BackgroundThough financial and policy level efforts are made to expand antiretroviral treatment (ART) service free of cost, survival outcome of ART program has not been systematically evaluated in Nepal. This study assesses the mortality rates and determinants among adult HIV-infected patients on ART in Far-western region of Nepal.MethodsThis retrospective cohort study included 1024 (51.2% men) HIV-infected patients aged ≥15 years, who started ART between May 15th 2006 and May 15th 2011 in five ART sites in the Far-western region, Nepal. Follow-up time was calculated from the date of ART initiation to date of death or censoring (loss to follow-up, transferred out, or 15 November 2011). Mortality rates (per 100 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore determinants of mortality.ResultsThe median follow-up time was 19.1 months. The crude mortality rate was 6.3 (95% confidence interval (CI) 5.3-7.6) but more than three-times higher in first 3 months after ART initiation (21.9 (95% CI 16.6- 28.8)). About 12% (83% men) of those newly initiated on ART died during follow-up. The independent determinants of mortality were male sex (hazard ratio (HR) 4.55, 95% CI 2.43-8.51), poor baseline performance scale (bedridden <50% of the day during the past month, HR 2.05, 95% CI 1.19-3.52; bedridden >50% of the day during the past month, HR 3.41, 95% CI 1.67-6.98 compared to normal activity), one standard deviation decrease in baseline bodyweight (HR 1.04, 95% CI 1.01-1.07), and poor WHO clinical stage (stage III, HR 2.96, 95% CI 1.31-6.69; stage IV, HR 3.28, 95% CI 1.30-8.29 compared to WHO clinical stage I or II).ConclusionsHigh mortality was observed within the first 3 months of ART initiation. Patients with poor baseline clinical characteristics had higher mortality, especially men. Earlier initiation of ART through expanded testing and counselling should be encouraged in HIV-infected patients.

BackgroundInfant mortality reflects not only the health of infants but societal well-being as a whole. This study explores distal socioeconomic and related proximate determinants of infant mortality and provides evidence for designing targeted interventions.MethodsSurvival information on 5391 live born infants (2006–2010) was examined from the nationally representative Nepal Demographic Health Survey 2011. Bivariate logistic regression and multivariate hierarchical logistic regression approaches were performed to analyze the distal-socioeconomic and related proximate determinants of infant mortality.ResultsSocio-economic distal determinants are important predictors for infant mortality. For example, in reference to infants of the richest class, the adjusted odds ratio of infant mortality was 1.66 (95 % CI: 1.00–2.74) in middle class and 1.87 (95 % CI: 1.14–3.08) in poorer class, respectively. Similarly, the populations of the Mountain ecological region had a higher odds ratio (aOR =1.39, 95 % CI: 0.90–2.16) of experiencing infant mortality compared with the populations of the Terai plain region. Likewise, the population of Far-western development region had a higher adjusted odds ratio (aOR =1.62, 95 % CI: 1.02–2.57) of experiencing infant mortality than the Western development region. Moreover, the association of proximate determinants with infant mortality was statistically significant. For example, in reference to size at birth, adjusted odds ratio of infant dying was higher for infants whose birth size, as reported by mothers, was very small (aOR = 3.41, 95 % CI: 2.16–5.38) than whose birth size was average. Similarly, fourth or higher birth rank infants with a short preceding birth interval (less than or equal to 2 years) were at greater risk of dying (aOR =1.74, 95 % CI: 1.16–2.62) compared to the second or third rank infants with longer birth intervals. A short birth interval of the second or the third rank infants also increased the odds of infant death (aOR = 2.03, 95 % CI: 1.23–3.35).ConclusionsSocioeconomic distal and proximate determinants are associated with infant mortality in Nepal. Infant mortality was higher in the poor and middle classes than the wealthier classes. Population of Mountain ecological region and Far western development region had high risk of infant mortality. Similarly, infant dying was higher for infants whose birth size, as reported by mothers, was very small and who has higher birth rank and short preceding birth interval. This study uniquely addresses both broader socioeconomic distal and proximate determinants side by side at the individual, household and community levels. For this, both comprehensive, long-term, equity-based public health interventions and immediate infant care programs are recommended.

SummaryWith the increasing availability of biobank-scale datasets that incorporate both genomic data and electronic health records, many associations between genetic variants and phenotypes of interest have been discovered. Polygenic risk scores (PRS), which are being widely explored in precision medicine, use the results of association studies to predict the genetic component of disease risk by accumulating risk alleles weighted by their effect sizes. However, limited studies have thoroughly investigated best practices for PRS in global populations across different diseases. In this study, we utilize data from the Global-Biobank Meta-analysis Initiative (GBMI), which consists of individuals from diverse ancestries and across continents, to explore methodological considerations and PRS prediction performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRS using heuristic (pruning and thresholding, P+T) and Bayesian (PRS-CS) methods. We found that the genetic architecture, such as SNP-based heritability and polygenicity, varied greatly among endpoints. For both PRS construction methods, using a European ancestry LD reference panel resulted in comparable or higher prediction accuracy compared to several other non-European based panels; this is largely attributable to European descent populations still comprising the majority of GBMI participants. PRS-CS overall outperformed the classic P+T method, especially for endpoints with higher SNP-based heritability. For example, substantial improvements are observed in East-Asian ancestry (EAS) using PRS-CS compared to P+T for heart failure (HF) and chronic obstructive pulmonary disease (COPD). Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma which has known variation in disease prevalence across global populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using the GBMI and highlight the importance of best practices for PRS in the biobank-scale genomics era.

BackgroundMen who have sex with men (MSM) are marginalized, hidden, underserved and at high risk for HIV in Nepal. We examined the association between MSM sub-populations, psychosocial health problems and support, access to prevention and non-use of condoms.MethodsBetween September-November of 2010, a cross-sectional survey on HIV-related risk behavior was performed across Nepal through snowball sampling facilitated by non-governmental organizations, recruiting 339 MSM, age 15 or older. The primary outcomes were: (a) non-use of condoms at least once in last three anal sex encounters with men and (b) non-use of condoms with women in the last encounter. The secondary outcome was participation in HIV prevention interventions in the past year.ResultsAmong the 339 MSM interviewed, 78% did not use condoms at their last anal sex with another man, 35% did not use condoms in their last sex with a woman, 70% had experienced violence in the last 12 months, 61% were experiencing depression and 47% had thought of committing suicide. After adjustment for age, religion, marital status, and MSM subpopulations (bisexual, ta, meti, gay), non-use of condoms at last anal sex with a man was significantly associated with non-participation in HIV interventions, experience of physical and sexual violence, depression, repeated suicidal thoughts, small social support network and being dissatisfied with social support. Depression was marginally associated with non-use of condoms with women. The findings suggest that among MSM who reported non-use of condoms at last anal sex, the ta subgroup and those lacking family acceptance were the least likely to have participated in any preventive interventions.ConclusionsMSM in Nepal have a prevalence of psychosocial health problems in turn associated with high risk behavior for HIV. Future HIV prevention efforts targeting MSM in Nepal should cover all MSM subpopulations and prioritize psychosocial health interventions.

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