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Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p 0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman's reports of social adversity during the third trimester were associated with their infant's resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants' cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

BackgroundCardiac rehabilitation (CR) is an exercise-based program prescribed after cardiac events associated with improved physical, mental, and social functioning; however, many patients return to a sedentary lifestyle leading to deteriorating functional capacity after discharge from CR. Physical activity (PA) is critical to avoid recurrence of cardiac events and mortality and maintain functional capacity. Leveraging mobile health (mHealth) strategies to increase adherence to PA is a promising approach. Based on the social cognitive theory, we sought to determine whether mHealth strategies (Movn mobile app for self-monitoring, supportive push-through messages, and wearable activity tracker) would improve PA and functional capacity over 2 months. ObjectiveThe objectives of this pilot randomized controlled trial were to examine preliminary effects of an mHealth intervention on group differences in PA and functional capacity and group differences in depression and self-efficacy to maintain exercise after CR. MethodsDuring the final week of outpatient CR, patients were randomized 1:1 to the intervention group or usual care. The intervention group downloaded the Movn mobile app, received supportive push-through messages on motivation and educational messages related to cardiovascular disease (CVD) management 3 times per week, and wore a Charge 2 (Fitbit Inc) activity tracker to track step counts. Participants in the usual care group wore a pedometer and recorded their daily steps in a diary. Data from the 6-minute walk test (6MWT) and self-reported questionnaires were collected at baseline and 2 months. ResultsWe recruited 60 patients from 2 CR sites at a community hospital in Northern California. The mean age was 68.0 (SD 9.3) years, and 23% (14/60) were female; retention rate was 85% (51/60). Our results from 51 patients who completed follow-up showed the intervention group had a statistically significant higher mean daily step count compared with the control (8860 vs 6633; P=.02). There was no difference between groups for the 6MWT, depression, or self-efficacy to maintain exercise. ConclusionsThis intervention addresses a major public health initiative to examine the potential for mobile health strategies to promote PA in patients with CVD. Our technology-based pilot mHealth intervention provides promising results on a pragmatic and contemporary approach to promote PA by increasing daily step counts after completing CR. Trial RegistrationClinicalTrials.gov NCT03446313; https://clinicaltrials.gov/ct2/show/NCT03446313

BackgroundAlcohol consumption and stimulant use are major public health problems and contribute to morbidity and mortality in the United States. To inform interventions for substance use, there is a need to identify the day-level correlates of substance use by collecting repeated measures data in one’s natural environment. There is also a need to use crowdsourcing platforms like Amazon Mechanical Turk (MTurk) to efficiently engage larger populations of people who use alcohol and stimulants in research. ObjectiveWe aimed to (1) utilize daily diaries to examine the temporal relationship between day-level cravings for alcohol and stimulant/substance use (ie, heavy drinking or any drug use) in a given day over 14 days and (2) assess whether depression, negative affect, and self-esteem measured at baseline predict substance use in a given day over 14 days among people who use alcohol and/or stimulants in the United States. MethodsIndividuals aged ≥18 years in the United States, who reported alcohol or stimulant (ie, cocaine, crack cocaine, and methamphetamine) use in the past year, were recruited using MTurk between March 26 and April 13, 2018. Eligible participants completed a baseline survey and 14 daily surveys online. The baseline survey assessed sociodemographics and psychosocial (ie, depression, affect, self-esteem, and stress) factors. Daily surveys assessed substance use and cravings for alcohol and stimulants. Four multivariable random-intercept logistic regression models were built to examine psychosocial constructs separately along with other significant predictors from bivariate analyses while controlling for age and education. ResultsAmong a total of 272 participants, 220 were White, 201 were male, and 134 were men who have sex with men (MSM). The mean age was 36.1 years (SD 10.5). At baseline, 173 participants engaged in any current or past hazardous alcohol consumption, 31 reported using cocaine, 19 reported using methamphetamine, 8 reported using crack cocaine, and 104 reported any noninjection or injection drug use in the past 6 months. Factors independently associated with substance use were depression (adjusted odds ratio [aOR] 1.11, 95% CI 1.02-1.21; P=.01), negative affect (aOR 1.08, 95% CI 1.01-1.16; P=.01), lower levels of self-esteem (aOR 0.90, 95% CI 0.82-0.98; P=.02), and cravings for alcohol (aOR 1.02, 95% CI 1.01-1.03; P

INTRODUCTION: We estimated the ages when associations between Alzheimers disease (AD) genes and brain volumes begin among middle-aged and older adults. METHODS: Among 45,616 dementia-free participants aged 45-80, linear regressions tested whether genetic risk score for AD (AD-GRS) had age-dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume. RESULTS: AD-GRS modified the estimated effect of age (per decade) on the amygdala (-0.41 mm3 [-0.42, -0.40]); hippocampus (-0.45 mm3 [-0.45, -0.44]), nucleus accumbens (-0.55 mm3 [-0.56, -0.54]), thalamus (-0.38 mm3 [-0.39, -0.37]), and medial orbitofrontal cortex (-0.23 mm3 [-0.24, -0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD-GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices. DISCUSSION: APOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.

BACKGROUND: Women are less physically active, report greater perceived barriers for exercise, and show higher levels of depressive symptoms. This contributes to high global disability. The relationship between perceived barriers for physical activity and depressive symptoms in women remains largely unexplored. The aims of this cross-sectional analysis were to examine the association between physical activity barriers and depressive symptoms, and identify types of barriers in physically inactive community-dwelling women. METHODS: Three hundred eighteen physically inactive women aged 25-65 years completed the Barriers to Being Active Quiz (BBAQ) developed by the Centers for Disease Control and Prevention, and the Center for Epidemiological Studies Depression Scale at the baseline visit of the mobile phone-based physical activity education trial. The BBAQ consists of six subscales (lack of time, social influence, lack of energy, lack of willpower, fear of injury, lack of skill, and lack of resources). We used multivariate regression analyses, correcting for sociodemographics. RESULTS: Higher physical activity barriers were associated with greater depressive symptoms scores (linear effect, estimate = 0.75, 95% confidence interval [CI]: 0.39-1.12, p

BACKGROUND: Adherence to antiretroviral therapy (ART) can substantially reduce morbidity and mortality among women living with HIV (WLWH) and prevent vertical transmission of HIV. However, in sub-Saharan Africa (SSA), more than 50% of new mothers discontinue ART and HIV care after childbirth. The role of water insecurity (WI) in ART adherence is not well-explored. We examined the relationship between WI and ART adherence among pregnant and postpartum WLWH in Greater Accra region of Ghana. METHODS: Using a cross-sectional survey, we recruited 176 pregnant and postpartum WLWH on ART across 11 health facilities. We examined the association between WI (measured using the Household Water Insecurity Experience Scale, and categorized as moderate and severe WI compard to low WI) and poor ART adherence (defined as scoring a below average observed CASE index score). Bivariate analysis was performed using chi-square test followed by multivariate logistic regression models. We included all variables with p-values less than 0.20 in the multivariate analysis. RESULTS: Most (79.5%) of the pregnant and postpartum WLWH enrolled on ART, were urban residents. Over 2/3 were aged 30 years and older. Overall, 33.5% of respondents had poor ART adherence. Proportion of poor ART adherence was 19.4% among those with low WI, 44.4% in those with moderate WI, and 40.0% among those with high WI. Respondents with moderate household water insecurity had a greater odds of reporting poor ART adherence, as compared to those with low water insecurity (adjusted Odds ratio (aOR) = 2.76, 95%CI: 1.14-6.66, p = 0.024), even after adjusting for food insecurity. Similarly, respondents with high WI had a greater odds of reporting poor ART adherence, as compared to those with low water insecurity (aOR = 1.49, 95%CI: 0.50-4.48, p = 0.479), even after adjusting for food insecurity. CONCLUSION: Water insecurity is prevalent among pregnant and postpartum WLWH and is a significant risk factor for poor ART adherence. Governments and other stakeholders working in HIV care provision should prioritize water security programming for WLWH along the HIV care continuum.

BACKGROUND: Mobile medical clinics have been used for decades to provide primary and preventive care to underserved populations. While several studies have examined their return on investment and impact on chronic disease management outcomes in the Mid-Atlantic and East Coast regions of the United States, little is known about the characteristics and clinical outcomes of adults who receive care aboard mobile clinics on the West Coast region. Guided by the Anderson Behavioral Model, this study describes the predisposing, enabling, and need factors associated with mobile medical clinic use among mobile medical clinic patients in Southern California and examines the relationship between mobile clinic utilization and presence and control of diabetes and hypertension. METHODS: We conducted a retrospective cohort study of 411 adults who received care in four mobile clinic locations in Southern California from January 1, 2018, to December 31, 2019. Data were collected from patient charts on predisposing (e.g., sex, race, age), enabling (e.g., insurance and housing status), and need (e.g., chronic illness) factors based on Andersens Behavioral Model. Zero-truncated negative binomial regression was used to examine the association of chronic illness (hypertension and diabetes) with number of clinic visits, accounting for potential confounding factors. RESULTS: Over the course of the 2-year study period, 411 patients made 1790 visits to the mobile medical clinic. The majority of patients were female (68%), Hispanic (78%), married (47%), with a mean age of 50 (SD = 11). Forty-four percent had hypertension and 29% had diabetes. Frequency of mobile clinic utilization was significantly associated with chronic illness. Patients with hypertension and diabetes had 1.22 and 1.61 times the rate of mobile medical clinic visit than those without those conditions, respectively (IRR = 1.61, 95% CI, 1.36-1.92; 1.22, 95% CI, 1.02-1.45). CONCLUSIONS: Mobile clinics serve as an important system of health care delivery, especially for adults with uncontrolled diabetes and hypertension.

BACKGROUND: Involvement in caregiving and tailored support services may reduce the risk of mental health symptoms for mothers after their preterm infants neonatal intensive care unit (NICU) discharge. We aimed to compare Family-Centered Care (FCC) with mobile-enhanced Family-Integrated Care (mFICare) on post-discharge maternal mental health symptoms. METHOD: This quasi-experimental study enrolled preterm infant (≤ 33 weeks)/parent dyads from three NICUs into sequential cohorts: FCC or mFICare. We analyzed post-discharge symptoms of perinatal post-traumatic stress disorder (PTSD) and depression using intention-to-treat and per protocol approaches. RESULTS: 178 mothers (89 FCC; 89 mFICare) completed measures. We found no main effect of group assignment. We found an interaction between group and stress, indicating fewer PTSD and depression symptoms among mothers who had higher NICU-related stress and received mFICare, compared with mothers who had high stress and received FCC (PTSD: interaction β=-1.18, 95% CI: -2.10, -0.26; depression: interaction β=-0.76, 95% CI: -1.53, 0.006). Per protocol analyses of mFICare components suggested fewer PTSD and depression symptoms among mothers who had higher NICU stress scores and participated in clinical team rounds and/or group classes, compared with mothers who had high stress and did not participate in rounds or classes. CONCLUSION: Overall, post-discharge maternal mental health symptoms did not differ between the mFICare and FCC groups. However, for mothers with high levels of stress during the NICU stay, mFICare was associated with fewer post-discharge PTSD and depression symptoms.

In-hospital electrocardiographic (ECG) monitors are typically configured to alarm for premature ventricular complexes (PVCs) due to the potential association of PVCs with ventricular tachycardia (VT). However, no contemporary hospital-based studies have examined the association of PVCs with VT. Hence, the benefit of PVC monitoring in hospitalized patients is largely unknown. This secondary analysis used a large PVC alarm data set to determine whether PVCs identified during continuous ECG monitoring were associated with VT, in-hospital cardiac arrest (IHCA), and/or death in a cohort of adult intensive care unit patients. Six PVC types were examined (i.e., isolated, bigeminy, trigeminy, couplets, R-on-T, and run PVCs) and were compared between patients with and without VT, IHCA, and/or death. Of 445 patients, 48 (10.8%) had VT; 11 (2.5%) had IHCA; and 49 (11%) died. Isolated and run PVC counts were higher in the VT group (p = 0.03 both), but group differences were not seen for the other four PVC types. The regression models showed no significant associations between any of the six PVC types and VT or death, although confidence intervals were wide. Due to the small number of cases, we were unable to test for associations between PVCs and IHCA. Our findings suggest that we should question the clinical relevance of activating PVC alarms as a forewarning of VT, and more work should be done with larger sample sizes. A more precise characterization of clinically relevant PVCs that might be associated with VT is warranted.

Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P

BackgroundThe syndemic effects of poverty, food insecurity and living with HIV are recognized as global health priorities, including through the United Nations Sustainability Goals 1, 2 and 3. Today, women and girls account for 63% of all new HIV infections in eastern and southern Africa, including Kenya. Pregnant and postpartum women living with HIV in this setting face unique challenges including increased financial insecurity as women leave the work force to care for their newborn infants. This contributes to poverty, food scarcity and stress.MethodsTo address financial insecurity, improve infant feeding and reduce stress among mothers living with HIV in this setting, we developed a multilevel intervention, Supporting Healthy Mothers, consisting of 10 monthly unconditional cash transfers (10,000 KES, ~$75 USD/month) and personalized infant feeding support from pregnancy to 7 months postpartum. We conducted a non-randomized feasibility trial of this intervention among women engaged in HIV care in Kisumu, Kenya. From February 23, 2022 to March 23, 2022, we enrolled a total of 40 women who were 20-35 weeks pregnant-20 women to the intervention group at a public clinic, and 20 women to the control group at a similar clinic. Our aim was to assess feasibility, acceptability, and the potential impact of the intervention on food security, infant feeding and maternal mental health.ResultsAnalyzing data from all 40 participants, we found a significant reduction in food insecurity scores from baseline for the intervention group when compared to the control group at 6 weeks and 6 months postpartum (p = 0.0008 and p

BackgroundPoor adherence and under-utilization of antiretroviral therapy (ART) services have been major setbacks to achieving 95-95-95 policy goals in Sub-Saharan Africa. Social support and mental health challenges may serve as barriers to accessing and adhering to ART but are under-studied in low-income countries. The purpose of this study was to examine the association of interpersonal support and depression scores with adherence to ART among persons living with HIV (PLWH) in the Volta region of Ghana.MethodsWe conducted a cross-sectional survey among 181 PLWH 18 years or older who receive care at an ART clinic between November 2021 and March 2022. The questionnaire included a 6-item simplified ART adherence scale, the 20-item Center for Epidemiologic Studies Depression Scale (CES-D), and the 12-item Interpersonal Support Evaluation List-12 (ISEL-12). We first used a chi-squared or Fisher's exact test to assess the association between these and additional demographic variables with ART adherence status. We then built a stepwise multivariable logistic regression model to explain ART adherence.ResultsART adherence was 34%. The threshold for depression was met by 23% of participants, but it was not significantly associated with adherence in multivariate analysis(p = 0.25). High social support was reported by 48.1%, and associated with adherence (p = 0.033, aOR = 3.45, 95% CI = 1.09-5.88). Other factors associated with adherence included in the multivariable model included not disclosing HIV status (p = 0.044, aOR = 2.17, 95% CI = 1.03-4.54) and not living in an urban area (p = 0.00037, aOR = 0.24, 95% CI = 0.11-0.52).ConclusionInterpersonal support, rural residence, and not disclosing HIV status were independent predictors of adherence to ART in the study area.

BackgroundDespite the health benefits of engaging in regular physical activity (PA), the majority of American adults do not meet the PA guidelines for aerobic and muscle-strengthening activities. Self-efficacy, the belief that one can execute specific actions, has been suggested to be a strong determinant of PA behaviors. With the increasing availability of digital technologies, collecting longitudinal real-time self-efficacy and PA data has become feasible. However, evidence in longitudinal real-time assessment of self-efficacy in relation to objectively measured PA is scarce.ObjectiveThis study aimed to examine a novel approach to measure individuals' real-time weekly self-efficacy in response to their personalized PA goals and performance over the 12-week intervention period in community-dwelling women who were not meeting PA guidelines.MethodsIn this secondary data analysis, 140 women who received a 12-week PA intervention were asked to report their real-time weekly self-efficacy via a study mobile app. PA (daily step counts) was measured by an accelerometer every day for 12 weeks. Participants rated their self-efficacy on meeting PA goals (ranging from "not confident" to "very confident") at the end of each week via a mobile app. We used a logistic mixed model to examine the association between weekly self-efficacy and weekly step goal success, controlling for age, BMI, self-reported White race, having a college education or higher, being married, and being employed.ResultsThe mean age was 52.7 (SD 11.5, range 25-68) years. Descriptive analyses showed the dynamics of real-time weekly self-efficacy on meeting PA goals and weekly step goal success. The majority (74.4%) of participants reported being confident in the first week, whereas less than half of them (46.4%) reported confidence in the final week of the intervention. Participants who met weekly step goals were 4.41 times more likely to be confident about achieving the following week's step goals than those who did not meet weekly step goals (adjusted odds ratio 4.41; 95% CI 2.59-7.50; P

BackgroundCOVID-19 is an ongoing global health crisis with prevention and treatment recommendations rapidly changing. Rapid response telephone triage and advice services are critical in providing timely care during pandemics. Understanding patient participation with triage recommendations and factors associated with patient participation can assist in developing sensitive and timely interventions for receiving the treatment to prevent adverse health effects of COVID-19.MethodsThis cohort study aimed to assess patient participation (percentage of patients who followed nursing triage suggestions from the COVID hotline) and identify factors associated with patient participation in four quarterly electronic health records from March 2020 to March 2021 (Phase 1: 14 March 2020-6 June 2020; Phase 2: 17 June 2020-16 September 2020; Phase 3: 17 September 2020-16 December 2020; Phase 4: 17 December 2020-16 March 2021). All callers who provided their symptoms (including asymptomatic with exposure to COVID) and received nursing triage were included in the study. Factors associated with patient participation were identified using multivariable logistic regression analyses, including demographic variables, comorbidity variables, health behaviors, and COVID-19-related symptoms.ResultsThe aggregated data included 9849 encounters/calls from 9021 unique participants. Results indicated: (1) 72.5% of patient participation rate; (2) participants advised to seek emergency department care had the lowest patient participation rate (43.4%); (3) patient participation was associated with older age, a lower comorbidity index, a lack of unexplained muscle aches, and respiratory symptoms. The absence of respiratory symptoms was the only factor significantly associated with patient participation in all four phases (OR = 0.75, 0.60, 0.64, 0.52, respectively). Older age was associated with higher patient participation in three out of four phases (OR = 1.01-1.02), and a lower Charlson comorbidity index was associated with higher patient participation in phase 3 and phase 4 (OR = 0.83, 0.88).ConclusionPublic participation in nursing triage during the COVID pandemic requires attention. This study supports using a nurse-led telehealth intervention and reveals crucial factors associated with patient participation. It highlighted the importance of timely follow-up in high-risk groups and the benefit of a telehealth intervention led by nurses serving as healthcare navigators during the COVID-19 pandemic.

BackgroundPrior studies of the glycemic effect of statins have been inconsistent. Also, most studies have only considered a short duration of statin use; the effect of long-term statin use on fasting glucose (FG) has not been well examined. The aim of this work is to investigate the effect of long-term statin exposure on FG levels.MethodsUsing electronic health record (EHR) data from a large and diverse longitudinal cohort, we defined long-term statin exposure in two ways: the cumulative years of statin use (cumulative supply) and the years' supply-weighted sum of doses (cumulative dose). Simvastatin, lovastatin, atorvastatin and pravastatin were included in the analysis. The relationship between statin exposure and FG was examined using linear regression with mixed effects modeling, comparing statin users before and after initiating statins and statin never-users.ResultsWe examined 593,130 FG measurements from 87,151 individuals over a median follow up of 20 years. Of these, 42,678 were never-users and 44,473 were statin users with a total of 730,031 statin prescriptions. FG was positively associated with cumulative supply of statin but not comulative dose when both measures were in the same model. While statistically significant, the annual increase in FG attributable to statin exposure was modest at only 0.14 mg/dl, with only slight and non-significant differences among statin types.ConclusionsElevation in FG level is associated with statin exposure, but the effect is modest. The results suggest that the risk of a clinically significant increase in FG attributable to long-term statin use is small for most individuals.

Genetic substudies of randomized controlled trials demonstrate that high coronary heart disease (CHD) polygenic risk score modifies statin CHD relative risk reduction; it is unknown if the association extends to statin users undergoing routine care. We sought to determine how statin effectiveness is modified by CHD polygenic risk score in a real-world cohort of participants without previous myocardial infarction. We determined CHD polygenic risk scores in participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Covariate-adjusted Cox regression models were used to compare the risk of cardiovascular outcomes between statin users and matched nonusers. Statin effectiveness on incident myocardial infarction showed no gradient with increasing 10-year Pooled Cohort Equations atherosclerotic cardiovascular disease (ASCVD) risk across low, borderline, intermediate, and high ASCVD risk score groups. In contrast, statin effectiveness by polygenic risk was largest in the high polygenic risk score group (hazard ratio (HR) 0.41, 95% confidence interval (CI), 0.31-0.53; P = 1.5E-11), intermediate in the intermediate polygenic risk score group (HR 0.56, 95% CI, 0.47-0.66; P = 8.4E-12), and smallest in the low polygenic risk score group (HR 0.67, 95% CI, 0.47-0.97; P = 0.03; P for high vs. low = 0.01). ASCVD risk and statin low-density lipoprotein cholesterol (LDL-C) lowering did not differ across polygenic risk score groups. In patients undergoing routine care, CHD polygenic risk modified statin relative risk reduction of incident myocardial infarction independent of LDL-C lowering. Our findings extend prior work by identifying a subset (i.e., self-identified White individuals with low CHD polygenic risk scores) with attenuated clinical benefit from statins.

Contemporary technology and artificial intelligence increasingly facilitate the delivery of justice by automating, accelerating, and supporting judicial procedures with digitisation and automation tools. This article analyses options for the automatisation of the European Small Claims Procedure. The authors propose the digitisation of the procedure to a greater extent by additional features, such as AI-powered translation and text-to-speech tools, as well as creation of a trustworthy system for submission and storing of procedural documents based on the Estonian e-File example within the framework of the ongoing EU-funded SCAN II-project.

AbstractThere is a lack of literature on the effects of physical activity and depression on resilience in women living with HIV. This cross-sectional study examined the associations of sociodemographic factors, physical activity, and depression on resilience among 97 women living with HIV using linear regression models. Among these women, the mean resilience score was 70.7 (SD 16.3), the majority were insufficiently active (67.0%), and 45.4% had a Patient Health Questionnaire-9 score that indicated at least moderate depression. In a multivariable analysis, depression was negatively associated with resilience, and education was positively associated with resilience (p < .0001; p = .031). There was no significant correlation between physical activity and depression or resilience. An exploratory analysis did not indicate that depression mediated the relationship between physical activity and resilience. There is a need to address low levels of physical activity in women living with HIV. Interventions that address resilience and depressive symptoms may lead to improved mental health.

IntroductionDespite playing an integral part in sexual and reproductive health care, including abortion care, nurses are rarely the focus of research regarding their attitudes about abortion.MethodsA sample of 1,820 nurse members of the Association of Women's Health, Obstetric and Neonatal Nurses were surveyed about their demographic and professional backgrounds, religious beliefs, and abortion attitudes. Scores on the Abortion Attitudes Scale were analyzed categorically and trichotomized in multinomial regression analyses.ResultsAlmost one-third of the sample (32%) had moderately proabortion attitudes, 29% were unsure, 16% had strongly proabortion attitudes, 13% had strongly antiabortion attitudes, and 11% had moderately antiabortion attitudes. Using trichotomized Abortion Attitudes Scale scores (proabortion, unsure, antiabortion), adjusted regression models showed that the following characteristics were associated with proabortion attitudes: being non-Christian, residence in the North or West, having no children, and having had an abortion.ConclusionsUnderstanding nurses' attitudes toward abortion, and what characteristics may influence their attitudes, is critical to sustaining nursing care for patients considering and seeking abortion. Additionally, because personal characteristics were associated with antiabortion attitudes, it is likely that personal experiences may influence attitudes toward abortion. A large percentage of nurses held attitudes that placed them in the "unsure" category. Given the current ubiquitous polarization of abortion discourse, this finding indicates that the binary narrative of this topic is less pervasive than expected, which lends itself to an emphasis on empathetic and compassionate nursing care.

Legislation has been passed in some states to reduce discrimination and victimization toward sexual and gender minority people (SGM; people who are not solely heterosexual and/or whose gender identity is not equal to what is socially associated with sex assigned at birth). The purpose of these analyses is to test whether state-level policy environments are associated with past-year discrimination and victimization among SGM people. Cross-sectional data from The Population Research in Identity and Disparities for Equality (PRIDE) Study annual questionnaire (collected 2018−2019), a national study of the health of SGM adults in the USA, were used for these analyses. Measures included related to discrimination, victimization, and demographic characteristics. State-level policy environments were measured using data from the Movement Advancement Project. Logistic regression analyses evaluated state-level policy environment scores and past-year discrimination and victimization among gender identity categories. In this sample, 7044 people (gender minority n = 2530) were included. Cisgender sexual minority (odds ratio [OR] = 1.007, p = 0.041) and the gender expansive subgroup of gender minority people (OR = 1.010, p = 0.047) in states with more protective policy environments had greater odds of discrimination. The gender expansive subgroup was found to have greater odds of victimization in states with more protective policy environments (OR = 1.003, p < 0.05). There was no relationship between state-level policy environments and victimization among any other study groups. SGM people may experience increased risk for discrimination and victimization despite legislative protections, posing continued risks for poor health outcomes and marginalization. Evaluation of factors (e.g., implementation strategies, systems of accountability) that influence the effectiveness of state-level polices on the reported experiences of discrimination and victimization among SGM people is needed.

BackgroundUp to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored.MethodsTo characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers.ResultsWe identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer.ConclusionsOverall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.

BackgroundFamily Integrated Care (FICare) benefits preterm infants compared with Family-Centered Care (FCC), but research is lacking in United States (US) Neonatal Intensive Care Units (NICUs). The outcomes for infants of implementing FICare in the US are unknown given differences in parental leave benefits and health care delivery between the US and other countries where FICare is used. We compared preterm weight and discharge outcomes between FCC and mobile-enhanced FICare (mFICare) in the US.MethodsIn this quasi-experimental study, we enrolled preterm infant (≤ 33 weeks)/parent dyads from 3 NICUs into sequential cohorts: FCC or mFICare. Our primary outcome was 21-day change in weight z-scores. Our secondary outcomes were nosocomial infection, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and human milk feeding (HMF) at discharge. We used intention-to-treat analyses to examine the effect of the FCC and mFICare models overall and per protocol analyses to examine the effects of the mFICare intervention components.Findings253 infant/parent dyads participated (141 FCC; 112 mFICare). There were no parent-related adverse events in either group. In intention-to-treat analyses, we found no group differences in weight, ROP, BPD or HMF. The FCC cohort had 2.6-times (95% CI: 1.0, 6.7) higher odds of nosocomial infection than the mFICare cohort. In per-protocol analyses, we found that infants whose parents did not receive parent mentoring or participate in rounds lost more weight relative to age-based norms (group-difference=-0.128, CI: -0.227, -0.030; group-difference=-0.084, CI: -0.154, -0.015, respectively). Infants whose parents did not participate in rounds or group education had 2.9-times (CI: 1.0, 9.1) and 3.8-times (CI: 1.2, 14.3) higher odds of nosocomial infection, respectively.ConclusionWe found indications that mFICare may have direct benefits on infant outcomes such as weight gain and nosocomial infection. Future studies using implementation science designs are needed to optimize intervention delivery and determine acute and long-term infant and family outcomes.Clinical trial registrationNCT03418870 01/02/2018.

We aimed to characterize knowledge and attitudes about rapid whole genome sequencing (rWGS) implementation of a broad constituency of healthcare professionals at hospitals participating in a statewide initiative to implement rWGS for hospitalized neonates and children up to 18 years of age meeting clinical criteria for testing. We surveyed 307 healthcare professionals from eight hospitals about their knowledge and attitudes regarding rWGS. We examined survey internal reliability using exploratory factor analysis and associations between respondent characteristics and attitudes toward rWGS with linear regression. We thematically analyzed free-text responses. Views about rWGS implementation in respondents' own setting and respondents' personal capability to implement rWGS were generally neutral (M = 3.44 (SD = 0.74); M = 3.30 (SD = 0.85), respectively). Views about the potential for rWGS in clinical practice were overall positive (M = 4.12 (SD = 0.57)). The degree of positivity of attitudes about rWGS was strongly influenced by perceived knowledge, clinical or non-clinical role, concerns about future insurance coverage for rWGS as a first-tier test, and future adverse impact of genomics health information on patients or families. We identified several actionable factors influencing attitudes toward rWGS of pediatric healthcare professionals. Expanded education and ongoing implementation research are needed for the full potential of rWGS in pediatrics to be realized.

BackgroundMother-to-infant transmission of HIV is a major problem in Sub-Saharan Africa despite free or subsidized antiretroviral treatment (ART), but is significantly reduced when mothers adhere to ART. Because potable water access is limited in low-resource countries, we investigated water access and ART adherence intention among HIV-positive pregnant women and new mothers in Zambia.MethodsOur convenience sample consisted of 150 pregnant or postpartum women receiving ART. Descriptive statistics compared type of water access by low and high levels of ART adherence intention.ResultsMost (71%) had access to piped water, but 36% of the low-adherence intention group obtained water from a well, borehole, lake or stream, compared to only 22% of the high-adherence intention group. The low-adherence intention group was more rural (62%) than urban (38%) women but not statistically significant [unadjusted Prevalence Ratio (PR) 0.73, 95% CI: 0.52-1.02; adjusted PR 1.06, 95% CI: 0.78-1.45].ConclusionProviding potable water may improve ART adherence. Assessing available water sources in both rural and urban locations is critical when educating women initiating ART.

ObjectiveThe global burden of HIV on women and pediatric populations are severe in sub-Saharan Africa. Global child HIV infection rates have declined, but this rate remains quite high in sub-Saharan Africa due to Mother-to-child transmission (MTCT). To prevent MTCT of HIV, postpartum women living with HIV (WLHIV) are required to return to a health facility for HIV care within 60 days after childbirth (Retention in HIV care). Studies suggest that interpersonal support was positively associated with retention in HIV care. However, information on this association is lacking among postpartum WLHIV in Uganda. Therefore, this study investigates the relationship between interpersonal support, measured with the Interpersonal Support Evaluation List (ISEL-12), and retention in HIV care.ResultsIn a total of 155 postpartum WLHIV, 84% were retained in HIV care. ISEL-12 was negatively associated with retention in HIV care. Postpartum WLHIV retained in care (24.984 ± 4.549) have lower ISEL-12 scores compared to the non-retained group (27.520 ± 4.224), t(35.572) = - 2.714, p = 0.01. In the non-income earning sample, respondents retained in care (24.110 ± 4.974) have lower ISEL scores compared to the non-retained group (27.000 ± 4.855), t(20.504) = -2.019, p = 0.049. This was not significant among income earning WLHIV.

The article ‘EGFR/Ras-induced CCL20 production modulates the tumour microenvironment’, written by Andreas Hippe, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber, Anne Schorr, Stephan Seeliger, Stephanie Holtz, Katharina Jannasch, Andor Pivarcsi, Bettina Buhren, Holger Schrumpf, Andreas Kislat, Erich Bünemann, Martin Steinhoff, Jens Fischer, Sérgio A. Lira, Petra Boukamp, Peter Hevezi, Nikolas Hendrik Stoecklein, Thomas Hoffmann, Frauke Alves, Jonathan Sleeman, Thomas Bauer, Jörg Klufa, Nicole Amberg, Maria Sibilia, Albert Zlotnik, Anja Müller- Homey and Bernhard Homey, was originally published electronically on the publisher’s internet portal on 30 June 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 16 September 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. Open Access funding enabled and organized by Projekt DEAL.

Weight loss or lower body mass index (BMI) could be an early symptom of Alzheimer disease (AD), but when this begins to emerge is difficult to estimate with traditional observational data. In an extension of Mendelian randomization, we leveraged variation in genetic risk for late-onset AD risk to estimate the causal effect of AD on BMI and the earliest ages at which AD-related weight loss (or lower BMI as a proxy) occurs. We studied UK Biobank participants enrolled in 2006-2010, who were without dementia, aged 39-73, with European genetic ancestry. BMI was calculated with measured height/weight (weight (kg)/height (m)2). An AD genetic risk score (AD-GRS) was calculated based on 23 genetic variants. Using linear regressions, we tested the association of AD-GRS with BMI, stratified by decade, and calculated the age of divergence in BMI trends between low and high AD-GRS. AD-GRS was not associated with BMI in 39- to 49-year-olds (β = 0.00, 95% confidence interval (CI): -0.03, 0.03). AD-GRS was associated with lower BMI in 50- to 59-year-olds (β = -0.03, 95% CI: -0.06, -0.01) and 60- to 73-year-olds (β = -0.09, 95% CI:-0.12, -0.07). Model-based BMI age curves for high versus low AD-GRS began to diverge after age 47 years. Sensitivity analyses found no evidence for pleiotropy or survival bias. Longitudinal replication is needed; however, our findings suggest that AD genes might begin to reduce BMI decades prior to dementia diagnosis.

The association between the c.521T>C variant allele in SLCO1B1 (reference single nucleotide polymorphism (rs)4149056) and simvastatin-induced myotoxicity was discovered over a decade ago; however, whether this relationship represents a class effect is still not fully known. The aim of this study was to investigate the relationship between rs4149056 genotype and statin-induced myotoxicity in patients taking atorvastatin and lovastatin. Study participants were from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. A total of 233 statin-induced myopathy + rhabdomyolysis cases met the criteria for inclusion and were matched to 2,342 controls. To validate the drug response phenotype, we replicated the previously established association between rs4149056 genotype and simvastatin-induced myotoxicity. In particular, compared with homozygous T allele carriers, there was a significantly increased risk of simvastatin-induced myopathy + rhabdomyolysis in homozygous carriers of the C allele (CC vs. TT, odds ratio [OR] 4.62, 95% confidence interval [CI] 1.58-11.90, P = 0.003). For lovastatin users, homozygous carriers of the C allele were also at increased risk of statin-induced myopathy + rhabdomyolysis (CC vs. TT, OR 4.49, 95% CI 1.68-10.80, P = 0.001). In atorvastatin users, homozygous carriers of the C allele were twice as likely to experience statin-induced myopathy, though this association did not achieve statistical significance (CC vs. TT, OR 2.00, 95% CI 0.44-6.59, P = 0.30). In summary, our findings suggest that the association of rs4149056 with simvastatin-related myotoxicity may also extend to lovastatin. More data is needed to determine the extent of the association in atorvastatin users. Altogether, these data expand the evidence base for informing guidelines of pharmacogenetic-based statin prescribing practices.

Plasma lipids are known heritable risk factors for cardiovascular disease, but increasing evidence also supports shared genetics with diseases of other organ systems. We devised a comprehensive three-phase framework to identify new lipid-associated genes and study the relationships among lipids, genotypes, gene expression and hundreds of complex human diseases from the Electronic Medical Records and Genomics (347 traits) and the UK Biobank (549 traits). Aside from 67 new lipid-associated genes with strong replication, we found evidence for pleiotropic SNPs/genes between lipids and diseases across the phenome. These include discordant pleiotropy in the HLA region between lipids and multiple sclerosis and putative causal paths between triglycerides and gout, among several others. Our findings give insights into the genetic basis of the relationship between plasma lipids and diseases on a phenome-wide scale and can provide context for future prevention and treatment strategies.