Jerry Avorn

Incidence and preventability of adverse drug events in nursing homes

PURPOSE Adverse drug events, especially those that may have been preventable, are among the most serious concerns about medication use in nursing homes. We studied the incidence and preventability of adverse drug events and potential adverse drug events in nursing homes. METHODS We performed a cohort study of all long-term care residents of 18 community-based nursing homes in Massachusetts during a 12-month observation period. Potential drug-related incidents were detected by stimulated self-report by nursing home staff and by periodic review of the records of nursing home residents by trained nurse and pharmacist investigators. Each incident was classified by 2 independent physician-reviewers, using a structured implicit review process, by whether or not it constituted an adverse drug event or potential adverse drug event (those that may have caused harm, but did not because of chance or because they were detected), by the severity of the event (significant, serious, life-threatening, or fatal), and by whether it was preventable. Examples of significant events included nonurticarial rashes, falls without associated fracture, hemorrhage not requiring transfusion or hospitalization, and oversedation; examples of serious events included urticaria, falls with fracture, hemorrhage requiring transfusion or hospitalization, and delirium. RESULTS During 28,839 nursing home resident-months of observation in the 18 participating nursing homes, 546 adverse drug events (1.89 per 100 resident-months) and 188 potential adverse drug events (0.65 per 100 resident-months) were identified. Of the adverse drug events, 1 was fatal, 31 (6%) were life-threatening, 206 (38%) were serious, and 308 (56%) were significant. Overall, 51% of the adverse drug events were judged to be preventable, including 171 (72%) of the 238 fatal, life-threatening, or serious events and 105 (34%) of the 308 significant events (P < 0.001). Errors resulting in preventable adverse drug events occurred most often at the stages of ordering and monitoring; errors in transcription, dispensing, and administration were less commonly identified. Psychoactive medications (antipsychotics, antidepressants, and sedatives/hypnotics) and anticoagulants were the most common medications associated with preventable adverse drug events. Neuropsychiatric events were the most common types of preventable adverse drug events. CONCLUSIONS Adverse drug events are common and often preventable in nursing homes. More serious adverse drug events are more likely to be preventable. Prevention strategies should target the ordering and monitoring stages of pharmaceutical care.

Scientific versus commercial sources of influence on the prescribing behavior of physicians

W hen a physician prescribes a medication for a patient, the act is often shaped, in a large part, by forces unrelated to the biochemical properties of the drug-a phenomenon which has been called “the non-pharmacological basis of therapeutics” [ 11. A number of papers have appeared which analyze how physicians arrive at therapeutic decisions, and generally, the scientific literature is accorded a prominent position in the list of influential sources. These studies have been the subject of several comprehensive reviews [2-51. However, such research has often relied heavily on self-report as a major source of data, introducing a strong potential bias. In contrast, surveys of actual prescribing practices indicate that irrational drug choices are made frequently, despite the availability of ample empirical evidence counseling otherwise. To study the relative contributions of scientific and commercial sources of information, we chose two index drugs whose pharmacologic effects have been shown by controlled studies to be minimal or not significantly different from those of nonprescription (over-thecounter) preparations, but which are heavily advertised as being effective. We then interviewed a random sample of primary care physicians in the greater Boston area, and sought to determine their use of the drugs, their perception of the drugs’ properties, and their beliefs concerning what influenced their choice of drugs. The nature of drug advertising is such that physicians often deny the relative importance of commercial sources in influencing their prescribing-either because they are unaware of it or because they are reluctant to admit to being influenced by nonscientific sources. This limits the value of self-report as a means of. determining how physicians make prescribing decisions. We attempted to overcome this problem by choosing drugs about which the content of information provided varied systematically from source to source. For both drug groups, commercial “channels” (advertisements, detail personnel) presented a message of efficacy and reliability, whereas scientific channels (published reports of clinical trials or review articles) presented a message of minimal efficacy or total uselessness. The content of physicians’ beliefs about these drugs could thus be used as a “marker,” indicating from which sources the information in fact came. For example, a physician may respond that he bases his prescribing on the scientific literature alone and never reads pharmaceutical advertisements or pays attention to drug salespeople. However, his answers in another part of the questionnaire may reveal that he believes that cerebral vasodilators are effective in the treatment of senile dementia. Such information is unlikely to have come from the scientific literature since it does not present this point of view.

High-dimensional propensity score adjustment in studies of treatment effects using health care claims data

Background: Adjusting for large numbers of covariates ascertained from patients’ health care claims data may improve control of confounding, as these variables may collectively be proxies for unobserved factors. Here, we develop and test an algorithm that empirically identifies candidate covariates, prioritizes covariates, and integrates them into a propensity-score-based confounder adjustment model. Methods: We developed a multistep algorithm to implement high-dimensional proxy adjustment in claims data. Steps include (1) identifying data dimensions, eg, diagnoses, procedures, and medications; (2) empirically identifying candidate covariates; (3) assessing recurrence of codes; (4) prioritizing covariates; (5) selecting covariates for adjustment; (6) estimating the exposure propensity score; and (7) estimating an outcome model. This algorithm was tested in Medicare claims data, including a study on the effect of Cox-2 inhibitors on reduced gastric toxicity compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Results: In a population of 49,653 new users of Cox-2 inhibitors or nonselective NSAIDs, a crude relative risk (RR) for upper GI toxicity (RR = 1.09 [95% confidence interval = 0.91–1.30]) was initially observed. Adjusting for 15 predefined covariates resulted in a possible gastroprotective effect (0.94 [0.78–1.12]). A gastroprotective effect became stronger when adjusting for an additional 500 algorithm-derived covariates (0.88 [0.73–1.06]). Results of a study on the effect of statin on reduced mortality were similar. Using the algorithm adjustment confirmed a null finding between influenza vaccination and hip fracture (1.02 [0.85–1.21]). Conclusions: In typical pharmacoepidemiologic studies, the proposed high-dimensional propensity score resulted in improved effect estimates compared with adjustment limited to predefined covariates, when benchmarked against results expected from randomized trials.

Nonadherence to Adjuvant Tamoxifen Therapy in Women With Primary Breast Cancer

PURPOSE Although clinical trials have clearly demonstrated the benefits of tamoxifen in women with primary breast cancer, little is known about how this drug is actually used in the general population. We sought to estimate adherence and predictors of nonadherence in women starting tamoxifen as adjuvant breast cancer therapy. PATIENTS AND METHODS Subjects were age 18 years or older initiating tamoxifen for primary breast cancer and enrolled in New Jerseys Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs during the study period, from 1990 to 1996 (N = 2,378). Main outcome measures were number of days covered by filled prescriptions for tamoxifen in the first year of therapy with the 4 years after tamoxifen initiation for a subset; predictors of good versus poor adherence. RESULTS Twenty-three percent of patients missed taking tamoxifen on more than one fifth of days studied, although on average, patients filled prescriptions for tamoxifen for 87% of their first year of treatment. The youngest, oldest, nonwhite, and mastectomy patients had significantly lower rates of adherence; patients who had seen an oncologist before taking tamoxifen had significantly higher rates of adherence. Overall adherence decreased to 50% by year 4 of therapy. CONCLUSION The mean level of adherence to tamoxifen is high compared with other chronic medications. However, nearly one fourth of patients may be at risk for inadequate clinical response because of poor adherence. Because of the efficacy of tamoxifen therapy in preventing recurrence and death in women with early-stage breast cancer, further efforts are necessary to identify and prevent suboptimal adherence.

Effects of Medicaid Drug-Payment Limits on Admission to Hospitals and Nursing Homes

BACKGROUND Many state Medicaid programs limit the number of reimbursable medications that a patient can receive. We hypothesized that such limitations may lead to exacerbations of illness or to admissions to institutions where there are no caps on drug reimbursements. METHODS We analyzed 36 months of Medicaid claims data from New Hampshire, which had a three-drug limit per patient for 11 of those months, and from New Jersey, which did not. The study patients in New Hampshire (n = 411) and a matched comparison cohort in New Jersey (n = 1375) were Medicaid recipients 60 years of age or older who in a base-line year had been taking three or more medications per month, including at least one maintenance drug for certain chronic diseases. Survival (defined as remaining in the community) and time-series analyses were conducted to determine the effect of the reimbursement cap on admissions to hospitals and nursing homes. RESULTS The base-line demographic characteristics of the cohorts were nearly identical. In New Hampshire, the 35 percent decline in the use of study drugs after the cap was applied was associated with an increase in rates of admission to nursing homes; no changes were observed in the comparison cohort (RR = 1.8; 95 percent confidence interval, 1.2 to 2.6). There was no significantly increased risk of hospitalization. Among the patients in New Hampshire who regularly took three or more study medications at base line, the relative risk of admission to a nursing home during the period of the cap was 2.2 (95 percent confidence interval, 1.2 to 4.1), and the risk of hospitalization was 1.2 (95 percent confidence interval, 0.8 to 1.6). When the cap was discontinued after 11 months, the use of medications returned nearly to base-line levels, and the excess risk of admission to a nursing home ceased. In general, the patients who were admitted to nursing homes did not return to the community. CONCLUSIONS Limiting reimbursement for effective drugs puts frail, low-income, elderly patients at increased risk of institutionalization in nursing homes and may increase Medicaid costs.

Relationship Between Selective Cyclooxygenase-2 Inhibitors and Acute Myocardial Infarction in Older Adults

Background—Although cyclooxygenase-2 inhibitors (coxibs) were developed to cause less gastrointestinal hemorrhage than nonselective nonsteroidal antiinflammatory drugs (NSAIDs), there has been concern about their cardiovascular safety. We studied the relative risk of acute myocardial infarction (AMI) among users of celecoxib, rofecoxib, and NSAIDs in Medicare beneficiaries with a comprehensive drug benefit. Methods and Results—We conducted a matched case-control study of 54 475 patients 65 years of age or older who received their medications through 2 state-sponsored pharmaceutical benefits programs in the United States. All healthcare use encounters were examined to identify hospitalizations for AMI. Each of the 10 895 cases of AMI was matched to 4 controls on the basis of age, gender, and the month of index date. We constructed matched logistic regression models including indicators for patient demographics, healthcare use, medication use, and cardiovascular risk factors to assess the relative risk of AMI in patients who used rofecoxib compared with persons taking no NSAID, taking celecoxib, or taking NSAIDs. Current use of rofecoxib was associated with an elevated relative risk of AMI compared with celecoxib (odds ratio [OR], 1.24; 95% CI, 1.05 to 1.46; P = 0.011) and with no NSAID (OR, 1.14; 95% CI, 1.00 to 1.31; P = 0.054). The adjusted relative risk of AMI was also elevated in dose-specific comparisons: rofecoxib ≤25 mg versus celecoxib ≤200 mg (OR, 1.21; 95% CI, 1.01 to 1.44; P = 0.036) and rofecoxib >25 mg versus celecoxib >200 mg (OR, 1.70; 95% CI, 1.07 to 2.71; P = 0.026). The adjusted relative risks of AMI associated with rofecoxib use of 1 to 30 days (OR, 1.40; 95% CI, 1.12 to 1.75; P = 0.005) and 31 to 90 days (OR, 1.38; 95% CI, 1.11 to 1.72; P = 0.003) were higher than >90 days (OR, 0.96; 95% CI, 0.72 to 1.25; P = 0.8) compared with celecoxib use of similar duration. Celecoxib was not associated with an increased relative risk of AMI in these comparisons. Conclusions—In this study, current rofecoxib use was associated with an elevated relative risk of AMI compared with celecoxib use and no NSAID use. Dosages of rofecoxib >25 mg were associated with a higher risk than dosages ≤25 mg. The risk was elevated in the first 90 days of use but not thereafter.

Full Coverage for Preventive Medications after Myocardial Infarction

BACKGROUND Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. METHODS We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. RESULTS Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group (P<0.001 for all comparisons). There was no significant between-group difference in the primary outcome (17.6 per 100 person-years in the full-coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full-coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending (

Payment Restrictions for Prescription Drugs under Medicaid

66,008 for the full-coverage group and

Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors.

71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). CONCLUSIONS The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trials primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774.).

A Randomized Trial of a Program to Reduce the Use of Psychoactive Drugs in Nursing Homes

Abstract In an attempt to contain costs, 27 Medicaid programs have implemented patient-level payment limits for medications, but the effects of these restrictions on quality of care, costs, and hea...