Risk Selection and Care Fragmentation at Medicare Accountable Care Organizations for Patients With Dementia.

BACKGROUND: Patients with dementia are a growing and vulnerable population within Medicare. Accountable care organizations (ACOs) are becoming Medicare's dominant care model, but ACO enrollment and care patterns for patients with dementia are unknown. OBJECTIVE: The aim of this study was to compare differences in ACO enrollment for patients with versus without dementia, and in risk profiles and ambulatory care among patients with dementia by ACO enrollment status. RESEARCH DESIGN: Cohort study assessing the relationships between patient dementia, following-year ACO enrollment, and ambulatory care patterns. SUBJECTS: A total of 13,362 (weighted: 45, 499,049) person-years for patients [2761 (weighted: 6,312,304) for dementia patients] ages 65 years and above in the 2015-2019 Medicare Current Beneficiary Survey. MEASURES: We assessed differences in ACO enrollment rates for patients with versus without dementia, and in dementia-relevant ambulatory care visit rates and validated care fragmentation indices among patients with dementia by ACO enrollment status. RESULTS: Patients with versus without dementia were less likely to be enrolled in (38.3% vs. 44.6%, P<0.001), and more likely to exit (21.1% vs. 13.7%, P<0.01) ACOs. Among patients with dementia, those enrolled versus not enrolled in ACOs had a more favorable social and health risk profile on 6 of 16 measures (P<0.05). There were no differences in rates of dementia-relevant, primary, or specialty care visits. ACO enrollment was associated with 45.7% higher wellness visit rates (P<0.001), and 13.4% more fragmented primary care (P<0.01) spread across 8.7% more distinct physicians (P<0.05). CONCLUSION: Medicare ACOs are less likely to enroll and retain patients with dementia than other patients and provide more fragmented primary care without providing additional dementia-relevant ambulatory care visits.

Personal Location as Health-Related Data: Public Knowledge, Public Concern, and Personal Action.

OBJECTIVES: Personal health information (PHI), including health status and behaviors, are often associated with personal locations. Smart devices and other technologies routinely collect personal location. Therefore, technologies collecting personal location do not just create generic questions of privacy, but specific concerns related to PHI. METHODS: To assess public opinion on the relationship between health, personal location, and privacy, a national survey of US residents was administered online in March 2020. Respondents answered questions about their use of smart devices and knowledge of location tracking. They also identified which of the locations they could visit were most private and how to balance possibilities that locations may be private but can also be useful to share. RESULTS: Of respondents that used smart devices (n = 688), a majority (71.1%) indicated they knew they had applications tracking their location, with respondents who were younger (P < .001) and male (P = .002) and with more education (P = .045) more likely to indicate "yes." When all respondents (N = 828) identified the locations on a hypothetical map they felt were most private, health-related locations (substance use treatment center, hospital, urgent care) were the most selected. CONCLUSIONS: The historical notion of PHI is no longer adequate and the public need greater education on how data from smart devices may be used to predict health status and behaviors. The COVID-19 pandemic brought increased attention to personal location as a tool for public health. Given healthcare's dependence upon trust, the field needs to lead the conversation and be viewed as protecting privacy while usefully leveraging location data.

Prevalence and correlates of antisocial personality disorder in older adults.

OBJECTIVES: There is a paucity of research on antisocial personality disorder (ASPD) in the geriatric population and the majority of knowledge on the disorder is drawn from young adult samples. Researchers posit that the prevalence of ASPD as well as other personality disorders (PDs) is underestimated among older adults. Using a nationally representative sample, the present study examines the prevalence and correlates of ASPD in adults ages 50 and older. METHODS: We analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions Waves I and III. Multivariate logistic regression analyses were employed to investigate associations between ASPD and sociodemographic characteristics. A series of logistic regression analyses were also conducted to study associations between ASPD and medical conditions (liver and cardiovascular disease, arthritis, and stomach ulcer), major psychiatric disorders (lifetime major depressive disorder, mania, and generalized anxiety disorder), and substance use disorders (lifetime alcohol, marijuana, cocaine, heroin, and nicotine use disorders). RESULTS: Findings indicated that the prevalence of ASPD increases through early adulthood, with a peak at 3.91% in younger adults and decline to 0.78% in adults ages ≥65. Older adults with ASPD are more likely to be diagnosed with a substance use disorder, major depression, mania, and generalized anxiety disorder as well as each medical condition. CONCLUSION: Older adults with ASPD experience increased rates of medical and psychiatric comorbidities. These conditions exacerbate the existing challenges associated with diagnosing and treating this population and may have serious consequences for the patient, their caregivers and society.

SARS-CoV-2 Transmission to Masked and Unmasked Close Contacts of University Students with COVID-19 - St. Louis, Missouri, January-May 2021.

Universities open for in-person instruction during the 2020-21 academic year implemented a range of prevention strategies to limit the transmission of SARS-CoV-2, the virus that causes COVID-19, including physical distancing, mask use, vaccination, contact tracing, case investigation, and quarantine protocols (1). However, in some academic programs, such as health-related programs, aviation, and kindergarten through grade 12 (K-12) education, maintaining physical distance while still providing instruction is difficult; for universities with such programs, a single confirmed case of COVID-19 could result in a large number of students, staff members, and instructors being designated close contacts and requiring quarantine if they are not fully vaccinated, even if masks were worn when contact occurred. In January 2021, the St. Louis City Health Department allowed Saint Louis University (SLU) to implement a modified quarantine protocol that considered mask use when determining which close contacts required quarantine.* To assess the impact of the protocol, SLU assessed positive SARS-CoV-2 test result rates by masking status of the persons with COVID-19 and their close contacts. During January-May 2021, 265 students received a positive SARS-CoV-2 test result; these students named 378 close contacts. Compared with close contacts whose exposure only occurred when both persons were masked (7.7%), close contacts with any unmasked exposure (32.4%) had higher adjusted odds ratios (aORs) of receiving a positive SARS-CoV-2 test result (aOR = 4.9; 95% confidence interval [CI] = 1.4-31.1). Any additional exposures were associated with a 40.0% increase in odds of a positive test result (aOR = 1.4; 95% CI = 1.2-1.6). These findings reinforce that universal masking and having fewer encounters in close contact with persons with COVID-19 prevents the spread of SARS-CoV-2 in a university setting. Universities opening for in-person instruction could consider taking mask use into account when determining which unvaccinated close contacts require quarantine if enforced testing protocols are in place. However, this study was conducted before the B.1.617.2 (Delta) variant became the dominant strain of SARS-CoV-2 in the United States, which could have affected these findings given that the Delta variant has been found to be associated with increased transmissibility compared to previous variants.

Acoustic characteristics in relation to intelligibility reduction in noise for speakers with Parkinson's disease.

Decreased speech intelligibility in noisy environments is frequently observed in speakers with Parkinson's disease (PD). This study investigated which acoustic characteristics across the speech subsystems contributed to poor intelligibility in noise for speakers with PD. Speech samples were obtained from 13 speakers with PD and five healthy controls reading 56 sentences. Intelligibility analysis was conducted in quiet and noisy listening conditions. Seventy-two young listeners transcribed the recorded sentences in quiet and another 72 listeners transcribed in noise. The acoustic characteristics of the speakers with PD who experienced large intelligibility reduction from quiet to noise were compared to those with smaller intelligibility reduction in noise and healthy controls. The acoustic measures in the study included second formant transitions, cepstral and spectral measures of voice (cepstral peak prominence and low/high spectral ratio), pitch variation, and articulation rate to represent speech components across speech subsystems of articulation, phonation, and prosody. The results show that speakers with PD who had larger intelligibility reduction in noise exhibited decreased second formant transition, limited cepstral and spectral variations, and faster articulation rate. These findings suggest that the adverse effect of noise on speech intelligibility in PD is related to speech changes in the articulatory and phonatory systems.

Single and Repeated Use of the Emergency Department for Chlamydia and Gonorrhea Care.

OBJECTIVE: Chlamydia and gonorrhea infection rates are rising in the United States, and the emergency department (ED) is increasingly a site where individuals seek care for these infections, sometimes more than once. This article investigates how individuals who use the ED more than once and receive chlamydia and gonorrhea care differ from individuals who are single users of the ED, as well as characteristics associated with being a repeat user of the ED. METHODS: We analyzed 46,964 visits made by individuals who attended 1 of 4 EDs from January 1, 2010, to May 31, 2016, and received a test for chlamydia and gonorrhea infection. We used negative binomial regression to test the ability of age, sex, race, infection status, and insurance status to predict number of visits. RESULTS: Individuals who used the ED more than once and received chlamydia and gonorrhea care were at their first visit more likely to be younger (incident rate ratio [IRR], 0.98; 95% confidence interval [CI], 0.97-0.98 per year) nonpregnant female (IRR, 1.23; 95% CI, 1.06-1.42), black (IRR, 1.27; 95% CI, 1.04-1.57), and have no or public insurance compared with single users of the ED. DISCUSSIONS: Individuals likely to make multiple visits to the ED and receive chlamydia and gonorrhea care may be identifiable on their first visit and potentially directed elsewhere during subsequent visits for more comprehensive and potentially less expensive sexually transmitted disease care.

Presenting to the Emergency Department Versus Clinic-Based Sexually Transmitted Disease Care Locations for Testing for Chlamydia and Gonorrhea: A Spatial Exploration.

BACKGROUND: Rates of sexually transmitted diseases (STDs) including chlamydia and gonorrhea are increasing in the United States while public health funding for STD services is decreasing. Individuals seek care in various locations including the emergency department (ED). The objective of this study is to investigate whether there are more physically proximal clinic-based STD care locations available to individuals who present to the ED in a major metropolitan area. METHODS: Addresses of EDs, clinics, and patients 13 years or older in St. Louis City or County given a nucleic acid amplification test and assigned an STD diagnosis (n = 6100) were geocoded. R was used to analyze clinics within 5 radii from the patients' home address and assess missed clinic opportunities (open, no charge, with walk-in availability) for those living in an urban versus suburban area. RESULTS: In urban areas, 99.1% of individuals lived closer to a clinic than the ED where they sought STD services; in suburban areas, 82.2% lived closer to a clinic than the ED where they presented. In the region, 50.6% lived closer to the health department-based STD care location than the hospital where they presented. Up to a third of ED patient visits for STD care could have occurred at a clinic that was closer to the patient's home address, open, no charge, and available for walk-in appointments. CONCLUSIONS: Clinic availability is present for most of the individuals in our study. Clinics providing STD services can increase advertising efforts to increase public awareness of the services which they provide.

Suicide risk among cancer survivors: Head and neck versus other cancers.

BACKGROUND: Cancer survivors face psychosocial issues that increase their risk of suicide. This study examined the risk of suicide across cancer sites, with a focus on survivors of head and neck cancer (HNC). METHODS: The Surveillance, Epidemiology, and End Results 18-registry database (from 2000 to 2014) was queried for the top 20 cancer sites in the database, including HNC. The outcome of interest was suicide as a cause of death. The mortality rate from suicide was estimated for HNC sites and was compared with rates for 19 other cancer sites that were included in the study. Poisson regression was used to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for 1) HNC versus non-HNC sites (the other 19 cancer sites combined), and 2) HNC versus each individual cancer site. Models were stratified by sex, controlling for race, marital status, age, year, and stage at diagnosis. RESULTS: There were 404 suicides among 151,167 HNC survivors from 2000 to 2014, yielding a suicide rate of 63.4 suicides per 100,000 person-years. In this timeframe, there were 4493 suicides observed among 4219,097 cancer survivors in the study sample, yielding an incidence rate of 23.6 suicides per 100,000 person-years. Compared with survivors of other cancers, survivors of HNC were almost 2 times more likely to die from suicide (aRR, 1.97; 95% CI, 1.77-2.19). There was a 27% increase in the risk of suicide among HNC survivors during the period from 2010 to 2014 (aRR, 1.27; 95% CI, 1.16-1.38) compared with the period from 2000 to 2004. CONCLUSIONS: Although survival rates in cancer have improved because of improved treatments, the risk of death by suicide remains a problem for cancer survivors, particularly those with HNC.

Determinants of organ donation registration.

Rates of organ donor registration range from 20% to 60% throughout the United States. The purpose of this study was to examine sociogeographic differences in organ donor registration rates throughout Missouri to identify varying patterns The organ donor registration rate from each Department of Motor Vehicle office in Missouri was extracted from the National Organ Registration database, office locations were geocoded, and census tract level sociodemographic characteristics were extracted. Spatial regression analyses were conducted to identify relationships between location of DMV offices and census tract-level concentrated disadvantage. Census tract-level concentrated disadvantage (education attainment, poverty, single-headed households) had a significant negative relationship with organ donor registration rates. Yet, census tract-level African American/Black resident concentration was not significantly related to organ donor registration rates. These findings suggest that race-based interventions to recruit organ donors may no longer be necessary. Yet, identifying how characteristics of concentrated disadvantage may be more influential in determining organ donor registration. Gaining a better understanding of how individual decisions are made is integral in the context of increased life expectancy in conjunction with the complex management of chronic conditions.

Pertussis Vaccination Among Childcare Center Staff, Administrators, and Parents: Uptake, Policies, and Beliefs.

Introduction Little is known about childcare staff's and parents' uptake of and attitudes towards pertussis vaccine. Methods Questionnaires were distributed to St. Louis parents and childcare staff in fall, 2014. Parents versus staff and vaccinated versus unvaccinated individuals' beliefs regarding pertussis vaccine were compared using chi square tests. Multivariate logistic regressions were run to develop predictive models for staff's and parents' vaccine uptake. Results Overall, 351 parents and staff from 23 agencies participated (response rate = 32%). Parents were more likely than staff to have received pertussis vaccine (66.5 vs. 45.8%, X 2 = 12.5, p < .001). Predictors for staff vaccination included willingness to get vaccinated even if there was a cost (OR 6.6; CI 1.8-24.6; p < .01), awareness of vaccination recommendations (OR 5.2; CI 1.2-22.8; p < .05), and healthcare provider recommendation (OR 4.2; CI 1.2-15.1; p < .05). Parents' predictors of vaccination included perceived importance of vaccination (OR 9.9; CI 4.1-23.8; p < .001), healthcare provider recommendation (OR 4.6; CI 1.7-12.6; p < .01), believing vaccination is effective (OR 4.4; CI 1.1-18.0; p < .05), and knowing where to get vaccine (OR 3.5; CI 1.5-8.1; p < .01). Among unvaccinated staff (n = 52), 74.5% (n = 38) and 70.0% (n = 35) would receive pertussis vaccine if it were offered free of charge and onsite, respectively. Conclusions for Practice Childcare staff's and parents' pertussis vaccine uptake was higher than overall U.S. rates, though significantly lower than the Global Pertussis Initiative target. Implementing an education campaign and providing free vaccine on-site are likely to result in increased vaccine uptake.

The acceptability of self-sampled screening for HPV DNA: a systematic review and meta-analysis.

OBJECTIVE: To examine whether or not self-sampled cervical screening for human papillomavirus (HPV) DNA is acceptable and if women prefer self-sampling to clinician-based sampling. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Thirty-seven primary studies obtained through a comprehensive search of six electronic bibliographic databases from 1986 to 2014 and other sources. Search keywords included HPV, screening, DNA testing, vaginal testing, self-collected specimen, self-collected sample, self-sampling, self-screening, preferences and acceptability. REVIEW METHODS: Studies eligible for analysis included those that had participants perform self-sampling, evaluated participant acceptance of or preference for self-sampled vaginal HPV DNA and reported data to calculate an effect size. There were no exclusion criteria for publication status or geographical location. Meta-analytic methods were used to quantitatively synthesise effect sizes across studies. RESULTS: The 37 studies included 18 516 female participants from 24 countries across five continents. Overall, there was a high level of acceptability of self-sampling among the participants. Participants reported preference for self-sampling over clinician sampling due to attractive characteristics such as ease and privacy. CONCLUSIONS: The overall acceptability of self-sampled cervical screening, coupled with economic and effective care, provides opportunities for expanding screening services. Importantly, this can provide a creative screening alternative for women who do not participate in traditional cytological screening, and may ultimately reduce health disparities and prevent cervical disease.

Factors Associated With Parents' Intent to Vaccinate Adolescents for Human Papillomavirus: Findings From the 2014 National Immunization Survey-Teen.

INTRODUCTION: While factors associated with receipt of human papillomavirus (HPV) vaccination have been well characterized, less is known about the characteristics associated with parents' intent to have their adolescent children vaccinated. This study aimed to examine factors associated with parental intention toward HPV vaccination. METHODS: We analyzed data on 10,354 adolescents aged 13 to 17 years from the 2014 National Immunization Survey-Teen. Weighted multivariable logistic regression was used to examine associations between sociodemographic characteristics of mothers and adolescents, as well as a health care provider recommendation with parents' intention to have their children receive HPV vaccine. RESULTS: Among unvaccinated adolescents, Hispanic ethnicity (boys adjusted odds ratio [AOR], 1.87, 95% confidence interval [CI], 1.34-2.61; and girls AOR, 1.57; 95% CI, 1.05-2.35), mothers with less than a high school diploma (boys AOR, 2.41; 95% CI, 1.58-3.67; and girls AOR, 1.86; 95% CI, 1.02-3.38), and having a health care provider recommend the vaccine (boys AOR, 1.87; 95% CI, 1.52-2.31; and girls AOR, 1.38; 95% CI, 1.05-1.82) were significantly associated with parents' intention to have their adolescent child vaccinated within the next 12 months. In addition, non-Hispanic black race was a significant predictor of parents' intent to vaccinate for boys (AOR, 1.89; 95% CI, 1.35-2.65). CONCLUSION: Maternal education and Hispanic ethnicity were the strongest predictors of parental intent to vaccinate against HPV, followed by provider recommendation. As HPV vaccination rates in the United States remain below the Healthy People 2020 goal, messages may need to be targeted based on maternal education, race/ethnicity, and provider recommendation.

Insufficient Evidence to Support or Refute the Association between Head and Neck Cancer and Marijuana Use.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies. de Carvalho MFF, Dourado MR, Fernandes IB, Araújo CTP, Mesquita AT, Ramos-Jorge ML. Arch Oral Biol 2015;60(12):1750-5. SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.

Randomization, matching, and propensity scores in the design and analysis of experimental studies with measured baseline covariates.

In many experimental situations, researchers have information on a number of covariates prior to randomization. This information can be used to balance treatment assignment with respect to these covariates as well as in the analysis of the outcome data. In this paper, we investigate the use of propensity scores in both of these roles. We also introduce a randomization procedure in which the balance of all measured covariates is approximately indexed by the variance of the empirical propensity scores and randomization is restricted to those permutations with the least variable propensity scores. This procedure is compared with recently proposed methods in terms of resulting covariate balance and estimation efficiency. Properties of the estimators resulting from each procedure are compared with estimates which incorporate the propensity score in the analysis stage. Simulation results show that analytical adjustment for the propensity score yields results on par with those obtained through restricted randomization procedures and can be used in conjunction with such procedures to further improve inferential efficiency.

Perinatal substance use disorder: Examining the impact on adverse pregnancy outcomes.

Objective: Substance use disorder is a growing concern in the USA, especially among pregnant women. This study was undertaken to assess the impact of substance use disorder on adverse pregnancy outcomes using a nationwide sample of inpatient pregnancy hospitalizations in the USA, and to elucidate the influence on each type of adverse pregnancy outcome. Study design: A cross-sectional analysis of inpatient pregnancy hospitalizations in the USA from the Healthcare Cost and Utilization Project National Inpatient Sample from 2016 to 2020 was conducted. International Classification of Diseases - 10th revision and diagnosis-related group codes were used to identify inpatient pregnancy-related delivery hospitalizations with a substance use disorder and/or adverse pregnancy outcomes. Propensity score matching and multiple logistic regression analyses were undertaken to predict the likelihood of adverse pregnancy outcomes among pregnancy hospitalizations with and without substance use disorder. Subgroup analyses were performed to estimate the impact of substance use disorder on each adverse pregnancy outcome. Results: From 3,238,558 hospitalizations, the prevalence of adverse pregnancy outcomes was substantially higher among pregnancy hospitalizations with substance use disorder (35.6 %) compared with pregnancy hospitalizations without substance use disorder (25.1 %, p < 0.001). After matching and model adjustment for sociodemographic covariates, substance use disorder was identified as an independent predictor of adverse pregnancy outcomes [adjusted odds ratio (aOR) 1.47, 95 % confidence interval (CI) 1.45-1.49]. In subgroup analyses based on type of adverse pregnancy outcome, the greatest exposure risks were fetal growth restriction (aOR 1.96, 95 % CI 1.91-2.01), antepartum hemorrhage (aOR 1.79, 95 % CI 1.73-1.85) and preterm birth (aOR 1.65, 95 % CI 1.62-1.68). Conclusion: Patients with substance use disorder are at higher risk of adverse pregnancy outcomes, particularly fetal growth restriction, antepartum hemorrhage and preterm birth.

A simple, flexible, and effective covariate-adaptive treatment allocation procedure.

We present a method for allocating treatment when subjects arrive in sequence. Based on the theory of propensity scores more commonly used in observational studies, the method balances both discrete and continuous covariates without assuming a model for the outcome. Although we allow for a number of possible specifications, we explore some specific instances in depth. The proposed method is compared with previously suggested sequential randomization and allocation procedures with relationships to some well-known methods highlighted. Through simulations, the deterministic version is shown to achieve both covariate balance and near optimum efficiency with minimal assumptions. We also investigate the properties of selected randomized versions with respect to both optimality and selection bias. We conclude with an application to a pilot study on weight loss. The proposed method is shown to be robust to the number of covariates balanced and the marginal and joint distributions of those covariates.

Trends in U.S. adolescent physical activity and obesity: A 20-year age-period-cohort analysis.

BACKGROUND: Adolescent obesity can lead to long-term health problems and is a topic of major concern in pediatric and broader medical and public health spheres. Numerous national and state-wide initiatives aimed at increasing physical activity and/or improving nutrition in this age group have assumed the goal of reducing the prevalence adolescent obesity. OBJECTIVES: We assess trends in U.S. adolescent physical activity and body mass index between 1999 and 2019. METHODS: Using data from the U.S. Youth Risk Behaviour Surveillance System, we analyse data from 144 544 14-to-18-year-old respondents. We use multilevel linear and logistic regression to perform age-period-cohort analyses attributing changes in physical activity and body mass index over time to these three sources. RESULTS: Age and period effects are strong in all outcomes studied. Physical activity consistently decreases with age across the study period. Age trends in obesity have reversed in recent years, with older adolescents now more likely to be have obesity than younger adolescents. Both female and Asian adolescents report less physical activity but lower rates of obesity than their male and non-Asian counterparts. CONCLUSIONS: The reversal of obesity trends by age with little change in physical activity over the study period suggests other lifestyle factors have changed over the study period to increase the prevalence of obesity in older adolescents.

No Improvement In Mental Health Treatment Or Patient-Reported Outcomes At Medicare ACOs For Depression And Anxiety Disorders.

Accountable care organizations (ACOs) have become Medicare's dominant care model because policy makers believe that ACOs will improve the quality and efficiency of care for chronic conditions. Depression and anxiety disorders are the most prevalent and undertreated chronic mental health conditions in Medicare. Yet it is unknown whether ACOs influence treatment and outcomes for these conditions. To explore these questions, this longitudinal study used data from the 2016-19 Medicare Current Beneficiary Survey, linked to validated depression and anxiety symptom instruments, among diagnosed and undiagnosed fee-for-service Medicare patients with these conditions. Among patients not enrolled in ACOs at baseline, those who newly enrolled in ACOs in the following year were 24 percent less likely to have their depression or anxiety treated during the year than patients who remained unenrolled in ACOs, and they saw no relative improvements at twelve months in their depression and anxiety symptoms. Better-designed incentives are needed to motivate Medicare ACOs to improve mental health treatment.

Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records.

BACKGROUND: Randomised clinical trials showed that compared with placebo, SGLT2 inhibitors and GLP-1 receptor agonists reduced risk of adverse cardiovascular events. The evidence base for the older antihyperglycaemic drug classes (DPP-4 inhibitors and sulfonylureas) is generally less well developed. Because most randomised trials evaluated one antihyperglycaemic medication versus placebo, a head-to-head comparative effectiveness analysis of the newer drug classes (SGLT2 inhibitors vs GLP-1 receptor agonists) or newer (SGLT2 inhibitors or GLP-1 receptor agonists) versus older (DPP-4 inhibitors or sulfonylureas) drug classes on risk of major adverse cardiovascular events (MACE) is not available. In this study, we aimed to evaluate the comparative effectiveness of incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas on risk of MACE. METHODS: We first specified the protocol of a four-arm randomised pragmatic clinical trial and then emulated it using the health-care databases of the US Department of Veterans Affairs. We built a cohort of metformin users with incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas between Oct 1, 2016 and Sept 30, 2021, and followed up until Dec 31, 2022. We used the overlap weighting approach to balance the treatment groups using a battery of predefined variables and a set of algorithmically selected variables from high-dimensional data domains. Both intention-to-treat and per-protocol analyses (the latter estimated the effect of maintained use of the antihyperglycaemic throughout follow-up) were conducted to estimate risk of MACE-defined as a composite endpoint of stroke, myocardial infarction, and all-cause mortality. FINDINGS: The final cohort consisted of 283 998 new users of SGLT2 inhibitors (n=46 516), GLP-1 receptor agonists (n=26 038), DPP-4 inhibitors (n=55 310), or sulfonylureas (n=156 134). In intention-to-treat analyses, compared with sulfonylureas, SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors were associated with lower risk of MACE (hazard ratio [HR] 0·77 [95% CI 0·74-0.80], 0·78 [0·74-0·81), and 0·90 [0·86-0.93], respectively). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of MACE when compared with DPP-4 inhibitors (HR 0·86 [0·82-0·89] and 0·86 [0·82-0·90], respectively). The risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists yielded an HR of 0·99 (0·94-1·04). In per-protocol analyses, compared with sulfonylureas, SGLT2 inhibitors, GLP1 receptor agonists, and DPP-4 inhibitors were associated with reduced risk of MACE (HR 0·77 [95% CI 0·73-0·82], 0·77 [0·72-0·82], and 0·88 [0·83-0·93], respectively). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of MACE when compared with DPP-4 inhibitors (HR 0·88 [0·83-0·93] and 0·88 [0·82-0·93], respectively). The risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists yielded an HR of 1·01 (0·94-1·07). INTERPRETATION: Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with reduced risk of MACE compared with DPP-4 inhibitors or sulfonylureas. DPP-4 inhibitors were associated with reduced risk of MACE compared with sulfonylureas. There was no statistically significant difference in risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists. The results provide evidence of the real-world comparative effectiveness of the four most commonly used second-line antihyperglycaemics and could guide choice of antihyperglycaemic therapy. FUNDING: US Department of Veterans Affairs and the American Society of Nephrology.