Use of transportability methods for real-world evidence generation: a review of current applications.

Aim: To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. Methods: We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive). Two reviewers screened abstracts/titles and reviewed the full text of candidate studies to identify the final set of articles. Data on the therapeutic area, exposure(s), outcome(s), original and target populations and details of the transportability analysis (e.g., analytic method used, estimate transported, stated assumptions) were abstracted from each article. Results: Of 458 unique records identified, six were retained in the final review. Articles were published during 2021-2023, focused on the US/Canada context, and covered a range of therapeutic areas. Four studies transported an RCT effect estimate, while two transported effect estimates derived from real-world data. Almost all articles used weighting methods to transport estimates. Two studies discussed all transportability assumptions, and one evaluated the likelihood of meeting all assumptions and the impact of potential violations. Conclusion: The use of transportability methods for RWE generation is an emerging and promising area of research to address evidence gaps in settings with limited data and infrastructure. More transparent and rigorous reporting of methods, assumptions and limitations may increase the use and acceptability of transportability for producing robust evidence on treatment effectiveness and safety.

Maintaining disorder: estimating the association between policing and psychiatric hospitalization among youth in New York City by neighborhood racial composition, 2006-2014.

PURPOSE: To assess whether neighborhood-level measures of policing are spatio-temporally associated with psychiatric hospialization among adolescents and young adults in New York City, and whether this association varies by neighborhood racial composition. METHODS: We derived population-based measures of policing from the New York City Police Department (NYPD), psychiatric hospitalization from Statewide Planning and Research Cooperative System (SPARCS) data, and socio-demographic data from the American Community Survey (ACS), aggregated by month and ZIP Code Tabulation Area (ZCTA) from 2006 to 2014. Multi-level negative binomial regression models assessed hospitalization-time of youth aged 10-24 as the dependent variable and the rate of policing events as the primary independent variable, adjusting for neighborhood poverty, unemployment, and educational attainment. Multiplicative interaction was assessed between policing and tertiles of the percentage of Black residents. RESULTS: A total of 11,900,192 policing incidents and 2,118,481 person-days of hospitalization were aggregated to 19,440 ZCTA-months. After adjusting for neighborhood-level sociodemographic characteristics, an increase in one policing incident per 1,000 residents was associated with a 0.3% increase in the rate of youth psychiatric hospitalization time (IRR 1.003 [1.001-1.005]). Neighborhood racial composition modified this effect; not only was the rate of psychiatric hospitalization and policing higher in neighborhoods with a higher proportion of Black residents, but the association between these was also significantly higher in neighorhoods with a larger share of Black residents compared with predominantly non-Black neighborhoods. CONCLUSION: Neighborhoods experiencing higher rates of policing during the study period experienced higher burdens of psychiatric hospitalization among adolescent and young adult residents. This association was larger in neighborhoods of color which have been disproportionately targeted by "hot spot" and order-maintenance policing practices and policies.

Characterizing Mental Health Status and Service Utilization in Chinese Americans With Type 2 Diabetes in New York City: Cross-Sectional Study.

BACKGROUND: Emerging evidence indicates that individuals with type 2 diabetes (T2D) are more prone to mental health issues than the general population; however, there is a significant lack of data concerning the mental health burden in Chinese Americans with T2D. OBJECTIVE: The aim of this study was to explore the comorbid mental health status, health-seeking behaviors, and mental service utilization among Chinese Americans with T2D. METHODS: A cross-sectional telephone survey was performed among 74 Chinese Americans with T2D in New York City. We used standardized questionnaires to assess mental health status and to gather data on mental health-seeking behaviors and service utilization. Descriptive statistics were applied for data analysis. RESULTS: A total of 74 Chinese Americans with T2D completed the survey. Most participants (mean age 56, SD 10 years) identified as female (42/74, 57%), were born outside the United States (73/74, 99%), and had limited English proficiency (71/74, 96%). Despite nearly half of the participants (34/74, 46%) reporting at least one mental health concern (elevated stress, depressive symptoms, and/or anxiety), only 3% (2/74) were currently using mental health services. Common reasons for not seeking care included no perceived need, lack of information about Chinese-speaking providers, cost, and time constraints. The cultural and language competence of the provider was ranked as the top factor related to seeking mental health care. CONCLUSIONS: Chinese Americans with T2D experience relatively high comorbid mental health concerns yet have low service utilization. Clinicians may consider team-based care to incorporate mental health screening and identify strategies to provide culturally and linguistically concordant mental health services to engage Chinese Americans with T2D.

Decline in use of high-risk agents for tight glucose control among older adults with diabetes in New York City: 2017-2022.

BACKGROUND: This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. METHODS: We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high-risk agent (insulin or insulin secretagogue). RESULTS: The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five-year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP-1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT-2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). CONCLUSIONS: We found an encouraging trend toward less use of high-risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population.

Higher unemployment benefits are associated with reduced drug overdose mortality in the United States before and during the COVID-19 pandemic.

OBJECTIVES: Overdose mortality rates in the United States remain critical to population health. Economic , such as unemployment, are noted risk factors for drug overdoses. The COVID-19 pandemic exacerbated economic hardship; as a result, the US government enacted income protection programs in conjunction with existing unemployment insurance (UI) to dampen COVID-19-related economic consequences. We investigate whether UI, operationalized as the weekly benefit allowance (WBA) replacement rate, is negatively associated with drug-related overdoses. METHODS: Data from the pooled 2014-2020 Detailed Restricted Mortality files for all counties from the Centers for Disease Control and Prevention, restricted to people ≥18 years of age, aggregated at the county-quarter level (n = 89,914). We included any fatal drug, opioid, and stimulant overdose. We modeled the association between WBA replacement rate (e.g., a greater proportion of weekly earnings replaced by UI) on each county-level age-adjusted mortality outcome using separate linear regression models during 2014-2020, pre-COVID (2014-2018), and post-COVID (2019-2020). We conducted sensitivity analyses using multi-level linear regression models. RESULTS: Results indicated that a more robust WBA replacement rate any drug (Risk Difference [RD]: -0.06, 95 % Confidence Interval [CI]: -0.08, -0.05), opioid (RD: -0.04, 95 % CI: -0.06, -0.03), and stimulant (RD: -0.03, 95 % CI: -0.04, -0.02) across the entire study period (2014-2020). A more robust WBA replacement rate was associated with fewer fatal drug, opioid and stimulant overdoses in the pre-COVID-19 period and on fatal any drug and stimulant overdoses in the COVID-19 period. CONCLUSIONS: Findings support the notion that income protection policies, such as robust UI, can have a supportive role in preventing fatal drug overdoses, calling for a broader discussion onthe role of the safety net programs to buffer drug-related harms.

Platelet RNA Biomarker of Ticagrelor-Responsive Genes Is Associated With Platelet Function and Cardiovascular Events.

BACKGROUND: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk. METHODS: Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor. RNA sequencing was used to discover platelet genes affected by ticagrelor, and a subset of the most informative was summarized into a composite score and tested for validation. This score was further analyzed (1) in CD34+ megakaryocytes exposed to an P2Y12 inhibitor in vitro, (2) with baseline platelet function in healthy controls, (3) in peripheral artery disease patients (n=139) versus patient controls (n=30) without atherosclerosis, and (4) in patients with peripheral artery disease for correlation with atherosclerosis severity and risk of incident major adverse cardiovascular and limb events. RESULTS: Ticagrelor exposure differentially expressed 3409 platelet transcripts. Of these, 111 were prioritized to calculate a Ticagrelor Exposure Signature score, which ticagrelor reproducibly increased in discovery and validation cohorts. Ticagrelor's effects on platelets transcripts positively correlated with effects of P2Y12 inhibition in primary megakaryocytes. In healthy controls, higher baseline scores correlated with lower baseline platelet function and with minor bleeding while receiving ticagrelor. In patients, lower scores independently associated with both the presence and extent of atherosclerosis and incident ischemic events. CONCLUSIONS: Ticagrelor-responsive platelet transcripts are a biomarker for platelet function and cardiovascular risk and may have clinical utility for selecting patients with optimal risk:benefit for ticagrelor use.

Longitudinal relationships among exclusionary school discipline, adolescent substance use, and adult arrest: Public health implications of the school-to-prison pipeline.

PURPOSE: Exclusionary school discipline is an initiating component of the school-to-prison pipeline that is racialized and may lead to short- and long-term negative substance use and criminal legal outcomes. However, these impacts, and racial disparities therein, have not been well explored empirically at the individual-level. PROCEDURES: We analyzed data from the National Longitudinal Study of Adolescent to Adult Health (1995-2009). We fit survey-weighted multivariable logistic regression models to estimate reciprocal relationships between exclusionary discipline and adolescent substance use, between these factors and subsequent exposure to the adult criminal legal system, and whether these relationships were modified by race or ethnicity. RESULTS: We found that students reporting substance use had 2.07 (95% CI 1.57, 2.75) times greater odds of reporting subsequent school discipline, and students exposed to school discipline had 1.59 (95% CI 1.26, 2.02) times greater odds of reporting subsequent substance use. Substance use and school discipline were associated with 2.69 (95% CI 2.25, 3.22) and 2.98 (95% CI 2.46, 3.60) times the odds of reporting subsequent adult criminal legal system exposure, respectively. There was little evidence of effect modification by race/ethnicity. CONCLUSIONS: Findings indicate that school discipline and substance use are reciprocally associated and have direct implications for adolescent health and future criminal legal system exposure.

Cannabis and Alcohol Use by U.S. Young Adults, 2008-2019: Changes in Prevalence After Recreational Cannabis Legalization.

INTRODUCTION: Young adults' cannabis and alcohol use patterns have changed after state recreational cannabis legalization according to studies based on college samples but not nationally representative samples. Associations between recreational cannabis legalization and changes in cannabis and alcohol use outcomes among young adults were examined, including differences by college enrollment and minor status (ages 18-20 vs 21-23 years). METHODS: Repeated cross-sectional data (2008-2019) were collected from college-eligible participants aged 18-23 years in the National Survey on Drug Use and Health. Self-reported past-month cannabis use and frequent use (≥20 days) and a proxy for past-year DSM-5 cannabis use disorder were primary outcomes; past-month frequent alcohol use and binge drinking were secondary outcomes. Multilevel logistic regression models quantified changes in outcome prevalence from the study years before to after recreational cannabis legalization, adjusting for secular trends. Analyses were conducted on March 22, 2022. RESULTS: Prevalence increased from before to after recreational cannabis legalization for past-month cannabis use (from 21% to 25%) and past-year proxy cannabis use disorder (from 11% to 13%); the increases were statistically significant [adjusted odds ratio (95% CI) = 1.20 (1.08-1.32) and 1.14 (1.003-1.30), respectively]. Increases were detected for young adults who were not in college and who were aged 21-23 years. Recreational cannabis legalization impacts were not detected for secondary outcomes. CONCLUSIONS: Some young adults appear sensitive to state recreational cannabis legalization, including in terms of cannabis use disorder risk. Additional prevention efforts should be directed to young adults who are not in college and timed to occur before age 21 years.

Recreational cannabis legislation and binge drinking in U.S. adolescents and adults.

BACKGROUND: Recreational cannabis laws (RCLs) may have spillover effects on binge drinking. Our aims were to investigate binge drinking time trends and the association between RCLs and changes in binge drinking in the United States (U.S.). METHODS: We used restricted National Survey on Drug Use and Health data (2008-2019). We examined trends in the prevalence of past-month binge drinking by age groups (12-20, 21-30, 31-40, 41-50, 51+). Then, we compared model-based prevalences of past-month binge drinking before and after RCL by age group, using multi-level logistic regression with state random intercepts, an RCL by age group interaction term, and controlling for state alcohol policies. RESULTS: Binge drinking declined overall from 2008 to 2019 among people aged 12-20 (17.54% to 11.08%), and those aged 21-30 (43.66% to 40.22%). However, binge drinking increased among people aged 31+ (ages 31-40: 28.11% to 33.34%, ages 41-50: 25.48% to 28.32%, ages 51+: 13.28% to 16.75%). When investigating model-based prevalences after versus before RCL, binge drinking decreased among people aged 12-20 (prevalence difference=-4.8%; adjusted odds ratio (aOR)=0.77, [95% confidence interval (CI) 0.70-0.85]), and increased among participants aged 31-40 (+1.7%; 1.09[1.01-1.26]), 41-50 (+2.5; 1.15[1.05-1.26]) and 51+ (+1.8%; 1.17[1.06-1.30]). No RCL-related changes were noted in respondents ages 21-30. CONCLUSIONS: Implementation of RCLs was associated with increased past-month binge drinking in adults aged 31+ and decreased past-month binge drinking in those aged < 21. As the cannabis legislative landscape continues to change in the U.S., efforts to minimize harms related to binge drinking are critical.

Implementation fidelity to a behavioral diabetes prevention intervention in two New York City safety net primary care practices.

BACKGROUND: It is critical to assess implementation fidelity of evidence-based interventions and factors moderating fidelity, to understand the reasons for their success or failure. However, fidelity and fidelity moderators are seldom systematically reported. The study objective was to conduct a concurrent implementation fidelity evaluation and examine fidelity moderators of CHORD (Community Health Outreach to Reduce Diabetes), a pragmatic, cluster-randomized, controlled trial to test the impact of a Community Health Workers (CHW)-led health coaching intervention to prevent incident type 2 Diabetes Mellitus in New York (NY). METHODS: We applied the Conceptual Framework for Implementation Fidelity to assess implementation fidelity and factors moderating it across the four core intervention components: patient goal setting, education topic coaching, primary care (PC) visits, and referrals to address social determinants of health (SDH), using descriptive statistics and regression models. PC patients with prediabetes receiving care from safety-net patient-centered medical homes (PCMHs) at either, VA NY Harbor or at Bellevue Hospital (BH) were eligible to be randomized into the CHW-led CHORD intervention or usual care. Among 559 patients randomized and enrolled in the intervention group, 79.4% completed the intake survey and were included in the analytic sample for fidelity assessment. Fidelity was measured as coverage, content adherence and frequency of each core component, and the moderators assessed were implementation site and patient activation measure. RESULTS: Content adherence was high for three components with nearly 80.0% of patients setting ≥ 1 goal, having ≥ 1 PC visit and receiving ≥ 1 education session. Only 45.0% patients received ≥ 1 SDH referral. After adjusting for patient gender, language, race, ethnicity, and age, the implementation site moderated adherence to goal setting (77.4% BH vs. 87.7% VA), educational coaching (78.9% BH vs. 88.3% VA), number of successful CHW-patient encounters (6 BH vs 4 VA) and percent of patients receiving all four components (41.1% BH vs. 25.7% VA). CONCLUSIONS: The fidelity to the four CHORD intervention components differed between the two implementation sites, demonstrating the challenges in implementing complex evidence-based interventions in different settings. Our findings underscore the importance of measuring implementation fidelity in contextualizing the outcomes of randomized trials of complex multi-site behavioral interventions. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov on 30/12/2016 and the registration number is NCT03006666 .