Crossover studies with continuous variables: power analysis.

The crossover design is a sensitive means of determining the efficacy of new drugs because it eliminates between-subject variability. However, if the response in the first period carries on into the second (carryover effect) or if time factors cannot be kept constant in a lengthy crossover (time effects), its statistical power may be jeopardized. This may be equally true if a negative correlation exists between treatment responses.

Daytime-selective antihypertensive activity of celiprolol.

Day-activity rhythms of heart rate and blood pressure are thought to be mediated mainly through the sympathetic nervous system and may have greater amplitudes in patients with hypertension owing to increased daytime and largely normal nighttime values. Drug-induced nighttime hypotension in patients with chronic hypertension has been associated with the precipitation of cardiac failure and a fall in cerebral flow. The authors examined the effects of a single dose and of a 4-week treatment with different classes of antihypertensive drugs on ambulatory blood pressure (ABP) in 10 patients with mild hypertension.

Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN).

The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed.

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin.

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms.

Low molecular weight heparins better than unfractionated heparin in unstable coronary artery disease? Unstable angina pectoris/non-Q wave infarction a partly outpatient clinic condition?

Important theoretical advantages of low molecular weight heparins compared to standard heparin include better inactivation of the coagulation mechanism as well as better bioavailability and pharmacokinetic properties. In patients with unstable angina pectoris/non-Q wave infarction these advantages may translate into a reduced combined risk of death, myocardial infarction, and recurrent angina as well as a reduced risk of bleeding, although data so far are limited. Data on quality of life, cost analysis, and patient compliance are missing.

An alternative analysis for crossover studies that accounts for between-group disparities in drug response.

Background: In crossover clinical trials comparing completely different treatments, patients tend to fall into different populations: those who respond better to treatment 1 and those who respond better to treatment 2. The correlation between treatment response in such trials is negative. The current ANCOVA analysis for crossover studies does not allow for correlations being negative, and is therefore not adequate for testing in this kind of trials.

Erythema multiforme and persistent erythema as early cutaneous manifestations of Lyme disease.

We report two cases of borreliosis (Lyme disease) with unusual cutaneous manifestations, erythema multiforme, and persistent erythema. The lesions in both of our patients had distinctive histopathologic features. To our knowledge, this is the first report of erythema multiforme and persistent erythema as early cutaneous manifestations of Lyme disease.

Depression and myocardial infarction. Implications for medical prognosis and options for treatment.

Depression and myocardial infarction (MI) are closely related. Various pathophysiological mechanisms could link depression to MI, and the different pharmacological and nonpharmacological treatment modalities that could be used have both advantages and disadvantages. Unlike tricyclic antidepressants, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) lack arrhythmogenic effects.

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol.

Hypertensive patients may be adversely affected by complications and other concomitant processes such as anxiety, sedation, and drug side effects. It has been suggested that some recently developed antihypertensive agents do not affect quality of life by causing adverse effects. We compared the effects of two antihypertensive drugs on quality of life: atenolol, a standard cardioselective beta-blocker, and celiprolol, one of a new class of selective beta-blockers with vasodilatory properties.

Nitrate-Induced Headache in Patients with Stable Angina Pectoris: Beneficial Effect of Starting on a Low Dosage.

BACKGROUND: Nitrates, although important for the management of angina pectoris, cause significant headache in many patients. METHODS: In a randomized, double-blind crossover study, 89 patients with stable angina pectoris were used to compare two different dosage strategies of isosorbide-5-mononitrate (5-ISMN). Patients were randomized to either 60 mg 5-ISMN once daily (o.

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol.

Background: The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of the prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life.

Object: We compared the effect on quality of life of a standard cardioselective beta-blocker atenolol to the effect of celiprolol as a representative of a new class of selective beta-blockers with vasodilatory properties.

Crossover trials with a binary response: a powerful method despite the carryover effect.

The two-period crossover trial has the evident advantage that, by use of within-patient comparisons, the usual large between-patient variability is not used as a measure to compare treatments. A prerequisite, however, is that the order of the treatments does not substantially influence the outcome of the treatment. Crossover studies with a binary response (such as yes/no or present/absent), although widely used for initial screening of new compounds, have not previously been studied for such order effects.

Clinical trials: relevance of correlation between treatment responses.

Objective: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities.

Methods: Using a hypothetical example and several published studies we examine the influence of correlation levels between treatment modalities on the sensitivity of testing.

Clinical trials: relevance of correlation between treatment modalities.

Background: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities.

Methods: Using a model, a simple test and several published studies we studied the influence of correlation levels on the statistical power of clinical trials.

Clinical trials: specific problems associated with the use of a placebo-control group.

In order to test hypotheses prospectively with hard data and against placebo, the scientific method of clinical trials has been developed. The present paper focuses on specific problems associated with the use of a placebo control group. (a) The placebo highlights the ethical dilemma that a controlled clinical trial can place us in.

Oscillatory potentials in early diabetic retinopathy.

To study the oscillatory potentials in early diabetic retinopathy the authors developed a new power measurement based on the fast Fourier transform. Three groups totalling 46 patients were examined, varying from nonvisible to preproliferative diabetic retinopathy. The oscillatory potentials expressed in microwatts were measured under scotopic and photopic conditions.

Measuring oscillatory potential during the course of an arterial occlusion: a method based on Fourier analysis.

Recently we developed a quantitative method of measuring the Oscillatory Potentials (OP's) for a clinical study in diabetic patients. Several problems were experienced in interpreting the results obtained with digital filtering. The main dilemma was the separation of the first OP from the a-wave, since their frequencies are within the same range.