Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Preventing Adverse Drug Reactions After Hospital Discharge (PADR-AD): Protocol for a randomised-controlled trial in older people

BackgroundAdverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs.ObjectivesThis trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12–24 months following hospital discharge.MethodsThe study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression.SummaryIt is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.     

FDA“治疗等效性评价供企业用指导原则”（草案）介绍

美国食品药品管理局（FDA）于2022年7月发布了"治疗等效性评价供企业用指导原则"（草案）。该指导原则阐明了FDA治疗等效性的标准以及治疗等效性编码系统，目的是准确评价仿制药与参比制剂的治疗等效性并通过治疗等效性代码，在"橙皮书"中迅速检索到治疗等效的仿制药。而中国目前尚无类似的指导原则，详细介绍FDA该指导原则主要内容，期望对中国加强仿制药的治疗等效性评价和加速完善和实施符合国情的治疗等效性编码系统有所帮助。     

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography

BackgroundInflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.MethodsCORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.ResultsThirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55–68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were ?74.9, ?74.2, and ?71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75–1.22, p ?= ?0.71), 1.31 (95% CI: 0.96–1.78, p ?= ?0.09), and 0.98 (95% CI: 0.78–1.22, p ?= ?0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44–1.07), 0.85 (0.56–1.29), and 0.57 (0.41–0.80), respectively.ConclusionsIn patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.     

Delayed haemolytic transfusion reaction due to Kidd antibodies

A delayed haemolytic transfusion reaction (DHTR) encompasses a positive direct antiglobulin test (DAT) developed anytime between 24 hours to 28 days after cessation of transfusion, a positive eluate or a newly identified alloantibody in the plasma or serum along with features of haemolysis in the patient. Routinely, it is expected that with the transfusion of one unit of packed red cells in a patient of average height and weight, the haemoglobin level and hematocrit increase by 1 g/dL and 3% respectively. However, in a patient with DHTR, an inadequate rise of post-transfusion haemoglobin (< 1 g/dL) or rapid fall in haemoglobin back to pre-transfusion levels is observed. Kidd antibodies are particularly known to cause DHTR, maybe alone or in unison with other antibodies. Detection of these alloantibodies is consequential in providing good transfusion support to these patients. These events may be difficult to detect as they may present as varied clinical features or immunological nuisances. In this case series, we have presented three cases of DHTR with special emphasis on their clinical presentations, immunohaematological evaluations, laboratory parameters and the role of proper transfusion support in these patients to avoid further complications.