International trials and national practice: A questionnaire survey of current physician practice in the treatment of acute myocardial infarction

To establish current national clinical practice in the care of patients with acute myocardial infarction (AMI), a questionnaire survey of 50 consultant physicians currently working in the Republic of Ireland was carried out. There were 45 (90%) respondants. 32/45 (71%) give thrombolysis in CCU only; 13/45 (29%) give thrombolysis in casualty also. Streptokinase (Stk) is the first choice thrombolytic agent for the majority. 14/45 (31%) use tPA for anterior AMI in patients under 60 years. Angiotensin converting enzyme (ACE) inhibitors are given by 34/45 (76%) to patients with evidence of left ventricular dysfunction. ACE inhibitors are neither used routinely nor are they prescribed in the first three days after the AMI by the majority of the physicians surveyed. Serum magnesium is checked routinely by 5/45 (11%) and intravenous magnesium is given routinely by 5/45 (11%). The percentage of AMI patients considered for angiography varied from 10–50%. Despite reports from randomised, controlled trials showing reduced mortality in patients given tPA (versus Stk), routine early ACE inhibition and intravenous magnesium post-AMI, most clinicians in Ireland use streptokinase, selective late ACE inhibition and no magnesium. The reasons for the dichotomy between the favourable results of randomised clinical trials and routine practice are speculative.     

“Watching time tick by…”: Decision making for Duchenne muscular dystrophy trials

ObjectiveThis interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials.MethodsData from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis.ResultsEleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit–risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain.Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers.ConclusionsThe majority of parents described undertaking benefit–risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm.     

Embedding clinical interventions into observational studies

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed.     

Safety of biologic treatments in solid organ transplant recipients: A systematic review

BackgroundThe development of biological treatments has transformed the management of a broad spectrum of autoimmune/inflammatory diseases. However, little is known about their use in solid-organ transplant recipients. This study aimed to evaluate complications occurring with biologic treatments in solid-organ transplant recipients.MethodsA systematic review of the literature was performed in the Medline, Embase and Cochrane databases, up to 01/10/2020, to identify published case reports or series reporting the use of biologic treatments in solid organ transplant recipients with chronic inflammatory diseases. We collected data on patient characteristics and reported complications.ResultsIn total, 57 articles were included, totalling 187 patients (141 liver, 42 kidney, 3 heart, and 1 liver-kidney transplant recipients). Inflammatory bowel diseases represented the most common indication for biologic treatment initiation (80.7%), followed by rheumatic diseases (7.5%), hereditary periodic fever syndromes (5.9%) and psoriasis (4.8%). Anti-TNFα were mainly used (77.5%; mainly monoclonal antibodies (70%) compared to soluble receptor etanercept (7.5%)), followed by the anti-α4β7 integrin, vedolizumab (27.3%) and the anti-IL-1R, anakinra (6.9%). Median treatment duration was 12 months. Infections occurred in 54 patients (28.9%) through 88 recorded events. No therapeutic or demographic factors were associated with occurrence of infection. Sixteen patients (8.6%) developed malignancies, and acute graft rejections occurred in 5 patients (2.7%). Among the 187 patients, 9 deaths were reported (4.8%).ConclusionsThis review assembles the largest number of published reports regarding the use of biological treatments in solid organ transplant recipients, providing data about their safety. Further comparative studies are needed to assess the safety of biological treatments in transplanted patients.     

Has the excess risk of acute myocardial infarction in rheumatoid arthritis relative to the general population declined? A population study of trends over time

ObjectiveTo evaluate secular trend in ten-year risk of incident acute myocardial infarction (AMI) in incident rheumatoid arthritis (RA) relative to the general population.MethodsWe conducted a retrospective study of population-based incident RA cohorts with RA incidence from 1997 to 2004 in British Columbia, Canada, with matched general population comparators, using administrative health data. RA and their matched cohorts were divided according to the year of RA incidence, defined according to the first RA visit of the case definition. Incident AMI was defined as the first event occurring within 10 years from RA incidence. Secular trend was assessed using delayed-entry Cox models with an interaction term between the year of RA onset and indicator of RA vs. general population. Linear, quadratic and spline functions of year of RA onset were compared to assess possibility of nonlinear trends. The model with the lowest AIC was selected to interpret the results. Sensitivity analyses were conducted to account for potential effect of unmeasured (e.g. smoking) or partially measured (e.g. obesity) confounders in administrative data, on the interaction term.ResultsOverall, 23,237 RA and 46,474 general population controls experienced 1,133 and 1,606 incident AMIs, respectively. A linear Cox model was selected as the model best fitting the AMI events. Overall, RA patients were found to have a 21% higher risk of AMI than the matched general population controls [1.21 (1.10, 1.32); p < 0.001]. A significant linear decline in risk of AMI was observed in RA patients [0.94 (95% CI 0.91, 0.97) p = <0.0001], and in the general population [0.93 (0.91, 0.95); p = <0.0001]. The change in AMI risk over time did not differ in RA compared to the general population [p-value of interaction term=0.49]. Our results remained similar after adjusting for the potential effect of confounders on the interaction term, and no difference in the change in risk of AMI over time was observed between RA and the general population.ConclusionOur findings suggest a decline in 10-year risk of AMI in RA, and in the general population. The decline in the risk of AMI over time did not differ between RA and the general population, such that the excess risk of AMI in RA relative to the general population, has remained the same.