IMPORTANCE: The protocol of a randomized trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Herein, we systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. OBSERVATIONS: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (harms, outcomes, nonpharmacological treatment) and other reporting guidelines (Template for Intervention Description and Replication [TIDieR]). The potential modifications were rated in a 3-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of 2 new protocol items, revision to 5 items, deletion/merger of 5 items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open-science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policy makers, regulators, and other reviewers.

OBJECTIVE: The 2023 American Academy of Pediatrics clinical practice guideline (CPG) recommends testing children aged ≥ 10 years with obesity for abnormalities in lipids, glucose metabolism, and liver function. We aimed to assess laboratory screening and test results for three obesity-related chronic conditions in a large cohort of US patients 10-18 years with obesity. METHODS: We used electronic health record data to estimate (1) prevalence of screening for diabetes, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD), individually and in combination, and (2) prevalence of abnormal test results, by obesity severity and demographics. RESULTS: Among 333,110 patients with obesity, only one-quarter (26%) were screened for diabetes, dyslipidemia, or NAFLD during 2020-2022. Among those screened, complete screening (all three conditions) occurred half of the time. Screening rates were significantly higher in those with more severe obesity, yet 64% of children with class 3 obesity remained unscreened. When screening occurred, results revealed a high proportion of abnormal lipid (56%), NAFLD (44% elevated or borderline), and diabetes markers (14% prediabetes or diabetes). CONCLUSIONS: Most youth with obesity were not screened for chronic conditions. Many who were screened had abnormal results. These findings establish baseline estimates and highlight opportunities for improvement in uptake of CPG recommendations to support evidence-based obesity pediatric care.

Obesity affects approximately one in five U.S. adolescents. Although an increasing number of medications are approved for adolescent obesity as an adjunct to health behavior and lifestyle treatment, national data on the prevalence and correlates of obesity medication prescribing for adolescents are sparse. Ambulatory electronic medical record data were analyzed to assess trends in the proportion of U.S. adolescents aged 12-17 years with obesity (body mass index ≥95th percentile) who were prescribed Food and Drug Administration (FDA) -approved obesity medications during 2018-2023. Log-binomial models were used to estimate characteristics of adolescents associated with receiving an obesity medication prescription in 2023. The proportion of U.S. adolescents who were prescribed obesity medications increased substantially in 2023 (by approximately 300% compared with 2020), the year after FDA expanded its approval of two obesity medications to include adolescents and after publication of the 2023 American Academy of Pediatrics clinical practice guideline. Despite this substantial relative increase, 0.5% of adolescents with obesity were prescribed an obesity medication in 2023, with a majority (83%) of prescriptions received by adolescents with severe obesity. Semaglutide (Wegovy, indicated for persons aged ≥12 years with obesity), and phentermine or phentermine-topiramate were most commonly prescribed. Prescribing prevalence was higher among girls than among boys (adjusted prevalence ratio [aPR] = 2.05), among adolescents aged 15-17 years than among those aged 12-14 years (aPR = 2.24), and among those with severe (class 2 or class 3) obesity than among those with class 1 obesity (aPR = 4.03 and 12.78, respectively). Prescribing prevalence was lower among Black or African American adolescents than among White adolescents (aPR = 0.61). Continued monitoring of the use of these medications could help guide strategies to ensure that all adolescents with obesity have access to evidence-based obesity treatment, including medications and health behavior and lifestyle interventions.

IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. OBJECTIVE: To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. DESIGN: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. FINDINGS: Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

The protocol of a randomized trial is the foundation for study planning, conduct, reporting and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Here, we aimed to systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. We completed a scoping review and developed a project-specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators and other reviewers.

IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. OBJECTIVE: To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. DESIGN: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. FINDINGS: Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

Critical appraisal of the quality of randomised trials is possible only if their design, conduct, analysis, and results are completely and accurately reported. Without transparent reporting of the methods and results, readers will not be able to fully evaluate the reliability and validity of trial findings. The CONSORT (Consolidated Standards of Reporting Trials) statement aims to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996 and was updated in 2001 and 2010. CONSORT comprises a checklist of essential items that should be included in reports of randomised trials and a diagram for documenting the flow of participants through a trial. The CONSORT statement has been updated (CONSORT 2025) to reflect recent methodological advancements and feedback from end users, ensuring that it remains fit for purpose. Here, we present the updated CONSORT explanation and elaboration document, which has been extensively revised and describes the rationale and scientific background for each CONSORT 2025 checklist item and provides published examples of good reporting. The objective is to enhance the use, understanding, and dissemination of CONSORT 2025 and provide guidance to authors about how to improve the reporting of their trials and ensure trial reports are complete, and transparent.

IMPORTANCE: Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of health care interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomized trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Herein, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. OBSERVATIONS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (harms, outcomes, nonpharmacological treatment), other related reporting guidelines (Template for Intervention Description and Replication [TIDieR]), and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, 3-round Delphi survey involving 317 participants and discussed at a 2-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added 7 new checklist items, revised 3 items, deleted 1 item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomized trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS AND RELEVANCE: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomized trials to ensure that trial reports are clear and transparent.

Cache Valley virus (CVV), a mosquito-borne orthobunyavirus, causes epizootics in ruminants characterized by congenital malformations and fetal death in North America. Only seven human infections have been identified; limited information exists on its potential as a human teratogen. Diagnosis of CVV infections relies on the plaque reduction neutralization test (PRNT), which requires live virus, is time-consuming, and cannot differentiate between recent and past infections. To improve diagnostics for CVV, we developed an IgM antibody capture ELISA (MAC-ELISA) for detection of anti-CVV human IgM in diagnostic specimens that can be performed faster than PRNT and is specific to IgM, which is essential to determine the timing of infection. Conjointly, a cell line constitutively expressing human-murine chimeric antibody with the variable regions of monoclonal antibody CVV-17 and constant regions of human IgM was developed to provide positive control material. The new cell line produced antibody with reactivity in the assay equivalent to that of a human serum sample positive for anti-CVV IgM. Five of seven archived human specimens diagnostically confirmed as CVV positive tested positive in the MAC-ELISA, whereas 44 specimens confirmed positive for another arboviral infection tested negative, showing good initial correlation of the CVV MAC-ELISA. Two of 27 previously collected serum samples from febrile patients in Yucatán, Mexico, who tested negative for a recent flaviviral or alphaviral infection were positive in both the MAC-ELISA and PRNT, indicating a possible recent infection with CVV or related orthobunyavirus. The MAC-ELISA described here will aid in making diagnostics more widely available for CVV in public health laboratories.

Background: Cardiomyopathy (CM) and other cardiovascular conditions (OCVs) are among the most frequent causes of pregnancy-related death in the United States. Objectives: The purpose of this paper was to report demographic and clinical characteristics, preventability, contributing factors, and Maternal Mortality Review Committee (MMRC) recommendations among pregnancy-related deaths with underlying causes of CM, OCVs, and the 2 combined (cardiovascular conditions, CV). Methods: We analyzed pregnancy-related death data from MMRCs in 32 states, occurring during 2017 to 2019, with MMRC-determined underlying causes of CVs. We describe distributions of demographic characteristics, present the most frequent contributing factor classes, and provide example MMRC prevention recommendations. Results: Among 210 pregnancy-related deaths due to CVs, 84 (40%) were due to CM and 126 (60%) to OCVs. More than half (51.2%) of CM deaths were among non-Hispanic Black persons. Two-thirds (66%) of all CV deaths occurred among people <35 years old. Approximately 53% of CM deaths and 31% of OCV deaths occurred 43 to 365 days postpartum. Over 75% of pregnancy-related deaths due to CVs were determined by MMRCs to be preventable. The 5 most frequent contributing factor classes accounted for 50% of the total MMRC-identified contributing factors. MMRC prevention recommendations occur at multiple levels. Conclusions: Most pregnancy-related deaths due to CM and OCV are preventable. Example MMRC recommendations provided in this report illustrate prevention opportunities that address contributing factors, including broader awareness of urgent warning signs, improved handoffs for care coordination and continuity, and expanded accessibility of community-based comprehensive and integrated care services. © 2024 The Authors

Background: Many studies rely on the International Classification of Diseases, 9th or 10th Revision, Clinical Modification codes to define obesity in electronic health records data. While prior studies found misclassification and low sensitivity of codes for pediatric obesity, it remains unclear whether this misclassification is random and what are the implications of combining different code types to define obesity. Methods: We assessed prevalence, sensitivity, and specificity of obesity codes among 7.4 million children aged 2-19 years over 2014-2021. Among those with obesity in 2021, we estimated the probability of receiving any code or a specific code type by patient characteristics. Results: Obesity code utilization increased in prevalence from 3.9% in 2014 to 9.8% in 2021; prevalence of obesity based on BMI increased from 17.4% to 20.5%. Code sensitivity increased from 19.8% to 40.8%. Among children with obesity in 2021, those with severe obesity (reference: no severe obesity) and chronic disease (reference: no chronic disease) were more likely to get a code, and the highest likelihood was associated with obesity diagnosis codes (vs. status codes). Conclusions: Despite increases, obesity code utilization remained low. Obesity code misclassification is not random and certain child characteristics (e.g., severe obesity or chronic disease) are associated with a higher probability of getting a code. There are also significant differences by code type; thus, caution should be taken before combining obesity codes as a proxy for obesity status, especially in longitudinal analyses. More universal documentation of obesity may improve the quality of care and the use of these data for evaluation and research purposes.

Objectives: To (1) determine associations between maternal risk conditions and severe adverse outcomes that may benefit from risk-appropriate care and (2) assess whether associations between risk conditions and outcomes vary by level of maternal care (LoMC). Methods: We used the 2017-2019 National Inpatient Sample (NIS) to calculate associations between maternal risk conditions and severe adverse outcomes. Risk conditions included severe preeclampsia, placenta accreta spectrum (PAS) conditions, and cardiac conditions. Outcomes included disseminated intravascular coagulation (DIC) with blood products transfusion or shock, pulmonary edema or acute respiratory distress syndrome (ARDS), stroke, acute renal failure, and a composite cardiac outcome. Then we used 2019 delivery hospitalization data from five states linked to hospital LoMC. We calculated associations between risk conditions and outcomes overall and stratified by LoMC and assessed for effect modification by LoMC. Results: We found positive measures of association between risk conditions and outcomes. Among patients with severe preeclampsia or PAS, the magnitudes of the associations with DIC with blood products transfusion or shock, pulmonary edema or ARDS, and acute renal failure were lower in Level III/IV compared with <Level III facilities. Among patients with cardiac conditions, the magnitudes of the associations with these outcomes, along with stroke, were also lower in Level III/IV compared with <Level III facilities. The proportion of patients with risk conditions that delivered in <Level III facilities was 19.8-46.8%. Conclusions: Odds of severe adverse outcomes among women with selected risk conditions were lower for births occurring at higher-level facilities, supporting the benefit of risk-appropriate care.

Equitable access to affordable, effective, and safe obesity prevention and treatment remains a problem for many children and families in the U.S. In 2023, the American Academy of Pediatrics (AAP) published its first Clinical Practice Guideline (CPG) for pediatric obesity evaluation and treatment, aiding the field's awareness of effective approaches. CDC has supported the adapting and packaging of existing, effective Family Healthy Weight Programs that deliver CPG-recommended intensive behavioral treatment for kids. Currently, at least six family-centered programs are recognized by CDC and can be implemented in clinical and community settings to support child health. CDC and other national partners are coordinating the movement of these research-tested FHWPs into public health practice. This work includes implementing FHWPs in over 60 US communities and supporting national-level infrastructure improvements. CDC is committed to engaging with stakeholders to help scale proven strategies that ensure all children receive the care they need to thrive.

IMPORTANCE: Universal screening to identify unfavorable lipid levels is recommended for US children aged 9 to 11 years and adolescents aged 17 to 21 years (hereafter, young adults); however, screening benefits in these individuals have been questioned. Current use of lipid screening and prevalence of elevated lipid measurements among US youths is not well understood. OBJECTIVE: To investigate the prevalence of ambulatory pediatric lipid screening and elevated or abnormal lipid measurements among US screened youths by patient characteristic and test type. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the IQVIA Ambulatory Electronic Medical Record database and included youths aged 9 to 21 years with 1 or more valid measurement of height and weight during the observation period (2018-2021). Body mass index (BMI) was calculated and categorized using standard pediatric BMI percentiles (9-19 years) and adult BMI categories (≥20 years). The data were analyzed from October 6, 2022, to January 18, 2023. MAIN OUTCOMES AND MEASURES: Lipid measurements were defined as abnormal if 1 or more of the following test results was identified: total cholesterol (≥200 mg/dL), low-density lipoprotein cholesterol (≥130 mg/dL), very low-density lipoprotein cholesterol (≥31 mg/dL), non-high-density lipoprotein cholesterol (≥145 mg/dL), and triglycerides (≥100 mg/dL for children aged 9 years or ≥130 mg/dL for patients aged 10-21 years). After adjustment for age group, sex, race and ethnicity, and BMI category, adjusted prevalence ratios (aPRs) and 95% CIs were calculated. RESULTS: Among 3 226 002 youths (23.9% aged 9-11 years, 34.8% aged 12-16 years, and 41.3% aged 17-21 years; 1 723 292 females [53.4%]; 60.0% White patients, 9.5% Black patients, and 2.4% Asian patients), 11.3% had 1 or more documented lipid screening tests. The frequency of lipid screening increased by age group (9-11 years, 9.0%; 12-16 years, 11.1%; 17-21 years, 12.9%) and BMI category (range, 9.2% [healthy weight] to 21.9% [severe obesity]). Among those screened, 30.2% had abnormal lipid levels. Compared with youths with a healthy weight, prevalence of an abnormal result was higher among those with overweight (aPR, 1.58; 95% CI, 1.56-1.61), moderate obesity (aPR, 2.16; 95% CI, 2.14-2.19), and severe obesity (aPR, 2.53; 95% CI, 2.50-2.57). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of prevalence of lipid screening among US youths aged 9 to 21 years, approximately 1 in 10 were screened. Among them, abnormal lipid levels were identified in 1 in 3 youths overall and 1 in 2 youths with severe obesity. Health care professionals should consider implementing lipid screening among children aged 9 to 11 years, young adults aged 17 to 21 years, and all youths at high cardiovascular risk.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals. METHODS: We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2-positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022-May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated. RESULTS: Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7). CONCLUSIONS: Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients.

Hemorrhage has been a leading cause of pregnancy-related death in the Centers for Disease Control and Prevention Pregnancy Mortality Surveillance System since 1987 when reporting began. Pregnancy Mortality Surveillance System data from 2012 to 2019 were analyzed to describe pregnancy-related deaths from hemorrhage. Pregnancy-related mortality ratios were estimated for hemorrhage overall and by hemorrhage subclassifications. Specific subclassifications of hemorrhage-related deaths were analyzed by sociodemographic characteristics. Overall, there were 606 deaths due to hemorrhage. The pregnancy-related mortality ratio for hemorrhage overall was 1.94 per 100,000 live births. Ruptured ectopic pregnancy was the most frequent subclassification (22.9%) of pregnancy-related hemorrhage deaths, followed by postpartum hemorrhage (21.2%). There were no significant trends in the pregnancy-related mortality ratio, overall or among any subclassification of hemorrhage deaths, from 2012 to 2019. Reporting subclassifications of pregnancy-related hemorrhage deaths could improve the ability to focus interventions and assess progress over time.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

BACKGROUND: Severe maternal morbidity (SMM) is broadly defined as an unexpected and potentially life-threatening event associated with labor and delivery. The Centers for Disease Control and Prevention (CDC) produced 21 different indicators based on International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) hospital diagnostic and procedure codes to identify cases of SMM. OBJECTIVES: To examine existing SMM indicators and determine which indicators identified the most in-hospital mortality at delivery hospitalization. METHODS: Data from the 1993-2015 and 2017-2019 Healthcare Cost and Utilization Project's National Inpatient Sample were used to report SMM indicator-specific prevalences, in-hospital mortality rates, and population attributable fractions (PAF) of mortality. We hierarchically ranked indicators by their overall PAF of in-hospital mortality. Predictive modeling determined if SMM prevalence remained comparable after transition to ICD-10-CM coding. RESULTS: The study population consisted of 18,198,934 hospitalizations representing 87,864,173 US delivery hospitalizations. The 15 top ranked indicators identified 80% of in-hospital mortality; the proportion identified by the remaining indicators was negligible (2%). The top 15 indicators were: restoration of cardiac rhythm; cardiac arrest; mechanical ventilation; tracheostomy; amniotic fluid embolism; aneurysm; acute respiratory distress syndrome; acute myocardial infarction; shock; thromboembolism, pulmonary embolism; cerebrovascular disorders; sepsis; both DIC and blood transfusion; acute renal failure; and hysterectomy. The overall prevalence of the top 15 ranked SMM indicators (~22,000 SMM cases per year) was comparable after transition to ICD-10-CM coding. CONCLUSIONS: We determined the 15 indicators that identified the most in-hospital mortality at delivery hospitalization in the US. Continued testing of SMM indicators can improve measurement and surveillance of the most severe maternal complications at the population level.

Background Hypertension and diabetes are associated with increased COVID-19 severity. The association between level of control of these conditions and COVID-19 severity is less well understood. Methods and Results This retrospective cohort study identified adults with COVID-19, March 2020 to February 2022, in 43 US health systems in the National Patient-Centered Clinical Research Network. Hypertension control was categorized as blood pressure (BP) <130/80, 130 to 139/80 to 89, 140 to 159/90 to 99, or ≥160/100 mm Hg, and diabetes control as glycated hemoglobin <7%, 7% to <9%, ≥9%. Adjusted, pooled logistic regression assessed associations between hypertension and diabetes control and severe COVID-19 outcomes. Among 1 494 837 adults with COVID-19, 43% had hypertension and 12% had diabetes. Among patients with hypertension, the highest baseline BP was associated with greater odds of hospitalization (adjusted odds ratio [aOR], 1.30 [95% CI, 1.23-1.37] for BP ≥160/100 versus BP <130/80), critical care (aOR, 1.30 [95% CI, 1.21-1.40]), and mechanical ventilation (aOR, 1.32 [95% CI, 1.17-1.50]) but not mortality (aOR, 1.08 [95% CI, 0.98-1.12]). Among patients with diabetes, the highest glycated hemoglobin was associated with greater odds of hospitalization (aOR, 1.61 [95% CI, 1.47-1.76] for glycated hemoglobin ≥9% versus <7%), critical care (aOR, 1.42 [95% CI, 1.31-1.54]), mechanical ventilation (aOR, 1.12 [95% CI, 1.02-1.23]), and mortality (aOR, 1.18 [95% CI, 1.09-1.27]). Black and Hispanic adults were more likely than White adults to experience severe COVID-19 outcomes, independent of comorbidity score and control of hypertension or diabetes. Conclusions Among 1.5 million patients with COVID-19, higher BP and glycated hemoglobin were associated with more severe COVID-19 outcomes. Findings suggest that adults with poorest control of hypertension or diabetes might benefit from efforts to prevent and initiate early treatment of COVID-19.

Introduction: We evaluated how the Affordable Care Act (ACA) Medicaid eligibility expansion affected perinatal insurance coverage patterns for Medicaid-enrolled beneficiaries who gave birth overall and by race/ethnicity. We also examined state-level heterogeneous impacts. Methods: Using the 2011–2013 Medicaid Analytic eXtract and the 2016–2018 Transformed Medicaid Statistical Information System Analytic File databases, we identified 1.4 million beneficiaries giving birth in 2012 (pre-ACA expansion cohort) and 1.5 million in 2017 (post-ACA expansion cohort). We constructed monthly coverage rates for the two cohorts by state Medicaid expansion status and obtained difference-in-differences estimates of the association of Medicaid expansion with coverage overall and by race/ethnicity group (non-Hispanic White, non-Hispanic Black, and Hispanic). To explore state-level heterogeneous impacts, we divided the expansion and non-expansion states into groups based on the differences in the income eligibility limits for low-income parents in each state between 2012 and 2017. Results: Medicaid expansion was associated with 13 percentage points higher coverage in the 9 to 12 months before giving birth, and 11 percentage points higher coverage at 6 to 12 months postpartum. Hispanic birthing individuals had the greatest relative increases in coverage, followed by non-Hispanic White and non-Hispanic Black individuals. In Medicaid expansion states, those who experienced the greatest increases in income eligibility limits for low-income parents generally saw the greatest increases in coverage. In non-expansion states, there was less heterogeneity between state groupings. Conclusions: Pregnancy-related Medicaid eligibility did not have major changes in the 2010s. However, states’ adoption of ACA Medicaid expansion after 2012 was associated with increased Medicaid coverage before, during, and after pregnancy. The increases varied by race/ethnicity and across states. © 2023

Suicide and unintentional overdose are leading manners of preventable death during and within a year of pregnancy. Recently, the Utah Maternal Mortality Review Committee (MMRC) developed 10 criteria to guide pregnancy-related classification of these deaths. Our objective was to (1) evaluate if consensus could be reached across experts in maternal mortality review when applying criteria to the determination of pregnancy-relatedness in mock MMRC case evaluation and (2) assess how additional case information shifted participants' determination of pregnancy-relatedness in these mock cases. We used a modified Delphi process to evaluate criteria for pregnancy-related suicides and unintentional overdose. The study team developed base case scenarios to reflect the 10 proposed criteria. Base scenarios varied in timing of death (prenatal or delivery, early postpartum (<6 months), late postpartum (6-12 months)) and level of additional information available (e.g., informant interviews, social media posts). Consensus in favor of a criterion was met when ≥75% of participants identified a case as pregnancy-related in at least 1 scenario. Fifty-eight participants, representing 48 MMRCs, reviewed scenarios. Of 10 proposed criteria, 8 reached consensus. Overall, participants classified 19.4% of base case scenarios as pregnancy-related, which increased to 56.8% with additional information. Pregnancy-related classification changed across timing of death and with availability of additional information (prenatal or delivery 27.7% versus 84.6%; early postpartum 30.0% versus 58.3%; late postpartum 0.0% versus 25.0%, respectively). We identified consensus supporting the application of 8 standardized criteria in MMRC determinations of pregnancy-relatedness among suicide and unintentional overdose deaths.

Cross-species virus transmission events can lead to dire public health emergencies in the form of epidemics and pandemics. One example in animals is the emergence of the H3N8 equine influenza virus (EIV), first isolated in 1963 in Miami, FL, USA, after emerging among horses in South America. In the early 21st century, the American lineage of EIV diverged into two 'Florida' clades that persist today, while an EIV transferred to dogs around 1999 and gave rise to the H3N8 canine influenza virus (CIV), first reported in 2004. Here, we compare CIV in dogs and EIV in horses to reveal their host-specific evolution, to determine the sources and connections between significant outbreaks, and to gain insight into the factors controlling their different evolutionary fates. H3N8 CIV only circulated in North America, was geographically restricted after the first few years, and went extinct in 2016. Of the two EIV Florida clades, clade 1 circulates widely and shows frequent transfers between the USA and South America, Europe and elsewhere, while clade 2 was globally distributed early after it emerged, but since about 2018 has only been detected in Central Asia. Any potential zoonotic threat of these viruses to humans can only be determined with an understanding of its natural history and evolution. Our comparative analysis of these three viral lineages reveals distinct patterns and rates of sequence variation yet with similar overall evolution between clades, suggesting epidemiological intervention strategies for possible eradication of H3N8 EIV.

California serogroup viruses (CSGVs) of medical importance in the United States include La Crosse virus, Jamestown Canyon virus (JCV), California encephalitis virus, and snowshoe hare virus. Current diagnosis of CSGVs relies heavily on serologic techniques for detecting immunoglobulin M (IgM), an indication of a recent CSGV infection. However, human-positive control sera reactive to viruses in the serogroup are scarce because detection of recent infections is rare. Here, we describe the development of new murine monoclonal antibodies (MAbs) reactive to CSGVs and the engineering of a human-murine chimeric antibody by combining the variable regions of the broadly CSGV cross-reactive murine MAb, 3-3B6/2-3B2 and the constant region of the human IgM. MAb 3-3B6/2-3B2 recognizes a tertiary epitope on the Gn/Gc heterodimer, and epitopes important in JCV neutralization were mapped to the Gc glycoprotein. This engineered human IgM constitutively expressed in a HEK-293 stable cell line can replace human-positive control sera in diagnostic serological techniques such as IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Compared to the parent murine MAbs, the human-chimeric IgM antibody had identical serological activity to CSGVs in ELISA and demonstrated equivalent reactivity compared to human immune sera in the MAC-ELISA.IMPORTANCEOrthobunyaviruses in the California serogroup cause severe neurological disease in children and adults. While these viruses are known to circulate widely in North America, their occurrence is rare. Serological testing for CSGVs is hindered by the limited availability and volumes of human-positive specimens needed as controls in serologic assays. Here, we described the development of a murine monoclonal antibody cross-reactive to CSGVs engineered to contain the variable regions of the murine antibody on the backbone of human IgM. The chimeric IgM produced from the stably expressing HEK293 cell line was evaluated for use as a surrogate human-positive control in a serologic diagnostic test.

Objective: To describe pregnancy-related mortality among Hispanic people by place of origin (country or region of Hispanic ancestry), 2009-2018. Materials and Methods: We conducted a cross-sectional descriptive study of pregnancy-related deaths among Hispanic people, stratified by place of origin (Central or South America, Cuba, Dominican Republic, Mexico, Puerto Rico, Other and Unknown Hispanic), using Pregnancy Mortality Surveillance System data, 2009-2018. We describe distributions of pregnancy-related deaths and pregnancy-related mortality ratios (number of pregnancy-related deaths per 100,000 live births) overall and by place of origin for select demographic and clinical characteristics. Results: For 2009-2018, the overall pregnancy-related mortality ratio among Hispanic people was 11.5 pregnancy-related deaths per 100,000 live births (95% confidence intervals [CI]: 10.8-12.2). In general, pregnancy-related mortality ratios were higher among older age groups (i.e., 35 years and older) and lower among those with higher educational attainment (i.e., college degree or higher). Approximately two in five pregnancy-related deaths among Hispanic people occurred on the day of delivery through 6 days postpartum. Place of origin-specific pregnancy-related mortality ratios ranged from 9.6 (95% CI: 5.8-15.0) among people of Cuban origin to 15.3 (95% CI: 12.4-18.3) among people of Puerto Rican origin. Hemorrhage and infection were the most frequent causes of pregnancy-related deaths overall among Hispanic people. People of Puerto Rican origin had a higher proportion of deaths because of cardiomyopathy. Conclusions: We identified differences in pregnancy-related mortality by place of origin among Hispanic people that can help inform prevention of pregnancy-related deaths.

IMPORTANCE: Information on the probability of weight loss among US adults with overweight or obesity is limited. OBJECTIVE: To assess the probability of 5% or greater weight loss, 10% or greater weight loss, body mass index (BMI) reduction to a lower BMI category, and BMI reduction to the healthy weight category among US adults with initial overweight or obesity overall and by sex and race. DESIGN, SETTING, AND PARTICIPANTS: This cohort study obtained data from the IQVIA ambulatory electronic medical records database. The sample consists of US ambulatory patients 17 years or older with at least 3 years of BMI information from January 1, 2009, to February 28, 2022. Minimum age was set at 17 years to allow for the change in BMI or weight starting at 18 years. Maximum age was censored at 70 years. EXPOSURES: Initial BMI (calculated as weight in kilograms divided by height in meters squared) category was the independent variable of interest, and the categories were as follows: lower than 18.5 (underweight), 18.5 to 24.9 (healthy weight), 25.0 to 29.9 (overweight), 30.0 to 34.9 (class 1 obesity), 35.0 to 39.9 (class 2 obesity), and 40.0 to 44.9 and 45.0 or higher (class 3 or severe obesity). MAIN OUTCOMES AND MEASURES: The 2 main outcomes were 5% or greater weight loss (ie, a ≥5% reduction in initial weight) and BMI reduction to the healthy weight category (ie, BMI of 18.5-24.9). RESULTS: The 18 461 623 individuals in the sample had a median (IQR) age of 54 (40-66) years and included 10 464 598 females (56.7%) as well as 7.7% Black and 72.3% White patients. Overall, 72.5% of patients had overweight or obesity at the initial visit. Among adults with overweight and obesity, the annual probability of 5% or greater weight loss was low (1 in 10) but increased with higher initial BMI (from 1 in 12 individuals with initial overweight to 1 in 6 individuals with initial BMI of 45 or higher). Annual probability of BMI reduction to the healthy weight category ranged from 1 in 19 individuals with initial overweight to 1 in 1667 individuals with initial BMI of 45 or higher. Both outcomes were generally more likely among females than males and were highest among White females. Over the 3 to 14 years of follow-up, 33.4% of persons with overweight and 41.8% of persons with obesity lost 5% or greater of their initial weight. At the same time, 23.2% of persons with overweight and 2.0% of persons with obesity reduced BMI to the healthy weight category. CONCLUSIONS AND RELEVANCE: Results of this cohort study indicate that the annual probability of 5% or greater weight loss was low (1 in 10) despite the known benefits of clinically meaningful weight loss, but 5% or greater weight loss was more likely than BMI reduction to the healthy weight category, especially for patients with the highest initial BMIs. Clinicians and public health efforts can focus on messaging and referrals to interventions that are aimed at clinically meaningful weight loss (ie, ≥5%) for adults at any level of excess weight.