Publications

PURPOSE: To characterize trajectories of nephrotoxic potential (NxP) drug use among older adults with Type 2 Diabetes (T2D) treated with SGLT2is and identify associated patient characteristics.

METHODS: Using 2012-2019 Medicare data, we selected patients with T2D who filled at least one prescription for SGLT2is. Index date was the date of the first SGLT2i prescription filled. We quantified the number of drugs with NxP used every month during the first 12 months following the index date. The monthly counts of drugs with NxP were incorporated into the group-based trajectory model to identify groups with similar drug use patterns. Finally, we performed a multinomial logistic regression model to examine the association between patient characteristics and group membership.

RESULTS: The study cohort comprised 8811 Medicare beneficiaries with T2D who initiated SGLT2i during the study period with the mean age 67.5 ± 10.6 years. We identified 3 trajectories NxP drug use: no (n = 2142, 24%), low (n = 4752, 54%) and high (n = 1917, 22%) use of drugs with NxP, with patients falling into these categories based on the number of drugs with NxP they used over the time: no drugs, one drug, or two or more drugs. Age, gender, low-income subsidy eligibility and clinical characteristics were associated with group membership.

CONCLUSIONS: We successfully identified three trajectory groups, with a substantial proportion of patients showing low use of drugs with NxP. Both social and clinical factors were associated with the use of NxP drugs.

IMPORTANCE: Veterans with mental health conditions (MHC) face unique challenges obtaining high-quality, coordinated health care. With a growing number of veterans receiving VA-purchased community care (CC) provided outside the Veterans Health Administration (VA), evidence is needed on how veterans in this high-prevalence, marginalized subgroup experience CC.

OBJECTIVE: To compare experiences with CC over time for US veterans with and without MHC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, cross-sectional survey study analyzed responses to the Survey of Healthcare Experiences of Patients-Community Care Survey (SHEP-CCS) from 2016 to 2021. Ratings of CC were examined across 9 domains and compared for veterans with and without MHC, adjusting for differences in baseline characteristics using regression models. Data were analyzed from March 2023 to September 2024.

EXPOSURE: Diagnosis of MHC, defined as bipolar disorder, major depression, posttraumatic stress disorder, schizophrenia, or psychosis.

MAIN OUTCOMES AND MEASURES: Veterans' ratings of CC across 9 domains, overall satisfaction, overall clinician rating, clinician communication, eligibility determination, first appointment access, recent appointment access, nonappointment access, care coordination, and billing, were assessed on a scale of 1 to 100. Unadjusted annual ratings of care experiences were analyzed by survey domain. A series of 4 respondent-level linear regression models were examined for each domain and survey responses were pooled to test for differences in experiences between veterans with vs without MHC.

RESULTS: This study included 231 869 veterans, including 62 911 veterans with MHC (27.1%) and 168 958 without MHC (72.9%). Veterans with MHC had a mean (SD) age of 55.8 (14.7) years, 8327 were female (18.5%), and 24 792 had 3 or more comorbidities (29.9%). Veterans without MHC had a mean (SD) age of 62.5 (15.2) years, 11 277 were female (11.0%), and 49 689 had 3 or more comorbidities (24.0%). In fully adjusted models, veterans with vs without MHC had lower adjusted overall satisfaction with CC by -1.8 (95% CI, -2.3 to -1.3) points (P < .001). Ratings in all domains were lower for veterans with vs without MHC (-0.09 to -0.05 SDs of domain scores) (P < .001 for all comparisons). Although ratings improved from 2016 to 2021, significant differences persisted over time for veterans with vs without MHC for all domains.

CONCLUSIONS AND RELEVANCE: In this survey study of veterans receiving CC from 2016 to 2021, those diagnosed with MHC reported lower ratings of CC across all measured domains, and these differences persisted over time. These findings highlight where focused care coordination and quality improvement efforts could improve CC experiences for this vulnerable subpopulation of veterans.

INTRODUCTION: Long-acting insulin analogues are the standard of care for people with type 1 diabetes (T1D) in high-income countries but remain largely inaccessible and understudied in low-resource settings. In settings where glycaemic control is typically poor and food insecurity is common, long-acting insulin analogues may offer tangible clinical benefits for people with T1D. To determine whether insulin glargine, a long-acting insulin analogue, reduces the risk of serious hypoglycaemia and/or improves glycaemic time-in-range (TIR) versus human insulin regimens in this population, we are conducting the Human vs Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings randomised controlled trial.

METHODS AND ANALYSIS: This is a 1:1 randomised, parallel-group clinical trial comparing biosimilar insulin glargine with human insulin (Neutral Protamine Hagedorn (NPH) or premixed 70/30 insulin) in 400 youth with type 1 diabetes (T1D) recruiting in Dhaka, Bangladesh (n=250) and Mwanza, Tanzania (n=150). Blinded continuous glucose monitors will be used to assess glycaemic control in both study arms over 14-day periods at baseline and at 3, 6 and 12 months after randomisation. The co-primary outcomes are the per cent time in serious hypoglycaemia (<54 mg/dL) and TIR (70-180 mg/dL) at 6 months of follow-up. Secondary outcomes include TIR at 12 months and time-in-hypoglycaemia, time-above-range, nocturnal hypoglycaemic events and glycaemic control (ie, haemoglobin A1C (HbA1c)) at 6- and 12-months of follow-up. Treatment satisfaction and quality of life are assessed at baseline, 6- and 12 month follow-up. Additionally, the study is conducting qualitative interviews, quantitative assessments of treatment satisfaction and quality of life, as well as assessing the cost-effectiveness of analogue insulin use in low-resource settings.

ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at the University of Pittsburgh (STUDY21110122), the National Health Research Ethics Committee at the National Institute for Medical Research in Tanzania (NIMR/HQ/R.8a/Vol.IX/4265) and the Ethical Review Committee (ERC) of Diabetic Association of Bangladesh (BADAS-ERC/EC/22/405). Research findings will be shared by the local partner organisations and institutions with relevant stakeholders including youth living with diabetes, policy makers, healthcare workers and the general public. Findings will also be shared at local, regional and international scientific meetings.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05614089.

BACKGROUND: Proton-pump inhibitors (PPIs) are effective in treating peptic ulcer disease (PUD), but they are often prescribed beyond the approved duration. Because PPIs are associated with adverse effects, there is a need for effective stewardship.

OBJECTIVE: To identify the frequency of and healthcare factors associated with PPI prescriptions exceeding the approved eight-week treatment duration for PUD.

METHODS: We conducted a retrospective cohort study of patients diagnosed with acute PUD without other indications for PPI use using data from the Veterans Health Administration in the United States. Exposures were patient, provider, and facility factors that could influence PPI prescribing. The outcome was time to a filled PPI prescription exceeding the approved treatment duration for PUD. Associations were assessed using a multivariable time-to-recurrent-event model to calculate adjusted hazard ratios (aHR) and population-attributable fractions. Patients who developed indications for long-term PPI use were censored.

RESULTS: We identified 7708 patients with PUD who met eligibility criteria and received PUD treatment (median age 79 [IQR 71-85], 7% female). Thirty-five percent had PPI prescriptions exceeding the approved duration for a median of 346 days (IQR 165-643) of overuse. On the patient level, inpatient PUD diagnosis (aHR 1.32, 95% CI 1.25-1.39), use of nonsteroidal anti-inflammatory drugs (NSAIDs) (aHR 1.26, 95% CI 1.18-1.34), use of anticoagulants (aHR 1.25, 95% CI 1.13-1.38), and moderate frailty (1.15, 95% CI 1.06-1.26) had the strongest associations with filled PPI prescriptions exceeding the approved duration. On the health-system level, inpatient PUD diagnosis had the highest peak population attributable fraction at 0.26, followed by NSAIDs and anticoagulants at 0.18.

CONCLUSIONS: Markers of patient complexity and medication use not meeting gastroprotection guidelines are associated with inappropriate PPI persistence among patients with PUD. These data may inform future targeted PPI deprescribing programs.

BACKGROUND: One of the largest-ever retail drug shortages began in 2018 when several angiotensin II receptor blockers (ARBs) for treating hypertension, heart failure, and chronic kidney disease-valsartan, losartan, and irbesartan-were recalled for carcinogenic impurities. The long-term consequences of the ARB shortages and whether certain groups experienced more adverse outcomes is unknown.

OBJECTIVE: To evaluate changes in adherence and health outcomes after ARB recalls and to identify patients who experienced greater changes in access and adverse clinical outcomes.

METHODS: Using an integrated claims and electronic health record dataset and a difference-in-differences design, we evaluated changes in the proportion of days covered (PDC) for ARBs and similar drugs (angiotensin-converting enzyme inhibitors [ACE-Is]), uncontrolled blood pressure, major cardiovascular event (MACE)-related acute care visits, and all-cause ambulatory care visits in the 12 months before vs 18 months after recalls for valsartan, losartan, and irbesartan users vs patients taking similar, nonrecalled drugs (ACE-Is, nonrecalled ARBs). Triple-difference models characterized heterogeneous associations by pre-recall patient demographic (race, ethnicity, age), clinical (baseline indication, mental health conditions), and adherence variables.

RESULTS: Adjusting for pre-recall patient characteristics, we observed no significant changes in PDC for ARBs and ACE-Is (combined), uncontrolled blood pressure, or ambulatory care visits among 86,507 recalled ARB users vs 123,583 comparison drug users in the 18 months after the recalls. Following the recalls, medication switches increased on average by an additional 2.08 percentage points (p.p.) per quarter (95% CI = 2.01-2.15) for recalled ARB vs comparison drug users, a 195.9% relative increase. We observed the most switches in the 90-day period immediately after valsartan's recall (difference-in-difference: 9.48 p.p.; 95% CI = 9.36-9.59; relative change = 892%). Cumulatively, 55.2% of valsartan, 7.6% of losartan, and 18.9% of irbesartan users switched medications after 18 months. We observed an increase in the proportion of recalled ARB vs comparison patients who experienced medication gaps exceeding 30 days (1.13 p.p. per quarter on average; 95% CI = 0.97-1.30), which was most apparent after approximately 15 months (5 quarters). Although MACE-related acute care visits did not change in the quarter (90 days) immediately after valsartan's recall, we observed an increase of 1.40 additional visits per 1,000 recalled ARB vs comparison drug patients in each subsequent quarter, a 9.3% relative increase. Results were similar across most subgroups.

CONCLUSIONS: The 2018 ARB recalls were associated with immediate changes in antihypertension medication use. Many patients transitioned to alternative medications. Although overall impacts on clinical outcomes were minimal and not statistically significant, small increases in medication gaps and MACE-related acute care visits among some patients occurred after more than 1 year. The ARB recalls may have been associated with fewer adverse events than other recent shortages owing to the widespread availability of alternative treatments in the same or similar drug class.

BACKGROUND: Clinical guidelines recommend the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) in patients with atherosclerotic cardiovascular disease (ASCVD) and nonoptimal low-density lipoprotein.

OBJECTIVE: To evaluate the association between discontinuation of statin use after PCSK9i initiation and subsequent ASCVD events.

METHODS: This pre-post retrospective comparative study used national administrative data of adult statin medication users (age ≥18 years) with an index PCSK9i claim (January 1, 2019, to April 30, 2021), prior ASCVD diagnosis, and a 2-year follow-up period. Proportions and probability of ASCVD events post-index (PCSK9i) vs pre-index (PCSK9i) for patients who discontinued statins (discontinued cohort) and those who continued statins (continued cohort) were compared. Propensity score weighting was used to balance patient baseline characteristics. Multivariate Poisson regression and time-to-event Cox regression models were used to assess the association between statin discontinuation and ASCVD events.

RESULTS: There were 294 and 46 patients in the continued and discontinued cohorts, respectively. Unweighted results showed that patients in the continued cohort were more likely to receive high-intensity statins (32% vs 22%; P = 0.4) and have a Charlson Comorbidity Index score of 3 or more (62% vs 54%; P  =  0.5) at baseline. Baseline statin adherence was lower in the discontinued cohort (6.7% vs 59%; P < 0.001) but 30% each in the propensity 1:1 matched cohort. The 2 cohorts (after matching) had similar ASCVD event prevalence (discontinued cohort: 24% vs continued cohort: 26%) in the baseline and the same lower prevalence (6.5% each; P > 0.9) in the 24-month follow-up period. The odds of any ASCVD event post-index was comparable between the 2 cohorts (reference: continued cohort; odds ratio = 1.88; 95% CI = 0.28-14.6; P = 0.51). There were no statistically significant differences between the 2 groups in the Cox regression (P = 0.47).

CONCLUSIONS: Post-ASCVD event rates were significantly lower in both cohorts, but discontinuation of statins was not associated with unfavorable ASCVD outcomes.

BACKGROUND: Migraine prevalence is estimated to be 15% (approximately 50 million people) in the United States, posing a significant burden on the health care system and a top cause of years lived with disability. Consequently, migraine leads to increased work-related disability, including presenteeism and absenteeism. Novel prophylactic treatments for migraine that target the calcitonin gene-related peptide pathway, including monoclonal antibodies to the calcitonin gene-related peptide ligand or the calcitonin gene-related peptide receptor (calcitonin gene-related peptide monoclonal antibodies) and gepants, offer new options for migraine prevention. The advent of new medications presents an opportunity for development of outcomes-based agreements, particularly because these agents are more costly than traditional, nonspecific treatment alternatives. Outcomes-based agreements are pricing agreements between pharmaceutical manufacturers and payers, centered around predefined performance metrics to better align incentives and create shared risk between them.

OBJECTIVE: To report results of an outcomes-based agreement that was executed in a large integrated delivery and finance health system for patients with migraine who were prescribed erenumab, an anti-calcitonin gene-related peptide pathway monoclonal antibody.

METHODS: This is a prospective real-world analysis of commercial or health insurance exchange data from a large regional health system, based on parameters of an outcomes-based agreement. Eligible patients were new to calcitonin gene-related peptide monoclonal antibodies. Outcomes of interest included an erenumab adherence metric and changes in work absenteeism and rescue medication use. Proportion adherent and rescue medication use were assessed for the entire eligible patient cohort, whereas work absenteeism was only evaluated for a subset of eligible patients for whom work outcomes data were available.

RESULTS: There were 5,507 patients who filled erenumab during the contract period, and 1,281 patients were new to calcitonin gene-related peptide monoclonal antibodies medications. Of those, 865 constituted the eligible patient cohort and 224 constituted the work outcomes cohort. Patient adherence to erenumab was 80.5% and 81.7% for the entire patient cohort and work outcomes cohort, respectively. Absenteeism was reduced by 5.5% (21.64 vs 20.44 hours; P = 0.664) and rescue medication use was decreased by 3.6% (0.362 vs 0.349 doses; P = 0.589). Absenteeism could have been impacted by the onset of the COVID-19 pandemic.

CONCLUSIONS: As measured, adherence to erenumab was high within the cohort. The inclusion of a work outcomes cohort provided valuable insights about the clinical benefits of erenumab for migraine prevention. Our findings provide additional insights on the real-world use of erenumab within the context of an outcomes-based agreement.

OBJECTIVE: This study sought to identify: (1) the demographic and clinical characteristics of very high-cost users (defined as patients with pharmaceutical expenditures that were equal to or greater than the 99th percentile), (2) whether or not these characteristics changed over time, (3) sociodemographic and clinical correlates of being very high-cost users, (4) the average pharmaceutical costs of very-high cost users, and (5) the therapeutic classes and medications that contributed to these high costs.

BACKGROUND: There are growing public concerns about rising drug costs, in part due to increased availability, greater effectiveness, and market considerations. There is a concentrated portion of patients that accounts for a disproportionately large portion of pharmaceutical expenditures.

METHODS: A large serial cross-sectional study was conducted with De-identified, member-level pharmacy claims (n = 65,739,791) from a large, national pharmacy benefits manager from January 1, 2018 to December 31, 2022. The main outcome and measures were 2018-2022 pharmaceutical expenditures; amounts were adjusted for inflation to reflect 2022-dollar values.

RESULTS: Across the study period, the odds of being classified as a very high-cost user were 1.31 times as high for those 45-64 years old compared with those 18-44 years old (reference category); the odds were 1.42 times as high for males compared with females; 1.13 times as high before those identifying as non-Hispanic Black compared with non-Hispanic white; 1.11 times as high for those enrolled in a health care exchange plan compared with a commercial plan. In addition, very high-cost users lived in areas with higher social needs. Human immunodeficiency virus, inflammatory conditions, multiple sclerosis, and cancer accounted for the largest share of costs among this group.

CONCLUSIONS: This study identified the unique characteristics of very high-cost pharmaceutical users and identified the top conditions and prescription drugs that drove high pharmaceutical expenditures among this population. These findings are essential to understanding rising pharmaceutical costs in the United States and can help identify the issues and solutions of specific cost drivers within our health care policies.