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Fulltext Paradoxical Manifestation is Common in HIV-negative Tuberculous Meningitis

Tai ML, Nor HM, Kadir KA, Viswanathan S, Rahmat K, Zain NR, et al.

Medicine (Baltimore), 2016 Jan;95(1):e1997.
PMID: 26735523 DOI: 10.1097/MD.0000000000001997

Paradoxical manifestation is worsening of pre-existing tuberculous lesion or appearance of new lesions in patients whose condition initially improved with antituberculous treatment. Our hypothesis was that paradoxical manifestation in non-HIV tuberculous meningitis (TBM) patients was underestimated and this could contribute to patients' prognosis. This was the first systemic study of paradoxical manifestation in HIV-negative TBM patients. Between 2009 and 2014, TBM patients were studied prospectively in 2 hospitals. Clinical features, cerebrospinal fluid, and radiological findings were monitored. Paradoxical manifestation was divided into definite (4 weeks or more) and probable (between 14 and 27 d) after commencement of antituberculous treatment. Forty-one non-HIV TBM patients were recruited. Definite paradoxical manifestation occurred in 23/41 (56%) of the patients. Time to onset of paradoxical manifestation was between 28 days and 9 months, and majority was between 28 and 50 days. Neuroimaging manifestation in the brain (22/41 patients, 54%) and clinical manifestation (22/41 patients, 54%) were most commonly seen, followed by cerebrospinal fluid manifestation (7/41 patients, 17%). Neuroimaging changes most commonly seen were worsening of leptomeningeal enhancement, new infarcts, new tuberculomas, and enlargement of tuberculoma. Initial Computed Tomography Angiography/magnetic resonance angiography brain showed vasculitis in 14 patients, with 2 (12.5%) showing paradoxical vasculitis during follow-up. Recurrence of the paradoxical manifestation was seen in 7/23 (30%) of the patients. More than half (14/23, 61%) of the patients improved, 6 (26%) patients died, and 3 (13%) patients had persistent neurological deficit. Paradoxical manifestation was very common in non-HIV TBM patients. Neuroimaging paradoxical manifestation of 2-4 weeks may not be paradoxical manifestation but could be delayed treatment response.
Fulltext Demographic and Socioeconomic Factors Influencing Public Attitudes Toward a Presumed Consent System for Organ Donation Without and With a Priority Allocation Scheme

Tumin M, Tafran K, Mutalib MA, Satar NM, Said SM, Adnan WA, et al.

Medicine (Baltimore), 2015 Oct;94(42):e1713.
PMID: 26496282 DOI: 10.1097/MD.0000000000001713

The influence of demographic and socioeconomic factors on the public's attitude towards a presumed consent system (PCS) of organ donation was estimated in 2 scenarios: without and with a priority allocation scheme (PAS). Self-administered questionnaires were completed by 775 respondents. Using multiple logistic regressions, respondents' objections to donating organs in both scenarios were estimated. In total, 63.9% of respondents would object to donating under a PCS, whereas 54.6% would object under a PCS with a PAS. Respondents with pretertiary education were more likely to object than were respondents with tertiary education, in both the first (adjusted odds ratio [AOR] = 1.615) and second (AOR = 1.728) scenarios. Young respondents were less likely to object than were middle-aged respondents, in both the first (AOR = 0.648) and second (AOR = 0.572) scenarios. Respondents with mid-ranged personal monthly income were more likely to object than were respondents with low income, in both the first (AOR = 1.994) and second (AOR = 1.519) scenarios. It does not seem that Malaysia is ready to implement a PCS. The educational level, age, and income of the broader public should be considered if a PCS, without or with a PAS, is planned for implementation in Malaysia.
Fulltext The Effect of Malaria and HIV Co-Infection on Anemia: A Meta-Analysis

Naing C, Sandhu NK, Wai VN

Medicine (Baltimore), 2016 Apr;95(14):e3205.
PMID: 27057848 DOI: 10.1097/MD.0000000000003205

Malaria and human immunodeficiency virus (HIV) infections are globally important public health concerns. The objectives of this study were (i) to determine the prevalence of malaria and HIV co-infections in people living in endemic countries, and (ii) to assess the effect of co-infection on anemia.Studies were searched on electronic databases including PubMed, Embase, Medline, Google Scholar, and African Journals Online. Observational studies, assessing the prevalence of co-infection and reporting its association with anemia, were included. The methodological quality of included studies was assessed using a tool called the risk of bias assessment for non-randomized studies. Heterogeneity among studies was investigated with the I-square test. Pooled prevalence of the co-infection and its 95% confidence interval (CI) were estimated using the random-effect model, reflected on heterogeneity among studies. Summary odds ratio (OR), summary standardized mean difference (SMD), and their corresponding 95% CIs were estimated, as appropriate. Subgroup analysis and meta-regression were performed for robustness of results. Publication bias was assessed by visualization of a funnel plot.Twenty-three studies were included in the present study. Overall, the pooled prevalence of co-infection was 19% (95% CI: 15-23%, I: 98.1%), showing 26% (95% CI: 20-32%, I: 98.7%) in adults, 12% (95% CI: 7-17%, I: 95.0) in pregnant women, and 9% (95% CI: 6-11%, I: 68.6%) in children. Anemia was comparable between the monoinfected and co-infected adults (summary OR: 1.49, 95% CI: 0.93-2.37) and increased by 49% in co-infected pregnant women (summary OR: 1.49, 95% CI: 1.14-1.94). The mean hemoglobin concentration was significantly lower in the co-infected group than the monoinfected group (summary SMD: -0.47, 95% CI: -0.61 to -0.33). The results of meta-regression on the prevalence of co-infection using the publication year and total population as covariates showed the I value remained high implying a de facto random distribution of heterogeneity. An asymmetrical funnel plot indicated the presence of publication bias. Due to heterogeneity of the studies in this review, the results have to be interpreted with caution.The findings of this study suggest that the prevalence of malaria and HIV co-infection, particularly in pregnant women, requires special attention from healthcare personnel. Better understanding of the co-infection is crucial for designing treatment strategies. Future well-powered, prospective designs assessing the interaction between malaria and HIV are recommended.
Fulltext Shearwave Elastography Increases Diagnostic Accuracy in Characterization of Breast Lesions

Ng WL, Rahmat K, Fadzli F, Rozalli FI, Mohd-Shah MN, Chandran PA, et al.

Medicine (Baltimore), 2016 Mar;95(12):e3146.
PMID: 27015196 DOI: 10.1097/MD.0000000000003146

The purpose of this study was to investigate the diagnostic efficacy of shearwave elastography (SWE) in differentiating between benign and malignant breast lesions.One hundred and fifty-nine lesions were assessed using B-mode ultrasound (US) and SWE parameters were recorded (Emax, Emean, Emin, Eratio, SD). SWE measurements were then correlated with histopathological diagnosis.The final sample contained 85 benign and 74 malignant lesions. The maximum stiffness (Emax) with a cutoff point of ≥ 56.0 kPa (based on ROC curves) provided sensitivity of 100.0%, specificity of 97.6%, positive predictive value (PPV) of 97.4%, and negative predictive value (NPV) of 100% in detecting malignant lesions. A cutoff of ≥80 kPa managed to downgrade 95.5% of the Breast Imaging-Reporting and Data System (BI-RADS) 4a lesions to BI-RADS 3, negating the need for biopsy. Using a combination of BI-RADS and SWE, the authors managed to improve the PPV from 2.3% to 50% in BI-RADS 4a lesions.SWE of the breast provides highly specific and sensitive quantitative values that are beneficial in the characterization of breast lesions. Our results showed that Emax is the most accurate value for differentiating benign from malignant lesions.
Factors associated with medical and nursing students' willingness to donate organs

Tumin M, Tafran K, Tang LY, Chong MC, Mohd Jaafar NI, Mohd Satar N, et al.

Medicine (Baltimore), 2016 Mar;95(12):e3178.
PMID: 27015207 DOI: 10.1097/MD.0000000000003178

Malaysia suffers from a chronic shortage of human organs for transplantation. Medical and nursing students (MaNS) are future health professionals and thus their attitude toward organ donation is vital for driving national donation rates. This study investigates MaNS' willingness to donate organs upon death and the factors influencing their willingness. A cross-sectional design was used with a sample of 500 students (264 medical and 236 nursing) at the University of Malaya. A self-administrated questionnaire was used. The responses were analyzed by using descriptive statistics and multiple logistic regression. Of all respondents, 278 (55.6%) were willing to donate organs upon death, while the remaining 222 (44.4%) were unwilling to donate. Only 44 (8.8%) had donor cards. The multiple logistic regression revealed that the minorities ethnic group was more willing to donate organs than Malay respondents (adjusted odds ratio [aOR] = 1.98, P = 0.010). In addition, medical students were more willing to donate than nursing students (aOR = 2.53, P = 0.000). Respondents who have a family member with a donor card were more willing to donate than respondents who do not (aOR = 3.48, P = 0.006). MaNS who believed that their religion permits deceased donation were more willing to donate than their counterparts (aOR = 4.96, P = 0.000). Household income and sex were not significant predictors of MaNS' willingness to donate organs upon death. MaNS have moderate willingness, but low commitment toward deceased organ donation. Strategies for improving MaNS' attitude should better educate them on organ donation, targeting the most the Malay and nursing students, and should consider the influence of family attitude and religious permissibility on MaNS' willingness.
Study site: University of Malaya, Kuala Lumpur, Malaysia
Fulltext Evaluation of Two New Indices of Blood Pressure Variability Using Postural Change in Older Fallers

Goh CH, Ng SC, Kamaruzzaman SB, Chin AV, Poi PJ, Chee KH, et al.

Medicine (Baltimore), 2016 May;95(19):e3614.
PMID: 27175670 DOI: 10.1097/MD.0000000000003614

To evaluate the utility of blood pressure variability (BPV) calculated using previously published and newly introduced indices using the variables falls and age as comparators.While postural hypotension has long been considered a risk factor for falls, there is currently no documented evidence on the relationship between BPV and falls.A case-controlled study involving 25 fallers and 25 nonfallers was conducted. Systolic (SBPV) and diastolic blood pressure variability (DBPV) were assessed using 5 indices: standard deviation (SD), standard deviation of most stable continuous 120 beats (staSD), average real variability (ARV), root mean square of real variability (RMSRV), and standard deviation of real variability (SDRV). Continuous beat-to-beat blood pressure was recorded during 10 minutes' supine rest and 3 minutes' standing.Standing SBPV was significantly higher than supine SBPV using 4 indices in both groups. The standing-to-supine-BPV ratio (SSR) was then computed for each subject (staSD, ARV, RMSRV, and SDRV). Standing-to-supine ratio for SBPV was significantly higher among fallers compared to nonfallers using RMSRV and SDRV (P = 0.034 and P = 0.025). Using linear discriminant analysis (LDA), 3 indices (ARV, RMSRV, and SDRV) of SSR SBPV provided accuracies of 61.6%, 61.2%, and 60.0% for the prediction of falls which is comparable with timed-up and go (TUG), 64.4%.This study suggests that SSR SBPV using RMSRV and SDRV is a potential predictor for falls among older patients, and deserves further evaluation in larger prospective studies.
Fulltext Healthy Lifestyle and Risk of Cancer in the European Prospective Investigation Into Cancer and Nutrition Cohort Study

McKenzie F, Biessy C, Ferrari P, Freisling H, Rinaldi S, Chajès V, et al.

Medicine (Baltimore), 2016 Apr;95(16):e2850.
PMID: 27100409 DOI: 10.1097/MD.0000000000002850

It has been estimated that at least a third of the most common cancers are related to lifestyle and as such are preventable. Key modifiable lifestyle factors have been individually associated with cancer risk; however, less is known about the combined effects of these factors.This study generated a healthy lifestyle index score (HLIS) to investigate the joint effect of modifiable factors on the risk of overall cancers, alcohol-related cancers, tobacco-related cancers, obesity-related cancers, and reproductive-related cancers. The study included 391,608 men and women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The HLIS was constructed from 5 factors assessed at baseline (diet, physical activity, smoking, alcohol consumption, and anthropometry) by assigning scores of 0 to 4 to categories of each factor, for which higher values indicate healthier behaviors. Hazard ratios (HR) were estimated by Cox proportional regression and population attributable fractions (PAFs) estimated from the adjusted models.There was a 5% lower risk (adjusted HR 0.952, 95% confidence interval (CI): 0.946, 0.958) of all cancers per point score of the index for men and 4% (adjusted HR 0.961, 95% CI: 0.956, 0.966) for women. The fourth versus the second category of the HLIS was associated with a 28% and 24% lower risk for men and women respectively across all cancers, 41% and 33% for alcohol-related, 49% and 46% for tobacco-related, 41% and 26% for obesity-related, and 21% for female reproductive cancers.Findings suggest simple behavior modifications could have a sizeable impact on cancer prevention, especially for men.
Fulltext Strategies to Make Ramadan Fasting Safer in Type 2 Diabetics: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Observational Studies

Lee SW, Lee JY, Tan CS, Wong CP

Medicine (Baltimore), 2016 Jan;95(2):e2457.
PMID: 26765440 DOI: 10.1097/MD.0000000000002457

Ramadan is the holy month for Muslims whereby they fast from predawn to after sunset and is observed by all healthy Muslim adults as well as a large population of type 2 diabetic Muslims.To determine the comparative effectiveness of various strategies that have been used for type 2 diabetic Muslim who fast during Ramadan.A systematic review and network meta-analysis of randomized controlled studies (RCT) as well as observational studies for patients with type 2 diabetes who fasted during Ramadan was conducted. Eight databases were searched from January 1980 through October 2015 for relevant studies. Two reviewers independently screened and assessed study for eligibility, assessed the risk of bias, and extracted relevant data. A network meta-analysis for each outcome was fitted separately, combining direct and indirect evidence for each comparison.Twenty-nine studies, 16 RCTs and 13 observational studies each met the inclusion criteria. The most common strategy used was drug changes during the Ramadan period, which found that the use of DPP-4 (Dipeptidyl peptidase inhibitor -4) inhibitors were associated with a reduction in incidence of experiencing hypoglycemia during Ramadan in both RCTs (pooled relative risk: 0.56; 95% confidence interval: 0.44-0.72) as well as in observational studies (pooled relative risk: 0.27; 0.09-0.75). Ramadan-focused education was shown to be beneficial in reducing hypoglycemia in observational studies but not RCTs (0.25 versus 1.00). Network meta-analyses suggest that incretin mimetics can reduce the risk of hypoglycemia by nearly 1.5 times.The newer antidiabetic agents appear to lower the risk of hypoglycemia and improved glycemic control when compared with sulfonylureas. Ramadan-focused education shows to be a promising strategy but more rigorous examination from RCTs are required.
Fulltext Hypertension in Malaysia: An analysis of trends from the national surveys 1996 to 2011

Naing C, Yeoh PN, Wai VN, Win NN, Kuan LP, Aung K

Medicine (Baltimore), 2016 Jan;95(2):e2417.
PMID: 26765422 DOI: 10.1097/MD.0000000000002417

This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia.The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable.Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%-35.8%) in 1996, 42.6% (37.5%-43.5%) in 2006, and 43.5% (40.4%-46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P
Fulltext A systematic review and meta-analysis of medical students' perspectives on the engagement in research

Naing C, Wai VN, Durham J, Whittaker MA, Win NN, Aung K, et al.

Medicine (Baltimore), 2015 Jul;94(28):e1089.
PMID: 26181541 DOI: 10.1097/MD.0000000000001089

Engaging students in active learning lies at the center of effective higher education. In medical schools, students' engagement in learning and research has come under increasing attention. The objective of this study was to synthesize evidence on medical students' perspectives on the engagement in research. We performed a systematic review and meta-analysis. Relevant studies were searched in electronic databases. The methodological quality of the included studies was assessed. Overall, 14 observational studies (with 17 data sets) were included. In general, many studies did not use the same questionnaires and the outcome measurements were not consistently reported; these presented some difficulties in pooling the results. Whenever data permitted, we performed pooled analysis for the 4 education outcomes. A Bayesian meta-analytical approach was supplemented as a measure of uncertainty. A pooled analysis showed that 74% (95% confidence interval [CI]: 1.57%-11.07%; I2: 95.2%) of those students who engaged in research (while at the medical school) had positive attitudes toward their research experiences, whereas 49.5% (95% CI: 36.4%-62.7%; I2: 93.4%) had positive attitudes toward the study of medical sciences, 62.3% (95% CI: 46.7%-77.9%; I2: 96.3%) had self-reported changes in their practices, and 64% (95% CI: 30.8%-96.6%; I2: 98.5%) could have published their work. There was substantial heterogeneity among studies. We acknowledged the caveats and the merit of the current review. Findings showed that engagement in research resulted in favorable reactions toward research and academic learning. Future well-designed studies using standardized research tools on how to engage students in research are recommended.
Fulltext Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds

Prando C, Samarina A, Bustamante J, Boisson-Dupuis S, Cobat A, Picard C, et al.

Medicine (Baltimore), 2013 Mar;92(2):109-122.
PMID: 23429356 DOI: 10.1097/MD.0b013e31828a01f9

Autosomal recessive interleukin (IL)-12 p40 (IL-12p40) deficiency is a rare genetic etiology of mendelian susceptibility to mycobacterial disease (MSMD). We report the genetic, immunologic, and clinical features of 49 patients from 30 kindreds originating from 5 countries (India, Iran, Pakistan, Saudi Arabia, and Tunisia). There are only 9 different mutant alleles of the IL12B gene: 2 small insertions, 3 small deletions, 2 splice site mutations, and 1 large deletion, each causing a frameshift and leading to a premature stop codon, and 1 nonsense mutation. Four of these 9 variants are recurrent, affecting 25 of the 30 reported kindreds, due to founder effects in specific countries. All patients are homozygous and display complete IL-12p40 deficiency. As a result, the patients lack detectable IL-12p70 and IL-12p40 and have low levels of interferon gamma (IFN-γ). The clinical features are characterized by childhood onset of bacille Calmette-Guérin (attenuated Mycobacterium bovis strain) (BCG) and Salmonella infections, with recurrences of salmonellosis (36.4%) more common than recurrences of mycobacterial disease (25%). BCG vaccination led to BCG disease in 40 of the 41 patients vaccinated (97.5%). Multiple mycobacterial infections were rare, observed in only 3 patients, whereas the association of salmonellosis and mycobacteriosis was observed in 9 patients. A few other infections were diagnosed, including chronic mucocutaneous candidiasis (n = 3), nocardiosis (n = 2), and klebsiellosis (n = 1). IL-12p40 deficiency has a high but incomplete clinical penetrance, with 33.3% of genetically affected relatives of index cases showing no symptoms. However, the prognosis is poor, with mortality rates of up to 28.6%. Overall, the clinical phenotype of IL-12p40 deficiency closely resembles that of interleukin 12 receptor β1 (IL-12Rβ1) deficiency. In conclusion, IL-12p40 deficiency is more common than initially thought and should be considered worldwide in patients with MSMD and other intramacrophagic infectious diseases, salmonellosis in particular.
Fulltext Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis

Sakthiswary R, D'Cruz D

Medicine (Baltimore), 2014 Oct;93(16):e86.
PMID: 25310743 DOI: 10.1097/MD.0000000000000086

Prepared from the plasma of thousands of blood donors, therapeutic intravenous immunoglobulin (IVIg) mostly consists of human polyspecific immunoglobulin G (IgG). The use of IVIg in systemic lupus erythematosus (SLE) is still considered experimental without any clear indications. The purpose of this systematic review is, therefore, to evaluate the available evidence to determine the therapeutic role of IVIg in SLE. A comprehensive, computerised search was performed in the MEDLINE (Pubmed), Scopus, EMBASE, and Cochrane controlled trials. The study eligibility criteria were randomized controlled trials, and prospective and retrospective observational studies that examined the efficacy of IVIg in adult patients with SLE who were considered the participants.IVIg therapy was the mode of intervention in these patients. Data abstracted included the study design, study population, changes in the disease activity scores (Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure, and Lupus Activity Index-Pregnancy), steroid dose, complement levels, autoantibodies, and renal function. Thereafter, data analysis established statistical procedures for meta-analysis. Thirteen studies (including 3 controlled and 10 observational) were eligible for inclusion. There was significant reduction in the SLE disease activity scores with IVIg therapy with a standard mean difference of 0.584 (P = 0.002, 95% confidence interval [CI] 0.221-0.947). In terms of rise in complement levels, the response rate was 30.9% (P = 0.001, 95 CI 22.1-41.3). The effects of IVIg on other clinical outcome measures including anti-double-stranded DNA, antinuclear antibody, average steroid dose, and renal function could not be determined because of the limited numbers of trials. The limitations of this review were lack of well-designed controlled trials with adequate sample size on the use of IVIg in SLE. In conclusion, the use of IVIg is associated with significant reduction in SLE disease activity and improvement in complement levels.
Fulltext Prevalence of and risk factors for anal high-risk HPV among HIV-negative and HIV-positive MSM and transgender women in three countries at South-East Asia

Somia IKA, Teeratakulpisarn N, Jeo WS, Yee IA, Pankam T, Nonenoy S, et al.

Medicine (Baltimore), 2018 Mar;97(10):e9898.
PMID: 29517698 DOI: 10.1097/MD.0000000000009898

This study aimed to assess the prevalence of and associated risk factors for anal high-risk human papillomavirus (hr-HPV) infection among men who have sex with men (MSM) and transgender women (TGW) in Indonesia, Thailand, and Malaysia.This was baseline data from a prospective cohort study with clinic sites in Jakarta and Bali (Indonesia), Bangkok (Thailand), and Kuala Lumpur (Malaysia).MSM and TGW aged 18 years and older from Indonesia, Thailand, and Malaysia were enrolled. Demographic and behavioral characteristics were assessed, and anal samples were collected for HPV genotyping. Multivariate logistic regression models were used to assess risk factors for anal hr-HPV overall and among HIV-positive participants.A total of 392 participants were enrolled, and 48 were TGW. As many as 245 were HIV-positive, and 78.0% of the participants were on combination antiretroviral therapy (cART). Median CD4 count was 439 cells/mm and 68.2% had undetectable HIV-RNA. HIV-positive participants had significantly more hr-HPV compared to HIV-negative participants (76.6% vs 53.5%, P
Fulltext The predictive accuracy of PREDICT: a personalized decision-making tool for Southeast Asian women with breast cancer

Wong HS, Subramaniam S, Alias Z, Taib NA, Ho GF, Ng CH, et al.

Medicine (Baltimore), 2015 Feb;94(8):e593.
PMID: 25715267 DOI: 10.1097/MD.0000000000000593

Web-based prognostication tools may provide a simple and economically feasible option to aid prognostication and selection of chemotherapy in early breast cancers. We validated PREDICT, a free online breast cancer prognostication and treatment benefit tool, in a resource-limited setting. All 1480 patients who underwent complete surgical treatment for stages I to III breast cancer from 1998 to 2006 were identified from the prospective breast cancer registry of University Malaya Medical Centre, Kuala Lumpur, Malaysia. Calibration was evaluated by comparing the model-predicted overall survival (OS) with patients' actual OS. Model discrimination was tested using receiver-operating characteristic (ROC) analysis. Median age at diagnosis was 50 years. The median tumor size at presentation was 3 cm and 54% of patients had lymph node-negative disease. About 55% of women had estrogen receptor-positive breast cancer. Overall, the model-predicted 5 and 10-year OS was 86.3% and 77.5%, respectively, whereas the observed 5 and 10-year OS was 87.6% (difference: -1.3%) and 74.2% (difference: 3.3%), respectively; P values for goodness-of-fit test were 0.18 and 0.12, respectively. The program was accurate in most subgroups of patients, but significantly overestimated survival in patients aged <40 years, and in those receiving neoadjuvant chemotherapy. PREDICT performed well in terms of discrimination; areas under ROC curve were 0.78 (95% confidence interval [CI]: 0.74-0.81) and 0.73 (95% CI: 0.68-0.78) for 5 and 10-year OS, respectively. Based on its accurate performance in this study, PREDICT may be clinically useful in prognosticating women with breast cancer and personalizing breast cancer treatment in resource-limited settings.
Fulltext Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a population-based case-control study

Chun-Lai T, Murad S, Erlandsson MC, Hussein H, Sulaiman W, Dhaliwal JS, et al.

Medicine (Baltimore), 2015 Jan;94(4):e468.
PMID: 25634192 DOI: 10.1097/MD.0000000000000468

Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.
Fulltext The influence of socioeconomic and demographic variables on willingness to donate cadaveric human organs in Malaysia

Rasiah R, Manikam R, Chandarsekaran SK, Thangiah G, Puspharajan S, Swaminathan D

Medicine (Baltimore), 2014 Nov;93(23):e126.
PMID: 25415665 DOI: 10.1097/MD.0000000000000126

The growing shortage in human organs has raised serious concerns. To address this problem, we examine in this article the association between demographic and socioeconomic factors, and respondents' willingness to donate cadaveric organs using a large survey of Malaysian adults aged 18 years and above.A convenience sampling method was used to extract information from a total of 10,350 participants from Metropolitan Kuala Lumpur over the period of April 2, 2013 to February 29, 2014. In addition to analyzing the data using incidence of willingness to donate by demographic and socioeconomic factors, we carried out logistic regression analysis to estimate the odds ratio of respondents' willingness to become cadaveric organ donors controlling for age.About less than a third of the participants pledged to donate their organs upon death with women (35.6%) showing a higher incidence compared with men (33.2%). The Chinese (35.7%) and Malays (35.0%) pledged to contribute more than the Indians (31.6%) and the logistic regressions show that Malays (adjusted odds ration [OR] = 1.18) and Chinese (adjusted OR = 1.21) are more likely to donate than Indians (reference group). The results by religion were significant among Muslims and Hindus but not Buddhists. The likelihood of Muslims donating was the lowest (adjusted OR = 0.26). Income was also highly significant but the relationship with willingness to donate was negative. Against tertiary education, all other occupations were significant. However, the respondents with primary education enjoyed the highest adjusted OR (5.46) whereas that of secondary (0.48) and higher secondary (0.83) education was low. Among occupations (against supervisory, clerical, and direct workers), it was significant only among the unemployed and managers with adjusted OR of 1.50 and 1.58, respectively.Sex, education, ethnicity, religion, and income are important demographic and socioeconomic influences on the likelihood of Malaysians willing to become cadaveric organ donors. The Malaysian evidence suggests that awareness programs should be targeted at men, Muslims, Hindus, Malays, and the rich more than the others.
Fulltext Prevalence and risk factors of hypertension in myanmar: a systematic review and meta-analysis

Naing C, Aung K

Medicine (Baltimore), 2014 Nov;93(21):e100.
PMID: 25380081 DOI: 10.1097/MD.0000000000000100

Hypertension (HPT) is the most common condition seen in primary care that can lead to health consequences and death if not detected early and treated appropriately.This study aimed to synthesize the prevalence, awareness, and control of HPT, and investigate the risk factors for HPT in Myanmar.We performed a meta-analysis of observational studies. Relevant studies were searched in electronic databases. The methodological quality of the included studies was assessed in 3 domains: selection bias, measurement bias, and bias related to data analysis. The overall prevalence and proportions was calculated using random-effect model of DerSimonian-Laird method. To identify the risk factors for HPT in Myanmar, we entered the ratio measures of the (adjusted) effect as a log odds ratio (OR) and the standard error of the log OR using generic inverse-variance weighting method. For stability of results, we performed leave-one-study-out sensitivity analysis by omitting individual studies one at a time from the meta-analysis.Seven studies (n = 20,901) were included in this analysis. Overall prevalence of HPT in Myanmar was 22% (95% confidence interval (CI): 14%-31.7%, I: 99.6%), stratified as 21.5% (95% CI: 14.1%-29.9%, I: 98.7%) in men and 22.7% (95% CI: 10.8%-34.6%, I: 99.5%) in women. Overall, prevalence of HPT increased with an advancing age of the participants. The proportions of awareness and controlled HPT were 55% (95% CI: 43%-67%, I: 97.7%) and 11% (95% CI: 6%-15%, I: 93.8%), respectively. A weak but significant association was observed between HPT and alcohol drinking (summary OR: 1.38, 95% CI: 1.14%-1.65, I: 0%) and smoking (summary OR: 1.32, 95% CI: 1.0%-1.74, I: 50%). In sensitivity analysis, when a study that made confirmation of HPT by the former World Health Organization criteria was dropped, the prevalence increased to 26% (95% CI: 20.8%-32.1%, I: 98.1%).HPT was considerably prevalent in Myanmar, while the levels of awareness and controlled HPT were low. Health promotion strategy tailored to the education on modifiable risk factors and establishment of blood pressure screening in primary health care context would be of immense value. Upcoming well-powered studies, using the standardized research design and covering more regions of the country are recommended.
Fulltext Clarifying the debate on population-based screening for breast cancer with mammography: A systematic review of randomized controlled trials on mammography with Bayesian meta-analysis and causal model

Chen TH, Yen AM, Fann JC, Gordon P, Chen SL, Chiu SY, et al.

Medicine (Baltimore), 2017 Jan;96(3):e5684.
PMID: 28099330 DOI: 10.1097/MD.0000000000005684

BACKGROUND: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality.
METHODS: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes.
RESULTS: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24-42%) and 13% (95% CI: 6-20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively.
CONCLUSION: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.
Fulltext The effectiveness of culturally tailored video narratives on medication understanding and use self-efficacy among stroke patients: A randomized controlled trial study protocol

Appalasamy JR, Tha KK, Quek KF, Ramaiah SS, Joseph JP, Md Zain AZ

Medicine (Baltimore), 2018 Jun;97(22):e10876.
PMID: 29851804 DOI: 10.1097/MD.0000000000010876

INTRODUCTION: A substantial number of the world's population appears to end with moderate to severe long-term disability after stroke. Persistent uncontrolled stroke risk factor leads to unpredicted recurrent stroke event. The increasing prevalence of stroke across ages in Malaysia has led to the adaptation of medication therapy adherence clinic (MTAC) framework. The stroke care unit has limited patient education resources especially for patients with medication understanding and use self-efficacy. Nevertheless, only a handful of studies have probed into the effectiveness of video narrative at stroke care centers.
METHOD: This is a behavioral randomized controlled trial of patient education intervention with video narratives for patients with stroke lacking medication understanding and use self-efficacy. The study will recruit up to 200 eligible stroke patients at the neurology tertiary outpatient clinic, whereby they will be requested to return for follow-up approximately 3 months once for up to 12 months. Consenting patients will be randomized to either standard patient education care or intervention with video narratives. The researchers will ensure control of potential confounding factors, as well as unbiased treatment review with prescribed medications only obtained onsite.
RESULTS: The primary analysis outcomes will reflect the variances in medication understanding and use self-efficacy scores, as well as the associated factors, such as retention of knowledge, belief and perception changes, whereas stroke risk factor control, for example, self-monitoring and quality of life, will be the secondary outcomes.
DISCUSSION AND CONCLUSION: The study should be able to determine if video narrative can induce a positive behavioral change towards stroke risk factor control via enhanced medication understanding and use self-efficacy. This intervention is innovative as it combines health belief, motivation, and role model concept to trigger self-efficacy in maintaining healthy behaviors and better disease management.
TRIAL REGISTRATION: ACTRN (12618000174280).
Fulltext Standing beat-to-beat blood pressure variability is reduced among fallers in the Malaysian Elders Longitudinal Study

Goh CH, Ng SC, Kamaruzzaman SB, Chin AV, Tan MP

Medicine (Baltimore), 2017 Oct;96(42):e8193.
PMID: 29049203 DOI: 10.1097/MD.0000000000008193

The aim of this study was to determine the relationship between falls and beat-to-beat blood pressure (BP) variability.Continuous noninvasive BP measurement is as accurate as invasive techniques. We evaluated beat-to-beat supine and standing BP variability (BPV) using time and frequency domain analysis from noninvasive continuous BP recordings.A total of 1218 older adults were selected. Continuous BP recordings obtained were analyzed to determine standard deviation (SD) and root mean square of real variability (RMSRV) for time domain BPV and fast-Fourier transform low frequency (LF), high frequency (HF), total power spectral density (PSD), and LF:HF ratio for frequency domain BPV.Comparisons were performed between 256 (21%) individuals with at least 1 fall in the past 12 months and nonfallers. Fallers were significantly older (P = .007), more likely to be female (P = .006), and required a longer time to complete the Timed-Up and Go test (TUG) and frailty walk test (P ≤ .001). Standing systolic BPV (SBPV) was significantly lower in fallers compared to nonfallers (SBPV-SD, P = .016; SBPV-RMSRV, P = .033; SBPV-LF, P = .003; SBPV-total PSD, P = .012). Nonfallers had significantly higher supine to standing ratio (SSR) for SBPV-SD, SBPV-RMSRV, and SBPV-total PSD (P = .017, P = .013, and P = .009). In multivariate analyses, standing BPV remained significantly lower in fallers compared to nonfallers after adjustment for age, sex, diabetes, frailty walk, and supine systolic BP. The reduction in frequency-domain SSR among fallers was attenuated by supine systolic BP, TUG, and frailty walk.In conclusion, reduced beat-to-beat BPV while standing is independently associated with increased risk of falls. Changes between supine and standing BPV are confounded by supine BP and walking speed.

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