Abstract: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02735707

Abstract: P3 Medial longitudinal arch development of school children Jasper W.K. Tong, Veni P. Kong P4 Is measuring the subtalar joint reliable? Lily Sze, Susie Gale, John Veto, Carla McArdle P5 Comparison of turning gait biomechanics between able‐bodied and unilateral transtibial amputee participants Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P6 Comparison of walking gait biomechanics between able‐bodied and unilateral transtibial amputee participants using a new model of energy‐storage‐and‐return (ESAR) prosthetic Thanaporn Tunprasert, Victoria Bradley, Siobhan Strike P7 An observational study of in‐shoe plantar and dorsal pressures of skilled downhill skiers on a dry ski slope Robert Ashford, Roozbeth Naemi, Nachiappan Chocklingam, Xavi de Blasc P8 If the shoe fits: a footwear choice toolkit informed by social science methodologies Lisa Farndon, Vicki Robinson, Emily Nicholls P9 The identification of emotions from gait Tabitha Birch, Ivan Birch P11 Experience of foot problems in patients with systemic lupus erythematosus Simon Otter, Sunil Kumar, Peter Gow, Nicola Dalbeth, Michael Corkill, Kevin Davies, Sam Panthakalam, Maheswaran Rohan, Keith Rome P14 Negative pressure wound therapy for the management of foot wounds in the diabetic population: a review of the literature Chloe Egan, Lisa Chandler P15 Lower limb vascular assessment in diabetes: a multifaceted assessment of objective screening techniques Peta Tehan, Vivienne Chuter, Jennifer Sonter, Sean Lanting P16 Improving outcomes for diabetes foot complications Lorna Hicks P17 Acupuncture… an alternative or adjunctive treatment option for diabetes‐related neuropathic pain? Christopher Joyce, David Watterson, Caroline McIntosh P18 “My back is in agony” – A cross‐sectional study into the relationship between musculoskeletal complaints and a whole body postural risk assessment in podiatry students Christopher Joyce, Nigel Roberts P19 Swabs of the treatment couches: Does the material type and texture of podiatric treatment couches increase microorganism contamination? Jacqueline Forss, Chrystalla Charalambous, Jack Kirby, Oluwakemi Ojo P20 Does increased exudate viscosity effect the absorption rate of exudate into four different wound dressings? Jacqueline Forss, Sarah Caukill, Jacqueline Capon, Radiance Fong, Louis Loy P21 An investigation into the microbial load of a 40 °C and 60 °C wash Matthew Diment, Madeleine Murray, Mairghread Ellis, Carla McArdle P23 The sensitivity and specificity of the toe brachial index in detecting peripheral arterial disease: a systematic review and meta‐analysis Peta Tehan, Vivienne Chuter, Christopher Oldmeadow P24 Medicines management activities and non‐medical prescribing within podiatry and physiotherapy: an integrative review of the literature Nicola Carey, Karen Stenner , Heather Gage, Jane Brown, Peter Williams, Simon Otter, Ann Moore, Jude Edwards, Freda Mold, Molly Courtenay A7.2 Non‐invasive vascular assessment in the foot with Diabetes: Diagnostic accuracy of ankle brachial index, toe brachial index and continuous wave Doppler Peta Tehan, Alan Bray, Vivienne Chuter A7.5 The efficacy of dressings on post nail surgery phenolised wounds Pamela Hindmoor B7.1 Cross‐sectional study investigating the role of proximal and distal factors in the development of patellofemoral joint pain Craig Gwynne, Sarah Curran B7.2 Podiatrist's interpretation and use of evidence in MSK practice Andy Bridgen B7.4 Predictors of falling in older podiatry patients – findings from the REFORM study Caroline Fairhurst, Dr Joy Adamson, Belen Corbacho Martin, Sarah Cockayne, Prof Catherine Hewitt, Kate Hicks, Anne‐Maree Keenan, Lorraine Loughrey‐Green, Hylton Menz, Anthony Redmond, Sara Rodgers, Jude Watson, David Torgerson, Robin Hull, Sarah Lamb, Caroline McIntosh, Wesley Vernon, Lisa Farndon B7.5 The REFORM study: Insole preference, requirements and compliance of podiatry patient's aged 65 and over and at risk of falling Lorraine Loughrey‐Green, Sarah Cockayne, Anthony Redmond, Anne‐Maree Keenan, Sara Rodgers, Lisa Farndon, Wesley Vernon, David Torgerson, Caroline Fairhurst, Jude Watson, Hylton Menz, Sarah Lamb, Robin Hull B7.6 A podiatry intervention to reduce falls in care home residents is feasible and demonstrates benefits: results from PIRFECT, a feasibility randomised controlled trial Gavin Wylie, Zoe Young, Brian Williams, Frank Sullivan, Hylton Menz, Simon Ogston, Jacqui Morris C7.1 A survey exploring footwear habits in people with stroke and people with Parkinson's Cathy Bowen, Dorit Kunkel, Mark Cole, Margaret Donovan‐Hall, Ruth Pickering, Malcolm Burnett, Dan Bader, Judy Robison, Louis Mamode, Ann Ashburn C7.2 Painful foot osteoarthritis; a common symptom in a common pathology? Peter McQueen, Maxine Daniels, Michael Doherty, Nigel Arden, Cathy Bowen C7.4 Clinical diagnosis of symptomatic forefoot neuroma in the general population: Delphi based recommendations Charlotte Dando, Lindsey Cherry, Cathy Bowen C7.5 The development and implementation of a Clinical Quality Improvement Framework suitable for use in community services Nichola Stefanou C7.6 The REFORM study ‐ methodological considerations in running a cohort randomised controlled trial within a podiatry patient caseload Sarah Cockayne, Joy Adamson, Caroline Fairhurst, Catherine Hewitt, Anne‐Maree Keenan, Sally Lamb, Lorraine Loughrey‐Green, Caroline McIntosh, Hylton Menz, Anthony Redmond, Sara Rodgers, Wesley Vernon, Jude Watson, Lisa Farndon, Belen Corbacho, Robin Hull, David Torgerson A31 Jewel in the crown: Exploring the factors contributing to the development and impact of foot problems in Systemic Sclerosis (SSc) Begonya Alcacer‐Pitarch, Anthony Redmond, Maya Buch, Anne‐Maree Keenan

Abstract: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90] ) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR & amp;gt;0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14] ), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29] ) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month surviva l across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

Abstract: We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS & gt;0.295, 95% CI 1.47–3.51; P = 0.0002). CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.

Abstract: There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A] , and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P & lt; 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.

Abstract: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%] ; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%] ; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%] ; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%] ; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.