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  1. Nhidza AF, Naicker T, Stray-Pedersen B, Gumbo F, Chisango T, Sibanda E, et al.
    Afr J Reprod Health, 2018 Sep;22(3):43-50.
    PMID: 30381931 DOI: 10.29063/ajrh2018/v22i3.5
    This study aimed at investigating the maternal characteristics that in turn influence the immunological status of infants in asymptomatic enteric pathogen carriers in mother baby pairs (MBPs) in a high HIV burdened population in Harare, Zimbabwe. BIOPLEX immunoassay was used to analyse serum samples from 39 MBPs for 27 cytokines and 6 immunoglobulins. The MBP were purposively selected based on HIV infection and Entamoeba histolytica carriage. Logistic regression was used to identify any link between maternal demographic and clinical data with infant cytokine and immunoglobulin levels. Maternal E. histolytica carriers were more likely to have infants with low levels of IL-12p70, FGF-basic, GM-CSF and TNF-α cytokines (OR: 0.14; 95% CI: 0.03-0.79) and high levels of IgA immunoglobulin (OR: 8.1; 95% CI: 1.45-45.06). HIV infected mothers were more likely to have infants with low levels of IgG2 (OR: 0.24; 95% CI: 0.06-1.00) and IgA (OR: 0.22; 95% CI: 0.05-0.90) immunoglobulins. Notably, it was highly likely to deliver infants with low IgG4 levels (OR: 0.24; 95% CI: 0.06-1.02) for maternal mean age above 30.38 years (Standard deviation 6.09) though not significant (p=0.05). Maternal E. histolytica asymptomatic carriage, and HIV-infection status result in low levels of pro-inflammatory cytokines IL-12p70, FGF-basic, GM-CSF and TNF-α and immunoglobulins IgG2, IgG4 and IgA on their infants.
    Matched MeSH terms: Infectious Disease Transmission, Vertical/statistics & numerical data*
  2. Bartlett AW, Lumbiganon P, Jamal Mohamed TA, Lapphra K, Muktiarti D, Du QT, et al.
    J Acquir Immune Defic Syndr, 2019 12 15;82(5):431-438.
    PMID: 31714422 DOI: 10.1097/QAI.0000000000002184
    BACKGROUND: Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions.

    SETTING: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.

    METHODS: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.

    RESULTS: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.

    CONCLUSIONS: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.

    Matched MeSH terms: Infectious Disease Transmission, Vertical*
  3. Yusoff FM, Kajikawa M, Matsui S, Hashimoto H, Kishimoto S, Maruhashi T, et al.
    Sci Rep, 2019 05 22;9(1):7711.
    PMID: 31118440 DOI: 10.1038/s41598-019-44176-5
    Critical limb ischemia (CLI) is associated with a high risk of limb amputation. It has been shown that cell therapy is safe and has beneficial effects on ischemic clinical symptoms in patients with CLI. The aim of this study was to further investigate the outcomes of intramuscular injection of autologous bone-marrow mononuclear cells (BM-MNCs) in a long-term follow-up period in atherosclerotic peripheral arterial disease (PAD) patients who have no optional therapy. This study was a retrospective and observational study that was carried out to evaluate long-term clinical outcomes in 42 lower limbs of 30 patients with atherosclerotic PAD who underwent BM-MNC implantation. The median follow-up period was 9.25 (range, 6-16) years. The overall amputation-free rates were 73.0% at 5 years after BM-MNC implantation and 70.4% at 10 years in patients with atherosclerotic PAD. The overall amputation-free rates at 5 years and at 10 years after implantation of BM-MNCs were significantly higher in atherosclerotic PAD patients than in internal controls and historical controls. There were no significant differences in amputation rates between the internal control group and historical control group. The rate of overall survival was not significantly different between the BM-MNC implantation group and the historical control group. Implantation of autologous BM-MNCs is feasible for a long-term follow-up period in patients with CLI who have no optional therapy.
    Matched MeSH terms: Peripheral Arterial Disease/complications
  4. Kemp Z, Turnbull A, Yost S, Seal S, Mahamdallie S, Poyastro-Pearson E, et al.
    JAMA Netw Open, 2019 05 03;2(5):e194428.
    PMID: 31125106 DOI: 10.1001/jamanetworkopen.2019.4428
    Importance: Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers.

    Objective: To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer.

    Design, Setting, and Participants: A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017.

    Main Outcomes and Measures: Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes.

    Results: Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion-breast cancer plus a parent, sibling, or child with any of the other criteria-can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process.

    Conclusions and Relevance: This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing.

    Matched MeSH terms: Genetic Predisposition to Disease*
  5. Jackson AA, Lai PSM, Alias AM, Atiya N, Ramdzan SN, Abdul Malik TF, et al.
    J Infect Dev Ctries, 2019 03 31;13(3):219-226.
    PMID: 32040451 DOI: 10.3855/jidc.11089
    INTRODUCTION: Diagnosis and management of urinary tract infection (UTI) are complex, and do not always follow guidelines. The aim of this study was to determine adherence to the 2014 Malaysian Ministry of Health guidelines for managing suspected UTI in a Malaysian primary care setting.

    METHODOLOGY: We retrospectively reviewed computerized medical records of adults with suspected UTI between July-December 2016. Excluded were consultations misclassified by the search engine, duplicated records of the same patient, consultations for follow-up of suspected UTI, patients who were pregnant, catheterised, or who had a renal transplant. Records were reviewed by two primary care physicians and a clinical microbiologist.

    RESULTS: From 852 records, 366 consultations were a fresh episode of possible UTI. Most subjects were female (78.2%) with median age of 61.5 years. The major co-morbidities were hypertension (37.1%), prostatic enlargement in males (35.5%) and impaired renal function (31.1%). Symptoms were reported in 349 (95.4%) consultations. Antibiotics were prescribed in 307 (83.9%) consultations, which was appropriate in 227/307 (73.9%), where the subject had at least one symptom, and leucocytes were raised in urine full examination and microscopic examination (UFEME). In 73 (23.8%) consultations antibiotics were prescribed inappropriately, as the subjects were asymptomatic (14,4.6%), urine was clear (17,5.5%), or UFEME did not show raised leucocytes (42,13.7%). In 7 (2.3%) consultations appropriateness of antibiotics could not be determined as UFEME was not available.

    CONCLUSION: Several pitfalls contributed to suboptimal adherence to guidelines for diagnosis and management of suspected UTI. This illustrates the complexity of managing suspected UTI in older subjects with multiple co-morbidities.

    Matched MeSH terms: Disease Management*
  6. Windecker S, Latib A, Kedhi E, Kirtane AJ, Kandzari DE, Mehran R, et al.
    N Engl J Med, 2020 03 26;382(13):1208-1218.
    PMID: 32050061 DOI: 10.1056/NEJMoa1910021
    BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited.

    METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority.

    RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority).

    CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

    Matched MeSH terms: Coronary Artery Disease/therapy*
  7. Al-Alimi KR, Razak AAA, Saub R
    Afr Health Sci, 2018 Dec;18(4):1036-1045.
    PMID: 30766570 DOI: 10.4314/ahs.v18i4.25
    Backgrounds: People in Yemen and in East African countries chew khat more than five hours daily.

    Objectives: The aim of this study was to assess the relationship between khat and occlusal caries progression.

    Methods: A cohort study was carried out among 98 Yemeni khat chewers and 101 non-chewers aged 18-35 years old with early occlusal caries lesions. All participants answered questions on socio-demographic, khat , oral hygiene , sugar intake, and oral health knowledge at baseline. All posterior teeth with an early enamel lesion on occlusal surfaces detected by visual inspection at baseline were also subjected to DIAGNOdent assessment to confirm early lesion (DIAGNOdent reading 13-24). Participants were re-examined after 12 weeks. Caries progression was considered to occur when the DIAGNOdent reading was >25. Data were analyzed using Relative risk, Mann-Whitney U test, a Wilcoxon Signed-Rank test and logistic regression analysis.

    Results: Occlusal caries progression incidence between khat chewers and non-chewers, with the relative risk was 1.68. There was no significant difference in occlusal caries progression on chewing side and non-chewing side among khat chewers. Khat chewing was a statistical predictor for those with low income.

    Conclusion: Khat is a risk factor for occlusion caries progression among low income group.

    Matched MeSH terms: Disease Progression*
  8. Colombo A, Chandrasekhar J, Aquino M, Ong TK, Sartori S, Baber U, et al.
    Int J Cardiol, 2019 05 15;283:67-72.
    PMID: 30826192 DOI: 10.1016/j.ijcard.2019.01.053
    BACKGROUND: The COMBO stent (OrbusNeich Medical, Ft. Lauderdale, Florida) is a new-generation bio-engineered drug eluting stent, combining an abluminal coating of a bioabsorbable polymer matrix for sustained release of sirolimus and luminal anti-CD34 coating for endothelial progenitor cell capture and rapid endothelialization.

    METHODS: The Multinational Abluminal Sirolimus Coated BiO-Engineered StenT (MASCOT) registry was a prospective post-marketing study conducted from June 2014-May 2017 across 60 centers globally. Patients were eligible if COMBO stent implantation was attempted, and they received dual antiplatelet therapy (DAPT) per local guidelines. Follow-up was conducted by trained research staff at 1, 6 and 12 months by phone or clinic visit to capture clinical events and DAPT cessation events. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, non-fatal myocardial infarction not clearly attributable to a non-target vessel, or ischemia-driven target lesion revascularization.

    RESULTS: A total of 2614 patients were enrolled over the study period with 96.7% completion of 1-year follow-up. The mean age of enrolled patients was 62.9 ± 11.2 years and 23.0% were female. Diabetes mellitus was present at baseline in 33.5%. A total of 56.1% patients underwent PCI for acute coronary syndrome (ACS). The 1-year primary endpoint of TLF occurred in 3.4% patients (n = 88). Definite stent thrombosis occurred in 0.5% patients (n = 12).

    CONCLUSION: The MASCOT post marketing registry provides comprehensive safety and efficacy outcomes following contemporary PCI using the novel COMBO stent in an all-comer population. This platform is associated with low rates of 1-year TLF and ST. CLINICALTRIALS.

    GOV IDENTIFIER: NCT02183454.

    Matched MeSH terms: Coronary Artery Disease/surgery*
  9. Zack R, Okunade O, Olson E, Salt M, Amodeo C, Anchala R, et al.
    Hypertension, 2019 05;73(5):990-997.
    PMID: 30929516 DOI: 10.1161/HYPERTENSIONAHA.118.11916
    High blood pressure is the leading modifiable risk factor for mortality, accounting for nearly 1 in 5 deaths worldwide and 1 in 11 in low-income countries. Hypertension control remains a challenge, especially in low-resource settings. One approach to improvement is the prioritization of patient-centered care. However, consensus on the outcomes that matter most to patients is lacking. We aimed to define a standard set of patient-centered outcomes for evaluating hypertension management in low- and middle-income countries. The International Consortium for Health Outcomes Measurement convened a Working Group of 18 experts and patients representing 15 countries. We used a modified Delphi process to reach consensus on a set of outcomes, case-mix variables, and a timeline to guide data collection. Literature reviews, patient interviews, a patient validation survey, and an open review by hypertension experts informed the set. The set contains 18 clinical and patient-reported outcomes that reflect patient priorities and evidence-based hypertension management and case-mix variables to allow comparisons between providers. The domains included are hypertension control, cardiovascular complications, health-related quality of life, financial burden of care, medication burden, satisfaction with care, health literacy, and health behaviors. We present a core list of outcomes for evaluating hypertension care. They account for the unique challenges healthcare providers and patients face in low- and middle-income countries, yet are relevant to all settings. We believe that it is a vital step toward international benchmarking in hypertension care and, ultimately, value-based hypertension management.
    Matched MeSH terms: Disease Management*
  10. Pinkham K, Park DJ, Hashemiaghdam A, Kirov AB, Adam I, Rosiak K, et al.
    Stem Cell Reports, 2019 04 09;12(4):712-727.
    PMID: 30930246 DOI: 10.1016/j.stemcr.2019.02.012
    Inherent plasticity and various survival cues allow glioblastoma stem-like cells (GSCs) to survive and proliferate under intrinsic and extrinsic stress conditions. Here, we report that GSCs depend on the adaptive activation of ER stress and subsequent activation of lipogenesis and particularly stearoyl CoA desaturase (SCD1), which promotes ER homeostasis, cytoprotection, and tumor initiation. Pharmacological targeting of SCD1 is particularly toxic due to the accumulation of saturated fatty acids, which exacerbates ER stress, triggers apoptosis, impairs RAD51-mediated DNA repair, and achieves a remarkable therapeutic outcome with 25%-100% cure rate in xenograft mouse models. Mechanistically, divergent cell fates under varying levels of ER stress are primarily controlled by the ER sensor IRE1, which either promotes SCD1 transcriptional activation or converts to apoptotic signaling when SCD1 activity is impaired. Taken together, the dependence of GSCs on fatty acid desaturation presents an exploitable vulnerability to target glioblastoma.
    Matched MeSH terms: Disease Models, Animal; Disease Susceptibility
  11. Zhang L, Tao Y, Woodring J, Rattana K, Sovannarith S, Rathavy T, et al.
    Int J Epidemiol, 2019 08 01;48(4):1327-1339.
    PMID: 30879066 DOI: 10.1093/ije/dyz037
    BACKGROUND: The Regional Framework for Triple Elimination of Mother-to-Child Transmission (EMTCT) of HIV, Hepatitis B (HBV) and Syphilis in Asia and the Pacific 2018-30 was endorsed by the Regional Committee of WHO Western Pacific in October 2017, proposing an integrated and coordinated approach to achieve elimination in an efficient, coordinated and sustainable manner. This study aims to assess the population impacts and cost-effectiveness of this integrated approach in the Cambodian context.

    METHODS: Based on existing frameworks for the EMTCT for each individual infection, an integrated framework that combines infection prevention procedures with routine antenatal care was constructed. Using decision tree analyses, population impacts, cost-effectiveness and the potential reduction in required resources of the integrated approach as a result of resource pooling and improvements in service coverage and coordination, were evaluated. The tool was assessed using simulated epidemiological data from Cambodia.

    RESULTS: The current prevention programme for 370,000 Cambodian pregnant women was estimated at USD$2.3 ($2.0-$2.5) million per year, including the duration of pregnancy and up to 18 months after delivery. A model estimate of current MTCT rates in Cambodia was 6.6% (6.2-7.1%) for HIV, 14.1% (13.1-15.2%) for HBV and 9.4% (9.0-9.8%) for syphilis. Integrating HIV and syphilis prevention into the existing antenatal care framework will reduce the total time required to provide this integrated care by 19% for health care workers and by 32% for pregnant women, resulting in a net saving of $380,000 per year for the EMTCT programme. This integrated approach reduces HIV and HBV MTCT to 6.1% (5.7-6.5%) and 13.0% (12.1-14.0%), respectively, and substantially reduces syphilis MCTC to 4.6% (4.3-5.0%). Further introduction of either antiviral treatment for pregnant women with high viral load of HBV, or hepatitis B immunoglobulin (HBIG) to exposed newborns, will increase the total cost of EMTCT to $4.4 ($3.6-$5.2) million and $3.3 ($2.7-$4.0) million per year, respectively, but substantially reduce HBV MTCT to 3.5% (3.2-3.8%) and 5.0% (4.6-5.5%), respectively. Combining both antiviral and HBIG treatments will further reduce HBV MTCT to 3.4% (3.1-3.7%) at an increased total cost of EMTCT of $4.5 ($3.7-$5.4) million per year. All these HBV intervention scenarios are highly cost-effective ($64-$114 per disability-adjusted life years averted) when the life benefits of these prevention measures are considered.

    CONCLUSIONS: The integrated approach, using antenatal, perinatal and postnatal care as a platform in Cambodia for triple EMTCT of HIV, HBV and syphilis, is highly cost-effective and efficient.

    Matched MeSH terms: Infectious Disease Transmission, Vertical/prevention & control*
  12. GBD 2016 Causes of Death Collaborators
    Lancet, 2017 Sep 16;390(10100):1151-1210.
    PMID: 28919116 DOI: 10.1016/S0140-6736(17)32152-9
    BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends.
    METHODS: We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016.
    FINDINGS: The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe.
    INTERPRETATION: The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.
    FUNDING: Bill & Melinda Gates Foundation.
    Malaysian collaborators: School of Medicine, Xiamen University Malaysia Campus, Sepang, Malaysia (Y J Kim PhD); School of Medical Sciences, University of Science Malaysia, Kubang Kerian, Malaysia (K I Musa MD); Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia (R Sahathevan PhD); Department of Community Medicine, International Medical University, Kuala Lumpur, Malaysia (C T Sreeramareddy MD)
    Matched MeSH terms: Global Burden of Disease/statistics & numerical data*
  13. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators
    Lancet, 2017 Sep 16;390(10100):1211-1259.
    PMID: 28919117 DOI: 10.1016/S0140-6736(17)32154-2
    BACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
    METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).
    FINDINGS: Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228).
    INTERPRETATION: The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.
    FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.
    Malaysian collaborators: School of Medicine, Xiamen University Malaysia Campus, Sepang, Malaysia (Y J Kim PhD); School of Medical Sciences, University of Science Malaysia, Kubang Kerian, Malaysia (K I Musa MD); Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia (R Sahathevan PhD); Department of Community Medicine, International Medical University, Kuala Lumpur, Malaysia (C T Sreeramareddy MD)
    Matched MeSH terms: Global Burden of Disease/statistics & numerical data*
  14. Shahar S, Vanoh D, Mat Ludin AF, Singh DKA, Hamid TA
    BMC Public Health, 2019 Jun 13;19(Suppl 4):549.
    PMID: 31196023 DOI: 10.1186/s12889-019-6866-2
    BACKGROUND: Poverty at old age is associated with poor dietary habit, nutritional status and higher rates of chronic diseases and psychosocial problems. However, there is limited information about this matter according to urban and rural settings. The aim of this study was to identify dietary, nutritional, physical and cognitive factors associated with poor socioeconomic status (SES) among older adults according to urban and rural settings in Malaysia.

    METHODS: An analysis was conducted among 2237 older adults who participated in a longitudinal study on aging (LRGS TUA). This study involved four states in Malaysia, with 49.4% from urban areas. Respondents were divided into three categories of SES based on percentile, stratified according to urban and rural settings. SES was measured using household income.

    RESULTS: The prevalence of low SES was higher among older adults in the rural area (50.6%) as compared to the urban area (49.4%). Factors associated with low SES among older adults in an urban setting were low dietary fibre intake (Adj OR:0.91),longer time for the Timed up and Go Test (Adj OR:1.09), greater disability (Adj OR:1.02), less frequent practice of caloric restriction (Adj OR:1.65), lower cognitive processing speed score (Adj OR:0.94) and lower protein intake (Adj OR:0.94). Whilst, among respondents from rural area, the factors associated with low SES were lack of dietary fibre intake (Adj OR:0.79), lower calf circumference (Adj OR: 0.91), lesser fresh fruits intake (Adj OR:0.91), greater disability (Adj OR:1.02) and having lower score in instrumental activities of daily living (Adj OR: 0.92).

    CONCLUSION: Lower SES ismore prevalent in rural areas. Poor dietary intake, lower fitness and disability were common factors associated with low in SES, regardless of settings. Factors associated with low SES identifiedin both the urban and rural areas in our study may be useful inplanning strategies to combat low SES and its related problems among older adults.

    Matched MeSH terms: Chronic Disease/epidemiology*
  15. Ankathil R, Mustapha MA, Abdul Aziz AA, Mohd Shahpudin SN, Zakaria AD, Abu Hassan MR, et al.
    Asian Pac J Cancer Prev, 2019 06 01;20(6):1621-1632.
    PMID: 31244280 DOI: 10.31557/APJCP.2019.20.6.1621
    AIM: To investigate the frequencies and association of polymorphic genotypes of IL-8 -251 T>A, TNF-α -308
    G>A, ICAM-1 K469E, ICAM-1 R241G, IL-6 -174 G>C, and PPAR-γ 34 C>G in modulating susceptibility risk in
    Malaysian colorectal cancer (CRC) patients. Methods: In this case-control study, peripheral blood samples of 560
    study subjects (280 CRC patients and 280 controls) were collected, DNA extracted and genotyped using PCR-RFLP
    and Allele Specific PCR. The association between polymorphic genotype and CRC susceptibility risk was determined
    using Logistic Regression analysis deriving Odds ratio (OR) and 95% CI. Results: On comparing the frequencies of
    genotypes of all single nucleotide polymorphisms ( SNPs ) in patients and controls, the homozygous variant genotypes
    IL-8 -251 AA and TNF-α -308 AA and variant A alleles were significantly higher in CRC patients. Investigation on
    the association of the variant alleles and genotypes singly, with susceptibility risk showed the homozygous variant A
    alleles and genotypes IL-8 -251 AA and TNF-α -308 AA to be at higher risk for CRC predisposition. Analysis based
    on age, gender and smoking habits showed that the polymorphisms IL8 -251 T>A and TNF – α 308 G>A contribute
    to a significantly higher risk among male and female who are more than 50 years and for smokers in this population.
    Conclusion: We observed an association between variant allele and genotypes of IL-8-251 T>A and TNF-α-308
    G>A polymorphisms and CRC susceptibility risk in Malaysian patients. These two SNPs in inflammatory response
    genes which undoubtedly contribute to individual risks to CRC susceptibility may be considered as potential genetic
    predisposition factors for CRC in Malaysian population.
    Matched MeSH terms: Genetic Predisposition to Disease*
  16. Tan HS, Balasubramaniam IS, Hss AS, Yeong ML, Chew CC, Singh RP, et al.
    BMC Pediatr, 2019 05 29;19(1):174.
    PMID: 31142302 DOI: 10.1186/s12887-019-1550-3
    BACKGROUND: Prolonged neonatal jaundice (PNNJ) is often caused by breast milk jaundice, but it could also point to other serious conditions (biliary atresia, congenital hypothyroidism). When babies with PNNJ receive a routine set of laboratory investigations to detect serious but uncommon conditions, there is always a tendency to over-investigate a large number of well, breastfed babies. A local unpublished survey in Perak state of Malaysia revealed that the diagnostic criteria and initial management of PNNJ were not standardized. This study aims to evaluate and improve the current management of PNNJ in the administrative region of Perak.

    METHODS: A 3-phase quasi-experimental community study was conducted from April 2012 to June 2013. Phase l was a cross-sectional study to review the current practice of PNNJ management. Phase ll was an interventional phase involving the implementation of a new protocol. Phase lll was a 6 months post-interventional audit. A registry of PNNJ was implemented to record the incidence rate. A self-reporting surveillance system was put in place to receive any reports of biliary atresia, urinary tract infection, or congenital hypothyroidism cases.

    RESULTS: In Phase I, 12 hospitals responded, and 199 case notes were reviewed. In Phase II, a new protocol was developed and implemented in all government health facilities in Perak. In Phase III, the 6-month post-intervention audit showed that there were significant improvements when comparing mean scores of pre- and post-intervention: history taking scores (p 

    Matched MeSH terms: Disease Management*
  17. Walli-Attaei M, Joseph P, Rosengren A, Chow CK, Rangarajan S, Lear SA, et al.
    Lancet, 2020 07 11;396(10244):97-109.
    PMID: 32445693 DOI: 10.1016/S0140-6736(20)30543-2
    BACKGROUND: Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies.

    METHODS: In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death.

    FINDINGS: From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease.

    INTERPRETATION: Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men.

    FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

    Matched MeSH terms: Coronary Disease/epidemiology
  18. Ng CC, Yew PY, Puah SM, Krishnan G, Yap LF, Teo SH, et al.
    J Hum Genet, 2009 Jul;54(7):392-7.
    PMID: 19478819 DOI: 10.1038/jhg.2009.49
    To identify a gene(s) susceptible to nasopharyngeal carcinoma (NPC), we carried out a genome-wide association study (GWAS) through genotyping of more than 500,000 tag single-nucleotide polymorphisms (SNPs), using an initial sample set of 111 unrelated NPC patients and 260 controls of a Malaysian Chinese population. We further evaluated the top 200 SNPs showing the smallest P-values, using a replication sample set that consisted of 168 cases and 252 controls. The combined analysis of the two sets of samples found an SNP in intron 3 of the ITGA9 (integrin-alpha 9) gene, rs2212020, to be strongly associated with NPC (P=8.27 x 10(-7), odds ratio (OR)=2.24, 95% confidence intervals (CI)=1.59-3.15). The gene is located at 3p21 which is commonly deleted in NPC cells. We subsequently genotyped additional 19 tag SNPs within a 40-kb linkage disequilibrium (LD) block surrounding this landmark SNP. Among them, SNP rs189897 showed the strongest association with a P-value of 6.85 x 10(-8) (OR=3.18, 95% CI=1.94-5.21), suggesting that a genetic variation(s) in ITGA9 may influence susceptibility to NPC in the Malaysian Chinese population.
    Matched MeSH terms: Genetic Predisposition to Disease*
  19. Tai ES, Lim SC, Chew SK, Tan BY, Tan CE
    Diabetes Res Clin Pract, 2000 Aug;49(2-3):159-68.
    PMID: 10963828 DOI: 10.1016/s0168-8227(00)00152-2
    We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.
    Matched MeSH terms: Coronary Disease/epidemiology*
  20. Gopalsamy B, Sambasevam Y, Zulazmi NA, Chia JSM, Omar Farouk AA, Sulaiman MR, et al.
    Neurochem Res, 2019 Sep;44(9):2123-2138.
    PMID: 31376053 DOI: 10.1007/s11064-019-02850-0
    Number of ligations made in the chronic constriction injury (CCI) neuropathic pain model has raised serious concerns. We compared behavioural responses, nerve morphology and expression of pain marker, c-fos among CCI models developed with one, two, three and four ligations. The numbers of ligation(s) on sciatic nerve shows no significant difference in displaying mechanical and cold allodynia, and mechanical and thermal hyperalgesia throughout 84 days. All groups underwent similar levels of nerve degeneration post-surgery. Similar c-fos level in brain cingulate cortex, parafascicular nuclei and amygdala were observed in all CCI models compared to sham-operated group. Therefore, number of ligations does not impact intensity of pain symptoms, pathogenesis and neuronal activation. A single ligation is sufficient to develop neuropathic pain, in contrast to the established model of four ligations. This study dissects and characterises the CCI model, ascertaining a more uniform animal model to surrogate actual neuropathic pain condition.
    Matched MeSH terms: Disease Models, Animal*
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