Michael E. Ernst

Dehydroepiandrosterone replacement in women with adrenal insufficiency.

BACKGROUND: The physiologic role of dehydroepiandrosterone in humans is still unclear. Adrenal insufficiency leads to a deficiency of dehydroepiandrosterone; we therefore, investigated the effects of dehydroepiandrosterone replacement, in patients with adrenal insufficiency. METHODS: In a double-blind study, 24 women with adrenal insufficiency received in random order 50 mg of dehydroepiandrosterone orally each morning for four months and placebo daily for four months, with a one-month washout period. We measured serum steroid hormones, insulin-like growth factor I, lipids, and sex hormone-binding globulin, and we evaluated well-being and sexuality with the use of validated psychological questionnaires and visual-analogue scales, respectively. The women were assessed before treatment, after one and four months of treatment with dehydroepiandrosterone, after one and four months of placebo, and one month after the end of the second treatment period. RESULTS: Treatment with dehydroepiandrosterone raised the initially low serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and testosterone into the normal range; serum concentrations of sex hormone-binding globulin, total cholesterol, and high-density lipoprotein cholesterol decreased significantly. Dehydroepiandrosterone significantly improved overall well-being as well as scores for depression and anxiety. For the global severity index, the mean (+/-SD) change from base line was -0.18+/-0.29 after four months of dehydroepiandrosterone therapy, as compared with 0.03+/-0.29 after four months of placebo (P=0.02). As compared with placebo, dehydroepiandrosterone significantly increased the frequency of sexual thoughts (P=0.006), sexual interest (P=0.002), and satisfaction with both mental and physical aspects of sexuality (P=0.009 and P=0.02, respectively). CONCLUSIONS: Dehydroepiandrosterone improves well-being and sexuality in women with adrenal insufficiency.

Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure

Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order–drug–time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = −12.4±1.8 mm Hg versus −7.4±1.7 mm Hg; P=0.054; nighttime mean = −13.5±1.9 mm Hg versus −6.4±1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (−15.7±2.2 mm Hg versus −4.5±2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (−17.1±3.7 versus −10.8±3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.

Hydrochlorothiazide Versus Chlorthalidone Evidence Supporting Their Interchangeability

Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure-lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is approximately 1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known.

Influence of Test Conditions on Antifungal Time-Kill Curve Results: Proposal for Standardized Methods

ABSTRACT This study was designed to examine the effects of antifungal carryover, agitation, and starting inoculum on the results of time-kill tests conducted with various Candida species. Two isolates each of Candida albicans, Candida tropicalis, and Candida glabrata were utilized. Test antifungal agents included fluconazole, amphotericin B, and LY303366. Time-kill tests were conducted in RPMI 1640 medium buffered with morpholinepropanesulfonic acid (MOPS) to a pH of 7.0 and incubated at 35°C. Prior to testing, the existence of antifungal carryover was evaluated at antifungal concentrations ranging from 1× to 16× MIC by four plating methods: direct plating of 10, 30, and 100 μl of test suspension and filtration of 30 μl of test suspension through a 0.45-μm-pore-size filter. Time-kill curves were performed with each isolate at drug concentrations equal to 2× MIC, using a starting inoculum of approximately 105 CFU/ml, and incubated with or without agitation. Last, inoculum experiments were conducted over three ranges of starting inocula: 5 × 102 to 1 × 104, >1 × 104 to 1 × 106, and >1 × 106 to 1 × 108 CFU/ml. Significant antifungal carryover (>25% reduction in CFU/milliliter from the control value) was observed with amphotericin B and fluconazole; however, carryover was eliminated with filtration. Agitation did not appreciably affect results. The starting inoculum did not significantly affect the activity of fluconazole or amphotericin B; however, the activity of LY303366 may be influenced by the starting inoculum. Before antifungal time-kill curve methods are routinely employed by investigators, methodology should be scrutinized and standardized procedures should be developed.

Use of Diuretics in Patients with Hypertension

This review focuses on thiazides, the diuretics most often indicated for long-term therapy for hypertension. Thiazide diuretics reduce blood pressure when administered as monotherapy; thiazides also enhance the efficacy of other antihypertensive agents and can reduce hypertension-related morbidity and mortality.

Assessment of Patients' Perceptions and Beliefs Regarding Herbal Therapies

We evaluated the demographics and beliefs regarding safety and efficacy of herbal therapy among individuals in Iowa and assessed the willingness to discuss the use of these products with health care providers. We distributed 1300 surveys to two random samples: patients attending eight clinics, and residents of the state (mailing). Data were categorized according to herb use and compared between users and nonusers. The response rate was 61% (794 people), with 41.6% of respondents reporting herb use. They were predominately white women and were likely to have had education beyond high school (p<0.05). Their use of prescription drugs was high (p<0.05). Although users rated safety and efficacy of herbs higher than nonusers (p<0.05), both groups believed that health care providers should be aware of use and would provide this information.

Antioxidants, Supplements, and Parkinson's Disease

Objective: To review the use of antioxidants and other supplements for the prevention and treatment of Parkinsons disease (PD). Data Sources: Biomedical literature was accessed through MEDLINE (1996–June 2005); key search terms included Parkinsons disease, coenzyme Q10 (CoQ10), antioxidants, supplements, and glutathione. Pertinent references cited in those articles were also evaluated for inclusion in this review. Data Synthesis: Three main antioxidants or supplements have been studied for use in the prevention or treatment of PD: tocopherol, CoQ10, and glutathione. These agents have been studied because of their potential to alter the course of 2 common theories of PD pathogenesis: free radical generation and mitochondrial complex-1 deficiency. The literature search revealed 3 large clinical studies of tocopherol (2 observational, 1 prospective randomized), 4 trials of CoQ10, and 1 study of glutathione. With the exception of the large observational studies with tocopherol and one study of CoQ10 that enrolled 80 patients, each of the other studies retrieved included fewer than 30 patients and were conducted for 3 months or less. Antioxident supplementation, in particular tocopherol, did not appear to alter the course of PD. However, in 2 of the studies of CoQ10 and in the study of glutathione, a small but statistically significant improvement in PD symptoms was observed. Conclusions: At present, antioxidants and supplements appear to have a limited role in the prevention or treatment of PD. Of those reviewed here, CoQ10 appears to provide some minor treatment benefits. More study is necessary to determine whether CoQ10 has a significant role as primary or adjunctive therapy in PD.

Implementation of a Community Pharmacy-Based Influenza Vaccination Program

OBJECTIVE To increase accessibility of influenza vaccine in a rural community by establishing a community pharmacy-based influenza vaccination program. SETTING An independent pharmacy in a rural eastern Iowa community of 5,000 people. PRACTICE DESCRIPTION Protocols for identification and screening of patients, administration of vaccine, and treatment of emergencies were developed by the pharmacist and approved by the county health department medical director. Administration of vaccine began October 15, 1996, and was completed on December 6, 1996. PRACTICE INNOVATION Patients were prospectively and retrospectively identified to receive the vaccination. Informed consent was obtained. Vaccine was administered by the pharmacist after screening for contraindications and counseling the patient. Weekly vaccination records were forwarded to the collaborating physician to update patient charts. MAIN OUTCOME MEASUREMENTS To determine whether accessibility of influenza vaccine in the community was increased through pharmacist administration, the proportion of patients immunized in the pharmacy who were not vaccinated the previous year was determined. RESULTS The pharmacist administered 343 doses of vaccine. Two-thirds of the immunized patients (67.9%) reported also being immunized the previous year. These patients were generally older (65 years of age +/- 13) than the previously nonimmunized patients (54 years of age +/- 16). However, 60.8% of the patients not immunized the previous year reported either they would not have gone elsewhere for the immunization (45.3%), or were unsure (25.5%). CONCLUSION The data collected suggest that pharmacist administration of influenza vaccination in a rural community pharmacy increases access and, possibly, immunization rates. This may be especially true among high-risk younger adults who are often overlooked and would not normally have received the immunization.

Antifungal dynamics of LY 303366, an investigational echinocandin B analog, against Candida ssp.

Two isolates each of Candida albicans, Candida tropicalis, and Candida glabrata were selected for time-kill curve testing against LY 303366 at concentrations ranging from 0.125 x MIC to 16 x MIC. RPMI 1640 buffered morpholinepropanesulfonic acid (MOPS) was utilized as growth medium. Samples were obtained at predetermined time points over 24 hours and streaked for colony count determination. Against C. albicans (one strain) and C. glabrata isolates, LY 303366 exhibited fungicidal (> or = three log10 reduction in CFU) activity. In contrast, fungistatic activity was observed with LY 303366 against C. albicans (one strain) and C. tropicalis isolates at all of the multiples of the MIC tested. With the exception of one C. glabrata strain, the rate and extent of activity against test isolates was not enhanced with concentrations exceeding the MIC. Our data indicate that maximal antifungal activity with LY 303366 may be achieved by optimizing the time of fungal exposure to the drug. Additionally, these data suggest that use of the current interpretive endpoint for MICs in RPMI may underestimate the antifungal activity of LY 303366. Thus, the MIC endpoint may need to be re-evaluated, or perhaps an alternative media, such as antibiotic medium #3, should be utilized for determination of LY 303366 MICs.

Renewed Interest in Chlorthalidone: Evidence From the Veterans Health Administration

J Clin Hypertens (Greenwich).