Symposium: New horizons in cost containment curricula.
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Biomedical subjects
Publications and source records attributed to W B Applegate.
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A method was devised to offer a group of internists a system by which to analyze their practices, allowing them to identify areas where a change in practice habits might be beneficial. More than 3000 encounters between patients and internists in an eight-man group were analyzed for a number of variables. Significant differences existed between physicians as to the percentage of encounters that were physician-initiated rather than patient-initiated. Disposition of the encounters also varied significantly. The effect that the recycling of patients has on productivity, cost, and use of hospital facilities is discussed. In addition to geographic and specialty maldistribution, the maldistribution of physician time is a significant barrier to meeting the demands for medical care.
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BACKGROUND: National guidelines recommend consideration of step down or withdrawal of medication in patients with well-controlled hypertension, but knowledge of factors that predict or mediate success in achieving this goal is limited. OBJECTIVE: To identify patient characteristics associated with success in controlling blood pressure (BP) after withdrawal of antihypertensive medication. DESIGN: The Trial of Nonpharmacologic Interventions in the Elderly tested whether lifestyle interventions designed to promote weight loss or a reduced intake of sodium, alone or in combination, provided satisfactory BP control among elderly patients (aged 60-80 years) with hypertension after withdrawal from antihypertensive drug therapy. Participants were observed for 15 to 36 months after attempted drug withdrawal. MAIN OUTCOME MEASURES: Trial end points were defined by (1) a sustained BP of 150/90 mm Hg or higher, (2) a clinical cardiovascular event, or (3) a decision by participants or their personal physicians to resume BP medication. RESULTS: Proportional hazards regression analyses indicated that the hazard (+/- SE) of experiencing an end point among persons assigned to active interventions was 75% +/- 9% (weight loss), 68% +/- 7% (sodium reduction), and 55% +/- 7% (combined weight loss/sodium reduction) that of the hazard for those assigned to usual care. Lower baseline systolic BP (P < .001), fewer years since diagnosis of hypertension (P < .001), fewer years of antihypertensive treatment (P < .001), and no history of cardiovascular disease (P = .01) were important predictors of maintaining successful nonpharmacological BP control throughout follow-up, based on logistic regression analysis. Age, ethnicity, baseline level of physical activity baseline weight, medication class, smoking status, and alcohol intake were not statistically significant predictors. During follow-up, the extent of weight loss (P = .001) and urinary sodium excretion (P = .04) were associated with a reduction in the risk of trial end points in a graded fashion. CONCLUSIONS: Withdrawal from antihypertensive medication is most likely to be successful in patients with well-controlled hypertension who have been recently (within 5 years) diagnosed or treated, and who adhere to life-style interventions involving weight loss and sodium reduction. More than 80% of these patients may have success in medication withdrawal for longer than 1 year.
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CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.
OBJECTIVE: To examine the effect of moderate coffee consumption on blood pressure over a prolonged period of time. Previous work in this area has used primarily purified caffeine. DESIGN: A prospective, randomized, crossover clinical trial. SETTING: A hypertension specialty outpatient clinic at the University of Tennessee, Memphis. PATIENTS: Healthy, young, white men who were moderate coffee drinkers (less than 6 cups/day) were recruited. Twenty-four subjects were randomized and 21 (average age 35.5 years) completed the trial. INTERVENTIONS: Subjects were randomized to one of two groups: Group A drank three or more cups of coffee/day for two months, then crossed over to abstaining from coffee for two months; group B abstained from coffee first, then crossed over to drinking coffee. Only filter-brewed coffee was used. Subjects were seen at monthly intervals for blood pressure measurements. MEASUREMENTS AND MAIN RESULTS: The average coffee consumption was 3.6 cups/day during the coffee-drinking phases. There was no difference between the coffee-drinking phase and the abstention phase in either systolic blood pressure (110.1 mmHg vs. 108.0 mmHg, respectively; 95% CI of difference -7.3, 2.5) or diastolic blood pressure (67.2 mmHg vs. 69.6 mmHg, respectively; 95% CI of difference -2.2, 6.4). CONCLUSIONS: Moderate daily consumption of coffee does not elevate blood pressure.
BACKGROUND: Repeated administration of psychometric instruments frequently results in a higher score on retesting, the so-called training effect. Yet, a training effect has been poorly considered in longitudinal studies of cognitive changes in older persons. METHODS: We investigated the presence, magnitude and potential adjustments for training effect in the older participants of the Systolic Hypertension in the Elderly Program (SHEP). SHEP evaluated the cognitive status effects of a diuretic-based treatment of isolated systolic hypertension versus placebo. Changes in the short Comprehensive Assessment and Referral Evaluation (short-CARE) questionnaire score, from baseline through 4 years of follow-up, were assessed in 4,718 participants. In this study, we used two regression techniques to adjust data for the training effect. RESULTS: In both study groups, a training effect was evident as a progressive improvement in the short-CARE score throughout year 1. Thereafter, cognitive scores tended to deteriorate, more in the placebo than in the active treatment group (p = 0.055). When follow-up scores were adjusted based upon baseline data, the difference between the study groups reached statistical significance (p = 0.019), but the apparent overall trend towards deterioration in cognitive score was no longer observed. Adjustment of baseline data preserved this apparent temporal course, but did not improve the discrimination between the two study groups (p = 0.165). CONCLUSIONS: In SHEP, repeated cognitive assessments were likely biased by a training effect which could be only partially corrected by statistical techniques. Studies of changes in the cognitive status of older persons should be designed appropriately to estimate and minimize the consequences of a training effect in follow-up data.
STUDY OBJECTIVES: To evaluate whether variability in S-metoprolol kinetics and lymphocyte beta 2-receptor-mediated cyclic adenosine monophosphate (cAMP) accumulation is related to the variability in antihypertensive response to metoprolol of black men. DESIGN: Prospective, unblinded study. SETTING: University-based preventive medicine clinic. PATIENTS: Twelve hypertensive black men. MEASUREMENTS AND MAIN RESULTS: Ambulatory blood pressure was measured over 24 hours before and after metoprolol administration. Ex vivo responsiveness of lymphocyte beta 2-receptors to isoproterenol was established for each subject before initiating metoprolol therapy. Plasma samples were collected over 12 hours at the conclusion of the study, from which metoprolol enantiomer concentrations were determined by chiral high-performance liquid chromatography, and kinetic values were calculated. The 24-hour ambulatory blood pressure responses to metoprolol were highly variable, with systolic blood pressure responses ranging from -13 to +33 mm Hg and diastolic blood pressure responses ranging from -15 to +15 mm Hg. There was a significant relationship between the metoprolol-induced change in systolic blood pressure and the maximum lymphocyte beta 2-receptor cAMP production (y = 0.47x-7.79; r2 = 0.49, p < 0.05) such that those with the highest maximum cAMP production had the greatest blood pressure increases during metoprolol therapy. There was no relationship between S-metoprolol concentration and blood pressure response. Mean oral clearance values for S- and R-metoprolol were 1320 and 2346 ml/minute, respectively. CONCLUSIONS: Lymphocyte beta 2-receptor data suggest that individuals most responsive to beta-receptor stimulation may be at greatest risk of blood pressure elevation during beta 2-receptor blockade. The metoprolol enantiomer kinetic data are markedly different from previously published data and may represent racial differences in pharmacokinetics.
STUDY OBJECTIVES: To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide (DTZ SR-HCTZ) with that of monotherapy with DTZ SR, HCTZ, or placebo in the treatment of essential hypertension; and to determine whether the addition of a diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial with a 6-week treatment phase. SETTING: Private and university-based clinics. PATIENTS AND PARTICIPANTS: Subjects of either sex, ranging in age from 18-70 years, with a diagnosis of stable essential hypertension made from two consecutive weekly mean supine diastolic blood pressure (DBP) readings of 95 mm Hg or above to 110 mm Hg or less that varied 7 mm Hg or less after 4-6 weeks in the baseline phase. Of the patients enrolled, 298 met the inclusion criteria. INTERVENTIONS: Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg, or placebo was administered twice daily. MEASUREMENTS AND MAIN RESULTS: Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly (p < 0.005) more than either single agent. The combination also lowered DBP and SBP significantly more than either monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintained efficacy, whereas the antihypertensive effects of HCTZ dissipated after 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo. CONCLUSIONS: The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent.
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