Preparing allied health students for placement: a contrast of learning modalities for foundational skill development.

BACKGROUND: With increasing pressure on placement capacity for allied health students, a need for novel and creative means through which students can develop foundational skills and prepare for practice-based learning opportunities has arisen. This study aimed to explore the experiences of domestic and international first-year students completing pre-clinical preparation programs, contrasting between in-person simulation and online options to contribute to best practice evidence for program design and delivery. METHODS: First-year students from physiotherapy, podiatry and occupational therapy self-selected to either a one-weeklong in-person simulation program or an online preparation for placement program. An integrative mixed-methods approach was employed. Qualitative findings from student focus groups were analyzed by reflexive thematic analysis and complemented by quantitative pre-post questionnaires which were examined for patterns of findings. RESULTS: There were 53 student participants in the study (simulation n = 29; online n = 24). Self-selecting, international students disproportionately opted for the simulation program while older students disproportionately selected the online program. Students appeared to benefit more from the simulation program than the online program, with alignment of focus group findings to the quantitative questionnaire data. The in-person simulation allowed students to apply their learning and practice patient communication. All simulation students reported asubsequent increase in confidence, although this seemed particularly marked for the international students. By contrast, the online program was most effective at developing students' clinical reasoning and proficiency with documentation. Both programs faced minor challenges to student perceived relevance and skill development. CONCLUSION: Both online and in-person simulation preparation programs were perceived to enhance readiness and foundational skills development for novice allied health students, with the practical nature of simulation generating more advantageous findings. This study provides useful information on the benefits and challenges of both types of delivery for foundational skills development and/or clinical preparation of allied health students.

The short-term impact of non-removable offloading devices on quality of life in people with recurrent diabetic foot ulcers.

OBJECTIVE: Recurrent diabetic foot ulcers (DFUs) are associated with poor health-related quality of life and reduced mobility. Current guidelines recommend application of non-removable offloading devices (NROLDs) as they may improve the healing of DFUs, but there is a lack of information on the wider effects of wearing these devices. Few studies have examined the impact of NROLDs on holistic wellbeing or physical activity. We aimed to investigate the short-term impact of NROLDs on physical activity and DFU-related quality of life (DFU-QoL) in a small sample of community-dwelling people with recurrent DFUs. METHOD: We measured DFU-QoL and physical activity (GPAQ) in people with DFUs, recruited from a single clinic before NROLD application, and at three and six weeks after device fitting. Participants were aged from 39-81 years (mean 58.4±10.1 years) with an equal number of male and female participants. RESULTS: The study cohort comprised 18 participants, of whom 14 (78%) completed six-week questionnaires. Although there was some interim decline observed within individual domains of the DFU-QoL (financial: mean difference (MD) 16.2 (95% confidence interval (CI) 2.1, 30.2); p=0.03); non-compliance: MD 12.5 (95% CI-0.2, 25.2); p=0.05), no differences were observed over six weeks. Levels of physical activity declined over time, with over half (56%) of participants classified as having low levels of physical activity at baseline, rising to two-thirds (67%) at follow-up. CONCLUSION: Future studies should explore the longer-term holistic impact of NROLDs and develop more personalised approaches to care at the point of prescription, during and post-device use.

Higher body fat percentage is associated with enhanced temperature perception in NAFLD: results from the randomised Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy trial (WELCOME) trial.

AIMS/HYPOTHESIS: The effect of n-3 fatty acid treatment on temperature perception as a sensory nerve function modality is uncertain. In patients with non-alcoholic fatty liver disease (NAFLD) both with and without type 2 diabetes, we: (1) tested whether 15-18 months' treatment with 4 g/day of docosahexaenoic plus eicosapentaenoic acid (DHA+EPA) improved hot (HPT) and cold (CPT) temperature perception thresholds and (2) explored factors associated with HPT and CPT, in a randomised, double-blind, placebo-controlled trial. METHODS: The effect of treatment (n = 44) on HPT, CPT and temperature perception index (TPI: difference between HPT and CPT) was measured at the big toe in 90 individuals without neuropathy (type 2 diabetes; n = 30). Participants were randomised 1:1, using sequential numbering, by personnel independent from the trial team. All participants and all members of the research team were blinded to group assignment. Data were collected in the Southampton National Institute for Health Research Biomedical Research Centre. Treatment effects and the independence of associations were testing by regression modelling. RESULTS: Mean ± SD age was 50.9 ± 10.6 years. In men (n = 53) and women (n = 37), HPTs (°C) were 46.1 ± 5.1 and 43.1 ± 6.4 (p = 0.02), CPTs (°C) were 22.7 ± 3.4 and 24.5 ± 3.6 (p = 0.07) and TPIs (°C) were 23.4 ± 7.4 and 18.7 ± 9.5 (p = 0.008), respectively. In univariate analyses, total body fat percentage (measured by dual-energy x-ray absorptiometry [DXA]) was associated with HPT (r = -0.36 p = 0.001), CPT (r = 0.35 p = 0.001) and TPI (r = 0.39 p = 0.0001). In multivariable-adjusted regression models, adjusting for age, sex and other potential confounders, only body fat percentage was independently associated with HPT, CPT or TPI (p = 0.006, p = 0.006 and p = 0.002, respectively). DHA+EPA treatment did not modify HPT, CPT or TPI (p = 0.93, p = 0.44 and p = 0.67, respectively). There were no important adverse effects or side effects reported. CONCLUSIONS/INTERPRETATION: Higher body fat percentage is associated with enhanced temperature perception. There was no benefit of treatment with high-dose n-3 fatty acids on the thresholds to detect hot or cold stimuli. TRIAL REGISTRATION: ClinicalTrials.gov NCT00760513 FUNDING: This work was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Unit grant and by a Diabetes UK allied health research training fellowship awarded to KMcC (Diabetes UK. BDA 09/0003937).

Impact of high dose n-3 polyunsaturated fatty acid treatment on measures of microvascular function and vibration perception in non-alcoholic fatty liver disease: results from the randomised WELCOME trial.

AIMS/HYPOTHESIS: The effect of n-3 fatty acid treatment on vibration perception thresholds (VPTs) and cutaneous microvascular reactivity is not known. We tested whether: (1) a 15-18 month treatment with high dose (4 g/day) docosahexaenoic (DHA) plus eicosapentaenoic (EPA) acid improved VPT and microvascular reactivity in patients with non-alcoholic fatty liver disease; and (2) there are associations between VPT, microvascular reactivity and metabolic variables. METHODS: In the completed single centre, randomised, parallel group, placebo controlled Wessex Evaluation of fatty Liver and Cardiovascular markers in non-alcoholic fatty liver disease with OMacor thErapy (WELCOME) trial, we tested the effect of DHA+EPA on VPT at 125 Hz (big toe) and the cutaneous hyperaemic response (forearm) to arterial occlusion (ratio of maximum to resting blood flux [MF/RF]). Allocation and dispensing was carried out by an independent research pharmacist; all participants and research team members were blinded to group assignment. RESULTS: In all, 51 and 49 patients were randomised to placebo and DHA+EPA, respectively (mean age 51.4 years). Of these, 32 had type 2 diabetes. Forty-six (placebo) and 47 (DHA+EPA) patients completed the study; there were no important adverse (or unexpected) effects or side effects. In multivariable-adjusted regression models (intention-to-treat analyses), DHA+EPA treatment was associated with an increase in VPT (ß coefficient 1.49 [95% CI 0.04, 2.94], p = 0.04). For VPT, the adjusted mean differences (95% CIs) in the placebo and DHA+EPA treatment groups were -0.725 (-1.71, 0.25) and 0.767 (-0.21, 1.75) m/s(2), respectively. With DHA+EPA treatment, there was no change in MF/RF (ß coefficient 0.07 [95% CI -0.56, 0.70], p = 0.84), the adjusted mean differences (95% CIs) in the placebo and DHA+EPA treatment groups were -0.549 (-1.03, -0.07) and -0.295 (-0.77, 0.18) respectively. VPT was independently associated with age (ß coefficient 0.019 [95% CI 0.010, 0.029], p < 0.0001) and MF/RF (ß coefficient -0.074 [95% CI -0.132, -0.016], p = 0.013), but not with diabetes (p = 0.38). CONCLUSIONS/INTERPRETATION: High dose n-3 fatty acid treatment did not improve measures of microvascular function or vibration perception. Ageing and microvascular reactivity are associated with a measure of peripheral nerve function. TRIAL REGISTRATION: ClinicalTrials.gov NCT00760513. FUNDING: The study was funded by the National Institute for Health Research UK and Diabetes UK.

Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: Results from the WELCOME trial.

BACKGROUND & AIMS: Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain. METHODS: One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15-18months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome. RESULTS: Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I=41, 148I/M=43, 148M/M=11; TM6SF2 E167K 167E/E=78, 167E/K+167K/K=17 participants) (mean ± SD age, 51 ± 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient -1.02 (95% CI -1.97, -0.07), p=0.036) but not percentage of EPA enrichment (B coefficient -0.31 (95% CI -1.38, 0.75), p=0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p=0.008), but not end of study triglyceride concentration (B coefficient -0.11 (95% CI -0.64, 0.42), p=0.68). CONCLUSIONS: PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration.

Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (ß=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, ß=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

Development and implementation of an enterprise-wide predictive model for early absorption, distribution, metabolism and excretion properties.

Background: Accurate prediction of absorption, distribution, metabolism and excretion (ADME) properties can facilitate the identification of promising drug candidates. Methodology & Results: The authors present the Janssen generic Target Product Profile (gTPP) model, which predicts 18 early ADME properties, employs a graph convolutional neural network algorithm and was trained on between 1000-10,000 internal data points per predicted parameter. gTPP demonstrated stronger predictive power than pretrained commercial ADME models and automatic model builders. Through a novel logging method, the authors report gTPP usage for more than 200 Janssen drug discovery scientists. Conclusion: The investigators successfully enabled the rapid and systematic implementation of predictive ML tools across a drug discovery pipeline in all therapeutic areas. This experience provides useful guidance for other large-scale AI/ML deployment efforts.

Self-management approaches to reduce the ill-health burden associated with musculoskeletal foot and ankle problems: A scoping review protocol.

INTRODUCTION: The high ill-health burden associated with musculoskeletal (MSK) disease has been widely reported, and various treatment approaches proposed. Increasingly, treatments have sought to reflect personalised care and incorporate self-management (SM). However, the range of SM approaches proposed for foot and ankle MSK problems, and their relative clinical or cost-effectiveness, has not been reviewed. A scoping review is required to understand the need/appropriateness of a systematic review on this topic. METHODS AND ANALYSIS: The scoping review will be conducted in line with the PRISMA-ScR framework. We will perform an initial search across two databases to confirm search syntax. We will then complete a full search across three databases (Embase [Ovid], CINAHL [EBSCO], and Medline [EBSCO]) and grey literature (Cochrane Library, The British Library, The Canadian Agency for Drugs and Technologies in Health [CADTH], The Health Foundation, The Kings Fund, and MedNar). We will use a snowballing strategy to review the reference list of retrieved texts, as per inclusion criteria, to identify previously unretrieved texts of potential relevance. In an iterative process, the protocol outlined above will be refined and repeated as new key terms come to light. ETHICS AND DISSEMINATION: The scoping review will synthesise what is known and not known about SM approaches for MSK foot and ankle problems. The review will form the first step in outlining future research recommendations and areas of potentially unmet clinical need. The findings will be submitted for publication and shared in written form with stakeholder groups involved in the design of future research.