NZ GP Research Review Issue 91

ISSN 1178-6124
GP
Research Review
TM
Making Education Easy
Issue 91 – 2014
Welcome to the ninety-first issue of GP Research Review.
In this issue:
Withdrawing inhaled steroids in
COPD
Carvedilol vs metoprolol:
similarly effective in HF
Risks/benefits of surveillance
colonoscopy in the elderly
Findings support expanded
bowel cancer screening
Communicating test results in
primary care
PPI use associated with
hypomagnesaemia
Validation of a Legionella score
Prevalence of B12 deficiency in
metformin users
Meditation programs can
reduce psychological stress
Micronutrient supplements
slow HIV disease progression
Abbreviations used in this issue
COPD = chronic obstructive pulmonary disease
HF = heart failure
HR = hazard ratio
PPI = proton pump inhibitor
Withdrawal of inhaled glucocorticoids does not appear to worsen exacerbations in patients with severe chronic obstructive
pulmonary disease (COPD), reports a paper in The New England Journal of Medicine. “The findings may prompt clinicians to
consider other preventive interventions, such as daily azithromycin, in patients who continue to have frequent exacerbations
while receiving long-acting bronchodilators”, notes an accompanying editorial.
A UK study offers interesting insights into the communication of test results in the complex environment of primary care.
The researchers conducted focus groups with primary care staff, to explore staff perceptions of strengths and weaknesses
of existing systems for communicating test results in primary care; how they felt the service could be improved; the role of
patients in the process and how different patient wishes could best be accommodated.
A proposed clinical prediction rule has been validated as having high accuracy for discrimination of Legionella from other
pneumonia causes in patients presenting with community-acquired pneumonia. Use of this rule may improve empiric
antibiotic choices.
One of the papers in our Natural Health section this issue systematically reviewed the evidence about the efficacy of
meditation programs for psychological stress and stress-related health problems. It reports that such programs can help to
improve multiple negative dimensions of psychological stress. Might be worth prescribing mindfulness meditation instead of
a course of antidepressants?
I hope you enjoy this issue and I welcome your comments and feedback.
Kind Regards
Jim
Associate Professor Jim Reid
[email protected]
Withdrawal of inhaled glucocorticoids and exacerbations
of COPD
Authors: Magnussen H et al.
Summary: This study recruited 2485 patients with severe chronic obstructive pulmonary disease (COPD) into an initial
6-week run-in period, consisting of treatment with triple therapy (tiotropium 18 μg once daily, salmeterol 50 μg twice daily
and inhaled fluticasone propionate 500 μg twice daily), after which they were randomised to continue triple therapy or taper off
fluticasone in 3 steps over 12 weeks. At 1 year, the primary endpoint (time to the first moderate or severe COPD exacerbation
during the 12-month study) was similar between the groups. At 18 weeks, after completion of fluticasone withdrawal, the
adjusted mean reduction from baseline in the trough FEV1 was 38 mL greater in the fluticasone-withdrawal group than in
the continuation group (p<0.001); the between-group difference persisted at 52 weeks (43 mL; p=0.001). No change in
dyspnoea and minor changes in health status occurred in the fluticasone-withdrawal group.
Comment: There are a number of “triad” inhalers coming on to the market (not in NZ as yet) containing a long-acting
muscarinic antagonist (LAMA), a long-acting beta-agonist (LABA), and a corticosteroid (IHC). This study demonstrated
that the inclusion of IHC had no effect on exacerbations when included with a combination of a LABA and LAMA. The
group who had the IHC withdrawn had a slight deterioration in lung function as compared to when they were inhaling the
steroid, however, there was no change in dyspnoea index or health status. There are a number of other studies about to
be published that have demonstrated an alternative outcome. Confusion reigns.
Reference: N Engl J Med. 2014;371(14):1285-94
Abstract
START SPIRIVA®* before COPD symptoms impact everyday life
SPIRIVA
®
(tiotropium 18 mcg)
For more information, please go to http://www.medsafe.govt.nz
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GP Research Review
Association of treatment
with carvedilol vs metoprolol
succinate and mortality in
patients with heart failure
Authors: Pasternak B et al.
Summary: Data from a Danish national heart failure (HF)
registry were linked with health care and administrative
databases to identify patients with incident HF with
reduced left ventricular ejection fraction (LVEF) (≤40%)
treated with carvedilol (n=6026) or metoprolol succinate
(n=5638). The aim of the study was to determine whether
survival is improved with carvedilol over metoprolol
succinate. Over half of all patients (51%) were hospitalised
at index HF diagnosis. During a median 2.4-year
follow-up, 875 carvedilol users and 754 metoprolol users
died; the cumulative incidence of mortality was 18.3%
and 18.8%, respectively. The adjusted hazard ratio
(HR) for carvedilol users vs metoprolol users was 0.99
(95% CI, 0.88 to 1.11), corresponding to an absolute
risk difference of –0.07 (95% CI, –0.84 to 0.77) deaths
per 100 person-years. Estimates were consistent across
subgroup analyses by sex, age, levels of LVEF, New York
Heart Association classification, and history of ischaemic
heart disease. The recommended daily target dose was
achieved by a higher proportion of carvedilol users
(50 mg; 52%) compared with metoprolol users (200
mg; 12%); among patients who reached the target
dose, the adjusted HR was 0.97 (95% CI, 0.72 to 1.30).
A robustness analysis with 1:1 propensity score matching
confirmed the primary findings (HR 0.97; 95% CI, 0.84 to
1.13). The adjusted HR for cardiovascular mortality was
1.05 (95% CI, 0.88 to 1.26).
Comment: We really need more “real-life” studies
such as this. Most pharmaceutical studies (whether
sponsored or not) use cohorts of highly selected
patients with very specific characteristics. This one
identified patients with similarly matched degrees of
heart failure and entered them “warts and all” – one
group on metoprolol and the other on carvedilol. Even
though more in the carvedilol group reached the
recommended daily dose there was no difference in
outcome, and the authors concluded that the outcome
of treatment with carvedilol and metoprolol was the
same. There are significant cost implications here!
Reference: JAMA Intern Med. 014;174(10):1597-604
Abstract
Surveillance colonoscopy in elderly patients: a retrospective
cohort study
Authors: Tran AH et al.
Summary: These investigators retrospectively analysed data from patients aged ≥50 years undergoing surveillance
colonoscopy for a history of colorectal cancer (CRC) or adenomatous polyps at an integrated health care system in southern
California from 2001 through 2010. The study cohort was divided into 2 groups: elderly patients (age ≥75 years; n=4834)
and a reference group (age 50–74 years; n=22,929). Of a total of 373 colon cancers detected following surveillance
colonoscopy, far fewer occurred among the elderly patients as compared with the reference group (5 vs 368, respectively).
However, a higher number of elderly patients compared with the younger group were hospitalised within the 30-day
postprocedure period (527 vs 184). The CRC incidence was lower among the older group compared with the younger
group (0.24/1000 person-years vs 3.61/1000 person-years; p<0.001). In Cox regression analysis adjusted for comorbid
illness, sex, and race/ethnicity, the HR for CRC in the elderly patients compared with the younger group was 0.06 (95% CI,
0.02 to 0.13; p<0.001). In logistic regression analysis, age ≥75 years was independently associated with increased risk of
postprocedure hospitalisation (adjusted odds ratio [OR] 1.28; 95% CI, 1.07 to 1.53; p=0.006), as was a Charlson score of
2 (adjusted OR 2.54; 95% CI, 2.06 to 3.14; p<0.001).
Comment: There could be a lesson in this. In any medical procedure (investigation, prescription, operation, etc.) there is
a risk/benefit ratio. This paper demonstrated that the risk of colon cancer recurrence was low in patients above the age of
75 years, and risk of complication requiring hospitalisation was much higher. Some of the complications were serious
and life threatening (perforations). The authors suggest that comorbidities and age need to be included in the overall risk
assessment.
Reference: JAMA Intern Med. 2014;174(10):1675-82
Abstract
Optimising the expansion of the National Bowel Cancer
Screening Program
Authors: Cenin DR et al.
Summary: This modelling study simulated the effects of bowel cancer screening in Australian residents aged 50–74 years
over a 50-year period, starting in 2006. The model parameters included rates of participation in screening and follow-up,
rates of identification of cancerous and precancerous lesions, bowel cancer incidence, mortality and the outcomes of the
National Bowel Cancer Screening Program (NBCSP). Five implementation scenarios, based on biennial screening using an
immunochemical faecal occult blood test (FOBT), were compared for the number of bowel cancer deaths prevented and
demand for colonoscopy. The researchers calculated that the current FOBT screening (at the ages of 50, 55 and 60 years)
would be expected to prevent 35,169 bowel cancer deaths in the coming 40 years. Compared with the current situation,
accelerating the expansion of the program to achieve biennial screening by 2020 would prevent more than 70,000 deaths.
If complete implementation of biennial screening is accompanied by a corresponding increase in participation to 60%, the
number of deaths prevented will increase across all scenarios, states the study.
Comment: New Zealand currently has a pilot screening study for colon cancer in progress. This Australian study seems
to present a no-brainer with respect to positive outcome, and it is difficult to justify (on grounds of effectiveness) delay
introducing a similar program in this country. Our major problem is the resource needed for colonoscopy of those with
positive screens. This will be a challenge in the near future.
Reference: Med J Aust. 2014;201(8):456-61
Abstract
‘Ebola: Everything that you thought you
would never need to know’
1,2
Live link to video of seminar run by Auckland University
Goodfellow Unit available now at
http://www.goodfellowlearning.org.nz/ebola
symposium 2015
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Independent commentary by
Associate Professor Jim Reid.
Jim Reid has a private family medicine practice at the
Caversham Medical Centre, Dunedin, New Zealand.
For full bio CLICK HERE.
Registrations will open soon at
www.goodfellowsymposium.org
NEW FORMAT: There will be skills stations,
essentials and updates, solution clinics
as well as an exciting range of topical
presentations.
Contact [email protected]
or Phone 923 6266 for more info
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Test result communication in primary care:
clinical and office staff perspectives
Ruling out Legionella in community-acquired
pneumonia
Authors: Litchfield IJ et al.
Authors: Haubitz S et al.
Summary: Focus groups with staff in four UK primary care practices explored staff
perceptions of strengths and weaknesses surrounding the communication of test results
to patients. An analysis of the transcripts revealed 5 main themes: (i) the default method
for communicating results differed between practices; (ii) clinical impact of results and
patient characteristics such as anxiety level or health literacy influenced methods by
which patients received their test result; (iii) which staff member had responsibility for
the task was frequently unclear; (iv) barriers to communicating results existed, including
there being no system or failsafe in place to determine whether results were returned to a
practice or patient; (v) staff envisaged problems with a variety of test result communication
methods discussed, including use of modern technologies, such as SMS messaging or
online access.
Summary: These researchers investigated the diagnostic performance of a predictive score
for the probability of Legionella in patients presenting with community-acquired pneumonia
(CAP). This clinical score is based on 6 clinical and laboratory variables: fever, cough,
hyponatremia, lactate dehydrogenase, C-reactive protein (CRP), and platelet count. The analysis
included 1939 adult patients with CAP who were treated between 2001 and 2012 with more
than 4 of the 6 prespecified clinical variables available. The infectious cause was known in
594 (28.9%),including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%).
All 6 predictors were associated or tended to be associated with Legionella cause. A logistic
regression analysis including all these predictors showed excellent discrimination (AUC 0.91;
95% CI, 0.87 to 0.94). The original dichotomised score showed good discrimination (AUC
0.73; 95% CI, 0.65 to 0.81) and a high negative predictive value to exclude Legionella sp. as
the origin of pneumonia (99.6% for a score of <2 points).
Comment: An interesting and important study. All practices should have a robust
method of imparting results to patients. They should also have a method of ensuring
results are received, and some practice management systems are better than others
with this. Soon patients will be able to access their own results via the PMS and in
some instances anxiety will be created by results being “just outside” the range of
normal, but clinically are of no concern. We will need to invent an online method of
reassurance!
Reference: Fam Pract. 2014;31(5):592-7
Abstract
Impact of proton pump inhibitor use on
magnesium homoeostasis: a cross-sectional
study in a tertiary emergency department
Authors: Lindner G et al.
Summary: These researchers undertook measurements of serum magnesium in
5118 outpatients admitted to a tertiary emergency department in Switzerland between
January 2009 and December 2010. Hypomagnesaemia (defined as a serum magnesium
concentration <0.75 mmol/L) was identified in 1246 patients (24%); the prevalence
of out-of-hospital proton pump inhibitor (PPI) use and diuretic use was higher in these
patients than in those with magnesium levels >0.75 mmol/L (p<0.0001 for both
comparisons). In multivariable regression analyses adjusted for PPIs, diuretics, renal
function and the Charlson comorbidity index score, the association between use of PPIs
and risk for hypomagnesaemia remained significant (OR 2.1; 95% CI, 1.54 to 2.85).
In addition, hospital stay was prolonged in the patients with hypomagnesaemia, even after
adjustment for underlying comorbid conditions (p<0.0001).
Comment: The prevalence of hypomagnesaemia (24% of total) in patients on PPIs
all cause presenting to a tertiary ED department is concerning. This reduced level of
magnesium was associated with prolonged hospitalisation. The take-home message
is to check magnesium levels on patients on long-term PPIs. Or better still – consider
whether they still need to be on them. How frequently should the Mg be checked?
That is for another study!!!!
Reference: Int J Clin Pract. 2014;68(11):1352-7
Abstract
Comment: So it is important to measure the clinical predictors including fever, cough,
hyponatremia, lactate dehydrogenase, CRP, and platelet count in all patients with CAP.
Legionnaires’ is not an easy disease to diagnose and much is dependent on the history
and clinical presentation. Predictors such as those described are certainly a help in
increasing suspicion and may influence early treatment of what is a potentially fatal
disease.
Reference: Am J Med. 2014;127(10):1010.e11-9
Abstract
LAM for GPs - information available here
CONGRATULATIONS
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GP Research Review
The prevalence of low vitamin
B12 status in people with
type 2 diabetes receiving
metformin therapy in
New Zealand – a clinical audit
Authors: Haeusler S et al.
Summary: This study sought to determine the prevalence
of low serum vitamin B12 concentrations (<220 pmol/L)
among patients taking metformin for management of
type 2 diabetes, in both primary and secondary care in
New Zealand. Data were reviewed for all patients attending
the diabetes outpatient clinics at Wellington Regional
Hospital and Kenepuru Hospital between February 2013
and April 2014. In addition, patients from 4 primary health
care providers were identified using metformin prescription
data and offered the chance to participate in the audit.
The prevalence of low serum B12 was 18.7%. Positive
correlations were observed between B12 concentration,
age and dosage and duration of metformin treatment.
Māori and Pacific Islanders had higher mean serum
B12 concentrations than Europeans but no difference in
prevalence of low serum B12 concentrations.
Comment: This month it has been magnesium levels
in those patients on PPIs as well as low B12 levels in
those type 2 diabetic patients on metformin. This study
suggests that B12 deficiency (the deficiency level in
the study was generous) is not uncommon (almost
20%) in those on metformin. The deficiency was more
prevalent in those who had been on the medication for
some time, and in older patients. Another take-home
message – it is worth checking B12 levels on patients
on metformin. Perhaps annually???
Reference: N Z Med J. 2014;127(1404):8-16
Abstract
Evidence-based natural health by Dr Chris Tofield
Meditation programs for psychological stress and
well-being: a systematic review and meta-analysis
Authors: Goyal M et al.
Summary: Findings are reported from an analysis of the efficacy of mediation programs in improving stress-related
outcomes (anxiety, depression, stress/distress, positive mood, mental health-related quality of life, attention, substance
use, eating habits, sleep, pain, and weight) using data from 47 randomised clinical trials (n=3515 adults) with active
controls for placebo effects through November 2012. Mindfulness meditation programs had moderate evidence
of improved anxiety (effect size 0.38 [95% CI, 0.12 to 0.64] at 8 weeks and 0.22 [0.02 to 0.43] at 3–6 months),
depression (0.30 [0.00 to 0.59] at 8 weeks and 0.23 [0.05 to 0.42] at 3–6 months), and pain (0.33 [0.03 to 0.62]) and
low evidence of improved stress/distress and mental health-related quality of life. There was low evidence of no effect
or insufficient evidence of any effect of meditation programs on positive mood, attention, substance use, eating habits,
sleep, and weight. There was no evidence to support the contention that meditation programs were better than any active
treatment (i.e., drugs, exercise, and other behavioural therapies).
Comment: One circulating theory to explain the increasing incidence of anxiety and mental health issues is that
modern lives have become too driven and stressful, overtaxing the mind. The fact that we need to maintain a healthy
equilibrium will not be disputed by many, and according to this study, meditation can help to achieve this. Definite
thumbs-up from me.
Reference: JAMA Intern Med. 2014;174(3):357-68
Abstract
Effect of micronutrient supplementation on disease
progression in asymptomatic, antiretroviral-naive,
HIV-infected adults in Botswana
Authors: Baum MK et al.
Summary: Outcomes are reported for 878 antiretroviral therapy (ART)-naïve adults infected with HIV subtype C who
were randomised to supplementation with daily multivitamins (B vitamins and vitamins C and E), selenium alone,
multivitamins with selenium, or placebo for 24 months. All patients had a CD4 cell count >350/μL and were treated at
the Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. Participants receiving
the combined supplement of multivitamins plus selenium had a lower risk compared with placebo of reaching a CD4
cell count ≤250/µL (a measure consistent with the standard of care in Botswana for initiation of ART at the time of the
study) (adjusted HR 0.46; 95% CI, 0.25 to 0.85; p=0.01). This supplement also reduced the risk of a combination of
measures of disease progression (CD4 cell count ≤250/µL, AIDS-defining conditions, or AIDS-related death, whichever
occurred earlier [adjusted HR 0.56; 95% CI, 0.33 to 0.95; p=0.03). Supplementation had no effect upon HIV viral load.
Comment: This is one of the few studies I have seen that shows some positive outcomes for multivitamin use.
Admittedly, most of us won’t have many patients who are HIV-positive, and also this study was performed in Africa,
where people likely have a very different diet. But the study results look convincing enough – better CD4 counts,
and less risk of AIDS-related death and AIDS-defining conditions.
Time spent reading this publication has been approved for
CME for Royal New Zealand College of General Practitioners
(RNZCGP) General Practice Educational Programme
Stage 2 (GPEP2) and the Maintenance of Professional
Standards (MOPS) purposes, provided that a Learning
Reflection Form is completed. Please CLICK HERE to
download your CPD MOPS Learning Reflection Form. One
form per review read would be required.
Reference: JAMA. 2013;310(20):2154-63
Abstract
Dr Christopher Tofield
Dr Tofield completed his medical training at St Bartholomew’s and the Royal London Hospital in London
and is now a fulltime General Practitioner in Tauranga. Chris has extensive experience in medical writing
and editing and while at medical school published a medical textbook on pharmacology.
For full bio CLICK HERE.
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