Publications

Although studies have suggested that a patient's perceived cost-benefit of a medical intervention could affect his or her utilization of the intervention, the economic value of influenza vaccine from the patient's perspective remains unclear. Therefore, we developed a stochastic decision analytic computer model representing an adult's decision of whether to get vaccinated. Different scenarios explored the impact of the patient being insured versus uninsured, influenza attack rate, vaccine administration costs and vaccination time costs. Results indicated that the cost of avoiding influenza was fairly low (with one driver being required vaccination time). To encourage vaccination, decision makers may want to focus on ways to reduce this time, such as vaccinating at work, churches, or other normally frequented locations.

BACKGROUND: Cost-related underuse of medications is common among older adults, who seldom discuss medication costs with their physicians. Some older adults may use free drug samples or industry-sponsored patient assistance programs (PAP) in hopes of lowering out-of-pocket costs, although the long-term effect of these programs on drug spending is unclear.

OBJECTIVE: To examine older adults' use of industry-sponsored strategies to reduce out-of-pocket drug costs and the association between doctor-patient communication and use of these programs.

DESIGN: Cross-sectional analysis of a 2006 nationally representative survey of Medicare beneficiaries.

PARTICIPANTS: 14,322 community-dwelling Medicare beneficiaries age ≥65.

MAIN MEASURES: We conducted bivariate and multivariate analyses of the association between receipt of free samples and participation in PAPs with sociodemographic characteristics, health status, access to care, drug coverage, medication cost burden, and doctor-patient communication.

KEY RESULTS: 51.4% of seniors reported receiving at least one free sample over the last 12 months and 29.2% reported receiving free samples more than once. In contrast, only 1.3% of seniors reported participating in an industry-sponsored PAP. Higher income respondents were more likely to report free sample receipt than low-income respondents (50.8% vs. 43.8%, p < 0.001) and less likely to report participating in a PAP (0.42% vs. 2.2%, p < 0.001). In multivariate analyses, those who reported talking to their doctor about the cost of their medications had more than twice the odds of receiving samples as those who did not (OR 2.17, 95% CI 1.95-2.42).

CONCLUSIONS: In 2006, over half of seniors in Medicare received free samples, but only 1.3% reported receiving any medications from a patient assistance program. Doctor-patient communication is strongly associated with use of these programs, which has important implications for clinical care regardless of whether these programs are viewed as drivers of prescription costs or a remedy for them.

OBJECTIVE: To examine the prevalence and correlates of non-opioid and opioid analgesic use and descriptively evaluate potential undertreatment in a sample of community-dwelling elders with symptomatic knee and/or hip osteoarthritis (OA).

DESIGN: Cross-sectional.

SETTING: Health, Aging, and Body Composition Study.

PATIENTS: Six hundred and fifty-two participants attending the year 6 visit (2002-03) with symptomatic knee and/or hip OA.

OUTCOME MEASURES: Analgesic use was defined as taking ≥1 non-opioid and/or ≥1 opioid receptor agonist. Non-opioid and opioid doses were standardized across all agents by dividing the daily dose used by the minimum effective analgesic daily dose. Inadequate pain control was defined as severe/extreme OA pain in the past 30 days from a modified Western Ontario and McMaster Universities Osteoarthritis Index.

RESULTS: Just over half (51.4%) reported taking at least one non-opioid analgesic and approximately 10% was taking an opioid, most (88.5%) of whom also took a non-opioid. One in five participants (19.3%) had inadequate pain control, 39% of whom were using <1 standardized daily dose of either a non-opioid or opioid analgesic. In adjusted analyses, severe/extreme OA pain was significantly associated with both non-opioid (adjusted odds ratio [AOR] = 2.44; 95% confidence interval [95% CI] = 1.49-3.99) and opioid (AOR = 2.64; 95% CI = 1.26-5.53) use.

CONCLUSIONS: Although older adults with severe/extreme knee and/or hip OA pain are more likely to take analgesics than those with less severe pain, a sizable proportion takes less than therapeutic doses and thus may be undertreated. Further research is needed to examine barriers to optimal analgesic use.

OBJECTIVES: To evaluate the literature regarding the effect of Medicare Part D on the under- and overuse of specific medications and corresponding health outcomes.

DESIGN: Systematic review.

SETTING: Medline search of the peer-reviewed literature from January 1, 2006, to October 8, 2010.

PARTICIPANTS: Medicare beneficiaries who obtained drug insurance from the Part D program.

MEASUREMENTS: The review evaluated changes in the use of specific drugs or drug classes after implementation of Part D, as described in original, peer-reviewed articles.

RESULTS: Nineteen articles met inclusion criteria. Part D's implementation was associated with greater use of essential medications such as clopidogrel and statins, especially in beneficiaries who had been previously uninsured, but increases in inappropriate antibiotic use for the treatment of acute respiratory tract infections and increases in claims for the often overused proton pump inhibitor drug class were also observed. In the Part D transition period, dually eligible beneficiaries' drug use remained largely unchanged. When beneficiary cost sharing increased in the coverage gap, use of essential and overused medications declined.

CONCLUSION: Increasing drug coverage led to greater use of underused essential medications and inappropriate, or overused, medications under Medicare Part D. Despite efforts to have it do so, the Part D benefit did not sufficiently discriminate between essential and nonessential medication use.

CASE: Opioids are commonly prescribed for pain, and are often connected to mental status adverse events. Delirium is a side effect associated with narcotic analgesics, with a higher incidence in the elderly. This report describes an elderly male that received a total knee arthroplasty and received morphine post-operatively. On post-operative day 2, morphine was discontinued due to mental status changes and switched to oxycodone/acetaminophen. Twenty-four hours after administering oxycodone, the patient's mental status declined. After the patient returned to baseline he was transferred to rehabilitation and re-challenged with oxycodone/acetaminophen. The re-challenge was inadvertent due to inadequate documentation of the adverse event and lack of understanding by the health care team of delirium associated with opioids. A similar rapid decline in mental status occurred.

CONCLUSION: Clinicians should be cognizant of narcotic analgesics inducing mental status changes, even with an alternative. Detailed documentation of adverse events should occur to avoid accidental re-challenges.

STUDY OBJECTIVES: The primary objective was to evaluate the change in publication rate of noninferiority trials over a 20-year interval (1989-2009). Secondary objectives were to analyze the frequency of noninferiority trials by therapeutic category, the frequency of noninferiority trial publication by journal, the impact factors of the publishing journals, any potential special advantages of the study drug over the control, the funding sources of the trials, pharmaceutical industry affiliation of the authors, and the use of ghostwriters in the creation of manuscripts.

DESIGN: Retrospective literature review of 583 articles.

DATA SOURCES: PubMed (January 1989-December 2009) and EMBASE (first quarter 1989-fourth quarter 2009) databases.

MEASUREMENTS AND MAIN RESULTS: A total of 583 articles of the results of randomized controlled clinical trials with a noninferiority study design that evaluated drug therapies, published in English, between 1989 and 2009, were included in the analysis. A consistent increase was noted in their yearly publication rates, with no trials published in 1989 versus 133 in 2009. One hundred twenty-six articles (21.6%) were in the therapeutic category of infectious diseases, followed by 78 (13.4%) in cardiology. Among the journals identified, The New England Journal of Medicine had the highest publication rate of trials with a noninferiority design, with 29 (5.0%) of the identified trials published in this journal. The median impact factor of the journals publishing noninferiority trials was 4.807 (interquartile range 3.064-7.5). The most common advantage of the study drug over the control was reduced duration of treatment or reduced pill burden (80 studies [22.9%]). A total of 425 trials (72.9%) listed the pharmaceutical industry as the only funding source. Among 369 trials with authors employed by the pharmaceutical industry, 101 (17.3%) disclosed an acknowledgment to an individual, other than those listed as authors, who contributed to writing the manuscript and who was affiliated with a medical information company and/or a pharmaceutical company (i.e., potential ghostwriters).

CONCLUSION: The publication of noninferiority trials increased during the 20 years from 1989 until 2009, particularly in the therapeutic areas of infectious diseases and cardiology. Because of this growth, clinicians and researchers need to be familiar with the caveats of the noninferiority study design to appropriately interpret and design these clinical studies.

OBJECTIVE: To report an incident of rapid development of profound hypotension, differing from the time described in previous reports, during the infusion of rituximab chemotherapy in a patient without prior exposure to the drug.

CASE SUMMARY: An 84-year-old white male with Rai stage IV chronic lymphocytic leukemia was prescribed rituximab 375 mg/m(2) by intravenous infusion. Rituximab 50 mg/h was initiated after premedication with acetaminophen, diphenhydramine, dexamethasone, and ondansetron 3 days into his hospital course. Five minutes after the infusion had begun, he experienced a significant decrease in blood pressure to 76/45 mm Hg, and the infusion was stopped. After 30 minutes, the blood pressure returned to normal. Rechallenge with rituximab 25 mg/h was attempted, but the blood pressure again declined and the patient experienced chills and rigors. The infusion was discontinued, and the symptoms resolved 1 hour later.

DISCUSSION: Infusion-related adverse reactions associated with rituximab are reported at a higher rate than with other monoclonal antibodies. Hypotension with rituximab has been reported to occur 30 minutes to 2 hours after initiation of the infusion. In contrast, severe hypotension in our patient occurred within 5 minutes after the infusion was started in a patient with no previous exposure to the drug. While many studies hypothesize that cytokine release from lymphocytes and tumor cell agglutination might contribute to severe infusion-related reactions with rituximab, the mechanism of action is not yet known. Use of the Naranjo probability scale indicated that the hypotension was probably associated with rituximab administration.

CONCLUSIONS: Awareness of the rapidity of this adverse effect in patients who have not received prior treatment with monoclonal antibodies is important during chemotherapy treatment.

OBJECTIVES: To evaluate faculty members' and students' perceptions of study strategies and materials.

METHODS: Focus groups were conducted with course directors and first- and second-year students to generate ideas relating to use of course materials, technology, class attendance, and study strategies for mastering class concepts.

RESULTS: Students and faculty members differed in their opinions about the utility of textbooks and supplemental resources. The main learning method recommended by students and faculty members was repeated review of course material. Students recommended viewing classroom lectures again online, if possible. Course directors reported believing that class attendance is important, but students based their opinions regarding the importance of attendance on their perceptions of lecture and handout quality. Results did not differ by campus or by student group (first-year vs. second-year students).

CONCLUSIONS: Students and faculty members have differing opinions on the process that could influence learning and course design. Faculty members should understand the strategies students are using to learn course material and consider additional or alternative course design and delivery techniques based on student feedback.

BACKGROUND: Bacterial resistance presents a constant challenge in the treatment of hospitalized patients, particularly with Gram-negative infections. Carbapenems have an important role in the treatment of resistant nosocomial organisms. Doripenem, a recently approved carbapenem, has shown efficacy in clinical trials, but there is little published data on utilization in a general patient population.

OBJECTIVE: The clinical utilization of doripenem in a general adult inpatient population was evaluated during a carbapenem formulary conversion.

SETTING: A 706-bed acute care tertiary hospital serving an urban community.

METHODS: After formulary conversion to doripenem, the first 100 patients to receive doripenem were included in the analysis. Baseline characteristics were recorded for each patient, along with indication for treatment, prescribing physician, dose and frequency of doripenem and duration of treatment. Patients were monitored for adverse reactions to doripenem. Bacterial culture results were recorded. For positive cultures, doripenem susceptibility was determined by Etest. Patients were followed until discontinuation of antibiotic therapy, discharge or death to determine treatment outcomes. Successful treatment was defined as clinical or microbiological cure, while patients with infection-related mortality or requiring subsequent antibiotics for the index infection were considered treatment failure.

MAIN OUTCOME MEASURES: Clinical utilization of doripenem, including indications and doses used.

RESULTS: Doripenem treatment was recorded in 102 patients. The most common indications for treatment were pneumonia and sepsis. The majority of doripenem orders were written by Infectious Disease or Pulmonology Services. Forty-nine patients were treated successfully with doripenem and six patients experienced treatment failure. The remainder of patients were not evaluable by predefined outcomes criteria. Adverse events were reported in eight patients and included acute renal failure, Clostridium difficile-associated diarrhea and seizures. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common organisms in culture results. Doripenem demonstrated in vitro activity against 81% of all organisms and susceptibility results had >90% correlation with meropenem and imipenem susceptibilities.

CONCLUSION: In our limited sample size, doripenem was safe and effective against various types of infections in a general inpatient population with similar bacterial susceptibilities to other cabapenems. Doripenem was utilized for appropriate indications, but doses were frequently outside the manufacturers labeling. Adverse events were uncommon, and no serious adverse events were directly associated with doripenem treatment.