Publications

BACKGROUND: Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described.

METHODS: We conducted a retrospective cohort study of children and young adults (≤24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional "step-up" approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the "top-down" approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies.

RESULTS: A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%-95.4%).

CONCLUSIONS: Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

IMPORTANCE: Antibiotic therapy is the cornerstone of medical management for community-acquired pneumonia.

OBJECTIVE: To assess the associations between 3 key aspects of antibiotic therapy (optimal time to antibiotic initiation, initial antibiotic selection, and criteria for the transition from intravenous to oral therapy) and short-term mortality in adults hospitalized with community-acquired pneumonia.

EVIDENCE REVIEW: Bibliographic databases of MEDLINE, EMBASE, and the Cochrane Collaboration were searched for studies of adults hospitalized with radiographically confirmed community-acquired pneumonia published from January 1, 1995, until November 5, 2015.

FINDINGS: Twenty studies (17 observational and 3 randomized trials) met eligibility criteria. Among 8 observational studies identified, the 4 largest (study populations of 2878 to 1,170,022) found that antibiotic initiation within 4 to 8 hours of hospital arrival was associated with relative reductions of 5% to 43% in mortality; the 4 smallest studies (study populations of 451 to 2076) found no associations between the timing of antibiotic initiation and mortality. One cluster randomized trial (n = 1737) demonstrated noninferiority of β-lactam monotherapy (n = 506) vs β-lactam plus macrolide combination therapy (n = 566), with an absolute adjusted difference of 2.5% (90% CI, -0.6% to 5.2%) in 90-day mortality favoring β-lactam monotherapy. A second randomized trial (n = 580) failed to demonstrate noninferiority of β-lactam monotherapy vs β-lactam plus macrolide combination therapy, with an absolute difference of 7.6% (1-sided 90% CI upper limit, 13.0%) in attainment of clinical stability on hospital day 7 favoring β-lactam plus macrolide combination therapy. Six of 8 observational studies (study populations of 1188 to 24,780) found that β-lactam plus macrolide combination therapy was associated with relative reductions of 26% to 68% in short-term mortality and all 3 observational studies (study populations of 2068 to 24,780) reported that fluoroquinolone monotherapy was associated with relative reductions of 30% to 43% in mortality compared with β-lactam monotherapy. One randomized trial (n = 302) reported significantly reduced hospital length of stay (absolute difference, 1.9 days; 95% CI, 0.6 to 3.2 days), but no differences in treatment failure when objective clinical criteria were used to decide when to transition patients from intravenous to oral therapy.

CONCLUSIONS AND RELEVANCE: In adults hospitalized with community-acquired pneumonia, antibiotic therapy consisting of β-lactam plus macrolide combination therapy or fluoroquinolone monotherapy initiated within 4 to 8 hours of hospital arrival was associated with lower adjusted short-term mortality, supported predominantly by low-quality observational studies. One randomized trial supports the use of objective clinical criteria to guide the transition from intravenous to oral antibiotic therapy.

When possible, chronic noncancer pain (CNCP) in older adults should be managed by nonpharmacologic modalities in conjunction with nonopioid analgesics. If moderate-to-severe pain persists despite these approaches, however, nonparenteral opioids may be considered as adjunctive therapy. This article reviews the epidemiology of opioid use and their effectiveness for CNCP in older adults and summarizes important age-related changes in opioid pharmacokinetics and pharmacodynamics that increase the risks of adverse effects in the elderly. Finally, to assist clinicians with selecting appropriate therapy, the article concludes with an evidence-based approach to optimize opioid prescribing in older adults with CNCP.

BACKGROUND: Numerous interventions are available to boost medication adherence, but the targeting of these interventions often relies on crude measures of poor adherence. Group-based trajectory models identify individuals with similar longitudinal prescription filling patterns. Identifying distinct adherence trajectories may be more useful for targeting interventions, although the association between adherence trajectories and clinical outcomes is unknown.

OBJECTIVE: To examine the association between adherence trajectories for oral hypoglycemics and subsequent hospitalizations among diabetes patients.

DESIGN: Retrospective cohort study.

PATIENTS: A total of 16,256 Pennsylvania Medicaid enrollees, non-dually eligible for Medicare, initiating oral hypoglycemics between 2007 and 2009.

MAIN MEASURES: We used group-based trajectory models to identify trajectories of oral hypoglycemics in the 12 months post-treatment initiation, using monthly proportion of days covered (PDC) as the adherence measure. Multivariable Cox proportional hazard models were used to examine the association between trajectories and time to first diabetes-related hospitalization/emergency department (ED) visits in the following year. We used the C-index to compare prediction performance between adherence trajectories and dichotomous cutpoints (annual PDC <80 vs. ≥80 %).

RESULTS: The mean annual PDC was 0.58 (SD 0.32). Seven trajectories were identified: perfect adherers (9 % of the cohort), nearly perfect adherers (31.4 %), moderate adherers (21.0 %), low adherers (11.0 %), late discontinuers (6.8 %), early discontinuers (9.7 %), and non-adherers with only one fill (11.1 %). Compared to perfect adherers, trajectories of moderate adherers (HR = 1.48, 95 % CI 1.25, 1.75), low adherers (HR = 1.51, 95 % CI 1.25, 1.83), and non-adherers with only one fill (HR = 1.35, 95 % CI 1.09, 1.67) had greater risk of diabetes-related hospitalizations/ED visits. Predictive accuracy was improved using trajectories compared to dichotomized cutpoints (C-index = 0.714 vs. 0.652).

CONCLUSIONS: Oral hypoglycemic treatment trajectories were highly variable in this large Medicaid cohort. Low and moderate adherers and those filling only one prescription had a modestly higher risk of hospitalizations/ED visits compared to perfect adherers. Trajectory models may be valuable in identifying specific non-adherence patterns for targeting interventions.

BACKGROUND: All Department of Veterans Affairs Medical Centers (VAMCs) operate under a single national drug formulary, yet substantial variation in prescribing and spending exists across facilities. Local management of the national formulary may differ across VAMCs and may be one cause of this variation.

OBJECTIVE: To characterize variation in the management of nonformulary medication requests and pharmacy and therapeutics (P&T) committee member perceptions of the formulary environment at VAMCs nationwide.

METHODS: We performed an online survey of the chief of pharmacy and an additional staff pharmacist and physician on the P&T committee at all VAMCs. Respondents were asked questions regarding criteria for use for nonformulary medications, specific procedures for ordering nonformulary medications in general and specific lipid-lowering and diabetes agents, the appeals process, and the formulary environment at their VAMCs. We compared responses across facilities and between chiefs of pharmacy, pharmacists, and physicians.

RESULTS: A total of 212 chief pharmacists (n = 80), staff pharmacists (n = 78), and physicians (n = 54) responded, for an overall response rate of 49%. In total, 107/143 (75%) different VAMCs were represented. The majority of VAMCs reported adhering to national criteria for use, with 38 (36%) being very adherent and 69 (65%) being mostly adherent. There was substantial variation between VAMCs regarding how nonformulary drugs were ordered, evaluated, and appealed. The nonformulary lipid-lowering drugs ezetimibe, rosuvastatin, and atorvastatin were viewable to providers in the order entry screen at 67 (63%), 67 (63%), and 64 (60%) VAMCs, respectively. The nonformulary diabetes medication pioglitazone was only viewable at 58 (55%) VAMCs. In the remaining VAMCs, providers could not order these nonformulary drugs through the normal order-entry process. For questions about the formulary environment, physician respondent perceptions differed from those of staff pharmacists and chief pharmacists. Compared with pharmacy chiefs and staff pharmacists, physicians were less likely to agree that providers at their VAMC prescribed too many nonformulary medications (47% and 44% vs. 12%, P < 0.001), more likely to agree that providers must jump through too many hoops to prescribe nonformulary medication (5% and 3% vs. 25%, P < 0.001), and more likely to agree that providers make an effort to convert new patients from nonformulary to formulary lipid-lowering (65% and 73% vs. 94%, P <0.02) and diabetic medications (49% and 50% vs. 88%, P < 0.001).

CONCLUSIONS: Although the Department of Veterans Affairs (VA) operates under a single national formulary, we found significant differences among VAMCs regarding their management of nonformulary medication requests. We also found differences among formulary leaders regarding their perception of the environment in which their VAMC's formulary is managed. These findings have important implications not just for VA, but for any organization that develops, implements, and manages drug formularies across multiple facilities.

BACKGROUND: Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes.

AIMS OF THE STUDY: To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing.

METHODS: Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOSTM database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to 10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing.

RESULTS: There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average.

DISCUSSION: Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties regularly prescribing a therapeutic category, some physicians rely heavily on a small number of agents.

IMPLICATIONS FOR HEALTH POLICIES, HEALTH CARE PROVISION AND USE: Health systems may need to offer educational interventions to clinicians in order to improve their ability to tailor treatment decisions to the needs of individual patients.

IMPLICATIONS FOR FUTURE RESEARCH: Future studies should examine the impact of the diversity of antipsychotic prescribing to determine whether more diversified prescribing improves patient adherence and outcomes.

OBJECTIVES: To examine racial and ethnic differences in initiation and time to discontinuation of antidementia medication in Medicare beneficiaries.

DESIGN: Retrospective cohort study.

SETTING: Secondary analysis of 2009-10 enrollment, claims, and Part D prescription data for a 10% national sample of U.S. Medicare fee-for-service beneficiaries.

PARTICIPANTS: Beneficiaries aged 65 and older with Alzheimer's disease or related dementia (ADRD) before 2009 and no fills for antidementia medications in the first half of 2009 (N = 84,043).

MEASUREMENTS: Initiation was defined as having one or more fills for antidementia medication in the second half of 2009 and discontinuation as a gap in coverage of 30 days or more during the year after initiation. The Andersen Behavioral Model was used to guide covariate selection.

RESULTS: Overall, 3,481 (4.1%) of previous nonusers initiated antidementia medication in the second half of 2009. Of those initiating one drug class (acetylcholinesterase inhibitors (AChEIs) or memantine), 9% later added the other class, and 2% switched classes. Of initiators, 23% discontinued within 1 month, and 62% discontinued within 1 year. Hispanic beneficiaries were more likely than white beneficiaries to initiate (adjusted odds ratio = 1.25, 95% confidence interval (CI) = 1.10-1.41). Black and white beneficiaries did not differ in likelihood of initiation. Hispanic (adjusted hazard ratio (aHR) = 1.56, 95% CI = 1.34-1.82) and black (aHR = 1.25, 95% CI = 1.08-1.44) beneficiaries discontinued at a faster rate than white beneficiaries.

CONCLUSION: Initiation of antidementia medications was no different in black and white beneficiaries and more likely in Hispanic beneficiaries; black and Hispanic beneficiaries discontinued at a faster rate. More research into reasons explaining these differences is needed.