitors . Maximum sales levels (1982-2008) were
reached in 2008, half of maximum level was reached in 1999.
For six of the participating countries, the implementation rate was between 48 and 61 % in 199917
2000 .
60
References:
1.http://emc.medicines.org.uk/medicine/550/SPC/Capoten+Tablets+12.5mg%2c+25mg%2c+50mg/#
AUTHDATE
2. Latini R, Maggioni AP, Flather M, Sleight P, Tognoni G.ACE inhibitor use in patients with
myocardial infarction. Summary of evidence from clinical trials. Circulation 1995;92:3132-7.
3. Moyses C, Higgins TJ.Safety of long-term use of lisinopril for congestive heart failure
Am J Cardiol 1992;70:91C-97C.
4. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with
clinical evidence of heart failure. The acute infarction ramipril efficacy (AIRE) study
investigators. lancet 1993;342:821-8.
5. Clarke KW, Gray D, Hampton JR.Evidence of inadequate investigation and treatment of patients
with heart failure Br Heart J. 1994;71:584-7.
6. Doyle JC, Mottram DR, Stubbs H.Prescribing of ACE inhibitors for cardiovascular disorders in
general practice. J Clin Pharm Ther 1998;23:133-6.
7. Sparrow N, Adlam D, Cowley A, Hampton JR.Difficulties of introducing the National Service
Framework for heart failure into general practice in the UK. Eur J Heart Fail 2003;5:355-61.
8. Gnani S, Gray J, Khunti K, Majeed A.Managing heart failure in primary care: first steps in
implementing the National Service Framework. J Public Health 2004;26:42-7.
9. Majeed A, Williams J, de Lusignan S, Chan T.Management of heart failure in primary care after
implementation of the National Service Framework for Coronary Heart Disease: a crosssectional study. Public Health 2005;119:105-11.
10. NICE guidelines on heart failure. Clin Med. 2003 2003;3:399-401.
11. Fijn R, Engels SAG, Brouwers JRBJ, Knaap RJ, De Jong-Van den Berg LTW. Dutch hospital drug
formularies: pharmacotherapeutic variation and conservatism, but concurrence with
national pharmacotherapeutic guidelines. Br J Clin Pharmacol 49,254-263) 2000;49:254-63.
12. Dunselman PH, van der Mark TW, Kuntze CE, van Bruggen A, Hamer JP, Scaf AH, Wesseling H,
Lie KI.Different results in cardiopulmonary exercise tests after long-term treatment with
felodipine and enalapril in patients with congestive heart failure due to ischaemic heart
disease. . Eur Heart J 1990;11:200-6.
13. Sturm HB, van Gilst WH, Swedberg K, Hobbs FD, Haaijer-Ruskamp FM.Heart failure guidelines
and prescribing in primary care across Europe. BMC Health Serv Res 2005;5:57.
14. www. cbg-med.nl.
15. Remme WJ.Towards the better treatment of heart failure. Eur Heart J. 1998 1998;Oct;19:Suppl
L:L36-42.
17. Cleland JG, Cohen-Solal A, Aguilar JC, Dietz R, Eastaugh J, Follath F, Freemantle N, Gavazzi A,
van Gilst WH, Hobbs FD, Korewicki J, Madeira HC, Preda I, Swedberg K, Widimsky
J:Management of heart failure in primary care (the IMPROVEMENT of Heart Failure
Programme): an international survey. . Lancet 2002;360:1631-39.
18. Bounhoure JP, Bottineau G, Lechat P, Garnham J, Lapeyre G.Value of perindopril in the
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19. Rachet F, Boissel JP, Dubois V, Aulagner G.PHOLY: a pilot study of drug utilization in civil
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of angiotensin-converting enzyme inhibitor prescription in severe heart failure with left
ventricular systolic dysfunction: the EPICAL study. Am Heart J 2000;139:624-31.
21. Maison P, Cunin P, Hemery F, Fric F, Elie N, Del'volgo A, Dubois-Randé JL, Hittinger L, MacquinMavier I.Utilisation of medications recommended for chronic heart failure and the
relationship with annual hospitalisation duration in patients over 75 years of age. A
pharmacoepidemiological study. Eur J Clin Pharmacol. 2005;61:445-51.
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61
26. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart
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62
Table 17 (Chapter 3) Expected time period for a favourable shift in mortality trend for stroke
influenced by the introduction of intensive management of stroke
Intensive
management1
of acute
stroke
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1998-2005
1996-2003
1996-2003
19921999
N.h.
d.
19982005
N.h.d.
1
CT scan; thrombolytic therapy (main basis for hypothesis); surgical treatment of aneurysms in
subarachnoid haemorrhage
n.h.d: No hypothesis defined.
United Kingdom: In the literature, in 1992/93 only 5% of patients were admitted to stroke units, while
1
two third had access to CT scan . An audit from 1998 concluded that the best compliance with
standards of intensive management was achieved for the 18% of patients who at that time spent at
2
least 50% of their time in a stroke unit . There was however large variations in stroke care between
3
4
different areas. The proportion was increased to 26% in 1999 and 27% in 2002 . The case fatality
5
rate was found to decline by 25% in the stoke unit care provided in routine clinical practice .
6
Guidelines were published in 2004 . The general implementation in UK was shown by the Sentinel
7-11
Stroke Audit report in 2006 .
12
The Netherlands: Guidelines for acute management 2000 . Guidelines for intravenous thrombolytic
13
14
therapy and CT 2008 and recommendations for operations for aneurysms around 1980 .
15
16
Germany: Clinical trials on stroke units and thrombolytic therapy (performed 1996-1998) has been
reported in 2000. However, in 2002 only 4% of stroke unit patients were reported treated with
17
thrombolysis . In 2002 a congress report was published announcing the coming implementation of
18
19
guidelines . The method has been reported generally implemented in Germany in 2008 .
20 21
22
. Guidelines in 2000 and 2002France: Clinical trials mainly based in France started in 1992
23 24
25
2003
. In 2001, it was reported that CT scan was performed in most patients . Intensive
26
management has been reported generally implemented in France in 2007 .
Spain: Stroke units have been presented and argued for in the literature in the 2000s
no data showing that this has been generally implemented in Spain.
27 28
but we have
29
Estonia: Implementation in Estonia was in the late 1990’s . En evaluation study from Tartu stated
that the main difference between 1991-1993 and 2001-2003 was the availability of CT scans which
30
31
was introduced between these two periods . Guidelines in 2005 .
Sweden: Thrombolytic therapy reported in small scale use in 2006 based on experiences from
32
international clinical trials . The safe implementation was in practice was evaluated in a multicenter
33
study from 2002-2006 in which half of the centres had no previous experience of this method.
However, in 2010, it was reported that nationwide the diffusion was slow:; the use of thrombolysis
34
increased from 0.9% in 2003 to 6.6% in 2008 . For subarachnoid aneurysms a shift in strategy
35
towards surgical interventions was reported in the mid 1980s
63
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(In German). MMW Fortschr Med 2002;144:12.
19. Akuttherapie des ischämischen Schlaganfalls: AWMF-Leitlinien-Register, Nr. 030/046,
Entwicklungsstufe 1, letzte Aktualisierung 10/2008: AWMF - Arbeitsgemeinschaft der
Wissenschaftlichen Medizinischen Fachgesellschaften <http://www.awmf-leitlinien.de/>.
20. Hommel M, Cornu C. Rationale for testing thrombolysis in acute ischaemic stroke. MAST Group.
Clin Trials Metaanal 1993;28:345-56.
21. The Multicenter Acute Stroke Trial - Europe Study Group.Thrombolytic Therapy with
Streptokinase in Acute Ischemic Stroke. N Engl J Med 1996;335:145-50.
22. Larrue V. Guidelines for the use of intravenous thrombolytic therapy cerebrovascular ischemic
accident. French Society for Neurovascular Disease. (In French). Presse Med 2000;29:372-8.
23. Recommandations professionnelles: Prise en charge initiale des patients adultes atteints
d'accidents vasculaires cérébraux. Aspects médicaux ANAES. Septembre 2002.
24. Circulaire ministérielle. DHOS/DGS/DGAS N°517 du 3/11/2003 relative à la prise en charge des
AVC
25. Guillon B, Planchon B, Woimant F, Magne C, Barrier JH. Stroke management in a general
internal medicine department: results of a survey regarding practice (In French). Rev Med
Interne 2001:830-44.
26. La prise en charge précoce des accidents vasculaires cérébraux. Office parlementaire
d'évaluation des politiques de santé. N°236. Assemblée nationale
27. Fuentes B, Díez-Tejedor E.The advantages of a stroke unit in the treatment of intracerebral
hemorrhage (In Spanish). Rev Neurol 2000;31:171-4.
28. Kase CS.The stroke unit: key in the modern management of stroke (In Spanish). Rev Neurol
2001;32:133.
29. Personal communication:Dr Janika Kõrv and dr Irja Kalbe at the Tartu University neurology
clinic.
64
30. Vibo R, Ko˜rv J, Roose M.The Third Stroke Registry in Tartu, Estonia. Decline of Stroke
Incidence and 28-Day Case-Fatality Rate Since 1991. Stroke. 2005;36:2544-48.
31. Kõrv J, Roose M, Kaasik AE, Asser T, Kreis A, Lüüs SM; Antsov Insuldi K. Eesti ravijuhend. Eesti
Arst (In Estonian) 2005;84(3):203 -24.
32. Wahlgren NG, Terent A, Norrving B, Lindqvist M, Svendsen P, Rådberg J, Hårdemark
HG.Thrombolysis changes the care of stroke.(In Swedish). Läkartidningen 1998 95:3202-11.
33. Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens
S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G; SITS-MOST
investigators.Thrombolysis with alteplase for acute ischaemic stroke in the Safe
Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational
study Lancet 2007;369:275-82.
34. Eriksson M, Jonsson F, Appelros P, Asberg KH, Norrving B, Stegmayr B, Terént A, Asplund K; RiksStroke Collaboration.Dissemination of thrombolysis for acute ischemic stroke across a
nation: experiences from the Swedish stroke register, 2003 to 2008. Stroke 2010;41 1115-22.
35. Cesarini KG, Hårdemark HG, Persson L.Cesarini KG, Hårdemark HG, Persson L. J Neurosurg 1999
90:564-72.
65
Table 18 (Chapter 3) Expected time period for a favourable shift in mortality trend for stroke
influenced by prevention of stroke by treatment of hypertension.
Prevention of
stroke by
treatment of
hypertension
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
19811990
1986-1995
19942003
19932002
19912000
19972005
19701979
Comments
1
2
United Kingdom: Clinical trials were set up in 1981 and reported in the late 1980s and early
3
4
1990s . In the 1990s the need for standards and guidelines . For antihypertensive treatment of
patients aged 70-79 years only a minority (23% and 9%) of general practitioners reported treating
patients in accordance with recommendations and it was stated that there was a need for
5
6
improvements . In 2003 the method was generally implemented . National guidelines were published
7
in 2004 .
8
9
The Netherlands: Clinical trials for TIA patients started in 1986 . First guidelines published in 1990 .
Later there are revised stroke guideline from 2000 including recommendations on secondary
10
prevention with antihypertensives
Germany: There were statements supporting prevention of stroke by hypertensive treatment in I
11
national conference report from 1998 . There are reports from 2007 and 2008 that the method was
12 13
reported generally implemented
.
14
15
France: There are guidelines from 1997 , 2000
17
implemented in 2007 .
16
and 2005 . The method was reported generally
18
Spain: There is a report about guidelines from 1995 . The sales of hypertensive drugs continued to
increase also in the 2000s (maximum level in the latest year available in 2008). In the literature there
are reports indicating that the diffusion of the method may have been slow (a third of hypertensive
19
patients treaded in one area in 1997) .
20
Estonia: There are country reports about guidelines from 2006 preceded by an introduction in 1995
21 22
when the antihypertensive society was founded and a textbook supported the introduction
. In
23
2001-2003 59% of patients was found to use antihypertensives .
24
Sweden: A clinical trial started in 1970 . Antihypertensive prevention was more generally introduced
25
in a national programme in 1979 developed by professional leaders active in the field of
24 26
antihypertensive prevention at that time
.
66
References:
1. Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC
Working Party. BMJ 1992 1992;304:405-12.
2. Peart S. Results of MRC (UK) trial of drug therapy for mild hypertension. Clin Invest Med
1987;10:616-20.
3. Miall WE.Beta-blockers vs. thiazides in the treatment of hypertension: a review of the experience
of the large national trials. Cardiovascular Pharmacol 1990;16:suppl 5:S58-63.
4. Stroke. Towards better management. Summary and recommendations of a report of the Royal
College of Physicians. 1990;24:15-17.
5. Coppola WG, Whincup PH, Walker M, Ebrahim S. Identification and management of stroke risk in
older people: a national survey of current practice in primary care. J Hum Hypertension
1997(11):185-91.
6.http://www.ic.nhs.uk/statistics-and-data-collections/supporting-information/audits-andperformance/the-quality-and-outcomes-framework/qof-information/introduction-to-qof
8. The Dutch TIA trial: protective effects of low-dose aspirin and atenolol in patients with transient
ischemic attacks or nondisabling stroke. The Dutch TIA Study Group Stroke. 1988;19:512-7.
9. Stuyvenberg A. Hypertensie consensus in Nederland. NTVG 1990;, 1990.
10. CBO guideline 'Stroke' (revision) Dutch Institute for Healthcare Improvement. Ned Tijdschr
Geneeskd 2000(144):1058-62.
11. Prevention of cardiovascular diseases. 1998 guidelines of the National Cardiovascular
Conference (NCC). Dtsch Med Wochenschr 1999;124:1249-52.
12. Schlaganfall: AWMF-Leitlinienregister, Nr. 053/014, Entwicklungsstufe 3, letzte Aktualisierung
08/2006.
13. Primär- und Sekundärprävention der zerebralen Ischämie: AWMF-Leitlinienregister, Nr. 030/075,
Entwicklungsstufe 1, letzte Aktualisierung 10/2008: AWMF - Arbeitsgemeinschaft der
Wissenschaftlichen Medizinischen Fachgesellschaften.http://www.awmf-leitlinien.de/
14. http://www.soc-nephrologie.org/PDF/enephro/recommandations/HAS/1997/HTA_20_80.pdf
15.http://www.sld.cu/galerias/pdf/servicios/hta/guia_practica_para_tto._hta_esencial__en_adulto
s_francia.pdf.
16. Haute Autorité de Santé. Prise en charge des patients adultes atteints d'hypertension artérielle
essentielle.(http://www.has-sante.fr/portail/jcms/c_272459/prise-en-charge-des-patientsadultes-atteints-dhypertension-arterielle-essentielle-actualisation-2005)
17. La prise en charge précoce des accidents vasculaires cérébraux. Office parlementaire
d'évaluation des politiques de santé. N°236. Assemblée nationale
19. Tormo MJ, Navarro C, Chirlaque MD, Pérez-Flores D.Prevalence and control of arterial
hypertension in the south-east of Spain: a radical but still insufficient improvement Eur J
Epidemiol 1997;13:301-8.
20. Viigimaa M, Eha J, Hedman A, Kampus P jt. Estonian Guidelines of Cardiovascular Prevention
Estonian Physician 2006;85(3):183-216.
21. Viigimaa M (jt). Arteriaalne hupertensioon- praktilised aspektid (Arterial hypertension practical aspects). Tartu, 1995.
22. Personal communication, prof Margus Viigimaa, leading cardiologist in Estonia.
23. http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0404.2006.00773.x/pdf.
24. Wilhelmsen L, Berglund G, Sannerstedt R, Hansson L, Andersson O, Sievertsson R, Wikstrand
J.Effect of treatment of hypertension in the primary preventive trial, Göteborg, Sweden. Br
J Clin Pharmacology 1979;7:Suppl 2:261S-65S.
Welfare, 1979.
26. Berglund G. Experiences from hypertension trials--effects on stroke and coronary heart
disease.Drugs 1988;36:Suppl 3:5-8.
67
Table 19 (Chapter 3) Expected time period for a favourable shift in mortality trend for peptic ulcer
influenced by the introduction of treatment with cimetidine
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
1981-1988
1977-1984
1979-1986
1976-1983
1977-1984
1993-2002
1978-1985
1
United Kingdom: Registration in 1981 . For Cimetidine in the UK, in 1999 the number of prescription
23
items dispensed was 1738 thousand .
4
The Netherlands: Approved in 1977 . There is references to DRA guidelines in a paper from 1983
6
5
7
Germany: Registration in 1981 . A clinical trial was published in 1982
France: Registration in 1978. In France, maximum sales level (2002-2007) of Cimetidine was
8
reached in 2002 (501731 reimbursements). There is a small clinical trial starting in 1976 . Also clinical
9
trial from 1977 published in 1978
10
Spain:
Registration in 1977 . In Spain, maximum sales level (2000-2008; hospital data not
included) of Cimetidine was in 2000 (109936 Packages). Also registered for oesophageal reflux and
10
intestinal prophylaxis of bleeding births with general anaesthesia . There is a small clinical trial
11
published in 1980 .
12
Estonia: Country reports on registration in 1993 . For cimetidine in Estonia, maximum sales level
(1999-2008) was reached in 2000 (3,199 DDD/1000 inhabitants per year). Half of maximum level was
13
reached in 1999 (Registered also for reflux oesophagitis).
14
Sweden: Registration in 1978 . For Cimetidine in Sweden, maximum sales level (1978-2008) was
reached in 1986 (2,61 DDD/1000 inhabitants per year). Half of maximum levels were reached in
15
1982 . Registered also for gastroeophageal reflux, refluxesophagitis and Zollinger-Ellisons syndrome.
16
A clinical trial published in 1987 .
68
References:
1.BritishNationalFormulary.http://www.bnf.org/bnf/
2. http://www.ic.nhs.uk/statistics-and-data-collections/primary-care/prescriptions
3. http://www.nhsbsa.nhs.uk/PrescriptionServices.aspx
4. 25 Jaar maagzuursecretieremmende medicamenten Lamers Nederlands Tijdschrift voor
Geneeskunde 1999:11 December;143(50).
5. Haayer FM, van der Werf GT, Wieringa NF, Wesseling H.Use of cimetidine; parallels and
discrepancies between the views of drug regulatory agencies and practicing physicians. Eur
J Clin Pharmacol 1983;25:601-7.
7. Eckardt VF, Kanzler G, Willems D, Feyerabend H, Backwinkel KP, Hentschel E, Schütze K,
Schwamberger K.Treatment of duodenal ulcer with cimetidine: comparison of two dosage
regimens. (In German) Dtsch Med Wochenschr 1982;107:60-2.
8. Galmiche JP, Bernades P, Capron JP, Colin R, Dupas JL, Dupuy P, Gendre JP, Gompel H,
Laverdant C, Le Quintrec Y, Molinié C.Cimetidine versus combined therapy (antacid,
anticholinergic drugs and oxyferriscorbone sodique) in short-term treatment of gastric and
duodenal ulcer. A multicenter controlled trial. (In French). Gastroenterol Clin Biol.
1979:355-61.
9. Galmiche JP, Colin R, Hecketsweiler P, Le Grix A, Métayer P, Le Bihan M, Ténière P, Geffroy
Y.Treatment of bleeding due to peptic ulcer with cimetidine. A double blind trial. (In
French). Gastroenterol Clin Biol 1978;2:771-6.
11. Gilsanz V, Rebollar JL, Chantres MT, Rosso C, Pérez Oteyza C, Ballarin M. Cimetidine in the
treatment of gastric ulcer. Double blind study. (In Spanish). Rev Clin Esp 1980;158:57-60.
12. State Agency of Medicines, Estonia.
http://193.40.10.165/register/register.php?keel=eng&inim_vet=inim.
16. Kagevi I, Anker-Hansen O, Carling L, Glise H, Hallerbäck B, Solhaug JH, Svedberg LE, Wählby
L.Swedish multicenter study on prepyloric and gastric ulcer. Scand J Gastroenterol Suppl
1987;127:67-76.
69
Table 20 (Chapter 3) Expected time period for a favourable shift in mortality trend for nephritis
and nephrosis influenced by immunosuppressive treatment with Cyklosporin for kidney
transplantation of patients with acute nephritis and nephrosis
Immunosuppressive
treatment with
Cyklosporin for
kidney
transplantation of
patients with acute
nephritis and
nephrosis
United
Kingdom
The
Netherlands
Germany
France
Spain
Estonia
Sweden
19801987
1983-1990
19801987
19821989
19851992
19932002
19831992
Comments:
1
2
United Kingdom: Registration 1983 . A multicenter clinical trial reported on in 1983 a clinical trial
3
4
starting in 1982 and a clinical study starting in 1983 . Evaluation papers referring to introduction of
5
5
treatment in 1982 and 1983 . In 1999 the number of prescription items dispensed was 278 thousand
(114, 115) also for bone marrow transplant; psoriasis, atopic dermatitis, rheumatoid arthritis and
nephritic syndrome.
6
The Netherlands: Registration in 1983 . Registered also for marrow transplantation, uveitis, psoriasis,
7
nephrotic syndrome, rheumatoid arthritis, atopic dermatitis . Clinical trial with cyclosporine group
8
9
10
starting in 1983 .Small-scale clinical study published in 1985 . Clinical trials reported on in 1986 and
11
12 13
1988 . Reported in use in papers from 1987
. Kidney transplantation as an indication for
Cyklosporin was first described in the NTVG by Van Oers in 1994.
2
14
Germany: A multicenter clinical trial reported on in 1983 . Clinical study starting in 1982 .
15
16
Registration in 1991 . Evaluation studies in 1991 referring to an introduction in 1982 and an
17
international multicenter evaluation in 1993 based on patient data starting in 1982 .
18
19
20
France: Clinical studies starting in 1982 , 1984 and 1985 .In France, maximum sales level (20022007) of Cyklosporin was reached in 2002 (377166 reimbursements).
21
18
Spain: Clinical trials starting in 1985 , 1986 and follow-up studies for patients treated in 198622
7
1990 . Registration in 1986 . In Spain, maximum sales level (2000-2008;hospital data not included) of
Cyklosporin was reached in 2000 (704972 packages).
23
Estonia: Registration 1993 . For Cyclosporin in Estonia, maximum sales level (1999-2008) was
reached in 2008 (0,197 DDD/1000 inhabitants per year). Half of maximum level was reached in 2001
24
. No papers.
25 26
27
Sweden:
Smaller clinical studies from the late 1970s
. Multicenter clinical trial starting in 1983
28
29
and 1985 . Registration in 1985 . For Cyklosporin in Sweden, maximum sales level (1985-2008) was
reached in 1999 (0, 51 DDD/1000 inhabitants per year). Half of maximum level was reached in 1991
30
. Registered also for other transplantations.
70
References:
1. British National Formulary. http://www.bnf.org/bnf/http://emc.medicines.org.uk/ medicine/
10629/SPC/Cimetidine+200mg+5ml+Oral+Solution++(Rosemont+Pharmaceuticals+Ltd)/
2. European Multicenter Traíal Group. Cyclosporin in cadaveric renal transplantation: One-year
follow-up of a multicentre trial. The Lancet 1983;2:986-89.
3. Salaman JR, Gomes Da Costa CA, Griffin PJ. Renal transplantation without steroids. J Pediatr
1987;111:1026-8.
4. Venning MC, Lennard TW, Stevens ME, Proud G, Ward MK, Elliott RW, Taylor RM, Wilkinson
R.Cyclosporin A treatment with successful selective conversion after six months in 70 renal
allograft recipients. Transplant Proc 1989:1633-4.
5. Gilks WR, Bradley BA, Gore SM. Cyclosporine: its time of impact on kidney graft survival.
Transplant Proc 1990;22:2282.
6. www. cbg-med.nl.
7. National Data of Medicines, and National Vademecun. Spain.
8. Henny FC, van Es A, Oljans PJ, Baldwin WM, Tanke HJ, van Es LA, Paul LC.Prognostic value of T
lymphocyte subset ratios for renal transplant survival in patients on different
immunosuppressive regimens. Clin Exp Immunol 1986;65:373-80.
9. Henny FC, Kleinbloesem CH, Moolenaar AJ, Paul LC, Breimer DD, van Es LA. Pharmacokinetics and
nephrotoxicity of cyclosporine in renal transplant recipients. Transplantation 1985;40:
261-5.
10. Henny FC, Kootte AMM, van Bockel H, Baldwin WM, Hermans J, Bos B, van Es LA, Paul LC. A
prospective randomised comparative study on the influence of cyclosporin and azathioprine
on renal allograft survival and function. Nephrology, Dialysis, Transplantation 1986;1:44-49.
11. Kootte AM, Lensen LM, van Bockel JH, Paul LC.A randomized study comparing high- and lowdose regimens of cyclosporine in renal transplantation. Transplant Proc 1988;20:(Suppl
3):136-9.
12. Kootte AM, Henny FC, Moolenaar AJ, van Es LA, Paul LC.A prospective study on the influence of
cyclosporine and azathioprine on renal allograft survival and function. Transplant Proc
1987;19:1853-5.
13. Kootte AM, Lensen LM, van Bockel JH, van Es LA, Paul LC.High- and low-dose regimens of
cyclosporin in renal transplantation: immunosuppressive efficacy and side-effects. Nephrol
Dial Transplant 1988;3:666-70.
14. Opelz G.Collaborative transplant study data on efficacy of cyclosporine A in renal
transplantation. Transplant Proc. 1988 Oct;20. 1988:(Suppl 6):41-4.
16. Land W, Schneeberger H, Schleibner S, Illner WD, Abendroth D, Hillebrand G, Gokel JM, Albert
E, Fornara P.Long-term results in cadaveric renal transplantation under cyclosporine
therapy. Transplant Proc 1991;23:1244-6.
17. Opelz G.Superior long-term kidney graft survival in patients on maintenance immunosuppression
with cyclosporine and azathioprine. Transplant Proc 1993;25:1289-90.
18. Hourmant M, Buzelin F, Dubigeon P, Soulillou JPHigh long-term graft survival rates in kidney
transplantation with the sequential association of antithymocyte globulin and cyclosporine A
monotherapy. Transplant Proc 1987;19:2113-4.
19. Fries D, Hiesse C, Santelli G, Gardin JP, Cantarovich M, Lantz O, Charpentier B, Paillard M,
Benoit G.Triple therapy with low-dose cyclosporine, azathioprine, and steroids: long-term
results of a randomized study in cadaver donor renal transplantation. Transplant Proc. 1988
Jun;20 1988;20:(Suppl 3):130-5.
20. Broyer M, Gagnadoux MF, Guest G, Niaudet P.Triple therapy including cyclosporine A versus
conventional regimen--a randomized prospective study in pediatric kidney transplantation.
Transplant Proc 1987;19:3582-5.
21. Andreu J, Ricart MJ, Oppenheimer F, Vilardell J, Sans A. The efficacy of low doses of
cyclosporine A plus azathioprine. Transplant Proc 1988;20:(Suppl 6):28-9.
22. Andreu J, Campistol JM, Oppenheimer F, Torregrosa V, Ricart MJ, Vilardell J, Carretero
P.Cyclosporine monotherapy as primary immunosuppression in renal transplantation--fiveyear experience. Transplant Proc 1994;26:337-40.
25. Linder R, Restifo AC, Lindholm A, Groth CG.Long-term cyclosporine A treatment does not
progressively impair renal graft function: a 5-year follow-up study. Transplant Proc
1991;23:2210.
71
26. Backman U, Bohman SO, Johansson G, Lindgren PG, Wahlberg J.Morphological and functional
findings in renal transplant recipients on cyclosporine and azathioprine treatment.
27. Lundgren G, Groth CG, Albrechtsen D, Brynger H, Flatmark A, Frödin L, Gäbel H, Husberg B,
Klintmalm G, Maurer W, et al.HLA-matching and pretransplant blood transfusions in
cadaveric renal transplantation--a changing picture with cyclosporin. Lancet 1986;2:66-9.
28. Persson H, Andersson C, Lundgren C, Albrechtsen D, Gäbel H, Frödin L, Fehrman I, Flatmark A,
Brynger H.Improved renal graft function in triple-drug treatment with low-dose
cyclosporine. Transplant Proc 1987;19:3586-8.
72
Table 21 (Chapter 7) Availability of mortality data from Eurostat per country and sex, per year
Country
Austria
Austria
Belgium
Belgium
Bulgaria
Bulgaria
Croatia
Croatia
Cyprus
Cyprus
Czech republic
Czech republic
Denmark
Denmark
Estonia
Estonia
Finland
Finland
France
France
Germany
Germany
Greece
Greece
Hungary
Hungary
Iceland
Iceland
Italy
Italy
sex
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
2001
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2002
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2003
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2004
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
2005
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
2006
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2007
1
1
0
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2008
1
1
0
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
2009
1
1
0
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
Latvia
Latvia
Lithuania
Lithuania
Luxembourg
Luxembourg
Macedonia
Macedonia
Malta
Malta
Netherlands
Netherlands
Norway
Norway
Poland
Poland
Portugal
Portugal
Romania
Romania
Slovakia
Slovakia
Spain
Spain
Sweden
Sweden
Switzerland
Switzerland
UK
UK
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
males
females
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1=data are available, 0= data are not available
74
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
0
1
1
1
1
1
1
0
0
1
1
0
0
1
1
0
0
0
0
0
0
1
1
1
1
0
0
0
0
0
0
1
1
B. Questionnaire to obtain information on the timing of the
introduction of innovations
75
Second questionnaire AMIEHS WP2, 2009-07-24
This questionnaire aims at exploring the data on the timing of introduction of medical innovations
related to the set of selected avoidable death indicators. Each partner in the AMIEHS project
describing the situation in each partner country, respectively, should answer the questionnaire.
(Answers are requested for the country as a whole. Please, indicate if any answer is valid only for a
specific region in your country). The answered questionnaire should be mailed to WP2 coordinator
[email protected] before12 september 2009. (Please, indicate if you still are waiting
for an answer from an expert on any of the questions at that time and when the answer will be
expected to arrive.)
Country: _____________________________________________________________
HIV
Question 1
a) Are there any data on the year of registration of the anti-retroviral drugs Azidothymidine and
Zidovudine respectively as a licensed drug in your country?
0 Yes (define the year of registration, indication and the source of information below)
0 No (go to next question)
Year for registration of Azidothymidine:
--------------------------------------------Year for registration of HIV as an indication for Azidothymidine:
--------------------------------------------Is HIV the only indication for Azidothymidine?
0 Yes 0 No, also for -----------------------------------------------------------------------------------------------------Source of information for Azidothymidine
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Year for registration of Zidovudine:
--------------------------------------------Year for registration of HIV as an indication for Zidovudine:
--------------------------------------------Is HIV the only indication for Zidovudine?
0 Yes 0 No, also for -----------------------------------------------------------------------------------------------------Source of information foe Zidovudine
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Question 2
a) Are there any available statistics on the yearly trends in sales (or purchases or prescriptions) of the
anti-retroviral drugs Azidothymidine and Zidovudine respectively in your country?
0 Yes (define the source of database)
Source of database: ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------b) If available, please enclose data on the yearly sales (second choice: purchases or prescriptions) if
possible expressed by DDD per population number (second choice: other measure) since the year of
76
registration (or if applicable, introduction year if this was before registration). If possible, also include
data on indication
Peptic ulcer
Question 3
a) Are there any data on the year of registration of Cimetidine as a licensed drug in your country?
Year for registration of Cimetidine:
--------------------------------------------Year for registration of peptic ulcer as an indication for Cimetidine:
--------------------------------------------Is Peptic ulcer the only indication for Cimetidine?
0 Yes
0 No, also for ----------------------------------------------------------------------------------------------------Source of information
Question 4
a) Are there any available statistics on the yearly trends in sales (or purchases or prescriptions) of
Cimetidine in your country?
Source of database: --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------b) If available, please enclose data on the yearly sales (second choice: purchases or prescriptions) if
data on indications.
Hypertension
Question 5
antihypertensive drugs (total group) in your country?
77
Question 6
a) Are there any committee reports or scientific papers or any other sources describing an increase in
the number of patients (per population number) treated for hypertension in any time period after the
1960s in your country? If available, what is the reference document?
0 Yes,
b) the time period of increasing number of patients treated for hypertension is
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------and the reference document for this information is:
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Stroke
Question 7
a) Are there any documents (e.g.national decisions, guidelines or programs) stating that treatment of
hypertension would be a standard for prevention of stroke in your country?
0 Yes
b) Please define the year when this method first was defined as a standard (e.g. by a national
decision, guidelines or program) and the reference document for this.
Year
--------------------------------Reference document
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 8
a) Are there any documents (e.g. committee reports or scientific papers) or any other sources showing
that treatment of hypertension has been generally implemented as a method for prevention of stroke in
your country?
0 Yes
b) Please define the year or time period for that general implementation and the reference document
for this.
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
78
Question 9
a) Are there any documents (e.g.national decisions, guidelines or programs) stating that intensive
management (CT scan;thrombolytic therapy; surgical treatment of aneurysms in subarachnoid
hemorrhage) of acute stroke would be the standard in your country?
0 Yes
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 10
a) Are there any documents (e.g. committee reports or scientific papers), health administrative data or
any other sources showing that intensive management (CT scan;thrombolytic therapy; surgical
treatment of aneurysms in subarachnoid hemorrhage) of acute stroke has been generally
implemented in your country ?
0 Yes
for this.
Year
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
IHD
Question 11
a) Are there any data on the year of registration of secondary prevention after myocardial infarction as
an indicator for any betablocker (such as Pindolol, Propranolol and Acebutolol) as a licensed drug in
your country?
0 Yes (define the year of registration, the beta-blocker, and the source of information below)
Name of beta-blocker registered for secondary prevention of myocardial infarction:
---------------------------------------------
Year for registration of secondary prevention for myocardial infarction as an indication:
---------------------------------------------
79
Source of information
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 12
a) Are there any documents (e.g.national decisions, guidelines or programs) stating that medication
with beta blockers or other drugs (specify which) would be a standard for secondary prevention of
myocardial infarction in your country?
0 Yes
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 13
a) Are there any documents (e.g. committee reports or scientific papers) or any other sources showing
that medication with beta-blocker or other drugs (specify which) has been generally implemented for
secondary prevention of myocardial infarction in your country ?
0 Yes
for this.
Year
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
80
Question 14
a) Are there any documents (e.g. national decisions, guidelines or programs) stating that coronary
care units would be a standard for acute management of myocardial infarction in your country?
0 Yes
Year
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Question 15
any other sources showing that coronary care units has been generally implemented for acute
management of myocardial infarction in your country ?
0 Yes
for this.
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Heart failure
Question 16
a) Are there any data on the year of registration of the ACE-inhibitors Captopril or Enalapril as a
licensed drug in your country?
Year for registration of Captopril
-------------------------------------------Year for registration of heart failure an indication for Captopril:
--------------------------------------------Is heart failure the only indication for Captopril ?
0 Yes
0 No, also for ------------------------------------------------------------------------------------------
81
Source of information
Year for registration of Enalapril
--------------------------------------------Year for registration of heart failure an indication for Enalapril:
--------------------------------------------Is heart failure the only indication for Enalapril?
0 Yes
0 No, also for -----------------------------------------------------------------------------------------Source of information
Question 17
ACE-inhibitors (total group) in your country?
Colorectal cancer
Question 26
a) Are there any data on the year of registration of Oxaliplatin as a licensed drug in your country?
Year for registration of Oxaliplatin:
--------------------------------------------Year for registration of colorectal cancer as an indication for Oxaliplatin:
--------------------------------------------Is colorectal cancer the only indication for Oxaliplatin?
0 Yes
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
82
Question 27
Oxaliplatin in your country?
Question 28
a) Are there any documents (e.g. national decisions, guidelines or programs) stating that examination
with colonoscopy/sigmoidoscopy would be a standard when diagnosing colorectal cancer in your
country?
0 Yes
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 29
any other sources showing that examination with colonoscopy/sigmoidoscopy has been generally
implemented when diagnosing colorectal cancer in your country?
0 Yes
for this.
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
83
Cervical cancer
Question 34
a) Are there any documents (e.g.national decisions, guidelines or programs) stating that cervical
screening would be a standard for prevention of cervical cancer in your country?
0 Yes
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 35
any other sources showing that cervical screening has been generally implemented for prevention of
cervix cancer in your country?
0 Yes
for this.
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Testicular cancer
Question 40
a) Are there any data on the year of registration of Cisplatin as a licensed drug in your country?
Year for registration of Cisplatin:
--------------------------------------------Year for registration of testicular cancer as an indication for Cisplatin:
--------------------------------------------Is testicular cancer the only indication for Cisplatin?
0 Yes
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
84
Question 41
Cisplatin in your country?
Hodgkin’s disease
Question 42
a) Are there any documents (e.g. national decisions, guidelines or programs) stating that high dose
therapy or peripheral blood stem cell transplantation would be a standard for treatment of Hodgkin’s
disease in your country?
0 Yes
.
Year
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Question 43
any other sources showing that high dose therapy or peripheral blood stem cell transplantation has
been generally implemented for treatment of Hodgkin’s disease in your country?
0 Yes
Year
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
85
Acute nephritis and nephrosis
Question 45
a) Are there any data on the year of registration of Cyklosporin as a licensed drug in your country?
Year for registration of Cyklosporin:
--------------------------------------------Year for registration of kidney transplantation as an indication for Cyklosporin:
--------------------------------------------Is kidney transplantation the only indication for Cyklosporin?
0 Yes
Question 46
cyklosporin in your country?
86
Appendix C: Standardized cause-specific all-age mortality trends for the
age range 0-74 yrs, by gender and by country with the lines for the
mortality trend, and (below) lines for the periods of expected mortality
decline (on top of each graph there is the cause of death, gender (M or
F) and the innovation)
87
Figure 1: Standardized mortality trend (ages 0-74) from HIV/AIDS for men and expected period
of mortality decline based on timing of introduction of anti-retroviral drugs
Figure 2: Standardized mortality trend (ages 0-74) from HIV/AIDS for women and expected
period of mortality decline based on timing of introduction of anti-retroviral drugs
88
Figure 3: Standardized mortality trend (ages 0-74) from malignant colorectal neoplasm for men
and expected period of mortality decline based on timing of introduction of colonscopy
Figure 4: Standardized mortality trend (ages 0-74) from malignant colorectal neoplasm for
women and expected period of mortality decline based on timing of introduction of colonscopy
89
Figure 5: Standardized mortality trend (ages 0-74) from malignant colorectal neoplasm for men
and expected period of mortality decline based on timing of introduction of oxaliplatin
Figure 6: Standardized mortality trend (ages 0-74) from malignant colorectal neoplasm for
women and expected period of mortality decline based on timing of introduction of oxaliplatin
90
Figure 7: Standardized mortality trend (ages 0-74) from malignant neoplasm of cervix uteri and
expected period of mortality decline based on timing of introduction of cervical screening
Figure 8: Standardized mortality trend (ages 0-74) from malignant neoplasm of testes and
expected period of mortality decline based on timing of introduction of Cisplatin
91
Figure 9: Standardized mortality trend (ages 0-74) from Hodgkin’s disease (men) and expected
period of mortality decline based on timing of introduction of high dose therapy/stem cell
transplantation
Figure 10: Standardized mortality trend (ages 0-74) from Hodgkin’s disease for women and
expected period of mortality decline based on timing of introduction of high dose therapy/stem
cell transplantation
92
Figure 11: Standardized mortality trend (ages 0-74) from malignant neoplasm of breast (women)
and expected period of mortality decline based on timing of introduction of mammography
Figure 12: Standardized mortality trend (ages 0-74) from malignant neoplasm of breast for
women and expected period of mortality decline based on timing of introduction of Tamoxifen
93
Figure 13: Standardized mortality trend (ages 0-74) from leukaemia for men and expected
period of mortality decline based on timing of introduction of improved treatment
Figure 14: Standardized mortality trend (ages 0-74) from leukaemia for women and expected
period of mortality decline based on timing of introduction of improved treatment
94
Figure 15: Standardized mortality trend (ages 0-74) from rheumatic heart disease for men and
expected period of mortality decline based on timing of introduction of artificial valve
replacement
Figure 16: Standardized mortality trend (ages 0-74) from rheumatic heart disease for women
and expected period of mortality decline based on timing of introduction of artificial valve
replacement
95
Figure 17: Standardized mortality trend (ages 0-74) from hypertension for men and expected
period of mortality decline based on timing of an increased number of patients
Figure 18: Standardized mortality trend (ages 0-74) from hypertension for women and expected
period of mortality decline based on timing of an increased number of patients
96
Figure 19: Standardized mortality trend (ages 0-74) from ischaemic heart disease for men and
expected period of mortality decline based on timing of introduction of betablockers
Figure 20: Standardized mortality trend (ages 0-74) from ischaemic heart disease for women
and expected period of mortality decline based on timing of introduction of betablockers
97
Figure 21: Standardized mortality trend (ages 0-74) from ischaemic heart disease for men and
expected period of mortality decline based on timing of introduction of coronary care units
Figure 22: Standardized mortality trend (ages 0-74) from ischaemic heart disease for women
and expected period of mortality decline based on timing of introduction of coronary care units
98
Figure 23: Standardized mortality trend (ages 0-74) from heart failure for men and expected
period of mortality decline based on timing of introduction of ACE inhibitors
Figure 24: Standardized mortality trend (ages 0-74) from heart failure for women and expected
period of mortality decline based on timing of introduction of ACE inhibitors
99
Figure 25: Standardized mortality trend (ages 0-74) from cerebrovascular disease for men and
expected period of mortality decline based on timing of introduction of prevention by
treatment of hypertension
Figure 26: Standardized mortality trend (ages 0-74) from cerebrovascular disease for women
and expected period of mortality decline based on timing of introduction of prevention by
treatment of hypertension
100
Figure 27: Standardized mortality trend (ages 0-74) from cerebrovascular disease for men and
expected period of mortality decline based on timing of introduction of intensive management
Figure 28: Standardized mortality trend (ages 0-74) from cerebrovascular disease for women
and expected period of mortality decline based on timing of introduction of intensive
management
101
Figure 29: Standardized mortality trend (ages 0-74) from peptic ulcer for men and expected
period of mortality decline based on timing of introduction of Cimetidine
Figure 30: Standardized mortality trend (ages 0-74) from peptic ulcer for women and expected
period of mortality decline based on timing of introduction of Cimetidine
102
Figure 31: Standardized mortality trend (ages 0-74) from renal failure for men and expected
period of mortality decline based on timing of introduction of Cyklosporin
Figure 32: Standardized mortality trend (ages 0-74) from renal failure for women and expected
period of mortality decline based on timing of introduction of Cyklosporin
103
Appendix D: Standardized mortality trends (all ages), Percent
Annual Chance (PAC) for each period (with confidence intervals),
by gender (M/F) and by country (alphabetical order)
104
HIV (M) Estonia
PAC: 90.1% (44.3%;150.43%)
2
●
●
1
standardised rates per 1e+05
3
●
PAC: 31.06% (−15.32%;102.83%)
−47.72% (−89.1%;150.75%)
PAC: 51.91% (−72.97%;753.9%)PAC:
●
●
●
●
●
●
●
1996
1998
2000
2002
xyear
105
2004
14
HIV (M) France
●
●
12
●
PAC: 11.99% (11.18%;12.81%)
●
●
8
●
6
●
PAC: −38.89% (−39.59%;−38.18%)
4
●
●
●
●
●
2
PAC: 64.66% (62.22%;67.13%)
●
PAC: −5% (−6.74%;−3.22%)
●
●
●
●
●
●
●
●
1985
1990
1995
2000
2005
xyear
3.0
HIV (F) France
●
●
2.5
●
●
2.0
●
PAC: 20.3% (18.33%;22.3%)
1.5
●
●
1.0
●
PAC: −35.37% (−36.72%;−34%)
●
●
0.5
●
●
●
●
PAC: 1.05% (−2.66%;4.91%
●
PAC: 59.2% (53.77%;64.82%)
●
●
0.0
●
0
10
●
●
●
●
●
●
●
1985
1990
1995
xyear
106
2000
2005
HIV (M) Germanyeast
0.5
●
0.3
●
●
●
●
●
PAC: 31.88% (10.78%;56.99%)
●
PAC: 46.19% (29.95%;64.46%)
PAC: −15.4% (−28.26%;−0.23%)
0.2
●
●
●
●
●
●
0.1
●
1992
1994
1996
1998
2000
2002
2004
xyear
HIV (F) Germanyeast
●
●
●
0.08
●
●
●
●
PAC: −100% (−100%;Inf%)
0.04
0.06
PAC: −100% (−100%;Inf%)
●
●
●
●
0.02
0.4
●
PAC: −100% (−1
0% (−100%;Inf%)
●
●
1992
1994
1996
1998
xyear
107
2000
2002
2004
HIV (M) Germanywest
●
5
●
●
●
●
●
3
PAC: −36.84% (−38.02%;−35.65%)
2
●
●
●
●
●
PAC: −3.69% (−4.93%;−2.44%)
●
●
●
1
●
●
●
●
●
PAC: 149.21% (135.36%;163.88%)
●
1985
1990
1995
2000
2005
xyear
0.8
HIV (F) Germanywest
●
●
●
0.6
●
−29.93% (−33.17%;−26.53%)
PAC: 16.72%PAC:
(13.05%;20.5%)
●
●
0.4
●
●
●
PAC: 0.61% (−2.02%;3.32%)
●
●
●
●
●
●
●
0.2
●
●
PAC: 57.76% (48.84%;67.22%)
●
●
0.0
●
●
0
4
●
PAC: 15.45% (14.49%;16.42%)
●
●
1985
1990
1995
xyear
108
2000
2005
HIV (M) Netherlands
5
●
●
●
●
4
PAC: 11.32% (8.83%;13.86%)
●
PAC: −34.58% (−37.17%;−31.89%)
3
●
2
●
●
●
●
●
●
●
●
PAC: −10.17% (−12.13%;−8.17%)
1
PAC: 50.03% (44.12%;56.17%)
●
●
●
●
●
●
●
●
●
●
0
1985
1990
1995
2000
2005
xyear
0.8
HIV (F) Netherlands
●
0.6
●
●
●
0.4
PAC: −53.27% (−63.67%;−39.9%)
PAC: 27.47% (20.61%;34.72%)
●
●
●
●
●
●
PAC: −8.27% (−11.67%;−4.75%)
●
●
0.2
●
●
AC: 17.92% ●(3.23%;34.7%)
●
●
●
●
●
●
●
●
●
●
●
1985
1990
1995
xyear
109
2000
2005
HIV (M) Spain
PAC:● −47.06% (−48.07%;−46.03%)
20
●
●
15
PAC: 19.85% (19.04%;20.65%)
●
●
10
●
●
●
●
PAC: −6.25% (−6.77%;−5.73%)
●
●
●
●
5
●
●
●
●
●
●
PAC: 97.19% (92.41%;102.09%)
●
●
1985
1990
1995
2000
2005
xyear
HIV (F) Spain
PAC: −52.22% (−54.19%;−50.17%)
●
5
●
4
●
●
3
PAC: 25.1% (23.4%;26.82%)
●
●
2
●
●
●
●
PAC: −4.24% (−5.32%;−3.14%)
●
●
●
●
●
1
●
●
●
●
●
●
PAC: 88.86% (79.1%;99.15%)
0
●
0
●
●
●
●
●
1985
1990
1995
xyear
110
2000
2005
●
●
3.0
HIV (M) Sweden
●
2.5
●
PAC: −63.48% (−68.56%;−57.59%)
●
2.0
●
●
●
1.0
1.5
PAC: 19.49% (16.19%;22.88%)
●
●
●
PAC: 9.51% (−0.39%;20.39%)
●
●
●
PAC:●−3.43% (−7.84%;1.2%)
●
●
●
●
●
1985
1990
1995
●
2000
HIV (F) Sweden
●
0.6
PAC: −66.84% (−75.86%;−54.47%)
●
0.4
0.5
●
●
●
0.3
●
PAC: 23.28% (16.63%;30.32%)
27.31% (−38.45%;−14.15%)
●
0.2
●
●
●
●
●
●
●
PAC: 1.1% (−7.79%;10.86%)
●
●
0.1
●
●
●
●
●
●
●
●
1985
1990
1995
xyear
111
2000
●
●
●
2005
xyear
0.5
●
2005
●
HIV (M) UK
●
2.0
●
●
●
PAC: 6.33% (5.09%;7.59%)
●
PAC: −52.01% (−54.66%;−49.21%)
●
●
●
1.0
●
●
●
PAC: 2.2% (0.27%;4.17%)
●
●
0.5
●
PAC: 76.78% (67.38%;86.71%)
●
●
●
●
●
●
●
●
1985
1990
1995
2000
2005
xyear
HIV (F) UK
●
0.25
●
PAC: −23.75%
(−38.02%
●
●
●
●
●
●
0.20
●
PAC: −43.43% (−53.06%;−31.82%)
●
●
PAC: −2.21% (−17.9%;16.49%)
0.15
●
●
●
●
●
●
PAC: −7.77% (−21.46%;8.31%)
0.10
1.5
●
●
●
●
●
● ●
1935,1945,1955,1965,1975
●
1985
1990
1995
xyear
112
2000
2005
●
Malignant colorectal neoplasm (M) Estonia
(
●
30
●
●
●
●
●
●
●
●
●
●
PAC: −3.09% (−10.6%;
●
●
●
25
●
●
●
●
●
●
●
●
PAC: 2.41% (1.87%;2.95%)
●
●
●
20
PAC: −0.06%
● (−1.14%;1.04%)
●
●
●
●
●
●
●
● ●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Malignant colorectal neoplasm (F) Estonia
●
●
20
●
●
●
PAC: 0.48% (−0.84%;1.83%)
PAC: −8.79% (−16.37%;−0.53%)
●
18
●
●
●
●
●
●
●
●
●
●
●
PAC: 2.08% (1.52%;2.64%)
16
●
●
●
●
●
●
●
●
●
●
−1.56% (−4.61%;1.58%)
●
●
●
14
●
●
●
1970
●
●
●
1975
1980
1985
1990
xyear
113
1995
2000
2005
Malignant colorectal neoplasm (M) France
●
●
● ●
●
30
●
●
●
PAC: −0.42%
(−0.52%;−0.33%)
●
●
●
AC: 1.87% (1.56%;2.17%)
●
●
●
●
●
●
●
●
●
28
●
PAC: −1.34%●(−1.56%;−1.12%)
●
●
●
● ●
●
●
26
●
PAC: −1.74%
(−2.07%;−1.4
●
●
●
24
●
●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
Malignant colorectal neoplasm (F) France
20
●
●
C: 1.38% (0.94%;1.81%)
● ●
●
PAC: −1.16%
● ● (−1.33%;−0.99%)
● ●
● ●
●
●
18
●
●
PAC: −0.72%
(−0.93%;−0.51%)
●
● ●
●
17
●
●
● ●
16
●
●
●
●
15
PAC: −1.57%
●
● (−1.71%;−1.44%)
●
●
14
19
●
● ●
●
1970
1975
1980
1985
1990
xyear
114
1995
2000
●
2005
36
Malignant colorectal neoplasm (M) Germanyeast
●
●
●
PAC: −4.07% (−7.2%;−0.83%)
●
PAC: 0.76% (0.28%;1.25%)
●
●
34
●
●
●
●
PAC: −0.19% (−0.89%;0.51%)
● ●
●
●
●
●
32
●
●
●
PAC: −1.72% (−2.11%;−1.34%)
●
●
●
30
●
●
28
●
●
1980
1985
1990
1995
2000
2005
xyear
Malignant colorectal neoplasm (F) Germanyeast
●
PAC: −0.51% (−0.74%;−0.28%)
●
● ●
AC: 4.36% (1.41%;7.39%)
●
●
●
●
●
●
●
●
●
●
22
●
●
●
●
20
PAC: −3.33% (−3.6%;−3.05%)
●
●
18
24
●
●
.77% (−5.15%;3.8%)
●
●
●
●
1980
1985
1990
1995
xyear
115
2000
2005
38
Malignant colorectal neoplasm (M) Germanywest
PAC: −5.75% (−6.82%;−4.67%)
●
●
●
36
●
PAC: 1.36% (1.08%;1.65%)
●
●
●
●
●PAC: −0.33%
●
● ●
●
34
●
●
(−0.42%;−0.24%)
●
●
● ●
●
●
●
●
32
●
●
●
● ●
●
PAC: −1.9% (−2.03%;−1.78%)
●
30
●
●
●
28
●
●
26
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Malignant colorectal neoplasm (F) Germanywest
28
PAC: −6.44% (−7.55%;−5.31%)
●
●
PAC: 0.94% (0.69%;1.19%)
●
●
26
● ●
●
●
●
●
●
●
PAC: −0.54%●(−0.63%;−0.45%)
●
●
● ●
●
●
24
●
●
●
●
●
●
●
22
●
PAC: −2.29% (−2.39%;−2.19%)
● ●
●
20
●
●
●
●
18
●
●
1970
1975
1980
1985
1990
xyear
116
1995
2000
2005
Malignant colorectal neoplasm (M) Netherlands
●
30
●
●
● ●
●
●
● (−0.46%;0.47%)
PAC: 0.01%
●
●
(0.78%;2.8%)
●
●
28
AC: 1.79%
●
●
●
●
●
●
●
●
●
●
●
●
●
27
PAC:●−0.61% (−0.75%;−0.47%)
● ●
●
●
26
29
PAC: −0.86% (−1.73%;0.03%)
●
●
●
●
●
●
25
●
●
1970
1980
1990
2000
xyear
Malignant colorectal neoplasm (F) Netherlands
●
●
24
●
●
●
●
PAC:●−0.91% (−1.07%;−0.74%)
●
●
●
●
●
22
●
●
●
●
●
●
20
● ●
●
●
●
PAC: −1.28% (−1.43%;−1.12%)
●
●
●
●
●
●
PAC: −0.93% (−3.73%
18
●
●
●
●
●
●
PAC: 4.21%
(−0.02%;8.62
●
●
●
1970
1980
1990
xyear
117
2000
Malignant colorectal neoplasm (M) Spain
PAC: −0.16% (−0.53%;0.2
●
●
●
●
PAC: 1.49% (1.24%;1.74%)
●
●
● ●
●
●
● ●
●
● ●
●
PAC: 4.19% (3.99%;4.39%)
20
●
●
●
●
●
●
15
25
● ● ●
●
● ●
PAC: 1.99% (1.72%;2.27%)
● ● ● ●
●
● ● ●
●
●
1970
1980
1990
2000
xyear
Malignant colorectal neoplasm (F) Spain
● ●
●
●
●
●
●
15
PAC: 1.5% (1.27%;1.72%)
●
●
14
●
●
●
13
●
12
PAC: 5.84% (5.13%;6.54%)
●
●
11
●
●
●
PAC: 0.51% (0.24%;0.78%)
●
●
●
●
●
●
●
●
●
1970
1980
1990
xyear
118
●
●
● ●
●
●
●
●
●
●
10
●
PAC: −0.91% (−1.11%;−0.7%)
2000
32
Malignant colorectal neoplasm (M) Sweden
● ●
●
PAC: −1.41% (−2.46%;−0.34%)
3.04% (1.08%;5.03%)
30
●
●
●
●
●
28
PAC: −3.94% (−5.09%;−2.78%)
●
26
●
●
●
● ●
●
● ●
●
●
● ●
PAC: −0.66%
● (−0.81%;−0.51%)
24
●
●
● ●
●
●
●
●
22
●
●
●
● ●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Malignant colorectal neoplasm (F) Sweden
● ●
C: 2.84% (1%;4.72%)
●
●
22
●
●
●
●
●
20
●
●
●
●
18
●
●
●
●
●
●
PAC:
−1.19% (−1.44%;−0.93%)
●
●
●
●
●
●
●
●
16
●
PAC: −2.07% (−2.44%;−1.7%)
●
PAC: −0.16%
(−0.71%;0.4%
● ●
1970
1975
1980
1985
1990
xyear
119
1995
●
●
●
2000
●
●
●
2005
34
Malignant colorectal neoplasm (M) UK
●
●
●
PAC: −0.56%
● ● (−0.71%;−0.42%)
●
●
●
32
●
●
PAC: 0.12% (−0.06%;0.3%)
●
●
●
● ●
● ●
● ●
●
●
30
●
PAC: −2.65% (−2.83%;−2.47%)
28
●
●
●
●
●
26
●
●
●
●
24
●
PAC: −1.52%
● (−1.82%;−1.2
●
●
●
22
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
26
Malignant colorectal neoplasm (F) UK
−0.44%
●
(−0.82%;−0.06%)
●
●
● ●
● ●
●
PAC:●−1.2%
(−1.29%;−1.12%)
● ●
●
22
●
●
● ● ●
●
● ●
20
●
● ●
PAC: −3.11% (−3.26%;−2.96%)
18
●
●
●
16
●
●
PAC: ●
−1.17%
(−1.58%;−0.
● ●
● ●
14
24
● ●
1970
1975
1980
1985
1990
xyear
120
1995
2000
●
●
2005
121
122
123
124
Malignant neoplasm of cervix uteri (F) Estonia
14
●
●
12
●
●
●
PAC: ●−3.24% (−4.48%;−1.98%)
●
●
10
●
●
●
●
●
●
●
PAC: 4.19% (−1.45%;10.16%)
PAC: −0.86% (−2.9%;1.22%)
●
●
●
●
●
●
●
●
●
8
●
PAC: −4.01% (−5.56%;−2.45%)
●
●
●
●
●
●
●
●
●
6
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
3.5
Malignant neoplasm of cervix uteri (F) France
●
●
●
● (−1.63%;−0.64%)
PAC: −1.14%
●
●
●
●
●
3.0
●
●
PAC: −2.13%
(−2.74%;−1.51%)
●
●
●
● ●
●
2.5
●
●
PAC: −2.73%
(−3.38%;−2.07%)
●
●
●
●
●
●
●
●
●
PAC: −1.39% (−2.06%;−0.72%)
●
2.0
●
●
●
1970
1975
1980
1985
1990
xyear
125
1995
2000
● ●
●
●
2005
Malignant neoplasm of cervix uteri (F) Germanyeast
●
C: −1.65%
(−3.08%;−0.2%)
●
9
●
●
●
●
8
●
PAC: −3.07% (−3.71%;−2.43%)
●
●
●
●
7
●
●
6
●
●
●
PAC: −5.4% (−6.25%;−4.53%)
●
●
5
●
●
●
●
PAC:
−3.34%
(−5.35%;−1.3
●
4
●
1980
1985
1990
1995
●
2000
●
2005
xyear
Malignant neoplasm of cervix uteri (F) Germanywest
: 0.08% ( 1%;1.17%)
●
● ●
●
●
7
●
● ●
6
●
●
●
●
●
●
●
5
PAC: −2.7% (−3.06%;−2.34%)
●
●
● ●
●
4
●
●
● ●
●
PAC: −3.15%
(−3.39%;−2.92%)
●
●
●
●
3
PAC: −4.06% (−4.43%;−3.69%)
●
●
●
●
●
●
1970
1975
1980
1985
1990
xyear
126
1995
2000
●
2005
7
Malignant neoplasm of cervix uteri (F) Netherlands
●
●
●
●
●
●
PAC: −4.39% (−4.91%;−3.88%)
5
● ●
● ●
●
4
PAC: 1.32% (−1.61%;4.35%)
●
●
●
●
PAC:●−5.79% (−7.4%;−4.15%)
●
●
● ●
●
3
6
●
●
●
●
(−3.25%;−1.78%)
● ●
● PAC: −2.52%
●
● ●
●
2
●
●
1970
1980
1990
●
●
●
●
2000
xyear
Malignant neoplasm of cervix uteri (F) Spain
2.5
●
PAC: ●
0.24% (−0.42%;0.91%)
●
●
● ●
●
●
●
PAC: −2.65% (−3.84%;−1.45%)
PAC: 2.65% (0%;5.3
●
●
●
●
2.0
●
● ●
●
●
PAC: 4.7% (4.25%;5.14%)
1.5
● ●
●
●
●
●
1970
● ●
●
●
●
1.0
●
●
●
● ●
●
1980
1990
xyear
127
2000
●
●
●
Malignant neoplasm of cervix uteri (F) Sweden
7
●
●
●
6
●
●
●
●
●
5
PAC: ●
−3.68% (−4.01%;−3.36%)
● ● ●
●
●
●
4
●
●
●
●
●
●
●
●
3
●
PAC:
8.28% (−2.74%;20.54%)
●
PAC: −2.47%
(−7.22%;2.51%)
●
●
●
PAC:● −4.96%
(−7.66%;−2.1
●
●
●
●
●
●
●
2
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Malignant neoplasm of cervix uteri (F) UK
●
8
●
●
● −1.64% (−1.87%;−1.4%)
PAC:
●
●
● ●
●
●
●
PAC: −0.34% (−1.13%;0.46%)
●
●
●
●
●
●
●
6
●
●
●
●
5
PAC: −5.57% (−5.96%;−5.18%)
●
●
●
4
●
●
●
●
●
PAC: −4.37%
(−4.96%;−3.79%
●
3
7
●
●
● ●
●
●
1970
1975
1980
1985
1990
xyear
128
1995
2000
2005
Malignant neoplasm of testes (M) France
1.0
●
●
● (−2.43%;1.58%)
C: −0.45%
●
●
●
●
●
PAC: −3.2%
(−4.31%;−2.07%)
0.8
●
●
●
●
●
●
●
0.6
PAC: −14.1% (−19.22%;−8.66%)
●
●
● ● ●
PAC: −3.28%
(−4.07%;−2.49%)
●
0.4
●
●
●
●
● ●
●
●
●
●
●
●
●
●
●
1970
1975
1980
1985
1990
xyear
129
1995
2000
2005
Malignant neoplasm of testes (M) Germanyeast
2.0
●
PAC: 0.72%●(−1.89%;3.39%)
●
●
●
●
●
●
●
1.5
PAC: −6.64% (−8.34%;−4.9%)
●
●
●
●
1.0
●
●
●
PAC: −13.47% (−17.57%;−9.16%)
●
●
●
PAC: 1.56% (−2.25%;5.51%)
●
●
●
1980
1985
1990
●
1995
●
●
●
2000
2005
xyear
1.6
Malignant neoplasm of testes (M) Germanywest
●
1.4
●
●
PAC: −1.17% (−2.87%;0.57%)
●
2.73% (−1.37%;7%)
●
●
●
●
1.2
●
●
●
●
1.0
●
●
PAC: −6.58% (−7.08%;−6.07%)
0.8
●
● ●
0.6
● ● ●
●
●
●
PAC:
(−3.68%;−2.08%)
● ● −2.88%
●
●
● ●
●
0.4
●
●
●
1970
1975
1980
1985
1990
xyear
130
1995
2000
●
● ●
2005
1.4
Malignant neoplasm of testes (M) Netherlands
● ●
●
●
PAC: −6.97% ●(−8.44%;−5.48%)
● ● ●
0.8
1.0
●
●
●
0.6
1.2
●
●
PAC: −3.95% (−6%;−1.87%)
●
● ●
●
● ●
PAC: −22.14% (−40.05%;1.11%)
●
0.4
●
●
●
●
●
●
PAC:●0.27% (−2.24%;2.85%)
●
●
0.2
●
●
●
●
●
●
●
●
●
1970
1980
1990
2000
xyear
Malignant neoplasm of testes (M) Spain
0.40
●
●
0.35
●
●
●
●
PAC: −2.03% (−3.23%;−0.81%)
109.83% (42.66%;208.62%)
0.30
●
●
●
●
●
●
0.25
●
●
●
●
●
●
●
.13% (−35.71%;4.25%)
●
●
●
PAC: −2.8% (−3.72%;−1.87%)
0.20
●
●
●
●
●
● ●
●
●
0.15
●
●
1980
1990
xyear
131
●
● ●
●
1970
●
2000
Malignant neoplasm of testes (M) Sweden
●
0.8
● ●
PAC: −3%
● (−5.43%;−0.52%)
●
●
● ●
●
0.6
●
●
●
●
●
PAC: −8.58% (−11.03%;−6.05%)
0.4
●
●
●
●
●
●
●
●
0.2
●
●
●
PAC: 6.56% (−4.82%;19
●
PAC:
−1.28%
(−6.32%;4.04%)
●
●
●
●
●
●
●
●
1970
1975
1980
1985
1990
1995
●
●
●
2000
2005
xyear
1.2
Malignant neoplasm of testes (M) UK
●
● (−1.88%;1.68%)
C: −0.11%
●
●
●
●
●
PAC: −9.77% (−11.51%;−8.01%)
●
0.8
●
●
●
0.6
●
●
●
●
●
0.4
●
●
●
PAC: −4.88%
(−5.49%;−4.26%)
●
●
●
●
●
●
●
●
PAC: −0.87% (−5.05%;3
●
● ●
● ●
0.2
1.0
● ●
1970
1975
1980
1985
1990
xyear
132
1995
2000
● ●
●
2005
2.0
Hodgkin...s disease (M) France
●
0.19% (−2.86%;3.34%)
●
●
1.5
● ●
● ●
●
● ●
PAC: −5.26% (−5.62%;−4.89%)
●
● ●
● ●
1.0
●
●
●
●
●
●
●
PAC: ●−3.19%●(−4.95%;−1.39%)
● ●
PAC: −0.79% (−3.09%;1.56
0.5
● ● ●
1970
1975
1980
1985
1990
1995
●
● ●
●
●
●
2000
●
2005
xyear
Hodgkin...s disease (F) France
●
0.28% (−2.92%;3.58%)
●
0.9
●
●
●
0.8
0.7
●
●
●
●
●
●
0.6
●
PAC: −5.29% (−5.76%;−4.82%)
0.5
●
●
●
●
●
0.4
●
●
●
PAC: 0.29%
● (−1.23%;1.84%)
●
●
●
0.3
●
1970
1975
1980
1985
1990
xyear
133
● ●
●
●
●
PAC:
−4.41% (−8.72%
●
●
1995
2000
● ●
●
●
2005
Hodgkin...s disease (M) Germanyeast
●
●
●
●
●
PAC:
−1.32%●(−2.42%;−0.21%)
●
●
●
1.5
●
●
●
●
●
●
PAC: −11.08% (−15.33%;−6.61%)
●
1.0
●
●
PAC: −29.65% (−43.52%;−12.37%)
●
●
PAC:
● −4.64% (−9.61%;0.61%)
0.5
●
●
●
●
●
1980
1985
1990
1995
2000
2005
xyear
Hodgkin...s disease (F) Germanyeast
●
1.0
●
●
●
PAC: 1.52%
(−2%;5.17%)
●
●
●
●
●
●
●
0.8
●
●
●
●
●
PAC: −33.91% (−45.9%;−19.26%)
●
0.6
●
●
0.4
PAC: −2.8% (−4.19%;−1.38%)
●
PAC: ●−5.07% (−9.48%;−0.44%)
●
●
●
●
●
1980
1985
1990
1995
xyear
134
2000
2005
Hodgkin...s disease (M) Germanywest
2.0
●
●
● (−5.06%;−0.74%)
PAC: 11.01%
(5.12%;17.23%)
PAC: −2.92%
AC: −3% ●(−4.33%;−1.66%)
●
●
●
●
●
●
●
●
●
1.5
●
●
●
●
●
● ●
1.0
●
●
●
●
PAC: −6.91% (−7.23%;−6.6%)
●
● ●
0.5
●
●
●
●
●
●
1970
1975
1980
1985
1990
1995
2000
●
● ●
2005
xyear
Hodgkin...s disease (F) Germanywest
●
1.2
●
●
●
PAC: 0.72% (0%;1.45%)
●
●
●
1.0
●
●
●
PAC:
●
−7.72%
●
(−8.95%;−6.47%)
0.8
●
●
PAC: 2.08% (−0.33%;4.56%)
●
●
●
●
0.6
●
● ●
●
PAC: −7.42% (−8.14%;−6.68%)
● ●
0.4
● ●
●
● ●
●
●
●
● ● ●
1970
1975
1980
1985
1990
xyear
135
1995
2000
●
2005
Hodgkin...s disease (M) Netherlands
2.0
● ●
●
●
●
●
●
1.5
●
●
●
●
●
PAC: 1.99% (−3.24%;7.5%)
●
●
●
●
●
●
●
1.0
PAC: −4.44% (−5.61%;−3.26%)
●
● (−10.49%;−6.69%)
PAC: −8.61%
●
●
●
●
0.5
●
●PAC: −1.72%
●
●
●
●
●
(−3.5%;0.1%)
● ●
●
●
●
●
1970
1980
1990
2000
xyear
Hodgkin...s disease (F) Netherlands
1.4
●
.93% (−16.7%;−4.75%)
1.2
●
●
1.0
●
●
●
0.8
●
●
●
●
●
●
●
●
PAC:●−3.67% (−4.24%;−3.09%)
0.6
●
●
●
●
0.4
●
●
●
●
●
●
●
●
● ●
●
● ● 12.82% (2.1%;24.
PAC:
PAC: −27.71% (−42.55%;−9.03%)
●
●
●
0.2
●
●
1970
1980
1990
xyear
136
2000
●
Hodgkin...s disease (M) Spain
●
1.8
●
●
● ●
●
1.4
PAC: −3.64% (−4.42%;−2.85%)
●
●
●
●
●
1.2
●
PAC:
−0.2% (−2.69%;2.35%)
●
●
●
●
●
PAC: −5.53% ●(−7.46%;−3.56%)
1.0
●
●
●
●
0.8
1.6
●
●
●
●
●
●
●
PAC: −3.71%
(−4.58%;−2.84%)
●
●
0.6
●
●
1970
1980
1990
●
●
●
● ●
2000
xyear
Hodgkin...s disease (F) Spain
●
0.8
●
0.7
●
PAC: −2.1% (−3.21%;−0.98%)
●
●
●
●
●
●
●
0.6
●
● ●
PAC: −1.85% (−2.83%;−0.85%)
● ●
●
●
●
0.5
●
●
●
●
●
●
●
●
PAC: −3.32% (−4.63%;−1.98%)
●
●
0.4
●
●
●
PAC: −0.45% (−5.05%
●
●
●
●
1970
1980
1990
xyear
137
2000
●
●
●
Hodgkin...s disease (M) Sweden
●
●
●
PAC: −3.52% (−5.62%;−1.38%)
●
●
●
●
●
1.5
●
●
PAC: −16.56% (−23.45%;−9.06%)
●
●
1.0
2.0
●
●
●
PAC: −6.84%
(−9.38%;−4.22%)
●
●
●
●
●
0.5
●
●
1970
1975
1980
1985
●
●
PAC: −2.6% (−4.46%;−0.7%)
●
● ●
● ●
1990
1995
●
● ●
●
●
●
2000
●
●
2005
xyear
1.4
Hodgkin...s disease (F) Sweden
●
1.2
●
●
1.0
●
●
0.8
●
●
●
●
●
0.6
●
●
●
●
PAC: −12.65% (−15.74%;−9.44%)
●
●
●
0.4
●
●
●
● −5.09% (−8.32%;−1.74%)
PAC: 9.02% (2.14%;16.36%)
PAC:
●
●
●
●
●
●
●
0.2
●
●
PAC: −4.18%
(−5.96%;−2.36%)
●
1970
1975
1980
1985
●
●
1990
xyear
138
●
1995
2000
● ●
●
2005
Hodgkin...s disease (M) UK
● ●
● ● ●
●
1.5
● ●(−5.08%;−4.3%)
PAC: −4.69%
●
●
●
●
●
●
●
●
●
1.0
2.0
●
●
●
●
●
● −5.5%●(−6.15%;−4.84%)
PAC:
● ●
●
PAC: −0.7% (−6.83%;5
PAC: 8.8% (0.77%;17.48%)
0.5
●
1970
1975
1980
1985
1990
●
1995
●
● ●
●
● ●
2000
●
●
2005
xyear
Hodgkin...s disease (F) UK
1.2
●
●
●
1.0
●
●
PAC: −4.8% (−5.47%;−4.12%)
●
0.8
●
●
●
●
●
PAC: −0.92%
(−4.13%;2.41%)
●
0.6
●
●
●
●
●
●
●
●
●
PAC: −4.75%
●
● (−5.62%;−3.88%)
●
0.4
●
●
● ● ●
●
PAC: 4.46% (1.31%;7.71
●
●
1970
1975
1980
1985
1990
xyear
139
1995
●
●
2000
●
●
●
2005
140
141
142
143
144
145
146
147
Rheumatic heart disease (M) Estonia
●
●
●
10
●
●
●
●
●
●
8
●
PAC: 22.73% (1.87%;47.87%)
●
●
PAC: −2.28% (−3.21%;−1.34%)
●
●
●
●
●
●
●
● ●
6
●
●
●
●
●
●
●
●
PAC: −9.8% (−12.73%;−6.76%
●
4
−7.18% (−14.38%;0.63%)
●
●
●
2
● ●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Rheumatic heart disease (F) Estonia
9
10
●
●
●
8
● ●
PAC:
●
0.31% (−0.84%;1.47%)
●
●
●
●
●
●
●
7
●
●
●
PAC: −3.42% (−5.12%;−1.7%)
●
●
●
6
●
●
●
●
● ● ●
PAC: 21.78% (4.46%;41.96%)
●
●
5
●
●
PAC: −9.17% (−12.75%;−5.45
●
●
●
4
●
●
3
●
1970
1975
1980
1985
1990
xyear
148
1995
2000
2005
2.6
Rheumatic heart disease (M) France
●
●
2.4
●
●
●
●
●
2.2
●
●
2.0
●
●
●
●
●PAC: −2.43%
●
(−2.81%;−2.06%)
●
●
●
●
PAC: 16.24% (7.71%;25.44%)
●
●
●
●
●
1.8
●
●
●
PAC: 2.04% (1.47%;2.61%)
PAC: −2.84% (−4.2%;−1.47
●
●
●
●
●
1.6
●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Rheumatic heart disease (F) France
3.5
●
●
●
●
●
●
●
3.0
●
●
PAC: 2.52% (2.18%;2.85%)
●
●
●
●
●
PAC: −3.32%●(−3.68%;−2.96%)
●
●
●
PAC: 20.99% (14.14%;28.26%)
●
2.5
● ●
●
●
●
●
●
●
●
●
PAC: −4.23% (−5.25%;−3.2
●
●
●
●
2.0
●
1970
1975
1980
1985
1990
xyear
149
1995
2000
●
●
2005
Rheumatic heart disease (M) Germanyeast
5
●
C: −7.48% (−10.2%;−4.67%)
●
●
4
● (−6.94%;0.26%)
PAC: −3.41%
●
●
●
3
●
●
PAC: −14.74% (−17.41%;−11.97%)
●
2
●
●
●
●
PAC:●−3.5% (−4.46%;−2.54%)
●
●
●
●
●
●
●
●
●
●
1
●
1980
1985
1990
1995
2000
2005
xyear
Rheumatic heart disease (F) Germanyeast
7
8
●
AC: −7.63% (−8.9%;−6.34%)
●
6
●
●
5
●
●
PAC: −4.83% (−7%;−2.6%)
●
●
● 0.18% (−2.79%;3.24%)
PAC:
●
4
●
●
●
●
●
●
3
PAC: −5.94%
● (−6.69%;−5.19%)
●
●
●
●
●
●
●
2
●
●
1980
1985
1990
1995
xyear
150
2000
2005
Rheumatic heart disease (M) Germanywest
3.0
●
●
●
●
●
2.5
●
● ●
●
PAC: −20.24% (−22.83%;−17.55%)
2.0
PAC: −3.19% (−3.75%;−2.63%)
●
●
●
●
●
●
●
PAC: −1.44% (−1.94%;−0.94%)
●
●
●
● ●
●
●
●
PAC: 1.69%
● (1.14%;2.25%)
●
1.5
●
●
●
●
● ● ●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
5.0
Rheumatic heart disease (F) Germanywest
●
4.5
●
●
PAC: −3.15% (−3.6%;−2.69%)
4.0
●
●
●
●
3.5
●
●
3.0
●
PAC: −13.37% (−14.28%;−12.45%)●
●
●
2.5
●
●
●
●
●
●
● (−1.38%;−0.98%)
PAC: −1.18%
●
● ●
●
PAC: 10.33% (9.1%;11.58%)
● ●
●
●
●
●
●
●
●
●
●
●
1970
1975
1980
1985
1990
xyear
151
1995
2000
2005
Rheumatic heart disease (M) Netherlands
C: 0.32% (−1.65%;2.33%)
●
●
●
●
6
●
4
●
PAC: −33.03% (−34.93%;−31.07%)
●
●
2
8
10
● ●
●
●
●
● ●
PAC: −12.15% (−13.04%;−11.25%)
● ●
●
0
● ●
1970
1980
PAC: −19.95% (−23.87%;−15.82%)
●
● ● ● ● ● ●
1990
● ● ● ● ● ● ● ● ● ● ●
2000
xyear
Rheumatic heart disease (F) Netherlands
12
●
−2.76% (−4.46%;−1.04%)
●
●
8
●
6
PAC: −31.85% (−34.18%;−29.44%)
●
4
●
●
2
● ●
●
● ●
PAC: −12.76% (−13.4%;−12.12%)
●
●
● ●
●
1970
1980
1990
xyear
152
PAC: −17.94% (−20.29%;−15.51%)
● ● ● ● ● ●
●
0
10
● ●
●
● ● ● ● ● ● ● ● ● ● ●
2000
Rheumatic heart disease (M) Spain
25
●
●
15
: −11.91% (−12.36%;−11.47%)
●
●
●
●
●
10
20
●
●
●
5
● (−16.25%;−15.16%)
PAC: −15.71%
●
●
● ●
PAC: −1.3% (−1.63%;−0.96%)
PAC: −8.12% (−9.8%;−6
● ● ●
● ● ● ● ● ● ●
● ● ● ● ● ● ● ● ●
● ●
● ●
1970
1980
1990
2000
xyear
Rheumatic heart disease (F) Spain
●
●
20
●
●
●
15
●
PAC: −11.95%●(−12.12%;−11.78%)
●
10
●
●
●
● ●
●
●
5
25
30
5% (−5.83%;3.77%)
●
1970
PAC: −1.23% (−1.42%;−1.04%)
● ● ● ● ● ●
PAC: −8.62% (−9.82%;−7
● ● ● ● ● ● ● ● ●
● ● ●
● ●
● ●
1980
1990
xyear
153
2000
Rheumatic heart disease (M) Sweden
12
●
●
●
PAC:●−3.41% (−4.3%;−2.5%)
●
●
● (−62.37%;−50.72%)
PAC: −56.93%
●
●
6
8
●
●
●
4
10
●
●
●
●
2
● (−10.08%;−7.69%)
PAC: −8.89%
●
1970
1975
1980
●
1985
● ●
● ●
1990
● ●
PAC: −1.91% (−3.61%;−0.18%)
● ●
1995
●
●
●
● ●
2000
● ● ●
●
●
2005
xyear
14
Rheumatic heart disease (F) Sweden
●
●
12
●
PAC: −4.25% (−5.04%;−3.45%)
10
●
●
●
●
●
●
6
8
●
PAC: −51.54% (−56.38%;−46.17%)
● ●
4
●
●
●
PAC: −7.15% (−7.95%;−6.34%)
● ●
2
●
●
●
1970
1975
1980
1985
●
● ● ● ●
●
1990
xyear
154
PAC: −4.15% (−5.74%;−2.52%
● ● ● ●
1995
●
● ● ●
●
●
●
2000
2005
Rheumatic heart disease (M) UK
(
;
)
5
●
●
● ●
4
●
● ●(−4.29%;−3.6%)
PAC: −3.95%
● ●
●
3
●
● ● ●
● (−7.01%;−5.12%)
PAC: −6.07%
●
●
●
2
●
●
●
●
● ●
●
● ●
PAC: −4.11% (−4.48%;−3.74%)
●
● ●
● ●
1
●
1970
1975
1980
1985
1990
1995
●
2000
● ●
●
2005
xyear
Rheumatic heart disease (F) UK
●
●
●
●
6
●
●
●
●
PAC: −3.64% (−3.73%;−3.54%)
●
5
●
●
● ●
●
4
●
●
●
● ●
●
●
●
PAC: −13.23%
(−17.23%;−9.04%)
●
●
3
PAC: −1.16% (−3.67%;1.41%)
● ● ●
● ●
PAC: −4.83%
(−5.88%;−3.7
●
2
●
●
7
8
●
● ●
●
●
1970
1975
1980
1985
1990
xyear
155
1995
2000
2005
Hypertension (M) Estonia
●
30
PAC: 13.71% (11.41%;16.05
● ●
●
●
●
20
40
●
●
●
●
●
PAC: 8.18% (6.76%;9.63%)
●
PAC: −3.19%
(−4.15%;−2.23%)
●
● ●
10
● ●
●
●
●
●
% (138.37%;2698.78%)
●
●
●
●
●
●
●
●
●
1970
1975
1980
●
●
● ●
1985
●
●
1990
1995
2000
2005
xyear
Hypertension (F) Estonia
35
●
25
●
PAC: 18.29% (16.08%;20.56
20
●
15
●
●
PAC: −2.02% (−5.54%;1.63%)
●
●
● ●
10
● ●
●
● ●
●
5
30
●
●
1970
PAC: −1.02% (−1.79%;−0.24%)PAC: 150.91% (117.13%;189.95%)
●
●
●
1975
●
● ●
● ●
1980
●
●
●
●
●
●
●
1985
●
1990
xyear
156
●
●
●
1995
2000
2005
Hypertension (M) France
12
●
●
●
●
11
●
●
●
10
●
●
PAC:(0.87%;6.38%)
12.91% (10.4%;15.48%)
.59%
●
● ●
●
●
●
PAC: −1.19% (−1.26%;−1.11%)
●
: −10.89%
(−15.78%;−5.72%)
●
●
●
●
●
●
●
●
●
9
●
● ●
●
●
●
● ●
8
●
●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
10.5
Hypertension (F) France
●
PAC: 16.31% (12.67%;20.07%)
●
PAC: −1.89% (−2.22%;−1.55%)
●
●
9.5
●
●
●
● ● ●
●
9.0
●
●
C: 1.62% (0.63%;2.63%)
●
●
●
●
●
●
8.5
●
PAC: −0.76% (−0.84%;−0.67%)
●
●
●
●
●
●
●
● ●
●
8.0
●
●
7.5
10.0
●
●
●
●
1970
1975
1980
1985
1990
xyear
157
1995
2000
2005
Hypertension (M) Germanyeast
●
●
PAC:
−1% (−1.29%;−0.72%)
●
●
●
40
●
●
●
●
35
30
●
●
25
PAC: −16.28% (−16.99%;−15.56%)
●
●
●
20
●
●
PAC: 8.11% (7.29%;8.95%)
●
●
●
PAC: −6.02% (−6.98%;−5.05%)
15
●
●
●
●
1980
1985
1990
●
1995
●
●
2000
2005
xyear
Hypertension (F) Germanyeast
50
●
●
●
PAC: −1.82%
(−2.02%;−1.62%)
●
●
●
●
●
40
●
30
●
PAC: −19.45% (−19.93%;−18.96%)
●
●
●
●
PAC: 10.84% (10.29%;11.39%)
●
●
20
●
●
PAC:
−5.41% (−6.07%;−4.75%)
●
●
●
●
●
●
●
●
1980
1985
1990
1995
xyear
158
2000
2005
Hypertension (M) Germanywest
●
PAC:
●
●
●
−0.68% (−0.91%;−0.46%)
18
● ●
●
● ●
●
●
16
●
●
●
●
●
●
14
●
PAC: −9.02% (−9.35%;−8.68%)
PAC: 5.39% (5.12%;5.65%)
●
●
●
●
12
●
●
●
10
● PAC:
●
●
1.21% (0.87%;1.55%)
● ●
●
●
●
●
● ●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
22
24
Hypertension (F) Germanywest
●
●
PAC: ●−1.65% ●(−1.8%;−1.5%)
●
●
●
20
●
●
●
18
●
●
● ●
●
●
●
16
●
PAC: −8.71% (−8.91%;−8.51%)
PAC: 7.24% (7.06%;7.42%)
14
●
●
12
●
●
●
● ●
●
PAC: 0.84% (0.59%;1.09%)
●
●
●
●
10
●
●
1970
1975
1980
1985
1990
xyear
159
● ●
●
●
1995
2000
2005
8
Hypertension (M) Netherlands
●
●
C: −7.31% (−8.58%;−6.02%)
6
●
●
●
●
● −0.41% (−1.34%;0.52%)
PAC:
●
5
7
●
● ● ●
●
●
●
●
●
●
●
PAC: ●
−1.86%
● (−2.68%;−1.03%)
PAC:
● −0.05% (−0.66%;0.57%)
4
●
●
●
●
● ●
● ●
●
1980
●
●
●
1970
● ●
●
●
1990
2000
xyear
Hypertension (F) Netherlands
9
●
●
8
7
●
●
●
6
PAC: −6.93% (−7.49%;−6.36%)
●
●
●
5
●
●
●
●
PAC: 1.38% (0.44%;2.33%)
●
● −2.83% (−3.6%;−2.06%)
PAC:
●
● ●
●
● ●
●
●
●
4
●
●
PAC: 0.45% (−0.17%;1.07%)
●
●
● ●
●
●
●
●
1970
1980
1990
xyear
160
2000
●
●
●
● ●
Hypertension (M) Spain
(
;
)
14
10
12
●
●
●
8
16
18
●
●
PAC: −8.63%
● (−9.48%;−7.78%)
●
● ●
PAC: 2.06% (1.88%;2.25%)
●
6
●
●
PAC: −0.07% (−0.49%;0.35%)
●
●
1970
●
●
●
●
●
● ● ●
● ●
1980
●
●
●
●
●
●
● ● ●
●
● ● ● ●
1990
2000
xyear
Hypertension (F) Spain
●
10
12
38% (−28.92%;−25.82%)
●
PAC: 1.7% (1.42%;1.98%)
●
●
● ● ●
8
●
●
●
●
PAC: 3.33% (3.16%;3.5%)
● ●
●
●
●
●
●
●
●
●
●
●
PAC: −6.26%
(−6.71%;−5.82%)
1970
●
●
●
6
14
16
●
●
●
●
●
● ● ●
1980
●
1990
xyear
161
●
2000
●
●
10
Hypertension (M) Sweden
●
8
●
1.11% (−23.73%;−18.4%)
●
●
●
6
●
PAC: 2.03% (1.46%;2.59%)
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
PAC: 6.23% (4.32%;8.18%)
●
PAC: −2.4% (−3.39%;−1.4%)
●
●
4
●
●
●
●
● ●
●
●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Hypertension (F) Sweden
8
●
●
●
22.48% (−24.3%;−20.61%)
PAC: 6.55% (5.2%;7.91
6
●
●
● ●
●
●
PAC: 2.94%
● (2.4%;3.49%)
●
● ●
PAC:
● ● −1.12% (−1.79%;−0.45%)
●
●
●
1970
●
●
●
4
10
●
1975
● ●
1980
● ●
●
●
●
●
●
●
●
●
● ● ●
1985
1990
xyear
162
1995
2000
2005
Hypertension (M) UK
20
●
●
●
C: −5.37% (−5.8%;−4.95%)
●
15
●
●
●
●
●
●
PAC: −7.46% (−7.71%;−7.22%)
●
10
●
●
●
●
●
●
● −4.51% (−5%;−4.01%)
PAC:
● ●
●
PAC: 0.52% (0.17%;0.88%)
5
●
1970
1975
1980
1985
● ●
1990
●
● ● ● ●
1995
●
●
● ● ● ● ● ●
2000
2005
xyear
16
Hypertension (F) UK
●
14
−5.23% (−5.8%;−4.65%)
●
●
12
●
●
●
10
●
●
●
8
PAC: −7.36% (−7.54%;−7.17%)
●
●
●
6
●
● ●
●
●
PAC: −4.95%
(−5.35%;−4.54%)
●
PAC: 2.48% (2.17%;2.79%)●
●
4
●
1970
1975
1980
1985
●
●
●
1990
xyear
163
●
●
●
● ● ●
●
1995
●
●
● ●
2000
●
●
2005
650
Ischaemic heart disease (M) Estonia
●
600
●
●
●
●
PAC: −0.83% (−1.05%;−0.6%)
●
● ●
●
●
PAC: 2.22% (1.88%;2.55%)
●
●
● ●
●
550
●
PAC: ●4.56% (3.23%;5.9%)
●
●
●
● ●
●
●
●
500
●
●
●
●
PAC: −4.82% (−5.1%;−4.55%)
●
450
●
●
●
400
●
350
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Ischaemic heart disease (F) Estonia
●
●
●
●
●
●
PAC: 0.59% (0.44%;0.73%)
350
●
●
●
●
●
● ●
●
● ● ●
●
● (−2.54%;−2.25%)
PAC: −2.4%
●
●
●
●
300
●
●
●
●
250
●
● ●
PAC: −5.8% (−6.4%;−5.2%)
●
200
●
●
PAC: −15.77% (−17.52
●
150
●
●
1970
1975
1980
1985
1990
xyear
164
1995
2000
2005
Ischaemic heart disease (M) France
130
●
●
●
PAC: −0.99%
(−1.07%;−0.91%)
110
●
● ●
● ●
●
● ● ●
●
●
●
●
100
●
●
●
●
PAC: −2.85% (−2.9%;−2.8%)
90
● ●
● ●
●
●
80
120
●
C: 2.59% (2.36%;2.83%)
●
●
● ●
●
70
●
PAC: −3.88% (−4.16%;−
●
●
60
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Ischaemic heart disease (F) France
●
55
●
PAC: −0.43% (−0.52%;−0.34%)
●
●
C: 2.45% (2.18%;2.72%)
● ●
●
●
●
●
●
●
●
●
●
●
●
45
●
●
●
●
40
●
PAC: −3.05%
(−3.1%;−3%)
●
●
●
35
● ●
●
●
●
●
30
50
●
●
●
PAC: −5.83% (−6.41%
●
1970
1975
1980
1985
1990
xyear
165
1995
2000
●
2005
Ischaemic heart disease (M) Germanyeast
●
●
●
●
●
300
PAC: 1.83% (1.72%;1.93%)PAC: −6.92% (−7.22%;−6.61%)
●
●
1.01% (−1.67%;−0.34%)
●
●
●
●
●
●
●
●
●
●
250
●
●
●
●
●
PAC: −4.74% (−4.95%;−4.54%)
●
200
●
●
●
1980
1985
1990
1995
2000
2005
xyear
Ischaemic heart disease (F) Germanyeast
170
●
●
●
●PAC:
●
●
−5.52% (−5.84%;−5.2%)
●
●
●
●
●
150
●
●
●
●
●
●
●
140
●
PAC: −3.24% (−3.52%;−2.96%)
130
●
●
●
120
●
PAC: −8.09% (−8.88%;
●
110
160
●
PAC: 1.44% (1.37%;1.52%)
●
1980
1985
1990
1995
xyear
166
2000
2005
Ischaemic heart disease (M) Germanywest
PAC: 0.32% (0.25%;0.38%)
260
240
●
●
● ●
●
●
●
●
●
●
C: 2.15% (2.01%;2.28%)
●
●
●
●
●
●
220
●
●
PAC: −2.45% (−2.48%;−2.42%)
●
200
● ●
●
●
●
● ●
180
●
●
PAC: −4.33%
● (−4.44%;−4.
160
● ●
●
●
●
140
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Ischaemic heart disease (F) Germanywest
●
●
PAC: 0.38% (0.32%;0.45%)
●
●
●
●
●
●
●
●
●
●
●
●
●
●
PAC: −1.08% (−1.1%;−1.05%)
●
●
C: 3.16% (2.99%;3.33%)
●
●
●
●
100
● ●
●
● ●
●
●
●
●
●
90
●
PAC: −7.62% (−7.94%
●
80
110
●
●
1970
1975
1980
1985
1990
xyear
167
1995
2000
2005
300
Ischaemic heart disease (M) Netherlands
●
C: −0.49% (−0.73%;−0.25%)
●
●
●
●
●
●
●
●
PAC: −1.92% (−2.04%;−1.8%)
● ●
●
● ● ●
●
●
200
●
●
●
PAC: −3.96%
(−4.05%;−3.88%)
●
●
●
● ●
150
250
●
●
●
●
●
●
●
PAC: −7.35% (−7.54%;−7.16%
100
●
●
●
●
●
●
1970
1980
1990
2000
xyear
Ischaemic heart disease (F) Netherlands
●
C: −1.57%
(−1.86%;−1.27%)
● ●
●
120
● ● ●
●
●
PAC: −2.65% (−2.8%;−2.5%)
100
● ● ●
● ● ●
●
●
●
80
PAC: −3.18%
(−3.28%;−3.08%)
● ●
●
●
●
●
● ●
60
● ●
●
●
●
PAC: −6.71%
● (−6.92%;−6.49%
●
●
40
●
●
●
1970
1980
1990
xyear
168
2000
●
Ischaemic heart disease (M) Spain
● ●
●
●
PAC: −0.67% (−0.71%;−0.64%)
●
AC: 5.31% (4.94%;5.68%)
●
●
●
● ●
●
● ●
●
●
●
100
●
● ●
●
●
●
●
● ●
90
110
●
● ● ● ● ●
●
●
PAC: −3.48% (−3.59%;−3.36%
●
80
●
●
% (25.79%;31.99%)
●
●
1970
1980
1990
2000
xyear
55
Ischaemic heart disease (F) Spain
●
●
●
●
●
●
50
● ●
●
●
●
PAC: −0.74% (−0.78%;−0.7%)
AC: 4.59% (4.1%;5.08%)
●
● ● ●
●
● ●
●
45
●
●
●
● ●
●
● ●
●
●
40
● ● ●
PAC: −3.44% (−3.58%;−3.3%
●
% (21.68%;30.45%)
●
●
35
●
●
●
1970
1980
1990
xyear
169
2000
Ischaemic heart disease (M) Sweden
450
PAC: −0.16%
(−0.3%;−0.02%)
●
●
●
●
● ●
% (11.24%;19.07%) ●
●
●
●
●
●
●
●
●
350
●
●
300
●
● ●
●
● ●
● ● (−4.21%;−4.1%)
PAC: −4.15%
250
400
PAC: −3.39%
● (−3.59%;−3.18%)
●
●
200
●
●
●
● ●
●
150
● ●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
Ischaemic heart disease (F) Sweden
250
●
●
PAC: −1.73%
● (−1.88%;−1.58%)
●
● ●
●
200
●
PAC: −4.14% (−4.37%;−3.92%)
●
●
● ●
●
150
PAC: −6.4% (−6.88%;−5.92%)
● ●
● ●
● ● ●
● ●
PAC: −3.4%
● (−3.49%;−3.32%)
●
100
● ● ●
●
1970
1975
1980
1985
1990
xyear
170
1995
●
●
● ●
●
2000
●
●
● ●
2005
400
Ischaemic heart disease (M) UK
.72% (2.43%;3.02%)
●
●
● ● ●
PAC: ●−0.96% (−1%;−0.93%)
●
●
●
●
●
350
●
● ●
●
●
●
●
PAC: −3.13% (−3.18%;−3.09%)
●
300
●
●
● ●
250
●
●
●
●
●
●
200
●
PAC: −5.35%
(−5.4%;−5.29%)
●
●
●
●
150
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Ischaemic heart disease (F) UK
● ●
.59% (2.25%;2.93%)
●
●
●
● (−1.08%;−1%)
PAC: −1.04%
●
160
● ●
●
● ●
●
●
● ●
●
●
140
●
●
●
● ●
●
120
●
●
●
●
100
PAC: −4.76%●(−4.81%;−4.71%)
●
●
80
PAC: −1.72%
(−1.79%;−1.64%)
●
●
●
●
●
●
1970
1975
1980
1985
1990
xyear
171
1995
2000
2005
Heart failure (M) France
●
●
140
●
120
● ●
100
●
● ●
PAC: −5.55% (−5.6%;−5.49%)
● ●
80
●
●
●
●
●
●
60
●
●
●
PAC:
● −1.32% (−1.51%;−1.13%)
● ●
● ●
●
40
● ●(−15.96%;−13.22%)
PAC:●−14.6%
PAC:
● −3.91% (−4.2%;−3.62
●
1970
1975
1980
1985
1990
1995
● ●
●
●
2000
● ●
2005
xyear
120
Heart failure (F) France
● ●
● (−6.45%;−6.23%)
PAC: −6.34%
● ●
80
●
● ●
● ●
60
●
● ●
PAC: −5.03%●(−5.1%;−4.95%)
●
●
40
●
●
●
PAC: ●−1.86% (−2.09%;−1.62%)
●
● ●
●
● ●
PAC: ●−5.03% (−5.17%;−4.89%)
● ●
●
● ● ●
20
100
●
1970
1975
1980
1985
1990
xyear
172
1995
2000
● ●
2005
90
Heart failure (M) Germanyeast
●
−4.13%●(−4.91%;−3.35%)
80
●
PAC:
−0.13% (−0.64%;0.38%)
●
●
●
●
●
70
●
●
60
●
50
●
PAC: −9.8% ●(−10.09%;−9.5%)
●
40
●
●
●
30
●
●
PAC: ●−2.96%
(−3.51%;−2.41%)
●
●
●
●
1980
1985
1990
1995
2000
●
●
2005
xyear
70
Heart failure (F) Germanyeast
●
●
−4.21% (−4.95%;−3.46%)
60
●
●
PAC: −2.22%
(−2.56%;−1.87%)
●
●
●
●
50
●
●
●
40
PAC: −9.76% (−10.08%;−9.45%)
●
●
●
30
●
●
●
PAC: −2.38% (−2.64%;−2.11%)
●
●
●
1980
1985
1990
1995
xyear
173
●
●
2000
●
●
●
●
2005
200
Heart failure (M) Germanywest
●
●
●
●
150
●
●
● ●
●
●
● (−4.92%;−4.85%)
PAC: −4.88%
●
100
●
●
●
●
●
● ●
●
● ●
50
● ●
PAC: −2.37%
● ●
● ●
(−2.48%;−2.26%)
● ●
● ● ● ●
PAC:PAC:
−20.28%
(−21.73%
−4.58%
(−6.78
●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
180
Heart failure (F) Germanywest
●
● (−6.15%;−5.97%)
PAC: −6.06%
●
●
120
140
●
●
100
● ●
PAC: −14.8%●(−15.62%;−13.97%)
●
●
●
80
PAC: −6.33%
● (−6.45%;−6.21%)
●
●
●
60
● ● ●
●
●PAC: −2.7% (−2.74%;−2.66%)
● ●
● ● ●
●
● ● ● ● ● ●
40
160
●
● ●
1970
1975
1980
1985
1990
xyear
174
1995
2000
2005
Heart failure (M) Netherlands
55
●
11% (−7.43%;−4.77%)
●
●
● ●
●
50
PAC: 1.03% (0.75%;1.31%)
●
●
●
●
45
●
●
PAC: −14.29% (−15.39%;−13.18%)
●
●
●
40
● ●
●
●
●
● ● ●
●
PAC: −0.88% (−1.01%;−0.76%)
●
●
●
●
35
●
●
●
●
●
●
● ●
●
1970
1980
1990
●
2000
xyear
Heart failure (F) Netherlands
45
●
●
●
●
40
●
●
PAC: 0.81% (0.51%;1.11%)
●
●
●
●
●
●
●
●
35
●
●
PAC: −8.89% (−9.42%;−8.35%)
30
●
●
●
●
●
●
● ●
PAC:
●
●
−0.65% (−0.76%;−0.55%)
● ●
●
●
●
● ● ●
25
5.48% (−6.43%;−4.53%)
●
●
1970
1980
1990
xyear
175
2000
● ●
● ●
100
−10.17% (−10.44%;−9.89%)
● ●
●
80
●
●
●
● ●
PAC:
−2.31% (−2.39%;−2.23%)
● ●
●
●
60
120
140
Heart failure (M) Spain
●
●
●
● ● ●
● ●
● ●
●
●
PAC: −6.38%
(−6.57%;−6.19%)
40
●
● ●
●
PAC:
−1.84% (−2.18%;−1.5
●
1970
1980
1990
● ● ● ● ●
● ●
2000
xyear
120
Heart failure (F) Spain
●
10.71% (−11.04%;−10.38%)
●
80
●
●
●
PAC: −2.67%
(−2.91%;−2.42%)
●
60
● ●
● PAC:
● ●
−0.46% (−0.59%;−0.32%)
●
●
●
●
●
●
● ●
●
●
●
●
●
●
●
PAC: −4.25%
(−4.31%;−4.19%)
40
100
●
● ●
●
●
1970
1980
1990
xyear
176
● ● ●
2000
● ●
● ●
70
Heart failure (M) Sweden
●
●
●
●
●
● (−12.8%;−8.53%)
10.69%
●
●
50
PAC: 5.01%●(4.06%;5.97%)
●
●
●
●
PAC: −4.93%
●
● (−5.31%;−4.54%)
●
● ●
●
● ●
40
60
●
●
●
●
●PAC: −1.38% (−1.68%;−1.09%)
●
●
●
●
●
●
●
●
● ●
30
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
●
40
●
●
35
3.15% (−15.56%;−10.67%)
● ●
●
●
PAC: 2.15%●(1.46%;2.84%)
●
●
30
●
●
●
PAC: −3.19% (−3.6%;−2.78%)
●
●
●
●
● ●
●
●
●
●
●
● ●
PAC: −1.04%●(−1.3%;−0.79%)
25
45
50
Heart failure (F) Sweden
● ●
●
●
1970
1975
1980
1985
1990
xyear
177
1995
●
● ● ●
2000
●
●
2005
Heart failure (M) UK
●
100
●
−7.1% (−7.76%;−6.44%)
●
80
●
●
60
●
PAC: −11.02% (−11.42%;−10.63%)
● ●
●
●
40
●
● ●
●
●
PAC: −6.68%
(−6.8%;−6.56%)
●
● ●
●
20
●
1970
1975
1980
1985
●
PAC: −2.25%
● ● ●
● ●
● ●
● ●
1990
1995
(−2.43%;−2.07%)
●
● ● ●
2000
● ●
●
2005
xyear
100
Heart failure (F) UK
●
●
80
●
●
60
●
PAC: −8.66% (−8.78%;−8.54%)
●
●
●
40
●
●
●
●
● ●
●
●
PAC: −6.24%
● ● (−6.31%;−6.17%)
●
20
●
●
1970
1975
1980
1985
●
1990
xyear
178
● ●
PAC: 0.84% (0.5%;1.17%)
PAC: −8.26% (−9.05%
● ● ● ●
● ●
● ● ●
● ●
●
●
1995
2000
2005
Cerebrovascular disease (M) Estonia
260
●
220
240
●
● ●
●
●
●
PAC: 0.39%●(0.14%;0.64%)
●
●
●
● ●
PAC: 1.53% (0.99%;2.08%)
●
●
●
●
●
●
●
PAC: −4.21% (−4.68%;−3.75%)
●
● ● ●
200
●
●
●
●
180
●
●
●
●
160
●
●
140
PAC: −11.66% (−14.63
●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
Cerebrovascular disease (F) Estonia
●
200
●
●
●
●
● ●
● −0.22% (−0.33%;−0.11%)
PAC:
●
●
●
●
●
● ●
●
●
●
●
●
●
180
●
●
160
●
PAC: −4.6%
(−4.9%;−4.31%)
●
● ●
140
●
● ●
PAC: −20.44% (−24.44%;−
●
120
●
PAC: −5.42% (−11.36
100
●
●
●
●
1970
1975
1980
1985
1990
xyear
179
1995
2000
2005
Cerebrovascular disease (M) France
−1.39%
(−1.59%;−1.18%)
●
●
●
●
●
●
●
●
PAC: −4.16% (−4.25%;−4.08%)
● ●
120
●
●
●
100
● ●
●
PAC: −8.61%●(−8.96%;−8.25%)
●
80
140
160
●
●
● ●
● ●
60
PAC: −4.28%
(−4.34%;−4.21%)
● ●
●
●
●
●
●
40
●
●
●
● ●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
120
Cerebrovascular disease (F) France
: −0.34% (−0.53%;−0.15%)
●
●
● PAC:
−9.71% (−10.45%;−8.97%)
●
●
●
●
PAC: −2.4% (−2.64%;−2.16%)
● ●
●
80
●
●
● ●
●
●
60
●
●
●
●
PAC: −4.8% (−4.84%;−4.77%)
●
●
●
40
100
● ●
● ●
●
●
●
●
●
● ●
● ●
1970
1975
1980
1985
1990
xyear
180
1995
2000
2005
160
Cerebrovascular disease (M) Germanyeast
●
PAC: 4.8%●(4%;5.61%)
●
●
●
●
●
●
●
●
●
140
●
PAC: −5.11% (−5.31%;−4.91%)
●
●
120
●
●
●
●
100
●
● −0.38% (−0.72%;−0.05%)
PAC:
●
PAC: −7.36% (−7.71%;−7%)
●
●
80
●
●
60
●
1980
1985
1990
1995
2000
2005
xyear
140
Cerebrovascular disease (F) Germanyeast
2.78%
● (−3.4%;−2.16%)
●
●
PAC: 0.62% (0.43%;0.81%)
●
●
●
●
●
●
●
●
100
●
●
●
●
PAC: −5.04% (−5.14%;−4.95%)
●
●
80
●
●
●
●
●
PAC: −10.11% (−11.04
60
120
●
●
●
●
1980
1985
1990
1995
xyear
181
2000
2005
200
Cerebrovascular disease (M) Germanywest
● ●
●
●
● (−2.71%;−2.58%)
PAC: −2.64%
●
150
●
●
●
●
●
●
●
PAC: −4.69% (−4.79%;−4.59%)
●
●
●
●
●
100
●
PAC: ●−3.11%
(−3.22%;−3.01%)
●
●
● ●
●
●
●
●
●
●
PAC: −5.98%
(−6.11%;−5.86%
●
●
●
50
●
●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
Cerebrovascular disease (F) Germanywest
●
160
●
●
●
●
● ● ●
120
● ●
●
100
PAC: −4.83%
● (−4.91%;−4.74%)
●
●
●
●
●
80
● ● (−3.14%;−2.96%)
PAC: −3.05%
●
● ●
●
●
●
60
●
PAC: −4.85%
(−4.93%;−4.77%)
●
●
●
● ●
●
●
40
140
●
PAC: −3.05%
● (−3.11%;−3%)
1970
1975
1980
1985
1990
xyear
182
1995
2000
●
2005
Cerebrovascular disease (M) Netherlands
●
●
●
●
●
●
PAC: −2.55% (−2.66%;−2.44%)
●
●
●
● ●
●
80
● ●
PAC:
−0.61% (−1.05%;−0.16%)
● ●
●
● ●
● ●
● ●
●
PAC: −2.39% (−2.59%;−2.19%)
● ●
60
100
●
●
● ●
●
●
●
●
● (−7.95%;−6
PAC: −7.39%
●
40
●
●
1970
1980
1990
2000
xyear
Cerebrovascular disease (F) Netherlands
●
100
●
●
●
●
●
PAC: −3.42% (−3.52%;−3.31%)
80
●
●
●
●
● ●
● ●
PAC:
● 0.26% (−0.04%;0.56%)
●
60
●
● ● ● ● ●
●
PAC: −2.2%
(−2.36%;−2.03%)
●
●
●
●
● ●
●
● ●
●
PAC: −6.65%
● (−7.13%;−6
●
40
●
●
●
1970
1980
1990
xyear
183
2000
180
Cerebrovascular disease (M) Spain
●
4.21% (3.78%;4.65%)
● ●
●
●
PAC: −3.47% (−3.57%;−3.37%)
● ●
●
●
140
● ●
●
120
● ●
●
●
PAC: −4.5%
(−4.59%;−4.41%)
100
●
●
●
● ●
●
80
160
●
●
●
●
●
PAC: ●
−4.18%
● ● (−4.26%;−4.09%)
60
●
●
● ●
● ●
● ●
1970
1980
1990
2000
xyear
160
Cerebrovascular disease (F) Spain
●
●
●
6.27% (5.74%;6.8%)
140
●
●
PAC: −3.15% (−3.23%;−3.08%)
●
●
● ●
120
●
●
●
●
●
100
●
●
●
●
80
●
●
●
● (−4.46%;−4.38%)
PAC: −4.42%
●
●
60
●
●
●
● ●
●
●
● ●
PAC: −5.41% (−5.7%;−
● ●
40
●
● ●
1970
1980
1990
xyear
184
2000
: 0.76% (0.04%;1.48%)
●
●
●
●
● (−2.71%;−2.27%)
PAC: −2.49%
●
● ●
●
90
●
●
●
● ●
●
● (−1.13%;−0.88%)
PAC:
−1.01%
● ●
●
80
●
●
●
● ●
●
●
●
●
70
●
●
●
100
110
Cerebrovascular disease (M) Sweden
●
●
PAC: −4.86% (−5.26%;−4.4
60
●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Cerebrovascular disease (F) Sweden
●
100
−0.84% (−1.34%;−0.34%)
●
● ●
●
●
●
●
●
●
●
80
●
●
●
● ●
●
PAC: −1.51%●(−1.58%;−1.43%)
70
● ●
●
●
●
●
●
● ● ●
60
●
●
●
● ●
●
PAC: −6.44% (−7.04%;−
●
50
90
PAC: −5.39% (−6.06%;−4.71%)
● ●
1970
1975
1980
1985
1990
xyear
185
1995
2000
2005
180
Cerebrovascular disease (M) UK
●
●
●
●
160
●
PAC: −3.05%
● (−3.13%;−2.98%)
140
● ● ●
●
PAC: 2.32% (1.73%;2.9%)
●
●
● ●
120
●
●
●
●
100
●
●
●
●
●
PAC: −3.61% (−3.66%;−3.56%)
●
80
● ●
●
●
●
●
● ● ●
●
60
PAC: −7.13% (−7.55%
●
●
1970
1975
1980
1985
1990
1995
2000
●
2005
xyear
160
Cerebrovascular disease (F) UK
●
●
●
140
●
●
PAC: −2.95%
● (−3.01%;−2.9%)
120
●
● ●
●
PAC: 2.14% (1.68%;2.61%)
●
● ●
●
●
●
100
●
●
●
● ●
●
PAC: −3.09% (−3.13%;−3.05%)
80
●
● ● ●
● ●
●
●
60
●
● ●
●
PAC: −6.44% (−6.77%
●
●
●
1970
1975
1980
1985
1990
xyear
186
1995
2000
2005
Peptic ulcer (M) Estonia
12
●
●
●
●
10
●
●
●
PAC: −11.79% (−17.78%;−5.38%)
●
●
●
●
PAC: 3.13% (1.18%;5.12%)
●
PAC: 6.29%
(2.34%;10.39%)
●
●
●
●
●
●
●
PAC: −3.54% (−5.14%;−1.93%)
●
●
●
●
●
8
●
●
●
●
●
●
●
●
●
●
6
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Peptic ulcer (F) Estonia
4.0
●
●
3.5
PAC: 27.1% (11.25%;45.21%)
3.0
PAC: −35.46% (−53.77%;−9.91%)
●
●
●
●
PAC: −1.85% (−4.73%;1.11%)
2.5
●
●
●
●
●
●
2.0
●
●
●
●
●
PAC: 1.39% (−0.04%;2.85%)
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
1.5
●
●
1970
1975
1980
1985
1990
xyear
187
1995
2000
2005
Peptic ulcer (M) France
3.5
● ●
C: 3.17% (2.22%;4.13%)
●
●
●
●
●
●
PAC: −3.37% (−3.68%;−3.07%)
●
●
●
●
2.5
● ●
●
●
2.0
● ●
PAC: −9.26%●(−10.09%;−8.43%)
●
1.5
3.0
●
●
●
●
1.0
● ● ●
PAC: −3.36%
● ●(−4.04%;−2.68%)
●
●
● ●
● ● ●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Peptic ulcer (F) France
●
●
1.2
●
●
●
●
●
PAC: 3.27% (2.85%;3.69%)
●
1.0
●
● ●
●
PAC: −6.66%●(−7.13%;−6.2%)
●
● ●
● ●
0.8
●
●
●
5% (10.57%;20.66%)
●
●
●
●
0.6
●
●
●
●
PAC: −3.21%
● (−3.9%;−2.53%)
●
●
● ●
●
1970
1975
1980
1985
1990
xyear
188
1995
2000
●
2005
12
Peptic ulcer (M) Germanyeast
●
●
●
PAC: −4.28% (−5.33%;−3.21%)
●
PAC: 15.63% (8.29%;23.47%)
●
10
●
●
●
●
8
●
●
●
●
PAC: −9.07% (−9.76%;−8.37%)
6
●
●
●
●
●
4
PAC: −0.97% (−2.37%;0.45%)
●
1980
1985
1990
●
1995
●
●
●
●
●
●
2000
2005
xyear
Peptic ulcer (F) Germanyeast
●
●
4.0
●
●
PAC: 0% (−0.66%;0.66%)
●
●
●
●
●
●
3.5
●
●
●
●
PAC: −5.21%
● (−5.98%;−4.44%)
3.0
●
●
PAC: −15.2% (−23.54%
PAC: 3.69% (1.28%;6.16%)
●
●
●
●
2.5
●
●
●
●
●
1980
1985
1990
1995
xyear
189
2000
2005
12
Peptic ulcer (M) Germanywest
: −1.14%
(−1.77%;−0.51%)
●
●
● ●
●
●
●
●
8
PAC: −7.05%
(−7.36%;−6.74%)
●
●
●
●
●
6
10
●
●
●
● ●
●
●
PAC: −4.38%
● (−4.67%;−4.1%)
●
4
● ●
●
1970
1975
1980
1985
1990
●
●PAC: −2.8%
● ● ●
●
1995
(−3.39%;−2.22%
● ●
● ●
2000
●
2005
xyear
Peptic ulcer (F) Germanywest
●
●
PAC: 3.2% (1.68%;4.74%)
3.5
●
●
●
●
●
●
●
●
●
●
3.0
●
●
PAC: −2.44% (−2.58%;−2.3%)
●
●
●
●
●
●
●
2.5
●
●
●
●
●
●
PAC: 0.04%
(−0.45%;0.53%
●
●
● ●
●
●
● ●
2.0
2% (−2.45%;4.62%)
1970
1975
1980
1985
1990
xyear
190
1995
2000
●
2005
Peptic ulcer (M) Netherlands
●
7
●
●
PAC: −5.17% (−5.99%;−4.35%)
●
●
●
5
●
●
●
4
● ●
●
●
PAC: −4.11%
(−4.82%;−3.4%)
●
●
●
●
●
3
6
●
●
●
●
●
●
PAC:
(−4.68%;−3.28%)
● −3.98%
●
●
2
● ●
● ●
●
PAC: −21.08%
(−32.6
● ●
●
●
●
1
●
1970
1980
1990
2000
xyear
Peptic ulcer (F) Netherlands
●
3.0
●
●
2.5
●
●
●
PAC: −1.88% (−2.25%;−1.52%)
●
● ●
● ●
●
●
●
● ●
●
2.0
●
●
●
●
●
●
●
PAC: −5.82% (−7.85%;−3.74%)
PAC:
● ● 1.54% (−1.31%;4.48%)
●
1.5
●
● ●
●
●
●
●
PAC: −13.86% (−17.16%;−
● ●
1.0
●
●
1970
1980
1990
xyear
191
2000
Peptic ulcer (M) Spain
14
●
●
●
●
●
10
●
●
8
●
● (−9.2%;−8.68%)
PAC: −8.94%
●
6
●
●
●
●
●
4
12
2% (13.03%;24.69%)
● ●
●
PAC:
(−5.25%;−4.13%)
● −4.69%
●
●
●
● ●
● ● ●
2
PAC:
● ●−8.61% (−9.32%;−7.89%)
●
1970
1980
1990
●
● ● ●
● ●
● ●
2000
xyear
3.0
Peptic ulcer (F) Spain
2.67%●(−4.7%;−0.61%)
●
●
●
●
●
●
2.0
PAC: −5.84% (−6.37%;−5.31%)
● ●
1.5
● ●
● ●
●
●
●
●
● −3.29%
● (−3.87%;−2.71%)
PAC:
●
●
1.0
● ● ●
● ● ●
● ●
PAC: −8.67%
(−9.55%;−7.78%)
●
● ●
0.5
2.5
●
● ● ●
1970
1980
1990
xyear
192
2000
●
●
Peptic ulcer (M) Sweden
●
14
● (−1.09%;5%)
: 1.91%
●
●
12
10
●
●
●
PAC: −7.33% (−7.96%;−6.69%)
●
●
8
●
●
●
●
PAC: 1.55% (−0.78%;3.94%)
● ●
● ●
6
●
●
●
●
● ●
●
●
PAC: −5%
(−5.53%;−4.47%)
4
●
●
●
●
●
●
● ●
●
●
●
2
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
7
Peptic ulcer (F) Sweden
●
% (−0.67%;245.43%)
●
●
●
● ●
5
PAC: −5.1% (−5.71%;−4.49%)
● ●
●
4
● ●
●
●
●
PAC:
−1.4% (−2.92%;0.14%)
● ● ● ●
●
3
●
●
●
●
●
●
PAC:
−4.89% (−5.52%;−4.25%)
2
●
●
● ●
● ●
● ●
●
●
●
1
6
●
1970
1975
1980
1985
1990
xyear
193
1995
2000
2005
Peptic ulcer (M) UK
●
●
●
●
●
●
9
10
0.65% (−0.52%;1.84%)
●
●
●
●
8
●
●
PAC: ●
−2.86% (−2.99%;−2.73%)
●
●
7
●
●
●
●
●
●
6
●
●
●
PAC:
● 0.54% (−0.46%;1.54%)
●
●
●
●
●
5
●
PAC: −4.64%
(−5.33%;−3.9
● ●
●
●
4
● ●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
5.0
Peptic ulcer (F) UK
●
● ●
●
●
PAC: 2.44% (2.13%;2.75%)
●
●
●
PAC: −2.3% (−2.53%;−2.08%)
●
●
● ●
●
●
4.0
●
●
●
●
●
●
●
●
●
●
●
3.5
PAC:
● −1.38%
●
● (−1.8%;−0.96%)
●
●
●
● ●
3.0
●
PAC: −9.12% (−11%;
●
2.5
4.5
●
●
1970
1975
1980
1985
1990
xyear
194
1995
2000
2005
18
Renal failure (M) France
●
●
●
●
AC: −2.93% (−3.41%;−2.44%)
●
PAC: 3.65% (1.6%;5.73%)
●
●
14
●
●
●
12
● ●
●
●
PAC: −4.62% (−4.84%;−4.4%)
●
●
10
16
●
●
● ●
8
● ●
PAC: −0.6%
● ●
●
●
●
●
(−0.81%;−0.39%)
●
●
●
1970
1975
1980
1985
1990
1995
● ●
2000
●
● ●
2005
xyear
9
Renal failure (F) France
●
● ●
●
●
PAC: −1.47% (−1.75%;−1.19%)
●
●
●
●
●
7
●
●
●
6
PAC: −5.2%●(−5.47%;−4.93%)
●
●
5
●
● ●
●
●
PAC: −2.17%
● (−2.49%;−1.84%)
●
4
8
●
● ● ●
PAC: 1.24% ●(0.68%;1.8%
●
●
●
1970
1975
1980
1985
1990
xyear
195
1995
●
●
● ●
●
2000
2005
Renal failure (M) Germanyeast
●
7
PAC: 2.37% (0.47%;4.31%)
●
●
●
●
●
6
●
PAC: 6.6% (4.11%;9.16%)
PAC:
−7.55% (−10.45%;−4.55%)
●
●
●
●
5
●
●
●
●
●
●
PAC: 7.64% (6.77%;8.52%)
4
●
●
●
●
3
●
●
●
●
●
1980
1985
1990
1995
2000
2005
xyear
Renal failure (F) Germanyeast
●
PAC: 4.36% (2.24%;6.5
5
●
●
●
PAC: 7.12% (5.26%;9.01%)
4
●
●
PAC: −0.9%●(−2.81%;1.05%)
●
●
●
●
●
●
3
●
●
●
PAC: 7.59% (6.74%;8.44%)
●
2
●
●
●
●
●
●
●
●
●
1980
1985
1990
1995
xyear
196
2000
2005
Renal failure (M) Germanywest
10
●
● ●
● ●
●
9
PAC: −5.41% (−5.91%;−4.91%)
●
C: 6.4% (5.47%;7.35%)
●
●
●
●
●
PAC: 2.23%●(1.98%;2.48%)
●
●
●
8
●
●
●
●
●
●
●
●
PAC: −0.15% (−0.37%;0.08%)
●
●
●
●
●
●
●
7
●
●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
7.0
Renal failure (F) Germanywest
●
●
●
6.0
●
PAC: 4.74% (4.42%;5.06%)
●
●
●
5.5
PAC: −6.14% (−6.77%;−5.52%)
●
●
●
C: 6.13% (5.19%;7.09%) ●
●
●
●
5.0
●
●
●
●
●
●
PAC: ●0.09% (−0.05%;0.24%)
●
●
●
●
●
●
●
●
4.5
6.5
●
●
● ●
●
●
●
1970
1975
1980
1985
1990
xyear
197
1995
2000
2005
Renal failure (M) Netherlands
9
●
●
●
●
PAC: −5.58% (−6.8%;−4.33%)
●
8
●
● (0.13%;0.73%)
PAC: 0.43%
●
●
7
●
●
●
●
●
●
●
● ●
●
●
●
6
●
●
●
5
PAC: 83.87% (72.11%;96.44%)
●
●
4
●
●
●
●
PAC: 3.16% (1.9%;4.44%)
●
●
●
●
3
●
●
●
●
1970
1980
1990
2000
xyear
7
Renal failure (F) Netherlands
●
● ●
●
6
●
●
●
●
● ● ●
5
●
●
PAC: 3.84% (1.47%
●
●
PAC: 46.1% (41.64%;50.7%)
●
●
●
●
4
3
●
●
●
●
PAC: 2.88% (1.49%;4.28%)
●
●
●
●
●
●
1970
● ●
● ●
●
●
2
●
● −1.88% (−2.1%;−1.66%)
PAC:
●
1980
1990
xyear
198
2000
Renal failure (M) Spain
18
16
●
●
●
●
●
● ●
14
●
PAC: −5.24% (−5.74%;−4.74%)
●
.51% (−21.78%;−19.22%)
PAC: 2.96% (2.72%;3.19%)
●
●
●
●
●
12
20
●
● ●
● ●
PAC:●−0.98%
(−1.21%;−0.74%)
● ●
●
● ●
●
●
●
●
●
●
●
●
10
●
●
●
●
●
1970
1980
1990
2000
xyear
●
●
●
●
9
●
●
●
●
PAC:
−3.23% (−3.52%;−2.94%)
8
● ●
●
●
●
0.44% (−21.7%;−19.16%)
●
PAC: 4.57% (4.3%;4.84%)
7
●
●
●
●
●
PAC: −0.66%
● (−0.95%;−0.37%)
●
●
● ●
●
●
●
●
●
●
●
6
●
●
●
●
●
5
10
11
Renal failure (F) Spain
●
1970
1980
1990
xyear
199
2000
●
Renal failure (M) Sweden
●
●
●
● (−0.73%;0.54%)
PAC: −0.1%
●
●
●
●
●
●
● ●
●
●
● ●
●
●
4
PAC: 6.35% (4.99%;7.73%)
●
●
●
3
● ●
PAC: 45.56% (33.23%;59.03%)
●
2
5
●
●
●
PAC:
1.39% (−0.68%;3.49%) ●
●
● ●
●
●
●
●
1
● ●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
3.0
Renal failure (F) Sweden
●
●
PAC: 0.22% (−0.78%;1.23%)
2.5
●
●
●
2.0
●
●
●
●
●
●
●
●
PAC: 4.58%●(3.73%;5.44%)
●
●
1.5
●
●
●
●
1.0
●
PAC: 97.73% (64.2%;138.11%)
●
●
●
PAC: −0.71% (−3.37%;2.02%)
● ●
●
● ●
●
0.5
●
●
●
●
●
1970
●
●
1975
1980
1985
1990
xyear
200
1995
2000
2005
18
Renal failure (M) UK
●
●
●
16
●
●
● ●
●
PAC: 3.34% (2.83%;3.84%)
PAC: −3.76% (−4.17%;−3.35%)
14
●
●
●
● ● ●
●
12
●
●
●
10
●
8
●
6
●
●
PAC: −44.61% (−46.03%;−43.14%)
● ●
PAC: −1.23% (−1.56%;−0.91%)
● ●
4
● ●
● ● ● ●
1970
1975
1980
1985
1990
1995
● ●
●
● ●
2000
2005
xyear
Renal failure (F) UK
●
10
●
●
●
PAC: −3.49%●(−3.93%;−3.05%)
●
●
● ●
PAC: 5.03% (4.56%;5.51%)
●
8
●
●
●
●
●
6
●
● ●
●
●
●
PAC: −22.77% (−23.47%;−22.07%)
4
●
● ●
1970
1975
1980
1985
1990
xyear
201
PAC: −0.05% (−0.38%;0.28%)
● ●
●
●
● ● ●
●
1995
2000
●
● ● ●
●
2005
Appendix E: Standardized mortality trends (ages 0-74), Percent
Annual Chance (PAC) for each period (with confidence intervals),
by gender (M/F) and by country (alphabetical order)
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
Malignant neoplasm of cervix uteri (F) Estonia
●
12
●
●
●
10
PAC: −3.62%
(−5.01%;−2.22%)
●
● ●
●
● ●
●
●
●
●
●
●
●
8
PAC: 8.15% (−1.33%;18.53%)
PAC: −1.08% (−3.46%;1.37%) ●
●
●
●
●
●
●
PAC: −3.91% (−5.56%;−2.23%)
●
●
●
●
6
●
●
●
● ●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Malignant neoplasm of cervix uteri (F) France
●
3.0
27.47% (3.06%;57.66%)
●
●
●
●
●
●
●
●
PAC: −1.68% (−2.08%;−1.28%)
●
●
●
●
2.5
●
●
●
●
●
●
PAC: −2.82% (−3.23%;−2.4%)
●
●
●
●
●
2.0
●
●
●
●
PAC: −1.19% (−1.92%;−0.46%)
●
●
1970
1975
1980
1985
1990
xyear
223
1995
●
●
2000
●
●
●
●
2005
9
Malignant neoplasm of cervix uteri (F) Germanyeast
●
●
PAC: −2.62% (−3.71%;−1.51%)
●
●
●
8
●
●
●
7
●
PAC: −4.09% (−4.89%;−3.28%)
●
6
●
●
●
●
●
5
●
●
●
PAC: −5.72% (−6.88%;−4.54%)
●
4
●
PAC: −2.73% (−5.39%;0%)
●
●
●
●
●
3
●
1980
1985
1990
1995
2000
2005
xyear
Malignant neoplasm of cervix uteri (F) Germanywest
PAC: −0.9% (−1.87%;0.07%)
●
7
●
●
●
●
●
●
●
●
●
●
5
●
●
●
●
●
PAC: −3.52% (−3.74%;−3.3%)
4
●
●
●
●
●
●
●
●
3
6
PAC: −5.07% (−5.59%;−4.54%)
●
●
●
●
●
PAC: −2.62% (−3.14%;−2.1%)
●
●
●
●
●
●
1970
1975
1980
1985
1990
xyear
224
1995
2000
●
2005
Malignant neoplasm of cervix uteri (F) Netherlands
●
6
●
●
●
5
●
● ●
●
PAC: −4.36%
(−4.65%;−4.07%)
●
4
●
●
●
●
●
●
●
●
3
●
●
●
● ●
●
PAC: 1.66% (−1.36%;4.78%)
2
●
● ●
●
PAC: −19.29%
● (−26.58%;−11.27%)
●
●
●
●
PAC:●2.04% (−1.87%;6.1
●
●
1970
1980
1990
●
● ●
2000
xyear
Malignant neoplasm of cervix uteri (F) Spain
●
●
PAC: 0.83% (−0.22%;1.88%)
●
●
●
●
●
●
●
●
2.0
●
PAC: −2.18% (−3.04%;−1.31%)
●
●
1.5
●
●
●
●
●
●
●
●
●
●
1970
●
●
●
●
●
●
●
●
1.0
●
PAC: 4.54% (4.04%;5.04%)
PAC: 1.92% (−1.44%;5.39%
●
●
●
●
●
1980
1990
xyear
225
2000
●
Malignant neoplasm of cervix uteri (F) Sweden
7
●
●
●
6
●
●
●
●
●
5
●
●
●
●
●
●
●
4
PAC: −4.08% (−4.79%;−3.37%)
●
●
●
PAC: −4.53% (−5.45%;−3.6%)
3
●
●
●
●
●
PAC: 0.63% (−2.67%;4.05%)
●
●
●
●
●
●
● PAC:
●
−3.97% (−6.87%;−0.98%)
●
●
2
●
●
●
●
1970
1975
1980
1985
1990
1995
2000
2005
xyear
Malignant neoplasm of cervix uteri (F) UK
●
●
●
● (−1.76%;−1.22%)
PAC: −1.49%
7
●
●
●
●
●
●
●
●
PAC: 0.49% (−0.52%;1.51%)
●
●
●
●
●
●
●
5
●
●
●
PAC: −6.58% (−6.99%;−6.17%)
4
●
●
●
●
●
3
●
●
●
PAC: −4.91% (−5.68%;−4.14%)
●
●
●
●
●
●
2
6
●
1970
1975
1980
1985
1990
xyear
226
1995
2000
2005
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
Appendix F. Vignettes send out for Delphi exercise (Chapter 7)
Cause of death
Trends in incidence
Number of deaths in 2000: UK
(2001), Netherlands, Spain,
Hungary
Death rate trend (% reduction
1979-2000, E&W)
Published evidence from clinical
research
Published evidence of
improvements in population
outcomes
Mortality trends
Observed associations between
population level mortality and
specific interventions in our
analysis of 7 European countries
HIV/AIDS
Varies among countries, reflecting patterns of sexual
behaviour and, especially, migration
198/132/1,711/15
n/a (AIDS not identified in 1979)
The mainstay of treatment has been antiretroviral drugs,
beginning with azidothymidine (AZT). The first RCT of AZT in
patients with acquired immunodeficiency syndrome (AIDS)
found that, over a period of 8-24 weeks, mortality among
those receiving AZT was <1% and among controls was 14%
while all intermediate measures (opportunistic infections,
CD4 counts) were significantly better in the intervention
group Subsequent developments have included a range of
additional antiretroviral drugs that are now administered in
combination therapy to reduce the risk of resistance,
prophylaxis against maternal to child transmission (now
reduced to 2% with optimal treatment), improved and
earlier diagnosis, and improved management of
complications.
Between 1996 and 1998, HIV-related mortality decreased by
60% in the United States of America (USA) regardless of sex,
race, age, and risk factors for transmission of HIV, coinciding
with the introduction of antiretroviral drugs. There has
been a similar decline in AIDS-related deaths in Europe.
After steep increases in mortality from AIDS in the late 1980s
and early 1990s, there was a sudden decline, beginning in
the mid 1990s. For males in Estonia we see an exceptional
increase in mortality after 2002 (low female death rates
made it impossible to discern a clear trend).
We looked at the association between the introduction of
AZT and mortality in each country. The introduction of
antiretroviral drugs coincided with a favourable change in
mortality trend in 6 out of 7 countries.
300
Distribution of scores
1st round
HIV_AIDS
Scores
1
2
Number of
responses
Total (%)
3
4
5
6
7
8
9
Total
2
1
5
3
6
4
2
23
9%
4%
22%
13%
26%
17%
9%
100%
9
Total
2nd round
HIV_AIDS
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
1
1
5
2
10
4
4%
4%
22%
9%
43%
17%
23
100%
*Cell shaded in RED represents the MEDIAN; those shaded in YELLOW represent the range after excluding
outliers where only a single person has allocated a score
301
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Malignant neoplasm of rectum and colon
Increasing, in part due to increased obesity
16,195/4,300/11,653/4,886
31
Historically, the mainstay of treatment was surgical
resection, with progressive advances in surgical technique as
well as general improvements in the safety of major
abdominal surgery. However, no RCT’s have been performed
comparing surgical resection with older forms of treatment.
The addition of chemotherapy in patients following curative
resection seems to confer a small survival benefit. One RCT
showed that the addition of chemotherapy to radical surgery
reduced mortality by 18%. Oxaliplatin is a constituent of the
most common chemotherapy regimes and is widely believed
to reduce the rate of recurrence but its individual effects
are difficult to disentangle from the other treatments it is
used with.
RCTs examining different forms of surgical treatment of
colo-rectal cancer have largely compared open and
laparoscopic methods, finding little difference in outcome.
More recently, attention has turned to screening for early
disease. Faecal-occult-blood (FOB) screening undertaken in
an unselected population-based RCT showed a 15% reduction
in cumulative colorectal cancer mortality in the screening
group (a recent systematic review found a reduction of 25%).
A RCT in people aged 50-64 found a 23% reduction in cancer
mortality among those having a single screening
sigmoidoscopy.
There have been no RCTs of the use of colonoscopy for
screening (a large European one will report in 2026).
However, a case control study reported a reduction in
advanced cancer of almost 50% in those who have previously
undergone colonoscopy.
Reliable population-based data from the 1970s report five
year survivals of about 40%. By the mid 1990s this had
increased to 55% (colon cancer) and 53% (rectal cancer). In
some countries, five-year survival is now about 60%, a 50%
improvement since 1970.
Mortality trends from colorectal cancer are very diverse,
with most countries showing steep mortality declines but
Spain and Estonia showing increasing mortality, giving rise to
a degree of convergence.
We looked at the association between mortality and
introduction of two interventions, Oxaliplatin in
chemotherapy regimes and the introduction of screening
sigmoidoscopy. The introduction of treatment with
Oxaliplatin coincided with a favourable change in mortality
in 2 out of 7 countries. The introduction of diagnostic
examination with colonoscopy or sigmoidoscopy coincided
with a favourable trend in mortality in 5 out of 6 countries
for which information was available, but in one of these
countries the effect was only seen in men.
302
1st round
Scores
1
2
Number of
responses
Total (%)
3
4
5
6
7
8
9
Total
1
2
2
4
9
3
2
23
4%
9%
9%
17%
39%
13%
9%
100%
9
Total
2nd round
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
23
1
5
13
4
4%
22%
57%
17%
100%
*Cell shaded in RED represents the MEDIAN; those shaded in YELLOW represent the range after
excluding outliers where only a single person has allocated a score
303
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Decreasing
1,183/258/597/481
57
Five randomised trials of concurrent chemo-irradiation for
patients with locally advanced cervical cancer showed that
overall mortality and recurrence was reduced by 50%.
However, the outcome for metastatic disease is very poor
and, ultimately, therapy is palliative in nature. Although
cervical cancer screening is widely believed to reduce
mortality from cervical cancer, no RCTs have ever been
performed.
Organised population-based screening programmes have
been linked to a reduction in mortality. Sweden experienced
a reduction in cervical cancer of 50% between 1965 and
1982. Denmark, whose organised programmes covered only
40% of the population, experienced a reduction of 25%, while
in Norway, where only 5% of the population were covered,
mortality fell by only 10%. The UK, which at the time offered
only opportunistic screening, saw a decrease in mortality of
only 7% between 1974 and 1982 and incidence fell by 42 per
cent between 1988 and 1997.
Five year survival of invasive cancer increased only from 61
to 64% between the late 1970s and mid 1990s across
Northern Europe.
All countries show a steep continuous decline in mortality
from cervical cancer, except for Spain that experienced an
increase but which levelled off after 1989.
The introduction of cervical cancer screening coincided
with a favourable change in mortality trend in 2 out of 5
countries for which information was available.
304
1st round
Scores
1
2
3
Number of
responses
Total (%)
4
5
6
7
8
9
Total
1
3
5
6
5
3
23
4%
13%
22%
26%
22%
13%
100%
2nd round
Scores
1
2
3
4
5
Number of
responses
Total (%)
6
7
8
9
Total
6
9
7
1
23
26%
39%
30%
4%
100%
305
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Malignant neoplasm of the testis
Increasing (reasons unknown)
69/25/43/48
68
Testicular cancer has been described as one of the success
stories of modern medicine, with overall cure rates of over
90% in this disease which is believed to have been universally
fatal. The main breakthrough was the introduction of
combination chemotherapy in the late 1960s. This was
followed by further improvements in the chemotherapy
regime, particularly through the introduction of Cisplatin in
the 1980s. More recently the focus has been on reducing
toxicity of treatment. We have not found RCTs documenting
a mortality lowering effect of chemotherapy (versus no
chemotherapy). A systematic review looked at different
combinations of treatment. Two-drug compared with fivedrug regimen may not increase overall survival rates at 5
years in men with good-prognosis, or mixed tumours, but
may reduce toxicity, compared with a five-drug regimen.
Data from the EUROCARE study shows an increase in fiveyear survival from 79 to 93% between the late 1970s and the
late 1990s.
All countries show declining mortality from testicular cancer
throughout the study-period (i.e. since at least the early
1970s), although these began to level out in the 1990s. In
Spain the decline is preceded by a sharp increase in
mortality.
The introduction of treatment with Cisplatin coincided with
a favourable change in mortality in 2 out of 7 countries.
306
1st round
Scores
1
Number of
responses
Total (%)
2
3
4
5
6
7
8
9
Total
2
2
1
5
2
4
4
3
23
9%
9%
4%
22%
9%
17%
17%
13%
100%
2nd round
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
9
Total
1
1
2
4
6
6
2
1
23
4%
4%
9%
17%
26%
26%
9%
4%
100%
307
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Hodgkin’s disease
Stable
265/86/280/106
65
Previously believed to be uniformly fatal, effective
treatment for Hodgkins Disease was introduced in the 1940s,
involving various combinations of radiotherapy and alkylating
agents. A major breakthrough occurred in the late 1960s
with the introduction of combination chemotherapy. The
mainstay of treatment in the USA is now ABVD (Adriamycin,
bleomycin, vinblastine, and dacarbazine) while in Europe a
regime termed BEACOPP is more often used (comprising, in
addition, cyclophosphamide, prednisone, and etoposide).
More recently high dose therapy and blood cell
transplantation were introduced; We have not found RCTs
documenting treatment effects of combination
chemotherapy or high dose therapy and blood cell
transplantation on mortality.
Five-year relative survival for Hodgkin’s disease improved
from 24 to 41% between 1940 and 1964. Currently, five year
survival varies by stage of disease but ranges from 85-98%
In all countries mortality from Hodgkin’s disease has
decreased throughout the study-period, although with
several fluctuations. In Germany the decline in mortality is
preceded by a short period of increasing mortality before
1980.
The main treatment regimes were already in use in the
1970s so we looked at the introduction of high dose therapy
and peripheral blood stem cell transplantation. This
coincided with a favourable change in mortality trend only
for females in 1 out of 6 countries for which information was
available. The Soviet classification of disease used in Estonia
before the mid 1990s did not separately identify Hodgkins
Disease.
308
1st round
Hodgkin’s disease
Scores
1
Number of
responses
Total (%)
3
4
5
6
7
8
9
Total
2
2
2
2
4
4
5
2
23
9%
9%
9%
9%
17%
17%
22%
9%
100%
9
Total
2
2nd round
Hodgkin’s disease
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
2
5
4
9
3
23
9%
22%
17%
39%
13%
100%
309
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Rheumatic heart disease
Decrease
1,525/15/1,800/401 (the low figure for the Netherlands may
reflect a coding issue)
77
The much more widespread use of antibiotics for
streptococcal infections, which already started in the 1940s,
has been linked to the declining incidence of rheumatic
fever, although there are no relevant RCTs.
Once rheumatic fever occurs, aspirin is commonly used to
prevent cardiac damage. However one RCT showed that
patients treated with aspirin for 12 weeks had a similar
prevalence of murmurs 1 year later as did untreated
controls. Findings of meta-analyses indicate no benefit of
salicylates over corticosteroids or vice-versa in reducing the
subsequent development of rheumatic heart disease.
Damaged heart valves are treated surgically, according to
the nature of the valve disease. Again, there are no RCTs but
much observational evidence of improvement in cardiac
function.
Deaths from rheumatic heart disease have fallen rapidly.
However, studies have found it difficult to distinguish and
quantify the contributions of the various factors implicated.
They include improvements in living conditions, leading to
lower rates of streptococcal infections, antibiotic treatment
of these infections, possibly the use of salicylates in acute
rheumatic fever, and advances in valve surgery for
established disease.
Mortality from rheumatic heart disease continued to decline
steeply in most countries in the 1970s. In France and
Estonia, however, there was a short period of increasing
mortality in the 1970s and early 1980s.
We examined the effect of artificial valve replacement.
This coincided with a favourable change in the mortality
trend in 2 out of 3 countries for which information was
available. In both cases this was only apparent for one sex.
310
1st round
Rheumatic Heart Disease
Scores
1
2
3
Number of
responses
2
1
9%
4%
Total (%)
5
6
7
8
9
Total
3
4
3
3
5
2
23
13%
17%
13%
13%
22%
9%
100%
9
Total
4
2nd round
Scores
1
Number of
responses
Total (%)
2
3
4
5
6
7
8
2
1
3
8
5
4
23
9%
4%
13%
35%
22%
17%
100%
311
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Hypertension
Not known (as definitions have changed)
3,703/797/5,055/4,729
66
Large clinical trials have found that antihypertensive drugs
are effective in reducing cardiovascular morbidity and
mortality in patients with mild hypertension.
Some of the earliest drugs, such as reserpine and clonidine,
are now largely abandoned and the remaining classes,
including beta-blockers, calcium channel blockers, reninangiotensin system inhibitors, and thiazide diuretics are all
very effective in lowering blood pressure, with the choice
largely being determined by the potential for other effects
that may be important in an individual patient.
The introduction of thiazide diuretics in the early 1960s and
the publication of major studies in the UK and USA showing
that treatment reduced subsequent strokes markedly
changed the management of hypertension. Initially,
treatment was limited to younger people with severe
hypertension but the threshold for treatment has steadily
lowered. Historical studies show a progressive increase in
the percentage of people whose hypertension is controlled,
with treatment increasingly involving beta blockers,
introduced in the mid-1970s, and angiotensin-converting
enzyme (ACE) inhibitors and calcium antagonists (CAs),
introduced in the 1980s, often in combination, although
there is no evidence that they achieve better control than
thiazides alone.
In almost all countries mortality from hypertension
decreased in the 1970s, and in some countries it increased
again in the 1990s resulting in a U-shaped trend in mortality.
In France mortality from hypertension has increased,
followed by a sharp decrease in the late 1980s. In Estonia a
very limited decline of mortality was observed followed by a
sharp increase after 1995.
Evidence of expansion of drug treatment of hypertension
coincided with a favourable change in the mortality trend in
2 out of 6 countries for which information was available.
312
1st round
Hypertension
Scores
1
2
Number of
responses
Total (%)
3
4
5
6
7
8
9
Total
4
1
4
3
6
4
1
23
17%
4%
17%
13%
26%
17%
4%
100%
9
Total
2nd round
Hypertension
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
1
1
1
8
10
2
23
4%
4%
4%
35%
43%
9%
100%
313
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Ischaemic heart disease (IHD)
Decrease due to reduced risk factors (especially smoking)
121,168/17,443/39,315/29,799
56
The management of acute myocardial infarction has been
transformed, although by many different interventions
rather than a single one. These interventions include
thrombolytic drugs (e.g. streptokinase), acute reperfusion
(e.g, angioplasty), and improved treatment of arrhythmias.
A large meta-analysis reported a reduction of mortality after
myocardial infarction associated with streptokinase of about
25%.
Coronary care units: A RCT published in 1976 compared
outcome in men with an acute myocardial infarction
allocated either to home care or admission to an intensive
care unit. Mortality was slightly higher in those admitted to
an intensive care unit.(Mather et al. 925-29) Clearly, the
scope of treatment available now is vastly different from
that in the early 1970s but it remains the case that the
benefits of admission to a coronary care unit remain
unproven in RCTs.
Trials of secondary prevention with drugs: Three RCTs
revealed that the regular oral use of these beta blockers
after acute myocardial infarction resulted in a significant
reduction in total mortality, averaging about 35% at one year
with evidence of continued effect as long as three years
after infarct. Two RCTs, confirmed that betablockers
prolong life in post-Ml patients.
The substantial decline in deaths from ischaemic heart
disease over the past three decades is believed to be due to
a combination of a reduction in exposure to risk factors,
especially smoking and diet, and improvements in health
care.
In many European countries, mortality from IHD has declined
since the 1970’s but with variations in the speed of mortality
decline. This decline was preceded by an increase in
mortality in the early 1970s in some countries.
The introduction of beta-blockers as secondary prevention
of ischemic heart disease coincided with a favourable
change in mortality trend in 5 out of 7 countries, however in
1 country this was observed only for men. The introduction
of coronary care units coincided with a favourable change
in mortality trend in 3 out of 5 countries for which
information was available, but only in one out of the 3
countries was the effect seen for both sexes.
314
1st round
Ischaemic heart disease
Scores
1
2
3
Number of
responses
Total (%)
4
5
6
7
8
9
Total
3
3
5
6
5
1
23
13%
13%
22%
26%
22%
4%
100%
9
Total
2nd round
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
2
6
10
5
23
9%
26%
43%
22%
100%
315
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Heart failure
Decrease, due to reduced risk factors for and better
treatment of heart disease
11,517/5,908/18,990/818
64
A systematic review of a number of small RCTs indicated a
possible benefit from diuretics in terms of mortality,
compared to placebo. Although digitalis has been the
mainstay of treatment of heart failure for over two
centuries, while improving symptoms its effect on mortality
from heart failure is less clear. This was addressed in a
Cochrane review which included 13 RCTs. . There was no
evidence of a significant difference in mortality between the
digitalis treatment and control groups. All-cause mortality
did not differ between the digoxin and placebo groups
(34.8% compared to 35.1%). However, a systematic review of
five trials found that ACE-inhibitors significantly reduced
the number of deaths compared with placebo showing an
improvement in survival by 16%.
A study of hospitalised heart failure patients in Scotland
between 1986 and 1995 found a decline in 30 day case
fatality rates of 26% in men and 17% in women, after
adjustment for severity. The precise reasons for this
improvement have not been quantified although the role of
earlier initiation and better management of treatment is
believed to be responsible.
In most countries mortality from health failure decreased
steeply in the 1970s, but the decline slowed down in later
decades, and in some countries periods of decreasing
mortality alternate with periods of increasing mortality. In
East-Germany we see a strong acceleration of mortality
decline after 1990.
The introduction of ACE inhibitors for treatment of heart
failure coincided with a favourable change in the mortality
trend in 2 out of 6 countries for which information was
available. The Soviet classification of disease used in Estonia
before the mid 1990s did not separately identify heart
failure.
316
1st round
Heart failure
Scores
1
2
3
4
5
6
7
8
Number of
responses
1
1
1
2
5
4
4
5
4%
4%
4%
9%
22%
17%
17%
22%
Total (%)
9
Total
23
100%
2nd round
Heart failure
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
1
1
1
8
5
4
3
4%
4%
4%
35%
22%
17%
13%
9
Total
23
100%
317
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Stroke /Cerebrovascular Disease
Decrease
66,838/12,184/36,596/18,939
58
Early RCTs of the effect of antihypertensives in
hypertension showed that they reduced deaths from stroke
(MRC trial of treatment of mild hypertension: principal
results. Medical Research Council Working Party 97-104;Freis
76-77;Gifford S17-S18;Hypertension Detection and Follow-up
Program Cooperative Group 633-38;Turnbull 1527-35). The
introduction of stroke units with intensive management of
stroke patients has been shown in RCTs to reduce mortality
at 1 and 5 years, although interpretation is complicated by
the difficulty in defining the intervention.
A major breakthrough came in the 1960s with the
publication of two studies showing that control of essential
hypertension reduced the incidence of stroke. Subsequent
declines in stroke incidence have been attributed primarily
to better control of hypertension. There is, however, also
evidence of a decline in case fatalities, in one American
study from 33% in 1967-71 to 18% in 1981-85.
In all countries mortality from cerebrovascular disease has
decreased markedly throughout the study-period with
several fluctuations of this decline. The exceptions are
Estonia and East Germany where mortality was almost stable
until 1993, followed by a steep decline.
The introduction of antihypertensive drug treatment to
prevent stroke coincided with an acceleration of mortality
decline in 5 out of 7 countries. The introduction of intensive
management of acute stroke coincided with an acceleration
of mortality decline in 4 out of 5 countries for which
information was available, although in one country this was
only seen for men.
318
1st round
Stroke/Cerebrovascular disease
Scores
1
2
3
Number of
responses
Total (%)
6
7
8
9
Total
1
3
9
8
2
23
4%
13%
39%
35%
9%
100%
4
5
2nd round
Stroke/Cerebrovascular disease
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
9
Total
1
2
10
9
1
23
4%
9%
43%
39%
4%
100%
319
Cause of death
Trends in incidence
(2001), Netherlands, Spain, Hungary
Death rate trend (% reduction 19792000, E&W)
research
outcomes
Mortality trends
specific interventions in our analysis
of 7 European countries
Peptic ulcer
Decrease, due to declining rates of infection with
Helicobacter Pylori in each generation.
4,191/392/753/942
40
Treatment of peptic ulcer was transformed in the early
1980s by the discovery of Cimetidine, the first H2 blocker,
prior to which it mainly involved conservative treatment
(diet and bed rest) or surgery, which was associated with
often severe side effects.
Early RCTs comparing Cimetidine and placebo are difficult
to interpret due to methodological inconsistencies and
design problems. A review of 16 RCTs testing cimetidine in
endoscopically documented duodenal ulcer concluded that
variations in study methodology explained such disparate
results.
The main source of evidence for population-level
effectiveness of treatment is the observation of period
effects in mortality data since the advent of H2 blocking
drugs in the 1980s. An age-period-cohort analysis between
1955 and 1989 in 24 European countries found that
mortality declined by an overall 25% in the West and 15% in
the East. Earlier declines for males in Western Europe were
chiefly related to a cohort effect suggesting a historic
decline in childhood infection with Helicobacter Pylori.
In most countries mortality from peptic ulcer has
decreased throughout the study-period. Only for women in
the UK and France there was a steep increase until the
early 1980s followed by a steep decline. In Estonia a period
of sharp fluctuations is observed.
The introduction of Cimetidine coincided with a favourable
change in mortality in 2 out of 7 countries, but only for
females.
320
1st round
Peptic ulcer
Scores
1
2
3
4
5
6
7
8
9
Total
Number of
responses
1
3
1
1
2
5
2
6
2
23
4%
13%
4%
4%
9%
22%
9%
26%
9%
100%
6
7
8
9
Total
Total (%)
2nd round
Peptic ulcer
Scores
Number of
responses
Total (%)
1
2
3
4
5
2
1
2
8
7
3
9%
4%
9%
35%
30%
13%
23
100%
321
Cause of death
Trends in incidence
research
outcomes
Mortality trends
specific interventions in our analysis
of 7 European countries
Renal Failure
Increase (in part due to diabetes)
3,567/1,200/5,516/296
57
Although there are many effective treatments for the
range of specific causes of renal failure (e.g. improved
control of diabetes and hypertension, antibiotics for
streptococcal infections that cause acute
glomerulonephritis etc.), the mainstays of treatment of
renal failure as such is dialysis or transplant. Both were
introduced before the 1970s. Although neither has been
evaluated in RCTs, without treatment end stage renal
disease is believed to be uniformly fatal.
Most evidence of effectiveness of treatment has focused on
immunosupression following transplantation. A major
advance was the introduction of Cyclosporin A, in addition
to the first drug to be used, prednisolone. An RCT found
cyclosporin A plus prednisone to achieve an actuarial graft
survival at 1 year of 93% for patients treated with
cyclosporin A and 81% for patients treated with
prednisolone alone.
Studies of the survival of renal failure patients suggest that
advances in transplantation seem to have been more
important than in dialysis. A comparison of cohorts on
treatment from six European registries in 1980-84 and
1995-99 found only a small (12%) reduction in mortality
among those on dialysis but a much greater one (56%)
among those who had received a transplant.
Mortality trends from renal failure are very diverse across
countries with increasing and decreasing trends, as well as
countries with a peak in mortality in the 1980s.
The introduction of immunosuppressive treatment with
Cyclosporine for kidney transplantation coincided with a
favourable change in mortality trend in 3 out of 7 countries
for which information was available. In one country the
association was only seen for men. The Soviet classification
of disease used in Estonia before the mid 1990s did not
separately identify renal failure.
322
1st round
Renal failure
Scores
1
Number of
responses
Total (%)
5
6
7
8
9
Total
1
4
7
5
4
1
23
4%
17%
30%
22%
17%
4%
100%
9
Total
2
3
1
4%
4
2nd round
Renal failure
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
2
10
9
2
23
9%
43%
39%
9%
100%
323
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Congenital heart disease
Stable
821/179/541/176
69
Congenital heart disease is treated largely with heart
surgery. Cardiopulmonary bypass was used in the mid
1950s, followed by deep hypothermia and circulatory
arrest (DHCA) in the late 1960s and early 1970s.No RCTs
have been performed documenting an effect of surgical
repair on mortality . A cohort study of children with one of
eight congenital heart defects repaired surgically showed
that age at surgery and operative mortality decreased
significantly over a 30 year period. Late cardiac mortality
at 25 years after surgery ranged between 17% for aortic
stenosis and and less than 1% for patent ductus arteriosus.
Many of these abnormalities (exceptions being ventricular
and atrial septal defects) were associated with a very high
mortality prior to surgery, which seems to indicate that
advances in surgery have produced substantial reductions
in mortality.
n/a
Trends in mortality have been decreasing steadily in all
countries since 1979 with the exception of Estonia. Since
1989 mortality has been fluctuating in Estonia but at
present is increasing. However, numbers are small.
324
1st round
Scores
1
2
Number of
responses
2
9%
Total (%)
4
5
6
7
8
9
Total
1
2
4
2
6
5
1
23
4%
9%
17%
9%
26%
22%
4%
100%
9
Total
3
2nd round
Scores
1
Number of
responses
Total (%)
2
3
4
5
6
7
8
1
1
1
2
4
8
6
23
4%
4%
4%
9%
17%
35%
26%
100%
325
Cause of death
Trends in incidence
Number of deaths in 2000: UK (2001),
Netherlands, Spain, Hungary
research
Published evidence of improvements
in population outcomes
Mortality trends
Conditions originating in the perinatal period
Stable/ potentially increasing in countries where there are
more IVF related multiple births)
1,937/531/859/534
Coding change
As with some of the other conditions, management has
been transformed by a large number of specific
interventions whose impact on mortality is difficult to
distinguish from each other. These include the whole
panoply of neonatal intensive care, including
administration of surfactant, a substance that is
responsible for maturing of the foetal lungs. In addition,
there has been great progress in miniaturisation of
equipment and in understanding of the physiological
responses of very young babies.
Experiments carried out in the USA, England and Canada
showed that Rh immunisation was prevented by the
administration of Rh antibody A Canadian trial over a twoyear period (1966-1968) looked at the effectiveness of Rh
Immune Globulin in the prevention of primary Rh
immunisation amongst 1216 treated, and 500 non-treated
childbearing women. Given in doses to unimmunised Rh
negative women within three days of the birth of an ABOcompatible, Rh positive baby gives almost 100% protection
against Rh immunisation by the pregnancy.
Although perinatal mortality has fallen steeply in most
countries over recent decades, a number of factors have
played a role. Historically, these have included improved
antenatal care, better care during labour and availability
of antibiotics. However, assessment of recent
developments is complicated by developments such as
changes in maternal age, the number of low birth weight
babies, and multiple deliveries as a consequence of in vitro
fertilization.
Comparisons across countries and over time are
complicated by definitional issues. There have been
substantial declines in perinatal mortality rates. However,
many specific innovations are indicated for only small
proportions of births (rhesus immunisation, 1950s, special
care baby units, 1960s, surfactant, 1990) and the overall
improvements are like to have been due to the incremental
introduction of a wide range of treatments, coupled with
the accumulation of experience using them. Perinatal
deaths in Spain and France have continually declined since
the 1980s. The UK and Sweden also followed this trend but
the UK saw a slight increase in mortality in the early 1990s
and has since stabilised. Sweden has now stabilised at a
very low death rate. Until the early 1990s Estonia had seen
fluctuations in mortality but since has also seen a continual
decline in mortality. In The Netherlands, where perinatal
mortality has been declining steadily, there was a sharp
increase (although from a very low level) in 2008.
326
1st round
Conditions originating in the perinatal condition
Scores
1
Number of
responses
Total (%)
2
3
4
5
6
7
8
9
Total
2
2
1
6
3
3
2
4
23
9%
9%
4%
26%
13%
13%
9%
17%
100%
2nd round
Conditions originating in the perinatal condition
Scores
Number of
responses
Total (%)
1
2
9
Total
3
4
5
6
7
8
1
2
6
5
3
6
23
4%
9%
26%
22%
13%
26%
100%
327
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Cancer of the Stomach
Decrease, due to falling rates of infection by Helicobacter
in more recent generations
6,490/1,719/6,092/2,167
61
We could identify no specific intervention related to
stomach cancer that was associated with a substantial
improvement in mortality although improvements in
operative safety are likely to have played a role.
Overall mortality and survival results have improved over
the last 20 years. Five-year age-standardised relative
survival for stomach cancer across Europe varies from the
lowest ≤20% to the highest 32%. Consecutive prospective
series of gastric cancer patients have shown much
improved rates in resected cases. Prognostic factors and
policy/guidelines deployed have influenced the survival of
gastric cancer patients radically operated. Other factors
that have been implemented include earlier detection (due
to greater awareness of symptoms and greater use of
endoscopy), the standardisation of surgical procedures,
and lower postoperative complications.
Treatment of stomach cancer with Fluorouracil and
combination chemotherapy has been widely used in the
UK, Germany, France, the Netherlands and Sweden. Only
Estonia saw the introduction of these regimes much later in
the mid 1990s. Overall mortality from stomach cancer has
decreased steadily since the 1980s for all countries with
the exception of Estonia. The numbers of deaths have been
fluctuating since the mid 1980s but since 2006 mortality
has started to decline steadily.
328
1st round
Cancer of the stomach
Scores
1
Number of
responses
2
3
4
5
6
7
8
3
3
2
7
5
1
2
13%
13%
9%
30%
22%
4%
9%
9
Total
23
Total (%)
100%
2nd round
Cancer of the stomach
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
1
1
6
8
7
4%
4%
26%
35%
30%
7
8
9
Total
23
100%
329
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Primary Cancer of the bone
Stable
291/92/259/119
34
We could identify no specific therapeutic intervention
associated with a substantial reduction in mortality.
Survival has improved since the late 1970s for bone cancer,
with surgery dominating treatment. Bone cancer is
uncommon constituting less than 1% of all malignancies
worldwide. The variation in relative survival for bone
cancer between countries was substantial with the lowest
5-year rates (20-40%) seen in the Eastern European
countries and the highest (61-70%) were seen in Western
Europe
Surgery in the late 1800s, early 1900s was the only
treatment of bone cancer, followed by the introduction of
chemotherapy and radiotherapy in the 1970s. Our trend
analysis showed that mortality from bone cancer has
indeed declined steadily in both Spain and France. From
the late 1970s, the number of deaths from bone cancer
have remained low the Netherlands, Sweden Germany and
the UK with the trend remaining stable ever since.
330
1st round
Scores
1
2
3
4
5
6
7
8
Number of
responses
1
4
4
4
2
5
2
1
4%
17%
17%
17%
9%
22%
9%
4%
Total (%)
9
Total
23
100%
2nd round
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
3
5
7
4
3
1
13%
22%
30%
17%
13%
4%
8
9
Total
23
100%
331
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Leukaemia
Stable
4,228/1,098/2,881/948
20
Studies in children with acute lymphatic leukaemia have
been small, including fewer than 200 children. In this
previously uniformly fatal disease, Monotherapy achieved
complete remission in 21% (methotrexate), 27% (6
Mercaptopurine), and 47 %( Vincristine) and 72%
(Prednisone). However, a major problem was recurrence of
disease, attributed to development of resistance to
chemotherapeutic agents. This observation led to the use
of combination chemotherapy, with 6-Mercaptopurine +
Prednisone achieving a complete remission rate of 82% and
Vincristine + Prednisone achieving 84%.
International differences in survival, varies from 32% to
80%. Variations in survival in relation to age, country,
histological subtype and period of diagnosis (1978–1992)
showed overall survival was 44% (95% CI 33–55) for chronic
myeloid leukaemia (CML) and 37% (95% CI 32–43) for acute
non-lymphocytic leukaemia (ANLL). The risk of death from
ANLL and CML fell by 7% per year and 5% per year,
respectively, after adjustment for age, gender and
country.
Since the mid 1970s, continued improvements in the
treatment of disease process and complications for
leukaemia have been observed. Leukaemia mortality
trends have remained stable since the 1970s for all
countries with the exception of Estonia. Estonia has
observed fluctuations in mortality hitting peaks and
troughs, despite a stability during the earlier part of this
decade, but has since continued to fluctuate.
332
1st round
Leukaemia
Scores
1
Number of
responses
2
3
4
5
6
7
8
1
1
5
3
4
8
1
4%
4%
22%
13%
17%
35%
4%
9
Total
23
Total (%)
100%
2nd round
Leukaemia
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
1
3
3
6
9
1
4%
13%
13%
26%
39%
4%
9
Total
23
100%
333
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Abdominal hernias
Stable
842/106/460/128
52
Surgical treatment has been in use for many decades. We
could find no RCTs looking at mortality outcomes.
Following the development of laparoscopic surgery in the
late 1980s, this has now become standard practice. The
use of mesh during laparoscopic hernia repair is associated
with a relative reduction in the risk of hernia recurrence of
around 30-50%. However, there is no apparent difference
in recurrence between laparoscopic and open mesh
methods of hernia repair.
With the exception of Estonia, mortality from abdominal
hernias has been declining since the late 1970s. In 1997,
the introduction of the ICD in Estonia coincides with a
dramatic decline in mortality but rates peaked again in
1999 and have since fluctuated before, now, starting to
decline steadily.
334
1st round
Abdominal hernias
Scores
1
2
3
4
5
6
7
8
9
Total
Number of
responses
1
2
2
1
3
1
3
5
5
23
4%
9%
9%
4%
13%
4%
13%
22%
22%
100%
Total (%)
2nd round
Abdominal hernias
3
4
5
6
7
8
9
Total
1
1
1
3
3
5
7
2
23
4%
4%
4%
13%
13%
22%
30%
9%
100%
Scores
1
Number of
responses
Total (%)
2
335
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Suicide
Variable
4,127/1,500/3,393/3,269
23
Treatment of mood disorders with Lithium for suicide
prevention has been available since the mid 1970s with
cognitive behaviour therapy for suicide attempters being
adopted by some countries since the 1990s.
Observational studies suggest that long-term lithium
treatment is effective in reducing the risk of suicide
among those with mood disorders, but it is uncertain
whether this association is a genuine therapeutic effect or
is due to confounding factors in nonrandomized studies. A
Cochrane review selected studies that included RCTs
comparing lithium with placebo or all other compounds
used in long-term treatment for mood disorders. There
were fewer deaths overall in patients who received lithium
suggesting that lithium is effective in the prevention of
suicide.
Direct evidence that antidepressants prevent suicide is
hard to find. A meta-analysis of data on the serotonin reuptake inhibitors (SSRIs) fluoxetine, found no evidence that
suicidal acts were less frequent among adults taking
antidepressants. Most clinical trials have insufficient power
to provide clear evidence on the effect of antidepressants
on suicide. The pooled results of four studies on cognitivebehavioural therapies showed a significant preventive
effect on repeated suicide attempts. At present, only the
cognitive-behavioural approach appears to have a
beneficial effect on repeated suicide attempts.
Many widely-used suicide prevention programmes have
never been scientifically assessed, thus making it uncertain
which are effective. However, due to the limited evidence
and the heterogeneity of the interventions, it is not
possible to determine if one single intervention is more
effective than another and also not one single intervention
in a well conducted randomised controlled trial has been
shown reduce suicide
In the early 1990s there was a sharp mortality increase in
Estonia, but since has seen a dramatic decline. Deaths in
the Netherlands, UK and Spain have been low and stable.
For Sweden, France and Germany mortality has been
steadily declining since the 1990s.
336
1st round
Suicide
Scores
1
2
3
4
5
6
Number of
responses
1
5
5
3
1
4%
22%
22%
13%
4%
Total (%)
8
9
Total
3
3
2
23
13%
13%
9%
100%
7
8
9
Total
7
2nd round
Suicide
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
5
7
6
3
1
1
23
22%
30%
26%
13%
4%
4%
100%
337
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Cancer of the larynx
Decrease
895/252/1,816/586
28
Surgery was the initial mode of treatment for laryngeal
cancer now coupled with chemotherapy and biological
regimes and radiotherapy. We could find no specific
intervention associated with a substantial reduction in
mortality.
Radiotherapy, open surgery and endolaryngeal excision
(with or without laser) are all accepted modalities of
treatment for early stage glottic cancer. Case series
suggest that they confer similar survival advantage.
Opinions on optimal therapy vary across disciplines and
between countries. Reported five-year survival rates
following treatment of these early tumours are around
85%.
Mortality trends in cancer of the larynx have stabilised
since the 1980s in Germany, UK, Sweden and the
Netherlands. The greatest rates of decline were only
observed in France. Although the number of deaths has
been higher in Spain, it too has seen a stable trend in
mortality. The trend in Estonia has been fluctuating since
the mid 1980s with mortality peaking in the mid 1990s but
has since gradually decreased and increased.
338
1st round
Scores
1
2
3
4
5
6
7
8
5
7
6
2
2
1
22%
30%
26%
9%
9%
4%
9
Total
23
Number of
responses
Total (%)
100%
2nd round
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
1
3
9
6
2
1
1
4%
13%
39%
26%
9%
4%
4%
9
Total
23
100%
339
Cause of death
Trends in incidence
Hungary
1979-2000, E&W)
research
outcomes
Mortality trends
Cancer of the female breast
Increasing, thought to be due to a combination of
later child bearing, post-menopausal hormone
replacement therapy, and improved nutrition in
childhood.
13,035/3,425/5,677/2,316
27
Mammographic screening: A systematic review
concluded that breast cancer mortality was an
unreliable outcome that was biased in favour of
screening, mainly because of differential
misclassification of cause of death. Based on all
trials, the reduction in mortality is 20%, but as the
effect is lower in the highest quality trials, a more
reasonable estimate is a 15% relative risk reduction.
The benefits are greatest where there is a
comprehensive population-based screening
programme
Adjuvant tamoxifen reduces recurrence of breast
cancer. In trials of 1 year, 2 years, and about 5 years
of adjuvant tamoxifen, the proportional recurrence
reductions after about 10 years of follow-up were
21%, 29%, and 47% respectively, with a highly
significant trend towards greater effect with longer
treatment. The absolute reduction in recurrence was
greater during the first 5 years, whereas the
improvement in survival grew steadily larger
throughout the first 10 years. Its effects are confined
to those with oestrogen receptor positive tumours.
Breast cancer screening with mammography was
adopted in the European countries we looked at in
the late 1980s, with the exception of Estonia where
mammography began around 2005. Tamoxifen, in
some countries was available since the early 1970s. It
has been difficult to separate the timing of the two
interventions.
The mean European age- and area-standardised fiveyear relative survival of women diagnosed with breast
cancer in 1995–1999 (EUROCARE-4) improved to 79%
from 76% in 1990–1994 (EUROCARE-3). Betweencountry survival differences had also narrowed in
EUROCARE-4 compared to EUROCARE-3.
Mortality trends from breast cancer have been
steadily decreasing since the mid 1990s with the
sharpest continual decline seen in the UK. This
decrease was observed in all countries except
Estonia. Estonia experienced a peak in mortality in
2000, but since there has been a sharp decrease in
mortality.
340
1st round
Scores
1
2
Number of
responses
Total (%)
6
7
8
9
Total
1
5
5
9
2
23
4%
22%
22%
39%
9%
100%
3
4
1
4%
5
2nd round
Scores
Number of
responses
Total (%)
1
2
3
4
5
6
7
8
9
Total
1
2
8
10
2
23
4%
9%
35%
43%
9%
100%
341
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Diabetes
Increases in both Type 1 and 2 (the latter due to obesity)
6,999/3,345/9,253/2,280
17
Insulin transformed the management of diabetes in the
1920s but, by the 1950s, the long-term complications of
diabetes (cardiovascular, renal, neurological and
ophthalmic) were becoming apparent and the debate
shifted to how intensive therapy should be.
The effect of intensive blood-glucose control was
compared with either sulphonylurea or insulin and
conventional treatment as a means of reducing the risk of
microvascular and macrovascular complications in patients
with type 2 diabetes. Compared with the conventional
group, mortality in the intensive treatment group was 12%
lower. Intensive blood-glucose control substantially
decreases the risk of microvascular complications, but not
macrovascular disease, in type 2 diabetes.
A UK trial examined whether tight control of blood
pressure prevents macrovascular and microvascular
complications in patients with type 2 diabetes. There was a
non-significant reduction in all cause mortality. After nine
years of follow up 29% of patients in the group assigned to
tight control required three or more treatments to lower
blood pressure to achieve target blood pressures. Tight
blood pressure control in patients with hypertension and
type 2 diabetes achieves a clinically important reduction in
the risk of deaths related to diabetes
Mortality and causes of death using 13 population-based
EURODIAB registers in 12 European countries followed-up
28,887 children diagnosed with type 1 diabetes from 19891999. There were 141 deaths in the cohort during follow-up
compared with 69.1 deaths expected among all children in
the same age group. One-third of deaths were classified as
directly attributable to diabetes. By the 1950s it became
apparent that people living with diabetes were
experiencing a range of vascular complications.
Since the 1980s, most European countries have adopted
tight glucose control/monitoring for management of
diabetes and more recently have implemented evidenced
based guidelines on tight blood pressure control . Since
then death rates from diabetes have fallen by more than
half in Spain. Sweden, the UK and Germany experienced a
smaller but steady decline. In France a slow decline was
reversed in 1998. Estonia has seen a fluctuating trend but
generally increasing deaths. The situation in the
Netherlands is complex with a marked increase in the mid
1980s, followed by a slow decline.
342
1st round
Diabetes
Scores
1
2
3
5
6
7
8
9
Total
4
7
7
3
2
23
17%
30%
30%
13%
9%
100%
6
7
8
9
Total
1
7
13
2
23
4%
30%
57%
9%
100%
4
Number of
responses
Total (%)
2nd round
Diabetes
Scores
Number of
responses
Total (%)
1
2
3
4
5
343
Cause of death
Trends in incidence
research
outcomes
Mortality trends
Acute appendicitis
Decrease
139/33/57/33
45
Appendicectomy has been standard treatment since the
19th century. We found no RCTs.
Mortality after appendectomy is low and related to the
stage of disease and presence of perforation; mortality
after perforation is 5.1 per 1000.
The main innovations have been the introduction of
antibiotics in the mid 1940s, with subsequent
enhancements in diagnostic testing (ultrasound). Deaths
from acute appendicitis have been low in all countries
except for Estonia. Mortality in Estonia peaked in 1987 and
has since seen dramatic fluctuations. More recently the
trend in mortality appears to be on the increase.
344
1st round
Acute Appendicitis
Scores
1
2
3
4
Number of
responses
1
2
3
4%
9%
13%
Total (%)
6
7
8
9
Total
2
1
4
3
7
23
9%
4%
17%
13%
30%
100%
5
2nd round
Acute Appendicitis
Scores
1
2
3
4
5
6
7
8
9
Total
Number of
responses
1
1
2
1
1
1
5
7
4
23
4%
4%
9%
4%
4%
4%
22%
30%
17%
100%
Total (%)
345
Cause of death
Cancer of the lung, bronchus and trachea
Trends in incidence
Decreasing in men, plateauing in women in some
countries
33,523/8,559/17,363/7,824
Number of deaths in 2000: UK (2001),
Netherlands, Spain, Hungary
research
Published evidence of improvements
in population outcomes
Mortality trends
38
We could identify no specific intervention with a
substantial impact on mortality
The use of low-dose computer tomography screening in
high risk populations as way of reducing lung cancer
mortality is being investigated in the US and Europe.
Survival with lung cancer is poor and data from the
EUROCARE study showed that mean five year European
survival increased from 11% in 1988–1990 to 13% in 1997–
1999.
The mortality trend for females has increased in all
countries with the exception of the UK, whereby a steady
decline has been observed since the late 1980s. Estonia
has had fluctuating trends but is also on the increase.
However, the trend is reversed in males as declines have
been observed in the Netherlands, Germany and the UK.
Estonia has seen more marked fluctuation but generally
decreasing. In Sweden deaths have been low and stable
but for both France and Spain deaths were rising until
1990 but have since plateaued.
346
1st round
Scores
1
2
3
4
5
6
7
8
9
Total
Number of
responses
5
3
2
1
4
4
2
1
1
23
22%
13%
9%
4%
17%
17%
9%
4%
4%
100%
9
Total
Total (%)
2nd round
Scores
1
2
3
Number of
responses
2
5
9%
22%
Total (%)
4
5
6
7
8
4
6
4
2
23
17%
26%
17%
9%
100%
347
Appendix 2 Collective comments given by the participants
Condition
Comments on ratings
The complex interplay of migration and incidence (both external factors)
make this an unacceptably poor health system indicator in low-incidence
countries
Success of therapy in turning this into a chronic disease
Clear evidence for effectiveness of anti-retroviral rx, condoms, Caesarean
Section. Marked down a point as numbers are relatively small (in NZ anyway)
and incidence may not be stable
HIV
Need to consider how the effect of values and resources in a country
interacts with this
becoming "chronic disease" in developed countries
Clearly amenable to treatment and good indicator...
Quoted as high since depending on health systems organisations for
immigrants
Role of general policy cultural, societal issues
Dependent on therapeutic advances but also individual choices, primary
prevention
effective treatment (+), changing/different incidence (-)
Education may be at least important as health system (drugs)
348
Condition
Comments on ratings
To be meaningful, there needs to be some age cut-off to reflect
"avoidability" (this is true for most cancers), but with an
appropriate age cut-off this is a fair indicator
Screening to detect early disease
Malignant neoplasm
of rectum and
colon
Still plenty of room for improvement in speed of diagnostic testing
and surgical rx; impact from screening may be small, however, so
marked down 2 points
important to follow public health policies
Great potential of population based screenings
Amenable to early diagnosis and potential treatment
Too many confounding factors
Role of individual early diagnosis
modern health systems include screening for these conditions
screening (+), treatment (+ -), diverse mortality trends and levels
(-),
Improved diagnosis and treatment (chemo) seem critical
349
Condition
Comments on ratings
Screening is policy not health care
HPV vaccination presumably strengthens the case for this
indicator
Malignant neoplasm
of cervix uteri
Less aggressive disease, screening
Well-run screening programmes and well-organised high-coverage
HPV vaccine programmes should see further reductions. Relatively
small numbers in NZ.
Reasonable treatment in combination with successful population
based screening programmes
Early screening effective although change in mortality is not
consistent in all countries (2 out of 5)
Hope with vaccination
Role of access to healthcare, social factors
Malignant neoplasm of cervix uteri - preventive measures and
screening should reduce incidence and mortality
screening (+), treatment (+,-)
Again, strong evidence of health system factors
350
Condition
Comments on ratings
Incidence trends and small numbers make this less useful
Not clear what early intervention has to offer
Malignant neoplasm
of the testis
Not much more to be gained. If mortality went up would be an
indicator of possible problems with health system ie this is only a
‘uni’ as opposed to a ‘bi’ directional indicator. Also limited by small
numbers in NZ
Small numbers
Low figures... Cisplatin seems effective but not consistent evidence
(2 out of 7 countries...)
Low death rates
Small numbers
gender issues here on early detection
small numbers (-), treatment (+)
New treatment modalities since late 1960s seem instrumental to
lowering death rates
351
Condition
Comments on ratings
Stable incidence and reducing mortality would (for this and other
conditions) provide an argument for using this
Treatable cancer
Hodgkin’s disease
Would expect further refinements in treatment regimes. However
relatively low numbers. Also would not indicate much beyond
performance of medical oncology service
High dose therapy and blood cell transplantation could be effective
and strong decline is documented (65%), although only in 1 out of 6
countries the favourable change is demonstrated
No new intervention
Small numbers
therapeutic and health services offer are important factors
treatment/survival (+), rather small numbers (-)
No good correlation between introduction of high dose therapy and
transplantation with death rate trends
352
Condition
Comments on ratings
Rheumatic heart
disease
NONE GIVEN
Condition
Comments on ratings
Hypertension
NONE GIVEN
Condition
Comments on ratings
Health promotion is policy not health care
You have left out Rheumatic Heart Disease and Hypertension; for
Rheumatic Heart Disease an increase in mortality would represent a
major system failure, so arguably this has a place - but whether we
could expect further improvement is a different question
Ischemic heart
disease
Good success in healthcare but much due to lifestyle
Expect further falls from improved and more extensive treatment
with absolute risk protocols, but increases with diabetes and
obesity. Caution re coding issues with troponin diagnosis thresholds.
Need to adjust for extra-health system drivers.
Important with regards to prevalence rates (also hypertension which
is not indicated here)
High sensitivity to non-medical factors
56% decline! and apparent effectiveness of streptokinase... and
beta-blockers in 5 out of 7 analysed countries
Role of prevention plus clinical care – reverse trends may appear
with obesity and diabetes epidemics
depends also on performance of pre-hospital emergency systems and
on behavioural changes not dependent only on Health Systems
treatment/secondary prevention (+), differences/changes in risk
factors (-)
Difficult to separate health system from non- health system factors
through latter appears important
353
Condition
Comments on ratings
Poor outlook irrespective of healthcare interventions
Difficulty here is in coding and diagnostic thresholds. However,
robust evidence for benefit from ARBs, spirolactone, beta blockers
etc.
Multiple pathways to CHF mean that the cause of CHF may vary
Heart failure
64% reduction but the effectiveness of ACE-inhibitors is not that
clear (only 2 out of 6 countries)...9
Too many confounding factors
Possible modifications of case incidence due to successful
treatment of ischemic heart disease
- must take into consideration differences in management practices
across countries
treatment (?), possible differences in diagnosis (-)
ACE inhibitors for treatment seemed good on clinical evidence but
country evidence not as convincing
Condition
Comments on ratings
Good stroke care has much to offer esp early dx
Better preventive coverage with absolute risk protocols, better
stroke unit care. Maybe exclude sub-arachnoid?
Stroke/
Cerebrovascular
disease
important as information and prevention is concerned as well as
health services organisation
Concrete interventions difficult to disentangle
58% reduction. Not only antihypertensives but also intensive
management seems to obviously have an impact
Stroke/ cerebrovascular disease - as for some other conditions
important issues regarding information systems and differences in
cause of death coding and statistics
secondary prevention, treatment (+), changing/different incidence
(-)
Between antihypertensive drug treatment and intensive
management of stroke heart system factors seem critical
354
Condition
Comments on ratings
I have heard some clinicians suggest that this is an obsolete
indicator but again an increase in mortality would represent a
major failure so it has a place
Preventable cause of mortality with effective care
Peptic ulcer
Would expect continuing improvements e.g. with expanded PPI
coverage. Low numbers and declining incidence of H pylori
infection are limitations
Although Cimetidine (and alike) seems effective the introduction
coincided with a favourable change in mortality in only 2 out of 7
countries, and only for females
Low death rates
Acute episodes amenable to good quality prehospital and
emergency services.
Declining incidence - confounding (-), treatment (?)
Problem with cimetidine and change in mortality
355
Condition
Comments on ratings
Age limit?
Complex and immune driven frequently, or diabetic
Marked down 2 points because of varying classification and coding
of COD. Also RRT is a specialised service so doesn’t provide a broad
indicator of health system performance. Incidence may also be
unstable.
Is this now really a proxy for diabetes care?
Renal failure
important as ageing is developing
The potential of immunosuppresive treatment and transplant has
made a difference clearly demonstrated in 3 out of 7 countries
Screening should improve but confounding factors
Changes in the indicator may happen in the future if new effective
treatment appears
access to dialysis
strong effect of transplantation (+ -)
Stronger correlation between introduction of immunosuppressive
treatment with Cyclosporine for kidney transplants in prolonging
life
356
Condition
Comments on ratings
Depends on the complexity of the condition
Congenital heart
disease
Small numbers, likely to be reaching limits to what can do
surgically. Also casemix can vary even if overall incidence stable.
Again, a specialised service so not great signalling quality.
69% reduction and amenability to good surgery (Estonia data are not
clear?)
influenced by high quality pre-natal and perinatal offer of services
and screening
treatment (+), numbers not too big (-)
Improvements in cardiac surgery = higher survival
357
Condition
Comments on ratings
Conceptually this is clear but it sounds like there are real issues
on data comparability and complexity
I would also add maternal mortality which is viewed in France as a
very important marker of something that should never happen in a
properly oganized system of healthcare delivery
Related to inequalities but ante-natal care can help
Conditions
originating in the
perinatal condition
Package of interventions rather than specific intervention – not
clear what scope for improvement remains. Would need to be
adjusted for birth weight / duration of gestation.
indicator which can be a "light" for determinants of health (social
factors)
There are perhaps many factors (accessibility, prenatal care and
so on...); it is not very clear as a solid indicator...
Good indicator for developing countries
Complex issue effective early neonatal care may increase the load
of living neonates with severe disease that need special
interventions
influenced by high quality pre-natal and perinatal offer of services
and screening
treatment (+), definitions (-), other factors LBW etc. (-)
Too many non-health care system factors
358
Condition
Comments on ratings
Preventable by policy
I find this unclear – no rationale but continuous decline makes this
harder to interpret
Cancer of the
stomach
Aggressive but amenable to effective early surgery
Declining mortality mainly reflects declining H pylori infection rates
decades earlier – at least partly resulting from extra-health system
factors. Health system still has a role in eliminating H pylori
infection and improving cancer treatment and organisation of
cancer services.
More evidence of mortality decline to individual prevention
Both incidence and mortality have been decreasing and it seems to
be a relatively good indicator, although with
fluctuations/inconsistencies
Same as stroke at least in Portugal. trends difficult to interpret
cause of decline but infection not known (-)
Evidence ambiguous
359
Condition
Comments on ratings
I find this unclear – no rationale but continuous decline makes this
harder to interpret
Potentially mutilating surgery but avoidable mortality
Small numbers, straightforward care well organised in NZ although
some room for improvement no doubt remains. Limited also by
problems in clinical staging
Primary Cancer of
the bone
Since there is no specific therapeutic intervention associated with a
substantial reduction in mortality...
No new intervention
Small numbers
- difficult to interpret due to low rates in general population but
infant cases perhaps meriting more close attention.
specific therapeutic intervention (-), disparate RS (-)
No specific therapeutic intervention but improvements in surgery?
360
Condition
Comments on ratings
Depends on the cell type - aggressive dx are poor responders
ALL in childhood continues to improve, plus recent ‘breakthroughs’
e.g. oral tyrosine kinase inhibitors for CML. But would need to
adjust for variations in case mix. Also a specialised service so
limited signalling utility.
Leukaemia
Differential by age suggests need to use of lower age limit if to be
considered amenable to health care
Here we have different diseases (natural history and amenability to
treatment of CML, AMS, ANLL and so on iare heterogeneous)
depends on age group and agressivity of subtypes
stable mortality rates (-), large differences in survival (-)
Evidence ambiguous
361
Condition
Comments on ratings
This is pretty unambiguous
Avoidable cause of mortality
Small numbers. Again, this would be a unidirectional indicator only
– that is, an increase in mortality would indicate a health system
failure.
Abdominal hernias
52% reduction with good impact of proper surgical procedures
(except in Estonia?!)
Low death rates
Global effect of care
Not a useful indicator in stable health systems. Should be regarded
as sentinel indicator
treatment (+)
No clear linkage between improvements in surgery and declining
mortality
362
Condition
Comments on ratings
Very hard to see why the health system can really drive overall
suicide mortality
Definitely not much evidence here of the impact of health care
Suicide
Perhaps 50% are causally linked to mental health disorders,
predominantly depressive disorders – and robust evidence for
effectiveness of antidepressants. Cohort effects and extra-health
system drivers more generally are at least equally important, so
would have to adjust for this confounding – which would be
difficult. Yet absence of other indicators of performance of the
mental health subsystem argues for use of this indicator
important, but the relation with health interventions is not clear
In spite of the lithium and new antidepressants, and good mental
health programmes, evidence is not that clear... to strongly support
this indicator
Are national health programmes effective?
Possible effects largely outside healthcare system per se
dependent on risk factors outside the immediate scope of the
health system
lack of evidence of good interventions (-), differences in incidence
(-)
No evidence on suicide prevention program: little or no connection
with health system
363
Condition
Comments on ratings
Aggressive disease, multiple lifestyle influences
Cancer of the
larynx
Some evidence for effectiveness of rx of early stage disease, but
stable rates since early ‘80s suggests no recent advances – nor (as
far as I know) are any in the pipeline
Too fluctuating figures...
Role of preventive care (alcohol, tobacco)
same as cancer of the trachea
no specific intervention associated with reduction in mortality
Evidence unclear
364
Condition
Comments on ratings
Screening is policy dependent
Increasing incidence combined with declining mortality suggests
this is a fair health system indicator
Surprisingly controversial still and not fully understood
Cancer of the
female breast
Benefit from screening is not great, but evidence for adjuvant
chemotherapy (e.g. tamoxifen) is robust and further
improvements can be expected. Also incremental improvement in
general organisation / coverage of diagnostic and treatment
services is likely. Marked down a point mainly because of
relatively small decline in mortality.
essential, no doubt
Great potential of population based screenings
Evidence on the impact of new treatments - consistent decline in
mortality...
Combined preventive care and cure
high profile from society and health systems
screening & treatment (+), differences in incidence (-)
Improved nutrition and later child-bearing may be far more
important than healthcare interventions
365
Condition
Comments on ratings
Policy, socioeconomic relations
Increasing incidence combined with declining mortality suggests this
is a fair health system indicator
Gloomy outlook with huge rise in incidence of obesity
Large numbers of deaths and robust evidence of effectiveness of
several interventions at various points along the disease pathway
(although less so for mortality as endpoint). Marked down 2 points
because of poor quality coding of diabetes as the underlying COD in
official mortality statistics.
Diabetes
Application of upper age limit (e.g. <45) might be indicated if to be
considered amenable to health care
Increasing in France.
Large individual responsibility may reduce success of medical
treatment
Good control is obviously a must, but the quality/robustness of the
indicator is not as clear as ideal...)
As for hypertension an organised screening and collaborative
management system should be efficient? But many risk factors
Preventive care on obesity may help reduce incidence
should be progressively lower due to primary, secondary and
tertiary prevention interventions
glucose control/monitoring (+), different mortality trends (-),
coding CoD (-)
Intensive/tight blood-glucose control and monitoring seems critical
– requires access to sophisticated healthcare system
366
Condition
Comments on ratings
..... no longer surgery1
This is pretty unambiguous
Preventable cause of mortality
Acute appendicitis
Tiny numbers, no great changes expected. However, could serve as
a unidirectional indicator – significant increase in mortality would
signal a collapse of our health system
45% decrease and evidence... although small numbers may make
this indicator not very robust...
Global effect of care
Small numbers
should be very low, but in older ages not an initial suspicion
treatment (+), small numbers (-)
No clear connection between health care interventions and
declining mortality
1
Hansson J, Körner U, Khorram-Manesh A, Solberg A, Lundholm K. Randomized clinical trial of antibiotic
therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg
96(5): 473-481, 2009
367
Condition
Comments on ratings
I think deciding the incidence and the complexity of historic smoking
trends make mortality less useful as a system indicator
Poor outlook with very disappointing therapy results, smoking and
non-smoking both suffer this fate
Cancer of the lung,
bronchus and
trachea
Little evidence that healthcare is effective (except perhaps for early
stage disease). Strongly affected by cohort effects and smoking rates
(with long lag period).
witness of prevention's programs, even if a long time after
Unclear because health care interventions not yet successful at broad
scale
No evidence of specific intervention with a significant impact on
mortality
attention given to major risk factors should make this progressively
lower
treatment (-), differences in incidence (-)
No specific intervention identified and no data on relationship
between low dose CT screening
368
G. Country specific reports
The country specific reports present the insight of country experts on the mortality trends and
the results of the association analyses. These reports have been written by the participants
of the AMIEHS study.
Country specific report on mortality trends in Estonia
Country specific report on mortality trends in France
Country specific report on mortality trends in Germany
Country specific report on mortality trends in the Netherlands
Country specific report on mortality trends in Spain
Country specific report on mortality trends in Sweden
Country specific report on mortality trends in the UK
369
Country specific report on mortality trends in Estonia
Authors: Katrin Lang, Kersti Parna
Affiliation: University of Tartu, Estonia
The Estonian Health system
Estonia is the most northern of the Baltic states, which lies on the east coast of the Baltic Sea, with
Latvia to the south and Russia to the east. It is a democratic parliamentary republic and belongs to the
North Atlantic Treaty Organizaton (NATO) and the European Union (EU) since 2004. Since regaining
independence from the USSR in 1991, the political environment has been stable enough to implement
various economic and social sector reforms which aim to further ensure stability in Estonia. The
country had a population of 1,340,415 in 2009. Since the late 1990s, an increasing birth rate has been
observed, and due to decreasing mortality the gap between these two rates is closing (natural
increase -0.24 in 2009). The life expectancy in 2009 for women was 80.1 years and for men 69.8
years, which is lower than the EU averages, but has been steadily increasing since 1994. The main
challenge in terms of disease burden is premature mortality caused by lifestyle-related risk factors and
external causes.
1
The steward of the health system in Estonia is the Ministry of Social Affairs. The organizational
structure in the health system is advanced and comprises numerous actors, including various
agencies under the Ministry of Social Affairs (e.g. State Agency of Medicines, Health Care Board,
National Institute for Health Development, Health Protection Inspectorate); public independent bodies
(the Estonian Health Insurance Fund); (mainly publicly owned) hospitals under private regulation and
private primary care units; and various non-governmental organizations and professional associations.
The Estonian health care system is mainly publicly funded through solidarity based mandatory health
insurance contributions in the form of earmarked social payroll tax, which mounts to almost two thirds
of total health care expenditure. The Ministry of Social Affairs is responsible for financing emergency
care for uninsured people, as well as for ambulance services and public health programmes. The core
purchaser of health care services for insured people is the Estonian Health Insurance Fund.
Reforms which started in the early 1990s introduced the principles of a purchaser and provider split;
strengthening primary care; free choice of provider, and a high level of provider autonomy in the
Estonian health care system. As a result, the current Estonian health care system is built around
countrywide primary care which is centered around family medicine, with specially trained doctors and
nurses.
We were not able to detect research papers on the impact of health care on mortality trends in
Estonia.
The general remarks about Estonia in the context of this research and particularly when comparing
with other countries participating in AMIEHS are the following. First, lifestyle-related risk factors (most
importantly alcohol consumption and smoking) have relatively high prevalence and are influencing
mortality to a larger extent than changes/innovations in health-care.
2-4
Second, very large societal and
health-care reforms took place during the period under observation (see above). The rather big
increase in mortality that peaked in 1994 has largely been attributed to transition to market economy.
5
Third, scientific evidence regarding these issues in international peer-reviewed papers as well as in
Estonian research reports/papers is very scarce, especially those relating to the Soviet period.
370
Cerebrovascular disease
The incidence rate of first-ever stroke age-standardised to the European population in Estonia in 2002
was 195/100,000, 214 (95% CI, 185-243) for men and 181 (95% CI, 155-208) per 100,000 for women.
6
The decline in incidence (standardized to European standard population) from 230 to 188 per
100,000 occurred during the last decade.
7
These estimates are based on one registry based on one
city.
Figure 1a: Time trends in cardiovascular mortality, Estonia, men
Figure 1b: Time trends in cardiovascular mortality, Estonia, women
In Figure 1a and 1b, a clear decrease in mortality between 1997-2005 can be seen for both sexes.
Still, cross-classification of causes of death between cerebrovascular disease and hypertension can
be observed. This was confirmed by Dr A Hedman
8
: increasing number of doctors certify
hypertension as underlying cause of death (instead of ischaemic heart disease or cerebrovascular
disease). Thus the decrease in cerebrovascular mortality may be ascribed to cross-classification,
371
although there is some evidence that introduction of intensive management of stroke took place in the
late 1990’s.
9
Matching knots for interventions (treatment of hypertension and intensive management) were detected
with borderline significance. Still, it can not be confirmed that decrease in mortality is caused by
intervention as other changes in recording underlying cause of death and in decrease incidence also
occur.
On the mortality graphs for Estonia, a sharp decrease is seen for both sexes around 1980. Since
1975, all Estonian patients with congenital heart defects have been treated at the only university
10
hospital in Estonia, located in Tartu.
It seems plausible that concentrating all cases of congenital
heart disease at one (university) hospital enabled effective development of resources and training of
the staff, resulting in decrease of mortality.
Heart failure
In Figure 1a and 1b, a steep increase is seen from around the year 2000. Registration of ACEinhibitors for heart failure took place in 1994-1996.
9,11
No additional information is available whether
ACE-inhibitors were in use for treatment of heart failure before the years of registration or when a 15
% coverage rate was achieved or any other data from reports about the implementation rates at any
specific year. It seems that this medication did not have a positive effect on mortality. The recent
increase since 2000 seems to be explained by cross-classification of causes of death with regard to
diseases of the circulatory system. The cardiologist
8
agrees that according to a recent tradition heart
failure (and hypertension) are coded more frequently as causes of death (previously ischaemic heart
disease or cerebrovascular disease were recorded). No data on the incidence of specific
cerebrovascular diseases are available for Estonia.
372
HIV
The knot in 1997 is not statistically significant. The intervention, the antiretroviral drug Zidovudine, was
registered in 1995
11
and the expected favourable shift in mortality trend 1995-2004 seems to occur as
a result of this intervention. In recent years there is a steep increase in AIDS mortality. Looking at
cumulative numbers, from the total of 263 deaths during 1996 (the first AIDS death occurred that year)
to 2009, 59 were reported in 2009.
Highly active antiretroviral treatment is available free of charge to all patients in need, including those
without health insurance.
12
Studies have found very high HIV prevalence among intravenous drug
users (40-90%), revealing the fact that the epidemic is concentrated among i/v drug users. This is
different from other countries in the AMIEHS project where HIV is mainly concentrated among MSM
(man having sex with men). Drug users may not be motivated to get treated. According to Professor
Anneli Uusküla
13
, when drug users want to start antiretroviral treatment, the doctors tell them they
need to stop injecting drugs and because of that they refuse treatment. Also, some people who start
treatment abstain later.
373
Hodgkin’s disease
According to Figure 2, mortality decreased in 1994. On the other hand, there is information that in
Estonia the intervention – peripheral blood stem cell transplantation – was not available/not widely
spread. It was introduced in 1993, and the rates per 100,000 persons are presented in Figure 1, with
absolute numbers of interventions ranging from 1 to 11, pointing to very low coverage of intervention.
This has been confirmed by and international collaboration,
14
which reported only one team
conducting peripheral blood stem cell transplantation in Estonia.
0.90
intervention rate per 100 000
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
19
93
19
94
19
95
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
0.00
Figure 2. Rates per 100,000 for peripheral blood stem cell transplantation for Hodgkin´s disease
Hypertension
In Figure 1a and 1b, a decrease in mortality is seen for both sexes from about 1970 until 1988 (males)
and 1994 (females). For both sexes this change is reversed, and followed by a steep increase. This
can be explained by the increasing number of doctors who certify hypertension as underlying cause of
death (instead of ischaemic heart disease or cerebrovascular disease) and was reported by Dr
Hedman, one of the leading cardiologists.
8
No conclusion can be reached as there is a problem of
increasing trend of reporting hypertension as underlying cause of death.
374
No data on incidence time trends is available for this condition. In Figures 1a and 1b, a remarkable
decrease in mortality is seen for women from around 1985 and for men, we see a steep decrease
from 1994 onwards. For women this decrease coincides with both interventions: B-blockers as
secondary intervention and the introduction of coronary care units (matching knots statistically
significant). For men the start of mortality decrease is a little too soon for B-blockers as a secondary
intervention to have had an effect, but the overall conclusion is that these health care innovations are
associated with the mortality decrease in Estonia.
Malignant colorectal neoplasm
There is a significant increase in colorectal cancer incidence from 1983/87 to 1998/2002 in Estonia,
similarly to other economically transitioning countries.
15
According to the mortality graphs for Estonia,
the mortality increase stopped for both sexes in the early 1990s. This change is most probably
attributable to earlier diagnosing as intervention is not available. Treatment with Oxaliplatin only
became available in 1999.
Malignant neoplasm cervix uteri
According to a paper by Aareleid et al., a decrease has taken place in the cervical cancer incidence
(and mortality) in Estonia since the mid-1960s.
16
The mortality graphs for Estonia also reflects a
decreasing trend. The nation-wide screening was started later, in 2006.
Peptic ulcer
No data is available on the incidence trend of peptic ulcer in Estonia. The spiky pattern of mortality
from peptic ulcer is seen for both sexes in Estonia, caused by annual changes of small numbers of
deaths. For women a steep decrease is seen in 1993. This coincides with the expected time period for
a favourable shift in mortality expected after introduction of treatment with Cimetidine. This is not
reflected in male mortality from this cause. It is not possible to conclude that this decrease in women
was caused by this intervention, although it is possible that the coverage of treatment and treatment
adherence are higher in women.
375
Testicular cancer
No data is available on the incidence trend of testicular cancer in Estonia. The decreasing trend in
17
mortality, with no big acceleration of decrease at any time. Data from a recent international study
reveals that the survival rates in Estonia are significantly lower than reference hazard ratios in survival
in Estonia (and Poland) suggesting inadequacy or unavailability of treatments.
Renal failure
No data is available on the incidence trend of renal failure in Estonia. On the mortality graphs for
Estonia, a positive trend is seen until the year 2000, with a small increase after that. No matching knot
is detected. It is thus not possible to owe the decrease in mortality to intervention (favourable shift
expected in the period 1993-2002).
No data is available on the incidence trend of rheumatic heart disease in Estonia. On the mortality
graphs for Estonia, a decrease starts in the late 1970s for men and early 1980s for women. For
women this coincides with the introduction and expected favourable shift in mortality for the
intervention artificial valve replacement. Artificial heart valves have been generally implemented as a
method for treatment of rheumatic heart disease in Estonia with 15% coverage from around 1980. Yet
there is no data to support the fact that this intervention had higher coverage in women than in men.
Malignant neoplasm of breast
From the mortality graphs for Estonia, an increase in breast cancer mortality is seen until the year
2000. This is parallel to the increase in incidence. A notable decrease in breast cancer mortality is
starting in the year 2000. A match with this change was detected with sales of Tamoxifen for which
half of the sales level was achieved in 1999.
11
Leukaemia
For women the mortality trend from leukaemia is rather stable. For men, an increase is seen over the
recent years. The incidence of leukaemia was observed for 1982-1996.
improved treatment for leukaemia is available for Estonia.
376
18
No information about
References:
1. Koppel A Kahur K, Habicht T, Saar P, Habicht J, van Ginneken E . Estonia: Health system review.
Health Systems in Transition. 10(1): 1-230. 2008.
2. Parna K, Rahu K. Dramatic increase in alcoholic liver cirrhosis mortality in Estonia in 19922008Alcohol Alcohol 2010; 45(6):548-551.
3. Rahu K, Parna K, Palo E, Rahu M. Contrasts in alcohol-related mortality in Estonia: education and
ethnicity. Alcohol Alcohol 2009; 44(5):517-522.
4. Leinsalu M, Vagero D, Kunst AE. Estonia 1989-2000: enormous increase in mortality differences
by education. Int J Epidemiol 2003; 32(6):1081-1087.
5. Leinsalu M. Troubled transitions. Social variation and long-term trends in health and mortality in
Estonia [ Centre for Health Equity Studies, Stockholm University/Karolinska Institutet; 2004.
6. Vibo R, Korv J, Haldre S, Roose M. First-year results of the third stroke registry in Tartu, Estonia.
Cerebrovasc Dis 2004; 18(3):227-231.
7. Vibo R, Korv J, Roose M. The Third Stroke Registry in Tartu, Estonia, from 2001 to 2003. Acta
Neurol Scand 2007; 116(1):31-36.
8. Dr A Hedman, cardiologist at East Tallinn Central Hospital. 2011. Personal Communication
9. Dr Janika Kõrv and Dr Irja Kalbe at the Tartu University neurology clinic. 2011.
Personal Communication
10. Kohler F, Schierbaum C, Konertz W, Schneider M, Kern H, Int E et al. Partnership for the heart.
German-Estonian health project for the treatment of congenital heart defects in Estonia.
Health Policy 2005; 73(2):151-159.
11. State Agency of Medicine. Estonia. http://www sam ee/ [ 2011 Available from:
URL:http://www.sam.ee/
12. Laisaar KT, Avi R, Dehovitz J, Uuskula A. Estonia at the Threshold of the Fourth Decade of the
AIDS Era in Europe. AIDS Res Hum Retroviruses 2011.
13. Prof Anneli Uusküla. 2011. Personal Communication
14. Gratwohl A, Baldomero H, Horisberger B, Schmid C, Passweg J, Urbano-Ispizua A. Current trends
in hematopoietic stem cell transplantation in Europe. Blood 2002; 100(7):2374-2386.
15. Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer
Epidemiol Biomarkers Prev 2009; 18(6):1688-1694.
16. Aareleid T, Pukkala E, Thomson H, Hakama M. Cervical cancer incidence and mortality trends in
Finland and Estonia: a screened vs. an unscreened population. Eur J Cancer 1993;
29A(5):745-749.
17. Sant M, Aareleid T, Artioli ME, Berrino F, Coebergh JW, Colonna M et al. Ten-year survival and
risk of relapse for testicular cancer: a EUROCARE high resolution study. Eur J Cancer 2007;
43(3):585-592.
18. Luik E, Palk K, Everaus H, Varik M, Aareleid T, Wennstrom L et al. The incidence and survival of
acute de novo leukaemias in Estonia and in a well-defined region of western Sweden during
1982-1996: a survey of patients aged > or =65 years. J Intern Med 2004; 256(1):79-85.
377
Country specific report on mortality trends in France
Authors: Gregoire Rey, Eric Jougla
Affiliation: Institut national de la santé et de la recherché médicale - CepiDc-Paris, France
The French health system
In France, since 1946, health expenditures are partly reimbursed by the social security system. In
2009, the French health care system expenditures are accounting for 9.2% of the French GDP. Of
these expenditures, 44% where affected to hospital care (33.5% dedicated to the public sector and
10.1% to the private sector), and 25.6% to drugs and other medical goods.
Before being sold and reimbursed, new medicines have to acquire an authorization delivered by
French authorities (Afsapps). Such authorizations are well documented and provide accurate
information of the time of widespread introduction of drugs in the population. Since 2004, the HAS
(French National Authority for Health) is in charge of publishing official guidelines and
recommendations to health practitioners. Therefore, the documentation regarding recent medical
practices national decisions is more easily available. Such information is less centralized before 2004,
implying several actors.
Impact of healthcare system on mortality trends in France was rarely assessed formally. However,
some studies have described mortality trends for specific causes of death and attributed
1-5
or not
6
their variations to the improvement of the health care system. To our knowledge, only one study
considered the association between mortality and health care at the population level, but it was under
7
a spatial angle . Therefore, the AMIEHS attempt to emphasize the temporal association between the
introduction of therapeutic innovations and the evolution of cause-specific mortality at the population
level in France is unique.
This chapter describes the specific outcomes of the AMIEHS project for France and brings some
additional elements to the understanding of the results.
HIV
Mortality by HIV strongly increased from 1982 to 1995, and then strongly decreased until 2000. This
change in trends is clearly matching with the introduction and massive spread of antiretroviral drugs. A
broad prevention campaign advising the use of condom could also have played a role in this
decrease. However, it is very likely that the introduction of antiretroviral drugs has led to a large
decrease in mortality from HIV.
378
A large decrease in mortality by conditions originating in the perinatal period is observed from 1970 to
1986. No innovation was specifically studied to explain this variation.
However, some health policies, specifically dedicated to the perinatal period, have been implemented
in the 1970's in France. Free of charge medical consultations were offered during pregnancy and
during the first year of life of the new born. This plan also included compulsory screening of
toxoplasmosis and rubella.
Congenital heart diseases
Mortality by congenital heart diseases has strongly decreased from 1970 to 2005. No specific
innovation was suspected for this decrease. However, prenatal ultrasound screening and the early
management of congenital heart disease have continuously improved during this period.
Cerebrovascular disease mortality markedly and continuously decreased from 1970 to 2005. This fall
was very regular and no specific break in the time series trend could be observed. Therefore, the
direct impact of innovation on mortality is hardly discernable. This could be due either to a slow
diffusion of the introduction of intensive management of acute stroke and treatment of hypertension
associated to the concomitant and diffused reduction of potential risk factors like alcohol consumption
5
and tobacco smoking in the general population. In the only French stroke register, in Dijon, incidence
8
was found to increase over the same period , which increases the likelihood that the intensive
management of acute stroke may have played a role in the reduction of mortality.
Hypertension
Hypertension mortality increased from 1970 to 1975, and then slowly decreased. This decrease is
compatible with the rise in the number of patients treated for hypertension. However the time trend for
this cause of death has to be considered with cautious, as it could also reflect variations in both the
death certification and codification process.
Ischaemic heart disease mortality decreased sharply after 1986 until 2005 for both sexes in a quite
homogeneous manner. The slight change in the mortality trend observed in 2001 is of far smaller
amplitude than the reversion of the trend observed between 1975 and 1985. Therefore, the most part
of the variation of this specific cause of death is hardly attributable to the introduction of coronary care
unit, as suggested by the knot match. The expected time period for a favourable shift in mortality trend
related to the introduction of beta-blockers (1987-1994) corresponds to a large decrease of the
379
mortality. Then, even if it has not initiated the mortality shift, it may have contributed to the decrease in
mortality.
Heart failure
Mortality from heart failure has strongly and regularly decreased from 1970 to 2005. No influence of
the introduction of ACE-inhibitors could have been highlighted. However, such a time trend has to be
considered with caution, as it could reflect variations in the death certification and codification process
Rheumatic heart diseases
Rheumatic heart diseases mortality increased from 1970 to 1980, and then decreased until 2005.
Considering the amplitude of the correction factors applied to the time series, the comparability of the
figures between each ICD revision is questionable. However, the estimated period of a possible effect
of the introduction of treatment with artificial valve replacement on a mortality decrease (between 1970
and 1977) occurs during the same ICD revision, thus limiting the comparability issues. No substantial
effect of this introduction is observed on mortality at the population level.
Hodgkin's disease
Hodgkin's disease mortality has continuously decreased from 1970 to 2005. Between 1980 and 2005,
9
Hodgkin's disease incidence has slightly decreased for males and remained stable for females . No
association between a specific decrease and the introduction of high dose therapy and peripheral
blood stem cell transplantation was observed during the 1990's. It seems that several previous
innovations were already implemented before, explaining the fast decrease in mortality during the
1980's.
Leukemia
Leukemia mortality increased until 1978 and then slowly and continuously decreased until 2005.
9
Between 1980 and 2005, leukemia incidence slightly increased . The shift in the mortality trend occurs
during the expected shift period related to the introduction of improved treatment (1980-1987) for both
sexes. The decrease in leukemia could be largely attributable to the introduction of improved
treatment.
380
Malignant colorectal neoplasm mortality increased from 1970 to 1976 and then decreased slowly until
2005. An acceleration of the fall, specifically for males, was detected as a knot in 1992. This knot
coincides both with the expected period of an effect related to the introduction of treatment with
oxaliplatin (1988-1995) and colonoscopy (1990-1997). However, the main shift was observed well
before, in 1976. Considering that colorectal cancer incidence remained stable between 1980 and
9
2005 , most of the decrease in mortality could be attributed to survival improvement. Therefore, most
of the mortality variations may not be specifically attributed to the introduction of these innovations,
even if it has probably contributed to it.
Malignant neoplasm of cervix uteri mortality has been continuously decreasing from 1970 to 2005 in
France. No specific break in the time series could be observed. Between 1980 and 2005, malignant
9
neoplasm of cervix uteri incidence has decreased in a manner similar to mortality . Since no
innovation or cervical screening was set at the national level in France during the study period, no
association was expected. However, the decrease in mortality could be partly attributable to the slow
diffusion of opportunistic cervical screening.
Malignant neoplasm of testes
Malignant neoplasm of testes mortality strongly and quite continuously decreased from 1976 to 2005,
while the use of cisplatin was expected to have an impact on mortality from 1977 to 1984. Meanwhile,
9
between 1980 and 2005, testicular cancer incidence increased and survival has increased. As the
knot is close to the expected period, in absence of other explaining factor of this decrease, the
expected period could have been slightly overestimated. Indeed, the level of evidence used to infer it
is low in France. In this case, the major part of the decrease would indeed be attributable to the use of
cisplatin. However, we have no additional elements to support this hypothesis.
Malignant neoplasm of breast
Malignant neoplasm of breast mortality is quite stable over the whole period, with a slight decrease
beginning in 1989. The shift in mortality trend coincides with the expected time period for an effect of
the introduction of screening with mammography, between 1989 and 1996. Breast cancer incidence
9
increased steadily over the same period . Then, it is likely that breast cancer screening has played a
role in the increase of survival for people having breast cancer. However, the decrease in mortality
since 1990 is too slight to consider that breast cancer screening is explaining a substantial fraction of
breast cancer mortality variations. The expected time period corresponding to an effect of the
introduction of Tamoxifen is not coinciding with any mortality trend shift. The role it could have played
on mortality variations is not strong enough to be observable.
381
Peptic ulcer
Peptic ulcer mortality trends have very different pattern depending on gender. It increased between
1970 and 1976 for males, and then strongly decreased until 2005. For females, it increased until 1985,
and then decreased in the same manner as males. If cimetidine is implicated in the decrease for
males, the difference in its impact by gender would result from a differential indication by gender. This
is plausible, given that cimetidine could have interactions with oral contraceptive. Overall, the level of
evidence of the effect of cimetidine on the decrease of mortality remains low.
Renal failure
Renal failure mortality decreased from 1970 to 1992. Then, it remained stable until 2005. The
immunosuppressive treatment with cyklosporin for kidney transplantation was estimated to potentially
influence mortality trends in France between 1982 and 1989 in France. It is not possible from such
results to establish an association between the introduction of therapeutic innovation and a shift in the
mortality trends. Then introduction of cyklosporin may have only explained a fraction of the decrease.
382
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1994;23(3):545-52.
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development of the care system and the level of "preventable" mortality according to
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8. Khellaf M, Quantin C, d'Athis P, Fassa M, Jooste V, Hervieu M, et al. Age-period-cohort analysis of
stroke incidence in Dijon from 1985 to 2005. Stroke 2010;41(12):2762-7.
9. Belot A, Grosclaude P, Bossard N, Jougla E, Benhamou E, Delafosse P, et al. Cancer incidence and
mortality in France over the period 1980-2005. Rev Epidemiol Sante Publique
2008;56(3):159-75.
383
Country specific report on mortality trends in Germany
Author: Wolfgang Hellmeier
Affiliation: Landesinstitut für Gesundheit und Arbeit NRW, Bielefeld, Germany
The German Health system
The Federal Republic of Germany (FRG) has about 80 millions inhabitants and is organised in 16
states (Länder) which have a considerable political role. During the time interval which was studied in
AMIEHS (1970 – 2005) there was the reunification of the former German Democratic Republic to the
FRG in 1990, which brought about 17 millions people to the country. Until the reunification there were
substantial differences between the health status and the health systems of the two states.
The health care system of Germany is special in the way that several political levels (national and
state level) and several non governmental institutions act together with different duties and tasks.
More that 85 % of the population are covered by a statutory health insurance.
The trend of some causes of death in Germany
Mortality of malignant neoplasm of cervix uteri has to be described differently for former East and
West Germany because the mortality rates are quite different.
In West Germany a constant decline can be seen starting in 1975 bringing the rate from more than 7
deaths per 100 000 women (age standardised) to less than 3 in 2005 while in East Germany mortality
from malignant neoplasm of the cervix uteri were more than 9 per 100 000 in 1980 and went down to
about 4 per 100 000 in 2005.
The main intervention is screening which was introduced in West Germany beginning about 1971 with
growing attendance rates and which was extended to East Germany after the reunification. While the
data for West Germany show a clear change of trend in 1973, which can be attributed to the starting of
the nation wide screening this link is not so clear in East Germany. Data show a downward trend in
mortality due to neoplasm of the cervix uteri not only after the introduction of the screening in 1991 but
already from 1980. Probably screening was performed in growing numbers in East Germany as well
without having official guidelines.
Again, trends of mortality by cerebrovascular disease were quite different in East and West Germany.
In West Germany there was a steady decline between 1970 and 2005, lowering the standardised
mortality to a quarter. In East Germany a substantial decline can only be seen after 1991 resulting in
slightly higher figures compared to the western part of the country in 2005.
Looking at cerebrovacular disease there is no clear relationship between the interventions – treatment
of hypertension as prevention of stroke and the establishment of clinical stroke units – and mortality.
384
Both interventions were reported to have been used for 1995 or later while the decline – at least in
West Germany – was quite constant during the last 40 years.
Congenital heart disease and conditions originating in the perinatal period
Mortality from congenital heart disease and conditions originating in the perinatal period are equal in
both parts of Germany until 1990 and in 2005. The trend after 1992 is different, having a peak around
1998 in East Germany while the mortality stays on a constant level since that time in the western part
of the country.
HIV
Mortality from HIV in West Germany had its peak around 1994 with 6 cases per 100 000 men and 1
case per 100 000 women. After a very fast decline until 1998 to a quarter of the peak values the trend
for men lowered very slowly whereas the trend for women remained nearly constant.
Looking at the time of introduction of anti-viral drugs in Germany, the sudden change in HIV mortality
can be linked to it. However the change in HIV mortality in 1995 can also be linked to a similar decline
in HIV incidence which took place in 1985 after a steep rise from 1978 (RKI: Epidemiologisches
Bulletin 46/2010). This indicates that the falling mortality rates were to a great extend linked to falling
incidence rate due to primary prevention and growing awareness and changes in sexual behaviour in
the population.
Heart failure
In West Germany mortality from heart failure dropped from nearly 190 cases per 100 000 in 1970 to
less than 40 in 2005. Absolute figures and trend were quite similar for men and women with slightly
smaller numbers for women. The numbers were smaller in East Germany in 1980, the first year where
data are available and are still smaller in 2005. The trend is not as steady as in West Germany with a
slower decline between 1983 and 1988 and a steeper slope until 1998.
A link between the mortality from heart failure and the prescription of ACE-inhibitors cannot be shown
in the mortality data.
Mortality from ischaemic heart disease rose until 1984 in West Germany. From this year on the
numbers fell permanently. In East Germany not only the peak of the trend was about 10 years later
but the figures were also higher than in West Germany during the whole time interval.
The change of trend in West Germany can very well be linked to the use of beta-blockers for
secondary prevention. The differences between West and East Germany indicate that it lasted some
time after the reunification until beta-blockers were used in the eastern part as well.
AMIEHS also looked at the introduction of coronary care units. Though it was not possible to get
appropriate data about the time of introduction and the degree of diffusion of coronary care units
throughout Germany which could have been entered into the project, it is known that coronary care
units exist in many hospitals. It can be assumed that they also played a significant role in lowering
mortality from myocardial infarction. Many preventive actions were initiated in order to increase the
385
awareness of symptoms of myocardial infarctions in the population and to encourage people having
these symptoms to call an ambulance immediately.
Hypertension
Mortality rates from hypertension were decreasing between 1970 and 1989 in West Germany, rose
slightly until 1995 and increased much faster since then. In East Germany a similar development can
be seen but the numbers were more than double of the western ones in 1980, being still higher in
2005.
In West Germany there was a sudden change in the trend around 1982 which could be attributed to
the guidelines on treatment of hypertension which existed at least since 1982 and were probably
discussed and used already around 1980.
Peptic ulcer
In West Germany mortality from peptic ulcer declined from 12 cases per 100 000 men and 3 to 3.5
cases per 100 000 women in 1970 to slightly more than 2 cases per 100 000 for both, men and
women in 2005. Between 1970 and 1975 the decline was relatively slow for men and for women the
mortality even raised in this time interval. In East Germany mortality for peptic ulcer was higher than in
West Germany. In 1980 rates were as high as they had been in 1970 in West Germany. In 2005
mortality rates are quite similar for men and women in East and West Germany.
Treatment with Cimetidine which was taken as intervention in AMIEHS was started about 1980 and an
effect which could be attributed to Cimetidine should show up between 1980 and 1985. But the trends
do not show any distinct change during this time.
Mortality rates for cancer of the testes were about 1.5 cases per 100 000 men in the early seventies
and went down to less than 0.4 cases per 100 000 in 2005 in West Germany. The decline started in
1975, being strongest between 1979 and 1992. East German figures show the highest rates in 1987
with 2 cases per 100 000 men and a straight decline until 1998 to values similar to those in West
Germany. Since then mortality rates have been stable.
Cisplatin was registered in West Germany in 1979 for treatment of cancer of the testes. Mortality rates
started to decline during the same time. The steep decline of the mortality trend could be attributed to
the drug.
Colorectal cancer was responsible for a similar mortality rate in the western and the eastern parts of
Germany throughout the time interval from 1980 to 2005. In West Germany, they rose between 1970
and 1978 to 37 cases per 100 000 men and 28 cases per 100 000 women, showed a steep step
downwards until 1979 and declined more steadily to 26 cases per 100 000 men and 18 cases per 100
000 women in 2005. In East Germany the decline started in 1990 for men and 1984 for women.
Treatment with Oxaliplatin was not very common in Germany before 2000 and its introduction does
not correspond to any sudden change in trends. The sudden change from rising rates to declining
386
ones is also too early to correspond to the introduction of colonoscopy for diagnostic examinations, at
least regarding the publishing of guidelines. As with some other causes of death discussed in the
study it could be assumed that some interventions are used in practical work before guidelines and
official recommendations are published, thus causing a change in mortality earlier and slower than
expected.
Hodgkin’s Disease
Hodgkin’s Disease is relatively rare. Mortality rates are between 1 and 2 cases per 100 000 in 1970
and below 0,4 cases per 100 000 in 2005. The mortality rate is slightly higher in men. Differences
between West and East Germany are not very large and the data show the same trend.
There is a relatively large change in mortality rates from 1993 to 1994 in West Germany and between
1997 and 1998 in East Germany which could be attributed to the introduction of high dose therapy and
blood stem cell transplantation in the treatment of the disease. Both interventions were more
frequently used in Germany since the first part of the 1990s.
Rheumatic heart diseases
In 2005 mortality rates for rheumatic heart disease were 1 to 1,3 cases per 100 000 men and 2 to 2,5
cases per 100 000 women, both values are slightly higher in West Germany, while the rates were
higher in East Germany in 1980. In West Germany there was a steep decline between 1970 and 1983,
resulting in rates below those of 2005. Around 1985 the mortality from rheumatic heart disease rose
for some years and declined steadily from 1987 until 2005. For East Germany data show a permanent
decline from 1980 until 2005.
Renal failure
Renal failure is the only cause of death analysed in the study where mortality rates went up
considerably during the last years. Since 1970 the rates went up until 1975 to go down steeply until
1985. From 1985 to 1998 they stayed around 4.7 cases per 100 000 women and 7.2 cases per 100
000 men to rise since then. Mortality rates are 7 cases per 100 000 women and 9 cases per 100 000
men in West Germany in 2005.
In East Germany a constant rise can be seen from 1980 to 2005 resulting in rates of around 7 cases
per 100 000 men and slightly more than 5 cases per 100 000 women.
387
Breast cancer
Mortality due to malignant neoplasm of breast increased in both parts of Germany between 1970 and
1990 and went down since then. Mortality rates are higher in West Germany while the trends in both
parts of the country are comparable. Several reasons for the difference between the two parts of
Germany are discussed. Differences in lifestyle and in prescription of hormones might be responsible.
(RKI, Beiträge zur Gesundheitsberichterstattung des Bundes: 20 Jahre nach dem Fall der Mauer: Wie
hat sich die Gesundheit in Deutschland entwickelt? Berlin, RKI, November 2009).
The decline of mortality due to breast cancer began some years earlier than mammography screening
is reported for West Germany. It can be assumed, that mammography took place earlier without being
named as screening.
The increase of mortality from breast cancer in West Germany nearly stopped in 1986. This change
can be linked to the fact that Tamoxifen was registered in West Germany as a treatment of breast
cancer in 1983.
Leukaemia
The standardised mortality rate between 1970 and 1980 was about 8.5 per 100 000 for men and
between 5 and 5.5 per 100 000 for women. In 1980 the rates dropped by about 2 deaths per 100 000
for men as well as for women and since 1980 they rose again to reach nearly the level of 1970 in
2005. The trends were quite similar in East Germany.
Papers about improved treatment of Leukaemia show that several clinical trials were performed
around 1980. For example bone marrow transplantation was started in 1980. Though there is a
statistical coincidence of the sudden change in mortality from Leukaemia and the improvements in
treatment, the change in trends seems to be too early to be a result of the new treatments. The
growing trend since 1980 cannot be explained by changes in treatment at all.
Summary
Due to the separation of Germany into two states until the reunification in 1990 there were many
differences between the health systems which were harmonised since 1990. Data availability for East
Germany was worse than for West Germany. Not only were the available mortality data for East
Germany restricted to the time interval from 1980 to 2005 but it was also not possible to gain
information about the introduction of the interventions which are looked at in this study. Therefore the
possible links between the introduction of certain interventions and positive changes in mortality rates
could only be discussed for West Germany.
On the other hand the data collected for the study gave a good opportunity to compare mortality rates
from certain causes for the two parts of Germany. In general the trends were similar with slightly
higher levels in East Germany, with a few exceptions.
388
Country specific report on mortality trends in the Netherlands
Authors: Iris Plug, Johan Mackenbach
Affiliation: Erasmus MC, Rotterdam, The Netherlands
The Dutch health care system
Since 2006 all residents of the Netherlands and those paying income tax are required to purchase
health
insurance
coverage.
Coverage
is
statutory
under
the
Health
Insurance
act
(Zorgverzekeringswet; ZVW) but provided by private health insurers and regulated under private law.
1
The uninsured proportion of the population is estimated at 1.5% . The statutory health insurance
system is financed by a mixture of income related contributions and premiums paid by the insured.
Employers must reimburse their employees for this contribution and employees must pay tax on this
reimbursement.
Private health insurance was abolished in 2006. Most of the population purchases a mixture of
complementary and supplementary private health insurance from the same health insurer.
Insurers are private and governed by private law.
A key feature of the Dutch system is that premiums may not be related to health status or age.
Children under 18 are covered for free. Those on low income are compensated to help them pay
health care.
Most hospitals are private non-profit organizations. Physicians practice directly or indirectly under
contracts negotiated with private health insurers. GPs receive a capitation payment for each patient on
their practice list and a fee per consultation. Most specialists are hospital employed.
Quality of care
At the health system level, quality of care is ensured through legislation regarding professional
performance, quality in health care institutions, patient rights and health technologies. A national
inspectorate for health is responsible for monitoring and other activities. Mechanisms to ensure quality
in care provided by professionals involve re-registration/revalidation for specialists based on
compulsory continuous medical education, regular on site peer assessments organized by
professional bodies, profession owned clinical guidelines, indicators and peer review. The main
methods to ensure the quality in institutions include accreditation and certification, compulsory and
voluntary performance assessment based on indicators and peer review.
The main approach to improving efficiency in the Dutch health systems rests on regulated competition
between insurers combined with central steering on performance and transparency about outcomes
via the use of performance indicators.
389
Causes of death
HIV
Innovation: Antiretroviral therapy
Since 1985 a strong increase in mortality from HIV has been observed both in males and in females. A
peak level was reached around 1994, after which mortality declined dramatically. For both males and
females a favourable change in the mortality trend has been observed that falls within the period in
which an effect on mortality is expected (1987-1994), however the most important decline falls outside
this period. This may be explained by the small effect that can be expected from the first trials with
AZT that started in 1987 and only included a small number of patients. The most important decline in
mortality that started in 1994 can probably be explained by the introduction of cART, combination
antiretroviral therapy, which was introduced in 1996. In conclusion we can say that mortality from HIV
2
in the Netherlands declined as a result of medical innovations .
Innovation:
Diagnostic examination with colonscopy
Oxaliplatin treatment
For mortality from colorectal neoplasm an ongoing decline in mortality is observed in the Netherlands.
This is present for both males and females. In females this decline is rather steady, while in males a
sudden decline is observed after 1987. A study performed in the South of the Netherlands shows that
the incidence of colon cancer increased since 1975, while the survival increased dramatically (ref).
These advances in survival explain the declining mortality rates.
Earlier detection of colorectal cancer possibly has its effect on survival; an effect was expected
between 1985 and 1992. For both males and females a favourable change in mortality was observed
in 1987, which implicates a possible association between early detection with colonscopy and
decreasing mortality. A Dutch national study has shown that although the use of colonscopy is part of
3
Dutch guidelines the use of this early detection method could be improved . Only around 2002 the
adherence to clinical practice guidelines increased, therefore we may need to conclude that next to
colonscopy other aspects like better staging and surgery also had their effects on decreasing
mortality.
The effect of adjuvant chemotherapy (Oxaliplatin) is expected between 1999 and 2005. We have
observed no favourable changes in the mortality trend within this period. Therefore we can not
conclude that the use of oxaliplatin is associated with a decline in mortality. This may also be due to
the fact that already since the 1980’s improvement in survival has been achieved in randomized
clinical trials, in particular due to advances in chemotherapy. Only in recent years oxaliplatin replaced
previous types of chemotherapy. The effect of this specific change is most likely to be limited.
We can conclude that in the Netherlands both early detection by means of colonscopy and the
introduction of chemotherapy have had a positive effect on mortality.
390
Malignant neoplasm of female breast
Innovation:
Screening with mammography
Introduction tamoxifen
The mortality trend of breast cancer shows periods of decline and increase in mortality between 1970
and 1990, in the early 1990’s breast cancer mortality declines progressively. Studies show an
increasing incidence with increasing survival. The time period in which an effect of screening on
mortality is expected is 1975 to 1982. No favourable change in mortality is detected within this period.
However mass screening in the Netherlands has been introduced between 1991 and 1996, in this
4
period an important decline in mortality is detected . In the earlier period screening was done
opportunistic or only within certain regions of the Netherlands. The expected period for the effect of
tamoxifen, a chemotherapeutic, on mortality was 1981 to 1988. No favourable change is detected
within this period. However the proportion of women that received this treatment has increased over
the years, indicating that within the defined period this may have been limited, but an increasing use
has contributed to the decrease detected in the 1990’s. Overall we can conclude that health care has
contributed to a decline in mortality from breast cancer, but we have not been able to detect this.
Innovation: Cervical screening
Mortality from cervical carcinoma shows an ongoing decline since the 1970’s. There seems to be a
small increase in mortality in the late 1980’s. Population screening has had a positive effect on
mortality which has been shown in previous studies. However in our study we have not been able to
determine a favourable change in mortality which falls within the period in which screening should
have had its effect on mortality (1980-1987). However, we need to take into consideration that the
introduction of screening has been a gradual process, which has evolved from opportunistic screening
(introduced in the 1970’s), into regional programs, and finally an official national program (introduced
in 1996). Taking into account earlier studies we have to conclude that there is a positive effect of
5
screening on mortality also in the Netherlands , however we were not able to detect this.
Innovation: Cisplatin
Since the 1970 mortality from testicular cancer shows an ongoing decline, with stabilization around the
1990’s. In the Netherlands incidence of testicular cancer has been increasing, although it is not clear
when this started. The increasing incidence but declining mortality can be attributed to the higher
percentage of less-aggressive tumours, which have higher survival rates. The increased survival rates
can possibly be attributed to the introduction of cisplatin containing chemotherapy. However we have
not observed a favourable change in the mortality trend which coincides with the period in which an
391
effect of cisplatin is expected (1976-1983). Taking into account other studies we can conclude that
6
there is an effect of cisplatin, however we were not able to detect this .
Hodgkin’s disease
Innovation: Introduction of high dose therapy and peripheral blood stem cell transplantation
Since 1970 mortality from Hodgkin’s disease shows a decline both for males and for females. For
males a small increase is observed in the 1980’s. Hodgkin lymphoma is a disease which is especially
occurring in the younger ages and in the ages above 55. Survival has improved in the Netherlands;
currently this is about 80%. The introduction of high dose therapy and peripheral blood stem cell
transplantation occurred in the Netherlands around 1994 and is not related to a favourable change in
mortality. Decline in mortality was already started in the 1970, possibly induced by the introduction of
radio- and chemotherapy. Another point of decline is observed in the late 1980’s which could be due
to the detection of risk factors influencing individual treatment. Therefore we can conclude that the
decline in mortality from Hodgkin’s disease is responsive to medical innovations, but in our analyses
we have not been able to show this.
Leukaemia
Innovation: Improved treatment of disease process and complications
Mortality of leukaemia shows a gradual decline between 1970 and the early 1990’s. This is followed by
a period of in- and decreasing mortality rates. This is observed for both males and females. The period
in which an effect on mortality is expected is from 1972 to 1979, we do not observe a favourable
change in mortality within this period. In the Netherlands survival from leukemia has improved.
Innovation: Artificial valve replacement
Since 1970 a decline in mortality is observed, which is very sharp around 1975. After this sudden drop
the decline continues, but stabilizes around the 1990’s. This is seen for both males and females.
There is no information on the timing of introduction of artificial valve replacement in the Netherlands;
therefore we can not associate the sudden decline to the introduction of this innovation.
392
Hypertension
Innovation: Increased number of patients treated
Since 1970 mortality from hypertension has declined for both males and females. This decline was
very strong between 1970 and 1975, after which periods of reduced decline followed. In females we
also observe a period of increasing mortality during the 1980’s. In males on a moment of favourable
change in mortality coincides with the period defined as the period in which the number of patients
treated for hypertension increased. It is however unlikely that this had a major influence on mortality.
Innovation:
Secondary prevention with beta blockers
Introduction of coronary care units
Mortality from ischemic heart disease decreased gradually but constantly between 1970 and 2005.
The period in which an effect of secondary prevention with beta blockers is expected is between 1985
and 1992. For both males and females a favourable change in mortality is observed within this period,
although for females the change is not significant. From this finding we can conclude that there is an
association between beta blockers and an improvement in mortality. A meta-analyses has also shown
7
the positive effect of beta-blockers on survival . The period in which the introduction of coronary care
units may have influenced mortality was between 1977 and 1984. No favourable changes in mortality
are observed within this period. The effect of coronary care units is also debated in the literature and it
is sometimes mentioned to have a positive effect on mortality. From our data and based on literature
we can conclude that medical innovations had an effect on mortality. However it is important to also
8
take into account the impact of primary prevention efforts .
Heart failure
Innovation: ACE inhibitors
The trend in mortality from heart failure is inconsistent, periods of decline and increase in mortality can
be observed. It is hard to explain this uneven pattern, and although coding changes have been taken
into consideration this can not be excluded as one of the explanations. This uneven pattern is also
9
observed in the Nationaal Kompas Volksgezondheid . The incidence of heart failure has been showing
a moderate decline in the 1990’s, for both males and females. The survival after myocardial infarction
has improved due to medical interventions; however this increases the risk of heart failure and
contributes to the increasing mortality from heart failure. The period in which an effect of the
introduction of ACE inhibitors on mortality from heart failure is expected was1990-1997. No favourable
changes are observed within this period. In conclusion we can not relate treatment with ACE inhibitors
with declining mortality from heart failure.
393
Innovation:
Treatment of hypertension
Introduction of intensive management
Since 1970 a continuous decline in mortality can be observed for cerebrovascular disease for both
males and females. The period in which the introduction of treatment of hypertension is expected to
have an effect on mortality is between 1986 and 1995, within this period a favourable change in
mortality occurred. As this is observed for both males and females an association can be expected.
The same is observed for intensive treatment of stroke patients. The effect of primary and secondary
10
prevention on mortality from stroke have also been described in literature .
In conclusion mortality of cerebrovascular disease has declined due to treatment of hypertension and
introduction of intensive management.
Peptic Ulcer
Innovation: Cimetidine
The mortality trend for peptic ulcer shows an ongoing decline both for males and females. Cimetidine
was introduced in the Netherlands around 1977 and an influence on mortality is expected between
1977 and 1984. Within this period no favourable changes in mortality are observed, indicating that
there is no association between the innovation and mortality decline. However in the literature the
effectiveness of cimetidine for the treatment of peptic ulcer has been shown. In conclusion we find no
association, but that does not prove that there is no effect of health care on mortality from peptic ulcer.
Renal failure
Innovation: Immunosuppressive therapy
Both in males and females an increasing mortality is observed between 1970 and 1980, which is
followed by a decline in mortality. The period in which the introduction of immunosuppressive
treatment with cyclosporine for kidney transplantation can have its influence on mortality is between
1983 and 1990. No favourable knots are observed within this period, indicating that there is no
association between the innovation and mortality decline.
394
Innovation: not available
Mortality of congenital heart disease shows a stepwise decrease since 1970, a short period in which
mortality stabilizes is present in the 1980’s for females. Advances in cardiovascular treatment and
surgery have enabled patients to reach older ages, and survival has increased.
Innovation: due to the large amount of innovations, it is not possible to pinpoint one innovation
Mortality from conditions originating in the perinatal period shows an ongoing gradual decrease since
1970. A rather steep decrease is detected in the late 1970’s. After 1990 mortality stabilizes.
Studies have shown that perinatal mortality is higher in the Netherlands than in surrounding countries.
In comparing mortality rates the definition of perinatal mortality is of importance. Current research
11
aims at the identification of factors explaining the high rates in the Netherlands .
395
References:
1. Klazinga N. The Dutch Health care system. Amsterdam: Common Wealth Fund, 2008.
2. monitoring SH. Monitoring of Human Immunodeficiency Virus Infection (HIV) in the Netherlands.
AMSTERDAM: Stichting HIV monitoring, 2010.
3. van Steenbergen LN, Elferink MA, Krijnen P, Lemmens VE, Siesling S, Rutten HJ, et al. Improved
survival of colon cancer due to improved treatment and detection: a nationwide populationbased study in The Netherlands 1989-2006. Ann Oncol;21(11):2206-12.
4. Louwman MJ. Breast cancer incidence and survival, 2007.
5. van der Aa MA, Pukkala E, Coebergh JW, Anttila A, Siesling S. Mass screening programmes and
trends in cervical cancer in Finland and the Netherlands. Int J Cancer 2008;122(8):1854-8.
6. Verhoeven R, Houterman S, Kiemeney B, Koldewijn E, Coebergh JW. Testicular cancer: marked
birth cohort effects on incidence and a decline in mortality in southern Netherlands since
1970. Int J Cancer 2008;122(3):639-42.
7. Soriano JB, Hoes AW, Meems L, Grobbee DE. Increased survival with beta-blockers: importance of
ancillary properties. Prog Cardiovasc Dis 1997;39(5):445-56.
8. Bots ML, Grobbee DE. Decline of coronary heart disease mortality in The Netherlands from 1978
to 1985: contribution of medical care and changes over time in presence of major
cardiovascular risk factors. J Cardiovasc Risk 1996;3(3):271-6.
9. Hoes AW, Mosterd A, Rutten, F.H, Poos, M.J.J.C. Neemt het aantal mensen met hartfalen toe of
af? . Nationaal Kompas Volksgezondheid. Bilthoven: RIVM, 2006.
10. Limburg M, Schade E, van Crevel H. [The acute stage of cerebrovascular accident (CVA);
characteristics and management]. Ned Tijdschr Geneeskd 1992;136(28):1370.
11. Bais JM, Eskes M, Bonsel GJ. [The determinants of the high Dutch perinatal mortality in a
complete regional cohort, 1990-1994]. Ned Tijdschr Geneeskd 2004;148(38):1873-8.
396
Country specific report on mortality trends in Spain
Author: J.L. Alfonso
Affiliation: Fundación de investigación. Hospital General Universitario de Valencia
The Spanish Health Care system
Spain’s National Health Service model guarantees access to health care for all citizens. The
healthcare system is divided into two levels: the first or primary healthcare level serves the population
through family physicians, while the second level of care provided is specialized care, accessible
through referral from primary care. Health centres provide primary healthcare services that include
family and GP services, nursing and paediatrics, social assistance, and physiotherapy. The healthcare
centres should be located within fifteen minutes of a person’s place of residence, and if circumstances
require it, medical professionals may pay a home visit.
Total health expenditure accounts for about 8% of the GDP.
HIV/AIDS
The mortality rate due to HIV/AIDS in Spain has followed a similar pattern for both sexes, although the
rate for men was four times higher than for women throughout most of the study period. The trend in
mortality has two periods: a first period in which the rates increase, reaching their peak in 1995 (five
years after the peak incidence rate in 1990) (1), and a second period which stretches from 1995 to the
present, when a steady decline can be observed. Although in 1985 the National Anti-Drug Plan was
first implemented, it was not until 1995 that there was a decrease in mortality rates. Likewise,
Zidovudine was introduced in Spain in 1987, but dramatic reductions in mortality in both sexes (nearly
50%) were reached only in 1995, coinciding with the expected time period for a favourable shift in
trend for AIDS mortality influenced by the introduction of HIV/AIDS treatment with antiretroviral drugs.
The importance of antivirals in reducing HIV/AIDS mortality in both sexes is worth highlighting, as is
the impact of various international publications, the effect of participation in a European multi-centre
clinical trial starting in 1993 (2), and the publication of a clinical study in 1993(3).
Heart Failure
Mortality rates from heart failure in Spain were almost 20% higher in men than in women throughout
the study period. Notably, the baseline rate in 1970 was very high; however, it has been declining
continuously since then. The period of greatest decline coincides with the expected time period for a
favourable shift in the mortality trend of health influenced by treatment with ACE-inhibitors, with a
reduction of 4.25% per year.
Thus, the mortality rate for both sexes was positively influenced by the introduction of Captopril
(reported registered in 1981), the period of maximum shift, and even the evolution of the sales figures
397
of ACE-inhibitors. Although there was a decrease in unit sales of Captopril, there was an increase in
sales of Enalapril.
International guidelines published in 1995 (4), 1997 (5) and 2001 (6), could also have had an effect in
reducing mortality.
398
Ischaemic Heart Disease (IHD)
The evolution of mortality rates for ischaemic Heart Disease in Spain was also quite similar among
men and women, but rates were almost always twice as high for men compared to women.
In the study of the evolution of these rates, there are two periods: a first period with a significant
increase in rates, from 1970 to 1975, and a second period which followed until 2007, characterized by
gradual but steady declines until the rates from 1970 were eventually achieved.
However, it is worth noting that the rates in Spain were the lowest of all the European countries
studied; elsewhere, rates were fairly stable, albeit declining, confirming previous studies on the
evolution of mortality due to this cause (7).
The distribution of medication for the prevention of myocardial infartion, whose greatest impact was
observed from 1995 onwards (after the publication of clinical guidelines (8)), had a special significance
in the trend of mortality from this disease. The expected time period for a favourable shift in the
mortality trend for myocardial infarction influenced by the introduction of medication for secondary
prevention with beta-blockers (1982-1989), and with coronary care units (1991-1998) had much to do
with the decline in the mortality rate.
Regarding the influence of coronary care units, it must be noted that according to some studies,
between 1996-98, 89% of IHD patients aged 25-74 were admitted to coronary care units (9), and since
1999, there have been Spanish consensus guidelines for best practice available to health
professionals (10).
In conclusion, both the availability of medication and the distribution of coronary care units have
coincided with declining mortality rates, suggesting that these factors have had an influence on the
evolution of the mortality rates due to this disease.
Peptic ulcer
The trend in mortality from peptic ulcer in Spain shows a decline from the early 1970s to the present.
The outcomes have been very similar in men and in women, although the declines in the former group
were consistently higher than in the latter. Thus, the ratio between male and female mortality
decreased from 4:1 in 1970 to almost 2:1 in 2007.
The adoption in 1977 of Cimetidine marked a significant advancement in the treatment of this disease,
and the largest reductions were in line with the expected time period for a favourable shift in mortality
trend for peptic ulcer influenced by the introduction of treatment with Cimetidine. This translated to
reductions of nearly 9% per year during that period in men and nearly 6% in women.
399
The dissemination of knowledge on this treatment through published clinical studies, such as the small
clinical trial published in 1980 (11), may also have had an effect.
Cerebrovascular disease (CVD)
The trend in mortality from cerebrovascular disease in both women and men in Spain was similar, but
rates were always slightly higher in the latter group.
The gender ratio has
remained virtually constant throughout the study period at 1:1.
The trend of mortality rates in both sexes shows an initial period of 3-4 years in duration in which
mortality rates increased; however, since 1975, they have been declining. The introduction of
antihypertensive medication has coincided with the greatest decreases in these rates and the
expected time period for a favourable shift due to the introduction of treatment of hypertension. The
reduction reached 4.5% annually, and over a period of about thirty years (from 1975 to 2007), the
mortality rates dropped from 180 to 60 per 100.000 inhabitants.
Another development during this period of improvement includes the publication of the clinical
guidelines in 1995 (12).
In Spain, scientific societies and health authorities are making great efforts to implement a plan for
stroke care, both at a national and regional level (13).
While the actual incidence of stroke in Spain cannot be precisely quantified, it seems that unlike
mortality, incidence is increasing every year. According to data from the survey of hospital morbidity,
in 2006 there were 114,807 hospital discharges with primary diagnosis of CVD, 32% more than in the
year 1997 (14). The ageing of the population seems to be the cause; whereas the incidence rate
stands at around 132-174 cases of stroke per 100,000 inhabitants per year, it reaches 3,000 cases in
populations over 85 years old.
Hypertension
An analysis of trends for mortality rates in Spain due to hypertension show a similar evolution in men
and women. A first period lasting around ten years (from 1970 to 1980) shows a steady decline, while
the next decade is characterized by stability. Since about 1990, mortality rates have been gradually
rising.
The use of antihypertensive medication was closely related to the decrease and subsequent
stabilization of mortality rates, coinciding with the expected time period for a favourable shift in
mortality trend influenced by the number of patients treated for hypertension in both males and
females. However, additional factors appearing after 1990 may have contributed to a gradual increase
in mortality rates, which have been rising among both sexes by almost 2% per year.
400
Among the factors to be blamed for the increase, clinical inertia (15) and therapeutic non-adherence
by patients may be responsible for up to 66% (16). Increases in incidence and prevalence should also
be considered. The latter rate among the general adult population of Spain is about 35%, reaching
40% in middle age and more than 60% in those over 60 years. In total, hypertension affects about ten
million adults (17).
Rheumatic Heart disease
With regard to mortality rates observed in the study period due to rheumatic heart disease in Spain,
these used to be the highest in Europe, tripling those of its neighbours in 1970. However, mortality
began to fall sharply after that, and by 1980, figures were comparable to those seen in other countries.
Rates are currently quite stable, although slight declines are still apparent. It should be noted that
mortality rates have consistently been higher in women than in men.
We must highlight the important decline that occurred in Spain in those first ten years, a phenomenon
which was studied at the time by some Spanish authors (18). The introduction of the artificial valve
replacement was very important; this contributed to the 12% annual decline observed in both sexes
and coincided with the expected time period for a favourable shift.
Cervix uteri
Regarding the trend of the cervix uteri cancer mortality in Spain, it may be said to have shown
practically
the
lowest
mortality
rates
among
all
European
countries
studied.
Its evolution is divided into two distinct periods: the first saw a gradual increase, beginning in 1970
with rates close to 1 per 100,000 inhabitants and ending in 1990 with rates close to 2.5; the second
period was characterized by fairly constant rates of about 2.3 per 100,000 inhabitants, although there
has been a further decline in recent years. This decline is attributable to the introduction of cervical
cancer screening at a national level in Spain in 1995.
Until then, organised screening had been implemented only unevenly. A Pap smear screening
programme was first established by the National Health Service in the mid-1970s and offered by
family planning clinics, but this programme did not reach more than 30-46% of sexually active women
until the mid-1980s (19). In addition, women attending the first screening often did not continue in the
programme. Any positive effect of this programme has been considered to be inappreciable before
1990. This changed in 1995 (12), coinciding also with the publication of national clinical guidelines.
In terms of incidence, invasive cervical cancer is the sixth most common type of cancer in Spain,
responsible for 4.8% of cancers in women. This is one of the world's lowest rates, between 3.4 and
12.2 cases per 100,000 women per year (20). It remained constant from 1983-1997, regardless of
age, although there was increased incidence among women born in the 1930s and ‘40s.
401
Testicular cancer
An analysis of the evolution of testis cancer mortality in Spain reflects two distinct periods: first, from
1970 to 1975, when the mortality rate showed very significant increases, reaching 0.4 per 100,000
population; and secondly, from 1975 onwards, when the rate began to fall by more than 2% per year.
By 2007, it stood at 0.15.
In comparison with the other European countries studied (and even with all countries in the European
Union) Spain had the lowest mortality rate. Likewise, while incidence has increased in most European
countries, this does not seem to be the case in Spain (21).
Treatment with the drug Cisplatin was introduced in Spain in 1981, coinciding with the period of fastest
decline in mortality and also with the expected time period for a favourable shift in the mortality trend.
Colorectal cancer
The evolution of mortality rates due to colorectal cancer in Spain was similar for both men and women
during the study period, although these were much higher for men (by nearly 40%).
Among men, there was a steady increase every year, from rates of 11 per 100,000 inhabitants in
1970, to almost 28 in 2000. Since then, mortality has slowly decreased, with a reduction in rates of
about 0.16% per year. On the other hand, women experienced mortality rates of 10 per 100,000
inhabitants in 1970, and these rose to almost 16 per 100,000 inhabitants in 1995. After that, however,
important declines (higher than those observed in men) began to occur, reaching reductions of 1%
annually.
Upon comparison with other European countries studied, it should be noted that in the early years,
around 1970, Spain was among the countries with the lowest figures. However, this trend was not
sustained, and in recent years, mortality rates in Spain have been comparable to those in other
European countries.
The evolution in Spain has been somewhat different from other European countries, and especially
from the USA, where a reduction of nearly 20% in mortality and 7% in incidence was achieved from
1973 to 1999, i.e., almost the same period as the present study (22).
Regarding the introduction of medication, Oxaliplatin is associated with the reduction of annual
increases in mortality rates; that is, the rise in mortality was moderated from sharp annual increases of
about 4.2% to a more gradual 1.5% increment.
402
The introduction of colonoscopy may have had a similar effect, at least for women. The rise in their
mortality rate slowed from a 5.8% annual increase to a much more restrained rise of about 1.5%. On
the other hand, the introduction of colonoscopy has not seemed to have had any effect in men.
The incidence data in European countries ranks Spain below the European average age-adjusted rate
of 35.54 per 100,000 in men and 16.46 per 100,000 women. With the exceptions of Finland, Sweden
and Greece, all other countries have higher incidence of colorectal cancer than Spain (23).
Hodgkin’s disease
The evolution of Hodgkin's disease mortality in Spain declined throughout the study period for both
men and women, although it should be noted that the figures were always higher for men (2:1). The
37 years of the study saw an overall decrease of 70%. These significant decreases are in line with
improvements in other European countries, the USA and Japan (24).
Regarding the influence of the introduction of high dose therapy and peripheral blood stem cell
transplantation as a treatment and its impact on the overall reduction in mortality, it is worth noting that
the expected period of maximum effect (i.e., from 1992- 1999) coincided with the most significant
decreases in female mortality, which reached 3.3% annually. Conversely, and despite a considerable
fall in male mortality in the same period, the greatest reductions for men were observed from about
1984 on.
Renal failure
The evolution of mortality in Spain due to renal failure during the study period was similar in men and
women, although the rates for men were twice as high as for women.
Three different periods are apparent upon closer examination of mortality trends. The first period, in
1970-1975, saw very sharp declines, whereas the second period (lasting until 1985) was
characterized by annual increases of 3% in men to 5% in women. The third and final period, beginning
approximately in 1986, is distinguished by progressive decreases of 1-5% in men and 0.5-3% in
women.
The introduction of Cyclosporine in 1986 in Spain coincides with the period of greatest decreases and
mainly with the expected time period for a favourable shift in mortality trend for nephritis and nephrosis
immunosuppressive influenced by treatment with Cyklosporin for kidney transplantation.
In the case of men, the rate fell from 15.7 per 100,000 inhabitants in 1985 to 14 in 1992; for women, it
dropped from 9.5 per 100,000 inhabitants in 1985 to 8.7 in 1992. This fact could be highly influenced
by some Spanish papers published internationally: a clinical trial initiated in 1985 (25) and the followup studies for patients treated in 1986-1990 (26).
403
Moreover, registration of Cyclosporin was in 1986 but sales during the 2000-08 period were also
closely related to corresponding mortality rates.
Leukaemia
The trend in mortality from Leukaemia in Spain was similar for men and women, though the latter had
lower numbers throughout the period.
Mortality can be analyzed by decades. During the 1970s, the rate quickly increased; over the next two
decades (1980-1999), it continued to increase, though at a much lower pace—indeed, these were the
lowest rates of increase in the study period. In 1999-2000, there was a dramatic rise: mortality rates
peaked and stood at the highest level in the period. From 2000 to 2007, rates began to decline once
again.
It is important to note that throughout most of the study period, mortality due to leukaemia was lower in
Spain than in any other European country. Only at the end of this period rates began to match those in
neighbouring countries, coinciding with the above-mentioned rises.
Figures from Spain are in line with the expected time period for a favourable shift in mortality trend for
leukaemia influenced by the introduction of improved treatment of disease process and complications
for patients leukaemia <45 years (1978-1985), although after this time, mortality began to rise.
The rise in mortality may also be explained by the increased incidence. Importantly, according to the
new Spanish leukaemia register (SRL) (27), incidence is 30% higher than that declared by the IARC,
at 12 per 100,000 in men and 8.6 in women. IARC had underestimated these figures, attributing Spain
with a rate of 7.8 per 100,000 in men and 4.7 in women. SRL data places Spain above the average
incidence in the European Union, which is 8.6 for men and 5.5 for women (per 100,000 inhabitants per
year) according to the WHO.
Breast cancer
During most of the study period, Spain saw the lowest mortality rates among all of the European
countries studied. Two periods are worth noting, the first from 1970 to 1995, with annual increases of
0.5 per 100,000 population (annual increases rates between 2 and 6%), and a second period from that
year on, when decreases were around 2%. However, mortality rates as low as those observed in 1970
have not been obtained.
Another point worth noting is the fact that the appearance of tamoxifen on the Spanish market did
translate to a decrease in mortality rates (changing the annual increase rate from 5,6% to 1%). By
contrast, the implementation of mammography screening for breast cancer in 1995 can be strongly
associated with the significant decreases observed after that year (with net annual decreases rates of
2%).
404
The trend in mortality from congenital heart disease in Spain was similar for men and women, though
the latter had higher numbers (about 20%) throughout the period.
It is possible to distinguish four periods during that time. The first one, from 1970 to 75, with an annual
increase of 12%. A second period, a little longer, that goes up to 1986 with an annual decreases of
7%. Followed by a period with constant values in women while there was an increase of 6% in men.
And the last period with decreases at the mortality rate in men and women (5% and 8% respectively).
405
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407
Country specific report on mortality trends in Sweden
Author: R. Westerling,
Affiliation: Department of Public Health and Caring Sciences, Uppsala University, Sweden
Medical care and avoidable mortality in Sweden
According to the Swedish medical care act the objective of Swedish medical care is health for the
population and medical care on equal terms. Medical care is regulated on the national level. In
practice, however the county councils are responsible for organising and delivering the care. In earlier
international comparisons access to health care in Sweden was found to be comparatively equal
1
across different population groups . In the last decades, however, the economic limitations of the
2
health care system have been obvious which have put the Swedish medical care under pressure .
Avoidable mortality in Sweden has been studied based on previous lists of avoidable death indicators.
3
The mortality from avoidable causes of death has been shown to decline more than total mortality .
The decline has been sharper for males than for females. Since the mortality rates were higher for
4
males the faster mortality decline for males has resulted in decreasing gender differences .
During the 1970s and 1980s the mortality rates for potentially avoidable causes of death were low in
5
Sweden when compared to other European countries . In 1974-1985, total mortality in the age group
5-64 years, the Swedish SMR (Standardised Mortality Ratio) was 15 percent lower than the mean
value of the EC countries. For most of the avoidable death indicators the difference was larger. The
Swedish avoidable death rates were usually 25-80 percent lower than the EC death rates. For most
indicators the Swedish death rates were among the three lowest of the countries studied (EC
countries + Sweden). In the latest international comparisons the Swedish death rates was at a level
6
positioned in the middle of the levels in the OECD countries .
7
In Sweden, the regional variation in avoidable mortality has decreased over time . Differences in
avoidable mortality rates have also been found with respect to socioeconomic position. In Sweden, the
socioeconomic gradients have been found to be highest between the working and the non-working
8
population . In the late 1980s, the death rates for several avoidable causes of death were between
three and eight times greater in the non-working population than in the working force. The largest
differences were found for preventable causes of death. The differences in avoidable mortality
between blue-collar workers and white-collar workers and self-employed were, however, much
smaller.
408
HIV
For HIV, there was a steep increase in mortality during a ten year period from the mid 1980s to the
mid 1990s. For both sexes, there was a dramatic favourable shift in mortality trend in 1995 after which
the mortality rates were back to the same levels as in the mid 1980s i.e. before the steep increase.
9
10
Antiretroviral drugs were registered in Sweden in 1987 followed by a start of clinical trials in 1988 .
For Zidovudine in Sweden, maximum sales level (1987-2008) was reached in 1997 (0,09 DDD/1000
11
inhabitants and year). Half of maximum level was reached in 1993 . Consensus recommendations
were published later on in 2005
12
when the drugs already was generally implemented. There is a clear
association in time between the introduction of antiretroviral drugs and the favourable shift in mortality
trends in Sweden. It seems reasonable that the mortality declined was caused by the introduction of
antiviral drugs.
Heart failure
For heart failure, there was an increase in mortality rates among both males and females from the mid
1970s to the mid1980s. In 1983-85 there was a clear shift downwards in mortality rates among both
males and females. This shift seems to have been somewhat earlier for males then for females.
ACE-inhibitors has been available in Sweden since 1982. In the beginning, however, the registered
indication was for hypertension and not for heart failure, although the patients groups may partly
13-15
overlap. Published clinical trials for congestive heart failure started in 1985
, i.e. fairly close to the
16
favourable mortality shift and for chronic heart failure in the 1990s . ACE-inhibitors were registered for
9
the indication heart failure in 1994 .
In the late 1990s there was a report on underuse of ACE-inhibitors in heart failure patients
17
. There
18
are guidelines on the treatment of heart failure from 1998 (National Board of Health and Welfare) . In
2002, 50 % of heart failure patients at a primary care centre were reported to have optimal treatment
19
with ACE-inhibitors . Maximum sales level (1982-2008) was reached in 2008, half of maximum level
was reached in 1999. Thus, there seems to have been a fairly slow diffusion of the innovation.
However, it seems reasonable that the mortality decline for heart failure in Sweden from the mid
1980s was explained by the introduction of ACE-inhibitors.
Ischemic heart disease
In Sweden, mainly the mortality rates for ischemic heart disease have declined for both males and
females during the whole study period. The declines accelerated from 1979 for females and 1980 for
males. This acceleration coincides with the introduction of several improvements in medical care.
20
Coronary care units were reported in use in 1975
21
in twelve Swedish hospitals . However, the
22
diffusion seems to have been fairly slow. Coronary care units were widely implemented in 1994 .
23
There was also a consensus report on intensive care in 1995
in line with this.
Also, beta-blockers were introduced for secondary prevention of myocardial infarction in the late part
of the 1970s. There are reports in the literature on involvement in large clinical trials from the
409
beginning of the 1980s
24-26
27
28
, starting in 1976 . Guidelines were published in 1998
and represent a
later phase of the diffusion process.
For both coronary care units and secondary prevention with beta-blockers the introduction was
statistically associated with the timing of an acceleration of the mortality decline. Thus, improvements
in medical care should explain at least part of the reduction in mortality. However, since the
introduction period for the two innovations were close in time it is not possible to decide which of the
innovations was most important for the mortality decline. Also, since the mortality has been declining
during the whole study period and the incidence rates have declined other factors may also have been
29
of importance, such as lifestyle factors and primary prevention .
In Sweden, the mortality rates for cerebrovascular disease have decreased for both males and
females since the 1970s. For females the decrease started to accelerate in 1975 while for males a
previously increasing mortality trend shifted to a decreasing trend in 1974. Also in the early 2000s the
mortality decline accelerated.
The favourable mortality shift in the 1970s coincides with the introduction of antihypertensives for
primary prevention of stroke. A clinical trial of antihypertensive treatments started in 1970
Antihypertensive prevention was more generally introduced in a national program in 1979
30
.
31
30 32
developed by professional leaders active in the field of antihypertensive prevention at that time
.
Already in the late 1970s a broader approach of primary prevention was at hand including also the
discussion of life-style factors with the patients.
For intensive treatment of acute stroke the innovations were implemented later. Thrombolytic therapy
33
reported in small scale use in 2006 based on experiences from international clinical trials . The safe
34
implementation was evaluated in a multicenter study from 2002-2006
in which half of the centres had
no previous experience of this method. However, in 2010, it was reported that nationwide the diffusion
was slow: the use of thrombolysis increased from 0.9% in 2003 to 6.6% in 2008
35
. For subarachnoid
aneurysms a shift in strategy towards surgical interventions was reported in the mid 1980s
36
It seems reasonable that the primary prevention efforts including antihypertensive treatment starting in
the 1970s had an impact on the declining mortality trends. For the intensive treatment of acute stroke
the association is not that clear, although it may have had an influence on the continued decrease in
mortality and the acceleration of the decrease in the early 2000s.
Hypertension
For hypertension there was a U-shaped curve for both males and females. The mortality rates
decreased from the 1970s to the mid 1980s. Since then, the mortality rates have increased.
There are reports from clinical trials of new safer antihypertensive drugs (beta-blockers) in the 1970s
published in 1976
37 38
program
31
in 1979
39
and a program implemented in a county in 1977 . There was a national
further
supporting the diffusion.
antihypertensives were in use in the first part of the 1970s
410
An evaluation report indicates
40
.
that
Since the mortality rates was decreasing already in the beginning of the 1970s and precise historical
data on the diffusion of antihypertensive medication is hard to find it was not possible to illustrate a
clear statistical connection between the introduction of the innovation and the shift in mortality trend.
However, it seems reasonable that the wider use of antihypertensives have been an important factor
for the mortality decline in the 1970s and first part of the 1980s. The later increase in mortality rates
are more difficult to explain. For circulatory disease several diagnosis may be corresponding and the
validity of causes of death for the more unspecific diagnostic alternatives have been reported to be
41
problematic .Thus, changing classification habits may be one explanation for the pattern of the
mortality trends for hypertensive disease.
The mortality rates for rheumatic heart disease have decreased during the whole study period for both
males and females in Sweden. Artificial valve replacement was reported in use already before the
42
study period . Therefore, it was not possible to test whether any shift in mortality was influenced by
the introduction of the innovation.
Peptic ulcer
Besides a slight increase for males in the early 1970s, the mortality trend for peptic ulcer decreased
during the whole study period for both males and females in Sweden. The fastest decline was in the
1970s and first part of the 1980s.
9
Cimetidine was registered for peptic ulcer in Sweden in 1978 . For Cimetidine in Sweden, the diffusion
seems to have been fairly rapid during the late 1970s and 1980s. (Half of maximum level was reached
in 1982
11
and maximum sales level for the study period in 1986).
The timing of the diffusion process coincides with the period with the steepest decline in mortality.
However, the favourable shift in mortality trend occurred some years before the introduction of
Cimetidine indicating that Cimetidine at least was not the only explanation for the steep mortality
decline.
Cervical cancer
In Sweden, mainly the death rates have decreased during the whole study period. Organized cervical
screening was first implemented in the mid-1960s (implemented in different counties 1967-73) and
has been considered to be nationwide in the beginning of the 1970s
decision was established first in 1985
80 %
. However, the national
45 46
. Already in 1985 a decline in mortality in the 1970s was
interpreted to be due to increased screening
48
43 44
47
. In 1997 the coverage rate was reported to be around
.
It seems reasonable that cervical screening have had an impact on mortality trends but it
411
was not possible to test empirically since the mortality trend was already declining at the start of the
study period and since there were reports of early adopters using the method already before the
1970s.
Breast cancer
Mortality from breast cancer declined considerably and continuously during the study period. There
were also improvements in medical care, both concerning medical treatment and screening with
mammography.
9
Tamoxifen was registered for treatment of breast cancer in 1976 and in that year clinical trials also
started
49 50
. Also, for mammography clinical trials started in the late 1970s
51 52 53
. However, the time
period for introduction of screening with mammography varied considerably between health
administrative areas in Sweden
46
and the national decision to organize mammography generally was
54
taken in 1986 .
Since the mortality decline started already before the introduction of innovations in the late 1970s it
was not possible to link the introduction to a shift in mortality trend. However, the continued decline in
mortality during the study period was striking and it is reasonable that improvements in medical care
have had an impact on this trend.
Testicular cancer
For testicular cancer, the mortality rates decreased during the 1970s and 1980s. The decline was
faster in the 1980s then in the 1970s. However, the number of deaths was small and the mortality
shifts not statistically significant. Cisplatin was introduced for treatment of testicular cancer in the early
1980s. A Swedish/NorwFegian clinical trial of treatment of testicular cancer with Cisplatin was
55
9
performed in 1981-1986 . Cisplatin was registered for treatment of testicular cancer in 1983 . The
diffusion was quick and the maximum sales level of the study period was reached already in 1984
11
(13331 packages/year) .
It seems reasonable that the tendency for a steeper mortality decline in the 1980s was influenced by
the introduction of treatment with Cisplatin.
Colorectal cancer
Since mid the 1970s there has been a steady decrease in mortality from colorectal cancer in Sweden
for both males and females. The decrease was most rapid between the mid 1970s and mid 1980s.
The first reports on systematic use of diagnostic colonoscopy were from the beginning of the 1980s.
There is a clinical study of post-operative surveillance with colonoscopy of patients 1981-1990
published in 1992
56
and clinical trial of post-operative surveillance starting in 1983 published in
57
58
1995 . Guidelines for hereditary colon cancer were published in 2000 . In 1979-2005 only about 8 %
59
of cancers in a county were reported detected by colonoscopy . This proportion increased in the
1990s and reached 15 % in 1993.
9
Oxaliplatin was registered for colorectal cancer in 1999 and by the end of the study period (2005) the
diffusion of the drug was still ongoing. (Maximum sales level (1977-2008) was reached in 2008 (20076
packages/ year). Half of maximum level was reached in 2004.
60
one alternative in a SBU review from 2001 .
412
11
) Oxaliplatin was recommended as
During the study period the incidence of colorectal cancer has been increasing in Sweden. Still, the
mortality declined indicating improved outcome of treatment. However, it was not possible to link the
improvement in time to the introduction of any of the studied specific innovations.
Hodgkin’s disease
For Hodgkin’s disease the mortality has decreased during the study period. The decrease accelerated
somewhat in the 1980s and was more moderate from the 1990s.
A national program was developed in 1985
61
in which recommendations concerning high-dose
therapy followed by antilogous bone marrow transplantation as a second line treatment were given.
Stem cell transplantation in combination with high dose therapy was first reported in a clinical trial from
62
2000 . In 2001 an expert group from the Swedish Council of Technology Assessment in Health Care
stated that although high dose chemotherapy with stem cell support often is used in patients with
chemotherapy induction failures, this use is based on data from uncontrolled or small controlled
63
studies, not being fully convincing with respect to effect on survival .
The favourable shift in mortality occurred some years before the national program for Hodgkin’s
disease. However, high-dose therapy principles may have been in use before the national program.
Also, in the 1970s the incidence rates for Hodgkin’s decrease decreased which may have influenced
the mortality trends towards an earlier favourable shift in mortality. On the whole, it seems reasonable
that improvement in management of Hodgkin’s disease may have contributed to the mortality decline
especially in the 1980s.
Leukemia
For leukaemia at ages less than 45 years, the mortality declined in the 1970s and increasingly so in
the 1980s. However, during the 1990s there was increasing mortality followed by a shift to decreasing
mortality in the 2000s.
There are reports on the introduction of bone marrow transplantations from the late part of the 1970s
and the first part of the 1980s. Clinical studies started in 1975
64
36
and reports from a clinical trials
65
1982 . Furthermore, intensive treatment has been reported starting in 1978
improvements of the management was reported in the 1980s
and continued
66 67
.
It seems reasonable that the faster decline in mortality during the 1980s was caused by medical
improvements in the late 1970s and in the 1980s.
Renal failure
For renal failure the death rates increased considerably in the 1980s. For males this increase ended in
the 1991 while for females the sharp increase continued also in the first part of the 1990s.
413
In Sweden multicenter clinical trial of Cyclosporine treatment of kidney transplanted patients started in
1983
68
69
9
and 1985 . Cyclosporine was registered for that indication in 1985 . The diffusion process
seems to have been fairly slow (maximum sales level (1985-2008) was reached in 1999 (0,51
DDD/1000 inhabitants and year). Half of maximum level was reached in 1991
11
).
For males, the introduction of cyclosporine coincides with the favourable shift in mortality in 1991, i.e.
when the sharp mortality increase ended. Thus, it is reasonable that the introduction of Cyclosporine
have contributed to this shift. For females, however, the favourable shift occurred some years later
indicating that there may have been gender differences in the outcome of medical care which should
be further analyzed.
Mainly perinatal mortality decreased during the study period in Sweden. However, this general pattern
was slightly changed for a shorter time period around 2000 for females and around 1985 for males.
Perinatal mortality is influenced by causes of death due to different conditions originating in the
perinatal period. Therefore the mortality decline was not linked to any specific key intervention.
However, it seems reasonable that a general improvement in perinatal care had an influence on the
results.
Mortality from congenital heart disease decreased during the whole study period for both males and
females. Since the surgical intervention was developed in the 1950s and 1960s it was not possible to
analyse the potential linkage in time between the introduction of innovations and mortality trends.
However, it seems reasonable that a continued improvement in the medical management of this
condition may have had an impact on the declining mortality trend.
414
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Country specific report on mortality trends in UK
Authors: B. Khosbhaba, M. McKee
Affiliation: London School of Hygiene and Tropical Medicine, London, UK
HIV/AIDS
There is a need for some caution in interpreting trends in deaths recorded as due to AIDS as there
may be some misclassification of HIV-related deaths which are instead recorded as being due to
1
complications of AIDS, such as certain infections (especially pneumonia) and cancers.
Observed trends in mortality are broadly similar in males and females until the year 2000. From this
point onwards there has been a slight increase in mortality for men but a sharp rise in females,
peaking in 2003 after which it started to decline slowly. However, the actual numbers of deaths (under
100 per year) among women mean that the rates are susceptible to relatively small changes in the
population at risk. This may be the case here. First, the majority of infections in the 1980s and 1990s
2
were among homosexual men, by 2003/4 the majority of new cases were among heterosexuals ,
2
whose numbers more than tripled between 1998 and 2004 . Second, the epidemiology of AIDS in the
UK is heavily influenced by the migration of HIV infected individuals from high prevalence countries, to
a greater extent than many other industrialised countries. Surveillance data indicate that three2;3
quarters of heterosexual individuals diagnosed since 2000 were probably infected in Africa .
Notwithstanding the recent increase in female deaths, the marked reduction in mortality since the mid4
1990s is widely accepted as being due to the introduction of antiretroviral therapy . There is evidence
of a high level of coverage. Between 2000 and 2007, approximately 70% of diagnosed HIV-infected
individuals were receiving antiretroviral therapy; this increased to 76% in 2008 and 78% in 2009. The
2008 British HIV Association (BHIVA) guidelines recommend the initiation of treatment when CD4
counts reach 350 per mm3 or below. The proportion of individuals with a CD4 cell count <350 per
mm3 who did not receive treatment was 17% in 2009, compared to 25% in 2007; one in five of these
4
were late presenters.
418
Malignant neoplasm of the colon and rectum
5
In both males and females, mortality trends have been declining since 1970, at all ages . However, the
joinpoint analysis indicates a temporary plateau for men in the late 1980s. The overall downward trend
has taken place against a background of rising incidence rates at older ages (partly counterbalanced
by a reduced age-specific incidence at younger ages). The increasing incidence has been slightly
5
greater among men but it is not obvious that this could explain the difference in mortality trend in the
late 1980s. Survival rates have been lower in England than in other European countries. Agestandardised five year survival was 51.1% (95% CI 50.1% to 52.0%) and rectal cancer survival was
52.3% (95% CI 51.1% to 53.5%) in England. The difference has been attributed to lower survival
6
among older patients . Data from the Thames Cancer Registry show a steady decrease in mortality for
all ages, although slightly greater in women than in men. The 10-year survival for both sexes
combined increased from just over 30% among those treated in 1981–1986 to just over 45% among
7
those treated in 1997–2001 . Hence, it seems likely that the improvement is due largely to improved
outcomes of treatment. Although a national population-based screening programme began to roll-out
in England in 2006, achieving national coverage in 2010, this was too late to explain the observed
8
changes .
Cervical Cancer
There has been a sharp increase in the rate of decline in mortality from the late 1980s, This slightly
predates the introduction of a comprehensive population based screening programme that replaced
the previous opportunistic screening. However, the attention given to cervical screening prior to the
formal launch of the programme, and in particular the recognition that opportunistic screening was not
reaching those most at risk, is likely to have increased the effectiveness of screening before the new
programme was introduced.
The effectiveness of the comprehensive programme is seen in the way that incidence almost halved
(from 16.2 to 8.3 per 100,000 female population) in the past two decades and mortality rates reduced
9
by almost two-thirds (from 6.4 to 2.2 per 100,000) . However, the rate of reduction in incidence has
slowed in recent years. This is due to the declines in older women being counterbalanced by an
increase in younger ones. Between 1998 and 2008, incidence in women aged 25–29 increased by
10
77% and in women aged 30–34 by 29% .
Cervical cancer survival has improved since the mid-1980s but only very slightly, from 82.2% to 86.2%
(for patients diagnosed between 2005 and 2007) and five-year relative survival from 62.3% to 68.3%
(for patients diagnosed between 2001 and 2003). The greatest increase in survival is in women aged
15–39, among whom it has increased from 77.5% in 1986–1988 to 86.4% in 2001–2003. Five year
survival increased among women aged 40–49 from 71.6% in 1986–1988 to 77.3% in 2001–2003.
However, among women aged between 60 and 79, five year survival is slightly lower than 15 years
10
ago .
419
In summary, the observed reductions in mortality seem largely to reflect lower incidence, attributable
to screening. The increase in incidence in younger women, below the age at which screening is
offered, is likely to reflect higher incidence due to higher rates of HPV infection. Improved survival has
played at best a minor role.
There has been a decline in perinatal mortality in both sexes from the 1970s until the 1980s. The
reason for the discontinuity in female deaths around 1990 is not obvious, especially as it was not seen
among males (so making it unlikely to be a coding artefact). In the absence of an alternative
explanation, it may be that this is simply random fluctuation given the very low numbers.
It is relevant to note that the infant mortality rate in 2009 (based on death registrations) was the lowest
ever recorded in England and Wales and has fallen 64% since 1978. In 2009, there were 3,312 infant
deaths (under one year of age) registered in England and Wales giving a rate of 4.7 deaths per
thousand live births.
There are several factors that are changing and that influence the risk of death in newborns. A
population-based congenital anomaly register in England covering 646,342 births was used to analyse
terminations of pregnancy for foetal anomaly (TOPFAs) over a 10-year period (1990-2000). The rate
of TOPFA at all gestations and at less than 16 weeks increased significantly. The proportion of live
born TOPFAs after 22 weeks of gestation decreased significantly but below 22 weeks remained
11
unchanged. TOPFA increased in frequency, and occurred earlier in pregnancy .
Babies born at low birthweights and multiple births are at particular risk. These increased since the
1990s as a consequent of the expansion of in vitro fertilisation. However, there was also a decrease in
12
low birth weights attributed to a general improvement in living standards .
In summary, it is difficult to disentangle differing changes in the numbers of high risk babies. However,
it is likely that the enormous increase in the scope of neonatal care and in particular the management
of respiratory distress syndrome has played a substantial part in the observed reduction in deaths.
The term “Congenital heart disease” (CHD) includes a wide spectrum of conditions from relatively
minor atrial septal defects to major malformations incompatible with survival without immediate
surgical intervention (such as transposition of the great vessels). Most of the research has looked at
specific disorders and therefore it is difficult to identify a specific intervention given the diversity of
disorders under this broad diagnostic category.
The incidence of CHD is thought to have remained relatively stable over the past 50 years. In their
review of more than 60 studies of CHD incidence published since 1955, Hoffman and Kaplan found no
evidence for a change in the incidence of heart defects over time, after taking into account variations
in case definition and methods of ascertainment between studies.
420
Advances in paediatric heart surgery over the past few decades have led to increasing numbers of
long term survivors from both palliative and corrective surgery. Between 1994 and 2003 the largest
proportionate decrease was in the 1-4-year age group
13
. Currently 80–85% of patients born with
14
congenital heart disease can expect to reach adulthood . This has led to an increasing population of
adults who have had surgery as children in addition to patients who present as adults with congenital
heart disease. There are now as many adults with congenital heart disease as children. This can be
expected to continue with an estimated 167 805 adults with congenital heart disease in the UK by
15
2010 . Surgery for adult congenital heart disease is not decreasing despite the impact of
interventional cardiology. The percentage of operations that involve repeat surgery and complex
diagnoses is increasing. Nevertheless, these patients continue to do well with a low mortality and
16
hospital stay and cost implication that compare favourably with those for CABG surgery .
In summary, the observed reduction in mortality is likely to be due mainly to improved outcomes of
care.
Heart failure
Mortality has declined between 1970 and 2005 in both males and females. However, the beginning of
the decline predated the introduction of a number of specific new treatments. ACE-inhibitors were
17
registered in England in 1981 (Captopril) and licensed for use in heart failure (Enalapril) in 1985.
18
Reports of coverage of patients with appropriate indications found 17 % use in 1994 , 40 % use in
1998
19
20
and 2003
21
, 54 % in 2004
22
and about 70 % in 2005 . In 2003, the first NICE guidelines on
23
heart failure were published . Before that the National Service Framework (NSF) for Coronary Heart
Disease (CHD) (in 2000) set national standards for the management of people with heart failure in
7
England .
The decline in mortality since the early 1970s is seen for both sexes up to the age of 84, and it is only
in the over 85 group that the number has risen over this period, perhaps reflecting the fact that
everyone must die of something.
In summary, the observed reductions in mortality may reflect greater coverage with specific
medication but this does not explain the early reductions before they became available. Evidence from
24
the USA suggests that this may have been due to improved management of hypertension .
Hodgkin’s disease
Mortality in both males and females has dramatically declined since the 1970s. Over the period 1988–
1995, five year survival with Hodgkin’s disease increased from 77% to 83%. This has been attributed
25
to a combination of improved chemotherapy and radiotherapy regimens first developed in the 1970s .
It seems likely that this has been accompanied by greater experience in treatment. However, it is
apparent that the reduction in mortality has now stalled, with the rate slightly higher in males than
females. This is consistent with a body of evidence that men with cancer present at a later stage,
421
although this hypothesis requires formal testing. It is too early to say whether the apparent increase in
the last few years is real or an artefact related to small numbers.
Hypertension
Mortality from hypertensive disease has been declining from 1970 until 1994 when it started to rise
5
gradually in both males and females . This is somewhat puzzling, as data from the Health Survey for
26;27
England (HSE) have shown improving blood pressure control between 1994 and 1998
and
28
subsequently in 2003 . Since 1994 mean systolic blood pressure fell by 1.6 and 4.3 mmHg in male
and female adults, respectively. However, it is apparent that there is still a great deal to be done.
Although rates of awareness and treatment have increased, and achievement of control (<140 mmHg
systolic and <90 mmHg diastolic) among hypertensive men and women has increased markedly, it
remains at only 22 and 23%, respectively. Of those on treatment for hypertension, the majority (56%)
were on two or more agents compared with 40% in 1994 and 1998. It has thus been concluded that
hypertension management improved greatly since 1994, with more awareness, treatment and control.
The Quality and Outcomes Framework (QOF) was introduced in the UK in 2004, has been linked with
29
improved blood pressure monitoring and control in the United Kingdom . However, this is too late to
impact on the observed trends.
In summary, the decline in mortality seems likely to be due, largely, to improved treatment but there is
still much to be done.
Age-standardised coronary heart disease (CHD) rates in England and Wales were high between 1950
and the mid 1970s. After this time CHD mortality rates began to fall and have been falling since.
Improvements in population risk factors and in medical treatments for patients with CHD both
30
contributed substantially to the declines seen between 1981 and 2000
. More than half the coronary
heart disease mortality decrease in Britain between 1981 and 2000 was attributable to reductions in
major risk factors, principally smoking.
Given the contribution of circumstances in early life to several risk factors for ischaemic heart disease,
it is necessary to consider the possibility of period and cohort effects. There is strong evidence of a
major period effect: all age groups experienced a peak in the mid 1970s. However there is also some
evidence of a cohort effect. More recent generations have had far lower CHD mortality rates than
th
th
31
those born in the late 19 and early 20 centuries .The rate of decline at older ages, among men and
31
women, has been especially fast .
Recent work has suggested that CHD mortality rates in younger men and women are heading for a
plateau, based on an estimation of the average annual change in mortality rates since 1984, and may
even be reversing
30;32
.
In summary mortality has decreased due to a combination of reductions in major risk factors and
improved treatment.
422
Peptic ulcer
Mortality in males peaked during the mid 1970s, whereas the peak was not observed until the early
1980s for females. Cimetidine, which transformed the management of peptic ulcer,
33
was licensed in
17
34
1976 . Its introduction led to a marked reduction in elective surgery for peptic ulcer disease . The
next therapeutic advance was the introduction of proton pump inhibitors, such as Omeprazole, in
1988. However, mortality from, and admission for, peptic ulcer had been declining over the previous
33
20 years, although at a much slower rate . This may reflect earlier advances in surgical technique,
but there has also been a cohort effect, reflecting the role of childhood circumstances in levels of
34
infection with Helicobacter pylori, the causal agent .
There are some other factors to be considered. These include lower rates of smoking and greater
consumption of analgesic and anti-inflammatory non-steroidal drugs by an ageing population with a
35
high rate of arthritis and arthrosis .
In summary, the observed changes in mortality are consistent with the introduction of cimetidine and
subsequent H2 blockers and proton pump inhibitors, although there is also likely to have been a
reduction in incidence due to a combination of cohort effects
34
(due to changing rates of Helicobacter
infection) and period effects, due to lower rates of smoking.
Renal failure
Mortality in both males and females, peaked around the early 1980s when it began to decline rapidly
until the mid 1990s and has remained relatively stable since. Incidence is reported to be slightly lower
5
in females than in males . Since renal replacement therapy (RRT) for end-stage renal disease became
widely available in the 1960s, the number of prevalent patients on RRT has continued to rise and
improved survival due to dialysis or kidney transplantation (cited in Kramer et al. 2009)
36
. More recent
data seemed to indicate stabilization in the incidence rates of RRT in a number of European
36
countries .
The observed turnaround in mortality occurred at around the same time as the introduction of
Cyclosporine as a treatment for rejection of transplants but the relatively small additional benefit that
this conferred does not seem enough to explain the very large reduction in mortality. A much more
likely explanation is the marked expansion of renal replacement therapy in the UK since the mid
1980s, before which there were very strict criteria for dialysis and transplant. The risk of death on RRT
has fallen since 2001. Death rates on dialysis in the UK remained lower than when compared with a
37
similar aged population on dialysis in the USA .
In summary, while there have been many improvements in the management of renal failure, the
observed changes seem most likely to be due to expansion of provision.
Rheumatic fever is common worldwide and responsible for many cases of damaged heart valves. In
Western countries, it became rare since the 1960s, due largely to widespread use of antibiotics to
treat streptococcus infections. The key intervention in treatment of established disease is valve
423
38
surgery, with progressive enhancements since the 1950s . In 1985, the UK Department of Health
(then the Department of Health & Social Security) and representatives of the UK Society of
Cardiothoracic Surgeons agreed on a national registry for all artificial heart valves implanted through
39
the National Health Service (NHS) hospitals within the UK .
Best practice standards for processes and outcomes for mitral repair services have been agreed by
consensus of a multidisciplinary group of clinicians and lead to improvements in the undertaking of
40
mitral valve repair. There is as yet no accepted definition of exactly what constitutes best practice in
mitral valve repair or what constitutes an expert centre.
In summary, mortality has been falling steadily since the 1970s for both males and females. While
there may have been some small gains from improved treatment, these are likely to be marginal as an
effective treatment (valve replacement) has been in use for many years. The sustained trend is most
likely to be due to a cohort effect consequent on lower rates of rheumatic fever.
An estimated 150,000 people have a stroke in the UK each year
41
. Stroke accounts for around 53,000
42
deaths each year in the UK; 9% in men and 13% in women in the UK . However, mortality has
43
substantially declined in England and Wales over the last five decades . During the mid 1990s, it was
recognised that outcomes in the UK were among the worst in Europe. Proposed explanations included
44
low intervention rates in relation to both risk factors (hypertension) and acute events .
There has been a steady and consistent decline in stroke mortality; recorded as underlying cause and
as mentions, in England, year on year, over the past 25 years with no evidence of any slow-down in
45
both sexes and all age groups, over a recent 26-year period . National data on stroke incidence and
survival are lacking and therefore it is not clear how much of these reductions in mortality are due to
prevention and how much to changes in stroke management. Data from Oxfordshire have reported a
45;46
reduced incidence
. However, there is also evidence that the expansion of stroke units has
impacted on survival; stroke patients in general wards have a 14% to 25% higher mortality rate than
42
47
those in stroke units . Proposed factors include better social conditions , declines in smoking
46;48
prevalence
lowering drugs
and increased uptake of preventive medication such as antihypertensives
46
antiplatelets
46;48
, lipid-
46;48
.
The discontinuity observed in both sexes in 1984 is likely to be due to a change in coding rules to
address the situation where someone had a stroke in the past but this had little relevance to the
49
death .
In summary, much of the improvement in mortality seems likely to be due to reduced incidence, itself
reflecting better treatment of hypertension. However, improvements in treatment seem also to have
contributed. The implementation of the National Stroke Audit Program in England should result in
continued improvements in survival
50
424
Testicular cancer
There has been a dramatic decline in mortality from testicular cancer between the 1970 and 2001.
Survival from testicular cancer has increased most for older men, possibly reflecting how effective
51
chemotherapy regimens, available since the 1970s, have been extended to this age group . The
documented improvements in mortality from the 1970s onwards appear to coincide with the
introduction of cisplatin as a therapeutic agent for advanced tumours
52
Testicular carcinoma accounts for ≈ 1% of all cancers in men, but is the commonest cancer in men
aged <40 years in England and Wales [Quinn M, Babb PJ & Jones J et al. CD-ROM Cancer 1971–
97: Registration of cancer cases and deaths in England and Wales by sex, age, year, health region
52
and type of cancer. London: Office for National Statistics, 1999 cited in Power et al, 2001 ]. Mortality
from testicular cancer appears to have declined, particularly since the mid-1970s. Overall mortality
rates have decreased dramatically, with a directly age-standardized mortality rate of 0.3 per 100 000
in 1999 compared with 1.0 in 1971, with an associated improvement in 5-year survival.
52
From the EUROCARE studies, the European average 5-year survival rate was approximately 2–12%
higher for adults diagnosed in 1987–1989 than for those diagnosed in 1978–1980, an average of 9
years earlier. The largest absolute increases were for cancers of the testis (12.0%, from 79.9 to
91.9%)
51
In summary, the dramatic reduction in mortality most likely reflects improvements in treatment.
Leukaemia
Mortality trends in both males and females exhibit marked fluctuations in recent years. For males,
there is a steady decline in mortality from 1970 up until early 1990s, which then appears to fall steeply
up until the year 2000. From this point onwards the trend appears as a steep rise until it begins to tail
off and resumes gradual decline up until 2005. For females the picture seems similar, but the increase
in mortality begins much earlier i.e. mid 1990s. It has been suggested that older age groups, low
recruitment into clinical trials and differences between diagnostic groups of Leukaemia can contribute
to lower survival.
There have been no major therapeutic advances since the 1970s. However, there is believed to have
been improvement in the quality of care with many more patients included in trials. Another factor is
thought to be greater awareness and thus earlier diagnosis although there are persisting differences in
survival by socio-economic status
53 54
.
The observed fluctuations in mortality may be due to automated coding of mortality, introduced in
1993. As treatment improves, there may be fewer cases where leukaemia is recorded as the
underlying cause of death, instead considering it as a contributory cause.
Breast cancer
425
55
Mortality trends for female breast cancer in England and Wales peaked around the early 1990s since
when they have rapidly declined. At least three factors may have played a role. First, the national
breast screening programme began to roll out in 1988. National coverage was achieved by the mid
1990s. Second, in 1973 tamoxifen was licensed for use. Third, recognizing the failings of cancer
provision in the 1980s, there were extensive reviews of the organization of cancer services. All of
these led to improvements; there has been high screening coverage of women aged 50-64 after
1995
56
rapid uptake of priced tamoxifen and adjuvant chemotherapy by UK doctors
57;58
and the
reorganisation of breast cancer services on the basis of the Calman-Hine and Campbell evaluation
59;60
reports has improved access to more integrated forms of care
.
In summary, the lower mortality from breast cancer probably reflects the combined impact of several
61
important changes in its diagnosis and management over the last two decades . These include the
61
widespread adoption of adjuvant chemotherapy , the reduced use of post menopausal hormone
replacement therapy, the use of radiotherapy after breast-conserving surgery
61
and the establishment
of the National Health Service Breast Screening Programme for women aged 50–64 years in 1988.
426
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Appendix H. Evaluation report
Introduction
The general objective of the AMIEHS project was to develop an agreed definition of amenable
mortality for Europe, and to derive a set of validated amenable mortality-based indicators of the
effectiveness of health systems which can be used in routine surveillance systems. In this evaluation
report we assess the achievement of this objective, as well as the achievement of the specific
objectives of this project.
Achievement of the specific objectives
Objective 1: To identify causes of death that can now be considered “amenable” based on
systematic review of the literature
Indicator 1: A list of causes of death for which the literature review indicates a reasonable level of
evidence of amenability
The process started with the establishment of pre-selection criteria which would limit the number of
causes of death to be studied. Two important criteria were 1) mortality from a cause of death declined
more than 30% in England and Wales after 1970 and 2) a distinct medical innovation with proven
effectiveness has been introduced after 1970.
England and Wales was selected because it was among the largest European countries with
consistent data over the time period 1970-2005 and it was also a country where any changes in
coding are generally well understood.
Each of the criteria was operationalised in a stepwise approach using the mortality data set of the
office of National Statistics for England and Wales and the interval between the beginning and the end
th
of the use of the 9
Revision of the International Classification of Diseases between 1979-2000.
Having established a preliminary list of conditions for possible inclusion evidence was sought to
identify health care innovations that could prevent deaths from such causes. After reviewing the
literature, one or two key innovations for each cause of death were selected. To be included in the list
the specific key innovation must be shown (by either patient level studies, e.g. a randomized
controlled trial, or by population level studies or both) to be capable of reducing the associated
mortality. The strength of the evidence on the effectiveness of interventions and whether the mortality
decline could be attributed to health care was scored on a 4-point scale. The strength of the evidence
was variable, with only few interventions having the highest grade (evidence from systematic review or
meta-analysis) and many interventions being underpinned by evidence from single trials or
observational studies only.
- Constructed in draft version by the project coordinator and agreed on by the Advisory Board
430
As a result of these efforts, we created a list of 16 causes of death for which the literature review
indicates a reasonable level of evidence of amenability.
Objective 2: For seven countries, to analyze the introduction of health care innovations that might
have reduced amenable mortality
Indicator 2: An overview of the introduction and implementation of relevant health care innovations in
seven countries
Once this preliminary list of indicators was identified, in a second step of the project information was
obtained on the timing of the introduction of the key medical innovation(s). This was done by sending
out a questionnaire to all involved partner countries to obtain country specific information on the
introduction of innovations. This way of obtaining information proved not to be sufficiently reliable.
Therefore country-specific reviews of national and international literature were performed per
innovation, after which new country-specific questions were sent to the partner countries.
This
provided the approximate period of introduction in each of the countries, and, using information on the
delay between introduction and a possible mortality-lowering effect, the approximate period in which a
decline in mortality could be expected. These periods proved to be different for different countries,
which suggested that an analysis of differences in timing of mortality decline would be feasible. Not all
conditions could be included in these analyses: conditions originating in the perinatal period and
congenital heart disease were not covered for various reasons. For East-Germany it was not possible
to obtain information on the timing of introduction of innovations.
The estimation of periods in which an innovation was introduced proved to be a difficult task as for
some innovations there was no obvious beginning and end-point. Within countries there also was
variation in the available information on introduction of innovations which obviously has had its
influence on the estimations. To give insight into these uncertainties a dichotomous scoring system for
the quality of the estimation (good/bad) was developed as input for sensitivity analyses.
As a result of these efforts, we created an overview of the timing of introduction of interventions.
Objective 3: To build a harmonized data base on trends in amenable mortality in 1971-2005 in
seven European countries
Indicator 3: Availability of a harmonized and documented database on trends in amenable mortality in
seven countries
Mortality trends were studied for the period 1970 to 2005, using data obtained from national statistical
offices. From all seven countries data on numbers of death were obtained for each year, by 5-year
age group, sex and cause of death. For Germany we were able to obtain data for both East- and West
Germany. From the available national databases on harmonized data base was formed which has
been the basis for the analyses reported below.
431
Objective 4: To evaluate the effect of coding changes and to develop correction factors to adjust
observed mortality trends.
Indicator 4: An overview of the effect of coding changes on trends in amenable mortality in seven
countries, with correction factors.
In the comparison of mortality data over different time periods and countries changes and differences
in ICD coding may affect the level of mortality. Therefore the effect of coding needed to be taken into
account in the trend analyses in the AMIEHS project. Different traditional methods for correcting for
coding changes have been compared. Subsequently, an automatic jump detection method was
developed, based on the Polydect method (Zhang et al. 2009), to identify abrupt changes in mortality,
i.e. “jumps”. The jump detection reveals age and gender specific jumps and provides the year of the
jump and an overview of all correction factors (multiplicative). The observed jumps have been
communicated with the national data producers in order to reach agreement on the cause of the jump.
They have been interpreted in relationship to possible documented changes in coding practices. By
the application of correction factors according to sex and gender the trend analyses have been
successfully adjusted for possible biases due to ICD changes and the corrected time trends have
been used for further analysis. An article describing the jump detection method has been accepted for
publication at the Journal “Population Health Metrics” (Rey et al.)
Objective 5: To determine whether the introduction of innovations coincided with declines in
mortality from selected amenable causes.
Indicator 5: An overview of trends in mortality in seven countries, with a list of amenable causes for
which there is evidence for an association with innovations in health care.
Cause–specific mortality trends for the period 1970-2005 from Estonia, France, Germany (East and
West), The Netherlands, Spain, Sweden and the UK were analyzed. A pre-selection of 14 causes of
death were considered that were selected as potential amenable mortality indicators and for which
national data on the introduction of important innovations in health care had been collected. First,
gender-specific graphs of mortality trends for all ages and ages 0-74 were fitted using joinpoint models
based on linear spline regression to identify turning points in the mortality trend. Second, associations
between changes in the mortality trends and the introduction of health care innovations were
examined, first, through counts of the countries where such an association was found and, second, by
Ordinary Least Squares-regression.
Only for HIV a clear association between the mortality trend and the introduction of antiretroviral
therapy could be found. The results for other conditions (malignant colorectal neoplasms, leukaemia,
rheumatic heart disease, hypertension, ischaemic heart disease and cerebrovascular disease) differed
by methodological approach and age range. Although there was often a general mortality decline for
most of the studied conditions, this was not uniform and there were striking variations between
countries in the mortality trends as well as in the timing of ‘knots’. For many conditions it has not been
possible to establish an association between the introduction of a medical innovation and mortality
432
decline. Because for some conditions cohort effects could have an impact, Age Period Cohort
analyses were performed, but removal of cohort effects had no effect on the outcome of the analysis.
As a result of these efforts, we have created and overview of associations between innovations in
health care and favourable changes in mortality trends from amenable conditions.
Objective 6: To develop and agree on a set of validated amenable mortality-based indicators
through expert consensus
Indicator 6: A high level of agreement among experts and stakeholders on the final set of amenable
mortality indicators.
Finally the usefulness of the indicators was established during a Delphi procedure. All invited experts
(n=23) were provided with vignettes containing information on the effectiveness of the innovation
based on the literature, the period of introduction of the innovation and the empirical evidence on the
association of the innovation to mortality. The invited experts were either producers or users of
evidence on health systems performance, seeking participation by both genders, a range of countries,
and health professionals and non-health professionals. The experts had to state whether they thought
a condition is a good indicator of variations in health care effectiveness.
In the Delphi procedure after two rounds the experts reached consensus on only 3 conditions
(malignant colorectal neoplasm, cervical cancer and cerebrovascular disease). Although some of the
other conditions were labelled as appropriate indicators by some panel members, it has not been
possible to achieve a sufficient level of agreement among experts. Possible explanations may be in
the divergent scope of health care among the experts, but also in the effort to bring together as much
of the relevant information for all conditions as done in the AMIEHS study, going far beyond what had
ever been done before for conditions potentially amenable to health care. Scoring of the conditions
was very much influenced by how the experts rated this information, and this proved to be very
diverse.
Objective 7: To illustrate the use of amenable mortality indicators by preparing an e-atlas of
variations in amenable mortality
Indicator 7: availability of a web-based electronic atlas of amenable mortality in at least 25 countries
An electronic atlas has been prepared presenting mortality from 45 conditions in 30 European
countries. International mortality data have been obtained from Eurostat. The list of conditions consists
of the causes of death used as input for the Delphi procedure (24 conditions) and some causes of
death that have been studied in previous lists of amenable mortality (21). The electronic atlas,
constructed with the InstantAtlas software, gives insight in the trends in age standardized mortality in
all countries and enables a comparison in levels between countries. The electronic atlas is accessible
through the AMIEHS website.
433
Achievement of the general objective
Although each of the specific objectives 1 through 5 was achieved, the Delphi panel did not reach
agreement on the final set of amenable mortality indicators. We have therefore been unable to derive
a set of validated amenable mortality-based indicators of the effectiveness of health systems which
can be used in routine surveillance systems.
We did, however, obtain a number of useful results. We developed a unique and scientifically rigorous
approach, which can be used in further research. We found a number of clear indications that mortality
from amenable conditions is sensitive to improvements in health care effectiveness. We also
developed a method for correcting mortality trends for coding changes which can be used in other
analyses of mortality trends. Our main recommendation to policy makers is that the objective of using
amenable mortality indicators should be clearly defined at the outset, and that policy makers should be
reluctant in using amenable mortality indicators for other than exploratory purposes.
434

Volume 2: Appendices - Avoidable Mortality in the European Union

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