Cross-sectional and longitudinal associations among healthcare costs and deficit accumulation.

BACKGROUND: Type 2 diabetes mellitus and overweight/obesity increase healthcare costs. Both are also associated with accelerated aging. However, the contributions of this accelerated aging to increased healthcare costs are unknown. METHODS: We use data from a 8-year longitudinal cohort followed at 16 U.S. clinical research sites. Participants were adults aged 45-76 years with established type 2 diabetes and overweight or obesity who had enrolled in the Action for Health in Diabetes clinical trial. They were randomly (1:1) assigned to either an intensive lifestyle intervention focused on weight loss versus a comparator of diabetes support and education. A validated deficit accumulation frailty index (FI) was used to characterize biological aging. Discounted annual healthcare costs were estimated using national databases in 2012 dollars. Descriptive characteristics were collected by trained and certified staff. RESULTS: Compared with participants in the lowest tertile (least frail) of baseline FI, those in the highest tertile (most frail) at Year 1 averaged $714 (42%) higher medication costs, $244 (22%) higher outpatient costs, and $800 (134%) higher hospitalization costs (p < 0.001). At Years 4 and 8, relatively greater increases in FI (third vs. first tertile) were associated with an approximate doubling of total healthcare costs (p < 0.001). Mean (95% confidence interval) relative annual savings in healthcare costs associated with randomization to the intensive lifestyle intervention were $437 ($195, $579) per year during Years 1-4 and $461 ($232, $690) per year during Years 1-8. These were attenuated and the 95% confidence interval no longer excluded $0 after adjustment for the annual FI differences from baseline. CONCLUSIONS: Deficit accumulation frailty tracks well with healthcare costs among adults with type 2 diabetes and overweight or obesity. It may serve as a useful marker to project healthcare needs and as an intermediate outcome in clinical trials.

Association of Intensive Lifestyle Intervention for Type 2 Diabetes With Labor Market Outcomes.

Importance: An intensive lifestyle intervention (ILI) has been shown to improve diabetes management and physical function. These benefits could lead to better labor market outcomes, but this has not been previously studied. Objective: To estimate the association of an ILI for weight loss in type 2 diabetes with employment, earnings, and disability benefit receipt during and after the intervention. Design, Setting, and Participants: This cohort study included participants with type 2 diabetes and overweight or obesity and compared an ILI with a control condition of diabetes support and education. Data for the original trial were accrued from August 22, 2001, to September 14, 2012. Trial data were linked with Social Security Administration records to investigate whether, relative to the control group, the ILI was associated with improvements in labor market outcomes during and after the intervention period. Difference-in-differences models estimating relative changes in employment, earnings, and disability benefit receipt between the ILI and control groups were used, accounting for prerandomization differences in outcomes for linked participants. Outcome data were analyzed from July 13, 2020, to May 17, 2023. Exposure: The ILI consisted of sessions with lifestyle counselors, dieticians, exercise specialists, and behavioral therapists on a weekly basis in the first 6 months, decreasing to a monthly basis by the fourth year, designed to achieve and maintain at least 7% weight loss. The control group received group-based diabetes education sessions 3 times annually during the first 4 years, with 1 annual session thereafter. Main Outcomes and Measures: Employment and receipt of federal disability benefits (Supplemental Security Income and Social Security Disability Insurance), earnings, and disability benefit payments from 1994 through 2018. Results: A total of 3091 trial participants were linked with Social Security Administration data (60.1% of 5145 participants initially randomized and 97.0% of 3188 of participants consenting to linkage). Among the 3091 with fully linked data, 1836 (59.4%) were women, and mean (SD) age was 58.4 (6.5) years. Baseline clinical and demographic characteristics were similar between linked participants in the ILI and control groups. Employment increased by 2.9 (95% CI, 0.3-5.5) percentage points for the ILI group relative to controls (P = .03) with no significant relative change in disability benefit receipt (-0.9 [95% CI, -2.1 to 0.3] percentage points; P = .13). Conclusions and Relevance: The findings of this cohort study suggest that an ILI to prevent the progression and complications of type 2 diabetes was associated with higher levels of employment. Labor market productivity should be considered when evaluating interventions to manage chronic diseases.

Clinical and pharmacy utilization outcomes with brand to generic antiepileptic switches in patients with epilepsy.

PURPOSE: To determine if switching from select branded to generic equivalent antiepileptic drugs (AEDs) in patients with epilepsy is associated with adverse outcomes. METHODS: A retrospective cohort study using a large health insurance plan claims database comparing patients with epilepsy who switched from brand to generic equivalent phenytoin, lamotrigine, or divalproex after 6 months (switch cohorts) to matched patients who remained on the brand (nonswitch cohorts). Primary outcomes measured include the incidence rate ratio (IRR) of discontinuation of the index AED; change in dose of index AED or addition of another AED; and the event rate ratio (ERR) of the composite of all-cause emergency department (ED) visits or hospitalizations. KEY FINDINGS: Lamotrigine and divalproex showed no differences in AED utilization changes between the switchers and nonswitchers [IRR for lamotrigine 1.00, 95% confidence interval (CI) 0.84-1.19; IRR for divalproex 1.02, 95% CI, 0.88-1.42]. Compared with nonswitchers, the phenytoin switch cohort had greater incidence of AED utilization changes (IRR 1.85, 95% CI 1.50-2.29). The switch versus nonswitch cohorts did not demonstrate differences in ED visits or hospitalizations for the studied AEDs (ERR for phenytoin 0.96, 95% CI 0.80-1.16; ERR for lamotrigine 0.97, 95% CI 0.80-1.17; ERR for divalproex 0.83, 95% CI 0.66-1.06). SIGNIFICANCE: Brand to generic switching of phenytoin was not associated with more clinical events but was associated with increased index drug discontinuations, dose changes, or therapy augmentations. Lamotrigine or divalproex brand to generic switching was not associated with increased incidence of events or utilization changes compared with patients remaining on the branded product. Changes in AED utilization may be more sensitive than ED visits and hospitalizations for detecting adverse outcomes.

Outcomes of a rheumatoid arthritis disease therapy management program focusing on medication adherence.

BACKGROUND: A national pharmacy benefits management company implemented a rheumatoid arthritis (RA) disease therapy management (DTM) program as an enhanced offering to patients receiving specialty pharmacy services. The program was designed to improve medication adherence, maximize therapeutic outcomes, and enhance physical functioning and health-related quality of life (HRQOL) by empowering patients and improving their knowledge of RA. OBJECTIVES: To evaluate (a) adherence to injectable RA medications for patients participating in an RA DTM program compared with nonparticipating patients receiving injectable RA medications at specialty or community pharmacies and (b) HRQOL, work productivity, and physical functioning before versus after completing the RA DTM program. METHODS: Patients who had an RA diagnosis and a pharmacy claim for an injectable RA medication during the identification period (August 2007 through September 2008) and were continuously enrolled with the plan from 4 months before through 8 months after the identification date were stratified into 3 patient cohorts: DTM, specialty pharmacy, and community pharmacy. DTM patients were further categorized into a DTM intent-to-treat (ITT) cohort (all 340 DTM-enrolled patients) and a DTM completer cohort (subset of 266 ITT patients who completed the month 6 consultation). DTM completer, specialty, and community pharmacy cohorts were matched 1:1:1 (n = 244 in each cohort after matching) using a propensity score that represented the likelihood of completing the DTM program. The primary outcome was adherence to injectable RA medications, measured as the proportion of days covered (PDC) over an 8-month post-identification period. Patient-reported outcomes (short form [SF]-12, Work Productivity Activity Impairment [WPAI], and Health Assessment Questionnaire-Disability Index [HAQ-DI]) were evaluated among all 371 DTM patients who completed the month 0 and month 6 consultations regardless of whether they met continuous enrollment requirements (patient-reported sample). RESULTS: Of specialty pharmacy patients, approximately 14% chose DTM participation. During the post-identification period, mean PDC was 0.83 for DTM ITT, 0.89 for DTM completer, 0.81 for specialty pharmacy, and 0.60 for community pharmacy patients. Differences were statistically significant for both DTM cohorts compared with the community pharmacy cohort (P < 0.001) and for the DTM completer cohort compared with the specialty pharmacy cohort (P < 0.001), but not for the DTM ITT cohort compared with the specialty pharmacy cohort (P = 0.291). In the patient-reported sample, mean SF-12 physical component scores significantly increased by 1.1 points (P = 0.048); mean SF-12 mental component scores were not significantly changed (P = 0.679); mean WPAI work productivity decreased by 10.8 percentage points (P = 0.045); and mean HAQ-DI scores significantly improved by 0.08 points (P < 0.001). CONCLUSIONS: Patients participating in the RA DTM program had significantly higher injectable RA medication adherence compared with community pharmacy patients. Adherence to injectable RA medications was significantly higher for patients completing the RA DTM program, but not for the DTM ITT group, compared with patients receiving specialty pharmacy services alone. Patients completing the RA DTM program experienced improvements in SF-12 physical component and HAQ-DI scores but did not demonstrate improvements to SF-12 mental scores or work productivity.

Risk of acute myocardial infarction in patients treated with thiazolidinediones or other antidiabetic medications.

PURPOSE: Controversy surrounds the question whether thiazolidinediones (TZDs) increase the risk of acute myocardial infarction (AMI). This study examined risk of AMI in patients with type 2 diabetes mellitus (T2DM) who were taking TZDs or other antidiabetic medications. METHODS: Using a nested case-control design, a cohort of patients aged 18-84 years with T2DM and use of an oral antidiabetic medication or exenatide between January 2002 and June 2006 was identified. Cases of AMI were matched with up to four controls based on age, gender, health plan, geography, and diabetes therapy regimen. Over the 1-year pre-index period, TZD exposure was compared with no TZD exposure, after adjustment for potential confounders. RESULTS: Overall, 1681 cases were identified and matched with 6653 controls. Compared with no TZD exposure, an increased risk of AMI was not observed among TZD exposed patients (adjusted OR 1.01; 95%CI, 0.85-1.20; adjusted p = 0.98). When exposure proximity to the event was examined, the risk of AMI was significantly increased with recent rosiglitazone exposure between 1 and 60 days prior to the case date (adjusted OR 1.69; 95%CI, 1.18-2.44; adjusted p = 0.045) and was not significantly increased with current or remote rosiglitazone exposure or current, recent, or remote pioglitazone exposure. CONCLUSION: TZD exposure did not increase the risk of AMI when exposure proximity was not considered. However, when evaluating exposure proximity to the event, the risk of AMI was increased with recent rosiglitazone exposure between 1 and 60 days prior to the case date.

Effect of an intervention to increase statin use in medicare members who qualified for a medication therapy management program.

BACKGROUND: The cardiovascular (CV) benefits of lipid-lowering therapy in older adults with hypercholesterolemia and underlying risk factors for coronary artery disease (CAD) have been well documented. Significant reductions in the risk of myocardial infarction (MI) and coronary death have been demonstrated with statin therapy, benefits that are of particular relevance in patients with diabetes. Managed care interventions with prescribers have increased the use of selected drugs such as statins. OBJECTIVES: To (1) measure the increase in new users of statins associated with the implementation of a statin initiation intervention aimed at prescribers for Medicare Part D Medication Therapy Management Program (MTMP) members with diabetes or CAD and (2) estimate the potential cost savings associated with the projected reduction in CV events based on published controlled trials. METHODS: Medicare Advantage Prescription Drug (MA-PD) and prescription drug plan (PDP) members of a pharmacy benefits manager (PBM) were identified for the intervention who (1) met the criteria for MTMP (expected to incur at least dollars 4,000 in annual pharmacy expenditures for Part D-covered medications, filled at least 10 distinct Part D-covered medications, and had at least 3 of 5 chronic diseases of interest); (2) were identified as having diabetes or CAD (patients with a history of MI were considered to have CAD); and (3) had no pharmacy claims for a statin between January and June 2006. In August 2006, the primary prescribers for antidiabetic or CV medications of 1,144 identified members were sent educational materials and a report listing their patients with diabetes or CAD who were not receiving statin therapy. A comparison group of MA-PD members (N = 700) with diabetes or CAD was identified who did not receive the intervention but who met all of the MTMP criteria except the presence of at least 3 of 5 chronic diseases of interest. Logistic regression was conducted to evaluate the intervention effectiveness after adjusting for age, gender, geography, and chronic disease score. To determine the implications of this intervention for routine practice, outcome measures included estimates of (1) the number of patient interventions necessary to prevent 1 major CV event and (2) the coronary event costs avoided by the intervention. The number of interventions necessary to prevent 1 major CV event was estimated by (1) calculating the number of members requiring interventions in order for 1 member to initiate statin therapy, based on the present study's findings, and then (2) calculating the number of statin initiations necessary to avoid a major CV event, based on clinical trial estimates of the effect of statin treatment on CV event rates. RESULTS: During the 4-month period following the intervention, 12.1% (n = 138) of the intervention members started a statin medication compared with 7.3% (n =51) of comparison members (P = 0.001). After covariate adjustment, the odds of initiating a statin medication were 65% higher (adjusted odds ratio [OR] = 1.65; 95% confidence interval [CI] = 1.15-2.36; P = 0.006) in the intervention than in the comparison group. The estimated number of members requiring interventions to prevent 1 major CV event was 220. The estimated coronary event cost avoidance is dollars 12,323 per 220 members who received the intervention, after subtraction of program administrative costs and the cost of statin drug therapy. CONCLUSION: A statin initiation intervention aimed at prescribers for MA-PD and PDP members with diabetes or CAD who qualified for MTMP services was successful in increasing statin use among this group of members at high risk for CV events.

Acute and continuation treatment adequacy with venlafaxine extended release compared with fluoxetine.

STUDY OBJECTIVE: To compare treatment adequacy in the management of depression during the acute and continuation phases between patients newly treated with venlafaxine extended release (XR) and those newly treated with fluoxetine. DESIGN: Retrospective observational analysis of pharmacy claims data. SETTING: Large California-based managed care organization. PATIENTS: A total of 11,298 patients newly prescribed venlafaxine XR or fluoxetine between January 1, 2000, and February 28, 2001, and continuously enrolled throughout the study, as well as a subset of 7430 patients who continued taking venlafaxine XR or fluoxetine during the follow-up period. MEASUREMENTS AND MAIN RESULTS: The Health Plan Employer Data and Information Set definition was used for continuous antidepressant treatment during the acute and continuation phases. Treatment adequacy was determined for those deemed continuous. Patients receiving within +/- 10% of the target dose for each drug (venlafaxine XR 75-150 mg, fluoxetine 20 mg) were defined as receiving an adequate dose. Logistic regression was used to evaluate venlafaxine XR versus fluoxetine on treatment adequacy, controlling for age, sex, physician specialty, and pharmacy benefit. The unadjusted adequacy rate for the venlafaxine XR-only group was 79% versus 57% for the fluoxetine-only group for 84 continuous days (p<0.0001) and 77% versus 52%, respectively, for 180 continuous days (p<0.0001). The adjusted odds ratios of achieving treatment adequacy with venlafaxine XR only versus that with fluoxetine only were 3.05 (95% confidence interval [CI] 2.65-3.52) for 84 continuous days and 3.57 (95% CI 3.00-4.24) for 180 continuous days. CONCLUSION: Patients newly prescribed venlafaxine XR were at least 3 times more likely to achieve treatment adequacy for 84 and 180 days compared with those newly prescribed fluoxetine. Treatment adequacy as a proxy for optimal treatment may be an important factor to consider when selecting an antidepressant drug.

New-onset treatment-dependent diabetes mellitus and hyperlipidemia associated with atypical antipsychotic use in older adults without schizophrenia or bipolar disorder.

OBJECTIVES: To examine the association between atypical antipsychotic medications and incident treatment for diabetes mellitus or hyperlipidemia in elderly adults without diagnoses of schizophrenia or bipolar disorder. DESIGN: Two case-control studies using medical and pharmacy claims data. SETTING: United States managed care population from multiple insurance plans. PARTICIPANTS: Individuals aged 65 and older enrolled in a Medicare Advantage or commercial (health maintenance organization) managed care health plan in the western United States with no claims indicating diagnosis of schizophrenia or bipolar disorder in the 1 year pre-index period. Cases were defined as persons newly initiated on an antidiabetic (n = 13,075) or antihyperlipidemic (n = 63,829) medication on the index date. For the new diabetes mellitus analysis, 65,375 controls were matched to cases based on age, sex, health-plan type, and index date year. In the new hyperlipidemia analysis, 63,829 controls were matched to cases based on the same variables. MEASUREMENTS: Conditional logistic regressions were performed to determine the odds of initiated antidiabetic or antihyperlipidemic medication for participants exposed to atypical antipsychotics compared with those with no exposure. The models included comorbidities possibly associated with the outcome. RESULTS: Exposure to atypical antipsychotics was associated with significantly greater adjusted odds of starting an antidiabetic medication (1.32, 95% confidence interval (CI) = 1.10-1.59) but significantly lower odds of starting an antihyperlipidemic medication (0.76, 95% CI = 0.67-0.87). CONCLUSION: Use of atypical antipsychotics in older adults for conditions other than schizophrenia and bipolar disorder was associated with incident treatment of diabetes mellitus but not of hyperlipidemia, suggesting that older adults may be susceptible to the adverse metabolic consequences of these agents.

Mail-order pharmacy use and medication adherence among Medicare Part D beneficiaries with diabetes.

OBJECTIVE: To examine medication adherence among Medicare Part D beneficiaries initiating oral anti-diabetic medications and explore whether there is any association of using mail-order pharmacy (vs. retail pharmacy) with better adherence in this patient population. RESEARCH DESIGN AND METHODS: Using administrative pharmacy claims data, we conducted a retrospective cohort study on Medicare Part D beneficiaries who newly initiated oral anti-diabetic treatment between July 1, 2008 and December 31, 2008. Mail-order pharmacy users were matched to retail pharmacy users via propensity scoring, controlling for patient demographic and clinical characteristics. Adherence with oral anti-diabetic medications during the benefit year of 2009 was assessed using the proportion of days covered (PDC). Comparison of medication adherence between the mail-order pharmacy group and retail pharmacy group was conducted in the propensity matched sample using the paired t-tests and McNemar's tests. RESULTS: A total of 22,546 patients who initiated oral anti-diabetic medications were identified. The average PDC was 0.60 and only 41.6% of the study population attained good adherence (defined as PDC ≥ 0.8) with oral anti-diabetic medications during calendar year 2009. The matched sample included 1361 patients in each of the mail-order and retail pharmacy cohorts. Compared with the retail pharmacy group, mail-order pharmacy users demonstrated a significantly higher PDC (0.68 vs. 0.61; P < 0.001) throughout the benefit year. More patients in the mail-order pharmacy group (49.7%) attained good adherence with their oral anti-diabetic medications compared to 42.8% in the retail pharmacy group (P < 0.001). LIMITATIONS: The study was subject to limitations inherent in retrospective claims database analysis. CONCLUSIONS: Adherence with oral anti-diabetic medications among Medicare Part D beneficiaries is suboptimal. Patients using mail-order pharmacy had better adherence to oral anti-diabetic medications than those who used retail pharmacies. However, the causal relationship between mail-order pharmacy use and adherence should be further examined in a randomized study setting.

Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor.

BACKGROUND: Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors (PPIs) may modify the antiplatelet effects of clopidogrel bisulfate. METHODS: We conducted a retrospective cohort study of persons enrolled in a multistate health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone. Patients who were discharged from the hospital after myocardial infarction (MI) or coronary stent placement and treated with clopidogrel plus a PPI (n = 1033) were matched 1:1 (using propensity scoring) with patients with similar cardiovascular risk factors treated with clopidogrel alone. Rehospitalizations for MI or coronary stent placement were evaluated for up to 360 days. A subanalysis was conducted to study the impact of pantoprazole sodium, the most used PPI. RESULTS: Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for MI (adjusted hazard ratio, 1.93; 95% confidence interval, 1.05-3.54; P = .03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64; 1.16-2.32; P = .005) than did patients receiving clopidogrel alone. Increased risk of rehospitalization for MI or coronary stent placement was also observed for the subgroup of patients receiving clopidogrel plus pantoprazole (adjusted hazard ratio, 1.91; 95% confidence interval, 1.19-3.06; P = .008). CONCLUSIONS: Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone. Prospective clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel.

Improving patient self-management of multiple sclerosis through a disease therapy management program.

OBJECTIVE: To examine the effect of a multiple sclerosis (MS) disease therapy management (DTM) program that incorporates a disease self-management component and a medication therapy management component within a structured 7-month program. STUDY DESIGN: Observational cohort study. METHODS: Pharmacy claims were evaluated over an 8-month follow-up period to calculate injectable MS medication adherence and persistence among 156 continuously eligible patients who completed the DTM program compared with 156 patients in each of 2 propensity score-matched control groups (retail pharmacy patients and specialty pharmacy patients). For 283 patients completing the DTM program, the Short Form 12, Work Productivity Activity Impairment questionnaire, and MS relapses were assessed at month 0 and at month 6. RESULTS: Injectable MS medication adherence was significantly higher for DTM patients compared with retail pharmacy patients (0.92 vs 0.86, P <.001) and was similar for DTM patients and specialty pharmacy patients (0.92 vs 0.90, P = .23). The DTM patients demonstrated significantly greater persistence on therapy (220 days) compared with the specialty pharmacy patients (188 days) (P = .002) and the retail pharmacy patients (177 days) (P <.01). The Short Form 12 and Work Productivity Activity Impairment results did not significantly change from month 0 to month 6. Multiple sclerosis relapses were reported by 14.0% of patients at month 0 and by 9.3% of patients at month 6 (P = .03). Ninety-seven percent of patients at month 6 reported that the DTM program was very helpful or somewhat helpful in enabling them to better manage their health. CONCLUSIONS: An MS DTM program incorporating medication management resulted in increased adherence and persistence to injectable MS medications and decreased MS relapses. Quality of life and work productivity were not significantly changed. Patients reported improved ability to manage their health.

Use of controller medications in patients initiated on a long-acting beta2-adrenergic agonist before and after safety alerts.

PURPOSE: The utilization of controller medications before initiating a long-acting beta(2)-adrenergic agonist (LABA) before and after the Food and Drug Administration (FDA) alerts is examined. METHODS: Electronic claims from a health insurer in the Western United States were examined during two distinct identification periods: before FDA alerts (October 1, 2003, through September 30, 2005) and after FDA alerts (December 1, 2005, through September 30, 2006). Identified patients were at least 12 years old, newly initiated on an LABA, and continuously enrolled during the preperiod (six months before the identification date). Previous controller use was defined as a prescription for an inhaled corticosteroid, mast-cell stabilizer, theophylline, leukotriene modifier, or oral or injectable corticosteroid during the preperiod. RESULTS: Overall, 18,115 patients were identified before the alerts and 7,347 after the alerts. Use of a controller before an LABA was observed in 40% of patients with asthma only, 37% with chronic obstructive pulmonary disease (COPD) only, 65% with COPD plus asthma, and 21% with no asthma or COPD diagnosis. Controller use decreased significantly after FDA alerts as compared with before FDA alerts for patients with asthma only (38% versus 41%, p = 0.005) and patients with no asthma or COPD (17% versus 23%, p < 0.0001). CONCLUSION: Previous use of a controller medication before initiation of an LABA was observed in 40% of study patients with a diagnosis of asthma, 37% with COPD, 65% with COPD and asthma, and 21% of patients with no diagnosis of asthma or COPD. Use of a controller medication decreased significantly in patients with asthma or no diagnosis of asthma or COPD following alerts issued by FDA regarding the increased risk of asthma-related death in patients receiving LABAs.