Medicaid Expansion and Racial-Ethnic and Sex Disparities in Cardiovascular Diseases Over 6 Years: A Generalized Synthetic Control Approach.

BACKGROUND: Studies have suggested Medicaid expansion enacted in 2014 has resulted in a reduction in overall cardiovascular disease (CVD) mortality in the United States. However, it is unknown whether Medicaid expansion has a similar effect across race-ethnicity and sex. We investigated the effect of Medicaid expansion on CVD mortality across race-ethnicity and sex. METHODS: Data come from the behavioral risk factor surveillance system and the US Centers for Disease Control's Wide-ranging Online Data for Epidemiologic Research, spanning the period 2000-2019. We used the generalized synthetic control method, a quasi-experimental approach, to estimate effects. RESULTS: Medicaid expansion was associated with -5.36 (mean difference [MD], 95% confidence interval [CI] = -22.63, 11.91) CVD deaths per 100,000 persons per year among Blacks; -4.28 (MD, 95% CI = -30.08, 21.52) among Hispanics; -3.18 (MD, 95% CI = -8.30, 1.94) among Whites; -5.96 (MD, 95% CI = -15.42, 3.50) among men; and -3.34 (MD, 95% CI = -8.05, 1.37) among women. The difference in mean difference (DMD) between the effect of Medicaid expansion in Blacks compared with Whites was -2.18; (DMD, 95% CI = -20.20, 15.83); between that in Hispanics compared with Whites: -1.10; (DMD, 95% CI = -27.40, 25.20) and between that in women compared with men: 2.62; (DMD, 95% CI = -7.95, 13.19). CONCLUSIONS: Medicaid expansion was associated with a reduction in CVD mortality overall and in White, Black, Hispanic, male, and female subpopulations. Also, our study did not find any difference or disparity in the effect of Medicaid on CVD across race-ethnicity and sex-gender subpopulations, likely owing to imprecise estimates.

The role of perceived health in retention disparity: A HIV-testing-related behavioral intervention among African American and Latinx men who have sex with men in the United States.

Retention in healthcare and health behavior remains a critical issue, contributing to inequitable distribution of intervention benefits. In diseases such as HIV, where half of the new infections occur among racial and sexual minorities, it is important that interventions do not enlarge pre-existing health disparities. To effectively combat this public health issue, it is crucial that we quantify the magnitude of racial/ethnic disparity in retention. Further, there is a need to identify mediating factors to this relationship to inform equitable intervention design. In the present study, we assess the racial/ethnic disparity in retention in a peer-led online behavioral intervention to increase HIV self-testing behavior and identify explanatory factors. The research used data collected from the Harnessing Online Peer Education (HOPE) HIV Study that included 899 primarily African American and Latinx men who have sex with men (MSM) in the United States. Results show that African American participants had higher lost-to-follow-up rates at 12-week follow-up compared to Latinx participants (11.1% and 5.8% respectively, Odds Ratio = 2.18, 95% confidence interval: 1.12 - 4.11, p = 0.02), which is substantially mediated by participants' self-rated health score (14.1% of the variation in the African American v.s. Latinx difference in lost-follow-up, p = 0.006). Thus, how MSM perceive their health may play an important role in their retention in HIV-related behavioral intervention programs and its racial/ethnic disparity.

Treatment of portosystemic shunt-borne hepatic encephalopathy in a 97-year-old woman using balloon-occluded retrograde transvenous obliteration: A case report.

BACKGROUND: Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts. Surgical shunt occlusion has been standard treatment, although recently the less invasive balloon-occluded retrograde transvenous obliteration (B-RTO) has gained increasing attention. Thus far, there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years. In this study, we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins, successfully treated with B-RTO. CASE SUMMARY: A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness. She had no jaundice, spider angioma, palmar erythema, hepatosplenomegaly, or asterixis. Her blood tests showed hyperammonemia, and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein. She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt. The patient did not improve with conservative treatment: Lactulose, rifaximin, and a low-protein diet. B-RTO was performed, which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness. Moreover, there was no abdominal pain or elevated levels of liver enzymes due to complications. The patient was discharged without further consciousness disturbance. CONCLUSION: Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance, including abnormal behavior and speech.

Different time scales used for sexual partner surveys pose a challenge in modelling dynamics of sexually transmitted infections.

Mathematical models for sexually transmitted infections (STIs) are parameterised by empirical data on sexual behaviour (e.g. the number of partners over a given period) obtained from surveys. However, the time window for reporting sexual partnerships may vary between surveys and how data for different windows can be translated from one to another remains an open question. To highlight this issue, we compared the distributions of the number of sexual partners over one year and four weeks from the British National Surveys of Sexual Attitudes and Lifestyles. The results show that simple linear rescaling did not render the one-year and four-week partner distributions aligned. Parameterising STI models using survey-based sexual encounter rates without considering the implication of the reporting window used can lead to misleading results.

Social network correlates of free and purchased insecticide-treated bed nets in rural Uganda.

BACKGROUND: Malaria is a major cause of mortality and morbidity in Uganda. Despite Uganda's efforts to distribute bed nets, only half of households have achieved the World Health Organization (WHO) Universal Coverage Criteria (one bed net for every two household members). The role of peer influence on bed net ownership remains underexplored. Data on the complete social network of households were collected in a rural parish in southwestern Uganda to estimate the association between household bed net ownership and peer household bed net ownership. METHODS: Data on household sociodemographics, bed net ownership, and social networks were collected from all households across one parish in southwestern Uganda. Bed nets were categorized as either purchased or free. Purchased and free bed net ownership ratios were calculated based on the WHO Universal Coverage Criteria. Using network name generators and complete census of parish residents, the complete social network of households in the parish was generated. Linear regression models that account for network autocorrelation were fitted to estimate the association between households' bed net ownership ratios and bed net ownership ratios of network peer households, adjusting for sociodemographics and network centrality. RESULTS: One thousand seven hundred forty-seven respondents were interviewed, accounting for 716 households. The median number of peer households to which a household was directly connected was 7. Eighty-six percent of households owned at least one bed net, and 41% of households met the WHO Universal Coverage Criterion. The median bed net ownership ratios were 0.67 for all bed nets, 0.33 for free bed nets, and 0.20 for purchased bed nets. In adjusted multivariable models, purchased bed net ownership ratio was associated with average household wealth among peer households (b = 0.06, 95% CI 0.03, 0.10), but not associated with average purchased bed net ownership ratio of peer households. Free bed net ownership ratio was associated with the number of children under 5 (b = 0.08, 95% CI 0.05, 0.10) and average free bed net ownership ratios of peer households (b = 0.66, 95% CI 0.46, 0.85). CONCLUSIONS: Household bed net ownership was associated with bed net ownership of peer households for free bed nets, but not for purchased bed nets. The findings suggest that public health interventions may consider leveraging social networks as tools for dissemination, particularly for bed nets that are provided free of charge.

The consequence of financial incentives for not prescribing antibiotics: a Japan's nationwide quasi-experiment.

BACKGROUND: For addressing antibiotic overuse, Japan designed a health care policy in which eligible medical facilities could claim a financial reward when antibiotics were not prescribed for early-stage respiratory and gastrointestinal infections. The policy was introduced in a pilot manner in paediatric clinics in April 2018. METHODS: We conducted a quasi-experimental, propensity score-matched, difference-in-differences (DID) design to determine whether the nationwide financial incentives for appropriate non-prescribing of antibiotics as antimicrobial stewardship [800 JPY (≈7.3 US D) per case] were associated with changes in prescription patterns, including antibiotics, and health care use in routine paediatric health care settings at a national level. Data consisted of 9 253 261 cases of infectious diseases in 553 138 patients treated at 10 180 eligible or ineligible facilities. RESULTS: A total of 2959 eligible facilities claimed 316 770 cases for financial incentives and earned 253 million JPY (≈2.29 million USD). Compared with ineligible facilities, the introduction of financial incentives in the eligible facilities was associated with an excess reduction in antibiotic prescriptions [DID estimate, -228.6 days of therapy (DOTs) per 1000 cases (95% CI, -272.4 to -184.9), which corresponded to a relative reduction of 17.8% (95% CI, 14.8 to 20.7)]. The introduction was also associated with excess reductions in drugs for respiratory symptoms [DID estimates, -256.9 DOTs per 1000 cases (95% CI, -379.3 to -134.5)] and antihistamines [DID estimate, -198.5 DOTs per 1000 cases (95% CI, -282.1 to -114.9)]. There was no excess in out-of-hour visits [DID estimate, -4.43 events per 1000 cases (95% CI, -12.8 to 3.97)] or hospitalizations [DID estimate, -0.08 events per 1000 cases (95% CI, -0.48 to 0.31)]. CONCLUSIONS: Our findings suggest that financial incentives to medical facilities for not prescribing antibiotics were associated with reductions in prescriptions for antibiotics without adverse health care consequences. Japan's new health policy provided us with policy options for immediately reducing inappropriate antibiotic prescriptions by relatively small financial incentives.

Change in clinical practice variations for antibiotic prescriptions across different pediatric clinics: A Japan's nationwide observational study.

BACKGROUND: In 2016, the Japanese government set the National Action Plan on antimicrobial resistance to reduce antibiotic prescriptions. However, the trends and variations of antibiotic prescription patterns in a routine healthcare setting during the fiscal year 2013-2018 across different clinics at a national level are unclear. METHODS: This retrospective cohort study included all clinics with >100 pediatric outpatients with infectious diseases per month during the fiscal year 2013-2018 using a national database in Japan. We investigated the trends in antibiotic prescription rates and their patterns and variations across different clinics over the six years following the 2019 World Health Organization Access, Watch, Reserve antibiotic groups, and Amoxicillin Index. RESULTS: A total of 2278 clinics with 94,414,170 infectious disease-related visits were eligible for the study. Most clinics showed higher Watch percentages (median 85.4%; IQR, 68.5-95.1) than Access percentages (median, 13.8%; IQR, 4.2-30.7) and Amoxicillin Index (median, 13.3%; IQR, 3.9-30.4). The introduction of the Action Plan changed annual absolute reductions in the antibiotic prescription rates from -16.0 DOTs/1000 visitors (95%CI, -16.4-15.6) to -239.3 per 1000 visitors (95%CI, -240.0-238.6). However, these impacts were heterogeneous across clinics. From 2013 to 2018, 41.4% reduced the antibiotic prescription rates by >33.3% (median, -1035.5 DOTs/1000 visitors; IQR, -1519.4-680.2), 18.7% did not change the rates (median, -40.3 DOTs/1000 visitors; IQR, -168.4-68.6), and 7.3% increased the rates by >10% (499.5 DOTs per 1000 visitors; IQR, 232.6-837.5). CONCLUSIONS: We observed the National Action Plan's impacts and extensive prescription variations across different pediatric clinics. However, one-fourth of clinics did not improve antibiotic prescription patterns even after introducing the Action Plan.

Revisiting social MPE: an integration of molecular pathological epidemiology and social science in the new era of precision medicine.

INTRODUCTION: Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework. AREAS COVERED: Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimer's disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimer's disease to date. EXPERT OPINION: With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.

DNA methylation signatures associated with prognosis of gastric cancer.

BACKGROUND: Few studies have examined prognostic outcomes-associated molecular signatures other than overall survival (OS) for gastric cancer (GC). We aimed to identify DNA methylation biomarkers associated with multiple prognostic outcomes of GC in an epigenome-wide association study. METHODS: Based on the Cancer Genome Atlas (TCGA), DNA methylation loci associated with OS (n = 381), disease-specific survival (DSS, n = 372), and progression-free interval (PFI, n = 383) were discovered in training set subjects (false discovery rates < 0.05) randomly selected for each prognostic outcome and were then validated in remaining subjects (P-values < 0.05). Key CpGs simultaneously validated for OS, DSS, and PFI were further assessed for disease-free interval (DFI, n = 247). Gene set enrichment analyses were conducted to explore the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways simultaneously enriched for multiple GC prognostic outcomes. Methylation correlated blocks (MCBs) were identified for co-methylation patterns associated with GC prognosis. Based on key CpGs, risk score models were established to predict four prognostic outcomes. Spearman correlation analyses were performed between key CpG sites and their host gene mRNA expression. RESULTS: We newly identified DNA methylation of seven CpGs significantly associated with OS, DSS, and PFI of GC, including cg10399824 (GRK5), cg05275153 (RGS12), cg24406668 (MMP9), cg14719951(DSC3), and cg25117092 (MED12L), and two in intergenic regions (cg11348188 and cg11671115). Except cg10399824 and cg24406668, five of them were also significantly associated with DFI of GC. Neuroactive ligand-receptor interaction pathway was suggested to play a key role in the effect of DNA methylation on GC prognosis. Consistent with individual CpG-level association, three MCBs involving cg11671115, cg14719951, and cg24406668 were significantly associated with multiple prognostic outcomes of GC. Integrating key CpG loci, two risk score models performed well in predicting GC prognosis. Gene body DNA methylation of cg14719951, cg10399824, and cg25117092 was associated with their host gene expression, whereas no significant associations between their host gene expression and four clinical prognostic outcomes of GC were observed. CONCLUSIONS: We newly identified seven CpGs associated with OS, DSS, and PFI of GC, with five of them also associated with DFI, which might inform patient stratification in clinical practices.

Socio-demographic determinants of motorcycle speeding in Maha Sarakham, Thailand.

Thailand has the highest road traffic fatality rate in Southeast Asia, making road safety a critical public health concern. A 2015 World Health Organization (WHO) Report showed that speeding behavior was the most important determinant for road traffic crashes in Thailand. Here, we aimed to examine associations of socio-demographic factors (gender, age, socioeconomic status) with self-reported motorcycle speeding behavior. Additionally, we examined a potential role of time discounting and risk preference as mediators in the association of socio-demographic factors with speeding. We used data obtained from the Mahasarakham University Social Network Survey 2018 (MSUSSS) (N = 150). We ran linear network autocorrelation models (lnam) to account for the data's social network structure. We found that males are more likely than females to engage in speeding behavior (ß = 0.140, p = 0.001) and to discount the future (ß = 5.175, p = 0.017). However, further causal mediation analysis showed that time discounting does not mediate the gender-speeding association (p for mediation = 0.540). Although socioeconomic status (subjective social class) was not associated with speeding (ß = 0.039, p = 0.177), age was marginally associated with speeding (ß = 0.005, p = 0.093). Future studies may consider using a larger sample.

Network interventions for managing the COVID-19 pandemic and sustaining economy.

Sustaining economic activities while curbing the number of new coronavirus disease 2019 (COVID-19) cases until effective vaccines or treatments become available is a major public health and policy challenge. In this paper, we use agent-based simulations of a network-based susceptible-exposed-infectious-recovered (SEIR) model to investigate two network intervention strategies for mitigating the spread of transmission while maintaining economic activities. In the simulations, we assume that people engage in group activities in multiple sectors (e.g., going to work, going to a local grocery store), where they interact with others in the same group and potentially become infected. In the first strategy, each group is divided into two subgroups (e.g., a group of customers can only go to the grocery store in the morning, while another separate group of customers can only go in the afternoon). In the second strategy, we balance the number of group members across different groups within the same sector (e.g., every grocery store has the same number of customers). The simulation results show that the dividing groups strategy substantially reduces transmission, and the joint implementation of the two strategies could effectively bring the spread of transmission under control (i.e., effective reproduction number ≈ 1.0).

Effectiveness of Steroid Therapy on Pneumonic Chronic Obstructive Pulmonary Disease Exacerbation: A Multicenter, Retrospective Cohort Study.

Purpose: To date, no consensus exists on the effects of systemic steroid use on pneumonic chronic obstructive pulmonary disease (COPD) exacerbation owing to trial design issues in previous trials involving these conditions. This multicenter study aimed to evaluate more precisely the effectiveness of the use of systemic steroids in treating pneumonic COPD exacerbation in a larger sample by adjusting for confounding factors. Patients and Methods: This multicenter, retrospective, observational study was conducted across five acute general hospitals in Japan. We analyzed the association between parenteral/oral steroid therapy and time to clinical stability in pneumonic COPD exacerbation. We used a validated algorithm derived from the 10th revision of the International Classification of Diseases and Related Health Problems (ICD-10) to include patients with pneumonic COPD exacerbation. We excluded patients with other hypoxia causes (asthma exacerbation, pneumothorax, heart failure) and complicated pneumonia (obstructive pneumonia, empyema), those who required tracheal intubation/vasopressors, and those who were clinically stable on day of admission. The primary outcome was the time to clinical stability. Multiple imputation was used for missing data. Propensity scores within each imputed dataset were calculated using potential confounding factors. The Fine and Gray model was used within each dataset to account for the competing risk of death and hospital discharge without clinical stability, and we combined the results. Results: Altogether, 1237 patients were included. Systemic steroid therapy was administered to 658 patients (53%). The pooled estimated subdistribution hazard ratio of time to clinical stability in steroid vs non-steroid users was 0.89 (95% confidence interval, 0.78 to 1.0). Conclusion: This study revealed that systemic steroid therapy may not improve the time to clinical stability in patients with pneumonic COPD exacerbation of mild to moderate severity. Further randomized controlled trials including more severe patients will be needed to evaluate the effectiveness of systemic steroid therapy accurately.

Mindfulness Meditation Activates Altruism.

Clinical evidence suggests that mindfulness meditation reduces anxiety, depression, and stress, and improves emotion regulation due to modulation of activity in neural substrates linked to the regulation of emotions and social preferences. However, less was known about whether mindfulness meditation might alter pro-social behavior. Here we examined whether mindfulness meditation activates human altruism, a component of social cooperation. Using a simple donation game, which is a real-world version of the Dictator's Game, we randomly assigned 326 subjects to a mindfulness meditation online session or control and measured their willingness to donate a portion of their payment for participation as a charitable donation. Subjects who underwent the meditation treatment donated at a 2.61 times higher rate than the control (p = 0.005), after controlling for socio-demographics. We also found a larger treatment effect of meditation among those who did not go to college (p < 0.001) and those who were under 25 years of age (p < 0.001), with both subject groups contributing virtually nothing in the control condition. Our results imply high context modularity of human altruism and the development of intervention approaches including mindfulness meditation to increase social cooperation, especially among subjects with low baseline willingness to contribute.

Assortative mating at loci under recent natural selection in humans.

Genetic correlation between mates at specific loci can greatly alter the evolutionary trajectory of a species. Genetic assortative mating has been documented in humans, but its existence beyond population stratification (shared ancestry) has been a matter of controversy. Here, we develop a method to measure assortative mating across the genome at 1,044,854 single-nucleotide polymorphisms (SNPs), controlling for population stratification and cohort-specific cryptic relatedness. Using data on 1683 human couples from two data sources, we find evidence for both assortative and disassortative mating at specific, discernible loci throughout the entire genome. Then, using the composite of multiple signals (CMS) score, we also show that the group of SNPs exhibiting the most assortativity has been under stronger recent positive selection. Simulations using realistic inputs confirm that assortative mating might indeed affect changes in allele frequency over time. These results suggest that genetic assortative mating may be speeding up evolution in humans.

A Systematic Review on Epidemiology and Promotion of Motorcycle Helmet Use in Thailand.

Background. Road traffic accidents are the fourth leading cause of death in the entire population, and the first among the youth (ages 15-19 years) in Thailand. The situation in Thailand is worse than in neighboring low- to middle-income countries in the Southeast Asia region. Seventy-three percent of the deaths in the country are motorcycle drivers or passengers. Although motorcyclists (both drivers and passengers) have been obligated to wear helmets by law, the prevalence of helmet use nationwide is not high (43.7% in 2010). Methods. We performed a systematic review to examine potential social determinants of helmet use behavior (observational studies) and to summarize previous intervention studies to promote helmet use (interventional studies) in the country. Studies were identified in PubMed and Web of Science, and by additional review of Thai-written literature. Results. We identified 16 relevant studies for social determinants of helmet use and 5 relevant studies for promoting helmet use in Thailand. Our review shows that several factors such as teens and children (age), women (gender), rural areas (geography), and alcohol drinking (interaction with another behavior) are associated with non-helmet use. We also identified 4 interventional studies implemented in Thailand: 1 law enforcement program and 4 community-based educational programs. Although all the studies improved the prevalence of helmet use after the interventions, only 2 studies exceeded 50%. Conclusion. There is consistent evidence that being younger, being a woman, living in non-Bangkok areas, and drinking alcohol are associated with non-helmet use among motorcycle users in Thailand. We also observed that the effect of past intervention programs is limited.

The social network context of HIV stigma: Population-based, sociocentric network study in rural Uganda.

RATIONALE: HIV-related stigma profoundly affects the physical and social wellbeing of people living with HIV, as well as the community's engagement with testing, treatment, and prevention. Based on theories of stigma elaborating how it arises from the relationships between the stigmatized and the stigmatizer as well as within the general community, we hypothesized that social networks can shape HIV-related stigma. OBJECTIVE: To estimate social network correlates of HIV-related stigma. METHODS: During 2011-2012, we collected complete social network data from a community of 1669 adults ("egos") in Mbarara, Uganda using six culturally-adapted name generators to elicit different types of social ties ("alters"). We measured HIV-related stigma using the 9-item AIDS-Related Stigma Scale. HIV serostatus was based on self-report. We fitted linear regression models that account for network autocorrelation to estimate the association between egos' HIV-related stigma, alters' HIV-related stigma and alters' self-reported HIV serostatus, while adjusting for egos' HIV serostatus, network centrality, village size, perceived HIV prevalence, and sociodemographic characteristics. RESULTS: The average AIDS-Related Stigma Score was 0.79 (Standard Deviation = 0.50). In the population 116 (7%) egos reported being HIV-positive, and 757 (46%) reported an HIV-positive alter. In the multivariable model, we found that egos' own HIV-related stigma was positively correlated with their alters' average stigma score (b=0.53; 95% confidence interval [CI] 0.42-0.63) and negatively correlated with having one or more HIV-positive alters (b=-0.05; 95% CI -0.10 to -0.003). CONCLUSION: Stigma-reduction interventions should be targeted not only at the level of the individual but also at the level of the network. Directed and meaningful contact with people living with HIV may also reduce HIV-related stigma.

Lack of social support and social trust as potential risk factors for dry eye disease: JPHC-NEXT study.

PURPOSE: To investigate whether social support and social trust are associated with DED. METHODS: Cross-sectional data from the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) were used. Subjects are 96,227 Japanese men and women aged 40 to 74. Data from respondents included information on DED, social support and social trust. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Social support was measured by emotional support and tangible support. Social trust was measured by level of general trust in others. Multiple logistic regression analysis was conducted to assess the association of social determinants for DED. RESULTS: Individuals with high levels of social support and social trust were less likely to have severe symptoms of DED and clinically diagnosed DED (P for trend < 0.001 in both cases). Those with the highest levels of social support and social trust were least likely to have DED (odds ratios [OR] = 0.64 [0.61-0.67], 95% confidence interval [CI] = 0.63 [0.60-0.67] for severe symptoms of DED; OR = 0.88 [0.83-0.93] and 0.85 [0.80-0.91] for clinically diagnosed DED). CONCLUSIONS: High levels of social support and social trust were associated with a lower prevalence of DED.

Hemoglobin E, malaria and natural selection.

It is known that there has been positive natural selection for hemoglobin S and C in humans despite negative health effects, due to its role in malaria resistance. However, it is not well understood, if there has been natural selection for hemoglobin E (HbE), which is a common variant in Southeast Asia. Therefore, we reviewed previous studies and discussed the potential role of natural selection in the prevalence of HbE. Our review shows that in vitro studies, evolutionary genetics studies and epidemiologic studies largely support an involvement of natural selection in the evolution of HbE and a protective role of HbE against malaria infection. However, the evidence is inconsistent, provided from different regions, and insufficient to perform an aggregated analysis such as a meta-analysis. In addition, few candidate gene, genome-wide association or epistasis studies, which have been made possible with the use of big data in the post-genomic era, have investigated HbE. The biological pathways linking HbE and malaria infection have not yet been fully elucidated. Therefore, further research is necessary before it can be concluded that there was positive natural selection for HbE due to protection against malaria. Lay summary: Our review shows that evidence largely supports an involvement of natural selection in the evolution of HbE and a protective role of HbE against malaria. However, the evidence is not consistent. Further research is necessary before it is concluded.