Short-term effects of a park-based group mobility program on increasing outdoor walking in older adults with difficulty walking outdoors: the Getting Older Adults Outdoors (GO-OUT) randomized controlled trial.

BACKGROUND: We estimated the short-term effects of an educational workshop and 10-week outdoor walk group (OWG) compared to the workshop and 10 weekly reminders (WR) on increasing outdoor walking (primary outcome) and walking capacity, health-promoting behavior, and successful aging defined by engagement in meaningful activities and well-being (secondary outcomes) in older adults with difficulty walking outdoors. METHODS: In a 4-site, parallel-group randomized controlled trial, two cohorts of community-living older adults (≥ 65 years) reporting difficulty walking outdoors participated. Following a 1-day workshop, participants were stratified and randomized to a 10-week OWG in parks or 10 telephone WR reinforcing workshop content. Masked evaluations occurred at 0, 3, and 5.5 months. We modeled minutes walked outdoors (derived from accelerometry and global positioning system data) using zero-inflated negative binomial regression with log link function, imputing for missing observations. We modeled non-imputed composite measures of walking capacity, health-promoting behavior, and successful aging using generalized linear models with general estimating equations based on a normal distribution and an unstructured correlation matrix. Analyses were adjusted for site, participation on own or with a partner, and cohort. RESULTS: We randomized 190 people to the OWG (n = 98) and WR interventions (n = 92). At 0, 3, and 5.5 months, median outdoor walking minutes was 22.56, 13.04, and 0 in the OWG, and 24.00, 26.07, and 0 in the WR group, respectively. There was no difference between groups in change from baseline in minutes walked outdoors based on incidence rate ratio (IRR) and 95% confidence interval (CI) at 3 months (IRR = 0.74, 95% CI 0.47, 1.14) and 5.5 months (IRR = 0.77, 95% CI 0.44, 1.34). Greater 0 to 3-month change in walking capacity was observed in the OWG compared to the WR group (ßz-scored difference = 0.14, 95% CI 0.02, 0.26) driven by significant improvement in walking self-efficacy; other comparisons were not significant. CONCLUSIONS: A group, park-based OWG was not superior to WR in increasing outdoor walking activity, health-promoting behavior or successful aging in older adults with difficulty walking outdoors; however, the OWG was superior to telephone WR in improving walking capacity through an increase in walking self-efficacy. Community implementation of the OWG is discussed. TRIAL REGISTRATION: ClinicalTrials.gov NCT03292510 Date of registration: September 25, 2017.

'I have to remind myself that everyone's search is different': experiences and outcomes of searching and not searching for donor connections among donor conceived adults.

STUDY QUESTION: What are the experiences and outcomes of donor conceived adults who are actively searching for, open to contact with, or not searching for donor connections? SUMMARY ANSWER: Most participants were actively searching or open to contact, and 67% had found or been found by a connection; finding or not finding experiences were complex. WHAT IS KNOWN ALREADY: There is variation among donor conceived individuals in their interest in donor connections. Individual reasons for searching for connections, and which donor connections are searched for, also vary. Most research studies have focussed on individuals who are actively searching for their donor or donor siblings. Global increases in direct-to-consumer DNA testing and social media participation mean that connections may be made to individuals unaware of their (or their relatives') involvement with donor conception. These social and technological changes have also increased the chances of donor conceived individuals being contacted without expecting or desiring contact. STUDY DESIGN, SIZE, DURATION: This study included 88 donor conceived adults, in the UK, who participated in an online multi-method survey between January and August 2022. The survey was designed in consultation with staff and volunteers from the UK's largest community networks for donor conception families (Donor Conception Network, DCN) and donor conceived people (Donor Conceived Register Registrants' Panel, DCRRP). It was piloted by five donor conceived people before its launch. Participants were recruited with assistance from DCN and DCRRP, via social media, university mailing lists, and snowballing. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were mostly female (n = 65, 74%) and sperm donor conceived (n = 79, 90%). Of the 88 participants, 39 (44%) were actively searching for their donor connections, 44 (50%) were open to contact but not actively searching, and 5 (6%) were not searching. Questions were closed (yes/no, rating scale, or multiple choice) or open-ended, addressing experiences of donor conception, searching for connections, and finding or not finding connections. Data were analysed both quantitatively and qualitatively. MAIN RESULTS AND THE ROLE OF CHANCE: Quantitative results showed no differences between the groups on any demographic variables or in when or how they found out about being donor conceived, and no differences between active searchers and those open to contact in whether they had found their donor connections. Significant differences were found between groups in their interest in their genetic history and the perceived importance of genetics to their sense of identity, with active searchers being more interested and rating this as more important than those open to contact. Methods of searching significantly differed across groups, with active searchers using genetic testing and social media more than those open to contact. 59 participants across all groups (active searchers (n = 29, 74%), open to contact (n = 27, 61%), not open to contact (n = 3, 60%)) had found or been found by a donor connection. Experiences of finding or not finding donor connections among participants actively searching or open to contact were captured by the theme complexities, with six subthemes: uncertainties in searching and relating; searching as open-ended; different donor connections, different experiences; expectations and realities; searching and finding or not finding as catalysing change; and experiences of other donor conceived people. LIMITATIONS, REASONS FOR CAUTION: Most participants were members of relevant community organizations. As is common in research in this area, the sample was mostly female and conceived using donor sperm. Donor conceived people who are disinterested in donor connections may be unlikely to participate in research on this topic. WIDER IMPLICATIONS OF THE FINDINGS: The nature and impact of the search process itself should be considered when developing appropriate mechanisms of support for all donor conceived people, regardless of whether they are actively searching for connections or not. Further research should seek to better understand how donor conceived people with varying levels of interest in searching for donor connections differ from one another. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the UK Economic and Social Research Council [New Investigator Award ES/S015426/1]. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Candidacy 2.0 (CC) - an enhanced theory of access to healthcare for chronic conditions: lessons from a critical interpretive synthesis on access to rheumatoid arthritis care.

BACKGROUND: The Dixon-Woods et al. Candidacy Framework, a valuable tool since its 2006 introduction, has been widely utilized to analyze access to various services in diverse contexts, including healthcare. This social constructionist approach examines micro, meso, and macro influences on access, offering concrete explanations for access challenges rooted in socially patterned influences. This study employed the Candidacy Framework to explore the experiences of individuals living with rheumatoid arthritis (RA) and their formal care providers. The investigation extended to assessing supports and innovations in RA diagnosis and management, particularly in primary care. METHODS: This systematic review is a Critical Interpretive Synthesis (CIS) of qualitative and mixed methods literature. The CIS aimed to generate theory from identified constructs across the reviewed literature. The study found alignment between the seven dimensions of the Candidacy Framework and key themes emerging from the data. Notably absent from the framework was an eighth dimension, identified as the "embodied relational self." This dimension, central to the model, prompted the proposal of a revised framework specific to healthcare for chronic conditions. RESULTS: The CIS revealed that the eight dimensions, including the embodied relational self, provided a comprehensive understanding of the experiences and perspectives of individuals with RA and their care providers. The proposed Candidacy 2.0 (Chronic Condition (CC)) model demonstrated how integrating approaches like Intersectionality, concordance, and recursivity enhanced the framework when the embodied self was central. CONCLUSIONS: The study concludes that while the original Candidacy Framework serves as a robust foundation, a revised version, Candidacy 2.0 (CC), is warranted for chronic conditions. The addition of the embodied relational self dimension enriches the model, accommodating the complexities of accessing healthcare for chronic conditions. TRIAL REGISTRATION: This study did not involve a health care intervention on human participants, and as such, trial registration is not applicable. However, our review is registered with the Open Science Framework at https://doi.org/10.17605/OSF.IO/ASX5C .

Perspectives on Academic Training in Clinical Oncology in the United Kingdom: A National Cross-Sectional Analysis.

AIMS: There are longstanding concerns relating to clinical academic training pipelines, with evidence for multiple barriers and enablers to clinical academic career progression. We sought to assess the extent to which these and other factors apply to academic training in clinical oncology in the United Kingdom. MATERIALS AND METHODS: A cross-sectional survey was undertaken using a bespoke, pre-piloted online electronic questionnaire that was distributed to clinical oncology specialty trainees and consultants who had at any point between January 2013-January 2024 commenced an academic post whilst in training. Collated information included demographic data, location and stage of training, research experience and ambitions, research skill confidence and academic career progression. RESULTS: Seventy eligible responses were included, representing 84% (n = 16/19) of UK training deaneries. Thirty-seven (53%) of the respondents had obtained their certificate of completion of training (CCT) whilst 11% (n = 8/70) and 40% (n = 28/70) were at specialty trainee level and respectively pre- or within-/post-doctoral studies. Of 34 post-CCT respondents, 58% (n = 20) had ongoing research commitments but this reached 30% of their overall activity for just 30% (n = 10). Barriers to academic progression included clinical training requirements, post availability and limited mentorship. Most (60%; n = 35/58) undertook doctoral studies in their final two training years. A majority of respondents lacked confidence in radiation oncology (RO) skills relevant to their career ambitions, with 60%, 40% and 30%, respectively, confident in RO clinical research outcome evaluation, in vitro radiation analyses and using RO animal models. CONCLUSION: These data provide a granular, long-term analysis of academic clinical oncology training at a national level; identifying poor progression to research independence underlined by limited confidence in RO research skills and multiple barriers to academic career progression. These data provide areas in which policy makers, research funders and training programmes can focus to improve academic training in clinical oncology.

T staging esophageal tumors with x rays.

With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor T staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment.

Global availability and uptake of psychological services for adults, caregivers and children with food allergy.

BACKGROUND: Food allergy (FA) is associated with poor health-related quality of life and high levels of psychological distress. Psychological support is extremely important but not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) study, we aimed to assess psychological distress and service use among adults, caregivers and children with FA in a global survey. METHODS: Participants (n = 1329 adults with FA; n = 1907 caregivers of children with FA) from >20 countries were recruited through patient organisations, social media advertisements and online survey panels to complete an online survey. Surveys were available in six languages. RESULTS: A total of 67.7% of adults and 77.2% of caregivers reported direct experience, and 51.6% of caregivers said their child had experienced FA-related psychological distress. The most commonly reported issue was anxiety about having an allergic reaction. Less than 20% had been assessed for FA-related psychological distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA-related mental health disorder (all p < .001). The United Kingdom, Australia and Brazil had the highest number of participants reporting distress. The most commonly reported barrier to seeing a mental health professional was cost. CONCLUSIONS: FA-related distress is common across countries, but with substantial country-to-country variability. Allergy providers are encouraged to routinely assess families for psychological distress and provide access to appropriate mental health resources. Development and implementation of evidence-based, patient-informed accessible, affordable FA interventions in multiple languages is urgently needed.

A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

The limitations of testicular organoids: are they truly as promising as we believe?

Organoid systems have revolutionised various facets of biological research by offering a three-dimensional (3D), physiologically relevant in vitro model to study complex organ systems. Over recent years, testicular organoids have been publicised as promising platforms for reproductive studies, disease modelling, drug screening, and fertility preservation. However, the full potential of these systems has yet to be realised due to inherent limitations. This paper offers a comprehensive analysis of the current challenges associated with testicular organoid models. Firstly, we address the inability of current organoid systems to fully replicate the intricate spatial organisation and cellular diversity of the in vivo testis. Secondly, we scrutinise the fidelity of germ cell maturation within the organoids, highlighting incomplete spermatogenesis and epigenetic inconsistencies. Thirdly, we consider the technical challenges faced during organoid culture, including nutrient diffusion limits, lack of vasculature, and the need for specialised growth factors. Finally, we discuss the ethical considerations surrounding the use of organoids for human reproduction research. Addressing these limitations in combination with integrating complementary approaches, will be essential if we are to advance our understanding of testicular biology and develop novel strategies for addressing reproductive health issues in males.

Participants' perceived benefits from the GLA:D™ program for individuals living with hip and knee osteoarthritis: a qualitative study.

BACKGROUND: The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip osteoarthritis (OA), has been shown to benefit participants by reducing pain, improving function, and quality of life. Standardized reporting in the GLA:D databases enabled the measurement of self-reported and performance-based outcomes. There is a paucity of qualitative research on the participants' perceptions of this program, and it is important to understand whether participants' perceptions of the benefits of the program align with reported quantitative findings. METHODS: We conducted semi-structured telephone interviews with individuals who participated in the GLA:D program from January 2017 to December 2018 in Alberta, Canada. Data were analyzed using an interpretive description approach and thematic analysis to identify emergent themes and sub-themes associated with participants perceived benefits of the GLA:D program. We analyzed the data using NVivo Pro software. Member checking and bracketing were used to ensure the rigour of the analysis. RESULTS: 30 participants were interviewed (70% female, 57% rural, 73% knee OA). Most participants felt the program positively benefited them. Two themes emerged from the analysis: wellness and self-efficacy. Participants felt the program benefited their wellness, particularly with regard to pain relief, and improvements in mobility, strength, and overall well-being. Participants felt the program benefited them by promoting a sense of self-efficacy through improving the confidence to perform exercise and routine activities, as well as awareness, and motivation to manage their OA symptoms. Twenty percent of participants felt no benefits from the program due to experiencing increased pain and feeling their OA was too severe to participate. DISCUSSION: The GLA:D program was viewed as beneficial to most participants, this study also identified factors (e.g., severe OA, extreme pain) as to why some participants did not experience meaningful improvements. Early intervention with the GLA:D program prior to individuals experiencing severe OA could help increase the number of participants who experience benefits from their participation. CONCLUSION: As the GLA:D program expands across jurisdictions, providers of the program may consider recruitment earlier in disease progression and targeting those with mild and moderate OA.

Exploring the influence of weather variability and climate change on health outcomes in people living with dementia: A scoping review protocol.

Environmental factors resulting from climate change and air pollution are risk factors for many chronic conditions including dementia. Although research has shown the impacts of air pollution in terms of cognitive status, less is known about the association between climate change and specific health-related outcomes of older people living with dementia. In response, we outline a scoping review protocol to systematically review the published literature regarding the evidence of climate change, including temperature and weather variability, on health-related quality of life, morbidity, mobility, falls, the utilization of health resources, and mortality among older adults living with dementia. This scoping review will be guided by the framework proposed by Arksey and O'Malley. Electronic search (Medline, Embase, PsycINFO, CINAHL, Scopus, Web of Science) using relevant subject headings and synonyms for two concepts (older people with dementia, weather/ climate change). No publication date or other restrictions will be applied to the search strategy. No language restriction will be applied in order to understand the impact of non-English studies in the literature. Eligible studies must include older adults (65+years) with dementia living in the community and investigate the impacts of climate change and/or weather on their health-related quality of life, morbidity, mobility, falls, use of health resources and mortality. Two independent reviewers will screen abstracts and select those for a full-text review, perform these reviews, select articles for retention, and extract data from them in a standardized manner. This data will then be synthesized and interpreted. OSF registration: DOI: 10.17605/OSF.IO/YRFM8.

The effect of coronal plane angulation on patient reported outcome measures of operatively treated distal femur fractures: A multi-center prospective evaluation.

OBJECTIVES: The goal of this trial was to determine whether coronal plane angulation affects functional and clinical outcomes after the fixation of distal femur fractures. DESIGN: Multicenter, randomized controlled trial SETTING: 20 academic trauma centers PATIENTS/PARTICIPANTS: 156 patients with distal femur fractures were enrolled. 123 patients were followed 12 months. There was clinical outcome data available for 105 patients at 3 months, 95 patients at 6 months and 81 patients at one year. INTERVENTION: Lateral locked plating or retrograde intramedullary nailing MAIN OUTCOME MEASUREMENTS: Radiographic alignment, functional scoring including SMFA, Bother Index, and EQ-5D. Clinical scoring of walking ability, need for ambulatory support and ability to manage stairs. RESULTS: At 3 months, there was no difference between groups (varus, neutral or valgus) with respect to any of the clinical functional outcome scores measured. At 6 months, compared to those with neutral alignment, patients with varus angulation had a worse Stair Climbing score (4.33 vs. 2.91, p = 0.05). At 12 months, the average patient with neutral or valgus alignment needed less ambulatory support than the average patient in varus. Walking distance ability was no different between the groups at any time point. With respect to the validated patient-based outcome scores, we found no statistical difference in in the SMFA, Bother, or EQ-5D between patients with valgus or varus mal-alignment and those with neutral alignment at any time point (p > 0.05). Regardless of coronal angulation, the SMFA trended towards lower (improved) scores over time, while EQ-5D scores for patients with varus angulation did not improve over time. CONCLUSIONS: Valgus angulation and neutral angulation may be better tolerated in terms of clinical outcomes like stair climbing and need for ambulatory support than varus angulation, though patient reported outcome measures like the SMFA, Bother Index and EQ-5D show no statistical significance. Most patients with distal femur fractures tend to improve during the first year after injury but many remain significantly affected at 12 months post injury.

Farming and the risk of developing osteoarthritis in Alberta, Canada.

INTRODUCTION: Because farming is a physically demanding occupation, farmers may be susceptible to developing osteoarthritis (OA). The aim of this study was to determine the risk of developing OA in Canadian farm, non-farm rural and urban residents. METHODS: A retrospective cohort study of five Alberta health administrative databases examined the risk of developing OA among three groups: farm (n=143 431), non-farm rural (n=143 431) and urban (n=143 431) residents over the fiscal years 2000-2001 through 2020-2021. The algorithm for OA ascertainment defined cases based on criteria including one hospital admission, two physician visits within a 2-year interval, or two ambulatory care visits within 2 years. Incidence rates, lifetime risk, and mortality rates were calculated. Cox proportional hazard models compared the incidence of OA for the three groups over the 21 years. RESULTS: A total of 26 957 OA cases were identified among 1 706 256 person-years (PYs) in the farm cohort. The crude incidence rate of OA over a period of 21 years ranged from 19.1 (95% confidence interval (CI) 18.6-19.6) per 1000 PYs in 2001 to 10.0 (95% CI 9.6-10.5) per 1000 PYs in 2021. The overall incidence rate was higher in the farm group (15.8 (95%CI 15.6-16.0) per 1000 PYs) as compared to the non-farm rural (14.7 (95%CI 14.5-14.9) per 1000 PYs) and the urban groups (13.3 (95%CI 13.1-13.4) per 1000 PYs). After adjusting for age and sex, the farm (6%; 95%CI 4-8%), and non-farm rural (9%; 95%CI 7-12%) groups had higher incidence rates than the urban group. The unadjusted non-injury mortality rate for the farm group with OA was lower (13.2 (95%CI 12.9-13.5) per 1000 PYs) than both the urban (14.5; 95%CI 14.1-14.8) and rural (18.0; 95%CI 17.6-18.4) groups. After adjusting for mortality, the lifetime risk of developing OA was 27.7% for farm residents, 25.6% for the non-farm rural cohort, and 24.0% for the urban cohort. CONCLUSION: When accounting for age and sex, farm and non-farm rural residents have a higher risk of developing OA as compared to the urban population. The higher mortality-adjusted lifetime risk of developing OA among farm residents highlights the necessity of specific interventions aimed at reducing the impact of this condition in rural communities. Further research is required to identify specific occupational and lifestyle risk factors associated with OA among farmers and to develop effective strategies for prevention and management.

Objective Linguistic Markers Associated with Callous-Unemotional Traits in Early Childhood.

BACKGROUND: Callous-unemotional (CU) traits are associated with interpersonal difficulties and risk for severe conduct problems (CP). The ability to communicate thoughts and feelings is critical to social success, with language a promising treatment target. However, no prior studies have examined objective linguistic correlates of childhood CU traits in early childhood, which could give insight into underlying risk mechanisms and novel target treatments. METHODS: We computed lexical (positive emotion, sad, and anger words) and conversational (interruptions and speech rate) markers produced by 131 children aged 5-6 years (M = 5.98; SD = 0.54, 58.8% female) and their parents while narrating wordless storybooks during two online visits separated by 6-8 weeks (M = 6.56, SD = 1.11; two books, order counterbalanced). Audio recordings were diarized, time-aligned, and orthographically transcribed using WebTrans. Conversational markers were calculated using R and word frequencies were calculated using Linguistic Inquiry and Word Count (LIWC) software. We examined links between child CU traits and linguistic markers, and explored whether relationships were moderated by child sex. RESULTS: Higher CU traits were associated with fewer positive emotion words produced by parents and children. Higher CU traits were also associated with greater concordance in the degree of interruptions and expression of anger emotion words by parents and children. CONCLUSIONS: Results suggest that objective linguistic correlates of CU traits are detectable during early childhood, which could inform adjunctive treatment modules that improve outcomes by precisely tracking and targeting subtle communication patterns.

Evaluating Readmission Rates for a Statewide In-Home Ecosystemic Family-Based Treatment Program for Youth with Serious Emotional Disturbance.

Family Based Mental Health Services (FBMHS) with an embedded clinical model, Ecosystemic Structural Family Therapy, is an intervention designed for youth with a serious emotional disturbance (SED) who are at risk of out-of-home placement. The current evaluation examines the association between receipt of FBMHS and rates of out-of-home and community-based care during and after an episode of FBMHS. We identified 25,016 Medicaid-enrolled youth ages 3 to 17 years with receipt of a new FBMHS episode from 1/1/2015 to 6/30/2021. 14% of youth received out-of-home services. Rates of out-of-home service decreased during receipt of FBMHS (14.25-6.98%, p < .0001) and remained lower 6 months following discharge (to 6.95%, p < .0001). Short and longer doses of service were both associated with decreased rates of out-of-home services. FBMHS has been scaled across a large geographic area and is associated with lower rates of out-of-home placement for youth with SED.

Attentional, anticipatory and spatial cognition fluctuate throughout the menstrual cycle: Potential implications for female sport.

Current research suggests that menstruating female athletes might be at greater risk of musculoskeletal injury in relation to hormonal changes throughout the menstrual cycle. A separate body of work suggests that spatial cognition might also fluctuate in a similar manner. Changes in spatial cognition could, in theory, be a contributing risk factor for injury, especially in fast-paced sports that require precise, millisecond accuracy in interactions with moving objects in the environment. However, existing theories surrounding causes for increased injury risk in menstruating females largely focus on biomechanical mechanisms, with little consideration of possible cognitive determinants of injury risk. Therefore, the aim of this proof-of-principle study was to explore whether menstruating females exhibit fluctuations in cognitive processes throughout their cycle on a novel sport-oriented cognitive test battery, designed to measure some of the mental processes putatively involved in these sporting situations. A total of 394 participants completed an online cognitive battery, a mood scale and a symptom questionnaire twice, 14 days apart. After exclusions, 248 eligible participants were included in the analyses (mean: 28 ± 6 years) (male = 96, female(menstruating) = 105, female(contraception) = 47). Cycle phase for menstruating females was based on self-reported information. The cognitive battery was designed to measure reaction times, attention, visuospatial functions (including 3D mental rotation) and timing anticipation. Three composite scores were generated using factor analysis with varimax rotation (Errors, Reaction Time, Intra-Individual Variability). Mixed model ANOVAs and repeated measures ANOVAs were performed to test for between and within-subject effects. There was no group difference in reaction times and accuracy between males and females (using contraception and not). However, within subject analyses revealed that regularly menstruating females performed better during menstruation compared to being in any other phase, with faster reaction times (10ms c.ca, p < 0.01), fewer errors (p < 0.05) and lower dispersion intra-individual variability (p < 0.05). In contrast they exhibited slower reaction times (10ms c.ca, p < 0.01) and poorer timing anticipation (p < 0.01) in the luteal phase, and more errors in the predicted ovulatory phase (p < 0.01). Self-reported mood, cognitive and physical symptoms were all worst during menstruation (p < 0.01), and a significant proportion of females felt that their symptoms were negatively affecting their cognitive performance during menstruation on testing day, which was incongruent with their actual performance. These findings suggest that visuospatial and anticipatory processes may fluctuate throughout the menstrual cycle in the general population, with better performance during the menstrual phase and poorer performance during the luteal phase. If these extend to associations between phase-specific cognitive performance and injury incidence, they would support a cognitive theory of determinants of injury risk in cycling female athletes, opening an opportunity to develop mitigation strategies where appropriate.

Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma.

BACKGROUND AND AIM: There has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. METHODS: A systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. RESULTS: Ninety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5-3.125Gy per fraction (total dose 50-60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6-88.0%. CONCLUSION: These data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. REGISTRATION DETAILS: PROSPERO; CRD42023457791.

Bone-anchored prostheses for transfemoral amputation: a systematic review of outcomes, complications, patient experiences, and cost-effectiveness.

Introduction: Bone-anchored prostheses (BAP) are an advanced reconstructive surgical approach for individuals who had transfemoral amputation and are unable to use the conventional socket-suspension systems for their prostheses. Access to this technology has been limited in part due to the lag between the start of a new procedure and the availability of evidence that is required before making decisions about widespread provision. This systematic review presents as a single resource up-to-date information on aspects most relevant to decision makers, i.e., clinical efficacy, safety parameters, patient experiences, and health economic outcomes of this technology. Methods: A systematic search of the literature was conducted by an information specialist in PubMed, MEDLINE, Embase, CINAHL, Cochrane Library, the Core Collection of Web of Science, CADTH's Grey Matters, and Google Scholar up until May 31, 2023. Peer-reviewed original research articles on the outcomes of clinical effectiveness (health-related quality of life, mobility, and prosthesis usage), complications and adverse events, patient experiences, and health economic outcomes were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and ROBINS-I, as appropriate. Results: Fifty studies met the inclusion criteria, of which 12 were excluded. Thirty-eight studies were finally included in this review, of which 21 reported on clinical outcomes and complications, 9 case series and 1 cohort study focused specifically on complications and adverse events, and 2 and 5 qualitative studies reported on patient experience and health economic assessments, respectively. The most common study design is a single-arm trial (pre-/post-intervention design) with varying lengths of follow-up. Discussion: The clinical efficacy of this technology is evident in selected populations. Overall, patients reported increased health-related quality of life, mobility, and prosthesis usage post-intervention. The most common complication is a superficial or soft-tissue infection, and more serious complications are rare. Patient-reported experiences have generally been positive. Evidence indicates that bone-anchored implants for prosthesis fixation are cost-effective for those individuals who face significant challenges in using socket-suspension systems, although they may offer no additional advantage to those who are functioning well with their socket-suspended prostheses.

A novel electronic health record-based, machine-learning model to predict severe hypoglycemia leading to hospitalizations in older adults with diabetes: A territory-wide cohort and modeling study.

BACKGROUND: Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes. METHODS AND FINDINGS: We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation. CONCLUSIONS: Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk.

Using Inundation Extents to Predict Microbial Contamination in Private Wells after Flooding Events.

Disaster recovery poses unique challenges for residents reliant on private wells. Flooding events are drivers of microbial contamination in well water, but the relationship observed between flooding and contamination varies substantially. Here, we investigate the performance of different flood boundaries─the FEMA 100 year flood hazard boundary, height above nearest drainage-derived inundation extents, and satellite-derived extents from the Dartmouth Flood Observatory─in their ability to identify well water contamination following Hurricane Florence. Using these flood boundaries, we estimated about 2600 wells to 108,400 private wells may have been inundated─over 2 orders of magnitude difference based on boundary used. Using state-generated routine and post-Florence testing data, we observed that microbial contamination rates were 7.1-10.5 times higher within the three flood boundaries compared to routine conditions. However, the ability of the flood boundaries to identify contaminated samples varied spatially depending on the type of flooding (e.g., riverine, overbank, coastal). While participation in testing increased after Florence, rates were overall still low. With <1% of wells tested, there is a critical need for enhanced well water testing efforts. This work provides an understanding of the strengths and limitations of inundation mapping techniques, which are critical for guiding postdisaster well water response and recovery.