Search

Nathan Cardy,1 Andrew Hunter,2 Daniel Carter,1 Mairead O’Donoghue,1 Márcia Carvalho,3 Emma Carr,1 Jane C Walsh,3 Julie Bernhardt,4 Claire Fitzsimons,5 Ita Richardson,6 Jon Salsberg,7 Liam Glynn,7 Cathal Walsh,8 Edina O’Driscoll,9 Pauline Boland,1 Nora Cunningham,10 John Forbes,7 Rose Galvin,1 Sara Hayes1 1School of Allied Health, Ageing Research Centre, Health Research Institute, University of Limerick, Limerick, Ireland; 2School of Nursing and Midwifery, University of Galway, Galway, Ireland; 3School of Psychology, University of Galway, Galway, Ireland; 4Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia; 5Physical Activity for Health Research Centre, Institute Sport, Physical Education and Health Sciences, University of Edinburgh, Edinburgh, Scotland; 6Department of Computer Science and Information Systems, University of Limerick, Limerick, Ireland; 7School of Medicine, University of Limerick, Limerick, Ireland; 8School of Medicine, Trinity College Dublin, Dublin, Ireland; 9Health Service Executive, Dublin, Ireland; 10University Hospital Limerick, Limerick, IrelandCorrespondence: Sara Hayes, Email sara.hayes@ul.ieIntroduction: Engaging in regular physical activity (PA) is associated with lower mortality following stroke, and PA reduces the chance of recurrent stroke. Despite recent guidelines to optimise PA following stroke, people with stroke are known to be less active than their age-matched counterparts. Given the heterogenous nature of stroke, adaptive PA interventions are recommended for people with stroke. Empirical data is lacking on adaptive PA or behavioural change interventions following stroke. Suggested strategies in the prevention of stroke recommend the use of mobile health (mHealth) interventions in the primary prevention of stroke. A structured stakeholder consultation process is key to successful implementation of complex interventions. This paper reports the findings of our consultation process to inform the development of an adaptive mHealth PA.Methods: We used a qualitative study design to explore the perspectives of key stakeholders on the development of an adaptive PA intervention delivered via mHealth post-stroke. Healthcare workers, carers and people with stroke participated in semi-structured one-to-one or focus group interviews. A reflexive thematic analysis was undertaken on transcribed interviews; key themes and sub-themes were developed using coding and summarised by two researchers, then reviewed by the full research team.Results: Twenty-eight stakeholders were interviewed and three main themes were identified; Key feature of a mHealth intervention, delivering a mHealth intervention, Challenges to development and use. There was widespread agreement across stakeholder groups that an adaptive mHealth PA intervention following stroke would be beneficial to people with stroke, following discharge from acute care.Conclusion: Our consultation supports the development of an adaptive PA programme that addresses specific impairments that can hinder exercise participation after stroke.Keywords: physical activity, stroke, adaptive intervention, intervention design

Background: Pediatric oncology patients have increased risk for critical illness; outcomes are well described in high-income countries (HICs); however, data is limited for low- and middle-income countries (LMICs)., Methods: We systematically searched PubMed, EMBASE, Web of Science, CINAHL and Global Health databases for articles in 6 languages describing mortality in children with cancer admitted to intensive care units (ICUs) in LMICs. Two investigators independently assessed eligibility, data quality, and extracted data. We pooled ICU mortality estimates using random effect models., Results: Of 3641 studies identified, 22 studies were included, covering 4803 ICU admissions. Overall pooled mortality was 30.3 % [95 % Confidence-interval (CI) 21.7-40.6 %]. Mechanical ventilation [odds ratio (OR) 12.2, 95 %CI:6.2-24.0, p-value<0.001] and vasoactive infusions [OR 6.3 95 %CI:3.3-11.9, p-value<0.001] were associated with ICU mortality., Conclusions: ICU mortality among pediatric oncology patients in LMICs is similar to that in HICs, however, this review likely underestimates true mortality due to underrepresentation of studies from low-income countries., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There has been an increasing call for employing ultrashort exercise activity questionnaires as a clinical "vital sign". To-date, this has not been applied to patients undergoing cardiac stress testing., Methods: We evaluated 1,136 patients who completed a one-item exercise questionnaire before undergoing stress SPECT myocardial perfusion imaging (MPI). This question asked patients to grade how much they exercise during daily life on an 11-point scale (0= none, 10 = always). Patients were divided into four exercise activity groups based on their response: no, low, moderate, and high exercise activity. The results of this questionnaire were compared to patients clinical risk profile, mode of stress testing (exercise versus pharmacologic), and exercise treadmill duration., Results: We noted a stepwise inverse relationship between exercise activity and patients' frequency of hypertension, diabetes, and obesity (p<0.001 for each). Patients with no reported exercise activity were more likely to complain of dyspnea. There was a stepwise increase in the number of patients performing treadmill exercise with increasing reported exercise activity (p<0.001). The duration on treadmill exercise increased in stepwise fashion with higher patient reported exercise activity (p<0.001)., Conclusion: Our single-item, self-reported questionnaire was correlated to patients' risk profiles, their mode of stress testing, and cardiorespiratory fitness. These correlates, along with the pragmatic nature of this ultrashort questionnaire, and its built-in identification of patients who may warrant exercise counseling, augurs for adopting ultrashort questionnaires regarding exercise activity among patients undergoing stress MPI and other cardiac imaging tests where functional capacity is not routinely assessed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel Berman reports financial support was provided by Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Daniel Berman reports a relationship with Dr. Miriam and Sheldon G. Adelson Medical Research Foundation that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate the effect of propofol versus midazolam on vasopressor requirements in patients with septic shock to better guide sedative selection., Methods: This was a multicenter, retrospective, observational, IRB-approved, non-inferiority cohort study. Included individuals were ≥ 18 years of age, had a diagnosis of septic shock, and exclusive administration of propofol or midazolam for at least 12 h. The primary outcome was maximum increase in vasopressor requirements within the first 12 h following sedative initiation., Results: For the primary outcome of maximum increase in norepinephrine equivalents (NEE) within 12 h, propofol was non-inferior to midazolam (0.09 vs. 0.129 μg/kg/min, p = 0.002). No difference was seen between the propofol and midazolam groups for the secondary outcome of maximum increase in NEE within 3 h (0.02 vs 0.04 μg/kg/min, p = 0.208), however, the propofol group had a significantly lower increase within 6 h (0.06 vs 0.086 μg/kg/min, p = 0.043) and 24 h (0.11 vs 0.25 μg/kg/min, p = 0.013)., Conclusion: In patients with septic shock, vasopressor requirement increases with propofol were non-inferior to midazolam within the first 12 h., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Staphylococcus aureus remains a leading global cause of bacterial infection-associated mortality and has eluded prior vaccine development efforts. S. aureus α-toxin (Hla) is an essential virulence factor in disease, impairing the T cell response to infection. The anti-Hla antibody response is a correlate of human protective immunity. Here we observe that this response is limited early in human life and design a vaccine strategy to elicit immune protection against Hla in a neonatal mice. By targeted disruption of the interaction of Hla with its receptor ADAM10, we identify a vaccine antigen (Hla H35L/R66C/E70C , Hla HRE ) that elicits an ~100-fold increase in the neutralizing anti-Hla response. Immunization with Hla HRE enhances the T follicular helper (T FH ) cell response to S. aureus infection, correlating with the magnitude of the neutralizing anti-toxin response and disease protection. Furthermore, maternal Hla HRE immunization confers protection to offspring. Together, these findings illuminate a path for S. aureus vaccine development at the maternal-infant interface., (© 2024. The Author(s).)

Background: Internationally, there has been a move towards fostering diverse healthcare workforces that are representative of the patient populations they serve. Selection criteria for academic-clinicians often aim to capture skills and attributes that demonstrate both clinical and academic excellence. Currently, it is not known whether the selection criteria for early academic-clinical careers advantage or disadvantage certain ethnic or socioeconomic groups. The UK has a structured route of integrated clinical academic training with entry level training for newly qualified doctors administered through the 'Specialised Foundation Programme' which provides protected time for research within the first two years of postgraduate clinical training. In this study, we aim to identify what selection criteria are used within the UK Specialised Foundation Programme, and how these relate to demographic factors., Methods: We will perform a mixed methods study consisting of a document analysis of person specifications and selection criteria used in the 2024 UK Specialised Foundation Programme, and a national cross-sectional survey of current medical students in the UK. We will obtain the person specifications, selection criteria, white space (open ended questions used during shortlisting) and interview questions and mark schemes from each Specialised Unit of Applications via information available on their websites or through Freedom of Information requests. Our survey will collect information relating to demographic data, selection criteria, and perceptions of specialised foundation programme selection., Discussion: International literature has demonstrated inequity in academic markers used in selection of post-graduate clinicians and that disadvantages caused by selection can compound over time. As such it is important to understand what inequity exists within the selection of early academic-clinicians, as this can help inform more equitable selection practices and help nurture a more diverse academic-clinical workforce., (© 2024. The Author(s).)

Background: Breast cancer is the most commonly diagnosed cancer among women worldwide. While previous studies have reported urban and rural differences in breast cancer outcomes, the level of heterogeneity within these broad regions is currently unknown., Methods: Population-level data from Queensland Cancer Register including 58,679 women aged at least 20 years who were diagnosed with breast cancer in Queensland, Australia, 2000-2019 were linked to BreastScreen Queensland and Queensland Hospital Admitted Patients Data Collection to estimate five breast cancer outcomes: incidence, proportion of localised disease and screen-detected cases (via public-funded program), surgical rates, and 5-year survival. Bayesian spatial models were used to smooth outcomes across 512-517 small areas in Queensland., Results: The incidence of breast cancer was not proportionally distributed, with urban regions having higher rates. Less than half (47 %) of women were diagnosed with localised disease, 91 % had surgery, with five-year relative survival of 92 %. There was no evidence of geographic variation in the proportion of localised disease, surgical rates, or survival over Queensland. Publicly-funded screening detected 38 % of cases, with lower proportion of screen-detected cases observed in Queensland's urbanised south-east corner., Conclusion: Although the disparities in health outcomes faced by Australians living in rural areas have received increased attention, this study found limited evidence for spatial variation in breast cancer outcomes along the continuum of care across Queensland. These results suggest the detection and management practices for breast cancer may provide an achievable benchmark for other cancer types in reducing the geographical disparity in cancer outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cetuximab was initially developed and approved as a first-line treatment in patients with unresectable metastatic colorectal cancer (mCRC) for weekly administration (250 mg/m 2 Q1W with 400 mg/m 2 loading dose). An every-2-weeks schedule (500 mg/m 2 Q2W) was approved recently by several health authorities. Being synchronized with chemotherapy, Q2W administration should improve patients' convenience and healthcare resource utilization. Herein, we present evidence of non-inferiority of Q2W cetuximab, compared with Q1W dosing using pharmacometrics modeling and clinical trial simulation (CTS). Pooled data from five phase I-III clinical trials in 852 patients with KRAS wild-type mCRC treated with Q1W or Q2W cetuximab were modeled using a population exposure-tumor size (TS) model linked to overall survival (OS); exposure was derived from a previously established population pharmacokinetic model. A semi-mechanistic TS model adapted from the Claret model incorporated killing rate proportional to cetuximab area under the concentration-time curve over 2 weeks (AUC) with Eastern Cooperative Oncology Group (ECOG) status as covariate on baseline TS. The OS was modeled with Weibull hazard using ECOG, baseline TS, primary tumor location, and predicted percent change in TS at 8 weeks as covariates. Model-based simulations revealed indistinguishable early tumor shrinkage and survival between Q2W vs. Q1W cetuximab. CTS evaluated OS non-inferiority (predefined margin of 1.25) in 1,000 trials, each with 2,000 virtual patients receiving Q2W or Q1W cetuximab (1:1), and demonstrated non-inferiority in 94% of cases. Taken together, these analyses provide model-based evidence for clinical non-inferiority of Q2W vs. Q1W cetuximab in mCRC with potential benefits to patients and healthcare providers., (© 2024 Emd Serono Research & Development Institute, Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Maribavir is approved for management of post-transplant cytomegalovirus (CMV) infections refractory and/or resistant to CMV therapies at a dose of 400 mg twice daily (BID). Population pharmacokinetic (PopPK) and exposure-response analyses were conducted to support the appropriateness of 400 mg BID dosing. A PopPK model was developed using non-linear mixed-effects modeling with pooled maribavir plasma concentration-time data from phase 1 and 2 studies (from 100 mg up to 1200 mg as single or repeated doses) and the phase 3 SOLSTICE study (400 mg BID). Exposure-response analyses were performed for efficacy, safety, and viral resistance based on data collected in the SOLSTICE study. Maribavir PK after oral administration was adequately described by a two-compartment model with first-order elimination, first-order absorption, and an absorption lag-time. There was no evidence that maribavir PK was affected by age, sex, race, diarrhea, vomiting, disease characteristics, or concomitant use of histamine H 2 blockers, or proton pump inhibitors. In the SOLSTICE study, higher maribavir exposure was not associated with increased probability of achieving CMV DNA viremia clearance, nor with reduced probability of treatment-emergent maribavir-resistant CMV mutations. A statistically significant association with maribavir exposure was identified for taste disturbance, fatigue, and treatment-emergent serious adverse events, while transplant type, enrollment region, CMV DNA level at baseline, and/or CMV resistance at baseline were identified as additional risk factors for these safety outcomes. In conclusion, the findings of these PopPK and exposure-response analyses provide further support for the recommended maribavir dose of 400 mg BID., (© 2024. The Author(s).)

The electrophysiological properties of the hearts of women and men are different. These differences are at least partly mediated by the actions of circulating estrogens and androgens on the cardiomyocytes. Experimentally, much of our understanding in this field is based on studies focusing on ventricular tissue, with considerably less known in the context of atrial electrophysiology. The aim of this investigation was to compare the electrophysiological properties of male and female atria and assess responses to acute sex steroid exposure. Age-matched adult male and female C57BL/6 mice were anesthetized (4 % isoflurane) and left atria isolated. Atria were loaded with Di-4-ANEPPS voltage sensitive dye and optical mapping performed to assess action potential duration (APD; at 10 %, 20 %, 30 %, 50 %, and 70 % repolarization) and conduction velocity in the presence of 1 nM and 100 nM 17β-estradiol or testosterone. Male and female left atria demonstrated similar baseline action potential duration and conduction velocity, with significantly greater APD 70 spatial heterogeneity evident in females. 17β-estradiol prolonged action potential duration in both sexes - an effect that was augmented in females. Atrial conduction was slowed in the presence of 100 nM 17β-estradiol in both males and females. Testosterone prolonged action potential duration in males only and did not modulate conduction velocity in either sex. This study provides novel insights into male and female atrial electrophysiology and its regulation by sex steroids. As systemic sex steroid levels change and intra-cardiac estrogen synthesis capacity increases with aging, these actions may have an increasingly important role in determining atrial arrhythmia vulnerability., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: James Bell reports financial support was provided by the 10.13039/501100000925National Health and Medical Research Council. Lea Delbridge reports financial support was provided by the 10.13039/501100000925National Health and Medical Research Council. Lea Delbridge reports financial support was provided by the 10.13039/501100000923Australian Research Council. Davor Pavlovic reports financial support was provided by the 10.13039/501100000274British Heart Foundation. Christopher O’Shea reports financial support was provided by the 10.13039/100010269Wellcome Trust. Kate Weeks reports financial support was provided by the 10.13039/501100001030National Heart Foundation of Australia. James Bell (co-corresponding author) serves on the Editorial Board of the Journal of Molecular and Cellular Cardiology Plus. Davor Pavlovic (co-corresponding author) serves as the Editor-in-Chief of the Journal of Molecular and Cellular Cardiology Plus. Christopher O’Shea (co-author) serves as a Guest Editor for the relevant Call for Papers of the Journal of Molecular and Cellular Cardiology Plus. Lea Delbridge (co-corresponding author) serves on the Editorial Board of the Journal of Molecular and Cellular Cardiology (sister journal to JMCC Plus). Davor Pavlovic (co-corresponding author) and Kate Weeks (co-author) serve as Social Media Editors of the Journal of Molecular and Cellular Cardiology (sister journal to JMCC Plus). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Novel supportive care interventions designed for an aging population with lung cancer are urgently needed. We aimed to determine the feasibility of a novel supportive care physical therapy (PT) plus progressive muscle relaxation (PMR) intervention delivered to older adults with advanced lung cancer in the United States (US)., Materials and Methods: This clinical trial, Resiliency Among Older Adults Receiving Lung Cancer Treatment (ROAR-LCT: NCT04229381), recruited adults aged ≥60 years with unresectable stage III/IV non-small cell (NSCLC) or small cell lung cancer (SCLC) receiving cancer treatment at The James Thoracic Oncology Center (planned enrollment, N = 20). There were no exclusion criteria pertaining to performance status, laboratory values, prior cancer diagnoses, comorbidities, or brain metastases. Participants were evaluated by PT and psychology and given an exercise pedaler, resistance bands, a relaxation voice recording, and instructions at study initiation. Participants were evaluated in-person by PTs and psychologists at the start and end of the 12-session intervention, with the intervening sessions conducted via virtual health. Participants completed self-reported measures of functional status, symptoms, and mood longitudinally with the following instruments: EQ-5D-5L, Patient Health Questionnaire-9, and General Anxiety Disorder-7. PT assessments included the Short Physical Performance Battery (SPPB) and the two-minute walk test. Feasibility was defined as at least 60% of participants completing at least 70% of all intervention sessions. Optional gut microbiome samples and activity monitoring data (ActiGraph®) were also collected., Results: The ROAR-LCT study concluded after consenting 22 patients. Among the 22 consented, 18 (81.8%) started the intervention; 11 participants (61.1%) completed at least 70% of all study sessions. All participants with SCLC completed the intervention. Reasons for withdrawal included progression of disease or hospitalization. The majority (88.9%) of patients who started were able to complete at least one virtual health session. Participants' functional status, SPPB, depression, and anxiety scores were stable from pre- to post-intervention. Participants who withdrew had worse baseline scores across domains. Seven microbiome and six ActiGraph® samples were collected., Discussion: This is one of the first PT + PMR supportive care interventions using virtual health among older adults with advanced lung cancer to achieve feasibility in the US., Competing Interests: Declaration of Competing Interest EP reports grants from Pfizer, Merck Foundation, Genentech, Guardant Health, and AstraZeneca and is on Advisory Boards for GSK and Merck. DC is on the Executive Steering Committee for Lumanity, participated in the Merck Global Lung Expert Input Forum and a Pfizer Egypt Meet the Expert session, and has provided scientific input to Merck. CJP reports grants from the Bristol Myers Squibb Foundation, The Rising Tide Foundation, and is a consultant for Regeneron, RAPT Therapeutics, OncLIVE, and Bristol Myers Squibb., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Limited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects., Methods: Data from California birth certificates (2007-2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories., Results: Offspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings., Conclusions: Offspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We would like to acknowledge Dr. Christina Chambers (Department of Pediatrics, University of California San Diego) and Dr. Jessica Block (University of California San Diego). The study was supported by the San Diego Study of Mothers and Infants at the University of California San Diego, United States. Gretchen Bandoli is funded by a NIH award (K01 AA027811). No specific funding was received for this project, and the funders for the parent study had no input into the design, analysis, interpretations, or preparation of the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: The American Thoracic Society recommended a single reference equation for spirometry, but the impact on patients is not known. Objectives: To estimate the effect of changing to a single reference equation among veterans with chronic obstructive pulmonary disease (COPD). Methods: A cross-sectional study was conducted including veterans aged ⩾40 to ⩽89 years with COPD and spirometry results from 21 facilities between 2010 and 2019. We collected race and ethnicity data from the electronic health record. We estimated the percentage change in the number of veterans with lung function meeting clinical thresholds used to determine eligibility for lung resection for cancer, lung volume reduction surgery (LVRS), and lung transplantation referral. We estimated the change for each level of U.S. Department of Veterans Affairs service connection and financial impact. Results: We identified 44,892 veterans (Asian, 0.5%; Black, 11.8%; White, 80.8%; and Hispanic, 1.8%). When changing to a single reference equation, Asian and Black veterans had reduced predicted lung function that could result in less surgical lung resection (4.4% and 11.1%, respectively) while increasing LVRS (1.7% and 3.8%) and lung transplantation evaluation for Black veterans (1.2%). White veterans had increased predicted lung function and could experience increased lung resection (8.1%), with less LVRS (3.3%) and lung transplantation evaluation (0.9%). Some Asian and Black veterans could experience increases in monthly disability payments (+$540.38 and +$398.38), whereas White veterans could see a decrease (-$588.79). When aggregated, Hispanic veterans experienced changes attributable to their racial identity and, because this sample was predominantly Hispanic White, had similar results to White veterans. Conclusions: Changing the reference equation could affect access to treatment and disability benefits, depending on race. If adopted, the use of discrete clinical thresholds needs to be reassessed, considering patient-centered outcomes.

Behavioral health professionals are at high risk for burnout and poor mental health. Our objective was to understand the impact of the Behavioral Health Providers Workforce Resiliency (BHPWR) ECHO Program on the resilience and burnout of participating behavioral health professionals. We assessed the first two years (March 2022 to March 2024) of the BHPWR ECHO, a national program operating from the University of New Mexico (N = 1585 attendees), using a mixed-methods design. We used a retrospective pre/post survey (n = 53 respondents) and focus interviews with 1-3 participants (n = 9 participants) to assess for changes in knowledge and confidence and assess changes in burnout and resilience. We found that participants increased their knowledge of how to respond when (1) their workload was more than they could manage, (2) they felt that they lacked control, (3) their work did not feel rewarding, and (4) they were experiencing compassion fatigue. They increased their confidence in (1) building a support system and (2) using the wellness tools taught in the course. Respondents were less burnt out (score: 26.0 versus 17.8, p < 0.01) and more resilient (29.9 versus 34.9, p < 0.01) compared to when they started attending the program. Tele-mentoring programs like the BHPWR ECHO Program may improve wellness among health care professionals.

Social prescribing is a healthcare model designed to reduce loneliness and improve individuals' health by addressing unmet social needs. The present study adopted the Social Cure framework to provide an understanding of the psychosocial processes involved in helping participants to engage with social activities, from both the link workers' and clients' perspectives. Semi-structured interviews were conducted with 15 link workers ( M age = 40.12; 87% female) and 15 clients ( M age = 55.33; 73% female, 7% non-binary) of social prescribing programmes across Australia and the transcripts were analysed using reflexive thematic analysis. Three overarching themes were identified: (1) Breaking Down Barriers, (2) Finding Fit with Others, and (3) Rebuilding a Sense of Self. These findings communicate how social prescribing addressed the psychosocial barriers of clients, and how joining groups that fostered positive shared social identities resulted in meaningful improvements to clients' well-being., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Conflicts of interest The author is an Executive board member of the International Dermoscopy Society and declares no other conflicts of ­interest.

Objectives: Lung cancer is the second most common cancer diagnosed worldwide, resulting in significant physical and psychological consequences. In this narrative review, we explore the role of exercise as an adjunct therapy to counteract health issues experienced by people before, during and after treatment for lung cancer, and offer recommendations for exercise prescription and future research., Design: Narrative cornerstone review., Methods: A narrative review was conducted to explore the role of exercise in cancer care for people diagnosed with lung cancer., Results: Improvements in fitness, strength and quality of life have been demonstrated in people with lung cancer following participation in exercise programmes before, during and post treatment. Whilst combined aerobic (50-100 % heart rate maximum) and resistance (50-85 % of 1 repetition maximum) training, 2-5 times per week across the cancer continuum is typically prescribed, few people with lung cancer currently access exercise services. 'Optimal' exercise prescription is unclear, although is likely individual-specific. The immediate priority is to identify a tolerable starting exercise dosage, with the side effects of lung cancer and its treatment on the respiratory system, particularly shortness of breath (dyspnoea), likely driving the initial maximum threshold for session mode, duration and intensity. To date, exercise safety for people with lung cancer has been poorly evaluated and reported - few trials report it, but those that do report small numbers of serious adverse events., Conclusions: Recommendations for health professionals prescribing exercise therapy to people with lung cancer are provided, with consideration of the strengths and limitations of the current evidence base., Competing Interests: Declaration of interest statement No conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Dolutegravir (DTG) is a once-daily HIV-1 integrase inhibitor approved for the treatment of HIV-1 infection in adults and children from 4 weeks of age. The posology of DTG in children has been driven by exposure-matching relative to the adult dose for efficacy and safety. However, higher variability in pediatric exposures raises concern that efficacy may not be reliably extrapolated from adult trials. Therefore, we evaluated the relationship between DTG exposure and virologic response in children., Design/methods: A population exposure-response analysis using logistic regression for virologic response was undertaken based on DTG exposure and covariate data from 146 pediatric participants with HIV-1 from age at least 4 weeks to less than 18 years treated for up to 48 weeks with DTG in IMPAACT P1093 study., Results: None of the DTG exposure metrics were predictive of virologic response over the range of exposures in this analysis. Of the covariates tested, viral load at least 100 000 copies/ml at enrolment was a significant predictor of virologic response showing a lower probability of achieving a virologic response of HIV-1 RNA less than 50 copies/ml compared with participants with viral load less than 100 000 copies/ml at enrolment. Baseline viral load was also a significant predictor at week 48 whereby the probability of achieving a virologic response at week 48 decreased with increasing baseline viral load., Conclusion: This exposure-response analysis suggests that DTG exposures in children are all above the plateau of the exposure-response relationship. These results suggest that matching pediatric pharmacokinetic exposure parameters to those in adults is a reasonable approach for dose determination of DTG-containing formulations in pediatrics., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C 3 N 4 ) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C 3 N 4 QDs and riboflavin/g-C 3 N 4 QDs composites (RF@g-C 3 N 4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C 3 N 4 QDs or RF@g-C 3 N 4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C 3 N 4 QDs in A-CXL for corneal ectasias and other corneal diseases., (© 2024. The Author(s).)

Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library ( n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A ( 1 ) and B ( 2 ). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC 90 ) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC 90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.

Background: Adopting high-value, cost-conscious care (HVCCC) principles into medical education is growing in importance due to soaring global healthcare costs and the recognition that efficient care can enhance patient outcomes and control costs. Understanding the current opportunities and challenges doctors face concerning HVCCC in healthcare systems is crucial to tailor education to doctors' needs. Hence, this study aimed to explore medical students, junior doctors, and senior doctors' experiences with HVCCC, and to seek senior doctors' viewpoints on how education can foster HVCCC in clinical environments., Methods: Using a mixed-methods design, our study involved a cross-sectional survey using the Maastricht HVCCC-Attitude Questionnaire (MHAQ), with a subset of consultants engaging in semi-structured interviews. Descriptive analysis provided insights into both categorical and non-categorical variables, with differences examined across roles (students, interns, junior doctors, senior doctors) via Kruskal-Wallis tests, supplemented by two-group analyses using Mann-Whitney U testing. We correlated experience with MHAQ scores using Spearman's rho, tested MHAQ's internal consistency with Cronbach's alpha, and employed thematic analysis for the qualitative data., Results: We received 416 responses to the survey, and 12 senior doctors participated in the semi-structured interviews. Overall, all groups demonstrated moderately positive attitudes towards HVCCC, with more experienced doctors exhibiting more favourable views, especially about integrating costs into daily practice. In the interviews, participants agreed on the importance of instilling HVCCC values during undergraduate teaching and supplementing it with a formal curriculum in postgraduate training. This, coupled with practical knowledge gained on-the-job, was seen as a beneficial strategy for training doctors., Conclusions: This sample of medical students and hospital-based doctors display generally positive attitudes towards HVCCC, high-value care provision, and the integration of healthcare costs, suggesting receptiveness to future HVCCC training among students and doctors. Experience is a key factor in HVCCC, so early exposure to these concepts can potentially enhance practice within existing healthcare budgets., (© 2024. The Author(s).)

The Statistics Expert Group was convened at the request of the Infected Blood Inquiry to provide estimates of the number of infections and deaths from blood-borne infections including hepatitis B virus, human immunodeficiency virus, hepatitis C virus (HCV) and variant Creutzfeldt Jakob disease, as a direct result of contaminated blood and blood products administered in the United Kingdom of Great Britain and Northern Ireland (UK). In the absence of databases of HCV infections and related deaths for all nations of the UK, a statistical model was required to estimate the number of infections and subsequent deaths from HCV acquired from blood transfusions from January 1970 to August 1991. We present this statistical model in detail alongside the results of its application to each of the four nations in the UK. We estimated that 26 800 people (95% uncertainty interval 21 300-38 800) throughout the UK were chronically infected with HCV because of contaminated blood transfusions between January 1970 and August 1991. The number of deaths up to the end of 2019 that occurred as a result of this chronic infection is estimated to be 1820 (95% uncertainty interval 650-3320)., Competing Interests: S.H., R.M., D.S. and S.B. received funding from the Infected Blood Inquiry to support this work., (© 2024 The Authors.)

A detailed understanding of the ultrafast dynamics of halogen-bonded materials is desired for designing supramolecular materials and tuning various electronic properties by external stimuli. Here, a prototypical halogen-bonded multifunctional material containing spin crossover (SCO) cations and paramagnetic radical anions is studied as a model system of photo-switchable SCO hybrid systems using ultrafast electron diffraction and two complementary optical spectroscopic techniques. Our results reveal a sequential dynamics from SCO to radical dimer softening, uncovering a key transient intermediate state. In combination with quantum chemistry calculations, we demonstrate the presence of halogen bonds in the low- and high-temperature phases and propose their role during the photoinduced sequential dynamics, underscoring the significance of exploring ultrafast dynamics. Our research highlights the promising utility of halogen bonds in finely tuning functional properties across diverse photoactive multifunctional materials., (© 2024. The Author(s).)

Purpose: To gain knowledge of the experiences and perceptions of using fitness apps by full-time wheelchair users with spinal cord injury (SCI) and to explore experiences and perceptions of using these apps in relation to barriers to and facilitators of physical activity (PA)., Materials and Methods: A qualitative design was employed. Semi-structured interviews were conducted with ten manual wheelchair users with SCI. Data were analysed using reflexive thematic analysis., Results: Four themes were developed: 1) App functionality and experience , 2) Enhancing motivation , 3) Precursors to engagement and 4) Knowledge gaps . Experience and perception were strongly influenced by app design, particularly the presence or absence of features tailored for wheelchair users. Many apps incorporated the use wearable or mountable sensors. Fitness apps were perceived to increase motivation, although, this had its limitations. Conversely, apps were reported to have limited influence on commonly reported barriers to PA. Furthermore, the data highlighted gaps in knowledge which created barriers to effective app use., Conclusions: Fitness apps were perceived to increase motivation to engage in PA in manual wheelchair users with SCI. However, more needs to be done to further develop app features for wheelchair users with SCI and to address remaining barriers to engagement.

Background: Augmented reality head-worn displays (HWDs) may enable efficient remote support in the prehospital environment due to their hand-free operability, their "see-what-I-see" features, and their ability to superimpose digital content over the environment. Methods: In this simulation-based randomized controlled study, a remote mentor used either a phone or HWD to instruct 23 physicians on how to insert a Multi-Lumen Access Catheter into a mannequin. In the phone condition, information could be exchanged only verbally. In the HWD condition, the mentor could additionally see the participant's first-person view and show reference images. We hypothesized that participants who received instructions via the HWD would achieve better procedural performance (lower task completion times, fewer errors advancing the catheter) and exhibit different communication patterns than participants who received instructions via phone. Results: The HWD did not significantly reduce task completion times or errors during catheter advancement. However, by analyzing the frequency of communication events with a Poisson regression, we could demonstrate that with the HWD, the mentor had to request situation reports less often ( p < 0.001) but provided more instructions ( p  = 0.004) and more feedback ( p  = 0.008). As a possible consequence, participants in the HWD condition rated their workload as lower than participants who used a phone to communicate ( p  = 0.45). Conclusion: The study demonstrates that HWD-based telemedicine systems can be rated positively by physicians, can benefit communication, and can provide more opportunities for the detection of clinical errors.

Introduction: There have been few controlled evaluations of Social Prescribing (SP), in which link workers support lonely individuals to engage with community-based social activities. This study reports early outcomes of a trial comparing General Practitioner treatment-as-usual (TAU) with TAU combined with Social Prescribing (SP) in adults experiencing loneliness in Queensland., Methods: Participants were 114 individuals who were non-randomly assigned to one of two conditions (SP, n  = 63; TAU, n  = 51) and assessed at baseline and 8 weeks, on primary outcomes (loneliness, well-being, health service use in past 2 months) and secondary outcomes (social anxiety, psychological distress, social trust)., Results: Retention was high (79.4%) in the SP condition. Time × condition interaction effects were found for loneliness and social trust, with improvement observed only in SP participants over the 8-week period. SP participants reported significant improvement on all other outcomes with small-to-moderate effect sizes (ULS-8 loneliness, wellbeing, psychological distress, social anxiety). However, interaction effects did not reach significance., Discussion: Social prescribing effects were small to moderate at the 8-week follow up. Group-based activities are available in communities across Australia, however, further research using well-matched control samples and longer-term follow ups are required to provide robust evidence to support a wider roll out., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dingle, Sharman, Hayes, Haslam, Cruwys, Jetten, Haslam, McNamara, Chua, Baker and Johnson.)

Recent breakthroughs in artificial intelligence (AI) and machine learning (ML) have ushered in a new era of possibilities across various scientific domains. One area where these advancements hold significant promise is model-informed drug discovery and development (MID3). To foster a wider adoption and acceptance of these advanced algorithms, the Innovation and Quality (IQ) Consortium initiated the AI/ML working group in 2021 with the aim of promoting their acceptance among the broader scientific community as well as by regulatory agencies. By drawing insights from workshops organized by the working group and attended by key stakeholders across the biopharma industry, academia, and regulatory agencies, this white paper provides a perspective from the IQ Consortium. The range of applications covered in this white paper encompass the following thematic topics: (i) AI/ML-enabled Analytics for Pharmacometrics and Quantitative Systems Pharmacology (QSP) Workflows; (ii) Explainable Artificial Intelligence and its Applications in Disease Progression Modeling; (iii) Natural Language Processing (NLP) in Quantitative Pharmacology Modeling; and (iv) AI/ML Utilization in Drug Discovery. Additionally, the paper offers a set of best practices to ensure an effective and responsible use of AI, including considering the context of use, explainability and generalizability of models, and having human-in-the-loop. We believe that embracing the transformative power of AI in quantitative modeling while adopting a set of good practices can unlock new opportunities for innovation, increase efficiency, and ultimately bring benefits to patients., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Human experiences with nature are important for our culture, economy, and health. Anthropogenically-driven climate change is causing widespread shifts in biodiversity and resident urban wildlife are no exception. We modelled over 2,000 animal species to predict how climate change will impact terrestrial wildlife within 60 Canadian and American cities. We found evidence of an impending great urban shift where thousands of species will disappear across the selected cities, being replaced by new species, or not replaced at all. Effects were largely species-specific, with the most negatively impacted taxa being amphibians, canines, and loons. These predicted shifts were consistent across scenarios of greenhouse gas emissions, but our results show that the severity of change will be defined by our action or inaction to mitigate climate change. An impending massive shift in urban wildlife will impact the cultural experiences of human residents, the delivery of ecosystem services, and our relationship with nature., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Filazzola et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Corneal cross-linking (CXL) using riboflavin and ultraviolet-A light (UVA) is a treatment used to prevent progression of keratoconus. This ex vivo study assesses the impact on CXL effectiveness, as measured by tissue enzymatic resistance and confocal microscopy, of including a pre-UVA corneal surface rinse with balanced salt solution (BSS) as part of the epithelium-off treatment protocol., Methods: Sixty-eight porcine eyes, after epithelial debridement, were assigned to six groups in three experimental runs. Group 1 remained untreated. Groups 2-6 received a 16-min application of 0.1% riboflavin/Hydroxypropyl methylcellulose (HPMC) drops, after which Group 3 was exposed to 9 mW/cm 2 UVA for 10 min, and Groups 4-6 underwent corneal surface rinsing with 0.25 mL, 1 mL or 10 mL BSS followed by 9 mW/cm 2 UVA exposure for 10 min. Central corneal thickness (CCT) was recorded at each stage. Central 8.0 mm corneal buttons from all eyes were subjected to 0.3% collagenase digestion at 37 °C and the time required for complete digestion determined. A further 15 eyes underwent fluorescence confocal microscopy to assess the impact of rinsing on stromal riboflavin concentration., Results: Application of riboflavin/HPMC solution led to an increase in CCT of 73 ± 14 µm (P < 0.01) after 16 min. All CXL-treated corneas displayed a 2-4 fold greater resistance to collagenase digestion than non-irradiated corneas. There was no difference in resistance between corneas that received no BSS rinse and those that received a 0.25 mL or 1 mL pre-UVA rinse, but each showed a greater level of resistance than those that received a 10 mL pre-UVA rinse (P < 0.05). Confocal microscopy demonstrated reduced stromal riboflavin fluorescence after rinsing., Conclusions: All protocols, with and without rinsing, were effective at enhancing the resistance to collagenase digestion, although resistance was significantly decreased, and stromal riboflavin fluorescence reduced with a 10 mL rinse. This suggests that a 10 mL surface rinse can reduce the efficacy of CXL through the dilution of the stromal riboflavin concentration., (© 2024. The Author(s).)

Public engagement with science is a core facet of the broader science ecosystem, in particular the science research and science education sectors. In this article we demarcate the benefits of dedicated laboratories along with practitioner advice pertaining to the design and running of a public engagement learning environment. A practicing public engagement laboratory and one that is currently being developed are used as illustrative cases to provide real-world insights to public engagement practitioners., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society and Division of Chemical Education, Inc.)

The cornea needs to be transparent to visible light and precisely curved to provide the correct refractive power. Both properties are governed by its structure. Corneal transparency arises from constructive interference of visible light due to the relatively ordered arrangement of collagen fibrils in the corneal stroma. The arrangement is controlled by the negatively charged proteoglycans surrounding the fibrils. Small changes in fibril organisation can be tolerated but larger changes cause light scattering. Corneal keratocytes do not scatter light because their refractive index matches that of the surrounding matrix. When activated, however, they become fibroblasts that have a lower refractive index. Modelling shows that this change in refractive index significantly increases light scatter. At the microscopic level, the corneal stroma has a lamellar structure, the parallel collagen fibrils within each lamella making a large angle with those of adjacent lamellae. X-ray scattering has shown that the lamellae have preferred orientations in the human cornea: inferior-superior and nasal-temporal in the central cornea and circumferential at the limbus. The directions at the centre of the cornea may help withstand the pull of the extraocular muscles whereas the pseudo-circular arrangement at the limbus supports the change in curvature between the cornea and sclera. Elastic fibres are also present; in the limbus they contain fibrillin microfibrils surrounding an elastin core, whereas at the centre of the cornea, they exist as thin bundles of fibrillin-rich microfibrils. We present a model based on the structure described above that may explain how the cornea withstands repeated pressure changes due to the ocular pulse., (© 2024. The Author(s).)

Measles and rubella serological diagnoses are done by IgM detection. The World Health Organization Global Measles and Rubella Laboratory Network previously endorsed Siemens Enzygnost enzyme-linked immunosorbant assay kits, which have been discontinued. A recommended replacement has not been determined. We aimed to search for suitable replacements by conducting a systematic review and meta-analysis of IgM detection methods that are currently available for measles and rubella. A systematic literature search was performed in Medline, Embase, Global Health, Cochrane Central, and Scopus on March 22 and on 27 September 2023. Studies reporting measles and/or rubella IgM detection with terms around diagnostic accuracy were included. Risk of bias was assessed using QUADAS tools. Meta-DiSc and R were used for statistical analysis. Clinical samples totalling 5,579 from 28 index tests were included in the measles meta-analysis. Sensitivity and specificity of the individual measles studies ranged from 0.50 to 1.00 and 0.53 to 1.00, respectively. Pooled sensitivity and specificity of all measles IgM detection methods were 0.94 (CI: 0.90-0.97) and 0.94 (CI: 0.91-0.97), respectively. Clinical samples totalling 4,983 from 15 index tests were included in the rubella meta-analysis. Sensitivity and specificity of the individual rubella studies ranged from 0.78 to 1.00 and 0.52 to 1.00, respectively. Pooled sensitivity and specificity of all rubella IgM detection methods were 0.97 (CI: 0.93-0.98) and 0.96 (CI: 0.93-0.98), respectively. Although more studies would be ideal, our results may provide valuable information when selecting IgM detection methods for measles and/or rubella., Competing Interests: The authors declare no conflict of interest.

Competing Interests: EP has received funding from the NHMRC and NSW Health. She is a clinical geneticist at Sydney Children’s Hospitals Network-Randwick and a member of the medical and scientific advisory committee for Rare Voices Australia, the national peak body for Australians living with a rare condition. IS has received funding from the NHMRC and the NSW Department of Health. She is also a Board member of Self Advocacy Sydney, an organisation run by and for people with intellectual disability. JS is Director of the Disability Innovation Institute, which has received funding from the NHMRC and the NSW Department of Health. JL, OAM has received funding from the NHMRC and the NSW Department of Health. She is also a Board member of Self Advocacy Sydney, an organisation run by and for people with intellectual disability. SS has received funding from the NHMRC and the NSW Department of Health. She is also an employee at Self-Advocacy Sydney, an organisation run by and for people with intellectual disability. JB and BT have received funding from the NHMRC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Asbestos identification is a complex environmental and economic challenge. Typical commercial identification of asbestos involves sending samples to a laboratory where someone learned in the field uses light microscopy and specialized mounting to identify the morphologically distinct signatures of Asbestos. In this work we investigate the use of a portable (30x) microscope which works with a smart phone camera to develop an image recognition system. 7328 images from over 1000 distinct samples of cement sheet from Melbourne, Australia were used to train a phone-based image recognition system for Asbestos identification. Three common CNN's were tested ResNet101, InceptionV3 and VGG&#95;16 with ResNet101 achieving the best result. The distinctiveness of Asbestos was found to be identified correctly 90% of the time using a phone-based system and no specialized mounting. The image recognition system was trained with ResNet101 a convolutional neural network deep learning model which weights layers with a residual function. Resulting in an accuracy of 98.46% and loss of 3.8% ResNet101 was found to produce a more accurate model for this use-case than other deep learning neural networks., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Meaghan Smith and Rosalie Hocking report financial support from Swinburne University of Technology. Michael Rolfe, Rosalie K. Hocking, Samantha Hayes, Michael Spruth, Chris MacCarthy have a provision patent "A System and Method for Asbestos Identificiation", WO2021012019A1., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Stroke is the second-leading cause of death and disability globally. Participation in physical activity (PA) is a cornerstone of secondary prevention in stroke care. Given the heterogeneous nature of stroke, PA interventions that are adaptive to individual performance are recommended. Mobile health (mHealth) has been identified as a potential approach to supporting PA poststroke. To this end, we aim to use a Sequential Multiple Assignment Randomised Trial (SMART) design to develop an adaptive, user-informed mHealth intervention to improve PA poststroke., Methods and Analysis: The components included in the 12-week intervention are based on empirical evidence and behavioural change theory and will include treatments to increase participation in Structured Exercise and Lifestyle or a combination of both. 117 participants will be randomly assigned to one of the two treatment components. At 6 weeks postinitial randomisation, participants will be classified as responders or non-responders based on participants' change in step count. Non-responders to the initial treatment will be randomly assigned to a different treatment allocation. The primary outcome will be PA (steps/day), feasibility and secondary clinical and cost outcomes will also be included. A SMART design will be used to evaluate the optimum adaptive PA intervention among community-dwelling, ambulatory people poststroke., Ethics and Dissemination: Ethical approval has been granted by the Health Service Executive Mid-Western Ethics Committee (REC Ref: 026/2022). The findings will be submitted for publication and presented at relevant national and international academic conferences TRIALS REGISTRATION NUMBER: NCT05606770., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)