The use of ACE inhibitors as renoprotective agents in Medicaid patients with diabetes.

OBJECTIVE: To establish a relationship between angiotensin-converting enzyme (ACE) inhibitor therapy and renal outcomes in Medicaid patients with diabetes, and compare the use of ACE inhibitors between 1994 and 1998. METHODS: One thousand patients with either type 1 or type 2 diabetes were randomly selected from the Iowa Medicaid database and followed retrospectively from 1994 through 1998. Data on medication use (insulin, oral antidiabetic agents, or both) and medical services were collected from prescription claims and diagnostic codes. Differences were evaluated with nonparametric statistics. RESULTS: Overall, 402 patients (40.2%) were prescribed an ACE inhibitor during the study period before any adverse renal outcomes occurred; 25 of the patients in this group (6.2%) had a subsequent adverse renal outcome. One hundred patients (16.7%) not receiving an ACE inhibitor had an adverse renal outcome (p = 0.006). We evaluated four subgroups and found that patients with hypertension had fewer adverse renal outcomes if they were receiving ACE inhibitors whether they were taking (p = 0.0006) or not taking insulin (p = 0.047). There was no difference in adverse renal outcomes and ACE inhibitor use in normotensive patients who were taking (p = 0.15) or not taking insulin (p = 0.96). The pattern of use of ACE inhibitors in this population increased more than twofold between 1994 and 1998 (38.1% vs. 80.1%; p < 0.001). Of those patients who had adverse renal outcomes, almost one-half (43.2%) were not taking an ACE inhibitor in 1998. CONCLUSIONS: ACE inhibitors were renoprotective in patients with diabetes in the Iowa Medicaid population. All patients with diabetes who had hypertension had fewer renal outcomes when taking an ACE inhibitor. ACE inhibitors were used more frequently in 1998 than in 1994. The use of ACE inhibitors in this population is improving, but remains less than optimal.

Treatment of Medicaid patients with asthma: comparison with treatment guidelines using disease-based drug utilization review methodology.

OBJECTIVE: To compare asthma drug therapy in the Iowa Medicaid population with international treatment guideline recommendations and relate differences to patient outcomes. METHODS: Data on asthma drug therapy and respiratory-related medical services (clinic visits, emergency visits, hospital admissions) were abstracted from prescription claims and diagnostic codes of adult Iowa Medicaid patients with asthma (n = 1029). RESULTS: About two-thirds of the population received a prescription for a short-acting beta 2-agonist during the study period. Patients with greater daily use of short-acting beta 2-agonists had more clinic visits (p = 0.004), likely related to illness severity. Almost one-third (29.3%) of 58 patients receiving a prescription of salmeterol did not receive the recommended prescription of a short-acting beta 2-agonist inhaler in the 6-month period. About one-half of patients who should have been prescribed inhaled corticosteroids according to the international guidelines did not receive such a prescription in the 6-month study period. Increased use of inhaled corticosteroids was associated with fewer (p = 0.04) emergency visits. CONCLUSIONS: Suboptimal asthma treatment in the Iowa Medicaid population, especially in regard to the use of inhaled corticosteroids as preventive therapy, was evident after comparison with treatment guidelines. Increased daily use of inhaled corticosteroids was associated with positive patient outcomes in accordance with guideline recommendations. Educational efforts to improve closer adherence to international guidelines both in prescribing practices and patient compliance with medication for asthma management should be undertaken.

Pharmacoepidemiology of urinary tract infections in Iowa Medicaid patients in urban long-term-care facilities.

OBJECTIVE: To describe the therapeutic management of Medicaid patients with urinary tract infections (UTIs) in urban long-term-care facilities (LTCFs) and to link individual therapies to patient outcomes. DESIGN: Retrospective review of medical records in LTCFs of patients who had documented UTIs. METHODS: Patient data were collected from 17 LTCFs in the Des Moines, IA, metropolitan area during a 1-year period starting January 1, 1995. Patients with UTIs were selected from the LTCF infection control logs. Data collected on patients included demographics, concomitant diseases, type of UTI (i.e., symptomatic, asymptomatic, catheter-related), process measures for management, UTI treatment, patient outcomes, and follow-up. Patient outcome data were defined as either cure or no cure. A UTI cure was defined as a negative urine culture while taking antibiotic therapy and/or complete resolution of signs and symptoms, as well as no further treatment given within 2 weeks after the end of treatment. RESULTS: Data were collected on 310 patients who had at least one UTI over the 1-year study period. Patients were primarily elderly (mean age 82.2 +/- 12.3 y), white (95.1%), and female (83.9%). Concomitant diseases were common and about one-fourth (23.0%) of the patients were catheterized. There were 536 UTI events (the unit of analysis) documented over the 1-year period, with about one-half (45.9%) being UTIs with symptoms consistent with uncomplicated lower UTI. Nearly two-thirds (62.3%) of the patients were cured, based on the study definition; there was no association between cure and type of antimicrobial therapy (p = 0.99). Over one-third (35.2%) of the UTIs were treated with a quinolone antibiotic. Others were treated with trimethoprim/sulfamethoxazole (24.4%), nitrofurantoin (13.9%), cephalosporin (10.4%), or ampicillin/amoxicillin (9.8%). Sixty-day follow-up showed no association between type of therapy and hospital readmission, physician follow-up visits, or subsequent UTIs. CONCLUSIONS: There were no differences in cure rates when comparing LTCF UTI patients receiving various regimens. With outcomes being the same, the clinician should closely consider costs of drug therapy in selecting a treatment preference.

Assessment of methods and outcomes: using modified inpatient ciprofloxacin criteria in community-based drug use evaluation.

OBJECTIVE: To determine if published drug use evaluation (DUE) criteria for inpatients could be modified to describe and evaluate drug therapy in outpatients. DESIGN: Retrospective review of drug profiles and diagnostic codes in outpatients included in the Iowa Medicaid Management Information System database. METHODS: Criteria specifying clinical indication, process indicators, complications, and outcomes were modified from existing inpatient DUE criteria for ciprofloxacin. The Iowa Medicaid database provided demographics, drug profiles, and diagnostic codes for outpatients prescribed ciprofloxacin between March 1 and March 15, 1993. RESULTS: 539 patients were evaluated. Mean (+/- SD) age was 62.1 +/- 23.8 years; 70.9 percent were women, 44.9 percent were nursing home patients who received lower doses (p = 0.04). Of 146 patients (27.1 percent) with infection-related International Classification of Diseases-Clinical Modification, 9th Revision (ICD-9CM) codes, 43.8 percent did not meet indication for use criteria, 15.8 percent met criteria, and 40.4 percent were equivocal/other. Process indicators in 539 patients revealed that 2.4 percent were < 18 years old and potential interactions existed for theophylline (9.3 percent), iron (9.7 percent), warfarin (4.8 percent), sucralfate (2.2 percent). Two patients (0.4 percent) received prenatal vitamins. Dosage and duration of therapy could not be linked to disease severity. Complications of therapy were not evaluable. Outcomes were assessed indirectly by using concurrent antibiotic histories. These histories showed that patients received a mean 2.7 +/- 2.4 (median 2, range 1-16) ciprofloxacin prescriptions during the study period. There was frequent concurrent use of antibiotics, and 29 percent of prescriptions were preceded or followed by additional quinolone therapy within 30 days. CONCLUSIONS: Evaluating appropriateness of therapy with this methodology is feasible if validated ICD-9CM codes are reported consistently in sufficient numbers of patients. Low levels of reporting of relevant disease codes require that large numbers of patients be screened to use this method effectively. Descriptive use data are readily obtained. Data obtained by this method indicated several apparent deficiencies in ciprofloxacin therapy.

Effect of pharmacists on health care outcomes in hospitalized patients.

The cost-effectiveness of pharmacists and their effect on inpatient health care outcomes were evaluated. For one year, data were collected on all patients receiving care from general medicine and general surgery teams at Walter Reed Army Medical Center, Washington, D.C. Two of five medicine teams and one of three surgery teams included a pharmacist. Teams that included a pharmacist were compared with teams that did not, in terms of patients' length of stay (LOS), mortality, and drug cost per admission. Data were compared for 3081 patients and collected for another 557 who were not included in the comparative study design. Health care teams that included a pharmacist had a shorter log LOS and lower log drug cost per admission but no difference in mortality. The average cost savings for teams that included a pharmacist was $377 per inpatient admission, and the benefit-to-cost ratio was 6.03:1. The inclusion of pharmacists on health care teams was cost-effective and provided a favorable benefit-to-cost ratio.

Prolonged recurrence of pentamidine-induced torsades de pointes.

OBJECTIVE: To report a case of recurrent pentamidine-induced torsades de pointes (TdP) and to review previously reported cases in the literature. DATA SOURCES: Medical records of the subject patient, case reports, and relevant studies identified by MEDLINE. DATA EXTRACTION: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. DATA SYNTHESIS: A 43-year-old woman with AIDS experienced pentamidine-induced TdP. TdP and other cardiac arrhythmias recurred repeatedly for 13 days after pentamidine therapy was discontinued and in the presence of normal magnesium and potassium serum concentrations. Infusions of magnesium, lidocaine, and isoproterenol were used to treat the arrhythmias. The exact mechanism of pentamidine-induced TdP has not been clearly established. It is postulated, however, that the similarity of pentamidine's structure to procainamide may contribute to its proarrhythmic effects. The tissue-binding capacity of pentamidine may result in a prolongation of its effects. No distinctive characteristic appears to predispose people to the development of cardiac arrhythmias. Laboratory values that should be monitored include serum magnesium, potassium, and creatinine. The corrected QT interval also should be monitored. CONCLUSIONS: Recurrent arrhythmias may be seen for many days after intravenous administration of pentamidine has been discontinued. Clinicians should consider this phenomenon as they decide how to monitor patients who have received this drug.

Aerosolized pentamidine and Pneumocystis carinii pneumonia: patient compliance and outcomes.

OBJECTIVE: The study objectives were to compare compliance between every-two-week and every-four-week aerosolized pentamidine regimens, and to determine if patients who were more compliant with the use of aerosolized pentamidine were at decreased risk for developing Pneumocystis carinii pneumonia (PCP). DESIGN: Nonrandomized observational study of patients receiving aerosolized pentamidine for PCP prophylaxis using the hospital pharmacy computer system to document aerosolized pentamidine use and compliance, and the Patient Administration Division's computer to document cases of PCP. SETTING: Tertiary care, US Army medical center. PATIENTS: All patients who were prescribed aerosolized pentamidine (60 mg every two weeks, 300 mg every four weeks, or both) over a 3.5-year period. MAIN OUTCOME MEASURES: Mean percent compliance was determined and compared between every-two-week and every-four-week regimens. The relationship between compliance and cases of PCP as determined using nonparametric statistics. RESULTS: Patients (n = 146) who were prescribed aerosolized pentamidine 60 mg every two weeks were more compliant (p = 0.006) than those prescribed 300 mg every four weeks. In addition, those patients who initially received the 60-mg regimen and were switched to the 300-mg regimen were more compliant when taking the 60-mg dose (p = 0.027). There was no association between compliance with either regimen and cases of PCP. Compliance generally was poor with both regimens. CONCLUSIONS: Patients on every-two-week regimens of aerosolized pentamidine were more compliant than those on every-four-week regimens. However, regardless of compliance, some patients failed aerosolized pentamidine over the 3.5-year period. Other agents that lend themselves to compliance may be more appropriate for PCP prophylaxis than aerosolized pentamidine.

Pharmacoepidemiology and military medical automation: opportunity for excellence.

Fielding of the Composite Health Care System (CHCS) brings an unparalleled opportunity for medical research. This sophisticated automated medical record system promises pharmacoepidemiologic research of a quality and quantity never before possible. Pharmacoepidemiology provides answers about the validity of beneficial and adverse drug events and aids in individualizing drug therapy. When CHCS eventually encompasses an estimated 9.1 million patients at 166 military hospitals and 588 clinics around the world, it will provide a database capable of supporting sophisticated automated research. In addition to the unprecedented size of this resource, advantages of pharmacoepidemiology performed with the CHCS database include integration of inpatient and outpatient care records, the completeness of prescription and medical records, and the wide socioeconomic spectrum covered in a defined population. Limitations and potential biases of such a database include separate drug formularies at each medical treatment facility, only limited information about nonprescription drug use and single-dose drug orders in clinics, and the mobility of military service members and their families. Pharmacoepidemiology is a tool that will benefit individual members of the military family, as well as advancing the sciences of pharmacy and medicine. Using the CHCS database for this form of research is in the best tradition of military medical research.

The relationship between outpatient drug costs and disease progression in the human immunodeficiency virus-infected population. The Military Medical Consortium for Applied Retroviral Research.

As the focus of the management of human immunodeficiency virus (HIV) infection turns from the treatment of AIDS to the entire continuum of the disease, projection of long-term healthcare costs becomes increasingly important. Rather than a fulminant disease treated primarily inside the hospital, HIV infection will become a chronic condition requiring years of outpatient monitoring and pharmacologic intervention with attending increases in pharmacy costs. The objective of this study was to characterize outpatient drug costs by Walter Reed (WR) disease stage in order to estimate the association of disease progression and outpatient prescription drug costs. We hypothesized that there was an association between HIV disease progression, measured by the WR Staging Classification System, and outpatient prescription drug costs. Outpatient drug costs were summarized for 190 HIV-positive patients during a three-month period who presented at Walter Reed Army Medical Center for staging and follow-up. The overall median cost per day per patient for all stages was $3.21 (range $0.01-53.45) with wide variation between patients. Daily costs for patients in WR stage V were the greatest (median $9.26). There was a significant association between WR stage of disease and outpatient drug costs (Spearman rho = 0.51, t = 6.9, df = 188, p less than 0.001). The association was not completely linear because costs in WR stage VI were less than WR stages IV or V. Annual extrapolated outpatient drug costs for these 190 patients would be nearly $0.5 million.

Impact of a drug-use review program intervention on prescribing after publication of a randomized clinical trial.

The effect of a drug-use review (DUR) program intervention on physician prescribing after the results of a randomized clinical trial were published was studied. A Veterans Administration (VA) cooperative study published in June 1986 showed that congestive heart failure (CHF) patients who had hydralazine and isosorbide added to their drug therapy had less mortality than patients given digoxin and diuretics with or without prazosin. Physicians with at least one CHF patient who was receiving the less effective therapy were randomly assigned to intervention and control groups. In September 1986, intervention-group physicians (n = 288) were mailed a letter and questionnaire from the DUR program coordinator, the journal article, and a drug history profile of a CHF patient who might benefit from the information. Control physicians received no mailing. The questionnaire asked whether the physicians already knew about the VA study, intended to alter their prescribing, and could identify factors that would affect their decision. Two thirds of intervention-group physicians were already aware of the VA study. One third indicated that they intended to alter drug therapy based on the study results; factors significantly associated with the intent to adopt a change were physician training and experience, comments by peers, new drug availability, and the size of the reduction in mortality. During four months after the intervention, only 5 physicians in the two groups switched their patients to both hydralazine and isosorbide (full change); 23 switched them to at least one of the drugs or discontinued prazosin (partial change). There was no significant difference in the number of full or partial changes between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Prescription drug use patterns of human immunodeficiency virus-infected patients taking zidovudine. Walter Reed Retrovirus Research Group.

Prescription drug profiles of 116 human immunodeficiency virus (HIV)-infected patients taking zidovudine in 1988 were surveyed. Patients received the drug an average of 236 days. About one-third (32 percent) required reduced dosage presumably because of hematologic toxicity and this was associated with length of time on the drug. Zidovudine dosage reduction was not associated with concurrent therapy with either acetaminophen or acyclovir. Concomitant drug therapy was common, especially with systemic antifungals (47 percent), antivirals (33 percent), nonsteroidal antiinflammatory drugs (23 percent), and antidepressants (20 percent), as well as topical fungicides (35 percent) and antiinflammatory agents (28 percent). Over three-fourths of patients on zidovudine were on chemoprophylaxis for Pneumocystis carinii pneumonia, most often with pentamidine inhalation therapy. This study showed that the HIV-infected patient population is being treated concomitantly with many pharmacologic agents prescribed by various medical specialties.

Impact of HIV infection on pharmaceutical services at Walter Reed Army Medical Center.

Services developed by the pharmacy department at Walter Reed Army Medical Center (WRAMC) relating to the treatment and study of patients infected with the human immunodeficiency virus (HIV) are described. The WRAMC pharmacy department closely monitored use of azidothymidine (renamed zidovudine) before and after its approval by FDA. It has also done pharmaceutical cost studies for HIV-infected patients by disease stage according to the Walter Reed Classification System. An Army pharmacist at the U.S. Army Centralized Allergen Extract Laboratory is involved with the development and distribution of delayed hypersensitivity skin tests used to determine the progression of the disease; the current test battery correlates with the CD4 T-lymphocyte count, low numbers of which indicate disease progression. The Walter Reed Retrovirus Research Group includes an Army pharmacist who not only is involved with the traditional distributive and clinical aspects of the position but also is involved in clinical pharmacy, pharmacoepidemiology, and social and behavioral research. This pharmacist is the principal investigator on protocols studying the relationship of various factors to the frequency and distribution of both beneficial and adverse pharmaceutical outcomes in this patient population. The pharmacy department at WRAMC has taken an active role in both the treatment of HIV-infected patients and HIV-associated research, as part of an aggressive overall Army effort to develop effective treatment and chemoprophylaxis or immunoprophylaxis for this disease.

Career patterns of pioneer clinical pharmacists.

The career paths of some early clinical pharmacists from their first positions during the years 1965-1974 to their current positions were studied. In August 1985 a group of pharmacists was surveyed to determine (1) the extent to which they had maintained a clinical practice (defined as direct patient contact, including evaluating and planning drug regimens), (2) the number of job-function changes, and (3) the degree of the pharmacists' commitment to public service, as measured by Hall's Belief in Public Service and Allport-Vernon-Lindzey Personality Values. The response rate for the 337 questionnaires was 73.5%. The average age of the group was 40 years; 83% were men, and 79% possessed Doctor of Pharmacy degrees. The respondents had changed job functions an average of 2.1 +/- 1.5 times over the last 13 years since the highest professional degree. The percentage in the job functions of hospital pharmacist and pharmacy faculty declined over time while those in hospital pharmacy administration, academic administration, and the pharmaceutical industry increased. Clinical-practice activity declined over time, with a twofold net increase in those reporting no direct patient-care responsibilities. Male respondents with fewer years after their highest professional degree, a greater belief in public service, higher theoretical values, and no residency experience were more likely to be currently involved in direct patient care than others. Although attrition among pioneer clinical pharmacists is not excessive for those who began their careers with a relatively small percentage of their time devoted to clinical practice, most pharmacists who began with substantial clinical commitments have reduced or eliminated clinical activities over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug utilization study methodologies: national and international perspectives.

This paper in the series on pharmacoepidemiology describes the history, development, and present status of drug utilization activities. The various methodologies employed in drug utilization studies are evaluated and presented along with a listing of the principal drug databases available for drug utilization research. An analysis is presented comparing the validity of drug consumption rates based on individual patient usage or drug cost data as adopted in North America and the defined daily dose unit as developed in Europe. Drug utilization derives its importance in pharmacoepidemiology from the fact that it provides the methodological rigor for defining the denominator data needed in pharmacoepidemiological research.