Drug tolerability: How much ambiguity can be tolerated? A systematic review of the assessment of tolerability in clinical studies.

Aims: Drug tolerability refers to the degree to which drugs' overt adverse effects can be tolerated by patients. The tolerability profile is of comparative importance to its efficacy and safety, as it largely determines adherence to treatment and ultimately treatment success or failure. However, the term is frequently used imprecisely, and it is unclear if tolerability is limited to subjective patient-reported symptoms or also covers certain objective signs and findings.

Monoclonal Antibodies as Neurological Therapeutics.

Over the last 30 years the role of monoclonal antibodies in therapeutics has increased enormously, revolutionizing treatment in most medical specialties, including neurology. Monoclonal antibodies are key therapeutic agents for several neurological conditions with diverse pathophysiological mechanisms, including multiple sclerosis, migraines and neuromuscular disease. In addition, a great number of monoclonal antibodies against several targets are being investigated for many more neurological diseases, which reflects our advances in understanding the pathogenesis of these diseases.

Drug rechallenge following drug-induced liver injury.

Unlabelled: Drug-induced hepatocellular injury is identified internationally by alanine aminotransferase (ALT) levels equal to or exceeding 5× the upper limit of normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decrease by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT level of 3-5× ULN or greater.

Earlier identification of risks: cumulative probability analysis of time to safety alerts for therapeutic monoclonal antibodies.

Objective: Previous analysis of US FDA Medwatch safety alerts for monoclonal antibody therapeutics demonstrated that premarketing clinical trials can predict more than half of safety concerns. We expanded this analysis to assess whether the predictable alerts are detected sooner than the unpredictable alerts.

Methods: Times to alert were compared using Mann-Whitney test, Kolmogorov-Smirnov test, and using curves displaying cumulative frequencies of alerts over time.

Intentional rechallenge: does the benefit outweigh the risk?

Rechallenge is defined as the readministration of a medication suspected of being a possible cause of an adverse reaction and which has been discontinued as result. It may be unintentional when the appearance of a reaction was initially not attributed to the medication. A rechallenge may be intentional when a prescriber decides that the benefit of rechallenge will outweigh its risk.

Atrio-ventricular block as the first presentation of disseminated Lyme disease.

A 36 year old male patient presented to emergency cardiology department because of fatigability. ECG revealed high grade II atrio-ventricular block and bradycardia of 31 beats/min. An erythema increasing in size to up to 7-8 cm in diameter appeared a month earlier and spontaneously resolved within 10 days.

[Clinical trials of statins and fibrates --a meta-analysis].

Introduction: Several clinical trials of hypolipidemics showed a decrease in mortality by 30-40%, while others showed detrimental or no effects. The question remains: which trial should be the basis of clinical decision making in the choice of hypolipidemic therapy?

Material And Methods: Meta-analysis is a method for combining research results of several studies. Effects of statins and fibrates with respect to placebo, were assessed by systematic literature review and meta-analysis.