Economics of antihypertensive therapy in the elderly.

Because of the high incidence of morbidity and mortality associated with hypertension in the elderly, the treatment of hypertension in this patient group must involve consideration of clinical, humanistic and economic outcomes. The most frequently used method of pharmacoeconomic analysis for antihypertensive therapy involves cost-effectiveness analysis, although several other methods are available. Current evidence reveals a trend toward cost effectiveness of antihypertensive treatment in elderly patients. However, these formal analyses are limited by the need for extrapolation of data regarding efficacy and level of risk from epidemiological and randomised trials, information which is often lacking. To incorporate economic factors into clinical decision making, other measures of economic impact should be explored. The economic impact of antihypertensive therapy is affected by the level of risk for the patient and the efficacy of the treatment. Data indicate that the risk of morbidity and mortality related to hypertension increases with age and that current antihypertensive drugs reduce this risk. When choosing an antihypertensive agent, the following parameters should be considered: acquisition cost, likelihood of adverse effects and other determinants of treatment adherence, and individual predictors of response. The economic outcomes will be maximised if prudent drug selection is supplemented by appropriate diagnostic and classification procedures and reduction of cardiovascular risk factors other than hypertension. The accumulation of data addressing the risks and benefits of therapy for the very old and the comparative efficacy of newer antihypertensive therapies will further clarify the decision-making process.

Obesity: managing comorbidities of the disease.

Obesity poses a serious health risk and is associated with a wide range of comorbid conditions. Obese patients with comorbid conditions such as type 2 diabetes and hypertension should be educated about the potential benefits of weight loss therapy. Pharmacists can offer consultative weight loss programs either on their own or by forming multidisciplinary teams with other practitioners, such as dietitians.

The impact of disease management on outcomes and cost of care: a study of low-income asthma patients.

An asthma disease management program designed specifically for low-income patients experiencing significant adverse events can improve health outcomes substantially, while lowering costs. The Virginia Health Outcomes Partnership aimed to help physicians in a fee-for-service primary care case management program manage asthma in Medicaid recipients. Approximately one-third of physicians treating asthma in an area designated as the intervention community volunteered to participate in training on disease management and communication skills. This large-scale study discovered that the rate of emergency visit claims for patients of participating physicians who received feedback reports dropped an average of 41% from the same quarter a year earlier, compared to only 18% for comparison community physicians. Although only a third of the intervention community physicians participated in the training, emergency visit rates for all intervention community physicians nonetheless declined by 6% relative to the comparison community among moderate-to-severe asthma patients when data for participating and nonparticipating physicians were combined. At the same time, the dispensing of some reliever drugs recommended for asthma increased 25% relative to the comparison community. A cost-effectiveness analysis projected direct savings to Medicaid of $3 to $4 for every incremental dollar spent providing disease management support to physicians. The results of this study demonstrate the potential this program offers, especially for Medicaid programs in other states that want to improve the care of their primary care case management networks and, at the same time, manage costs.

Pharmacists' knowledge and attitudes toward herbal medicine.

OBJECTIVE: The use and sales of herbal medications have increased dramatically over the past several years. Pharmacists are in an ideal position to educate patients about herbal medicines. This study was intended to determine the knowledge and attitudes of pharmacists regarding herbal medications. METHODS: A survey was distributed to pharmacists at several state and regional meetings in Virginia and North Carolina between August and October 1998. The survey evaluated demographic data, attitudinal scales, and a 15-item herbal medicine knowledge test. Pharmacists immediately returned the surveys to the distributor on completion. RESULTS: Of the 217 surveys distributed, 164 met the inclusion criteria for further evaluation. Of the pharmacists surveyed, 68.0% practiced in a community pharmacy, 45.1% had previous continuing education on herbal medications, and 73.6% sold herbal medications in their practice settings. The average score on the herbal knowledge test was 6.3 (maximum score of 15). Pharmacists with previous continuing education scored significantly higher than those without prior continuing education (p < 0.001). Of the 15 questions, the five that pharmacists were most likely to answer correctly assessed the uses of herbal medications. Additionally, pharmacists with prior continuing education or with access to herbal medication information at their practice site were more likely to agree that providing information about herbal medication is a pharmacist's professional responsibility (p = 0.02 and p = 0.01, respectively). CONCLUSIONS: The findings from this study demonstrate that pharmacists were more likely to answer correctly about the uses of herbal medications than about drug interactions, adverse drug effects, and precautions of herbal medications. Additionally, pharmacists with previous continuing education on herbal medications were more knowledgeable about these products. With the increasing use of herbal medications, there is a greater need for pharmacy training programs in this area.

Tumor necrosis factor microsatellite markers TNFa5b5 and TNFa6b5 influence adverse reactions to parenteral gold in Caucasians.

OBJECTIVE: To investigate which HLA haplotypes identified by DRB1 or tumor necrosis factor (TNF) microsatellite markers are associated with adverse reactions to parenteral gold injections. METHODS: We retrospectively studied 193 Caucasian subjects with rheumatoid arthritis (RA) who had received parenteral gold injections from a university faculty outpatient practice (n = 163) and outpatient clinics at a Department of Veterans Affairs Medical Center (n = 30). DRB1 typing was done by several DNA based techniques. TNF microsatellite genotypes were derived by polymerase chain reaction amplification, sequencing-type gel electrophoresis, and silver staining. RESULTS: Seventy-six subjects had experienced adverse reactions to gold injections (other than nitritoid reactions), 18 of whom had 2 concurrent toxicities. The numbers with adverse reactions included: mucocutaneous (57), proteinuria (25), hematuria without proteinuria (5), thrombocytopenia (3), and miscellaneous (11). By frequency comparisons, no DR was associated with adverse reactions to parenteral gold (chi-squared 4.7, 6 df, NS). Specifically, there was no increased risk of proteinuria or mucocutaneous side effects in the DR3 positive RA group, almost all of whom had the DRB1 allele *0301. By logistic regression modeling controlling for sex and onset age, DR12 and the TNF microsatellite markers a5b5 and a6b5 were associated with mucocutaneous reactions (p < 0.05 for each). The odds ratios favoring mucocutaneous adverse reactions were 3.72 with TNFa5b5 and 2.03 with TNFa6b5. TNFa5b5 was commonly found on the HLA haplotypes bearing DRB1*0101, and TNFa6b5 was on the ones bearing DRB1 alleles of the DR1, DR2, DR3, DR5, or DR6 groups or the DRB1*0401 allele. CONCLUSION: HLA haplotypes conferring risk of gold induced mucocutaneous reactions were better identified by certain HLA class III markers, namely TNFa5b5 and TNFa6b5, than by any previously associated DR groups.

Migraine: a comprehensive review of new treatment options.

Headaches are among the most common complaints reported to health care professionals and are classified by the International Headache Society as migraine, tension-type, or cluster, with additional subtypes. Classification and etiology of headache should be determined after thorough review of the patient's history. Once diagnosed, migraine can be treated by preventive or abortive measures. Recent developments add new options, including availability of drugs for intranasal administration (sumatriptan, dihydroergotamine) and 5-HT1B/1D agonists (rizatriptan, zolmitriptan, naratriptan, eletriptan). Although placebo-controlled trials are available, few comparative clinical trials of these agents have been conducted; however, important pharmacologic, pharmacokinetic, and clinical differences exist among the drugs.

HLA-DRB1 genotype influences risk for and severity of rheumatoid arthritis.

OBJECTIVE: To examine how HLA-DRB1 genotypes influence rheumatoid arthritis (RA) risk and clinical severity. METHODS: We performed polymerase chain reaction based DRB1 and tumor necrosis factor (TNF) genotyping of 309 Caucasian RA and 283 Caucasian control subjects. For risk analyses, we grouped the DRB1 alleles encoding each specific shared epitope: *0401 alone, *0404 with *0102, *0405 with *0408 and *0101, and *1001 alone. For estimates of RA outcome, we retrospectively obtained data regarding ARA classification criteria, age of disease onset and disease duration, number of slow acting antirheumatic drugs (SAARD) used, and rheumatoid factor (RF). RESULTS: Homozygous shared-epitope DRB1 genotypes, compound heterozygous genotypes, and simple heterozygous genotypes all conferred elevated relative risk (RR) for RA (RR 4.3, 11.7, and 3.5, respectively). However, compound heterozygous genotypes conferred more risk than either simple heterozygous genotype (RR 3.3, p = 0.004) or homozygous genotype (RR 2.8, p = 0.036). There was a trend toward more compound heterozygous genotypes in the male RA group than in the female RA group (p < 0.1), and male sex was associated with higher frequency of rheumatoid nodules (56 vs 35% for female RA). RA outcome was estimated by number of SAARD used; mean SAARD used was higher in male than in female RA (p < 0.01) and higher in genotypes containing one or 2 shared epitope DRB1 alleles than in those negative for shared epitope DRB1 alleles (p < 0.05). Analyses also suggested that shared epitope DRB1 genotype significantly influenced the occurrence of seropositive RA. Seropositive RA fraction was related to either number of shared epitope alleles (0, 1, or 2) represented in the DRB1 genotype, or, alternatively, to the combination of sex with shared epitope DRB1 genotype. The presence of one or 2 shared epitope DRB alleles influenced the occurrence of high titer seropositive RA as defined by sheep cell agglutination test (p < 0.01). TNFab microsatellite markers and TNF promoter polymorphisms did not influence SAARD number, seropositive RA, or high titer seropositive RA. CONCLUSION: Not all shared epitope DRB1 genotypes conferred the same relative risk, and the male RA group tended to have more compound heterozygous genotypes and more severe RA as indicated by rheumatoid nodules and SAARD usage. DRB1 genotypes with one or 2 shared epitope DRB1 alleles influenced the RA outcome as estimated by numbers of SAARD used and RF.

Home blood glucose monitoring.

OBJECTIVE: To provide a review of self-monitoring blood glucose including home blood glucose meters and patient education. DATA SOURCES: A MEDLINE search (January 1966-January 1998) was conducted to identify original and review articles. Search terms included self-monitoring blood glucose and blood glucose monitoring. Owner's manuals and package inserts were reviewed to determine specific characteristics for each glucose meter. DATA EXTRACTION: All current original and review articles about self-monitoring blood glucose and home blood glucose meters were included if they contained information about benefits of self-monitoring blood glucose, technology and performance of blood glucose meters, quality control, selection characteristics of blood glucose meters, and patient education. DATA SYNTHESIS: Self-monitoring of blood glucose has become an increasingly vital component of the care of the diabetic patient. Many glucose monitors are available with various features that may be confusing to pharmacists. Pharmacists need to be able to aid patients in the selection of an appropriate glucose meter and provide the education necessary for proper use and follow-up. Patient education is a key component in optimizing the potential benefits of self-monitoring. CONCLUSIONS: Self-monitoring of blood glucose, if used properly, can have a positive effect by increasing patient involvement in overall diabetes care. Pharmacists are accessible and can teach patients necessary skills that will enhance their ability to self-manage blood glucose.

Perceptions of pharmacists about adverse effects of corticosteroid therapy: focus on osteoporosis.

OBJECTIVE: To assess the perceptions of pharmacists regarding the adverse effects of corticosteroids, in particular corticosteroid-induced osteoporosis. DESIGN: Mailed survey of a random sample of pharmacists. SETTING: Richmond, Virginia. PARTICIPANTS: 350 community and hospital pharmacists. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Respondents' knowledge of adverse effects of corticosteroid therapy in men, premenopausal women, and postmenopausal women; the content of respondents' usual patient counseling for low- and high-dose therapy; and respondents' opinions of regimens for prevention of osteoporosis. RESULTS: Pharmacists associated gastritis, weight gain, and mood changes with corticosteroid use in a hypothetical 45-year-old man or 45-year-old premenopausal woman. For a hypothetical 65-year-old postmenopausal woman, pharmacists more frequently counseled about weight gain, osteoporosis, and gastritis. Patient counseling focused on these adverse effects for both low-dose (5 to 10 mg/day) and high-dose (> or = 30 mg/day) prednisone use. Osteoporosis was considered more likely in patients receiving high-dose corticosteroids on a long-term basis. CONCLUSION: Pharmacists responding to this survey frequently overlooked the association between low- and high-dose corticosteroid use and decreased bone density. Educational efforts are needed so that pharmacists can fulfill their potential for educating patients, monitoring corticosteroid therapy, and detecting drug-induced complications.

Variations in physicians' judgments about corticosteroid induced osteoporosis by physician specialty.

OBJECTIVE: Longterm corticosteroid use is associated with an increased risk of osteoporosis and fractures. Calcium and vitamin D supplementation and estrogen replacement therapy can decrease this risk, but the majority of patients receiving longterm corticosteroid treatment do not receive treatments to prevent bone loss. We assess whether this is due to variations in physicians' judgments about risks and efficacy of treatments to prevent corticosteroid-induced osteoporosis. METHODS: Questionnaires were mailed to 425 physicians, who were sampled so that half were generalists and half were specialists. Physicians were given hypothetical clinical scenarios involving patients taking corticosteroids and asked to judge the importance of osteoporosis as a risk of corticosteroid treatment, the importance of discussing this side effect with patients, and to indicate how often they would use calcium with vitamin D and estrogen for a hypothetical postmenopausal patient receiving longterm corticosteroid treatment. RESULTS: In total 198 physicians (50%) responded to this survey. Most physicians rated osteoporosis as one of the 3 most significant side effects of corticosteroid treatment for postmenopausal women, but there was significant variation in physician judgments about the importance of corticosteroid induced osteoporosis for premenopausal women (p=0.03) and men (p=0.001). There was also significant variation in physician judgments about the importance of discussing osteoporosis as a side effect with patients (p=0.001), and their use of both calcium and vitamin D (p=0.002) and estrogen replacement therapy (p=0.001) for a hypothetical postmenopausal patient. The physician characteristics most associated with these differences were physician specialty and experience with corticosteroid use. Primary care physicians and physicians who more commonly prescribe corticosteroids were more likely to report that they would use estrogen and calcium to prevent corticosteroid induced bone loss. Physician age, sex, and university affiliation had no association with physician assessments. CONCLUSION: Physicians' judgments varied significantly by physician specialty and experience with corticosteroid use. These data suggest that patients cared for by physicians in different specialties will get varying advice about osteoporosis risk and preventive treatments when receiving longterm corticosteroid treatment.

Selection of peak flowmeters in ambulatory asthma patients: a review of the literature.

The National Asthma Education and Prevention Program recently published updated guidelines that stress the importance of peak flow monitoring for patients with moderate-to-severe persistent asthma. In this specific patient population, a peak flowmeter provides a simple, quantitative, objective measurement of large airway function. The purpose of this article is to describe indications for peak flow monitoring in asthmatic patients, review technical requirements for peak flowmeters as described by the National Heart, Lung, and Blood Institute, and evaluate the literature on commercially available peak flow devices to aid the health professional in selecting an appropriate meter for the patient with moderate-to-severe persistent asthma.

Budesonide inhalation powder: a review of its pharmacologic properties and role in the treatment of asthma.

Budesonide inhalation powder, available as Pulmicort Turbuhaler, is a corticosteroid with a high ratio of local to systemic effects that is administered to treat persistent asthma. The Turbuhaler achieves lung deposition approximately twice that of a metered-dose inhaler (MDI) with or without a spacer device. Budesonide inhalation powder has clinical efficacy equivalent to that of fluticasone and beclomethasone, but it has lower systemic bioavailability and fewer systemic side effects. As with other inhaled corticosteroids, dysphonia and oral candidiasis are the most frequent adverse effects, and systemic effects are infrequent. The initial starting dosage is 200 microg (1 puff) twice/day and may be increased to 800 microg twice/day in adults or 400 microg twice/day in children. Patients prefer the Turbuhaler to the MDI, Diskhaler, and Rotahaler because it is easier to use and more convenient to carry.

Implementing disease management in community pharmacy practice.

Disease management (DM) is a comprehensive approach to preventing and treating disease that: (1) targets patients with specific diseases; (2) provides integrated services across organizational and professional boundaries; (3) utilizes services based on the best scientific evidence available; and (4) focuses on outcomes. DM differs from pharmaceutical care in that pharmaceutical care targets not only patients with specific diseases but also those with risk factors for drug-related problems, a history of nonadherence, and frequent changes in medication regimens. Steps to starting a DM program include: (1) identifying a target population based on the population's strategic importance to the goals and aims of the organization; (2) assessing the organization's available resources, both internal and external; (3) defining key indicators with which to assess the program for the purposes of internal quality control and of obtaining compensation from third-party payers; (4) implementing the program using the best scientific methods available; and (5) assessing the impact of the program. The development of a smoking cessation program at a nationwide retail pharmacy chain is used as an example of a DM program initiated in community pharmacy practice. Pharmacists are well positioned to take a major role in DM, because they are accessible to the community and because DM frequently involves drug therapy. DM is also widely used in managed care. It is important that community pharmacists be closely involved in the DM approach as it evolves.

The role of academia in community-based pharmaceutical care.

Developing models of pharmaceutical care (PC) for educating students and practitioners represents a fundamental role for schools of pharmacy. Virginia Commonwealth University has sought to facilitate the implementation of PC in the community by hiring faculty to practice in this setting. The mission of the faculty is to implement PC in a community pharmacy practice, to develop clerkship sites for Pharm.D. students, and to evaluate the impact of PC services in the community. Examples of an independent pharmacy model, a grocery chain model, and a retail chain model of care may serve a dual purpose for faculty members, that is, define responsibilities for the academic institution and for the community practice environment.

Evaluation of the total cost of treating elderly hypertensive patients with ACE inhibitors: a comparison of older and newer agents.

We compared total costs and adherence to the regimen of older versus newer angiotensin-converting enzyme (ACE) inhibitors for the treatment of elderly patients with hypertension. A computer search using the data base of a health care insurer identified 6176 subjects age 65 years or older who had ICD-9 coding for hypertension only and had a new prescription for an ACE inhibitor dispensed between April 1, 1992, and January 31, 1993. Subjects receiving concurrent antihypertensive drugs were included. Total cost of therapy included acquisition costs for the ACE inhibitors and concurrent antihypertensive agents, and nondrug costs. Other costs were laboratory tests, hospitalization, and clinic visits associated with monitoring outcomes of antihypertensive therapy. Total median cost per month was greater for older than for newer agents, $59.82 versus $53.09 (p<0.0009). The mean percentage of patients complying with therapy as determined by refill data was greater with newer than with older agents, 66% versus 58% (p<0.0001). Based on our results, newer ACE inhibitors should be first-line antihypertensive therapy in elderly patients. They also should be considered for elderly patients who are unresponsive to older ACE inhibitors.

The effect of flurbiprofen on steady-state plasma lithium levels.

STUDY OBJECTIVE: To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium. DESIGN: Placebo-controlled, single-blind, crossover study. SETTING: University-affiliated hospital. PATIENTS: Eleven healthy women with bipolar disorder. INTERVENTIONS: The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study. MEASUREMENTS AND MAIN RESULTS: Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (Cmin) and area under the curve were statistically significantly increased (p < 0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in Cmin appeared to be associated with a greater than 1000-microgram/24 hour decrease in urinary excretion of prostaglandin E2. CONCLUSION: Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.

B lymphocytic clonal expansion in rheumatoid arthritis.

OBJECTIVE: To learn whether rheumatoid factor (RF), HLA-DR4, or current therapy influences clonal expansion of B lymphocytes (B cells) in persons with rheumatoid arthritis (RA). METHODS: We measured clonal expansion by analysis of cell surface staining for immunoglobulin light chains. Double staining methods detected a B cell marker (CD19) plus either kappa or lambda on peripheral blood lymphocytes from subjects with RA (n = 26) and controls (n = 26). The difference between frequency histograms of surface kappa and lambda staining was determined by the Kolmogorov-Smirnov statistic D that represents the fraction of clonally expanded B cells. RESULTS: The mean D value in RA was over 50% higher than in the controls [0.225 +/- SD 0.155 versus 0.144 +/- 0.025 (p < 0.0001)]. Ten subjects with RA had values exceeding +2 SD for controls (p = 0.0007). Mean D correlated with RF titer (Spearman's rank correlation coefficient rSp + 0.53, p = 0.006). All 10 high D values were found in the RA subgroups with positive serum tests for RF and with the HLA-DR4 positive genotype. The channel of maximal difference between kappa and lambda staining was higher in the RA group than in controls, showing that clonal expansion was most marked among brightly staining cells. Patients with RA currently receiving low dose methotrexate (MTX) tended to have higher D values than those not receiving MTX (mean 0.29 versus 0.18, respectively, p < 0.025). The RA group currently receiving MTX had a higher frequency of abnormal D values (7 of 11 versus 3 of 15 not currently receiving MTX, p = 0.03). This probably reflects preferential use of MTX for severely affected individuals. Confirmatory studies to detect clonal immunoglobulin gene rearrangements were attempted in selected individuals with high D values, but none was demonstrated in total leukocytic or B cell enriched fractions. CONCLUSION: Findings consistent with B cell clonal expansion occur in about 40% of persons with RA, particularly in the subgroups with positive serum tests for RF and with the HLA-DR4 genotype. However, the clonal expansion level must be below the sensitivity of confirmatory methods.

A comprehensive investigation of inpatient intravenous colchicine use shows more education is needed.

OBJECTIVE: To test the hypothesis that colchicine therapy for patients in whom treatment was guided by rheumatology consultation was more appropriately prescribed than therapy for patients not receiving consultation. METHODS: A retrospective chart review of all inpatients with acute crystal induced arthritis who received intravenous (iv) colchicine was performed to assess iv colchicine prescribing errors and any adverse outcomes of iv colchicine therapy. RESULTS: Errors in the prescribing of iv colchicine occurred in 5 of 19 patients (26%). A rheumatology consultation was not obtained in any of these cases. Overall, there was a significant increase in the prescribing error rate in the no-consultation versus the consultation groups (p = 0.045). These 5 errors did not lead to serious adverse outcomes, but leukopenia occurred in one patient and the white blood cell count decreased from 7.3 to 4.3 cells/mm3 in another patient. Leukopenia also occurred in 3 patients in whom iv colchicine was used appropriately. CONCLUSION: (1) Previously published guidelines for iv colchicine use appeared successful at preventing serious colchicine toxicity. (2) These guidelines do not protect against leukopenia occurring from colchicine use. (3) Rheumatology consultation may help prevent errors in the use of iv colchicine. (4) Further education is needed in the correct use of iv colchicine.