Orlistat--a novel weight loss therapy.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of obesity. DATA SOURCES: English-language articles were identified from MEDLINE (1966-July 2000), Roche Laboratories, organizational guidelines, National Institutes of Health and Food and Drug Administration Web sites, and Doctor's Guide online. Key words included obesity, orlistat, and lipase inhibitors. References were also identified from reference sections of published articles. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled, human trials were selected for review and discussion. DATA SYNTHESIS: Orlistat is the first agent in the lipase inhibitor class of antiobesity drugs. Orlistat is minimally absorbed and has been shown to reduce body weight by inhibiting absorption (by approximately 30%) of ingested dietary fat. Safety and efficacy have been established in one- and two-year double-blind, placebo-controlled trials; adverse effects were primarily, and almost exclusively, gastrointestinal. Due to its ability to block fat absorption, orlistat also has the capability to inhibit absorption of fat-soluble vitamins. Therefore, a daily multiple vitamin is recommended while taking orlistat. CONCLUSIONS: By inhibiting fat absorption, orlistat offers a new treatment modality for weight loss and maintenance. Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia. However, further studies during postmarketing surveillance are needed to fully establish orlistats long-term benefits and safety. Orlistat should be considered a useful adjunctive therapy for weight loss and maintenance in obese patients (i.e., body mass index > or = 30 kg/m2 or > or = 27 kg/m2 if other risk factors are present) committed to lifestyle changes including diet, exercise, and behavioral modification.

Effectiveness and costs of omeprazole vs ranitidine for treatment of symptomatic gastroesophageal reflux disease in primary care clinics in West Virginia.

OBJECTIVE: To compare clinical, health-related quality of life (HRQL), and medical cost outcomes in patients with symptomatic gastroesophageal reflux disease (GERD) receiving omeprazole sodium or ranitidine hydrochloride treatment. METHODS: A multicenter, randomized, open-label, medical effectiveness trial conducted in 5 university-based family medicine clinics. Two hundred sixty-eight patients with GERD were recruited and randomly assigned to omeprazole sodium, 20 mg once daily, or ranitidine hydrochloride, 150 mg twice daily, for up to 6 months. Main outcome assessments included the Gastrointestinal Symptom Rating Scale (GSRS) Reflux score, Psychological General Well-Being Index, and Short-Form-36 Health Survey administered at baseline and 2, 4, 12, and 24 weeks. Medical resource use and cost data were collected. RESULTS: More omeprazole-treated patients reported improved heartburn resolution at 2 weeks (49.0% vs 33.3%; P=.007) and 4 weeks (58.6% vs 35.0%; P<.001) compared with ranitidine-treated patients. The GSRS Reflux scores across 3 months showed overall differences between omeprazole (mean, 2.67) and ranitidine (mean, 2.95) groups (P=.04). Mean total 6-month medical costs were $915 lower ($8371 vs $9286; P=.64), and no difference in mean outpatient medical costs ($1198 vs $1158; P=.76) were observed in the omeprazole group compared with the ranitidine group. A post hoc secondary analysis showed that, at 12 and 24 weeks, patients treated with omeprazole for 8 weeks or more reported greater heartburn resolution (ie, 24 [43%] of 56 patients at both intervals) than patients treated with ranitidine for 8 weeks or more (12 [24%] and 13 [26%] of 50 patients, respectively; P=.001). CONCLUSIONS: Ranitidine and omeprazole were both effective at improving heartburn symptoms; however, omeprazole provided greater resolution of heartburn symptoms at 2 and 4 weeks. Despite omeprazole's higher acquisition cost, there were no significant differences in total or outpatient costs between groups.

Magnesium for the next millennium.

BACKGROUND: Magnesium is a trace mineral in several hundred chemical reactions in the body. It has therapeutic potential in many medical conditions. In this review, we attempted to clarify the current information on the role of magnesium as a therapeutic agent. METHODS: A MEDLINE search from 1966 through March 1999 was conducted, using PubMed and "Magnesium" and "Therapeutic Usage" as the two initial key headings. Important articles were also identified from the bibliographies of the initial articles. RESULTS: A total of 51 articles were included in this review. Articles were excluded if they were based on animal study or were in a language other than English. CONCLUSION: Magnesium has long been used as an ingredient in laxatives and antacids. It seems clear that intravenous magnesium also is effective for the suppression of ventricular ectopy in the hospital setting and is a first-line agent for torsades de pointes. It is less clear whether it is useful in patients with congestive heart failure or acute myocardial infarction (MI). Although effective for treatment of preeclampsia/eclampsia, its use in the termination of preterm labor has recently been questioned. In asthma and chronic lung disease, intravenous magnesium may be useful when conventional treatment has failed. Finally, magnesium may have a role in the prevention and treatment of vascular headaches.

Therapeutic uses of vitamin E in prevention of atherosclerosis.

UNLABELLED: The purpose of this review is to present the evidence-based pharmacotherapeutic properties of vitamin E and provide clinical recommendations for use in the arena of atherosclerosis. METHODS: A literature search was conducted from 1966 through March 1999. All usable papers were retrieved, with large, randomized, double-blinded, clinical trials and epidemiological trials receiving emphasis. RESULTS: Vitamin E, a lipid soluble vitamin, is a potent antioxidant. Several epidemiological studies have demonstrated positive relationships between vitamin E intake and the prevention of atherosclerotic heart disease; however, only one, large randomized clinical trial (The CHAOS Trial) has been conducted using more than 400 IU per day of vitamin E. Positive outcomes included a 77-percent reduction in nonfatal myocardial infarction (MI), but no corresponding reduction in mortality. Several large clinical trials are ongoing, investigating vitamin E for the prevention of atherosclerosis. Much less work has been undertaken studying vitamin E for prevention of cerebro- and peripheral vascular disease, but there appears to be promise in these areas as well. CONCLUSIONS: On the basis of the literature search, the authors recommend 400 IU or more per day of vitamin E to patients at high risk or already diagnosed with coronary artery disease. Vitamin E supplementation may also be beneficial in the prevention of cerebro- and peripheral vascular diseases.

Health-related quality of life in primary care patients with gastroesophageal reflux disease.

OBJECTIVE: To describe the clinical characteristics and health-related quality of life of family medicine patients with clinically diagnosed gastroesophageal reflux disease (GERD). METHODS: The study involved the baseline assessment of 268 patients enrolled in a randomized clinical trial comparing treatments for GERD. The study was conducted in a five-center, university-based family practice in southeastern West Virginia. Patients with a clinical diagnosis of GERD and who had not received treatment in the past 30 days were eligible; pregnant and lactating women and patients with severe renal or hepatic insufficiency were excluded. RESULTS: Two hundred sixty-eight patients were included in the analysis. Mean +/- SD age was 44.9 +/- 14.1 years; 61.2% were women and 91.4% were white. Mean +/- SD body mass index was 30.3 +/- 6 kg/m2, and >15.3% of patients had no insurance. One hundred seventy-four (64.9%) patients were enrolled from nonurban primary care clinics. One hundred sixty-four patients (61.2%) were prescribed at least one medication prior to study enrollment (mean +/- SD 2.88 +/- 1.71; range 1-9). When adjusted for age, gender, comorbidity status, and rural status, severity of GERD was associated with decreased health-related quality of life. GERD patients without comorbidity demonstrated decrements in health-related quality of life when compared with the US general population. When compared with another GERD population, the study patients reported fairly consistent GERD symptomatology and health-related quality of life. CONCLUSIONS: GERD symptom severity was associated with impaired health-related quality of life in a predominantly rural primary care population.

The cyclooxygenase-2 inhibitors: safety and effectiveness.

OBJECTIVE: To review the development of cyclooxygenase-2 (COX-2) inhibitors and discuss specific agents that are currently under investigation or have been marketed. DATA SOURCES: Primary literature on selective COX inhibitors was identified from a comprehensive MEDLINE, English-literature search from January 1966 through September 1998, with additional studies selected by review of the references. Abstracts from recent meetings and package insert literature from approved agents were also used as source material. Indexing terms included COX-2 inhibitors, meloxicam, celecoxib, rofecoxib, flosulide, SC-58635, and MK-966. STUDY SELECTION: Human clinical, pharmacokinetic, and dose-ranging trials performed in Europe and the US and randomized comparative trials were reviewed. DATA SYNTHESIS: With the discovery of at least two COX isoforms, a better understanding of the mechanism of action and gastrointestinal toxicity of nonsteroidal antiinflammatory drugs (NSAIDs) has been realized. While COX-1 is involved in physiologic maintenance, COX-2 seems to be involved in inflammation, mitogenesis, and specialized signal transductions. Selective COX-2 inhibitors may allow maximum antiinflammatory activity while improving the safety profile associated with NSAID therapy. Celecoxib and rofecoxib have been approved by the Food and Drug Administration for the treatment of osteo- and rheumatoid arthritis; meloxicam is undergoing Phase III clinical trials. Preliminary data indicate that the selective COX-2 inhibitors provide analgesic and antiinflammatory efficacy comparable with older NSAIDs, with fewer adverse gastrointestinal effects. CONCLUSIONS: Specific COX-2 inhibitors offer promising benefits over older NSAIDs with regard to gastrointestinal safety while maintaining analgesic and antiinflammatory efficacy. Further study is required to determine long-term efficacy and safety in clinical use.

Tetravalent rotavirus vaccine.

OBJECTIVE: To review the clinical efficacy, safety, and pharmacoeconomic data about the use of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) in infants and children. DATA SOURCES: A MEDLINE search (January 1990-December 1998) was conducted to identify all publications on the RRV-TV vaccine including pharmacology, clinical trials, adverse effects, and pharmacoeconomics in infants and children. Bibliographies of articles were also used. STUDY SELECTION: All randomized and placebo-controlled clinical efficacy trials were reviewed. Additionally, pharmacoeconomic studies focusing on the potential impact on healthcare costs were chosen for review. DATA SYNTHESIS: Rotavirus-induced gastroenteritis is a significant problem in developed and developing countries. Various forms of a rotavirus vaccine have been studied worldwide. The tetravalent vaccine appears to have similar efficacy in developed and developing countries. It seems to be most effective against the most severe forms of gastroenteritis, with an 80% overall efficacy rate. This vaccine is well tolerated; the most common adverse effect is fever after the first dose. Pharmacoeconomic studies indicate that although the vaccine may be only moderately effective against less severe gastroenteritis, over $1 billion annually could potentially be saved in the US with its universal use. CONCLUSIONS: The new rotavirus vaccine is effective in preventing and reducing the incidence of rotavirus-induced gastroenteritis. The morbidity, mortality, and healthcare costs from this disease may be reduced if this vaccine is provided to children worldwide.