Prioritisation of clinical trials ensures that the research conducted meets the needs of stakeholders, makes the best use of resources and avoids duplication. The aim of this review was to identify ...and critically appraise approaches to research prioritisation applicable to clinical trials, to inform best practice guidelines for clinical trial networks and funders.
A scoping review of English-language published literature and research organisation websites (January 2000 to January 2020) was undertaken to identify primary studies, approaches and criteria for research prioritisation. Data were extracted and tabulated, and a narrative synthesis was employed.
Seventy-eight primary studies and 18 websites were included. The majority of research prioritisation occurred in oncology and neurology disciplines. The main reasons for prioritisation were to address a knowledge gap (51 of 78 studies 65%) and to define patient-important topics (28 studies, 35%). In addition, research organisations prioritised in order to support their institution's mission, invest strategically, and identify best return on investment. Fifty-seven of 78 (73%) studies used interpretative prioritisation approaches (including Delphi surveys, James Lind Alliance and consensus workshops); six studies used quantitative approaches (8%) such as prospective payback or value of information (VOI) analyses; and 14 studies used blended approaches (18%) such as nominal group technique and Child Health Nutritional Research Initiative. Main criteria for prioritisation included relevance, appropriateness, significance, feasibility and cost-effectiveness.
Current research prioritisation approaches for groups conducting and funding clinical trials are largely interpretative. There is an opportunity to improve the transparency of prioritisation through the inclusion of quantitative approaches.
Background: Mechanical ventilation is mandatory in patients undergoing general anaesthesia for major surgery. Tidal volumes higher than 10 mL/kg of predicted body weight have been advocated for ...intraoperative ventilation, but recent evidence suggests that low tidal volumes may benefit surgical patients. To date, the impact of low tidal volume compared with conventional tidal volume during surgery has only been assessed in clinical trials that also combine different levels of positive end-expiratory pressure (PEEP) in each arm. We aimed to assess the impact of low tidal volume compared with conventional tidal volume during general anaesthesia for surgery on the incidence of postoperative respiratory complications in adult patients receiving moderate levels of PEEP.
Study design and methods: Single-centre, two-arm, randomised clinical trial. In total, 1240 adult patients older than 40 years scheduled for at least 2 hours of surgery under general anaesthesia and routinely monitored with an arterial line were included. Patients were ventilated intraoperatively with a moderate level of PEEP (5 cmH2O) and randomly assigned to tidal volume of 6 mL/kg predicted body weight (low tidal volume) or 10 mL/kg predicted body weight (conventional tidal volume in Australia).
Main outcome measure: The primary outcome is the occurrence of postoperative respiratory complications, recorded as a composite endpoint of adverse respiratory events during the first 7 postoperative days.
Results and conclusions: This is the first well powered study comparing the effect of low tidal volume ventilation versus high tidal volume ventilation during surgery on the incidence of postoperative respiratory complications in adult patients receiving moderate levels of PEEP.
Coronary artery aneurysms are seen in 1.5-5% of patients presenting for coronary angiography, but giant aneurysms, defined as being greater than 2 cm in diameter, are rare. Given the paucity of cases ...and limited experience in diagnosis and management of the disease, each case is a learning tool in itself.
We report the rare case of a 78-year-old Caucasian man who presented to a peripheral emergency department with chest pain and was subsequently found to have a giant right coronary artery aneurysm. Following initial investigation and treatment he was referred to our hospital for definitive management.
The case described illustrates one of the varied presentations and subsequent management of an ill-defined and heterogeneous disease process. Given the limited experience with giant aneurysms in the coronary circulation, this case provides valuable insight into the clinical presentation of the disease and gives an example of the management of the most recent such case at our hospital.
Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the ...international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials.
We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity.
We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined.
These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.
Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised ...Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.
We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures.
A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use.
We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.
Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these ...measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials.
Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process.
A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien–Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien–Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus.
Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien–Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.
Summary
Theoretical modelling predicts that the concentrating effect of nitrous oxide (N2O) uptake on alveolar oxygenation is a persisting phenomenon at typical levels of ventilation – perfusion ...(V/Q) inhomogeneity under anaesthesia. We sought clinical confirmation of this in 20 anaesthetised patients. Arterial oxygen pressure (Pao2) was measured after a minimum of 30 min of relaxant general anaesthesia with an inspired oxygen (FIo2) of 30%. Patients were randomly allocated to two groups. The intervention group had N2O introduced following baseline blood gas measurements, and the control group continued breathing an identical FIo2 in nitrogen (N2). The primary outcome variable was change in Pao2. Mean (SD) in Pao2 was increased by 1.80 (1.80) kPa after receiving a mean of 47.5 min of N2O compared with baseline conditions breathing O2/N2 (p = 0.01). This change was significantly greater (p = 0.03) than that in the control group: + 0.09 (1.37) kPa, p = 0.83 and confirms the presence of significant persisting concentrating and second gas effects.
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