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1.  Predictors of Death during Tuberculosis Treatment in TB/HIV Co-Infected Patients in Malaysia 
PLoS ONE  2013;8(8):e73250.
Mortality among TB/HIV co-infected patients is still high particularly in developing countries. This study aimed to determine the predictors of death in TB/HIV co-infected patients during TB treatment.
We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all newly registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in the Klang Valley between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes and survival. We analysed using Kaplan-Meier and conducted multivariate Cox proportional hazards analysis to identify predictors of death during TB treatment in TB/HIV co-infected patients.
Of the 227 patients studied, 53 (23.3%) had died at the end of the study with 40% of deaths within two months of TB diagnosis. Survival at 2, 6 and 12 months after initiating TB treatment were 90.7%, 82.8% and 78.8% respectively. After adjusting for other factors, death in TB/HIV co-infected patients was associated with being Malay (aHR 4.48; 95%CI 1.73-11.64), CD4 T-lymphocytes count < 200 cells/µl (aHR 3.89; 95% CI 1.20-12.63), three or more opportunistic infections (aHR 3.61; 95% CI 1.04-12.55), not receiving antiretroviral therapy (aHR 3.21; 95% CI 1.76-5.85) and increase per 103 total white blood cell count per microliter (aHR 1.12; 95% CI 1.05-1.20)
TB/HIV co-infected patients had a high case fatality rate during TB treatment. Initiation of antiretroviral therapy in these patients can improve survival by restoring immune function and preventing opportunistic infections.
PMCID: PMC3741191  PMID: 23951346
2.  A Systematic Review of Statistical Methods Used to Test for Reliability of Medical Instruments Measuring Continuous Variables 
Objective(s): Reliability measures precision or the extent to which test results can be replicated. This is the first ever systematic review to identify statistical methods used to measure reliability of equipment measuring continuous variables. This studyalso aims to highlight the inappropriate statistical method used in the reliability analysis and its implication in the medical practice.
Materials and Methods: In 2010, five electronic databases were searched between 2007 and 2009 to look for reliability studies. A total of 5,795 titles were initially identified. Only 282 titles were potentially related, and finally 42 fitted the inclusion criteria.
Results: The Intra-class Correlation Coefficient (ICC) is the most popular method with 25 (60%) studies having used this method followed by the comparing means (8 or 19%). Out of 25 studies using the ICC, only 7 (28%) reported the confidence intervals and types of ICC used. Most studies (71%) also tested the agreement of instruments.
Conclusion: This study finds that the Intra-class Correlation Coefficient is the most popular method used to assess the reliability of medical instruments measuring continuous outcomes. There are also inappropriate applications and interpretations of statistical methods in some studies. It is important for medical researchers to be aware of this issue, and be able to correctly perform analysis in reliability studies.
PMCID: PMC3758037  PMID: 23997908
ICC; Intra-class correlation coefficient; Reliability; Statistical method; Validation study
3.  Towards an effective control programme of soil-transmitted helminth infections among Orang Asli in rural Malaysia. Part 1: Prevalence and associated key factors 
Parasites & Vectors  2013;6:27.
Despite the continuous efforts to improve the quality of life of Orang Asli (Aborigines) communities, these communities are still plagued with a wide range of health problems including parasitic infections. The first part of this study aimed at determining the prevalence of soil-transmitted helminth (STH) infections and identifying their associated factors among rural Orang Asli children.
A cross-sectional study was carried out among 484 Orang Asli children aged ≤ 15 years (235 females and 249 males) belonging to 215 households from 13 villages in Lipis district, Pahang, Malaysia. Faecal samples were collected and examined by using formalin-ether sedimentation, Kato Katz and Harada Mori techniques. Demographic, socioeconomic, environmental and behavioural information were collected by using a pre-tested questionnaire.
Overall, 78.1% of the children were found to be infected with one or more STH species. The prevalence of trichuriasis, ascariasis and hookworm infections were 71.7%, 37.4% and 17.6%, respectively. Almost all, three quarters and one fifth of trichuriasis, ascariasis and hookworm infections, respectively, were of moderate-to-heavy intensities. Multiple logistic regression analysis showed that age of ≥ 6 years (school-age), using unsafe water supply as a source for drinking water, absence of a toilet in the house, large family size (≥ 7 members), not washing hands before eating, and not washing hands after defecation were the key factors significantly associated with STH among these children.
This study reveals an alarmingly high prevalence of STH among Orang Asli children and clearly brings out an urgent need to implement school-based de-worming programmes and other control measures like providing a proper sanitation, as well as a treated drinking water supply and proper health education regarding good personal hygiene practices. Such an integrated control program will help significantly in reducing the prevalence and intensity of STH in Orang Asli communities.
PMCID: PMC3564908  PMID: 23356952
Soil-transmitted helminths; Ascaris; Trichuris; Hookworm; Orang Asli; Malaysia
4.  Towards an effective control programme of soil-transmitted helminth infections among Orang Asli in rural Malaysia. Part 2: Knowledge, attitude, and practices 
Parasites & Vectors  2013;6:28.
In the first part of this study, we investigated the prevalence and associated key factors of soil-transmitted helminth (STH) infections among Orang Asli children in rural Malaysia; an alarming high prevalence and five key factors significantly associated with infections were reported. Part 2 of this study aims to evaluate the knowledge, attitude and practices (KAP) on STH infections among Orang Asli in Peninsular Malaysia.
A cross-sectional study was carried out among 215 households from 13 villages in Lipis district, Pahang, Malaysia. Demographic and socioeconomic information of the participants and their KAP on STH were collected by using a pre-tested questionnaire.
Overall, 61.4% of the participants had prior knowledge about intestinal helminths with a lack of knowledge on the transmission (28.8%), signs and symptoms (29.3%) as well as the prevention (16.3%). Half of the respondents considered STH as harmful, while their practices to prevent infections were still inadequate. Significant associations between the KAP and age, gender, educational and employment status, family size, and household monthly income were reported. Moreover, significantly lower prevalence of STH infections was reported among children of respondents who wear shoes/slippers when outside the house (72.8%; 95% CI= 62.6, 80.5 vs 87.0%; 95% CI= 81.4, 91.1), wash their hands before eating (32.4%; 95% CI= 24.3, 42.2 vs 51.4%; 95% CI= 44.7, 60.1), and wash their hands after defecation (47.8%; 95% CI= 35.7, 57.1 vs 69.2%; 95% CI= 63.7, 78.7) as compared to their counterparts. Multiple logistic regression analysis indicated that the educational level of the respondents was the most important factor significantly associated with the KAP on STH among this population.
This study reveals inadequate knowledge, attitude and practices on STH infections among Orang Asli in rural Malaysia. Hence, there is a great need for a proper health education programme and community mobilisation to enhance prevention and instil better knowledge on STH transmission and prevention. This is crucial for an effective and sustainable STH control programme to save the lives and future of the most vulnerable children in rural Malaysia.
PMCID: PMC3571980  PMID: 23356968
Knowledge; Attitude; Practice; Soil-transmitted helminths; Malaysia
5.  From west to east; experience with adapting a curriculum in evidence-based medicine 
Perspectives on Medical Education  2012;1(5-6):249-261.
Clinical epidemiology (CE) and evidence-based medicine (EBM) have become an important part of medical school curricula. This report describes the implementation and some preliminary outcomes of an integrated CE and EBM module in the Faculty of Medicine Universitas Indonesia (UI), Jakarta and in the University of Malaya (UM) in Kuala Lumpur. A CE and EBM module, originally developed at the University Medical Center Utrecht (UMCU), was adapted for implementation in Jakarta and Kuala Lumpur. Before the start of the module, UI and UM staff followed a training of teachers (TOT). Student competencies were assessed through pre and post multiple-choice knowledge tests, an oral and written structured evidence summary (evidence-based case report, EBCR) as well as a written exam. All students also filled in a module evaluation questionnaire. The TOT was well received by staff in Jakarta and Kuala Lumpur and after adaptation the CE and EBM modules were integrated in both medical schools. The pre-test results of UI and UM were significantly lower than those of UMCU students (p < 0.001). The post test results of UMCU students were comparable (p = 0.48) with UI, but significantly different (p < 0.001) from UM. Common problems for the modules in both UI and UM were limited access to literature and variability of the tutors’ skills. Adoption and integration of an existing Western CE-EBM teaching module into Asian medical curricula is feasible while learning outcomes obtained are quite similar.
PMCID: PMC3518799  PMID: 23240103
Curriculum; Medical students; Under-graduate education; Evidence-based medicine
6.  Ethnic Differences in the Prevalence of Metabolic Syndrome: Results from a Multi-Ethnic Population-Based Survey in Malaysia 
PLoS ONE  2012;7(9):e46365.
The prevalence of metabolic syndrome is increasing disproportionately among the different ethnicities in Asia compared to the rest of the world. This study aims to determine the differences in the prevalence of metabolic syndrome across ethnicities in Malaysia, a multi-ethnic country.
In 2004, we conducted a national cross-sectional population-based study using a stratified two-stage cluster sampling design (N = 17,211). Metabolic syndrome was defined according to the International Diabetes Federation/National Heart, Lung and Blood Institute/American Heart Association (IDF/NHLBI/AHA-2009) criteria. Multivariate models were used to study the independent association between ethnicity and the prevalence of the metabolic syndrome.
The overall mean age was 36.9 years, and 50.0% participants were female. The ethnic distribution was 57.0% Malay, 28.5% Chinese, 8.9% Indian and 5.0% Indigenous Sarawakians. The overall prevalence of the metabolic syndrome was 27.5%, with a prevalence of central obesity, raised triglycerides, low high density lipoprotein cholesterol, raised blood pressure and raised fasting glucose of 36.9%, 29.3%, 37.2%, 38.0% and 29.1%, respectively. Among those <40 years, the adjusted prevalence ratios for metabolic syndrome for ethnic Chinese, Indians, and Indigenous Sarawakians compared to ethnic Malay were 0.81 (95% CI 0.67 to 0.96), 1.42 (95% CI 1.19 to 1.69) and 1.37 (95% CI 1.08 to 1.73), respectively. Among those aged ≥40 years, the corresponding prevalence ratios were 0.86 (95% CI 0.79 to 0.92), 1.25 (95% CI 1.15 to 1.36), and 0.94 (95% CI 0.80, 1.11). The P-value for the interaction of ethnicity by age was 0.001.
The overall prevalence of metabolic syndrome in Malaysia was high, with marked differences across ethnicities. Ethnic Chinese had the lowest prevalence of metabolic syndrome, while ethnic Indians had the highest. Indigenous Sarawakians showed a marked increase in metabolic syndrome at young ages.
PMCID: PMC3460855  PMID: 23029497
7.  Statistical Methods Used to Test for Agreement of Medical Instruments Measuring Continuous Variables in Method Comparison Studies: A Systematic Review 
PLoS ONE  2012;7(5):e37908.
Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice.
Five electronic databases were searched between 2007 and 2009 to look for agreement studies. A total of 3,260 titles were initially identified. Only 412 titles were potentially related, and finally 210 fitted the inclusion criteria. The Bland-Altman method is the most popular method with 178 (85%) studies having used this method, followed by the correlation coefficient (27%) and means comparison (18%). Some of the inappropriate methods highlighted by Altman and Bland since the 1980s are still in use.
This study finds that the Bland-Altman method is the most popular method used in agreement research. There are still inappropriate applications of statistical methods in some studies. It is important for a clinician or medical researcher to be aware of this issue because misleading conclusions from inappropriate analyses will jeopardize the quality of the evidence, which in turn will influence quality of care given to patients in the future.
PMCID: PMC3360667  PMID: 22662248
8.  Ethnic Differences in Survival after Breast Cancer in South East Asia 
PLoS ONE  2012;7(2):e30995.
The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia.
Methodology/Principal Findings
Using the Singapore-Malaysia hospital-based breast cancer registry, we analyzed the association between ethnicity and mortality following breast cancer in 5,264 patients diagnosed between 1990 and 2007 (Chinese: 71.6%, Malay: 18.4%, Indian: 10.0%). We compared survival rates between ethnic groups and calculated adjusted hazard ratios (HR) to estimate the independent effect of ethnicity on survival. Malays (n = 968) presented at a significantly younger age, with larger tumors, and at later stages than the Chinese and Indians. Malays were also more likely to have axillary lymph node metastasis at similar tumor sizes and to have hormone receptor negative and poorly differentiated tumors. Five year overall survival was highest in the Chinese women (75.8%; 95%CI: 74.4%–77.3%) followed by Indians (68.0%; 95%CI: 63.8%–72.2%), and Malays (58.5%; 95%CI: 55.2%–61.7%). Compared to the Chinese, Malay ethnicity was associated with significantly higher risk of all-cause mortality (HR: 1.34; 95%CI: 1.19–1.51), independent of age, stage, tumor characteristics and treatment. Indian ethnicity was not significantly associated with risk of mortality after breast cancer compared to the Chinese (HR: 1.14; 95%CI: 0.98–1.34).
In South East Asia, Malay ethnicity is independently associated with poorer survival after breast cancer. Research into underlying reasons, potentially including variations in tumor biology, psychosocial factors, treatment responsiveness and lifestyle after diagnosis, is warranted.
PMCID: PMC3283591  PMID: 22363531
9.  Direct short-term effects of EBP teaching: change in knowledge, not in attitude; a cross-cultural comparison among students from European and Asian medical schools 
Medical Education Online  2012;17:10.3402/meo.v17i0.19623.
We report about the direct short-term effects of a Clinical Epidemiology and Evidence-based Medicine (CE-EBM) module on the knowledge, attitude, and behavior of students in the University Medical Center Utrecht (UMCU), Universitas Indonesia (UI), and University of Malaya (UM).
We used an adapted version of a 26-item validated questionnaire, including four subscales: knowledge, attitude, behavior, and future use of evidence-based practice (EBP). The four components were compared among the students in the three medical schools before the module using one-way ANOVA. At the end of the module, we measured only knowledge and attitudes. We computed Cronbach's α to assess the reliability of the responses in our population. To assess the change in knowledge and attitudes, we used the paired t-test in the comparison of scores before and after the module.
In total, 526 students (224 UI, 202 UM, and 100 UMCU) completed the questionnaires. In the three medical schools, Cronbach's α for the pre-module total score and the four subscale scores always exceeded 0.62. UMCU students achieved the highest pre-module scores in all subscales compared to UI and UM with the comparison of average (SD) score as the following: knowledge 5.04 (0.4) vs. 4.73 (0.69) and 4.24 (0.74), p<0.001; attitude 4.52 (0.64) vs. 3.85 (0.68) and 3.55 (0.63), p<0.001; behavior 2.62 (0.55) vs. 2.35 (0.71) and 2.39 (0.92), p=0.016; and future use of EBP 4.32 (0.59) vs. 4.08 (0.62) and 3.7 (0.71), p<0.01. The CE-EBM module increased the knowledge of the UMCU (from average 5.04±0.4 to 5.35±0.51; p<0.001) and UM students (from average 4.24±0.74 to 4.53±0.72; p<0.001) but not UI. The post-module scores for attitude did not change in the three medical schools.
EBP teaching had direct short-term effects on knowledge, not on attitude. Differences in pre-module scores are most likely related to differences in the system and infrastructure of both medical schools and their curriculum.
PMCID: PMC3487025  PMID: 23121993
Evidence Based Medicine; knowledge; attitude; behavior; medical students
10.  High prevalence of vitamin D insufficiency and its association with obesity and metabolic syndrome among Malay adults in Kuala Lumpur, Malaysia 
BMC Public Health  2011;11:735.
Vitamin D status, as indicated by 25-hydroxyvitamin D is inversely associated with adiposity, glucose homeostasis, lipid profiles, and blood pressure along with its classic role in calcium homeostasis and bone metabolism. It is also shown to be inversely associated with metabolic syndrome and cardiovascular diseases in western populations. However, evidence from the Asian population is limited. Therefore, we aim to study the prevalence of vitamin D insufficiency (< 50 nmol/L) and the association of 25-hydroxyvitamin D with metabolic risk factors among an existing Malay cohort in Kuala Lumpur.
This is an analytical cross sectional study. A total of 380 subjects were sampled and their vitamins D status (25-hydroxyvitamin D), fasting blood glucose, full lipid profile were assessed using venous blood. Systolic and diastolic blood pressure, weight, height and waist circumference were measured following standard protocols. Socio-demographic data such as sex, age, smoking status etc were also collected. Data was analysed using t-test, chi-square test, General Linear Model and multiple logistic regression.
Females made up 58% of the sample. The mean age of respondents was 48.5 (SD 5.2) years. Females had significantly lower mean Vitamin D levels (36.2; 95% CI: 34.5, 38.0 nmol/L) compared to males (56.2; 95% CI: 53.2, 59.2 nmol/L). Approximately 41% and 87% of males and females respectively had insufficient (< 50 nmol/L) levels of 25-hydroxyvitamin D (p < 0.001). The prevalence of Metabolic Syndrome for the whole sample was 38.4 (95% CI: 33.5, 43.3)%. In the multivariate model (adjusted for age, sex, abdominal obesity, HDL-cholesterol, diastolic blood pressure), insufficient Vitamin D status was significantly associated with 1-year age increments (OR: 0.93; 95% CI: 0.88, 0.98), being female (OR: 8.68; 95% CI: 5.08, 14.83) and abdominal obesity (OR: 2.57; 95% CI: 1.51, 4.39). Respondents with insufficient vitamin D were found to have higher odds of having Metabolic Syndrome (OR: 1.73; 95% CI: 1.02, 2.92) after adjusting for age and sex.
Our results highlight the high prevalence of vitamin D insufficiency among Malay adults in Kuala Lumpur. Vitamin D insufficiency is independently associated with younger age, female sex and greater abdominal obesity. Vitamin D insufficiency is also associated with Metabolic Syndrome.
PMCID: PMC3198705  PMID: 21943301
11.  Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: A case control study 
BMC Public Health  2011;11:333.
With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs.
A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome.
Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic syndrome. However, for ethnicity, Indians were found to have higher odds (OR = 5.5; 95%CI 1.5, 20.5) compared to Malays, with Chinese children (OR = 0.3; 95%CI 0.0, 2.7) having the lowest odds.
We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are required to prevent this problem from escalating.
PMCID: PMC3111384  PMID: 21592367
12.  The modified NCEP ATP III criteria maybe better than the IDF criteria in diagnosing Metabolic Syndrome among Malays in Kuala Lumpur 
BMC Public Health  2010;10:678.
Metabolic Syndrome is associated with increased risk for type 2 diabetes and cardiovascular diseases. However, different diagnostic criteria have been recommended by different expert groups. In Malaysia, there is a lack of research comparing these different diagnostic criteria. Therefore, it is our aim to study the concordance between the IDF and the modified NCEP ATP III definitions of Metabolic Syndrome among a Malay cohort in Kuala Lumpur; and to demonstrate if all participants have the same cardiometabolic risks.
This was an analytical cross sectional study. Ethics approval was obtained and informed consent was given by all participants. Anthropometric measurements, blood pressure, fasting blood glucose and lipid profile were taken following standard protocols.
Metabolic Syndrome was diagnosed in 41.4% and 38.2% participants using the modified NCEP and IDF criteria respectively. Among those diagnosed with Metabolic Syndrome by modified NCEP, 7.6% were missed by the IDF criteria. Participants diagnosed by the modified NCEP criteria had lower BMI and waist circumference but had higher cardiometabolic risks than those diagnosed with both criteria. Their blood pressure, glucose, total cholesterol and triglyceride were more adverse than the IDF group. This demonstrated that central obesity may not be a prerequisite for the development of increased cardiometabolic risks within this Malay cohort.
Metabolic syndrome is common in this Malay cohort regardless of the criterion used. The modified NCEP ATP III criteria may be more suitable in diagnosis of metabolic syndrome for this Malay cohort.
PMCID: PMC2989964  PMID: 21054885
13.  Prevalence and correlates of physical disability and functional limitation among community dwelling older people in rural Malaysia, a middle income country 
BMC Public Health  2010;10:492.
The prevalence and correlates of physical disability and functional limitation among older people have been studied in many developed countries but not in a middle income country such as Malaysia. The present study investigated the epidemiology of physical disability and functional limitation among older people in Malaysia and compares findings to other countries.
A population-based cross sectional study was conducted in Alor Gajah, Malacca. Seven hundred and sixty five older people aged 60 years and above underwent tests of functional limitation (Tinetti Performance Oriented Mobility Assessment Tool). Data were also collected for self reported activities of daily living (ADL) using the Barthel Index (ten items). To compare prevalence with other studies, ADL disability was also defined using six basic ADL's (eating, bathing, dressing, transferring, toileting and walking) and five basic ADL's (eating, bathing, dressing, transferring and toileting).
Ten, six and five basic ADL disability was reported by 24.7% (95% CI 21.6-27.9), 14.4% (95% CI 11.9-17.2) and 10.6% (95% CI 8.5-13.1), respectively. Functional limitation was found in 19.5% (95% CI 16.8-22.5) of participants. Variables independently associated with 10 item ADL disability physical disability, were advanced age (≥ 75 years: prevalence ratio (PR) 7.9; 95% CI 4.8-12.9), presence of diabetes (PR 1.8; 95% CI 1.4-2.3), stroke (PR 1.5; 95% CI 1.1-2.2), depressive symptomology (PR 1.3; 95% CI 1.1-1.8) and visual impairment (blind: PR 2.0; 95% CI 1.1-3.6). Advancing age (≥ 75 years: PR 3.0; 95% CI 1.7-5.2) being female (PR 2.7; 95% CI 1.2-6.1), presence of arthritis (PR 1.6; 95% CI 1.2-2.1) and depressive symptomology (PR 2.0; 95% CI 1.5-2.7) were significantly associated with functional limitation.
The prevalence of physical disability and functional limitation among older Malaysians appears to be much higher than in developed countries but is comparable to developing countries. Associations with socio-demographic and other health related variables were consistent with other studies.
PMCID: PMC2933720  PMID: 20716377

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