Syncope and presyncope associated with probable adverse drug reactions.

The purpose of this study was to determine whether syncope and presyncope were associated with drug therapy in 70 patients referred to a tertiary care ambulatory clinic. Drug use information was obtained, validated, and classified by its potential to cause syncope and presyncope. Utilizing a standardized adverse drug reaction algorithm, nine (13%) of the 70 patients were rated as having probable drug-induced syncope and presyncope events. Overall, 12 medications were implicated. Patients with probable adverse drug reactions were older, and taking more medications, or taking an antihypertensive. Seven of the nine patients with probable adverse drug reactions were previously classified as having syncope of unknown origin after their initial clinic evaluation. Syncope and presyncope are commonly associated with adverse drug reactions, especially in the elderly and those taking multiple medications.

Benzodiazepine use and cognitive function among community-dwelling elderly.

OBJECTIVE: To evaluate the relation between benzodiazepine use and cognitive function among community-dwelling elderly. METHODS: This prospective cohort study included 2765 self-reporting subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly. The subjects were cognitively intact at baseline (1986-1987) and alive at follow-up data collection 3 years later. Cognitive function was assessed with the Short Portable Mental Status Questionnaire (unimpaired versus impaired and change in score) and on the basis of the number of errors on the individual domains of the Orientation-Memory-Concentration Test. Benzodiazepine use was determined during in-home interviews and classified by dose, half-life, and duration. Covariates included demographic characteristics, health status, and health behaviors. RESULTS: After control for covariates, current users of benzodiazepine made more errors on the memory test (beta coefficient, 0.35; 95% confidence interval [CI], 0.10 to 0.61) than nonusers. Further assessment of the negative effects on memory among current users suggested a dose response in which users taking the recommended or higher dose made more errors (beta coefficient, 0.57; 95% CI, 0.26 to 0.88) and a duration response in which long-term users made more errors (beta coefficient, 0.39; 95% CI, 0.05 to 0.73) than nonusers. Users of agents with long half-lives and users of agents with short half-lives both had increased memory impairment (beta coefficient, 0.32; 95% CI, 0.01 to 0.64 and beta coefficient, 0.38; 95% CI, 0.02 to 0.75, respectively) relative to nonusers. Previous benzodiazepine use was unrelated to memory problems, and current and previous benzodiazepine use was unrelated to level of cognitive functioning as measured with the other 4 tests. CONCLUSIONS: The results suggested that current benzodiazepine use, especially in recommended or higher doses, is associated with worse memory among community-dwelling elderly.

A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy.

PURPOSE: To evaluate the effect of sustained clinical pharmacist interventions involving elderly outpatients with polypharmacy and their primary physicians. PATIENTS AND METHODS: Randomized, controlled trial of 208 patients aged 65 years or older with polypharmacy (> or = 5 chronic medications) from a general medicine clinic of a Veterans Affairs Medical Center. A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians. Outcome measures were prescribing appropriateness, health-related quality of life, adverse drug events, medication compliance and knowledge, number of medications, patient satisfaction, and physician receptivity. RESULTS: Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months (decrease 24% versus 6%, respectively; P = 0.0006) and was sustained at 12 months (decrease 28% versus 5%, respectively; P = 0.0002). There was no difference between groups at closeout in health-related quality of life (P = 0.99). Fewer intervention than control patients (30.2%) versus 40.0%; P = 0.19) experienced adverse drug events. Measures for most other outcomes remained unchanged in both groups. Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients (55.1% versus 19.8%; P <0.001). CONCLUSIONS: This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life.

A method for assessing drug therapy appropriateness.

This study evaluated the reliability of a new medication appropriateness index. Using the index, independent assessments were made of chronic medications taken by 10 ambulatory, elderly male patients by a clinical pharmacist and an internist-geriatrician. Their overall inter-rater agreement for medication appropriateness (ppos) was 0.88, and for medication inappropriateness (pneg) was 0.95; the overall kappa was 0.83. Their intra-rater agreement for ppos was 0.94 overall, for pneg was 0.98 overall while the overall kappa was 0.92. The chronic medications taken by 10 different ambulatory elderly male patients were independently evaluated by two different clinical pharmacists. Their overall inter-rater agreement for ppos was 0.76, and for pneg was 0.93, while the overall kappa was 0.59. This new index provides a reliable method to assess drug therapy appropriateness. Its use may be applicable as a quality of care outcome measure in health services research and in institutional quality assurance programs.

A summated score for the medication appropriateness index: development and assessment of clinimetric properties including content validity.

Inappropriate medication prescribing is an important problem in the elderly, but is difficult to measure. As part of a randomized controlled trial to evaluate the effectiveness of a pharmacist intervention among elderly veterans using many medications, we developed the Medication Appropriateness Index (MAI), which uses implicit criteria to measure elements of appropriate prescribing. This paper describes the development and validation of a weighting scheme used to produce a single summated MAI score per medication. Using this weighting scheme, two clinical pharmacists rated 105 medications prescribed to 10 elderly veterans from a general medicine clinic. The summated score demonstrated acceptable reliability (intraclass correlation co-efficient = 0.74). In addition, the summated MAI adequately reflected the putative heterogeneity in prescribing appropriateness among 1644 medications prescribed to 208 elderly veterans in the same general medicine clinic. These data support the content validity of the summated MAI. The MAI appears to be a relatively reliable, valid measure of prescribing appropriateness and may be useful for research studies, quality improvement programs, and patient care.

Adverse drug events in high risk older outpatients.

OBJECTIVE: To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy. DESIGN: A cohort study. SETTING: General Medicine Clinic at the Durham Veterans Affairs Medical Center. PATIENTS: A total of 167 high risk (taking > or = 5 scheduled medications) ambulatory older veterans who participated in a year long health service intervention trial. MEASUREMENTS: Potential ADEs were identified by asking patients during closeout interviews whether, in the past year, they had experienced any side effects, unwanted reactions, or other problems from any medication. All reported medications and corresponding adverse experiences were assessed for plausibility by a research clinical pharmacist using two standard pharmacological textbooks and categorized by predictability, therapeutic class, and organ system. RESULTS: Eighty self-reported ADEs involving 72 medications taken by 58 (35%) of 167 patients were textbook confirmed. Seventy-six of 80 (95%) ADEs were classified as Type A (predictable) reactions. Cardiovascular (33.3%) and central nervous system (27.8%) medication classes were most commonly implicated. Gastrointestinal (30%) and central nervous system (28.8%) ADE symptoms were common. Sixty-three percent of patients with ADEs required physician contacts, 10% emergency room visits, and 11% hospitalization. Twenty percent of medications implicated with ADEs required dosage adjustments, and 48% of ADE-related medications were discontinued. No significant differences (P > .05) were observed when ADE reporters (n = 58) and nonreporters (n = 109) were compared. CONCLUSION: Predictable ADEs are common in high risk older outpatients, resulting in considerable medication modification and substantial healthcare utilization.

The cost-effectiveness of a clinical pharmacist intervention among elderly outpatients.

We estimated the cost and cost-effectiveness of a clinical pharmacist intervention known to improve the appropriateness of drug prescribing. Elderly veteran outpatients prescribed at least five drugs were randomized to an intervention (105 patients) or control (103) group and followed for 1 year. The intervention pharmacist provided advice to patients and their physicians during all general medicine visits. Mean fixed and variable costs/intervention patient were $36 and $84, respectively Health services use and costs were comparable between groups. Intervention costs ranged from $7.50-30/patient/unit change in drug appropriateness. The cost to improve the appropriateness of drug prescribing is thus relatively low.

Use of medications with potential oral adverse drug reactions in community-dwelling elderly.

Prevalence and indicators of medication use with potential oral health implications among 4,163 people from the Duke Established Populations for Epidemiologic Studies of the Elderly were studied. Medications were grouped into seven potential oral adverse drug reaction (POADR) categories. Eighty percent of participants were taking at least one medication from any of the seven categories. Drugs with the potential to cause xerostomia were taken by 56.1%, abnormal hemostasis by 51.7%, soft tissue reactions by 23.4%, taste changes by 11.0%, alteration in host resistance by 8.7%, gingival overgrowth by 5.0%, and movement disorders by 2.4% of participants. Race-stratified analyses revealed that medication use with any POADR was significantly associated (p < 0.001) with being female for both races. Among nonblacks, being > or = 75 years old was associated with higher POADR use. Blacks who had a dental visit in the previous six months were more likely to take medications with POADR than those who did not. POADR medication use was not related to place of residence. Elderly often take medications with potential oral health impact.

Inappropriate prescribing and health outcomes in elderly veteran outpatients.

OBJECTIVE: To determine the relationship of inappropriate prescribing in the elderly to health outcomes. SETTING: General Medical Clinic of the Durham Veterans Affairs Medical Center. PATIENTS: A total of 208 veterans more than 65 years old who were each taking five or more drugs and participated in a pharmacist intervention trial. MEASUREMENTS: Prescribing appropriateness was assessed by a clinical pharmacist using the medication appropriateness index (MAI). A summed MAI score was calculated, with higher scores indicating less appropriate prescribing. The health outcomes were hospitalization, unscheduled ambulatory or emergency care visits, and blood pressure control. RESULTS: Bivariate analyses revealed that mean MAI scores at baseline were higher for those with hospital admissions (18.9 vs. 16.9, p = 0.07) and unscheduled ambulatory or emergency care visits (18.8 vs. 16.3, p = 0.05) over the subsequent 12 months than for those without admissions and emergency care visits. MAI scores for antihypertensive medications were higher for patients with inadequate blood pressure control (> 160/90 mm Hg) than for those whose blood pressure was controlled (4.7 vs. 3.1, p = 0.02). CONCLUSIONS: Inappropriate prescribing appeared to be associated with adverse health outcomes. This findings needs to be confirmed in future studies that have larger samples and control for potential confounders.

Reliability of drug utilization evaluation as an assessment of medication appropriateness.

OBJECTIVE: To test the reliability of drug utilization evaluation (DUE) applied to medications commonly used by the ambulatory elderly. METHODS: A DUE model was developed for four domains: (1) justification for use, (2) critical process indicators, (3) complications, and (4) clinical outcomes. DUE criteria specific to use in the elderly were developed for angiotensin-converting enzyme (ACE) inhibitors and histamine2 (H2)-antagonists, and consensus was reached by an external expert panel. After pilot testing, two clinical pharmacists independently evaluated these medications, applying the DUE criteria and rating each item as appropriate or inappropriate. Interrater and intrarater reliability was assessed by using kappa statistics. RESULTS: In a sample of 208 ambulatory elderly veterans, 42 (20.2%) were taking an ACE inhibitor and 56 (26.9%) an H2-antagonist. The interrater agreement for individual domains, represented by kappa statistics, were 0.10-0.58 and 0-0.83 for ACE inhibitors and H2-antagonists, respectively. The kappa statistic for overall agreement, which considered ratings from all criteria across all domains, was 0.24 for ACE inhibitors and 0.18 for H2-antagonists. Intrarater reliability was assessed 3 months later, and kappa statistics were 0.61-0.65 (0.49 overall) and 0-0.96 (0.81 overall) for ACE inhibitors and H2-antagonists, respectively. CONCLUSIONS: Intrarater reliability for DUE was good to excellent. However, interrater reliability exhibited only marginal reproducibility, particularly where evaluators were required to use subjective judgement (i.e., complications, clinical outcomes). DUE may not be a suitable standard for assessing medication appropriateness in ambulatory elderly patients.