INVEST substudies: design and patient characteristics.

The INternational VErapamil SR/trandolapril STudy (INVEST) will provide a large database of information. Proposed substudies for analysis include ambulatory blood pressure monitoring (ABPM), depression, genotyping, atrial fibrillation, electrocardiogram (ECG), echocardiography, renal dysfunction, diabetes, and cardiac care cost estimate. This paper reviews the design and status of several of the INVEST substudies. The ABPM substudy will obtain objective blood pressure recordings during daily life masked to both the patient and the investigator. Ambulatory blood pressure monitoring is an especially useful technology because of the role of nocturnal hypertension and circadian blood pressure irregularities in the development of hypertensive disease. The depression substudy, which enrolled 2,393 patients in the United States, will report quality-of-life (QOL) data, including information regarding energy and fatigue. The genotyping substudy will provide genomic DNA samples from approximately 15,000 patients in the United States, including Puerto Rico. Many candidate genes will be examined for polymorphisms that may predict outcomes and/or responses to various treatments.

Patients' perceptions of the benefits of pharmaceutical care.

OBJECTIVE: To investigate patients' perceptions of the benefits of regular participation in pharmaceutical care services. DESIGN: Written survey of a convenience sample. SETTING: Pharmacist-run anticoagulation clinic in a Veterans Administration Medical Center. PATIENTS: 154 patients who had regularly scheduled appointments in the clinic. INTERVENTIONS: Patients were asked to complete a written survey. The survey was read to those who had trouble reading it. MAIN OUTCOME MEASURES: Patients' perceptions about the benefit of services provided in the clinic and the relationship between those services and reduced risks of medication-related problems. RESULTS: All components of anticoagulant-related pharmaceutical care were rated as at least fairly beneficial. Monitoring of warfarin blood levels and information on the appropriate use of warfarin were rated highest. The perceived benefits of the pharmaceutical care components were associated with patients' perceptions of the extent to which pharmaceutical care reduced their risk of experiencing blood clots or warfarin-related problems. Patients also perceived that their risk of developing blood clots or bleeding problems would be higher if they did not regularly visit the anticoagulation clinic. CONCLUSION: Patients' perceptions of the benefits of pharmaceutical care were associated with the perceived threat reduction capacity of the pharmacist's services. Pharmaceutical care providers may be able to enhance patient participation in their services by educating patients on the risks of medication-related problems and how frequent monitoring of key clinical indicators may help reduce those risks.

Patients' satisfaction and their perception of the pharmacist.

OBJECTIVE: To explore the relationships between patients' satisfaction and (1) the level of pharmaceutical care services received, (2) patients' perceptions of the personal attention paid to them by the pharmacist, and (3) patients' perceptions of the pharmacist's ability to help them manage their asthma and prevent asthma-related problems. DESIGN: Exploratory study using mail or telephone survey methods. PATIENTS OR OTHER PARTICIPANTS: Asthma patients (n = 250) enrolled in one of two Florida managed care organizations. MAIN OUTCOME MEASURES: Predictor variables were level of pharmaceutical care and patients' perceptions of personal attention and their pharmacist's ability to help them control their asthma. Outcome variable was patients' overall satisfaction with the care they received from their pharmacist. RESULTS: The direct causal effects of level of care (standardized regression coefficient, beta = 0.07) and patients' perception of pharmacists' ability to help (beta = 0.01) on satisfaction were nonsignificant. Only personal attention had a significant direct path coefficient to patient satisfaction (beta = 0.63). Although the level of care was associated with patient satisfaction (r = 0.32), its direct effect was not significant because of its joint association (r = 0.27) with personal attention. Patients' satisfaction was associated with the level of pharmaceutical care and their perception of the pharmacist's ability to help them with their asthma. However, personal attention from the pharmacist was most influential. CONCLUSION: Patients may be less able to judge the technical quality of the care they receive, but they do judge their social interaction with the pharmacist. Pharmacy professionals must increase patients' awareness of the value of pharmaceutical care services and make it important to their judgment of satisfaction.

Evaluation of patient's Health-Related Quality of Life using a modified and shortened version of the Living With Asthma Questionnaire (ms-LWAQ) and the medical outcomes study, Short-Form 36 (SF-36).

OBJECTIVE: The specific objectives of this study were to: 1) study the effect of moderate-to-severe asthma on patient's Health-Related Quality of Life (HRQoL) as measured by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and 2) evaluate the construct validity of a modified and shortened version of the Living With Asthma Questionnaire (ms-LWAQ) using the SF-36 as a concomitant measure of HRQoL. METHODS: Cross-sectional, telephone or mail surveys of asthmatic patients enrolled in two central Florida managed care organizations. RESULTS: All subscales of the SF-36 and four subscales of the ms-LWAQ demonstrated adequate reliability in this population (Cronbach alpha > 0.72). The subscales of the SF-36 most affected by patient's asthma were: general health perceptions, vitality and physical role functioning. These three subscales were correlated with four subscales of the ms-LWAQ: consequences, seriousness, affect and leisure. Six of the eight SF-36 subscales and all of the ms-LWAQ subscales were associated with patient's emergency department and hospital utilization. CONCLUSION: The ms-LWAQ and SF-36 are valid as useful measures of asthma patient's HRQoL in this cross-sectional study. Severity of disease, as measured by health care utilization, was significantly associated with HRQoL.

Beta-blockers and depression: the more the murkier?

OBJECTIVE: To review the literature regarding the purported association between oral ingestion of beta-blocker drugs and depressed mood. DATA SOURCE: MEDLINE was searched for published articles using the key words propranolol, atenolol, metoprolol, nadolol, timolol, beta-blocker, beta-adrenergic antagonist, or beta-adrenergic blocker in combination with the key words depression, depressive symptomatology, major depressive disorder, or depressed mood from January 1966 through December 1996. DATA SYNTHESIS: Findings regarding the association are equivocal. Plausible explanations include study design, case definition, and confounding disease states. Most of the evidence supporting an association has used case series and case reports. Findings from cross-sectional observational studies and case-control studies are equivocal. Case definition and measurement instruments may partially explain these inconsistencies. Studies using a diagnosis of depression generally do not support the relationship. Trials using depressive symptoms are about evenly split, but they have generally enrolled a small number of patients and have questionable statistical power. Studies defining antidepressant prescriptions dispensed as a marker for depression generally support the association. Evidence exists both for and against the hypothesis that lipophilic beta-blockers cause more depression than do hydrophilic beta-blockers. CONCLUSIONS: beta-Blockers may have been unjustly associated with depression and their use avoided for that reason. Future studies into the association between depression and beta-blocker use should evaluate whether the association is affected by case definition and study design characteristics, including disease, dose-response, bias, measurement error, or ability to precisely measure the length of the exposure.

Benzodiazepine exposure and functional status in older people.

OBJECTIVE: To determine the association between benzodiazepine exposure and functional status in older patients. DESIGN: A nonexperimental, observational study design. SETTING: Kaiser Permanente, Northwest Division, a health maintenance organization (HMO) providing prepaid, comprehensive inpatient and outpatient care for more than 410,000 persons. PATIENTS: Patients were the 4192 Social HMO Project members 65 years of age and older, enrolled for 1 full year, who returned their annual health status survey during 1990. MEASUREMENTS: Functional status was measured using self-reported activities of daily living and instrumental activities of daily living. Predictor variables were self-reported medical conditions and benzodiazepine exposure during the previous 12 months. RESULTS: Age, gender, and living status were associated with functional status. Severe memory loss, stroke, Parkinson's disease, circulation problems, lung problems, hip fracture, urinary problems, arthritis, heart trouble, diabetes, stomach/bowel problems, and cancer were associated independently with functional status. Persons exposed to a benzodiazepine scored lower on the functional status measure. Benzodiazepine exposure added significantly to the prediction of functional status after controlling for patients' socio-demographic characteristics and medical conditions. CONCLUSIONS: Age and medical conditions were the most significant predictors of functional status. Benzodiazepine exposure was associated with functional status to the same extent as several chronic medical conditions. When prescribing benzodiazepines for older people, caution should be taken to minimize the possibility of iatrogenic-functional limitations.

Influence of gender on outcomes of medication-history interviewing.

This study investigated the influence of patient and provider gender on the outcomes of medication-history interviewing. In a previous study, 112 pharmacy students conducted medication-history interviews with 2 simulated patients. A secondary analysis was accomplished using complete data from 85 of the original 112 pharmacy students. The other 27 students were eliminated because of missing data. Factor analysis and canonical correlation were used to assess associations between the prior study's set of predictor variables and measures of interview completeness and patient satisfaction with the interview. Female and male pharmacy students appear to use different expressive, interactive, and interrogative skills. Allergy-asking was more complete when female pharmacy students interviewed a male patient. Emotive patient satisfaction was found to be associated more positively with a female student and female patient while teleological patient satisfaction between a male student and male patient was nearly double the result of the female-female dyad. Medication-history interview outcomes appear to differ as a consequence of the use of different sets of skills during same-sex or opposite-sex interviews.

OTC drug use in an HMO: comparing the elderly and younger adults.

The study described the self-reported use of over-the-counter (OTC) drugs among older adult and younger adult HMO members, and identified the factors associated with their use. The study population was 1,642 HMO members aged 65 and over, and 3,417 members 18 through 64 years of age. Sources of data were a mail questionnaire, and automated outpatient pharmacy, and visit data. The findings showed the elderly were less likely to use most kinds of common OTC drugs. They also used them less intensely, and were less likely to use OTC drugs in conjunction with prescription drugs, than young adults. For both age groups, OTC drug use did not appear to be a substitute for formal medical services. The major factors associated with the use of OTCs in both age groups were female gender and increased bodily pain.

Medical care utilization among older HMO members with and without hypertension.

OBJECTIVES: To compare hospital utilization, health status, and sociodemographic characteristics of older persons with and without hypertension and to examine the nature of the association of hypertension with medical care utilization. DESIGN: A retrospective, nonexperimental study. SETTING: A large health maintenance organization (HMO), located in the Portland, Oregon and Vancouver, Washington areas, that provides comprehensive, prepaid benefits to its members. PARTICIPANTS: Approximately 4200 older (> or = 65 years) members enrolled in the Social HMO Demonstration Project. MEASUREMENTS: The dependent variables were (1) whether a member was hospitalized (0 = no; 1 = yes) and (2) the number of hospitalizations during the 12-month period before the return of the Health Status Form, a mail questionnaire. The predictor variables were high blood pressure and other medical conditions, health status, and sociodemographic characteristics. Patients classified as hypertensive were those who self-reported high blood pressure and who received two or more dispensings for antihypertensive medications. RESULTS: Older hypertensives were more likely than older nonhypertensives to have been hospitalized (odds ratio (OR) = 1.14 (95% CI 1.01, 1.27)), self-report their health as only good or fair (P < .001), self-report IADL functional limitations (P < .001), and to be younger than nonhypertensives (P < .001). Utilization differences were similar after controlling for patients' age and gender. Factors independently associated with an increased likelihood of hospitalization were male gender (OR = 1.14 (1.00,1.31)), age (OR = 1.35 (1.00,1.81)), poor (OR = 1.32 (1.02,1.72)) or fair (OR = 1.20 (1.01,1.44)) self-rated health status, functional limitations in activities of daily living (OR = 1.74 (1.48,2.03), and self-reported heart trouble (OR = 1.50 (1.34,1.68)), stroke (OR = 1.37 (1.15,1.64)), or cancer (OR = 2.89 (1.72,4.84)). Factors independently associated with a decreased likelihood of hospitalization were excellent self-reported health (OR = 0.65 (0.47,0.90)), no physical impairments (OR = 0.59 (0.48,0.72)), and no circulation problems (OR = 0.85 (0.74,0.98)). CONCLUSIONS: Older hypertensive patients had poorer self-reported health, more functional limitations, used more hospital services, and were not as old as nonhypertensive older patients. To the extent that general health is improved by treatment of hypertension, appropriate treatment of high blood pressure may not only improve health, it may also reduce medical care utilization. Our findings offer further support for hypertension prevention, detection, and treatment programs designed to reduce or minimize hypertension's later medical complications and to reduce future utilization.

Comparing health-related indicators of very old hypertensives and nonhypertensives in an HMO.

The purpose of this study was to determine if very old hypertensives (85 years of age and over) were sicker and in poorer health than very old nonhypertensives. The authors compared the frequency of comorbidities, medical care and drug use, self-reported functional and health status, and health-related behaviors of very old hypertensive and nonhypertensive health maintenance organization (HMO) enrollees. Very old male hypertensives were less healthy than very old male nonhypertensives, female hypertensives, and nonhypertensives. In contrast, very old female hypertensives were healthy or healthier than very old female nonhypertensives. Hypertension may be a more serious condition among the very old males than very old females, or treatment may be more efficacious (or prevalent) for very old female hypertensives. These relationships require further study to determine if treatment guidelines should differ by sex among very old hypertensives.

Evaluation of the reliability and validity of a measure of anxiolytic drug-use intensity for pharmacoepidemiologic studies.

OBJECTIVE: To assess the reliability and validity of a proposed new standard of drug-use intensity, the minimum marketed dose (MMD), using anxiolytic drugs as models. DESIGN: Retrospective, cohort design. SETTING: Staff model, nonprofit health maintenance organization. PATIENTS/PARTICIPANTS: Eighty-five patients who obtained one or more prescriptions for an anxiolytic, antidepressant, or sedative-hypnotic drug during three consecutive one-year time periods. Fifty-nine patients had a prescription filled during the year before the study. RESULTS: For anxiolytic drugs, the magnitude of the average correlation for the MMD measure of drug-use intensity was greater than the total number of prescriptions and the total number of dosage units. Discriminant validity was demonstrated because the MMD was not correlated with measures in unrelated therapeutic categories. Summed MMD units were shown to significantly predict physical impairment (criterion validity). CONCLUSIONS: The MMD measure of drug-use intensity was reliable and valid for anxiolytic drugs. These findings suggest that information gathered from automated prescription records may be a useful indicator of drug-use intensity in pharmacoepidemiologic studies.

Multidimensional work sampling to study the activities of decentralized clinical pharmacists.

Self-reported multidimensional work sampling (MDWS) was used to study the activities of decentralized clinical pharmacists at six hospitals in Portland, Oregon, and Seattle-Tacoma, Washington, in March through June 1989. A community hospital, a university hospital, and a hospital associated with a health maintenance association were selected in each city, and pharmacists at each site who provided clinical services were recruited. Each pharmacist wore a random reminder device and recorded the activity during which the device sounded by writing on a card numbers assigned to describe work activity, contact, location, and function. Of 6609 classifiable observations, 34.5% (2280) were of clinical activities and 35.8% distributive activities. Pharmacists spent 28.6% of their clinical time reviewing and assessing patients' charts, 17.1% on clinical rounds, 15.9% on activities related to therapeutic drug monitoring, 10.2% providing drug information, 11.6% attending or giving formal education, 6.1% doing research, and 2.6% attending meetings. The average pharmacist spent less than 10 minutes each day with patients but spent a substantial portion of time providing clinical services to other health professionals. Self-reported, multidimensional work sampling appears to be a valuable method for describing and monitoring decentralized pharmacists' work activities at multiple sites and work settings.

Medical and psychosocial factors predictive of psychotropic drug use in elderly patients.

The purpose of this study was to investigate medical and psychosocial factors that may be used to identify patients at risk of psychotropic drug use. Population-based surveys were completed by 278 elderly health maintenance organization (HMO) patients in August 1984. Physical and mental health status and social support were measured in the survey. Automated prescription records from the year prior to and the year after the survey were linked to data from the survey. Patients received 737 prescriptions for psychotropic drugs during the two-year period under study. Doxepin (20.2 percent), flurazepam (15.2 percent), and diazepam (14.8 percent) were dispensed most frequently. Nearly 30 percent of the patients received a prescription for at least one psychotropic drug during the two-year period, and 14 percent received at least one prescription during both years. Three significant predictors of subsequent psychotropic drug use were: prior use (odds ratio = 17.2, 95% CI = 6.25, 47.33), the number of physical impairments (OR = 1.73, 95% CI = 1.05, 2.84), and the respondent's rating on the Alameda Health Scale (OR = 1.65, 95% CI = 0.99, 2.75). Patients' self-reported mental health status and sociodemographic characteristics were not significant predictors of subsequent use.

The effect of drug co-payments on utilization and cost of pharmaceuticals in a health maintenance organization.

This study analyzed how the use and cost of pharmaceuticals varied by level of drug co-payment in a staff model health maintenance organization (HMO). An historical cohort design was used to study changes in drug utilization and drug costs in 19,982 continuously enrolled beneficiaries less than the age of 65. The beneficiaries initially had no drug co-payments, but experienced co-payment rates of $1.50, $3.00, and $3.00 plus other benefit changes during a three-year period. A comparison cohort of 23,164 beneficiaries was selected from the same setting who were subject to no drug co-payment during the same time period. Data on the use and cost of medications were obtained from an automated data system. Adjusted analyses for each time period controlled for age, sex, years in the Group Health Cooperative (GHC), and prior year utilization (or cost). The initial $1.50 drug co-payment was associated with a drop of 10.7% in the number of prescriptions filled relative to change in the comparison cohort. The decrease was greatest for discretionary drugs at each level of co-payment. The implementation of progressively greater levels of co-payments continued to have a significant effect on drug utilization since each co-payment level resulted in an additional reduction in drug utilization; 10.6% with the $3 co-payment and 12.0% when the $3 drug co-payment was combined with other cost-sharing provisions. Co-payments were associated with lower per capita drug costs and higher per prescription unit costs.

Effect of a clinical pharmacist program on the cost of hypertension treatment in an HMO family practice clinic.

This study evaluated the impact of a clinical pharmacy service on the cost of antihypertensive drug therapy in an HMO family practice clinic. The service was provided to five family practice physicians. Pharmacists identified hypertensive patients prior to their regularly scheduled office visits from April through June 1986. Patient's medical records and computerized drug files were reviewed, and written recommendations for drug therapy changes were placed in patients' medical record by the pharmacists. When appropriate, pharmacists alerted prescribers to lower cost alternatives. A matched control group of physicians was selected. Hypertensive patients were identified retrospectively in the control group. We found that the cost of antihypertensive drug therapy was significantly higher for study physicians' patients when compared with control physicians' patients in the period prior to implementing the service. The difference between the two groups was not significant after six months. Clinical pharmacist intervention decreased the average cost of antihypertensive treatment from 33.4 to 27.2 cents per day.

Therapeutic drug monitoring reduces toxic drug reactions: a meta-analysis.

Therapeutic drug monitoring (TDM) is commonly employed to optimize the dosing of certain drugs, including digoxin, aminoglycosides, theophylline, and phenytoin. Studies were reviewed in order to (a) evaluate the effect of TDM on the occurrence of toxic drug reactions (TDRs) and (b) identify factors that may modify or invalidate the relationship. In 14 studies, monitored patients suffered fewer toxic drug reactions than nonmonitored patients (odds ratio = 0.35, 95% confidence interval, 0.13 to 0.89). The average effect size was larger in studies that utilized a control group for comparisons rather than a before-and-after study design. TDM appeared to be most beneficial for patients taking theophylline or digoxin. Issues that must be addressed in future TDM service evaluations include (a) study design, (b) adverse patient selection, (c) insufficient sample size, (d) incomplete or inconsistent description of the TDM service, and (e) incomplete, inconsistent, or absent description of criteria for reporting TDRs.

Meta-analysis of research on the effect of clinical pharmacokinetics services on therapeutic drug monitoring.

A meta-analysis of 27 published and unpublished studies of the impact of clinical pharmacokinetics services on patients' serum drug concentrations, the appropriate collection of blood samples, and the appropriate use of assay results was conducted. An individual study's effect size (ES) was determined by subtracting probits or by calculating the Bayesian estimate of pi derived from the percentages observed in the experimental and control groups. Weights based on an individual study's sample size were used to estimate the overall ES. Patients monitored by clinical pharmacokinetics services were significantly more likely to have serum drug concentrations within an acceptable therapeutic range than were patients who were not monitored. When each of the monitoring parameters was investigated individually, monitored patients were more likely to have therapeutic peak (ES = 0.51, 95% confidence interval = -0.34 to 1.36) and trough (ES = 1.15, 95% CI = -0.37 to 2.68) serum drug concentrations, to be within therapeutic range (ES = 0.91, 95% CI = 0.19 to 1.63), and to have fewer toxic peak (ES = 0.06, 95% CI = -0.53 to 0.65) and trough (ES = 0.96, 95% CI = 0.12 to 1.82) serum drug concentrations. Clinical pharmacokinetics services were also more likely to have collected blood samples appropriately (ES = 0.87, 95% CI = -0.25 to 2.00) and to have used assay results appropriately (ES = 1.21, 95% CI = -0.46 to 2.88). Clinical pharmacokinetics services appeared to have a significant influence on the proportion of patients with desirable serum drug concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)