Clinical trial managers play a vital role in the design and conduct of clinical trials in the UK. There is a current recruitment and retention crisis for this specialist role due to a complex set of ...factors, most likely to have come to a head due to the COVID-19 pandemic. Academic clinical trial units and departments are struggling to recruit trial managers to vacant positions, and multiple influences are affecting the retention of this highly skilled workforce. Without tackling this issue, we face major challenges in the delivery on the Department of Health and Social Care's Future of UK Clinical Research Delivery implementation plan. This article, led by a leading network of and for UK Trial Managers, presents some of the issues and ways in which national stakeholders may be able to address this.
Summary Background Our aim was to investigate whether a nurse-coordinated multidisciplinary, family-based preventive cardiology programme could improve standards of preventive care in routine ...clinical practice. Methods In a matched, cluster-randomised, controlled trial in eight European countries, six pairs of hospitals and six pairs of general practices were assigned to an intervention programme (INT) or usual care (UC) for patients with coronary heart disease or those at high risk of developing cardiovascular disease. The primary endpoints—measured at 1 year—were family-based lifestyle change; management of blood pressure, lipids, and blood glucose to target concentrations; and prescription of cardioprotective drugs. Analysis was by intention to treat. The trial is registered as ISRCTN 71715857. Findings 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC, respectively. In patients with coronary heart disease who smoked in the month before the event, 136 (58%) in the INT and 154 (47%) in the UC groups did not smoke 1 year afterwards (difference in change 10·4%, 95% CI −0·3 to 21·2, p=0·06). Reduced consumption of saturated fat (196 55% vs 168 40%; 17·3%, 6·4 to 28·2, p=0·009), and increased consumption of fruit and vegetables (680 72% vs 349 35%; 37·3%, 18·1 to 56·5, p=0·004), and oily fish (156 17% vs 81 8%; 8·9%, 0·3 to 17·5, p=0·04) at 1 year were greatest in the INT group. High-risk individuals and partners showed changes only for fruit and vegetables (p=0·005). Blood-pressure target of less than 140/90 mm Hg was attained by both coronary (615 65% vs 547 55%; 10·4%, 0·6 to 20·2, p=0·04) and high-risk (586 58% vs 407 41%; 16·9%, 2·0 to 31·8, p=0·03) patients in the INT groups. Achievement of total cholesterol of less than 5 mmol/L did not differ between groups, but in high-risk patients the difference in change from baseline to 1 year was 12·7% (2·4 to 23·0, p=0·02) in favour of INT. In the hospital group, prescriptions for statins were higher in the INT group (810 86% vs 794 80%; 6·0%, −0·5 to 11·5, p=0·04). In general practices in the intervention groups, angiotensin-converting enzyme inhibitors (297 29% INT vs 196 20% UC; 8·5%, 1·8 to 15·2, p=0·02) and statins (381 37% INT vs 232 22% UC; 14·6%, 2·5 to 26·7, p=0·03) were more frequently prescribed. Interpretation To achieve the potential for cardiovascular prevention, we need local preventive cardiology programmes adapted to individual countries, which are accessible by all hospitals and general practices caring for coronary and high-risk patients. Funding European Society of Cardiology through an unconditional educational grant from AstraZeneca.
The Anatomical Society has developed a series of learning outcomes in consultation with nursing educators delivering anatomical content to undergraduate (preregistration) nursing students. A Delphi ...panel methodology was adopted to select experts within the field that would recommend core anatomical content in undergraduate nursing programmes throughout the UK. Using the Anatomical Society's Core Gross Anatomy Syllabus for Medical Students as a foundation, a modified Delphi technique was used to develop discipline‐specific outcomes to nursing graduates. The Delphi panel consisted of 48 individuals (n = 48) with a minimum of 3 years' experience teaching anatomy to nursing students, representing a broad spectrum of UK Higher Education Institutions. The output from this study was 64 nursing specific learning outcomes in anatomy that are applicable to all undergraduate (preregistration) programmes in the UK. The new core anatomy syllabus for Undergraduate Nursing offers a basic anatomical framework upon which nurse educators, clinical mentors and nursing students can underpin their clinical practice and knowledge. The learning outcomes presented may be used to develop anatomy teaching within an integrated nursing curriculum.
Lecithotrophic, or non-feeding, marine invertebrate larvae generally have shorter pelagic larval durations (PLDs) than planktotrophic larvae. However, non-feeding larvae of scleractinian corals have ...PLDs far exceeding those of feeding larvae of other organisms and predictions of PLD based on energy reserves and metabolic rates, raising questions about how such longevity is achieved. Here, we measured temporal changes in metabolic rates and total lipid content of non-feeding larvae of four species of reef corals to determine whether changes in energy utilization through time contribute to extended larval durations. The temporal dynamics of both metabolic rates and lipid content were highly consistent among species. Prior to fertilization, metabolic rates were low (2.73–8.63 nmol O
2
larva
−1
h
−1
) before rapidly increasing to a peak during embryogenesis and early development 1–2 days after spawning. Metabolic rates remained high until shortly after larvae first became competent to metamorphose and then declined by up to two orders of magnitude to levels at or below rates seen in unfertilized eggs over the following week. Larvae remained in this state of low metabolic activity for up to 2 months. Consistent with temporal patterns in metabolic rates, depletion of lipids was extremely rapid during early development and then slowed dramatically from 1 week onward. Despite the very low metabolic rates in these species, larvae continued to swim and retained competence for at least 2 months. The capacity of non-feeding coral larvae to enter a state of low metabolism soon after becoming competent to metamorphose significantly extends dispersal potential, thereby accruing advantages typically associated with planktotrophy, notably enhanced population connectivity.
The pattern of atrial fibrillation (AF) occurrence-paroxysmal, persistent, or permanent-is associated with progressive stages of atrial dysfunction and structural changes and may therefore be ...associated with progressively higher stroke risk. However, previous studies have not consistently shown AF pattern to predict stroke but have been hampered by methodological shortcomings of low power, variable event ascertainment, and variable anticoagulant use.
We analysed the rates of stroke and systemic embolism in 6563 aspirin-treated patients with AF from the ACTIVE-A/AVERROES databases. There was thorough searching for events and adjudication. Multivariable analyses were performed with the adjustment for known risk factors for stroke. Mean age of patients with paroxysmal, persistent, and permanent AF was 69.0 ± 9.9, 68.6 ± 10.2, and 71.9 ± 9.8 years (P < 0.001). The CHA2DS2-VASc score was similar in patients with paroxysmal and persistent AF (3.1 ± 1.4), but was higher in patients with permanent AF (3.6 ± 1.5, P < 0.001). Yearly ischaemic stroke rates were 2.1, 3.0, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjusted hazard ratio of 1.83 (P < 0.001) for permanent vs. paroxysmal and 1.44 (P = 0.02) for persistent vs. paroxysmal. Multivariable analysis identified age ≥ 75 year, sex, history of stroke or TIA, and AF pattern as independent predictors of stroke, with AF pattern being the second strongest predictor after prior stroke or TIA.
In a large population of non-anticoagulated AF patients, pattern of AF was a strong independent predictor of stroke risk and may be helpful to assess the risk/benefit for anticoagulant therapy, especially in lower risk patients.
Cognitive dysfunction is the most common form of neurologic impairment after subarachnoid hemorrhage (SAH).
To evaluate the impact of global and domain-specific cognitive impairment on functional ...recovery and quality of life (QOL) after SAH.
One hundred thirteen patients (mean age 49 years; 68% women) were evaluated 3 months after SAH. Three simple tests of global mental status and neuropsychological tests to assess seven specific cognitive domains were administered. Four aspects of outcome (global handicap, disability, emotional status, and QOL) were compared between cognitively impaired and unimpaired patients with analysis-of-covariance models controlling for age, race/ethnicity, and education. Multiple linear regression was used to evaluate the relative contribution of global and domain-specific cognitive status for predicting concurrent modified Rankin Scale (mRS) and Sickness Impact Profile (SIP) scores.
Impairment of global mental status on the Telephone Interview of Cognitive Status (TICS) was associated with poor performance in all seven cognitive domains (all p < 0.0005) and was the only cognitive measure associated with poor recovery in all four aspects of outcome (all p < or = 0.005). Cognitive impairment in four specific domains was also associated with functional disability or reduced QOL. After accounting for global cognitive impairment with the TICS, however, neuropsychological testing did not contribute additional predictive value for concurrent mRS or SIP total scores.
Cognitive impairment impacts broadly on functional status, emotional health, and QOL after SAH. The TICS may be a useful alternative to more detailed neuropsychological testing for detecting clinically relevant global cognitive impairment after SAH.
Accurate detection and estimation of true exposure-outcome associations is important in aetiological analysis; when there are multiple potential exposure variables of interest, methods for detecting ...the subset of variables most likely to have true associations with the outcome of interest are required. Case-cohort studies often collect data on a large number of variables which have not been measured in the entire cohort (e.g. panels of biomarkers). There is a lack of guidance on methods for variable selection in case-cohort studies.
We describe and explore the application of three variable selection methods to data from a case-cohort study. These are: (i) selecting variables based on their level of significance in univariable (i.e. one-at-a-time) Prentice-weighted Cox regression models; (ii) stepwise selection applied to Prentice-weighted Cox regression; and (iii) a two-step method which applies a Bayesian variable selection algorithm to obtain posterior probabilities of selection for each variable using multivariable logistic regression followed by effect estimation using Prentice-weighted Cox regression.
Across nine different simulation scenarios, the two-step method demonstrated higher sensitivity and lower false discovery rate than the one-at-a-time and stepwise methods. In an application of the methods to data from the EPIC-InterAct case-cohort study, the two-step method identified an additional two fatty acids as being associated with incident type 2 diabetes, compared with the one-at-a-time and stepwise methods.
The two-step method enables more powerful and accurate detection of exposure-outcome associations in case-cohort studies. An R package is available to enable researchers to apply this method.
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