Antiviral susceptibility of influenza viruses is monitored by the World Health Organization Global Influenza Surveillance and Response System. This study describes a global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs, oseltamivir, zanamivir, peramivir, laninamivir) and the cap-dependent endonuclease inhibitor (CENI, baloxavir) for three periods (May to May for 2020-2021, 2021-2022 and 2022-2023). In particular, global influenza activity declined significantly in 2020-2021 and 2021-2022 when compared to the pre-pandemic period of COVID-19. Combined phenotypic and NA sequence-based analysis revealed that the global frequency of seasonal influenza viruses with reduced or highly reduced inhibition (RI/HRI) by NAIs remained low, 0.09% (2/2224), 0.12% (27/23465) and 0.23% (124/53917) for 2020-2021, 2021-2022 and 2022-2023, respectively. As in previous years, NA-H275Y in A(H1N1)pdm09 viruses was the most frequent substitution causing HRI by oseltamivir and peramivir. Sequence-based analysis of polymerase acidic (PA) protein supplemented with phenotypic testing revealed low global frequencies of seasonal influenza viruses with reduced susceptibility (RS) to baloxavir, 0.07% (1/1376), 0.05% (9/18380) and 0.12% (48/39945) for 2020-2021, 2021-2022 and 2022-2023, respectively; commonly associated substitutions were PA-I38T/M/L. In Japan, the rate was 3.3% (16/488) during 2022-2023, with 11 A(H3N2) viruses having PA-I38T/M substitutions. For zoonotic viruses, 2.7% (3/111) contained substitutions, one each NA-H275Y, NA-S247N and NA-N295S, associated with RI/HRI NAI phenotypes, and none contained PA substitutions associated with RS to baloxavir. In conclusion, the great majority of seasonal and zoonotic influenza viruses remained susceptible to NAIs and CENI baloxavir.

The Kessler 6 (K6) scale has been widely used to screen for serious mental illness (SMI) in general populations. Given that populations with high burden of HIV may be more likely to experience poor mental health outcomes, it is important to validate measures used to assess SMI among these groups. Using data from CDC's National HIV Behavioral Surveillance (NHBS) system in the United States, we examined psychometric characteristics of the K6 scale, including exploratory factor analysis, scale reliability, construct validity, and review of interviewer feedback to explore scale performance in the field. Analyses confirmed a single factor structure and demonstrated that the K6 scale had high internal consistency and construct validity. Although interviewers noted that the effort item was difficult for some participants to understand, psychometric properties were not greatly improved with the deletion of the item. The results of this analysis suggest that the K6 scale is appropriate for use among NHBS populations with a high burden of HIV, including persons who inject drugs, heterosexually active adults at increased risk for HIV infection, women who exchange sex for money or drugs, and gay, bisexual, and other men who have sex with men.

INTRODUCTION: Given the increasing usage of vaping during pregnancy and limited longitudinal health-related data, there is an urgent need to assess the potential risks of vaping. AIMS AND METHODS: A cross-sectional study was conducted among pregnant UK adults (n = 140). Five study groups were purposively recruited: exclusive-smokers (n = 38), exclusive-vapers (former smokers) (n = 35), dual users of smoking and vaping (n = 25), dual users of smoking and nicotine replacement therapy (n = 10), and "never-users" of nicotine or tobacco products (n = 32). Sociodemographic, smoking, and vaping characteristics were assessed. Participants' urine samples were analyzed for biomarkers of exposure to tobacco alkaloids, and toxicants, including 14 volatile organic compounds (VOCs), tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), heavy metals (cadmium, lead, chromium, nickel, copper, and tin) and a polycyclic aromatic hydrocarbon (2-naphthol). Regression analysis was used to compare biomarkers by group. RESULTS: Nicotine levels varied across product users, but not significantly. After controlling for confounders, for most VOCs, biomarker levels were similar for exclusive-vapers and never-users and significantly lower than for exclusive-smokers and any dual users. There were generally no significant differences between groups for 2-naphthol or heavy metals. For NNAL, cadmium and chromium, a high percentage of values were below the limit of detection, making analyses unreliable. CONCLUSIONS: During pregnancy, former smokers who are established exclusive vapers, but not dual users, had levels of selected VOCs that were substantially lower than those for exclusive smokers and comparable with those who have never used nicotine or tobacco products. IMPLICATIONS: Based on the biomarkers assessed in this study, during pregnancy, on average, exclusive-vapers are likely to have similar levels of exposure to selected VOCs as never-users and far lower levels than exclusive-smokers or dual-users (although dual-vaping and smoking may result in less exposure than exclusive-smoking). This provides preliminary information about exposure to vaping during pregnancy and suggests that, for some biomarkers, exclusive vaping is likely to result in lower exposures than exclusive smoking or dual-use. There may be exposure to other vaping toxicants that were not explored in this study. Studies are needed to assess pregnancy and birth outcomes as well as early life effects.

BACKGROUND: Randomized control trials in sub-Saharan countries found male circumcision may prevent high-risk human papillomavirus (HR-HPV) acquisition. Using 2013-2016 National Health and Nutrition Examination Survey data, we explored the association between circumcision and HR-HPV among sexually experienced 18-59-year-old males. METHODS: Self-collected penile specimens were tested for HPV DNA. We estimated weighted HR-HPV prevalence (positivity to ≥1 HR type: HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68) by circumcision status. The association between circumcision and HR-HPV was assessed using multivariable logistic regression models. Effect modification by circumcision on the association between number of lifetime sex partners and HR-HPV was explored. RESULTS: Overall, 77.7% of males reported being circumcised, with large variation by race/ethnicity and country of birth. HR-HPV prevalence was significantly higher among circumcised (25.7%) than uncircumcised (20.4%) males; this was attenuated after adjustment for lifetime and new past-year sex partners (adjusted prevalence ratio: 1.10, 95%CI: 0.92-1.32). There was evidence circumcision modified the association between lifetime partners and HR-HPV, but HR-HPV prevalence increased with increasing number of partners in circumcised and uncircumcised males. CONCLUSIONS: Our observed lack of statistical association between circumcision and HR-HPV may differ from randomized trial results due to the differences between circumcised and uncircumcised males or differences in anatomic site sampled or timing of circumcision.

OBJECTIVE: To describe the association between syphilis treatment status and adverse pregnancy and neonatal outcomes among pregnancies complicated by syphilis. METHODS: Six jurisdictions that participated in SET-NET (Surveillance for Emerging Threats to Mothers and Babies Network) reported data on women with syphilis during pregnancy and outcomes that occurred during 2018-2021. Frequencies of adverse outcomes were reported by syphilis treatment status during pregnancy as defined by the 2021 Sexually Transmitted Infections Treatment Guidelines (inadequate, adequate, and no treatment). Adjusted risk ratios (aRRs) were modeled for each outcome comparing adequate treatment with no treatment and with inadequate treatment, controlling for the pregnant woman's age at infection, education level, insurance status, reported substance use, number of prenatal visits, and stage of syphilis. RESULTS: As of June 7, 2024, 1,682 singleton pregnancies complicated by syphilis were reported, with more than half of pregnant women adequately treated for syphilis (57.6%). Pregnant women with no or inadequate treatment had higher relative frequencies of adverse outcomes (stillbirth, prematurity, low birth weight [LBW], and neonatal intensive care unit [NICU] admission) than those with adequate treatment. The aRRs for stillbirth (9.9% vs 1.4%, aRR 3.72, 95% CI, 1.73-8.03), LBW (30.1% vs 9.9%, aRR 1.51, 95% CI, 1.07-2.14), and NICU admission (66.7% vs 27.0%, aRR 1.60, 95% CI, 1.28-1.98) were higher in pregnant women with no treatment compared with those with adequate treatment. Inadequate treatment was associated with LBW and NICU admission (24.9% vs 9.9%, aRR 1.81, 95% CI, 1.29-2.52; and 57.2% vs 27.0%, aRR 1.61, 95% CI, 1.31-1.99, respectively) compared with adequate treatment. CONCLUSION: The high relative frequencies of adverse pregnancy and neonatal outcomes associated with inadequately treated or untreated syphilis during pregnancy reinforce the importance of adequate treatment in mitigating the effects of syphilitic infection. Increased attention and systematic strategies are needed to address gaps in screening and treatment before and during pregnancy to reduce adverse pregnancy and neonatal outcomes.

BACKGROUND: Improvements in outcomes among children and adolescents diagnosed with cancer are attributable to many factors-including clinical trials such as those administered through the Children's Oncology Group (COG), as well as population-based resources like the National Childhood Cancer Registry (NCCR). The objective of this study was to link COG trial data with the NCCR to evaluate overall enrollment patterns. METHODS: Data were received from the NCCR and COG, which were linked using an array of variables and then compared to evaluate enrollment patterns in COG studies from 2007-2018. Multivariable logistic regression was used to identify characteristics associated with not being enrolled in a COG study. RESULTS: Among 134,696 NCCR cancer patients, 51,062 matched with COG study enrollees. There were several differences in demographic and clinical characteristics between those enrolled and not enrolled in COG studies. Enrollment was higher among children aged 0-4 years compared to adolescents aged 15-19 years (53.7% vs 20.1%). Differences by race/ethnicity were also observed; for example, those who identified as non-Hispanic White were more likely to be enrolled than those who identified as non-Hispanic Asian/Pacific Islander (38.8% vs 32.9%). In a multivariable logistic regression model, several characteristics were significantly associated with not being enrolled in a COG study, including age at diagnosis, year of diagnosis, race/ethnicity, and cancer type. CONCLUSION: Our results suggest that several groups are underrepresented in COG clinical trials. This information can help guide the prioritization of population groups for engagement in future studies.

BACKGROUND: Human papillomavirus (HPV)-associated cancers are vaccine preventable. In 2016, the previously recommended three-dose HPV vaccination series was changed to a two-dose series and nine-valent HPV vaccine (9vHPV) became the only HPV vaccine available in the United States. Data on longer-term duration of antibodies following a 9vHPV two-dose series are limited. We evaluated the immunogenicity and duration of antibodies up to three years after vaccination with a two-dose series of 9vHPV in a cohort of Alaska Native children. METHODS: We enrolled Alaska Native children aged 9-14 years who received 9vHPV in Anchorage, Alaska during 2017-2018. We collected sera at six months after dose one and at one month, one year, and three years after dose two to measure type-specific immunoglobulin G (IgG) concentrations for the 9vHPV types (HPV6/11/16/18/31/33/45/52/58). Aggregate type-specific IgG concentrations were reported as geometric mean concentrations (GMC). RESULTS: A total of 227 children completed the two-dose series of 9vHPV and provided ≥ 1 blood sample. The median age at enrollment was 11.0 years (range: 9.0-14.6) and was similar between males and females (p = 0.11). At one month after dose two, all 197 participants with available serum were seropositive for all 9vHPV types. Among 145 participants who had a specimen available at three years after dose two, 134 (92%) remained seropositive for all 9vHPV types. GMC peaked for all types at one month post dose two and remained higher at three years post dose two compared to six months post dose one. CONCLUSIONS: We found high immunogenicity and antibody persistence after a two-dose series of 9vHPV in this cohort of Alaska Native children. Further follow-up will determine duration of antibody detection in this cohort.

Although lead poisoning can cause detrimental health effects, it is largely preventable. Common exposure sources include contaminated soil, water, and lead-based paint in homes built before the 1978 ban on residential lead-containing paint. In North Carolina, testing for lead is encouraged for all children at ages 1 and 2 years, and is required for children covered by Medicaid. In October 2023, routine pediatric blood lead testing and follow-up investigations conducted by the North Carolina Department of Health and Human Services identified four asymptomatic cases of lead poisoning associated with consumption of cinnamon-containing applesauce packaged in pouches. The Food and Drug Administration (FDA) identified lead in the cinnamon as the source of contamination; chromium was later also detected in the cinnamon. FDA alerted the public on October 28, and the distributor initiated a voluntary recall the following day. To estimate the impact of the event and characterize reported cases, CDC initiated a national call for cases (defined as a blood lead level [BLL] ≥3.5 μg/dL in a person of any age in ≤3 months after consuming a recalled cinnamon-containing applesauce product). During November 22, 2023-April 12, 2024, a total of 44 U.S. states, the District of Columbia, and Puerto Rico reported 566 cases (55% in children aged <2 years, including 20% that were temporally associated with symptoms). The median maximum venous BLL was 7.2 μg/dL (range = 3.5-39.3 μg/dL). The hundreds of children poisoned by this incident highlight the importance of preventing toxic metal contamination of food and promoting routine childhood blood lead testing and follow-up to identify lead exposure sources. Clinicians and public health practitioners should be aware of the potential for exposure to toxic metals from less common sources, including food.

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.

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.

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.

BACKGROUND: Seasonal influenza causes an estimated 120 000 to 710 000 hospitalizations annually in the United States. Treatment with antiviral medications, such as oseltamivir, can reduce risks of hospitalization among people with influenza-associated illness. The US Centers for Disease Control and Prevention recommends initiating antiviral treatment as soon as possible for outpatients with suspected or confirmed influenza who have severe or progressive illness or are at higher risk of influenza complications. METHODS: We developed a probabilistic model to estimate the impact of antiviral treatment in reducing hospitalizations among US outpatients with influenza. Parameters were informed by seasonal influenza surveillance platforms and stratified by age group and whether individuals had a condition associated with higher risk of influenza complications. We modeled different scenarios for influenza antiviral effectiveness and outpatient testing and prescribing practices, then compared our results with a baseline scenario in which antivirals were not used. RESULTS: Across the modeled scenarios, antiviral treatment resulted in 1215 to 14 184 fewer influenza-associated hospitalizations on average when compared with the baseline scenario (0.2%-2.7% reduction). The greatest effects occurred among adults aged ≥65 years and individuals with conditions associated with higher risk of influenza complications. Modeling 50% improvements in access to care, testing, prescribing, and treatment resulted in greater potential impacts, with over 71 000 (13.3%) influenza-associated hospitalizations averted on average compared to baseline. CONCLUSIONS: Our results support recommendations to prioritize outpatient antiviral treatment among older adults and others at higher risk of influenza complications. Improving access to prompt testing and treatment among outpatients with suspected influenza could reduce hospitalizations substantially.

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.

BACKGROUND: The 2023-2024 influenza season included sustained elevated activity from December 2023-February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season. METHODS: During September 1, 2023-May 31, 2024, a multistate sentinel surveillance network of 24 medical centers in 20 U.S. states enrolled adults aged ≥18 years hospitalized with acute respiratory illness (ARI). Consistent with a test-negative design, cases tested positive for influenza viruses by molecular or antigen test, and controls tested negative for influenza viruses and SARS-CoV-2. Vaccine effectiveness (VE) against influenza-associated hospitalization was calculated as (1 - adjusted odds ratio for vaccination) × 100%. RESULTS: Among 7690 patients, including 1170 influenza cases (33% vaccinated) and 6520 controls, VE was 40% (95% CI: 31%-48%) with varying estimates by age (18-49 years: 53% [34%-67%]; 50-64 years: 47% [31%-60%]; ≥65 years: 31% [16%-43%]). Protection was similar among immunocompetent patients (40% [30%-49%]) and immunocompromised patients (32% [7-50%]). VE was statistically significant against influenza B (67% [35%-84%]) and A(H1N1) (36% [21%-48%]) and crossed the null against A(H3N2) (19% [-8%-39%]). VE was higher for patients 14-60 days from vaccination (54% [40%-65%]) than >120 days (18% [-1%-33%]). CONCLUSIONS: During 2023-2024, influenza vaccination reduced the risk of influenza A(H1N1)- and influenza B-associated hospitalizations among adults; effectiveness was lower in patients vaccinated >120 days prior to illness onset compared with those vaccinated 14-60 days prior.

IMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts. OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines. DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional study from 26 hospitals in 20 US states. Sociodemographic and clinical data were abstracted from health records, and structured interviews were conducted for knowledge and attitudes about RSV disease and RSV vaccines. EXPOSURES: Age, sex, race and ethnicity, pulmonary disease, immunocompromised status, long-term care facility residence, medical insurance, social vulnerability index (SVI), and educational level. MAIN OUTCOMES AND MEASURES: The exposures were identified a priori as possible factors associated with RSV vaccine receipt and were entered into a modified Poisson regression model accounting for state clustering, to assess for association with RSV vaccine receipt. Knowledge and attitudes were summarized with frequencies and proportions. RESULTS: Among 6746 hospitalized adults 60 years or older, median age was 73 (IQR, 66-80) years and 3451 (51.2%) were female. Among the 6599 patients with self-reported race and ethnicity, 699 (10.6%) were Hispanic, 1288 (19.5%) were non-Hispanic Black, 4299 (65.1%) were non-Hispanic White, and 313 (4.7%) were other race or ethnicity. There were 700 RSV-vaccinated (10.4%) and 6046 unvaccinated (89.6%) adults. Among 3219 unvaccinated adults who responded to RSV knowledge questions, 1519 (47.2%) had not heard of RSV or were unsure; 2525 of 3218 (78.5%) were unsure if they were eligible for RSV vaccine or thought they were not. In adjusted analyses, characteristics associated with RSV vaccination were being 75 years or older (adjusted risk ratio [ARR], 1.23; 95% CI, 1.10-1.38, P < .001), being male (ARR, 1.15; 95% CI, 1.01-1.30; P = .04), and having pulmonary disease (ARR, 1.39; 95% CI, 1.16-1.67; P < .001), immunocompromised status (ARR, 1.30; 95% CI, 1.14-1.48; P < .001), low (ARR, 1.47; 95% CI, 1.18-1.83, P < .001) or moderate (ARR, 1.47; 95% CI, 1.21-1.79; P < .001) SVI, and educational level consisting of 4 or more years of college (ARR, 2.91; 95% CI, 2.14-3.96; P < .001), at least some college or technical training (ARR, 1.85; 95% CI, 1.35-2.53; P < .001), or grade 12 education or General Educational Development (ARR, 1.44; 95% CI, 1.03-2.00; P = .03). RSV vaccination was less likely among residents of long-term care facilities, patients with Medicaid coverage, and uninsured patients. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of hospitalized adults, knowledge of RSV disease and RSV vaccine eligibility was low. Older adults and those with certain medical conditions were more likely to have received vaccine, suggesting appropriate prioritization, but sociodemographic differences in vaccine uptake occurred.

This article is an example of "Lessons from the Field." In early 2021, a call to action resulted in an unprecedented surge of volunteers for Utah's public health system. This call to action was in support of the rollout of COVID-19 vaccine across the state and the need to vaccinate the population as quickly and efficiently as possible. In this case study, we describe the events that preceded the surge of volunteers as well as challenges and resolutions to volunteer onboarding. Additionally, we discuss the importance of collaboration between local health departments and the Utah Department of Health and Human Services and describe how the partnership was strengthened by this specific emergency response.

BACKGROUND: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. However, they lack specimen collection and diagnosis dates to assign location of onset. Algorithms to classify CDI onset location using claims data have been published, but the degree of misclassification is unknown. METHODS: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016-2021 to Medicare beneficiaries with fee-for-service Part A/B coverage. We calculated sensitivity of ICD-10-CM codes in claims within ±28 days of EIP specimen collection. CDI was categorized as hospital, long-term care facility, or community-onset using three different Medicare claims-based algorithms based on claim type, ICD-10-CM code position, duration of hospitalization, and ICD-10-CM diagnosis code presence-on-admission indicators. We assessed concordance of EIP case classifications, based on chart review and specimen collection date, with claims case classifications using Cohen's kappa statistic. RESULTS: Of 12,671 CDI cases eligible for linkage, 9,032 (71%) were linked to a single, unique Medicare beneficiary. Compared to EIP, sensitivity of CDI ICD-10-CM codes was 81%; codes were more likely to be present for hospitalized patients (93.0%) than those who were not (56.2%). Concordance between EIP and Medicare claims algorithms ranged from 68% to 75%, depending on the algorithm used (κ = 0.56-0.66). CONCLUSION: ICD-10-CM codes in Medicare claims data had high sensitivity compared to laboratory-confirmed CDI reported to EIP. Claims-based epidemiologic classification algorithms had moderate concordance with EIP classification of onset location. Misclassification of CDI onset location using Medicare algorithms may bias findings of claims-based CDI studies.

COVID-19 vaccination averted approximately 68,000 hospitalizations during the 2023-24 respiratory season. In June 2024, CDC and the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥6 months receive a 2024-2025 COVID-19 vaccine, which targets Omicron JN.1 and JN.1-derived sublineages. Interim effectiveness of 2024-2025 COVID-19 vaccines was estimated against COVID-19-associated emergency department (ED) or urgent care (UC) visits during September 2024-January 2025 among adults aged ≥18 years in one CDC-funded vaccine effectiveness (VE) network, against COVID-19-associated hospitalization in immunocompetent adults aged ≥65 years in two networks, and against COVID-19-associated hospitalization among adults aged ≥65 years with immunocompromising conditions in one network. Among adults aged ≥18 years, VE against COVID-19-associated ED/UC visits was 33% (95% CI = 28%-38%) during the first 7-119 days after vaccination. Among immunocompetent adults aged ≥65 years from two CDC networks, VE estimates against COVID-19-associated hospitalization were 45% (95% CI = 36%-53%) and 46% (95% CI = 26%-60%) during the first 7-119 days after vaccination. Among adults aged ≥65 years with immunocompromising conditions in one network, VE was 40% (95% CI = 21%-54%) during the first 7-119 days after vaccination. These findings demonstrate that vaccination with a 2024-2025 COVID-19 vaccine dose provides additional protection against COVID-19-associated ED/UC encounters and hospitalizations compared with not receiving a 2024-2025 dose and support current CDC and ACIP recommendations that all persons aged ≥6 months receive a 2024-2025 COVID-19 vaccine dose.

Annual influenza vaccination is recommended for all persons aged ≥6 months in the United States. Interim influenza vaccine effectiveness (VE) was calculated among patients with acute respiratory illness-associated outpatient visits and hospitalizations from four VE networks during the 2024-25 influenza season (October 2024-February 2025). Among children and adolescents aged <18 years, VE against any influenza was 32%, 59%, and 60% in the outpatient setting in three networks, and against influenza-associated hospitalization was 63% and 78% in two networks. Among adults aged ≥18 years, VE in the outpatient setting was 36% and 54% in two networks and was 41% and 55% against hospitalization in two networks. Preliminary estimates indicate that receipt of the 2024-2025 influenza vaccine reduced the likelihood of medically attended influenza and influenza-associated hospitalization. CDC recommends annual receipt of an age-appropriate influenza vaccine by all eligible persons aged ≥6 months as long as influenza viruses continue to circulate locally.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals. Although mucocutaneous candidiasis is generally not life-threatening, it can cause considerable discomfort, recurrent infections, and complications, particularly in patients with underlying conditions such as diabetes or in those taking immunosuppressive therapies. The rise of difficult-to-treat Candida infections is driven by new host factors and antifungal resistance. Pathogens, such as Candida auris (Candidozyma auris) and fluconazole-resistant Candida parapsilosis, pose serious global health risks. Recent taxonomic revisions have reclassified several Candida spp, potentially causing confusion in clinical practice. Current management guidelines are limited in scope, with poor coverage of emerging pathogens and new treatment options. In this Review, we provide updated recommendations for managing Candida infections, with detailed evidence summaries available in the appendix.

BACKGROUND: While evidence suggests Medicaid expansion can reduce overdose, some expressed concern expansion fueled the US opioid overdose crisis by increasing access to low-cost prescription opioids diverted for non-prescribed use. Ecologic studies find a protective relationship or no relationship between expansion and area-level opioid prescribing. Little is known about the relationship between expansion and opioid use among people experiencing poverty who inject drugs (PWID), a population at heightened risk of overdose likely to benefit from Medicaid expansion. We examined whether expansion was associated with prescription opioid and benzodiazepine misuse among PWID experiencing poverty and whether associations varied by race/ethnicity and HIV status. METHODS: This serial cross-sectional observational study used generalized difference-in-differences models to analyze data (2012, 2015, 2018) from 19,728 PWID aged 18-64 with income ≤138 % of federal poverty line from 13 states in the CDC's National HIV Behavioral Surveillance. Outcomes included past 12-month non-injection and injection prescription opioid misuse and benzodiazepine misuse. RESULTS: The sample (N = 19,728) was 40 % non-Latinx Black persons and 22 % Latinx persons. Past 12-month non-injection prescription opioid misuse was 33 %, injection prescription opioid misuse was 16 %, and benzodiazepine use was 40 %. Across all models, there was no association between expansion and prescription opioid misuse (confidence intervals included 0) or prescription benzodiazepine misuse (confidence intervals included 0). Associations did not vary by race/ethnicity or HIV status. CONCLUSIONS: We found no association between Medicaid expansion and opioid or benzodiazepine misuse overall, by race/ethnicity, or HIV status among a large, geographically diverse sample of PWID. These findings provide empirical evidence that expansion is not associated with prescription opioid or benzodiazepine misuse in a population likely to benefit from expansion.

BACKGROUND: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial. OBJECTIVE: This simulation study aimed to investigate alternative methods to adjust for confounding in VE studies that have a test-negative design. METHODS: Adjustment for a disease risk score (DRS) is compared with multivariable logistic regression. Both stratification on the DRS and direct covariate adjustment of the DRS are examined. Multivariable logistic regression with all the covariates and with a limited subset of key covariates is considered. The performance of VE estimators is evaluated across a multinomial vaccination exposure in simulated datasets. RESULTS: Bias in VE estimates from multivariable models ranged from -5.3% to 6.1% across 4 levels of vaccination. Standard errors of VE estimates were unbiased, and 95% coverage probabilities were attained in most scenarios. The lowest coverage in the multivariable scenarios was 93.7% (95% CI 92.2%-95.2%) and occurred in the multivariable model with key covariates, while the highest coverage in the multivariable scenarios was 95.3% (95% CI 94.0%-96.6%) and occurred in the multivariable model with all covariates. Bias in VE estimates from DRS-adjusted models was low, ranging from -2.2% to 4.2%. However, the DRS-adjusted models underestimated the standard errors of VE estimates, with coverage sometimes below the 95% level. The lowest coverage in the DRS scenarios was 87.8% (95% CI 85.8%-89.8%) and occurred in the direct adjustment for the DRS model. The highest coverage in the DRS scenarios was 94.8% (95% CI 93.4%-96.2%) and occurred in the model that stratified on DRS. Although variation in the performance of VE estimates occurred across modeling strategies, variation in performance was also present across exposure groups. CONCLUSIONS: Overall, models using a DRS to adjust for confounding performed adequately but not as well as the multivariable models that adjusted for covariates individually.

Disparities are evident in viral hepatitis morbidity, mortality, and outcomes. Disparities are considered an outcome of social determinants of health (SDoH), as systemic differences in the conditions in which people are born, grow, live, work, and age can lead to differences in health outcomes and access to health care services among population groups.1,2 Disparities in viral hepatitis incidence and mortality are described in surveillance reports 3 and the literature4,5; however, an examination of the influence of SDoH on disparities in viral hepatitis incidence, mortality, and outcomes is missing from the literature. This gap in the literature could be a direct result of limitations in viral hepatitis surveillance data in capturing relevant measures. However, examining data on social, economic, physical, and political environments of people affected by viral hepatitis is important for understanding the incidence and outcomes of the disease, developing interventions, and assessing progress toward achieving health equity. 1 This commentary discusses existing disparities in viral hepatitis, explores how SDoH may contribute to these disparities, and highlights opportunities to examine the influence of SDoH on viral hepatitis outcomes.

Black women are disproportionately affected by HIV. We analyzed data from two Centers for Disease Control and Prevention's HIV surveillance systems to better understand HIV prevention strategies used by Black women at risk for and with HIV to help inform efforts to end HIV. Among sexually active Black women, we analyzed 2019 National HIV Behavioral Surveillance data on women without HIV (n = 4,033) and 2018-2020 Medical Monitoring Project data on women with HIV (n = 967). We reported percentages of HIV prevention strategies and services used and assessed differences between groups using Rao-Scott chi-square tests. Among Black women without HIV, 39% were aware of pre-exposure prophylaxis (PrEP); of these, 7% discussed PrEP with a healthcare provider, and 1% used PrEP in the past 12 months. Approximately 16% used a condom with their last sex partner; 36% reported that their last sex partner did not have HIV. Among Black women with HIV, 58% had condom-protected sex, 56% reported having sex while having sustained viral suppression, 3% had condomless sex with a partner on PrEP, and 24% had sex with a partner with HIV; 12% engaged in sex without using any HIV prevention strategy. HIV prevention strategies and services differed by selected demographic characteristics and social determinants of health. Although many sexually active Black women reported using HIV prevention strategies, there is room for improvement among those at risk for or with HIV. Tailoring prevention efforts based on individual needs and circumstances is essential for ending the HIV epidemic.

BACKGROUND: People who inject drugs (PWID) are especially vulnerable to harms from opioid use disorder (OUD). Medications for OUD (MOUD) effectively reduce overdose and infectious disease transmission risks. OBJECTIVE: We investigate whether state Medicaid coverage for methadone and buprenorphine is related to past-year MOUD use among PWID using cross-sectional, multilevel analyses with individual-level data on PWID from the Centers for Disease Control and Prevention's 2018 National HIV Behavioral Surveillance. The sample included 8,142 PWID aged 18-64 who reported daily opioid use from 22 U.S. metropolitan areas. Our outcome was any self-reported MOUD use in the past 12 months. Exposures were state Medicaid coverage and prior authorization requirements for methadone and buprenorphine. We interacted these exposures with PWID race/ethnicity, insurance status, and spatial access to treatment and harm reduction resources. RESULTS: Compared with PWID in states without Medicaid methadone coverage, odds of past-year MOUD use were 73% (p<0.05) higher among PWID in states with methadone coverage requiring prior authorization and 80% (p<0.05) higher among PWID in states with coverage without prior authorization. Insured PWID were twice as likely to report MOUD use than uninsured PWID, with no statistically significant differences between Medicaid versus other insurance. Medicaid prior authorization requirements for buprenorphine were not significantly associated with MOUD use. Non-Hispanic Black PWID were significantly less likely to use MOUD than non-Hispanic White and Hispanic PWID. CONCLUSIONS: State Medicaid methadone coverage was strongly associated with higher odds that PWID utilized MOUD, suggesting that expanding methadone insurance coverage could improve MOUD treatment in a vulnerable population.

BACKGROUND: clinical guidelines recommend initiation of antiviral therapy as soon as possible for patients hospitalized with confirmed or suspected influenza. METHODS: A multicenter US observational sentinel surveillance network prospectively enrolled adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza at 24 hospitals during October 1, 2022-July 21, 2023. A multivariable proportional odds model was used to compare peak pulmonary disease severity (no oxygen support, standard supplemental oxygen, high-flow oxygen/non-invasive ventilation, invasive mechanical ventilation, or death) after the day of hospital admission among patients starting oseltamivir treatment on the day of admission (early) versus those who did not (late or not treated), adjusting for baseline (admission day) severity, age, sex, site, and vaccination status. Multivariable logistic regression models were used to evaluate the odds of intensive care unit (ICU) admission, acute kidney replacement therapy or vasopressor use, and in-hospital death. RESULTS: A total of 840 influenza-positive patients were analyzed, including 415 (49%) who started oseltamivir treatment on the day of admission, and 425 (51%) who did not. Compared with late or not treated patients, those treated early had lower peak pulmonary disease severity (proportional aOR: 0.60, 95% CI: 0.49-0.72), and lower odds of intensive care unit admission (aOR: 0.24, 95% CI: 0.13-0.47), acute kidney replacement therapy or vasopressor use (aOR: 0.40, 95% CI: 0.22-0.67), and in-hospital death (aOR: 0.36, 95% CI: 0.18-0.72). CONCLUSION: Among adults hospitalized with influenza, treatment with oseltamivir on day of hospital admission was associated reduced risk of disease progression, including pulmonary and extrapulmonary organ failure and death.