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PurposeAmong Latina breast cancer survivors, explore associations between rural/urban residence and health-related quality of life (HRQL), and whether associations are moderated by financial strain and low neighborhood cohesion.MethodsWe combined baseline data from two randomized controlled trials of a stress management intervention conducted among 151 urban and 153 rural dwelling Latinas with nonmetastatic breast cancer. Generalized linear models estimated associations between rural/urban status and HRQL (overall, emotional, social-family, physical, and functional well-being), and we examined moderation effects of financial strain and low neighborhood cohesion, controlling for age, marital status, and breast cancer characteristics.ResultsRural women reported better emotional (β = 1.85; 95% CI = 0.37, 3.33), functional (β = 2.23; 95% CI = 0.69, 3.77), and overall (β = 5.68; 95% CI = 1.12, 10.25) well-being than urban women, regardless of degree of financial strain or neighborhood cohesion; moderation effects were not statistically significant. Financial strain was inversely associated with emotional (β = -2.34; 95% CI = 3.63, -1.05), physical (β = -2.56; 95% CI = -4.12, -1.01), functional (β = -1.61; 95% CI = -2.96, -0.26), and overall (β = -6.67; 95% CI = -10.96, -2.98) well-being. Low neighborhood cohesion was inversely associated with emotional (β = -1.27; 95% CI = -2.50, -0.04), social-family (β = -1.72; 95% CI = -3.02, -0.42), functional (β = -1.63; 95% CI = -2.92, -0.34), and overall (β = -5.95; 95% CI = 9.76, -2.14) well-being.ConclusionsRural Latina breast cancer survivors reported better emotional, functional and overall well-being than their urban counterparts. Greater financial strain and less neighborhood cohesion were associated with worse HRQL on most domains regardless of rural/urban context.Implications for cancer survivorsInterventions that focus on increasing perceived neighborhood cohesion and reducing or better managing financial strain, could help improve Latina cancer survivors' well-being.

BACKGROUND: Social desirability can negatively affect the validity of self-reported measures, including underreporting of stigmatized behaviors like alcohol consumption. The Marlowe-Crowne Social Desirability Scale (SDS) is widely implemented and comprised of Denial and Attribution Domains (i.e., tendencies to deny undesirable traits or attribute socially desirable traits to oneself, respectively). Yet, limited psychometric research has been conducted in sub-Saharan Africa, where the prevalence of unhealthy alcohol consumption is high as well as religiosity and hierarchical social norms. To address this gap, we (a) conducted an exploratory study assessing certain psychometric properties of the 28-item SDS (Runyankole-translated) among persons with HIV (PWH) in Uganda, and (b) examined the relationship between social desirability and self-reported alcohol use. METHODS: We pooled baseline data (N = 1153) from three studies of PWH engaged in alcohol use from 2017 to 2021. We assessed the translated scales construct validity (via confirmatory factor analysis), internal consistency, item performance, differential item functioning by gender, concurrent validity with the DUREL religiosity index domains, and the association between social desirability and self-reported alcohol use. RESULTS: Participants had a mean age of 40.42 years, 63% were men, and 91% had an undetectable HIV viral load. The 28-item SDS had satisfactory construct validity (Model fit indices: RMSEA = 0.07, CFI = 0.84, TLI = 0.82) and internal consistency (Denial Domain ΩTotal = 0.82, Attribution Domain ΩTotal = 0.69). We excluded Item 14 (I never hesitate to help someone in trouble) from the Attribution Domain, which mitigated differential measurement error by gender and slightly improved the construct validity (Model fit indices: RMSEA = 0.06, CFI = 0.86, TLI = 0.85) and reliability (Attribution Domain ΩTotal = 0.72) of the 27-item modified SDS. Using the 27-item SDS, we found that social desirability was weakly correlated with religiosity and inversely associated with self-reported alcohol use after adjusting for biomarker-measured alcohol use and other confounders (β = -0.05, 95% confidence interval: -0.09 to -0.01, p-value = 0.03). CONCLUSIONS: We detected and mitigated measurement error in the 28-item Runyankole-translated SDS, and found that the modified 27-item scale had satisfactory construct validity and internal consistency in our sample. Future studies should continue to evaluate the psychometric properties of the Runyankole-translated SDS, including retranslating Item 14 and reevaluating its performance.

COVID-related discrimination towards historically marginalized racial-ethnic groups in the United States has been well-documented; however, its impact on psychological distress and sleep (overall and within specific racial-ethnic groups) is largely unknown. We used data from our nationally representative, online survey of 5,500 American Indian/Alaska Native, Asian, Black/African American, Native Hawaiian/Pacific Islander, Latino, White, and multiracial adults, conducted from 12/2020-2/2021. Participants were asked how often they experienced discriminatory behaviors "because they think you might have COVID-19" (modified Everyday Discrimination Scale). Psychological distress was captured as having experienced anxiety-depression symptoms (Patient Health Questionairre-4, PHQ-4), perceived stress (modified Perceived Stress Scale), or loneliness-isolation ("How often have you felt lonely and isolated?"). Sleep disturbances were measured using the Patient-Reported Outcomes Information System Short Form Sleep Disturbance scale (PROMIS-SF 4a). Overall, 22.1% reported COVID-related discriminatory behaviors (sometimes/always: 9.7%; rarely: 12.4%). 48.4% of participants reported anxiety-depression symptoms (moderate/severe: 23.7% mild: 24.8%), 62.4% reported feeling stressed (moderate/severe: 34.3%; mild: 28,1%), 61.0% reported feeling lonely-isolated (fairly often/very often: 21.3%; almost never/sometimes: 39.7%), and 35.4% reported sleep disturbances (moderate/severe:19.8%; mild: 15.6%). Discrimination was only associated with increased psychological distress among racial-ethnic minorities. For example, COVID-related discrimination was strongly associated with anxiety-depression among Black/African American adults (mild: aOR=2.12, 95% CI=1.43-5.17; moderate/severe: aOR=5.19, 95% CI=3.35-8.05), but no association was observed among White or multiracial adults. Mitigating pandemic-related discrimination could help alleviate mental and sleep health disparities occurring among minoritized racial-ethnic groups.

BackgroundObstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation.Methods and resultsInsurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution.

BACKGROUND: Almost half of all women in the US experience intimate partner violence (IPV) in their lifetime. The US Preventive Services Task Force recommends IPV screening paired with intervention for women of reproductive age. We aim to understand clinical practices and policies that are beneficial, detrimental, or insufficient to support survivors of IPV in a safety-net healthcare system. METHODS: We sampled 45 women who were 18-64 years old, had experienced IPV within the prior year and were patients in the San Francisco Health Network. We conducted in-depth, semi-structured interviews to elicit their perspectives on disclosing IPV and obtaining support within the healthcare system. We analyzed our data using thematic analysis and grounded theory practices informed by ecological systems theory. FINDINGS: We identified four themes regarding factors that impeded or facilitated discussing and addressing IPV across interpersonal and systemic levels relating to relationship-building, respect, autonomy and resources. (1) Interpersonal barriers included insufficient attention to relationship-building, lack of respect or concern for survivor circumstances, and feeling pressured to disclose IPV or to comply with clinicians recommended interventions. (2) Interpersonal facilitators consisted of patient-centered IPV inquiry, attentive listening, strength-based counseling and transparency regarding confidentiality. (3) Systemic barriers such as visit time limitations, clinician turn-over and feared loss of autonomy from involvement of governmental systems leading to separation from children or harm to partners, negatively affected interpersonal dynamics. (4) Systemic facilitators involved provision of resources through IPV universal education, on-site access to IPV services, and community partnerships. CONCLUSIONS: Women experiencing IPV in our study reported that relationship-building, respect, autonomy, and IPV-related resources were essential components to providing support, promoting safety, and enabling healing in the healthcare setting. Successful trauma-informed transformation of healthcare systems must optimize interpersonal and systemic factors that improve survivor wellbeing while eliminating barriers.

Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity disorder (ADHD) display strong male sex bias, due to a combination of genetic and biological factors, as well as selective ascertainment. While the hemizygous nature of chromosome X (Chr X) in males has long been postulated as a key point of male vulnerability, rare genetic variation on this chromosome has not been systematically characterized in large-scale whole exome sequencing studies of idiopathic ASD, TS, and ADHD. Here, we take advantage of informative recombinations in simplex ASD families to pinpoint risk-enriched regions on Chr X, within which rare maternally-inherited damaging variants carry substantial risk in males with ASD. We then apply a modified transmission disequilibrium test to 13,052 ASD probands and identify a novel high confidence ASD risk gene at exome-wide significance (MAGEC3). Finally, we observe that rare damaging variants within these risk regions carry similar effect sizes in males with TS or ADHD, further clarifying genetic mechanisms underlying male vulnerability in multiple neurodevelopmental disorders that can be exploited for systematic gene discovery.

ObjectivesTo assess access to abortion pills offered by clinics providing state-funded family planning services in California.MethodsWe attempted to make two scripted calls to a 20% random sample of family planning clinics in California, stratified by county, as "secret shoppers" in 2020 and 2021.ResultsClinic staff responded to 407 calls. Only 50 respondents (12%) reported their clinic offered abortion pills and 23 respondents (6%) accurately indicated to callers that abortion pills were available free to low-income individuals in California. Most (68%) clinics that did not offer abortion pills could not direct callers to a clinic that did offer abortion pills.ConclusionsEfforts are needed to increase the number of clinics providing medication abortion services in California. Clinic staff need training to provide accurate information about medication abortion.

BACKGROUND: The gut microbiome has been linked to many diseases with sex bias including autoimmune, metabolic, neurological, and reproductive disorders. While numerous studies report sex differences in fecal microbial communities, the role of the reproductive axis in this differentiation is unclear and it is unknown how sex differentiation affects microbial diversity in specific regions of the small and large intestine. METHODS: We used a genetic hypogonadal mouse model that does not produce sex steroids or go through puberty to investigate how sex and the reproductive axis impact bacterial diversity within the intestine. Using 16S rRNA gene sequencing, we analyzed alpha and beta diversity and taxonomic composition of fecal and intestinal communities from the lumen and mucosa of the duodenum, ileum, and cecum from adult female (n = 20) and male (n = 20) wild-type mice and female (n = 17) and male (n = 20) hypogonadal mice. RESULTS: Both sex and reproductive axis inactivation altered bacterial composition in an intestinal section and niche-specific manner. Hypogonadism was significantly associated with bacteria from the Bacteroidaceae, Eggerthellaceae, Muribaculaceae, and Rikenellaceae families, which have genes for bile acid metabolism and mucin degradation. Microbial balances between males and females and between hypogonadal and wild-type mice were also intestinal section-specific. In addition, we identified 3 bacterial genera (Escherichia Shigella, Lachnoclostridium, and Eggerthellaceae genus) with higher abundance in wild-type female mice throughout the intestinal tract compared to both wild-type male and hypogonadal female mice, indicating that activation of the reproductive axis leads to female-specific differentiation of the gut microbiome. Our results also implicated factors independent of the reproductive axis (i.e., sex chromosomes) in shaping sex differences in intestinal communities. Additionally, our detailed profile of intestinal communities showed that fecal samples do not reflect bacterial diversity in the small intestine. CONCLUSIONS: Our results indicate that sex differences in the gut microbiome are intestinal niche-specific and that sampling feces or the large intestine may miss significant sex effects in the small intestine. These results strongly support the need to consider both sex and reproductive status when studying the gut microbiome and while developing microbial-based therapies.

Providers disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes.We conducted a cross-sectional analysis of the associations between disrespect/abuse from health providers as a barrier to care and the following HIV care outcomes: (i) anti-retroviral treatment (ART) uptake ever, (ii) past 6-month visit to HIV provider, and (iii) CD4 count. Participants (N = 221) were people living with HIV who injected drugs and were not on ART at enrollment.Two in five participants (42%) reported a history disrespect/abuse from a healthcare provider that they cited as a barrier to care. Those reporting this concern had lower odds of ever use of ART (adjusted odds ratio 0.46 [95% CI 0.22, 0.95]); we found no significant associations for the other HIV outcomes. We additionally found higher representation of women among those reporting prevalence of disrespect/abuse from provider as a barrier to care compared to those not reporting this barrier (58.1% versus 27.3%).Almost half of this sample of PWH who inject drugs report disrespect/abuse from a provider as a barrier to healthcare, and this is associated with lower odds of receipt of ART but not with other HIV outcomes studied. There is need for improved focus on quality of respectful and dignified care from providers for PWH who inject drugs, and such focus may improve ART uptake in Russia.

Adverse pregnancy outcomes (APOs) are major risk factors for womens health during pregnancy and even in the years after pregnancy. Due to the heterogeneity of APOs, only few genetic associations have been identified. In this report, we conducted genome-wide association studies (GWASs) of 479 traits that are possibly related to APOs using a large and racially diverse study, Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). To display extensive results, we developed a web-based tool GnuMoM2b (https://gnumom2b.cumcobgyn.org/) for searching, visualizing, and sharing results from a GWAS of 479 pregnancy traits as well as phenome-wide association studies of more than 17 million single nucleotide polymorphisms. The genetic results from 3 ancestries (Europeans, Africans, and Admixed Americans) and meta-analyses are populated in GnuMoM2b. In conclusion, GnuMoM2b is a valuable resource for extraction of pregnancy-related genetic results and shows the potential to facilitate meaningful discoveries.

BackgroundParticipation and active engagement in meaningful activities support the emotional and physical well-being of older adults. In 2020, the onset of the COVID-19 pandemic altered lives, including the ability to participate in meaningful activities. This study compared meaningful activity engagement before and at the beginning of the COVID-19 pandemic in a nationally representative, diverse sample >65 years between 2015 and 2020.MethodsWe described the proportions and characteristics of National Health and Aging Trends Study participants and their engagement in four activities: visiting friends or family, attending religious services, participating in clubs/classes/other organized activities, and going out for enjoyment. We used mixed effects logistic regressions to compare probabilities of activity engagement before 2020 and in 2020, adjusting for age, sex, functional status, income, geographic region, anxiety-depression, and transportation issues.ResultsOf 6815 participants in 2015, the mean age was 77.7 (7.6) years; 57% of participants were female; 22% were Black, 5% Hispanic, 2% were American Indian, and 1% were Asian; 20% had disability; and median income was $33,000. Participation in all four activities remained consistent between 2015 and 2019 and declined in 2020. Significant differences existed in attending religious services (p

Intimate partner violence (IPV) has been associated with delays throughout the HIV care continuum. This study explored prospective associations between experiences of past-year IPV and two HIV care outcomes in the context of current universal test and treat guidelines using two consecutive rounds of an ongoing HIV surveillance study conducted in the Rakai region of Uganda. Longitudinal logistic regression models examined associations between IPV, use of antiretroviral therapy (ART) and viral load suppression (VS), adjusting for outcome variables at baseline. To address differences in ART retention by IPV, propensity scores were used to create inverse-probability-of-treatment-and-censoring-weighted (IPTCW) models. At baseline, of 1923 women with HIV (WWH), 34.6%, 26.5%, 13.5% reported past-year verbal, physical and sexual IPV; a lower proportion of persons who experienced physical IPV (79.4%) were VS than those who did not (84.3%; p = 0.01). The proportion VS at baseline also significantly differed by exposure to verbal IPV (p = 0.03). However, in adjusted longitudinal models, IPV was not associated with lower odds of ART use or VS at follow-up. Among WWH in the Rakai region, IPV does not appear to be a barrier to subsequent ART use or VS. However, given the prevalence of IPV in this population, interventions are needed.

Background Obstructive sleep apnea (OSA) is common in heart failure with preserved ejection fraction (HFpEF). However, current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in HFpEF. This study assessed the association between adherence to PAP therapy and health care resource use in patients with OSA and HFpEF. Methods and Results Administrative insurance claims data linked with objective PAP therapy usage data from patients with OSA and HFpEF were used to determine associations between PAP adherence and a composite outcome including hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 4237 patients (54.0% female, mean age 64.1 years); 40% were considered adherent to PAP therapy (30% intermediate adherent, 30% nonadherent). In the matched cohort, PAP-adherent patients had fewer health care resource use visits than nonadherent patients, a 57% decrease in hospitalizations, and a 36% decrease in emergency room visits versus the year before PAP initiation. Total health care costs were lower in adherent patients than nonadherent patients ($12 732 versus $15 610, P

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second Edition. Four LA-derived oxylipins were analyzed by ultra-high-pressure-LC/MS, and the 12,13-dihydroxyoctadecamonoenoic acid (12,13-DiHOME) considered the main species of interest. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F1,98 = 7.513, P = 0.007). The CYP450-derived 12(13)-epoxyoctadecamonoenoic acid (12(13)-EpOME) was associated with poorer executive function and verbal memory scores (F1,98 = 7.222, P = 0.008 and F1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent.

BackgroundThe distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.

OBJECTIVES: Globalisation and industrialisation can increase economic opportunity for low/middle-income nations, but these processes may also increase industrial accidents and harm workers. This paper examines the long-term, cohort-based health effects of the Bhopal gas disaster (BGD), one of the most serious industrial accidents in history. DESIGN: This retrospective analysis uses geolocated data on health and education from Indias National Family Health Survey-4 (NFHS-4) and the 1999 Indian Socio-Economic Survey by the National Sample Survey Organization (NSSO-1999) to examine the health effects of exposure to the BGD among men and women aged 15-49 years living in Madhya Pradesh in 2015-2016 (women n=40 786; men n=7031 (NFHS-4) and n=13 369 (NSSO-1999)), as well as their children (n=1260). A spatial difference-in-differences strategy estimated the relative effect of being in utero near Bhopal relative to other cohorts and to those further from Bhopal separately for each dataset. RESULTS: We document long-term, intergenerational impacts of the BGD, showing that men who were in utero at the time were more likely to have a disability that affected their employment 15 years later, and had higher rates of cancer and lower educational attainment over 30 years later. Changes in the sex ratio among children born in 1985 suggest an effect of the BGD up to 100 km from the accident. CONCLUSIONS: These results indicate social costs stemming from the BGD that extend far beyond the mortality and morbidity experienced in the immediate aftermath. Quantifying these multigenerational impacts is important for policy consideration. Moreover, our results suggest that the BGD affected people across a substantially more widespread area than has previously been demonstrated.

BackgroundNiger has the highest rate of adolescent fertility in the world, with early marriage, early childbearing and high gender inequity. This study assesses the impact of Reaching Married Adolescents (RMA), a gender-synchronized social behavioral intervention designed to improve modern contraceptive use and reduce intimate partner violence (IPV) among married adolescent couples in rural Niger.MethodsWe conducted a four-armed cluster-randomized trial in 48 villages across three districts in Dosso region, Niger. Married adolescent girls (ages 13-19) and their husbands were recruited within selected villages. Intervention arms included home visits by gender-matched community health workers (CHWs) (Arm 1), gender-segregated, group discussion sessions (Arm 2), and both approaches (Arm 3). We used multilevel mixed-effects Poisson regression models to assess intervention effects for our primary outcome, current modern contraceptive use, and our secondary outcome, past year IPV.ResultsBaseline and 24-month follow-up data were collected April-June 2016 and April-June 2018. At baseline, 1072 adolescent wives were interviewed (88% participation), with 90% retention at follow-up; 1080 husbands were interviewed (88% participation), with 72% retention at follow-up. Adolescent wives had higher likelihood of modern contraceptive use at follow-up relative to controls in Arm 1 (aIRR 3.65, 95% CI 1.41-8.78) and Arm 3 (aIRR 2.99, 95% CI 1.68-5.32); no Arm 2 effects were observed. Relative to those in the control arm, Arm 2 and Arm 3 participants were significantly less likely to report past year IPV (aIRR 0.40, 95% CI 0.18-0.88 for Arm 2; aIRR 0.46, 95% CI 0.21-1.01 for Arm 3). No Arm 1 effects were observed.ConclusionsThe RMA approach blending home visits by CHWs and gender-segregated group discussion sessions is the optimal format for increasing modern contraceptive use and decreasing IPV among married adolescents in Niger. Trial registration This trial is retrospectively registered with ClinicalTrials.gov, Identifier NCT03226730.

Student absenteeism affects students' engagement in school and academic and professional success. While research documents a significant association between school bullying/fighting and student absenteeism due to fear of being at school or getting to school, little research has examined the association of adolescent dating violence (ADV) victimization with this type of absenteeism. This study examined the relationship between physical and/or sexual ADV victimization in the past year (dichotomized as yes or no), and number of days of student absenteeism due to feeling unsafe at school or on the way to school in the past month (dichotomized as any vs. none). We analyzed cross-sectional data from the 2019 Youth Risk Behavior Survey (YRBS), a nationally representative survey of U.S. high school students (n = 9507). We conducted crude and multivariate regression models for the total sample and stratified by sex to assess our hypothesized association of ADV victimization and absenteeism; sex, grade, race/ethnicity, and sexual identity were included as covariates in adjusted models. Findings demonstrate that students reporting past year ADV victimization had 3.69 times the odds of student absenteeism due to feeling unsafe, when compared to students who did not report ADV victimization (95% CI: 3.06-4.45, p < 0.001). Sex-stratified models reveal that this effect is significantly stronger for males than for females, as indicated by non-overlapping confidence intervals (male AOR: 5.67, 95% CI: 4.18-7.68; female AOR: 2.95, 95% CI: 2.32-3.74). The multivariate models also show that Black and Latinx compared with White students, and lesbian/gay/bisexual/unsure compared with heterosexual students, had higher odds of student absenteeism due to feeling unsafe. Findings indicate the need to address ADV victimization and student absenteeism with integrated and gender-tailored responses, and with consideration of greater vulnerabilities for queer students and students of color.

Background Obstructive sleep apnea (OSA) is a common comorbidity in patients with heart failure, although current evidence is equivocal regarding the potential benefits of treating OSA with positive airway pressure (PAP) therapy in patients with heart failure. This study assessed the impact of adherence to PAP therapy on health care resource utilization in patients with OSA and heart failure with reduced ejection fraction. Methods and Results Administrative insurance claims data linked with objective PAP therapy use data from patients with OSA and heart failure with reduced ejection fraction were used to determine associations between PAP adherence and a composite outcome of hospitalizations and emergency room visits. One-year PAP adherence was based on an adapted US Medicare definition. Propensity score methods were used to create groups with similar characteristics across PAP adherence levels. The study cohort included 3182 patients (69.9% male, mean age 59.7 years); 39% were considered adherent to PAP therapy (29% intermediate adherent, 31% nonadherent). One year after PAP initiation, adherent patients had fewer composite visits than matched nonadherent patients, driven by a 24% reduction in emergency room visits for adherent patients. Composite visit costs were lower in adherent versus nonadherent patients ($3500 versus $5879, P=0.031), although total health care costs were not statistically different ($13 028 versus $14 729, P=0.889). Conclusions PAP therapy adherence in patients with OSA with heart failure with reduced ejection fraction was associated with a reduction in health care resource utilization. This suggests that greater emphasis should be placed on diagnosing and effectively treating OSA with PAP in patients with heart failure with reduced ejection fraction.

OBJECTIVES: There is little research on moral uncertainties and distress of palliative and hospice care providers (PHCPs) working in jurisdictions anticipating legalising voluntary assisted dying (VAD). This study examines the perception and anticipated concerns of PHCPs in providing VAD in the State of Queensland, Australia prior to legalisation of the practice in 2021. The findings help inform strategies to facilitate training and support the health and well-being of healthcare workers involved in VAD. DESIGN: The study used a qualitative approach to examine and analyse the perception and anticipated concerns of PHCPs regarding challenges of providing assisted dying in Queensland. Fourteen PHCPs were recruited using a purposive sampling strategy to obtain a broad representation of perspectives including work roles, geographical locations and workplace characteristics. Data were collected via one in-depth interview per participant. The transcripts were coded for patterns and themes using an inductive analysis approach following the tradition of Grounded Theory. SETTING: The study was conducted in hospital, hospice, community and residential aged care settings in Queensland, Australia. These included public and private facilities, secular and faith-based facilities, and regional/rural and urban facilities. PARTICIPANTS: Interviews were conducted with fourteen PHCPs: 10 nurses and 4 physicians; 11 female and 3 male. The median number of years of palliative care practice was 17, ranging from 2 to 36 years. For inclusion, participants had to be practising palliative and hospice care providers. RESULTS: PHCPs are divided on whether VAD should be considered part of palliative care. Expectations of moral distress and uncertainty about practising VAD were identified in five areas: handling requests, assessing patient capacity, arranging patient transfers and logistical issues, managing unsuccessful attempts, and dealing with team conflicts and stigma. CONCLUSIONS: The possibility of having to practise VAD causes moral distress and uncertainty for some PHCPs. Procedural clarity can address some uncertainties; moral and psychological distress, however, remains a source of tension that needs support to ensure ongoing care of both patients and PHCPs. The introduction of VAD post-legalisation may present an occasion for further moral education and development of PHCPs.

Background and objectivesPrevious studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.MethodsWe included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

In the face of imminent predatory danger, animals quickly detect the threat and mobilize key survival defensive actions, such as escape and freezing. The dorsomedial portion of the ventromedial hypothalamus (VMH) is a central node in innate and conditioned predator-induced defensive behaviours. Prior studies have shown that activity of steroidogenic factor 1 (sf1)-expressing VMH cells is necessary for such defensive behaviours. However, sf1-VMH neural activity during exposure to predatory threats has not been well characterized. Here, we use single-cell recordings of calcium transients from VMH cells in male and female mice. We show this region is activated by threat proximity and that it encodes future occurrence of escape but not freezing. Our data also show that VMH cells encoded proximity of an innate predatory threat but not a fear-conditioned shock grid. Furthermore, chemogenetic activation of the VMH increases avoidance of innate threats, such as open spaces and a live predator. This manipulation also increased freezing towards the predator, without altering defensive behaviours induced by a shock grid. Lastly, we show that optogenetic VMH activation recruited a broad swath of regions, suggestive of widespread changes in neural defensive state. Taken together, these data reveal the neural dynamics of the VMH during predator exposure and further highlight its role as a critical component of the hypothalamic predator defense system.

In India, traditional social practices around marriage, such as non-involvement of prospective brides in choice of partner and timing of marriage, child/early marriage, dowry and purdah, compromise womens agency at the time of marriage and may also affect contraceptive practices in marriage. This paper examines the associations between traditional marital practices and contraceptive behaviours, including womens control over contraceptive decision-making, couples communication about contraception, and ever use of contraceptives, among married women aged 18-29 years (N = 1,200) and their husbands in rural Maharashtra, India. Multivariable logistic regression was used to examine the association between these marginalising social practices and family planning behavioural outcomes, adjusting for demographic and parity confounders. Wives who were the primary decision-makers on who to marry had higher odds of ever having communicated with their husband on pregnancy prevention (AOR 1.76, 95% CI 1.16-2.68), and ever using modern contraceptives (AOR 2.19, 95% CI 1.52-3.16). Wives who were the primary decision-makers on when to marry also had higher odds of ever having used modern contraceptives (AOR 1.86, 95% CI 1.21-2.93). Womens involvement in marital choice may facilitate couples engagement related to family planning, possibly via the establishment of better communication between partners.

INTRODUCTION: Most patients with esophageal adenocarcinoma (EAC) do not have a previous diagnosis of Barretts esophagus (BE), demonstrating a failure of current screening practices. An understanding of patient attitudes and barriers is essential to develop and implement interventions to improve BE screening adherence. METHODS: We conducted a Web-based survey of patients aged >50 years with chronic gastroesophageal reflux disease at 3 academic medical centers and 1 affiliated safety net health systems. Survey domains included patient characteristics, endoscopy history, familiarity with screening practices, perceived BE/EAC risk, and barriers to screening. RESULTS: We obtained a response rate of 22.6% (472/2,084) (74% men, mean age 67.9 years). Self-identified race and ethnicity of participants was 66.5% non-Hispanic White, 20.0% non-Hispanic Black, 13.4% other race, and 7.1% Hispanic. Screening for BE was recommended in only 13.2%, and only 5.3% reported previous screening. Respondents had notable gaps in knowledge about screening indications; only two-thirds correctly identified BE risk factors and only 19.5% believed BE screening was needed for gastroesophageal reflux disease. More than 1 in 5 respondents believed they would get BE (31.9%) or EAC (20.2%) but reported barriers to screening. Compared with White respondents, more Black respondents were concerned about getting BE/EAC and interested in screening but report higher barriers to screening. DISCUSSION: Patients at risk for BE, particularly racial and ethnic minorities, are worried about developing EAC but rarely undergo screening and have poor understanding of screening recommendations.

BACKGROUND AND OBJECTIVES: GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases) are rare, autosomal recessive, neurodegenerative diseases with no available symptomatic or disease-modifying treatments. This clinical trial investigated N-acetyl-l-leucine (NALL), an orally administered, modified amino acid in pediatric (≥6 years) and adult patients with GM2 gangliosidoses. METHODS: In this phase IIb, multinational, open-label, rater-blinded study (IB1001-202), male and female patients aged ≥6 years with a genetically confirmed diagnosis of GM2 gangliosidoses received orally administered NALL for a 6-week treatment period (4 g/d in patients ≥13 years, weight-tiered doses for patients 6-12 years), followed by a 6-week posttreatment washout period. For the primary Clinical Impression of Change in Severity analysis, patient performance on a predetermined primary anchor test (the 8-Meter Walk Test or the 9-Hole Peg Test) at baseline, after 6 weeks on NALL, and again after a 6-week washout period was videoed and evaluated centrally by blinded raters. Secondary outcomes included assessments of ataxia, clinical global impression, and quality of life. RESULTS: Thirty patients between the age of 6 and 55 years were enrolled. Twenty-nine had an on-treatment assessment and were included in the primary modified intention-to-treat analysis. The study met its CI-CS primary end point (mean difference 0.71, SD = 2.09, 90% CI 0.00, 1.50, p = 0.039), as well as secondary measures of ataxia and global impression. NALL was safe and well tolerated, with no serious adverse reactions. DISCUSSION: Treatment with NALL was associated with statistically significant and clinically relevant changes in functioning and quality of life in patients with GM2 gangliosidosis. NALL was safe and well tolerated, contributing to an overall favorable risk:benefit profile. NALL is a promising, easily administered (oral) therapeutic option for these rare, debilitating diseases with immense unmet medical needs. TRIAL REGISTRATION INFORMATION: The trial is registered with ClinicalTrials.gov (NCT03759665; registered on November 30, 2018), EudraCT (2018-004406-25), and DRKS (DRKS00017539). The first patient was enrolled on June 7, 2019. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that NALL improves outcomes for patients with GM2 gangliosidoses.

Social norms related to fertility may be driving pregnancy desire, timing and contraceptive use, but measurement has lagged. We validated a 10-item injunctive Fertility Norms Scale (FNS) and examined its associations with family planning outcomes among 1021 women and 1020 men in India. FNS captured expectations around pronatalism, childbearing early in marriage and community pressure. We assessed reliability and construct validity through Cronbachs alpha and exploratory factor analysis (EFA) respectively, examining associations with childbearing intention and contraceptive use. FNS demonstrated good reliability (α = 0.65-0.71) and differing sub-constructs by gender. High fertility norm among women was associated with greater likelihood of pregnancy intention [RRR = 2.35 (95% CI: 1.25,4.39); ARRR = 1.53 (95% CI: 0.70,3.30)], lower likelihood of delaying pregnancy [RRR = 0.69 (95% CI: 0.50,0.96); ARRR = 0.72 (95% CI: 0.51,1.02)] and greater ambivalence on delaying pregnancy [RRR = 1.92 (95% CI: 1.18,3.14); ARRR = 1.99 (95% CI: 1.21,3.28)]. Womens higher FNS scores were also associated with higher sterilization [RRR = 2.17 (95% CI: 1.28,3.66); ARRR = 2.24 (95% CI: 1.32,3.83)], but the reverse was noted for men [RRR = 0.61 (95% CI: 0.36,1.04); ARRR = 0.54 (95% CI: 0.32,0.94)]. FNS indicated better predictive value among women compared to men for key reproductive outcomes. This measure may be useful for social norms-focused evaluations in family planning and warrants cross-contextual study.

PURPOSE: To test the efficacy of two interventions to reduce alcohol use and increase viral suppression compared to a control in persons with HIV (PWH). METHODS: In a three-arm (1:1:1) randomized controlled trial (N = 269), we compared in-person counselling (45-70 minutes, two sessions over three months) with interim monthly booster phone calls (live call arm) or twice-weekly automated booster sessions (technology arm) to a brief advice control arm. We enrolled PWH self-reporting unhealthy alcohol use (Alcohol Use Disorders Identification Test - Consumption, prior three months, women ≥3, men ≥4). Primary outcomes were number of self-reported drinking days (NDD) in the prior 21 and biomarker phosphatidylethanol (PEth) at six and nine months and viral suppression (

OBJECTIVES: The CHARM2 (Counseling Husbands and wives to Achieve Reproductive Health and Marital Equity) intervention engages health care providers to deliver gender-equity and family planning sessions to couples using a person-centered shared decision-making approach for contraception counseling. We previously showed that the intervention improved contraceptive use at 9-month follow-up. We sought to assess whether the intervention was further associated with the quality of care reported by participants and whether the quality of care reported mediated the effect of the intervention on contraceptive use. STUDY DESIGN: This is a planned secondary analysis of the effect of the CHARM2 intervention on 1201 married couples in rural Maharashtra, India in a cluster randomized controlled trial completed between 2018 and 2020. We assessed the effect of CHARM2 on perceived quality of care as measured by the Interpersonal Quality of Family Planning (IQFP) scale using a difference-in-differences linear regression approach including a mixed-effects model with nested random effects to account for clustering. We assessed whether the association between CHARM2 and modern contraceptive use was mediated by quality of family planning care. RESULTS: Intervention participants had higher mean IQFP scores than control participants at 9-month follow-up (intervention 3.2, SD 0.6 vs. control 2.3 mean, SD 0.9, p < 0.001). The quality of care reported mediated the effect of the intervention on contraceptive use (indirect effect coefficient 0.29, 95% CI 0.07-0.50). CONCLUSION: Family planning interventions such as CHARM2, which utilize person-centered shared decision-making contraceptive counseling approaches improve womens perceived quality of care. Effects on quality of care mediate observed effects of the intervention on contraceptive use. IMPLICATIONS: Contraceptive interventions should focus on improving person-centered outcomes, such as quality of care, rather than contraceptive use targets. By focusing on improving person-centered care, interventions will improve contraceptive use among those who desire a method while meeting the holistic reproductive health needs of clients and couples.

We evaluated the association between implementation of state-mandated pulse oximetry screening (POS) and rates of emergency hospitalizations among infants with Critical Congenital Heart Disease (CCHD) and assessed differences in that association across race/ethnicity. We hypothesized that emergency hospitalizations among infants with CCHD decreased after implementation of mandated POS and that the reduction was larger among racial and ethnic minorities compared to non-Hispanic Whites. We utilized statewide inpatient databases from Arizona, California, Kentucky, New Jersey, New York, and Washington State (2010-2014). A difference-in-differences model with negative binomial regression was used. We identified patients with CCHD whose hospitalizations between three days and three months of life were coded as emergency or urgent or occurred through the emergency department. Numbers of emergency hospitalizations aggregated by month and state were used as outcomes. The intervention variable was an implementation of state-mandated POS. Difference in association across race/ethnicity was evaluated with interaction terms between the binary variable indicating the mandatory policy period and each race/ethnicity group. The model was adjusted for state-specific variables, such as percent of female infants and percent of private insurance. We identified 9,147 CCHD emergency hospitalizations. Among non-Hispanic Whites, there was a 22% (Confidence Interval [CI] 6%-36%) decline in CCHD emergency hospitalizations after implementation of mandated POS, on average. This decline was 65% less among non-Hispanic Blacks compared to non-Hispanic Whites. Our study detected an attenuated association with decreased number of emergency hospitalizations among Black compared to White infants. Further research is needed to clarify this disparity.

IntroductionShort interpregnancy interval (IPI) is a well-known risk factor for preterm births and low birth weights. However, research on the association between interpregnancy interval (IPI) and health outcomes in children under age 5 is limited in India. We examined the associations between IPI and five child health outcomes in India.MethodsWe used nationally representative cross-sectional data from three rounds of National Family Health Survey (NFHS) conducted in India during 2005-06, 2015-16 and 2019-21 to examine the associations between IPI [categorized as

Clinicians in the emergency department (ED) face challenges in concurrently assessing patients with suspected COVID-19 infection, detecting bacterial coinfection, and determining illness severity since current practices require separate workflows. Here, we explore the accuracy of the IMX-BVN-3/IMX-SEV-3 29 mRNA host response classifiers in simultaneously detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and bacterial coinfections and predicting clinical severity of COVID-19. A total of 161 patients with PCR-confirmed COVID-19 (52.2% female; median age, 50.0 years; 51% hospitalized; 5.6% deaths) were enrolled at the Stanford Hospital ED. RNA was extracted (2.5 mL whole blood in PAXgene blood RNA), and 29 host mRNAs in response to the infection were quantified using Nanostring nCounter. The IMX-BVN-3 classifier identified SARS-CoV-2 infection in 151 patients with a sensitivity of 93.8%. Six of 10 patients undetected by the classifier had positive COVID tests more than 9 days prior to enrollment, and the remaining patients oscillated between positive and negative results in subsequent tests. The classifier also predicted that 6 (3.7%) patients had a bacterial coinfection. Clinical adjudication confirmed that 5/6 (83.3%) of the patients had bacterial infections, i.e., Clostridioides difficile colitis (n = 1), urinary tract infection (n = 1), and clinically diagnosed bacterial infections (n = 3), for a specificity of 99.4%. Two of 101 (2.8%) patients in the IMX-SEV-3 "Low" severity classification and 7/60 (11.7%) in the "Moderate" severity classification died within 30 days of enrollment. IMX-BVN-3/IMX-SEV-3 classifiers accurately identified patients with COVID-19 and bacterial coinfections and predicted patients' risk of death. A point-of-care version of these classifiers, under development, could improve ED patient management, including more accurate treatment decisions and optimized resource utilization. IMPORTANCE We assay the utility of the single-test IMX-BVN-3/IMX-SEV-3 classifiers that require just 2.5 mL of patient blood in concurrently detecting viral and bacterial infections as well as predicting the severity and 30-day outcome from the infection. A point-of-care device, in development, will circumvent the need for blood culturing and drastically reduce the time needed to detect an infection. This will negate the need for empirical use of broad-spectrum antibiotics and allow for antibiotic use stewardship. Additionally, accurate classification of the severity of infection and the prediction of 30-day severe outcomes will allow for appropriate allocation of hospital resources.

Womens contraceptive decision-making control is crucial for reproductive autonomy, but research largely relies on the Demographic and Health Survey (DHS) measure which asks who is involved with decision-making. In India, this typically assesses joint decision-making or male engagement. Newer measures emphasize female agency. We examined three measures of contraceptive decision-making, the DHS and two agency-focused measures, to assess their associations with marital contraceptive communication and use in rural Maharashtra, India. We analyzed follow-up survey data from women participating in the CHARM2 study (n = 1088), collected in June-December 2020. The survey included the DHS (measure 1), Reproductive Decision-Making Agency (measure 2), and Contraceptive Final Decision-Maker measures (measure 3). Only Measure 1 was significantly associated with contraceptive communication (adjusted odds ratio [AOR]: 2.75, 95 percent confidence interval [CI]: 1.69-4.49) and use (AOR: 1.73, 95 percent CI: 1.14-2.63). However, each measure was associated with different types of contraceptive use: Measure 1 with condom (adjusted relative risk ratio [aRRR]: 1.99, 95 percent CI: 1.12-3.51) and intrauterine device (IUD) (aRRR: 4.76, 95 percent CI: 1.80-12.59), Measure 2 with IUD (aRRR: 1.64, 95 percent CI: 1.04-2.60), and Measure 3 with pill (aRRR: 2.00, 95 percent CI: 1.14-3.52). Among married women in Maharashtra, India, male engagement in decision-making may be a stronger predictor of contraceptive communication and use than womens agency, but agency may be predictive of types of contraceptives used.

This study evaluated the association between impulsivity and linkage to HIV care among Russians living with HIV recruited from an inpatient narcology hospital. Linking Infectious and Narcology Care (LINC) study participants who completed the Barratt Impulsiveness Scale (BIS) were included in these analyses. The primary independent variable was impulsivity score which was categorized as high impulsivity (BIS score > 71) vs. low impulsivity (BIS score

BackgroundPrior cross-sectional research suggests that both men's and women's attitudes towards intimate partner violence (IPV) are predictive of women's IPV experience, although this can vary greatly by context. In general, women who have experienced IPV are likely to report attitudes accepting of it. Men who perpetrate IPV may also report attitudes accepting of it, although some research has found that there is not always an association. Studies that investigate these dynamics often conflate attitudes with social norms, or use attitudes as a proxy for social norms, given that valid measures on social norms are usually lacking. Here we conduct a secondary data analysis to ask how are men's and women's IPV-related attitudes associated with women's reports of IPV and how are men's and women's perceived social norms associated with women's reports of IPV.MethodsDyadic data were collected from a representative sample of married adolescent girls and their husbands in 48 rural villages of the Dosso region of Niger (N = 1010). Assessments included logistic regression analyses of husbands' and wives' reports of individual attitudes towards IPV, and social norms based on husbands' and wives' perceptions of their communities' beliefs related to gender roles and acceptability of IPV.ResultsEight percent of women in this sample reported IPV. We found that, consistent with other research, wives who have reported IPV are more likely to report attitudes in support of IPV, while for husbands whose wives report IPV, that relationship is insignificant. On the other hand, husbands who report that people in their community believe there are times when a woman deserves to be beaten are more likely to have perpetrated IPV, while for wives there is no association between the community norm and IPV reporting. Finally, wives who report that people in their community hold inequitable gender norms in general are more likely to have experienced IPV, while for husbands, community gender norms are not predictive of whether their wives have reported IPV.ConclusionsOur results are evidence that IPV prevention interventions focused solely on individual attitudes may be insufficient. Targeting and assessment of social norms are likely critical to advancing understanding and prevention of IPV.

Prior research has shown collective efficacy to be a key determinant of women's well-being. However, much of the work around measuring this construct has been done in high-income geographies, with very little representation from low- and middle-income countries (LMIC). To fill this gap, and guide future research in low resource settings, we aim to summarize best evidence measures of collective efficacy for women and girls from LMICs. Following PRISMA guidelines, we systematically searched five databases for English language peer-reviewed literature on measures of collective efficacy, published between 1 January 2009 and 25 August 2020. In addition, we sought expert input for relevant papers in this area. Research staff screened titles, abstracts, and full-text articles in a double-blind review. Inclusion criteria were: (i) original quantitative analysis, and (ii) sample limited to women/girls only (≥ 100), residing in LMICs. We identified 786 unique articles, 14 of which met inclusion criteria. Eligible studies captured a diversity of population groups, including pregnant women, recent mothers, adolescent girls, and female sex workers, from across national settings. Two broad constructs of collective efficacy were captured by the measures: (i) group dynamics, and (ii) collective action. All 14 studies included items on group dynamics in their measures, whereas seven studies included items on collective action. Four studies validated new measures of collective efficacy, and seven provided evidence supporting the relationship between collective efficacy and outcomes related to women's well-being. Overall, measures demonstrated good reliability and validity when tested, and those testing for associations or effects found a positive relationship of collective efficacy with women's health behaviors. The past decade has resulted in a number of new collective efficacy measures demonstrating good validity in terms of their associations with key health outcomes among women and girls from across LMIC settings, but there remains no standard measure in the field. Those that exist focus on group dynamics, but less often on collective action. A standard measure of collective efficacy inclusive of group dynamics and collective action can support better understanding of the value of women's collectives across national settings and populations.

BackgroundAn often heard and justifiable concern of ethnic minorities is related to researchers' lack of attention to sharing the results of a study with participants after the study has concluded. Few studies have examined the effects of returning overall study results on participants' attitudes, especially among populations underrepresented in research. Among Latina research participants, providing a summary of study results could enhance participation in research. We assess Latina breast cancer survivors' reactions to receiving study results and their attitudes about participating in future studies.MethodsFor this cross-sectional survey study, all women who had participated in two behavioral randomized controlled trials (RCTs) were mailed a letter summarizing the study results (using written and graphic formats) and a questionnaire assessing problems and understanding the results, importance of sharing results, willingness to participate in future studies, and format preferences for receiving the results. A postage-paid envelope for returning the completed questionnaire was included. Logistic regression examined the associations of age, education, and rural/urban residence on format preferences and willingness to participate. The survey sample consisted of 304 low-income, predominantly Spanish-speaking Latina breast cancer survivors (151 from urban and 153 from rural communities) who had participated in two RCTs testing a stress management program designed for Latina breast cancer survivors.ResultsNinety-two women returned the questionnaires (30.3%). Most of the women (91.1%) indicated that they had no trouble understanding the results of the study, and 97% agreed that it is very/extremely important for researchers to share the study result with the participants. The majority (60.2%) reported that receiving the results increased their willingness to participate in future studies. About half (51.7%) did not have a format preference, 37.4% preferred written summaries, and 10.9% preferred graphs.ConclusionsThis study is an important first step to understanding the impact of returning study results among a population that is underrepresented in research. Returning the results of studies and understanding the impact of doing so is consistent with maintaining community involvement in all phases of research. The findings suggest that sharing aggregate research results in simple language yields few problems in participants' understanding of the results and is viewed as important by participants.Trial registrationClinicalTrials.gov NCT02931552 Date registered: October 13, 2016 and NCT01383174 Date registered: June 28, 2011.

Unmet need for family planning (FP) continues to be high in India, especially among young and newly married women. Mothers-in-law (MILs) often exert pressure on couples for fertility and control decision making and behaviors around fertility and FP, yet there is a paucity of literature to understand their perspectives. Ten focus group discussions (FGDs) were carried out with MILs of young married women (aged 18-29 years) participating in a couple-focused FP intervention as a part of a cluster-randomized intervention evaluation trial (the CHARM2 study) in rural Maharashtra, India. FGDs included questions on their roles, attitudes, and decision making around fertility and FP. Audio-recorded data were translated/transcribed into English and analyzed for key themes using a deductive coding method. MILs reported having social norms of early fertility and son preference. They understood that family size norms are lower among daughters-in-law and that spacing can be beneficial but were not supportive of short-term contraceptives, especially before the first child. They preferred female sterilization, opposed abortion, had apprehensions around side effects from contraceptive use, and had misconceptions about the intrauterine device, with particular concerns around its coercive insertion. MILs mostly believed that decision making should be done jointly by a husband and wife, but that as elders, they should be consulted and involved in the decision-making process. These findings highlight the need for engagement of MILs for FP promotion in rural India and the potential utility of social norms interventions.

Due to the high HIV incidence among the general population of Eswatini, pre-exposure prophylaxis (PrEP) for HIV-exposed individuals is recommended. However, little is known about PrEP uptake and preferences in PrEP delivery healthcare setting among the general population. We conducted a secondary analysis of a randomized trial that aimed to increase PrEP uptake. All clients eligible for PrEP in one of six public-sector healthcare facilities in Eswatini were included. PrEP uptake was stratified by initial reason for visit (e.g. outpatient). Preferences in PrEP delivery setting were collected among those clients who initiated PrEP. A total of 1782 clients had their HIV acquisition risk assessed. Of these, 72% (1277/1782) were considered at risk by healthcare providers and, among them, 40% (517/1277) initiated PrEP. Uptake was higher among clients visiting specifically to initiate PrEP (93%), followed by HIV testing visits (45.8%) and outpatient visits (40%). Among those who initiated PrEP, preferred delivery settings were outpatient services (31%), HIV testing services (26%), family planning (21%) and antenatal services (14%). Men or those at high risk of HIV acquisition were more likely to prefer HIV testing and outpatient services, while young women were more likely to visit and express a preference for antenatal and family planning services. Outpatient services and HIV testing services could be preferable choices for PrEP delivery integration, due to the high PrEP uptake and delivery setting preferences of the populations who use these services. Antenatal and family planning could also be considered with a view to targeting the youngest women.

Ki67 has potential clinical importance in breast cancer but has yet to see broad acceptance due to inter-laboratory variability. Here we tested an open source and calibrated automated digital image analysis (DIA) platform to: (i) investigate the comparability of Ki67 measurement across corresponding core biopsy and resection specimen cases, and (ii) assess section to section differences in Ki67 scoring. Two sets of 60 previously stained slides containing 30 core-cut biopsy and 30 corresponding resection specimens from 30 estrogen receptor-positive breast cancer patients were sent to 17 participating labs for automated assessment of average Ki67 expression. The blocks were centrally cut and immunohistochemically (IHC) stained for Ki67 (MIB-1 antibody). The QuPath platform was used to evaluate tumoral Ki67 expression. Calibration of the DIA method was performed as in published studies. A guideline for building an automated Ki67 scoring algorithm was sent to participating labs. Very high correlation and no systematic error (p = 0.08) was found between consecutive Ki67 IHC sections. Ki67 scores were higher for core biopsy slides compared to paired whole sections from resections (p ≤ 0.001; median difference: 5.31%). The systematic discrepancy between core biopsy and corresponding whole sections was likely due to pre-analytical factors (tissue handling, fixation). Therefore, Ki67 IHC should be tested on core biopsy samples to best reflect the biological status of the tumor.

ObjectivesTo examine associations of coping resources for psychological distress among newly diagnosed Spanish-speaking Latina women with breast cancer (LWBC).Sample & settingAnalyses used baseline data from a randomized controlled trial of a stress management intervention among 151 LWBC.Methods & variablesDependent variables were health distress and anxiety. Coping resources at the intrapersonal, interpersonal, and organizational/community levels were included.ResultsAt the intrapersonal level, self-efficacy for coping with breast cancer treatment was associated inversely with health distress and anxiety, and coping confidence with general problems was associated inversely with health distress. At the interpersonal level, having a sense of neighborhood cohesion was associated inversely with health distress. No organizational/community level resources were associated with health distress or anxiety.Implications for nursingInterventions that enhance self-efficacy in coping and foster skills to identify sources of neighborhood support may decrease psychological distress for Spanish-speaking LWBC.

BackgroundThe use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.MethodsWe conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants.ResultsThe use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P

The subplate is a transient brain structure which plays a key role in the maturation of the cerebral cortex. Altered brain growth and cortical development have been suggested in fetuses with complex congenital heart disease (CHD) in the third trimester. However, at an earlier gestation, the putative role of the subplate in altered brain development in CHD fetuses is poorly understood. This study aims to examine subplate growth (i.e., volume and thickness) and its relationship to cortical sulcal development in CHD fetuses compared with healthy fetuses by using 3D reconstructed fetal magnetic resonance imaging. We studied 260 fetuses, including 100 CHD fetuses (22.3-32 gestational weeks) and 160 healthy fetuses (19.6-31.9 gestational weeks). Compared with healthy fetuses, CHD fetuses had 1) decreased global and regional subplate volumes and 2) decreased subplate thickness in the right hemisphere overall, in frontal and temporal lobes, and insula. Compared with fetuses with two-ventricle CHD, those with single-ventricle CHD had reduced subplate volume and thickness in right occipital and temporal lobes. Finally, impaired subplate growth was associated with disturbances in cortical sulcal development in CHD fetuses. These findings suggested a potential mechanistic pathway and early biomarker for the third-trimester failure of brain development in fetuses with complex CHD.Significance statementOur findings provide an early biomarker for brain maturational failure in fetuses with congenital heart disease, which may guide the development of future prenatal interventions aimed at reducing neurological compromise of prenatal origin in this high-risk population.

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.

The CA1 region of the hippocampus contains both glutamatergic pyramidal cells and GABAergic interneurons. Numerous reports have characterized glutamatergic CAMK2A cell activity, showing how these cells respond to environmental changes such as local cue rotation and context re-sizing. Additionally, the long-term stability of spatial encoding and turnover of these cells across days is also well-characterized. In contrast, these classic hippocampal experiments have never been conducted with CA1 GABAergic cells. Here, we use chronic calcium imaging of male and female mice to compare the neural activity of VGAT and CAMK2A cells during exploration of unaltered environments and also during exposure to contexts before and after rotating and changing the length of the context across multiple recording days. Intriguingly, compared to CAMK2A cells, VGAT cells showed decreased remapping induced by environmental changes, such as context rotations and contextual length resizing. However, GABAergic neurons were also less likely than glutamatergic neurons to remain active and exhibit consistent place coding across recording days. Interestingly, despite showing significant spatial remapping across days, GABAergic cells had stable speed encoding between days. Thus, compared to glutamatergic cells, spatial encoding of GABAergic cells is more stable during within-session environmental perturbations, but is less stable across days. These insights may be crucial in accurately modeling the features and constraints of hippocampal dynamics in spatial coding.

ImportanceIdentifying the associations between severe COVID-19 and individual cardiovascular conditions in pediatric patients may inform treatment.ObjectiveTo assess the association between previous or preexisting cardiovascular conditions and severity of COVID-19 in pediatric patients.Design, setting, and participantsThis retrospective cohort study used data from a large, multicenter, electronic health records database in the US. The cohort included patients aged 2 months to 17 years with a laboratory-confirmed diagnosis of COVID-19 or a diagnosis code indicating infection or exposure to SARS-CoV-2 at 85 health systems between March 1, 2020, and January 31, 2021.ExposuresDiagnoses for 26 cardiovascular conditions between January 1, 2015, and December 31, 2019 (before infection with SARS-CoV-2).Main outcomes and measuresThe main outcome was severe COVID-19, defined as need for supplemental oxygen or in-hospital death. Mixed-effects, random intercept logistic regression modeling assessed the significance and magnitude of associations between 26 cardiovascular conditions and COVID-19 severity. Multiple comparison adjustment was performed using the Benjamini-Hochberg false discovery rate procedure.ResultsThe study comprised 171 416 pediatric patients; the median age was 8 years (IQR, 2-14 years), and 50.28% were male. Of these patients, 17 065 (9.96%) had severe COVID-19. The random intercept model showed that the following cardiovascular conditions were associated with severe COVID-19: cardiac arrest (odds ratio [OR], 9.92; 95% CI, 6.93-14.20), cardiogenic shock (OR, 3.07; 95% CI, 1.90-4.96), heart surgery (OR, 3.04; 95% CI, 2.26-4.08), cardiopulmonary disease (OR, 1.91; 95% CI, 1.56-2.34), heart failure (OR, 1.82; 95% CI, 1.46-2.26), hypotension (OR, 1.57; 95% CI, 1.38-1.79), nontraumatic cerebral hemorrhage (OR, 1.54; 95% CI, 1.24-1.91), pericarditis (OR, 1.50; 95% CI, 1.17-1.94), simple biventricular defects (OR, 1.45; 95% CI, 1.29-1.62), venous embolism and thrombosis (OR, 1.39; 95% CI, 1.11-1.73), other hypertensive disorders (OR, 1.34; 95% CI, 1.09-1.63), complex biventricular defects (OR, 1.33; 95% CI, 1.14-1.54), and essential primary hypertension (OR, 1.22; 95% CI, 1.08-1.38). Furthermore, 194 of 258 patients (75.19%) with a history of cardiac arrest were younger than 12 years.Conclusions and relevanceThe findings suggest that some previous or preexisting cardiovascular conditions are associated with increased severity of COVID-19 among pediatric patients in the US and that morbidity may be increased among individuals children younger than 12 years with previous cardiac arrest.