Allan Ellsworth

Role of Diuretics in the Prevention of Heart Failure The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Background— Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. Methods and Results— ALLHAT was a double-blind, randomized, clinical trial in 33 357 high-risk hypertensive patients aged ≥55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. Conclusions— HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis

Forty-seven climbers participated in a double-blind, randomized trial comparing acetazolamide 250 mg, dexamethasone 4 mg, and placebo every eight hours as prophylaxis for acute mountain sickness during rapid, active ascent of Mount Rainier (elevation 4,392 m). Forty-two subjects (89.4 percent) achieved the summit in an average of 34.5 hours after leaving sea level. At the summit or high point attained above base camp, the group taking dexamethasone reported less headache, tiredness, dizziness, nausea, clumsiness, and a greater sense of feeling refreshed (p less than or equal to 0.05). In addition, they reported fewer problems of runny nose and feeling cold, symptoms unrelated to acute mountain sickness. The acetazolamide group differed significantly (p less than or equal to 0.05) from other groups at low elevations (1,300 to 1,600 m), in that they experienced more feelings of nausea and tiredness, and they were less refreshed. These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness. Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone. This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease.

Collaborative Care Model to Improve Outcomes in Major Depression

OBJECTIVE: To develop a pharmacist intervention to improve depression care and outcomes within a primary care setting. METHODS: Pragmatic, randomized trial of a clinical pharmacist collaborative care intervention versus usual care in a busy, academic family practice clinic. RESULTS: Seventy-four patients diagnosed with a new episode of major depression and started on antidepressant medications were randomized to enhanced care (EC) or usual care (UC) groups. EC consists of a clinical pharmacist collaborating with primary care providers (PCPs) to facilitate education, initiation, and titration of acute-phase antidepressant treatment to monitor treatment adherence and to prevent relapse. Control patients receive UC by their PCP. The main end point is reduction of depression symptoms over time as measured by the Hopkins Symptom Checklist (SCL-20). Other outcomes include the Diagnostic and Statistical Manual of Mental Disorders, (DSM-IV) criteria for major depression, health-related quality of life measured by the Medical Outcomes Study Short Form 12 (SF-12), medication adherence, patient satisfaction, and healthcare utilization. The main end point and the cost of treating major depression will be used to estimate the cost-effectiveness of the collaborative care model. CONCLUSIONS: The study is a unique, ongoing trial that may have important implications for the treatment of depression in primary care settings as well as new roles for clinical pharmacists.

A multifaceted intervention in support of diabetes treatment guidelines: a cont trial

OBJECTIVE in an academic family practice clinic, we performed a controlled trial of a multifaceted intervention versus usual care for managing diabetes. Providers received didactic training and computerized compliance feedback to support staged diabetes management, an evidenced-based approach to diabetes care. RESEARCH DESIGN AND METHODS one firm of the clinic practice received the intervention, the other served as the control group during a 14-month baseline period and a 14-month study period. HbA1(c) was the principal outcome measure. RESULTS there was a significant 0.71% difference in change in HbA1(c) values between the intervention and control firms (P=0.02). The subgroup with the greatest improvement in HbA1(c) was those subjects who started the intervention with a HbA1(c) above 8%. The overall improvement in glycemic control could not be explained by differences in visit frequency or the aggressiveness of drug therapy. There were no changes in healthcare utilization or costs between the two firms. CONCLUSION in an academic family practice clinic, a multifaceted intervention in support of diabetes treatment guidelines modestly improved glycemic control without incurring additional costs. The improvement was mostly due to mitigation of the natural deterioration in control usually seen. Further efforts are required to involve all patients in co-managing their diabetes.

Effect of high altitude on blood glucose meter performance.

Participation in high-altitude wilderness activities may expose persons to extreme environmental conditions, and for those with diabetes mellitus, euglycemia is important to ensure safe travel. We conducted a field assessment of the precision and accuracy of seven commonly used blood glucose meters while mountaineering on Mount Rainier, located in Washington State (elevation 14,410 ft). At various elevations each climber-subject used the randomly assigned device to measure the glucose level of capillary blood and three different concentrations of standardized control solutions, and a venous sample was also collected for later glucose analysis. Ordinary least squares regression was used to assess the effect of elevation and of other environmental potential covariates on the precision and accuracy of blood glucose meters. Elevation affects glucometer precision (p = 0.08), but becomes less significant (p = 0.21) when adjusted for temperature and relative humidity. The overall effect of elevation was to underestimate glucose levels by approximately 1-2% (unadjusted) for each 1,000 ft gain in elevation. Blood glucose meter accuracy was affected by elevation (p = 0.03), temperature (p < 0.01), and relative humidity (p = 0.04) after adjustment for the other variables. The interaction between elevation and relative humidity had a meaningful but not statistically significant effect on accuracy (p = 0.07). Thus, elevation, temperature, and relative humidity affect blood glucose meter performance, and elevated glucose levels are more greatly underestimated at higher elevations. Further research will help to identify which blood glucose meters are best suited for specific environments.

Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study.

Insulin resistance underlies most glucose disorders in adults and is associated with an increased risk of cardiovascular disease. Alpha blockers decrease insulin resistance, whereas diuretics increase insulin resistance.

Analgesia for colposcopy : Double-masked, randomized comparison of ibuprofen and benzocaine gel

Objective To evaluate pain relief effectiveness of oral ibuprofen and topical benzocaine gel during colposcopy. Methods In a double-masked, randomized controlled trial, women who attended a family medicine colposcopy clinic received one of four treatments, 800 mg of oral ibuprofen, 20% topical benzocaine, both, or placebos. Using visual analog scales, women recorded their pain after speculum placement, endocervical curettage (ECC), and cervical biopsy. Participants were 18–55 years old, spoke English, and were not taking other pain or psychotropic medications. Demographic and historical information was collected from each participant. Results Ninety-nine subjects participated. Twenty-five received oral ibuprofen and topical benzocaine (median pain scores on a 10-point scale for speculum placement, ECC, and biopsy were 0.75, 3.00, and 3.38, respectively), 24 received oral placebo and topical benzocaine (1.00, 3.75, and 2.63), 24 received oral ibuprofen and topical placebo (0.63, 3.75, and 2.25), and 26 received oral and topical placebos (0.75, 3.50, and 3.00). There were no statistically significant differences in patient visual analogue pain scale scores across the four groups (statistical power, ECC = 0.74, cervical biopsy = 0.62). Younger women and women who had pain with speculum placement were more likely to have increased pain during ECC. Increased pain during biopsy was associated with history of severe dysmenorrhea but no other demographic or historical factors. Women overall reported ECC and biopsy to be mildly painful, with median scores of 3.5 for ECC and 2.75 for biopsy on a 10-point scale. The range in pain scores was large, with some women reporting severe pain (for ECC minimum = 0.25, maximum = 10.0; biopsy: minimum = 0.0, maximum = 9.0). Conclusion Colposcopy is perceived as somewhat painful, but oral ibuprofen and topical benzocaine gel, alone or together, provided no advantage over placebo in decreasing colposcopy pain.

Community patterns of transdermal nicotine use and provider counseling

OBJECTIVES: To examine bow transdermal nicotine is prescribed and used in the general population, and to identity variables associated with successful smoking cessation in patch users.DESIGN: Retrospective cohort survey.SETTING: A random sample of 70 pharmacies in King County, Washington, were asked to participate. Of those, 33 pharmacies ran computer searches of prescriptions for any nicotine patch dispensed between July 1 and December 31,1992. A total of 1,087 individuals receiving patches were identified.PATIENTS: At least eight months after the nicotine patches were purchased, 972 subjects received questionnaires by mail from the participating pharmacies. The survey was completed by 433 (45.2%) subjects.MAIN RESULTS: Eighty percent of the respondents requested patches from a provider, 81% of whom were primary care physicians. Ninety-six percent used the patch, 45% smoked while using the patch, and 37% reported having quit smoking. Smoking cessation was associated with daily patch application (odds ratio [OR] 1.6,95% confidence interval [CI] 1.2–2.2), abstinence during patch use (OR 7.7, 95% CI 4.8–12.5), and a longer duration of patch use (p=0.001). A score reflecting counseling intensity by the provider was associated with abstinence while using patches and smoking cessation (x2 for trend=0.01 and 0.04, respectively).CONCLUSIONS: Most nicotine patch users request treatment from a primary care physician, suggesting motivation to quit. Almost half continue to smoke while using the patch, a behavior that appears related to a lower level of counseling and an inability to quit. Increasing counseling may positively impact nicotine-patch-assisted smoking cessation in the general population.

Zomepirac, Interstitial Nephritis, and Renal Failure

Excerpt To the editor: We report severe renal failure and nephrotic syndrome in three patients taking zomepirac sodium, a nonsteroidal anti-inflammatory drug. A 46-year-old woman who had been takin...

Treatment Of Atopic Dermatitis With Antihistamines: Lessons From A Single-Patient, Randomized Clinical Trial

Background: Single-patient randomized clinical trials (RCTs) can be utilized to maintain methodologic precision in the analysis of treatment effect in individual patients. We describe the results of a single-patient RCT in a patient with atopic dermatitis and review practical considerations regarding the use of antihistamines. Methods: Using double-blind, crossover techniques, the patient was randomly allocated to four 2-week treatment periods with the following regimens: chlorpheniramine, 8 mg twice daily; chlorpheniramine, 12 mg twice daily; terfenadine, 120 mg twice daily; and placebo (phase 1). The drug that produced superior results from phase 1 (chlorpheniramine, 8 mg) was subsequently compared with astemizole, 10 mg/d, during phase 2, consisting of four 4-week, double-blind, crossover trial periods with random allocation of study drugs. Daily symptom scores, as well as end of treatment period summary impressions by patient and investigator, were analyzed. Results: In both phases, chlorpheniramine produced the most noticeable positive therapeutic effect on the patient’s mild but most disturbing symptoms (pruritus and eye irritation) associated with atopic dermatitis. Drowsiness was reported with chlorpheniramine. Tolerance to this side effect, however, developed quickly. Conclusions: A single-patient RCT with different antihistamines in a patient with chronic atopic dermatitis was a useful tool in achieving a favorable balance among efficacy, toxicity, and cost of therapy.