The BRASH syndrome, a synergistic arrhythmia phenomenon.

BRASH syndrome is a relatively novel clinical entity with profound bradycardia secondary to simultaneous metabolic derangement and drug toxicity. The syndrome is a clinical pentad of bradycardia, acute kidney injury, use of atrioventricular nodal blocking agents, shock, and hyperkalemia. It is widely underrecognized with selectively few reports, mainly in the elderly population. We present a 43-year-old woman on two oral atrioventricular blocking agents who presented with 1 week of increasing lethargy with rapid deterioration into cardiac arrest with subsequent shock postresuscitation. She was found to have hyperkalemia, metabolic acidosis, and acute kidney injury on arrival. Her initial electrocardiogram was remarkable for sinus arrest and junctional bradycardia. She was treated with a temporary pacemaker, renal replacement therapy, and potassium-lowering agents, with subsequent improvement resulting in conversion to normal sinus rhythm.

Butane-induced acute global myocardial ischemia without coronary artery pathology.

The case report describes a case of acute myocardial ischemia precipitated by propane butane inhalation. The dependency of this substance around the world is still moderate but is increasing due to the easy availability of the substance and the facility with which the effects can be concealed. The toxicity of the substance is significant; affecting the heart, the brain and the liver. The most common outcome is sudden death. In this article, we describe a survivor after an episode of acute poisoning and his interesting cardiac pathology.

Bladder cancer risk from the perspective of genetic polymorphisms in the carcinogen metabolizing enzymes.

Urinary bladder cancer is a socially significant healthcare problem. A diverse array of aromatic and heterocyclic amines, derived from the chemical and transport industry, diet, and cigarette smoke are considered carcinogens for the bladder. To exert their carcinogenic effect and to initiate the carcinogenic response, the arylamines require a metabolic activation by the host enzymes to chemically reactive compounds. The aim of this article was to review the latest and basic research developments on the role of the polymorphisms in the carcinogen metabolizing enzymes N-acetyltransferase (NAT), Glutathione S-transferases (GST), and Soluble sulfotransferases (SULT), with emphasis on the susceptibility to urinary bladder cancer. A PubMed search was conducted to identify original and review articles containing information about these polymophic variants in different populations and according to their prevalence in bladder cancer patients. We noticed that some genotypes were found to be predisposing and some protective for bladder cancer development. The NAT2 slow genotype, together with GSTM1 null genotype facilitated the development of bladder cancer in almost all ethnic groups. The 213His allele of the SULT1A1 gene which is associated with lower enzyme activity and decreased mutagen activation was reported to protect from bladder cancer in almost all studies.

Pharmacotherapeutic recommendations for application of target oncological drug therapies for treatment of breast cancer in Bulgaria - therapeutic efficacy and cost effectiveness.

PURPOSE: The purpose of this study was to determine the direct costs of targeted cancer therapies for the treatment of breast cancer, calculating the effectiveness of the additional costs (ICER) and the cost of life years gained (LYG), using data from randomized clinical trials cited in the summary of product characteristics (SPC) of medicinal products approved for use under the centralized procedure. METHODS: Data from the SPC and clinical trials was analyzed. ICER and LYG of the medicinal therapies were compared using data from Phase III clinical trials cited in the Summary of product characteristics. The perspective of the payer was adopted. RESULTS: The SPCs of five drugs were analyzed. Targeted therapies were compared to placebo or to best supportive care (BSC) in some of them, while in others monoclonal antibodies (mAbs) and tyrosine kinase inhibitors were compared to existing drug therapies. Cost-effectiveness of each therapy was calculated. The value of ICER was between 56 470 Bulgarian Levs/LYG and 879 480 Bulgarian Levs/LYG. CONCLUSION: The current pharmacotherapeutic recommendations for targeted therapies for the treatment of breast cancer are based on evidence of therapeutic efficacy and cost effectiveness. Their application in therapeutic practice in Bulgaria is necessary to ensure patient access to effective therapies within the limited public funds.

Practical tool to assess reliability of web-based medicines information.

AIM: Information disseminated by medicines information systems is not always easy to apply. Nowadays internet provides access to enormous volume and range of health information that was previously inaccessible both for medical specialists and consumers. The aim of this study is to assess internet as a source of drug and health related information and to create test methodology to evaluate the top 10 visited health-related web-sites in Bulgaria. METHODS: Using existing scientific methodologies for evaluation of web sources, a new algorithm of three-step approach consisting of score-card validation of the drug-related information in the 10 most visited Bulgarian web-sites was created. RESULTS: In many cases the drug information in the internet sites contained errors and discrepancies. Some of the published materials were not validated; they were out-of-date and could cause confusion for consumers. CONCLUSION: The quality of the online health information is a cause for considerable information noise and threat to patients' safety and rational drug use. There is a need of monitoring the drugs information available online in order to prevent patient misinformation and confusion that could lead to medication errors and abuse.

Physicians' knowledge and attitude towards adverse event reporting system and result to intervention--randomized nested trial among Bulgarian physicians.

AIM: To identify the factors that influence physicians' under-reporting in Bulgaria and their attitude towards adverse event reporting system and to estimate the role of self-education by providing educational materials. METHODS: A randomized nested trial among physicians-general practitioners and specialists in Bulgaria was conducted by a validated questionnaire in order to evaluate their knowledge and attitude towards adverse event reporting system. One month after the intervention the participants were re-visited and were asked to answer the same questions again in order to estimate the change in their knowledge and attitude towards pharmacovigilance system and to obtain their evaluation for the materials provided. RESULTS: The response rate was 91. Fifty seven (46.3%) physicians were not familiar with the pharmacovigilance system. The most common reason for non-reporting adverse drug reactions (ADRs) was uncertainty concerning the relationship between the suspected drug and ADRs, the ADRs were already known and the fact that the physician was not aware where they should report. Although 103 (83.7%) respondents in the entry survey and by 102 (82.9%) of those participating in the exit survey consider ADRs reporting as their obligation (p more than 0.05), only 50 (40.7%) and 31 (25.2%), respectively answered that they had ever reported ADRs; 109 (88.6%) of the surveyed physicians assessed the provided educational materials as useful for them. CONCLUSION: The physicians in Bulgaria have poor knowledge for the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude towards ADRs reporting system. National drug regulatory authority should play a more active role in improving physicians' adherence to the ADRs reporting systems and the developed educational pack can be used in nationwide campaign.

Study of obligations defined in agreements between parties involved in clinical trials of medicinal products in Bulgaria.

AIM: To analyse and assess the legislative and contractual obligations of the parties involved in the conduct of clinical trials, with identification of the needs for comprehensive contractual regulation of their rights and responsibilities. METHODS: This survey has been carried out by means of review, analysis of comprehensiveness, comparative legislative analysis and assessment of compliance with the legislation of sample of investigator and site agreements governing the process of conducting clinical trials. RESULTS: The survey comprises analyses of contractual relations between the sponsor of the study and the investigator, and between the sponsor of the study and the trial site, respectively, relevant to clinical trials which are actually conducted in Bulgaria at the time of and following the survey. Comparative method based on pre-defined structured indices was employed to outline the major variances in the volume of responsibilities and obligations of the said parties to the clinical trial, as regulated by the investigator and site agreements. The analysis of comprehensiveness showed evident omissions in the regulation of relations and interactions between the parties to the agreements. CONCLUSION: The detailed contractual regulation providing for the statutory obligations and responsibilities of the parties involved in the conduct of clinical trials is a good guarantee for proper understanding of the obligations of each party and for compliance with their relevant responsibilities in view of protecting the rights of the participants in the clinical trials - patients or healthy volunteers.