Sex-specific associations between habitual snoring and cancer prevalence: insights from a US Cohort Study.

Study Objectives: To investigate the sex-specific association between habitual snoring and overall cancer prevalence and subtypes, and to examine the influence of age, body mass index (BMI), and sleep duration on this association. Methods: This study utilized data from the National Health and Nutrition Examination Survey cycles between 2005 and 2020 and included 15 892 participants aged 18 and over. We employed inverse probability of treatment weighting based on propensity scores to adjust for confounders when comparing the prevalence of cancer between habitual snorers and non-habitual snorers for each sex and cancer type. Subgroup analyses were conducted based on sleep duration, age, and BMI categories. Results: The cohort (mean age 48.2 years, 50.4% female, and 30.5% habitual snorers) reported 1385 cancer cases. In men, habitual snoring was linked to 26% lower odds of any cancer (OR 0.74, 95% CI: 0.66 to 0.83), while in women, it showed no significant difference except lower odds of breast cancer (OR 0.77, 95% CI: 0.63 to 0.94) and higher odds of cervix cancer (OR 1.54, 95% CI: 1.18 to 2.01). Age and sleep duration significantly influenced the snoring-cancer relationship, with notable variations by cancer type and sex. Conclusions: Habitual snoring exhibits sex-specific associations with cancer prevalence, showing lower prevalence in men and varied results in women. These findings emphasize the critical need for further research to uncover the biological mechanisms involved. Future investigations should consider integrating sleep characteristics with cancer prevention and screening strategies, focusing on longitudinal research and the integration of genetic and biomarker analyses to fully understand these complex relationships.

Learning implementation of a guideline based decision support system to improve hypertension treatment in primary care in China: pragmatic cluster randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a clinical decision support system (CDSS) in improving the use of guideline accordant antihypertensive treatment in primary care settings in China. DESIGN: Pragmatic, open label, cluster randomised trial. SETTING: 94 primary care practices in four urban regions of China between August 2019 and July 2022: Luoyang (central China), Jining (east China), and Shenzhen (south China, including two regions). PARTICIPANTS: 94 practices were randomised (46 to CDSS, 48 to usual care). 12 137 participants with hypertension who used up to two classes of antihypertensives and had a systolic blood pressure <180 mm Hg and diastolic blood pressure <110 mm Hg were included. INTERVENTIONS: Primary care practices were randomised to use an electronic health record based CDSS, which recommended a specific guideline accordant regimen for initiation, titration, or switching of antihypertensive (the intervention), or to use the same electronic health record without CDSS and provide treatment as usual (control). MAIN OUTCOME MEASURES: The primary outcome was the proportion of hypertension related visits during which an appropriate (guideline accordant) treatment was provided. Secondary outcomes were the average reduction in systolic blood pressure and proportion of participants with controlled blood pressure (<140/90 mm Hg) at the last scheduled follow-up. Safety outcomes were patient reported antihypertensive treatment related events, including syncope, injurious fall, symptomatic hypotension or systolic blood pressure <90 mm Hg, and bradycardia. RESULTS: 5755 participants with 23 113 visits in the intervention group and 6382 participants with 27 868 visits in the control group were included. Mean age was 61 (standard deviation 13) years and 42.5% were women. During a median 11.6 months of follow-up, the proportion of visits at which appropriate treatment was given was higher in the intervention group than in the control group (77.8% (17 975/23 113) v 62.2% (17 328/27 868); absolute difference 15.2 percentage points (95% confidence interval (CI) 10.7 to 19.8); P<0.001; odds ratio 2.17 (95% CI 1.75 to 2.69); P<0.001). Compared with participants in the control group, those in the intervention group had a 1.6 mm Hg (95% CI -2.7 to -0.5) greater reduction in systolic blood pressure (-1.5 mm Hg v 0.3 mm Hg; P=0.006) and a 4.4 percentage point (95% CI -0.7 to 9.5) improvement in blood pressure control rate (69.0% (3415/4952) v 64.6% (3778/5845); P=0.07). Patient reported antihypertensive treatment related adverse effects were rare in both groups. CONCLUSIONS: Use of a CDSS in primary care in China improved the provision of guideline accordant antihypertensive treatment and led to a modest reduction in blood pressure. The CDSS offers a promising approach to delivering better care for hypertension, both safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov NCT03636334.

Internal tremors and vibrations in long COVID: a cross-sectional study.

BACKGROUND: Internal tremors and vibrations are symptoms previously described as part of neurologic disorders but not fully described as a part of long COVID. This study compared pre-pandemic comorbidities, new-onset conditions, and long COVID symptoms between people with internal tremors and vibrations as part of their long COVID symptoms and people with long COVID but without these symptoms. METHODS: The Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study surveyed 423 adults who had long COVID between May 12, 2022 and June 1, 2023. The exposure variable was long COVID symptoms of internal tremors and vibrations. The outcome variables were demographic characteristics, pre-pandemic comorbidities, new-onset conditions, other symptoms, and quality of life. RESULTS: Among study participants with long COVID, median age was 46 years [IQR, 38-56]), 74% were female, 87% were Non-Hispanic White, and 158 (37%) reported "internal tremors, or buzzing/vibration" as a long COVID symptom. The 2 groups reported similar pre-pandemic comorbidities, but people with internal tremors reported worse health as measured by the Euro-QoL visual analogue scale (median: 40 points [IQR, 30-60] vs. 50 points [IQR, 35-62], P = 0.007) and had higher rates of new-onset mast cell disorders (11% [95% CI, 7.1-18] vs. 2.6% [1.2-5.6], P = 0.008) and neurologic conditions (22% [95% CI, 16-29] vs. 8.3% [5.4-12], P = 0.004). CONCLUSIONS: Among people with long COVID, those with internal tremors and vibrations had different conditions and symptoms and worse health status compared with others who had long COVID without these symptoms.

Derivation of an Annualized Claims-Based Major Adverse Cardiovascular Event Estimator in Type 2 Diabetes.

Background: Major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality among adults with type 2 diabetes. Currently, available MACE prediction models have important limitations, including reliance on data that may not be routinely available, narrow focus on primary prevention, limited patient populations, and longtime horizons for risk prediction. Objectives: The purpose of this study was to derive and internally validate a claims-based prediction model for 1-year risk of MACE in type 2 diabetes. Methods: Using medical and pharmacy claims for adults with type 2 diabetes enrolled in commercial, Medicare Advantage, and Medicare fee-for-service plans between 2014 and 2021, we derived and internally validated the annualized claims-based MACE estimator (ACME) model to predict the risk of MACE (nonfatal acute myocardial infarction, nonfatal stroke, and all-cause mortality). The Cox proportional hazards model was composed of 30 covariates, including patient age, sex, comorbidities, and medications. Results: The study cohort comprised 6,623,526 adults with type 2 diabetes, mean age 68.1 ± 10.6 years, 49.8% women, and 73.0% Non-Hispanic White. ACME had a concordance index of 0.74 (validation index range: 0.739-0.741). The predicted 1-year risk of the study cohort ranged from 0.4% to 99.9%, with a median risk of 3.4% (IQR: 2.3%-6.5%). Conclusions: ACME was derived in a large usual care population, relies on routinely available data, and estimates short-term MACE risk. It can support population risk stratification at the health system and payer levels, participant identification for decentralized clinical trials of cardiovascular disease, and risk-stratified observational studies using real-world data.

Effectiveness of glucose-lowering medications on cardiovascular outcomes in patients with type 2 diabetes at moderate cardiovascular risk.

Cardiovascular disease (CVD) is the leading cause of death among people with type 2 diabetes1-5, most of whom are at moderate CVD risk6, yet there is limited evidence on the preferred choice of glucose-lowering medication for CVD risk reduction in this population. Here, we report the results of a retrospective cohort study where data for US adults with type 2 diabetes and moderate risk for CVD are used to compare the risks of experiencing a major adverse cardiovascular event with initiation of glucagon-like peptide-1 receptor agonists (GLP-1RA; n = 44,188), sodium-glucose cotransporter 2 inhibitors (SGLT2i; n = 47,094), dipeptidyl peptidase-4 inhibitors (DPP4i; n = 84,315) and sulfonylureas (n = 210,679). Compared to DPP4i, GLP-1RA (hazard ratio (HR) 0.87; 95% confidence interval (CI) 0.82-0.93) and SGLT2i (HR 0.85; 95% CI 0.81-0.90) were associated with a lower risk of a major adverse cardiovascular event, whereas sulfonylureas were associated with a higher risk (HR 1.19; 95% CI 1.16-1.22). Thus, GLP-1RA and SGLT2i may be the preferred glucose-lowering agents for cardiovascular risk reduction in patients at moderate baseline risk for CVD. ClinicalTrials.gov registration: NCT05214573.

Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy.

OBJECTIVE: To investigate whether the choice of glucose-lowering agent for type 2 diabetes (T2D) impacts a patient's risk of developing sight-threatening diabetic retinopathy complications. DESIGN: Retrospective observational database study emulating an idealized target trial. SUBJECTS: Adult (≥21 years) enrollees in United States commercial, Medicare Advantage, and Medicare fee-for-service plans from January 1, 2014, to December 31, 2021, with T2D and moderate cardiovascular disease (CVD) risk who had no baseline history of advanced diabetic retinal complications, initiating treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sulfonylureas. METHODS: We used inverse propensity scoring weights in time-to-event Cox proportional hazards models. MAIN OUTCOME MEASURES: Treatment for either diabetic macular edema or proliferative diabetic retinopathy. RESULTS: The final study population included 371 698 patients, of whom 42 265 initiated GLP-1 RA, 53 476 initiated SGLT2i, 78 444 initiated DPP-4i, and 197 513 initiated sulfonylurea agents. The probability of treatment for sight-threatening retinopathy within 2 and 5 years was 0.3% and 0.7% for patients initiating SGLT2i (median follow-up 830 [interquartile range (IQR), 343-1401] days), 0.4% and 1.0% for GLP-1 RA (669 [IQR, 256-1167] days), 0.4% and 0.9% for DPP-4i (1263 [IQR, 688-1938] days), and 0.5% and 1.2% for sulfonylurea (1223 [IQR, 662-1879] days). Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of treatment for sight-threatening retinopathy compared with all other medication classes, including GLP-1 RA (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.97), DPP-4i (HR, 0.79; 95% CI, 0.64-0.97), and sulfonylurea (HR, 0.61; 95% CI, 0.50-0.74). Glucagon-like peptide-1 receptor agonists use was associated with a similar risk of sight-threatening retinopathy as DPP-4i (HR, 1.07; 95% CI, 0.85-1.35) and sulfonylurea (HR, 0.83; 95% CI, 0.67-1.03). CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors use was associated with a lower risk of sight-threatening diabetic retinopathy among adults with T2D and moderate CVD risk compared with other glucose-lowering therapies. Glucagon-like peptide-1 receptor agonists do not confer increased retinal risk, relative to DPP-4i and sulfonylurea medications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Calculation of Overall Hospital Quality Star Ratings With and Without Inclusion of the Peer Grouping Step.

Importance: The Centers for Medicare & Medicaid Services (CMS) Overall Star Rating is widely used by patients and consumers, and there is continued stakeholder curiosity surrounding the inclusion of a peer grouping step, implemented to the 2021 Overall Star Rating methods. Objective: To calculate hospital star rating scores with and without the peer grouping step, with the former approach stratifying hospitals into 3-, 4-, and 5-measure group peer groups based on the number of measure groups with at least 3 reported measures. Design, Setting, and Participants: This cross-sectional study used Care Compare website data from January 2023 for 3076 hospitals that received a star rating in 2023. Data were analyzed from April 2023 to December 2023. Exposure: Peer grouping vs no peer grouping. Main Outcomes and Measures: The primary outcome was the distribution of star ratings, with 1 star being the lowest-performing hospitals and 5 stars, the highest. Analyses additionally identified the number of hospitals with a higher, lower, or identical star rating with the use of the peer grouping step compared with its nonuse, stratified by certain hospital characteristics. Results: Among 3076 hospitals that received a star rating in 2023, most were nonspecialty (1994 hospitals [64.8%]), nonteaching (1807 hospitals [58.7%]), non-safety net (2326 hospitals [75.6%]), non-critical access (2826 hospitals [91.9%]) hospitals with fewer than 200 beds (1822 hospitals [59.2%]) and located in an urban geographic designations (1935 hospitals [62.9%]). The presence of the peer grouping step resulted in 585 hospitals (19.0%) being assigned a different star rating than if the peer grouping step was absent, including considerably more hospitals receiving a higher star rating (517 hospitals) rather than a lower (68 hospitals) star rating. Hospital characteristics associated with a higher star rating included urbanicity (351 hospitals [67.9%]), non-safety net status (414 hospitals [80.1%]), and fewer than 200 beds (287 hospitals [55.6%]). Collectively, the presence of the peer grouping step supports a like-to-like comparison among hospitals and supports the ability of patients to assess overall hospital quality. Conclusions and Relevance: In this cross-sectional study, inclusion of the peer grouping in the CMS star rating method resulted in modest changes in hospital star ratings compared with application of the method without peer grouping. Given improvement in face validity and the close association between the current peer grouping approach and stakeholder needs for peer-comparison, the current CMS Overall Star Rating method allows for durable comparisons in hospital performance.

The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-Blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.

BACKGROUND: Individuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID. METHODS: The PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders. CONCLUSION: The PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.

Long COVID Characteristics and Experience: A Descriptive Study From the Yale LISTEN Research Cohort.

BACKGROUND: The experience of people with long COVID needs further amplification, especially with a comprehensive focus on symptomatology, treatments, and the impact on daily life and finances. Our intent is to describe the experience of people with long COVID symptomatology and characterize the psychological, social, and financial challenges they experience. METHODS: We collected data from individuals aged 18 and older reporting long COVID as participants in the Yale Listen to Immune, Symptom and Treatment Experiences Now study. The sample population included 441 participants surveyed between May 2022 and July 2023. We evaluated their demographic characteristics, socioeconomic and psychological status, index infection period, health status, quality of life, symptoms, treatments, prepandemic comorbidities, and new-onset conditions. RESULTS: Overall, the median age of the participants with long COVID was 46 years (interquartile range [IQR]: 38-57 years); 74% were women, 86% were non-Hispanic White, and 93% were from the United States. Participants reported a low health status measured by the Euro-QoL visual analog scale, with a median score of 49 (IQR: 32-61). Participants documented a diverse range of symptoms, with all 96 possible symptom choices being reported. Additionally, participants had tried many treatments (median number of treatments: 19, IQR: 12-28). They were also experiencing psychological distress, social isolation, and financial stress. CONCLUSIONS: Despite having tried numerous treatments, participants with long COVID continued to experience an array of health and financial challenges-findings that underscore the failure of the healthcare system to address the medical needs of people with long COVID. These insights highlight the need for crucial medical, mental health, financial, and community support services, as well as further scientific investigation to address the complex impact of long COVID.

Enrollment in High-Deductible Health Plans and Incident Diabetes Complications.

Importance: Preventing diabetes complications requires monitoring and control of hyperglycemia and cardiovascular risk factors. Switching to high-deductible health plans (HDHPs) has been shown to hinder aspects of diabetes care; however, the association of HDHP enrollment with microvascular and macrovascular diabetes complications is unknown. Objective: To examine the association between an employer-required switch to an HDHP and incident complications of diabetes. Design, Setting, and Participants: This retrospective cohort study used deidentified administrative claims data for US adults with diabetes enrolled in employer-sponsored health plans between January 1, 2010, and December 31, 2019. Data analysis was performed from May 26, 2022, to January 2, 2024. Exposures: Adults with a baseline year of non-HDHP enrollment who had to switch to an HDHP because their employer offered no non-HDHP alternative in that year were compared with adults who were continuously enrolled in a non-HDHP. Main Outcomes and Measures: Mixed-effects logistic regression models examined the association between switching to an HDHP and, individually, the odds of myocardial infarction, stroke, hospitalization for heart failure, lower-extremity complication, end-stage kidney disease, proliferative retinopathy, treatment for retinopathy, and blindness. Models were adjusted for demographics, comorbidities, and medications, with inverse propensity score weighting used to account for potential selection bias. Results: The study included 42 326 adults who switched to an HDHP (mean [SD] age, 52 [10] years; 19 752 [46.7%] female) and 202 729 adults who did not switch (mean [SD] age, 53 [10] years; 89 828 [44.3%] female). Those who switched to an HDHP had greater odds of experiencing all diabetes complications (odds ratio [OR], 1.11; 95% CI, 1.06-1.16 for myocardial infarction; OR, 1.15; 95% CI, 1.09-1.21 for stroke; OR, 1.35; 95% CI, 1.30-1.41 for hospitalization for heart failure; OR, 2.53; 95% CI, 2.38-2.70 for end-stage kidney disease; OR, 2.23; 95% CI, 2.17-2.29 for lower-extremity complication; OR, 1.17; 95% CI, 1.13-1.21 for proliferative retinopathy; OR, 2.35; 95% CI, 2.18-2.54 for blindness; and OR, 2.28; 95% CI, 2.15-2.41 for retinopathy treatment). Conclusions and Relevance: This study found that an employer-driven switch to an HDHP was associated with increased odds of experiencing all diabetes complications. These findings reinforce the potential harm associated with HDHPs for people with diabetes and the importance of affordable and accessible chronic disease management, which is hindered by high out-of-pocket costs incurred by HDHPs.

Disparities in Acute and Chronic Complications of Diabetes Along the U.S. Rural-Urban Continuum.

OBJECTIVE: To determine the relative hazards of acute and chronic diabetes complications among people with diabetes across the U.S. rural-urban continuum. RESEARCH DESIGN AND METHODS: This retrospective cohort study used the OptumLabs Data Warehouse, a deidentified data set of U.S. commercial and Medicare Advantage beneficiaries, to follow 2,901,563 adults (age ≥18 years) with diabetes between 1 January 2012 and 31 December 2021. We compared adjusted hazard ratios (HRs) of diabetes complications in remote areas (population <2,500), small towns (population 2,500-50,000), and cities (population >50,000). RESULTS: Compared with residents of cities, residents of remote areas had greater hazards of myocardial infarction (HR 1.06 [95% CI 1.02-1.10]) and revascularization (HR 1.04 [1.02-1.06]) but lower hazards of hyperglycemia (HR 0.90 [0.83-0.98]) and stroke (HR 0.91 [0.88-0.95]). Compared with cities, residents of small towns had greater hazards of hyperglycemia (HR 1.06 [1.02-1.10]), hypoglycemia (HR 1.15 [1.12-1.18]), end-stage kidney disease (HR 1.04 [1.03-1.06]), myocardial infarction (HR 1.10 [1.08-1.12]), heart failure (HR 1.05 [1.03-1.06]), amputation (HR 1.05 [1.02-1.09]), other lower-extremity complications (HR 1.02 [1.01-1.03]), and revascularization (HR 1.05 [1.04-1.06]) but a smaller hazard of stroke (HR 0.95 [0.94-0.97]). Compared with small towns, residents of remote areas had lower hazards of hyperglycemia (HR 0.85 [0.78-0.93]), hypoglycemia (HR 0.92 [0.87-0.97]), and heart failure (HR 0.94 [0.91-0.97]). Hazards of retinopathy and atrial fibrillation/flutter did not vary geographically. CONCLUSIONS: Adults in small towns are disproportionately impacted by complications of diabetes. Future studies should probe for the reasons underlying these disparities.

Healthy immigrant community study protocol: A randomized controlled trial of a social network intervention for cardiovascular risk reduction among Hispanic and Somali adults.

BACKGROUND: Immigrants to the United States face structural barriers that contribute to rising cardiovascular risk factors and obesity after immigration. This manuscript describes the development of the Healthy Immigrant Community protocol and baseline measures for a stepped wedge cluster randomized trial to test the effectiveness of a social network intervention for cardiovascular risk reduction among two immigrant populations. METHODS: We developed a social network-informed, community-based, participatory research-derived health promotion intervention with Hispanic and Somali immigrant communities in Minnesota consisting of mentoring, educational and motivational sessions, group activities, and a community toolkit for healthy weight loss delivered by culturally concordant health promoters (HPs) to their social networks. Using a stepped wedge cluster randomized design, social network-based groups were randomly assigned to receive the intervention either immediately or after a delay of one year. Outcomes, measured at baseline, 6 months, 12 months, and 24 months, were derived from the American Heart Association's "Life's Simple 7": BMI and waist circumference, blood pressure, fasting blood glucose, total cholesterol, physical activity level, and dietary quality. RESULTS: A total of 51 HPs were enrolled and randomized (29 Hispanic; 22 Somali). There were 475 participants enrolled in the study, representing a mean social network group size of 8 (range, 5-12). The mean BMI of the sample (32.2) was in the "obese" range. CONCLUSION: Processes and products from this Healthy Immigrant Community protocol are relevant to other communities seeking to reduce cardiovascular risk factors and negative health behaviors among immigrant populations by leveraging the influence of their social networks.

Measuring Equity in Readmission as a Distinct Assessment of Hospital Performance.

Importance: Equity is an essential domain of health care quality. The Centers for Medicare & Medicaid Services (CMS) developed 2 Disparity Methods that together assess equity in clinical outcomes. Objectives: To define a measure of equitable readmissions; identify hospitals with equitable readmissions by insurance (dual eligible vs non-dual eligible) or patient race (Black vs White); and compare hospitals with and without equitable readmissions by hospital characteristics and performance on accountability measures (quality, cost, and value). Design, Setting, and Participants: Cross-sectional study of US hospitals eligible for the CMS Hospital-Wide Readmission measure using Medicare data from July 2018 through June 2019. Main Outcomes and Measures: We created a definition of equitable readmissions using CMS Disparity Methods, which evaluate hospitals on 2 methods: outcomes for populations at risk for disparities (across-hospital method); and disparities in care within hospitals' patient populations (within-a-single-hospital method). Exposures: Hospital patient demographics; hospital characteristics; and 3 measures of hospital performance-quality, cost, and value (quality relative to cost). Results: Of 4638 hospitals, 74% served a sufficient number of dual-eligible patients, and 42% served a sufficient number of Black patients to apply CMS Disparity Methods by insurance and race. Of eligible hospitals, 17% had equitable readmission rates by insurance and 30% by race. Hospitals with equitable readmissions by insurance or race cared for a lower percentage of Black patients (insurance, 1.9% [IQR, 0.2%-8.8%] vs 3.3% [IQR, 0.7%-10.8%], P < .01; race, 7.6% [IQR, 3.2%-16.6%] vs 9.3% [IQR, 4.0%-19.0%], P = .01), and differed from nonequitable hospitals in multiple domains (teaching status, geography, size; P < .01). In examining equity by insurance, hospitals with low costs were more likely to have equitable readmissions (odds ratio, 1.57 [95% CI, 1.38-1.77), and there was no relationship between quality and value, and equity. In examining equity by race, hospitals with high overall quality were more likely to have equitable readmissions (odds ratio, 1.14 [95% CI, 1.03-1.26]), and there was no relationship between cost and value, and equity. Conclusion and Relevance: A minority of hospitals achieved equitable readmissions. Notably, hospitals with equitable readmissions were characteristically different from those without. For example, hospitals with equitable readmissions served fewer Black patients, reinforcing the role of structural racism in hospital-level inequities. Implementation of an equitable readmission measure must consider unequal distribution of at-risk patients among hospitals.

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-ß and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

Multilevel Implementation Strategies for Adolescent Human Papillomavirus Vaccine Uptake: A Cluster Randomized Clinical Trial.

Importance: Despite availability of a safe and effective vaccine, an estimated 36 500 new cancers in the US result from human papillomavirus (HPV) annually. HPV vaccine uptake falls short of national public health goals and lags other adolescent vaccines. Objective: To evaluate the individual and combined impact of 2 evidence-based interventions on HPV vaccination rates among 11- and 12-year-old children. Design, Setting, and Participants: The study team conducted a cluster randomized clinical trial with a stepped-wedge factorial design at 6 primary care practices affiliated with Mayo Clinic in southeastern Minnesota. Using block randomization to ensure balance of patient volumes across interventions, each practice was allocated to a sequence of four 12-month steps with the initial baseline step followed by 2 intermediate steps (none, 1, or both interventions) and a final step wherein all practices implemented both interventions. Each month, all eligible children who turned 11 or 12 years in the 2 months prior were identified and followed until the end of the step. Data were analyzed from April 2018 through March 2019. Participants included children who turned 11 or 12 years old and were due for a dose of the HPV vaccine. Interventions: Parents of eligible patients were mailed reminder/recalls following their child's birthdays. Health care professionals received confidential audit/feedback on their personal in-office success with HPV vaccine uptake via intra-campus mail. These 2 interventions were assessed separately and in combination. Main Outcomes and Measures: Eligible patients' receipt of any valid dose of HPV vaccine during the study step. Results: The cohort was comprised of 9242 11-year-olds (5165 [55.9%]) and 12-year-olds (4077 [44.1%]), and slightly more males (4848 [52.5%]). Parent reminder/recall resulted in 34.6% receiving a dose of HPV vaccine, health care professional audit/feedback, 30.4%, both interventions together resulted in 39.7%-all contrasted to usual care, 21.9%. Compared with usual care, the odds of HPV vaccination were higher for parent reminder/recall (odds ratio [OR], 1.56; 95% CI, 1.23-1.97) and for the combination of parent reminder/recall and health care professional audit/feedback (OR, 2.03; 95% CI, 1.44-2.85). Health care professional audit/feedback alone did not differ significantly from usual care (OR, 1.19; 95% CI, 0.94-1.51). Conclusions and Relevance: In this cluster randomized trial, the combination of parent reminder/recall and health care professional audit/feedback increased the odds of HPV vaccination compared with usual care. These findings underscore the value of simultaneous implementation of evidence-based strategies to improve HPV vaccination.

Why Are There So Few Women Medical School Deans? Debunking the Myth That Shorter Tenures Drive Disparities.

PURPOSE: Gender disparities among the senior echelons of academic medicine are striking and persistent. The role of medical school dean has been particularly immune to gender diversity, and limited prior research identified women's shorter decanal tenures as a potential driver. The authors assessed gender differences in tenure length of deanships in the current era to elucidate this finding. METHOD: From October 2020 to June 2021, the authors collected information about medical school deanships that were held from January 1, 2006, to June 30, 2020. All schools were members of the Association of American Medical Colleges (AAMC). The authors collected data from online public records and augmented their findings via direct outreach to medical schools. They used time-to-event analyses before and after adjustment for interim vs permanent status of the initial appointment, school ownership (public/private), and school size to assess for gender differences in length of deanship tenure during the study period. The unit of analysis was deanships, and the primary outcome was length of deanships measured in years. RESULTS: Authors included data on 528 deanships. Women held 91 (17%) of these terms. Men held the majority of permanent deanships (n = 352 [85%]). A greater percentage of the deanships held by women were interim only (n = 27 [30%]) compared with men (n = 85 [20%]). In unadjusted and adjusted analyses, there were no significant gender differences in length of deanship tenures. CONCLUSIONS: Analysis of appointments of AAMC-member medical school deans from 2006 to 2020 revealed that women have remained in their deanships as long as their male counterparts. The myth about women deans' shorter longevity should no longer be promulgated. Academic medicine should consider novel solutions to addressing women's persistent underrepresentation in the dean role, including employing the gender proportionality principle used in the business and legal communities.

Post-Vaccination Syndrome: A Descriptive Analysis of Reported Symptoms and Patient Experiences After Covid-19 Immunization.

Introduction: A chronic post-vaccination syndrome (PVS) after covid-19 vaccination has been reported but has yet to be well characterized. Methods: We included 241 individuals aged 18 and older who self-reported PVS after covid-19 vaccination and who joined the online Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study from May 2022 to July 2023. We summarized their demographics, health status, symptoms, treatments tried, and overall experience. Results: The median age of participants was 46 years (interquartile range [IQR]: 38 to 56), with 192 (80%) identifying as female, 209 (87%) as non-Hispanic White, and 211 (88%) from the United States. Among these participants with PVS, 127 (55%) had received the BNT162b2 [Pfizer-BioNTech] vaccine, and 86 (37%) received the mRNA-1273 [Moderna] vaccine. The median time from the day of index vaccination to symptom onset was three days (IQR: 1 day to 8 days). The time from vaccination to symptom survey completion was 595 days (IQR: 417 to 661 days). The median Euro-QoL visual analogue scale score was 50 (IQR: 39 to 70). The five most common symptoms were exercise intolerance (71%), excessive fatigue (69%), numbness (63%), brain fog (63%), and neuropathy (63%). In the week before survey completion, participants reported feeling unease (93%), fearfulness (82%), and overwhelmed by worries (81%), as well as feelings of helplessness (80%), anxiety (76%), depression (76%), hopelessness (72%), and worthlessness (49%) at least once. Participants reported a median of 20 (IQR: 13 to 30) interventions to treat their condition. Conclusions: In this study, individuals who reported PVS after covid-19 vaccination had low health status, high symptom burden, and high psychosocial stress despite trying many treatments. There is a need for continued investigation to understand and treat this condition.

Uncovering heterogeneous cardiometabolic risk profiles in US adults: the role of social and behavioral determinants of health.

INTRODUCTION: Social and behavioral determinants of health (SBDH) have been linked to diabetes risk, but their role in explaining variations in cardiometabolic risk across race/ethnicity in US adults is unclear. This study aimed to classify adults into distinct cardiometabolic risk subgroups using SBDH and clinically measured metabolic risk factors, while comparing their associations with undiagnosed diabetes and pre-diabetes by race/ethnicity. RESEARCH DESIGN AND METHODS: We analyzed data from 38,476 US adults without prior diabetes diagnosis from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The k-prototypes clustering algorithm was used to identify subgroups based on 16 SBDH and 13 metabolic risk factors. Each participant was classified as having no diabetes, pre-diabetes or undiagnosed diabetes using contemporaneous laboratory data. Logistic regression was used to assess associations between subgroups and diabetes status, focusing on differences by race/ethnicity. RESULTS: Three subgroups were identified: cluster 1, primarily middle-aged adults with high rates of smoking, alcohol use, short sleep duration, and low diet quality; cluster 2, mostly young non-white adults with low income, low health insurance coverage, and limited healthcare access; and cluster 3, mostly older males who were the least physically active, but with high insurance coverage and healthcare access. Compared with cluster 2, adjusted ORs (95% CI) for undiagnosed diabetes were 14.9 (10.9, 20.2) in cluster 3 and 3.7 (2.8, 4.8) in cluster 1. Clusters 1 and 3 (vs cluster 2) had high odds of pre-diabetes, with ORs of 1.8 (1.6, 1.9) and 2.1 (1.8, 2.4), respectively. Race/ethnicity was found to modify the relationship between identified subgroups and pre-diabetes risk. CONCLUSIONS: Self-reported SBDH combined with metabolic factors can be used to classify adults into subgroups with distinct cardiometabolic risk profiles. This approach may help identify individuals who would benefit from screening for diabetes and pre-diabetes and potentially suggest effective prevention strategies.

Comparative effectiveness of second line glucose lowering drug treatments using real world data: emulation of a target trial.

Objective: To build on the recently completed GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) randomised trial examining the comparative effectiveness of second line glucose lowering drugs in achieving and maintaining glycaemic control in adults with type 2 diabetes. Design: Emulation of a target trial. Setting: Medical and pharmacy claims data from the OptumLabs Data Warehouse, a de-identified US national dataset of beneficiaries of commercially insured and Medicare Advantage plans, 29 March 2013 to 30 June 2021. Participants: Adults (≥18 years) with type 2 diabetes who first started taking glimepiride, sitagliptin, liraglutide, insulin glargine, or canagliflozin between 29 March 2013 and 30 June 2021. Participants were treatment naive or were receiving metformin monotherapy at the time of starting the study drug. Main outcome measures: The main outcomes were time to primary and secondary metabolic failure of the assigned treatment, calculated as days to haemoglobin A1c levels of ≥7.0% and >7.5%, respectively. Secondary metabolic, cardiovascular, and microvascular outcomes were analysed as specified in the GRADE statistical analysis plan. Propensity scores were estimated with the gradient boosting method, and inverse propensity score weighting was used to emulate randomisation to the treatment groups, which were then compared with Cox proportional hazards regression. Results: The study cohort included participants starting treatment with glimepiride (n=20 511), liraglutide (n=5569), sitagliptin (n=13 039), insulin glargine (n=7262), and canagliflozin (n=5290). The insulin glargine arm was excluded because of insufficient control of confounding. Median times to primary metabolic failure were 439 (95% confidence interval 400 to 489) days in the canagliflozin arm, 439 (426 to 453) days in the glimepiride arm, 624 (567 to 731) days in the liraglutide arm, and 461 (442 to 482) days in the sitagliptin arm. Median time to secondary metabolic failure was also longest in the liraglutide arm. Adults receiving liraglutide had the lowest one year cumulative incidence rate of primary metabolic failure (0.37, 95% confidence interval 0.35 to 0.40) followed by sitagliptin (0.44, 0.43 to 0.45), glimepiride (0.45, 0.44 to 0.45), and canagliflozin (0.46, 0.44 to 0.48). Similarly, the one year cumulative incidence rate of secondary metabolic failure was 0.27 (0.25 to 0.29) in the canagliflozin arm, 0.28 (0.27 to 0.29) in the glimepiride arm, 0.23 (0.21 to 0.26) in the liraglutide arm, and 0.28 (0.27 to 0.29) in the sitagliptin arm. No differences were observed between the study arms in the rates of microvascular and macrovascular complications. Conclusions: In this target trial emulation of an expanded GRADE study framework, liraglutide was more effective in achieving and maintaining glycaemic control as a second line glucose lowering drug than canagliflozin, sitagliptin, or glimepiride.

Assessing the use of observational methods and real-world data to emulate ongoing randomized controlled trials.

BACKGROUND/AIMS: There has been growing interest in better understanding the potential of observational research methods in medical product evaluation and regulatory decision-making. Previously, we used linked claims and electronic health record data to emulate two ongoing randomized controlled trials, characterizing the populations and results of each randomized controlled trial prior to publication of its results. Here, our objective was to compare the populations and results from the emulated trials with those of the now-published randomized controlled trials. METHODS: This study compared participants' demographic and clinical characteristics and study results between the emulated trials, which used structured data from OptumLabs Data Warehouse, and the published PRONOUNCE and GRADE trials. First, we examined the feasibility of implementing the baseline participant characteristics included in the published PRONOUNCE and GRADE trials' using real-world data and classified each variable as ascertainable, partially ascertainable, or not ascertainable. Second, we compared the emulated trials and published randomized controlled trials for baseline patient characteristics (concordance determined using standardized mean differences <0.20) and results of the primary and secondary endpoints (concordance determined by direction of effect estimates and statistical significance). RESULTS: The PRONOUNCE trial enrolled 544 participants, and the emulated trial included 2226 propensity score-matched participants. In the PRONOUNCE trial publication, one of the 32 baseline participant characteristics was listed as an exclusion criterion on ClinicalTrials.gov but was ultimately not used. Among the remaining 31 characteristics, 9 (29.0%) were ascertainable, 11 (35.5%) were partially ascertainable, and 10 (32.2%) were not ascertainable using structured data from OptumLabs. For one additional variable, the PRONOUNCE trial did not provide sufficient detail to allow its ascertainment. Of the nine variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 6 (66.7%). The primary endpoint of time from randomization to the first major adverse cardiovascular event and secondary endpoints of nonfatal myocardial infarction and stroke were concordant between the emulated trial and published randomized controlled trial. The GRADE trial enrolled 5047 participants, and the emulated trial included 7540 participants. In the GRADE trial publication, 8 of 34 (23.5%) baseline participant characteristics were ascertainable, 14 (41.2%) were partially ascertainable, and 11 (32.4%) were not ascertainable using structured data from OptumLabs. For one variable, the GRADE trial did not provide sufficient detail to allow for ascertainment. Of the eight variables that were ascertainable, values in the emulated trial and published randomized controlled trial were discordant for 4 (50.0%). The primary endpoint of time to hemoglobin A1c ≥7.0% was mostly concordant between the emulated trial and the published randomized controlled trial. CONCLUSION: Despite challenges, observational methods and real-world data can be leveraged in certain important situations for a more timely evaluation of drug effectiveness and safety in more diverse and representative patient populations.