rifampin and Myocardial-Infarction

A December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9-11-month MDR-TB treatment regimens.. Health system costs of delivering a 9-month injectable-containing regimen and a 9-month all-oral bedaquiline-containing regimen will be collected in Ethiopia, India, Moldova and Uganda, using 'bottom-up' and 'top-down' costing approaches. Patient costs will be collected using questionnaires that have been developed based on the STOP-TB questionnaire. The primary objective of the study is to estimate the cost utility of the two regimens, from a health system perspective. Secondary objectives include estimating the cost utility from a societal perspective as well as evaluating the cost-effectiveness of the regimens, using both health system and societal perspectives. The effect measure for the cost-utility analysis will be the quality-adjusted life years (QALY), while the effect measure for the cost-effectiveness analysis will be the efficacy outcome from the clinical trial.. The study has been evaluated and approved by the Ethics Advisory Group of the. ISRCTN18148631.

Topics: Antitubercular Agents; Cost-Benefit Analysis; Diarylquinolines; Ethiopia; Humans; India; Moldova; Myocardial Infarction; Rifampin; Tuberculosis, Multidrug-Resistant; Uganda

Topics: Aged, 80 and over; Diabetes Mellitus, Type 2; Doxycycline; Echocardiography; Electroencephalography; Embolism; Endocarditis; Fever; Fluorodeoxyglucose F18; Heart Valve Prosthesis; Humans; Hypertension; Magnetic Resonance Imaging; Male; Myocardial Infarction; Positron Emission Tomography Computed Tomography; Rifampin; Treatment Outcome

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Coronary Restenosis; Drainage; Drug Therapy, Combination; Emergencies; Humans; Male; Middle Aged; Myocardial Infarction; Pericardial Effusion; Pericarditis; Prosthesis-Related Infections; Rifampin; Staphylococcal Infections; Stents; Teicoplanin

Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure. This report outlines our efforts to identify a compound suitable for once daily, oral administration with low drug-drug interaction potential starting from NHE1 inhibitor sabiporide. Substitution of a piperidine for the piperazine of sabiporide followed by replacement of the pyrrole moiety and subsequent optimization to improve potency and eliminate off-target activities resulted in the identification of N-[4-(1-acetyl-piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine (60). Pharmacological evaluation of 60 revealed a remarkable ability to prevent ischemic damage in an ex vivo model of ischemia reperfusion injury in isolated rat hearts.

Topics: Animals; Benzamides; Biological Availability; Blood Platelets; Cell Line; Cell Membrane Permeability; Cell Size; Cytochrome P-450 Enzyme Inhibitors; Dogs; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Guanidines; Humans; Male; Membranes, Artificial; Microsomes, Liver; Models, Molecular; Myocardial Infarction; Myocardial Reperfusion Injury; Permeability; Protein Isoforms; Rats; Rats, Sprague-Dawley; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers; Structure-Activity Relationship

Drug-induced thrombocytopenia is a challenging diagnosis in the clinical practice because of the many drugs or alternative causes that may be implicated. Exact identification of such drug(s) is required to guide future management and avoid re-exposure. We describe two cases of isolated thrombocytopenia in which cytometric analysis, a readily available technique, allowed the identification of the causative drug in the context of complex therapies (rifampicin and abciximab causing late onset thrombocytopenia).

Topics: Abciximab; Angioplasty, Balloon, Coronary; Anti-Bacterial Agents; Antibodies, Monoclonal; Anticoagulants; Autoantibodies; Ciprofloxacin; Drug Therapy, Combination; Flow Cytometry; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Male; Middle Aged; Myocardial Infarction; Osteomyelitis; Purpura, Thrombocytopenic, Idiopathic; Rifampin