Mei Lu

Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review.

Untreated attention-deficit/hyperactivity disorder (ADHD) can lead to substantial adverse social, economic, and emotional outcomes for patients. The effectiveness of current pharmacologic treatments is often reduced, due to low treatment adherence and medication discontinuation. This current systematic literature review analyzes the current state of knowledge surrounding ADHD medication discontinuation, focusing on: 1) the extent of patient persistence; 2) adherence; and 3) the underlying reasons for patients’ treatment discontinuation and how discontinuation rates and reasons vary across patient subgroups. We selected 91 original studies (67 with persistence/discontinuation results, 26 with adherence results, and 41 with reasons for discontinuation, switching, or nonadherence) and 36 expert opinion reviews on ADHD medication discontinuation, published from 1990 to 2013. Treatment persistence on stimulants, measured by treatment duration during the 12-month follow-up periods, averaged 136 days for children and adolescents and 230 days for adults. Owing to substantial study heterogeneity, comparisons across age or medication type subgroups were generally inconclusive; however, long-acting formulations and amphetamines were associated with longer treatment duration than short-acting formulations and methylphenidates. The medication possession ratio, used to measure adherence, was <0.7 for all age groups and medication classes during a 12-month period. Adverse effects were the most commonly cited reason for discontinuation in all studies. Original research studies reported the lack of symptom control as a common discontinuation reason, followed by dosing inconvenience, social stigma associated with ADHD medication, and the patient’s attitude. In summary, although there was a lack of consistency in the measurement of adherence and persistence, these findings indicate that drug adherence and persistence are generally poor among patients with ADHD. Clinicians may be able to help improve adherence and persistence to ADHD treatment by educating caregivers and patients on treatment goals, administering long-acting medications, and following-up with patients to verify if medication is still effective and well-tolerated.

Matching-adjusted indirect comparisons: a new tool for timely comparative effectiveness research.

OBJECTIVE In the absence of head-to-head randomized trials, indirect comparisons of treatments across separate trials can be performed. However, these analyses may be biased by cross-trial differences in patient populations, sensitivity to modeling assumptions, and differences in the definitions of outcome measures. The objective of this study was to demonstrate how incorporating individual patient data (IPD) from trials of one treatment into indirect comparisons can address several limitations that arise in analyses based only on aggregate data. METHODS Matching-adjusted indirect comparisons (MAICs) use IPD from trials of one treatment to match baseline summary statistics reported from trials of another treatment. After matching, by using an approach similar to propensity score weighting, treatment outcomes are compared across balanced trial populations. This method is illustrated by reviewing published MAICs in different therapeutic areas. A novel analysis in attention deficit/hyperactivity disorder further demonstrates the applicability of the method. The strengths and limitations of MAICs are discussed in comparison to those of indirect comparisons that use only published aggregate data. RESULTS Example applications were selected to illustrate how indirect comparisons based only on aggregate data can be limited by cross-trial differences in patient populations, differences in the definitions of outcome measures, and sensitivity to modeling assumptions. The use of IPD and MAIC is shown to address these limitations in the selected examples by reducing or removing the observed cross-trial differences. An important assumption of MAIC, as in any comparison of nonrandomized treatment groups, is that there are no unobserved cross-trial differences that could confound the comparison of outcomes. CONCLUSIONS Indirect treatment comparisons can be limited by cross-trial differences. By combining IPD with published aggregate data, MAIC can reduce observed cross-trial differences and provide decision makers with timely comparative evidence.

Treatment patterns and symptom control in patients with GERD: US community-based survey

ABSTRACT Background: Proton pump inhibitors (PPIs) are the most commonly used pharmacological treatment for gastroesophageal reflux disease (GERD). Objective: To examine the utilization patterns of PPIs and other GERD-related medications, satisfaction with PPI treatment and presence of GERD symptoms. Patients and methods: GERD patients using prescription PPIs were identified from a mixed-model HMO health plan. Utilization patterns of PPIs and other GERD medications, satisfaction with PPI treatment and presence of GERD symptoms were assessed using questionnaires. Results: Among the 617 patients who completed the survey, 71.0% used PPIs once a day (QD), 22.2% used twice a day (BID) and 6.8% more than twice a day or on an as-needed basis. Approximately 42.1% of all patients supplemented their prescription PPIs with other GERD medications, including over-the-counter medications and H2-receptor antagonists. Over 85% of the patients still experienced GERD symptoms and 82.7% nighttime symptoms. Overall, 72.8% of all patients were satisfied or very satisfied with their PPI treatment. Limitations: The study used self-reported data which may have been subject to recall bias. As the study was conducted in a specific region of the US, the results may have limited generalizability to other US regions or countries. Conclusions: Patients on PPI treatment often experience GERD symptoms and supplement their prescription PPIs with other GERD medications. A substantial proportion of GERD patients receiving PPI treatment are on a BID regimen. Furthermore, more than a quarter of the patients are not completely satisfied with their PPI treatment.

Comparative effectiveness research using matching-adjusted indirect comparison: an application to treatment with guanfacine extended release or atomoxetine in children with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

To illustrate a matching‐adjusted indirect comparison by comparing the efficacy of guanfacine extended release (GXR) and atomoxetine (ATX) in reducing oppositional symptoms in children with attention‐deficit/hyperactivity disorder and comorbid oppositional defiant disorder.

Clinical and Economic Benefits Associated With the Achievement of Both HbA1c and LDL Cholesterol Goals in Veterans With Type 2 Diabetes

OBJECTIVE This study compared the clinical and economic benefits associated with dual-goal achievement, glycated hemoglobin (HbA1c) <7% (53 mmol/mol) and LDL cholesterol (LDL-C) <100 mg/dL, with achievement of only the LDL-C goal or only the HbA1c goal in veterans with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS This retrospective cohort analysis evaluated electronic medical records (Veterans Integrated Service Network 16) in adult T2DM patients with two or more measurements of LDL-C and HbA1c between 1 January 2004 and 30 June 2010 (N = 75,646). Cox proportional hazards models were used to compare microvascular and cardiovascular outcomes by goal achievement status; generalized linear regression models were used to assess diabetes-related resource utilization (hospitalization days and number of outpatient visits) and medical service costs. RESULTS Relative to achievement of only the LDL-C goal, dual-goal achievement was associated with lower risk of microvascular complications (adjusted hazard ratio [aHR] 0.79), acute coronary syndrome (0.88), percutaneous coronary intervention (0.78), and coronary artery bypass graft (CABG) (0.74); it was also associated with fewer hospitalization days (adjusted incidence rate ratio [aIRR] 0.93) and outpatient visits (0.88), as well as lower diabetes-related annual medical costs (−

The benefits of timely intervention with zoledronic acid in patients with metastatic prostate cancer to bones: a retrospective study of the US Veterans Affairs population.

130.89). Compared with achievement of only the HbA1c goal, dual-goal achievement was associated with lower risk of the composite cardiovascular-related end point (aHR 0.87) and CABG (aHR 0.62), as well as fewer outpatient visits (aIRR 0.98). CONCLUSIONS Achieving both HbA1c and LDL-C goals in diabetes care is associated with additional clinical and economic benefits, as compared with the achievement of either goal alone.

Outcomes Associated with Post-Discharge Insulin Continuity in US Patients with Type 2 Diabetes Mellitus Initiating Insulin in the Hospital

To examine the effect of timely zoledronic acid (ZA) treatment on clinical outcomes and health care utilization in patients with bone-metastatic prostate cancer. Patients with prostate cancer and bone metastasis were identified in a Veterans Affairs database (01/2002–09/2009). Eligible patients had no documented skeletal-related events (SREs) before the index date (that is, the first bone metastasis diagnosis date). Patients who received early ZA treatment, defined as having a ZA infusion after the index date and before any recorded SREs, were matched 1:1 on propensity score to patients not treated with bisphosphonates (BPs). Risks of SREs, hospitalization and death during the 6-month post-index period were compared between matched cohorts using Kaplan–Meier analyses. Baseline characteristics were well balanced between the matched cohorts (n=73 per group). 6-month SRE-free survival and hospitalization-free survival were higher in patients receiving timely ZA than patients without BP treatment (91.7 versus 71.5%, P<0.01; 80.5 versus 66.3%, P=0.05, respectively). 6-month mortality risk was significantly lower in patients treated with ZA versus those without BP treatment (4.3 versus 13.8%, P=0.04). Timely ZA intervention in bone-metastatic prostate cancer patients was associated with significant reductions in 6-month risks of SREs, hospitalization and mortality, as compared with no BP treatment.

Outcomes associated with insulin therapy disruption after hospital discharge among patients with type 2 diabetes mellitus who had used insulin before and during hospitalization.

Abstract Aim: Hyperglycemia in hospitalized patients is associated with adverse outcomes; treatment of hyperglycemia in the hospital improves outcomes. We investigated clinical outcomes and hospital readmissions associated with insulin continuation and discontinuation post-discharge in patients with type 2 diabetes mellitus (T2DM) who initiated insulin therapy during hospitalization. Materials and Methods: This observational retrospective database analysis was performed using medical records obtained from a US coordinated health system. Patients with T2DM, glycated hemoglobin (HbA1c) levels ≥ 8.0%, naïve to insulin, and initiating insulin during hospitalization were included. Clinical outcomes and hospital readmissions were compared between patients who continued and discontinued insulin post-discharge. Results: Of 732 patients initiating insulin during hospitalization, 180 (24.6%) continued and 552 (75.4%) discontinued insulin. Higher mean baseline HbA1c levels were observed in patients continuing insulin compared with those discontinuing insulin (11.1 % vs 9.5%; P < 0.001). A significantly higher percentage of patients continuing insulin achieved target HbA1c levels (< 7.0%) compared with those discontinuing insulin (P = 0.023), with no difference in hypoglycemia rates. In patients with a baseline HbA1c of ≥ 9.0%, insulin continuation was significantly associated with lower risks of all-cause (adjusted hazard ratio, 0.58; 95% CI, 0.36−0.93; P = 0.0276) and diabetes-related (adjusted hazard ratio, 0.46; 95% CI, 0.23−0.87; P = 0.0204) hospital readmissions. Conclusion: Continuation of insulin post-discharge in insulin-naïve patients with T2DM is associated with better HbA1c target level achievement, no difference in hypoglycemia rates, and a reduced risk of hospital readmission in patients with baseline HbA1c levels ≥ 9.0%).

Erratum to: Cost Effectiveness of Guanfacine Extended-Release versus Atomoxetine for the Treatment of Attention-Deficit/ Hyperactivity Disorder

OBJECTIVE To evaluate outcomes associated with insulin therapy disruption after hospital discharge in patients with type 2 diabetes mellitus who had used insulin before and during hospitalization. METHODS In this observational, retrospective analysis of medical records obtained from a coordinated health system in the United States, patients with type 2 diabetes mellitus who had used insulin 30 days before and during hospitalization were included. Clinical and cost outcomes were compared between patients who continued insulin therapy and those who had disrupted insulin therapy after hospital discharge. RESULTS In total, 2160 records were analyzed (851 patients with continued insulin therapy and 1309 patients with disrupted insulin therapy). Mean baseline glycated hemoglobin A1c levels were 8.56% and 7.73% in patients who continued insulin therapy and patients who disrupted insulin therapy, respectively (P<.001), suggesting that patients who discontinued insulin therapy had better glycemic control at baseline. Continued insulin therapy was associated with an expected greater reduction in glycated hemoglobin A1c (P<.001); similar hypoglycemia rates; lower risks of all-cause hospital readmission, diabetes-related readmission, and all-cause emergency department visits; and improved survival. Continued insulin therapy was associated with

Cost Effectiveness of Guanfacine Extended-Release versus Atomoxetine for the Treatment of Attention-Deficit/Hyperactivity Disorder: Application of a Matching-Adjusted Indirect Comparison

3432 lower total medical service costs than disrupted therapy over the 6-month postdischarge period. CONCLUSION Ensuring adherence to insulin therapy in patients who require insulin therapy after hospitalization should be a priority for postdischarge patient care programs. However, the clinical implications of this study are limited by the fact that it could not be determined whether all patients required insulin therapy after hospital discharge.