41 research outputs found
Environmental-mechanistic modelling of the impact of global change on human zoonotic disease emergence: A case study of Lassa fever
1. Human infectious diseases are a significant threat to global human health and economies (e.g., Ebola, SARs), with the majority of infectious diseases having an animal source (zoonotic). Despite their importance, the lack of a quantitative predictive framework hampers our understanding of how spill-overs of zoonotic infectious diseases into the human population will be impacted by global environmental stressors. 2. Here, we create an environmental-mechanistic model for understanding the impact of global change on the probability of zoonotic disease reservoir host-human spill-over events. As a case study, we focus on Lassa fever virus (LAS). We firstly quantify the spatial determinants of LAS outbreaks, including the phylogeographic distribution of its reservoir host Natal multimammate rat (Mastomys natalensis) (LAS host). Secondly, we use these determinants to inform our environmental-mechanistic model to estimate present day LAS spill-over events and the predicted impact of climate change, human population growth, and land use by 2070. 3. We find phylogeographic evidence to suggest that LAS is confined to only one clade of LAS host (Western clade Mastomys natalensis), and that the probability of its occurrence was a major determinant of the spatial variation in LAS historical outbreaks (69.8%), along with human population density (20.4%). Our estimates for present day LAS spill-over events from our environmental-mechanistic model were consistent with observed patterns, and we predict an increase in events per year by 2070 from 195,125 to 406,725 within the LAS endemic western African region. Of the component drivers, climate change and human population growth are predicted to have the largest effects by increasing landscape suitability for the host and human-host contact rates, while land use change has only a weak impact on the number of future events. 4. LAS spill-over events did not respond uniformly to global environmental stressors, and we suggest that understanding the impact of global change on zoonotic infectious disease emergence requires an understanding of how reservoir host species respond to environmental change. Our environmental-mechanistic modelling methodology provides a novel generalizable framework to understand the impact of global change on the spill-over of zoonotic diseases
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
Double Jeopardy : Acute myocardial infarction complicated by cardiogenic shock and contrast mediated anaphylactoid reaction
A 63 year-old woman who developed a severe anaphylactoidreaction to iodinated contrast in the setting of emergent percutaneous intervention(PCI) for a large anterior wall ST elevation myocardial infarction (STEMI) resulting incardiogenic shock followed by cardiopulmonary arrest necessitating placement of the patient on the arterio-venous extra corporeal membrane oxygenation (ECMO). While anaphylactoid/anaphylactic reactions to radiocontrast agents have been well documentedin literature, the development of an anaphylactoid reaction secondary to radiocontrastmedia in the setting of an ST elevation myocardial infarction (STEMI) and resultingin cardiogenic shock has never been reported. We discuss naphylactoidreactions to contrast media occurs by non-immunologic (i.e. non IgE ) mechanisms. Premedication does not abate or prevent all types of iodinated contrastmediated reactions. However, studies have shown that premedication is effective fora cutaneous reaction to iodinated contrast media (ICM). Due to the relative excellentsafety profiles of the premedication, physicians should continue to use them prior to asuspected ICM reaction
Kidney Function Trajectories and Right Heart Failure Following LVAD Implantation
Background Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after postâLVAD RHF are uncertain, so we investigated this. Methods and Results We identified individuals who received primary continuousâflow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of baseline kidney function with RHF risk at the different time points, were assessed. We identified 8076 LVAD recipients who met inclusion criteria. Incident RHF was present at 1âmonth in 26.4%. There were 4850 individuals with followâup at 3âmonths, with incident RHF in 4.2%. Kidney function trajectories differed from preâLVAD implantation to 1âmonth followâup by RHF category, with those developing persistent RHF having no improvement in baseline kidney function. For trajectories before the 3âmonth RHF ascertainment time, the shape was similar for those with and without RHF, with lower estimated glomerular filtration rate levels among those who developed RHF. Baseline estimated glomerular filtration rate levels below the normal range were associated with higher risk of RHF at 1 and 3âmonths. Conclusions In LVAD recipients, preimplantation kidney function and subsequent kidney function trajectories differed substantially by RHF at 1 and 3âmonths postimplantation, even after adjustment for several confounders. This may demonstrate bidirectional associations between kidney function and right ventricular function in LVAD recipients