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The mechanisms underlying the relationship between health literacy, numeracy, and glycemic control are unclear. We explored the role of diabetes self-efficacy in the predicted pathway linking health literacy and numeracy to glycemic control (A1C). Adults with type 1 or type 2 diabetes mellitus (N = 383) were enrolled in a cross-sectional study at primary care and diabetes clinics at three medical centers. Data collected included demographic information, health literacy, general numeracy, and A1C. Path models estimated relations among health literacy, numeracy, and diabetes self-efficacy as predictors of A1C. Health literacy (r = 0.14, p < .01) and numeracy (r = 0.17, p < .001) were each associated with greater diabetes self-efficacy, and greater diabetes self-efficacy was associated with lower A1C levels (r = -0.25, p < .001). When considered in combination, numeracy was related to diabetes self-efficacy (r = 0.13, p < .05), and the effect of health literacy on diabetes self-efficacy was reduced to non-significance (r = 0.06, p = .30). Health literacy and numeracy are each associated with greater diabetes self-efficacy, and greater diabetes self-efficacy is associated with lower A1C levels. Diabetes self-efficacy may be an important target of interventions to improve diabetes control and promote health equity related to health literacy and general numeracy skills needed for diabetes management. [ABSTRACT FROM AUTHOR]

Depression and low self-efficacy are both associated with worse glycemic control in adults with diabetes, but the relationship between these variables is poorly understood. We conducted a cross-sectional study examining associations between depressive symptoms, self-efficacy, and glycemic control among men ( n = 64) and women ( n = 98) with type 2 diabetes to see if self-efficacy mediates the relationship between depression and glycemic control. Correlational and mediational analyses examined the relationship between these three variables for the sample as a whole and separately by sex. A significant association between depressive symptoms and glycemic control was found for men (0.34, P < 0.01) but not for women (0.05, P = 0.59). Path analysis suggested that, among men, self-efficacy mediates the relationship between depressive symptoms and glycemic control. We conclude that men with depressive symptoms and type 2 diabetes may need tailored interventions that improve their self-efficacy in order to achieve glycemic control. [ABSTRACT FROM AUTHOR]

Objective: Diabetic patients with lower literacy or numeracy skills are at greater risk for poor diabetes outcomes. This study evaluated the impact of providing literacy- and numeracy-sensitive diabetes care within an enhanced diabetes care program on A1C and other diabetes outcomes.Research Design and Methods: In two randomized controlled trials, we enrolled 198 adult diabetic patients with most recent A1C >or=7.0%, referred for participation in an enhanced diabetes care program. For 3 months, control patients received care from existing enhanced diabetes care programs, whereas intervention patients received enhanced programs that also addressed literacy and numeracy at each institution. Intervention providers received health communication training and used the interactive Diabetes Literacy and Numeracy Education Toolkit with patients. A1C was measured at 3 and 6 months follow-up. Secondary outcomes included self-efficacy, self-management behaviors, and treatment satisfaction.Results: At 3 months, both intervention and control patients had significant improvements in A1C from baseline (intervention -1.50 [95% CI -1.80 to -1.02]; control -0.80 [-1.10 to -0.30]). In adjusted analysis, there was greater improvement in A1C in the intervention group than in the control group (P = 0.03). At 6 months, there were no differences in A1C between intervention and control groups. Self-efficacy improved from baseline for both groups. No significant differences were found for self-management behaviors or satisfaction.Conclusions: A literacy- and numeracy-focused diabetes care program modestly improved self-efficacy and glycemic control compared with standard enhanced diabetes care, but the difference attenuated after conclusion of the intervention. [ABSTRACT FROM AUTHOR]

Objective: Understanding the reasons and eliminating the pervasive health disparities in diabetes is a major research, clinical, and health policy goal. We examined whether health literacy, general numeracy, and diabetes-related numeracy explain the association between African American race and poor glycemic control (A1C) in patients with diabetes.Research Design and Methods: Adults with type 2 diabetes (n = 383) were enrolled in a cross-sectional study at primary care and diabetes clinics at three medical centers. Data collected included the following: self-reported race, health literacy, general numeracy, diabetes-related numeracy, A1C, and sociodemographic factors. A series of structural equation models were estimated to explore the interrelations between variables and test for mediation.Results: In model 1, younger age (r = -0.21, P < 0.001), insulin use (r = 0.27, P < 0.001), greater years with diabetes (r = 0.16, P < 0.01), and African American race (r = 0.12, P < 0.01) were all associated with poorer glycemic control. In model 2, diabetes-related numeracy emerged as a strong predictor of A1C (r = -0.46, P < 0.001), reducing the association between African American and poor glycemic control to nonsignificance (r = 0.10, NS). In model 3, African American race and older age were associated with lower diabetes-related numeracy; younger age, insulin use, more years with diabetes, and lower diabetes-related numeracy were associated with poor glycemic control.Conclusions: Diabetes-related numeracy reduced the explanatory power of African American race, such that low diabetes-related numeracy, not African American race, was significantly related to poor glycemic control. Interventions that address numeracy could help to reduce racial disparities in diabetes. [ABSTRACT FROM AUTHOR]

PURPOSE: Diabetes self-management education is an important component of comprehensive diabetes care. Patients with low health literacy and numeracy may have difficulty translating information from traditional diabetes educational programs and materials into effective self-care. METHODS: To address this potential barrier to successful diabetes teaching and counseling, the authors developed the Diabetes Literacy and Numeracy Education Toolkit (DLNET). CONCLUSION: The DLNET is composed of 24 interactive modules covering standard diabetes care topics that can be customized to individual patient needs and used by all members of the multidisciplinary diabetes care team. The material's content and formatting aims to improve the ease of use for diabetes patients with low literacy and numeracy by adhering to a lower text reading level, using illustrations for key concepts, and color-coding and other accommodations to guide patients through instructions for self-care. Individual sections of the DLNET may be provided to patients for initial teaching, as well as for reinforcement. Although designed for lower literacy and numeracy skills, the DLNET provides unique materials to facilitate diabetes education for all patients. [ABSTRACT FROM AUTHOR]

Patients with chronic medical conditions such as diabetes mellitus need to self-manage their condition for optimal outcomes. The degree to which patients with diabetes feel competent or self-efficacious in managing their diabetes has been related to behaviors such as dieting or exercise as well as to indicators of glycemic control. A diabetes-specific adaptation of the Perceived Medical-Condition Self-Management Scale was administered to 398 patients with either type 1 (n=57) or type 2 (n=341) diabetes. Cronbach's alpha of the 8-item Perceived Diabetes Self-Management Scale (PDSMS) was .83 indicating internal consistency. PDSMS scores were uncorrelated with age, years since diagnosis, and years of schooling, but were negatively correlated with body mass index. Those with type 1 DM had higher PDSMS scores than those with type 2 DM. PDSMS scores were positively correlated with a number of self-reported self-care activities and negatively related to measures of glycemic control. The PDSMS is a valid measure of diabetes self-efficacy, and the more generic template from which it was adapted can easily be altered for use with other chronic medical conditions. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic illness that affects the world on an epidemic scale. It requires complex healthcare and considerable economic resources. Diabetes disease management programs use a variety of strategies to improve clinical outcome measures and reduce costs. Studies have demonstrated the effectiveness of these programs on reducing glycosylated hemoglobin levels, improving cardiovascular risks, and reducing utilization of services. However, the most effective components of disease management strategies or combination of strategies remain unknown. This narrative review explores the components, impact, benefits, and barriers of current diabetes disease management models and also presents a novel hybrid model incorporating elements of both on-site and off-site programs.On-site disease management programs include strategies characterized by unique patient identification and evaluation, implementation of intervention methods, on-site health provider team members, and specific environmental resources. Advantages of this model include the face-to-face encounter between patients and providers, the proximity of the healthcare team members to facilitate ease of communication and build independence and trust between patients and providers, and technology resources, such as the electronic medical record. A number of clinical trials have demonstrated the effectiveness and cost effectiveness of on-site diabetes disease management programs. However, because of the methodological limitations of many studies, further studies are needed to confirm such findings. Barriers to the implementation of on-site programs may include patient population characteristics such as complexity of co-morbid illness and social stressors, including low health literacy, that require adaptation of the disease management model. In comparison, off-site disease management programs utilize administrative resources to identify patients with chronic illnesses. Other key elements include the evaluation of clinical care practices using established guidelines with auditing and feedback to providers based on their performance, and the use of reminders for both patients and providers to influence better processes of care. This process is often independent of the traditional on-site care delivered directly by providers.A hybrid disease management model that incorporates both on-site and off-site disease management components could be the ideal model for optimizing care of patients with chronic illness. The suggested hybrid model incorporates many features of previous models of disease management but gives a new construct that can be customized to different clinic settings, provider practices, and patient populations, including patients with other complex chronic illness. This hybrid model could be applied to a variety of individual or multiple chronic illnesses. This model would engage both on-site healthcare providers and support staff along with off-site administrative staff and electronic medical data to provide patients optimal care while potentially reducing overall costs. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of this study was to develop and validate a new knowledge scale for patients with type 2 diabetes and poor literacy: the Spoken Knowledge in Low Literacy patients with Diabetes (SKILLD). METHODS: The authors evaluated the 10-item SKILLD among 217 patients with type 2 diabetes and poor glycemic control at an academic general medicine clinic. Internal reliability was measured using the Kuder-Richardson coefficient. Performance on the SKILLD was compared to patient socioeconomic status, literacy level, duration of diabetes, and glycated hemoglobin (A1C). RESULTS: Respondents' mean age was 55 years, and they had diabetes for an average of 8.4 years; 38% had less than a sixth-grade literacy level. The average score on the SKILLD was 49%. Less than one third of patients knew the signs of hypoglycemia or the normal fasting blood glucose range. The internal reliability of the SKILLD was good (0.72). Higher performance on the SKILLD was significantly correlated with higher income (r = 0.22), education level (r = 0.36), literacy status (r = 0.33), duration of diabetes (r = 0.30), and lower A1C (r = -0.16). When dichotomized, patients with low SKILLD scores (< or = 50%) had significantly higher A1C (11.2% vs 10.3%, P < .01). This difference remained significant when adjusted for covariates. CONCLUSION: The SKILLD demonstrated good internal consistency and validity. It revealed significant knowledge deficits and was associated with glycemic control. The SKILLD represents a practical scale for patients with diabetes and low literacy. [ABSTRACT FROM AUTHOR]

Context: Low literacy is an important barrier for patients with diabetes, but interventions to address low literacy have not been well examined.Objective: To examine the role of literacy on the effectiveness of a comprehensive disease management program for patients with diabetes.Design, Setting, and Participants: Analysis of the influence of literacy on glycemic control and systolic blood pressure using data from a randomized controlled trial (conducted from February 2001 through April 2003) of a comprehensive diabetes management program. Participants were 217 patients aged 18 years or older with type 2 diabetes and poor glycemic control (glycosylated hemoglobin [HbA1c] levels > or =8.0%) and presenting to a US academic general internal medicine practice.Interventions: All communication to patients was individualized and delivered to enhance comprehension among patients with low literacy. Intervention patients received intensive disease management from a multidisciplinary team. Control patients received an initial management session and continued with usual care.Main Outcome Measures: Achievement of goal HbA1c levels and systolic blood pressure at 12-month follow-up for control and intervention patients stratified by literacy status.Results: Complete 12-month data were available for 193 patients (89%). Among patients with low literacy, intervention patients were more likely than control patients to achieve goal HbA1c levels (< or =7.0%) (42% vs 15%, respectively; adjusted odds ratio [OR], 4.6; 95% confidence interval [CI], 1.3 to 17.2; P = .02). Patients with higher literacy had similar odds of achieving goal HbA1c levels regardless of intervention status (24% vs 23%; adjusted OR, 1.0; 95% CI, 0.4 to 2.5; P = .98). Improvements in systolic blood pressure were similar by literacy status.Conclusions: Literacy may be an important factor for predicting who will benefit from an intervention for diabetes management. A diabetes disease management program that addresses literacy may be particularly beneficial for patients with low literacy, and increasing access to such a program could help reduce health disparities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Type 2 diabetes is a growing problem among adolescents, but little is known about self-management behaviors in this population. Our aim was to examine self-management behaviors and glycemic control among adolescents with type 2 diabetes. METHODS: From 2003 to 2005, a telephone survey of adolescents with type 2 diabetes was performed. Chart review obtained most recent glycated hemoglobin and clinical characteristics. Analyses compared patient characteristics and self-management behaviors to recent glycated hemoglobin levels. RESULTS: Of 139 patients contacted, 103 (74%) completed the study. The mean age was 15.4 years: 69% were girls, 47% were white, and 46% were black. Mean glycated hemoglobin was 7.7%, and the average duration of diabetes was 2.0 years. More than 80% of patients reported > or = 75% medication compliance, and 59% monitored blood glucose > 2 times daily. However, patients reported frequent episodes of overeating, drinking sugary drinks, and eating fast food. More than 70% of patients reported exercising > or = 2 times a week, but 68% reported watching > or = 2 hours of television daily. Nonwhite patients had higher glycated hemoglobin and hospitalizations per year compared with white patients. In multivariable analyses, nonwhite race remained significantly associated with higher glycated hemoglobin even after adjusting for age, gender, BMI, insurance status, and other factors. Nonwhite patients were more likely to watch > or = 2 hours of television per day (78% vs 56%), to report exercising < or = 1 time per week (35% vs 21%), and to drink > or = 1 sugary drink daily (27% vs 13%). CONCLUSION: Although patients reported good medication and monitoring adherence, they also reported poor diet and exercise habits and multiple barriers. Nonwhite race was significantly associated with poorer glycemic control even after adjusting for covariates. This may, in part, be related to disparities in lifestyle behaviors. Additional studies are indicated to further assess self-management behaviors and potential racial disparities in adolescents with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Smoking after a cancer diagnosis shortens survival time, increases risk of recurrence and the development of another primary tumor, reduces treatment efficacy, and increases treatment complications. Nevertheless, many patients who smoked prior to their illness continue to smoke after diagnosis and treatment. The development of effective smoking cessation interventions for cancer patients has been slowed by the lack of data concerning psychological correlates of smoking in this population. This study, with 74 cancer patients, showed that smoking and lower readiness to quit was associated with: having relatives at home who smoke, a longer time between diagnosis and assessment, completion of medical treatment, greater nicotine dependence, lower self-efficacy, quitting pros, and risk perceptions, and higher quitting cons, fatalistic beliefs, and emotional distress. Thus, smoking cessation treatments for cancer patients should include pharmacotherapy, relapse prevention, and counseling designed to facilitate self-efficacy, quitting pros, and risk awareness and to reduce the quitting cons, fatalism, and distress. [ABSTRACT FROM AUTHOR]

Importance: Infant growth predicts long-term obesity and cardiovascular disease. Previous interventions designed to prevent obesity in the first 2 years of life have been largely unsuccessful. Obesity prevalence is high among traditional racial and ethnic minority groups., Objective: To compare the effectiveness of adding a digital childhood obesity prevention intervention to health behavior counseling delivered by pediatric primary care clinicians., Design, Setting, and Participants: Individually randomized, parallel-group trial conducted at 6 US medical centers and enrolling patients shortly after birth. To be eligible, parents spoke English or Spanish, and children were born after 34 weeks' gestational age. Study enrollment occurred between October 2019 and January 2022, with follow-up through January 2024., Interventions: In the clinic-based health behavior counseling (clinic-only) group, pediatric clinicians used health literacy-informed booklets at well-child visits to promote healthy behaviors (n = 451). In the clinic + digital intervention group, families also received health literacy-informed, individually tailored, responsive text messages to support health behavior goals and a web-based dashboard (n = 449)., Main Outcomes and Measures: The primary outcome was child weight-for-length trajectory over 24 months. Secondary outcomes included weight-for-length z score, body mass index (BMI) z score, and the percentage of children with overweight or obesity., Results: Of 900 randomized children, 86.3% had primary outcome data at the 24-month follow-up time point; 143 (15.9%) were Black, non-Hispanic; 405 (45.0%) were Hispanic; 185 (20.6%) were White, non-Hispanic; and 165 (18.3%) identified as other or multiple races and ethnicities. Children in the clinic + digital intervention group had a lower mean weight-for-length trajectory, with an estimated reduction of 0.33 kg/m (95% CI, 0.09 to 0.57) at 24 months. There was also an adjusted mean difference of -0.19 (95% CI, -0.37 to -0.02) for weight-for-length z score and -0.19 (95% CI, -0.36 to -0.01) for BMI z score. At age 24 months, 23.2% of the clinic + digital intervention group compared with 24.5% of the clinic-only group had overweight or obesity (adjusted risk ratio, 0.91 [95% CI, 0.70 to 1.17]) based on the Centers for Disease Control and Prevention criteria of BMI 85th percentile or greater. At that age, 7.4% of the clinic + digital intervention group compared with 12.7% of the clinic-only group had obesity (adjusted risk ratio, 0.56 [95% CI, 0.36 to 0.88])., Conclusions and Relevance: A health literacy-informed digital intervention improved child weight-for-length trajectory across the first 24 months of life and reduced childhood obesity at 24 months. The intervention was effective in a racially and ethnically diverse population that included groups at elevated risk for childhood obesity., Trial Registration: ClinicalTrials.gov Identifier: NCT04042467.

Objective: To examine the association between social capital and household food insecurity among US families with newborns., Study Design: This cross-sectional analysis used enrollment data from 881 newborn-caregiver dyads at 6 geographically-diverse US academic sites enrolled in the Greenlight Plus Trial, a comparative effectiveness trial to prevent childhood obesity. Ordinal proportional-odds models were used to characterize the associations of 2 self-reported measures of social capital: (1) caregiver social support and (2) neighborhood social cohesion, with household food insecurity after controlling for sociodemographic characteristics., Results: Among 881 newborn-caregiver dyads (49% Hispanic, 23% non-Hispanic White, 17% non-Hispanic Black; 49% with annual household income <$50 000), food security was high for 75%, marginal for 9%, low for 11% and very low for 4%. In covariate-adjusted analyses, caregivers with a low social support score of 18 had 5 times the odds (aOR = 5.03 95% CI = 3.28-7.74) of greater food insecurity compared with caregivers with a high social support score of 30. Caregivers with a low neighborhood social cohesion score of 10 had nearly 3 times the odds (aOR = 2.87 95% CI 1.61-5.11) of greater food insecurity compared with caregivers with a high neighborhood social cohesion score of 20. These associations remained robust when both social capital measures were included in one model., Conclusions: Caregiver social support and neighborhood social cohesion each appear to be inversely associated with food insecurity among US families with newborns. Longitudinal research is needed to determine the directionality of these relationships and whether improving social capital for families with young children reduces household food insecurity., Competing Interests: Declaration of Competing Interest This secondary analysis utilized data from the Greenlight Plus Trial which was supported by the Patient Centered Outcomes Research Institute (PCORI) [contract number AD-2018C1-11238]. Study data were collected and managed using REDCap electronic data capture tools hosted by Vanderbilt University Medical Center and supported by NCATS/NIH grant number: UL1 TR000445. The funders of the Greenlight Plus Trial, PCORI, and NCATS/NIH, had no role in the design and conduct of the study, collection and analysis of the data, preparation of the manuscript, or the decision to submit the manuscript for publication. J. O. L. is a postdoctoral fellow supported by NIH-NIDDKT32DK062707 grant. K. B. F. previously reviewed abstracts for Patient Centered Outcomes Research Institute funded studies unrelated to this study. L. M. S. reported serving as a paid advisor to Medeloop.ai, an artificial intelligence-driven platform that supports clinical research, but this activity was unrelated to this study. The authors have no other conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVID-19 trials. The paper adopts a descriptive approach, eschewing analysis of data-driven efficacy of these efforts, and instead provides a comprehensive account of strategies utilized. The Accelerate COVID-19 Treatment Interventions and Vaccines (ACTIV) public-private partnership launched early in the COVID-19 pandemic to develop clinical trials to advance SARS-CoV-2 treatments. In this paper, ACTIV investigators share challenges in conducting research during an evolving pandemic and approaches selected to engage communities when traditional strategies were infeasible. Lessons from this experience include importance of community representatives' involvement early in study design and implementation and integration of well-developed public outreach and communication strategies with trial launch. Centralization and coordination of outreach will allow for efficient use of resources and the sharing of best practices. Insights gleaned from the ACTIV program, as outlined in this paper, shed light on effective strategies for involving communities in treatment trials amidst rapidly evolving public health emergencies. This underscores critical importance of community engagement initiatives well in advance of the pandemic., Competing Interests: None., (© The Author(s) 2024.)

Type 2 Diabetes (T2D) is a chronic multifaceted metabolic condition characterized by elevated blood glucose levels with varying degrees of insulin resistance and abnormal insulin production. Lifestyle modifications, such as those defined by the guidelines for diabetes self-management education and support (DSMES), are foundational for glycemic control. A current gap in T2D management is addressing DSMES which is tailored to best serve the diversity of patients with this disease. The purpose of this narrative review is to discuss the current literature related to lifestyle modification for T2D, the importance of culturally sensitive T2D management programs, and the impact culturally sensitive and diverse T2D management programs have on cardiometabolic health. Despite being disproportionately affected by T2D, racial and ethnic minorities have low referral rates for DSMES. This growing disparity may be exacerbated by a lack of awareness of how to adapt lifestyle modifications in a culturally competent manner and how social determinants of health (SDOH) may affect the infrastructure and resources available to diverse patient populations. Currently, there is limited research on how DSMES is addressed to include culturally and literacy-sensitive recommendations in the United States. Patient-centered care, emphasizing personalized DSMES, can lead to improved glycemic control, reduced healthcare costs, and improved cardiometabolic health. A key component of effective DSMES should include culturally and literacy-sensitive approaches with an awareness of the impact of SDOH. Understanding how ethnicity, race, and culture influence experiences with T2D management can help providers prescribe more patient-centered and sustainable recommendations.

Background: The relative contributions of common patient-reported social determinants of health on 30- and 90-day post-discharge outcomes among patients with acute coronary syndromes (ACS) is unclear., Objective: The aim of this article is to examine the independent associations of social determinants with readmission or death, accounting for medical history., Methods: Participants included adults who were hospitalized with ACS at an academic medical center. Domains measured were social support, health literacy/numeracy, and socioeconomic status (SES) (including education and difficulty paying bills). We employed multivariable Cox proportional hazard models to study associations with time to all-cause readmission or death, up to 30 or 90 days after discharge, and adjusted for demographics and medical history (prior admissions and Elixhauser comorbidity index)., Key Results: Among 1,168 patients with ACS and no history of heart failure, more prior admissions, and higher comorbidity index (the medical history domain) were associated with higher rates of 30- and 90-day readmission or death (domain p values <.01 and <.0001, respectively). The social support domain was not associated with outcomes. Higher health literacy and numeracy were associated with lower rates of 30- and 90-day readmission or death (domain p values .016 and .002, respectively). Higher education and less difficulty paying bills (the SES domain) was marginally associated with lower rates of 90-day readmission or death (domain, p = .052)., Conclusions: In addition to medical history, the domain of health literacy and numeracy was independently associated with readmission or death of patients with ACS during the 90 days after hospital discharge. [ HLRP: Health Literacy Research and Practice . 2024;8(4):e212-e223. ]., Competing Interests: Disclosure: ASM has served as a data safety and monitoring board member for the Clinical Science Research and Development Veterans Affairs Merit Grant: Personalizing Veteran Lung Cancer Screening and Diagnosis. RLR has received support for travel through the Engel Research Award from the Academy for Communication in Healthcare; and has received grants from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, Duke Clinical Research Institute/Novartis, Centers for Disease Control and Prevention Global Health Foundation, Centers for Medicare and Medicaid Services/Center for Medicare and Medicaid Innovation, paid to the institution. EEV has received grants from the National Heart, Lung, and Blood Institute and National Institute of Nursing Research (UG3HL165740), and the National Institutes of Health/National Institute on Aging (R01-AG065249), and served on a COVID-19 Advisory Board for Gilead Sciences. LSM has received grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases through the University of Utah (R01 DK124719), the Helmsley Charitable Trust (R-2203-05822), and the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK119282 and R01 DK119282-S), paid to the institution. SPB has received grants from the National Institutes of Health/National Institute of Aging (1K23AG048347-A101), National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12-HD043483), paid to the institution. SK has received grants from the National Institutes of Health, Patient-Centered Outcomes Research Institute, Agency for Healthcare Research and Quality, Centers for Medicare and Medicaid Services, and Esperion Therapeutics, paid to the institution; and has served as a consultant to Gilead Sciences and Bayer. The remaining authors have disclosed no potential conflicts of interest, financial or otherwise.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain., Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19., Design, Setting, and Participants: This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites., Interventions: Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days., Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis., Results: Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group)., Conclusions and Relevance: In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19., Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems. The operational and design features of clinically integrated trials include a focused scope, simplicity in design and requirements, the leveraging of existing data structures, and patient participation in the entire trial process. These features are designed to minimize barriers to participation and trial execution and reduce additional research burdens for participants and clinicians alike. Broad adoption and scalability of clinically integrated trials are dependent, in part, on continuing regulatory, healthcare system, and payer support. This analysis presents a framework of the strengths and challenges of clinically integrated trials and is based on a multidisciplinary expert "Think Tank" panel discussion that included representatives from patient populations, academia, non-profit funding agencies, the U.S. Food and Drug Administration, and industry., Competing Interests: Disclosures Dr. Peters is supported by the National Heart Lung and Blood Institute (T32HL069749) and has received honoraria from Cytokinetics. Dr. Jones has received grants from Bayer, Boehringer Ingelheim, and Merck. Dr. Broedl is an employee of Boehringer Ingelheim. Dr. Hornik received a research grant from Before Brands and consulting fees from SC Pharma. Dr. Knowlton received a salary from Intermountain Health Care. Dr. Krofah had leadership roles in Protas, the Reagan Udall Foundation, Clinical Trials Transformation Initiative (CTTI), Duke Margolis Center for Health Policy, Alliance for a Stronger FDA, Patient Focused Medicines Development (PFMD), and Medical Device Innovation Consortium (MDIC). Dr. Landray received grants from Janssen, FluLab, Schmidt Futures, Google Ventures, the National Institute for Health Research, UK Research & Innovation, Wellcome, and the Bill & Melinda Gates Foundation, as well as study drugs from Regeneron, Roche, AbbVie, and GSK. Dr. Rockhold received grants from the NIH, PCORI, BMS, AstraZeneca, American Regent, the Gates Foundation, and Eidos and consulting fees from Janssen, Clover, Doctor Evidence, and Intercept. He also participated on Data Safety Monitoring Boards for Lilly, AstraZeneca, Merck, Gilead, Novartis, Icosavax, Sanofi, UCB, Amgen, Biogen, BMS, Pulmocide, Alkermes, and Diurnal. He had an unpaid leadership role for the Frontier Science Foundation. He has stock or stock options for GSK, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr. Roessig is a full-time employee of Bayer AG. Dr. Rothman has received grants from PCORI, the CDC, NIH, and AHRQ. Lesley Schofield is an employee of Novartis and has stock or stock options from Novartis. Dr. Tenaerts is an employee of Medable, Inc., and has a stock option grant with Medable, Inc. Dr. Tenaerts also received an honorarium for participation on a data monitoring committee., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Pragmatic randomized clinical trials (RCTs) often use multiple data sources to examine clinical events, but the relative contribution of data sources to clinical end-point rates is understudied., Objective: To assess the contribution of data sources (electronic health records [EHRs], public/private insurance claims, and/or participant-reported data) to clinical end points among ADAPTABLE participants who had available data., Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic RCT from April 2016 through June 2019 conducted in research networks within clinical practice. Participants had existing atherosclerotic cardiovascular disease and available data to analyze. The characteristics of patients by combinations of data source availability were compared to examine the contribution of each of the data sources to end-point ascertainment. Data for this prespecified analysis were examined from January 2022 to June 2023., Exposures: Randomized exposure to 81 mg or 325 mg of aspirin daily., Main Outcomes and Measures: Number of events for the primary end point (composite of death, hospitalization for myocardial infarction, and hospitalization for stroke) that were contributed by EHR or claims data and then number of events contributed by each additional data source., Results: Of 15 006 participants randomized with at least 1 other source of data available beyond participant-reported data, there were 8756 (58.3%) with participant-reported and EHR data; 4291 (28.6%) with participant-reported, EHR, and claims data; 1412 (9.4%) with EHR-only data; 262 (1.7%) with participant-reported and claims data; 202 (1.3%) with EHR and claims data; and 83 (0.6%) with claims-only data. Participants with EHR-only data were younger (median age, 63.7 years; IQR, 55.8-71.4) compared with the other groups (range, 65.6-71.9 years). Among participants with both EHR and claims data, with or without participant-reported data (n = 4493), for each outcome, most events (92%-100%) were identified in the EHR or in claims data. For all clinical end points, participant-reported data contributed less than 10% of events not otherwise available from claims or EHR data., Conclusions and Relevance: In this analysis of a pragmatic RCT, claims and EHR data provided the most clinical end-point data when compared with participant-reported events. These findings provide a framework for collecting end points in pragmatic clinical trials. Further work is needed to understand the data source combinations that most effectively provide clinical end-point data in RCTs.

Importance: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the US. Although aspirin is recommended for secondary prevention of ASCVD, there was no difference in safety and effectiveness of aspirin dosed daily at 81 mg or 325 mg in the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) randomized clinical trial. However, it is unknown whether differences by sex exist in the safety and effectiveness of the different aspirin doses., Objective: To evaluate sex-specific differences in the safety and effectiveness of 2 aspirin doses in the ADAPTAPLE trial., Design, Setting, and Participants: The ADAPTABLE study was an open-label, pragmatic, randomized clinical trial that randomly assigned participants with chronic, stable ASCVD to 81 mg vs 325 mg of aspirin daily. Using Cox proportional-hazard models, male and female participants were compared for outcomes. In addition, it was assessed whether sex was an effect modifier in the association between aspirin dose and outcomes. The ADAPTABLE trial was conducted at 40 medical centers and 1 health plan. Eligible patients were 18 years and older and had established ASCVD. Study data were analyzed from December 2021 to March 2024., Interventions: Patients received 81 mg or 325 mg of aspirin daily for the secondary prevention of ASCVD., Main Outcomes and Measures: The primary effectiveness outcomes included all-cause death and hospitalization for myocardial infarction (MI) or stroke. The primary safety outcome was hospitalization for major bleeding requiring transfusion., Results: A total of 15 076 patients (median [IQR] age, 67.6 [60.7-73.6] years; 10 352 male [68.7%]) were followed up for a median (IQR) of 26.2 (19.0-34.9) months. Overall, 4724 (31.3%) were female, and 2307 of the female participants (48.8%) received aspirin 81 mg. Compared with males, female participants were younger (median [IQR] age, 66.3 [59.4-72.6] years vs 68.2 (61.4-73.9) years, less likely to self-report White race (3426 [72.5%] vs 8564 [82.7%]), more likely to smoke (564 [12.9%] vs 818 [8.4%]), and more likely to have a history of peripheral arterial disease (1179 [25.7%] vs 2314 [23.0%]). The primary effectiveness outcome of all-cause death and hospitalization for MI or stroke occurred in 379 female participants (8.1%) and 780 male participants (7.1%). There was no significant interaction by sex for the primary effectiveness end point between the 2 aspirin doses (female adjusted hazard ratio [aHR], 1.01; 95% CI, 0.82-1.26 and male aHR, 1.06; 95% CI, 0.91-1.23; P interaction term for sex = .74). During the trial, female participants had fewer revascularization procedures (237 [5.0%] vs 680 [6.6%]; aHR, 0.79; 95% CI, 0.68-0.92; P = .002) but had a higher risk of hospitalization for stroke (aHR, 1.72; 95% CI, 1.27-2.33; P < .001). Among female participants, there was a slightly higher rate of bleeding in the 81-mg aspirin cohort compared with the 325-mg cohort (20 [0.83%] vs 13 [0.52%]; aHR, 2.21; 95% CI, 1.04-4.70; P interaction term for sex = .07). There were no significant differences between female and male participants regarding aspirin dose adherence., Conclusions and Relevance: In this secondary analysis of the ADAPTABLE trial, there were no significant sex-specific differences in the effectiveness and safety of 2 aspirin doses for secondary prevention of ASCVD events., Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Objective: This study aimed to describe caregiver satisfaction with physician communication over the first two years of life and examine differences by preferred language and the relationship to physician continuity., Methods: Longitudinal data were collected at well visits (2 months to 2 years) from participants in a randomized controlled trial to prevent childhood obesity. Satisfaction with communication was assessed using the validated Communication Assessment Tool (CAT) questionnaire. Changes in the odds of optimal scores were estimated in mixed-effects logistic regression models to evaluate the associations between satisfaction over time and language, interpreter use, and physician continuity., Results: Of 865 caregivers, 35% were Spanish-speaking. Spanish-speaking caregivers without interpreters had lower odds of an optimal satisfaction score compared with English speakers during the first 2 years, beginning at 2 months [OR 0.64 (95% CI: 0.43, 0.95)]. There was no significant difference in satisfaction between English-speaking caregivers and Spanish-speaking caregivers with an interpreter. The odds of optimal satisfaction scores increased over time for both language groups. For both language groups, odds of an optimal satisfaction score decreased each time a new physician was seen for a visit [OR 0.82 (95% CI: 0.69, 0.97)]., Conclusion: Caregiver satisfaction with physician communication improves over the first two years of well-child visits for both English- and Spanish-speakers. A loss of physician continuity over time was also associated with lower satisfaction. Future interventions to ameliorate communication disparities should ensure adequate interpreter use for primarily Spanish-speaking patients and address continuity issues to improve communication satisfaction., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: SARS-CoV-2-infected patients may develop new conditions in the period after the acute infection. These conditions, the post-acute sequelae of SARS-CoV-2 infection (PASC, or Long COVID), involve a diverse set of organ systems. Limited studies have investigated the predictability of Long COVID development and its associated risk factors., Methods: In this retrospective cohort study, we used electronic healthcare records from two large-scale PCORnet clinical research networks, INSIGHT (~1.4 million patients from New York) and OneFlorida+ (~0.7 million patients from Florida), to identify factors associated with having Long COVID, and to develop machine learning-based models for predicting Long COVID development. Both SARS-CoV-2-infected and non-infected adults were analysed during the period of March 2020 to November 2021. Factors associated with Long COVID risk were identified by removing background associations and correcting for multiple tests., Results: We observed complex association patterns between baseline factors and a variety of Long COVID conditions, and we highlight that severe acute SARS-CoV-2 infection, being underweight, and having baseline comorbidities (e.g., cancer and cirrhosis) are likely associated with increased risk of developing Long COVID. Several Long COVID conditions, e.g., dementia, malnutrition, chronic obstructive pulmonary disease, heart failure, PASC diagnosis U099, and acute kidney failure are well predicted (C-index > 0.8). Moderately predictable conditions include atelectasis, pulmonary embolism, diabetes, pulmonary fibrosis, and thromboembolic disease (C-index 0.7-0.8). Less predictable conditions include fatigue, anxiety, sleep disorders, and depression (C-index around 0.6)., Conclusions: This observational study suggests that association patterns between investigated factors and Long COVID are complex, and the predictability of different Long COVID conditions varies. However, machine learning-based predictive models can help in identifying patients who are at risk of developing a variety of Long COVID conditions., (© 2024. The Author(s).)

Background: While several studies examine the relationship between screen time and dietary practices in children and teenagers, there is limited research in toddlers. This study evaluates the association between television (TV) exposure and dietary practices in 2-year-old children., Methods: We conducted a cross-sectional, secondary data analysis from the Greenlight Intervention Study. Toddlers' daily TV watching time, mealtime TV, and dietary practices were assessed by caregiver report at the 24-month well-child visit. Separate regression models were used and adjusted for sociodemographic/household characteristics and clinic site., Results: Five hundred and thirty-two toddlers were included (51% Latino; 30% non-Latino Black; 59% ≤$20,000 annual household income). Median daily TV watching time was 42 minutes (interquartile range: 25, 60); 25% reported the TV was "usually on" during mealtimes. After adjustment, toddlers who watched more TV daily had higher odds of consuming sugar-sweetened beverages, fast food, and more junk food; those watching less TV had higher odds of consuming more fruits/vegetables. Those with the TV "usually on" during mealtimes were more likely to consume sugar-sweetened beverages (aOR 3.72 [95% confidence interval {CI} 2.16-6.43]), fast food (aOR 2.83 [95%CI 1.54-5.20]), and more junk food (aOR 4.25 [95%CI 2.71-6.65])., Conclusions: Among toddlers from primarily minoritized populations and of lower socioeconomic status, those who watched more TV daily and usually had the TV on during meals had significantly less healthy dietary practices, even after adjusting for known covariates. This study supports the current American Academy of Pediatrics screen time guidelines and underscores the importance of early counseling on general and mealtime TV., 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 © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Importance: The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant., Objective: To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021., Design: Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021., Setting: Healthcare facilities in New York and Florida., Participants: Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period., Exposure: Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time., Main Outcome(s) and Measure(s): Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31-180 days after a positive COVID-19 test compared to persons without a COVID-19 test or diagnosis during the 31-180 days after the last negative test., Results: We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those without a COVID-19 test or diagnosis (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons)., Conclusions and Relevance: We documented a substantial relative risk of pulmonary embolism and a large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Varma 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: Adults hospitalized for cardiovascular events are at high risk for postdischarge mortality. Screening of psychosocial risk is prioritized by the Joint Commission. We tested whether key patient-reported psychosocial and behavioral measures could predict posthospitalization mortality in a cohort of adults hospitalized for a cardiovascular event., Methods: We conducted a prospective cohort study to test the prognostic utility of validated patient-reported measures, including health literacy, social support, health behaviors and disease management, and socioeconomic status. Cox survival analyses of mortality were conducted over a median of 3.5 years., Results: Among 2977 adults hospitalized for either acute coronary syndrome or acute decompensated heart failure, the mean age was 53 years, and 60% were male. After adjusting for demographic, clinical, and other psychosocial factors, mortality risk was greatest among patients who reported being unemployed (hazard ratio [HR]: 1.99, 95% confidence interval [CI]): 1.30-3.06), retired (HR: 2.14, 95% CI: 1.60-2.87), or unable to work due to disability (HR: 2.36, 95% CI: 1.73-3.21), as compared to those who were employed. Patient-reported perceived health competence (PHCS-2) and exercise frequency were also associated with mortality risk after adjusting for all other variables (HR: 0.86, 95% CI: 0.73-1.00 per four-point increase in PHCS-2; HR: 0.86, 95% CI: 0.77-0.96 per 3-day increase in exercise frequency, respectively)., Conclusions: Patient-reported measures of employment status, perceived health competence, and exercise frequency independently predict mortality after a cardiac hospitalization. Incorporating these brief, valid measures into hospital-based screening may help with prognostication and targeting patients for resources during post-discharge transitions of care., (© 2024 The Authors. Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Background: Understanding how different populations respond to a childhood obesity intervention could help optimize personalized treatment strategies, especially with the goal to reduce disparities in obesity. Methods: We conducted a secondary analysis of the Greenlight Cluster Randomized Controlled Trial, a health communication focused pediatric obesity prevention trial, to evaluate for heterogeneity of treatment effect (HTE) by child biological sex, caregiver BMI, caregiver reported race and ethnicity, primary language, and health literacy. To examine HTE on BMI z-score from 2 to 24 months of age, we fit linear mixed effects models. Results: We analyzed 802 caregiver-child pairs, of which 52% of children were female, 58% of households reported annual family income of <$20,000, and 83% did not have a college degree. We observed evidence to suggest HTE by primary language ( p  = 0.047 for Spanish vs. English) and the combination of primary language and health literacy ( p  = 0.01). There was insufficient evidence to suggest that the Greenlight intervention effect differed by biological sex, caregiver BMI, or by race/ethnicity. Conclusions: This HTE analysis found that the Greenlight obesity prevention intervention had a more beneficial effect on child BMI z-score over 2 years for children of caregivers with limited health literacy and for caregivers for whom Spanish was the primary language.

Background and Objectives: The American Academy of Pediatrics designed The Injury Prevention Program (TIPP) in 1983 to help pediatricians prevent unintentional injuries, but TIPP's effectiveness has never been formally evaluated. We sought to evaluate the impact of TIPP on reported injuries in the first 2 years of life., Methods: We conducted a stratified, cluster-randomized trial at 4 academic medical centers: 2 centers trained their pediatric residents and implemented TIPP screening and counseling materials at all well-child checks (WCCs) for ages 2 to 24 months, and 2 centers implemented obesity prevention. At each WCC, parents reported the number of child injuries since the previous WCC. Proportional odds logistic regression analyses with generalized estimating equation examined the extent to which the number of injuries reported were reduced at TIPP intervention sites compared with control sites, adjusting for baseline child, parent, and household factors., Results: A total of 781 parent-infant dyads (349 TIPP; 432 control) were enrolled and had sufficient data to qualify for analyses: 51% Hispanic, 28% non-Hispanic Black, and 87% insured by Medicaid. Those at TIPP sites had significant reduction in the adjusted odds of reported injuries compared with non-TIPP sites throughout the follow-up (P = .005), with adjusted odds ratios (95% CI) of 0.77 (0.66-0.91), 0.60 (0.44-0.82), 0.32 (0.16-0.62), 0.26 (0.12-0.53), and 0.27 (0.14-0.52) at 4, 6, 12, 18, and 24 months, respectively., Conclusions: In this cluster-randomized trial with predominantly low-income, Hispanic, and non-Hispanic Black families, TIPP resulted in a significant reduction in parent-reported injuries. Our study provides evidence for implementing the American Academy of Pediatrics' TIPP in routine well-child care., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: Understand the patient's decision-making process regarding colectomy for recurrent diverticulitis., Background: The decision to pursue elective colectomy for recurrent diverticulitis is highly preference-sensitive. Little is known about the patient's perspective in this decision-making process., Methods: We performed a qualitative study utilizing focus groups of patients with recurrent diverticulitis at 3 centers across the United States. Using an iterative inductive/deductive approach, we developed a conceptual framework to capture the major themes identified in the coded data., Results: From March 2019 to July 2020, 39 patients were enrolled across 3 sites and participated in 6 focus groups. After coding the transcripts using a hierarchical coding system, a conceptual framework was developed. Major themes identified included participants' beliefs about surgery, such as normative beliefs (eg, subjective, value placed on surgery), control beliefs (eg, self-efficacy, stage of change), and anticipated outcomes (eg, expectations, anticipated regret); the role of behavioral management strategies (eg, fiber, eliminate bad habits); emotional experiences (eg, depression, embarrassment); current symptoms (eg, severity, timing); and quality of life (eg, cognitive load, psychosocial factors). Three sets of moderating factors influencing patient choice were identified: clinical history (eg, source of diagnosis, multiple surgeries), clinical protocols (eg, pre-op and post-op education), and provider-specific factors (eg, specialty, choice of surgeon)., Conclusions: Patients view the decision to undergo colectomy through 3 major themes: their beliefs about surgery, their psychosocial context, and moderating factors that influence participant choice to undergo surgery. This knowledge is essential both for clinicians counseling patients who are considering colectomy and for researchers studying the process to optimize care for recurrent diverticulitis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Infants with high birthweight have increased risk for adverse outcomes at birth and across childhood. Prenatal risks to healthy food access may increase odds of high birthweight. We tested whether having a poor neighborhood food environment and/or food insecurity had associations with high birthweight., Methods: We analyzed cross-sectional baseline data in Greenlight Plus, an obesity prevention trial across six US cities (n = 787), which included newborns with a gestational age greater than 34 weeks and a birthweight greater than 2500 g. We assessed neighborhood food environment using the Place-Based Survey and food insecurity using the US Household Food Security Module. We performed logistic regression analyses to assess the individual and additive effects of risk factors on high birthweight. We adjusted for potential confounders: infant sex, race, ethnicity, gestational age, birthing parent age, education, income, and study site., Results: Thirty-four percent of birthing parents reported poor neighborhood food environment and/or food insecurity. Compared to those without food insecurity, food insecure families had greater odds of delivering an infant with high birthweight (adjusted odds ratios [aOR] 1.96, 95% confidence intervals [CI]: 1.01, 3.82) after adjusting for poor neighborhood food environment, which was not associated with high birthweight (aOR 1.35, 95% CI: 0.78, 2.34). Each additional risk to healthy food access was associated with a 56% (95% CI: 4%-132%) increase in high birthweight odds., Conclusions: Prenatal risks to healthy food access may increase high infant birthweight odds. Future studies designed to measure neighborhood factors should examine infant birthweight outcomes in the context of prenatal social determinants of health., 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 © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease., Methods and Results: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant ( P =0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points ( P >0.05 for all)., Conclusions: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Objective: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events., Research Design and Methods: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome., Results: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772)., Conclusions: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population., (© 2023 by the American Diabetes Association.)

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain., Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19., Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less., Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607)., Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28., Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths., Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms., Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

PCORnet, the National Patient-Centered Clinical Research Network, provides the ability to conduct prospective and observational pragmatic research by leveraging standardized, curated electronic health records data together with patient and stakeholder engagement. PCORnet is funded by the Patient-Centered Outcomes Research Institute (PCORI) and is composed of 8 Clinical Research Networks that incorporate at total of 79 health system "sites." As the network developed, linkage to commercial health plans, federal insurance claims, disease registries, and other data resources demonstrated the value in extending the networks infrastructure to provide a more complete representation of patient's health and lived experiences. Initially, PCORnet studies avoided direct economic comparative effectiveness as a topic. However, PCORI's authorizing law was amended in 2019 to allow studies to incorporate patient-centered economic outcomes in primary research aims. With PCORI's expanded scope and PCORnet's phase 3 beginning in January 2022, there are opportunities to strengthen the network's ability to support economic patient-centered outcomes research. This commentary will discuss approaches that have been incorporated to date by the network and point to opportunities for the network to incorporate economic variables for analysis, informed by patient and stakeholder perspectives. Topics addressed include: (1) data linkage infrastructure; (2) commercial health plan partnerships; (3) Medicare and Medicaid linkage; (4) health system billing-based benchmarking; (5) area-level measures; (6) individual-level measures; (7) pharmacy benefits and retail pharmacy data; and (8) the importance of transparency and engagement while addressing the biases inherent in linking real-world data sources., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations., Objective: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes., Design, Setting, and Participants: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023., Intervention: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months., Main Outcomes and Measures: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population., Results: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07)., Conclusions and Relevance: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population., Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Background The ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high- versus low-dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22-1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91-2.22]). We found no interaction in the relative effectiveness and safety of high- versus low-dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high-dose compared with low-dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high- versus low-dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Background: Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD)., Methods: ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups., Results: After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P = .95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P = .79) between ASA groups., Conclusions: Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD., Competing Interests: Disclosures The authors have no competing interests to declare regarding the current publication. The authors are solely responsible for the design and conduct of this study; all study analyses, the drafting and editing of the paper and its final contents., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To assess if 100% fruit juice intake prior to 6 months is associated with juice and sugar-sweetened beverage (SSB) intake at 24 months and whether this differs by sociodemographic factors., Methods: We used longitudinal data from infants enrolled in the control (no obesity intervention) arm of Greenlight, a cluster randomized trial to prevent childhood obesity which included parent-reported child 100% fruit juice intake at all well child checks between 2 and 24 months. We studied the relationship between the age of juice introduction (before vs after 6 months) and juice and SSB intake at 24 months using negative binomial regression while controlling for baseline sociodemographic factors., Results: We report results for 187 participants (43% Hispanic, 39% non-Hispanic Black), more than half (54%) of whom had reported 100% fruit juice intake before 6 months. Average 100% fruit juice intake at 24 months was greater than the recommended amount (of 4 oz) and was 8.2 oz and 5.3 oz for those who had and had not, respectively, been introduced to juice before 6 months. In adjusted models, early introduction of juice was associated with a 43% (95% confidence interval: 5%-96%) increase in juice intake at 24 months., Conclusions: 100% fruit juice intake exceeding recommended levels at 6 and 24 months in this diverse cohort was prevalent. Introducing 100% fruit juice prior to 6 months may put children at greater risk for more juice intake as they age. Further research is necessary to determine if early guidance can reduce juice intake., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background Internet-based participation has the potential to enhance pragmatic and decentralized trials, where representative study populations and generalizability to clinical practice are key. We aimed to study the differences between internet and noninternet/telephone participants in a large remote, pragmatic trial. Methods and Results In a subanalysis of the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) study, we compared internet participants with those who opted for noninternet participation. Study process measures examined included participant characteristics at consent, study medication adherence, and study retention. The clinical outcome examined was a composite of all-cause mortality, hospitalization for myocardial infarction, or hospitalization for stroke. Noninternet participants were older (mean 69.4 versus 67.4 years), more likely to be female (38.9% versus 30.2%), more likely to be Black (27.3% versus 6.0%) or Hispanic (11.1% versus 2.0%), and had a higher number of comorbid conditions. The composite clinical outcome was more than twice as high in noninternet participants. The hazard of nonadherence to the assigned aspirin dosage was 46% higher in noninternet participants than internet participants. Conclusions Noninternet participants differed from internet participants in notable demographic characteristics while having poorer baseline health. Over the course of ADAPTABLE, they also had worse clinical outcomes and greater likelihood of study drug nonadherence. These results suggest that trials focused on internet participation select for younger, healthier participants with a higher proportion of traditionally overrepresented patients. Allowing noninternet participation enhances diversity; however, additional steps may be needed to promote study retention and study medication adherence. Registration Information clinicaltrials.gov. Identifier: NCT02697916.

Importance: The COVID-19 pandemic stressed the healthcare field, resulting in a worker exodus at the onset and throughout the pandemic and straining healthcare systems. Female healthcare workers face unique challenges that may impact job satisfaction and retention. It is important to understand factors related to healthcare workers' intent to leave their current field., Objective: To test the hypothesis that female healthcare workers were more likely than male counterparts to report intention to leave., Design: Observational study of healthcare workers enrolled in the Healthcare Worker Exposure Response and Outcomes (HERO) registry. After baseline enrollment, two HERO 'hot topic' survey waves, in May 2021 and December 2021, ascertained intent to leave. Unique participants were included if they responded to at least one of these survey waves., Setting: HERO registry, a large national registry that captures healthcare worker and community member experiences during the COVID-19 pandemic., Participants: Registry participants self-enrolled online and represent a convenience sample predominantly composed of adult healthcare workers., Exposure(s): Self-reported gender (male, female)., Main Outcome: Primary outcome was intention to leave (ITL), defined as having already left, actively making plans, or considering leaving healthcare or changing current healthcare field but with no active plans. Multivariable logistic regression models were performed to examine the odds of intention to leave with adjustment for key covariates., Results: Among 4165 responses to either May or December surveys, female gender was associated with increased odds of ITL (42.2% males versus 51.4% females reported intent to leave; aOR 1.36 [1.13, 1.63]). Nurses had 74% higher odds of ITL compared to most other health professionals. Among those who expressed ITL, three quarters reported job-related burnout as a contributor, and one third reported experience of moral injury., Conclusions and Relevance: Female healthcare workers had higher odds of intent to leave their healthcare field than males. Additional research is needed to examine the role of family-related stressors., Trial Registration: ClinicalTrials.gov identifier NCT04342806., Competing Interests: The authors declare competing financial interests as follows. Dr. Linzer is supported through his employer Hennepin Healthcare for work by large healthcare organizations to reduce burnout (ABIM, ACP, AMA, IHI, Optum Office for Provider Advancement, Essentia Health Systems, Gillette Children’s Hospital and California AHEC). He is supported for other scholarly work by NIH and AHRQ, and consults for Harvard University on a grant to assess relationships between work conditions and diagnostic accuracy (consulting funds donated to Hennepin Healthcare). This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Apple 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.)

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively. With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations., (© 2023. The Author(s).)

Objective: The purpose of this study is to understand how families from diverse sociodemographic backgrounds perceived the impact of the pandemic on the development of their children., Methods: We used a multimethod approach guided by Bronfenbrenner's Ecological Systems Theory, which identifies 5 developmental systems (micro, meso, exo, macro, and chrono). Semistructured interviews were conducted in English or Spanish with parents living in 5 geographic regions of the United States between July and September 2021. Participants also completed the COVID-19 Exposure and Family Impact Survey., Results: Forty-eight families participated, half of whose preferred language was Spanish, with a total of 99 children ages newborn to 19 years. Most qualitative themes pertained to developmental effects of the microsystem and macrosystem. Although many families described negative effects of the pandemic on development, others described positive or no perceived effects. Some families reported inadequate government support in response to the pandemic as causes of stress and potential negative influences on child development. As context for their infant's development, families reported a variety of economic hardships on the COVID-19 Exposure and Family Impact Survey, such as having to move out of their homes and experiencing decreased income., Conclusion: In addition to negative impacts, many parents perceived positive pandemic-attributed effects on their child's development, mainly from increased time for parent-child interaction. Families described economic hardships that were exacerbated by the pandemic and that potentially affect child development and insufficient government responses to these hardships. These findings hold important lessons for leaders who wish to design innovative solutions that address inequities in maternal, family, and child health., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs)., Methods: In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected)., Results: Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P = 0.20) was identified nor any significant safety issues., Conclusion: Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection., Trial Registration: NCT04334148., Competing Interests: Declaration of competing interest All authors have completed the International Committee of Medical Journal Editors uniform disclosure form and declare: support from the Patient-Centered Outcomes Research Institute (PCORI) for the reported work; Vir Biotechnology (SC); AstraZeneca, GSK, Novartis, Pulmatric, Sanofi-Aventis, Genentech, Teva (MC); Vir Biotechnology (KA); Centers for Disease Control, Infection Control Education for Major Sports, LLC, UpToDate, AHRQ, NIAID (DA); NIH (KA); Pfizer (EO); Abbott (RR)., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)