Absorption of oral intramuscular chlordiazepoxide by alcoholics.

The effect of chronic alcoholism on oral and intramuscular plasma levels of chlordiazepoxide (CDX) was assessed. A 50-mg oral dose of CDX resulted in significantly higher plasma levels in the 2 hr following CDX than a 50-mg intramuscular dose administered to acute withdrawing alcoholic subjects. The same CDX dose was administered 7 days later and the same differences were observed between the mean oral and intramuscular plasma levels during the first 2 hr after administration of CDX. Peak concentration occurred significantly sooner after the oral than intramuscular dose of CDX in both the initial dose and the dose given a week later. It was also observed that the areas under the curve for CDX were significantly greater initially than 1 wk later. It is suggested this effect may be at least partially the result of the longer CDX half-lives initially than a week later. The active metabolite, N-desmethylchlordiazepoxide, peaked significantly earlier with the oral dose than with the intramuscular dose after the patient was alcohol free for a week.

Pharmaceutical care and specialty practice.

The practice of pharmaceutical care is a possible goal for all pharmacists' professional maturation. Six issues exist in which pharmaceutical care may represent a radical departure from some contemporary clinical practices. Because no profession is capable of providing pharmaceutical care singlehandedly at an acceptable level of quality, it is necessary to construct systems that organize the necessary variety of professionals and patients for managing drug therapy. In such a system, pharmacists can organize specialty practice around a strong general practice of pharmacy that is able to coordinate drug therapy and manage for outcomes, organize around the practice of medicine as if pharmacy were a medical specialty, or merge into the organization of a hospital or other healthcare organization.

[Quality assurance of drug therapy for patients with asthma. Health economic analysis]. / Kvalitetssikring af astmapatienters laegemiddelbehandling. Sundhedsøkonomisk analyse.

The cost-effectiveness of a community pharmacy based programme for therapeutic outcomes monitoring of asthma patients' drug therapy is evaluated. Five hundred asthma patients, aged 16-60 and treated in primary care, with moderate to severe asthma, 31 community pharmacies and 139 general practitioners participated in the study. The total programme costs, costs of drugs, health care resource costs and indirect costs were evaluated together with the effects of the programme on: asthma symptoms status, days of sickness, quality of life, satisfaction with health care, peak-flow (PEF), inhalation technique and knowledge. The evaluation of the programme shows it to be cost-effective with cost-effectiveness ratios between 0.18 and 0.56. The pay off time for the programme is 23 months (range 9-64 months in the sensitivity analysis). It is concluded that the community pharmacist can contribute to identify and solve drug-related problems in a cost-effective way with positive impact on asthma patients health, clinical and psycho-social outcomes, even though the program is time consuming and intensive.

Unresolved issues in the future of pharmacy.

The effect of the major forces shaping pharmacy's future--technology, economics, and social values--is discussed. Pharmacy can best respond to these forces by expanding the informational component of pharmacy practice and by returning to its fundamental relationship with society--that is, by accepting responsibility for drug-use control. To accomplish this, pharmacy must go through a process of occupational reconstruction and self-renewal. Technological forces shaping pharmacy practice include computers and robotics, communications, and therapeutics. Regarding economic changes, medical-care decisions are shifting away from individuals toward "third parties." This factor, combined with output-based payment systems, may lead to a consolidation of service providers. Marketing pharmaceutical services and organizing pharmacy's internal structure will become important. Some of the social forces affecting pharmacy's future include the aging population, the weakening of professional authority, and pharmacy's public image. Just as society goes through the "information revolution," pharmacy will need to undergo a "reprofessionalization." Pharmacy's societal function should involve "pharmaceutical care," a concept that includes both drug-product control and clinical pharmacy services. Pharmacy should return to its preindustrial origins in valued, complex, specific, and committed public service if it wishes a happy postindustrial future.

Economic aspects of clinical decision making: evaluating clinical programs.

The importance of program evaluation is discussed, and issues to consider when designing and conducting program evaluations in the restructuring health-care environment are identified. Program evaluation is carried out for the purpose of supporting specific decisions for individual organizations. Unlike scientific research, program evaluation accepts time as a constraint, and its audience is composed of managers. Considering the likelihood of being fixed-dollar contractors or employees in an era of managed care, professionals must try to understand the cost objectives of management; similarly, managers must understand the patient-care objectives of professionals. Program evaluation can help provide the necessary documentation of a program's impact on the outcome of health care, which influences the total cost of care. Successful program evaluation requires careful planning, and issues related to six steps in the planning process are described: defining the objective of the evaluation, choosing and defining the program to be evaluated, choosing indicator variables, designing the evaluation, presenting the results, and planning follow-through. While program evaluation is too often understood in negative terms, particularly as something done because of external pressure, it is as much a part of management as is directing day-to-day operations or developing a long-range plan.

Problems and hypotheses.

The formulation and relationship of precisely defined research questions and hypotheses and their importance in the research process are discussed. A hypothesis is defined as a linkage of two or more abstract variables, each of which is derived from the observational level. The successive abstractions of the derivation process, the characteristics of the variables so derived, and the relationship of both to study design and measurement are defined and discussed.

Pharmaceutical care.

Drug-treatment failures can be prevented by applying a Pharmaceutical Care system. Therapeutic outcome monitoring is such a system, which can be applied to the (drug) treatment of several diseases like asthma, diabetes and cardiovascular diseases. Pharmaceutical Care is an outcome oriented, cooperative, systematic approach to providing drug therapy directed at the improvement of all dimensions of health related quality of life.

Regulating for outcomes as a systems response to the problem of drug-related morbidity.

OBJECTIVE: To describe the evidence that preventable adverse outcomes of drug therapy are prevalent in the United States and Europe, to describe the causes of this problem, to outline a systems response that would correct or improve the problem, to discuss pharmacy's contribution to that solution, and to propose a strategy for implementation. SUMMARY: The causes of the widespread problem of preventable drug-related morbidity (PDRM) that have been identified in the literature constitute system failure. Health professionals can understand an individual patient's care system if they organize their thinking about systems as efficiently as they organize their thinking about medical or pharmaceutical problems. Six essential system characteristics are proposed, based on the PDRM literature. Regulations should mandate regular patient and system performance assessments--specifically, that health professionals (1) identify, resolve, and document specific pharmacotherapy problems; (2) assess system performance and identify recurring root causes of problems; and (3) document assessments, problems found, actions taken, and follow-up. These regulations would, in essence, mandate individual quality improvement (QI) programs. QI and pharmaceutical care require similar processes of decisions and actions, one from a practice (multipatient) perspective and the other from a patient perspective. CONCLUSION: Health care accreditation agencies are moving toward regulation for outcomes. Pharmacy managers should embrace and regulatory boards should participate in this movement. Such regulations would clarify pharmacy's role in support of safe and effective pharmacotherapy and would constitute a commitment to pharmaceutical care as public service. A widely adopted system of measuring and improving the quality of medication use and outcomes could eventually lead to quality benchmarks in the community pharmacy setting, which would more firmly establish the value of the pharmacist in pharmacotherapy.

Use of simulation to develop multiple-dose regimens for drugs exhibiting nonlinear elimination kinetics.

A mathematical model and resulting computer program for simulating blood-level versus time profiles of drugs exhibiting saturable elimination processes are described and evaluated. The iterative digital-analog simulator (IDAS) program consists of two sections--a simulation (SIM) module and an iteration control (IC) module. The SIM module predicts minimum and maximum serum drug levels based on a dose and a dosing interval. The IC module takes the minimum and maximum serum levels from the SIM module and produces a new dose (for a new maximum serum level) and a new dosing interval (for a new minimum serum level). The new dosing information is fed back into the SIM module and the iteration process is repeated until the predicted minimum and maximum levels converge on desired levels set by the user of the program. The model and program were tested by comparing simulation results with actual patient data for phenytoin (seven patients) and theophylline (three patients). The ability of the program to converge on correct doses and dosing intervals was evaluated under a variety of given conditions. The mean difference between actual and simulated profiles was 0.286 mg/liter and 1.5 mg/liter for phenytoin and theophylline, respectively. IDAS produced dose and dosing interval estimates within desired precision given a variety of initial input data. The results encourage prospective clinical investigation of the reliability and validity of the method.

Prescribers' beliefs and values as predictors of drug choices.

A cognitive model of the drug-prescribing process, which incorporates prescribers' attitudes (valences) about treatment outcomes and beliefs (instrumentalities) about drug effects, was tested. Twelve physicians were interviewed to identify common outcomes associated with drug therapy; six distinct outcomes were identified. Then 50 family practice residents were given a hypothetical description of a mildly hypertensive patient and three treatment choices. The physicians completed a questionnaire that identified (1) the instrumentalities of each of the alternative treatments for each of the six outcomes and (2) the valences for each outcome. The physicians were also asked to respond to an open-ended question on how they would treat the patient described in the case. Forty-six physicians proposed 39 treatments that corresponded to the three treatments for which instrumentalities and valences were available. The drug-choice model correctly predicted 28 of 39 (72%) therapeutic decisions, which was significantly more than would be expected by chance (p less than 0.01). Both valences and instrumentalities appear important for predicting prescribing intention. Pharmacists can use this model in their attempts to influence prescribing.

Opportunities and responsibilities in pharmaceutical care.

Pharmacy's opportunity to mature as a profession by accepting its social responsibility to reduce preventable drug-related morbidity and mortality is explored. Pharmacy has shed the apothecary role but has not yet been restored to its erst-while importance in medical care. It is not enough to dispense the correct drug or to provide sophisticated pharmaceutical services; nor will it be sufficient to devise new technical functions. Pharmacists and their institutions must stop looking inward and start redirecting their energies to the greater social good. Some 12,000 deaths and 15,000 hospitalizations due to adverse drug reactions (ADRs) were reported to the FDA in 1987, and many went unreported. Drug-related morbidity and mortality are often preventable, and pharmaceutical services can reduce the number of ADRs, the length of hospital stays, and the cost of care. Pharmacists must abandon factionalism and adopt patient-centered pharmaceutical care as their philosophy of practice. Changing the focus of practice from products and biological systems to ensuring the best drug therapy and patient safety will raise pharmacy's level of responsibility and require philosophical, organizational, and functional changes. It will be necessary to set new practice standards, establish cooperative relationships with other health-care professions, and determine strategies for marketing pharmaceutical care. Pharmacy's reprofessionalization will be completed only when all pharmacists accept their social mandate to ensure the safe and effective drug therapy of the individual patient.

Controversies in antimicrobial therapy: critical analysis of clinical trials.

Problems with design and statistical evaluation of clinical efficacy trials of antimicrobial agents are reviewed. Of the three major criteria used for evaluating antimicrobial agents (efficacy, toxicity, cost), the most important is efficacy. Clinical efficacy can be evaluated in uncontrolled or controlled clinical trials. Uncontrolled trials are often conducted to satisfy Food and Drug Administration requirements during premarketing testing; the response rate is typically high because only patients with susceptible infections may be treated and large doses are given. Controlled antibiotic trials should be randomized, blinded, parallel comparisons of an investigational agent versus the best available agent at an accepted dose. However, interpretation of these studies is frequently clouded by poor study design, small sample sizes, and heterogeneous patient populations. Controlled trials are usually centered around a null hypothesis (i.e., that no difference will be found between the agents being compared). All conclusions (to reject or not reject the null hypothesis) should be carefully evaluated by clinicians seeking to apply the available data to patient care. Researchers can incorrectly conclude that two therapies have equal efficacy because of insufficient statistical power (i.e., small sample size) or poor study design. Likewise, researchers may incorrectly conclude that there is a statistical difference between two therapies because of poor design or improper sample selection. For the clinician, clinical relevance takes precedence over statistical significance. Before the results of a study are allowed to affect drug use in an institution, strong similarities between subjects and methods in the study and patients and care in the institution should be demonstrated.

Drug choice as a problem-solving process.

A model of the drug prescribing process, which incorporates prescribers' personal values about treatment outcomes and beliefs about treatment effects, was tested under actual clinical conditions. Forty physicians were given two fictional case histories and six disguised case histories of patients whom they had recently treated for hypertension or maturity-onset diabetes mellitus. The physicians completed questionnaires based on each case history that measured 1) the beliefs about the probability that seven treatment-related outcomes would result from the prescribing of several alternative treatments and 2) the values placed on each outcome. The physicians were also asked, in an open-ended question, how they would treat the patient described in the case. The 40 physicians proposed 172 drug treatments that corresponded to treatment alternatives for which beliefs about treatment effects had been measured. The model correctly predicted 1) prescribing intent in 81% of hypertension cases and in 87% of the diabetes cases and 2) actual prescribing in 76% of hypertension cases and in 70% of the diabetes cases, significantly more than would be expected at random (P less than 0.01). The prescribing model appears useful for predicting drug choices for the outpatient treatment of hypertension and diabetes by resident physicians.

Antibiotic use review in ambulatory care using computer-assisted medical record audit.

The use of a computer-assisted medical record audit (CAMRA) for reviewing antibiotic use in ambulatory patients was evaluated. A random sample of 40 medical records documenting treatment of streptococcal pharyngitis, otitis media, or acute, uncomplicated urinary tract infections at two family practice clinics was used to evaluate the accuracy and efficiency of computerized prescription screening and CAMRA relative to medical record audit (MRA) alone. Accuracy was the ability to correctly classify antibiotic therapy as appropriate or inappropriate. The initial computerized prescription screening criteria were modified to reduce the proportion of false positives and negatives and a second random sample of 40 medical records was audited. The computerized prescription screening was the most efficient method, requiring less than one hour of professional time to audit 80 medical records. MRA and CAMRA took 17.4 and 3.0 hours, respectively. By definition, MRA was 100% accurate. Computerized prescription screening and CAMRA correctly classified 73% and 78% of the medical records, respectively. The results of this study are similar to a previous study reviewing antihypertensive therapy, but this study showed CAMRA less favorably. This is primarily because of the many diagnoses for which a particular antibiotic can be prescribed and the wide dosage ranges for antibiotics based on body weight. CAMRA could be more useful for evaluating antibiotic therapy if diagnostic information were available before doing the computerized prescription screening and if the computerized prescription screening criteria included patient diagnosis and body weight.