Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults.

WHAT IS KNOWN AND OBJECTIVE: There are few studies examining both drug-drug and drug-disease interactions in older adults. Therefore, the objective of this study was to describe the prevalence of potential drug-drug and drug-disease interactions and associated factors in community-dwelling older adults. METHODS: This cross-sectional study included 3055 adults aged 70-79 without mobility limitations at their baseline visit in the Health Aging and Body Composition Study conducted in the communities of Pittsburgh PA and Memphis TN, USA. The outcome factors were potential drug-drug and drug-disease interactions as per the application of explicit criteria drawn from a number of sources to self-reported prescription and non-prescription medication use. RESULTS: Over one-third of participants had at least one type of interaction. Approximately one quarter (25·1%) had evidence of had one or more drug-drug interactions. Nearly 10·7% of the participants had a drug-drug interaction that involved a non-prescription medication. % The most common drug-drug interaction was non-steroidal anti-inflammatory drugs (NSAIDs) affecting antihypertensives. Additionally, 16·0% had a potential drug-disease interaction with 3·7% participants having one involving non-prescription medications. The most common drug-disease interaction was aspirin/NSAID use in those with history of peptic ulcer disease without gastroprotection. Over one-third (34·0%) had at least one type of drug interaction. Each prescription medication increased the odds of having at least one type of drug interaction by 35-40% [drug-drug interaction adjusted odds ratio (AOR) = 1·35, 95% confidence interval (CI) = 1·27-1·42; drug-disease interaction AOR = 1·30; CI = 1·21-1·40; and both AOR = 1·45; CI = 1·34-1·57]. A prior hospitalization increased the odds of having at least one type of drug interaction by 49-84% compared with those not hospitalized (drug-drug interaction AOR = 1·49, 95% CI = 1·11-2·01; drug-disease interaction AOR = 1·69, CI = 1·15-2·49; and both AOR = 1·84, CI = 1·20-2·84). WHAT IS NEW AND CONCLUSION: Drug interactions are common among community-dwelling older adults and are associated with the number of medications and hospitalization in the previous year. Longitudinal studies are needed to evaluate the impact of drug interactions on health-related outcomes.

Pharmacological and clinical aspects of antiepileptic drug use in the elderly.

In this article, epidemiological and clinical aspects related to the use of antiepileptic drugs (AEDs) in the elderly are highlighted. Studies have shown that people with epilepsy receiving AED treatment show important deficits in physical and social functioning compared with age-matched people without epilepsy. To what extent these deficits can be ascribed to epilepsy per se or to the consequences of AED treatment remains to be clarified. The importance of characterizing the effects of AEDs in an elderly population is highlighted by epidemiological surveys indicating that the prevalence of AED use is increased in elderly people, particularly in those living in nursing homes. Both the pharmacokinetics and the pharmacodynamics of AEDs may be altered in old age, which may contribute to the observation that AEDs are among the drug classes most commonly implicated as causing adverse drug reactions in an aged population. Age alone is one of several contributors to alterations in AED response in the elderly; other factors include physical frailty, co-morbidities, dietary influences, and drug interactions. Individualization of dosage, avoidance of unnecessary polypharmacy, and careful observation of clinical response are essential for an effective and safe utilization of AEDs in an elderly population.

Hemodynamic responses to combined therapy with captopril and hydralazine in patients with severe heart failure.

The hemodynamic benefits and safety of combined therapy with captopril and hydralazine were studied during invasive hemodynamic monitoring in 14 patients with severe heart failure. In eight patients, the individual effects of both drugs were evaluated before the administration of combined therapy, whereas hydralazine was added to maintenance captopril therapy in the other six patients. In the first group, captopril alone produced a marked decrease in pulmonary wedge pressure (28 +/- 4 to 18 +/- 5 mm Hg) and mean arterial pressure (85 +/- 20 to 69 +/- 13 mm Hg) (both p less than 0.001) without a significant increase in cardiac index. Hydralazine alone produced a marked increase in cardiac index (1.6 +/- 0.4 to 2.7 +/- 0.5 liters/min per m2) (p less than 0.001), but with a minimal decrease in pulmonary wedge pressure (28 +/- 4 to 23 +/- 4 mm Hg) (p less than 0.05) and without a significant change in mean arterial pressure. The combination of captopril and hydralazine produced an increase in cardiac index similar to that of hydralazine alone and decreases in pulmonary wedge pressure and mean arterial pressure similar to those with captopril alone. Most important, when hydralazine was added to captopril in the entire group of 14 patients, cardiac index increased markedly with little additional decrease in mean arterial pressure and no significant increase in heart rate. The one patient who experienced symptomatic hypotension with combination therapy also had dizziness with captopril alone. Seven of the nine patients maintained on long-term treatment experienced symptomatic improvement. Thus, in patients with severe chronic heart failure, the combined use of captopril and hydralazine is feasible and produces acute hemodynamic improvement superior to that from either drug alone.

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.

Adverse events after discontinuing medications in elderly outpatients.

BACKGROUND: Discontinuation of drug therapy is an important intervention in elderly outpatients receiving multiple medications, but it may be associated with adverse drug withdrawal events (ADWEs). OBJECTIVE: To determine the frequency, types, timing, severity, and factors associated with ADWEs after discontinuing medications in elderly outpatients. PATIENTS: One hundred twenty-four ambulatory elderly participants in 1-year health service intervention trial at the Durham Veterans Affairs General Medicine Clinic in Durham, NC, who stopped taking medications. METHODS: A geriatrician retrospectively reviewed computerized medication records and clinical charts to determine medications no longer being taken and adverse events in the subsequent 4-month period. Possible ADWEs, determined by using the Naranjo causality algorithm, were categorized by therapeutic class, organ system, and severity. RESULTS: Of 238 drugs stopped, 62 (26%) resulted in 72 ADWEs among 38 patients. Cardiovascular (42%) and central nervous system (18%) drug classes were most frequently associated with ADWEs. The ADWEs most commonly involved the circulatory (51%) and central nervous (13%) systems, and 88% were attributed to exacerbations of underlying disease. Twenty-six ADWEs (36%) resulted in hospitalization or an emergency department or urgent care clinic visit. Only the number of medications stopped was associated with ADWE occurrence (adjusted odds ratio, 1.89; 95% confidence interval, 1.33-2.67). CONCLUSIONS: Most medications can be stopped in elderly outpatients without an ADWE occurrence. However, when ADWEs occur they resulted in substantial health care utilization. Practitioners should strive to discontinue drug therapy in the elderly but be vigilant for disease recurrence.

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.

Marked differences in antidepressant use by race in an elderly community sample: 1986-1996.

OBJECTIVE: Prescriptions of antidepressant medications have increased significantly over the past 15 years across the life cycle. One overall correlate of medication use in older adults is race, with African Americans using fewer medications than whites. Given the frequency of depressive symptoms among elderly populations, as well as the increased potential for adverse side effects from antidepressants, the relative contribution of race in the use of antidepressants is critical for determining well-designed studies. The authors analyzed data from a community-based cohort of elders followed for 10 years to determine the association of race to the use of antidepressants between 1986 and 1996, with control for known correlates of depression in late life. METHOD: Information on antidepressant use and demographic and health characteristics were obtained from a stratified, probability-based sample of 4,162 elders (equally distributed between African American and white community-dwelling subjects) in the Piedmont region of North Carolina during four in-person interviews spanning 10 years. Descriptive statistics were calculated. Logistic regression was used for the final models. RESULTS: A total of 4.6% of whites and 2.3% of African Americans used antidepressants in 1986. Approximately 14.3% of whites and 5.0% of African Americans used antidepressants in 1996. In controlled analyses, the prevalence odds ratio for antidepressant use in whites, compared to African Americans, was 1. 76 in 1986 and 3.77 in 1996. CONCLUSIONS: African American elders are much less likely to take antidepressants, and the difference in use increased over the 10 years of the survey.

Calcium channel blockers and cancer.

PURPOSE: We sought to explore the relation that has been previously reported between calcium channel blockers and an increased risk of cancer. SUBJECTS AND METHODS: We followed 3,511 participants, age 65 years or older, in the Duke Established Populations for Epidemiologic Studies of the Elderly for up to 10 years. Information about use of medications was obtained at baseline and 3 and 6 years later. Information about hospitalization for cancer, or death from cancer, was obtained from Health Care Financing Administration data and death certificates. RESULTS: Of the 133 users of calcium channel blockers, 16 (12%) developed cancer, compared with 548 (16%) of 3,378 nonusers (hazard ratio = 0.9; 95% confidence interval, 0.5 to 1.5). Adjusting for baseline and time-dependent covariates, such as race, diabetes, or blood pressure, for dose or class of calcium channel blockers, or for length of follow-up, had no effect. CONCLUSIONS: Use of calcium channel blockers does not appear to be related to cancer risk. Earlier reports showing such a relation may have been the result of chance.

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.

Relation of prescription nonsteroidal antiinflammatory drug use to cognitive function among community-dwelling elderly.

PURPOSE: To evaluate the relationship of nonsteroidal antiinflammatory drug (NSAID) use to level of cognitive function in community-dwelling elderly persons. METHODS: The prospective cohort study included 2765 nonproxy subjects from the Duke University Established Populations for Epidemiologic Studies of the Elderly who were cognitively intact at baseline (1986-1987) and alive at follow-up three year later. Cognitive function was assessed by the Short Portable Mental Status Questionnaire (i.e., intact vs. impaired and change in score) and by the individual domains of the Orientation-Memory-Concentration Test (i.e., number of errors). NSAID use, determined from in-home interviews, was coded for chronicity, dose, frequency of use, and prescription status. RESULTS: After controlling for demographic factors as well as health status and behavior, continuous, regularly-scheduled, prescription use of NSAID was associated with preservation of one aspect of cognitive functioning: concentration (beta coefficient, 0.29; 95% confidence interval [CI] -0.54 to -0.04, indicating fewer errors). However, no consistent dose-response relationship was found. Current and prior NSAID use was unrelated to level of cognitive functioning across all five measures; among current users, those taking moderate or high doses (beta coefficient, 0.41; 95% CI, 0.08 to 0.74) made more errors on the memory test compared with those taking low doses (beta coefficient 0.03; 95% CI, -.85 to 0.91). CONCLUSIONS: These results suggest no substantial or consistent protective effect of prescription NSAID use on cognitive function in community-dwelling elderly. However, recent use at higher doses may be associated with memory deterioration in this population.

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.

Factors predicting change in prescription and nonprescription drug use in a community-residing black and white elderly population.

The current study identifies characteristics that predict change in use of prescription and nonprescription drugs over a period of 3 years. A modified health care services use model was applied to information obtained from a probability-based sample of black (n = 1778) and white (n = 1446) community-resident elderly, interviewed in 1986-1987 and 1989-1990. Analysis was by means of logistic and ordinary least-squares regression, with sample weights and design effects taken into account. The number of users and average number of prescription drugs used increased over the 3 years, and was best predicted by extent of prior drug use, older age, white race, poorer health, and number of health care visits. Conversely, nonprescription drug use declined significantly, and was best predicted by prior use, white race, and female gender. The reduced use of prescription drugs by blacks as compared to whites is of concern, suggesting that attention is needed to assure equitable access to prescription drugs.

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.

The contribution of echocardiography to the community practice of cardiology. A prospective study.

The utility of echocardiography in a clinical office practice was assessed by prospectively studying 93 patients. Each patient was examined by a cardiologist and a diagnosis and management plan was outlined. An M-mode and 2D echocardiogram was then obtained and interpreted by a second cardiologist without knowledge of the clinical findings. Patients were then categorized as follows: group 1, clinical and echo diagnosis agree, management unchanged (67 patients); group 2, clinical and echo diagnosis agree, management changed (two patients); group 3, clinical and echo diagnosis disagree, management unchanged (16 patients); and group 4, clinical and echo diagnosis disagree, management changed (eight patients). Echocardiography significantly altered management of 11 percent of patients, provided additional important information in 48 percent, and confirmed the clinical impression in 74 percent of patients. It was particularly helpful in determining left ventricular structure and function, valvular anatomy, and in the diagnosis of clinically unsuspected idiopathic hypertrophic subaortic stenosis.

Combined intracardiac and extracardiac repair of scimitar syndrome with anomalous pulmonary veins to both cavae.

Anomalous pulmonary venous drainage from the right lung to the inferior vena cava (scimitar syndrome) is a rare finding. This paper briefly discusses this syndrome and presents a case of anomalous pulmonary venous return to both the superior and the inferior cavae, which was corrected with a combined extracardiac and intracardiac approach. Polytetrafluoroethylene was utilized for reconstruction of pathways to the left atrium. To our knowledge, this is the first time this technique has been used to correct this anomaly.

Rapidly progressive coronary artery bypass graft atherosclerosis. Report of a case documented by serial coronary arteriograms and pathologic examination.

Atherosclerosis occurred in a coronary artery saphenous vein bypass graft. Serial angiograms are presented documenting subtotal occlusion of this graft which occurred over a nine-month period. Pathologic examination of graft material obtained at surgery demonstrated ulcerating atherosclerotic plaque. The occurrence of early saphenous vein graft atherosclerosis is discussed with particular reference to the possible effects of hyperlipidemia, which was present in this patient.

Cardiac tamponade following minimally invasive direct coronary artery bypass.

We report a case of cardiac tamponade resulting in a death following minimally invasive direct coronary artery bypass. Despite absence of clinical symptoms at the time of hospital discharge, cardiac tamponade physiology may have been evident on close evaluation of Doppler studies of the left internal mammary artery. Performance of a predischarge transthoracic echocardiogram may have been confirmatory and lifesaving.

Sedative, hypnotic, and antianxiety medication use in an aging cohort over ten years: a racial comparison.

OBJECTIVES: Prescriptions of sedatives, hypnotics, and antianxiety medications have decreased over the past 15 years. However, racial differences have not been well investigated in controlled analyses. DESIGN: A prospective cohort study. SETTINGS AND PARTICIPANTS: The authors analyzed data from a community-based, biracial cohort of older adults (n = 4,000 at baseline) followed for 10 years to determine sociodemographic and health characteristics associated with the use of these medications between 1986 and 1996. MAIN OUTCOME MEASURES: Information about sedative, hypnotic, and antianxiety medication use and demographic and health characteristics was obtained from a race-stratified, probability-based sample of black and white community-dwelling older adults in the Piedmont region of North Carolina during four in-person interviews spanning 10 years. Descriptive statistics were calculated. Logistic regression was used for the final models. RESULTS: A total of 13.3% of the subjects were taking these medications in 1986, with the frequency of use declining only to 11.8% in 1996 despite the cohort aging 10 years. Correlates of use at baseline were female gender, white race, depressive symptoms, poor self-rated health, impaired physical function, and health services use. These correlates persisted for each of the three follow-up waves of the survey. In 1996, the odds for being white and using these medications was 4.70 in controlled analyses. CONCLUSIONS: Despite the overall decline in the use of sedative, hypnotics, and antianxiety agents in the general population in recent years, over the 10 years of this survey, an aging cohort continued to use these medications at a frequency greater than the general population and did not demonstrate a significant decline in use. Factors unrelated to health status, specifically being white, were among the strongest correlates of use throughout the years of follow-up.

Suboptimal prescribing in older inpatients and outpatients.

Investigators searched Medline and HealthSTAR databases from January 1, 1985 through June 30, 1999 to identify articles on suboptimal prescribing in those age 65 years and older. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. The definitions for various types of suboptimal prescribing (polypharmacy, inappropriate, and underutilization) are numerous, and measurement varies from study to study. The literature suggests that suboptimal prescribing is common in older outpatients and inpatients. Moreover, there is significant morbidity and mortality associated with suboptimal prescribing for these older patients. Evidence from well-controlled studies suggests that multidisciplinary teams and clinical pharmacy interventions can modify suboptimal drug use in older people. Future research is necessary to measure and test other methods for tackling this major public health problem facing older people.

Do older women use estrogen replacement? Data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE)

OBJECTIVES: The primary purpose of this study was to determine the prevalence of current and past estrogen use among older, community-dwelling, postmenopausal women. The secondary purpose was to describe factors associated with estrogen use in this population. DESIGN: A survey. SETTING: The Piedmont region of North Carolina. PARTICIPANTS: The sample included 2602 community-dwelling women over the age of 65 who were interviewed for the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). MEASUREMENTS: Current and past use of estrogen. RESULTS: Of the women surveyed, 6.1% reported current estrogen use, and 18.5% reported past use. Approximately half of the participants reported using estrogen for more than 2 years. Multivariate analysis demonstrated that current estrogen users were younger, more affluent, had smaller families, and were more likely to be white and to live in an urban area than were never users. Current users were also more likely to drink alcohol and to take calcium supplements; and compared with past estrogen users, they were more likely to be white, have smaller families, and to drink alcohol. CONCLUSION: Estrogen replacement therapy is used by a small minority of older women, especially blacks. Moreover, although women with some risk factors for osteoporosis are more likely to use estrogen, the chief determinants of estrogen utilization are socioeconomic.