Comparative safety and cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in nursing homes.

AIM: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents. MATERIALS AND METHODS: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates. RESULTS: The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference. CONCLUSIONS: SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA.

Use of electronic health record data to examine administrations of pro re nata analgesics during hip fracture post-acute care.

PURPOSE: Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture. METHODS: Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration. RESULTS: Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day. CONCLUSIONS: EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care.

Evaluation of post-acute care and one-year outcomes among Medicare beneficiaries with hip fractures: a retrospective cohort study.

BACKGROUND: Post-acute care (PAC) services after hospitalization for hip fracture are typically provided in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), or at home via home health care (HHC). Little is known about the clinical course following PAC for hip fracture. We examined the nationwide burden of adverse outcomes by PAC setting in the year following discharge from PAC for hip fracture. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries > 65 years who received PAC services in U.S. SNFs, IRFs, or HHC following hip fracture hospitalization between 2012 and 2018. Individuals who had a fall-related injury (FRI) during PAC or received PAC services in multiple settings were excluded. Primary outcomes included FRIs, all-cause hospital readmissions, and death in the year following discharge from PAC. Cumulative incidences and incidence rates for adverse outcomes were reported by PAC setting. Exploratory analyses examined risk ratios and hazard ratios between settings before and after inverse-probability-of-treatment-weighting, which accounted for 43 covariates. RESULTS: Among 624,631 participants (SNF, 67.78%; IRF, 16.08%; HHC, 16.15%), the mean (standard deviation) age was 82.70 (8.26) years, 74.96% were female, and 91.30% were non-Hispanic White. Crude incidence rates (95%CLs) per 1000 person-years were highest among individuals receiving SNF care for FRIs (SNF, 123 [121, 123]; IRF, 105 [102, 107]; HHC, 89 [87, 91]), hospital readmission (SNF, 623 [619, 626]; IRF, 538 [532, 544]; HHC, 418 [414, 423]), and death (SNF, 167 [165, 169]; IRF, 47 [46, 49]; HHC, 55 [53, 56]). Overall, rates of adverse outcomes generally remained higher among SNF care recipients after covariate adjustment. However, inferences about the group with greater adverse outcomes differed for FRIs and hospital readmissions based on risk ratio or hazard ratio estimates. CONCLUSIONS: In this retrospective cohort study of individuals hospitalized for hip fracture, rates of adverse outcomes in the year following PAC were common, especially among SNF care recipients. Understanding risks and rates of adverse events can inform future efforts to improve outcomes for older adults receiving PAC for hip fracture. Future work should consider calculating risk and rate measures to assess the influence of differential time under observation across PAC groups.

Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy : A Propensity Score-Matched Cohort Study.

BACKGROUND: An osteoporosis drug holiday is recommended for most patients after 3 to 5 years of therapy. Risedronate has a shorter half-life than alendronate, and thus the residual length of fracture protection may be shorter. OBJECTIVE: To examine the comparative risks of drug holidays after long-term (≥3 years) risedronate versus alendronate therapy. DESIGN: Population-based, matched, cohort study. SETTING: Province-wide health care administrative databases providing comprehensive coverage to Ontario residents aged 65 years or older between November 2000 and March 2020. PATIENTS: Persons aged 66 years or older who had long-term risedronate therapy and a drug holiday were matched 1:1 on propensity score to those who had long-term alendronate therapy and a drug holiday. MEASUREMENTS: The primary outcome was hip fracture within 3 years after a 120-day ascertainment period. Secondary analyses included shorter follow-up and sex-specific estimates. Cox proportional hazards models were used to estimate hazard ratios (HRs) for fracture risk between groups. RESULTS: A total of 25 077 propensity score-matched pairs were eligible (mean age, 81 years; 81% women). Hip fracture rates were higher among risedronate than alendronate drug holidays (12.4 and 10.6 events, respectively, per 1000 patient-years; HR, 1.18 [95% CI, 1.04 to 1.34]; 915 total hip fractures). The association was attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00 to 1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85 to 1.24]; 2 years: HR, 1.14 [CI, 0.96 to 1.32]). LIMITATION: Analyses were limited to health care administrative data (potential unmeasured confounding), and some secondary analyses contained few events. CONCLUSION: Drug holidays after long-term therapy with risedronate were associated with a small increase in risk for hip fracture compared with alendronate drug holidays. Future research should examine how best to mitigate this risk. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Control yourself: ISPE-endorsed guidance in the application of self-controlled study designs in pharmacoepidemiology.

PURPOSE: Consensus is needed on conceptual foundations, terminology and relationships among the various self-controlled "trigger" study designs that control for time-invariant confounding factors and target the association between transient exposures (potential triggers) and abrupt outcomes. The International Society for Pharmacoepidemiology (ISPE) funded a working group of ISPE members to develop guidance material for the application and reporting of self-controlled study designs, similar to Standards of Reporting Observational Epidemiology (STROBE). This first paper focuses on navigation between the types of self-controlled designs to permit a foundational understanding with guiding principles. METHODS: We leveraged a systematic review of applications of these designs, that we term Self-controlled Crossover Observational PharmacoEpidemiologic (SCOPE) studies. Starting from first principles and using case examples, we reviewed outcome-anchored (case-crossover [CCO], case-time control [CTC], case-case-time control [CCTC]) and exposure-anchored (self-controlled case-series [SCCS]) study designs. RESULTS: Key methodological features related to exposure, outcome and time-related concerns were clarified, and a common language and worksheet to facilitate the design of SCOPE studies is introduced. CONCLUSIONS: Consensus on conceptual foundations, terminology and relationships among SCOPE designs will facilitate understanding and critical appraisal of published studies, as well as help in the design, analysis and review of new SCOPE studies. This manuscript is endorsed by ISPE.

Derivation and assessment of the opioid use disorder severity scale: prediction of health, psychological and social adjustment problems.

Background: Severity of substance use disorder (SUD) is typically evaluated by tabulating the number of symptoms. The resulting estimate of disorder severity is, however, biased due to intercorrelations among symptoms and their unequal salience. Objective. Employing item response theory (IRT) methodology, opioid use disorder symptoms were calibrated to derive the Opioid Use Disorder Severity Scale (OUDSS) and assess its predictive ability in men and women separately. Methods: A two-parameter IRT model was utilized to derive the OUDSS from DSM-IV symptoms recorded on the Structured Clinical Interview for DSM-IV (SCID) in 438 men and 429 women who reported at least one lifetime opioid consumption event. The predictive ability of the OUDSS was evaluated using the 10 health, psychological, and social adjustment domains of the revised Drug Use Screening Inventory (DUSI-R) assessed 2 years later. Results: The OUDSS score predicted the severity of problems in all 10 DUSI-R domains in men and women. The OUDSS also predicted the DUSI-R diagnostic cutoff score of overall problem density score in men and women (OR = 2.21 and OR = 4.83, respectively). Withdrawal was the most frequently endorsed symptom in this sample of opioid users. The other symptoms' frequencies, while somewhat lower than withdrawal's, did not differ from it substantially, indicating a similar severity threshold. Conclusions: OUDSS enables dimensional measurement of opioid use severity on an interval scale. The OUDSS and DUSI-R together can identify problem areas requiring prevention or treatment.

Methodological guidance for the use of real-world data to measure exposure and utilization patterns of osteoporosis medications.

Observational studies of osteoporosis medications can provide critical real-world evidence (RWE) that fills knowledge gaps left by clinical trials. However, careful consideration of study design is needed to yield reliable estimates of association. In particular, obtaining valid measurements of exposure to osteoporosis medications from real-world data (RWD) sources is complicated due to different medication classes, formulations, and routes of administration, each with different pharmacology. Extended half-lives of bisphosphonates and extended dosing of denosumab and zoledronic acid require particular attention. In addition, prescribing patterns and medication taking behavior often result in gaps in therapy, switching, and concomitant use of osteoporosis therapies. In this review, we present important considerations and provide specialized guidance for measuring osteoporosis drug exposures in RWD. First, we compare different sources of RWD used for osteoporosis drug studies and provide guidance on identifying osteoporosis medication use in these data sources. Next, we provide an overview of osteoporosis pharmacology and how it can influence decisions on exposure measurement within RWD. Finally, we present considerations for the measurement of osteoporosis medication exposure, adherence, switching, long-term exposures, and drug holidays using RWD. Ultimately, a thorough understanding of the differences in RWD sources and the pharmacology of osteoporosis medications is essential to obtain valid estimates of the relationship between osteoporosis medications and outcomes, such as fractures, but also to improve the critical appraisal of published studies.

Sliding Scale Insulin Use in Nursing Homes Before and After Onset of the COVID-19 Pandemic.

OBJECTIVE: To characterize sliding-scale insulin (SSI) use in US nursing homes (NHs) before and after the COVID-19 pandemic. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 129,829 US NH residents on SSI (01/2018-06/2022) across 12 NH chains with a common electronic health record system. METHODS: Among all residents with at least 1 administration of SSI documented in the electronic medication administration record, we described resident demographics, frequency of SSI monotherapy vs combination therapy with another diabetes medication, number of daily capillary blood glucose readings ("fingersticks"), and hypoglycemia (capillary blood glucose <70 mg/dL) and hyperglycemia after first SSI use. We used interrupted time series analysis (ITS) with segmented linear regression models to examine whether the monthly prevalence of SSI use changed at and after the onset of the COVID-19 pandemic (March 2020). RESULTS: There were 129,829 unique NH residents with SSI use [51% women, average age 71.3 (SD 11.7) years]. Of these, 36% of residents received SSI monotherapy and 64% received SSI combination therapy. Residents on SSI received an average of 3.96 (SD 1.41) fingersticks per day. Overall, 26% of SSI users experienced a hypoglycemic event within 30 days of the first SSI dose. The ITS analysis identified a step decrease in the rate of SSI use following the onset of the COVID-19 pandemic (43 fewer SSI users per 1000 insulin users) but no change in overall trend over time from before the onset of the pandemic. CONCLUSIONS AND IMPLICATIONS: SSI use and fingerstick burden are high in NH residents. Hypoglycemia occurred commonly among residents on SSI. Future research should compare the safety and effectiveness of SSI monotherapy vs other diabetes medication regimens to guide person-centered prescribing decisions in NHs.

Differences in opioid prescriptions by race among U.S. older adults with a hip fracture transitioning to community care.

BACKGROUND: Appropriate pain management can facilitate rehabilitation after a hip fracture as patients transition back to the community setting. Differences in opioid prescribing by race may exist during this critical transition period. METHODS: We conducted a retrospective cohort study of older adult U.S. Medicare beneficiaries with a hip fracture to examine whether the receipt and dose of opioids differs between Black and White patients as they transitioned back to the community setting. We stratified beneficiaries by whether they received institutional post-acute care (PAC). Outcomes were (1) receipt of an opioid and (2) opioid doses in the first 90 days in the community in milligram morphine equivalents (MMEs; also presented in mg oxycodone). We estimated relative rates and risk differences of opioid receipt and dose differences using Poisson and linear regression models, respectively, using the parametric g-formula to standardize for age and sex. RESULTS: We identified 164,170 older adults with hip fracture (mean age = 82.7 years; 75% female; 72% with PAC; 46% with opioid use after fracture). Overall use of opioids in the community was similar between Black and white beneficiaries. Black beneficiaries had lower average doses in their first 90 days in both total cumulative doses (PAC group: 165 [95% CI -264 to -69] fewer MMEs [-248 mg oxycodone]; no PAC: 167 [95% CI -274 to -62] fewer MMEs [-251 mg oxycodone]) and average MME per days' supply of medication (PAC: -3.0 [-4.6 to -1.4] fewer MMEs per day [-4.5 mg oxycodone]; no PAC: -4.7 [-4.6 to -1.4] fewer MMEs per day [-7.1 mg oxycodone]). In secondary analyses, Asian beneficiaries experienced the greatest differences (e.g., 617-653 fewer cumulative mg oxycodone). CONCLUSION: Racial differences exist in pain management for Medicare beneficiaries after a hip fracture. Future work should examine whether these differences result in disparities in short- and long-term health outcomes.

Health equity in COVID-19 testing among patients of a large national pharmacy chain.

Background: Several social determinants of health and other structural factors drive racial and ethnic disparities in COVID-19 risk, morbidity, and mortality. Public-private collaborations with community pharmacies have been successful in expanding access to COVID-19 testing and reaching historically underserved communities. The objectives of this study were to describe individuals who sought testing for COVID-19 at a national community pharmacy chain and to understand potential racial and ethnic inequities in testing access, positivity, and infection with emerging variants of concern. Methods: We conducted a cross-sectional study of individuals aged ≥18 who were tested for COVID-19 (SARS-CoV-2) at a Walgreens pharmacy or Walgreen-affiliated mass testing site between May 1, 2021 and February 28, 2022. Positivity was defined as the proportion of positive tests among all administered tests. A geographically balanced random subset of positive tests underwent whole genome sequencing to identify specific viral variants (alpha, delta, and omicron). Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) to compare the likelihood of testing positive and testing positive with an emerging variant of concern across race and ethnicity groups. Results: A total of 18,576,360 tests were analyzed (16.0% tests were positive for COVID-19; 59.5% of tests were from White individuals and 13.1% were from Black individuals). American Indian or Alaska Native (OR = 1.12; 95%CI = 1.10-1.13), Hispanic or Latino (1.20; 95%CI = 1.120, 1.21), and Black (1.12; 95%CI = 1.12, 1.13) individuals were more likely to test positive for COVID-19 compared to White individuals. Non-White individuals were also more likely to test positive for emerging variants of concern (e.g., Black individuals were 3.34 (95%CI = 3.14-3.56) times more likely to test positive for omicron compared to White individuals during the transition period from delta to omicron). Discussion: Using a national database of testing data, we found racial and ethnic differences in the likelihood of testing positive for COVID-19 and testing positive for emerging viral strains. These results demonstrate the feasibility of public-private collaborations with local pharmacies and pharmacy chains to support pandemic response and reach harder to reach populations with important health services.

Cholinesterase Inhibitor Initiation Does Not Increase the Risk of Fall-Related Injury in Older Adults Treated With Beta-Blockers: A Self-Controlled Case Series Design.

BACKGROUND: Prescribing cholinesterase inhibitors (ChEIs) concurrently with beta-blockers might cause syncope that increases the risk of fall-related injuries (FRIs). This self-controlled case series study assesses the risk of FRIs associated with initiating ChEIs while receiving beta-blockers among Medicare fee-for-service-insured nursing home (NH) residents in the United States. METHODS: We identified individuals at their first dispensing of a beta-blocker between 2016 and 2019 after at least 45 days of long-stay NH residency. Individuals were followed from the first day of beta-blocker use until beta-blocker discontinuation, Medicare disenrollment, death, or study end. ChEI initiation was classified as the first 60 days of new ChEI dispensing after 45 days of no ChEI exposure. FRIs were assessed during beta-blocker use periods, and age-adjusted incidence rate ratios (IRR) for ChEI-initiation days versus other days were calculated using conditional Poisson regression models. Analyses were weighted for event-dependent observation periods due to the high risk of mortality after an FRI in this population. Subgroup analyses were conducted for several key time-fixed variables, including sex, age, ChEI type, ChEI dose, beta-blocker selectivity, and beta-blocker dose. RESULTS: The FRI risk after ChEI initiation was not elevated among 837 residents who experienced an FRI while using beta-blockers (IRR=0.90 [95%CLs 0.71, 1.15]). Analyses of ChEI initiation in several subgroups yielded similar results. CONCLUSIONS: There was no substantial difference in FRI risk when initiating ChEIs among older NH residents receiving beta-blocker therapy versus periods without ChEI initiation, suggesting that there is no clinically significant pharmacodynamic drug-drug interaction between beta-blockers and ChEIs.

COVID-19 Vaccines: Moderna And Pfizer-BioNTech Use Varied By Urban, Rural Counties.

We investigated county-level variation in mRNA COVID-19 vaccine use among Medicare beneficiaries throughout the United States. There was greater use of Pfizer-BioNTech vaccines than Moderna vaccines in urban areas for first and booster doses.

COVID-19 and Influenza Vaccine Coadministration Among Older U.S. Adults.

INTRODUCTION: Coadministering COVID-19 and influenza vaccines is recommended by public health authorities and intended to improve uptake and convenience; however, the extent of vaccine coadministration is largely unknown. Investigations into COVID-19 and influenza vaccine coadministration are needed to describe compliance with newer recommendations and to identify potential gaps in the implementation of coadministration. METHODS: A descriptive, repeated cross-sectional study between September 1, 2021 to November 30, 2021 (Period 1) and September 1, 2022 to November 30, 2022 (Period 2) was conducted. This study included community-dwelling Medicare beneficiaries ≥ 66 years who received an mRNA COVID-19 booster vaccine in Periods 1 and 2. The outcome was an influenza vaccine administered on the same day as the COVID-19 vaccine. Adjusted ORs and 99% CIs were estimated using logistic regression to describe the association between beneficiaries' characteristics and vaccine coadministration. Statistical analysis was performed in 2023. RESULTS: Among beneficiaries who received a COVID-19 vaccine, 78.8% in Period 1 (N=6,292,777) and 89.1% in Period 2 (N=4,757,501), received an influenza vaccine at some point during the study period (i.e., before, after, or on the same day as their COVID-19 vaccine), though rates were lower in non-White and rural individuals. Vaccine coadministration increased from 11.1% to 36.5% between periods. Beneficiaries with dementia (aORPeriod 2=1.31; 99%CI=1.29-1.32) and in rural counties (aORPeriod 2=1.19; 99%CI=1.17-1.20) were more likely to receive coadministered vaccines, while those with cancer (aORPeriod 2=0.90; 99%CI=0.89-0.91) were less likely. CONCLUSIONS: Among Medicare beneficiaries vaccinated against COVID-19, influenza vaccination was high, but coadministration of the 2 vaccines was low. Future work should explore which factors explain variation in the decision to receive coadministered vaccines.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making.

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

Adoption of sodium-glucose cotransporter-2 inhibitors among prescribers caring for nursing home residents.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitor (SGLT2I) use has increased among community-dwelling populations, but little is known about how clinicians have prescribed them for US nursing home (NH) residents. We described the adoption of SGLT2Is by prescribers caring for long-stay NH residents by clinician specialty and over time, compared with sulfonylureas, an older diabetes medication class. METHODS: We conducted a retrospective cohort study of prescribers of SGLT2Is and sulfonylureas for all long-stay US NH residents aged 65 years or older (2017-2019). Using 100% of Medicare Part D claims linked to prescriber characteristics data, we identified all dispensings of SGLT2Is and sulfonylureas for long-stay NH residents and their associated prescribers. We described the distribution of prescriber specialties for each drug class over time as well as the number of NH residents prescribed SGLT2s versus sulfonylureas. We estimated the proportions of prescribers who prescribed both drug classes versus only sulfonylureas or only SGLT2Is. RESULTS: We identified 36,427 unique prescribers (SGLT2I: N = 5811; sulfonylureas: N = 35,443) for 117,667 NH residents between 2017 and 2019. For both classes, family medicine and internal medicine physicians accounted for most prescriptions (75%-81%). Most clinicians (87%) prescribed only sulfonylureas, 2% prescribed SGLT2Is only, and 11% prescribed both. Geriatricians were least likely to prescribe only SGLT2Is. We observed an increase in the number of residents with SGLT2I use from n = 2344 in 2017 to n = 5748 in 2019. CONCLUSIONS: Among NH residents, most clinicians have not incorporated SGLT2Is into their prescribing for diabetes, but the extent of use is increasing. Family medicine and internal medicine physicians prescribed the majority of diabetes medications for NH residents, and geriatricians were the least likely to prescribe only SGLT2Is. Future research should explore provider concerns regarding SGLT2I prescribing, particularly adverse events.

Comparative safety of sulfonylureas among U.S. nursing home residents.

BACKGROUND: The comparative safety of sulfonylureas (SUs) in nursing home (NH) residents remains understudied despite widespread use. We compared the effects of three SU medications and initial SU doses on adverse glycemic and cardiovascular events among NH residents. METHODS: This national retrospective cohort study linked Medicare claims with Minimum Data Set 2.0 assessments for long-stay NH residents aged ≥65 years between January 2008 and September 2010. Exposures were the SU medication initiated (glimepiride, glipizide, or glyburide) and doses (standard or reduced). One-year outcomes were hospitalizations or emergency department visits for severe hypoglycemia, heart failure (HF), stroke, and acute myocardial infarction (AMI). After the inverse probability of treatment and inverse probability of censoring by death weighting, we estimated hazard ratios (HR) using Cox regression models with robust 95% confidence intervals (CI). RESULTS: The cohort (N = 6821) included 3698 new glipizide, 1754 glimepiride, and 1369 glyburide users. Overall, the mean (standard deviation) age was 81.4 (8.2) years, 4816 (70.6%) were female, and 5164 (75.7%) were White non-Hispanic residents. The rates of severe hypoglycemia were 30.3 (95% CI 22.3-40.1), 49.0 (95% CI 34.5-67.5), and 35.9 (95% CI 22.2-54.9) events per 1000 person-years among new glipizide, glimepiride, and glyburide users, respectively (glimepiride versus glipizide HR 1.6, 95% CI 1.0-2.4, p = 0.04; glyburide versus glipizide HR 1.2, 95% CI 0.7-1.9, p = 0.59). The rates of severe hypoglycemia were 27.1 (95% CI 18.6-38.0) and 42.8 (95% CI 33.6-53.8) events per 1000 person-years among new users of reduced and standard SU doses, respectively (HR 2.2, 95% CI 1.4-3.5, p < 0.01). Rates of HF, stroke, and AMI were similar between medications and doses. CONCLUSIONS: Among long-stay NH residents, new use of glimepiride and standard SU doses resulted in higher rates of severe hypoglycemic events. Cardiovascular outcomes may not be affected by the choice of SU medication or dose.

Post-Acute Care Setting After Hip Fracture Hospitalization and Subsequent Opioid Use in Older Adults.

OBJECTIVE: Pain management in post-acute care (PAC) requires careful balance, with both opioid use and inadequate pain treatment linked to poor outcomes. We describe opioid use among older adults following discharge from PAC for hip fracture in skilled nursing facilities (SNFs) and inpatient rehabilitation facilities (IRFs). DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: Medicare beneficiaries with Medicare Provider Analysis (MedPAR) claims, aged 66 years and older with a hip fracture hospitalization between 2012 and 2018 followed by PAC in SNFs or IRFs and then discharge to the community. METHODS: Individuals were followed from PAC discharge for up to 1 year to assess opioid use. Covariate-standardized risk ratios (RR) and risk differences (RD) for opioid use within 7 days of PAC discharge were estimated via parametric g-formula with modified Poisson regression, and hazard ratios (HRs) for any post-PAC opioid use and long-term opioid use via Fine-Gray sub-distribution hazards regression. RESULTS: Of 101,021 individuals, 80% (n = 80,495) were discharged from SNFs and 20% (n = 20,526) from IRFs. Opioids were dispensed to 50,433 patients (50%) overall and the 1-year cumulative incidence was notably higher in IRF (68%) than SNF (46%) patients. The adjusted risk of discharge from PAC with an opioid was 41% lower after SNFs versus IRFs [RR: 0.59; 95% confidence limits (CLs): 0.57-0.61; and RD: -0.16; 95% CLs: -0.17 to -0.15]. The adjusted rate of any opioid use in the year after PAC discharge was 44% lower (HR: 0.56; 95% CLs: 0.54-0.57) and of long-term opioid use was 17% lower (HR: 0.83; 95% CLs: 0.80-0.87) after SNFs versus IRFs. CONCLUSIONS AND IMPLICATIONS: Opioid use is highly prevalent upon discharge from PAC after hip fracture, with lower use after SNF versus IRF care. Future research should assess the benefits and harms of post-PAC opioid prescribing and whether care practices during PAC can be improved to optimize long-term opioid use.

Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

Trends in COVID-19-Related Medication Use in US Nursing Homes, 2018-2022.

OBJECTIVES: Little is known about how COVID-19 treatment patterns have evolved over time in nursing homes (NHs) despite the devastating effects of COVID-19 in this setting. The aim was to describe changes in COVID-19-related medication use over time among NH residents in the United States. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: This study used electronic health records (EHR) from 11 different US NH corporations between January 1, 2018, and March 31, 2022. METHODS: The use of medications approved for COVID-19-related conditions or known to be used off-label for COVID-19 during the study period is identified. We described trends in the use of each drug and combined use per 1000 NH residents over calendar time [quarters (Q)]. RESULTS: A total of 59,022 unique residents with the use of an eligible medication were identified. Hydroxychloroquine use sharply increased from 9.8 in 2020Q1 to 30.2 orders per 1000 individuals in 2020Q2. Dexamethasone use increased sharply from 14.8 in 2020Q2 to a peak of 121.9 orders per 1000 individuals in 2020Q4. Azithromycin use increased from 44.1 in 2019Q3 to a peak of 99.9 orders per 1000 individuals in 2020Q4, with a drop in 2020Q3 of 51.3 per 1000 individuals in 2020Q3. Concurrent use of azithromycin and hydroxychloroquine increased sharply from 0.3 in 2020Q1 to 10.6 orders per 1000 residents in 2020Q2 and then drastically decreased to 0.6 per 1000 residents in 2020Q3. Concurrent use of dexamethasone and azithromycin rose considerably from 0.7 in 2020Q2 to 28.2 orders per 1000 residents in 2020Q4. CONCLUSIONS AND IMPLICATIONS: As in other settings, COVID-19-related medication use in NHs appears to have changed in response to the shifting evidence base and availability of medications during the pandemic. Providers should continue to diligently modify their prescribing as new evidence accrues.