Patrick P. Gleason

The Emerging Role of Atypical Pathogens in Community‐Acquired Pneumonia

Community‐acquired pneumonia (CAP) constitutes a major cause of morbidity and mortality. Although Streptococcus pneumoniae remains the bacterium most commonly implicated in CAP, the atypical respiratory pathogens Mycoplasma pneumoniae, Legionella species, and Chlamydia pneumoniae are being isolated with increasing frequency. Contrary to previous beliefs, these agents are capable of causing severe as well as mild‐to‐moderate illness. Moreover, they can affect all age groups. Indeed, atypical pathogens are implicated in up to 40% of CAP cases and commonly occur as copathogens in mixed‐infection CAP, an etiology associated with particularly high mortality (up to 25%). Laboratory methods for detecting atypical pathogens are slow, and there is significant overlap between atypical and typical CAP manifestations. For these reasons, accurate prediction of etiology cannot be made purely on clinical or radiologic grounds. Consequently, empiric antimicrobial therapy for atypical pathogens (with agents such as macrolides, fluoroquinolones, in some cases tetracyclines, or the new ketolides) warrants careful consideration and now is recommended for the treatment of CAP.

Are Incentive-Based Formularies Inversely Associated with Drug Utilization in Managed Care?

OBJECTIVE: To review recent studies comprehensively assessing the impact of incentive-based multitier formularies on pharmaceutical costs and utilization. DATA SOURCES: PubMed (2001–December 2003) was searched using the key terms formularies, cost-sharing, and drug costs. STUDY SELECTION AND DATA EXTRACTION: Studies addressing the impact of implementing multitiered incentive-based formularies as a central component of an outpatient drug benefit were selected. DATA SYNTHESIS: One study using pharmacy claims from 25 employers with data from 402 786 members modeled the range of anticipated plan/employer savings associated with single- to 3-tier shifts and found that, going from a single- to 3-tier benefit results in decreased plan/employer pharmaceutical costs from

Debilitating Reaction following the Initial Dose of Tramadol

650 to

Effect of a retrospective drug utilization review on potentially inappropriate prescribing in the elderly

494 (24% decrease) per member per year and decreased pharmaceutical utilization from 12.3 to 9.4 (23.6% decrease) prescriptions per member per year. Another study demonstrated that adding an additional tier decreased pharmaceutical utilization, with a dramatic increase in member contribution offsetting the plans expected increase in expenditures. This shift in pharmaceutical expenditures appeared to have no effect on overall medical utilization over a 3-year follow-up. Finally, a study converting members from a single- to 3-tier incentive-based formulary, associated with two- to fourfold copayment increases, resulted in a 10% discontinuation rate for angiotensin-converting enzyme inhibitors, statins, and proton-pump inhibitors among members who were primarily hourly employees. For salaried workers, the addition of a tier to their benefit appeared to have minimal impact on pharmaceutical utilization. CONCLUSIONS: Emerging data suggest a potential inverse relationship between pharmaceutical utilization and incentive-based formularies that increase member contribution to drug costs. Future research should focus on identifying price points and percentage increases at which members are likely to begin discontinuing necessary medications.

Medical and Pharmacy Expenditures After Implementation of a Cyclooxygenase‐2 Inhibitor Prior Authorization Program

OBJECTIVE: To describe a debilitating reaction following a single oral dose of tramadol. CASE SUMMARY: A 32-year-old white man with no prior medical problems, allergies, or previous medication reactions experienced ataxia, dilation of the pupils, numbness in his arms and legs, tremulousness, and dysphoria lasting approximately 4 hours following an initial tramadol dose (100 mg). The patient recovered with no sequelae. DISCUSSION: Central nervous system (CNS) stimulation during therapy with tramadol was reported in 7% of patients in clinical trials. These reactions are usually mild and transient. This report describes a debilitating CNS-mediated reaction to an initial dose of tramadol in an otherwise healthy adult. The patient was phenotyped for CYP2D6 activity, the major metabolic pathway for tramadol elimination, and was determined to be an extensive metabolizer with very high CYP2D6 activity. CONCLUSIONS: The exact mechanism of the adverse response is not known; however, based on phenotyping results, we suspect that it may be related to high concentrations of the active O-desmethyl metabolite of tramadol.

Impact of a drug utilization review program on high‐risk use of prescription controlled substances

BACKGROUND Use of potentially inappropriate medications or drugs to be avoided in the elderly (DAE) continues to be widespread. Although the literature suggests DAE are associated with negative health outcomes, educational interventions have had a positive impact on inappropriate prescribing. OBJECTIVES The objectives of this study were to identify those members aged > or =65 years participating in a Medicare Part D Blue Cross and Blue Shield (BCBS) benefit plan who were receiving medications that may be inappropriate for use in older adults and, through a retrospective drug utilization review (RetroDUR), to notify their prcscribers of the possible safety concerns with continued use. METHODS The analysis used retrospective administrative pharmacy claims data from 3 Medicare Part D BCBS plans across 4 states. Plan members aged > or =65 years who had a claim for > or =1 DAE during a 30-day review period (August 15, 2007-September 14, 2007) with a minimum supply of 7 days of medication were identified. The National Committee for Quality Assurance 2007 Healthcare Effectiveness Data and Information Set measures for Medicare were used to determine DAE. A packet of information was mailed to prescribers identifying patients who had a claim for > or =1 DAE. Members were then assessed for the presence of a drug in the same drug class 6 months after the initial analysis. RESULTS Of a possible 328,000 eligible members, 16,973 (5.2%) had a claim for > or =1 DAE during the 30-day review period. A total of 7963 intervention prescriber letters were mailed, affecting 13,198 members with 14,267 DAE claims. The final analyzable intervention cohort consisted of 10,364 members with 11,062 DAE claims. Overall, 5403 claims (48.8%) for DAE were defined as discontinued after 6 months. The most common DAE in the study were estrogens, propoxyphene, muscle relaxants, anticholinergics, antihistamines, and nitrofurantoin, accounting for 9682 claims (87.5%). At the 6-month follow-up, reductions in claims for each of the top 6 drug/drug classes ranged from 31.3% to 66.7%. As a class, the anticholinergics had the highest rate of discontinuation. CONCLUSIONS The DAE RetroDUR was associated with a possible reduction in the use of potentially inappropriate prescription medications in these older adults. Further research, using a control population, is needed to show the impact on health care utilization and costs, adverse drug events, and health care and quality-of-life outcomes.

Impact of provider mailings on medication adherence by Medicare Part D members

Study Objective. To evaluate the effects of a cyclooxygenase (COX)‐2 inhibitor prior authorization (PA) program on direct medical and pharmacy costs.

Erlotinib and patterns of pharmacogenomic (PGx) testing.

Prescription drug abuse has prompted considerable concern. We evaluated a retrospective drug utilization review program to reduce controlled substance use among individuals with high‐risk utilization.

Erlotinib patterns of use and out-of-pocket (OOP) expenses.

BACKGROUND The Medicare 5-Star Rating System measures and provides incentive for improving Medicare Part D plans through a quality-based payment program. Adherence to medications for chronic conditions is key to the Star ratings. Our objective was to assess the impact of direct-to-provider letters on improving medication adherence. METHODS Members of a large US pharmacy benefits manager (PBM) who did not adhere to prescription of oral diabetes (antidiabetics), cholesterol-reducing (statins), or hypertension (renin angiotensin system [RAS] antagonists) drug therapy were identified from the prescriptions claims data of>600,000 continuously enrolled Medicare members. Nonadherence was defined by the Star ratings definition of proportion of days covered (PDC)<80%. The PBM sent letters to prescribing physicians of nonadherent members, requesting that they discuss adherence barriers and potential solutions with their patients. A historical control cohort was constructed from the PBM satisfying the same eligibility criteria as the intervention cohort. Both binary (≥80%) and continuous PDC measures were assessed as outcomes through multivariate logistic regression and difference-in-difference models, respectively. RESULTS Final sample sizes were 21,044; 106,829; and 73,560 patients for antidiabetic, statin, and RAS antagonist use, respectively, with approximately equal number of intervention and control subjects in each drug class. Physician mailing was associated with 11%, 16%, and 7% higher odds of being adherent by members in antidiabetic, statin, and RAS antagonist cohorts, respectively (all P<.001). CONCLUSIONS Within limitations of historical controls, physician mailing was associated with improved medication adherence. IMPLICATIONS Physician mailing can be an impactful tool for improving medication adherence. LEVEL OF EVIDENCE II.

Rosiglitazone and Pioglitazone Utilization from January 2007 Through May 2008 Associated With Five Risk-Warning Events

182 Background: Erlotinib is an oral oncology drug that costs approximately