Why do people sell their kidneys? A thematic synthesis of qualitative evidence.

Globally, demands for the kidneys have surpassed supply both living and deceased donors. High demands relative to the availability have made the kidney one of the most saleable human organs. The main objective was to explore the drivers of kidney selling. Literature related to kidney selling and its drivers was explored in three databases including MEDLINE (PubMed), Scopus (Elsevier), and JSTOR covering the period from 1987 to 2022. A total of 15 articles were selected, which underwent thematic analysis. Investigators independently assessed the articles for relevance and study quality to synthesize the data. The thematic analysis involved a critical approach to understanding the reasons for kidney selling by examining power disparities and social inequities. Kidney selling and the underlying reasons for it showed similarities across various geographic regions. Several factors were identified which increased individuals' vulnerability for kidney selling. At the micro level, poverty and illiteracy emerged as significant factors. Lack of financial safety nets obliged family to resort to kidney selling which helped to alleviate poverty, resolve debt, and other urgent financial issues. Nonetheless, the revenues from kidney selling were also used to purchase luxury items (diverting away from investing in livelihood expenses) such as buying motorbikes, mobile phones and televisions. Family, and gender responsibilities also played roles in kidney selling such as obligations related to paying dowry made parents particularly vulnerable. Surprisingly, a few victims of kidney selling later adopted kidney brokering role to support their livelihood. Kidney selling was further fostered by lack of stringent policy to regulate and monitor background checks for kidney transplantation. There were myriad factors that affected individual's vulnerability to kidney selling which stemmed from micro (poverty, illiteracy), meso (weak legal system, lacking stringent institutional policy, regulatory framework) and macro (social inequalities, corruption, organ shortage, insufficient health infrastructure) levels.

Synergistic associations of antenatal care visits and iron-folic acid supplementation with low birth weight: a pooled analysis of national surveys from six south Asian countries.

BACKGROUND: The prevalence of low birth weight (LBW) has remained high (24.9%) in the South Asian region with a significant impact on newborn survival. This region bears nearly 40% of global burden of LBW. While antenatal care (ANC) and iron-folic acid supplementation independently have been considered effective for improving maternal and newborn outcomes, the evidence on the combined effect of these two supplements on LBW is lacking. This study aimed to examine the synergistic association of ANC and iron-folic acid supplementation on LBW in the South Asian region using pooled data from six South Asian countries. METHODS: Nationally representative surveys from Nepal, India, Bangladesh, Pakistan, Maldives, and Afghanistan were included in the study. Birth weight and the prevalence of LBW for singleton last-born children were reported using descriptive statistics. The association between LBW and ANC visits and the interaction between iron-folic acid consumption and ANC were examined using multiple logistic regression. RESULTS: The mean birth weight in the region was 2841.8 g with an LBW prevalence of 17.1%. Country-specific prevalence ranged from 11.4% in Nepal to 22.4% in Pakistan. Not attending ANC visits (adjusted odds ratio (AOR): 1.24; 95% confidence interval (CI): 1.16, 1.34) and not consuming iron-folic acid (AOR: 1.14; 95% CI: 1.08, 1.21) were significantly associated with a higher likelihood of LBW. Furthermore, jointly, having < 4 ANC visits and < 180 days of iron-folic acid supplementation was associated with a higher likelihood (AOR: 1.29; 95% CI: 1.22, 1.36) of having LBW compared to those who had ≥ 4 ANC visits and ≥ 180 days of iron-folic acid consumption after controlling for key confounding factors. CONCLUSIONS: The current study provides important evidence on the synergy between ANC visits and iron-folic acid consumption during pregnancy to capitalize on the existing national maternal health programs in the South Asian region, including low-and middle-income countries for positive foetal outcomes.

The total health gains and cost savings of eradicating cold housing in Australia.

BACKGROUND: Cold indoor temperature (<18 °C) is associated with hypertension-related and respiratory disease, depression, and anxiety. We estimate total health, health expenditure and income impacts of permanently lifting the temperature in living areas of the home to 18 °C in cold homes in South-eastern Australia (N = 17 million). METHODS: A proportional multistate lifetable model was used to estimate health adjusted life years (HALYs), health expenditure and income earnings, over the remainder of the lifespan of the population alive in 2021 (3% discount rate). Multiple data were integrated including the prevalence of cold housing (5.87%; mean temperature 15 °C), the effect of temperature to hypertension-related, respiratory disease, depression and anxiety. FINDINGS: Eradicating cold housing was predicted to lead to 89,600 (95% UI 47,700 to 177,000) lifetime HALYs gained over the population's remaining lifespan, nearly half of which occurred from 2021 to 2040. Respiratory disease (32.4%) and mental illness (60.6%) made large contributions to HALYs gained, but also had large uncertainty (95% UI 30.0%-42.9% and 45.1%-64.6%, respectively) due to uncertain estimates of their magnitude of causal association with cold housing. Health gains per capita were 6.1 times greater (95% UI 4.7 to 8.1) among the most compared to least deprived quintile. From 2021 to 2040, health expenditure decreased by AUD$0.87 billion (0.35-1.98) and income earnings increased by AUD$4.35 billion (1.89-9.81). INTERPRETATION: Eliminating cold housing would lead to substantial health gains, reductions in health inequalities, savings in health expenditure, and productivity gains. Next steps require research to reduce uncertainty about the magnitude of causal associations of cold with mental and respiratory health.

Dissecting antenatal care inequalities in western Nepal: insights from a community-based cohort study.

BACKGROUND: Antenatal care (ANC) ensures continuity of care in maternal and foetal health. Understanding the quality and timing of antenatal care (ANC) is important to further progress maternal health in Nepal. This study aimed to investigate the proportion of and factors associated with, key ANC services in western Nepal. METHODS: Data from a community-based cohort study were utilized to evaluate the major ANC service outcomes: (i) three or less ANC visits (underutilization) (ii) late initiation (≥ 4 months) and (iii) suboptimal ANC (< 8 quality indicators). Mothers were recruited and interviewed within 30 days of childbirth. The outcomes and the factors associated with them were reported using frequency distribution and multiple logistic regressions, respectively. RESULTS: Only 7.5% of 735 mothers reported not attending any ANC visits. While only a quarter (23.77%) of mothers reported under-utilizing ANC, more than half of the women (55.21%) initiated ANC visits late, and one-third (33.8%) received suboptimal ANC quality. A total of seven factors were associated with the suboptimal ANC. Mothers with lower education attainment, residing in rural areas, and those who received service at home, were more likely to attain three or less ANC visits, late initiation of ANC, and report receiving suboptimal ANC. Furthermore, mothers from poor family backgrounds appeared to initiate ANC late. Mothers from disadvantaged Madhesi communities tended to receive suboptimal ANC. CONCLUSIONS: Despite a high ANC attendance, a significant proportion of mothers had initiated ANC late and received suboptimal care. There is a need to tailor ANC services to better support women from Madhesi ethnic community, as well as those with poor and less educated backgrounds to reduce the inequalities in maternal health care.

Sleep Problems Associate With Multimorbidity: A Systematic Review and Meta-analysis.

Objectives: To summarize the evidence on the association between sleep problems and multimorbidity. Methods: Six electronic databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, VIP, and Wan fang) were searched to identify observational studies on the association between sleep problems and multimorbidity. A random-effects model was used to estimate the pooled odds ratios (ORs) and 95% confidence intervals for multimorbidity. Results: A total of 17 observational studies of 133,575 participants were included. Sleep problems included abnormal sleep duration, insomnia, snoring, poor sleep quality, obstructive sleep apnea (OSA) and restless legs syndrome (RLS). The pooled ORs (95% CIs) for multimorbidity were 1.49 (1.24-1.80) of short sleep duration, 1.21 (1.11-1.44) of long sleep duration and 2.53 (1.85-3.46) for insomnia. The association of other sleep problems with multimorbidity was narratively summarized due to limited number of comparable studies. Conclusion: Abnormal sleep duration and insomnia are associated with higher odds of multimorbidity, while the evidence on association of snoring, poor sleep quality, obstructive sleep apnea and restless legs syndrome with multimorbidity remains inconclusive. Interventions targeting sleep problems should be delivered for better management of multimorbidity.

Sustainability of a 12-month lifestyle intervention delivered by community health workers in reducing blood pressure in Nepal: 5-year follow-up of the COBIN open-label, cluster randomised trial.

BACKGROUND: The sustainability and scalability of limited-duration interventions in low-income and middle-income countries remain unclear. We aimed to investigate the sustainability in reduction of blood pressure through a 12-month lifestyle intervention led by community health workers to reduce blood pressure in Nepal, 4 years after the intervention ceased. METHODS: The Community-Based Intervention for Control of Hypertension in Nepal (COBIN) trial was a non-blinded, cluster-randomised trial done in Kaski, Nepal. Adults aged 25-65 years were eligible. People were excluded if they declined consent, were severely ill, unlikely to be in the community throughout the intervention, or pregnant. During the 12-month intervention, female community health volunteers (FCHVs) visited participants in the intervention groups and provided lifestyle counselling and blood pressure measurement every 4 months. At the end of the 12-month intervention, systolic blood pressure was significantly lower in the intervention group than in the usual care group in all cohorts, ranging from -2·3 mm Hg (95% CI -3·8 to -0·8) lower in those with normal blood pressure to -4·9 mm Hg (-7·8 to -2·0) in the hypertensive cohort. The primary outcome for this follow-up study was a mean change in systolic blood pressure from baseline to follow-up at 60 months. We did an intention-to-treat analysis. FINDINGS: Between April 1, 2015, and Dec 31, 2015, 1638 participants were recruited in COBIN (939 [57·3%] assigned to intervention and 699 [42·7%] assigned to usual care). Of the 1468 (89·6%) who completed the 12-month assessments, we followed up 1352 (92·1%) participants at 60 months, between Oct 11, 2020, and May 5, 2022. 964 (71·3%) participants were women and 388 (28·7%) were men. From baseline to 60 months, the mean systolic blood pressure increased by 10·4 mm Hg (95% CI 9·1-11·6) in the intervention group and 6·0 mm Hg (4·6-7·5) in the usual care group (adjusted mean difference 4·1 mm Hg [2·2 to 5·8]). INTERPRETATION: Lifestyle counselling and blood pressure monitoring by community health workers is effective in substantially reducing blood pressure while adults are being monitored in a trial but, following cessation of the intervention, this benefit is not maintained in the long term, with potential for harm. This finding could have important implications for funders and research communities to regularly target participants for education and follow-up at an optimal timepoint to reduce any likelihood of harm. FUNDING: Monash University (Melbourne, VIC, Australia) and the Jayanti Memorial Trust (Kathmandu, Nepal). TRANSLATION: For the Nepali translation of the abstract see Supplementary Materials section.

Number of Live Births, Age at the Time of Having a Child, Span of Births and Risk of Dementia: A Population-Based Cohort Study of 253,611 U.K. Women.

Objectives: The association between birth-related factors and dementia is unclear. We aimed to investigate their association and subsequent risk of dementia in a large-scale follow-up prospective study. Materials and Methods: This population-based cohort study used data from U.K. Biobank (2006-2010), and the median follow-up was 12.0 years. Multivariable-adjusted Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) between number of children, age of first live birth, age of last live birth, span of births, and dementia. Restricted cubic spline models were used to quantify dose-response relationships. Results: A total of 253,611 women with mean age (standard deviation) of 56.3 (8.0) years were included. Compared with women with no child, women who had three or more children and first birth at age before 25 years, had elevated risk of all-cause dementia (HR: 1.30, 95% CI: 1.10-1.54), Alzheimer's disease (AD; 1.21, 1.00-1.46), and vascular dementia (VD; 1.59, 1.19-2.13). Also, women with three or more children and the last birth at age before 30 years, had increased risk of all-cause dementia (1.33, 1.11-1.59), AD (1.27, 1.03-1.57), and VD (1.55, 1.12-2.13). Moreover, women who had three or more children in <7 years, had an increased risk of all-cause dementia (1.25, 1.04-1.49). Dose-response relationship showed a lowest risk of dementia at having two children, and having three or more children in 7-9 years. Conclusions: Number of children, age of births, and span of births were all related to risk of dementia. These findings may help developing fertility policies or dementia prevention programs.

Association between hearing aid use and all-cause and cause-specific dementia: an analysis of the UK Biobank cohort.

BACKGROUND: Dementia and hearing loss are both highly prevalent conditions among older adults. We aimed to examine the association between hearing aid use and risk of all-cause and cause-specific dementia among middle-aged and older-aged adults, and to explore the roles of mediators and moderators in their association. METHODS: We used data from the UK Biobank, a population-based cohort study, which recruited adults aged 40-69 years between 2006 and 2010 across 22 centres in England, Scotland, and Wales. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs between self-reported hearing aid use status (hearing loss with or without hearing aids) at baseline and risk of dementia (all-cause dementia, Alzheimer's disease, vascular dementia, and non-Alzheimer's disease non-vascular dementia). Dementia diagnoses were ascertained using hospital records and death-register data. We also analysed the roles of mediators (self-reported social isolation, loneliness, and mood) and moderators (self-reported education and income, smoking, morbidity, and measured APOE allele status). FINDINGS: After the exclusion of people who did not answer the question on hearing difficulties (n=25 081 [5·0%]) and those with dementia at baseline visit (n=283 [0·1%]), we included 437 704 people in the analyses. Compared with participants without hearing loss, people with hearing loss without hearing aids had an increased risk of all-cause dementia (HR 1·42 [95% CI 1·29-1·56]); we found no increased risk in people with hearing loss with hearing aids (1·04 [0·98-1·10]). The positive association of hearing aid use was observed in all-cause dementia and cause-specific dementia subtypes (Alzheimer's disease, vascular dementia, and non-Alzheimer's disease non-vascular dementia). The attributable risk proportion of dementia for hearing loss was estimated to be 29·6%. Of the total association between hearing aid use and all-cause dementia, 1·5% was mediated by reducing social isolation, 2·3% by reducing loneliness, and 7·1% by reducing depressed mood. INTERPRETATION: In people with hearing loss, hearing aid use is associated with a risk of dementia of a similar level to that of people without hearing loss. With the postulation that up to 8% of dementia cases could be prevented with proper hearing loss management, our findings highlight the urgent need to take measures to address hearing loss to improve cognitive decline. FUNDING: National Natural Science Foundation of China and Shandong Province, Taishan Scholars Project, China Medical Board, and China Postdoctoral Science Foundation.

Tobacco endgame intervention impacts on health gains and Maori:non-Maori health inequity: a simulation study of the Aotearoa/New Zealand Tobacco Action Plan.

BACKGROUND: The Aotearoa/New Zealand Government is aiming to end the tobacco epidemic and markedly reduce Maori:non-Maori health inequalities by legislating: (1) denicotinisation of retail tobacco, (2) 95% reduction in retail outlets and (c) a tobacco free-generation whereby people born after 2005 are unable to legally purchase tobacco. This paper estimates future smoking prevalence, mortality inequality and health-adjusted life year (HALY) impacts of these strategies. METHODS: We used a Markov model to estimate future yearly smoking and vaping prevalence, linked to a proportional multistate life table model to estimate future mortality and HALYs. RESULTS: The combined package of strategies (plus media promotion) reduced adult smoking prevalence from 31.8% in 2022 to 7.3% in 2025 for Maori, and 11.8% to 2.7% for non-Maori. The 5% smoking prevalence target was forecast to be achieved in 2026 and 2027 for Maori males and females, respectively.The HALY gains for the combined package over the population's remaining lifespan were estimated to be 594 000 (95% uncertainty interval (UI): 443 000 to 738 000; 3% discount rate). Denicotinisation alone achieved 97% of these HALYs, the retail strategy 19% and tobacco-free generation 12%.By 2040, the combined package was forcat to reduce the gap in Maori:non-Maori all-cause mortality rates for people 45+ years old by 22.9% (95% UI: 19.9% to 26.2%) for females and 9.6% (8.4% to 11.0%) for males. CONCLUSION: A tobacco endgame strategy, especially denicotinisation, could deliver large health benefits and dramatically reduce health inequities between Maori and non-Maori in Aotearoa/New Zealand.

Association of dietary patterns and food groups intake with multimorbidity: A prospective cohort study.

BACKGROUND: Although diet has been extensively studied in relation to individual chronic conditions, studies linking diet with multiple chronic conditions (multimorbidity) remained scarce. We aimed to undertake a comprehensive analysis evaluating associations of overall dietary patterns and specific food groups with long-term risk of multimorbidity. METHODS: The study included 348,290 participants from UK Biobank who completed eligible food frequency questionnaires (FFQ) and were not diagnosed with any of the 38 chronic or mental health conditions of interest at baseline (2006-2010). Dietary patterns were identified using exploratory factor analysis. Cox regression models were used to estimate corresponding hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The median follow-up was 8.01 years, and 50,837 (14.60%) participants developed multimorbidity. Among the three identified dietary patterns, the Western Pattern was associated with an increased risk of multimorbidity (HRQ5 vs Q1 = 1.06, 95% CI: 1.03-1.09), while inverse associations were observed for moderate adherence to the White Meat Pattern (HRQ3vs Q1 = 0.97, 95% CI: 0.94-0.99) and highest adherence to the Prudent Pattern (HRQ5 vs Q1 = 0.92, 95% CI: 0.90-0.95). For specific food groups, more frequent intakes of processed meat and poultry were associated with higher risks of multimorbidity, whereas higher intake frequency of fish and more intakes of fruits and cereal were associated with decreased risks. CONCLUSION: Dietary patterns and specific food groups are associated with the risk of multimorbidity. These findings suggest the importance of considering dietary interventions in the prevention and management of multimorbidity.

Association between socioeconomic status and health behaviour change before and after non-communicable disease diagnoses: a multicohort study.

BACKGROUND: Behavioural risk factors of non-communicable diseases (NCDs) are socially patterned. However, the direction and the extent to which socioeconomic status (SES) influences behaviour changes before and after the diagnosis of NCDs is not clearly understood. We aimed to investigate the influence of SES on behaviour changes (physical inactivity and smoking) before and after the diagnosis of major NCDs. METHODS: In this multicohort study, we pooled individual-level data from six prospective cohort studies across 17 countries. We included participants who were diagnosed with either diabetes, cardiovascular disease, chronic lung disease, or cancer after recruitment. Participants were surveyed every 2 years. Education and total household wealth were used to construct SES. We measured behaviour changes as whether or not participants continued or initiated physical inactivity or smoking after NCD diagnosis. We used multivariable logistic regression models to estimate odds ratios (ORs), prevalence ratios (PRs), and 95% CIs for the associations between SES and continuation or initiation of unfavourable behaviours. FINDINGS: We included 8107 individuals recruited between March, 2002, and January, 2016. Over the 4-year period before and after NCD diagnosis, 886 (60·4%) of 1466 individuals continued physical inactivity and 1018 (68·8%) of 1480 participants continued smoking; 1047 (15·8%) of 6641 participants with physical activity before diagnosis initiated physical inactivity after diagnosis and 132 (2·0%) of 6627 non-smokers before diagnosis initiated smoking after diagnosis. Compared with participants with high SES, those with low SES were more likely to continue physical inactivity (244 [70·3%] of 347 vs 23 [50.0%] of 46; PR 1·41 [95% CI 1·05-1·99]; OR 2·28 [1·18-4·41]), continue smoking (214 [75·4%] of 284 vs 39 [60·9%] of 64; PR 1·27 [1·03-1·59]; OR 2·08 [1·14-3·80]), but also to initiate physical inactivity (188 [26·1%] of 720 vs 47 [7·4%] of 639; PR 3·59 [2·58-4·85]; OR 4·31 [3·02 - 6·14]). INTERPRETATION: Low SES was associated with continuing or initiating physical inactivity and continuing smoking after NCD diagnosis. Reducing socioeconomic inequality in health behaviour changes should be prioritised and integrated into NCD-prevention programmes. FUNDING: Zhejiang University and Fundamental Research Funds for the Central Universities.

Housing and health: an updated glossary.

Recent crises have underscored the importance that housing has in sustaining good health and, equally, its potential to harm health. Considering this and building on Howden-Chapman's early glossary of housing and health and the WHO Housing and Health Guidelines, this paper introduces a range of housing and health-related terms, reflecting almost 20 years of development in the field. It defines key concepts currently used in research, policy and practice to describe housing in relation to health and health inequalities. Definitions are organised by three overarching aspects of housing: affordability (including housing affordability stress (HAS) and fuel poverty), suitability (including condition, accessibility and sustainable housing) and security (including precarious housing and homelessness). Each of these inter-related aspects of housing can be either protective of, or detrimental to, health. This glossary broadens our understanding of the relationship between housing and health to further promote interdisciplinarity and strengthen the nexus between these fields.

Sex differences in the association between cardiovascular diseases and dementia subtypes: a prospective analysis of 464,616 UK Biobank participants.

BACKGROUND: Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown. METHODS: We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), lifestyle (smoking, BMI, leisure activities, and physical activity), genetic factors (APOE allele status), and medical history were also analyzed. RESULTS: Compared to people who did not experience a CVD event, the HRs (95%CI) between CVD and all-cause dementia were higher in women compared to men, with an RHR (Female/Male) of 1.20 (1.13, 1.28). Specifically, the HRs for AD were higher in women with CHD and heart failure compared to men, with an RHR (95%CI) of 1.63 (1.39, 1.91) and 1.32 (1.07, 1.62) respectively. The HRs for VD were higher in men with heart failure than women, with RHR (95%CI) of 0.73 (0.57, 0.93). An interaction effect was observed between socioeconomic, lifestyle, genetic factors, and medical history in the sex-specific association between CVD and dementia. CONCLUSION: Women with CVD were 1.5 times more likely to experience AD than men, while had 15% lower risk of having VD than men.

State-Level Social Vulnerability Index and Healthcare Access: The Behavioral Risk Factor Surveillance System Survey.

INTRODUCTION: Access to health care is affected by social determinants of health. The social vulnerability index encompasses multiple social determinants of health simultaneously and may therefore be associated with healthcare access. METHODS: Cross-sectional data were used from the 2016‒2019 Behavioral Risk Factor Surveillance System, a nationally representative U.S. telephone-based survey of adults aged ≥18 years. State-level social vulnerability index was derived using county-level social vulnerability index estimates from the Centers for Disease Control and Prevention Agency for Toxic Substances and Disease Registry. Analyses were performed in October 2021. Social vulnerability index was ranked according to percentiles, which were divided into tertiles: Tertile 1 (0.10-0.32), Tertile 2 (0.33-0.53), and Tertile 3 (0.54-0.90). RESULTS: In multivariable-adjusted models comparing U.S. states in Tertile 3 with those in Tertile 1 of social vulnerability index, there was a higher prevalence of absence of healthcare coverage (OR=1.39 [95% CI=1.22, 1.58]), absence of primary care provider (OR=1.34 [95% CI=1.22, 1.48]), >1-year duration since last routine checkup (OR=1.18 [95% CI=1.10, 1.27]), inability to see a doctor because of cost (OR=1.38 [95% CI=1.23, 1.54]), and the composite variable of any difficulty in accessing healthcare (OR=1.15 [95% CI=1.08, 1.22]). CONCLUSIONS: State-level social vulnerability is associated with several measures related to healthcare access. These results can help to identify targeted interventions to improve access to health care in U.S. states with high social vulnerability index burden.

Transforming Nepal's primary health care delivery system in global health era: addressing historical and current implementation challenges.

Nepal's Primary Health Care (PHC) is aligned vertically with disease control programs at the core and a vast network of community health workers at the periphery. Aligning with the globalization of health and the factors affecting global burden of diseases, Nepal echoes the progressive increase in life expectancy, changes in diseases patterns, including the current impact of COVID-19. Nepal's health system is also accommodating recent federalization, and thus it is critical to explore how the primary health care system is grappling the challenges amidst these changes. In this review, we conducted a narrative synthesis of literature to explore the challenges related to transformation of Nepal's primary health care delivery system to meet the demands incurred by impact of globalization and recent federalization, covering following database: PubMED, Embase and Google Scholar. Of the 49 articles abstracted for full text review, 37 were included in the analyses. Existing theories were used for constructing the conceptual framework to explain the study findings. The results are divided into four themes. Additional searches were conducted to further support the narrative synthesis: a total of 46 articles were further included in the articulation of main findings. Transforming Nepal's primary health care system requires a clear focus on following priority areas that include i) Revised efforts towards strengthening of community based primary health care units; ii) Adapting vertical programs to federal governance; iii) Reinforcing the health insurance scheme; and iv) Strengthening an existing network of community health workers and health human resources. This review discusses how these broad goals bear challenges and opportunities.

Association of reproductive factors with dementia: A systematic review and dose-response meta-analyses of observational studies.

BACKGROUND: Associations between endogenous estrogen exposure indicators and risk of subtypes of dementia have been unclear. METHODS: Databases (PubMed, EMBASE and Web of Science) were searched electronically on 1st July and updated regularly until 12nd November 2021. Observational studies of English language were selected if reported an effect estimate [e.g., odds ratio (OR), rate ratio (RR) or hazard ratio (HR)] and 95% CI for the association between any exposure (age of menarche, age at menopause, reproductive period, estradiol level) and any endpoint variable [all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), cognitive impairment (CI)]. Random-effects models and dose-response meta-analyses were used to calculate estimates and to show the linear/nonlinear relationship. PROSPERO CRD42021274827. FINDINGS: We included 22 studies (475 9764 women) in this analysis. We found no clear relationship between late menarche (≥14 vs <14 years) and dementia, CI in categorical meta-analysis compared to a J-shape relationship in dose-response meta-analyses. Later menopause (≥45 vs <45 years) was consistently associated with a lower risk of all-cause dementia (pooled RR: 0.87, 95%CI: 0.78-0.97, I2=56.0%), AD (0.67, 0.44-0.99, I2=78.3%), VD (0.87, 0.80-0.94) and CI (0.82, 0.71-0.94, I2=19.3%) in categorical meta-analysis, showing similar results in dose-response meta-analyses. An inverse relationship between longer reproductive duration (≥35 vs <35 years) and dementia was observed in dose-response meta-analysis. In addition, estradiol levels after menopause were inversely correlated with the risk of AD and CI. INTERPRETATION: In this study, later menopause and longer reproductive period were associated with a lower risk of dementia, while the relationship for menarchal age was J-shaped. There was an inverse relationship between higher postmenopausal estrogen levels and risk of AD and CI. Longitudinal study are needed to further explore the association between life-time estrogen exposure and risk of subtypes of dementia. FUNDING: Start-up Foundation for Scientific Research in Shandong University.