A randomized phase 2 study of the 5-HT4 receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery.

BACKGROUND: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT4] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery. METHODS: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 â€‹mL or 0.5 mg/100 â€‹mL pre-surgery only, or pre-surgery and daily post-surgery until return of gastrointestinal function or for up to 10 days. PRIMARY ENDPOINT: time to recovery of gastrointestinal function. RESULTS: Median time to recovery of gastrointestinal function was 2.6 days for both felcisetrag 0.5 â€‹mg daily and 0.5 â€‹mg pre-surgery versus 1.9 days for placebo (p â€‹> â€‹0.05). There were no notable differences in adverse events between treatment arms. CONCLUSIONS: Felcisetrag was well tolerated with no new safety concerns. However, no clinically meaningful difference in time to recovery of gastrointestinal function versus placebo was observed. Further investigation of the utility of 5-HT4 agonists in complicated, open abdominal surgeries may be warranted.

Stratified Patient Profiling for Vedolizumab Effectiveness in Crohn's Disease: Identifying Optimal Subgroups for Enhanced Treatment Response in the EVOLVE Study.

INTRODUCTION: This analysis evaluated the relative performance of vedolizumab and anti-tumor necrosis factor alpha (anti-TNFα) agents in subpopulations of biologic therapy-naive patients with Crohn's disease (CD) and assessed whether patients in whom vedolizumab would have a larger treatment effect vs anti-TNFα agents could be identified. METHODS: Data were from EVOLVE, a real-world, multicountry, retrospective cohort study of patients with inflammatory bowel disease who initiated first-line biologic treatment with vedolizumab (n = 195) or anti-TNFα agents (n = 245). Prediction models for time to clinical remission were developed in vedolizumab- and anti-TNFα-treated patients and used to estimate effect scores, a metric of predicted comparative efficacy, for each patient. Patients were ranked by effect scores and potential subpopulations were investigated. Simplified rules to identify these subpopulations were also developed using classification tree analysis. RESULTS: Among all patients, median time to clinical remission was 7.8 months (vedolizumab) and 11.1 months (anti-TNFα) (P < 0.05). Among patients in the top 40% of the effect score distribution, the median time to clinical remission was 4.8 months (vedolizumab) vs 18.1 months (anti-TNFα) (adjusted hazard ratio 2.0, 95% confidence interval 1.3-2.9). A simplified rule for identifying a subpopulation more likely to benefit from vedolizumab was based on having an ongoing CD exacerbation, no prior emergency visits, and non-stricturing disease. CONCLUSIONS: Subpopulations of biologic-naive patients with CD in whom vedolizumab appeared to have a larger effect relative to anti-TNFα agents for the outcome of clinical remission were identified. Validation of the identified subpopulations and simplified rules are warranted to confirm these findings. GOV IDENTIFIER: NCT03710486. Graphical Abstract available for this article.

Effectiveness and safety of vedolizumab and infliximab in biologic-naive patients with Crohn's disease: results from the EVOLVE study.

OBJECTIVES: This study compared the real-world effectiveness and safety of α 4 ß 7 -integrin inhibitor vedolizumab and anti-tumor necrosis factor alpha (anti-TNFα) inhibitor infliximab in biologic-naive patients with Crohn's disease (CD). METHODS: EVOLVE was a retrospective, multicenter, medical chart review of biologic-naive adults with inflammatory bowel disease receiving vedolizumab or anti-TNFα treatment as first-line biologics in Canada, Greece, and the USA. Twelve-month outcomes were analyzed in vedolizumab- or infliximab-treated patients with moderate-to-severe CD (and subgroups with complicated and noncomplicated CD) including cumulative rates of clinical response, clinical remission, and mucosal healing, and incidence rates of serious adverse events (SAEs) and serious infections (SIs). Inverse probability weighting (IPW) was used to account for baseline differences between treatment groups. RESULTS: Data were analyzed from 167 patients. In the IPW dataset (99 vedolizumab-treated and 63 infliximab-treated), adjusted 12-month clinical remission rates were 73.1% and 55.2%, respectively ( P  = 0.31). Overall, effectiveness rates were similar across treatment and complicated/noncomplicated disease subgroups. Adjusted 12-month incidence rates (first occurrence/1000 person-years) of SAEs for vedolizumab vs. infliximab: 43.6 vs. 200.9 [hazard ratio (HR) 0.36 (0.09-1.54)]; SIs: 10.8 vs. 96.0 [HR 0.08 (<0.01-2.64)]. AE incidence was significantly lower in vedolizumab- vs. infliximab-treated patients for complicated [131.6 vs. 732.2; HR 0.19 (0.05-0.65)] and noncomplicated [276.3 vs. 494.8; HR 0.59 (0.35-0.99)] disease subgroups. CONCLUSION: These real-world data on first-line biologics show no differences in 12-month effectiveness outcomes for vedolizumab- vs. infliximab-treated biologic-naive patients with CD. Vedolizumab may have a more favorable safety profile vs. infliximab in patients with complicated and noncomplicated disease.

Real-World Effectiveness of Vedolizumab Dose Escalation in Patients With Inflammatory Bowel Disease: A Systematic Literature Review.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent approved for the treatment of moderate to severely active inflammatory bowel disease (IBD: ulcerative colitis [UC] and Crohn's disease [CD]). Methods: A systematic literature review (SLR) of real-world studies was conducted to assess the effectiveness of dose escalation of vedolizumab every 8 weeks (Q8W) during maintenance treatment to achieve a response in patients who were either vedolizumab responders experiencing secondary loss of response (SLOR) or non-responders. MEDLINE and EMBASE databases were searched from January 2014 to August 2021. Results: Screening of SLR outputs identified 72 relevant real-world study publications featuring dose escalation of vedolizumab maintenance therapy. After qualitative review, ten eligible studies (9 articles, 1 abstract) were identified as reporting clinical response and/or clinical remission rates following escalation of intravenous vedolizumab 300 mg Q8W maintenance dosing to every 4 weeks (Q4W) maintenance dosing in adult patients with UC/CD (≥10 patients per study). Overall, 196/395 (49.6%) patients with IBD had a response within 54 weeks of vedolizumab maintenance dose escalation. Although definitions for clinical response/remission varied across the 10 studies, clinical response rates after escalated vedolizumab Q8W maintenance dosing ranged from 40.0% to 73.3% (9 studies) and from 30.0% to 55.8% for remission (4 studies) over a range of 8 to <58 weeks' follow-up. Conclusions: This synthesis of real-world effectiveness data in vedolizumab-treated patients with IBD indicates that approximately half were able to achieve or recapture clinical response after escalating vedolizumab maintenance dosing.

Real-world Effectiveness of Liraglutide vs. Sitagliptin Among Older Patients with Type 2 Diabetes Enrolled in a Medicare Advantage Prescription Drug Plan: A Retrospective Observational Study.

INTRODUCTION: Liraglutide and sitagliptin were compared on glycemic control and all-cause healthcare costs over a 1-year period among older adults with type 2 diabetes (65-89 years) enrolled in a national Medicare Advantage Prescription Drug health plan. METHODS: This was a retrospective study in which the index date was the first prescription fill for liraglutide or sitagliptin between 25 January 2010 and 31 December 2014. Post-index treatment persistence and glycosylated hemoglobin (HbA1c) at baseline and 1 year (± 90 days) post-index date were required. Patients were excluded if their record included use of insulin during the baseline period. Inverse probability of treatment weighting using stabilized weights was employed with final covariate adjusted regression modeling to estimate the primary outcome (mean change in HbA1c) and secondary outcomes (achieving glycemic goal and costs), each at 1-year post-index date. RESULTS: Overall, 3056 patients met the selection criteria, of whom 218 filled prescriptions for liraglutide and 2838 for sitagliptin. Adjusted mean change in HbA1c at 1 year post-index was - 0.42 with liraglutide versus - 0.12 with sitagliptin (P = 0.0012). Adjusted odds of achieving the treatment goals of HbA1c < 7% and achieving an HbA1c reduction of ≥ 1% were higher for  those on liraglutide than for those on sitagliptin (1.68, 95% confidence interval [CI] 1.25-2.24 and 1.76, 95% CI 1.31-2.36), respectively. Total healthcare costs in those achieving an HbA1c of < 7% were not significantly different between treatment groups but were higher within the liraglutide group for those achieving an HbA1c < 8%. CONCLUSIONS: When compared to sitagliptin, liraglutide was associated with greater achievement of an HbA1c < 7% over a 1-year period in an older population. This finding was not associated with a statistically significant increase in all-cause total healthcare costs, although costs were slightly higher in the liraglutide group than in the sitagliptin group.

Cardiovascular Safety of Concomitant Use of Atypical Antipsychotics and Long-Acting Stimulants in Children and Adolescents With ADHD.

OBJECTIVE: This study examined cardiovascular safety of concomitant use of long-acting stimulants (LAS) and atypical antipsychotics (AAP) in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD). METHOD: The study used 2004-2007 IMS LifeLink™ claims data involving 6- to 16-year-old children with ADHD and at least one LAS prescription from July 2004 to December 2006. Time-dependent Cox regression analysis was performed to evaluate the risk of cardiovascular disease (CVD) events due to concomitant use of LAS and AAP. RESULTS: The analytical cohort consisted of 37,903 children: 538 (1.9%) used LAS and AAP concurrently and the rest used LAS monotherapy. Time-dependent Cox regression analysis revealed no difference in CVD risk among concomitant users of LAS and AAP (hazard ratio = 1.19; 95% confidence interval = [0.60, 2.53]) when compared with users of LAS monotherapy. CONCLUSION: Concomitant use of LAS and AAP was not associated with risk of CVD events in ADHD patients when compared with LAS monotherapy.

Healthcare utilization and costs with fixed-source versus variable-source tacrolimus in patients receiving a kidney transplant.

AIMS: Switching drug manufacturers in transplant patients may require an increased intensity of therapeutic monitoring, leading to additional healthcare visits, associated laboratory tests, and perhaps hospitalizations. As real-world studies examining the interchangeability of tacrolimus from different manufacturers are limited, the purpose of this study was to examine the healthcare resource utilization (HRU) and economic impact of tacrolimus-switching in kidney transplantation. MATERIALS AND METHODS: This cross-sectional, retrospective study examined HRU and healthcare costs (HCCs) among patients with a kidney transplant who were prescribed tacrolimus from fixed-source (FS) vs variable-source (VS) manufacturers using claims data from the large US health plan Humana from October 1, 2012, to December 31, 2013. RESULTS: Overall, 1,024 patients were identified (FS: n = 674, 66%; VS: n = 350, 34%). The number of therapeutic drug monitoring (TDM) events for the VS group was 13% greater than for the FS group after controlling for demographics, comorbidity score, and number of medications (incidence rate ratio = 1.13, p = .033). Adjusted total HCCs were 9% lower for VS (US$28,054 vs US$30,823, p = .045). In the unadjusted analysis, VS had greater emergency department (ED) utilization (45% vs 35%, p < .002). In the VS group, the mean (standard deviation [SD]) number of days from manufacturer switch to first outpatient visit was 23.8 (33.6), and the number of days (SD) to first TDM event was 43.6 (56.2). LIMITATIONS: Study limitations include the lack of availability of many transplant-specific variables within the Humana database, potential errors/omissions in claims coding, and restriction of cross-sectional data examination to a 1-year period. CONCLUSIONS: VS patients had greater TDM and lower total HCCs. Further research is warranted to understand the drivers of ED use among the VS group, and to determine factors associated with delayed TDM after regimen modification. Opportunities may exist to improve the quality of care for patients receiving immunosuppressant treatment with tacrolimus.

The Effect of an Educational Intervention on Adherence to Intraocular Pressure-Lowering Medications in a Large Cohort of Older Adults with Glaucoma.

BACKGROUND: Glaucoma is a progressive, irreversible disease that can lead to vision loss and lower quality of life if treatment is not optimized. Effective glaucoma therapies are available to lower intraocular pressure (IOP) and minimize or delay disease progression. Nonetheless, adherence to treatment remains suboptimal for many patients. OBJECTIVE: To identify potentially nonadherent patients and evaluate the effect of patient- and physician-centric educational interventions on adherence by using a validated predictive model of nonadherence to glaucoma medication. METHODS: This prospective, randomized, controlled, and interventional study included Humana Medicare Advantage Prescription Drug plan patients with a glaucoma diagnosis between May and October 2014, ≥ 1 pharmacy claim for glaucoma medication, and ≥ 50% likelihood of nonadherence. Patients and physicians were randomized to cohorts A (no interventions), B (physician intervention), or C (patient and physician interventions). Physicians in cohorts B and C received information on the model, adherence, and patient profiles at baseline and months 3, 6, and 9. Patients in cohort C received educational materials on glaucoma and adherence (same schedule). The primary outcome was the proportion of days covered (PDC) with medication over 12 months. Adherence was defined as PDC ≥ 0.80. RESULTS: Overall, 23,306 patients and 2,955 physicians were eligible. After excluding physicians with < 3 nonadherent patients, each cohort included 200 physicians and 600 patients. Mean PDC was 0.54-0.56 across cohorts. At 12 months, ≥ 90.5% of physicians and ≥ 75.5% of patients remained in the study; mean PDC was 0.53-0.54 across cohorts. No statistically significant between-cohort differences in PDC and adherence were observed. CONCLUSIONS: Intensive educational mailings to patients and their physicians did not improve PDC or adherence in this large population of potentially nonadherent patients with glaucoma. Findings highlight the difficulty of improving adherence in a disease that requires lifelong therapy despite being largely asymptomatic and can inform development of future interventions aimed at improving adherence to glaucoma therapy. DISCLOSURES: This study was sponsored by Allergan plc (Dublin, Ireland). Fiscella and Chandwani are employees of Allergan plc. Caplan, Kamble, Bunniran, and Uribe are employees of Comprehensive Health Insights, a Humana company. The authors did not receive honoraria or other payments for authorship.

Understanding Prediabetes in a Medicare Advantage Population Using Data Adaptive Techniques.

The objective was to identify individuals with undiagnosed prediabetes from administrative data using adaptive techniques. The data source was a national Medicare Advantage Prescription Drug (MAPD) plan administrative data set. A retrospective, cross-sectional study developed and evaluated data adaptive logistic regression, decision tree, neural network, and ensemble predictive models for metabolic syndrome and prediabetes using 3 mutually exclusive cohorts (N = 279,903). The misclassification rate (MCR), average squared error (ASE), c-statistics, sensitivity (SN), and false positive (FP) rates were compared to select the final predictive models. MAPD individuals with continuous enrollment from 2013 to 2014 were included. Metabolic syndrome and prediabetes were defined using clinical guidelines, diagnosis, and laboratory data. A total of 512 variables identified through subject matter expertise in addition to utilizing all data available were evaluated for the modeling. The ensemble model demonstrated better discrimination (c-statistics, MCR, and ASE of 0.83, 0.24, and 0.16, respectively), high SN, and low FP rate in predicting metabolic syndrome than the individual data adaptive modeling techniques. Logistic regression demonstrated better discrimination (c-statistics, MCR, and ASE of 0.67, 0.13, and 0.11 respectively), high SN, and low FP rate in predicting prediabetes than the other adaptive modeling techniques or ensemble methods. The scored data predicted prediabetes in 44% of the MAPD population, which is comparable to 2005-2006 National Health and Nutrition Examination Survey prediabetes rates of 41%. The logistic regression model demonstrated good performance in predicting undiagnosed prediabetes in MAPD individuals.

Association of obesity with healthcare resource utilization and costs in a commercial population.

OBJECTIVE: To examine the association of obesity with healthcare resource utilization (HRU) and costs among commercially insured individuals. METHODS: This retrospective observational cohort study used administrative claims from 1 January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from 2008 to 2012 classified body mass index (BMI) into the World Health Organizations' BMI categories. The date of first observed BMI code was defined as the index date and continuous eligibility for one year pre- and post- index date was ensured. Post-index claims determined individuals' HRU and costs. Sampling weights developed using the entropy balance method and National Health and Nutrition Examination Survey data ensured representation of the US adult commercially insured population. Baseline characteristics were described across BMI classes and associations between BMI categories, and outcomes were examined using multivariable regression. RESULTS: The cohort included 9651 individuals with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%), overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class III (5.4%). Increasing BMI was associated with greater prevalence of cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics, analgesics and antidepressants rose with increasing BMI. Greater BMI level was associated with increased inpatient, emergency department and outpatient utilization, and higher total healthcare, medical and pharmacy costs. CONCLUSIONS: Increasing BMI was associated with higher prevalence of cardiometabolic conditions and higher HRU and costs. There is an urgent need to address the epidemic of obesity and its clinical and economic impacts.

Positive predictive value between medical-chart body-mass-index category and obesity versus codes in a claims-data warehouse.

OBJECTIVE: To evaluate the positive predictive value of claims-based V85 codes for identifying individuals with varying degrees of BMI relative to their measured BMI obtained from medical record abstraction. METHODS: This was a retrospective validation study utilizing administrative claims and medical chart data from 1 January 2009 to 31 August 2015. Randomly selected samples of patients enrolled in a Medicare Advantage Prescription Drug (MAPD) or commercial health plan and with a V85 claim were identified. The claims-based BMI category (underweight, normal weight, overweight, obese class I-III) was determined via corresponding V85 codes and compared to the BMI category derived from chart abstracted height, weight and/or BMI. The positive predictive values (PPVs) of the claims-based BMI categories were calculated with the corresponding 95% confidence intervals (CIs). RESULTS: The overall PPVs (95% CIs) in the MAPD and commercial samples were 90.3% (86.3%-94.4%) and 91.1% (87.3%-94.9%), respectively. In each BMI category, the PPVs (95% CIs) for the MAPD and commercial samples, respectively, were: underweight, 71.0% (55.0%-87.0%) and 75.9% (60.3%-91.4%); normal, 93.8% (85.4%-100%) and 87.8% (77.8%-97.8%); overweight, 97.4% (92.5%-100%) and 93.5% (84.9%-100%); obese class I, 96.9 (90.9%-100%) and 97.2% (91.9%-100%); obese class II, 97.0% (91.1%-100%) and 93.0% (85.4%-100%); and obese class III, 85.0% (73.3%-96.1%) and 97.1% (91.4%-100%). CONCLUSIONS: BMI categories derived from administrative claims, when available, can be used successfully particularly in the context of obesity research.

Association of obesity with healthcare utilization and costs in a Medicare population.

OBJECTIVES: To examine the association of obesity with healthcare resource utilization and costs in a Medicare population. METHODS: This study was a retrospective cohort study using Humana Medicare Advantage (MA) claims data. Body mass index (BMI) was assessed using ICD-9-CM status codes (V85 hierarchy) that have been validated in the data source to classify patients into BMI categories: normal (N), overweight (Ow), obese class I (ObI), obese class II (ObII), and obese class III (ObIII). Healthcare resource utilization (HRU) and costs were determined based on claims data. Descriptive statistics were used to examine baseline characteristics and HRU across BMI classes. Multivariable analysis was used to examine the association between BMI class and outcome measures. RESULTS: Among the 172,866 patients aged ≥65 years that were identified, BMI distribution was: N, 21%; Ow 37%; ObI, 24%, ObII, 10%; and ObIII, 9%. Inpatient, emergency department and outpatient utilization increased with greater BMI level, and greater BMI level was associated with higher total healthcare, medical and pharmacy costs. Greater prevalence of several cardiometabolic conditions, total medication use, and use of specific medication classes was observed with increasing BMI class. CONCLUSIONS: Greater BMI was associated with greater HRU and costs and observed increase in prevalence of cardiometabolic conditions. These results reflect an urgent need to address the epidemic of obesity and the resulting excessive clinical and economic burden on the healthcare system.

A comparison of entropy balance and probability weighting methods to generalize observational cohorts to a population: a simulation and empirical example.

PURPOSE: We compared methods to control bias and confounding in observational studies including inverse probability weighting (IPW) and stabilized IPW (sIPW). These methods often require iteration and post-calibration to achieve covariate balance. In comparison, entropy balance (EB) optimizes covariate balance a priori by calibrating weights using the target's moments as constraints. METHODS: We measured covariate balance empirically and by simulation by using absolute standardized mean difference (ASMD), absolute bias (AB), and root mean square error (RMSE), investigating two scenarios: the size of the observed (exposed) cohort exceeds the target (unexposed) cohort and vice versa. The empirical application weighted a commercial health plan cohort to a nationally representative National Health and Nutrition Examination Survey target on the same covariates and compared average total health care cost estimates across methods. RESULTS: Entropy balance alone achieved balance (ASMD ≤ 0.10) on all covariates in simulation and empirically. In simulation scenario I, EB achieved the lowest AB and RMSE (13.64, 31.19) compared with IPW (263.05, 263.99) and sIPW (319.91, 320.71). In scenario II, EB outperformed IPW and sIPW with smaller AB and RMSE. In scenarios I and II, EB achieved the lowest mean estimate difference from the simulated population outcome ($490.05, $487.62) compared with IPW and sIPW, respectively. Empirically, only EB differed from the unweighted mean cost indicating IPW, and sIPW weighting was ineffective. CONCLUSION: Entropy balance demonstrated the bias-variance tradeoff achieving higher estimate accuracy, yet lower estimate precision, compared with IPW methods. EB weighting required no post-processing and effectively mitigated observed bias and confounding. Copyright © 2016 John Wiley & Sons, Ltd.

"Act on Threes" Paradigm for Treatment Intensification of Type 2 Diabetes in Managed Care: Results of a Randomized Controlled Study with an Educational Intervention Targeting Improved Glycemic Control.

BACKGROUND: Clinical inertia, which has been defined as the recognition of a problem with a patient's management but failing to act, is a concern in type 2 diabetes (T2D) because it places the patient at risk of diabetes-related complications. Despite managed care organizations making significant investment in this area, little is known about the impact of educational programs aimed at aligning patients and their physicians with diabetes guidelines and thus overcoming clinical inertia. OBJECTIVE: To assess the impact of an educational intervention specifically designed to align patients and their physicians with 2012 American Diabetes Association (ADA) guidelines on glycated hemoglobin (A1c) testing frequency and insulin initiation. METHODS: The "Act on Threes" educational intervention was a 12-month, randomized controlled prospective study that included Medicare Advantage patients aged 18-85 years with T2D, who received ≥ 3 oral antidiabetes drugs (OADs) and/or had A1c not at goal and/or had no recent A1c evaluation over 12 months, as identified through the analysis of administrative claims data (May 1, 2011-April 30, 2013) from the Humana database. Identified patients were randomized 3:1 to receive the Act on Threes educational intervention in conjunction with standard care (intervention group) or standard care alone (control group). For the educational intervention, patients and physicians were simultaneously mailed general and targeted information aimed at aligning them to 3 vital aspects of A1c control: timely measurement of A1c every 3 months; timely treatment intensification to meet A1c goals with treatment intensification every 3 months if A1c is not at goal; and insulin initiation when appropriate, including patients receiving ≥ 3 OADs with A1c not at goal. Control patients were only enrolled if the treating physician was not involved in the care of any patients in the intervention group. The primary outcome measures were A1c testing frequency based on the ADA standard for compliance of ≥ 2 tests per year and insulin initiation in the 12-month postintervention period. A1c levels were evaluated for the subgroup of patients with available A1c measurements in the pre- and postintervention periods. Descriptive statistics were used to analyze differences between the intervention and control groups. Multiple logistic regression analysis was used to identify determinants of insulin initiation in the full study cohort. RESULTS: 6,243 patients (mean age 70 years; 43.5% female) were identified: 4,555 were randomized to the intervention group and 1,688 to the control group. The percentage of patients with ≥ 2 A1c tests per year was not significantly different postintervention for patients in the intervention and control groups (47.7% vs. 46.8%, respectively; P = 0.995). Intriguingly, the frequency of A1c testing increased significantly from pre- to postintervention in the intervention and control groups. Change in A1c level from pre- to postintervention was also similar for the 2 groups (P = 0.240). A similar percentage of patients in the intervention and control groups initiated insulin during the postintervention period (6.3% vs. 7.6%, respectively; P = 0.059). CONCLUSIONS: This randomized controlled study demonstrated that, compared with standard care, the Act on Threes educational intervention combined with standard care did not result in any significant differences in the frequency of A1c testing or in the initiation of insulin in patients with T2D. These findings are in contrast to uncontrolled comparative studies showing significant improvements in outcomes postintervention and reinforce the importance of study design in evaluating the effectiveness of educational programs. DISCLOSURES: This study was funded by Sanofi U.S. Reynolds, Davis, Kamble, and Uribe are employees of Comprehensive Health Insights, which was contracted by Sanofi U.S. to conduct, publish, and present this study. Bieszk and Wei are employees of Sanofi U.S. Reynolds and Uribe provided expertise and key clinical insights for the study design and methodology, provided interpretations of the data, contributed to the discussion, and reviewed the manuscript. Bieszk and Wei codeveloped the study design, researched data, contributed to discussion, and reviewed the manuscript. Davis and Kamble collected the data, provided study design, clinical insights, statistical and analytic reflections of the data, drafted the study reports, and reviewed the manuscript. All authors had full access to all the data in the study. Reynolds is the guarantor of this work and, as such, takes responsibility for the integrity of the data and the accuracy of the data analysis. ACKNOWLEDGMENTS: Writing/editorial support in the preparation of this manuscript, which was funded by Sanofi U.S., was provided by Rosalie Gadiot, PhD, of Excerpta Medica, who wrote the initial draft of the manuscript.

Predictors of concomitant use of antipsychotics and stimulants and its impact on stimulant persistence in pediatric attention deficit hyperactivity disorder.

BACKGROUND: Concomitant use of stimulants and atypical antipsychotics is common in pediatric attention deficit hyperactivity disorder (ADHD). However, little is known about the determinants of concomitant use and its utility in the management of pediatric ADHD. OBJECTIVES: To (a) examine predictors of concomitant stimulant and atypical antipsychotic use and (b) evaluate the impact of concomitant atypical antipsychotic use on the persistence of stimulants in children and adolescents diagnosed with ADHD. METHODS: The retrospective cohort study was conducted using 4 years (January 2004-December 2007) of IMS LifeLink claims data. The study population included children and adolescents aged 6-16 years with a diagnosis of ADHD and those who initiated long-acting stimulants (LAS) from July 2004 to December 2006. Patients were followed for 1 year after index stimulant use. Concomitant use was defined as the concurrent prescription for LAS and atypical antipsychotic agents with at least 14 days overlap after the index LAS claim. Persistence was measured by summing the total number of days a patient remained on the index LAS from the index prescription date with an allowable gap of no more than 30 days. Multiple logistic regression within the conceptual framework of the Andersen Behavioral Model was performed to determine the predictors of concomitant stimulant and atypical antipsychotic use. Multivariate Cox proportional hazards regression within the conceptual framework of the Andersen Behavioral Model was used to examine the impact of concomitant atypical antipsychotic use on persistence of stimulants. RESULTS: The study cohort consisted of 39,981 children who initiated LAS treatment. Most (96.10%) received LAS monotherapy, and 3.90% received LAS and atypical antipsychotic concomitantly. The multiple logistic regression analysis found that gender, health insurance, region, year of cohort entry, season, physician specialty, coexisting mental health conditions, and general mental health status influenced the concomitant use of LAS and atypical antipsychotic agents. Bivariate analyses revealed that concomitant users had longer persistence (by 71 days) than the stimulant-alone users. Cox proportional hazards regression revealed that concomitant atypical antipsychotic was associated with improvement in LAS persistence by 15% (HR = 0.85, 95% CI = 0.76-0.94) in comparison with the LAS recipients who did not use atypical antipsychotic concomitantly. Other factors such as age, region, season, coexisting mental health conditions, use of comedications, and general mental health status influenced the LAS treatment persistence among children and adolescents. CONCLUSIONS: Various predisposing, enabling, and need factors were associated with the concomitant stimulant and atypical antipsychotic use. Concomitant use of atypical antipsychotics was associated with improved LAS treatment persistence in children and adolescents with ADHD.

Concurrent use of stimulants and second-generation antipsychotics among children with ADHD enrolled in Medicaid.

OBJECTIVE: This study examined the prevalence of and factors associated with concurrent use of long-acting stimulants (LAS) and second-generation antipsychotic agents among children and adolescents with attention-deficit hyperactivity disorder (ADHD). METHODS: The study involved retrospective longitudinal analysis of 2003-2007 Medicaid data from four states for children and adolescents between the ages of six and 17 years who were diagnosed as having ADHD and initiated LAS treatment. Concurrent use of LAS and second-generation antipsychotic medications was defined as simultaneous receipt of both medications for at least 14 days. On the basis of the conceptual framework of the Andersen behavioral model, multivariable logistic regression analysis was used to examine predisposing, enabling, and need factors associated with concurrent use. RESULTS: Among the 61,793 children who initiated LAS treatment for ADHD, 11,866 (19.2%) received LAS and second-generation antipsychotics concurrently for at least 14 days. Overall, the average length of concurrent use was 130±98 days. Multivariable logistic regression revealed that concurrent use was higher among boys, blacks, and foster care children compared with their respective counterparts. Comorbid psychiatric conditions, including disorders that are not approved indications for second-generation antipsychotic use, were associated with concurrent use of LAS and second-generation antipsychotics. CONCLUSIONS: Almost one in five children and adolescents who initiated LAS also received second-generation antipsychotics concurrently for at least 14 days. Approved and nonapproved indications of second-generation antipsychotics influenced concurrent use in pediatric ADHD.

Persistence of stimulants in children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine the persistence of three newly initiated stimulant preparations among Medicaid children and adolescents with attention-deficit/hyperactivity disorder (ADHD) diagnosis. METHODS: A retrospective longitudinal claims analysis was conducted by using Medicaid analytical eXtract data of four states. The study focused on patients between 6 and 19 years of age with ADHD diagnosis and a stimulant prescription from January 2003 to December 2005. Stimulants were grouped into short-acting stimulants (SAS), intermediate-acting stimulants (IAS), and long-acting stimulants (LAS). Persistence was measured by totaling the number of days the patient remained on the index stimulant therapy from the index prescription date provided the refill gap between two consecutive stimulant claims was no more than 30 days. All the stimulant recipients were uniformly followed for 1 year (365 days). Survival time ratios (STR) were calculated by using accelerated failure time models to examine variation in index stimulant persistence for each stimulant class. RESULTS: Among the 46,135 patients with ADHD continuously followed for 1 year, 8,260 were SAS users, 4,314 were IAS users, and 33,561 were LAS users. Children who received IAS medications had 4% shorter persistence (STR, 0.96 [95% confidence interval [CI], 0.93-0.98]) when compared with those who received SAS medications, whereas those who received index LAS medications had 29% longer persistence (STR, 1.29 [95% CI, 1.27-1.32]). Multivariate accelerated failure time models revealed that Blacks and Hispanics had consistently lower persistence than their counterparts. Foster care was positively associated with index stimulant persistence in the three stimulant types. Further, addition of another stimulant and other psychotropic medications significantly improved persistence of index stimulant in all three stimulant classes. CONCLUSIONS: LAS had comparatively longer persistence than other stimulants. An understanding of demographic and clinical characteristics that influence treatment continuation can help improve stimulant persistence rates in ADHD.

Prevalence and predictors of antidepressant prescribing in nursing home residents in the United States.

BACKGROUND: Late-life depression is a common psychiatric disorder associated with increased morbidity and mortality. Depression is often under-detected and undertreated in elderly nursing home residents. OBJECTIVES: The aim of this study was to examine the prevalence of antidepressant drug use and to identify the factors associated with its use among elderly nursing home residents. METHODS: The study involved the analysis of a nationally representative sample of prescription and resident files from the 2004 National Nursing Home Survey (NNHS). The study sample included all elderly nursing home residents ≥65 years of age. The analysis focused on prescribing from any antidepressant class, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin modulators, serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and others. Descriptive weighted analysis was performed to examine antidepressant use prevalence patterns in elderly nursing home residents. Multiple logistic regression analysis within the conceptual framework of Anderson's behavioral model was used to examine the predisposing, enabling, and need characteristics associated with antidepressant use. RESULTS: According to the 2004 NNHS, overall prevalence of antidepressant use among elderly nursing home residents was 46.22% (95% CI, 45.16-47.27). Most antidepressant users were ≥85 years of age (49.7%), female (75.7%), non-Hispanic (96.4%), and white (91.1%). The most prescribed class of antidepressants was SSRIs (31.09%; 95% CI, 30.12-32.07), followed by serotonin modulators (4.65%; 95% CI, 4.22-5.09), SNRIs (2.78%; 95% CI, 2.45-3.12), TCAs (2.34%; 95% CI, 2.03-2.65), and MAOIs (0.01%; 95% CI, 0.00-0.03). Citalopram (12.92%; 95% CI, 12.21-13.63) was the most prescribed individual antidepressant, followed by mirtazapine (10.19%; 95% CI, 9.55-10.84). Among the predisposing characteristics, age, race, and marital status were significantly associated with antidepressant use. The odds of receiving an antidepressant were lower for those aged ≥85 years and those who were unmarried elderly residents, when compared with their counterparts; whites were more likely to receive an antidepressant than nonwhites. Enabling factors such as Medicaid and bed capacity significantly predicted antidepressant use. Having Medicaid was positively associated with antidepressant prescription, whereas an increase in the total number of beds decreased the probability of an antidepressant prescription. Among need characteristics, the likelihood of antidepressant prescription use decreased with increased dependence in decision-making ability and out-of-bed mobility. The presence of depressed mood indicators and a history of falls/fractures increased the likelihood of antidepressant prescription use. The odds of receiving an antidepressant increased with diagnosis of depression but decreased with diagnosis of anxiety. CONCLUSION: Nearly half of elderly nursing home residents received antidepressants. In addition to need factors, predisposing and enabling factors played an important role in influencing the use of antidepressants in elderly nursing home residents.

Off-label use of second-generation antipsychotic agents among elderly nursing home residents.

OBJECTIVE: This study examined off-label and evidence-based use of second-generation antipsychotic agents among elderly nursing home residents and factors associated with off-label use. METHODS: This study involved a retrospective, cross-sectional analysis of data from the 2004 National Nursing Home Survey (NNHS). The sample included nursing home residents 65 years and older who received second-generation antipsychotic agents. This study used an indication-based definition of off-label use established by the U.S. Food and Drug Administration (FDA). Evidence-based use included FDA-approved indications and indications for which the Agency of Healthcare Research and Quality found at least moderate strength of evidence of effectiveness. Descriptive statistics were used to examine the prevalence of off-label and evidence-based use. Multiple logistic regression was used to examine the patient and facility factors associated with off-label use of second-generation antipsychotics. RESULTS: According to the 2004 NNHS, 308,990 (23.5%) elderly nursing home residents received at least one second-generation antipsychotic agent. Of those using second-generation antipsychotics, 86.3% received them for off-label indications and 56.9% received them for an evidence-based use. Multivariate analysis found that age (> or =75 years), self-pay for nursing home care, diagnosis of dementia, and residing in a nonprofit nursing home were positively associated with off-label use, whereas receiving Medicaid benefits was negatively associated with such use. CONCLUSIONS: Although second-generation antipsychotics were frequently used for off-label indications, most of the usage was evidence based among elderly nursing home residents. However, the high level of non-evidence-based use combined with recent safety and efficacy data suggests an urgent need to address the evidence base for this vulnerable population.