Progress in Reducing Inequalities in Reproductive, Maternal, Newborn and Child Health Services in Nepal.

BACKGROUND: Equity has emerged as a cross-cutting theme in the health sector, and countries across the world are striving to ensure that all people have access to the health services they need without undue financial hardship and educational, social, cultural and geographical barriers. In this context, this analysis has attempted to analyse Nepal's progress in reducing inequalities in reproductive, maternal, newborn and child health services based on economic status and place of residence. METHODS: In this analysis, we have used data available from the web version of the Health Equity Assessment Toolkit, a data visualisation tool developed by the World Health Organisation. We have analysed the inequalities in terms of a composite coverage index which combines eight reproductive, maternal, newborn and child health interventions along the continuum of care. RESULTS: Composite coverage of reproductive, maternal, newborn and child health services was 43% in 2001 which increased to 65% in 2016. The absolute difference in composite coverage of the services between the lowest and highest wealth quintiles decreased from 28-percentage points in 2001 to 8-percentage points in 2016. The difference in service coverage between the urban and rural settings reduced from 21-percentage points to six percentage points in the period. Among the eight various services, births attended by skilled birth attendants is the indicator with the highest scope for improvement.   Conclusions: Inequalities based on wealth quintiles and residence places have narrowed from 2001 to 2016. Additional efforts in expanding skilled birth attendants and antenatal care service coverage among the poorest quintile and rural residents could further improve the coverage of the indicators at the national level and narrow down the inequalities.

Mortality and risk factors of disease in Nepal: Trend and projections from 1990 to 2040.

BACKGROUND: Between 1990 and 2017, Nepal experienced a shift in the burden of disease from communicable, maternal, neonatal and nutritional (CMNN) diseases to non-communicable diseases (NCDs). With an increasing ageing population and life-style changes including tobacco use, harmful alcohol consumption, unhealthy diets, and insufficient physical activity, the proportion of total deaths from NCDs will continue to increase. An analysis of current diseases pattern and projections of the trends informs planning of health interventions. This analysis aims to project the mortality and risk factor of disease until 2040, based on past trends. METHODS: This study uses secondary data from the Global Burden of Disease (GBD) Study which analyses historic data from 1990 to 2016 to predict key variables such as, the mortality rates, life expectancy and Years of Life Lost for different causes of death from 2017 to 2040. 'GBD Foresight Visualization', a visualisation tool publicly available in the webpage of Institute for Health Metrics and Evaluation was the source of data for this analysis. GBD forecasting uses three-component modelling process: the first component captures variations due to risk factors and interventions, the second takes into consideration the variation due to measures of development quantified as social development index and the third uses an autoregressive integrated moving average model to capture the unexplained component correlated over time. We extracted Nepal specific data from it and reported number of deaths, mortality rates (per 100,000 population) as well as causes of death for the period 1990 to 2040. RESULTS: In 1990, CMNN diseases were responsible for approximately two-thirds (63.6%) of total deaths in Nepal. The proportion of the deaths from the CMNN diseases has reduced to 26.8% in 2015 and is estimated to be about a fifth of the 1990 figure (12.47%) in 2040. Conversely, deaths from NCDs reflect an upward trend. NCDs claimed a third of total deaths (29.91%) in the country in 1990, while in 2015, were responsible for about two-thirds of the total deaths (63.31%). In 2040, it is predicted that NCDs will contribute to over two-thirds (78.64%) of total deaths in the country. Less than a tenth (6.49%) of the total deaths in Nepal in 1990 were associated with injuries which increased to 13.04% in 2015 but is projected to decrease to 8.89% in 2040. In 1990, metabolic risk factors including high systolic blood pressure, high total cholesterol, high fasting plasma glucose, high body mass index and impaired kidney functions collectively contributed to a tenth of the total deaths (10.38%) in Nepal, whereas, in 2040 more than a third (37.31%) of the total deaths in the country could be attributed to it. CONCLUSION: A reverse of the situation in 1990, NCDs are predicted to be the leading cause of deaths and metabolic risk factors are predicted to contribute to the highest proportion of deaths in 2040. NCDs could demand a major share of resources within the health sector requiring extensive multi-sectoral prevention measures, re-allocation of resources and re-organisation of the health system to cater for long-term care.

Determinants of home delivery in Nepal - A disaggregated analysis of marginalised and non-marginalised women from the 2016 Nepal Demographic and Health Survey.

INTRODUCTION: In Nepal, a substantial proportion of women still deliver their child at home. Disparities have been observed in utilisation of institutional delivery and skilled birth attendant services. We performed a disaggregated analysis among marginalised and non-marginalised women to identify if different factors are associated with home delivery among these groups. MATERIALS AND METHODS: This study used data from the 2016 Nepal Demographic and Health Survey. It involves the analysis of 3,837 women who had experienced at least one live birth in the five years preceding the survey. Women were categorised as marginalised and non-marginalised based on ethnic group. Bivariate and multivariable logistic regression analysis were performed to identify factors associated with home delivery. RESULTS: A higher proportion of marginalised women delivered at home (47%) than non-marginalised women (26%). Compared to non-marginalised women (35%), a larger proportion of marginalised women (64%) felt that it was not necessary to give birth at health facility. The multivariable analysis indicated an independent association of having no or basic education, belonging to middle, poorer and the poorest wealth quintile, residing in Province 2 and not having completed of four antenatal care visits per protocol with home delivery among both marginalised and non-marginalised women. Whereas residing in a rural area, residing in Province 7, and at a distance of >30 minutes to a health facility were factors independently associated with home delivery only among marginalised women. CONCLUSION: We conclude that poor education, poor economic status, non-completion of four ANC visits and belonging to Province 2 particularly determined either group of women to deliver at home, whereas residing in rural areas, living far from health facility, and belonging to Province 7 determined marginalised women to deliver at home. Preventing mothers from delivering at home would thus require focusing on specific geographical areas besides considering wider socio-economic determinants.

Targeting NF-κB-mediated inflammatory pathways in cisplatin-resistant NSCLC.

OBJECTIVES: The majority of patients with non-small cell lung cancer (NSCLC) present with advanced stage disease, at which time chemotherapy is usually the most common treatment option. While somewhat effective, patients treated with platinum-based regimens will eventually develop resistance, with others presenting with intrinsic resistance. Multiple pathways have been implicated in chemo-resistance, however the critical underlying mechanisms have yet to be elucidated. The aim of this project was to determine the role of inflammatory mediators in cisplatin-resistance in NSCLC. MATERIALS AND METHODS: Inflammatory mediator, NF-κB, and its associated pathways were investigated in an isogenic model of cisplatin-resistant NSCLC using age-matched parental (PT) and corresponding cisplatin-resistant (CisR) sublines. Pathways were assessed using mass spectrometry, western blot analysis and qRT-PCR. The cisplatin sensitizing potential of an NF-κB small molecule inhibitor, DHMEQ, was also assessed by means of viability assays and western blot analysis. RESULTS: Proteomic analysis identified dysregulated NF-κB responsive targets in CisR cells when compared to PT cells, with increased NF-κB expression identified in four out of the five NSCLC sub-types examined (CisR versus PT). DHMEQ treatment resulted in reduced NF-κB expression in the presence of cisplatin, and re-sensitized CisR cells to the cytotoxic effects of the drug. CONCLUSION: This study identified NF-ĸB as a potential therapeutic target in cisplatin-resistant NSCLC. Furthermore, inhibition of NF-ĸB using DHMEQ re-sensitized chemo-resistant cells to cisplatin treatment.

Strategic targeting of the PI3K-NFκB axis in cisplatin-resistant NSCLC.

Chemoresistance is a major therapeutic challenge to overcome in NSCLC, in order to improve the current survival rates of<15% at 5 years. We and others have shown increased PI3K signaling in NSCLC to be associated with a more aggressive disease, and a poorer prognosis. In this study, targeted inhibition of three strategic points of the PI3K-NFκB axis was performed with the aim of exploiting vulnerabilities in cisplatin-resistant NSCLC cells. Cisplatin-resistant cell lines were previously generated through prolonged exposure to the drug. Expression of PI3K and NFκB pathway-related genes were compared between cisplatin-resistant cells and their matched parent cells using a gene expression array, qRT-PCR, DNA sequencing, western blot, and immunofluorescence. Targeted inhibition was performed using GDC-0980, a dual PI3K-mTOR inhibitor currently in Phase II clinical trials in NSCLC, and DHMEQ, an inhibitor of NFκB translocation which has been used extensively both in vitro and in vivo. Effects of the two inhibitors were assessed by BrdU proliferation assay and multiparameter viability assay. NFKBIA was shown to be 12-fold overexpressed in cisplatin-resistant cells, with no mutations present in exons 3, 4, or 5 of the gene. Corresponding overexpression of IκBα was also observed. Treatment with DHMEQ (but not GDC-0980) led to significantly enhanced effects on viability and proliferation in cisplatin-resistant cells compared with parent cells. We conclude that NFκB inhibition represents a more promising strategy than PI3K-mTOR inhibition for treatment in the chemoresistance setting in NSCLC.

Changes in STI services following a community based STI-intervention project in Cambodia.

The aim of this study was to assess changes in sexually transmitted infections (STI) related care following a STI project with a particular focus on registered brothel-based (direct) female sex workers (DFSWs) in four border provinces of Cambodia. A survey of health care facilities providing STI care was undertaken and the results compared with a baseline survey done two years previously. The main components of the project were: renovation of the STI clinics, STI training, formation of mobile teams, provision of STI drugs, and the introduction of basic laboratory tests at STI clinics. Interviews were held with health care providers and STI patients and a manual check was made of the STI register and special forms for DFSWs. Clinical management of STI cases was assessed for DFSWs, women with vaginal discharge and men with urethral discharge. Advice given to clients about condom use, partner notification and STI education was assessed and availability of STI drugs was reviewed. STI clinic attendance by DFSWs each month increased from 72% (296/412) to 93% (459/496). The proportion of DFSWs diagnosed with presumed STIs decreased from 86.5% (256/296) to 25.5% (117/459) and cervicitis from 32.8% (135/412) to 12.6% (58/459). The percentage of men attending STI clinics decreased from 26.9% (251/933) to 9.4% (102/1,080). The proportion of presumed STI cases/all cases attending health centers decreased from 7.0% (934/13,177) to 4.3% (739/17,224). The introduction of laboratory tests coincided with a marked reduction in DFSWs diagnosed with cervicitis. Further validation studies are required to determine whether this reduction was accompanied by a real decrease in gonorrhea and chlamydia.

Community action for preventing HIV in Cambodia: evaluation of a 3-year project.

The 'Community Action for Preventing HIV/AIDS Project' was implemented in four provinces in Cambodia (2001-04) to support a comprehensive set of HIV prevention efforts. Implementation was strictly monitored in terms of inputs, outputs and outcomes. We examine changes in these variables during the project period to assess the extent to which they were related to the project. Inputs and outputs were monitored regularly by supervision and quarterly project reports. Baseline and follow-up surveys were conducted on 10 target groups to measure changes in outcome indicators related to sexual risk behaviours, uses of HIV voluntary counselling and testing (VCT), self-reported sexually transmitted infections (STIs) and other indicators. The analyses use data from surveys and from project monitoring. Spending on HIV-related work at provincial level increased markedly, including investments in VCT, STI facilities and staff training. Yearly expenditure increased about 7-fold compared with years immediately preceding the project. VCT centres increased from 3 to 12, numbers of counsellors from 10 to 27, and numbers of client visits more than doubled. STI laboratory facilities increased from 0 to 6 with coverage of STI check-ups among sex workers increasing from 70% to 93% and a decline in men attending STI clinics. The survey results indicate significant changes in a number of major outcome indicators such as consistent condom use related to sex work (>80%), HIV testing and counselling after HIV tests, especially among police (42 to 72%, P < 0.001) and brothel-based sex workers (48 to 89%, P < 0.001). Self-reported STIs declined in most groups. Finally, the programmatic systems for planning, managing and monitoring implementation of activities at both central and provincial level, as well as technical guidelines, developed under the project have become the standard for the national programme. In conclusion, the project appears to have been comprehensive and a number of favourable changes in output and outcome indicators occurred. It seems likely that the project made a substantial contribution to these positive outcomes, though the extent is not clear. The project is likely to have powerful long-term effects through strengthening of capacity and establishment of systems for the national programme.

Impact of a community sexually transmitted infection/HIV intervention project on female sex workers in five border provinces of Vietnam.

OBJECTIVES: To determine changes in the prevalence of sexually transmitted infection (STI)/HIV in female sex workers (FSWs) after a community HIV prevention intervention project in five border provinces of Vietnam. METHODS: The project focused on providing user-friendly STI services for FSWs using mobile teams operating at multiple sites depending on local client preferences. 911 FSWs were enrolled at baseline and 982 in the exit survey. Study participants were interviewed about sociodemographic characteristics, sexual behaviour, history of STIs and selected features of their husbands or cohabiting partners, and were tested for STIs. RESULTS: The overall prevalence rates of HIV, syphilis, herpes simplex virus 2 (HSV-2) antibodies, gonorrhoea (GC), Chlamydia trachomatis (CT), and GC and/or CT among FSWs in the five border provinces in 2004 were 3.6%, 12.9%, 24.9%, 2.9%, 9.1% and 11.3%, respectively. Compared with baseline values, GC and/or CT decreased significantly from 19.9% to 11.3%, GC from 10.7% to 2.9% and CT from 11.9% to 9.1%. HIV decreased from 4.5% to 3.6%, and HSV-2 antibodies from 27.7% to 24.9%. After adjustment for possible confounders, a significant overall decrease in having GC and/or CT (OR = 0.46, 95% CI 0.33 to 0.65; p<0.001) and GC alone (OR = 0.22, 95% CI 0.13 to 0.37; p<0.001) was found, and the overall prevalence of syphilis increased significantly (OR = 1.55, 95% CI 1.11 to 2.17 p = 0.011). A marked increase in syphilis from 1.0% to 14.1% was identified in the Lai Chau province. CONCLUSIONS: Implementation of the project was associated with a reduction in GC and/or CT infections in FSWs, more so with GC than with CT. A notable increase in syphilis in Lai Chau was identified. HIV/STI interventions in FSWs can be implemented by government services and should be intensified and expanded to other provinces.

An evaluation of sexually transmitted infection case management in health facilities in 4 border provinces of Cambodia.

BACKGROUND: Cambodia has reported the highest prevalence of HIV in the general population in Asia. Sex work and high sexually transmitted infection (STI) prevalences are thought to be major contributory factors. GOAL: The goal of this study was to assess standards of STI care through a survey of public sector health facilities in 4 border provinces of Cambodia. METHODS: Healthcare facilities providing STI care were identified. Interviews were held with healthcare providers and STI patients and a manual check made of the STI register and standard medical history forms for female sex workers (SWs) registered with the 100% condom use program. Clinical management was assessed for SWs, women with vaginal discharge, and men with urethral discharge. Advice about condom use, partner notification, STI and HIV education, and availability of STI drugs were reviewed. RESULTS: Seven percent of all patients seeking health care at health centers (HCs) had STI-related problems. Coverage of sex workers was high in 3 provinces. Drug stock outs, particularly cefixime, occurred at all levels of assessment. In STI clinics, almost all (99-100%) cervicitis and urethritis cases were diagnosed and treated correctly. In HCs with integrated STI services, according to national guidelines, cervicitis was diagnosed in 65% of women with vaginal discharge of whom 47% were diagnosed correctly, and in these, 88% were treated correctly. Sixty-six percent of SWs seen at STI clinics were diagnosed with cervicitis and 54% at follow up. CONCLUSIONS: STI services should be expanded further to health centers not currently offering STI care. Overtreatment for cervicitis in both SWs at reattendance and low-risk women with vaginal discharge are continuing problems. The WHO/UNAIDS STI service indicator criteria had limited application for the assessment of SW services but were adapted for local needs. Attendance of SWs in designated STI clinics appears to be a useful indicator for the acceptability and efficiency of the current national STI program.