Background-Sirolimus reduces acute rejection in renal transplant recipients and prevents vasculopathy in nonhuman primates and in-stent restenosis in humans. Its effects on rejection and transplant vasculopathy in human heart transplant recipients are unknown. Methods and Results-In a randomized, open-label study, sirolimus was compared with azathioprine in combination with cyclosporine and steroids administered from the time of cardiac transplantation. We report 6-month rejection rates (primary end point), 12-month safety and efficacy data, and 6-and 24-month graft vasculopathy data in 136 cardiac allograft recipients randomly assigned (2:1) to sirolimus (nϭ92) or azathioprine (nϭ44). At 6 months, the proportion of patients with grade 3a or greater acute rejection was 32.4% for sirolimus 3 mg/d (Pϭ0.027), 32.8% for sirolimus 5 mg/d (Pϭ0.013), and 56.8% for azathioprine. Patient survival at 12 months was comparable among groups. Intracoronary ultrasound at 6 weeks, 6 months, and 2 years demonstrated highly significant progression of transplant vasculopathy in azathioprine-treated patients. At 6 months, a highly significant absence of progression in intimal plus medial proliferation and significant protection against luminal encroachment was evident in sirolimus-treated patients, and these effects were sustained at 2 years. Conclusions-Sirolimus use from the time of transplantation approximately halved the number of patients experiencing acute rejection. The measurable development of transplant vasculopathy at 6 months and 2 years in patients receiving azathioprine was not observed in patients receiving sirolimus.

Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

A safe and effective form of pain relief would be an advantage in the prehospital treatment of patients experiencing extreme pain. Although used by many emergency medical services, 50% nitrous oxide (an inhaled analgesic known to have good pain relief properties) is not widely used by volunteer and semiprofessional organisations. This review aimed to determine whether 50% nitrous oxide is safe for use by first responders who are not trained as emergency medical technicians. A thorough search of the literature identified 12 randomised controlled trials investigating the use of 50% nitrous oxide (as compared with placebo or conventional analgesic regimens) in a range of conditions. The outcomes analysed for this review were: adverse events, recovery time, and need for additional medication. None of the studies compared the treatments in the prehospital setting; children were well represented. Adverse effects were rare and significant adverse outcomes such as hypotension and oxygen desaturation could not be attributed to nitrous oxide. Compared with patients receiving conventional analgesia, those receiving 50% nitrous oxide did not require additional medication any more frequently and had a faster recovery from sedative effects. The low incidence of significant adverse events from 50% nitrous oxide suggests that this agent could be used safely by lay responders.

The Challenges Rural and remote Australians and New Zealanders have a higher rate of adverse outcomes due to acute myocardial infarction, driven by many factors. The prevalence of cardiovascular disease (CVD) is also higher in regional and remote populations, and people with known CVD have increased morbidity and mortality from coronavirus disease 2019 (COVID-19). In addition, COVID-19 is associated with serious cardiac manifestations, potentially placing additional demand on limited regional services at a time of diminished visiting metropolitan support with restricted travel. Inter-hospital transfer is currently challenging as receiving centres enact pandemic protocols, creating potential delays, and cardiovascular resources are diverted to increasing intensive care unit (ICU) and emergency department (ED) capacity. Regional and rural centres have limited staff resources, placing cardiac services at risk in the event of staff infection or quarantine during the pandemic.

BackgroundDelay in treatment and/or failure to provide reperfusion in ST-segment elevation myocardial infarction (STEMI) impacts on morbidity and mortality. This occurs more often outside metropolitan areas yet the reasons for this are unclear. This study aimed to describe factors associated with missed diagnosis of acute myocardial infarction (MAMI) in a rural and regional setting.MethodsUsing a retrospective cohort design, patients who presented with STEMI and failed to receive reperfusion therapy within four hours were identified as MAMI. Univariate analyses were undertaken to identify differences in clinical characteristics between the treated STEMI group and the MAMI group. Mortality, 30-day readmission rates and length of hospital stay are reported.ResultsOf 100 patients identified as MAMI (70 male, 30 female), 24 died in hospital. Demographics and time from symptom onset were similar in the treated STEMI and MAMI groups. Of the MAMI patients who died, rural hospitals recorded the highest inpatient mortality (69.6% p = 0.008). MAMI patients compared to treated STEMI patients had higher 30 day readmission (31.6% vs 3.3%, p = 0.001) and longer length of stay (5.5 vs 4.3 days p = 0.029). Inaccurate identification of STEMI on electrocardiogram (72%) and diagnostic uncertainty (65%) were associated with MAMI. The Glasgow algorithm to identify STEMI was utilised on 57% of occasions, with 93% accuracy.ConclusionMortality following MAMI is high particularly in smaller rural hospitals. MAMI results in increased length of stay and readmission rate. Electrocardiogram interpretation and diagnostic accuracy require improvement to determine if this improves patient outcomes.