S ã o P aulo - Associação Paulista de Medicina

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S ã o P aulo - Associação Paulista de Medicina
ISSN 1516-3180
São Paulo Medical Journal/Evidence for Health Care, 2013 July 4; 131(4):211-286
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July 4 - Volume 131 - Number 4
Reproducibility study:
• The IDEAL classification system:
a new method for classifying
fractures of the distal extremity
of the radius — description and
reproducibility
Cross-sectional study:
• Obstructive sleep apnea
syndrome: complaints and
housing characteristics in a
population in the United States
Validation study:
• Translation, cross-cultural
adaptation and validation of
the Brazilian version of the
Nonarthritic Hip Score
Retrospective study:
• Clinical and hematological
effects of hydroxyurea therapy
in sickle cell patients: a singlecenter experience in Brazil
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Index
Editorial
211 From classroom to bedside: integration of the basic science curriculum in medical teaching
Alessandro Wasum Mariani, Paulo Manuel Pêgo-Fernandes
Original article
213 Clustering and combining pattern of metabolic syndrome components in a rural Brazilian adult
population
Adriano Marçal Pimenta, Mariana Santos Felisbino-Mendes, Gustavo Velasquez-Melendez
220 Obstructive sleep apnea syndrome: complaints and housing characteristics in a population in
the United States
Khalil Ansarin, Leyla Sahebi, Siamak Sabur
228 Circumstances and factors associated with accidental deaths among children, adolescents and
young adults in Cuiabá, Brazil
Christine Baccarat de Godoy Martins, Maria Helena Prado de Mello-Jorge
238 Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center
experience in Brazil
Ana Cristina Silva-Pinto, Ivan Lucena Angulo, Denise Menezes Brunetta, Fabia Idalina Rodrigues
Neves, Sarah Cristina Bassi, Gil Cunha De Santis, Dimas Tadeu Covas
244 Translation, cross-cultural adaptation and validation of the Brazilian version of the Nonarthritic
Hip Score
Letícia Nunes Carreras Del Castillo, Gustavo Leporace, Themis Moura Cardinot, Roger Abramino
Levy, Liszt Palmeira de Oliveira
252 The IDEAL classification system: a new method for classifying fractures of the distal extremity of
the radius – description and reproducibility
João Carlos Belloti, João Baptista Gomes dos Santos, Vinícius Ynoe de Moraes, Felipe Vitiello Wink,
Marcel Jun Sugawara Tamaoki, Flávio Faloppa
257 Trends in treatment of anterior cruciate ligament injuries of the knee in the public and private
healthcare systems of Brazil
Diego Costa Astur, Rodrigo Ferreira Batista, Arliani Gustavo, Moises Cohen
Review article
264 Diagnosis and treatment of mast cell disorders: practical recommendations
Alex Freire Sandes, Raphael Salles Scortegagna Medeiros, Edgar Gil Rizzatti
Case report
275 Bilateral tibial hemimelia type 1 (1a and 1b) with T9 and T10 hemivertebrae: a novel association
Victor Michael Salinas-Torres, Leticia Oralia Barajas-Barajas, Nicolas Perez-Garcia, Guillermo PerezGarcia
Letter to the editor
279 Ginseng: potential for the antileishmanial arsenal?
Nader Pazyar, Reza Yaghoobi
281 Medicine and creativity in medical psychology
Décio Gilberto Natrielli Filho, Mailu Enokibara Silva, Décio Gilberto Natrielli
283 Should every adult patient in the hospital have an internist?
Mine Durusu Tanriover, Goksel Guven, Cagin Buldukoglu, Omer Diker, Burcin Halacli,
Gonul Yildirim, Arzu Topeli
Cochrane highlights
285 Prophylactic drug management for febrile seizures in children
Martin Offringa, Richard Newton
Correspondence to:
Associação Paulista de Medicina
Publicações Científicas
Av. Brig. Luís Antônio, 278 - 7o andar –
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Tel. (+55 11) 3188-4310 ou
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Comments: Lívia Cunha Elkis
286 Phlebotonics for haemorrhoids
Nirmal Pereira, Danae Liolitsa, Satheesh Iype, Anna Croxford, Muhhamed Yassin, Lang Peter,
Obioha Ukaegbu, Christopher van Issum
Comments: Sarhan Sydney Saad
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Sao Paulo Med J. 2013; 131(4):i-ii i
Organization
Founded in 1932, a bimonthly publication of the Associação Paulista de Medicina
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Hospital, South London and Maudsley NHS Trust, York Clinic, London), Marcelo Cypel
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Canada), Mário Viana de Queiroz (Hospital de Santa Maria, Lisbon), Wadih Arap (MD
Anderson Cancer Center, University of Texas, Houston, United States), Wellington
Cardoso (Boston University, Boston, United States).
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Scientific Council
Abrão Rapoport – Hospital Heliópolis, São Paulo
Adriana Costa e Forti – Faculdade de Medicina, Universidade Federal do Ceará
Alexandre Fogaça Cristante – Faculdade de Medicina da Universidade de São Paulo
Álvaro Nagib Atallah – Escola Paulista de Medicina, Universidade Federal de São Paulo
Auro del Giglio – Faculdade de Medicina da Fundação ABC
Carlos Alberto Morais Sá – Universidade do Rio de Janeiro - UNIRIO
Carmen Cabanelas Pazos de Moura – Instituto Carlos Chagas Filho, Universidade Federal do
Rio de Janeiro
Cármino Antonio De Souza – Faculdade de Ciências Médicas, Universidade Estadual de Campinas
Dario Birolini – Faculdade de Medicina, Universidade de São Paulo
Eduardo Katchburian – Escola Paulista de Medicina, Universidade Federal de São Paulo
Eduardo Maia Freese de Carvalho – Faculdade de Medicina, Universidade Federal de
Pernambuco, Centro de Pesquisas Aggeu Magalhães - CpqAM/FIOCRUZ.
Egberto Gaspar de Moura – Instituto de Biologia Roberto Alcantara Gomes, Universidade
Estadual do Rio de Janeiro
Eliézer Silva – Hospital Israelita Albert Einstein, São Paulo
Emílio Antonio Francischetti - Faculdade de Medicina da Universidade Estadual do Rio de Janeiro
Emmanuel de Almeida Burdmann – Faculdade de Medicina de São José do Rio Preto
Fabio Bessa Lima – Instituto de Ciências Biomédicas, Universidade de São Paulo
Florence Kerr-Corrêa – Faculdade de Medicina de Botucatu, Universidade Estadual de São Paulo
Francisco José Penna – Faculdade de Medicina Universidade Federal de Minas Gerais
Geraldo Rodrigues de Lima – Escola Paulista de Medicina, Universidade Federal de São Paulo
Irineu Tadeu Velasco – Faculdade de Medicina da Universidade de São Paulo
João Renato Rebello Pinho – Instituto Adolfo Lutz, Secretaria de Estado da Saúde de São Paulo
Joel Spadaro – Faculdade de Ciências Médicas de Botucatu, Universidade Estadual de São Paulo
Jorge Pinto Ribeiro – Faculdade de Medicina, Universidade Federal do Rio Grande do Sul
Jorge Sabbaga – Hospital Alemão Oswaldo Cruz, São Paulo
José Antonio Marin-Neto – Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo
José Carlos Nicolau – Instituto do Coração, Universidade de São Paulo
José Geraldo Mill – Faculdade de Medicina, Universidade Federal do Espírito Santo
José Mendes Aldrighi – Faculdade de Saúde Pública, Universidade de São Paulo
José Roberto Lapa e Silva – Instituto de Doenças do Tórax, Universidade Federal do Rio de Janeiro
Leopoldo Soares Piegas – Instituto Dante Pazzanese de Cardiologia, São Paulo
Luiz Jacintho da Silva – Faculdade de Ciências Médicas, Universidade Estadual de Campinas
Luiz Paulo Kowalski – Hospital AC Camargo, São Paulo
Márcio Abrahão – Escola Paulista de Medicina, Universidade Federal de São Paulo
Maria Inês Schmidt – Faculdade de Medicina, Universidade Federal do Rio Grande do Sul
Maurício Mota de Avelar Alchorne – Escola Paulista de Medicina, Universidade Federal de
São Paulo
Mauro Schechter – Hospital Universitário Clementino Fraga Filho, Universidade Federal do
Rio de Janeiro
Milton de Arruda Martins – Faculdade de Medicina, Universidade de São Paulo
Moysés Mincis – Faculdade de Ciências Médicas de Santos
Nelson Hamerschlak – Hospital Israelita Albert Einstein, São Paulo
Noedir Antônio Groppo Stolf – Faculdade de Medicina, Universidade de São Paulo
Pérsio Roxo Júnior – Faculdade de Medicina de Ribeirão Preto
Raul Cutait – Hospital Sírio-Libanês, São Paulo
Raul Negrão Fleury – Instituto Lauro de Souza Lima, Coordenadoria dos Institutos de Pesquisa
da Secretaria de Saúde de São Paulo
Raul Marino Junior – Faculdade de Medicina, Universidade de São Paulo
Ricardo Brandt de Oliveira – Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo
Roberto A. Franken – Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo
Ruy Laurenti – Faculdade de Saúde Pública, Universidade de São Paulo
Soubhi Kahhale – Faculdade de Medicina, Universidade de São Paulo
Wilson Roberto Catapani – Faculdade de Medicina do ABC, Santo André
Wilson Cossermelli – Reclin Reumatologia Clínica, São Paulo
Diretoria Executiva da Associação Paulista de Medicina (Triênio 2011-2014)
Presidente: Florisval Meinão
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ii
Sao Paulo Med J. 2013; 131(4):i-ii
Diretor Social: Alfredo de Freitas Santos Filho
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13º Diretor Distrital: Marcio Aguilar Padovani
14º Diretor Distrital: Wagner de Matos Rezende
Editorial
DOI: 10.1590/1516-3180.2013.1314730
From classroom to bedside: integration of the
basic science curriculum in medical teaching
Da sala de aula para a beira do leito: a integração da
ciência básica curricular no ensino da medicina
Alessandro Wasum MarianiI, Paulo Manuel Pêgo-FernandesII
Instituto do Coração (InCor), Hospital das Clínicas (HC), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil
MD. Thoracic Surgeon, Instituto do Coração
(InCor), Hospital das Clínicas (HC), Faculdade
de Medicina da Universidade de São Paulo
(FMUSP), São Paulo, Brazil.
I
MD, PhD. Associate Professor, Discipline
of Thoracic Surgery, Instituto do Coração
(InCor), Hospital das Clínicas (HC), Faculdade
de Medicina da Universidade de São Paulo
(FMUSP), São Paulo, Brazil.
II I
Around the world, universities have been rethinking not only the medical curriculum but also
the entire way of teaching medicine. The enormous torrent of new knowledge, medical specialization, ever-faster entry of technology and even the concepts of evidence-based medicine have
made it essential to discuss again and reorganize the medical curriculum.
In many medical schools, the undergraduate medical curriculum can classically be divided
into basic sciences, clinical sciences and clerkship (internship). The increases in the length of
time spent on clerkship that have been instituted in many medical schools is a sign of change in
teaching and a clear example of a significant curricular modification.
The problem-based learning (PBL) approach can be considered to be an effort towards making learning more dynamic. There are obviously pros and cons to this, with advocates and critics
of this approach. Here, we do not wish to discuss the complete reformulation of the curriculum,
or to go into the issue of what curricular proposal would be most appropriate, if only because we
take the view that different realities should have different teaching proposals. Rather, we would
like to discuss how to better integrate basic sciences and to highlight their importance.
In this regard, several authors have drawn attention to the need for better integration of
teaching. In 2000, Harden published an interesting article that proposed 11 consecutive and
progressively correlated steps that he named the “integration ladder”, which can be used for
assessing and planning the medical curriculum.1
A very interesting solution was produced by the University of California. In rethinking its
medical teaching, it considered that full integration of basic, clinical and social sciences was
important. The idea was that the final application of knowledge, which is dependent both on
practice and on deepening of the theory, could be better explored by schools through introducing multimodal teaching tools. This thinking resulted in implementation of a program named
“Human Biology and Disease”, which basically aimed to unify basic sciences and clinical sciences. This methodology was studied and described in a paper published in 2009.2
Another interesting experience at Harvard Medical School was described in 2007. This consisted of a new proposal that sought better integration of the curriculum through not dividing
the material into blocks over the academic year, thus ensuring that students were in contact with
their different subjects continuously and unceasingly throughout the year.3
There is a worldwide trend towards this curricular integration: both horizontally, between
subjects, and vertically, between basic sciences and clinical sciences. It is taking place through
the argument that it provides teaching that is more complete and effective in terms of knowledge and applicability.
In this regard, article three of the national curricular directives for undergraduate medical courses that have been issued by the Higher Education Chamber of the Brazilian National
Education Council states the following:4
Sao Paulo Med J. 2013; 131(4):211-2
211
Editorial | Mariani AW, Pêgo-Fernandes PM
“The undergraduate medical course provides entry/professional training for physicians with a profile of generalist, humanist, critical
and reflective training, who have the capacity to act, based on ethical principles, on the health-illness process at its different levels of
care, with actions to promote health, prevent disease, recover health and rehabilitate the individual, from a perspective of comprehensiveness of care, with a sense of social responsibility and commitment towards active citizenship, as a promoter of full health for
human beings.”
To fulfill this target, medical schools and educators should make every effort to constantly improve teaching. This should, without any doubt, include adaptation of the basic sciences program, thereby making it dynamic, efficient and (why not?) more attractive
to students. All of this has the aim that basic sciences should serve as a firm foundation for clinical knowledge and for development
of research.
REFERENCES
1. Harden RM. The integration ladder: a tool for curriculum planning
and evaluation. Med Educ. 2000;34(7):551-7.
2. Wilkerson L, Stevens CM, Krasne S. No content without context:
integrating basic, clinical, and social sciences in a pre-clerkship
curriculum. Med Teach. 2009;31(9):812-21.
3. Ogur B, Hirsh D, Krupat E, Bor D. The Harvard Medical SchoolCambridge integrated clerkship: an innovative model of clinical
education. Acad Med. 2007;82(4):397-404.
4. Brasil. Ministério da Educação. Conselho Nacional de Educação.
Câmara de Educação Superior. Resolução CNE/CES No. 4, de 7 de
novembro de 2001. Institui Diretrizes Curriculares Nacionais do Curso
de Graduação em Medicina. Diário Oficial da União, Brasília, 9 de
novembro de 2001. Seção 1, p. 38. Available from: http://portal.mec.
gov.br/cne/arquivos/pdf/CES04.pdf. Accessed in 2013 (Jun 13).
Sources of funding: None
Conflict of interest: None
Date of first submission: June 6, 2013
Last received: June 6, 2013
Accepted: June 19, 2013
Address for correspondence:
Alessandro Wasum Mariani
Rua Treze de Maio, 1217 — apto. 31
Bela Vista — São Paulo (SP) — Brasil
CEP 01327001
E-mail: [email protected]
E-mail: [email protected]
212
Sao Paulo Med J. 2013; 131(4):211-2
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314326
Clustering and combining pattern of metabolic syndrome
components in a rural Brazilian adult population
Agregação e padrão de combinação dos componentes da
síndrome metabólica em uma população rural adulta brasileira
Adriano Marçal PimentaI, Mariana Santos Felisbino-MendesII, Gustavo Velasquez-MelendezI
Department of Maternal and Child Nursing and Public Health, School of Nursing, Universidade Federal de Minas Gerais (UFMG), Belo
Horizonte, Minas Gerais, Brazil
PhD. Professor in the Department of Maternal
and Child Nursing and Public Health, School of
Nursing, Universidade Federal de Minas Gerais
(UFMG), Belo Horizonte, Minas Gerais, Brazil.
I
II
MSc. Doctoral Student in the Department of
Maternal and Child Nursing and Public Health,
School of Nursing, Universidade Federal de
Minas Gerais (UFMG), Belo Horizonte, Minas
Gerais, Brazil.
KEY WORDS:
Metabolic syndrome x.
Risk factors.
Rural population.
Cluster analysis.
Obesity, abdominal.
PALAVRAS-CHAVE:
Síndrome x metabólica.
Fatores de risco.
População rural.
Análise por conglomerados.
Obesidade abdominal.
ABSTRACT
CONTEXT AND OBJECTIVE: Metabolic syndrome is characterized by clustering of cardiovascular risk factors such as obesity, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance and arterial
hypertension. The aim of this study was to estimate the probability of clustering and the combination
pattern of three or more metabolic syndrome components in a rural Brazilian adult population.
DESIGN AND SETTING: This was a cross-sectional study conducted in two rural communities located in
the Jequitinhonha Valley, Minas Gerais, Brazil.
METHODS: The sample was composed of 534 adults (both sexes). Waist circumference, blood pressure
and demographic, lifestyle and biochemical characteristics were assessed. The prevalences of metabolic
syndrome and its components were estimated using the definitions of the National Cholesterol Education
Program – Adult Treatment Panel III. A binomial distribution equation was used to evaluate the probability
of clustering of metabolic syndrome components. The statistical significance level was set at 5% (P < 0.05).
RESULTS: Metabolic syndrome was more frequent among women (23.3%) than among men (6.5%). Clustering of three or more metabolic syndrome components was greater than expected by chance. The commonest combinations of three metabolic syndrome components were: hypertriglyceridemia + low levels
of HDL-c + arterial hypertension and abdominal obesity + low levels of HDL-c + arterial hypertension; and
of four metabolic syndrome components: abdominal obesity + hypertriglyceridemia + low levels of HDL-c
+ arterial hypertension.
CONCLUSION: The population studied presented high prevalence of metabolic syndrome among women and clustering of its components greater than expected by chance, suggesting that the combination
pattern was non-random.
RESUMO
CONTEXTO E OBJETIVO: A síndrome metabólica é caracterizada pela agregação de fatores de risco cardiovasculares como obesidade, dislipidemia, resistência à insulina, hiperinsulinemia, intolerância à glicose
e hipertensão arterial. Este estudo objetivou estimar a probabilidade de agregação e o padrão de combinação de três ou mais componentes da síndrome metabólica em população rural adulta brasileira.
TIPO DE ESTUDO E LOCAL: Estudo transversal, conduzido em duas comunidades rurais da região do Vale
do Jequitinhonha, Minas Gerais.
MÉTODOS: A amostra foi constituída de 534 adultos, de ambos os sexos, dos quais foram aferidas a circunferência da cintura, a pressão arterial e características demográficas, do estilo de vida e bioquímicas.
Prevalências da síndrome metabólica e seus componentes foram estimados usando a definição da National Cholesterol Education Program – Adult Treatment Panel III. A equação da distribuição binomial foi
utilizada para avaliar a probabilidade de agregação dos componentes da síndrome metabólica. O nível de
significância estatística estabelecido foi 5% (P < 0,05).
RESULTADOS: Síndrome metabólica foi mais frequente em mulheres (23,3%) que homens (6,5%). A agregação de três ou mais componentes da síndrome metabólica foi maior do que esperada ao acaso. Combinações mais comuns para três componentes da síndrome metabólica foram hipertrigliceridemia + baixos
níveis de HDL-c + hipertensão arterial, obesidade abdominal + baixos níveis de HDL-c + hipertensão arterial. Para quatro componentes, obesidade abdominal + hipertrigliceridemia + baixos níveis de HDL-c +
hipertensão arterial.
CONCLUSÃO: Na população estudada, a prevalência da síndrome metabólica foi alta entre mulheres e
houve agregação dos seus componentes acima do esperado que ocorra ao acaso, sugerindo padrão não
aleatório de combinação.
Sao Paulo Med J. 2013; 131(4):213-9
213
ORIGINAL ARTICLE | Pimenta AM, Felisbino-Mendes MS, Velasquez-Melendez G
INTRODUCTION
Metabolic syndrome is characterized by clustering of cardiovascular risk factors such as obesity, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance and hypertension.1
This syndrome is recognized as an important public health problem worldwide, due to prevalence greater than 20.0% in adult
populations living both in urban and in rural areas,2-7 and also to
its strong association with cardiovascular diseases and type 2 diabetes, which are both major causes of death worldwide.1,8-9
Despite this epidemiological context, the management of metabolic syndrome in clinical practice remains controversial,10,11
primarily because of the random clustering of its components.
Moreover, metabolic syndrome is diagnosed based upon the presence of three or more components out of a total of five,12 which
could lead to a plethora of combination patterns.13 These various combinations require different interventions and therapeutic approaches, and this is often neglected in clinical practice.13
Nonetheless, accurate management of metabolic syndrome, in
order to control the current global epidemics of cardiovascular disease and diabetes mellitus, is of fundamental importance.14
In Brazil, these issues have been poorly investigated, particularly in rural areas, given that studies have usually focused on
the prevalence of metabolic syndrome and associated factors in
urban populations. Furthermore, there may be a need for different
approaches towards evaluating metabolic syndrome in rural populations, which are also highly affected by this pathological condition4,5,7 and thus would benefit from interventions such as establishing preventive strategies and adequate treatment.
OBJECTIVE
The objective of the present study was to estimate the probability
of clustering and the combining pattern of three or more metabolic
syndrome components in a rural Brazilian adult population.
METHODS
Study population and design
A cross-sectional population-based study was conducted between
November 2004 and March 2005 in two communities, Virgem das
Graças and Caju, in the rural areas of the municipalities of Ponto
dos Volantes and Jequitinhonha, respectively. These communities
are located in the Jequitinhonha Valley, in the northeast of the state
of Minas Gerais, Brazil.
In other projects conducted in these areas, a census performed
by our research group in 2001 showed that 1216 individuals were
living in these communities. For the present study, 621 of these
subjects were excluded due to the following criteria: age less than
18 years (n = 522); emigration (n = 33); death (n = 6); pregnancy
(n = 14); diabetes diagnosis (n = 12); polymerase chain reaction
214
Sao Paulo Med J. 2013; 131(4):213-9
values above 10 mg/l [which could indicate acute infection or
inflammation] (n = 31);15 and physical impossibilities that compromised anthropometric measurements (n = 3). Moreover, 61
individuals were also lost because of their absence at the time of
the survey (n = 47) or refusal to participate (n = 14). Finally, data
from 534 participants remained available for analysis.
Ethics committee approval
This study was approved by the Research Ethics Committee of
Universidade Federal de Minas Gerais (UFMG), in accordance
with National Health Council Resolution 196/96. All of the subjects who took part in the study were informed about the objectives of the research and their rights as participants, and then were
asked to sign a consent form.
Data collection
An interview was conducted by nurses, in which the participants
answered a survey questionnaire covering various aspects of their
demographic characteristics (sex, age, skin color, marital status and
schooling) and lifestyle characteristics (smoking habits and alcohol
consumption). At the conclusion of the interview, a clini­cal evaluation was performed on the participants, which included waist circumference and blood pressure measurements, carried out in triplicate by well-trained staff in accordance with standard procedures.16
Blood samples were collected from each participant by means
of venous puncture following a fasting period of 12 hours. Serum
and plasma aliquots were obtained by centrifugation of each sample, and were appropriately treated and stored in vials maintained
at 4 °C until arrival at the laboratory for biochemical analysis, in
accordance with the recommended technical specifications for
avoiding damage to biological material.
Colorimetric enzymatic methods were used to determine glucose, triglyceride and total cholesterol values using a Roche Cobas
Mira Plus analyzer (Roche Diagnostics, Switzerland). The highdensity lipoprotein cholesterol (HDL-c) concentration was also
determined by means of colorimetric enzymatic assay, following
precipitation of the low-density lipoprotein cholesterol (LDL-c)
and very low-density lipoprotein cholesterol (VLDL-c) fractions,
using phosphotungstic acid and magnesium chloride. The LDL-c
concentrations were calculated by applying the Friedewald equation,17 since there were no triglyceride values > 400 mg/dl: LDL-c =
total cholesterol – (HDL-c + triglycerides/5).
Waist circumference was measured to the nearest millimeter,
using a non-extendable measuring tape, and this was done exactly
halfway between the margin of the lowest rib and the iliac crest,
with participants in a standing posi­tion (accurate to 0.1 cm).16
Blood pressure was measured by means of an indirect method,
using a sphygmomanometer (mercury manometer), in accordance with the Seventh Report of the Joint National Committee on
Clustering and combining pattern of metabolic syndrome components in a rural Brazilian adult population | ORIGINAL ARTICLE
Prevention, Detection, Evaluation and Treatment of High Blood
Pressure.18 Measurements were made three times in each participant’s right arm with two-minute intervals between measurements, after an initial resting period of at least five minutes.
Definition of metabolic syndrome
Metabolic syndrome was diagnosed in accordance with the definition of the National Cholesterol Education Program - Adult
Treatment Panel III (NCEP-ATP III), which requires the presence
of three or more of the following components:12
1. Abdominal obesity: waist circumference ≥ 102 cm for men
and ≥ 88 cm for women.
2. Hypertriglyceridemia: triglycerides ≥ 150 mg/dl;
3. Low HDL-c: HDL-c < 40 mg/dl for men and < 50 mg/dl for
women;
4. Hyperglycemia: fasting blood glucose ≥ 100 mg/dl.14
5. Arterial hypertension: systolic blood pressure ≥ 130 mmHg
and/or diastolic blood pressure (DBP) ≥ 85 mmHg and/or
hypertension treatment.
Statistical analyses
The study population characteristics were presented in terms of
the absolute and relative frequencies of the demographic and lifestyle variables, stratified by sex. These same procedures were used
to present the prevalence of metabolic syndrome and its components. Statistical differences were evaluated by means of Pearson’s
chi-square test, and the significance level was set at 5% (P < 0.05). The analyses on clustering of three or more metabolic syndrome components, independently of their cutoff points, were performed based on the quintile distribution of each factor according to sex. Thus, a given component was determined to be present
in an individual if he or she had values in the lowest quintile for
HDL-c and the highest quintile for the other factors.
The expected degree of clustering of three or more metabolic
syndrome components was estimated by calculating the probability of d occurrences for n factors, where the probability of each
occurrence was 0.20 (extreme quintile). Individual probabilities
were calculated from the binomial formula presented below.19
Finally, the expected probability was compared with the
observed proportion of subjects in the highest quintile for three
or more metabolic syndrome components, using the Pearson chisquare test.
In addition, the proportions of three or more metabolic syndrome component combinations were also calculated stratified by
sex. Statistical differences were evaluated by means of the Pearson
chi-square test, and the significance level was set at 5% (P < 0.05).
All the analyses were performed using the Statistical Package
for the Social Sciences (SPSS) software package for Windows, version 15.0 (SPSS Inc., Chicago, IL, United States).
RESULTS
The study population was composed of 270 men (50.6%) and 264
women (49.4%). The major demographic and lifestyle characteristics of the subjects, according to sex, are shown in Table 1. The age
intervals among the population presented homogenous distribution,
with a slightly higher proportion of individuals with ages between
18 and 29 years. Most of the subjects lived with a spouse (69.3%)
and were of mixed/black color (75.3%). This last characteristic was
observed more frequently among men. The proportion of individuals with less than five years of schooling was high (76.3%), as was
the proportion of illiterates (34.5%). The prevalences of alcohol consumption and smoking habit were 23.6% and 30.3%, respectively.
These habits were also more frequent among men.
The prevalence of metabolic syndrome and its components,
according to sex, are shown in Table 2. Metabolic syndrome was
diagnosed in 14.9% of the participants, and was four times more
frequent among women than among men (P < 0.05). Concerning
metabolic syndrome components, 11.6% of the population
Table 1. Study population distribution according to demographic and
lifestyle characteristics, stratified by sex. Virgem das Graças and Caju,
2004-2005
Sex
Variables
Male
n
Age (years)
18-29
74
30-39
55
40-49
45
50-59
45
≥ 60
51
Skin color*†
White
47
Mixed/black
223
Marital status
Living with partner
182
Living without partner
88
Schooling (years)
Illiterate
103
1-4
112
5-8
37
≥9
18
Smoking habits*
Nonsmoker
93
Former smoker
63
Smoker
114
Alcohol consumption (grams/day)*‡
No consumption
176
3.1-20
53
> 20
41
Female
n
%
%
Total
n
%
27.4
20.4
16.7
16.7
18.9
74
58
42
36
54
28.0
22.0
15.9
13.6
20.5
148
113
87
81
105
27.7
21.2
16.3
15.2
19.7
17.4
82.6
85
179
32.2
67.8
132
402
24.7
75.3
67.4
32.6
188
76
71.2
28.8
370
164
69.3
30.7
38.1
41.5
13.7
6.7
81
111
38
34
30.7
42.0
14.4
12.9
184
223
75
52
34.5
41.8
14.0
9.7
34.4
23.3
42.2
192
24
48
72.7
9.1
18.2
285
87
162
53.4
16.3
30.3
65.2
19.6
15.2
232
24
8
87.9
9.1
3.0
408
77
49
76.4
14.4
9.2
*P < 0.05 for differences between sexes; †Mixed/black includes all variations of
mixed or black; ‡Lowest ethanol consumption equals 3.1 grams/day.
Sao Paulo Med J. 2013; 131(4):213-9
215
ORIGINAL ARTICLE | Pimenta AM, Felisbino-Mendes MS, Velasquez-Melendez G
presented abdominal obesity, 15.2% hypertriglyceridemia, 44.1%
low levels of HDL-c, 10.6% hyperglycemia and 59.7% hypertension. Abdominal obesity and low levels of HDL-c were proportionally higher among women (P < 0.05).
Graph 1 presents the observed and expected frequencies of
metabolic syndrome components, according to sex. Observed
Table 2. Prevalence of metabolic syndrome and its components
according to sex. Virgem das Graças and Caju, 2004-2005
Sex
Male
Variables
Metabolic syndrome
Yes
No
Waist circumference*
< 102 (♂); < 88 (♀)
≥ 102 (♂); ≥ 88 (♀)
Triglycerides (mg/l)
< 150
≥ 150
HDL-c (mg/dl)*
< 40 (♂); < 50 (♀)
≥ 40 (♂); ≥ 50 (♀)
Fasting glucose (mg/dl)
< 100
≥ 100
Hypertension
No
Yes
Female
n
%
n
%
16
230
6.5
93.5
57
188
266
4
98.5
1.5
217
31
Total
n
%
23.3
76.7
73
418
14.9
85.1
206
58
78.0
22.0
472
62
88.4
11.6
87.5
12.5
208
45
82.2
17.8
425
76
84.8
15.2
75
173
30.2
69.8
146
107
57.7
42.3
221
280
44.1
55.9
221
26
89.5
10.5
219
26
89.4
10.6
440
52
89.4
10.6
105
165
38.9
61.1
110
154
41.7
58.3
215
319
40.3
59.7
*P < 0.05 for differences between sexes; ♂ = men; ♀ = women; HDL-c = high
density lipoprotein cholesterol; hypertension is defined as blood pressure ≥ 130/85
mmHg and/or hypertension due to drug treatment.
45
40
% of individuals
35
30
25
men
women
expected
20
15
10
05
00
0
1
2
3+
Number of components
*P-value = 0.003 (Pearson’s chi-square test comparing observed and expected
proportions of metabolic syndrome components).
Graph 1. Observed (bar) and expected (line) proportions of individuals
for each number of metabolic syndrome components, according to
sex. Virgem das Graças and Caju, 2004-2005
216
Sao Paulo Med J. 2013; 131(4):213-9
rates are represented by bars while expected rates are represented by lines. The observed frequencies were calculated based
on the quintile distribution of metabolic syndrome components
and are therefore not identical to the ones shown in Table 2.
The expected frequencies were calculated in order to ascertain the nature of the co-occurrence of metabolic syndrome
components and were based on the binomial distribution equation. Thus, for both sexes, the clustering of three or more metabolic syndrome components did not occur by chance, since
the observed frequency (14.7% for men and 16.0% for women)
was higher than the expected frequency (10.2%) (Table 2).
Additionally, these proportions were statistically tested and, in
fact, this confirmed the differences between the observed and
expected proportions (P-value < 0.05).
Table 3 shows the combinations of metabolic syndrome
components among the individuals who presented this condition, according to sex. The most common combinations of three
components in the population studied were hypertriglyceridemia +
low levels of HDL-c + hypertension, and abdominal obesity + low
levels of HDL-c + hypertension. The first pattern was more frequent among men and the second, among women. The most
frequent combination of four components was abdominal obesity + hypertriglyceridemia + low levels of HDL-c + hypertension. This pattern was also more common among women.
On the other hand, the most frequent four-component-pattern presented by men was hypertriglyceridemia + low levels of
HDL-c + hyperglycemia + hypertension.
DISCUSSION
In this study, the prevalence of metabolic syndrome was 14.9%.
The degree of clustering of its components was higher than
what would be expected by chance and standard combinations
between them.
Although the magnitude of the metabolic syndrome was not
as high as what was observed in other studies conducted in both
urban and rural areas, which was over 20%,2-7 metabolic syndrome is an important public health concern in the study population, since these two communities are located in one of the poorest regions of Brazil. Alternatively, in analyses stratified by sex,
the data have demonstrated high prevalence of metabolic syndrome among women (23.3%) and low prevalence among men
(6.5%). Similar findings have also been shown in studies developed in rural areas in Brazil4 and other countries.5,20 There seems
to be a pattern of metabolic syndrome occurrence in rural areas
that is characterized by higher prevalence among women. This
phenomenon might be determined by people’s occupations in
this region, which differ greatly according to sex. Men still perform the field activities that require high energy expenditure,
while women are devoted to housework.5 Another investigation
Clustering and combining pattern of metabolic syndrome components in a rural Brazilian adult population | ORIGINAL ARTICLE
developed using the same population as in this study showed that
men were more active than women in relation to leisure, commuting and work, while women were more active than men in
the household domain.21
We observed in this study that there were occurrences of three
or more metabolic syndrome components at rates greater than
would be predicted by chance. This may be indicative of the existence of underlying mechanisms that contribute towards these
cluster patterns. This is an important finding, since not all associations among the components have been fully elucidated, thus
leading researchers to ask whether the proposed definitions used
to diagnose metabolic syndrome might only be random cardiovascular risk factors.10,11 Similar results were found in an investigation conducted on a sample of 4,975 subjects aged between 18
and 74 years from the Framingham Offspring Study, which was
an urban population. In that study, it was also pointed out that
clustering of three or more cardiovascular risk factors (high levels of total cholesterol, low levels of HDL-c, hypertriglyceridemia, overall obesity, elevated systolic blood pressure and hyperglycemia) occurred at a rate greater than what would be expected
by chance and, hence, there ought to be a connection between
them.22 In other studies conducted on urban populations, it has
also been demonstrated that combinations of three or more metabolic syndrome components occurred more frequently than the
expected by chance.23-25
Physicians and researchers have been recognizing that cardiovascular disease determinants tend to cluster, and therefore
the risk of developing these illnesses rises in line with increases
in their clustering abilities.26-28 Therefore, our results corroborate
those found in other investigations, thus providing greater consistency regarding the affirmation that metabolic syndrome is
clinically useful as a diagnostic tool. Our results also show that, in
the rural population studied, the occurrence of clustering of metabolic syndrome components was systematic and not random,
thereby reinforcing the hypothesis that underlying pathophysiological mechanisms are involved in this process.
One important criticism of the clinical importance of metabolic syndrome relates to the fact that it is diagnosed based on
the presence of three or more components out of a total of five.
This creates the possibility of 16 combinations, with different
pathophysiological patterns and, consequently, multiple treatment options,13 although we only found 13 among the studied population. Additionally, longitudinal studies have demonstrated variations in the risk of mortality according to the
different combination patterns of metabolic syndrome components.29,30 In our study, we observed that the most frequent
combination of three components was hypertriglyceridemia +
low levels of HDL-c + arterial hypertension among men and
abdominal obesity + low levels of HDL-c + arterial hypertension
Table 3. Combinations of metabolic syndrome components among
the participants with this condition, according to sex. Virgem das
Graças and Caju, 2004-2005
Sex
Male
Combinations
Three components
HTG + LHDL-c + HBP
AO + LHDL-c + HBP
HTG + HGLY + HBP
AO + HGLY + HBP
LHDL-c + HGLY + HBP
AO + HTG + HBP
AO + HTG + LHDL-c
Four components
AO + HTG + LHDL-c + HBP
AO + LHDL-c + HGLY + HBP
HTG + LHDL-c + HGLY + HBP
AO + HTG + HGLY + HBP
AO + HTG + LHDL-c + HGLY
Five components
AO + HTG + LHDL-c + HGLY + HBP
Female
n
%
n
%
5
0
3
2
3
1
0
31.3
0.0
18.8
12.5
18.8
6.3
0.0
10
15
4
3
1
2
1
1
0
1
0
0
6.3
0.0
6.3
0.0
0.0
0
0.0
Total
n
%
17.5
26.3
7.0
5.3
1.8
3.5
1.8
15
15
7
5
4
3
1
20.5
20.5
9.6
6.8
5.5
4.1
1.4
8
4
3
1
1
14.0
7.0
5.3
1.8
1.8
9
4
4
1
1
12.3
5.5
5.5
1.4
1.4
4
7.0
4
5.5
HTG = hypertriglyceridemia (triglycerides ≥ 150 mg/dl); LHDL-c = low levels of
high density lipoprotein cholesterol (HDL-c < 40 mg/dl for men and < 50 mg/dl for
women); HBP = hypertension (blood pressure ≥ 130/85 mmHg and/or hypertension
due to drug treatment); HGLY = hyperglycemia; AO = abdominal obesity.
among women, while the most common combination of four
components was abdominal obesity + hypertriglyceridemia +
low levels of HDL-c + arterial hypertension, for the whole study
population. These combination patterns are similar to those
found in other studies that also used the NCEP-ATP III metabolic syndrome definition.13,20,31-33 As a result, it seems that the
factors of real relevance in clinical practice are the combination patterns of metabolic syndrome components, according to
sex. Consequently, healthcare professionals’ conduct could be
guided by these characteristics.
Furthermore, it could be seen that the most frequent combination patterns of metabolic syndrome components in most of
the study population were abdominal obesity and dyslipidemia
(hypertriglyceridemia and/or low levels of HDL-c). It was only
in the pattern of hypertriglyceridemia + low levels of HDL-c
+ arterial hypertension that co-occurrence of abdominal obesity and dyslipidemia was not observed. On the other hand, this
pattern was more frequent among men with an anthropometric profile consisting of low proportions of overall and abdominal obesity, thereby corroborating the findings of other studies.13,20 Obesity, especially the abdominal or visceral type, plays
a fundamental role in the pathophysiological mechanism of
metabolic syndrome, given that it triggers the insulin resistance
pathway as result of excessive free fatty acid accumulation in
the blood circulation.1,34
Sao Paulo Med J. 2013; 131(4):213-9
217
ORIGINAL ARTICLE | Pimenta AM, Felisbino-Mendes MS, Velasquez-Melendez G
We believe that our findings have a social impact because
the study population was still undergoing the process of epidemiological transition, i.e. high rates of morbidity and mortality
due to infectious and parasitic diseases35 were observed to coexist with increased occurrence of non-communicable illnesses.36
Moreover, the local health services are poor, thus hindering the
population’s access to actions aimed at health promotion and disease prevention, control and treatment.35
Thus, this evidence of clustering and combination patterns of
metabolic syndrome components contributes towards the existing knowledge. It corroborates the usefulness of metabolic syndrome as a diagnostic tool with simple clinical-laboratory criteria
that are easily applicable at the primary health care level, including isolated rural areas in one of the poorest regions of Brazil.
This study has the following limitations: a) the sample was
selected according to convenience, which means that caution is
required in interpreting the external validity of our findings; b) the
total number of individuals with a positive diagnosis of metabolic
syndrome was small (n = 73), which needs to be taken into consideration in evaluating component combination patterns.
6. Zubair N, Kuzawa CW, McDade TW, Adair LS. Cluster analysis reveals
important determinants of cardiometabolic risk patterns in Filipino
women. Asia Pac J Clin Nutr. 2012;21(2):271-281.
7. Kim TN, Kim JM, Won JC, et al. A decision tree-based approach
for identifying urban-rural differences in metabolic syndrome
risk factors in the adult Korean population. J Endocrinol Invest.
2012;35(9):847-52.
8. Lawes CM, Vander Hoorn S, Rodgers A, International Society of
Hypertension. Global burden of blood-pressure-related disease,
2001. Lancet. 2008;371(9623):1513-8.
9. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of
diabetes: estimates for the year 2000 and projections for 2030.
Diabetes Care. 2004;27(5):1047-53.
10. Kahn R, Buse J, Ferrannini E, et al. The metabolic syndrome: time
for a critical appraisal: joint statement from the American Diabetes
Association and the European Association for the Study of Diabetes.
Diabetes Care. 2005;28(9):2289-304.
11. Reaven GM. The metabolic syndrome: is this diagnosis necessary?
Am J Clin Nutr. 2006;83(6):1237-47.
12. Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. Executive Summary of The Third Report of The
CONCLUSION
The rural population studied here presented high prevalence of
metabolic syndrome among women. The metabolic syndrome
components presented clustering at a rate greater than what would
be expected by chance, suggesting that the combination patterns were non-random. The patterns that were most frequently
observed were the following: hypertriglyceridemia + low levels of
HDL-c + arterial hypertension; abdominal obesity + low levels
of HDL-c + arterial hypertension; and abdominal obesity + hypertriglyceridemia + low levels of HDL-c + arterial hypertension.
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, And Treatment of High Blood Cholesterol In
Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97.
13. Kuk JL, Ardern CI. Age and sex differences in the clustering of
metabolic syndrome factors: association with mortality risk. Diabetes
Care. 2010;33(11):2457-61.
14. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management
of the metabolic syndrome: an American Heart Association/National
Heart, Lung, and Blood Institute Scientific Statement. Circulation.
2005;112(17):2735-52.
15. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation
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Sao Paulo Med J. 2013; 131(4):213-9
219
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314451
Obstructive sleep apnea syndrome: complaints and
housing characteristics in a population in the United States
Síndrome de apneia obstrutiva do sono: queixas e características
da habitação em uma população dos Estados Unidos da América
Khalil AnsarinI, Leyla SahebiII, Siamak SaburIII
Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
MD. Internist, Pulmonologist and Chairman of
Tuberculosis and Lung Disease Research Center,
Tabriz University of Medical Sciences, Tabriz, Iran.
I
II
MSc. Doctoral Student of Epidemiology,
Tuberculosis and Lung Disease Research Center,
Tabriz University of Medical Science, Tabriz, Iran.
MD, PhD. Assistant Professor of Clinical
Epidemiology and Medicine, Department of
Clinical Epidemiology, School of Dentistry,
Shahid Beheshti University of Medical Sciences,
Tehran, Iran.
III
KEY WORDS:
Sleep apnea, obstructive.
Housing.
Nutrition surveys.
Snoring.
United States.
PALAVRAS-CHAVE:
Apnéia do sono tipo obstrutiva.
Habitação.
Inquéritos nutricionais.
Ronco.
Estados Unidos.
220
Sao Paulo Med J. 2013; 131(4):220-7
ABSTRACT
CONTEXT AND OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is one of the leading causes of
morbidity and mortality in adults. Early detection of the disorder and discovery of risk factors through
standardized questionnaires will lead to reduction of the OSAS burden. The main aim of this study was to
estimate the prevalence of OSAS symptoms and examine their association with housing characteristics.
DESIGN AND SETTING: Cross-sectional study at a medical school.
METHODS: Demographic, housing and body measurement data on 5,545 individuals aged 16 years and
over of various races were selected from the National Health and Nutrition Examination Survey. We analyzed the probability of OSAS based on habitual snoring combined with daytime sleepiness and/or witnessed apnea. Univariate and multiple linear regression were used.
RESULTS: 9.8% of the men and 6.9% of the women reported symptoms suggestive of OSAS (habitual snoring, daytime sleepiness and/or apnea). The following prevalences of symptoms were found among males
and females respectively: frequent snoring 35.1%, 22.3%, excessive daytime sleepiness 6.4%, 3.4% and frequent apnea 14.9%, 20.6%. Using multiple linear regression, OSAS symptoms were correlated with gender,
age, body mass index (BMI), marital status and education. Regarding housing characteristics, mildew or
musty smell and pets in the environment were associated with a high probability of OSAS.
CONCLUSION: OSAS symptoms were more prevalent than in developing countries. The environment was
an important risk factor, but environmental factors are easier to control and manage than other variables
like BMI or socioeconomic status.
RESUMO
CONTEXTO E OBJETIVO: Síndrome de apneia obstrutiva do sono (SAOS) é uma das principais causas de
morbidade e mortalidade em adultos. Detecção precoce da doença e descoberta de fatores de risco com
questionários padronizados levarão a redução dos danos por SAOS. O principal objetivo deste estudo foi
estimar a prevalência de sintomas de SAOS e examinar sua associação com características da habitação.
TIPO DE ESTUDO E LOCAL: Estudo transversal em faculdade de medicina.
MÉTODOS: Dados demográficos, habitacionais e de medidas corporais sobre 5.545 indivíduos de 16 anos
ou mais, de diversas raças, foram selecionados do National Health and Nutrition Examination Survey. Analisamos a probabilidade de SAOS com base no ronco habitual combinada com sonolência diurna e/ou
apneia testemunhada. Análise univariada e regressão linear múltipla foram usadas.
RESULTADOS: 9,8% dos homens e 6,9% das mulheres relataram sintomas sugestivos de SAOS (ronco habitual, sonolência diurna e/ou apneia). A prevalência de sintomas em homens e mulheres, respectivamente,
foi: ronco frequente 35,1%, 22,3%, sonolência excessiva diurna 6,4%, 3,4% e apneia frequente 14,9%, 20,6%.
Através de regressão linear múltipla, sintomas de SAOS foram relacionados com gênero, idade, índice de
massa corpórea (IMC), estado civil e educação. Das características da habitação, mofo ou cheiro de mofo e
animais de estimação no ambiente foram associados com alta probabilidade de SAOS.
CONCLUSÃO: Sintomas de SAOS foram mais prevalentes do que nos países em desenvolvimento. O meio
ambiente foi um fator de risco importante, porém é mais fácil controlar e manejar fatores ambientais do
que outras variáveis, como IMC ou status socioeconômico.
Obstructive sleep apnea syndrome: complaints and housing characteristics in a population in the United States | ORIGINAL ARTICLE
INTRODUCTION
Obstructive sleep apnea syndrome (OSAS) is a considerable issue
in public health. It is a highly prevalent disorder among middleaged adults1 and is independently associated with certain risk
factors. It is also related to many medical conditions such as
hypertension, cardiovascular morbidity and mortality, coronary
insufficiency, stroke, type 2 diabetes and pulmonary disease.2-5
Untreated OSAS can cause road accidents,1 loss of work productivity,5 occupational injuries1 and even sudden death.4 Therefore,
this disorder may lead to a huge multilateral problem unless
proper control and management is implemented. The prevalence
of obstructive sleep apnea among adults in the Western world
ranges from 3% to 28%,5 and in the United States of America
(USA), the prevalence is currently estimated to be 5% to 10%.6,7
The prevalence of OSAS in some studies based on various
questionnaires has been reported as follows: based on the Berlin
Criteria, in New Zealand (2009) 2.8%,2 Iran (2011) 4.9%8 and
USA (2006) 26%;5 based on a self-reported questionnaire, in
France (2007) 3.5%1 and Hong Kong (2001) 2.1%;9 and based on
the Epworth Sleepiness Scale (ESS), in Nigeria (2008) 1.2%10 and
India (2004) 3.6%.11 It is noteworthy that in some regions only
10% of the population has been adequately screened for appropriate diagnosis.4 Discrepancies in observed prevalence and
underreporting may be due to non-standardized definitions and
variation between diagnostic methods.1
OSAS screening, diagnosis and treatment entails some challenges. Polysomnography or respiratory polygraphy is a precise method for diagnosing OSAS, but this method has its disadvantages, such as expensiveness, inaccessibility and difficulty
to perform. Thus, in some cases, these disorders are not diagnosed and only a few cases are properly treated.1 Another diagnostic method is to screen by means of a questionnaire based on
three symptoms: reported habitual snoring, daytime sleepiness
and witnessed apnea.
Early detection of OSAS not only reduces the morbidity risk
but also leads to significant reduction in the cost of care for other
conditions.2,10 Many studies have been published in relation to
weight and demographic variables, which all have strong relationships with OSAS.1-3,8,11-13
Information on environmental factors affecting this outcome
is unavailable. Housing characteristics are an important environmental variable; adverse conditions are preventable and can
be dealt with cost-effectively, and thus may be a determinant in
decreasing the burden of disease.
OBJECTIVE
The purpose of this study was to assess the prevalence of symptoms of OSAS in a population in the USA and analyze housing
characteristic risks in relation to demographic and body mass
index (BMI) variables, using the National Health and Nutrition
Examination Survey (NHANES) Sleep Disorders Questionnaire
and dataset.14
METHODS
We used the NHANES dataset (2005 to 2006), publicly available
from: www.cdc.gov/nchs/nhanes.htm. NHANES was a major
program that was implemented by the United States National
Center for Health Statistics (NCHS). NCHS is part of the Centers
for Disease Control and Prevention (CDC) and is responsible
for producing vital and health statistics for the United States.
NHANES was conducted in all 50 states of the USA.
NHANES data were not obtained using a simple random sample. Rather, a complex, multistage, probability sampling design was
used to select participants such that they would be representative
of the civilian of the civilian, non-institutionalized US population.
Oversampling of certain population subgroups was done to increase
the reliability and precision of the health status indicator estimates
for these groups. The NCHS used four questionnaires: demographic
variables, housing characteristics, body measurements and OSAS.
After the datasets for demographic variables, housing characteristics, OSAS and body measurements had been merged, inconsistencies relating to 594 sequence numbers led these individuals to be
excluded from the study. Thus, 5,545 individuals aged 16 years and
over were selected, from several racial groups in the United States:
Mexican American, Other Hispanic, Non-Hispanic White, NonHispanic Black and Other Race Including Multiracial.
Demographic variables
The population for the demographics questionnaire was interviewed directly in the subjects’ homes and a proxy was provided
for individuals who could not answer the questions themselves.
The variables selected for this evaluation included age, gender,
marital status, education status, pregnancy status, household size
and family size.
Housing characteristics
One study participant in each family responded for the entire
family and these responses were released for all members of the
same family. The housing characteristics provided family-level
interview data on the type of home, number of apartments in
the building, age of home, number of rooms in home, time lived
in home, whether home was owned or rented, water source and
treatment, and allergy component-related questions about the
presence of furry animals.
Sleeping characteristics
This section included questions on sleep habits and disorders.
A subscale of eight questions, relating to general productivity,
Sao Paulo Med J. 2013; 131(4):220-7
221
ORIGINAL ARTICLE | Ansarin K, Sahebi L, Sabur S
from the Functional Outcomes of Sleep Questionnaire, was also
included.14 Variables pertaining to OSAS were selected in order
to analyze the probability of OSAS based on habitual snoring
(often or almost every night), combined with daytime sleepiness
(often or almost always) and/or witnessed apnea (often or almost
every night, as confirmed by self-reports).
Body mass index (BMI)
All survey participants were eligible for the body measurement
component. There were no medical, safety or other exclusions
for the body measurement protocol. The body measurement data
were collected by trained health technicians, who were accompanied by a recorder during each body measurement examination. The health technicians used their discretion to obtain as
many measurements as practical for individuals who were using
a wheelchair. Body weight data for individuals who had had limb
amputations and also those from pregnant women were excluded
from the analysis. Height was measured using a Seca electronic
stadiometer, in an upright standing position, with head and heels
against the stadiometer before taking the height, unless this position was anatomically impossible. Before the measurement, the
participants took a deep breath and held it while the headboard
was positioned. If the individuals were unable to stand with the
head and heels against the stadiometer, the trunk needed to be
vertical above the waist and the arms and shoulders needed to
be relaxed.14
Weight was measured on a Toledo digital scale, in pounds
with automatic conversion to kilograms. The participants
were weighed in their underwear. They were instructed
to stand still at the center of the scale platform facing the
recorder, with their hands at their sides, and to look straight
ahead. After they had been properly positioned and the digital
readout was stable, the recorder clicked on the capture button
on the screen. The weight, length and height measurements
were entered directly into the computer system by clicking
on the “Get” buttons.14 In accordance with the World Health
Organization (WHO) definitions, BMI (kg/m2) less than 18.5
was considered to be underweight, BMI greater than 25 was
considered to be overweight and greater than 30 was considered to be obese.15
Analysis
After assessment to check that the data presented normal distribution, all the continuous variables were summarized in terms of
mean ± standard deviation (SD) and categorical variables were
expressed as percentages. All significance tests were two-sided,
and P values less than 0.05 were considered to be statistically significant. Univariate and multiple linear regression were used for
the analysis. Variables showing associations with P values less
222
Sao Paulo Med J. 2013; 131(4):220-7
than 0.10 in univariate analyses were considered to be candidate
risk factors to be used in multiple analysis.
RESULTS
The participants’ mean age was 41.8 ± 20 years. Among this
sample of individuals ≥ 16 years of age from the USA, 2,826
(51%) were women and 2,719 were men (49%) and consisted of
the following: Mexican Americans (1,248 cases, 22.5%), Other
Hispanics (174 cases, 3.1%), Non-Hispanic Whites (2,468 cases,
44.5%), Non-Hispanic Blacks (1,428 cases, 22.5%) and Other
Race Including Multiracial (227 cases, 4.1%). The frequency distribution among the study participants is shown in Table 1.
The prevalence of habitual snoring (≥ 5 nights/week) was
28.7% (confidence interval, 95% CI: 27.6-29.8); habitual apnea
(≥ 5 nights/week) was 4.8% (95% CI: 4.6-5.0) and habitual excessive daytime sleepiness (EDS) (≥ 5 times a month) was 17.9%
(95% CI: 17.15-18.65). The prevalences of habitual snoring,
apnea and EDS were 35.1% (849 subjects; 95% CI: 33.2-36.8),
6.4% (160 subjects; 95% CI: 6.0-6.8) and 14.9% (405 cases; 95%
CI: 19.4-20.6) among the men and 22.3% (539 subjects; 95%
CI: 20.95-23.36), 3.4% (87 subjects; 95% CI: 3.2-3.7) and 20.6%
(584 subjects; 95% CI: 19.4-21.8) among the women, respectively.
The OSAS symptoms had strong correlations (snoring/apnea:
P < 0.0001 and ß = 0.39; snoring/EDS: P < 0.0001 and ß = 0.09;
and EDS/apnea: P < 0.001 and ß = 0.12). The estimated prevalence of OSAS was 8.3% (463 subjects; 95% CI: 7.6-9.0). The prevalence of symptoms associated with OSAS is shown in Graph 1.
The prevalence of symptoms associated with OSAS according to
house characteristics is presented in Table 2.
In order to investigate variables relating to OSAS, univariate and multiple linear regression tests were performed. Variables
with more than two categories were analyzed in the form of a
dummy variable. These variables included race, education status,
marital status and type of house.
In the univariate linear regression, BMI, age, gender, race,
education status, marital status, type of house, age of home,
rented or owned home, source of water, presence of mildew or
musty smell, living or spending time with pets and ratio of population density in the home were variables that had significant
relationships with OSAS.
The details the of analysis were as follows: the probability of
OSAS increased linearly with increasing age and BMI respectively (ß = 0.087, P < 0.0001; ß = 0.026, P < 0.0001); the probability among the women was less than among the men (ß = -0.026,
P = 0.0008); the probability among the Mexicans was greater than
among other races (ß = 0.43, P < 0.0001); the probability was less
among Non-Hispanic Blacks (ß = - 0.43, P < 0.0001).
The probability of OSAS among school students (16-20 years)
without delay (i.e. students who never failed in the end-of-year
Obstructive sleep apnea syndrome: complaints and housing characteristics in a population in the United States | ORIGINAL ARTICLE
Table 1. Distribution of participants according to demographic characteristics
Name of variable
Co-factors
Age (years), mean (standard
deviation)
Men, n (%)
Body mass index
(kg/m2), n (%)
Education status*
n (%)
Marital status
n (%)†
< 18.5
18.5-4.9
25-29.9
≥ 30
missing
1
2
3
4
5
6
7
missing
1
2
3
4
5
6
missing
Mexican American
n = 1248
Other Hispanic
n = 174
Non-Hispanic (White) Non-Hispanic (Black)
n = 2468
n = 1428
Other
n = 227
36 (17.8)
36 (16.7)
46.9 (20.6)
39.5 (19.5)
37.9 (16.9)
608 (47.7)
28 (2.3)
366 (30)
449 (36.8)
376 (30.8)
29
199 (16)
31 (2.5)
356 (28.6)
189 (15.2)
234 (18.8)
190 (15.3)
46 (3.7)
3
568 (45.5)
49 (3.9)
58 (4.6)
40 (3.2)
417 (33.4)
116 (9.3)
-
81 (46.6)
4 (2.3)
61 (35.3)
57 (32.9)
51 (29.5)
1
20 (11.6)
3 (1.7)
37 (21.4)
33 (19.1)
22 (12.7)
41 (23.7)
17 (9.8)
1
82 (47.4)
4 (2.3)
9 (5.2)
2 (1.2)
57 (32.9)
19 (11.0)
1
1224 (49.6)
68 (2.8)
829 (34.6)
759 (31.7)
738 (30.8)
74
159 (6.5)
12 (0.5)
102 (4.2)
223 (9.1)
633 (25.8)
721 (29.4)
602 (24.6)
16
1316 (53.4)
174 (7.1)
230 (9.3)
41 (1.7)
530 (21.5)
172 (7.0)
5
712 (49.9)
32 (2.3)
427 (30.7)
377 (27.1)
555 (39.9)
37
223 (15.7)
12 (0.8)
58 (4.1)
233 (16.4)
324 (22.9)
409 (28.9)
158 (11.2)
11
419 (29.3)
86 (6.0)
118 (8.3)
65 (4.6)
629 (44.0)
111 (7.8)
-
94 (41.4)
10 (4.6)
95 (43.6)
57 (26.1)
56 (25.7)
9
29 (12.9)
2 (0.9)
19 (8.4)
8 (3.6)
48 (21.3)
52 (23.1)
67 (29.8)
2
105 (46.3)
10 (4.4)
179 (7.5)
6 (2.6)
71 (31.3)
189(7.9)
-
*Education status. 1: school student for more than 4 years without any failure in end-of-year examinations and thus no repetition of the school year; 2: school
student for more than 4 years with failure in end-of-year examinations and the need to repeat the school year; 3: less than 9th grade, 4: 9-11th grade; 5: high
school graduate; 6: university student without a certificate; and 7: university graduate.
†
Marital status. 1: married; 2: widowed; 3: divorced; 4: separated; 5: never married; and 6: living with parent.
4500
4000
3500
3000
snoring
apnea
2500
EDS
2000
1500
1000
500
ve
r
Ne
re
ly
Ra
lly
na
sio
cy
en
Oc
ca
Fr
eq
u
os
ta
lw
ay
s
0
Al
m
examinations and thus never had to repeat the school year) was
less than among others (ß = 1.43, P < 0.0001), while university
students without a certificate and university graduates had higher
probability of disorders (ß = -0.36, P < 0.0001). Regarding marital status, married (ß = -0.3, P < 0.0001), widowed (ß = -0.59,
P < 0.0001, 95% CI: -0.94-0.23), divorced (ß = -0.94, P < 0.0001)
and separated participants (ß = -1.19, P < 0.0001) presented
higher probability of OSAS, while participants who had never
married (ß =1.03, P < 0.0001) had lower probability of OSAS.
From examining the associations shown between the home
environment and the disorder, the following results could be
inferred: living in a mobile home or trailer produced a higher
probability of OSAS than shown by other types of home
(ß = 0.79, P = 0.005). In addition, a direct linear relationship was
found between duration of living in a house and probability of
the disease.
Homes with a well as the water source (rather than from a
water supply company) and those with mildew or a musty smell
had higher probability of disorders (ß = 0.79, P = 0.005) and
(ß = -0.34, P = 0.003).
Living with pets was also associated with greater possibility of
OSAS (ß = - 0.33, P < 0.0001), but population density presented an
inverse relationship with OSAS (ß = -0.63, P < 0.0001). The variables
Snoring/apnea: never, rarely (1-2 nights/week), occasionally (3-4 nights/week),
frequently (5 or more nights/week); EDS: never, rarely (once a month), sometimes
(2-4 times a month), frequently (5-15 time a month), almost always (16-30 times a
month). EDS = excessive daytime sleepiness.
Graph 1. Prevalence of obstructive sleep apnea syndrome-related
symptoms based on intensity
Sao Paulo Med J. 2013; 131(4):220-7
223
ORIGINAL ARTICLE | Ansarin K, Sahebi L, Sabur S
Table 2. Prevalence of the symptoms of obstructive sleep apnea syndrome (OSAS) according to house characteristics
Housing characteristics
Sleep disorders
Snoring
Apnea
EDS
N (%)
Mobile home or trailer
185 (50)
47 (12.3)
85 (20.5)
One-family house, isolated
1350 (45)
315 (10)
586 (17.1)
Type of house
One-family house*
199 (40.9)
37 (7.2)
98 (17.7)
Apartment
358 (41.9)
92 (9.9)
188 (18.8)
Dormitory
27 (32.1)
5 (5.9)
27 (29.7)
1 or 2
24 (42.1)
5 (8.3)
10 (14.7)
3 or 4
49 (38.0)
20 (13.2)
31 (19.1)
5 to 9
104 (42.3)
27 (10.5)
45 (16.7)
How many apartments in the building?
10 to 19
97 (44.1)
23 (9.7)
49 (19.8)
20 to 49
36 (39.1)
3 (3.1)
20 (18.7)
50 or more
38 (42.7)
13 (13.1)
27 (22.9)
1990 to present
79 (45.7)
119 (11)
203 (17.5)
1978 to 1989
316 (42.8)
82 (10.7)
153 (18.7)
1960 to 1977
331 (46.8)
71 (9.7)
160 (20.3)
When was home built?
1950 to 1959
199 (47.7)
52 (11.6)
79 (16.3)
1940 to 1949
240 (45.3)
27 (9.2)
52 (16.4)
Before 1940
125 (44.5)
51 (9.5)
127 (21.4)
Owned
1418 (45.5)
336 (10.4)
597 (17)
Rented or owned
Rented
653 (41.9)
152 (9)
348 (19.1)
Other
48 (42.9)
8 (6.5)
38 (27.5)
Company
1761 (43.8)
404 (9.5)
809 (17.5)
Source of tap water
Well
328 (47.1)
82 (11.6)
152 (19.8)
Other
15 (46.9)
6 (19.4)
7 (20)
Yes
549 (45.1)
130 (10.3)
214 (15.6)
Water treatment devices
No
1559 (44)
360 (9.6)
760 (18.7)
Yes
324 (43.7)
81 (10.3)
188 (21.9)
Mildew or musty smell
No
1789 (44.3)
412 (9.7)
790 (17.1)
Yes
389 (42.5)
85 (8.6)
195 (18.4)
Cockroaches seen in home
No
1730 (44.6)
411 (10.1)
788 (17.8)
Yes
916 (47.3)
210 (10.4)
449 (20.7)
Living or spending time with animals
No
1203 (42.1)
286 (9.4)
535 (16.1)
Dog in house now
Yes
662 (47.2)
157 (10.8)
336 (21.4)
Cat in house now
Yes
408 (46.9)
98 (10.9)
202 (20.9)
Small furry animal in house now
Yes
69 (46.9)
12 (8.1)
42 (26.1)
>1
1767 (45.2)
434 (10.6)
812 (82.9)
1-2
322 (40.9)
58 (6.7)
150 (16.1)
Population density in house†
2
21 (32.8)
2 (3)
16 (23.9)
>2
7 (41.2)
2 (10)
1 (5)
Less than one year
402 (41.8)
96 (9.5)
193 (17.9)
1-2 years
375 (42.2)
92 (9.6)
201 (19.4)
How many years has family lived in home?
3-5 years
371 (43.4)
82 (9.2)
169 (17.4)
6-10 years
326 (47.1)
66 (9.1)
134 (17)
More than 10 years
645 (46.3)
160 (11)
286 (17.8)
EDS = excessive daytime sleepiness; *Attached to one or more houses; †Total number of people in the household divided by the number of rooms.
of number of apartments in the building, home age and having
cockroaches in the home did not show any association with OSAS.
In multiple linear regression analysis, the variables of age, gender, BMI, education status, marital status, mildew or musty smell,
and animals living or spending time in the home presented significant relationships with OSAS. The test results are shown in Table 3.
224
Sao Paulo Med J. 2013; 131(4):220-7
DISCUSSION
To the best of our knowledge, this study is the first broad study on
data from the USA to contain valuable information about sleep
disorders and risk factors relating to housing characteristics in
the presence of important variables like weight and demographic
variables. The prevalence of symptoms of OSAS was 8.3%.
Obstructive sleep apnea syndrome: complaints and housing characteristics in a population in the United States | ORIGINAL ARTICLE
We compared several studies conducted among adult in different countries using questionnaire instruments. The prevalence of OSAS was 1% in Nigeria10 (0.5% among women and
1.9% among men), 3.6% in India,16 3.1% in Hong Kong9 and 5%
in Iran;8 however, it was 7.4% in France1 and 26% in the USA.5
OSAS in the United States, like in other Western countries, is
more common than in developing countries. Obesity and aging
are probably crucial factors in the United States, and the rising trend of these two factors requires more attention to this
context.17,18
Although the prevalence of risky apnea in the present study
was similar to findings in Pakistan (10-12%),19 it was more common in Malaysia (15.2%).20 On the other hand, rates if 3.5%
and 6.1% were reported in France and Turkey, respectively.1,12
Nevertheless, it should be noted that 90% of individuals with
sleep apnea are undiagnosed.21
The prevalence of habitual snoring was similar to findings from studies conducted in the USA (46%) and Malaysia
(47.3%).5,20 The prevalence observed in our study was higher than
in the following other regions: Nigeria 31.6%,10 São Paulo 31%22
and France 22%.1
The rate of excessive daytime sleepiness in the present study
(15%) was similar to findings from France (16%) and Malaysia
(14.8%).1,20 On the other hand, the reported prevalence was 6.5%
in the USA (2005).5
Consistent with a study conducted in France,1 habitual snoring and apnea were more prevalent among men (35.1 and 6.4%)
than among women (22.3 and 3.4%). However, EDS was more
prevalent among women (20.6 versus 14.9%). The prevalence of
symptoms in the French study was consistently lower (61%, 7%
and 24%).1
OSAS was less common among women, and this was similar
to other studies; for instance in France, Japan, New Zealand1,2,4
and also in Nigeria, India, and Hong Kong.9,10 Epidemiological
studies have confirmed that the gender ratio of OSAS is 2 to
3.1,10,20,21 and this ratio was 1.42 in our study. In addition to cases
of more prevalent OSAS disorders among men, these differences
were statistically significant in our study and some other studies1,2,4,8,23 although a study conducted in Iran did not reach any
significant variation.8
BMI has been an important modifiable risk factor in relation to occurrences of OSAS.24-26 This has been confirmed in
several studies.1,8,10-13,17 For example, obese individuals presented a risk of OSAS that was 10 times higher in the study by
Salvador et al.27 There was also a strong relationship between
these in the presence of confounding variables. On the basis
of several studies, increased body weight can alter the normal
upper airway mechanics during sleep through a variety of distinct mechanisms.28
Table 3. Analytical statistics on the status of obstructive sleep apnea
syndrome, from multiple linear regression test
Variables*
Body mass index (kg/m2†)
Age
Gender: 1: male; 2: female
Race‡ (dummy)
Race 1
Race 3
Race 4
Education status† (dummy)
Education status 1
Education status 2
Education status 3
Education status 5
Education status 6
Marital status§ (dummy)
Marital status 1
Marital status 2
Marital status 3
Marital status 4
Marital status 5
Type of house|| (dummy)
Type of house 1
Type of house 2
When was home built?
How many years has family
lived in home?
Water source: 1: Company 2:
Well
Has home had mildew or a
musty smell? 1: Yes 2: No
Have you seen cockroaches in
your home? 1: Yes 2: No
Do animals live or spend time
in home? 1: Yes 2: No
Ratio of population density
ß
0.08
0.01
-0.36
SE
0.007
0.004
0.095
P-value
0.0001
0.004
0.0001
0.39
0.11
0.22
0.22
0.196
0.21
0.077
0.56
0.29
0.52
0.59
-0.19
-0.17
-0.16
0.21
0.597
0.21
0.131
0.121
0.012
0.33
0.37
0.20
0.20
0.22
-0.12
-0.34
-0.93
0.27
0.21
0.291
0.26
0.37
0.23
0.29
0.68
0.19
0.01
0.22
-0.13
-0.22
0.02
0.18
0.17
0.03
0.48
0.19
0.40
-0.03
0.04
0.50
0.11
0.131
0.39
-0.41
0.13
0.002
-0.09
0.14
0.516
-0.31
0.10
0.002
-0.10
0.15
0.49
*Variables with P < 0.1 are entered in the model; †Education status 1: school
student for more than 4 years without any failure in end-of-year examinations and
thus no repetition of the school year; 2: school student for more than 4 years with
failure in end-of-year examinations and the need to repeat the school year; 3: less
than 9th grade, 4: 9-11 grade; 5: high school graduate; 6: university student without
certificate; 7: university graduate; ‡Race: 1: Mexican American; 2: other Hispanic; 3:
non-Hispanic (white); 4: other; §Marital status: 1: married; 2: widowed; 3: divorced;
4: separated; 5: never married; 6: living with parent; ||Type of house: 1: mobile
home or trailer; 2: one-family house, detached from any other house; 3: one-family
house, attached to one or more houses; 4: apartment; 5: dormitory.
SE = standard error.
There was a direct trend between age and OSAS in the
present study. These results were consistent with reports from
different countries1,5 in which some of the results were analyzed from multiple tests, like in the present study.4,8 Thus,
the effect of age-related chronic diseases on OSAS needs to
be investigated.
Sao Paulo Med J. 2013; 131(4):220-7
225
ORIGINAL ARTICLE | Ansarin K, Sahebi L, Sabur S
Education was another variable significantly associated
with OSAS, with regard to confounding variables. It was found
that high school students who never failed in the end-of-year
examinations and thus never had to repeat the school year presented lower probability of OSAS. There was a direct association
between education status and OSAS.8
Participants whose marital status was “separated” showed
less possibility of OSAS than shown by other marital statuses. In
a report from Nigeria, being married was a risk factor for OSAS.10
Although Mexican Americans presented a high risk in univariate regression, multiple regressions did not support this
result. In other studies, Asian, African-American and Hispanic
racial groups presented higher risk.13
One main goal in the present study was to investigate the
association between housing characteristics and OSAS. Although
the home environment has been reported as a factor in people’s
health,29 its role in relation to sleep status had not been particularly studied.
Although the variables of type of house, population density
in the home, water source and the age of the house were significant in the test, their relationship did not maintain significance
in the multiple model.
An odor of mildew or a musty smell and living or spending
time with animals had strong relationships with OSAS both in
univariate and in multiple linear regression.
Our results are new in terms of exposure factors associated
with OSAS. Whether the mechanisms through which housing
characteristics correlate with OSAS are pathological mechanisms
(e.g. through the activity of some fungi such as Aspergillum in
damp environments or microorganisms found in the saliva of
wool or animal), or are autoimmune mechanisms (e.g. through
immune reactions against allergens such as wool and animal
hair), or are physiological (e.g. through affecting concentration
due to moisture and the air pressure in the home environment),
these can be evaluated and thus, eventually, effective management of OSAS may be achieved.
Housing characteristics should be taken into account for public health purposes for better management of OSAS in the US, as
well as in clinical decision-making relating to this syndrome.
syndrome. Study of a French middle-aged population]. Rev Mal
Respire. 2007;24(3 Pt 1):305-13.
2. Mihaere KM, Harris R, Gander PH, et al. Obstructive sleep apnea in
New Zealand adults: prevalence and risk factors among Māori and
non-Māori. Sleep. 2009;32(7):949-56.
3. Adewole O, Adeyemo H, Ayeni F, et al. Prevalence and correlates of
snoring among adults in Nigeria. Afr Health Sci. 2008;8(2):108-13.
4. Kayukawa Y, Shirakawa S, Hayakawa T, et al. Habitual snoring
in an outpatient population in Japan. Psychiatr Clin Neurosci.
2000;54(4):385-91.
5. Hiestand DM, Britz P, Goldman M, Phillips B. Prevalence of
symptoms and risk of sleep apnea in the US population: Results
from the national sleep foundation sleep in America 2005 poll.
Chest. 2006;130(3): 780-6.
6. de la Hoz RE, Aurora RN, Landsbergis P, et al. Snoring and obstructive
sleep apnea among former World Trade Center rescue workers and
volunteers. J Occup Environ Med. 2010;52(1):29-32.
7. Tishler PV, Larkin EK, Schluchter MD, Redline S. Incidence of sleepdisordered breathing in an urban adult population: the relative
importance of risk factors in the development of sleep-disordered
breathing. JAMA. 2003;289(17):2230-7.
8. Amra B, Farajzadegan Z, Golshan M, Fietze I, Penzel T. Prevalence of
sleep apnea-related symptoms in a Persian population. Sleep Breath.
2011;15(3):425-9.
9. Ip MS, Lam B, Lauder IJ, et al. A community study of sleep-disordered
breathing in middle-aged Chinese men in Hong Kong. Chest.
2001;119(1):62-9.
10. Adewole OO, Hakeem A, Fola A, et al. Obstructive sleep apnea among
adults in Nigeria. J Natl Med Assoc. 2009;101(7):720-5.
11. Sharma SK, Kumpawat S, Banga A, Goel A. Prevalence and risk factors
of obstructive sleep apnea syndrome in a population of Delhi, India.
Chest. 2006;130(1):149-56.
12. Onat A, Hergenç G, Uyarel H, et al. Obstructive sleep apnea syndrome
is associated with metabolic syndrome rather than insulin resistance.
Sleep Breath. 2007;11(1):23-30.
13. Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered
breathing, sleep apnea, and hypertension in a large communitybased study. Sleep Heart Health Study. JAMA. 2000;283(14): 1829-36.
14. Centers for Disease Control and Prevention. National Health and
Nutrition Examination Survey. NHANES 2005-2006. U.S. department
CONCLUSION
Symptoms of OSAS were more prevalent in the USA (8.3%)
than in developing countries. Moreover, the environment was an
important factor for OSAS.
of health and human services centers for disease control and
prevention national center for health statistics overview. Available
from:
http://www.cdc.gov/nchs/nhanes/nhanes2005-2006/
nhanes05_06.htm. Accessed in 2012 (Aug 16).
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Leyla Sahebi
Tuberculosis and Lung Disease Research Center, Tabriz University of
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Effect of increasing body mass index on obstructive sleep apnea in
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Sources of funding: None
Conflict of interest: None
Date of first submission: January 16, 2012
Last received: September 8, 2012
Accepted: October 19, 2012
Sao Paulo Med J. 2013; 131(4):220-7
227
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314459
Circumstances and factors associated with
accidental deaths among children, adolescents
and young adults in Cuiabá, Brazil
Circunstâncias e fatores associados às mortes por causas
acidentais entre crianças, adolescentes e jovens em Cuiabá, Brasil
Christine Baccarat de Godoy MartinsI, Maria Helena Prado de Mello-JorgeII
Universidade Federal do Mato Grosso (UFMT), Cuiabá, Mato Grosso, and Universidade de São Paulo (USP), São Paulo, Brazil
PhD. Associate Professor, School of Nursing,
Universidade Federal de Mato Grosso (UFMT),
Cuiabá, Mato Grosso, Brazil.
I
II
PhD. Associate Professor, School of Public
Health, Universidade de São Paulo (USP), São
Paulo, Brazil.
KEY WORDS:
Accidents.
Child.
Risk factors.
Mortality.
Epidemiology.
PALAVRAS-CHAVE:
Acidentes.
Criança.
Fatores de risco.
Mortalidade.
Epidemiologia.
ABSTRACT
CONTEXT AND OBJECTIVE: Analysis on accidents from the perspective of population segments shows
there is higher incidence among children, adolescents and young adults. Since the characteristics and
circunstances of the event are closely related to educational, economic, social and cultural issues, identifying them may contribute towards minimizing the causes, which are often fatal. The aim here was to identify the environmental, chemical, biological and cultural factors associated with deaths due to accidents
among children, adolescents and young adults in Cuiabá, in 2009.
DESIGN AND SETTING: This was a descriptive cross-sectional study conducted in Cuiabá, Mato Grosso, Brazil.
RESULTS: Thirty-nine accidental deaths of individuals aged 0 to 24 years were examined: 56.4% due to
traffic accidents; 25.6%, drowning; 10.3%, aspiration of milk; 5.1%, falls; and 2.6%, accidentally triggering a
firearm. Male victims predominated (82.1%). The presence of chemical, environmental and biological risk
factors was observed in almost all of the homes. Regarding cultural factors and habits, a large proportion
of the families had no idea whether accidents were foreseeable events and others did not believe that the
family’s habits might favor their occurrence. Delegation of household chores or care of younger siblings to
children under the age of 10 was common among the families studied.
CONCLUSION: The results point towards the need to have safe and healthy behavioral patterns and environments, and to monitor occurrences of accidents, thereby structuring and consolidating the attendance
provided for victims.
RESUMO
CONTEXTO E OBJETIVO: Ao analisar os acidentes sob o prisma dos segmentos populacionais, observa-se
grande incidência em crianças, adolescentes e jovens. A frequência e as características e circunstâncias
do evento estão intimamente relacionadas com fatores educacionais, econômicos, sociais e culturais, e a
identificação desses fatores pode contribuir para minimizar essas causas, muitas vezes fatais. O objetivo
foi identificar os fatores ambientais, químicos, biológicos e culturais associados com óbitos por acidentes,
ocorridos entre crianças, adolescentes e jovens em Cuiabá, em 2009.
TIPO DE ESTUDO E LOCAL: Este é um estudo descritivo, transversal, realizado em Cuiabá, Mato Grosso, Brasil.
RESULTADOS: Foram analisados 39 óbitos acidentais ocorridos de 0 a 24 anos (56,4% por acidente de
transporte, 25,6% por afogamento, 10,3% por aspiração de leite, 5,1% por queda e 2,6% por disparo acidental de arma de fogo). Houve predomínio no sexo masculino (82,1%). Observou-se a presença de fatores químicos, ambientais e biológicos na quase totalidade das residências. Quanto aos fatores culturais e
hábitos, grande parte das famílias não soube referir se o acidente constitui evento previsível e outra parte
não acredita que os hábitos da família favorecem sua ocorrência. Delegar aos filhos menores de 10 anos os
afazeres domésticos ou o cuidado de irmãos menores é comum entre as famílias estudadas.
CONCLUSÃO: Os resultados apontam para a necessidade de adotar comportamentos e ambientes seguros e saudáveis, bem como monitorizar a ocorrência dos acidentes, estruturando e consolidando o
atendimento às vítimas.
228
Sao Paulo Med J. 2013; 131(4):228-37
Circumstances and factors associated with accidental deaths among children, adolescents and young adults in Cuiabá, Brazil | ORIGINAL ARTICLE
INTRODUCTION
Unintentional events (accidents) give rise to direct and indirect
costs. The former consists of expenditure on medical attention
and treatment, complementary examinations, hospitalization and
rehabilitation; the latter relates to the loss of working days, lower
productivity and material damage.1
The highest incidence of accidents has been recorded
among children, adolescents and young adults, with important peculiarities regarding frequency and the characteristics
and circumstances of the event.2 Worldwide, the main causes
of death during childhood include traffic accidents (mortality
rate of 10.7/100,000), drowning (mortality rate of 7.2/100,000),
burns (mortality rate of 3.9/100,000), falls (mortality rate of
1.9/100,000) and poisoning (mortality rate of 1.8/100,000).3 In
Brazil, the deaths among children under ten years of age are
due to traffic accidents (29.3%), drowning (21.1%), suffocation
(15.4%), aggression (7.0%) and falls (5.1%). In 2009, the mortality rate from traffic accidents for this age group was 3.6/100,000,
followed by drowning (2.6/100,000) and accidental risks to
breathing (1.8/100,000).4
Accidents in the infant-juvenile group stand out not only
because of the deaths that they cause, but also because of the
resultant trauma, which leaves sequelae and drastically interrupts
the growth and development phase.5
Some authors have suggested that accidents are closely
related to educational, economic, social and cultural factors, such as low income, low maternal education, inadequate
spaces for leisure, poor facilitating physical structure within
the environments, high levels of street exposure, inadequate
supervision, dysfunctional family constitution, family conflicts and consumption of alcohol and drugs, among others.3,6,7 Therefore, identification and reduction of such factors
may contribute towards reducing accidents and, consequently,
these traumatic situations and their often irreversible or fatal
consequences.
OBJECTIVE
The present study aimed to identify environmental, chemical,
social and cultural factors present in the homes of children, adolescents and young adults who died in an accident.
METHODS
This was an epidemiological investigation in which the study
population comprised children, adolescents and young adults
(0 to 24 years of age) who lived in Cuiabá, Mato Grosso, Brazil,
and died in accidents between January 1 and December 31, 2009.
All the accidental deaths among individuals aged 0 to 24 years
that occurred in the municipality in 2009 were studied, thus
including the whole population and not just a sample.
Identification data for the victims were obtained from their
death certificates, which were available by the Births and Deaths
Registry of the Municipal Health Department of Cuiabá. The
inclusion criteria were as follows: age 0 to 24 years; resident in
Cuiabá; death occurred in 2009; and accidental cause was the
basic cause of death (chapter 20 of ICD-10; codes V01 to X59).
A domestic investigation among the victims’ families was
then performed using a form with closed questions.
The data were analyzed using the EpiInfo software, with simple and bivariate analyses, and p < 0.005 was taken to be the significance level.
The variables studied were: type of accident (subgroups)
according to age and sex of the victims; circumstances of death;
place of the accident; place of death; period of the day (morning,
afternoon or evening) and day of the week (beginning, middle or
end of the week) on which the accident occurred; who the victim was with at the time of the accident; and factors observed
during the domestic survey (environmental, chemical, biological
and cultural factors).
The “environmental factors” considered were: stairs, verandas, access ramps, windows and swimming pools without protection; furniture at windows; sharp pointed devices, tools, plastic
bags, matches and lighters within reach of children; access to the
bathroom, laundry, kitchen, stove and hot products; stove in an
area without ventilation; cookware with handles projecting out
from the stove or with lids that did not fit; tablecloths with corners that could be pulled; access to electrical wiring and sockets; glassware and cans in low places; toys and/or objects scattered on the floor; loose rugs; wet floors; buckets, basins or bath
with water; objects on the stairs; piles of firewood, tiles, bricks or
planks; garbage bins without lids; open water tank or cesspool;
access to machinery or equipment; wire fences; hammocks suspended at 1.0-1.5 m from the ground; fans with the propellers
exposed; uneven floors; slippery floors; or firearms in the home.
The “chemical factors” considered were: cleaning products
(detergent, soap and sanitary water); volatile chemicals (alcohol, kerosene and gasoline); solvents (thinner); poisons; cosmetics (cream,
nail polish, make-up and perfume); hygiene products (soap, shampoo and deodorant); and medicines within the reach of children,
according to the way in which they are stored and accessed.
The “biological factors” considered were: presence of animals, a garden with tall grass, plants within the reach of children
and trees in the yard.
The “cultural factors” considered were: the family’s perception of predictability of the event; the family’s beliefs about habits and lifestyle favoring accidents; the family’s supervision of the
child while in water (swimming pool, bucket, tank or river) or at
leisure; use of a baby walker; the habit of leaving the child alone
on a bed, sofa or diaper change table; the victim’s habit of playing
Sao Paulo Med J. 2013; 131(4):228-37
229
ORIGINAL ARTICLE | Martins CBG, Mello-Jorge MHP
on stairs, roofs or verandas, or flying a kite near electric wires;
and the habit of delegating household chores or the task of caring
for small children to children under ten years of age.
The mortality rate per accident was calculated based on the
population of the same age and year.
This research was authorized by the Health Department of
Cuiabá and the Research Ethics Committee of the University
Hospital Julius Müller University Hospital (Hospital Universitário
Júlio Müller, HUJM) of the Federal University of Mato Grosso
(Universidade Federal de Mato Grosso, UFMT) (protocol 929/CEPHUJM/2010). The participating families signed a free and informed
consent statement.
RESULTS
This study included 39 cases of death due to accidental
causes among children, adolescents and young adults aged 0
to 24 years of age, who were living in Cuiabá, Mato Grosso,
Brazil, in 2009. Regarding the accidents, 56.4% involved traffic accidents, followed by drowning (25.6%), risks relating to
breathing/aspirating milk (10.3%), falls (5.1%) and accidental triggering of firearm (2.6%). Regarding gender, males predominated (82.1%) (Table 1).
Transportation accidents occurred at a higher rate in the
age group from 20 to 24 years (50.0%), as did drowning (drowning in rivers), although this was also present in the age groups
from one to four years (drowning in pools and lakes) and from
five to 9 (drowning in lakes). The cases of asphyxia (aspiration
of milk) occurred most often among children under one year of
age, falls in the age group from 15 to 19 years (from scaffolding
during work) and accidental triggering of a firearm in the age
group from five to nine years, while playing with the father’s
weapon (Table 1).
The mortality coefficient from accidents, calculated on the basis
of the population and year of this study, showed higher mortality
rates among males, especially after the age of 15 years (Figure 1).
Most victims of accidents died in hospital. Among the victims whose accidents occurred at home, 85.7% died in hospital and the remainder (14.3%) died at the location of the event
(home). Among the victims whose accidents occurred on public
thoroughfares (in the case of transport accidents), 57.1% died in
hospital and 42.9% at the location of the accident. The workplace
accidents also led to death in hospital.
Transportation accidents occurred predominantly in the
morning (54.5%) and in the middle of the week (59.1%), whereas
drowning occurred in the evening (90.0%) and on the weekend
(80.0%). The cases of asphyxia (aspiration of milk) occurred in
the morning and evening, falls in the morning and accidents with
firearms in the afternoon. These last three events occurred in the
middle of the week (Table 2).
At the time of the accident, 68.2% of the victims of traffic
accidents were alone and 22.0% were with their parents, although
all the victims were the drivers. In the cases of drowning, 70.0%
of the victims were also alone and only 30.0% were in the company of their parents. The children who died from aspiration of
milk were with their parents; the adolescents who died due to
falls were alone; and the child who died from accidental triggering of a firearm was in the company of his grandfather while the
parents were working.
Table 1. Distribution of deaths due to accidental causes among children, adolescents and young adults, according to kind of accident,
age and gender, Cuiabá, 2009
Accidental cause (subgroup) and proportion
(%) in relation to total deaths
Ground transportation accident (22)
56.4%
Drowning (10)
25.6%
Accidental breathing risk (4)
10.3%
Fall (2)
5.1%
Inanimate mechanical force (1)
2.6%
Total deaths
230
Sao Paulo Med J. 2013; 131(4):228-37
Victim’s age
(in years)
n (f)
(%) in relation to the
subgroup of cause
10 to 14
2
9.1
15 to 19
9
40.9
20 to 24
11
50.0
1 to 4
5 to 9
2
1
20.0
10.0
15 to 19
2
20.0
20 to 24
5
50.0
< 1 year
4
100.0
15 to 19
2
100.0
(2) Male
5 to 9
1
100.0
(1) Female
39
100.0
Male = 32 (82.1%)
Female = 7 (17.9%)
Frequency by gender
(1) Male
(1) Female
(8) Male
(1) Female
(10) Male
(1) Female
(2) Male
(1) Male
(1) Male
(1) Female
(5) Male
(2) Male
(2) Female
Circumstances and factors associated with accidental deaths among children, adolescents and young adults in Cuiabá, Brazil | ORIGINAL ARTICLE
60
Coefficient (per 100,000 inhabitants)
Causes of accidents
50
40
30
20
10
0
Male
Female
Total
0 to 4 years
29
25
26
5 to 9 years
05
04
02
10 to 14 years
04
04
04
15 to 19 years
49
08
28
20 to 24 years
56
03
29
Figure 1. Mortality coefficient from cause of accidents among children, adolescents and young adults, according to age group and
gender, Cuiabá, 2009.
Table 2. Distribution of deaths due to accidental causes among children, adolescents and young adults, according to kind of accident,
part of the day and part of the week in which they occurred, Cuiabá, 2009
Accidental cause
Transport accident
Drowning
Milk aspiration
Fall
Accidental triggering of firearm
Total
Accidental cause
Transport accident
Drowning
Milk aspiration
Fall
Accidental triggering of firearm
Total
Part of the day in which the event occurred
Afternoon
Evening
Night
n
%
n
%
n
%
3
13.6
3
13.6
4
18.2
9
90.0
2
50.0
1
100.0
13
33.3
5
12.8
4
10.3
Part of the week in which the event occurred
Beginning of the week
Middle of the week
End of the week
n
%
n
%
n
%
2
9.1
13
59.1
7
31.8
1
10.0
1
10.0
8
80.0
4
100.0
2
100.0
1
100.0
3
7.7
21
53.8
15
38.5
Morning
n
%
12
54.5
1
10.0
2
50.0
2
100.0
17
43.6
Regarding environmental factors, most of the homes showed
the risk factors mentioned in this study, with the exception of
firearms (Table 3). These variables were listed in order to determine the frequency of each risk factor in the 39 houses studied.
The findings show that none of the homes was absolutely riskfree. Sharp-pointed materials, tools, plastic bags and matches
were observed to be within the reach of children in all the homes,
Total
n
22
10
4
2
1
39
%
100.0
100.0
100.0
100.0
100.0
100.0
Total
n
22
10
4
2
1
39
%
100.0
100.0
100.0
100.0
100.0
100.0
P-value
0.0002
P-value
0.0016
and the children had free access to the kitchen, bathroom, laundry and stove. The only homes that did not present open water
tanks or cesspools were the very ones that did not possess either
a water tank or a cesspool.
In most of the homes, chemical factors were in easy reach of
children and many of these products were even packed in food
jars or bottles (Table 4).
Sao Paulo Med J. 2013; 131(4):228-37
231
ORIGINAL ARTICLE | Martins CBG, Mello-Jorge MHP
Table 3. Distribution of deaths due to accidental causes among
children, adolescents and young adults, according to environmental
factors observed in the victims’ homes (n = 39), Cuiabá, 2009
Environmental factors observed in the victims’ homes
Sharp-pointed devices within children’s reach
Tools within children’s reach
Plastic bags within children’s reach
Matches/lighters within children’s reach
Access to bathroom
Access to laundry
Access to kitchen
Access to stove
Access to hot products
Verandas without protection
Access ramps without protection
Piles of firewood, tiles, bricks or planks in the backyard
Fan with exposed blades
Furniture at the window
Cookware with handle projecting out from stove
Garbage bins without lid
Access to electric wiring/sockets
Tablecloths with long tips
Buckets/basins/bath containing water
Objects on the stairs
Toys and objects scattered over the floor
Loose rugs
Hammocks suspended at 1.0 to 1.5 m from the ground
Windows without protection
Wet floors
Slippery floors
Stove in area without ventilation
Pans with lids that do not fit
Glassware and cans within children’s reach
Staircases with protection
Access to machinery/equipment
Uneven floor
Swimming pool without protection
Open water tank
Wire fences
Open cesspool
Firearm at home
n
39
39
39
39
39
39
39
39
39
39
37
37
37
35
35
35
35
34
34
34
33
33
33
31
31
31
31
27
27
27
24
24
8
7
4
2
1
Yes
%
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
94.9
94.9
94.9
89.7
89.7
89.7
89.7
87.2
87.2
87.2
84.6
84.6
85.0
74.5
74.5
74.5
74.5
69.2
69.2
69.2
61.5
61.5
20.5
17.9
10.3
5.1
2.6
No
n
2
2
2
4
4
4
4
5
5
5
6
6
6
8
8
8
8
12
12
12*
15
15
31†
32‡
35
37‡
38
%
5.1
5.1
5.1
10.3
10.3
10.3
10.3
12.8
12.8
12.8
15.4
15.4
15.0
20.5
20.5
20.5
20.5
30.8
30.8
30.8*
38.5
38.5
79.5†
82.1‡
89.7
94.9‡
97.4
*There were no stairs in the home. †There was no swimming pool in the home;
There was no water tank/cesspool in the home.
‡
Regarding biological factors, the presence of animals (82.1%),
trees in the yard (92.3%) and plants and tall grass was common to
most homes (Table 4).
Regarding cultural factors and the families’ habits, most of
the participants thought that accidents were neither foreseeable
events nor preventable (92.3%), while only 7.7% believed that
they were so. When inquired whether the family’s habits favored
occurrences of accidents, 51.3% said that they did (Table 4).
232
Sao Paulo Med J. 2013; 131(4):228-37
Table 4 also shows that many families were in the habit of
supervising children and adolescents in the water (76.9%) but
not during leisure time (74.4%). Moreover, playing on roofs
and running a kite in the street were common activities among
the children. It was also common for adults to delegate household chores or the care of younger siblings to children under
ten years of age.
DISCUSSION
Among the various types of accidents, the concentration of victims among males, from transport accidents and at younger ages
coincides with the results from other studies on causes of accidents.8,9 In view of this context, it has been suggested that legal
measures (relating to implementation and enforcement), in association with preventive measures and traffic education, as practiced in developed countries, are essential.10
Our findings draw attention to occurrences of drowning in
rivers and lakes, both at very young and at older ages. These cases
may be explained by the great number of natural water areas in the
region of Cuiabá, which are commonly used for leisure in view of
the hot climate. Whereas in rich countries drowning occurs predominantly in swimming pools, in poorer countries this type of
accident occurs mostly in rivers and public natural water areas.11
In view of the high lethality rate due to drowning, it is essential to implement surveillance of children and adolescents during leisure activities in water, as well as providing signs and infrastructure enhancements, with fences surrounding risk areas and
the presence of lifeguards. Nevertheless, the vast hydrographic
network with many waterfalls and natural water areas makes it
difficult to provide lifeguards and surveillance, thus showing the
importance of behavioral changes among families, such that safe
behavior and surveillance of children become habits.
It is important to highlight the deaths resulting from aspiration of milk, which have also been mentioned in other studies as
common among children under the age of one year.12 This points
towards the need for proper eructation after each breastfeeding
session and proper positioning in the cradle to prevent suffocation in the event of regurgitation.13
Falls while working, in turn, draw attention to the issue of
safety in the workplace. Statistics show that accidents in the workplace are one of the main causes of occupational death throughout the world, although with different coefficients for economically developed countries (5.9 deaths per 100,000 workers), Asian
countries (23.1 per 100,000) and Latin American countries (13.5
per 100,000).14 In Brazil, the estimated coefficient is 11.4 per
100,000 workers,15 which is much higher than in developed countries such as England (0.7 per 100,000).16 However, these statistics
relate to regular workers. In our study, the deaths from falls in the
workplace involved children under the age of 15 years, who are
Circumstances and factors associated with accidental deaths among children, adolescents and young adults in Cuiabá, Brazil | ORIGINAL ARTICLE
considered under Brazilian law to be apprentices.17 Nonetheless,
given that accidents in the workplace have a major impact on the
productive and economic capacity of the country, since they generally involve young people at the beginning of their professional
lives, reflection is required regarding the importance of prevention and safety measures and the use of appropriate equipment,
in order to avoid this kind of accident and the consequent injuries, which are often fatal.
Accidental death caused by triggering firearms raises the discussion about the danger of keeping firearms at home, since children and adolescents have natural curiosity and lack of perception of imminent risk form a dangerous combination.18 Therefore,
it is better not to have a firearm at home; and if this is really necessary, keeping it unloaded and out of reach of children/adolescents are important preventive measures.
With regard to the place of death, the fact that many transport
accidents occurred on public thoroughfares and that the victims
died at the location of the accident is indicative of the severity of
these traffic accidents and raises three important issues. Firstly, in
relation to safety equipment that may reduce the severity of injuries, seat belts should be used in automotive vehicles and helmets
should be used by drivers and passengers of motorcycles: these
are mandatory devices according to the new Brazilian National
Traffic Code.19 Furthermore, children should always use the correct child restraint such as a child car seat or seat belt, and should
travel in the rear seats.20 Many deaths can be avoided through
correct use of such equipment. However, not all drivers and passengers are using this equipment.21
The second issue relates to speedy and skillful care soon after
the accident, which is fundamental for reducing the injuries and
improving the chances of survival.10
Finally, the third issue relates to the need to study the places
in which the most serious accidents (with immediate fatal outcome) occur, since these places can be considered to present
risks and require careful planning and study. Studying accidents
according to their region of incidence (using geographical information systems, GIS) is now capable of generating effective solutions, particularly in relation to traffic accidents.22 In healthcare,
georeferencing has been highlighted as essential for evaluation
and assessment of risks, especially considering that injuries due
to traffic accidents (i.e. those responsible for deaths at the site
of the accident, in the present study) are responsible for 23% of
deaths due to external causes worldwide.23
The period of occurrence of transportation accidents in the
present study contradicts the findings of most other research,
which indicated that greater numbers of traffic accidents occur
on the weekends due to lower policing levels and greater numbers of inexperienced drivers, along with the intake of alcoholic
beverages.24 The difference found in the present study may have
Table 4. Distribution of deaths (n = 39) due to accidental causes
among children, adolescents and young adults, according to chemical
and biological factors observed in the victim’s home and cultural
factors and habits of the victim’s family, Cuiabá, 2009
n
Chemical factors observed in the victim’s home
Cleaning products within children’s reach
Solvents within children’s reach
Poison within children’s reach
Cosmetics within children’s reach
Hygiene products within children’s reach
Medicines within children’s reach
Cleaning product in food bottle
Poison in food bottle
Volatile products within children’s reach
Solvent in food bottle
Volatile product in food bottle
Biological factors observed in the victim’s homes
Animals
Plants within children’s reach
Tall grass
Tree in yard
Family habits and cultural factors
Children play on roof/stair/veranda
Children run kites in the street (under electric wiring)
Parents delegate household chores to children < 10 years
Parents delegate the care for younger siblings to child
Parents usually supervise the child in the water
Parents usually use a walker for small children
Family habits favor accidents
Parents usually leave child alone on bed/sofa/diaper
changing table
Parents usually supervise the child during leisure activities
Accidents are foreseeable and preventable
Yes
%
No
n
%
39
39
39
39
39
39
33
31
26
27
19
100.0 100.0 100.0 100.0 100.0 100.0 84.6 6 15.4
79.5 8 20.5
66.7 13 33.3
69.2 12 30.8
48.7 20 51.3
32
19
17
3
82.1 7 17.9
48.7 20 51.3
43.6 22 56.4
7.7 36 92.3
39 100.0 38 97.4 1 2.6
38 97.4 1 2.6
38 97.4 1 2.6
30 76.9 9 23.0
27 69.2 12 30.8
20 51.3 19 48.7
17 43.6 22 56.4
10
3
25.6 29 74.4
7.7 36 92.3
been due to the use of vehicles as a means of transport to go to
work, which would explain the greater numbers of traffic accidents in the morning and in the middle of the week. The fact that
most of the victims were alone may strengthen this hypothesis.
With regard to drowning, the fact that they occurred in
the afternoon and on the weekend may denote a relationship
between this kind of accident and leisure activities practiced by
many families on the weekends. This result has also been pointed
out by other researchers.25 In the case of Cuiabá, with its high
temperatures and great number of rivers, it is important to consider drowning to be a major cause of accidents. The fact that
most of the victims were alone again raises the essential issue of
surveillance. A study in China identified greater risk of drowning among children who swam in natural water bodies without
supervision from an adult (over the age of 30 years).26 In view of
the extensive hydrographic network surrounding Cuiabá, public
Sao Paulo Med J. 2013; 131(4):228-37
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ORIGINAL ARTICLE | Martins CBG, Mello-Jorge MHP
prevention policies, with indication of areas presenting risks,
mandatory lifeguard supervision and educational prevention
activities in schools and communities are also important, along
with monitoring and rescue training that teaches children and
adults the resuscitation techniques that are needed in order to
help victims efficiently.
Aspiration of milk during the night and in the morning,
which caused the death of children less than one year of age
and occurred in the presence of the parents, may be related to
times when the parents are tired, sleepy or even sleeping, with
consequent carelessness in relation to a child who has just suckled. Aspiration of milk was singled out as the major event among
small children. Effective prevention comes from the care provided by adults27 in feeding sessions.
Falls occurred in the morning and in the middle of the week,
and this picture is consistent with workplace accidents. Accidents
at work have been considered to be worrisome and to have a
great social impact in Latin American and Caribbean countries.15
Taking developed countries such as Denmark, with only 2.9 accidents per 100,000, as an example,28 the importance of policies for
worker protection in its various dimensions (technical, social,
economic, cultural and political) has been highlighted.29 In the
specific case of adolescents, besides raising awareness regarding
the use of personal protective equipment, the safety conditions at
work should be assessed in order to be able to reduce this important public health problem that affects the economically active
population at its fullest stage of professional development.
The death caused by a firearm in the afternoon and in the
middle of the week, at a time when the parents were working,
reveals the risk of having firearms at home, often without the
child’s caregiver knowing about them, such that this person also
becomes a victim of the circumstances. Since firearm injuries are
in most cases fatal,30 it becomes vital to resume oral discussions
on this issue in order to move forward on disarmament.
The environmental factors found in this study are consistent with the warnings given by other authors, who considered
such accidents to be the result from interaction between behavior
and environmental factors.6 Studies have shown that exposure to
stairs, windows and swimming pools without grids and to sharp
objects, among other factors, increases the risk of domestic accidents, with a high hospitalization rate,31 often with injuries and
significant sequelae.32 Therefore, changing the home environment is essential, combined with behavioral changes among the
family, focusing on prevention.
The chemical factors observed in this study have been
acknowledged in the scientific literature as significant causes of
intoxication that take many children and adolescents to emergency care worldwide.33 Most accidents with chemical products
relate to inadequate storage (within children’s reach and stored
234
Sao Paulo Med J. 2013; 131(4):228-37
in soft-drink bottles or food containers), along with people’s lack
of knowledge in relation to these products.34 The chemical factors combine with the family’s behavior such that, in most cases
of intoxication, the product is left within the child’s reach.35 This
once again highlights the importance of raising the awareness of
the population regarding the hazards of these products and teaching people how to handle them correctly. Manufacturers’ responsibility should also be taken into consideration, because many
types of packing are attractive to children and easy to open. In
this regard, special child-resistant packaging (which was initially
implemented in the United States and Canada) has proven to be
effective. It reduced the intoxication rate by up to 35% during the
period after its deployment.36 In Brazil, two bills of law relating to
this have been put forward: the first (PL 4841/94) makes special
child-resistant packaging mandatory for medicines and hazardous household products; and the second (PL 5802/01) establishes
different symbols on the packaging of cleaning products according to their degree of hazard. However, these bills are still going
through the legislative procedures.37 Although no deaths resulted
from chemical factors in the present study, reflection regarding occurrences of these events with emergency care and hospital internments is required, as shown by many other studies.38-40
Hence, environmental change is an urgent preventive measure.
The presence of certain plants in people’s backyards, seen in
the present study, matches the findings from a study conducted
at the Pediatric Clinic of the Pontifical Catholic University of
Rio Grande do Sul (Pontifícia Universidade Católica do Rio
Grande do Sul, PUCRS), in which 48.3% of the parents interviewed were growing toxic plants at home.41 It has been pointed
out that poisoning by plants is responsible for 2% of all poisoning cases and that lack of knowledge about hazardous species
lies at the root of the problem.42 This highlights the need for
guidance regarding the toxicological characteristics of plants,
including widely-used ornamental species.
The presence of animals, in turn, is of concern insofar as
bites can cause significant injuries, with sequelae in various
spheres: emotional (resulting from the stress of exposure),
physical (determined by scars and disfigurements) and economic (due to the cost of treatment and administration of vaccine and serum for rabies prevention).5 There are several reasons
why young children are more likely than adults to be attacked
on the head: first, children’s smaller stature; second, children
are more likely to lean towards or put their faces close to the
dog’s head, which is perceived by dogs as a threatening posture; third, adults tend to have better defenses against attacks.43
Since most of the accidents with animals occur in homes, there
is a need for educational action regarding care measures in relation to domestic animals (castration and vaccination, and identification of symptoms that indicate the presence of diseases,
Circumstances and factors associated with accidental deaths among children, adolescents and young adults in Cuiabá, Brazil | ORIGINAL ARTICLE
especially rabies) and measures to be taken in the event of
aggression (going immediately to a healthcare clinic for treatment against rabies).
Gardens with tall grass were examined, bearing in mind that
this may attract poisonous animals.7 Trees in the backyard may
give rise to falls, which have been reported to be the main cause of
emergency care, leading to serious sequelae and deficits.5 Keeping
the grass properly under control and preventing children and adolescents from climbing trees are important measures.
Regarding cultural factors, the fact that the families were
unable to say whether accidents and violence were preventable
or had the belief that they were not preventable was inconsistent
with the positive response given when asked whether the family’s
habits favored occurrences of these events. In this respect, a gap in
knowledge was observed, and this was consistent with studies in
which the families were unaware of the hazards at home and did
not know what each stage of children’s growth and development
represented in relation to accidents.44 Thus, it becomes important to bear to mind the epidemiological model of the accident,
in which the circumstance that generated the event comprises an
etiological agent (a form of energy that violates the organic tissues), a host (the child/adolescent whose stage of development
makes it possible to identify the risk) and the environment (the
situation in which the accident occurs),27 which replaces the concept of randomness.
The fact that the families supervised their children and adolescents in activities in the water but not in other leisure activities coincides with affirmations that the level of supervision is
still insufficient.45 Comparison between the findings relating to
the families’ perceptions of supervision and the fact that most
of the victims of drowning were alone at the time of the accident reveals a large gap in the families’ perceptions of the risks.
In the literature, this has been considered to be a factor directly
related to traumatic events.46 The same holds for delegation of
tasks, since the child is not always mature enough to take on
certain tasks.47
Prevention is a challenging task, in which broad intersectoral action that encourages behavioral change is necessary in
several social segments and in schools (both in formal and
in informal groups).
Our findings point towards a need to foster safe and healthy
behavior and environments, and to monitor occurrences of accidents through intersectoral actions. The importance of structuring
and consolidating the attendance provided for victims should also be
highlighted, in order to prevent deaths and promote rehabilitation.
Further progress is still needed with regard to the involvement of professionals in implementing the policies that have
been issued, as well as in relation to better quality of information.
Intersectoral actions will also be necessary, in view of the various
factors involved in occurrences of accidents.
In addition, there is still a need to incorporate the issues into
the curricula of various healthcare, educational and social science
courses, in order to encourage reflection and create actions that
contribute towards transforming the cruel reality of accidents.
Detailed knowledge of the risk factors, within a preventive
approach, is essential for enabling progress in controlling accidents. Therefore, direct action in relation to risk factors and promotion of education for children, families and society, along with
priority for specific policies, is urgently needed for effective control over accidents.
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Sources of funding: None
the American Association of Poison Control Centers Toxic Exposure
Conflict of interest: None
Surveillance System. Am J Emerg Med. 2000;18(5):517-74.
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Last received: September 18, 2012
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Sao Paulo Med J. 2013; 131(4):228-37
237
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314467
Clinical and hematological effects of hydroxyurea therapy
in sickle cell patients: a single-center experience in Brazil
Efeitos clínicos e hematológicos do tratamento com hidroxiureia
em pacientes falciformes: experiência de um centro no Brasil
Ana Cristina Silva-PintoI, Ivan Lucena AnguloII, Denise Menezes BrunettaIII, Fabia Idalina Rodrigues NevesIV, Sarah Cristina BassiIII,
Gil Cunha De SantisIII, Dimas Tadeu CovasV
Centro Regional de Hemoterapia de Ribeirão Preto, Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São
Paulo, (HC-FMRP-USP), Ribeirão Preto, São Paulo, Brazil
MD, PhD. Associate Hematologist and
Coordinator of the Sickle Cell Program, Centro
Regional de Hemoterapia de Ribeirão Preto,
Department of Internal Medicine, Faculdade de
Medicina de Ribeirão Preto (FMRP), Universidade
de São Paulo (USP), São Paulo, Brazil.
I
II
MD, PhD. Associate Hematologist, Centro
Regional de Hemoterapia de Ribeirão Preto,
Department of Internal Medicine, Faculdade de
Medicina de Ribeirão Preto (FMRP), Universidade
de São Paulo (USP), São Paulo, Brazil.
MD. Associate Hematologist, Centro Regional
de Hemoterapia de Ribeirão Preto, Department
of Internal Medicine, Faculdade de Medicina
de Ribeirão Preto (FMRP), Universidade de São
Paulo (USP), São Paulo, Brazil.
III
IV
MD. Associate Hematologist, Department of
Internal Medicine, Faculdade de Medicina de
Ribeirão Preto (FMRP), Universidade de São
Paulo (USP) São Paulo, Brazil.
MD, PhD. Professor, Department of Internal
Medicine, Faculdade de Medicina de Ribeirão
Preto (FMRP), Universidade de São Paulo (USP)
São Paulo, Brazil.
V
KEY WORDS:
Anemia, sickle cell.
Hydroxyurea.
Fetal hemoglobin.
Acute chest syndrome.
Erythrocyte indices.
PALAVRAS-CHAVE:
Anemia falciforme.
Hidroxiuréia.
Hemoglobina fetal.
Síndrome torácica aguda.
Índices de eritrócitos.
238
Sao Paulo Med J. 2013; 131(4):238-43
ABSTRACT
CONTEXT AND OBJECTIVES: Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the
only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective
was to analyze the effects of HU on SCD patients at our institution.
DESIGN AND SETTING: Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil.
METHODS: We analyzed clinical and laboratory data on 37 patients. The hematological parameters and
clinical events that occurred during the year before and the first year of treatment with HU were analyzed.
The mean dose of HU was 24.5 ± 5.5 mg/kg/day.
RESULTS: There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl,
P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute
chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53,
P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051).
CONCLUSION: The patients presented clinical and hematological improvements, with an increase in HbF
and a reduction in the infection rate, which had not been addressed in most previous studies.
RESUMO
CONTEXTO E OBJETIVO: A doença falciforme (SCD) é o distúrbio genético mais comum entre afrodescendentes, afetando aproximadamente 3.500 recém-nascidos a cada ano no Brasil. A hidroxiureia (HU) é
a única droga efetiva para o tratamento dos pacientes com SCD, reduzindo a morbidade e a mortalidade
da doença. O objetivo do estudo foi analisar os efeitos da HU em pacientes com SCD em nossa instituição.
TIPO DE ESTUDO E LOCAL: Estudo retrospectivo realizado em um centro de anemia falciforme em Ribeirão Preto, São Paulo, Brasil.
MÉTODOS: Nós analisamos os dados clínicos e laboratoriais de 37 pacientes. Os parâmetros hematológicos e eventos clínicos que ocorreram no ano anterior e durante o primeiro ano de tratamento com HU
foram analisados. A dose média de HU foi 24.5 ± 5.5 mg/kg/dia.
RESULTADOS: Houve aumento em três parâmetros estudados: hemoglobina (8,3 g/dl para 9,0 g/dl,
P = 0,0003), hemoglobina fetal (HbF) (2,6% para 19,8%, P < 0,0001) e volume corpuscular médio (VCM) (89
para 105 fl, P = 0,001); e redução do número de leucócitos (10.050/µl para 5.700/µl, P < 0,0001), neutrófilos (6.200/µl para 3.400/µl, P = 0,001), plaquetas (459.000/µl para 373.000/µl, P = 0,0002), crises dolorosas
(1,86 para 0,81, P = 0,0014), síndrome torácica aguda (0,35 para 0,08, P = 0,0045), infecções (1,03 para 0,5,
P = 0,047), hospitalizações (1,63 para 0,53, P = 0,0013) e número de transfusões (1,23 para 0,1, P = 0,0051).
CONCLUSÃO: Os pacientes apresentaram melhora clínica e hematológica, com aumento da HbF e redução da taxa de infecção, dado este não explorado na maioria dos estudos clínicos já publicados.
Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil | ORIGINAL ARTICLE
INTRODUCTION
Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately
3,500 newborns each year in Brazil. The underlying abnormality is a single nucleotide substitution (GTG for GAG) in the gene
that encodes the β-globin chain located on chromosome 11.
The mutated globin chain will form the abnormal hemoglobin
S (HbS) seen in sickle cell patients. Upon deoxygenation, HbS
molecules polymerize and change the red cell conformation into
sickle-shaped cells.1 These cells are more adherent to the endothelium and to other cells, thus leading to hemolysis and vasoocclusion, which are known to be painful episodes.2
Hydroxyurea (HU) is currently the only effective drug for
treating patients with SCD, thereby reducing morbidity and mortality.3-5 The first randomized multicenter study that proved the
efficacy of HU therapy among sickle cell patients (MSH), which
was conducted in the 1990s, had a major impact on the management of sickle cell disease. It showed that HU can reduce painful episodes, length of hospital stay and number of red blood
cell (RBC) transfusions, and can provide a 50% reduction in the
occurrence of new episodes of acute chest syndrome (ACS).6
Nevertheless, the mechanisms through which HU exerts
its clinical benefits in SCD cases are only partially known. The
drug enhances the production of fetal hemoglobin (HbF), which
decreases the polymerization of hemoglobin S (HbS),7,8 blocks the
formation of sickle erythrocytes and prevents vaso-occlusive crises (VOC).6,9,10 However, clinical improvement occurs before the
increment in HbF, thus suggesting that concurrent mechanisms
may exist.10-12 These include (i) reduction of the number of white
cells, platelets and reticulocyte counts; (ii) reduction of sickle cell
adhesiveness mediated by a lower expression of surface adhesion
molecules; (iii) induction of nitric oxide production (NO); and
(iv) increase in the cell volume of sickle erythrocytes.13-16 The mean
cell volume (MCV) increases during the first four to six weeks of
HU treatment, and this is associated with clinical improvement.
The increase in MCV occurs before the expansion of the F-cells
(cells bearing HbF), and this is the hematological parameter that
best correlates with a decrease in VOC episodes.17-19
Recently, a single center trial (LaSHS) reported the effect of
prolonged administration of HU on morbidity and mortality
among adult patients with SCD after 17 years of follow-up.5 The
study suggested that administration of HU to adult SCD patients
for a long period of time significantly reduced the incidence of
acute and chronic complications of SCD and that it conferred a
survival advantage.
Despite the growing body of evidence in the literature that
HU therapy provides many benefits for sickle cell patients, this
therapy is still underprescribed for many reasons (possible longterm side effects, low availability in emerging countries etc.). In
the present study, we analyzed the clinical and laboratory effects
of HU treatment among sickle cell patients followed up at our
sickle cell centre in Ribeirão Preto, São Paulo, Brazil.
OBJECTIVE
The objective of this study was to analyze the clinical and hematological effects of hydroxyurea on sickle patients followed up at
our institution.
METHODS
Study design
This was a retrospective study conducted at our sickle cell centre. All the clinical and laboratory data were obtained from the
patients’ medical records. This study was approved by the Ethics
Committee of our institution (protocol number 2455/2004).
Subjects
37 sickle cell patients (26 SS and 11 S-beta-thalassemia cases) followed up at our centre participated in the study. The inclusion criteria were: diagnosis of sickle cell anemia (SS) or S-beta-thalassemia
with a moderate to severe phenotype requiring HU therapy.
The indications for HU treatment were: VOC, priapism, pulmonary hypertension and acute chest syndrome (ACS). All the patients
signed an informed consent statement before starting on HU.
The mean duration of HU treatment was 4.8 ± 3.2 years and
the mean HU dose was 24.5 mg/kg/day ± 5.5 mg/kg/day. Some
patients (9/37) did not tolerate the maximum dose prescribed
(which started at 15 and could reach up to 35 mg/kg/day), due to
neutropenia (neutrophils < 2,000/µl).
A total of 37 out of the 105 sickle cell patients taking HU who
were being followed up at our institution met the above criteria
and had complete laboratory analysis and clinical data available in
the medical records. The patients’ median age was 23 years (range:
9 to 43) and the gender distribution was 19 males and 18 females.
The medication was provided by the Brazilian Ministry of
Health to all sickle cell patients through a program within the
Brazilian National Health System (Sistema Único de Saúde, SUS).
Hematological parameters and HbF quantification
Peripheral blood samples were collected for quantification of
hematological parameters (hemoglobin, MCV, white blood cells,
WBC, neutrophils and platelet counts) before HU therapy and 3,
6 and 12 months after HU therapy had started, and at their last
follow-up. HbF quantification was performed prior to the therapy and at least once a year.
The WBC and platelet counts, the hemoglobin concentration
and the MCV were determined using the automated Coulter Gen
S system 2 (Beckman-Coulter, CA, USA).
Sao Paulo Med J. 2013; 131(4):238-43
239
ORIGINAL ARTICLE | Silva-Pinto AC, Angulo IL, Brunetta DM, Neves FIR, Bassi SC, Santis GC, Covas DT
The HbF percentage was determined using the HPLC technique (Variant Express, Bio-Rad laboratories, Inc, Hercules, CA,
USA) and the beta-thalassemia short program (VariantTM, BioRad laboratories, Inc, Hercules, CA, USA).
Clinical data
We reviewed the patient medical records, including the number
of the following events: VOC, ACS, hospitalizations, infectious
episodes and transfusions of RBC that occurred during the year
before HU therapy and the first year of treatment.
Statistical analysis
The hematological parameters were tested using analysis of variance
(ANOVA) and the Tukey test if the samples had normal distribution.
The Friedman/Dunn test was used if the samples did not have normal
distribution. The clinical data and the percentage of HbF were analyzed
using the Wilcoxon non-parametric test. The results were expressed as
means and standard deviations or as medians (with range), respectively if they had normal distribution or did not. The statistical significance level was set at 5% (P < 0.05) for all analyses.
RESULTS
Hematological parameters
After one year of treatment, HU led to an increase of 0.7 g/dl in
the hemoglobin concentration: from a mean of 8.3 g/dl ± 1.29 to
9.0 ± 1.4 g/dl (P = 0.0003). The MCV increased from 88.7 ± 13.5 to
104.8 ± 15 fl (P = 0.001), and HbF increased from 2.6 (0.16-8.47)
to 19.8% (5.9-34.8, P < 0.0001). Additionally, HU treatment
decreased the WBC from 11,800/µl (4,100-27,300) to 9,100/µl
(1,000-17,900) (P < 0.0001), neutrophils from 6,200/µl (1,50018,300) to 3,400/µl (700-11,900) (P = 0.001) and platelets from
459,000/µl (192,000-893,000) to 373,000/µl (109,000-870,000)
(P = 0.0002). The reductions in those parameters could be seen
after three months of therapy and lasted over the years (Table 1).
Clinical data analysis
After one year of treatment with HU, we observed reductions
in the acute complications of sickle cell disease, such as VOCs,
ACS and infections, as well as reductions in the need for transfusions and hospitalizations (Figure 1). The mean VOC rate
dropped from 1.86 ± 1.58 events/year to 0.81 ± 1.47 events/year
(P = 0.0014). The overall ACS rate also reduced (0.35 ± 0.48
to 0.08 ± 0.28, P = 0.0045), along with the numbers of hospitalizations (1.63 ± 1.52 to 0.53 ± 0.82, P = 0.0013), infections
(1.03 ± 1.13 to 0.5 ± 0.78, P = 0.047) and RBC units transfused (1.23 ± 2.25 to 0.1 ± 0.3, P = 0.0051). We also analyzed
separately the occurrences of VOC in 14 patients and ACS in
10 patients in which these events were the indication for starting HU (Figure 2). There were significant reductions in VOC
(3.29 ± 1.07 to 1.36 ± 1.78, P = 0.01) and in ACS episodes (1.0 to
0.2 ± 0.42, P = 0.006) in these groups.
Adverse events
We focused on myelotoxicity as the most important adverse
effect of HU therapy. HU treatment can lead to decreased levels
of hemoglobin (Hb < 6.0 g/dl), neutrophils (NE < 2,000/µl) and
platelets (Pl < 80,000/µl) that can be life-threatening. Whenever
these thresholds are reached, HU therapy is suspended and then
restarted at a lower dose (MTD, maximum tolerated dose).
In this study, only neutropenia was observed, in 24.3% of the
patients (9/37), and the HU dose was reduced for these patients.
After adjusting the HU dose to the MTD, all these patients’ neutrophil counts recovered to greater than 2,000/µl.
DISCUSSION
This study showed that these patients presented considerable
clinical and hematological improvements, which is in accordance
with previous reports.17,19 After three months of HU treatment,
the patients presented a significant and persistent increase in
MCV and reductions in WBC and platelet counts. These results
are similar to what has been found in other studies (Table 2).5,20-22
HbF presented a remarkable increase up to the last follow-up
(median from 2.6% to 19.8%). This marked response was greater
than the response reported in the MSH study,17 probably due to
the inclusion of children in our study, who are known to have a
better HbF response under HU treatment.10,18 Among the studies shown in Table 2, Zimmerman et al.21 analyzed children and
Table 1. Hematological parameters before hydroxyurea therapy and three, six and twelve months after therapy started
Parameters
Hb (g/dl)
MCV (fl)
WBC (x103/ml)
Neutrophils (x103/ml)
Platelets (x103 U/ml)
HbF (%)
Before HU
M ± SD
8.3 ± 1.29
88.7 ± 13.5
12.3 ± 3.9
7.1 ± 3.6
493 ± 161
2.6 ± 2.1
3 months
M ± SD
8.6 ± 1.26
100.3 ± 13.3
9.6 ± 3.4
4.9 ± 2.1
390 ± 146
*
6 months
M ± SD
8.8 ± 1.28
102.3 ± 13.9
9.5 ± 3.1
4.6 ± 1.8
423 ± 161
*
12 months
M ± SD
9.0 ± 1.4
104.8 ± 15
9.6 ± 4.4
5.1 ± 3.5
396 ± 136
19.8 ± 7.2
Last follow-up
M ± SD
9.3 ± 1.4
114.2 ± 14.7
8.2 ± 3.5
4.4 ± 2.4
379 ± 124
20.3 ± 8.6
M ± SD = mean ± standard deviation; Hb = hemoglobin; MCV = mean cell volume; WBC = white blood cells; HbF = fetal hemoglobin; *data not available.
240
Sao Paulo Med J. 2013; 131(4):238-43
Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil | ORIGINAL ARTICLE
ACS
VOC
1.5
number of events
number of events
8
6
4
2
0
1.0
0.5
0.0
-0.5
-2
before
1 year later
before
1 year later
HU
HU
Hospitalizations
15
4
2
0
number of events
5
number of events
number of events
Transfusions
Infections
6
4
3
2
1
1 year later
5
0
0
before
10
before
HU
1 year later
before
1 year later
HU
HU
Figure 1. Change in the rates of vaso-occlusive crises (VOC) (mean 1.86 to 0.81 events/year, P = 0.0014), acute chest syndrome (ACS)
(mean 0.35 ± 0.48 to 0.08 ± 0.28, P = 0.0045), hospitalizations (mean 1.63 ± 1.52 to 0.53 ± 0.82, P = 0.0013) and infections (mean 1.03)
from before hydroxyurea (HU) therapy to one year later.
ACS
VOC
1.5
number of events
number of events
8
6
4
2
0
-2
1.0
0.5
0.0
-0.5
before
1 year later
before
1 year later
HU
HU
Figure 2. Change in the rate of vaso-occlusive crises (VOC) (mean 3.29 ± 1.07 to 1.36 ± 1.78, P = 0.01) among 14 patients for whom VOC
was the indication to start hydroxyurea (HU). Change in the rate of acute chest syndrome (ACS) episodes (mean 1.0 to 0.2 ± 0.42, P = 0.006)
among 10 patients for whom ACS was the indication to start HU. Comparisons were made from before to after one year of HU therapy.
Table 2. Hematological effects of hydroxyurea therapy reported in published clinical studies and the current study
Parameters
Number of patients
Average age (years)
Average dose (mg/kg/d)
Hb (g/dl)
MCV (fl)
WBC (x109/l)
Neutrophils (x109/l)
Platelets(x109/l)
HbF (%)
Current study
37
23
24.5
9.3
114
8.2
4.4
379
19.8
Kinneyet al.20
71
9.8
25.6
9.1
102
9.1
4.4
357
16.3
Zimmerman et al.21
106
10.3
25.9
9.5
107
7.2
3.6
392
19.7
Charache et al.22
32
27.6
21.3
9.7
117
8.4
4.6
364
15
Voskaridou et al.5
131
33
20
9.5
97
8.0
4.0
308
17.4
Hb = hemoglobin; MCV = mean cell volume; WBC = white blood cells; HbF = fetal hemoglobin.
Sao Paulo Med J. 2013; 131(4):238-43
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ORIGINAL ARTICLE | Silva-Pinto AC, Angulo IL, Brunetta DM, Neves FIR, Bassi SC, Santis GC, Covas DT
reported a similar percentage of HbF (19.7%), which was greater
than the HbF reported from another study on children20 and in
other two studies on adult patients.5,17 Another important factor
could be the diverse genetic determinants of the response to HU
among the subjects.23
There was a marked reduction in significant clinical events
during the HU treatment. After one year of therapy, the overall
rate of VOC events dropped from 1.86 to 0.81/year. In the LaSHS
study, this reduction was even greater (7.34 ± 6.5 to 0.05 ± 0.026),
but the decreases in numbers of hospitalizations (2.11 ± 2.96 to
0.03 ± 0.19) and numbers of transfusions (1.53 ± 5.92 to 0.22 ±
0.95) were similar to the results presented in our study (1.63 ± 1.52
to 0.53 ± 0.82 and 1.23 ± 2.25 to 0.1 ± 0.3, respectively). There was
also a five-fold reduction in occurrences of a second episode of
ACS among the patients during HU therapy (1.0 to 0.2 ± 0.42, P =
0.006). In the MSH study, the incidence of ACS decreased in 50%
of the patients and in the LaSHS study, the incidence dropped
from 6.1% to 0.8% of the patients during therapy. In a Brazilian
cohort of children, 224 patients were followed up for 10 years and
the median treatment duration was 1.9 years (range: 1.2-6.1) with
a median dose of 20 mg/kg/d (range: 15-28). There were significant reductions in hospitalization (67%), transfusions (36%) and
emergency room visits (48.7%).24
Surprisingly, we noticed that there was a significant reduction in the frequency of infectious episodes (1.03 ± 1.13 to 0.5 ±
0.78, P = 0.047). Although HU reduced the number of circulating
leukocytes and some patients took lower doses of HU because of
transient neutropenia, the number of severe infectious episodes
needing hospitalization was lower. The rate of infectious events
was not addressed in most previous studies, but the LaSHS study
reported two deaths caused by sepsis: one in a patient taking HU
and the other in a patient without treatment.5
In this study, we did not analyze the impact of HU on mortality, but the LaSHS study suggested that administration of HU
to adult sickle cell patients for a long period of time significantly
reduced the incidence of acute and chronic complications of SCD
and that these patients had a survival advantage.5 Patients who
had HbF values greater than 2% had a 10-year probability of survival of 89%, compared with 53% among patients with HbF lower
than 2%, thus showing the great impact of HbF on survival.5 In
the Brazilian cohort, HU also improved survival. The cumulative
survival rate at 17.9 years of age was 97.4% among patients taking
HU, compared with 66.3% among those who were not treated.24
A quality of life (QoL) study conducted among sickle cell
patients who participated in the MSH study showed that the benefit of HU was limited to the patients who maintained a high HbF
response, compared with those with low HbF or on placebo, thus
indicating that HbF response has a role not only in relation to
survival, but also in relation to quality of life.25
242
Sao Paulo Med J. 2013; 131(4):238-43
Nowadays, most children with HbSS or S-beta0-thalassemia
(93.9%) and nearly all children with HbSC or S-beta+thalassemia (98.4%) live and reach adulthood in developed
countries after the newborn screening program, with subsequent administration of prophylactic penicillin and immunization.26 In this cohort of children (DNC), ACS and multiple
organ failure surpassed bacterial sepsis as the leading cause of
death. According to the MSH and LaSHS studies, these two SCD
complications can be prevented or reduced by HU therapy.5,17
In the BABY HUG study, very young children (aged 9-17
months) started on HU despite their clinical severity, and there
were reductions in VOC, ACS, hospitalizations and transfusions,
in comparison with placebo treatment, without any apparent
increased risk of genotoxicity.27
Despite the growing body of evidence in the literature that
HU therapy has many benefits for sickle cell patients, this therapy
is still underused.28 After these recent studies, which have demonstrated remarkable benefits from HU treatment, this drug may
become soon the standard of care for young patients with sickle
cell disease.28,29 We hope that this study, in association with others that have recently been published,24,26,30 may encourage physicians, especially in emerging countries, to prescribe HU more
often for their sickle cell patients.
CONCLUSION
In this study, we showed that our patients had considerable clinical and hematological improvements with HU therapy that lasted
up to the last evaluation.
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trial (LaSHS). Blood. 2010;115(12):2354-63.
6. Steinberg MH, Lu ZH, Barton FB, et al. Fetal hemoglobin in sickle cell
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antigen-4 and CD36 on reticulocytes in sickle cell patients treated
with hydroxyurea. Blood. 1997;89(7):2554-9.
14. Covas DT, de Lucena Angulo I, Vianna Bonini Palma P, Zago MA. Effects
of hydroxyurea on the membrane of erythrocytes and platelets in
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interventions. Curr Opin Hematol. 2002;9(2):107-10.
Sources of funding: FUNDHERP (Fundação Hemocentro de Ribeirão Preto)
Conflict of interest: None
17. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the
frequency of painful crises in sickle cell anemia. Investigators of the
Date of first submission: February 9, 2012
Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med.
Last received: October 15, 2012
1995;332(20):1317-22.
Accepted: October 31, 2012
18. Ware RE, Eggleston B, Redding-Lallinger R, et al. Predictors of fetal
hemoglobin response in children with sickle cell anemia receiving
Address for correspondence:
hydroxyurea therapy. Blood. 2002;99(1):10-4.
Ana Cristina Silva Pinto
19. Ferster A, Tahriri P, Vermylen C, et al. Five years of experience with
Rua Tenente Catão Roxo, 2501
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Vila Monte Alegre — Ribeirão Preto (SP) — Brasil
Blood. 2001;97(11):3628-32.
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20. Kinney TR, Helms RW, O’Branski EE, et al. Safety of hydroxyurea in
E-mail: [email protected]
children with sickle cell anemia: results of the HUG-KIDS study, a
phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999;94(5):1550-4.
21. Zimmerman SA, Schultz WH, Davis JS, et al. Sustained long-term
hematologic efficacy of hydroxyurea at maximum tolerated dose in
children with sickle cell disease. Blood. 2004;103(6):2039-45.
22. Charache S, Dover GJ, Moore RD, et al. Hydroxyurea: effects on
hemoglobin F production in patients with sickle cell anemia. Blood.
1992;79(10):2555-65.
23. Ma Q, Wyszynski DF, Farrell JJ, et al. Fetal hemoglobin in sickle
cell anemia: genetic determinants of response to hydroxyurea.
Pharmacogenomics J. 2007;7(6):386-94.
24. Lobo C, Hankins JS, Moura P, Pinto JC. Hydroxyurea therapy reduces
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243
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314487
Translation, cross-cultural adaptation and validation
of the Brazilian version of the Nonarthritic Hip Score
Tradução, adaptação cultural e validação da versão
brasileira do questionário Nonarthritic Hip Score
Letícia Nunes Carreras Del CastilloI, Gustavo LeporaceII, Themis Moura CardinotIII, Roger Abramino LevyIV, Liszt Palmeira de OliveiraV
Department of Surgical Specialties, Faculdade de Ciências Médicas da Universidade do Estado do Rio de Janeiro (FCM-UERJ), Rio de Janeiro, Brazil
MSc. Physiotherapist, Department of Surgical
Specialties, Faculdade de Ciências Médicas da
Universidade do Estado do Rio de Janeiro (FCMUERJ), Rio de Janeiro, Brazil.
I
II
Physiotherapist, Laboratory of Biomechanics
and Motor Behavior, Instituto de Educação Física
e do Desporto (IEFD), Universidade do Estado
do Rio de Janeiro (UERJ), Rio de Janeiro, Brazil.
PhD. Associate Professor, Department of
Anatomy, Instituto de Biologia (IB), Universidade
Federal Rural do Rio de Janeiro (UFRRJ),
Seropédica, Brazil.
III
MD, PhD. Associate Professor, Department of
Rheumatology, Faculdade de Ciências Médicas
da Universidade do Estado do Rio de Janeiro
(FCM-UERJ), Rio de Janeiro, Brazil.
IV
MD, PhD. Associate Professor, Department of
Orthopedics, Faculdade de Ciências Médicas da
Universidade do Estado do Rio de Janeiro (FCMUERJ), Rio de Janeiro, Brazil.
V
KEY WORDS:
Questionnaires.
Quality of life.
Translations.
Reproducibility of results.
Hip.
PALAVRAS-CHAVE:
Questionários.
Qualidade de vida.
Traduções.
Reprodutibilidade dos testes.
Quadril.
244
Sao Paulo Med J. 2013; 131(4):244-51
ABSTRACT
CONTEXT AND OBJECTIVE: The Nonarthritic Hip Score (NAHS) is a clinical evaluation questionnaire that
was developed in the English language to evaluate hip function in young and physically active patients.
The aims of this study were to translate this questionnaire into the Brazilian Portuguese language, to adapt
it to Brazilian culture and to validate it.
DESIGN AND SETTING: Cohort study conducted between 2008 and 2010, at Universidade do Estado do
Rio de Janeiro (UERJ).
METHODS: Questions about physical activities and household chores were modified to better fit Brazilian
culture. Reproducibility, internal consistency and validity (correlations with the Algofunctional Lequesne
Index and the Western Ontario and McMaster Universities Arthritis Index [WOMAC]) were tested. The
NAHS-Brazil, Lequesne and WOMAC questionnaires were applied to 64 young and physically active
patients (mean age, 40.9 years; 31 women).
RESULTS: The intraclass correlation coefficient (which measures reproducibility) was 0.837 (P < 0.001).
Bland-Altman plots revealed a mean error in the difference between the two measurements of 0.42. The
internal consistency was confirmed through a Cronbach alpha of 0.944. The validity between NAHS-Brazil
and Lequesne and between NAHS-Brazil and WOMAC showed high correlations, r = 0.7340 and r = 0.9073,
respectively. NAHS-Brazil showed good validity with no floor or ceiling effects.
CONCLUSION: The NAHS was translated into the Brazilian Portuguese language and was cross-culturally
adapted to Brazilian culture. It was shown to be a useful tool in clinical practice for assessing the quality of
life of young and physically active patients with hip pain.
RESUMO
CONTEXTO E OBJETIVO: O Nonarthritic Hip Score (NAHS) é um questionário de avaliação clínica que foi
desenvolvido na língua inglesa para avaliar a função do quadril em pacientes jovens e fisicamente ativos.
O objetivo desse estudo foi traduzir o questionário NAHS para a língua portuguesa do Brasil, adaptá-lo à
cultura brasileira e validá-lo.
TIPO DE ESTUDO E LOCAL: Estudo de coorte, realizado entre 2008 e 2010, na Universidade do Estado do
Rio de Janeiro (UERJ).
MÉTODOS: Questões sobre atividades físicas e tarefas domésticas foram modificadas para melhor adaptação à cultura brasileira. Reprodutibilidade, consistência interna e validade (correlação entre o Algofunctional Lequesne Index e o Western Ontario McMaster Universities Arthritis Index [WOMAC]) foram testadas.
Os questionários NAHS-Brasil, Lequesne e WOMAC foram aplicados em 64 pacientes jovens e fisicamente
ativos (média de idade, 40,9 anos; 31 mulheres).
RESULTADOS: O coeficiente de correlação intraclasse que avalia reprodutibilidade mostrou valores de 0,837
(P < 0,001). O gráfico de Bland-Altman revelou um erro médio da diferença das duas medidas de 0,42. A consistência interna foi avaliada pelo alfa de Cronbach com valores de 0,944. A validade entre os questionários
NAHS-Brasil/Lequesne e NAHS-Brasil/WOMAC mostraram alta correlação, r = 0,7340 e r = 0,9073; respectivamente. O NAHS-Brasil mostrou boa validade sem efeitos de chão ou de teto.
CONCLUSÃO: O NAHS foi traduzido para a língua portuguesa do Brasil e adaptado para a cultura brasileira, mostrando ser uma ferramenta útil na prática clínica para avaliar a qualidade de vida de pacientes
jovens e fisicamente ativos com dor no quadril.
Translation, cross-cultural adaptation and validation of the Brazilian version of the Nonarthritic Hip Score | ORIGINAL ARTICLE
INTRODUCTION
Studies that evaluate outcomes from clinical or surgical treatments within orthopedics have become more frequent and the
emphasis on patients’ opinions has increased.1-3 The most frequently used instruments for hip disease that have been translated into the Portuguese language are the Algofunctional
Lequesne Index, Western Ontario and McMasters Universities
Arthritis Index (WOMAC) and the Harris Hip Score.4-6 These
instruments are used for patients with moderate to severe hip
osteoarthritis (OA) or for post-traumatic hip disorders with
significant physical limitations. There are questionnaires that
evaluate the functional capacity of patients with high physical demands: the Lower Extremity Functional Scale (LEFS), the
Modified Harris Hip Score, the Nonarthritic Hip Score (NAHS)
and the Hip Outcome Score.7-10 However, with increasing numbers
of cases of hip disorders among young and physically active patients,
and improvements in diagnostic methods, the need for an instrument that evaluates quality of life in this population has increased.
Our hypothesis was that patients with nearly normal range of
motion and pain specifically related to physical activities would
require a more specific and sensitive instrument to detect and evaluate functional changes. The NAHS is a simple, short and self-administered questionnaire. It has 20 questions divided into four domains:
pain, function, mechanical symptoms and physical activity level.
OBJECTIVE
The aims of this study were to translate the NAHS through crosscultural adaptation to Brazilian culture and to test the validity and
reproducibility of the Brazilian Portuguese version of the NAHS.
METHODS
Type of study
This was a cohort study using data obtained between 2008
and 2010.
Translation and cross-cultural adaptation procedures
This study was approved by the ethics committee of our
Institution and all the subjects provided written informed consent. The translation was approved by Christian P. Christensen,
the first author of the NAHS.9 To translate and adapt the instrument, the guidelines suggested by Guillemin et al. and revised by
Beaton et al. were followed.11,12 The process comprised five steps:
translation, back translation, review by a committee, pretesting
and final translation.
Two independent translators, who were orthopedic surgeons
with experience of hip surgery and were aware of the objectives
of the translation, did the initial translation from English into
Portuguese. After both initial translations (T1 and T2) had been
produced, a combined version (T1,2) was made, based on the two
initial translations. This version was then back translated into
English by two independent sworn translators (BT1 and BT2)
who were not aware of the objective of the translation. A multidisciplinary committee then compared these versions with the
original text and a consensus version in Brazilian Portuguese
was created (TC1). The option “non-applicable” was added to all
questions in the TC1 version.
The TC1 version (pretest) was completed by 10 patients with hip
pain and by 20 asymptomatic adults (10 male and 10 female; 10 had
had fewer than four years of education and 10 had had postgraduate
education). Subjects were excluded from the pretest if they had: (a)
visual or cognitive disturbances that did not allow them to read the
questionnaire; (b) severe hip limitation characterized by decreased
range of motion (less than 10º of internal rotation at 90º hip flexion).
During the translation reviews, questions that had been
answered as “non-applicable” were reassessed regarding semantic,
idiomatic, cultural and conceptual equivalencies. Conceptual and
cultural equivalencies relating to evaluations on physical activities that were not understood by more than 90% of the patients
were reevaluated and reworked until they were well understood.
During this phase, the TC1 application maintained the conceptual characteristics of the original questionnaire and the objective was to evaluate errors and deviations made during the translation. When there were no more situations that were not part of
daily activities, or questions or terms that were not well understood, the TC1 was considered to be the final translation of the
questionnaire, without the “non-applicable” option.
Patients and testing
A consecutive sample of 64 patients with hip injuries and diseases completed the Brazilian Portuguese version of the NAHS
and also the Lequesne and WOMAC questionnaires. The patients
answered these questionnaires in physicians’ waiting rooms. All
the patients completed the study protocol without any loss.
Reproducibility
We measured the reliability of the questionnaire scores using
internal consistency and the test-retest method across repeated
administration. To calculate test-retest reliability, all the patients
were asked to complete the NAHS-Brazil 48 hours after the first
assessment. To minimize the risk of short-term clinical change,
no treatment was provided during this period. Agreement was
assessed using graphical representations of the measurement
error variance between the test and retest answers.
Validity
Validity is the extent to which a score means what it is supposed to
mean, i.e. whether it has the intended interpretation.13 In this report,
Sao Paulo Med J. 2013; 131(4):244-51
245
ORIGINAL ARTICLE | Del Castillo LNC, Leporace G, Cardinot TM, Levy RA, Oliveira LP
validity was evaluated through two concepts: construct and content.
The construct validity of the NAHS-Brazil was evaluated by correlating it with the Brazilian versions of the Lequesne and WOMAC
questionnaires. The content validity was tested through the distribution and occurrences of floor and ceiling effects. The floor effect
occurs when the minimum possible value is achieved, while the ceiling effect occurs when the maximum possible score is achieved.
Statistical analysis
Construct validity was tested using Pearson’s correlation coefficient. Internal consistency was calculated using Cronbach’s
alpha. This technique was based on the number of items on a
scale and the homogeneity of the items. The intraclass correlation
coefficient (ICC) was calculated to assess the test-retest reliability. Paired t tests were used to compare and determine statistically
significant differences between the first and second assessments.
The level of agreement of the test-retest consistency was assessed
by plotting Bland-Altman curves. This analysis quantifies agreement through constructing limits of agreement. These statistical
limits are calculated by using the mean and standard deviation
(SD) of the differences.14,15 The statistical analysis was performed
using GraphPad Prism, version 5.00 for Windows (GraphPad
Software, USA) and Epi-Info version 3.5.2 (CDC, USA).
RESULTS
The translation and cross-cultural adaptation was performed based
on the original NAHS. The NAHS-Brazil, produced following the
cross-cultural adaptation (pretesting), is shown in the appendix.
The Brazilian version of WOMAC was used for the 10
questions that refer to pain and function that originate from
WOMAC.5 The four questions on mechanical symptoms did not
undergo any changes. Four questions on physical activity were
modified to better fit Brazilian realities. In the original question on sports with high physical demands, “football” refers to
American football, but this was changed to “futebol”, meaning
soccer, since this sport is more prevalent in Brazil. Two questions
referring to household chores were also modified. In one of the
questions, “lifting firewood” was changed to “house cleaning and
hand-washing your clothes”, since these are more frequent chores
among the Brazilian population. In the other question, “vacuuming and doing laundry” was changed to “doing laundry with a
washing machine”. All the changes were approved by the committee and were easily understood in the pretest.
In the final testing, the Brazilian versions of the Lequesne and
WOMAC questionnaires were completed concurrently with the
NAHS-Brazil by 64 patients with hip complaints. The patients
were literate, but their level of schooling was only up to high
school level. Some did fitness exercises or hydrotherapy, but none
of them were athletes or practiced sports regularly.
246
Sao Paulo Med J. 2013; 131(4):244-51
Thirty-one patients (48%) were female and 33 (52%) were
male. The mean age was 40.9 years (range, 18 to 76 years). The
patients had diagnoses of femoroacetabular impingement (24),
isolated labral tears (9), pertrochanteric pain syndrome (9),
osteonecrosis (6), deep gluteal pain syndrome (5), mild hip osteoarthritis (Tönnis grade 1) (3), rheumatoid arthritis (1), bilateral
chondrolysis (1), epiphysiolysis (1), Legg-Perthes disease (1),
synovitis (1) and periarticular tendonitis (3) (Table 1).
The mean, standard deviation, minimum and maximum and
confidence interval values of each outcome measurement of the
Nonarthritic Hip Score (NAHS-Brazil), Lequesne and Western
Ontario and McMasters Universities Arthritis Index (WOMAC)
questionnaires in the final testing are presented in Table 2.
Test-retest reliability and agreement
The intraclass correlation coefficient was 0.837 (P < 0.001) and
the confidence interval (95% CI) ranged from 0.732 to 0.901.
The paired t test did not demonstrate any statistically significant
Table 1. Clinical and sociodemographic characteristics of the
64 patients with hip pain
Characteristic
Gender
Female
Male
Age
Mean (standard deviation)
Femoroacetabular impingement
Isolated labral tears
Pertrochanteric pain syndrome
Osteonecrosis
Deep gluteal pain syndrome
Diagnoses
Mild hip osteoarthritis (Tönnis 1)
Periarticular tendonitis
Rheumatoid arthritis
Bilateral chondrolysis
Epiphysiolysis
Legg-Perthes disease
Synovitis
n
31
33
40.9 (24.8)
24
9
9
6
5
3
3
1
1
1
1
1
Table 2. Mean values, minimum and maximum values,
standard deviation and confidence intervals of the outcome
measurements of the Nonarthritic Hip Score (NAHS)-Brazil,
Lequesne and Western Ontario and McMasters Universities
Arthritis Index (WOMAC) questionnaires
Questionnaires
NAHS-Brazil Test
NAHS-Brazil Retest
Lequesne
WOMAC
Mean
60.7
61.7
68.7
66.1
Min-Max scores
16.2–96.2
8.7–98.7
16.6–100
13.5–100
SD
20.7
21.7
18.8
21.2
95% CI
55.4–65.9
56.3–67.1
63.9–73.4
60.7–71.5
SD = standard deviation; CI = confidence interval; NAHS-Brazil retest
was done 48 hours after NAHS-Brazil test
Translation, cross-cultural adaptation and validation of the Brazilian version of the Nonarthritic Hip Score | ORIGINAL ARTICLE
Validity
The NAHS-Brazil showed high correlations with Lequesne
(r = 0.7343) and WOMAC (r = 0.9073; P < 0.0001) (Figures 2 and 3).
Ceiling effects occurred with the WOMAC and Lequesne questionnaires (Table 2). The NAHS-Brazil showed good content validity; no floor or ceiling effects occurred (Figure 4).
DISCUSSION
Over the last 50 years, many questionnaires have been developed to evaluate pain and follow up the clinical outcomes
of patients with hip OA or subsequent to hip arthroplasty.
The most frequently used methods are the Merle D’Aubigné
and Postel (MD & Postel), Harris Hip Score (HHS) and
WOMAC.16-18 Nonetheless, these questionnaires focus on hip
pain and function among elderly people with osteoarthritis.19 In our study, we chose to exclude patients with severe
functional limitation and those with moderate or severe
osteoarthritis.
On this basis, our sample had a low average age (40.9 years
old), in relation to other validation studies on questionnaires
for hip assessment. In the validation of the Lequesne questionnaire, the patients’ average age was 67 years, and 66% of the
patients had moderate or severe osteoarthrosis.4 In the validation of the WOMAC questionnaire, the average age was 65 years,
and patients with severe osteoarthritis or functional classification IV, according to the criteria of the American College of
Rheumatology, were excluded.5,20
Use of these instruments among patients with great range of
motion and pain specifically related to physical activities is limited because of the low sensitivity to detection of small, albeit
significant, functional changes. With the new diagnostic methods and the new concepts that are applied to hip mechanical
alterations in young and physically active patients, questionnaires that evaluate hip OA or hips subsequent to arthroplasty
have poor discrimination capabilities with regard to patients
who do not have hip OA.21
Difference between the
two assessments
Internal consistency
Cronbach’s alpha was 0.944 in relation to the NAHS-Brazil total
score. Cronbach’s alpha showed values of 0.878, 0.869, 0.920 and
0.901 in relation to the NAHS-Brazil pain, mechanical symptom,
function and physical activity domains, respectively. Even with
exclusion of each item, the values remained similar to the analysis with all items together (Table 3).
40
Mean + 1.96 SD
20
0
20
40
60
80
100
-20
Mean - 1.96 SD
Mean of the two assessments
-40
Figure 1. Bland-Altman plot in which the two dotted lines represent
limits of agreement (upper and lower). Regression line almost parallel
to the X axis demonstrates a fixed bias. SD = standard deviation.
Table 3. NAHS-Brazil internal consistency of each domain according to
Cronbach’s α values
Domain
Pain
Mechanical symptoms
Function
Physical activity
Total score
Cronbach’s α
0.878
0.869
0.920
0.901
0.944
100
80
Lequesne
differences between the test-retest means (P = 0.719). BlandAltman plots revealed a mean error in the difference between
the two assessments of 0.42 (SD = 9.21, 95% limit of agreement = –17.62 to 18.48) (Figure 1).
60
40
20
0
0
20
40
60
80
100
NAHS-Brazil
Figure 2. Scatter plot for the Nonarthritic Hip Score (NAHS)-Brazil
versus Lequesne.
The NAHS is a clinical evaluation questionnaire that was
developed to evaluate hip function among young and physically active patients. The NAHS, as well as the majority of
the questionnaires evaluating quality of life, was created in
the English language. Because of this, these instruments must
be translated and cross-culturally adapted in such a way that
the semantic, idiomatic, cultural and conceptual equivalencies are maintained.22-24 In this study, some terms were modified, since they did not fit in with Brazilian culture. These
were exchanged for other terms that are habitually used in this
Sao Paulo Med J. 2013; 131(4):244-51
247
ORIGINAL ARTICLE | Del Castillo LNC, Leporace G, Cardinot TM, Levy RA, Oliveira LP
100
80
WOMAC
60
40
20
0
0
20
40
60
80
100
NAHS-Brazil
Figure 3. Scatter plot for the Nonarthritic Hip Score (NAHS)-Brazil
versus Western Ontario and McMasters Universities Arthritis Index
(WOMAC).
Number of patients
15
10
5
9
10
0
0
-9
90
0
-9
80
0
-8
70
0
-7
60
0
-6
50
0
-5
40
0
-4
30
0
-3
-2
20
10
10
1-
0
0
NAHS-Brazil = Nonarthritic Hip Score-Brazil
Figure 4. Distribution of patients between ranges of responses.
country, while still maintaining the idea of the effort involved
in the activity.
Some authors have taken the view that active participation by
the interviewer is required because of the low educational level
of the Brazilian population.25,26 However, in translating and validating the NAHS-Brazil, we strictly followed the proposal of the
original questionnaire, i.e. a self-administered format, without
active participation by the interviewer.
The ICC evaluates the intra and inter-observer reproducibility. It is considered to be excellent when greater than
0.75.27 The questionnaire showed excellent reproducibility
with ICC values of 0.837, and this is comparable with what
was reported for the original version (0.96). However, the values obtained were lower than those found in other validations
of hip questionnaires.4,5,10,28,29
248
Sao Paulo Med J. 2013; 131(4):244-51
The paired t test did not demonstrate any statistically significant differences between the test-retest means. Bland-Altman
plots revealed a mean error in the difference between the two
assessments of 0.42, with linear regression almost parallel to the
axis of the average of the two evaluations, thus indicating that
the concordance between the two answers was independent
of the patient’s clinical status. This result shows strong evidence
that the NAHS-Brazil presents good construct validity, i.e. our
results provide evidence that the NAHS-Brazil is a reproducible
and valid tool for self-assessment of physical function among
young and physically active patients with hip pain, independent
of the patient’s functional status. The Cronbach’s alpha values
were higher than 0.90 and thus indicate that the NAHS-Brazil
has high internal consistency, similar to what has been seen in
other studies on translation and validation.5,30,31
The construct validity was assessed by means of Pearson’s
correlation coefficient between NAHS-Brazil and Lequesne and
between NAHS-Brazil and WOMAC. We believe that the lower
correlation found with the Lequesne questionnaire occurred
because this instrument is designed to assess individuals with
greater impairment of hip function. The high value for Pearson’s
correlation coefficient between NAHS-Brazil and WOMAC
demonstrates that these two instruments have similar features;
this can be explained by the fact that NAHS includes 10 questions from WOMAC.
The content validity of questionnaires is assessed by means
of the distribution and occurrence of floor and ceiling effects.13
The NAHS-Brazil showed good content validity; no floor or
ceiling effect was observed, i.e. none of the questionnaires presented a score of zero, and none of them showed effects relating to maximum possible score effects. We saw in our study that
ceiling effects existed in the Lequesne and WOMAC questionnaires. This result indicates that the content of the NAHS-Brazil
seems to be more appropriate for hip evaluations in the population studied.
The NAHS-Brazil is a reliable and validated tool that can be
used in clinical practice to evaluate patients with hip pain without
osteoarthritis before and after treatment. It can be used with the
objective of greater accuracy of discrimination of the clinical hip
condition of relatively young patients with little joint degeneration.
The limitations of this study were that the WOMAC questionnaire was used for comparison purposes, given that it shares
some questions with the NAHS questionnaire; and that there was
no generic questionnaire for comparisons. Another limitation
was the need for active participation in questionnaire application
by the researcher, among patients with low educational levels.
And finally, it has to be considered that the questionnaire should
be further evaluated with regard to application among individuals in older age groups than the group studied here.
Translation, cross-cultural adaptation and validation of the Brazilian version of the Nonarthritic Hip Score | ORIGINAL ARTICLE
CONCLUSION
The Nonarthritic Hip Score was translated into the Brazilian
Portuguese language and was cross-culturally adapted to
Brazilian culture, following the guidelines for cultural adaptation
of quality of life instruments. Its reliability, internal consistency
and validity were demonstrated, thus showing that it is a useful
tool for assessing the quality of life of young and physically active
patients with hip pain, whether at research or at care levels.
process of cross-cultural adaptation of self-report measures. Spine
(Phila PA 1976). 2000;25(24):3186-91.
13. de Vet HC, Terwee CB, Knol DL, Bouter LM. When to use agreement
versus reliability measures. J Clin Epidemiol. 2006;59(10):1033-9.
14.Altman DG, Bland JM. Measurement in medicine: the analysis
of method comparison studies. The Statistician. 1983;32:307-17.
Available
from:
http://biostat.georgiahealth.edu/journalclub/
altmanbland1983.pdf. Accessed in 2012 (Sep 25).
15. Bland JM, Altman DG. Statistical methods for assessing agreement
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6. Guimarães RP, Alves DPL, Silva GB, et al. Tradução e adaptação
transcultural do instrumento de avaliação do quadril “Harris Hip
Score” [Translation and cultural adaptation of the Harris Hip Score
into portuguese]. Acta Ortop Bras. 2010;18(3):142-7.
21. Terwee CB, Bot SD, de Boer MR, et al. Quality criteria were proposed
for measurement properties of health status questionnaires. J Clin
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22. Guillemin F. Cross-cultural adaptation and validation of health status
measures. Scand J Rheumatol. 1995;24(2):61-3.
7. Binkley JM, Stratford PW, Lott SA, Riddlel DL. The Lower Extremity
23. Ferraz MB, Oliveira LM, Araujo PM, Atra E, Tugwell P. Crosscultural
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8. Byrd JW, Jones KS. Prospective analysis of hip arthroscopy with 2-year
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9. Christensen CP, Althausen PL, Mittleman MA, Lee JA, McCarthy JC.
25. Orfale AG, Araújo PM, Ferraz MB, Natour J. Translation into Brazilian
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26.Peccin MS, Ciconelli R, Cohen M. Questionário específico para
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27. Alonso KC, Sautchuk FG, Malfatti CRM, Artoni RF. Comparação de
percentuais de gordura corporal, utilizando impedância bioelétrica e a
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php/cinergis/article/viewFile/1236/942. Accessed in 2012 (Sep 25).
28. Martin RL, Philippon MJ. Evidence of reliability and responsiveness for
the hip outcome score. Arthroscopy. 2008;24(6):676-82.
29. Naal FD, Impellizzeri FM, Miozzari HH, Mannion AF, Leunig M. The
German Hip Outcome Score: validation in patients undergoing
surgical treatment for femoroacetabular impingement. Arthroscopy.
2011;27(3):339-45.
30. Metsavaht L, Leporace G, Ribeiro M, de Mello Sposito MM, Batista LA.
Translation and cross-cultural adaptation of the Brazilian version of the
International Knee Documentation Committee Subjective Knee Form:
validity and reproducibility. Am J Sports Med. 2010;38(9):1894-9.
31. Monteiro J, Faísca L, Nunes O, Hipólito J. Questionário de incapacidade
de Roland Morris. Adaptação e validação para os doentes de língua
portuguesa com lombalgia [Roland Morris disability questionnaire.
Adaptation and validation for the Portuguese speaking patients with
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pdf. Accessed in 2012 (Sep 25).
Sources of funding: None
Conflict of interest: None
Date of first submission: March 7, 2012
Last received: June 25, 2012
Accepted: October 1, 2012
Address for correspondence:
Letícia Nunes Carreras Del Castillo
Departamento de Fisioterapia, Policlínica Piquet Carneiro, Universidade
do Estado do Rio de Janeiro
Av. Marechal Rondon, 381
São Francisco Xavier (RJ) – Brasil
CEP 20950-003
Tel. (+55 21) 2234-3015
E-mail: [email protected]
250
Sao Paulo Med J. 2013; 131(4):244-51
Translation, cross-cultural adaptation and validation of the Brazilian version of the Nonarthritic Hip Score | ORIGINAL ARTICLE
Appendix. Nonarthritic Hip Score-Brazil (NAHS-Brazil)
NAHS – Brazil
Nome:
Data: Hora:
As cinco questões a seguir avaliam a intensidade da dor que você está sentindo no quadril que está sendo avaliado hoje. Para
cada situação, por favor, marque a resposta que reflete com maior precisão a intensidade da dor sentida nas últimas 48 horas.
Qual a intensidade da dor que você tem:
Nenhuma
Leve
Moderada
Forte
Muito Forte
1 – Andando em terreno plano
2 – Subindo ou descendo escadas
3 – Durante a noite, na cama
4 – Sentado ou deitado
5 – Em pé
As quatro questões a seguir se referem aos sintomas que você está sentindo no quadril que está sendo avaliado hoje. Para cada
situação, marque a resposta que reflete com maior precisão os sintomas experimentados nas últimas 48 horas.
Quanta dificuldade você tem com:
Nenhuma
Leve
Moderada
Forte
Muito forte
1 – Travamento ou bloqueio no seu quadril
2 – O seu quadril saindo do lugar
3 – Rigidez no seu quadril
4 – Diminuição do movimento no seu quadril
As cinco questões a seguir avaliam a sua condição física. Para cada uma destas atividades, marque a resposta que reflete com
maior precisão as dificuldades que você experimentou nas últimas 48 horas, por causa do seu quadril.
Qual o grau de dificuldade que você tem para:
Nenhuma
Leve
Moderada
Forte
Muito forte
1 – Descendo escadas
2 – Subindo escadas
3 – Levantando-se de uma cadeira
4 – Colocando as meias / meias-calças
5 – Levantando da cama
As seis questões a seguir avaliam sua capacidade de participar de certos tipos de atividades. Para cada uma das seguintes
atividades, marque a resposta que reflete com maior precisão, a dificuldade que você experimentou no último mês por causa
da dor no seu quadril. Se você não participou de um determinado tipo de atividade, imagine quanta dificuldade o seu quadril
poderia causar se você tivesse realizado aquela atividade.
Quanta dificuldade seu quadril causa quando você participa de:
Nenhuma
1 – Esportes de alta intensidade (por exemplo,
futebol, basquete, tênis e exercício aeróbico)
2 – Esportes de baixa intensidade (por exemplo,
golfe e boliche)
3 – Corrida (como exercício)
4 – Caminhada (como exercício)
5 – Atividades domésticas pesadas (por exemplo,
mover móveis, fazer faxina, lavar roupa no tanque)
6 – Atividades domésticas leves (por exemplo,
cozinhar, tirar poeira, lavar roupa na máquina)
Leve
Moderada
Forte
Muito forte
Nenhuma – 4; Leve – 3; Moderada – 2; Forte – 1; Muito forte – 0
Cada questão pode ser pontuada de 0 a 4, a soma dos pontos deve ser multiplicada por 1,25 que dará um valor entre 0 e 100 pontos.
Sao Paulo Med J. 2013; 131(4):244-51
251
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314496
The IDEAL classification system: a new method for
classifying fractures of the distal extremity of the radius –
description and reproducibility
Classificação IDEAL: um novo método de classificação para as fraturas da
extremidade distal do rádio – descrição e reprodutibilidade
João Carlos BellotiI, João Baptista Gomes dos SantosI, Vinícius Ynoe de MoraesII, Felipe Vitiello WinkIII,
Marcel Jun Sugawara TamaokiIV, Flávio FaloppaV
Hand Surgery Division, Universidade Federal de São Paulo/Escola Paulista de Medicina (Unifesp/EPM), São Paulo, Brazil
MD, PhD. Hand Surgeon and Professor,
Discipline of Hand Surgery, Universidade Federal
de São Paulo/Escola Paulista de Medicina
(Unifesp/EPM), São Paulo, Brazil.
I
II
MD. Hand Surgery Resident, Universidade
Federal de São Paulo/Escola Paulista de
Medicina (Unifesp/EPM), São Paulo, Brazil.
MD. Hand Surgeon, Discipline of Hand Surgery,
Universidade Federal de São Paulo/Escola Paulista
de Medicina (Unifesp/EPM), São Paulo, Brazil.
III
IV
MD, PhD. Orthopedic Surgeon, Discipline of
Hand Surgery, Universidade Federal de São
Paulo/Escola Paulista de Medicina, (Unifesp/
EPM), São Paulo, Brazil.
MD, PhD. Hand Surgeon, Full Professor,
Discipline of Hand Surgery, Universidade Federal
de São Paulo/Escola Paulista de Medicina
(Unifesp/EPM), São Paulo, Brazil.
V
KEY WORDS:
Colles’ fracture.
Classification.
Wrist.
Radius fractures.
Reproducibility of results.
PALAVRAS-CHAVE:
Fratura de Colles.
Classificação.
Punho.
Fraturas do rádio.
Reprodutibilidade dos testes.
252
Sao Paulo Med J. 2013; 131(4):252-6
ABSTRACT
CONTEXT AND OBJECTIVE: There is no consensus concerning which classification for distal radius fractures is best and the existing methods present poor reproducibility. This study aimed to describe and
assess the reproducibility of the new IDEAL classification, and to compare it with widely used systems.
DESIGN AND SETTING: Reproducibility study, Hand Surgery Section, Universidade Federal de São Paulo.
METHODS: The IDEAL classification and its evidence-based rationale are presented. Sixty radiographs
(posteroanterior and lateral) from patients with distal radius fractures were classified by six examiners: a
hand surgery specialist, a hand surgery resident, an orthopedic generalist, an orthopedic resident and two
medical students. Each of them independently assessed the radiographs at three different times. We compared the intra and interobserver concordance of the IDEAL, AO, Frykman and Fernandez classifications
using Cohen’s kappa (κ) (for two observers) and Fleiss’s κ (for more than two observers).
RESULTS: The concordance was high for the IDEAL classification (κ = 0.771) and moderate for Frykman
(κ = 0.556), Fernandez (κ = 0.671) and AO (κ = 0.650). The interobserver agreement was moderate for the
IDEAL classification (κ = 0.595), but unsatisfactory for Frykman (κ = 0.344), Fernandez (κ = 0.496) and AO
(κ = 0.343).
CONCLUSION: The reproducibility of the IDEAL classification was better than that of the other systems
analyzed, thus making the IDEAL system suitable for application. Complementary studies will confirm
whether this classification system makes adequate predictions for therapy and prognosis.
RESUMO
CONTEXTO E OBJETIVO: Não existe consenso sobre qual é a melhor classificação para as fraturas do
rádio distal e os métodos existentes apresentam baixa reprodutibilidade. Este estudo tem como objetivo
descrever e avaliar a reprodutibilidade de uma nova classificação (a IDEAL) comparando-a com as classificações mais amplamente utilizadas.
TIPO DE ESTUDO E LOCAL: Estudo de reprodutibilidade, Disciplina de Cirurgia da Mão, Universidade
Federal de São Paulo.
MÉTODOS: Apresentamos a classificação IDEAL e sua fundamentação teórica baseada em evidências.
Sessenta radiografias (anteroposterior e de perfil) de pacientes com fraturas do rádio distal foram classificadas por seis examinadores: um especialista e um residente de cirurgia da mão, um ortopedista, um
residente de ortopedia e dois estudantes de medicina. Cada um, independentemente, avaliou as radiografias em três momentos diferentes. Analisamos a concordância intra e interobservador da classificação
IDEAL, AO, Frykman e Fernandez, utilizando o kappa (κ) de Cohen (para dois observadores) e κ de Fleiss
(para mais de dois observadores).
RESULTADOS: A concordância demonstrou-se elevada para a classificação IDEAL (κ = 0,771) e moderada
para Frykman (κ = 0,556), Fernandez (κ = 0,671) e AO (κ = 0,650). A concordância interobservador foi
moderada para a classificação IDEAL (κ = 0,595), mas insatisfatória para Frykman (κ = 0,344), Fernandez
(κ = 0,496) e AO (κ = 0,343).
CONCLUSÃO: A reprodutibilidade da classificação IDEAL se demonstrou superior quando comparada às
analisadas neste estudo, tornando a classificação IDEAL adequada para aplicação. Estudos complementares confirmarão se esta classificação é adequada para previsão de terapia e prognóstico.
The IDEAL classification system: a new method for classifying fractures of the distal extremity of the radius - description and reproducibility | ORIGINAL ARTICLE
INTRODUCTION
Distal radius fractures occur in approximately one in every
10,000 people, accounting for 16% of skeletal fractures and 74%
of forearm fractures.1-3 The most common mechanism of injury
is a fall on the hand with hyperextension. The fracture characteristics (location, joint involvement, degree of comminution
and soft tissue injury) are directly related to the trauma energy,
position of the hand at the moment of trauma and bone quality.2
Appropriate fracture treatment requires a good understanding of
these fracture characteristics.4
Fracture classification systems were developed to divide fractures into different types and consequently serve as a guide to treatment. Starting more than a century ago, Colles, Smith, Barton,
Pouteau, Goyrand and others described the morphology of fractures for use in classification.2,5-7 The advent of radiology enabled
a more accurate analysis of fracture characteristics, including the
degree of displacement and presence of joint fracture. Lie-Nielsen
in 19398 and Gartland and Werley in 19519 based their classification
systems on the presence or absence of intra-articular involvement,
metaphyseal comminution and/or deformity; however, neither system evaluated fragment displacement. In 1959, Lindstrom expanded
these criteria into six groups, describing fragment displacement and
joint involvement in detail.10 In 1967, Frykman established a classification system that took into account involvement of the radiocarpal joint, distal radioulnar joint and ulnar styloid.11 The AO classification, which was created in 1986 and revised in 1990, determines
the seriousness of the fracture according to joint involvement and
metaphyseal comminution. The AO system is comprehensive,
but its intraobserver and interobserver reproducibility are not
high.12,13 Another classification, proposed by Fernandez, is based on
the mechanism of trauma.14 This classification was designed to be
practical, predict stability, identify equivalent lesions in children and
provide general recommendations for treatment.
An effective classification system must be valid, reliable and
reproducible, but it should also standardize a language for consistent communication, provide guidelines for appropriate treatment, indicate the likelihood of complications and fracture instability and predict a realistic prognosis for each fracture.15 The
system should also provide a mechanism for evaluating and comparing treatment results with results from similar fractures in different centers reported at different times.16,17
Currently, none of the classification systems available have
reproducibility that adequately provides evidence for treatment
and prognosis.13,15,18,19
OBJECTIVES
In this study, we aimed to describe a new classification method for
distal radius fractures, which we named the “IDEAL Classification”,
assess its reproducibility (intraobserver and interobserver
agreement) and compare IDEAL with established classification
systems (AO, Frykman and Fernandez classification systems)
METHODS
This study was approved by our institution’s ethics committee
(reference: 1225/10).
Description of IDEAL classification
The IDEAL fracture classification is based on the epidemiological and radiographic factors that are important for treatment and
prognosis. Using this method, we classified the fracture during
the first patient evaluation using two epidemiological criteria
(patient age and trauma energy) and three radiographic parameters assessed at the initial radiographic examination (posteroanterior and lateral): displacement of the fragments, joint incongruity and associated injuries (Table 1).
Each of the five characteristics is given a score of zero or
one (total score, 0–5 points). The criteria used to determine the
IDEAL score are as follows:
1. Incongruity: joint step or gap ≥ 2 mm (1 point); or < 2 mm (0
points);
2. Displacement: radial shortening > 3 mm, loss of volar tilt
> 10o or loss of radial inclination > 5o (1 point); minimal or
no displacement (0 points);
3. Energy: high-energy, e.g. fall from a height or traffic accident (1 point); or low-energy, e.g. fall from standing height
(0 points);
4. Age: > 60 years (1 point); or < 60 years (0 points);
5. Lesions: e.g. radiocarpal dislocation or subluxation, carpal
bone fracture, carpal or distal radioulnar instability or neurovascular injuries) (1 point); no lesions (0 points).
After scoring the five characteristics, the fractures can be
classified into one of three fracture types according to severity
and complexity (Table 2).
Type I fractures (0-1 points) are potentially stable. These are
fractures in the elderly without displacement or displaced fractures in young patients, caused by low-energy trauma, without joint
incongruity or associated injuries. They are generally treated conservatively with closed reduction and a cast and have a good prognosis.
Table 1. IDEAL classification system: rationale and scoring
I
D
E
A
L
Parameter
Joint incongruity
Displacemen
Energy1
Age
Associated lesions2
0 points
No
No
Low
< 60 years old
Absent
1 point
Step or gap > 2 mm
Requires reduction
High
≥ 60 years old
Present
Low = fall from standing height, or High = other; 2Open fracture/carpal fractures
and/or instability/distal ulnar fractures.
1
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ORIGINAL ARTICLE | Belloti JC, Santos JBG, Moraes VY, Wink FV, Tamaoki MJS, Faloppa F
Type II fractures (2-3 points) are potentially unstable fractures with displacement that have a high potential for loss of
reduction and malunion because of poor bone quality (elderly
patients) and/or associated high-energy trauma, joint incongruity
or correlated injuries (both young and elderly patients). Type II
fractures require surgical stabilization, such as percutaneous pinning, external fixation or internal fixation with plates. These fractures are more susceptible to the potential complications inherent to surgery. The prognosis depends on the success of surgery.
Type III fractures (4-5 points) are complex fractures with
displacement. They are usually caused by high-energy trauma
and are associated with joint incongruity and related injuries.
Because of their inherent instability and potential irreducibility,
they often require open reduction, associated methods of fixation
and, possibly, bone grafting. They are prone to complications and
have a poor prognosis, regardless of the treatment method.
Evaluation of reproducibility
Between November 2010 and May 2011, a convenience sample of
60 adult patients treated at institution X was included in this study.
We collected distal radius fracture radiographs, which were analyzed
and classified using the IDEAL, AO, Frykman and Fernandez classification systems by six observers with different degrees of experience: a hand surgeon with more than 20 years of experience, a
general orthopedic surgeon, a medical resident in hand surgery, a
medical resident in orthopedics and traumatology and two medical
students. All the assessments were performed prospectively.
The AO classification describes fractures in alphanumeric
terms. It mainly divides fracture types according to the presence
(B/C group) or the absence (A group) of joint fracture. Its main subgroup relates to specific fracture patterns, ranging from A1 to C3.
The Frykman classification is based on a description of eight categories. It takes ulnar/distal radioulnar involvement into consideration
and uses this as a differential. The Fernandez classification is based
on trauma mechanism and encompasses five categories, in which
the last category includes combined mechanisms.
The radiographs were digitized and numbered sequentially.
All identification was then concealed, and the radiographs
were randomized by an unique sequence of numbers generated by a computer program. Randomization was performed
by a researcher not involved in the assessments. The radiographs were assessed three times (T1, T2 and T3) in a random
sequence by each observer, with two-week intervals between
each of the assessments.
Statistical methods
To determine the intraobserver reproducibility, we used the
method proposed by Fleiss et al.,20 which calculates the degree of
agreement in relation to what would be expected by chance. We
also used this method to determine the interobserver agreement
between more than two observers. Cohen’s kappa (κ) coefficient
was used to determine the inter-rater agreement of two observers. In general, κ values less than 0.5 are considered unsatisfactory, values between 0.5 and 0.75 are considered satisfactory, and
values greater than 0.75 are considered excellent.21,22
Comparison of the intraobserver reproducibility between
the first two evaluations (T1 versus T2) with the intraobserver
reproducibility between the second two evaluations (T2 versus
T3) revealed the effect of conditioning on the classification. We
used the method of Giraudeau and Mary to determine sample
size according to the expected intraobserver agreement and confidence interval. For an expected κ of 0.70 and confidence interval of 90%, 50 samples would be needed.17
The study results were not influenced by the external funding
source and this source did not play any role in the investigation.
RESULTS
Six different observers each evaluated 60 radiographs on three different occasions using the four classification systems, to produce
a total of 4320 ratings during the study. The intraobserver reproducibility of the three assessments (T1, T2 and T3) was excellent
for the IDEAL classification (κ = 0.771) and satisfactory for the
Frykman (κ = 0.556), Fernandez (κ = 0.671) and AO (κ = 0.650)
classifications (Table 3). When the reproducibility of the first two
observations (T1 versus T2) was compared with the reproducibility of the last two (T2 versus T3), the results were similar without substantial improvement in the level of agreement.
As shown in Table 4, the interobserver agreement for the
three observations was satisfactory for the IDEAL classification
(κ = 0.595), but unsatisfactory for the other classifications, with the
AO classification showing the worst agreement (κ = 0.343). The
average concordance between observer pairs for the IDEAL classification was satisfactory at all three time points (T1: κ = 0.653;
T2: κ = 0.595; and T3: κ = 0.537) and for the Fernandez classification on two occasions (T1: κ = 0.515; and T2: κ = 0.534), but it was
unsatisfactory for the AO and Frykman classifications at all times.
The mean intraobserver agreement of the IDEAL classification was significantly higher than that of the Frykman classification (Table 5). Similarly, the mean interobserver agreement of
Table 2. IDEAL classification system: description and treatment/prognosis guidance
Type
I
II
III
254
Score
0-1 points
2-3 points
4-5 points
Sao Paulo Med J. 2013; 131(4):252-6
Description
Stable
Potentially unstable
Complex
Treatment
Conservative
Pins/external fixation/plating
Associated methods/bone graft
Prognosis
Good
Intermediate
Poor
The IDEAL classification system: a new method for classifying fractures of the distal extremity of the radius - description and reproducibility | ORIGINAL ARTICLE
the IDEAL classification was significantly higher than those
of the AO and Frykman classifications and was similar to that of
the Fernandez classification (Table 5).
DISCUSSION
The current classification systems for distal radial fractures are based
on fracture morphology11,12,23 or mechanism of injury.14,24 In the
IDEAL classification, we aimed to provide data that would be relevant for treatment guidance and prognosis, by using five key elements: two epidemiological factors (Age and trauma Energy) and
three radiographic factors (Displacement, joint Incongruity,
and associated Lesions).
An evidence-based rationale was used in order to develop
this classification. When planning treatment, advanced patient
age is one of the most important prognostic factors for instability,25,26 whereas low-energy fractures have less potential for instability.25,26 Fractures with joint incongruity > 2 mm or unacceptable angular or shortening displacement have higher morbidity
and worse prognosis than shown by fractures with little or no displacement.27 Associated injuries such as carpal instability, unstable distal radioulnar joint lesions or carpal/radiocarpal ligament
injury are also associated with worse prognosis26,28,29 and may
require additional interventions.
We believe that a combination of these factors can guide
proper planning of treatment. IDEAL is a mnemonic that is easy to
remember and categorizes fractures into three main types, numbered according to seriousness and requirement for stabilization,
which makes it feasible to apply this classification in clinical practice. Ilyas and Jupiter strengthened our classification rationale by
stating that surgical indications can be placed into four categories:
patient-related factors, fracture reduction, fracture stability and
presence of associated injuries.4
A reliable distal radius fracture classification is necessary for
systematic treatment of these fractures and is essential for comparing the results from different clinical studies.12,13,15,19,31,32 In the present study, the intraobserver and interobserver reproducibility of the
IDEAL classification was generally higher than that of the established classifications. We believe that this classification system is
more reliable because of clearness in assessing the classification features. The IDEAL classification system is easy to use and was reproducible, not only when used by the hand surgery specialist but also
when used by the medical students.
The AO and Frykman classifications, and to some extent the
Fernandez classification, aim to be comprehensive in describing fractures. However, the reliability of these systems is low, especially when subgroups are analyzed. van Leerdam et al.13 suggested
more realistic goals for distal radius fracture classification systems:
they should be simple, reproducible and clinically focused. We have
attempted to follow this in developing the IDEAL classification.
Table 3. Intraobserver reproducibility (T1, T2, T3) of the fracture
classification
Hand surgery resident
Hand surgery specialist
General orthopedic surgeon
Orthopedics resident
Medical student 1
Medical student 2
Mean
IDEAL
0.794
0.882
0.906
0.764
0.497
0.804
0.771
Frykman
0.604
0.682
0.677
0.596
0.336
0.491
0.556
Fernandez
0.734
0.720
0.737
0.768
0.456
0.612
0.671
AO
0.740
0.707
0.680
0.720
0.463
0.592
0.650
SE = standard error of the mean; T1 = first assessment; T2 = second assessment;
T3 = third assessment.
Table 4. Interobserver reproducibility (T1, T2, and T3) of the fracture
classification systems
First assessment (T1)
Second assessment (T2)
Third assessment (T3)
Mean
IDEAL
0.654
0.594
0.537
0.595
Frykman
0.328
0.391
0.314
0.344
Fernandez
0.509
0.533
0.447
0.496
AO
0.316
0.393
0.319
0.343
Table 5. Comparison of intraobserver and interobserver κ values
according to classification system
Intraobserver
agreement
P-value
0.06
0.02
0.21
0.13
0.17
0.25
0.74
Classification systems
IDEAL, Frykman, Fernandez and AO
IDEAL versus Frykman
IDEAL versus Fernandez
IDEAL versus AO
Frykman versus Fernandez
Frykman versus AO
Fernandez versus AO
Interobserver
agreement
P-value
0.04
0.03
0.82
0.03
0.02
0.96
0.01
Fisher F-test.
In the present study, six evaluators with varying degrees of
knowledge assessed radiographs according to the IDEAL system.
They demonstrated that the level of expertise in evaluating fractures
was not an important factor in relation to intraobserver reproducibility. In addition, no marked improvement in intraobserver reproducibility was seen between the second and third assessments. Thus,
experience with the IDEAL classification system itself did not affect
reproducibility, either.
The IDEAL classification is reliable and shows good reproducibility in comparison with the existing classification systems.
Prospective studies are needed in order to verify its clinical effectiveness in predicting instability, planning treatments and making prognoses for these fractures.
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Sources of funding: Fundação de Amparo à Pesquisa do Estado de São
Paulo (FAPESP) – Process number 10/52594-3
Conflict of interest: None
Date of first submission: April 2, 2012
Last received: October 5, 2012
Accepted: October 19, 2012
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Address for correspondence:
Sao Paulo Med J. 2013; 131(4):252-6
Vila Clementino — São Paulo (SP) — Brasil
CEP 04038-001
Tel. (+55) 5571-6621
E-mail: [email protected]
ORIGINAL ARTICLE
DOI: 10.1590/1516-3180.2013.1314498
Trends in treatment of anterior cruciate
ligament injuries of the knee in the public
and private healthcare systems of Brazil
Tendências de tratamento das lesões do ligamento cruzado
anterior do joelho nos sistemas de saúde pública e privada do Brasil
Diego Costa AsturI, Rodrigo Ferreira BatistaII, Arliani GustavoI, Moises CohenIII
Department of Orthopedics and Traumatology, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil
MD. Orthopedist, Department of Orthopedics
and Traumatology, Universidade Federal de São
Paulo (Unifesp), São Paulo, Brazil.
I
II
MD. Resident, Department of Orthopedics and
Traumatology, Universidade Federal de São
Paulo (Unifesp), São Paulo, Brazil.
MD, PhD. Full Professor and Head, Department
of Orthopedics and Traumatology, Universidade
Federal de São Paulo (Unifesp), São Paulo, Brazil.
III
KEY WORDS:
Anterior cruciate ligament.
Surgical procedures, operative.
Anterior cruciate ligament reconstruction.
Delivery of health care.
Healthcare disparities.
PALAVRAS-CHAVE:
Ligamento cruzado anterior.
Procedimentos cirúrgicos operatórios.
Reconstrução do ligamento cruzado anterior.
Assistência à saúde.
Disparidades em assistência à saúde.
ABSTRACT
CONTEXT AND OBJECTIVE: Orthopedic surgery implies high costs for both public and private healthcare.
The aim of this study was to better understand the differences between the public and private sectors
regarding treatment of a damaged anterior cruciate ligament, which is a common knee injury.
DESIGN AND SETTING: Descriptive cross-sectional study conducted during the Brazilian Orthopedics
Congress in Brasília.
METHODS: We applied questionnaires during the 2010 Brazilian Orthopedics Congress, with participation
by 241 knee surgeons from 24 Brazilian states. This was followed by statistical analysis on the data that
were obtained.
RESULTS: The orthopedic surgeons who were evaluated used different approaches and treatment options in different Brazilian states, comparing between the public and private systems.
CONCLUSION: Both in the public and in the private systems in Brazil, because of non-medical issues
surrounding the treatment, the best medical decision is not always made. This may be harmful both to
patients and to physicians.
RESUMO
CONTEXTO E OBJETIVO: Cirurgias ortopédicas implicam alto custo para a saúde pública e privada. O
objetivo deste estudo foi de entender melhor as diferenças entre os sistemas público e privado em relação
ao tratamento da lesão do ligamento cruzado anterior, que é uma lesão comum do joelho.
TIPO DE ESTUDO E LOCAL: Estudo transversal descritivo, realizado durante Congresso Brasileiro de Ortopedia em Brasília.
MÉTODOS: Aplicamos questionários durante o Congresso Brasileiro de Ortopedia de 2010, com a participação de 241 cirurgiões de joelho de 24 estados brasileiros. Posteriormente foi feita análise estatística
nos dados obtidos.
RESULTADOS: Diferentes condutas e opções de tratamento em diferentes estados brasileiros são realizadas pelos ortopedistas avaliados, quando comparadas em relação à atuação no sistema público e privado.
CONCLUSÃO: No Brasil, tanto no sistema público como no privado nem sempre a melhor decisão é tomada por conta de efeitos outros que não a decisão médica, fato que tem sido maléfico para o paciente
e para o médico.
Sao Paulo Med J. 2013; 131(4):257-63
257
ORIGINAL ARTICLE | Astur DC, Batista RF, Gustavo A, Cohen M
INTRODUCTION
The anterior cruciate ligament (ACL) is an important structure
that stabilizes the knee by minimizing anterior translational and
rotational instability.1-4 Injury to the ACL is extremely common
among young patients and is usually secondary to high-energy
and/or sports activity-related trauma.5,6
The ACL consists primarily of type 1 collagen fibers and
extends from the inner face of the lateral femoral condyle to a
fossa that is located anteriorly and laterally to the medial intercondylar tibial eminence.1-4 The ACL is composed of anteromedial and posterolateral bundles that are tense during flexion and
extension, respectively.1
The ACL has a region of poor vascularization that is located
5-10 mm proximally to the tibial insertion with a transition area
between the proximal sections. The blood supply to the ACL
is via the medial genicular artery, and the distal section is supplied by the lateral and medial branches of the inferior genicular
artery. This architecture confers low potential for healing in this
region.1,7 Therefore, there is an international consensus within
the field of orthopedics that surgical treatment is the best option
for athletes and active people and should be performed within
three weeks of the injury.1,6,8
In the United States, the incidence of ACL injury is rising:
80-100,000 reconstructions are performed annually, with an estimated associated cost of approximately 3 billion dollars.7,9-12 In Brazil,
little epidemiological information is available regarding this injury
or the reconstruction of the ligament. This issue has important social
and economic implications, and there is no consensus in the field
regarding the various issues that surround this therapy. As a consequence of this variability, decision-making regarding treatment
differs widely among surgeons.13 However, how much of this divergence is due to individual experience and how much is due to the
availability of potential resources are currently unknown.
OBJECTIVE
The aim of this study was to investigate the broader epidemiological issues in Brazil that create barriers against surgical treatment
of anterior cruciate ligament injuries. An additional aim was to
highlight the discrepancies between what are considered to be
ideal treatments and the treatments that are applied in practice
within the public and private healthcare systems.
METHODS
This descriptive study was conducted by administering a questionnaire to a sample of knee surgeons in Brazil. The questionnaire
was prepared in such a way that it would be both highly comprehensible and simple. It consisted of 16 multiple-choice questions
that covered a variety of topics, including the number of years
of experience, the annual number of ACL reconstructions
performed by the surgeon and several other factors relating
both to treatment and to rehabilitation after ACL reconstruction (Appendix 1).
The questionnaire was administered to Brazilian knee
surgeons during the three-day 2010 Brazilian Congress of
Orthopedics and Traumatology. Only orthopedists who had
previously performed ACL reconstruction surgeries completed
the questionnaire. A total of 241 questionnaires were completed, of which 15 were excluded. Three of the questionnaires
were excluded because the surgeon was from another country
(Portugal, Bolivia and Peru), and 12 were excluded due to incomplete responses. A total of 226 questionnaires were fully completed and were used for subsequent analysis. Two researchers
were available throughout administration of the questionnaires
to answer questions from the participants in the Congress.
To test associations shown by the types of service variables
(public or private) in relation to the other variables, we used the
chi-square or Fisher exact test, as appropriate. The data were analyzed using the Statistical Package for the Social Sciences (SPSS)
for Windows, version 16.0, at a significance level of 5%.
RESULTS
During the 2010 Brazilian Congress of Orthopedics and
Traumatology, 226 surgeons from 24 Brazilian states and the
Federal District completed the questionnaire, which asked questions regarding their surgical practices within the public healthcare system and private healthcare system (or both) and their
actions, in relation to 21 different topics.
The majority of the participant surgeons were from southeastern Brazil (54.4%), as show in Table 1. Two different groups
comprised the sample: Group 1 was composed of 86 surgeons
who operated predominantly within the public system; and
Group 2 was composed of 50 surgeons who operated predominantly within the private system (Table 2). The remaining 90
surgeons in the sample performed surgeries with equal frequency within the public and private systems and were therefore
excluded from further analyses.
The first question related to the surgeon’s number of years of
experience. In Group 1, the mean was 9.6 years of experience,
and in Group 2, the mean was 6.5 years (Table 2). Statistically,
there was no difference between the groups.
Table 1. Region of origin of the study participants
State distribution (%)
258
Sao Paulo Med J. 2013; 131(4):257-63
Southeast
54.5
South
12.4
Northeast
15
North
6.6
Center-West
11.5
Trends in treatment of anterior cruciate ligament injuries of the knee in the public and private healthcare systems of Brazil | ORIGINAL ARTICLE
We analyzed and compared the data regarding the following: the surgeon’s area of expertise, length of experience, number of surgeries performed annually, type of graft used, mode of
access, fixation used for femoral and tibial implants, technique
used, use of pretensioning, length of surgery that was considered to be ideal, use of preoperative physical therapy, use of a
rehabilitation protocol, use of an immobilizer after surgery, use
of a drain, associated meniscal injury sutures and the time taken
for patients to return to sports and/or activities. The results are
shown in Tables 3 to 6 according to the area of activity: public or
private systems (Groups 1 or 2).
DISCUSSION
In Brazil, patient management in the public healthcare system differs notably from that in the private healthcare system. In some respects, this difference in management does
not result in any harm; however, in other ways, this difference
may result in irreparable harm both to patients and to surgeons. This means that non-medical interference in orthopedic surgeons’ decisions can lead to a need to use outdated surgical techniques, thus making the surgery and postoperative
treatment harder.14
We observed that both less-experienced and more-experienced doctors work in the public healthcare system. The difficulties that are associated with health insurance companies can be
considered to be one of the primary reasons for choosing public
service, even among doctors with higher qualifications.
More than half of the orthopedic surgeons in Brazil believed
that patients with a cruciate ligament injury should receive surgery within four weeks of the injury. However, only 5.4% and
26.5% of the surgeons in groups 1 and 2, respectively, performed surgery within this timeframe. The literature is not consistent with regard to the optimal time to perform this surgery.
Historically, most studies showed that surgery should be performed within four to ten weeks of the injury.7,8 Today, the tendency is to focus on reducing edema and inflammation rather
than focusing on the length of time since the injury. In practice,
surgeons do not always perform the procedure within what they
themselves consider to be the ideal timeframe. This is usually due
to problems that are related to limited hospital resources, insufficient numbers of healthcare centers, budget reductions and the
operational difficulties of the public system, all of which usually
result in unmanageable queues and long waiting times for surgical procedures. As a consequence, more than 50% of surgeries
took place more than six months after the injury.
In the private system, the explanation for the disparity
between the ideal and actual times for performing surgery lay in
the difficulty in obtaining authorization from the health insurance company to perform the surgery. As a result, 45.1% of surgeons operated 4-12 weeks after the injury. Surgical technique
The three most commonly used techniques for anterior cruciate
ligament reconstruction were also performed by orthopedic surgeons in Brazil. Reconstruction using a transtibial single band was
the most widely performed technique and was the preferred option
for 68% and 62% of the surgeons in the public system and private
systems, respectively. Reconstructions using the transportal single
Table 2. Activity in the public, private system or both among study
participants
Surgeons
Years of experience
Group 1
(Public)
86
6.5
Group 2
(Private)
50
9.6
Others
90
-
Table 3. Time considered by the participant surgeon as the ideal between
lesion and surgical treatment according to the area of activity: public
(Group 1) or private (Group 2) sectors
Time for surgery (%)
Up to 4 weeks
4-12 weeks
12-24 weeks
6 months to 1 year
Ideal
59.8
33.2
4
3
Group 1
7.9
14.5
13.1
64.6
Group 2
31.1
45.1
18.1
5.7
Table 4. Surgical technique used by Brazilian orthopedic surgeons in anterior cruciate ligament lesion treatment, type of graft and type
of implant used according to the area of activity: public sector (Group 1) or private sector (Group 2)
Surgical technique (%)
Transtibial single branch
Transportal single branch
Double branch
Type of graft used (%)
Flexors
Patella
Allograft
Type of implant used (%)
Metal screw
Absorbable screw
Group 1
68
22
10
Group 1
61.4
35.7
1.4
Group 1 tibia
56
33.8
Group 2
53
21
12
Group 2
65.3
31.3
0.8
Group 1 femur
41
9.8
Group 2 tibia
41.1
55
Group 2 femur
30.2
19.3
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ORIGINAL ARTICLE | Astur DC, Batista RF, Gustavo A, Cohen M
Table 5. Frequency of use of meniscal sutures for treating anterior
cruciate ligament (ACL) injuries, among surgeons in the public sector
(Group 1) and private sector (Group 2) in Brazil (P = 0.16)
ACL + meniscal suture
< 3/month
> 3/month
Group 1
98 %
2%
Group 2
98.8 %
1.2 %
Table 6. Presciption of rehabilitation sessions and use of drain after
anterior cruciate ligament surgical treatment in Brazil and time taken
for recovery according to the area of activity: public sector (Group 1) or
private sector (Group 2)
Rehabilitation (%)
Drain
Recovery time (%)
4 months
5 months
6 months
> 6 months
Group 1
86
28
Group 2
90
31.4
6
8
52
34
1.1
6.9
55.8
36
P = 0.39
P = 0.7
P = 0.55
branch technique and the double branch technique were performed less often, although they have been reported to yield the
best results.7,15,16 The limited use of these latter two techniques was
likely due to a lack of availability of particular instruments and the
higher cost of the larger number of implants that were required.
Attempts to reduce public costs favor use of the transtibial technique in the Brazilian National Health System (Sistema Único de
Saúde, SUS). In the private system, the difficulty in getting health
insurance companies to accept the use of more costly techniques,
despite better surgical outcomes, favors the contractor. Thus,
patients and doctors do not obtain the best results from the anatomical reconstruction and reproduction technique.
The newly reconstructed ligament consists of either an
autogenous tendon graft or an allograft. The graft type preference, as selected by the surgeon, was similar in both groups,
and this was consistent with findings from other countries,
including the United States.6 The preferred types of grafts were
from the semitendinosus, gracilis and patellar muscle tendons.
However, in other countries, using a cadaver graft is becoming
more common due to decreased risks of disease transmission
and rejection and, in particular, because it causes less damage to
the patient during graft removal.17 However, because this is an
expensive practice, there are few situations in which this treatment option is permitted in Brazil.
The type of implant that is used also generates many conflicts between doctor and auditors in both the public and the private systems.17 For example, the surgeon is not always permitted
to choose which material to use. In the public healthcare system, metal interference screws were the most widely used type,
whereas in the private system, use of absorbable interference
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Sao Paulo Med J. 2013; 131(4):257-63
screws prevailed. Interference screws are essential for graft fixation in the bone tunnel. However, metal interference screws
have several disadvantages, including the possible need for their
removal after treatment has been completed, and this involves
another surgical procedure. In addition, these metal screws imply
the risk of more pronounced graft wear, and this can lead to premature rupture of the graft.
The association between anterior cruciate ligament injuries
and meniscal injuries is highly significant, reaching as high as
70% of the cases.5,18 The meniscus is a structure with little healing capacity in its central area, but good healing potential in its
peripheral portion. When dealing with a central lesion, partial
meniscectomy is indicated. However, when a patient has peripheral lesions, suturing is an option for preserving the meniscus.
Suturing the injured meniscus can also reduce the complications that may follow meniscus resection (e.g. osteoarthritis),
and it enables preservation of the structure’s function. In Brazil, a
meniscal suture requires costly implants, which makes it difficult
for surgeons to obtain the materials that are needed for surgery.
This was true for both the private and the public groups. Even
with the high incidence of this type of injury, in both groups,
fewer than 2% of surgeons routinely performed this procedure.
This equated to fewer than three times a year, which is one of the
lowest rates among all the prominent countries in which orthopedics is practiced.
Postoperative management
Studying the epidemiological profiles of orthopedic surgeons
who perform reconstructive surgery on the anterior cruciate ligament involves analysis on information that is collected from
the first contact with the patient and continues until the time the
patient is considered cured and is discharged from care. Most
orthopedic surgeons within the public and private systems prescribed a rehabilitation protocol and did not use a postsurgical
drain. The time taken for patients to return to sports activity was
similar for the two groups. Most of the orthopedic surgeons (86%
and 91.8% in the public and private systems, respectively) gave
their consent for patients to practice sports six months after the
surgery, and this is consistent with the literature.
CONCLUSIONS
Both in the public and in the private healthcare systems in Brazil,
non-medical issues surrounding the treatment can cause difficulties in making the best medical decision, and this may be harmful
both to patients and to physicians.
REFERENCES
1. Duthon VB, Barea C, Abrassart S, et al. Anatomy of the anterior cruciate
ligament. Knee Surg Sports Traumatol Arthrosc. 2006;14(3):204-13.
Trends in treatment of anterior cruciate ligament injuries of the knee in the public and private healthcare systems of Brazil | ORIGINAL ARTICLE
2. Matsumoto H, Suda Y, Otani T, et al. Roles of the anterior cruciate
16. Frobell RB, Roos EM, Roos HP, Ranstam J, Lohmander LS. A randomized
ligament and the medial collateral ligament in preventing valgus
trial of treatment for acute anterior cruciate ligament tears. N Engl J
instability. J Orthop Sci. 2001;6(1):28-32.
Med. 2010;363(4):331-42.
3. Sakane M, Fox RJ, Woo SL, et al. In situ forces in the anterior cruciate
17.Healy WL, Iorio R. Implant selection and cost for total joint
ligament and its bundles in response to anterior tibial loads. J Orthop
arthroplasty: conflict between surgeons and hospitals. Clin Orthop
Res. 1997;15(2):285-93.
4. Cohen M, Astur Dda C, Kaleka CC, et al. Introducing 3-dimensional
stereoscopic imaging to the study of musculoskeletal anatomy.
Relat Res. 2007;457:57-63.
18. Maffulli N, Longo UG, Denaro V. Anterior cruciate ligament tear. N
Engl J Med. 2009;360(14):1463; author reply 1463.
Arthroscopy. 2011;27(4):593-6.
5. Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term
consequence of anterior cruciate ligament and meniscus injuries:
Sources of funding: None
osteoarthritis. Am J Sports Med. 2007;35(10):1756-69.
Conflict of interest: None
6. Siegel L, Vandenakker-Albanese C, Siegel D. Anterior cruciate ligament
injuries: anatomy, physiology, biomechanics, and management. Clin
Date of first submission: April 4, 2012
J Sport Med. 2012;22(4):349-55.
Last received: October 4, 2012
7. Bottoni CR, Liddell TR, Trainor TJ, Freccero DM, Lindell KK. Postoperative
Accepted: October 26, 2012
range of motion following anterior cruciate ligament reconstruction
using autograft hamstrings: a prospective, randomized clinical
Address for correspondence:
trial of early versus delayed reconstructions. Am J Sports Med.
Rodrigo Ferreira Batista
2008;36(4):656-62.
Av. Onze de Junho, 685 — apto. 63
8. Farshad M, Gerber C, Meyer DC, et al. Reconstruction versus
Vila Clementino — São Paulo (SP) — Brasil
conservative treatment after rupture of the anterior cruciate ligament:
CEP 04041-052
cost effectiveness analysis. BMC Health Serv Res. 2011;11:317.
E-mail: [email protected]
9. Lubowitz JH, Appleby D. Cost-effectiveness analysis of the most
common orthopaedic surgery procedures: knee arthroscopy
and knee anterior cruciate ligament reconstruction. Arthroscopy.
2011;27(10):1317-22.
10. Gianotti SM, Marshall SW, Hume PA, Bunt L. Incidence of anterior
cruciate ligament injury and other knee ligament injuries: a national
population-based study. J Sci Med Sport. 2009;12(6):622-7.
11. Cháidez-Reyes JC, Almazán-Díaz A, Espinosa-Morales R, et al. Análisis
de costo e impacto económico de la reconstrucción de ligamento
cruzado anterior (LCA) [Cost analysis and economic impact of anterior
cruciate ligament reconstruction]. Acta Ortop Mex. 2009;23(6):331-5.
12. Cimino F, Volk BS, Setter D. Anterior cruciate ligament injury: diagnosis,
management, and prevention. Am Fam Physician. 2010;82(8):917-22.
13. Balsini N. Cirurgia ambulatorial no Centro de Ortopedia e Fraturas de
Joinville: experiência pessoal de 3 anos na reconstruçäo do ligamento
cruzado anterior [Outpatient surgery in “Centro de Ortopedia e
Fraturas de Joinville: a 3 years personal experience in the anterior
cruciate ligament reconstruction]. Rev Bras Ortop. 1995;30(5): 274-8.
14. Farnworth LR, Lemay DE, Wooldridge T, et al. A comparison of operative
times in arthroscopic ACL reconstruction between orthopaedic
faculty and residents: the financial impact of orthopaedic surgical
training in the operating room. Iowa Orthop J. 2001;21:31-5.
15.Linko E, Harilainen A, Malmivaara A, Seitsalo S. Surgical versus
conservative interventions for anterior cruciate ligament ruptures in
adults. Cochrane Database Syst Rev. 2005;(2):CD001356.
Sao Paulo Med J. 2013; 131(4):257-63
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ORIGINAL ARTICLE | Astur DC, Batista RF, Gustavo A, Cohen M
Appendix 1. Questionnaire on the epidemiological profile of knee surgeons in Brazil who perform anterior cruciate ligament (ACL)
reconstruction.
City/State:
1 – Number of years of ACL surgical experience:
2 – How many ACL reconstructions do you perform per year?
Number per year
< 10
10-20
20-30
30-40
> 40
Public healthcare system
Private healthcare system
3 – Type of grafts used:
Central third of patellar tendon on the same side

Central third of contralateral patellar tendon

Gracilis and semitendinosus flexor tendons

Allograft: graft from bank/cadavers

Synthetic graft

Semitendinosus flexor tendon

Others

4 – Type of fixation used:
Femur
Tibia
EndoButton
Metal interference screw
Transverse pin
Screw (pole)
Staples (AGRAF)
Absorbable interference screw
5 – Technique used:
• Transtibial single branch
• Transportal single branch
• Double branch
6 – Time elapsed between the injury and surgery; time you believe is ideal and the actual time in the public or private healthcare system:
Ideal
Up to 7 days
1-4 weeks
4-12 weeks
12-24 weeks
6 months to 1 year
> 1 year
7 – Do you routinely refer your patient to preoperative physiotherapy?
• Yes
• No
8 – Do you have a postoperative rehabilitation protocol?
• Yes
• No
9 – Do you prescribe a postoperative brace for your patients?
• Yes
• No
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Public healthcare system
Private healthcare system
Trends in treatment of anterior cruciate ligament injuries of the knee in the public and private healthcare systems of Brazil | ORIGINAL ARTICLE
10 – If YES, for how many weeks?
•1
•2
•3
•4
•5
•6
• > 6 weeks
11 – Do you perform intra-articular infiltration with local anesthetic/corticosteroids at the end of the surgery?
• Yes
• No
12 – Do you use a drain during the postoperative period?
• Yes
• No
13 – In patients with an ACL injury, how many meniscal sutures do you perform per month?
• None
•1
•2
•3
•>3
14 – What factors determine your decision to operate on the patient?
Absolute
Important
Irrelevant
Important
Irrelevant
Lachman positive
Pivot-shift positive
Complaints of sudden weight-bearing failure/instability
Patient’s desire to return to the same sports level
Protection of the meniscus/chondral surface
Failure of conservative treatment
Anterior cruciate ligament rupture seen in arthroscopy
Patient’s age
15 – Which criteria do you deem important for considering the surgery to be a success:
Absolute
Minimal pain or absence of pain
Return to routine activities without symptoms
Complete return to sports activities
No complaints of instability
Complete range of motion in the operated knee
Lachman negative
Pivot-shift negative
Patient satisfaction
16 – What length of time do you consider to be ideal before an athlete returns to sports after surgery?
• 4 months
• 5 months
• 6 months
• > 6 months
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REVIEW ARTICLE
DOI: 10.1590/1516-3180.2013.1314590
Diagnosis and treatment of mast cell disorders:
practical recommendations
Diagnóstico e tratamento de doenças mastocitárias: recomendações práticas
Alex Freire SandesI, Raphael Salles Scortegagna MedeirosII, Edgar Gil RizzattiI
Grupo Fleury, São Paulo, Brazil
I
MD, PhD. Medical Consultant in Hematology,
Division of Laboratory Medicine and Pathological
Anatomy, Grupo Fleury, São Paulo, Brazil.
II
MD. Medical Consultant in Pathological Anatomy,
Division of Laboratory Medicine and Pathological
Anatomy, Grupo Fleury, São Paulo, Brazil.
KEY WORDS:
Mastocytosis.
Diagnosis.
Anatomy.
Flow cytometry.
Therapeutics.
PALAVRAS-CHAVE:
Mastocitose.
Diagnóstico.
Anatomia.
Citometria de fluxo.
Terapêutica.
ABSTRACT
CONTEXT AND OBJECTIVE: The term mastocytosis covers a group of rare disorders characterized by
neoplastic proliferation and accumulation of clonal mast cells in one or more organs. The aim of this study
was to assess the principal elements for diagnosing and treating these disorders.
DESIGN AND SETTING: Narrative review of the literature conducted at Grupo Fleury, São Paulo, Brazil.
METHODS: This study reviewed the scientific papers published in the PubMed, Embase (Excerpta
Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) and Cochrane
Library databases that were identified using the search term “mastocytosis.”
RESULTS: The clinical presentation of mastocytosis is remarkably heterogeneous and ranges from skin
lesions that may regress spontaneously to aggressive forms associated with organ failure and short survival.
Currently, seven subtypes of mastocytosis are recognized through the World Health Organization classification
system for hematopoietic tumors. These disorders are diagnosed based on clinical manifestations and on
identification of neoplastic mast cells using morphological, immunophenotypic, genetic and molecular
methods. Abnormal mast cells display atypical and frequently spindle-shaped morphology, and aberrant
expression of the CD25 and CD2 antigens. Elevation of serum tryptase is a common finding in some subtypes,
and more than 90% of the patients present the D816V KIT mutation in mast cells.
CONCLUSION: Here, we described the most common signs and symptoms among patients with
mastocytosis and suggested a practical approach for the diagnosis, classification and initial clinical
treatment of mastocytosis.
RESUMO
CONTEXTO E OBJETIVO: O termo mastocitose abrange um grupo de raras doenças caracterizado por
proliferação neoplásica e acúmulo de mastócitos clonais em um ou mais órgãos. O objetivo do presente
estudo foi avaliar os principais elementos para o diagnóstico e tratamento dessas desordens.
TIPO DE ESTUDO E LOCAL: Revisão narrativa da literatura realizada no Grupo Fleury, São Paulo, Brasil.
MÉTODOS: O presente estudo revisou artigos científicos publicados nas bases de dados PubMed, Embase
(Excerpta Medica Database), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e
Cochrane Library, que foram identificados com o termo de busca “mastocitose”.
RESULTADOS: A apresentação clínica da mastocitose é marcadamente heterogênea, variando de lesões
cutâneas que podem regredir espontaneamente, até formas agressivas associadas a falência de órgãos e
curta sobrevida. Atualmente, sete subtipos de mastocitose são reconhecidos pela classificação de tumores
hematopoéticos da Organização Mundial de Saúde; o diagnóstico é realizado com base nas manifestações
clínicas e na identificação de mastócitos neoplásicos por métodos morfológicos, imunofenotípicos,
genéticos e moleculares. Mastócitos anômalos apresentam morfologia atípica, frequentemente fusiforme,
e expressão aberrante dos antígenos CD25 e CD2. Aumento de triptase sérica é um achado comum em
alguns subtipos; e mais que 90% dos pacientes apresentam mastócitos com a mutação KIT D816V.
CONCLUSÃO: No presente artigo, descrevemos os sintomas e sinais mais comuns em pacientes com
mastocitose e sugerimos uma prática abordagem para o diagnóstico, classificação e tratamento clínico inicial.
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Diagnosis and treatment of mast cell disorders: practical recommendations | REVIEW ARTICLE
INTRODUCTION
Mastocytosis is currently defined as a heterogeneous group of disorders characterized by clonal expansion and accumulation of mast
cells in one or more tissues, such as skin, bone marrow, liver, spleen,
gastrointestinal tract and lymph nodes, among others.1 Clonal mast
cells are detected in most cases and in all subtypes of the disease.
These clonal mast cells are most often characterized by the presence
of the D816V-activating KIT mutation; however, other classes of KIT
mutations have been detected.2 Mastocytosis is considered to be one
of the eight subcategories of myeloproliferative neoplasms, according to the 2008 World Health Organization classification system.3
There are two ages of peak onset for this disease: in the first
decade of life and between the fourth and fifth decades of life.4,5
The skin is the organ most affected in this class of disorders; in
fact, the skin is infiltrated in virtually all children and around
85% of adults with mastocytosis.4 The clinical presentation of
mastocytosis is heterogeneous and ranges from disease limited
to the skin (i.e. cutaneous mastocytosis) to cases with extracutaneous involvement (i.e. systemic mastocytosis). Cutaneous
mastocytosis occurs mainly during infancy and childhood (i.e.
most cases appear within the first year of life) and is commonly
associated with spontaneous regression of skin lesions, whereas
systemic mastocytosis is usually diagnosed in adults and ranges
from indolent to aggressive forms of mastocytosis. The latter is
associated with multiorgan failure and decreased survival.3
Mastocytosis is considered to be a rare disorder, but the true
incidence and prevalence in the general population are unknown. In
Brazil, it can reasonably be assumed that the diagnosis of mastocytosis is greatly underestimated, given the low clinical awareness of the
disease and the existence of very few specialized diagnostic centers. histamines, tryptase, prostaglandins and leukotrienes) and
tissue infiltration by neoplastic mast cells. Common symptoms include pruritus (i.e. generalized or restricted to cutaneous lesions), skin redness and swelling, sweating, palpitations,
thoracic pain and headache.1,5,6 Recurrent abdominal pain and
diarrhea are present in a significant number of cases and may
evolve to severe malabsorption, thereby leading to weight loss
and hypoalbuminemia. Osteoporosis can also be found in a
small number of cases.
Anaphylactic reactions associated with vascular collapse
and risk of death occur in approximately 20% of adults and 6%
of children, and these extreme symptoms are more frequent in
males.4 In some cases, the allergic triggering factor is not identified, whereas in others, a history of medication use (e.g. aspirin,
nonsteroidal anti-inflammatory drugs and iodinated radiocontrast agents) or insect bites has been linked to the onset of symptoms. In mast cell leukemia, repeated severe episodes of massive
release of mast cell mediators are typical, and these patients must
be treated in intensive care units. In clinical subtypes other than
mast cell leukemia, however, there may not be any direct relationship between mast cell mass, mast cell release and symptoms.7
In many patients, the first sign of the disease is a characteristic maculopapular rash known as urticaria pigmentosa. The
symptoms associated with these lesions are exacerbated with friction (Darier’s sign).7,8 In aggressive forms, the massive tissue infiltration can lead to signs and symptoms secondary to the existence of hepatic or bone marrow infiltration. These additional
signs and symptoms include abdominal pain, portal hypertension and ascites (i.e. relating to hepatic infiltration) and pancytopenia (i.e. relating to bone marrow infiltration).9
OBJECTIVES
The aim of the present study was to review the main signs and
symptoms of mastocytosis and suggest a practical approach for
diagnosis, classification and initial management of patients with
mast cell disorders.
Diagnosis and classification of mastocytosis
The diagnosis of mastocytosis is based on identification of neoplastic mast cells by means of morphological, immunophenotypic and/or genetic methods.10 The World Health Organization
Table 1. Database search results
METHODS
We conducted a narrative review by means of a systematic literature
search using the PubMed, Embase (Excerpta Medica Database),
Lilacs (Literatura Latino-Americana e do Caribe em Ciências da
Saúde ) and Cochrane Library databases to identify published scientific papers relating to the search term “mastocytosis.” Moreover,
the papers identified needed to focus on human subjects (Table 1).
RESULTS
Clinical manifestations
The clinical symptoms of mastocytosis are caused by acute and
chronic release of intracytoplasmic mast cell mediators (i.e.
Database
Search
PubMed
Mastocytosis
[Mesh]
2,747
papers
Embase (Excerpta Medica
Database)
Mastocytosis
[Emtree]
2,701
papers
Lilacs (Literatura Latino-Americana
Mastocytosis
e do Caribe em Ciências da Saúde)
81
papers
18
papers
Cochrane Library
Mastocytosis
Results
1,144 case reports
440 reviews
52 clinical trials
2 meta-analyses
1,109 others
962 case reports
554 reviews
168 clinical trials
1,017 others
45 case reports
36 others
18 clinical trials
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REVIEW ARTICLE | Sandes AF, Medeiros RSS, Rizzatti EG
classification system defines the following seven subtypes of the
disease: cutaneous mastocytosis, indolent systemic mastocytosis,
systemic mastocytosis associated with other clonal hematological non-mast cell lineage diseases, aggressive systemic mastocytosis, mast cell leukemia, mast cell sarcoma and extracutaneous
mastocytoma.3
Cutaneous mastocytosis is characterized by abnormal
mast cell infiltration in the dermis and no evidence of systemic
involvement. The following three variants of cutaneous mastocytosis have been described: urticaria pigmentosa, diffuse
cutaneous mastocytosis and solitary mastocytosis of the skin.
Urticaria pigmentosa is the most common presentation in children and represents 70-90% of cases of mastocytosis in this population. The most affected areas include the trunk and extremities, whereas the palms, soles, scalp, and face are less frequently
compromised.7
Diagnosing systemic mastocytosis requires identification of
major and minor criteria in the patient’s case history (Chart 1).
More specifically, the diagnosis of systemic mastocytosis is confirmed when one major plus one minor criterion or three minor
criteria are fulfilled. The subclassification of systemic mastocytosis is defined according to the tumor burden of mast cells
(B-findings), the clinical aggressiveness of the disease (C-findings)
and the involvement of hematopoietic lineages other than mast
cells (Table 2 and Figure 1). In this last situation, both systemic
mastocytosis and the components of systemic mastocytosis associated with other clonal hematological non-mast cell lineage diseases
are present, according to the World Health Organization’s criteria.3
Mast cell sarcoma and extracutaneous mastocytoma are
extremely rare and characterized by localized mast cell tumors
with no evidence of systemic mastocytosis. Mast cell sarcoma has
been reported as occurring in the uterus,11 intestine,12 bone13 and
skin.14 Moreover, it typically presents a destructive growth pattern
and high-grade cytology. On the other hand, extracutaneous mastocytoma cases have been reported to involve the lung and to present low-grade cytology and a non-destructive growth pattern.3
Recently, two new categories previously not included in the
World Health Organization classification system were described:
clonal mast cell activation disorders characterized by recurrent
episodes of idiopathic anaphylaxis, absence of skin lesions and the
presence of only one or two minor World Health Organization
criteria for systemic mastocytosis;15-17 and well differentiated
systemic mastocytosis characterized by mast cells with normal
morphology, absence of CD25 and CD2 expression and detection of KIT mutations other than D816V. Well differentiated systemic mastocytosis may be responsive to treatment with imatinib
(e.g. mutations of KIT-F522C).18,19
Another subtype previously not included in the World Health
Organization classification system is myelomastocytic leukemia,
an even rarer disease described in patients with advanced stages
of myeloid neoplasms (e.g. refractory anemia with excess of blasts
and acute myeloid leukemia). This manifestation is generally
associated with a high number of atypical mast cells that do not
meet the criteria for systemic mastocytosis.20,21 Myelomastocytic
leukemia typically involves an increased number of myeloblasts
(i.e. > 5%) and metachromatic blasts (i.e. > 10%) in the peripheral
Chart 1. Diagnostic criteria for systemic mastocytosis according to the World Health Organization (WHO) classification
Major criterion
1. Multifocal, dense infiltrates of mast cells (≥ 15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organ(s).
Minor criteria
1. In biopsy sections of bone marrow or other extracutaneous organs, > 25% of the mast cells in the infiltrate are spindle-shaped or have atypical
morphology or, out of all mast cells in bone marrow aspirate smears, > 25% are immature or atypical mast cells.
2. Detection of an activating point mutation at codon 816 of KIT in extracutaneous tissue (studying this in bone marrow is recommended).
3. Mast cells in bone marrow, blood or other extracutaneous organs express CD2 and/or CD25 in addition to normal mast cell markers.
4. Serum total tryptase persistently exceeds 20 ng/ml (unless there is an associated clonal myeloid disorder, in which case this parameter is not valid).
Table 2. B and C-findings in mastocytosis
B-findings
(Increased MC burden)
Bone marrow
- BM MC > 30%
- Serum tryptase > 200 ng/ml
- Hypercellular and dysplastic BM, without MDS criteria
Hepatomegaly or splenomegaly in absence of
functional impairment
Spleen and liver
Gastrointestinal tract
-
Skeletal lesions
-
C-findings
(Impaired organ function)
PB cytopenia:
Neutrophils < 1 x 109/l
Hemoglobin < 10 g/dl
Platelets < 100 x 109/l
- Hepatomegaly with ascites, abnormal liver function or portal hypertension
- Palpable splenomegaly with hypersplenism
Intestinal malabsorption, associated with hypoalbuminemia and weight loss
Osteolytic lesions, osteoporosis and pathological fractures associated
with local MC infiltration
BM = bone marrow; MC = mast cell; PB = peripheral blood; MDS = myelodysplastic syndrome.
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Diagnosis and treatment of mast cell disorders: practical recommendations | REVIEW ARTICLE
Systemic
mastocytosis (SM)
BM aspirate < 20%
MC
BM aspirate > 20%
MC
No B and Cfindings
PB <10% MC
“aleukemic”
mast cell
leukemia (MCL)
PB >10% MC
Mast cell
leukemia
Indolent SM
B-findings
Smoldering SM
C-findings
Aggressive SM
Clonal
hematological
non-mast cell
lineage disease
(WHO)
Clonal
hematological
non-mast cell
lineage disease
(WHO)
SM-AHDNM
MCL-AHDNM
BM = bone marrow; PB = peripheral blood; MC = mast cell; WHO = World Health Organization
Figure 1. Algorithm for classification of systemic mastocytosis (SM).
blood and/or bone marrow and lacks other features of mast cell
disorders, such as mast cell infiltrates, expression of CD25 and
CD2, or KIT-D816V mutation.
Bone marrow aspirate
Normal and reactive mast cells are round or oval and small to
medium sized cells that present a central round nucleus, condensed chromatin without a nucleolus, abundant cytoplasm (i.e.
low N/C ratio) and numerous metachromatic cytoplasmic granules, as identified via Romanowsky-based staining methods.
The cytomorphology of neoplastic mast cells have been classified into the following three subtypes:22 (1) metachromatic blasts
with a high N/C ratio, fine nuclear chromatin, prominent nucleoli
and few metachromatic granules; (2) atypical mast cells type I,
which are spindle-shaped cells with oval nuclei in an eccentric
position, elongated cytoplasmic projections and hypogranular
cytoplasm; and (3) atypical mast cells type II (promastocytes),
which exhibit bi- to multilobed nuclei associated with mature
morphology (i.e. condensed chromatin and low N/C ratio) or
immature morphology (i.e. fine chromatin and high N/C ratio)
(Figure 2). Moreover, these morphological features of mast cells
have been correlated with different clinical presentations of mastocytosis. Atypical mast cells type I are more commonly found
in systemic mastocytosis cases with an indolent course, whereas
atypical mast cells type II and metachromatic blasts are more frequently found in mast cell leukemia cases, which are commonly
associated with poor outcome and shorter survival time.
The percentage of mast cells in the bone marrow is decisive for the final diagnosis of systemic mastocytosis at advanced
stages, and an increase in the number of mast cells to ≥ 5% suggests an unfavorable prognosis. In patients with mast cell leukemia, the number of mast cells in the bone marrow smear is
≥ 20%. The differential count should be performed in areas far
from bone spicules, since mast cells tend to be present in higher
numbers near the spicules. It should be noted that the limit of
20% applies only to bone marrow smears but not to histological sections.22 In addition, a cytomorphological analysis contributes towards detection of eosinophilia, myelodysplasia and additional morphological features that might suggest coexistence
with another hematological malignancy.10
Bone marrow histopathology
Presence of multifocal, dense infiltrates of mast cells (i.e. > 15
mast cells in aggregates) in bone marrow trephine biopsy sections and/or other extracutaneous organs is a major criterion for systemic mastocytosis, according to the World Health
Sao Paulo Med J. 2013; 131(4):264-74
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Organization classification.1,3 Documentation of bone marrow
involvement accompanying systemic mastocytosis is often established by examination of a bone marrow trephine biopsy specimen. Indeed, histological sections demonstrate multifocal clusters or cohesive aggregates/infiltrates of mast cells mainly in the
form of peritrabecular and intertrabecular distribution. The presence of mast cells can be confirmed by Giemsa staining, which
enables observation of their main morphological features, i.e. a
blue to purple-colored pattern and the typical cytoplasmic granules. However, these features can also be observed under reactive
mast cell conditions and in cases of myelomastocytic leukemia.
Cytomorphological features can help to differentiate normal/reactive mast cells from neoplastic mast cells. In tissue sections stained with hematoxylin and eosin, normal/reactive mast
cells are usually loosely scattered throughout the sample and
display round to oval nuclei with clumped chromatin, a low
N/C ratio and an absent or indistinct nucleolus. The cytoplasm
is abundant and usually filled with small, faintly visible granules that are best highlighted by Giemsa staining. Dense aggregates of mast cells are only exceptionally detected in reactive
states or in patients treated with stem cell factor. For the diagnosis of systemic mastocytosis, atypical features of mast cell
must be observed, such as a compact cluster of both spindleshaped and round mast cells in varying numbers intermingled
A
B
with lymphocytes, eosinophils, histiocytes and fibroblasts, all of
which are more frequently seen in indolent systemic mastocytosis (Figure 3). Less often, the clusters are more monomorphic
and mainly composed of spindle-shaped mast cells that abut
or stream along the bony trabeculae. Significant reticulin fibrosis and thickening of the adjacent bone trabeculae are also frequently observed.
A diffuse pattern of infiltration is the predominant pattern in aggressive systemic mastocytosis and mast cell leukemia.23 In these patients, systemic mastocytosis can be diagnosed
without additional tests, since the presence of one major criterion (i.e. aggregates of mast cells) and one minor criterion (i.e.
abnormal morphology) match the World Health Organization’s
diagnostic criteria.
This is not the case in patients with tryptase-positive round
cell infiltrates of mast cells (TROCI), in which further tests are
necessary for diagnosis (e.g. staining for CD117, CD25 and CD34
by means of flow cytometry), given that basophils and myeloblasts can also express low levels of tryptase.24 Coexpression of
CD25 and CD117 in tryptase-positive round cell infiltrate cells is
highly suggestive of systemic mastocytosis.
In addition, detection of a single infiltrate of a mast cell or
presence of mast cell aggregates with less than 15 cells should
be considered to be a minor diagnostic criterion.1 It should be
C
D
Figure 2. Bone marrow aspirates from a healthy individual (panel A) and from systemic mastocytosis cases (panels B to D). Panel B
demonstrates an atypical mast cell type II, with a bilobed nucleus; panels C and D show spindle-shaped atypical mast cells type I, with
eccentric oval nuclei and cytoplasmic projections.
A
B
C
D
Figure 3. (A) Hematoxylin-eosin-stained photomicrograph of bone marrow showing a cluster of packed fusiform cells with eosinophilic
cytoplasm and some degree of atypia, in which there are large nuclei with clumped chromatin and nucleoli. These cells are permeated
by small reactive lymphocytes. The mast cell nature is highlighted on a Giemsa-stained slide (in inset detail), showing as bluish
hypogranulated cytoplasm. (B) Immunolabeled stain for CD 117 confirming the mast cell nature of the cells, which also aberrantly
express tryptase (C) and CD 25 (D). These findings confirm the diagnosis of bone marrow mastocytosis.
268
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Diagnosis and treatment of mast cell disorders: practical recommendations | REVIEW ARTICLE
noted that absence of mast cell infiltrates in bone marrow biopsies has been reported in around 20-30% of indolent systemic
mastocytosis cases,17,25 thereby suggesting that lower sensitivity towards the World Health Organization major criterion is
needed in diagnosing systemic mastocytosis at the initial stages
of the disease.10
The most specific methods for identifying immature or atypical mast cells in tissue sections are based on immunohistochemical staining for tryptase and CD117.23,26 These neoplastic mast
cells aberrantly express CD2 and CD25, which are the best markers for the definitive diagnosis of systemic mastocytosis.10
Finally, careful inspection of the hematopoietic characteristics other than the mast cells in the bone marrow is of crucial
importance. Often, the unaffected bone marrow is seemingly
typical with normal distribution of fat cells and hematopoietic precursors. Such cases usually either belong to indolent systemic mastocytosis with involvement of the skin and
bone marrow or represent scenarios of isolated mastocytosis of the bone marrow. In other cases, the bone marrow may
be extremely hypercellular due to proliferation of cells of nonmast cell lineage. These findings may be reactive (i.e. myeloid
hyperplasia) or may indicate a coexisting hematopoietic neoplasm. Lymphoproliferative diseases are less frequently identified in this setting. Clinicians must pay special attention to
increased cellularity of the bone marrow and disturbed maturation of hematopoietic cells, because these patterns may be associated with an unfavorable outcome or with a smoldering variant of systemic mastocytosis, even if the criteria for a coexisting
myeloid neoplasm are not fulfilled.
Multiparameter flow cytometry
Immunophenotyping by means of flow cytometry provides relevant information for diagnosis, classification and monitoring
of hematological malignancies.27-31 Normal and reactive mast
cells in the bone marrow present high forward and sideward
light scatter characteristics and are promptly detected through
strong expression of CD117.32 The normal mast cell phenotype
is characterized by expression of CD45, CD63, CD203c, FcRIe
and cytoplasmic total tryptase (CyB12); and by absence of CD2,
CD25, CD123 and CD34 antigens.33,34 HLA-DR is usually negative, but may also be partially expressed in a small fraction of
normal individuals.
Mast cells in systemic mastocytosis patients frequently present aberrant antigenic expression, thereby allowing a means of
clear differentiation from normal mast cells with diagnostic sensitivity higher than 98% and specificity of 100%.32 Thus, multiparameter flow cytometry is highly informative in this setting and
is currently considered to be the gold standard for identification
of aberrant mast cells.10
Neoplastic mast cells usually demonstrate aberrant expression
of CD25, with or without CD2, and abnormal expression of these
markers is considered to be a minor diagnostic criterion in the
World Health Organization’s classification system10,32-37 (Chart 1,
Figure 4). Other abnormal phenotypic profiles that have been
described include aberrant expression of CD123; overexpression of
CD203c, CD63, CD69 or CD45; and low expression of CyB12.34,38
It was recently shown that systemic mastocytosis is phenotypically heterogeneous and presents three different maturationassociated immunophenotypic profiles that correlate with molecular subtypes of the disease and have prognostic relevance.33,36
Patients with indolent systemic mastocytosis and clonal mast cell
activation disorders have an immunophenotypic profile similar to that observed in activated mast cells (i.e. overexpression
of CD63, CD69 and CD203c), in addition to high forward and
sideward light scatter characteristics, positivity to CD25 and high
expression of CD2. In contrast, mast cells from well differentiated systemic mastocytosis cases show normal expression of activation markers, lack of both CD25 and CD2, a phenotype similar to that of mature resting mast cells and high expression of
CD117 and FcRIe, as the main features. Finally, in cases of mastocytosis that are typically associated with unfavorable outcomes
(i.e. aggressive systemic mastocytosis and mast cell leukemia),
the mast cells exhibit aberrant expression of CD25 and usually
do not express CD2. This phenotype has been associated with
low light scatter values (i.e. forward and sideward light scatter,
but especially low sideward light scatter) and low expression of
CD117 and FcRIe, thereby reflecting an immature phenotype.
Expression of CD30 is also related to distinct subtypes of mastocytosis, i.e. it is strongly positive in cases of aggressive systemic
mastocytosis and negative or dimly expressed in cases of indolent
systemic mastocytosis.37,39
Serum tryptase
Serum tryptase levels are elevated in most patients with systemic
mastocytosis, and detection of serum tryptase levels higher than
20 ng/ml is considered to be a minor diagnostic criterion in the
World Health Organization’s classification system.1,5,40 Tryptase
levels tend to be higher in patients with a high mast cell burden;
patients with aggressive systemic mastocytosis generally present
tryptase levels > 200 ng/ml, especially as the disease progresses.41
However, tryptase levels are also elevated in a significant proportion of cases of acute myeloid leukemia, chronic myeloid leukemia
and myelodysplastic syndromes, and should not be considered to
be a diagnostic criterion for patients with suspected myeloid neoplasms associated with mastocytosis.3 Serum tryptase concentrations generally decrease after treatment of aggressive systemic
mastocytosis and mast cell leukemia, thus making this a suitable
marker for evaluating the response to cytoreductive drugs.1
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200000
200000
150000
150000
100000
100000
50000
50000
0
-1E2 0 1E2
CD117 APC
1E3
1E4
1E5
Side scatter
250000
Side scatter
250000
0
0
CD45 PerCP-Cy5.5
1E5
1E5
1E4
1E4
1E4
1E5
1E4
1E5
1E3
1E3
1E2
CD117 APC
1E2
CD117 APC
1E3
0
-1E2
CD2 FITC
0
1E3
1E4
1E5
0
-1E2
0
CD25 PE
1E2
1E3
Figure 4. Representative bivariate dot plots illustrating mast cells (black) identified by means of flow cytometry based on CD117 and
CD45 expression, with anomalous expression of CD2 and CD25, in a case of systemic mastocytosis.
c-KIT mutation and molecular studies
The KIT-D816V mutation is considered to be a minor diagnostic criterion according to the World Health Organization’s classification system. Indeed, it is detected in more than 90% of cases
of mastocytosis and, as the number of pathological cells in the
sample increases, the likelihood of detecting the KIT mutation
also increases.2,42 The sensitivity of KIT mutation detection can
be increased by enriching the mast cells in the sample by fluorescence-activated cell sorting and use of highly sensitive polymerase chain reaction techniques.1,10
In suspected systemic mastocytosis cases, the analysis should
be performed using bone marrow samples collected in ethylenediaminetetraacetic acid, and both non-fractionated and mononuclear
bone marrow cells can be examined for the KIT mutation. Peripheral
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blood should not be used as an alternative to bone marrow, since the
mutation is not found in the peripheral blood of most patients with
indolent systemic mastocytosis.1 Detection of the KIT mutation in
the dermis is indicative of mastocytosis in the skin, but it is not diagnostically indicative of systemic involvement.
In rare cases of systemic mastocytosis, no KIT-D816V
mutation is detected. In patients with small-sized mast cell
infiltrates, a negative result must be interpreted with caution
due to the small number of mast cells analyzed. Nevertheless,
in aggressive systemic mastocytosis and suspected well differentiated systemic mastocytosis cases, demonstration of absence
of D816V is clinically important since cases with wild typeKIT and certain types of KIT mutations other than D816V may
respond to imatinib therapy.19 If no mutation at codon 816 is
Diagnosis and treatment of mast cell disorders: practical recommendations | REVIEW ARTICLE
detected, sequencing of KIT should be considered.1 Moreover,
in female patients without the KIT mutation, the pattern of
chromosome X inactivation can be assessed by means of the
human-androgen receptor-a gene (HUMARA) assay, in order
to evaluate mast cell clonality.25
In the presence of peripheral blood eosinophilia (> 1500 cells/
ml), investigation of the CHIC-2 deletion and FIP1L1-PDGFRA
rearrangement by means of fluorescence in situ hybridization or the reverse transcriptase polymerase chain reaction is
indicated.1,5,40,43 Moreover, detection of translocations in regions
containing chromosome bands 5q31-5q33 via conventional cytogenetic analysis generally enables identification of cases associated with the PDGFRB rearrangement.43,44 Cases that have either
a PDGFRA or PDGFRB mutation associated with mast cell hyperplasia should be properly classified as “myeloid neoplasms with
PDGFRA or PDGFRB rearrangements,” according to the World
Health Organization’s classification system.3
Treatment
Treatment of mastocytosis is based on the specific clinical presentation and should take the following principles into account:1,4,40,45
(i) patients should receive detailed information about the disease
and specific information concerning avoidance of agents and situations that trigger mast cell degranulation (Chart 2); (ii) treatment of symptoms associated with acute and chronic release of
mast cell mediators should be part of the therapeutic regimen;
and (iii) cytoreductive treatment should be restricted to cases
involving advanced forms of the disease.
Patients with cutaneous mastocytosis and indolent forms of
mastocytosis (i.e. indolent systemic mastocytosis and smoldering
mastocytosis) must be treated symptomatically, i.e. with topical
and systemic drugs that act on the release of mast cell mediators,
such as histamine receptor antagonists (H1 and H2), sodium cromoglycate, and glucocorticoids (Oxford evidence level 1b). It is
important to emphasize that most patients should not receive
treatment to decrease the mast cell burden.1,4,7,40,43,45
Aggressive forms of mastocytosis (C-findings) should be
treated with cytoreductive drugs; more specifically, interferonalpha (i.e. 3 to 5 million units/m2/day) and cladribine (i.e. 5 mg/
m2/day x 5 days q 4-6 weeks; 3 cycles) are the most widely used
agents (Oxford evidence level 2b).46-50 Cases with the KIT-D816V
mutation are resistant to treatment with imatinib, and this drug
should be reserved for patients with KIT mutations other than
the D816V mutation (Oxford evidence level 2b).51,52 Despite the
fact that second-generation tyrosine kinase inhibitors (e.g. dasatinib) have shown in vitro efficacy against mast cells with the
D816V mutation,53 recent clinical studies have reported only
modest activity in D816V-positive systemic mastocytosis cases
(Oxford evidence level 2b).54 New tyrosine kinase inhibitors,
such as midostaurin (PKC412), are currently being evaluated
and appear promising as potential therapeutic agents for systemic mastocytosis cases.51,55 Bisphosphonates should be used
in cases with marked osteopenia and osteoporosis (Oxford evidence level 2b).56
Despite the limited evidence supporting hematopoietic stem
cell transplantation, this treatment is an alternative approach and
may induce remission in selected cases with advanced systemic
mastocytosis (i.e. aggressive systemic mastocytosis and mast cell
leukemia) (Oxford evidence level 3b).57,58 Valent et al. recommend that a debulking phase consisting of polychemotherapy or
repeated cycles of cladribine should be included before performing the hematopoietic stem cell transplantation.45
In contrast to C-findings, B-findings are not indicative of the
presence of aggressive forms of the disease and should not lead
to treatment decisions unless the symptoms progress (i.e. convert
to C-findings). The standard message is “B: Borderline, Benign,
Be careful — wait and watch whether progression occurs;
C: Consider cytoreduction.”1
Recently, hypomethylating agents (i.e. decitabine and 5-azacytidine) were tested in vitro and showed proapoptotic and
growth-inhibitory effects on cultured neoplastic mast cells
(Oxford evidence level 5).59 However, clinical trials are required
to confirm the clinical efficacy of these compounds.
Chart 2. Triggering agents in mastocytosis
Physical agents
Heat and cold
Sunlight
Sudden changes of temperature
Rubbing/pressure of skin lesions
Emotional factors
Stress/anxiety
Sleep deprivation
Drugs
Aspirin and other NSAIDs
Morphine, codeine and derivatives
Cough medications
Alcohol
Local anesthetics
Beta-blockers
Vancomycin
Venoms
Hymenoptera
Snakes
Infectious diseases with fever
Viral and bacterial
Others
Dental and endoscopic procedures
Vaccines
Surgery
Contrast media
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CONCLUSIONS
Mastocytosis refers to a heterogeneous group of disorders that
are characterized by accumulation of neoplastic mast cells in tissues. These disorders are diagnosed and classified based on clinical (i.e. B and C-findings), morphological, immunophenotypic
(i.e. aberrant expression of CD25 and CD2) and molecular (i.e.
KITD816V mutation) criteria. Correct subtype identification is
essential for treatment and management of these disorders.
15. Akin C, Scott LM, Kocabas CN, et al. Demonstration of an aberrant
mast-cell population with clonal markers in a subset of patients with
“idiopathic” anaphylaxis. Blood. 2007;110(7):2331-3.
16. Valent P, Akin C, Arock M, et al. Definitions, criteria and global
classification of mast cell disorders with special reference to mast
cell activation syndromes: a consensus proposal. Int Arch Allergy
Immunol. 2012;157(3):215-25.
17. Alvarez-Twose I, González de Olano D, Sánchez-Muñoz L, et al.
Clinical, biological, and molecular characteristics of clonal mast cell
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59. Ghanim V, Herrmann H, Heller G, et al. 5-azacytidine and
decitabine exert proapoptotic effects on neoplastic mast cells:
role of FAS-demethylation and FAS re-expression, and synergism
with FAS-ligand. Blood. 2012;119(18):4242-52.
Sources of funding: None
Conflict of interest: None
Date of first submission: August 28, 2012
Last received: December 28, 2012
Accepted: March 20, 2013
Address for correspondence:
Alex Freire Sandes
Grupo Fleury
Av. General Valdomiro de Lima, 508
São Paulo (SP) — Brasil
CEP 04344-903
Tel. (+55 11) 5014-4058
Fax. (+55 11) 5014-7223
E-mail: [email protected]
274
Sao Paulo Med J. 2013; 131(4):264-74
CASE REPORT
DOI: 10.1590/1516-3180.2013.1314494
Bilateral tibial hemimelia type 1 (1a and 1b)
with T9 and T10 hemivertebrae: a novel association
Bilateral tibial hemimelia tipo 1 (1a e 1b) com
hemivértebras T9 e T10: uma nova associação
Victor Michael Salinas-TorresI, Leticia Oralia Barajas-BarajasII, Nicolas Perez-GarciaIII, Guillermo Perez-GarciaIV
University Center of Health Sciences, University of Guadalajara, and “Fray Antonio Alcalde” Civil Hospital of Guadalajara, Guadalajara,
Jalisco, Mexico
I
MD. Specialty Student of Medical Genetics,
University Health Sciences Center, University of
Guadalajara, and “Fray Antonio Alcalde” Civil Hospital
of Guadalajara, Guadalajara, Jalisco, Mexico.
PhD. Professor of Clinical Genetics, University
Health Sciences Center, University of
Guadalajara, and Head of Department of Special
Care Clinic, Genetics Service, Integral Family
Development, Jalisco, Mexico.
II
MD. Professor of Radiology, University Health
Sciences Center, University of Guadalajara,
and Head of Department of Radiology, “Fray
Antonio Alcalde” Civil Hospital of Guadalajara,
Guadalajara, Jalisco, Mexico.
III
IV
PhD. Professor of Biochemistry, University
Health Sciences Center, University of
Guadalajara, and Head Department of
Genetics, “Fray Antonio Alcalde” Civil Hospital of
Guadalajara, Guadalajara, Jalisco, Mexico.
KEY WORDS:
Femur.
Ectromelia.
Tibia.
Thoracic vertebrae.
X-rays.
PALAVRAS-CHAVE:
Femur.
Ectromelia.
Tíbia.
Vértebras torácicas.
Raios X.
ABSTRACT
CONTEXT: Congenital absence of the tibia is a rare anomaly with an incidence of one per 1,000,000 live
births. It is mostly sporadic and can be identified as an isolated disorder or as part of malformation syndromes.
CASE REPORT: A male child, born to unaffected and non-consanguineous parents, presented with shortening of the legs and adduction of both feet. Physical examination at six months of age showed head
circumference of 44.5 cm (75th percentile), length 60 cm (< 3rd percentile), weight 7,700 g (50th percentile), shortening of the left thigh and both legs with varus foot. There were no craniofacial dysmorphisms
or chest, abdominal, genital or upper-extremity anomalies. Psychomotor development was normal. His
workup, including renal and cranial ultrasonography, brainstem auditory evoked potential, and ophthalmological and cardiological examinations, was normal. X-rays showed bilateral absence of the tibia
with intact fibulae, distally hypoplastic left femur, and normal right femur. In addition, spinal radiographs
showed hemivertebrae at T9 and T10.
CONCLUSION: This novel association expands the spectrum of tibial hemimelia. Moreover, this observation highlights the usefulness of this inexpensive diagnostic method (X-rays) for characterizing the great
clinical and radiological variability of tibial hemimelia.
RESUMO
CONTEXTO: Ausência congênita da tíbia é uma anomalia rara, com incidência em 1 por 1.000.000 de
nascidos vivos, é principalmente esporádica e pode ser identificada como um distúrbio isolado ou como
parte de síndromes de malformações.
RELATO DO CASO: Criança do sexo masculino, nascida de pais não afetados e não consanguíneos, apresentou-se com encurtamento das pernas e adução de ambos os pés. O exame físico realizado com seis
meses de idade mostrou perímetro cefálico 44,5 cm (percentil 75), comprimento de 60 cm (percentil < 3),
peso 7.700 g (percentil 50), encurtamento da coxa esquerda e as duas pernas com o pé varo bilateralhavia.
Não houve dismorfismos craniofaciais, nem tórax, abdômen, genitais e anomalias das extremidades superiores. O desenvolvimento psicomotor foi normal. Os exames, incluindo ultrassonografia renal e da cabeça,
potenciais auditivos evocados de tronco cerebral e exames oftalmológicos e cardiológicos, estavam normais. Raios-X revelou ausência bilateral da tíbia com fíbula intacta, hipoplasia distal do fêmur esquerdo e
fêmur direito normal. Além disso, as radiografias de coluna mostraram hemivértebras em T9 e T10.
CONCLUSÃO: Esta associação nova expande o espectro de hemimelia tibial. Além disso, esta observação
destaca a utilidade de tal método diagnóstico barato (raios-X), caracterizando a grande variabilidade clínica e radiológica de hemimelia tibial.
Sao Paulo Med J. 2013; 131(4):275-8
275
CASE REPORT | Salinas-Torres VM, Barajas-Barajas LO, Perez-Garcia N, Perez-Garcia G
INTRODUCTION
Tibial hemimelia is a rare anomaly characterized by deficiency of the tibia with a relatively intact fibula. This defect
was described by Otto in 1841 and has an incidence of one per
1,000,000 live births.1 Tibial hemimelia is mostly sporadic and
can be identified as an isolated disorder or as part of malformation syndromes.2 Based on the radiographic appearance, four
types of tibial hemimelia have been recognized: type 1a, with
absent tibia and hypoplastic lower femoral epiphysis; type 1b,
with absent tibia but normal lower femoral epiphysis; type 2,
in which the tibia is distally deficient and well developed proximally; type 3, in which the tibia is proximally deficient and well
ossified distally; and type 4, characterized by shortening of the
distal tibia, with distal tibiofibular diastasis and normally developed proximal tibia.3 Patients with this longitudinal deficiency
of the lower limb have unique clinical findings that vary in severity and are associated with a wide range of congenital anomalies.4 However, according to the International Clearinghouse
for Birth Defects Surveillance and Research, congenital amelia (absence of one or both limbs) is frequently associated with
intestinal defects, some renal and genital defects, oral clefts,
defects of cardiac septa, anencephaly and other types of musculoskeletal defects.5
This report describes an infant with the novel association of
bilateral tibial hemimelia type 1 (distally hypoplastic left femur
corresponding to type 1a and normal right femur corresponding
to type 1b) with hemivertebrae at T9 and T10.
CASE REPORT
A male infant was referred due to shortened legs and adduction of both feet (Figure 1). Renal and cranial ultrasonography,
Figure 1. Patient showing shortening of the left thigh and both legs
with bilateral varus foot.
276
Sao Paulo Med J. 2013; 131(4):275-8
brainstem auditory evoked potentials, and ophthalmological
and cardiological examinations were normal. X-rays (Figure 2)
showed bilateral absence of the tibia with intact fibulae, distally
hypoplastic left femur and normal right femur. In addition, spine
radiographs showed hemivertebrae at T9 and T10 (Figure 3).
The karyotype with G bands (> 550 bands) was reported as
46,XY. He was the first child of healthy and non-consanguineous parents who said that he had not been exposed to mutagens
or teratogens and that there was no history of affected relatives.
The pregnancy had been monitored from the 10th week onwards
and had not presented any complications. The patient was born
in the 38th week by vaginal delivery with Apgar scores of 9 and 9.
The birth weight was 2,800 g (25th percentile) and the length
was 42 cm (< 3rd percentile). Physical examination at six
months of age showed head circumference of 44.5 cm (75th percentile), length 60 cm (< 3rd percentile), weight 7,700 g (50th
percentile), shortening of the left thigh and both legs with bilateral varus foot. There were no craniofacial dysmorphisms or
chest, abdominal, genital or upper-extremity anomalies. His
psychomotor development was normal. Treatment consisting
of disarticulation of the knee joint and use of a prosthesis will
be attempted.
DISCUSSION
The patient’s bilateral absence of the tibia with intact fibulae
and distally hypoplastic left femur plus normal right femur
prompted the diagnosis of bilateral tibial hemimelia types 1a
and 1b (Figure 1 and 2); in addition, there were hemivertebrae at T9 and T10 (Figure 3). Over the past forty years, several studies have described over one hundred cases of congenital deficiency of the tibia.1,3,4,6 Among these patients, five
Figure 2. X-ray showing bilateral absence of the tibia with
intact fibulae and distally hypoplastic left femur plus normal
right femur.
Bilateral tibial hemimelia type 1 (1a and 1b) with T9 and T10 hemivertebrae: a novel association | CASE REPORT
had bilateral tibial hemimelia types 1a and 1b; 1,3,4 however,
none of them presented the combination of bilateral tibial
hemimelia types 1a and 1b with hemivertebrae at T9 and
T10. In our review of the literature, using the Medline (http://
www.ncbi.nlm.nih.gov/pubmed/), Scirus (http://www.scirus.
com/srsapp/), Embase (http://www.embase.com), Cochrane
Library (http://www.thecochranelibrary.com/view/0/index.
html), SciELO (http://www.scielo.org) and Lilacs (http://
lilacs.bvsalud.org/en/) databases, we did not find any articles describing this association (Table 1). A few tibial hemimelia cases have been recorded with hemivertebrae in the
lower spine.4
In the present case, the finding of mid-spine hemivertebrae (T9 and T10) could be a coincidence of two independent
defects. However, if this was just a random occurrence, the probability would be one in a billion (tibial hemimelia frequency1 =
1/1,000,000 x hemivertebrae frequency7 = 1/1000). Hence, this
small predictive ratio supports the notion that there is a true
association between tibial hemimelia and hemivertebrae, no
matter what the level is.
Tibial hemimelia encompasses a heterogeneous group
of disorders that are classified according to radiological
and clinical signs.3,4,6 It may occur as an isolated anomaly or
may be associated with a variety of skeletal and extraskeletal
malformations such as polysyndactyly, club hand, radioulnar
synostosis, bifid femur, cleft lip/palate and imperforate anus.
Tibial hemimelia may also constitute a part of a malformation complex or syndrome such as the Gollop-Wolfgang complex and tibial agenesis-ectrodactyly, triphalangeal thumbpolysyndactyly, tibial hemimelia/split-hand/split-foot and
Langer-Giedion syndromes.2,8,9 In our case, the previous
workup with full ultrasonography and X-ray body scan ruled
out malformations that had previously been associated with
this disorder.
Although tibial hemimelia is usually sporadic, several
affected families have shown either autosomal dominant
inheritance with great variability and reduced penetrance
or an autosomal recessive pattern with or without consanguineous unaffected parents. The tentative gene loci for tibial hemimelia are assigned to chromosome band 7q36 and
8q24, but identification of the gene(s) responsible remains
elusive.2,8 Richieri-Costa et al. (1987) reported on 37 patients
belonging to different families who had the tibial hemimelia/split-hand/split-foot syndrome. Citing other authors, they
suggested that the maximum risk to the offspring from an
affected person coupled with an unaffected person is 8.6%
and that the maximum risk to a sibling of an isolated patient
is 12.5%.8,9
Table 1. Review of medical databases using the descriptors
corresponding to the main features presented by the patient,
conducted on August 16, 2012
Database
Medline
(http://www.ncbi.nlm.nih.gov/
pubMed/)
Scirus
(http://www.scirus.com/srsapp/)
Embase
(http://www.embase.com)
Cochrane Library
(http://www.thecochranelibrary.
com/view/0/index.html)
SciELO
(http://www.scielo.org)
Figure 3. Spinal radiographs showing T9 and T10
hemivertebrae.
Lilacs
(http://lilacs.bvsalud.org/en/)
Search strategy
((“Absence of Tibia”
[Supplementary Concept]) OR
(Bilateral Tibial Hemimelia)) AND
(Hemivertebrae)
((“Absence of Tibia”
[Supplementary Concept]) OR
(Bilateral Tibial Hemimelia)) AND
(Hemivertebrae)
((“Absence of Tibia”
[Supplementary Concept]) OR
(Bilateral Tibial Hemimelia)) AND
(Hemivertebrae)
((“Absence of Tibia”
[Supplementary Concept]) OR
(Bilateral Tibial Hemimelia)) AND
(Hemivertebrae)
((“Absence of Tibia”
[Supplementary Concept]) OR
(Bilateral Tibial Hemimelia)) AND
(Hemivertebrae)
((“Absence of Tibia”
[Supplementary Concept]) OR
(Bilateral Tibial Hemimelia)) AND
(Hemivertebrae)
Results
0
articles
1
article
0
articles
0
articles
0
articles
0
articles
Sao Paulo Med J. 2013; 131(4):275-8
277
CASE REPORT | Salinas-Torres VM, Barajas-Barajas LO, Perez-Garcia N, Perez-Garcia G
CONCLUSIONS
In conclusion, X-ray imaging enables excellent assessment of
tibial hemimelia and its associated skeletal malformations,3,4,6 in
addition to its ready availability and minimal cost. The radiological features described in the present case expand the spectrum
of malformations associated with tibial hemimelia and further
illustrate the usefulness and sensitivity of such an inexpensive
diagnostic method. Thus, physicians need to be acutely aware of
the great clinical and radiological variability of tibial hemimelia. Newly available genomic technologies from biological models may begin to offer more answers regarding the causes of tibial
hemimelia in the near future.
REFERENCES
1. Fernandez-Palazzi F, Bendahan J, Rivas S. Congenital deficiency of the
tibia: a report on 22 cases. J Pediatr Orthop B. 1998;7(4):298-302.
2. Matsuyama J, Mabuchi A, Zhang J, et al. A pair of sibs with tibial
hemimelia born to phenotypically normal parents. J Hum Genet.
2003;48(4):173-6.
3. Jones D, Barnes J, Lloyd-Roberts GC. Congenital aplasia and dysplasia
of the tibia with intact fibula. Classification and management. J Bone
Joint Surg Br. 1978;60(1):31-9.
4. Schoenecker PL, Capelli AM, Millar EA, et al. Congenital longitudinal
deficiency of the tibia. J Bone Joint Surg Am. 1989;71(2):278-87.
5. Bermejo-Sánchez E, Cuevas L, Amar E, et al. Amelia: a multicenter descriptive epidemiologic study in a large dataset from
the International Clearinghouse for Birth Defects Surveillance and
Research, and overview of the literature. Am J Med Genet C Semin
Med Genet. 2011;157C(4):288-304.
6. Kalamchi A, Dawe RV. Congenital deficiency of the tibia. J Bone Joint
Surg Br. 1985;67(4):581-4.
7. Wax JR, Watson WJ, Miller RC, et al. Prenatal sonographic diagnosis
of hemivertebrae: associations and outcomes. J Ultrasound Med.
2008;27(7):1023-7.
8. Tibial hemimelia. OMIM® - Online Mendelian Inheritance in Man.
Available
from:
http://omim.org/entry/275220?search=tibial%20
hemimelia&highlight=hemimelia%20tibia Accessed in 2012 (Dec 18).
9. Richieri-Costa A, Ferrareto I, Masiero D, da Silva CR. Tibial hemimelia:
report on 37 new cases, clinical and genetic considerations. Am J
Med Genet. 1987;27(4):867-84.
Acknowledgements: We thank Maria de Lourdes Ramirez and Horacio
Rivera for their critical review of the manuscript
Sources of funding: None
Conflict of interest: None
278
Sao Paulo Med J. 2013; 131(4):275-8
Date of first submission: March 30, 2012
Last received: December 28, 2012
Accepted: December 28, 2012
Address for correspondence:
Victor Salinas
Hospital 278 Col. El Retiro, CP. 44280
Guadalajara, Jalisco, México
0453314834630
E-mail: [email protected]
LETTER TO THE EDITOR
DOI: 10.1590/1516-3180.2013.1314517
Ginseng: potential for the antileishmanial arsenal?
Ginseng: potencial para o arsenal “leishmanicida”?
Nader PazyarI, Reza YaghoobiII
Department of Dermatology, Jundishapur University of Medical Sciences, Ahvaz, Iran
MD. Assistant Professor, Department of
Dermatology, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran.
I
MD. Professor, Department of Dermatology,
Ahvaz Jundishapur University of Medical
Sciences, Ahvaz, Iran.
II
Cutaneous leishmaniasis (CL) develops after inoculation of the skin with parasites of the genus
Leishmania, transmitted by phlebotomines (sandflies). Every year, CL affects approximately
1-1.5 million people worldwide, with over 90% of the cases occurring in the Middle East and
South America.1
CL is regarded as a parasitic disease caused by Leishmania and no optimal medication protocol is available for this skin infection. Beneficial treatment regimens for CL should be based
on experience, efficiency and the toxicity of the drugs in each region.2
Importantly, it has been clarified that protective immunity against CL is related to induction
of Th1/Tc1 immune response, which leads to efficient parasite elimination.3 Interleukin (IL)-12
is unanimously believed to be a pivotal cytokine for induction of Th1/Tc1-dependent protection against Leishmania.4 Moreover, activated macrophages are the major source of IL-12, which
stimulates autocrine macrophage activation.5
One important point needing attention is that the polyamine biosynthetic pathway is fundamental for the growth and survival of Leishmania. Ornithine decarboxylase (ODC) is the first
enzyme in the polyamine biosynthetic pathway.6 Additionally, it has been recognized that ODC
catalyzes the conversion of ornithine to putrescine7 and that the levels of putrescine are elevated
in cases of resistant leishmaniasis.8
It has been revealed that P-glycoproteins mediate drug resistance to Leishmania and other
protozoa and that this is followed by development of cross-resistance to numerous structurally
and functionally unrelated drugs.9
Leishmania parasites are obligate intracellular organisms in mammals, and they invade
macrophages and dendritic cells. Notably, it has been demonstrated that nitric oxides produced
in macrophages possess a crucial role as leishmanicidal agents.10
Ginseng (Panax ginseng) has been used for thousands of years in phytomedicine and it has
captured a specific position on the list of the best-selling herbal agents in the world.11 Ginseng
modulates blood pressure, metabolism and immune functions.12
Interestingly, ginsenosides, which are the major active component of ginseng, have a range
of biomedical effects.13 They are triterpene saponins, and most ginsenosides are composed of a
dammarane skeleton (17 carbons in a four-ring structure) with various sugar moieties.12
It is noteworthy that ginseng therapy has been shown to stimulate a Th1-like immune
response, which improves the course of diseases in animal models.14 Importantly, ginseng modulates the peripheral blood mononuclear cells and leads to higher IL-12 production. Additionally,
elevated IL-12 levels can induce a more potent Th1 immune response.15
IH-901, a new intestinal bacterial metabolite extracted from protopanaxadiol-type ginsenosides, has been observed to suppress ornithine decarboxylase activity dose-dependently in animal skin.16
Protein-arginine N-methyltransferase (protein methylase I) catalyzes methylation of arginyl
residues on substrate protein post-translationally. It has been found that Korean red ginseng is
able to inhibit protein methylase I activity and, subsequently, polyamines in vitro.17
Lee et al. demonstrated that total saponin in ginseng and ginsenosides was capable of
decreasing the putrescine levels in immobilization-stressed gerbil mice.18
Sao Paulo Med J. 2013; 131(4):279-80
279
LETTER TO THE EDITOR | Pazyar N, Yaghoobi RY
Notably, an in vitro study has shown that purified Rg1 ginsenosides increase the production of nitric oxide from IFNgamma activated macrophages.19
Ginsenosides have been reported to be inhibitors of
P-glycoprotein (Pgp).20 Choi et al. explained that protopanaxatriol ginsenosides exert a chemosensitizing effect on Pgpmediated multidrug resistance cells. Correspondingly, this component increases the intracellular accumulation of drugs through
direct interaction with Pgp at the azidopine site.21
In summary, putting the above facts together, ginseng and
ginsenosides may open up a novel therapeutic opportunity for
treating cutaneous leishmaniasis. Combination of topical ginseng or ginsenosides with meglumine antimoniate might boost
the therapeutic effects of this drug, increase its intracellular accumulation and, subsequently, help to reduce the resistance of parasites against it.
11. Pazyar N, Yaghoobi R. A rationale of ginseng as a novel addition
to the antihirsutism armamentarium. J Altern Complement Med.
2012;18(3):210-1.
12. Leung KW, Wong AS. Pharmacology of ginsenosides: a literature
review. Chin Med. 2010;5:20.
13. Pazyar N, Omidian M, Jamshydian N. Ginseng as a potential novel
addition to the antikeloid weaponry. Phytother Res. 2012;26(10):1579-80.
14. Song Z, Moser C, Wu H, et al. Ginseng modulerer immunresponset
via
påvirkning
af
cytokinproduktionen--sekundaerpublikation
[Ginseng modulates the immune response via its effect on
cytokine production--secondary publication]. Ugeskr Laeger.
2005;167(33):3054-6.
15. Larsen MW, Moser C, Høiby N, Song Z, Kharazmi A. Ginseng modulates
the immune response by induction of interleukin-12 production.
APMIS. 2004;112(6):369-73.
16. Lee JY, Shin JW, Chun KS, et al. Antitumor promotional effects of
a novel intestinal bacterial metabolite (IH-901) derived from the
REFERENCES
1. Wise ES, Armstrong MS, Watson J, Lockwood DN. Monitoring toxicity
protopanaxadiol-type ginsenosides in mouse skin. Carcinogenesis.
2005;26(2):359-67.
associated with parenteral sodium stibogluconate in the day-case
17. Yoo BC, Park GH, Okuda H, et al. Inhibitory effect of arginine-
management of returned travellers with New World cutaneous
derivatives from ginseng extract and basic amino acids on protein-
leishmaniasis [corrected]. PLoS Negl Trop Dis. 2012;6(6):e1688.
arginine N-methyltransferase. Amino Acids. 1999;17(4):391-400.
2. Kumaresan M, Kumar P. Localized cutaneous leishmaniasis in South
18. Lee SH, Jung BH, Kim SY, Lee EH, Chung BC. The antistress effect of
India: successful treatment with ketoconazole. Indian J Dermatol
ginseng total saponin and ginsenoside Rg3 and Rb1 evaluated by
Venereol Leprol. 2007;73(5):361-2.
brain polyamine level under immobilization stress. Pharmacol Res.
3. von Stebut E, Udey MC. Requirements for Th1-dependent
immunity against infection with Leishmania major. Microbes Infect.
2004;6(12):1102-9.
4. Zahn S, Kirschsiefen P, Jonuleit H, Steinbrink K, Von Stebut E. Human
primary dendritic cell subsets differ in their IL-12 release in response
to Leishmania major infection. Exp Dermatol. 2010;19(10):924-6.
2006;54(1):46-9.
19. Fan ZH, Isobe K, Kiuchi K, Nakashima I. Enhancement of nitric oxide
production from activated macrophages by a purified form of
ginsenoside (Rg1). Am J Chin Med. 1995;23(3-4):279-87.
20. Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein.
Drug Metab Rev. 2004;36(1):57-104.
5. Ota H, Takashima Y, Matsumoto Y, Hayashi Y, Matsumoto Y.
21. Choi CH, Kang G, Min YD. Reversal of P-glycoprotein-mediated
Pretreatment of macrophages with the combination of IFN-gamma
multidrug resistance by protopanaxatriol ginsenosides from Korean
and IL-12 induces resistance to Leishmania major at the early phase
red ginseng. Planta Med. 2003;69(3):235-40.
of infection. J Vet Med Sci. 2008;70(6):589-93.
6. Singh S, Mukherjee A, Khomutov AR, et al. Antileishmanial effect
Sources of funding: None
of 3-aminooxy-1-aminopropane is due to polyamine depletion.
Conflict of interest: None
Antimicrob Agents Chemother. 2007;51(2):528-34.
7. Tang X, Kim AL, Feith DJ, et al. Ornithine decarboxylase is a target
Date of first submission: May 8, 2012
for chemoprevention of basal and squamous cell carcinomas in
Last received: February 8, 2013
Ptch1+/- mice. J Clin Invest. 2004;113(6):867-75.
Accepted: March 19, 2013
8. Namazi MR. Hypothesis: the potential utility of topical eflornithine
against cutaneous leishmaniasis. Indian J Dermatol Venereol Leprol.
Address for correspondence:
2008;74(2):158-9.
Nader Pazyar
9. Namazi MR. Potential utility of disulfiram against leishmaniasis. Indian
J Med Res. 2008;127(2):193-4.
10. Souza AS, Giudice A, Pereira JM, et al. Resistance of Leishmania
280
Department of Dermatology
Imam Hospital
Azadegan Street
(Viannia) braziliensis to nitric oxide: correlation with antimony
Ahvaz, Iran
therapy and TNF-alpha production. BMC Infect Dis. 2010;10:209.
E-mail: [email protected]
Sao Paulo Med J. 2013; 131(4):279-80
LETTER TO THE EDITOR
DOI: 10.1590/1516-3180.2013.1314638
Medicine and creativity in medical psychology
Medicina e criatividade em psicologia médica
Décio Gilberto Natrielli FilhoI, Mailu Enokibara SilvaII, Décio Gilberto NatrielliIII
Multidisciplinary Committee of Medical Psychology, Associação Paulista de Medicina (APM), São Paulo, Brazil
MD. Attending Psychiatrist, Irmãs Hospitaleiras
do Sagrado Coração de Jesus, São Paulo, Brazil.
I
MD. Resident, Department of Psychiatry, Centro
de Atenção Integrada a Saúde Mental (CAISM),
Santa Casa de Misericórdia de São Paulo, São
Paulo, Brazil.
II
MD. Scientific Coordinator, Multidisciplinary
Committee of Medical Psychology, Associação
Paulista de Medicina (APM), São Paulo, Brazil.
III
The art of medicine is related to a precise decision-making process, which has evolved from
strict scientific research towards the current practice of evidence-based medicine. Guided by
the need to have safe and precise practice, doctors can rely on guidelines and data published in
scientific journals to ensure both therapeutic and diagnostic success.
Creativity can be considered to be human beings’ capacity to promote growth of their own
and other people’s potentials.1 Through cognitive mechanisms acquired from the slow and persistent process of human evolution, the human mind is able to create an amazing field of ideas and
models that aim to describe or “translate” nature through mathematics, biology, history, geology,
physics and all other kinds of sciences. Use and improvement of these scientific concepts lead
towards a wide variety of tools aimed at controlling, transforming and manipulating our world.
The complexity of our behaviors and models are closely related to creativity. Regarding medical
practice, creativity is unlikely to be limited to scientific research. It has also been correlated with
day-to-day approaches towards patients: the so-called doctor-patient relationship.
Creativity can be seen as the possibility of transcending the boundary between a concrete
scenario determined by a certain disease (i.e. objective features such as physiological changes)
and the subjective world of people undergoing such pathological experiences. Listening to, looking forward to, holding onto and paying attention to all the words and effects or feelings experienced by patients could be a way to practice the use of creativity in medical settings. Despite the
simplicity of this practice, it is not widespread today, as can be deduced from the frequent complaints relating to the lack of “humanity” in the current medical environment.
De Masi2 argued that within evolution, our brain progressively miniaturized its circuits,
multiplied all the functional levels and built internal areas of the cortex. These adaptive mechanisms were fundamental for synthesizing data provided from other brain areas and for developing further mental processes such as abstraction, anticipation and symbolization. Within
this scenario, creativity appears as a mechanism for thinking about reality and its relationships.
Without creativity, reality becomes cold, flavorless, impoverished, logical, operative and concrete. Without creativity, medicine would be limited to a scientific approach to life; physics and
mathematics would be reduced to sciences without philosophy, and history would speak a language differing from literature.
Newton, Bacon, John Stuart Mill and Darwin2 followed the inductive method to develop
concepts regarding unknown processes. Their strategy was based on a mentalist approach that
aimed to reach “higher conclusions” and spread knowledge. In this process, mental work prevails over experimental research.
Developing creativity requires neurocognitive, affective and psychosocial development. We
take the view that creativity is an intellectual ability of fundamental relevance regarding interpersonal, working and group relationships. For medicine and doctors, we consider that all of
this process (of creativity) plays a major role in clinical practice, and that this can be quite helpful to doctors in three main scenarios:
1. When solving problems and complaints that would otherwise be perceived as less important
than the core symptoms of the diseases;
2. Promoting new solutions for conflicts;
Sao Paulo Med J. 2013; 131(4):281-2
281
LETTER TO THE EDITOR | Natrielli Filho DG, Silva ME, Natrielli DG
3. Strengthening the real and symbolic picture of a doctor as a confident person, open to all the needs of people who we care for.
Indeed, creativity promotes psychological growth among
those who are available to stimulate and work out hidden languages (non-verbal or pre-verbal), i.e. different forms of the
intrinsic human communication apparatus. This noble task may
lead to insights such as making defensive mechanisms adaptable
to worldwide demands, or transforming suffering into new positive or adaptive experiences, rather than being a simple dead end.
Finally, taking advantage of the evolution model, creativity would
transit through this adaptive scenario, thus supporting a “sense of
a purpose” and reinforcing the positive affective consequences
of guidelines, medical routines and evidence-based medicine.
As mentioned earlier, although this letter has focused on an
obvious issue, not all doctors are prepared to deal with the constellation of variables involved in medical practice. We should be
aware of this limitation as intrinsic to our practice, and therefore
spare some thought for the matter of exploring new languages to
describe patients.
Creativity demands energy and is a higher brain function, not
an automatic function. It can provide doctors with the ability to perceive different mechanisms underlying what patients tell them, such
as their fears, doubts, idealizations or depreciations. Each patient
has a unique history, and when physicians formulate diagnosis, they
are in fact rewriting their patients’ ideas about the past. Our aim is
to attenuate present suffering and prevent future occurrences.
REFERENCES
1. Natrielli Filho DG, Natrielli DG, Goes RD. Contribuições para a prática
da psiquiatria, psicodinâmica e psicologia médica. São Paulo: Leitura
Médica; 2008.
2. De Masi D. Criatividade e grupos criativos. Rio de Janeiro:
Sextante; 2003.
Sources of funding: None
Conflict of interest: None
Date of first submission: November 28, 2012
Last received: March 12, 2013
Accepted: April 3, 2013
Address for correspondence:
Décio Gilberto Natrielli Filho
Rua Roque Petrella, 153
Vila Cordeiro — São Paulo (SP) — Brasil
CEP 04581-050
Tel. (+55 11) 5542-5145
E-mail: [email protected]
282
Sao Paulo Med J. 2013; 131(4):281-2
LETTER TO THE EDITOR
DOI: 10.1590/1516-3180.2013.1314719
Should every adult patient in the
hospital have an internist?
Todo paciente adulto no hospital deve ter um internista?
Mine Durusu TanrioverI, Goksel GuvenII, Cagin BuldukogluII, Omer DikerII, Burcin HalacliII,
Gonul YildirimIII, Arzu TopeliIV
Hacettepe University Adult Hospital, Ankara, Turkey
MD. Associate Professor, Department of Internal
Medicine, Hacettepe University Faculty of
Medicine, Ankara, Turkey.
I
II
MD. Resident, Department of Internal Medicine,
Hacettepe University Faculty of Medicine,
Ankara, Turkey.
Nurse. Administrator, Adult Hospital Nursing
Administration, Hacettepe University Faculty of
Medicine, Ankara, Turkey.
III
IV
MD. Professor, Department of Internal
Medicine and Medical Intensive Care, Hacettepe
University Faculty of Medicine, Ankara, Turkey.
Hospital medicine is a new venue for practicing internal medicine. It is the fastest growing specialty in the United States. While it has some similarities to “European” acute medicine, it differs particularly in that it provides continuous care throughout the hospitalization
period and even beyond.1 Not only medical patients, but also surgical patients and patients
in psychiatry and neurology wards are now being co-managed by hospitalists in the United
States.2 Minor injuries might be managed by a nonsurgical hospitalist so as to improve the
overall efficiency of the system.3
Patients admitted to non-internal medicine wards may even be in greater need of general medical care. We conducted a one-day cross-sectional survey to gather data on all the
adult patients admitted to the wards (excluding intensive care and coronary care units and
internal medicine wards) of a university hospital. There were 301 patients in the non-internal medicine, non-intensive care wards on a single day. The mean age of the patients was
50.5 ± 18.1 years (range: 16 to 92 years). More than 60% of the patients had been admitted
for elective surgery (Table 1). Seventy-three percent of the patients (n = 220) presented at
least one medical comorbidity and a median of two drugs (minimum 0; maximum 12) on
the medication list (Table 1).
Recently, a Europe-wide study by Pearse et al. demonstrated that the mortality rate
among patients who had undergone non-cardiac surgery was higher (4%) than expected.4
Perhaps more importantly, 73% of the patients who died had never been admitted to the
intensive care unit. Accompanying diseases, such as cirrhosis, insulin diabetes and chronic
obstructive pulmonary disease, were associated with mortality with odds ratios of up to
3.6. This reflects the vital importance of perioperative care for surgical patients, especially
for those with medical comorbidities who would require effective, timely and high-quality
general medical care. Hospitalists function as key members of patient-centered care during
hospital admissions. Hospitalist co-management or consultation in nonmedical wards has
been shown to shorten the length of time until surgery and the length of hospital stay, and
to decrease the cost per stay.5
In conclusion, patients admitted to non-internal medicine wards present several medical comorbidities. Given the burden of chronic diseases in the aging population worldwide, the outcomes from implementing a hospitalist consultant or co-management system
in non-medical wards should be investigated in prospective, large-scale studies.
Sao Paulo Med J. 2013; 131(4):283-4
283
LETTER TO THE EDITOR | Tanriover MD, Guven G, Buldukoglu C, Diker O, Halacli B, Yildirim G, Topeli A
Table 1. Indications for admission and percentages of particular
medical comorbidities amongst the study population (n = 301)
% (n)
Reason for admission
Elective surgery
Medical treatment
Investigation for differential diagnoses
Emergency surgery
Complications from surgery
Procedural treatment
Other
Medical comorbidity
Hypertension
Cardiac disease
Diabetes
Malignancy
COPD/asthma
Renal dysfunction
Rheumatological disease
Transplantation
Infection
Chronic liver disease
Bedridden
Others*
62.1 (187)
14.3 (43)
12.0 (36)
4.7 (14)
4.0 (12)
2.0 (6)
1.0 (3)
31.2 (94)
19.9 (60)
17.9 (54)
16.9 (51)
7.3 (22)
6.0 (18)
3.7 (11)
2.3 (7)
1.7 (5)
1.3 (4)
0.7 (2)
23.6 (71)
Some patients presented more than one disease or condition. *Examples of other
medical comorbidities included osteoporosis, osteoarthritis, gout and so on. No matter
how many comorbidities in this group were present in a particular patient, they were
taken to be “one” comorbidity. COPD = chronic obstructive pulmonary disease.
REFERENCES
1. Wachter RM, Bell D. Renaissance of hospital generalists. BMJ.
2012;344:e652.
2. Auerbach AD, Wachter RM, Cheng HQ, et al. Comanagement of
surgical patients between neurosurgeons and hospitalists. Arch
Intern Med. 2010;170(22):2004-10.
3. Salottolo K, Slone DS, Howell P, et al. Effects of a nonsurgical
hospitalist service on trauma patient outcomes. Surgery.
2009;145(4):355-61.
4. Pearse RM, Moreno RP, Bauer P, et al. Mortality after surgery in Europe:
a 7 day cohort study. Lancet. 2012;380(9847):1059-65.
5. Peterson MC. A systematic review of outcomes and quality measures
in adult patients cared for by hospitalists vs nonhospitalists. Mayo
Clin Proc. 2009;84(3):248-54.
Acknowledgement: We would like to thank the head nurses of the
wards, who helped us in the process of data collection
Sources of funding: None
Conflict of interest: None
284
Sao Paulo Med J. 2013; 131(4):283-4
Date of first submission: May 20, 2013
Last received: June 11, 213
Accepted: July 5, 2013
Address for correspondence:
Mine Durusu Tanriover
Hacettepe University Faculty of Medicine
Department of Internal Medicine, 06100
Ankara, Turkey
Tel. 00 90 312 305 30 29
E-mail: [email protected]
COCHRANE HIGHLIGHTS
DOI: 10.1590/1516-3180.20131314T1
Prophylactic drug
management for febrile
seizures in children
Martin Offringa, Richard Newton
The independent commentary was written by
Lívia Cunha Elkis
ABSTRACT
BACKGROUND: Febrile seizures occurring in a child older than one
month during an episode of fever affect 2% to 4% of children in Great
Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been
used to avoid the adverse effects of continuous antiepileptic drugs.
OBJECTIVE: To evaluate the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with
febrile seizures.
METHODS:
Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011. Issue 3); MEDLINE
(1966 to May 2011); EMBASE (1966 to May 2011); Database of Abstracts
of Reviews of Effectiveness (DARE) (May 2011). No language restrictions
were imposed. We also contacted researchers in the field to identify
continuing or unpublished studies.
Selection criteria: Trials using randomized or quasi-randomized patient
allocation that compared the use of antiepileptic or antipyretic agents
with each other, placebo or no treatment.
Data collection and analysis: Two review authors (RN and MO) independently applied pre-defined criteria to select trials for inclusion and
extracted the pre-defined relevant data, recording methods for randomization, blinding and exclusions. Outcomes assessed were seizure
recurrence at 6, 12, 18, 24, 36 months and at age 5 to 6 years in the
intervention and non-intervention groups, and adverse medication effects. The presence of publication bias was assessed using funnel plots.
MAIN RESULTS: Thirty-six articles describing 26 randomized trials with
2740 randomized participants were included. Thirteen interventions
of continuous or intermittent prophylaxis and their control treatments
were analyzed. Methodological quality was moderate to poor in most
studies. We could not do a meta-analysis for 8 of the 13 comparisons
due to insufficient numbers of trials. No significant benefit for valproate,
pyridoxine, intermittent phenobarbitone or ibuprofen versus placebo
or no treatment was found; nor for diclofenac versus placebo followed
by ibuprofen, acetominophen or placebo; nor for intermittent rectal
diazepam versus intermittent valproate, nor phenobarbitone versus
intermittent rectal diazepam.
AUTHORS’ CONCLUSIONS: No clinically important benefits for children with febrile seizures were found for intermittent oral diazepam,
phenytoin, phenobarbitone, intermittent rectal diazepam, valproate,
pyridoxine, intermittent phenobarbitone or intermittent ibuprofen, nor
for diclofenac versus placebo followed by ibuprofen, acetominophen or
placebo. Adverse effects were reported in up to 30% of children. Apparent benefit for clobazam treatment in one recent trial needs to be replicated to be judged reliable. Given the benign nature of recurrent febrile
seizures, and the high prevalence of adverse effects of these drugs, parents and families should be supported with adequate contact details of
medical services and information on recurrence, first aid management
and, most importantly, the benign nature of the phenomenon.
This is the abstract of a Cochrane Review published in the Cochrane
Database of Systematic Reviews (CDSR) 2013, issue 4, Art. No.
CD003031. DOI: 10.1002/14651858.CD003031.pub4 (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003031.pub2/abstract). For
full citation and authors details, see reference 1.
The full text is freely available from: http://cochrane.bireme.br/cochrane/main.php?lang=pt&lib=COC (this link may be temporary)
REFERENCE
1. Offringa M, Newton R. Prophylactic drug management for febrile
seizures in children. Cochrane Database Syst Rev. 2012;4:CD003031.
COMMENTS
Out of 79 potential articles, only 36 met the inclusion criteria for the present systematic review. From these 36 papers, 26 original studies were
analyzed and 2740 children were included in the systematic review. The
drugs used were antiepileptics (phenytoin, phenobarbitone, valproate,
diazepam and clobazam), antipyretics (diclofenac, acetaminophen and
ibuprofen) and pyridoxine. The treatments were compared with each
other, or with non-treatment or placebo. Studies with non-treatment
controls were more frequent than those with placebo groups.
The following outcomes were measured: a) Efficacy: any type of seizure
(febrile/non-febrile) at certain time points (recurrence at 6, 12, 24, 48,
60 and 73 months, respectively); b) Safety (effectiveness), as measured
according to drug side-effects.
The following treatments were more effective for reducing seizures: intermittent oral diazepam, continuous phenobarbitone and intermittent
rectal diazepam. However, the effect size was small and the benefits
did not seem to be stable over time. These conclusions need to be regarded with caution since, except for the meta-analysis on continuous
phenobarbitone, most were based on only a few studies included (e.g.
there was only one study relating to intermittent oral diazepam versus
placebo at six months).
Given the long-term benign nature of the phenomenon of febrile seizures and the relatively high rate of adverse effects (up 30%), it seems
difficult to justify further research in this area, unless this involves improvement of the quality of randomization allocation and use of placebo as a control group.
The main conclusion is that treatment of recurrence of febrile seizures is
still performed in an empirical manner all over the world, and that more
elaborate studies are warranted in order to establish evidence-based
guidelines for children with febrile convulsions.
Lívia Cunha Elkis. MD, PhD. Professor of Child Neurology in the Pediatric Division, School of Medicine, Universidade Santo Amaro, São
Paulo (SP), Brazil.
Sao Paulo Med J. 2013; 131(4):285
285
COCHRANE HIGHLIGHTS
Phlebotonics for
haemorrhoids
Nirmal Pereira, Danae Liolitsa, Satheesh Iype, Anna
Croxford, Muhhamed Yassin, Lang Peter, Obioha
Ukaegbu, Christopher van Issum
The independent commentary was written by Sarhan
Sydney Saad
ABSTRACT
BACKGROUND: Haemorrhoids are variceal dilatations of the anal and
perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus. Phlebotonics are
a heterogenous class of drugs consisting of plant extracts (i.e. flavonoids)
and synthetic compounds (i.e. calcium dobesilate). Although their precise
mechanism of action has not been fully established, they are known to improve venous tone, stabilize capillary permeability and increase lymphatic
drainage. They have been used to treat a variety of conditions including
chronic venous insufficiency, lymphoedema and haemorrhoids.
OBJECTIVE: The aim of this review was to investigate the efficacy of
phlebotonics in alleviating the signs, symptoms and severity of haemorrhoidal disease and verify their effect post-haemorrhoidectomy.
METHODS:
Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2011 issue 9, MEDLINE
(1950 to September 2011) and EMBASE (1974 to September 2011).
Selection criteria: Only randomized controlled trials evaluating the use
of phlebotonics in treating haemorrhoidal disease were used. No crossover or cluster-randomized trials were included for analysis and any trial
which had a quasi-random method of allocation was excluded.
Data collection and analysis: Two authors independently extracted the
data and analyzed the eligibility of the data for inclusion. Disagreements were resolved by meaningful discussion.
MAIN RESULTS: We considered twenty-four studies for inclusion in the
final analysis. Twenty of these studies (enrolling a total of 2344 participants) evaluated the use of phlebotonics versus a control intervention.
One of these twenty studies evaluated the use of phlebotonics with
a medical intervention and another study with rubber band ligation.
AUTHORS’ CONCLUSIONS: The evidence suggests that there is a potential benefit in using phlebotonics in treating haemorrhoidal disease
as well as a benefit in alleviating post-haemorrhoidectomy symptoms.
Outcomes such as bleeding and overall symptom improvement show
a statistically significant beneficial effect and there were few concerns
regarding their overall safety from the evidence presented in the clinical
trials.Only randomized controlled trials evaluating the use of phlebotonics in treating haemorrhoidal disease were used. No cross-over or
cluster-randomized trials were included for analysis and any trial which
had a quasi-random method of allocation was excluded.
This is the abstract of a Cochrane Review published in the Cochrane
Database of Systematic Reviews (CDSR) 2013, issue 5, Art. No.
CD004322. DOI: 10.1002/14651858.CD004322.pub8 (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004322.pub3/abstract). For
full citation and authors details see reference 1
The full text is freely available from: http://cochrane.bvsalud.org/
cochrane/main.php?lib=COC&searchExp=Phlebotonics%20and%20
for%20and%20haemorrhoids&lang=pt (this link may be temporary)
286
Sao Paulo Med J. 2013; 131(4):286
DOI: 10.1590/1516-3180.20131314T2
REFERENCE
1. Perera N, Liolitsa D, Iype S, et al. Phlebotonics for haemorrhoids.
Cochrane Database Syst Rev. 2012;8:CD004322.
COMMENTS
Hemorrhoidal disease is responsible for frequent seeking of medical attention, due to a variable range of symptoms and signs. It is often treated through use of supplementary fiber in the diet and local medication.
Use of phlebotonics for treating hemorrhoids has always been a matter
of discussion because the evidence in the literature has not indicated
that they should be used routinely. Their action seems to be based on
increasing the strength and tone of the vessel wall, thereby improving
lymphatic drainage and normalizing capillary permeability.
The aim of this systematic review was to observe the action of these
substances in relieving the symptoms of hemorrhoids and their effect
during the postoperative period following hemorrhoidectomy. Twentyfour prospective randomized studies that evaluated the use of phlebotonics in hemorrhoidal disease were selected using strict criteria. These
studies compared use of phlebotonics with control interventions or
even elastic ligation.
The results, based on statistically significant numbers, showed that
these substances are safe to use, with a low rate of side effects, and that
they provide improvements in symptoms with regard to bleeding and
postoperative pain, and in other symptoms such as itching.
Thus, this systematic review has obtained the evidence that is needed for
phlebotonics to be used in medical treatments for hemorrhoidal disease.
Sarhan Sydney Saad. MD, PhD. Associate Full Professor and Head of
the Coloproctology Group, Discipline of Gastrointestinal Surgery, Escola Paulista de Medicina – Universidade Federal de São Paulo (EPMUnifesp), São Paulo (SP), Brazil.
SÃO PAULO MEDICAL JOURNAL/EVIDENCE FOR HEALTH CARE
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References
and epidemiological data in general should be followed by the refer-
The list of references (in the “Vancouver style”, as indicated by the
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Article in journal
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- Hurt AC, Hardie K, Wilson NJ, et al. Community transmis-
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sion of oseltamivir-resistant A(H1N1)pdm09 influenza.
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N Engl J Med. 2011;365(26):2541-2.
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- Miller WI, Achernabb JC, Fluck CE. The adrenal cortex and
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its disorder. In: Sperling M. Pediatric endocrinology. 3rd ed.
city and country;
Elsevier Health Sciences; 2008. p. 444-511.
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number, city) of the corresponding author, telephone and
environment State Indicator Report, 2011. Available from:
e-mail that can be published together with the article.
http://www.cdc.gov/obesity/downloads/ChildrensFoodEnvi-
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be prepared in Microsoft Excel (do not send them in image formats)
and must be accompanied by the tables of data from which they have
been generated. The number of illustrations must not exceed the total
number of pages minus one.
All figures and tables must contain legends or titles that precisely
describe their content and the context or sample from which the information was obtained (i.e. what the results presented are and what the
kind of sample or setting was). The legend or title sentence should be
short but comprehensible without depending on reading the article.
All the figures and tables should be cited in the text.
São Paulo Medical Journal/Evidence for Health Care is for now
published in black-and-white in its printed version. Photographs,
photomicrographs, bar and line graphs and any image to be published
must be prepared considering that there will be no color differentiation (any color information will be discarded). Shades of gray and
printing patterns (dots, stripes and others) should be used instead,
with good contrast.
Original articles
Clinical trials, cohort, case-control, prevalence, incidence, accuracy and cost-effectiveness studies, and systematic reviews with or
without meta-analysis, are considered to be original articles.
The São Paulo Medical Journal/Evidence for Health Care supports the clinical trial registration policies of the World Health
Organization (WHO) and the International Committee of Medical Journal Editors (ICMJE) and recognizes the importance of
these initiatives for registration and international dissemination
of information on randomized clinical trials, with open access.
Thus, from 2008 onwards, manuscripts on clinical trials have been
accepted for publication only if they have received an identification number from one of the clinical trial registers that have been
validated in accordance with the criteria established by WHO and
ICMJE. Authors of randomized clinical trials must thus register
their studies before submitting them for publication in the São
Paulo Medical Journal/Evidence for Health Care. The addresses
for these registers are available from the ICMJE website (http://
www.icmje.org). The identification number should be declared at
the end of the abstract.
Authors will be required to comply with the guidelines for writing
each type of original article, as follows:
1. Observational articles: STROBE Statement;5,6
2. Clinical trials: CONSORT Statement;2
3. Accuracy studies on diagnostic tests: STARD Statement;7,8
4. Systematic reviews of the literature and meta-analyses:
PRISMA4
The São Paulo Medical Journal takes the view that these guidelines not only aid in writing and organizing the content of articles in a
standardized manner, thereby improving their quality and facilitating
reading and assessment, but also these guidelines help to avoid situations in which important information on the methodology of studies
remains outside of the manuscript.
As a partner institution of the Cochrane Collaboration and the
Brazilian Cochrane Center, the Associação Paulista de Medicina considers that production of articles in accordance with these guidelines
also aids in future production of systematic reviews of the literature
and meta-analyses. Thus, articles submitted for publication that are
not in accordance with these norms may be returned to their authors
for readjustment before the peer review process begins.
Original articles must be structured so as to contain the following parts: Introduction, Objective, Methods, Results, Discussion and
Conclusion. The text must not exceed 5,000 words (excluding tables,
figures and references), from the introduction to the end of the conclusion, and must include a structured abstract with a maximum of
250 words.9 “Structured abstract” means that the abstract must contain the following items: Context and objective, Design and setting,
Method, Results and Conclusion.
The structure of the document should follow the format laid out below:
1) Title and abstract: the study design and/or the way participants were allocated to interventions, for example “randomized” or “retrospective” study, should be mentioned in the title
and in the abstract. The abstract should provide a summary of
what was done and what was found.
2)Introduction: specify the reasons for carrying out the study,
describing the present state of knowledge of the topic.
Describe the scientific background and “the state of the art”.
Do not include here any results or conclusions from the study.
Use the last paragraph to specify the principal question of the
study, and the principal hypothesis tested, if there is one. Do
not include discussions about the literature in the introduction; the introduction section should be short.
3)Objective: describe briefly what the main objective or question of the study was. Clearly describe the pre-specified
hypotheses.
4)Methods
4.1)Type of study: describe the design of the study and specify,
if appropriate, the type of randomization (the way in which
draws were conducted), the blinding (how this was ensured),
the diagnostic test standards (gold standard or range of normal values) and the time direction (retrospective or prospective). For example: “randomized clinical trial”, “double-blind
placebo-controlled clinical trial”, “cross-sectional accuracy
study”, “retrospective cohort study”, “cross-sectional prevalence study” or “systematic review of clinical trials”.
4.2)Sample, participants or patients: describe the eligibility criteria for participants (inclusion and exclusion criteria) and
the sources and procedures for selection or recruitment. In
case-control studies, describe the rationale for distributing
the subjects as cases and controls, and the matching criteria. The numbers of patients at the beginning and end of
the study (after exclusions) must be made clear. A flow diagram showing the initial recruitment, the exclusions and the
Sao Paulo Med J. 2013; 131(4):I-V
III
These instructions are updated periodically. We recommend that they are consulted online at: www.scielo.br/spmj
final sample of patients included should be produced and
inserted in the article.
4.3)Setting: indicate the place where the study was carried out,
including the type of healthcare provided (i.e. whether primary or tertiary; and whether in a private or in a public hospital). Avoid stating the name of the institution where the study
was developed (for blinding purposes in the peer review).
Only the type of institution should be made clear, for example: “public university hospital” or “private clinic”.
4.4)Procedures (intervention, diagnostic test or exposure):
describe the principal characteristics of any intervention,
including the method, the timing and the duration of its
administration or of data collection. Describe the differences
in interventions administered to each group (if the study is
controlled). Detail the procedures in such a way that other
researchers will be able to repeat them in other localities.
4.5)Main measurements, variables and outcome: state what the
primary and secondary outcomes analyzed in the study are.
Describe the method of measuring the primary result, in
the way in which it was planned before data collection. For
each variable of interest, detail the assessment methods. If
the hypothesis of the study was formulated during or after
data collection (and not before), this needs to be declared.
Describe the methods used to enhance the quality of measurements (for example, multiple observers, training, etc.) and
to avoid bias. Explain how quantitative variables were handled
in the analyses.
4.6)Sample size and statistical analysis: describe the sample size
calculation method, or the study period in the event that
patients were consecutively admitted over a period. Readers need to understand why a given number of patients was
used. The planned statistical analysis, the statistical tests used
and their significance levels, along with any post hoc analyses, should be presented in this section. Describe the methods used to control for confounding factors and variables, and
explain how missing data and cases lost from the follow-up
were dealt with.
4.7)Randomization: describe the method used to implement the
random allocation sequence (for example, sealed envelopes
containing random sequences of numbers or software for
generating random numbers). If appropriate, report that the
study used “quasi-randomization”.12 In addition, describe who
generated the random sequence, who assigned the participants to each group (in the case of controlled trials) and who
recruited the participants.
5)Results: describe the main findings. If possible, these should be
accompanied by their 95% confidence intervals and the exact
level of statistical significance (it is not enough to write “P <
0.05”: the exact P value should be supplied). For comparative
IV
Sao Paulo Med J. 2013; 131(4):I-V
studies, the confidence interval must be stated for the differences between the groups.
5.1)Participant flow diagram: describe the flow of participants
through each stage of the study (inclusions and exclusions)
and the follow-up period, and the number of participants
completing the study (or lost from the follow-up). Use a flow
diagram to demonstrate the numbers of patients, from the
initial recruitment to the end of the study, and the reasons
for exclusions. If there was any “intention-to-treat” analysis,
describe it.
5.2)Deviations: if there was any deviation from the protocol, away
from what was initially planned, describe it and the reasons
for it.
5.3)Adverse events: describe any side effect, adverse event or
complication.
6)Discussion: provide an interpretation of the results, taking
into account the study hypotheses and conclusions. Emphasize the new and important factors encountered in the study,
which will form part of the conclusion. Do not repeat data
presented in the introduction or results in detail. Mention any
limitations of the findings that should be noted and any possible implications for future research. Describe any potential bias. Report any relevant findings from other studies: it is
important to review the recent literature to seek new evidence
that may have been published, which needs to be discussed.
State whether the findings can be generalized to populations
(i.e. whether the findings have external validity). It is recommended that the last two paragraphs should contain implications for practice and for further research.
7)Conclusions: specify only the conclusions that can be sustained by the results, together with their clinical significance
(avoiding excessive generalization). Draw conclusions based
on the objectives and hypotheses of the study. The same
emphasis should be placed on studies with positive and negative results.
Systematic reviews with or without meta-analyses should comply
with the same publication norms established for original articles, and
be produced in accordance with PRISMA4 and the Cochrane Collaboration’s systematic review Handbook.13 The text should not exceed
5,000 words (excluding tables, figures and references)
Short communications, case reports or case series
Short communications and case reports must be limited to 3,000
words (from the introduction to the end of the conclusion). Short
communications are reports on the results from ongoing studies or
studies that have recently been concluded for which urgent publication is important. They should be structured thus: Introduction,
Objective, Methods, Results, Discussion and Conclusion, like in original articles. Individual case reports should contain: Introduction, Case
Report, Discussion and Conclusion. Reports on case series constitute
These instructions are updated periodically. We recommend that they are consulted online at: www.scielo.br/spmj
observational studies and these should be structured in accordance
with the norms of the STROBE Statement.5
Both short communications and case reports must be submitted
with abstracts and key words. The abstracts in short communications should be structured with: Context and objective, Design and
setting, Methods, Results and Conclusion, like in original articles.
The abstracts in case reports and case series should contain: Context, Case Report (with a description of the case and a pertinent discussion) and Conclusion.
The São Paulo Medical Journal/Evidence for Health Care is interested in publishing rare or instructive case reports, accompanied by
a systematic search of the literature, in which relevant studies found
(based on their level of evidence) are presented and discussed.14 The
results from the systematic search of the main databases — Medline
(via PubMed), Embase, Lilacs and Cochrane Library — should be
presented in a table with the search strategy for each database and the
number of articles obtained.
Narrative reviews
Narrative reviews may be accepted by the São Paulo Medical Journal/Evidence for Health Care and should be structured with: Introduction, Objectives, Methods, Results, Discussion and Conclusions.
The abstract must be structured with: Context and objective, Design
and setting, Methods, Results and Conclusions, like in original articles. The manuscript must comply with the norms of the Vancouver
style1 and must include a systematic search in the main databases:
Medline, Embase, Lilacs and Cochrane Library. The search strategy for each database and the number of articles obtained from each
database should be presented in a table. The access route to the electronic databases used should be stated (for example, PubMed, OVID,
Elsevier or Bireme). For the search strategies, MeSH terms must be
use for Medline, LILACS and Cochrane Library. DeCS terms must be
used for LILACS. EMTREE terms must be used for Embase. Also, for
LILACS, search strategy must be performed, at the same time, with
English (MeSH), Spanish (DeCS) and Portuguese (DeCS) terms. The
search strategies must be presented exactly as they were used during the search, including parentheses, quotation marks and Boolean
operators (AND, OR, AND NOT).
Letters to the editor
Letters to the editor may address articles published in the São
Paulo Medical Journal/Evidence for Health Care publication or may
deal with health issues of interest. Case reports must not be submitted
as letters. In the category of letters to the editor, the text has a free format, but must not exceed 500 words and five references.
Documents cited
1. Internal Committee of Medical Journal Editors. Uniform
requirements for manuscripts submitted to biomedical journals,
writing and editing for biomedical publications. Available from:
http://www.icmje.org. Accessed in 2012 (Aug 6).
2. The CONSORT Statement. Available from: http://www.consort-statement.org/consort-statement/. Accessed in 2012 (Aug 6).
3. Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the
QUOROM statement. Lancet. 1999;354(9193):1896-900. Available
from:
http://www.thelancet.com/journals/lancet/article/PIIS01406736(99)04149-5/abstract. Accessed in 2012 (Aug 6).
4. PRISMA. Transparent Reporting of Systematic Reviews and
Meta-Analyses. Available from: http://www.prisma-statement.org/
index.htm. Accessed in 2012 (Aug 6).
5. STROBE Statement. Strengthening the reporting of observational studies in epidemiology. What is strobe? Available from: http://
www.strobe-statement.org/. Accessed in 2012 (Aug 6).
6. von Elm E, Altman DG, Egger M, et al. The Strengthening the
Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344-9.
7. STARD Statement. STAndards for the Reporting of Diagnostic accuracy studies. Available from: http://www.stard-statement.org/.
Accessed in 2012 (Aug 6).
8. Rennie D. Improving reports of studies of diagnostic tests: the
STARD initiative. JAMA. 2003;289(1):89-90.
9. Haynes RB, Mulrow CD, Huth EJ, Altman DG,
Gardner MJ. More informative abstracts revisited. Ann Intern Med.
1990;113(1):69-76.
10. National Library of Medicine. Medical Subject Headings:
annotated alphabetic list. Bethesda: NLM; 1998. Available from: http://
www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?db=mesh. Accessed in
2012 (Aug 6).
11. BVS Biblioteca Virtual em Saúde. Descritores em Ciências da
Saúde. Available from: http://decs.bvs.br/. Accessed in 2012 (Aug 6).
12. Reeves BC, Deeks JJ, Higgins JPT, Wells GA. Including nonrandomized studies. In: Cochrane Non-Randomised Studies Methods Group. The Cochrane Book Series. England: John Wiley & Sons;
2008. Available from: http://hiv.cochrane.org/sites/hiv.cochrane.org/
files/uploads/Ch13_NRS.pdf. Accessed in 2012 (Aug 6).
13. The Cochrane Collaboration. Cochrane Handbook for Systematic Reviews of Interventions. Available from: http://www.cochrane.
org/training/cochrane-handbook/. Accessed in 2012 (Aug 6).
14. Phillips B, Ball C, Sackett D, et al. Oxford Centre for Evidencebased Medicine Levels of Evidence (May 2001). Available from: http://
www.cebm.net/index.aspx?o=1047. Accessed in 2012 (Aug 6).
Sao Paulo Med J. 2013; 131(4):I-V
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