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Early childhood researchers frequently use learning materials and assessments involving pictures, across different cultures and contexts. However, there is variation in when and how children across cultures and contexts begin to understand and learn from pictures. While children growing up in high-income contexts often have more experience with picture books and other kinds of two-dimensional visual symbols, children growing up in low-income, rural contexts in low- and middle-income countries often have less experience with pictures and other kinds of visual symbols. The current research leverages variation in picture experience within a geographical region to investigate whether previous picture experience is related to toddlers' (1) performance on a picture-based word learning task, and (2) referential understanding, controlling for maternal education, number of toys, caregiver talk, and caregiver play. One hundred and twenty-eight toddlers in urban and rural western Kenya (n = 64 per area), who had varying amounts of picture experience, participated in a picture-based word learning task. Preregistered analyses with the entire sample showed no relation between picture experience and performance on a picture-based word learning task, or between picture experience and referential understanding. However, exploratory analyses found a positive association between picture experience and performance on the picture-based word learning task in the urban sample, but not the rural sample. We found no association between toddlers' referential understanding and picture experience, in either sample. We discuss how these results may inform the efficacy of learning materials and the validity of assessments used with children from diverse global backgrounds., (© 2024 The Author(s). Developmental Science published by John Wiley & Sons Ltd.)

Importance: Heyde syndrome is the cooccurrence of aortic stenosis and gastrointestinal bleeding secondary to vascular lesions, including angiodysplasias. Several studies have demonstrated cessation of gastrointestinal bleeding after transcatheter aortic valve implantation (TAVI), but the etiology and effects on vascular lesions are largely unknown., Objective: To examine the associations of TAVI with gastrointestinal vascular lesions and identify factors associated with recovery among patients with iron deficiency anemia and severe aortic stenosis., Design, Setting, and Participants: In this prospective, single-center cohort study, patients with iron deficiency anemia on the TAVI waiting list from September 2020 to February 2022 were assessed by capsule endoscopy. Those with vascular lesions were reassessed 6 months after TAVI. Endoscopic images were anonymized and evaluated by 2 independent researchers. Data were analyzed from September 2022 to August 2024., Exposure: TAVI., Main Outcomes and Measures: The primary outcome was the mean difference in the number of vascular lesions before vs after TAVI., Results: A total of 24 patients (mean [SD] age, 77.4 [7.1] years; 18 [75.0%] male) underwent capsule endoscopy, and vascular lesions were present in 18 patients (75.0%). TAVI was performed in 15 of 18 patients with vascular lesions, of whom 11 agreed to a second capsule endoscopy. The mean (SD) number of vascular lesions across the gastrointestinal tract decreased from 6.4 (5.6) lesions before TAVI to 2.0 (2.1) lesions 6 months after TAVI (P = .04). The number of vascular lesions decreased in 9 of 11 patients (81.8%), including 6 patients (54.5%) who no longer had typical angiodysplasias. Resolution of angiodysplasias was less frequent in patients who had multiple valvular heart disease before TAVI (0 of 3 patients) vs those without multiple valvular heart disease (6 of 8 patients [75.0%]) and in patients with significant paravalvular leakage after TAVI (2 of 5 patients [40.0%]) vs those without significant leakage (4 of 6 patients [66.7%])., Conclusions and Relevance: In this cohort study of 24 patients with iron deficiency anemia and severe aortic stenosis, angiodysplasias were present in 75.0% of patients. TAVI was associated with reduced size and number of angiodysplasias in these patients. These findings suggest that TAVI not only improves aortic stenosis but may also reduce gastrointestinal bleeding by resolving vascular lesions, offering a dual benefit for patients with Heyde syndrome.

Gastrointestinal angiodysplasia (GIA) is a common, acquired, vascular abnormality of the digestive tract, and a frequent cause of bleeding. Refractory GIA criteria usually include recurrent bleeding, transfusions and/or repeat endoscopy. Pharmacological and interventional treatments have been the subject of recent high-quality publications. This review provides an overview of the latest updates on non-endoscopic management of refractory GIA. Aortic valve replacement has shown its efficacy in Heyde syndrome and should be considered if indicated. Anti-angiogenic drugs, such as Octreotide and Thalidomide, are efficient treatments of refractory GIA-related bleeding. Somatostatin analogs should, based on efficacy and tolerance profile, be considered first. In the future, a better understanding of the physiopathology of GIA might help develop new-targeted therapies., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Introduction: In low-resource settings, introducing child health programs into community services may compete for caregiver time. We analyzed the impact of a new early childhood development (ECD) program in rural Madagascar on family attendance at other health services and of adding at-home play materials on program attendance., Methods: We randomized 75 communities where community health workers (CHWs) implement an existing child health and nutrition program (Projet d'Amélioration des Résultats Nutritionnels or PARN), the status quo. We offered two 6-month cycles of 12 ECD sessions to eligible caregiver-child dyads (6-30 months) in 25 sites [T]; we added take-home play materials in Cycle 2 to 25 sites [T+]. We used differences-in-differences with administrative data to analyze the effect of offering ECD sessions on monthly PARN attendance (T+/T vs. C) among age-eligible children and the impact of toy boxes/libraries on monthly ECD session attendance (T + vs. T). We used random intercept models to analyze characteristics associated with program registration., Results: We analyzed data for 9,408 dyads; 30% and 32% registered for the program in Cycle 1 and 2 (respectively). On average, CHWs delivered 11.4 sessions (SD: 1.5). Children from wealthier households who already attended PARN sessions were more likely to register, and we found no effect of T or T + on PARN attendance. Adding play materials did not affect monthly ECD session attendance. Children from more populated sites were less likely to participate in both ECD and PARN sessions., Conclusions: Integrating new services for ECD into the health system was feasible and did not reduce dyad participation in existing services. Investment in health services in more populated areas is needed to provide coverage to all eligible children. Novel strategies should be explored to engage the most vulnerable children in new and existing health services., Trial Registration: AEA Social Science Registry (AEARCTR-0004704) on November 15, 2019 (prospective registration) and ClinicalTrials.gov (NCT05129696) on November 22, 2021 (retrospective registration)., (© 2024. The Author(s).)

Background: Pediatric urinary tract infections (UTIs) require early diagnosis and appropriate treatment to avoid short- and long-term morbidity. Baseline data from 13,000 children across a regional health system demonstrated wide variation in UTI management, including antibiotic choice, duration, and dosing. In 2019, the local antibiotic stewardship team recommended cephalexin as the ideal first-line UTI treatment due to its effectiveness, narrow spectrum, low cost, and palatability. This project aimed to improve first-line prescription of cephalexin as an empiric antibiotic treatment for uncomplicated UTIs from 34% to 75% in children 60 days to 18 years of age presenting to any site within the healthcare system within 6 months., Methods: A multidisciplinary team of key stakeholders reviewed baseline data and developed three key drivers. These included a standardized UTI pathway, electronic health record enhancements, and provider education. Interventions were supported by a literature review and implemented via Plan-Do-Study-Act cycles with data monitored bimonthly. The primary outcome was the percentage of patients prescribed cephalexin for presumed UTI over the total number of presumed UTI diagnoses treated with empiric antibiotics throughout the healthcare system. The balancing measure included 14-day return visits for a UTI-related diagnosis across the system., Results: After the release of the updated UTI pathway, first-line cephalexin prescribing for UTI improved from 34% to 66%. There was no change in 14-day revisits for UTI., Conclusions: Standardizing the diagnosis and management of UTIs across the spectrum of coordinated care led to improved system-wide adherence to local antibiotic stewardship guidelines for empiric UTI treatment., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Previous research demonstrates the joint association of self-reported physical activity and genotype with coronary artery disease. However, an existing research gap is whether accelerometer-measured overall physical activity or physical activity intensity can offset genetic predisposition to coronary artery disease. This study explores the independent and joint associations of accelerometer-measured physical activity and genetic predisposition with incident coronary artery disease. Incident coronary artery disease based on hospital inpatient records and death register data serves as the outcome of this study. Polygenic risk score and overall physical activity, measured as Euclidean Norm Minus One, and intensity, measured as minutes per day of moderate-to-vigorous intensity physical activity (MVPA), are examined both linearly and by decile. The UK Biobank population-based cohort recruited over 500,000 individuals aged 40 to 69 between 2006 and 2010, with 103,712 volunteers participating in a weeklong wrist-worn accelerometer study from 2013 to 2015. Individuals of White British ancestry (n = 65,079) meeting the genotyping and accelerometer-based inclusion criteria and with no missing covariates were included in the analytic sample. In the sample of 65,079 individuals, the mean (SD) age was 62.51 (7.76) and 61% were female. During a median follow-up of 6.8 years, 1,382 cases of coronary artery disease developed. At the same genetic risk, physical activity intensity had a hazard ratio (HR) of 0.41 (95% CI: 0.29-0.60) at the 90th compared to 10th percentile, equivalent to 31.68 and 120.96 minutes of moderate-to-vigorous physical activity per day, respectively, versus an HR of 0.61 (95% CI: 0.52-0.72) for overall physical activity. The combination of high genetic risk and low physical activity intensity showed the greatest risk, with an individual at the 10th percentile of genetic risk and 90th percentile of intensity facing an HR of 0.14 (95% CI: 0.09-0.21) compared to an individual at the 90th percentile of genetic risk and 10th percentile of intensity. Physical activity, especially physical activity intensity, is associated with an attenuation of some of the risk of coronary artery disease but this pattern does not vary by genetic risk. This accelerometer-based study provides the clearest evidence to date regarding the joint influence of genetics, overall physical activity, and physical activity intensity on coronary artery disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh., Methods: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables., Results: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development., Conclusions: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress., Competing Interests: Declaration of Competing Interest This work was supported by Global Development grants [OPPGD759 and OPP1165144] from the Bill & Melinda Gates Foundation to the University of California, Berkeley and by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health [grant number K01AI136885 to AL]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. In the interest of full disclosure and transparency, we would like to disclose the roles of co-authors. Douglas Granger is the founder and chief scientific and strategy advisor at Salimetrics LLC and SalivaBio LLC, and these relationships are managed by the policies of the committees on conflict of interest at the Johns Hopkins University School of Medicine and the University of California at Irvine. Liying Yan is the president of EpigenDx, Inc. Ann Meyer is the Associate Director of Operations at EpigenDx, Inc., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood., (© 2024. The Author(s).)

Background & Aims: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting., Methods: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up., Results: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5)., Conclusions: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia., Clinicaltrials: gov, NCT02384122., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the degree of openness of communication about illness and death between patients with advanced cancer and their relatives during the last three months of the patient's life, and its association with relatives' characteristics and bereavement distress., Methods: We used data from bereaved relatives of patients with advanced cancer from the prospective, longitudinal, multicenter, observational eQuipe study. Univariate and multivariable linear regression analyses were used to assess the association between the degree of openness of communication (measured using the validated Caregivers' Communication with patients about Illness and Death scale), the a priori defined characteristics of the relatives, and the degree of bereavement distress (measured using the Impact of Event Scale)., Results: A total of 160 bereaved relatives were included in the analysis. The average degree of open communication about illness and death between patients with advanced cancer and their relatives was 3.86 on a scale of 1 to 5 (SE=0.08). A higher degree of open communication was associated with a lower degree of bereavement distress (p=0.003). No associations were found between the degree of open communication and the relatives' age (p=0.745), gender (p=0.196), level of education (p>0.773), (religious) worldview (p=0.435), type of relationship with the patient (p>0.548), or level of emotional functioning before the patient's death (p=0.075)., Conclusions: Open communication about illness and death between patients and relatives seems to be important, as it is associated with a lower degree of bereavement distress. Healthcare professionals can play an important role in encouraging the dialogue. However, it is important to keep in mind that some people not feel comfortable talking about illness and death., (© 2024. The Author(s).)

Introduction: The U.S. safety net, which provides critical aid to households with low income, is composed of a patchwork of separate programs, and many people with low income benefit from accessing <1 program. However, little is known about multiprogram take-up, that is, participation conditioned on eligibility. This study examined individual and multiprogram take-up patterns and sociodemographic factors associated with multiprogram take-up of U.S. safety net programs., Methods: The Assessing California Communities' Experiences with Safety Net Supports study interviewed Californians and reviewed their 2019 tax forms between August 2020 and May 2021. Take-up of safety net programs was calculated among eligible participants ( n =365), including the Earned Income Tax Credit; Supplemental Nutrition Assistance Program; the Special Supplemental Nutrition Program for Women, Infants, and Children; and Medicaid. Multivariable regressions identified sociodemographic factors associated with take-up of multiple programs., Results: Take-up was highest for Medicaid (90.6%) and lowest for Supplemental Nutrition Assistance Program (57.5%). Among people who received benefits from at least 1 other program, take-up ranged from 81.7% to 84.8% for the Earned Income Tax Credit; 54.4%-62.0% for Supplemental Nutrition Assistance Program; 74.3%-80.1% for Special Supplemental Nutrition Program for Women, Infants, and Children; and 89.7%-98.1% for Medicaid. Having a lower income and being younger were associated with concurrent take-up of Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children. Among Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children recipients, having higher income, being older, and being primarily English speaking were associated with Earned Income Tax Credit take-up., Conclusions: Individual and multiprogram take-up vary between programs and by sociodemographic factors. Findings suggest opportunities to increase take-up of potentially synergistic programs by improving cross-program coordination, data sharing, and targeted recruitment of underenrolled subgroups (Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children)., (© 2024 The Authors.)

Safety-net programs in the United States offered critical support to counter food insecurity and poverty during the first year of the COVID-19 pandemic. The Supplemental Nutrition Assistance Program (SNAP) and the Earned Income Tax Credit (EITC) are both means-tested programs with significant benefits. Take-up of SNAP and EITC is lower in California than nationwide and reasons for this difference are unclear. We examined associations of participation in SNAP and receipt of the EITC and perceptions of the US government, 2 types of welfare stigma (program stigma and social stigma), and perceived discrimination. We interviewed a sample of 497 caregivers of young children from families with low income in California during the COVID-19 pandemic (August 2020-May 2021). We found that participation in SNAP (odds ratio [OR] = 1.24 [1.05, 1.47]) and receiving the EITC (OR = 1.39 [1.05, 1.84]) were both associated with greater reported perceptions of social stigma, but not with perceptions of government, program stigma, or discrimination. Among food-insecure respondents, we found that participation in SNAP was additionally associated with program stigma and discrimination. These findings suggest that perceived social stigma may be a reason that people with low income may not participate in programs for which they are eligible., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2023. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Neonatal hypoxic-ischemic encephalopathy (HIE) is a disease caused by insufficient blood supply in the brain in newborns during the perinatal period. Severe HIE leads to patient death, and patients with mild HIE are at increased risk of cognitive deficits and behavioral abnormalities. The NMDA receptor is an important excitatory receptor in the central nervous system, and in adult hypoxic-ischemic injury both subtypes of the NMDA receptor play important but distinct roles. The GluN2A-containing NMDA receptor (GluN2A-NMDAR) could activate neuronal protective signaling pathway, while the GluN2B-NMDAR subtype is coupled to the apoptosis-inducing signaling pathway and leads to neuronal death. However, the expression level of GluN2B is higher in newborns than in adults, while the expression of GluN2A is lower. Therefore, it is not clear whether the roles of different NMDA receptor subtypes in HIE are consistent with those in adults. We investigated this issue in this study and found that in HIE, GluN2B plays a protective role by mediating the protective pathway through binding with PSD95, which is quite different to that in adults. The results of this study provided new theoretical support for the clinical treatment of neonatal hypoxic ischemia.

Background: Up to 40% of vulvar cancer patients present with local recurrence within 10 years of follow-up. An inguinofemoral lymphadenectomy (IFL) is indicated if not performed at primary treatment. The incidence and risk factors for lymph node metastases (LNM) at first local recurrence, however, are unclear. Our aim was to determine the incidence of LNM at first local recurrence, in relation to previous groin treatment and clinicopathological factors., Methods: A multicenter cohort study including vulvar cancer patients with a first macroinvasive local recurrence after primary surgical treatment between 2000 and 2015 was conducted in the Netherlands. Groin status at local recurrence was defined as positive (N+), negative (N-) or unknown (N?) and based on histology, imaging and follow-up. Patient-, tumour- and treatment characteristics of primary and recurrent disease were analysed., Results: Overall, 16.3% (66/404) had a N+ groin status at first local recurrence, 66.4% (268/404) N- and 17.3% (70/404) N? groin status. The incidence of a N+ groin status was comparable after previous SLN and IFL, 11.5% and 13.8%, respectively. A N+ groin status was related to tumour size (25 vs.12 mm; P < 0.001), depth of invasion (5 vs. 3 mm; P < 0.001) and poorly differentiated tumours (22.9 vs. 11.9%; P = 0.050) at local recurrence., Conclusions: The incidence of LNM at first local recurrence in vulvar cancer patients was 16.3%, and independent of previous type of groin surgery. In accordance with primary diagnosis, tumour size, depth of invasion, and tumour grade were significantly associated with a positive groin status., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding., Methods and Results: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002)., Conclusion: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The earned income tax credit (EITC) is the largest U.S. poverty alleviation program for low-income families, disbursed annually as a lump-sum tax refund. Despite its well-documented health impacts, the mechanisms through which the EITC affects health are not well understood. The objective of this analysis was to examine self-reported spending patterns of tax refunds among EITC recipients to clarify potential pathways through which income may affect health., Methods: We first examined spending patterns among 2020-2021 Assessing California Communities' Experiences with Safety Net Supports (ACCESS) study participants (N = 241) and then stratified the analysis by key demographic subgroups., Results: More than half of EITC recipients reported spending their tax refunds on bills and debt (52.3%), followed by 49.4% on housing, and 37.8% on vehicles. Only 3.3% reported spending on healthcare. (Note: respondents could list more than one possible spending category.) Participants ages 30 + were more likely to spend on bills and debt relative to those ages 18-29 (57.6% versus 39.4%, respectively). Other subgroup analyses did not yield significant findings., Conclusions: Our findings suggest that EITC recipients primarily use their refunds on bills and debt, as well as on household and vehicle expenses. This supports the idea of the EITC as a safety net policy which addresses key social determinants of health., (© 2023. The Author(s).)

Background: Poor immune function increases children's risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period., Objectives: We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth., Methods: We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution., Results: At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36])., Conclusion: Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child's immune status., (© 2023 The Authors.)

Children in low- and middle-income countries face an increased risk of impaired cognitive development due to contaminated environments, poor nutrition, and inadequate responsive stimulation from caregivers. Implementing multi-component, community-level interventions may reduce these risks; however, there is little evidence supporting implementation of these interventions at scale. We assessed the feasibility of implementing a group-based intervention that included responsive stimulation, maternal and child nutrition, water and sanitation, and childhood lead exposure prevention through the government health system in Chatmohar, Bangladesh. After implementation, we conducted 17 in-depth interviews with frontline health service providers and 12 key informant interviews with their supervisors and managers to explore the facilitators and difficulties implementing such a complex programme within the health system. Factors facilitating implementation included: high quality training and skill level of providers, support from community members, family, and supervisors, positive relationships between providers and participants, and provision of children's toys and books free of cost. Difficulties included increased workload of the providers, complicated group-based yet stage-specific delivery where providers had to manage a large group of mother-child dyads representing many different child age-groups at once, and logistics difficulties in providing toys and books through a centralised health system process. Key informants made suggestions to ensure effective government-level scale-up including engaging relevant NGOs as partners, identifying feasible ways to make toys available, and offering providers meaningful even if non-monetary rewards. These findings can be used to shape the design and delivery of multi-component child development interventions to be delivered through the health system., (© 2023 John Wiley & Sons Ltd.)

Background: In South Asia, roughly half of women attend at least four antenatal care visits with skilled health personnel, the minimum number recommended by the World Health Organization for optimal birth outcomes. A much greater proportion of women attend at least one antenatal care visit, suggesting that a key challenge is ensuring that women initiate antenatal care early in pregnancy and continue to attend after their first visit. One critical barrier to antenatal care attendance may be that women do not have sufficient power in their relationships, households, or communities to attend antenatal care when they want to. The main goals of this paper were to 1) understand the potential effects of intervening on direct measures of women's empowerment-including household decision making, freedom of movement, and control over assets-on antenatal care attendance in a rural population of women in Bangladesh, and 2) examine whether differential associations exist across strata of socioeconomic status., Methods: We analyzed data on 1609 mothers with children under 24 months old in rural Bangladesh and employed targeted maximum likelihood estimation with ensemble machine learning to estimate population average treatment effects., Results: Greater women's empowerment was associated with an increased number of antenatal care visits. Specifically, among women who attended at least one antenatal care visit, having high empowerment was associated with a greater probability of ≥ 4 antenatal care visits, both in comparison to low empowerment (15.2 pp, 95% CI: 6.0, 24.4) and medium empowerment (9.1 pp, 95% CI: 2.5, 15.7). The subscales of women's empowerment driving the associations were women's decision-making power and control over assets. We found that greater women's empowerment is associated with more antenatal care visits regardless of socioeconomic status., Conclusions: Empowerment-based interventions, particularly those targeting women's involvement in household decisions and/or facilitating greater control over assets, may be a valuable strategy for increasing antenatal care attendance., Trial Registration: ClinicalTrials.gov Identifier: NCT04111016, Date First Registered: 01/10/2019., (© 2023. The Author(s).)

Background: The COVID-19 pandemic prompted rapid federal, state, and local government policymaking to buffer families from the health and economic harms of the pandemic. However, there has been little attention to families' perceptions of whether the pandemic safety net policy response was adequate, and what is needed to alleviate lasting effects on family well-being. This study examines the experiences and challenges of families with low incomes caring for young children during the pandemic., Methods: Semi-structured qualitative interviews conducted from August 2020 to January 2021 with 34 parents of young children in California were analyzed using thematic analysis., Results: We identified three key themes related to parents' experiences during the pandemic: (1) positive experiences with government support programs, (2) challenging experiences with government support programs, and (3) distress resulting from insufficient support for childcare disruptions. Participants reported that program expansions helped alleviate food insecurity, and those attending community colleges reported accessing a range of supports through supportive counselors. However, many reported gaps in support for childcare and distance learning, pre-existing housing instability, and parenting stressors. With insufficient supports, additional childcare and education workloads resulted in stress and exhaustion, guilt about competing demands, and stagnation of longer-term goals for economic and educational advancement., Conclusions: Families of young children, already facing housing and economic insecurity prior to the pandemic, experienced parental burnout. To support family well-being, participants endorsed policies to remove housing barriers, and expand childcare options to mitigate job loss and competing demands on parents. Policy responses that either alleviate stressors or bolster supports have the potential to prevent distress catalyzed by future disasters or the more common destabilizing experiences of economic insecurity., (© 2023. The Author(s).)

Background and Objectives: Evidence is needed on effective approaches to build parents' ability to promote child development feasible in low- and middle-income countries. Our objective was to synthesize impact of the Reach Up early childhood parenting program in several low- and middle-income countries and examine moderation by family and implementation characteristics., Methods: Systematic search using PubMed and Academic Search Elite/EBSCO Host. Randomized controlled trials of the Reach Up program from 1985 to February 2022 were selected. Data were extracted by 2 independent researchers. Primary outcomes were child cognitive, language, and motor development. Secondary outcomes were home stimulation and maternal depressive symptoms. We synthesized pooled effect sizes using random effect inverse-variance weighting and effect modification by testing pooled subgroup effect estimates using the χ2 test for heterogeneity., Results: Average effect size across 18 studies ranged from 0.49 (95% confidence interval [CI] 0.32 to 0.66) for cognition, 0.38 (CI 0.24 to 0.51) for language, 0.27 (CI 0.13 to 0.40) for motor development, 0.37 (CI 0.21 to 0.54) for home stimulation, and -0.09 (CI -0.19 to 0.01) for maternal depressive symptoms. Impacts were larger in studies targeted to undernourished children, with mean enrollment older than age 12 months and intervention duration 6 to 12 months. Quality of evidence assessed with the Cochrane Assessment of Risk of Bias and GRADE system was moderate. Instruments used to assess child development varied. In moderator analyses, some subgroups included few studies., Conclusions: Reach Up benefits child development and home stimulation and is adaptable across cultures and delivery methods. Child and implementation characteristics modified the effects, with implications for scaling., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Reliable and valid measurement of early child development are necessary for the design of effective interventions, programs, and policies to improve early child outcomes. One widely used measure in low- and middle-income countries (LMICs) is the Bayley Scales of Infant and Toddler Development III (Bayley-III). Alternatively, the Bangladeshi-adapted Ages and Stages Questionnaire Inventory (ASQ:I) can be administered more quickly, inexpensively, and with less training than the Bayley-III. We aimed to assess the concurrent validity of the Bangladeshi-adapted ASQ:I with the Bayley-III in children 4-27 months old in rural Bangladesh., Methods: The sample was a sub-sample (n = 244) of endline participants from an evaluation of an early child development intervention (July-August 2018). We assessed concurrent validity between internally age-standardized domain-specific and total scores using Pearson correlations both overall and stratified by age and intervention status. We also assessed correlations between scores and variables theoretically related to child development including maternal education and stimulation in the home., Results: The overall correlation between ASQ:I and Bayley-III total scores was moderate (r = 0.42 95% CI: 0.30-0.53), with no systematic differences by intervention status. Overall, concurrent validity was highest for the gross motor domain (r = 0.51, 0.40-0.60), and lowest for the fine motor domain (r = 0.20, 0.04-0.33). Total ASQ:I and Bayley-III scores were positively correlated with child stimulation and maternal education., Conclusion: The Bangladeshi-adapted ASQ:I is a low-cost tool that can be feasibly administered in rural Bangladesh, is moderately correlated with the Bayley-III, and can be used to measure child development when human, time, or financial resources are constrained., (© 2023. The Author(s).)

Introduction: In chronic diseases, disease-related distress can impact disease outcomes. Distress and haemophilia-related distress has been demonstrated in people with haemophilia (PwH). The association of haemophilia-related distress on disease outcomes among PwH is unknown., Aim: To study the association of haemophilia-related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work-impairment., Methods: In a cross-sectional study, adults with haemophilia A or B were enrolled in a study to validate the haemophilia-related distress questionnaire (HRDq). In this planned analysis, univariate and multivariate associations between the HRDq total score and disease outcomes were explored., Results: The 114 participants in this analysis were male, mostly with haemophilia A (92%) and severe disease (52%) with a median age of 31.9 years. On univariate analysis, HRDq total score (5-point change) was associated with the presence of a target joint (P = .002), high healthcare utilization (P = .011), poor adherence (P = .033) and work-impairment (P ≤ .001). After adjustment for age, race, severity and other potential confounders, adherence (aβ 0.33, 95% CI .17, .49) and work-impairment (aβ 4.69, 95% CI 3.27-6.1) remained statistically significantly associated with HRDq total score., Conclusion: Haemophilia-related distress is associated with poor adherence to factor prophylaxis and work-impairment. The direction of the association (causation) is yet to be determined and requires future study., (© 2023 John Wiley & Sons Ltd.)

This research had two aims: (1) to assess how often bisexual and lesbian women self-report screening and counseling for alcohol use in primary care settings; and (2) understand how bisexual and lesbian women respond to brief messages that alcohol increases breast cancer risk. The study sample consisted of 4891 adult U.S. women who responded to an online, cross-sectional Qualtrics survey in September-October 2021. The survey included the Alcohol Use Disorders Identification Test (AUDIT), questions about alcohol screening and brief counseling in primary care, and questions assessing awareness of the link between alcohol use and breast cancer. Bivariate analyses and logistic regression were conducted. Bisexual and lesbian women had higher odds of harmful drinking (AUDIT score ≥ 8) than heterosexual women (adjusted odds ratio [AOR] = 1.26, 95% confidence interval [CI] = 1.01-1.57 for bisexual women; AOR =1.78, 95% CI = 1.24-2.57 for lesbian women). However, bisexual and lesbian women were no more likely than heterosexual women to be advised about drinking in primary care. In addition, bisexual, lesbian, and heterosexual women had similar reactions to messages highlighting that alcohol is a risk factor for breast cancer. Women across all three sexual orientations who are harmful drinkers more often agreed to search for more information online or talk to a medical professional compared to non-harmful drinkers.

A greater risk of cardiovascular disease is associated with low educational attainment and high adiposity. Despite the correlation between low educational attainment and high adiposity, whether educational attainment modifies the risk of CVD caused by high adiposity remains poorly understood. We investigated the effect of adiposity (body mass index [BMI] and waist-to-hip ratio adjusted for BMI [WHRadjBMI]) on incident CVD among individuals with varying education levels, using associational and one-sample Mendelian randomization (MR) survival analyses. Data were collected from 2006 to 2021, and sample sizes were 254,281 (27,511 CVD cases) for BMI and 253,968 (27,458 CVD cases) for WHRadjBMI. In the associational model, a standard deviation (SD) higher BMI was associated with 19.81 (95% CI: 18.55-21.06) additional cases of incident CVD per 10,000 person-years for individuals with a secondary education, versus 32.96 (95% CI: 28.75-37.17) for those without. When university degree served as the education variable, education group differences attenuated, with 18.26 (95% CI: 16.37-20.15) cases from a one SD higher BMI for those with a university degree versus 23.18 [95% CI: 21.56-24.72] for those without. For the MR model, an SD higher BMI resulted in 11.75 (95% CI: -0.84-24.38) and 29.79 (95% CI: 17.20-42.44) additional cases of incident CVD per 10,000 person-years for individuals with versus without a university degree. WHRadjBMI exhibited no effect differences by education. While the associational model showed evidence of educational attainment modifying the relationship between adiposity and incident CVD, it does not modify the association between adiposity and incident CVD in the MR models. This suggests either less education does not cause greater risk of incident CVD from high adiposity, or MR models cannot detect the effect difference. The associational point estimates exist within the MR models' confidence intervals in all BMI analyses, so we cannot rule out the effect sizes in the associational models., Competing Interests: None declared., (© 2023 The Authors.)

The Earned Income Tax Credit (EITC) is the largest poverty alleviation program for families with children in the US, and it has well-documented health effects. However, not all eligible families receive benefits. The Assessing California Communities' Experiences with Safety Net Supports (ACCESS) Study interviewed 411 EITC-eligible Californians with young children to understand low take-up of the federal EITC and California's supplemental CalEITC. Interviews were conducted in English and Spanish in 2020 and 2021 to gather information on sociodemographic characteristics, tax filing, and EITC receipt (verified via tax forms). Among those eligible for the EITC or CalEITC, 9 percent of participants did not file taxes; among those who did file taxes, about 84 percent received the EITC, and 83 percent received the CalEITC. Lower likelihood of federal EITC receipt among those eligible and filing taxes was associated with being younger, not speaking English, and not having prior knowledge of the EITC. Lower likelihood of CalEITC receipt among those eligible and filing taxes was associated with not speaking English. These findings can inform policies and community interventions to increase EITC take-up and thereby help address health equity.

The gap between how health information is communicated and what people understand and can use to make informed health decisions is called health literacy. This gap was exacerbated by the rapidly changing and excessive volume of information, misinformation, and disinformation during the COVID-19 pandemic. People with lower health literacy may not have understood the importance of COVID-19 vaccination for themselves or for their communities. Our aim was to understand health literacy levels within Fulton County, Georgia, and their relationship to vaccine prevalence. Fulton county residents ages 18 and over (n = 425) completed an on-line Health Literacy Questionnaire. Individual, organizational, functional, interactive, and critical health literacy scales were created. Vaccination prevalence data were collected from the Georgia Vaccine Distribution Dashboard. All data were divided into one of three county areas. There were statistically significant variations in vaccine prevalence χ2(3) = 29.325, p < 0.001 among the three county areas. All levels of health literacy predicted overall county vaccination prevalence F (4,420) = 85.941, p < 0.001, There were significant differences in health literacy levels among two of the three county area pairs; the lowest resourced county area had the lowest vaccination prevalence and health literacy rates. This is the first example of relating direct health literacy measures across a major metropolitan US county with vaccine prevalence data.

The developments in targeted therapies and molecular pathology have changed the classification of tumors and precision oncology. Pathologists and clinical scientists in molecular pathology and oncologists have regular multidisciplinary meetings and are responsible for translating molecular results into an appropriate treatment plan. This requires expertise and skills to be effective team players. Interprofessional collaboration (IPC) is essential for professionals in medicine; however, learning opportunities in current resident training are limited. This narrative study explores the collaborative output and learning mechanisms of interprofessional learning (IPL) of residents of different disciplines in the Morphology & Molecular PLUS workshop and its preparation. Topics that were discussed in the workshop were technologies for the detection of mutations, copy number variations, tumor mutational burden, and circulating tumor DNA (ctDNA) analysis in the context of differential diagnosis and precision oncology. Data were collected by analyzing pre- and post-workshop questionnaires and interviews. An interprofessional team of three residents of each hospital had to be formed by one of the residents, which was challenging as not all residents from a hospital knew each other. Residents reported to have got to know each other and have learned about each other's roles and perspectives. They gained knowledge of molecular pathology and the added value of IPC, in particular, for residents early in their training. Enabling meetings for medical residents of different disciplines to get acquainted was perceived as the most facilitating factor for IPL. Time constraints as the biggest barrier in daily practice. We recommend offering IPL activities as early as possible in residency programs., Competing Interests: The authors report no conflicts of interest, no disclosures. The authors alone are responsible for the content and writing of this article., (© 2022 The Author(s).)

Background: The COVID-19 pandemic and efforts to mitigate transmission resulted in sudden and widespread socioeconomic disruptions including school and child care closures, unemployment and underemployment, and housing precarity. Understanding the extent to which these disruptions may have contributed to adverse health outcomes is critical for establishing policy priorities that can mitigate further harm., Methods: We explored the associations between pandemic-related child care, employment, and housing disruptions with depressive symptoms, self-rated health, and food security status among a sample of economically disadvantaged and racially diverse female caregivers of young children (n=464). Data were derived from the Assessing California Communities' Experiences with Safety Net Supports (ACCESS) study, which conducted survey-based interviews with California caregivers with low-income from August 2020 - May 2021. We implemented a series of multivariable Poisson regressions with robust standard errors to assess the potency of each exposure, independently and within the context of one another., Results: Most caregivers experienced disruptions to child care (70%) and employment (63%); few experienced major housing disruptions (8%). Women that experienced child care and housing disruptions had greater depressive symptoms, lower self-rated health, and greater food insecurity, although the relationships for housing and depressive symptoms were modified by the timing of participants' interviews. Employment disruptions were not associated with any of the examined adverse health outcomes., Conclusion: In the wake of socioeconomic stressors brought about by the COVID-19 pandemic, attending to structural deficits in the child care system and increasing housing supports may be critical for protecting the health of caregivers., (© 2022. The Author(s).)

Introduction: In 2020, the COVID-19 pandemic led to significant declines in cancer screening, including among women served by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). This study examined the spatial association between state-based COVID-19 test percent positivity and proportional change in NBCCEDP screening volume., Methods: Using the COVID-19 Diagnostic Laboratory Testing dataset, we calculated state-based monthly COVID-19 test percent positivity from July through December 2020 and categorized rates into low, medium, and high groups. We used data from 48 NBCCEDP state awardees to calculate the state-based monthly proportional change in screening volume and compared data for July-December 2020 with the previous 5-year average for those months. We categorized changes in screening volume into large decrease, medium decrease, and minimal change and created maps of the associations between variable subgroups by using bivariate mapping in QGIS., Results: Bivariate relationships between COVID-19 test percent positivity and proportional change in cancer screening volume varied over time and geography. In 5 of 6 months, 4 states had high COVID-19 test percent positivity and minimal change in breast or cervical cancer screening volume; 2 states had high COVID-19 test percent positivity and minimal change in breast and cervical cancer screening volume., Conclusion: Some states maintained pre-COVID-19 screening volumes despite high COVID-19 test percent positivity. Follow-up research will be conducted to determine how these states differ from those with consistent decreases in screening volume and identify factors that may have contributed to differences. This information could be useful for planning to maximize NBCCEDP awardees' ability to maintain screening volume during future public health emergencies.

Background: While the prevalence of undernutrition in children has decreased in many low- and middle-income countries since the 1990s, prevalences of overweight and obesity have increased. Frequent consumption of sugar-sweetened food might have contributed to this change, although very little is known about sugar-sweetened food consumption in early life., Objectives: The objective of this study was to explore the associations between individual, household, and maternal factors and the prevalence of sugar-sweetened food consumption in 6- to 24-month-old children in Bangladesh., Methods: Multistage sampling was used to select households with children aged 6-24 months in rural Chatmohar, a subdistrict of Bangladesh (n = 1635). Research assistants conducted a 24-hour qualitative dietary recall questionnaire with the enrolled child's primary caregiver to measure maternal and child dietary patterns. We examined factors associated with the prevalence of child sugar-sweetened food consumption with multivariate logistic regression models. We conducted tests of heterogeneity to explore differential associations between the child sugar-sweetened food consumption prevalence and household income by maternal nutrition knowledge and wealth., Results: Primary caregivers reported that 62% of toddlers had consumed sugar-sweetened food in the past 24 hours. A higher prevalence of child sugar-sweetened food consumption was associated with both a higher dietary diversity score (OR, 1.19; 95% CI, 1.09-1.29) and a higher prevalence of maternal sugar-sweetened food consumption (OR, 2.54; 95% CI, 1.97-3.28). At higher levels of maternal nutrition knowledge and wealth, more household income was associated with a lower prevalence of child sugar-sweetened food consumption., Conclusions: Almost two-thirds of 6- to 24-month-old children in rural Chatmohar, Bangladesh, had consumed sugar-sweetened food in the last day. This is a high and concerning prevalence, and the associated factors identified in this study should be investigated further to identify potential areas of intervention to decrease the prevalence of child sugar consumption in Bangladesh., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Pityriasis rubra pilaris is a papulosquamous inflammatory dermatosis that can be associated with HIV, autoimmunity, infections, certain medications, and neoplasms. Paraneoplastic pityriasis rubra pilaris has previously been reported in association with solid organ malignancies and once with leukemia. Herein, we present an elderly man with paraneoplastic pityriasis rubra pilaris, heralding the diagnosis of low-grade papillary urothelial carcinoma. Our patient's pityriasis rubra pilaris resolved after surgical resection of the tumor.

Background: Heyde syndrome is the co-occurrence of aortic stenosis and gastrointestinal bleeding secondary to angiodysplasias. Surgical aortic valve replacement effectively reduces bleeding, but the effects of transcatheter aortic valve implantation (TAVI) are largely unknown. This study aimed to describe the reduction of gastrointestinal bleeding in patients with Heyde syndrome after TAVI and to identify the factors associated with rebleeding., Methods: We enrolled patients with Heyde syndrome from a prospective TAVI registry. Gastrointestinal bleeding episodes were assessed by the Bleeding Academic Research Consortium classification, and cumulative incidence functions were used to calculate cessation rates. Factors potentially associated with rebleeding were analyzed using logistic regression. Differences between Heyde and non-Heyde patients were assessed through a case-cohort study., Results: Between December 2008 and June 2020, 1111 patients underwent TAVI. There were 70 patients with Heyde syndrome (6.3%). In the first year following TAVI, gastrointestinal bleeding ceased in 46 of 70 patients (62% [95% CI, 50%-74%]). Bleeding episodes decreased from 3.2 (95% CI, 2.5-4.2) to 1.6 ([95% CI, 1.2-2.2] P =0.001) and hemoglobin levels increased from 10.3 (95% CI, 10.0-10.8) to 11.3 (95% CI, 10.8-11.6) g/dL ( P =0.007). Between 1 and 5 years after TAVI (35 [interquartile range, 21-51] months), 53 of 62 patients (83% [95% CI, 72%-92%]) no longer experienced gastrointestinal bleeding. Paravalvular leakage (≥mild) was associated with rebleeding risk (odds ratio, 3.65 [95% CI, 1.36-9.80]; P =0.010). Periprocedural bleeding was more common in Heyde than in control patients (adjusted odds ratio, 2.55 [95% CI, 1.37-4.73]; P =0.003)., Conclusions: Patients with Heyde syndrome are at increased risk for periprocedural bleeding. Post-TAVI, gastrointestinal bleeding disappears in the majority of patients. Paravalvular leakage may curtail these clinical benefits.

Evidence on the role of father involvement in children's development from low-resource settings is very limited and historically has only relied on maternal reports of father's direct engagement activities such as reading to the child. However, fathers can also potentially influence their children's development via greater positive involvement with the mother, such as by offering interpersonal support or sharing decision-making duties. Such positive intrahousehold interactions can benefit maternal mental health and wellbeing, and ultimately children's development. We use data collected from mothers, fathers and children in the context of the cluster randomized controlled trial evaluation of Msingi Bora, a responsive parenting intervention implemented across 60 villages in rural western Kenya, to explore the various pathways through which fathers may influence their children's outcomes. In an endline survey in Fall 2019 among a sample of 681 two-parent households with children aged 16-34 months, fathers reported on measures of their behaviors towards children and with mothers, mothers reported on their wellbeing and behaviors, and interviewers assessed child cognitive and language development with the Bayley Scales. In adjusted multivariate regression analyses we found that greater father interpersonal support to mothers and greater participation in shared household decision-making were positively associated with children's development. These associations were partially mediated through maternal wellbeing and behaviors. We found no association between fathers' direct engagement in stimulation activities with children and children's outcomes. Inviting fathers to the program had no impact on their involvement or on any maternal or child outcomes, and fathers attended sessions at low rates. Overall, our results show the potential promises and challenges of involving fathers in a parenting intervention in a rural low-resource setting. Our findings do highlight the importance of considering intrahousehold pathways of influence in the design of parenting interventions involving fathers., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction : Limited data exists on the safety and efficacy of direct-acting oral anticoagulants (DOAC) use in morbidly obese patients with venous thromboembolism (VTE). Given the benefits of DOAC use over vitamin K antagonists (VKAs), in terms of monitoring requirements, and dietary and drug interactions, it is important to evaluate whether this is consistent in the higher risk for VTE recurrence morbidly obese group body mass index (BMI ≥ 40 kg/m 2 ). Materials and methods : This retrospective, single-center cohort study included patients with a BMI of at least 40 kg/m 2 who were admitted to Emory University Hospital from 1 st January 2012 to 31 st May 2020 with acute VTE, and subsequently initiated on anticoagulation treatment with either DOAC or VKA (warfarin). Univariate and bivariate analyses were used to evaluate differences in demographics by treatment type and BMI. Multivariate Cox proportional hazard regression was used to assess the risk of VTE recurrence by type of treatment among morbidly obese patient subgroup. Results : There were 247 (11.8%) morbidly obese (≥ 40 kg/m 2 ) patients who were more likely than non-obese patients to be younger, female, and of non-white race. Thirty percent of the study population (n=74) had a BMI >50 kg/m 2 . T ime-to-event analysis confirmed that the hazard of experiencing a recurrent thrombosis was not statistically significantly different among morbidly obese patients treated with a DOAC compared with VKA (hazard ratio [HR]: 0.28, confidence interval [CI] 0.07-1.11, p  = 0.07). Conclusions : This study aligns with previous literature and confirms that morbidly obese patients receiving DOAC or VKA have similar risks of recurrent VTE., Competing Interests: The authors declare no conflicts of interest. No funding was received in support of this study., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

The COVID-19 pandemic prompted rapid and innovative policymaking around the world at the national, regional, and local levels. There has been limited work to systematically document and characterize new and expanded local U.S. pandemic-era policies, which is imperative to better understand the policy variation and resulting health impacts during this unprecedented time. California, the most populous U.S. state, provides a case example of a particularly active policy response. The aim of this Brief Report is to summarize the creation and potential areas of application of a newly created publicly available California- and US-based COVID-19 policy database. We generated an extensive list of California and US policies that were modified or created in response to the COVID-19 pandemic. From July-November 2021, we searched current and historical California and federal government websites, press releases, social media, and news sources and recorded detailed information on these policies, including coverage dates, eligibility criteria, and benefit amounts. This comprehensive dataset includes 39 public health, economic, housing, and safety net programs and policies implemented at both federal and state levels and provides details of the complex and multifaceted policy landscape in California from March 2020 to November 2021. Our database is publicly available. Future investigators can leverage the information systematically recorded in this database to rigorously assess the short- and long-term effects of these policies, which will in turn inform future preparedness response plans in California and beyond.

Background: Hundreds of millions of children living in poverty worldwide are not reaching their full, developmental potential. Programs to promote nurturing and responsive caregiving, such as those in which community health workers (CHWs) conduct home visits to support optimal early childhood development (ECD), have been effective in small trials, but have not achieved similar success at scale. This study will explore two approaches to scale-up: converting a home-visiting model to a group-based model; and integrating the ECD curriculum into an existing government program. The objectives of the study are to: 1) Measure how the integration of ECD activities affects time and task allocation of CHWs and CHW psychosocial wellbeing; 2) Examine how the integration of ECD activities affects caregiver-child dyad participation in standard health and nutrition activities; and 3) Explore how the availability of age-appropriate play materials at home affects caregiver-child dyad participation rates in a group-based ECD program., Methods: We will randomize 75 communities in rural Madagascar into three arms: 1) [C], which is the status quo (community-based health and nutrition program); 2) [T], which is C + ECD group sessions [T]; and 3) [T +], which is T with the addition of an enhanced play materials package for home use. All children between 6-30 months old at the time of the intervention launch will be eligible to participate in group activities. The intervention will last 12 months and is comprised of fortnightly group sessions in which the CHWs provide caregiver-child dyads with information relating to ECD; CHWs will also include structured time for caregivers to practice the play and child stimulation activities they have learned. We will administer monthly surveys to measure CHW time use and task allocation, and we will leverage administrative data to measure caregiver-child dyad participation in the group sessions., Discussion: The results from the trial will provide the evidence base required to implement an integrated package of nutrition, health and ECD promotion activities at scale in Madagascar, and findings may be relevant in other low-income countries., Trial Registration: This trial is registered on the AEA Social Science Registry (AEARCTR-0004704) on November 15, 2019 and on ClinicalTrials.gov (NCT05129696) on November 22, 2021., (© 2022. The Author(s).)

The flagellum of Trypanosomatids is an organelle that contributes to multiple functions, including motility, cell division, and host-pathogen interaction. Trypanin was first described in Trypanosoma brucei and is part of the dynein regulatory complex. Tb Trypanin knockdown parasites showed motility defects in procyclic forms; however, silencing in bloodstream forms was lethal. Since Tb Trypanin mutants show drastic phenotypic changes in mammalian stages, we decided to evaluate if the Trypanosoma cru zi ortholog plays a similar role by using the CRISPR-Cas9 system to generate null mutants. A ribonucleoprotein complex of SaCas9 and sgRNA plus donor oligonucleotide were used to edit both alleles of Tc Trypanin without any selectable marker. Tc Trypanin -/- epimastigotes showed a lower growth rate, partially detached flagella, normal numbers of nuclei and kinetoplasts, and motility defects such as reduced displacement and speed and increased tumbling propensity. The epimastigote mutant also showed decreased efficiency of in-vitro metacyclogenesis. Mutant parasites were able to complete the entire life cycle in vitro ; however, they showed a reduction in their infection capacity compared with WT and addback cultures. Our data show that T. cruzi life cycle stages have differing sensitivities to Tc Trypanin deletion. In conclusion, additional work is needed to dissect the motility components of T. cruzi and to identify essential molecules for mammalian stages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saenz-Garcia, Borges, Souza-Melo, Machado, Miranda, Pacheco-Lugo, Moretti, Wheleer, Soares Medeiros and DaRocha.)

Delayed medical care is a negative consequence of the COVID-19 pandemic for families with young children. Our study used data from the Accessing California Communities' Experiences with Safety net Supports (ACCESS) survey, a cross-sectional study that assessed experiences with safety-net programs among working families with low incomes (n=491). From August 2020 to May 2021, we conducted interviewer-administered surveys of low-income families with young children (ages zero to eight) in California and asked questions about whether participants had delayed medical care for their children or themselves. We found that delaying care for children was associated with lack of childcare and with the child having pre-existing conditions. Delaying parental medical care was associated with lack of childcare, experiences of racism, government mistrust, and perceptions of welfare stigma. These results suggest that health care access may be improved through a focus on supporting childcare systems and addressing structural racism.

In the last decade, unprecedented arrivals of pelagic Sargassum (Sargassum influx) have been reported for the Caribbean coasts causing severe ecological and economical affectations and remarking the necessity to characterize the phenomenon. In the north coast of the Mexican Caribbean, spatial characterization of Sargassum influx was performed in terms of its abundance, species composition and chemical content using a combination of in situ sampling and remote sensing evaluations. Sargassum influx was detected within the 25 km fringe near to Quintana Roo coast in coincidence with beach-cast events during September 2018. Significant spatial variation in abundance and species composition of the stranded biomass was found for the six localities studied, which was related to the local environmental conditions. Pelagic species of Sargassum were the main component ranging from 78.1 to 99.6% of the total beach-cast (wrack) fresh biomass, whereas benthic macrophytes (seagrasses and macroalgae) were a minor component reaching up to 21% in some localities. The biochemical composition of beach-cast Sargassum resulted spatially homogeneous for most of the components analyzed; only carbon tissue content, ash metals (particularly Fe and As) and isotopic composition changed spatially. This study represents baseline information for the region. Long-term seasonal evaluations of Sargassum influx along Mexican Caribbean are required to define adequate management strategies and exploitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design., Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers., Results: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics., Conclusions: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design., Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons., Results: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation., Conclusions: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development., Objectives: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024)., Results: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11)., Conclusions: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy., Methods: We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie, <10 participants), studies in which patients had a specific aetiology of gastrointestinal angiodysplasias, and studies in which somatostatin analogue therapy was initiated simultaneously with other treatment modalities. Authors of eligible studies were invited to share individual patient data. Aggregated data was used if individual patient data were not provided. The primary outcome was the mean reduction in the number of red blood cell transfusions during somatostatin analogue therapy, compared with baseline, expressed as the incidence rate ratio (IRR) and absolute mean decrease. We defined patients as either good responders (≥50% reduction in the number of red blood cell transfusions) or poor responders (<50% reduction). A mixed-effects negative binomial regression was used to account for clustering of patients and skewness in data. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020213985., Findings: We identified 11 eligible studies (one randomised controlled trial and ten cohort studies) of moderate-to-high quality and obtained individual patient data from the authors of nine (82%) studies. The remaining two (18%) studies provided sufficient information in the published manuscript to extract individual patient data. In total, we analysed data from 212 patients. Somatostatin analogues reduced the number of red blood cell transfusions with an IRR of 0·18 (95% CI 0·14-0·24; p<0·0001) during a median treatment duration of 12 months (IQR 6·0-12·0) and follow-up period of 12 months (12·0-12·0), correlating with a mean absolute decrease in the number of red blood cell transfusions from 12·8 (95% CI 10·4-15·8) during baseline to 2·3 (1·9-2·9) during follow-up-ie, a reduction of 10·5 red blood cell transfusions (p<0·0001). 177 (83%) of 212 patients had a good response to somatostatin analogue therapy (defined as at least a 50% reduction in the number of red blood cell transfusions). Heterogeneity across studies was moderate (I 2 =53%; p=0·02). Location of gastrointestinal angiodysplasias in the stomach compared with angiodysplasias in the small bowel and colon (IRR interaction 1·92 [95% CI 1·13-3·26]; p=0·02) was associated with worse treatment response. Octreotide was associated with a better treatment response than lanreotide therapy (IRR interaction 2·13 [95% CI 1·12-4·04]; p=0·02). The certainty of evidence was high for the randomised controlled trial and low for the ten cohort studies. Adverse events occurred in 38 (18%) of 212 patients receiving somatostatin analogue therapy, with ten (5%) discontinuing this therapy because of adverse events. The most common adverse events were loose stools (seven [3%] of 212), cholelithiasis (five [2%]), flatulence (four [2%]), and administration site reactions (erythema, five [2%])., Interpretation: Somatostatin analogue therapy is safe and effective in most patients with red blood cell transfusion-dependent bleeding due to gastrointestinal angiodysplasias. Somatostatin analogue therapy is more effective in patients with angiodysplasias located in the small bowel and colon, and octreotide therapy seems to be more effective than lanreotide therapy., Funding: The Netherlands Organisation for Health Research and Development and the Radboud University Medical Center., Competing Interests: Declaration of interests GH has received research funding from Health Research Board Ireland. JPHD has received research funding from Gilead to support hepatitis C elimination in the Netherlands. EJMvG has received research funding from Mylan, Boston Scientific, and Olympus; and served as a consultant for MTW-Endoskopie. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Early child development has been influenced directly and indirectly by the COVID-19 pandemic, and these effects are exacerbated in contexts of poverty. This study estimates effects of the pandemic and subsequent population lockdowns on mental health, caregiving practices, and freedom of movement among female caregivers of children 6-27 months (50% female), in rural Bangladesh. A cohort (N = 517) was assessed before and during the pandemic (May-June, 2019 and July-September, 2020). Caregivers who experienced more food insecurity and financial loss during the pandemic reported larger increases in depressive symptoms (0.26 SD, 95% CI 0.08-0.44; 0.21 SD, 0.04-0.40) compared to less affected caregivers. Stimulating caregiving and freedom of movement results were inconsistent. Increases in depressive symptoms during the pandemic may have consequences for child development., (© 2021 The Authors. Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas., (Copyright © 2021 Elsevier B.V. All rights reserved.)