[What is clinical relevance?] / Was ist klinische Relevanz?

BACKGROUND: Statistical significance is not the same as clinical relevance. Clinical relevance exists only when the patient feels a clear improvement by a measure. METHOD: In six doctors' offices, 40 patients were interviewed on the outcome of which they would find an improvement that they could call satisfying. It can be assumed that these directly expressed patient data are an average of improvement. RESULTS: About 600 responses showed that the frequency of clinically relevant improvements was very different. The data varied depending on the severity of restriction, the level oft he initial values and the measure. On average 41% reported a clinically relevant improvement with a variation of 24% and 57% (95% confidence interval). The largest improvements according to the bootstrap method were e. g. hospitalization (59%) and sleep disturbances (56%), the slightest improvements were e.g. mobility (33%) and intellectual activity (24%). CONCLUSION: Clinically relevant improvements, regardless of age, for most severely impaired patients, were associated with only minor changes, while those with mild limitations rated only normal options as satisfactory.

[Serendipities in medicine]. / Serendipities in der Medizin.

Coincidences accompany our lives. This paper shows to which extent serendipity plays a role in important discoveries and developments in medicine. These include, among others, Mendel's laws, the determination of the human chromosome number, the discovery of DNA by Watson and Crick, the PAP test, or the discovery of X-rays and radioactivity. But also and especially in pharmacology, there are many examples of serendipity. Some go closely with serendipities in the discovery of bacteriology.

The rationale of a longer life span and nuclear medicine.

Routine nuclear cardiology examinations indicate heart rate, cardiac rhythm, the height of cardiac pulse and respiration rhythm. It would be of interest to study whether these data, especially if the same tests are repeated, can indicate patients' well being in the future and perhaps patients' life span, other factors being equal. Related old theories and suggestions are mentioned. Furthermore, some drugs like I-f channel antagonists and stress tests testing cardiac reserves could support such a study.

Instructions and methods for clinical testing of drugs for the treatment of atrial fibrillation.

Instructions and methods for clinical testing of drugs for the treatment of atrial fibrillation are the subject of this paper. Certain criteria must be considered to demonstrate the effectiveness and benefit/risk ratio of pharmacotherapy of atrial fibrillation for the planning and performance of clinical trials. These criteria include the various forms of atrial fibrillation, the corresponding definition of endpoints, the appropriate study design, randomization and blinding, and also the adequate dose, investigation methods, sample size determination, analysis, and early termination. Only the consideration of these criteria may allow an appropriate treatment decision.

[Instructions and methods for clinical trials of medicinal products for the treatment of chronic systolic heart failure]. / Anleitung und Methodik zur klinischen Prüfung von Arzneimitteln für die Therapie der chronischen systolischen Herzinsuffizienz.

To prove the efficacy of drugs in patients with chronic systolic heart failure, taking into consideration certain criteria is necessary for the planning and performance of the clinical investigation of medicinal products. For the different stages and the collective of patients those criteria include the definition of the corresponding endpoints, adequate study design, appropriate randomisation, blinding, the choice of an appropriate dose, valid methods of examination, the correct sample size estimation and analysis. If these criteria will b e used, the besttherapy for the different stages can be ascertained.

Drug development parameters for functional imaging in neurosciences.

State-of-the-art radioactive drug development has become a helpful tool in new functional imaging technologies in neurosciences. Drug development programs are evaluated in terms of effective biodistribution, costs and time. This article details the existing drug development parameters for neuroimaging and highlights some examples, as in Parkinson's disease, alcoholic neuritis and psychotic diseases, showing the benefit and the potential of using new functional neuroimaging technologies for specific studies of the central nervous system.

[Design and method of clinical trials of drugs used in the therapy of stable peripheral arterial occlusive disease]. / Anleitung und Methodik zur klinischen Prüfung von Arzneimitteln für die Therapie der stabilen peripheren arteriellen Verschlusskrankheit.

To prove the efficacy of the treatment of atherosclerotic stable peripheral arterial occlusive disease with drugs certain criteria are to be considered in the context of the design and performance of clinical trials. These criteria refer to the design of the study, randomisation, blinding, inclusion and exclusion criteria, definition of outcomes, methods of examination, sample size estimation, and evaluation of the results. If these criteria and conditions are not taken into consideration, false positive and negative results can arise. In the present study, the criteria to prove the efficacy of vasoactive substances in the treatment of atherosclerotic peripheral occlusive arterial diseases are presented.

[Magnesium, acute myocardial infarction and reperfusion injury].

Coronary artery disease (CAD) ranks top with respect to morbidity and mortality in humans. Development of high-tech diagnostic and therapeutic strategies has greatly improved the prognosis of CAD and acute myocardial infarction (AMI) over the past decade. Data from experimental and clinical research have provided important information on the role of magnesium in CAD and AMI. In relation to duration and severity of CAD, an adrenaline induced systemic stress arises, which provokes enhanced magnesium requirements, because magnesium is the co-factor in ATP dependent myocardial metabolism. The success of pharmacological or mechanical intervention in AMI can be compromised by reperfusion injury, which is probably caused by myocardial calcium accumulation. Since magnesium blocks myocardial calcium influx, reperfusion injury might be diminished or even prevented by magnesium application. Thus, the common procedure of invasive cardiac intervention and intravenous magnesium administration before reperfusion could become the gold standard in treatment of AMI.

Are beta-blockers efficacious as first-line therapy for hypertension in the elderly?

The aim of this paper is to assess antihypertensive efficacy of b-blockers and their effects on cardiovascular morbidity and mortality and all-cause mortality in elderly patients with hypertension. Randomized placebo-controlled trials, trials with untreated controls, and trials comparing antihypertensive drugs were selected from the literature. The relative risk reduction of primary endpoints and 95% confidence intervals were calculated. There were six trials in which elderly patients were treated with beta-blockers for hypertension (three trials were placebo-controlled, one trial had untreated controls, and two trials compared antihypertensive drugs). There was no study with monotherapy of beta-blockers. In combination with diuretics, beta-blockers were superior to placebo and untreated controls in preventing cardiovascular events, especially strokes, but there was no superiority of beta-blockers to angiotensin-converting enzyme inhibitors and calcium antagonists in preventing cardiovascular morbidity and mortality and total mortality in elderly patients with hypertension. Beta-blockers are only efficacious in combination with diuretics in preventing cardiovascular morbidity and mortality in elderly patients with hypertension.

[Guidelines and methods for clinical investigation of drugs for treatment of stable angina pectoris]. / Anleitungen und Methodik zur klinischen Prüfung von Arzneimitteln für die Therapie der stabilen Angina pectoris.

To prove the antianginal efficacy of drugs in patients with stable angina pectoris the notice of certain criteria is necessary for the planning and performance for the clinical investigation of medicinal products. They consist of the study design, the randomization, blinding, inclusion and exclusion criteria, definition of endpoints, the performance of the study, the doses and dosing scheme, the methods of investigation, the sample size estimation and the evaluation of the results. If there will be not paid enough attention to these criteria and conditions false positive but also false negative results can arise. The criteria necessary for proving the antianginal efficacy in patients with stable angina pectoris will be presented.