Longitudinal trajectories of a claims-based frailty measure during adjuvant chemotherapy in women with stage I-III breast cancer.

BACKGROUND: Frailty is a dynamic syndrome characterized by reduced physiological reserve to maintain homeostasis. Prospective studies have reported frailty worsening in women with breast cancer during chemotherapy, with improvements following treatment. We evaluated whether the Faurot frailty index, a validated claims-based frailty measure, could identify changes in frailty during chemotherapy treatment and identified predictors of trajectory patterns. METHODS: We included women (65+ years) with stage I-III breast cancer undergoing adjuvant chemotherapy in the SEER-Medicare database (2003-2019). We estimated the Faurot frailty index (range: 0-1; higher scores indicate greater frailty) at chemotherapy initiation, 4 months postinitiation, and 10 months postinitiation. Changes in frailty were compared to a matched noncancer comparator cohort. We identified patterns of frailty trajectories during the year following chemotherapy initiation using K-means clustering. RESULTS: Twenty-one thousand five hundred and ninety-nine women initiated adjuvant chemotherapy. Mean claims-based frailty increased from 0.037 at initiation to 0.055 4 months postchemotherapy initiation and fell to 0.049 10 months postinitiation. Noncancer comparators experienced a small increase in claims-based frailty over time (0.055-0.062). We identified 6 trajectory patterns: a robust group (78%), 2 resilient groups (16%), and 3 nonresilient groups (6%). Black women and women with claims for home hospital beds, wheelchairs, and Parkinson's disease were more likely to experience nonresilient trajectories. CONCLUSIONS: We observed changes in a claims-based frailty index during chemotherapy that are consistent with prior studies using clinical measures of frailty and identified predictors of nonresilient frailty trajectories. Our study demonstrates the feasibility of using claims-based frailty indices to assess changes in frailty during cancer treatment.

Glucagon-like peptide-1 receptor agonists do not increase aspiration during upper endoscopy in patients with diabetes.

BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP1-RA) have been associated with greater retention of gastric contents, however there have been no controlled, population-based studies performed to evaluate the potential adverse effects of GLP1-RA in the periprocedural setting. We aimed to determine if there is increased risk of aspiration and aspiration-related complications after upper endoscopy in patients using GLP1-RA. METHODS: We used a nationwide commercial administrative claims database to conduct a retrospective cohort study of patients aged 18-64 with type 2 diabetes who underwent outpatient upper endoscopy from 2005-2021. We identified 6,806,046 unique upper endoscopy procedures. We compared claims for aspiration and associated pulmonary adverse events in the 14 days following upper endoscopy between users of GLP1-RA, dipeptidyl peptidase 4 inhibitors (DPP4i), and chronic opioids. We adjusted for age, sex, Charlson Comorbidity score, underlying respiratory disease, and gastroparesis. RESULTS: We found that pulmonary adverse events following upper endoscopy are rare, ranging from 6-25 events per 10,000 procedures. When comparing GLP1-RA to DPP4i, crude relative risks of aspiration (0.67 95%CI 0.25,1.75), aspiration pneumonia (0.95 95%CI 0.40,2.29), pneumonia (1.07 95%CI 0.62,1.86), or respiratory failure (0.75 95%CI 0.38,1.48) were not higher in patients prescribed GLP1-RA. When comparing GLP1-RA to opioids, crude relative risks (95%CI) were 0.42 (0.15,1.16) for aspiration, 0.60 (0.24,1.52) for aspiration pneumonia, 0.30 (0.19,0.49) for pneumonia, and 0.24 (0.13,0.45) for respiratory failure. These results were consistent across several sensitivity analyses. CONCLUSIONS: GLP1-RA use is not associated with increased risk of pulmonary complications after upper endoscopy compared to DPP4i use in patients with type 2 diabetes.

Clarifying the causal contrast: An empirical example applying the prevalent new user study design.

PURPOSE: The prevalent new user design extends the active comparator new user design to include patients switching to a treatment of interest from a comparator. We examined the impact of adding "switchers" to incident new users on the estimated hazard ratio (HR) of hospitalized heart failure. METHODS: Using MarketScan claims data (2000-2014), we estimated HRs of hospitalized heart failure between patients initiating GLP-1 receptor agonists (GLP-1 RA) and sulfonylureas (SU). We considered three estimands: (1) the effect of incident new use; (2) the effect of switching; and (3) the effect of incident new use or switching, combining the two population. We used time-conditional propensity scores (TCPS) and time-stratified standardized morbidity ratio (SMR) weighting to adjust for confounding. RESULTS: We identified 76 179 GLP-1 RA new users, of which 12% were direct switchers (within 30 days) from SU. Among incident new users, GLP-1 RA was protective against heart failure (adjHRSMR = 0.74 [0.69, 0.80]). Among switchers, GLP-1 RA was not protective (adjHRSMR = 0.99 [0.83, 1.18]). Results in the combined population were largely driven by the incident new users, with GLP-1 RA having a protective effect (adjHRSMR = 0.77 [0.72, 0.83]). Results using TCPS were consistent with those estimated using SMR weighting. CONCLUSIONS: When analyses were conducted only among incident new users, GLP-1 RA had a protective effect. However, among switchers from SU to GLP-1 RA, the effect estimates substantially shifted toward the null. Combining patients with varying treatment histories can result in poor confounding control and camouflage important heterogeneity.

Multiple cardiovascular risk factor care in 55 low- and middle-income countries: A cross-sectional analysis of nationally-representative, individual-level data from 280,783 adults.

The prevalence of multiple age-related cardiovascular disease (CVD) risk factors is high among individuals living in low- and middle-income countries. We described receipt of healthcare services for and management of hypertension and diabetes among individuals living with these conditions using individual-level data from 55 nationally representative population-based surveys (2009-2019) with measured blood pressure (BP) and diabetes biomarker. We restricted our analysis to non-pregnant individuals aged 40-69 years and defined three mutually exclusive groups (i.e., hypertension only, diabetes only, and both hypertension-diabetes) to compare individuals living with concurrent hypertension and diabetes to individuals with each condition separately. We included 90,086 individuals who lived with hypertension only, 11,975 with diabetes only, and 16,228 with hypertension-diabetes. We estimated the percentage of individuals who were aware of their diagnosis, used pharmacological therapy, or achieved appropriate hypertension and diabetes management. A greater percentage of individuals with hypertension-diabetes were fully diagnosed (64.1% [95% CI: 61.8-66.4]) than those with hypertension only (47.4% [45.3-49.6]) or diabetes only (46.7% [44.1-49.2]). Among the hypertension-diabetes group, pharmacological treatment was higher for individual conditions (38.3% [95% CI: 34.8-41.8] using antihypertensive and 42.3% [95% CI: 39.4-45.2] using glucose-lowering medications) than for both conditions jointly (24.6% [95% CI: 22.1-27.2]).The percentage of individuals achieving appropriate management was highest in the hypertension group (17.6% [16.4-18.8]), followed by diabetes (13.3% [10.7-15.8]) and hypertension-diabetes (6.6% [5.4-7.8]) groups. Although health systems in LMICs are reaching a larger share of individuals living with both hypertension and diabetes than those living with just one of these conditions, only seven percent achieved both BP and blood glucose treatment targets. Implementation of cost-effective population-level interventions that shift clinical care paradigm from disease-specific to comprehensive CVD care are urgently needed for all three groups, especially for those with multiple CVD risk factors.

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity.

INTRODUCTION: People with type 2 diabetes are at heightened risk for severe outcomes related to COVID-19 infection, including hospitalization, intensive care unit admission, and mortality. This study was designed to examine the impact of premorbid use of glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy, sodium-glucose cotransporter-2 inhibitor (SGLT-2i) monotherapy, and concomitant GLP1-RA/SGLT-2i therapy on the severity of outcomes in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Utilizing observational data from the National COVID Cohort Collaborative through September 2022, we compared outcomes in 78,806 individuals with a prescription of GLP-1RA and SGLT-2i versus a prescription of dipeptidyl peptidase 4 inhibitors (DPP-4i) within 24 months of a positive SARS-CoV-2 PCR test. We also compared concomitant GLP-1RA/SGLT-2i therapy to GLP-1RA and SGLT-2i monotherapy. The primary outcome was 60-day mortality, measured from the positive test date. Secondary outcomes included emergency room (ER) visits, hospitalization, and mechanical ventilation within 14 days. Using a super learner approach and accounting for baseline characteristics, associations were quantified with odds ratios (OR) estimated with targeted maximum likelihood estimation (TMLE). RESULTS: Use of GLP-1RA (OR 0.64, 95% confidence interval [CI] 0.56-0.72) and SGLT-2i (OR 0.62, 95% CI 0.57-0.68) were associated with lower odds of 60-day mortality compared to DPP-4i use. Additionally, the OR of ER visits and hospitalizations were similarly reduced with GLP1-RA and SGLT-2i use. Concomitant GLP-1RA/SGLT-2i use showed similar odds of 60-day mortality when compared to GLP-1RA or SGLT-2i use alone (OR 0.92, 95% CI 0.81-1.05 and OR 0.88, 95% CI 0.76-1.01, respectively). However, lower OR of all secondary outcomes were associated with concomitant GLP-1RA/SGLT-2i use when compared to SGLT-2i use alone. CONCLUSION: Among adults who tested positive for SARS-CoV-2, premorbid use of either GLP-1RA or SGLT-2i is associated with lower odds of mortality compared to DPP-4i. Furthermore, concomitant use of GLP-1RA and SGLT-2i is linked to lower odds of other severe COVID-19 outcomes, including ER visits, hospitalizations, and mechanical ventilation, compared to SGLT-2i use alone. Graphical abstract available for this article.

Performance of a Claims-Based Frailty Proxy Using Varying Frailty Ascertainment Lookback Windows.

BACKGROUND: Frailty is an aging-related syndrome of reduced physiological reserve to maintain homeostasis. The Faurot frailty index has been validated as a Medicare claims-based proxy for predicting frailty using billing information from a user-specified ascertainment window. OBJECTIVES: We assessed the validity of the Faurot frailty index as a predictor of the frailty phenotype and 1-year mortality using varying frailty ascertainment windows. RESEARCH DESIGN: We identified older adults (66+ y) in Round 5 (2015) of the National Health and Aging Trends Study with Medicare claims linkage. Gold standard frailty was assessed using the frailty phenotype. We calculated the Faurot frailty index using 3, 6, 8, and 12 months of claims prior to the survey or all-available lookback. Model performance for each window in predicting the frailty phenotype was assessed by quantifying calibration and discrimination. Predictive performance for 1-year mortality was assessed by estimating risk differences across claims-based frailty strata. RESULTS: Among 4253 older adults, the 6 and 8-month windows had the best frailty phenotype calibration (calibration slopes: 0.88 and 0.87). All-available lookback had the best discrimination (C-statistic=0.780), but poor calibration. Mortality associations were strongest using a 3-month window and monotonically decreased with longer windows. Subgroup analyses revealed worse performance in Black and Hispanic individuals than counterparts. CONCLUSIONS: The optimal ascertainment window for the Faurot frailty index may depend on the clinical context, and researchers should consider tradeoffs between discrimination, calibration, and mortality. Sensitivity analyses using different durations can enhance the robustness of inferences. Research is needed to improve prediction across racial and ethnic groups.

Visualizing External Validity: Graphical Displays to Inform the Extension of Treatment Effects from Trials to Clinical Practice.

BACKGROUND: In the presence of effect measure modification, estimates of treatment effects from randomized controlled trials may not be valid in clinical practice settings. The development and application of quantitative approaches for extending treatment effects from trials to clinical practice settings is an active area of research. METHODS: In this article, we provide researchers with a practical roadmap and four visualizations to assist in variable selection for models to extend treatment effects observed in trials to clinical practice settings and to assess model specification and performance. We apply this roadmap and visualizations to an example extending the effects of adjuvant chemotherapy (5-fluorouracil vs. plus oxaliplatin) for colon cancer from a trial population to a population of individuals treated in community oncology practices in the United States. RESULTS: The first visualization screens for potential effect measure modifiers to include in models extending trial treatment effects to clinical practice populations. The second visualization displays a measure of covariate overlap between the clinical practice populations and the trial population. The third and fourth visualizations highlight considerations for model specification and influential observations. The conceptual roadmap describes how the output from the visualizations helps interrogate the assumptions required to extend treatment effects from trials to target populations. CONCLUSIONS: The roadmap and visualizations can inform practical decisions required for quantitatively extending treatment effects from trials to clinical practice settings.

Patterns of chemotherapy receipt among patients with hormone receptor-positive, HER2-negative breast cancer.

BACKGROUND: Breast cancer chemotherapy utilization not only may differ by race and age, but also varies by genomic risk, tumor characteristics, and patient characteristics. Studies in demographically diverse populations with both clinical and genomic data are necessary to understand potential disparities by race and age. METHODS: In the Carolina Breast Cancer Study Phase 3 (2008-2013), chemotherapy receipt (yes/no) and regimen type were assessed in association with age and race among hormone receptor (HR) positive and HER2-negative tumors (n = 1862). Odds ratios were estimated for the association between demographic factors and chemotherapy receipt. RESULTS: Monotonic decreases in frequency of adjuvant chemotherapy receipt were observed over time during the study period, while neoadjuvant chemotherapy was stable. Younger age was associated with chemotherapy receipt (OR [95% CI]: 2.9 [2.4, 3.6]) and with anthracycline-based regimens (OR [95% CI]: 1.7 [1.3, 2.4]). Participants who had Medicaid (OR [95% CI]: 1.8 [1.3, 2.5]), lived in rural settings (OR [95% CI]: 1.4 [1.0, 2.0]), or were Black (OR [95% CI]: 1.5 [1.2, 1.8]) had slightly higher odds of chemotherapy, but these associations were non-significant with adjustment for stage and grade. Associations between younger age and chemotherapy receipt were strongest among women who did not receive genomic testing. CONCLUSIONS: While race was not strongly associated with chemotherapy receipt, younger age remains a strong predictor of chemotherapy receipt, even with adjustment for clinical factors and among women who receive genomic testing.

Geriatric Assessment Impairment Profiles and Mortality in Older Adults with Gastrointestinal Cancers: Latent Class Analysis of the CARE Registry.

BACKGROUND: Many older adults with cancer have ≥2 impairments on geriatric assessment which impacts present and future frailty status, treatment tolerability, and outcomes. Our objective was to identify and describe distinct geriatric assessment impairment classes using latent class analysis (LCA) in older patients with gastrointestinal malignancies and assess 1-year mortality. METHODS: We used the Cancer & Aging Resilience Evaluation (CARE) Study, a registry of older adults (≥60 years) at University of Alabama at Birmingham. The analytic cohort included patients with gastrointestinal malignancies who completed a self-administered geriatric assessment (CARE tool) before chemotherapy and had ≥1 geriatric assessment impairment. Thirteen geriatric assessment impairments were used as indicators in LCA. Resultant classes were described, mortality was estimated, and risk contrasts (differences, hazard ratios) were calculated with 95% confidence intervals. For comparison, estimates were provided for frailty categories (robust, pre-frail, frail) determined from 44 items in the CARE tool. Stratified analyses included high-risk (pancreatic, hepatobiliary, esophageal) vs. low-risk gastrointestinal cancers, and stage (IV vs. I-III). RESULTS: Six geriatric assessment impairment classes were identified: Mild impairment (LC1); Social support impairment (LC2); Weight loss alone (LC3); Impaired, low anxiety/depression (LC4); Impaired with anxiety/depression (LC5); Global impairment (LC6). One-year mortality was 14%, 22%, 29%, 34%, 50% and 50% for LC1-LC6, respectively. For frailty categories, estimates ranged from 18% (robust) to 40% (frail). In stratified analyses, LC4-LC6 consistently had higher mortality estimates compared to LC1. CONCLUSIONS: The 6 geriatric assessment impairment classes showed a wider spread of mortality estimates compared to frailty categories and could be used to identify vulnerable patients and to plan interventions.

Comparative Effectiveness of Dual- Versus Mono-Sedative Therapy on Opioid Administration, Sedative Administration, and Sedation Level in Mechanically Ventilated, Critically Ill Children.

OBJECTIVE: We estimated the effect of early initiation of dual therapy vs monotherapy on drug administration and related outcomes in mechanically ventilated, critically ill children. METHODS: We used the electronic medical record at a single tertiary medical center to conduct an active comparator, new user cohort study. We included children <18 years of age who were exposed to a sedative or analgesic within 6 hours of intubation. We used stabilized inverse probability of treatment weighting to account for confounding at baseline. We estimated the average effect of initial dual therapy vs monotherapy on outcomes including cumulative opioid, benzodiazepine, and dexmedetomidine dosing; sedation scores; time to double the opioid or benzodiazepine infusion rate; initiation of neuromuscular blockade within the first 7 days of follow-up; time to extubation; and 7-day all-cause in-hospital death. RESULTS: The cohort included 640 patients. Children receiving dual therapy received 0.03 mg/kg (95% CI, 0.02-0.04) more dexmedetomidine over the first 7 days after initiation of mechanical ventilation than did monotherapy patients. Dual therapy patients had similar sedation scores, time to double therapy, initiation of neuromuscular blockade, and time to extubation as monotherapy patients. Dual therapy patients had a lower incidence of death. CONCLUSIONS: In this study, initial dual therapy compared with monotherapy does not reduce overall drug administration during mechanical ventilation. The identified effect of dual therapy on mortality deserves further investigation.

Cardiovascular Outcomes of α-Blockers vs 5-α Reductase Inhibitors for Benign Prostatic Hyperplasia.

Importance: The most prescribed class of medications for benign prostatic hyperplasia (BPH) is α-blockers (ABs). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood. Objective: To compare the safety of ABs vs 5-α reductase inhibitors (5-ARIs) for risk of adverse cardiovascular outcomes. Design, Setting, and Participants: This active comparator, new-user cohort study was conducted using insurance claims data from a 20% random sample of Medicare beneficiaries from 2007 to 2019 to evaluate the 1-year risk of adverse cardiovascular outcomes. Males aged 66 to 90 years were indexed into the cohort at new use of an AB or 5-ARI. Twelve months of continuous enrollment and at least 1 diagnosis code for BPH within 12 months prior to initiation were required. Data were analyzed from January 2007 through December 2019. Exposures: Exposure was defined by a qualifying prescription fill for an AB or 5-ARI after at least 12 months without a prescription for these drug classes. Main Outcomes and Measures: Follow-up began at a qualified refill for the study drug. Primary study outcomes were hospitalization for heart failure (HF), composite major adverse cardiovascular events (MACE; hospitalization for stroke, myocardial infarction, or death), composite MACE or hospitalization for HF, and death. Inverse probability of treatment and censoring-weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) were estimated for each outcome. Results: Among 189 868 older adult males, there were 163 829 patients initiating ABs (mean [SD] age, 74.6 [6.2] years; 579 American Indian or Alaska Native [0.4%], 5890 Asian or Pacific Islander [3.6%], 9179 Black [5.6%], 10 610 Hispanic [6.5%], and 133 510 non-Hispanic White [81.5%]) and 26 039 patients initiating 5-ARIs (mean [SD] age, 75.3 [6.4] years; 76 American Indian or Alaska Native [0.3%], 827 Asian or Pacific Islander [3.2%], 1339 Black [5.1%], 1656 Hispanic [6.4%], and 21 605 non-Hispanic White [83.0%]). ABs compared with 5-ARIs were associated with an increased 1-year risk of MACE (8.95% [95% CI, 8.81%-9.09%] vs 8.32% [95% CI, 7.92%-8.72%]; RR = 1.08 [95% CI, 1.02-1.13]; RD per 1000 individuals = 6.26 [95% CI, 2.15-10.37]), composite MACE and HF (RR = 1.07; [95% CI, 1.03-1.12]; RD per 1000 individuals = 7.40 [95% CI, 2.88-11.93 ]), and death (RR = 1.07; [95% CI, 1.01-1.14]; RD per 1000 individuals = 3.85 [95% CI, 0.40-7.29]). There was no difference in risk for HF hospitalization alone. Conclusions and Relevance: These results suggest that ABs may be associated with an increased risk of adverse cardiovascular outcomes compared with 5-ARIs. If replicated with more detailed confounder data, these results may have important public health implications given these medications' widespread use.

Iterative Causal Forest: A Novel Algorithm for Subgroup Identification.

Precisely and efficiently identifying subgroups with heterogeneous treatment effects (HTEs) in real-world evidence studies remains a challenge. Based on the causal forest (CF) method, we developed an iterative CF (iCF) algorithm to identify HTEs in subgroups defined by important variables. Our method iteratively grows different depths of the CF with important effect modifiers, performs plurality votes to obtain decision trees (subgroup decisions) for a family of CFs with different depths, then finds the cross-validated subgroup decision that best predicts the treatment effect as a final subgroup decision. We simulated 12 different scenarios and showed that the iCF outperformed other machine learning methods for interaction/subgroup identification in the majority of scenarios assessed. Using a 20% random sample of fee-for-service Medicare beneficiaries initiating sodium-glucose cotransporter-2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP1RA), we implemented the iCF to identify subgroups with HTEs for hospitalized heart failure. Consistent with previous studies suggesting patients with heart failure benefit more from SGLT2i, iCF successfully identified such a subpopulation with HTEs and additive interactions. The iCF is a promising method for identifying subgroups with HTEs in real-world data where the potential for unmeasured confounding can be limited by study design.

Vaccine patterns among patients diagnosed with Guillain-Barré Syndrome and matched counterparts in a Medicare supplemental population, 2000-2020.

Some vaccines have a small risk of Guillain-Barré Syndrome (GBS), a rare autoimmune disorder characterized by paralysis if untreated. The CDC's Advisory Committee on Immunization Practices (ACIP) guidelines do not consider GBS a precaution for future vaccines unless GBS developed within six weeks after a tetanus-toxoid-containing vaccine or influenza vaccine. Our goal was to describe vaccine patterns before and after GBS diagnosis. We matched each of 709 patients diagnosed with GBS from 2002 to 2020 with Medicare supplemental insurance to 10 counterparts without GBS (1:10) on age and sex. Propensity score-based weighting balanced covariates between groups, and we estimated weighted mean cumulative counts (wMCC) of vaccines/person before and after GBS diagnosis. Among patients with GBS, 7% were diagnosed within 42 days after a vaccine. Prior to GBS diagnosis, the wMCC of vaccines per person was similar between GBS cases and matched counterparts, but after two years of follow-up, GBS patients received 21 fewer vaccines/100 people than counterparts (wMCC difference -0.21 vaccines/person, 95% CI -0.24 to -0.18); GBS patients received 16 vaccines/100 people while matched counterparts received 36/100. Vaccine use was reduced following GBS diagnosis despite no ACIP precaution for most (93%) patients in this study. The observed drop in vaccines after GBS diagnosis indicates a disconnect between clinical practice and current recommendations.

Translation of a Claims-Based Frailty Index From the International Classification of Diseases, Ninth Revision, Clinical Modification to the Tenth Revision.

The Faurot frailty index (FFI) is a validated algorithm that uses enrollment and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based billing information from Medicare claims data as a proxy for frailty. In October 2015, the US health-care system transitioned from the ICD-9-CM to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Applying the Centers for Medicare and Medicaid Services General Equivalence Mappings, we translated diagnosis-based frailty indicator codes from the ICD-9-CM to the ICD-10-CM, followed by manual review. We used interrupted time-series analysis of Medicare data to assess the comparability of the pre- and posttransition FFI scores. In cohorts of beneficiaries enrolled in January 2015-2017 with 8-month frailty look-back periods, we estimated associations between the FFI and 1-year risk of aging-related outcomes (mortality, hospitalization, and admission to a skilled nursing facility). Updated indicators had similar prevalences as pretransition definitions. The median FFI scores and interquartile ranges (IQRs) for the predicted probability of frailty were similar before and after the International Classification of Diseases transition (pretransition: median, 0.034 (IQR, 0.02-0.07); posttransition: median, 0.038 (IQR, 0.02-0.09)). The updated FFI was associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, similar to findings from the ICD-9-CM era. Studies of medical interventions in older adults using administrative claims should use validated indices, like the FFI, to mitigate confounding or assess effect-measure modification by frailty.

A Road Map for Peer Review of Real-World Evidence Studies on Safety and Effectiveness of Treatments.

The growing acceptance of real-world evidence (RWE) in clinical and regulatory decision-making, coupled with increasing availability of health care data and advances in automated analytic approaches, has contributed to a marked expansion of RWE studies of diabetes and other diseases. However, a recent spate of high-profile retractions highlights the need for improvements in the conduct of RWE research as well as in the associated peer review and editorial processes. We review best pharmacoepidemiologic practices and common pitfalls regarding design, measurement, analysis, data validity, appropriateness, and generalizability of RWE studies. To enhance RWE study assessments, we propose that journal editors require 1) study authors to complete RECORD-PE, a reporting guideline for pharmacoepidemiological studies on routinely collected data, 2) availability of predetermined study protocols and analysis plans, 3) inclusion of pharmacoepidemiologists on the peer review team, and 4) provision of detail on data provenance, characterization, and custodianship to facilitate assessment of the data source. We recognize that none of these steps guarantees a high-quality research study. Collectively, however, they permit an informed assessment of whether the study was adequately designed and conducted and whether the data source used was fit for purpose.

Ethnoracial Differences in Premenopausal Hysterectomy: The Role of Symptom Severity.

OBJECTIVE: To evaluate whether greater symptom severity can explain higher hysterectomy rates among premenopausal non-Hispanic Black compared with White patients in the U.S. South rather than potential overtreatment of Black patients. METHODS: Using electronic health record data from 1,703 patients who underwent hysterectomy in a large health care system in the U.S. South between 2014 and 2017, we assessed symptom severity to account for differences in hysterectomy rates for noncancerous conditions among premenopausal non-Hispanic Black, non-Hispanic White, and Hispanic patients. We used Poisson generalized linear mixed modeling to estimate symptom severity (greater than the 75th percentile on composite symptom severity scores of bleeding, bulk, or pelvic pain) as a function of race-ethnicity. We calculated prevalence ratios (PRs). We controlled for factors both contra-indicating and contributing to hysterectomy. RESULTS: The overall median age of non-Hispanic White (n=1,050), non-Hispanic Black (n=565), and Hispanic (n=158) patients was 40 years. The White and Black patients were mostly insured (insured greater than 95%), whereas the Hispanic patients were often uninsured (insured 58.9%). White and Black patients were mostly treated outside academic medical centers (nonmedical center: 63.7% and 58.4%, respectively); the opposite was true for Hispanic patients (nonmedical center: 34.2%). Black patients had higher bleeding severity scores compared with Hispanic and White patients (median 8, 7, and 4 respectively) and higher bulk scores (median 3, 1, and 0, respectively), but pain scores differed (median 3, 5, and 4, respectively). Black and Hispanic patients were disproportionately likely to have severe symptoms documented on two or more symptoms (referent: not severe on any symptoms) (adjusted PR [Black vs White] 3.02, 95% CI 2.29-3.99; adjusted PR [Hispanic vs White] 2.61, 95% CI 1.78-3.83). Although Black and Hispanic patients were more likely to experience severe symptoms, we found no racial and ethnic differences in the number of alternative treatments attempted before hysterectomy. CONCLUSION: We did not find evidence of overtreatment of Black patients. Our findings suggest potential undertreatment of Black and Hispanic patients with uterine-sparing alternatives earlier in their disease progression.

Missing data approaches in longitudinal studies of aging: A case example using the National Health and Aging Trends Study.

PURPOSE: Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults. METHODS: We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1-2, frail: 3-5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data. RESULTS: Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty. CONCLUSIONS: Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research.

Permanent Supportive Housing Receipt and Health Care Use Among Adults With Disabilities.

This study assessed whether permanent supportive housing (PSH) participation is associated with health service use among a population of adults with disabilities, including people transitioning into PSH from community and institutional settings. Our primary data sources were 2014 to 2018 secondary data from a PSH program in North Carolina linked to Medicaid claims. We used propensity score weighting to estimate the average treatment effect on the treated of PSH participation. All models were stratified by whether individuals were in institutional or community settings prior to PSH. In weighted analyses, among individuals who were institutionalized prior to PSH, PSH participation was associated with greater hospitalizations and emergency department (ED) visits and fewer primary care visits during the follow-up period, compared with similar individuals who largely remained institutionalized. Individuals who entered PSH from community settings did not have significantly different health service use from similar comparison group members during the 12-month follow-up period.

Are fewer cases of diabetes mellitus diagnosed in the months after SARS-CoV-2 infection? A population-level view in the EHR-based RECOVER program.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.