Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs.

BACKGROUND: The outcomes of an inception cohort of patients seen at an anticoagulation clinic (AC) were published previously. The temporary closure of this clinic allowed the evaluation of 2 more inception cohorts: usual medical care and an AC. OBJECTIVE: To compare newly anticoagulated patients who were treated with usual medical care with those treated at an AC for patient characteristics, anticoagulation control, bleeding and thromboembolic events, and differences in costs for hospitalizations and emergency department visits. RESULTS: Rates are expressed as percentage per patient-year. Patients treated at an AC who received lower-range anticoagulation had fewer international normalized ratios greater than 5.0 (7.0% vs 14.7%), spent more time in range (40.0% vs 37.0%), and spent less time at an international normalized ratio greater than 5 (3.5% vs 9.8%). Patients treated at an AC who received higher-range anticoagulation had more international normalized ratios within range (50.4% vs 35.0%), had fewer international normalized ratios less than 2.0 (13.0% vs 23.8%), and spent more time within range (64.0% vs 51.0%). The AC group had lower rates (expressed as percentage per patient-year) of significant bleeding (8.1% vs 35.0%), major to fatal bleeding (1.6% vs 3.9%), and thromboembolic events (3.3% vs 11.8%); the AC group also demonstrated a trend toward a lower mortality rate (0% vs 2.9%; P= .09). Significantly lower annual rates of warfarin sodium-related hospitalizations (5% vs 19%) and emergency department visits (6% vs 22%) reduced annual health care costs by $132086 per 100 patients. Additionally, a lower rate of warfarin-unrelated emergency department visits (46.8% vs 168.0%) produced an additional annual savings in health care costs of $29 72 per 100 patients. CONCLUSIONS: A clinical pharmacist-run AC improved anticoagulation control, reduced bleeding and thromboembolic event rates, and saved $162058 per 100 patients annually in reduced hospitalizations and emergency department visits.

Efficacy of newer medications for treating depression in primary care patients.

PURPOSE: Several medications have recently been introduced for the treatment of depression. We reviewed the literature to summarize their efficacy in the treatment of depression in adult patients in primary care settings. METHODS: We searched the literature published from 1980 to January 1998 using the Cochrane Collaboration Depression Anxiety and Neurosis Group's specialized registry of 8,451 clinical trials, references from trials and 46 pertinent meta-analyses, and consultation with experts. We included randomized controlled trials of at least 6 weeks' duration that measured clinical outcomes and compared one of 32 newer medications with another newer antidepressant, an older antidepressant, a placebo, or a psychosocial intervention for the treatment of depressed patients in primary care settings. The primary outcome was response rate, defined as the proportion of patients experiencing a 50% or greater improvement in depressive symptoms. RESULTS: There were 28 randomized controlled trials involving 5,940 adult primary care patients with major depression, depression requiring treatment, dysthymia, or mixed anxiety depression. Newer agents, including selective serotonin re-uptake inhibitors, serotonin norepinephrine inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists, were usually compared with tricyclic agents. Average response rates were 63% for newer agents, 35% for placebo, and 60% for tricyclic agents. Newer agents were significantly more effective than placebo [risk ratio = 1.6; 95% confidence interval (CI), 1.2 to 2.1), but similar to tricyclic agents (risk ratio = 1.0; 95% CI, 0.9 to 1.1). Response rates were similar in the different types of depressive disorders, except that two small trials in frail older patients showed no significant effects of newer agents compared with placebo. Dropout rates as a result of adverse effects were 8% with newer agents and 13% with tricyclic agents (P <0.05). CONCLUSIONS: In primary care settings, newer antidepressants are more effective than placebo and have similar efficacy compared with tricyclic agents in the acute treatment of depression. Dropout rates as a result of adverse effects are lower with newer compared with tricyclic agents. Future studies should compare the effectiveness of different therapies among primary care patients with less severe depression and greater medical and psychiatric comorbidity.

Management of mild chronic hypertension during pregnancy: a review.

OBJECTIVE: To conduct a systematic review of evidence relating to management of mild chronic hypertension during pregnancy, including associated risks, benefits, and harms of treatment with antihypertensive agents, nonpharmacologic measures, and aspirin and benefits of various monitoring strategies. DATA SOURCES: Using four broad search strategies, we searched English and non-English-language citations in 16 electronic databases from their inception to February 1999 and consulted relevant textbooks, references, and experts. STUDY SELECTION: Reviewers screened 6228 abstracts and found 215 articles that met multiple prespecified patient selection, study population, and design criteria. TABULATION, INTEGRATION, AND RESULTS: Forty-six studies consistently showed that chronic hypertension triples the risk for perinatal mortality (odds ratio [OR] 3.4; 95% confidence interval [CI] 3.0, 3.7) and doubles the risk for placental abruption (OR 2.1; 95% CI 1.1, 3.9). Thirteen small, randomized controlled trials had inadequate power to rule in or rule out moderate-to-large (20%-50%) benefits of antihypertensive treatment. Possible adverse effects were fetal renal failure when angiotensin-converting enzyme inhibitors are used in the second or third trimester and growth restriction when atenolol is used early in pregnancy. Trials showed that aspirin neither reduces nor increases perinatal and maternal morbidity, but they did not rule out possible small-to moderate beneficial or adverse effects. No studies provide guidance on benefits or consequences of various nonpharmacologic therapies or monitoring strategies. CONCLUSION: Mild chronic hypertension is associated with increased maternal and fetal risks. Beneficial treatment and monitoring regimens are not clear, but some treatments, such as angiotensin-converting enzyme inhibitors, are best avoided.

A statistical and clinical evaluation of fingerstick and routine laboratory prothrombin time measurements.

STUDY OBJECTIVE: To compare prothrombin time measurements by fingerstick and routine laboratory methods. DESIGN: Prospective cohort study. SETTING: University-affiliated anticoagulation clinic. PATIENTS: Thirty-three patients receiving warfarin with stable anticoagulation for 3 months preceding the two studies. INTERVENTIONS: Groups 1 (17 patients) and 2 (16 patients) provided 150 and 125 paired samples, respectively, for fingerstick and routine laboratory analysis. The fact that no patient required a dosage change allowed for a clinical assessment. MEASUREMENTS AND MAIN RESULTS: Correlation and agreement between methods were good in group 1 but poor in group 2. Fingerstick results were less variable (smaller standard deviation and smaller coefficient of repeatability) in both groups. By analysis of discrepant pairs (25 in group 1, 63 in group 2), the routine laboratory results indicated dosage changes erroneously more often than did the fingerstick method. CONCLUSIONS: In these two trials, the fingerstick system was superior to the routine laboratory method in that it was more reliable (less variability and more repeatable) and less likely to indicate dosage changes erroneously.

Effects of Marine Fish Oils on the Anticoagulation Status of Patients Receiving Chronic Warfarin Therapy.

The purpose of this placebo-controlled, randomized, double-blinded, parallel study was to determine the existence and magnitude of effect of various doses of fish oil supplements on International Normalized Ratio (INR) determinations in patients receiving chronic warfarin therapy. Patients from anticoagulation clinics from both the Brady Green Community Health Center and Audie L. Murphy Veterans Administration in San Antonio, Texas were enrolled in the study. The enrolled subjects included 5 males and 11 females, all of whom were receiving chronic warfarin therapy for indications requiring oral anticoagulation. All enrolled patients underwent a 4-week placebo monitoring period in which INRs were determined on a weekly basis. If the INRs were found to be stable, patients were randomized to receive a 4-week treatment period of either placebo capsules (n = 6), 3 grams of fish oil daily (n = 5), or 6 grams of fish oil daily (n = 5). Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. Five patients were discontinued from the study due to noncompliance (2) and unstable INRs (3). There was no statistically significant difference in INRs between the placebo lead-in and treatment period within each group (P = 0.82). There was also no difference in INRs found between groups (P= 0.41). One bruising episode was reported, yet no major bleeding episodes were observed during the study. Fish oil supplementation in doses of 3-6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic warfarin therapy.

Antibiotics for acute maxillary sinusitis.

OBJECTIVES: For adults seeking care in ambulatory practices, sinusitis is the most common diagnosis treated with antibiotics. We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were identified from searches of MEDLINE and EMBASE in October 1998, contacts with pharmaceutical companies and bibliographies of included studies. SELECTION CRITERIA: Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes for acute maxillary sinusitis. Additional criteria were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement and a sample size of 30 or more adults. Of 1784 potentially relevant studies, two or more reviewers identified 32 studies meeting selection criteria. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by 2 persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were a) clinical cure and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. MAIN RESULTS: Thirty-two trials, involving 7,330 subjects evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic vs. control (n=5); newer, non-penicillin antibiotic vs. penicillin class (n=10); and amoxicillin-clavulanate vs. other extended spectrum antibiotics (n=10). Most trials were conducted in otolaryngology settings. Only 5 trials described adequate allocation and concealment procedures; 10 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72, 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53), but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins vs. penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins vs. amoxicillin-clavulanate (RR for cure 1.01, 95% CI 0.97 to 1.04). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics. Relapse rates within one month of successful therapy were 5%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.

Dieting to reduce body weight for controlling hypertension in adults.

OBJECTIVES: Evaluate whether weight-loss diets are more effective than regular diets or other antihypertensive therapies in controlling blood pressure and preventing morbidity and mortality in hypertensive adults. SEARCH STRATEGY: MEDLINE and The Cochrane Library were searched through November 1997. Trials known to experts in the field were included through June 1998. SELECTION CRITERIA: For inclusion in the review, trials were required to meet each of the following criteria: 1) randomized controlled trials with one group assigned to a weight-loss diet and the other group assigned to either normal diet or antihypertensive therapy; 2) ambulatory adults with a mean blood pressure of at least 140 mm Hg systolic and/or 90 mm Hg diastolic; 3) active intervention consisting of a calorie-restricted diet intended to produce weight loss (excluded studies simultaneously implementing multiple lifestyle interventions where the effects of weight loss could not be disaggregated); and 4) outcome measures included weight loss and blood pressure. DATA COLLECTION AND ANALYSIS: Studies were dual abstracted by two independent reviewers using a standardized form designed specifically for this review. The primary mode of analysis was qualitative; graphs of effect sizes for individual studies were also used. MAIN RESULTS: Eighteen trials were found. Only one small study of inadequate power reported morbidity and mortality outcomes. None addressed quality of life or general well being issues. In general, participants assigned to weight-reduction groups lost weight compared to control groups. Six trials involving 361 participants assessed a weight-reducing diet versus a normal diet. The data suggested weight loss in the range of 4% to 8% of body weight was associated with a decrease in blood pressure in the range of 3 mm Hg systolic and diastolic. Three trials involving 363 participants assessed a weight-reducing diet versus treatment with antihypertensive medications. These suggested that a stepped-care approach with antihypertensive medications produced greater decreases in blood pressure (in the range of 6/5 mm Hg systolic/diastolic) than did a weight-loss diet. Trials that allowed adjustment of participants' antihypertensive regimens suggested that patients required less intensive antihypertensive drug therapy if they followed a weight-reducing diet. Data was insufficient to determine the relative efficacy of weight-reduction versus changes in sodium or potassium intake or exercise. REVIEWER'S CONCLUSIONS: Weight-reducing diets in overweight hypertensive persons can affect modest weight loss in the range of 3-9% of body weight and are probably associated with modest blood pressure decreases of roughly 3 mm Hg systolic and diastolic. Weight-reducing diets may decrease dosage requirements of persons taking antihypertensive medications.

Antibiotics for acute maxillary sinusitis.

BACKGROUND: For adults seeking care in ambulatory medical practices, sinusitis is the most common diagnosis treated with antibiotics. OBJECTIVES: We examined whether antibiotics are indicated for acute sinusitis, and if so, which antibiotic classes are most effective. SEARCH STRATEGY: Relevant studies were identified from searches of MEDLINE and EMBASE in December 2001, contacts with pharmaceutical companies and bibliographies of included studies. SELECTION CRITERIA: Randomized trials were eligible that compared antibiotic to control or antibiotics from different classes, for acute maxillary sinusitis. Additional criteria for inclusion were diagnostic confirmation by radiograph or sinus aspiration, outcomes that included clinical cure or improvement, and a sample size of 30 or more adults. Of 2058 potentially relevant studies, two or more reviewers identified 49 studies meeting selection criteria. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two persons and synthesized descriptively. Some data were analyzed quantitatively using a random effects model. Primary outcomes were: a) clinical cure, and b) clinical cure or improvement. Secondary outcomes were radiographic improvement, relapse rates, and dropouts due to adverse effects. MAIN RESULTS: Forty-nine trials, involving 13,660 participants, evaluated antibiotic treatment for acute maxillary sinusitis. Major comparisons were antibiotic versus control (n of 5); newer, non-penicillin antibiotic versus penicillin class (n of 10); and amoxicillin-clavulanate versus other extended spectrum antibiotics (n of 17), where n is the number of trials. Most trials were conducted in otolaryngology settings. Only 8 trials described adequate allocation and concealment procedures; 20 were double-blind. Compared to control, penicillin improved clinical cures [relative risk (RR) 1.72; 95% CI 1.00 to 2.96]. Treatment with amoxicillin did not significantly improve cure rates (RR 2.06; 95% CI 0.65 to 6.53) but there was significant variability between studies. Radiographic outcomes were improved by antibiotic treatment. Comparisons between classes of antibiotics showed no significant differences: newer non-penicillins versus penicillins (RR for cure 1.07; 95% CI 0.99 to 1.17); newer non-penicillins versus amoxicillin-clavulanate (RR for cure 1.03; 95% CI 0.96 to 1.11). Compared to amoxicillin-clavulanate, dropouts due to adverse effects were significantly lower for cephalosporin antibiotics (RR 0.47; 95% CI 0.30 to 0.73). Relapse rates within one month of successful therapy were 7.7%. REVIEWER'S CONCLUSIONS: For acute maxillary sinusitis confirmed radiographically or by aspiration, current evidence is limited but supports the use of penicillin or amoxicillin for 7 to 14 days. Clinicians should weigh the moderate benefits of antibiotic treatment against the potential for adverse effects.

A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.

BACKGROUND: Depressive disorders are persistent, recurring illnesses that cause great suffering for patients and their families. PURPOSE: To evaluate the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and adolescents. DATA SOURCES: English-language and non-English-language literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts. STUDY SELECTION: Randomized trials evaluating newer antidepressants (such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort) that reported clinical outcomes were selected. DATA EXTRACTION: Two persons independently abstracted data that were then synthesized descriptively; some data were pooled by using a random-effects model. DATA SYNTHESIS: Of 315 eligible trials, most evaluated antidepressants in adults with major depression, were conducted among outpatients, and examined acute-phase treatment. Newer antidepressants were more effective than placebo for major depression (relative benefit, 1.6 [95% CI, 1.5 to 1.7]) and dysthymia (relative benefit, 1.7 [CI, 1.3 to 2.3]). They were effective among older adults and primary care patients. Efficacy did not differ among newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo for mild to moderate depression (risk ratio, 1.9 [CI, 1.2 to 2.8]), but publication bias may have inflated the estimate of benefit. Newer and older antidepressants did not differ for overall discontinuation rates, but side effect profiles varied significantly. Data were insufficient for determining the efficacy of newer antidepressants for subsyndromal depression, depression with coexisting medical or psychiatric illness, or depression in adolescents. CONCLUSIONS: Newer antidepressants are clearly effective in treating depressive disorders in diverse settings. Because of similar efficacy, both newer and older antidepressants should be considered when making treatment decisions. Better information is urgently needed on the efficacy of newer antidepressants in patients with nonmajor depression and in special populations, including adolescents.

Treatment of depression--newer pharmacotherapies.

OBJECTIVES: Depressive disorders are persistent, recurring illnesses that impose enormous personal suffering on individuals and their families. Major depression alone is estimated as the fourth most important cause of worldwide loss in disability-adjusted life years and is likely to become the second most important within 20 years. A continued quest for more effective treatments has spawned newer antidepressants and herbal treatments, which have contributed to explosive growth in antidepressant prescribing, increasing pharmacy costs, and wider but sometimes confusing choices for clinicians and patients. This evidence report provides a comprehensive evaluation of the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and children. SEARCH STRATEGY: Pertinent literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts. The registry contained trials addressing depression that had been identified from multiple electronic bibliographic databases, hand searches of journals, and pharmaceutical companies. The search, which yielded 1,277 records, combined terms "depression," "depressive disorder," or "dysthymic disorder" with a list of 32 specific "newer" antidepressant and herbal treatments. SELECTION CRITERIA: Randomized controlled trials were reviewed if they (1) were at least 6 weeks in duration; (2) compared a "newer" antidepressant with another antidepressant (newer or older), placebo, or psychosocial intervention; (3) involved participants with depressive disorders; and (4) had a clinical outcome. Two or more independent reviewers identified 315 trials that met these criteria. DATA COLLECTION AND ANALYSIS: Two persons independently abstracted data from each trial. Data were synthesized descriptively, paying attention to participant and diagnostic descriptors, intervention characteristics, study designs and clinical outcomes. Some data were analyzed quantitatively using an empirical Bayes random-effects estimator method. Primary outcomes were response rate, total discontinuation rates (dropouts), and discontinuation rates due to adverse events. Response rates were defined as a 50 percent or greater improvement in symptoms as assessed by a depression symptoms rating scale or a rating of much or very much improved as assessed by a global assessment method. MAIN RESULTS: There were 264 trials that evaluated antidepressants in patients (adults and children) with major depression. Of these, 81 compared newer agents with placebo, 150 newer with older agents, 32 newer agents with newer agents, and 1 newer agent with psychotherapy. There were 14 trials evaluating hypericum (St. John's wort), 27 trials each in primary care patients and older adults, 10 trials limited to patients with specific concomitant illnesses, 9 trials in patients with dysthymia, 3 trials each in patients with mixed anxiety depression and subsyndromal depression, 2 trials in adolescents, and 1 in the postpartum setting. Most trials were conducted in outpatients and examined only acute phase treatment of less than 12 weeks' duration. Newer antidepressants were more effective than placebo in treating major depression (risk ratio 1.6, 95% CI 1.5 to 1.7) and dysthymia (risk ratio 1.7, 95% CI 1.3 to 2.3). They were effective among older adults and in primary care patients. In general, there were no significant differences in efficacy among individual newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo in treating mild to moderately severe depressive disorders (risk ratio 1.9, 95% CI 1.2 to 2.8). Whether hypericum (St. John's wort) is as effective as standard antidepressant agents given in adequate doses was not established. No significant differences were found between newer and older antidepressants in overall discontinuation rates. Selective serotonin reuptake inhibitors (SSRIs), reversi