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Introduction: One-third of adults aged 65+ fall annually. Injuries from falls can be devastating for individuals and account for 1.5% of annual healthcare spending. With the growing ageing population, falls place increased strain on scarce health resources. Prevention strategies that target individuals at high risk for falls demonstrate the best value for money; however, limited efficiency (ie, cost-effectiveness) information for fall prevention interventions hinders the implementation of effective falls prevention programmes. Living systematic reviews provide a timely up-to-date evidence-based resource to inform clinical guidelines and health policy decisions. This protocol details the methodology for a living systematic review of the efficiency (ie, cost-effectiveness) of fall prevention interventions for older adults in three settings: community-dwelling, aged care and hospitals., Methods and Analysis: This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. Peer-reviewed economic evaluations of controlled clinical trials or health state models will be included. Reports will be obtained through monthly systematic searches of CENTRAL (Ovid), CINAHL (EBSCO), Embase (Ovid), MEDLINE (Ovid), SCOPUS (Elsevier) and Web of Science (Clarivate) alongside snowballing and handsearching EconLit and the Tufts Cost Effectivness Analysis Registry. Screening, data extraction, quality assessment and risk of bias will be assessed by multiple reviewers. The primary outcomes will be the incremental cost-effectiveness (ie, incremental cost per fall prevented), incremental cost-utility (ie, incremental cost per quality-adjusted life year gained) or cost-benefit ratio. Additional outcomes will include falls and cost-related measures. All economic outcomes will be reported in a common year and currency. Results will be reported as a narrative synthesis; meta-analysis will be considered based on data quality, suitability and availability., Ethics and Dissemination: Ethical approval is not required as primary human data will not be collected. Results will be disseminated through peer-reviewed publications and a dedicated website., Prospero Registration Number: CRD42024532485., 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.)

Objective: This review evaluates current literature on intensity selection, perceptual responses, activity enjoyment and adherence rates of exergaming., Methods: The literature search identified manuscripts that investigated exercise intensity, perceptual responses, or exercise adherence of exergaming in young adults., Results: Based on results of 29 studies, the current review suggest some exergaming activities have the potential to elicit moderate to vigorous exercise intensity and could potentially be substituted for traditional exercise. Additionally, exergame activities may aid in the start of exercise adherence by lowering the individual's perceived exertion when playing exergames. Exergaming not only has the potential to enhance enjoyment through an exercise objective but also through the distracting nature of video games., Conclusions: Exergaming shows potential to be substituted for traditional exercise and could offer a new, varied form of exercise for sedentary individuals. Future research should examine the influence of exergaming experience on intensity selection and adherence rates.

Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK oncoproteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but their influence on lipid metabolite levels remain unknown. To measure RON- and DEK-dependent steady-state lipid metabolite levels, a nuclear magnetic resonance (NMR)-based approach was utilized. The observed differences identified a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis-free survival (DMFS), post-progression survival (PPS), and recurrence-free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, whereas DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts poor outcomes for patients with breast cancer patients. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence., 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 Vicente-Muñoz, Davis, Lane, Lane, Waltz and Wells.)

Coordination of adaptive metabolism through cellular signaling networks and metabolic response is essential for balanced flow of energy and homeostasis. Post-translational modifications such as phosphorylation offer a rapid, efficient, and dynamic mechanism to regulate metabolic networks. Although numerous phosphorylation sites have been identified on metabolic enzymes, much remains unknown about their contribution to enzyme function and systemic metabolism. In this study, we stratify phosphorylation sites on metabolic enzymes based on their location with respect to functional and dimerization domains. Our analysis reveals that the majority of published phosphosites are on oxidoreductases, with particular enrichment of phosphotyrosine (pY) sites in proximity to binding domains for substrates, cofactors, active sites, or dimer interfaces. We identify phosphosites altered in obesity using a high fat diet (HFD) induced obesity model coupled to multiomics, and interrogate the functional impact of pY on hepatic metabolism. HFD induced dysregulation of redox homeostasis and reductive metabolism at the phosphoproteome and metabolome level in a sex-specific manner, which was reversed by supplementing with the antioxidant butylated hydroxyanisole (BHA). Partial least squares regression (PLSR) analysis identified pY sites that predict HFD or BHA induced changes of redox metabolites. We characterize predictive pY sites on glutathione S-transferase pi 1 (GSTP1), isocitrate dehydrogenase 1 (IDH1), and uridine monophosphate synthase (UMPS) using CRISPRi-rescue and stable isotope tracing. Our analysis revealed that sites on GSTP1 and UMPS inhibit enzyme activity while the pY site on IDH1 induces activity to promote reductive carboxylation. Overall, our approach provides insight into the convergence points where cellular signaling fine-tunes metabolism.

Aberrant endoplasmic reticulum (ER) and inner nuclear membrane (INM) proteins are destroyed through ER-associated degradation (ERAD) and INM-associated degradation (INMAD). We previously showed the Hrd1, Doa10, and Asi ERAD and INMAD ubiquitin ligases (E3s) in Saccharomyces cerevisiae confer resistance to hygromycin B, which distorts the ribosome decoding center. Here, we assessed the requirement of Ubc6 and Ubc7, the primary ERAD and INMAD ubiquitin-conjugating enzymes (E2s) for hygromycin B resistance. Loss of either E2 sensitized cells to hygromycin B, with UBC7 deletion having a greater impact, consistent with characterized roles for Ubc6 and Ubc7 in ER and INM protein quality control., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

The development and growth of cancer is fundamentally dependent on pro-tumor changes in metabolism. Cancer cells generally shift away from oxidative phosphorylation as the primary source of energy and rely more heavily on glycolysis. Receptor tyrosine kinases (RTKs) are a type of receptor that is implicated in this shift to pro-tumor metabolism. RTKs are important drivers of cancer growth and metastasis. One such family of RTKs is the MET family, which consists of MET and RON (MST1R). The overexpression of either MET or RON has been associated with worse cancer patient prognosis in a variety of tumor types. Both MET and RON signaling promote increased glycolysis by upregulating the expression of key glycolytic enzymes via increased MYC transcription factor activity. Additionally, both MET and RON signaling promote increased cholesterol biosynthesis downstream of glycolysis by upregulating the expression of SREBP2-induced cholesterol biosynthesis enzymes via CTTNB1. These changes in metabolism, driven by RTK activity, provide potential targets in limiting tumor growth and metastasis via pharmacological inhibition or modifications in diet. This review summarizes pro-tumor changes in metabolism driven by the MET family of RTKs. In doing so, we will offer our unique perspective on metabolic pathways that drive worse patient prognosis and provide suggestions for future study.

Background: Image-guided reduction of intussusception is considered a radiologic urgency requiring 24-h radiologist and technologist availability., Objective: To assess whether a delay of 6-12 h between US diagnosis and fluoroscopic reduction of ileocolic intussusception affects the success frequency of fluoroscopic reduction., Materials and Methods: Retrospective review of 0-5-year-olds undergoing fluoroscopic reduction for ileocolic intussusception from 2013 to 2023. Exclusions were small bowel intussusception, self-reduced intussusception, first fluoroscopic reduction attempt>12 h after US, prior bowel surgery, inpatient status, and patient transferred for recurrent intussusception. Data collected included demographics, symptoms, air/contrast enema selection, radiation dose, reduction failure, 48-h recurrence, surgery, length of stay, and complications. Comparisons between<6-h and 6-12-h delays after ultrasound diagnosis were made using chi-square, Fisher's exact test, and Mann-Whitney U tests (P< 0.05 considered significant)., Results: Of 438 included patients, 387 (88.4%) were reduced in <6 h (median age 1.4 years) and 51 (11.7%) were reduced between 6 and 12 h (median age 2.05 years), with median reduction times of 1:42 and 7:07 h, respectively. There were no significant differences between the groups for reduction success (<6 h 87.3% vs. 6-12 h 94.1%; P-value = 0.16), need for surgery (<6 h 11.1% vs. 6-12 h 3.9%; P-value=0.112), recurrence of intussusception within 48 h after reduction (<6 h 9.3% vs. 6-12 h 15.7%; P-value=0.154), or length of hospitalization (<6 h 21:07 h vs. 6-12 h 20:03 h; P-value=0.662)., Conclusion: A delay of 6-12 h between diagnosis and fluoroscopic reduction of ileocolic intussusception is not associated with reduced fluoroscopic reduction success, need for surgical intervention after attempted reduction, recurrence of intussusception following successful reduction, or hospitalization duration after reduction., (© 2024. The Author(s).)

Objective: Clinicians treating patients with patellofemoral pain (PFP) rely on consensus statements to make the best practice recommendations in the absence of definitive evidence on how to manage PFP. However, the methods used to generate and assess agreement for these recommendations have not been examined. Our objective was to map the methods used to generate consensus-based recommendations for PFP and apply four novel questions to assess the rigour of consensus development., Design: Scoping review., Data Sources: We searched Medline, SPORTDiscus, CINAHL and Embase from inception to May 2022 to identify consensus-derived statements or practice guidelines on PFP. The Joanna Briggs Institute Manual for Evidence Synthesis was followed to map the existing evidence. We measured the consensus methods based on four sets of questions addressing the panel composition, application of the consensus method chosen, agreement process and the use of evidence mapping., Eligibility Criteria: All consensus statements or clinical guidelines on PFP were considered., Results: Twenty-two PFP consensus statements were identified. Panel composition: 3 of the 22 (14%) consensus groups reported the panellists' experience, 2 (9%) defined a desired level of expertise, 10 (45%) reported panellist sex and only 2 (9%) included a patient. Consensus method: 7 of 22 (32%) reported using an established method of consensus measurement/development. Agreement process: 10 of 22 (45%) reported their consensus threshold and 2 (9%) acknowledged dissenting opinions among the panel. Evidence mapping: 6 of 22 (27%) reported using systematic methods to identify relevant evidence gaps., Conclusions: PFP consensus panels have lacked diversity and excluded key partners including patients. Consensus statements on PFP frequently fail to use recognised consensus methods, rarely describe how 'agreement' was defined or measured and often neglect to use systematic methods to identify evidence gaps., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: None disclosed.

Purpose: Cognitive deficits are common among stroke survivors and impact their functional independence. Despite the prevalence of cognitive deficits after stroke, cognitive function is largely overlooked in post-stroke care. The aim of this qualitative study was to explore the experiences of individuals living with post-stroke cognitive changes to understand the impact of these changes on their daily lives., Materials and Methods: Semi-structured interviews were conducted with a purposeful sample of thirteen community-dwelling adults 50 years and older with chronic stroke who self-identified cognitive changes post-stroke. Interviews were transcribed and an inductive thematic analysis was completed., Results: Four key themes were identified: 1) inability to maintain everyday activities; 2) experiencing emotional responses to living with post-stroke cognitive changes; 3) a shrinking social world and; 4) seeking care for cognitive health post-stroke., Conclusions: Post-stroke cognitive changes were described by participants as a driving force behind negative shifts in their daily lives, emotional health, and social connections after stroke. Despite seeking care for their post-stroke cognitive changes, many participants were unable to find support in mainstream healthcare. There is a demonstrated need to further elucidate the gaps in care for post-stroke cognitive deficits and implement community interventions targeting cognitive health post-stroke.

Background: Treatment-resistant depression (TRD) occurs more commonly in women. Deep brain stimulation (DBS) is an emerging treatment for TRD, and its efficacy continues to be explored. However, differences in treatment outcomes between males and females have yet to be explored in formal analysis., Methods: A PRISMA-compliant systematic review of DBS for TRD studies was conducted. Patient-level data were independently extracted by two authors. Treatment response was defined as a 50 % or greater reduction in depression score. Percent change in depression scores by gender were evaluated using random-effects analyses., Results: Of 737 records, 19 studies (129 patients) met inclusion criteria. The mean reduction in depression score for females was 57.7 % (95 % CI, 64.33 %-51.13 %), whereas for males it was 35.2 % (95 % CI, 45.12 %-25.23 %) (p < 0.0001). Females were more likely to respond to DBS for TRD when compared to males (OR = 2.44, 95 % CI 1.06, 1.95). These differences varied in significance when stratified by DBS anatomical target, age, and timeframe for responder classification., Limitations: Studies included were open-label trials with small sample sizes., Conclusions: Our findings suggest that females with TRD respond at higher rates to DBS treatment than males. Further research is needed to elucidate the implications of these results, which may include connectomic sexual dimorphism, depression phenotype variations, or unrecognized symptom reporting differences. Methodological standardization of outcome scales, granular demographic data, and individual subject outcomes would allow for more robust comparisons between trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To decrease call burden on pediatric neuroradiologists, we developed guidelines for appropriate use of MR overnight. These guidelines were implemented using triage by in-house generalist pediatric radiologists. Process measures and balancing measures were assessed during implementation., Methods: For this improvement project, interdepartmental consensus guidelines were developed using exploratory mixed-methods design. Implementation of triage used plan-do-study-act cycles. Process measures included reduction in the number of telephone calls, frequency of calls, triage decisions, and number and type of examinations ordered. Balancing measures included burden of time and effort to the generalist radiologists. Differences in examination orders between implementation intervals was assessed using Kruskal-Wallis, with significance at P < .05., Results: Consensus defined MR requests as "do," "defer," or "divert" (to CT). Guidelines decreased neuroradiologist calls 74% while adding minimal burden to the generalist radiologists. Most nights had zero or one triage request and the most common triage decision was "do," and the most common examination was routine brain MR. Number of MR ordered and completed overnight did not significantly change with triage., Discussion: Multidisciplinary consensus for use of pediatric neurological MR during limited resource hours overnight is an example of imaging stewardship that decreased the burden of calls and burnout for neuroradiologists while maintaining a comparable level of service to the ordering clinicians., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic presented unforeseen obstacles to prospective medical students such as Medical College of Admission Test (MCAT) scheduling postponements and technical challenges during virtual interviews. Students were also faced with difficult decisions post-submission such as having to choose a program without ever visiting a school in person. The primary objective of the present study is to assess the changes in medical school interview preferences and experiences in the post-COVID-19 era., Methods: A retrospective survey of the class of 2024 (in-person interview group) and class of 2025 (virtual interview group) at an allopathic medical school was conducted in the Fall of 2021 via the Qualtrics XM online survey software (Qualtrics, Provo, UT, USA)., Results: There were 195 survey respondents: 77 students from the in-person interview group and 89 students from the virtual group. More students in the virtual cohort had to reschedule their MCAT compared to the in-person cohort (56.1% versus 14.3%; p<0.001). The in-person group had higher travel-related expenses (>$500) compared to the group who interviewed virtually (65.1% versus 2.4%; p<0.001). More students from the in-person cohort preferred the in-person interview format compared to the virtual cohort (85.7% versus 22.5%; p<0.001). Lastly, 87% of the in-person group and 24.7% of the virtual group felt they were able to gather a clear impression of the atmosphere and culture of a school from the interview trail alone (p<0.001)., Conclusion: Matriculated medical students at an allopathic medical school who applied during the COVID-19 pandemic had more pre-application hurdles when compared to the cohort who applied just prior to the pandemic. Students who primarily had virtual interviews during the pandemic had less travel-related costs but felt more limited in their experience of a school's culture and ability to establish rapport with interviewers. Despite this, however, the virtual group still expressed a preference for virtual interviews., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Mamaril-Davis et al.)

Objective: Nonaccidental trauma (NAT) is a major cause of traumatic death during infancy and early childhood. Several findings are known to raise the index of clinical suspicion: subdural hematoma (SDH), retinal hemorrhage (RH), fracture, and external trauma. Combinations of certain injury types, determined via statistical frequency associations, may assist clinical diagnostic tools when child abuse is suspected. The present study sought to assess the statistical validity of the clinical triad (SDH + RH + fracture) in the diagnosis of child abuse and by extension pediatric NAT., Methods: A retrospective review of The University of Arizona Trauma Database was performed. All patients were evaluated for the presence or absence of the components of the clinical triad according to specific International Classification of Diseases (ICD)-10 codes. Injury type combinations included some variation of SDH, RH, all fractures, noncranial fracture, and cranial fracture. Each injury type was then correlated with the ICD-10 codes for child abuse or injury comment keywords. Statistical analysis via contingency tables was then conducted for test characteristics such as sensitivity, specificity, positive predictive value, and negative predictive value., Results: There were 3149 patients younger than 18 years of age included in the quantitative analysis, all of whom had at least one component of the clinical triad. From these, 372 patients (11.8%) had a diagnosis of child abuse. When compared to a single diagnosis of either SDH, RH, all fractures, noncranial fracture, or cranial fracture, the clinical triad had a significantly greater correlation with the diagnosis of child abuse (100% of cases) (p < 0.0001). The dyad of SDH + RH also had a significantly greater correlation with a child abuse diagnosis compared to single diagnoses (88.9%) (p < 0.0001). The clinical triad of SDH + RH + fracture had a sensitivity of 88.8% (95% CI 87.6%-89.9%), specificity of 100% (95% CI 83.9%-100%), and positive predictive value of 100% (95% CI 99.9%-100%). The dyad of SDH + RH had a sensitivity of 89.1% (95% CI 87.9%-90.1%), specificity of 88.9% (95% CI 74.7%-95.6%), and positive predictive value of 99.9% (95% CI 99.6%-100%). All patients with the clinical triad were younger than 3 years of age., Conclusions: When SDH, RH, and fracture were present together, child abuse and by extension pediatric NAT were highly likely to have occurred.

Background: Limited mobility in older adults consistently predicts both morbidity and mortality. As individuals age, the rates of mobility disability increase from 1.0% in people aged 15-24 to 20.6% in adults over 65 years of age. Physical activity can effectively improve mobility in older adults, yet many older adults do not engage in sufficient physical activity. Evidence shows that increasing physical activity by 50 min of moderate intensity physical activity in sedentary older adults with mobility limitations can improve mobility and reduce the incidence of mobility disability. To maximize the healthy life span of older adults, it is necessary to find effective and efficient interventions that can be delivered widely to prevent mobility limitations, increase physical activity participation, and improve quality of life in older adults. We propose a randomized controlled trial to assess the effect of a physical activity health coaching intervention on mobility in older adults with mobility limitations., Methods: This randomized controlled trial among 290 (145 per group) community-dwelling older adults with mobility limitations, aged 70-89 years old, will compare the effect of a physical activity health coaching intervention versus a general healthy aging education program on mobility, as assessed with the Short Physical Performance Battery. The physical activity health coaching intervention will be delivered by exercise individuals who are trained in Brief Action Planning. The coaches will use evidence-based behavior change techniques including goal-setting, action planning, self-monitoring, and feedback to improve participation in physical activity by a known dose of 50 min per week. There will be a total of 9 health coaching or education sessions delivered over 26 weeks with a subsequent 26-week follow-up period, wherein both groups will receive the same duration and frequency of study visits and activities., Discussion: The consequences of limited mobility pose a significant burden on the quality of life of older adults. Our trial is novel in that it investigates implementing a dose of physical activity that is known to improve mobility in older adults utilizing a health coaching intervention., Trial Registration: ClinicalTrials.gov Protocol Registration System: NCT05978336; registered on 28 July 2023., (© 2023. The Author(s).)

Importance: Cognitive impairment is prevalent in survivors of stroke, affecting approximately 30% of individuals. Physical exercise and cognitive and social enrichment activities can enhance cognitive function in patients with chronic stroke, but their cost-effectiveness compared with a balance and tone program is uncertain., Objective: To conduct a cost-effectiveness and cost-utility analysis of multicomponent exercise or cognitive and social enrichment activities compared with a balance and tone program., Design, Setting, and Participants: This economic evaluation used a Canadian health care systems perspective and the Vitality study, a randomized clinical trial aimed at improving cognition after stroke with a 6-month intervention and a subsequent 6-month follow-up (ie, 12 months). The economic evaluation covered the duration of the Vitality trial, between June 6, 2014, and February 26, 2019. Participants were community-dwelling adults aged 55 years and older who experienced a stroke at least 12 months prior to study enrollment in the Vancouver metropolitan area, British Columbia, Canada. Data were analyzed from June 1, 2022, to March 31, 2023., Interventions: Participants were randomly assigned to twice-weekly classes for 1 of the 3 groups: multicomponent exercise program, cognitive and social enrichment activities program, or a balance and tone program (control)., Main Outcomes and Measures: The primary measures for the economic evaluation included cost-effectiveness (incremental costs per mean change in cognitive function, evaluated using the Alzheimer Disease Assessment Scale-Cognitive-Plus), cost-utility (incremental cost per quality-adjusted life-year gained), intervention costs, and health care costs. Since cognitive benefits 6 months after intervention cessation were not observed in the primary randomized clinical trial, an economic evaluation at 12 months was not performed., Results: Among 120 participants (mean [SD] age, 71 [9] years; 74 [62%] male), 34 were randomized to the multicomponent exercise program, 34 were randomized to the social and cognitive enrichment activities program, and 52 were randomized to the balance and tone control program. At the end of the 6-month intervention, the cost per mean change in Alzheimer Disease Assessment Scale-Cognitive-Plus score demonstrated that exercise was more effective and costlier compared with the control group in terms of cognitive improvement with an incremental cost-effectiveness ratio of CAD -$8823. The cost per quality-adjusted life-year gained for both interventions was negligible, with exercise less costly (mean [SD] incremental cost, CAD -$32 [$258]) and cognitive and social enrichment more costly than the control group (mean [SD] incremental cost, CAD $1018 [$378]). The balance and tone program had the lowest delivery cost (CAD $777), and the exercise group had the lowest health care resource utilization (mean [SD] $1261 [$1188]) per person., Conclusions and Relevance: The findings of this economic evaluation suggest that exercise demonstrated potential for cost-effectiveness to improve cognitive function in older adults with chronic stroke during a 6-month intervention.

Introduction: Patients affected by autoimmune pathologies such as rheumatoid arthritis require surgery for various reasons. However, the systemic inflammatory nature of these disease processes often necessitates therapy with disease-modifying antirheumatic drugs (DMARDs). Alteration of these agents in the perioperative period for surgery requires a careful risk-benefit analysis to limit disease flares, infection rates, and secondary revisions. We therefore queried North and South American practices for perioperative management of DMARDs in patients undergoing elective spine surgery., Methods: An institutional review board-approved pilot survey was disseminated to spine surgeons regarding how they managed DMARDs before, during, and after spine surgery., Results: A total of 47 spine surgeons responded to the survey, 37 of whom were neurosurgeons (78.7%) and 10 orthopedic surgeons (21.3%). Of the respondents, 80.9% were from North America, 72.3% were board-certified, 51.1% practiced in academic institutions, and 66.0% performed 50-150 spine surgeries per year. Most respondents consulted a rheumatologist before continuing or withholding a DMARD in the perioperative period (70.2%). As such, a majority of the spine surgeons in this survey withheld DMARDs at an average of 13.8 days before and 19.6 days after spine surgery. Of the spine surgeons who withheld DMARDs before and after spine surgery, the responses were variable with a trend toward no increased risk of postoperative complications., Conclusions: Based on the results of this pilot survey, we found a consensus among spine surgeons to withhold DMARDs before and after elective spine surgery., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2024 The Japanese Society for Spine Surgery and Related Research.)

Introduction The use of the Thoracolumbar Injury Classification and Severity Score (TLICS) and other classification systems for guiding the management of traumatic spinal injuries remains controversial. TLICS is one of the few classifications that provides treatment recommendations.We sought to analyze intervention modality selection based on the TLICS scoring system. Methods A retrospective review of patients presenting with traumatic thoracolumbar fractures at a level 1 trauma center over a two-year period was performed. Primary endpoints for comparison analysis included visual analog scale (VAS) scores and Cobb angles during follow-up. Results There were 272 patients with thoracolumbar fractures, of whom 212 had TLICS of ≤3, six with TLICS of 4, and 54 with TLICS of ≥5. Of the 272 total patients, 59 were treated via surgery and 213 via non-surgical conservative methods. The VAS scores significantly decreased from presentation to last follow-up in both surgically treated and conservative groups (p<0.0001). This remained consistent in subgroup analyses of TLICS ≤ 3, TLICS = 4, and TLICS ≥ 5 (p<0.0001). Burst fractures treated conservatively had larger fracture Cobb angles versus those treated via surgery at the last follow-up, although this was not significantly associated (p=0.07). The only significant relationship with Cobb angles was in distraction fractures of the TLICS > 4 conservative group, who had significantly lower Cobb angles at the last follow-up than the TLICS > 4 surgical group (p<0.04). The "surgeon's choice" for TLICS = 4 was surgical intervention (4/6 patients, 66.7%). Conclusion Using the TLICS score, thoracolumbar injuries in a level 1 trauma center are more commonly TLICS ≤ 3. For patients with TLICS = 4, the surgeon's choice was most commonly surgical repair. VAS scores decreased over time from presentation between surgically and conservatively managed patients (as well as within-group analyses). The data concerning Cobb angles were more ambiguous, as larger Cobb angles in burst fractures treated conservatively did not show statistically significant differences with surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gonzales-Portillo et al.)

Background and Objective: For chronic subdural hematoma (cSDH), bedside subdural drains (SDD) provide a useful alternative to more invasive neurosurgical techniques, including evacuation through multiple burr holes or formal craniotomy. However, no scale currently exists adequately predicting SDD candidacy or treatment response. The present study sought to characterize predictors of revision surgery after initial treatment with bedside SDD for cSDH., Methods: We conducted a retrospective case control study of cSDH patients treated with bedside SDD at a level one trauma center between 2018 and 2022. Binomial regression was used to compare SDD patients and generate odds ratios associated with revision surgery, which were compared using a binary random effects model., Results: Ninety six cSDH patients were included, of whom 13 (13.5%) required a revision surgery after initial treatment failure with bedside SDD. Patients requiring revision surgery demonstrated an increased male predominance (84.6% vs. 69.9% of SDD patients not requiring revision surgery), tended to be younger (67.8 vs. 70.5 years) with a greater body mass index (28.7 vs. 25.6 kg/m 2 ), and have a lower Glasgow Coma Scale (GCS) score on presentation of 12.5 (versus 14). Patients with an initial GCS score less than 13 (OR 11.0 95% CI 2.8 - 43.3), midline shift greater than 10 mm on CT (OR 6.5 95% CI 1.7 - 25.7), or duration of SDD placement longer than 3 days (OR 10.5 95% CI 2.6 - 41.9) demonstrated a greater likelihood of needing a revision surgery after initial treatment with bedside SDD., Conclusion: Among patients treated with SDD, we identified 3 independent factors predicting the need for revision surgery: GCS score, midline shift, and duration of drain placement. Craniotomy may be favored over bedside SDD in patients presenting with a GCS score less than 13 or midline shift greater than 10 mm and for SDD patients demonstrating inadequate clinical response after 3 days., Competing Interests: Declaration of Competing Interest There are no competing or conflicting interests for any author., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Telerehabilitation is an accessible service delivery model that may support innovative lower extremity rehabilitation programmes that extend the stroke recovery continuum into the community. Unfortunately, there is limited evidence on the provision of exercises for lower extremity recovery after stroke delivered using telerehabilitation. In response, we developed the TeleRehabilitation with Aims to Improve Lower extremity recovery poststroke (TRAIL) programme, a 4-week progressive exercise and self-management intervention delivered synchronously using video-conferencing technology. Our primary hypothesis is that individual within 1-year poststroke who participate in TRAIL will experience significantly greater improvements in functional mobility than individuals in an attention-controlled education programme (EDUCATION)., Methods and Analysis: In this multisite, parallel group, assessor-blinded randomised attention-controlled trial, 96 community-living stroke survivors within 1-year poststroke will be recruited from five sites (Vancouver, Winnipeg, Toronto, London and Halifax, Canada) from the CanStroke Recovery Trials Platform which is a network of Canadian hospital sites that are affiliated with academic institutions to facilitate participant recruitment and quality trial practices. Participants will be randomised on a 1:1 basis to TRAIL or EDUCATION. Participants randomised to TRAIL will receive eight telerehabilitation sessions where they will perform exercises and receive self-management support to improve lower extremity recovery from a TRAIL physical therapist. The primary outcome will be measured using the Timed Up and Go. Secondary outcomes include lower extremity muscle strength, functional balance, motor impairment, balance self-efficacy, health-related quality of life and health service use for our economic evaluation. Measurements will be taken at baseline, immediately after the intervention, 3-month and 6-month postintervention., Ethics and Dissemination: Ethics approval for this research has been obtained by all participating sites. All study participants will provide their informed consent prior to enrolling them in the study. Findings from this trial will be disseminated in peer-reviewed journals and presentations at international scientific meetings., Trial Registration Number: ClinicalTrials.gov, NCT04908241., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Double-blind, sham-controlled neurosurgical trials for neurodegenerative disorders are debated as an ethical dilemma, particularly regarding subjects randomized to the sham surgery group with general anesthesia., Objective: The objective of this study was to examine the safety of sham surgeries in Parkinson's disease (PD) clinical trials through complications related to the procedure., Methods: A systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Rates and odds ratios (OR) were compared using random effects analysis., Results: Seven studies, all randomized, double-blind, sham surgery-controlled trials, with 309 patients with PD, were qualitatively and quantitatively analyzed: 141 patients in sham groups and 168 patients in the experimental arms of gene or cell therapy trials. Sham subjects had lower rates of gastrointestinal, positioning, incision-site, respiratory (hypoxic or hypercapnic respiratory failure), cardiovascular, thromboembolism, postoperative cognitive decline, skull fracture, and intracranial or spinal complications when compared with active treatment subjects. Sham subjects, however, had a higher rate of perioperative respiratory infections, such as pneumonia or sinusitis. Further, sham subjects were less likely to experience postoperative cognitive decline (OR, 0.23; 95% confidence interval [CI]: 0.11-0.47), intracranial or spinal complications (OR, 0.10; 95% CI: 0.01-0.75), total major morbidity (OR, 0.30; 95% CI: 0.19-0.47), or overall complications (OR, 0.59; 95% CI: 0.47-0.75) when compared with patients receiving experimental therapy., Conclusions: Patients with PD in the sham surgery control arm of cell transplantation or gene therapy clinical trials have a low risk of procedure-related adverse events overall and fewer complications than patients in the experimental groups. There were no reported deaths attributed to sham surgery-controlled PD clinical trials. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Adrenal tumors other than neuroblastoma are uncommon in children. The most frequently encountered are adrenocortical carcinoma and pheochromocytoma. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary adrenal malignancy other than neuroblastoma at diagnosis and during follow-up., (© 2022 Wiley Periodicals LLC.)

Pediatric thyroid cancer is rare in children; however, incidence is increasing. Papillary thyroid cancer and follicular thyroid cancer are the most common subtypes, comprising about 90% and 10% of cases, respectively. This paper provides consensus imaging recommendations for evaluation of pediatric patients with thyroid cancer at diagnosis and during follow-up., (© 2022 Wiley Periodicals LLC.)

Primary hepatic malignancies are relatively rare in the pediatric population, accounting for approximately 1%-2% of all pediatric tumors. Hepatoblastoma and hepatocellular carcinoma are the most common primary liver malignancies in children under the age of 5 years and over the age of 10 years, respectively. This paper provides consensus-based imaging recommendations for evaluation of patients with primary hepatic malignancies at diagnosis and follow-up during and after therapy., (© 2022 Wiley Periodicals LLC.)

Recurrence remains a significant clinical barrier to improving breast cancer patient outcomes. The RON receptor is a predictor of metastatic progression and recurrence in breast cancers of all subtypes. RON directed therapies are in development, but preclinical data directly testing the impact of RON inhibition on metastatic progression/recurrence are lacking, and mechanisms to exert this function remain unclear. Herein, we modeled breast cancer recurrence using implantation of RON-overexpressing murine breast cancer cells. Recurrent growth was examined after tumor resection via in vivo imaging and ex vivo culture of circulating tumor cells from whole blood samples from tumor bearing mice. In vitro functional assessment of was performed using mammosphere formation assays. Transcriptomic pathway enrichment identified glycolysis and cholesterol biosynthesis pathways, transcription factor targets, and signaling pathways enriched in RON-overexpressing breast cancer cells. BMS777607, a RON inhibitor, abrogated CTC colony formation tumor cells and tumor recurrence. RON promoted mammosphere formation through upregulated cholesterol production that utilizes glycolysis-derived substrates. In mouse models with RON overexpression, statin-mediated inhibition of cholesterol biosynthesis impeded metastatic progression and recurrence but does not affect the primary tumor. RON upregulates glycolysis and cholesterol biosynthesis gene expression by two pathways: MAPK-dependent c-Myc expression and β-catenin -dependent SREBP2 expression., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To compare the cost-effectiveness of exercise as a unimodal intervention versus multimodal interventions that included exercise in conjunction with other falls prevention strategies to prevent falls among community-dwelling older adults., Design: Systematic review and meta-analysis., Data Sources: MEDLINE, EMBASE, NHS EED, and CINAHL (1 January 1946 to June 2022)., Eligibility Criteria: Economic evaluations of fall prevention strategies that included exercise delivered as a unimodal intervention or a multimodal intervention that included exercise in conjunction with other falls prevention strategies among community-dwelling adults aged 60 years and over., Results: Eighteen studies were included in this review: 9 unimodal, 6 multimodal, and 3 that included exercise delivered as both a unimodal and a multimodal intervention. In the cost-effectiveness analyses, 61.5 % (n = 8/13) of exercise-only unimodal interventions demonstrated cost-effectiveness, compared with 33.3 % (n = 2/6) of multimodal interventions. In the cost-utility analyses, 60 % (n = 6/10) of unimodal interventions compared with zero multimodal interventions (n = 0/4) demonstrated cost-effectiveness. Sixteen studies (25,017 participants) were included in our meta-analysis. Incremental costs were $128 [-$661, $1644] (2021 US dollars) for exercise-only unimodal interventions and $786 [-$72, $1644] for multimodal interventions. Estimated incremental quality-adjusted life-years was 0.09 [-0.37, 0.55] for exercise-only unimodal interventions and 0.00 [-0.04, 0.04] for multimodal interventions. Both exercise-only and multimodal interventions had an estimated 28 % reduction in falls versus the control, with incidence rate ratios for exercise-only unimodal interventions of 0.72 [0.62, 0.83] and for multimodal interventions of 0.72 [0.25, 2.09]., Conclusion: Exercise delivered as a unimodal intervention, particularly resistance training, provided the best value for money for fall prevention. Multimodal interventions that included exercise did not demonstrate additional benefits in terms of costs, quality of life, or fall prevention compared with exercise-only unimodal interventions. This finding may be due to the smaller number of multimodal interventions available., Review Registration: PROSPERO CRD42022295561., Registration Title: Comparing the cost-effectiveness of multimodal versus unimodal interventions that include exercise to prevent falls among community-dwelling older adults: A systematic review., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

RON is a receptor tyrosine kinase (RTK) of the MET receptor family that is canonically involved in mediating growth and inflammatory signaling. RON is expressed at low levels in a variety of tissues, but its overexpression and activation have been associated with malignancies in multiple tissue types and worse patient outcomes. RON and its ligand HGFL demonstrate cross-talk with other growth receptors and, consequentially, positions RON at the intersection of numerous tumorigenic signaling programs. For this reason, RON is an attractive therapeutic target in cancer research. A better understanding of homeostatic and oncogenic RON activity serves to enhance clinical insights in treating RON-expressing cancers., Competing Interests: The authors declare that they have no conflict of interests.

Objectives: Physical activity (PA) and total sleep time (TST) are each associated with cognition; however, whether these relationships vary by age and biological sex is unclear. We examined the relationships of PA or TST with cognition, and whether age and sex moderated these relationships, using baseline data from the Canadian Longitudinal Study on Aging (CLSA; 2010-2015)., Study Design: A cross-sectional analysis of participants from the Comprehensive cohort of the CLSA with complete PA and sleep data (n = 20,307; age range 45-86 years)., Main Outcome Measures: PA and TST were measured using the Physical Activity Scale for the Elderly (PASE) and self-reported TST over the past month. Cognition was indexed using a three-factor structural equation model (i.e., memory, executive function, and verbal fluency)., Results: Non-linear restricted cubic spline models indicated that PA and TST explained statistically significant (p < 0.01) but modest variance of each cognitive domain (<1 % of 23-24 % variance). Age and sex did not moderate associations of PA with any cognitive domain. However, age and sex moderated relationships of TST with cognition, whereby: 1) associations of TST with memory decreased with age for males and females; and 2) males and females had different age-associated relationships of TST with executive function and verbal fluency., Conclusions: PA and TST modestly contribute to multiple domains of cognition across middle and older adulthood. Importantly, the association of PA with cognition does not appear to vary across middle or older adulthood, nor does it vary by biological sex; however, TST appears to have a complex relationship with multiple domains of cognition which is both age- and sex-dependent., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Poor sleep and chronic fatigue are common in people with chronic stroke (i.e. ≥ 6 months post-stroke). Exercise training is a viable, low-cost therapy for promoting sleep and reducing fatigue; however, the effects of exercise on sleep and fatigue in people with chronic stroke are unclear. Thus, we conducted a systematic review ascertaining the effects of exercise on sleep and fatigue in people with chronic stroke. We systematically searched EMBASE, MEDLINE, AgeLine, the Cochrane Database of Systematic Reviews, CINAHL, SPORTDiscus, SCOPUS, and reference lists of relevant reviews for articles that examined the effects of exercise on sleep or fatigue in chronic stroke. Search results were limited to adults ≥ 18 years, randomized controlled trials, non-randomized trials, and pre-post studies, which were published in English and examined the effects of exercise on sleep or fatigue in people with chronic stroke. We extracted study characteristics and information on the measurement of sleep and fatigue, and assessed study quality and risk of bias using the CONSORT criteria and Cochrane risk-of-bias tool, respectively. We found two studies that examined the effects of exercise on sleep, and two that examined the effects of exercise on fatigue. All studies reported positive effects of exercise training on sleep and fatigue; however, there were concerns of bias and study quality in all studies. There is preliminary evidence that exercise promotes sleep and reduces fatigue in people with chronic stroke; however, the extent to which exercise impacts these health parameters is unclear., (© 2022 European Sleep Research Society.)

Background and Objectives: Telehealth holds potential for inclusive and cost-saving health care; however, a better understanding of the use and acceptance of telehealth for health promotion among rural older adults is needed. This systematic review aimed to synthesize evidence for telehealth use among rural-living older adults and to explore cost-effectiveness for health systems and patients., Research Design and Methods: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study designs reporting health promotion telehealth interventions with rural-living adults aged 55 and older were eligible for review. Following screening and inclusion, articles were quality-rated and ranked by level of evidence. Data extraction was guided by the Technology Acceptance Model and organized into outcomes related to ease of use, usefulness, intention to use, and usage behavior along with cost-effectiveness., Results: Of 2,247 articles screened, 42 were included. Positive findings for the usefulness of telehealth for promoting rural older adults' health were reported in 37 studies. Evidence for ease of use and usage behavior was mixed. Five studies examined intention to continue to use telehealth and in 4 of these, patients preferred telehealth. Telehealth was cost-effective for health care delivery (as a process) compared to face to face. However, findings were mixed for cost-effectiveness with both reports of savings (e.g., reduced travel) and increased costs (e.g., insurance)., Discussion and Implications: Telehealth was useful for promoting health among rural-living older adults. Technological supports are needed to improve telehealth ease of use and adherence. Cost-effectiveness of telehealth needs more study, particularly targeting older adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Among older adults, health-related quality of life (HRQoL) and falls are associated. Generic patient-reported outcomes measures (PROMs) assess individual's HRQoL. The role for PROMs, a potential tool for predicting subsequent falls, remains under-explored. Our primary aim was to determine whether a baseline PROMs assessment of HRQoL may be a useful tool for predicting future falls., Methods: A secondary analysis of a 12-month randomized clinical trial (RCT) of a home-based exercise program among 344 adults (67% female), aged ≥ 70 years, with ≥ 1 falls in the prior year who were randomized (1:1) to either a home-based exercise program (n = 172) or usual care (n = 172). A negative binomial regression model with total falls count as the dependent variable evaluated the main effect of the independent variable-baseline HRQoL (measured by the Short-Form-6D)-controlling for total exposure time and experiment group (i.e., exercise or usual care) for the total sample. For the usual care group alone, the model controlled for total exposure time., Results: For the total sample, the rate of subsequent total falls was significantly predicted by baseline HRQoL (IRR = 0.044; 95% CI [0.005-0.037]; p = .004). For the usual care group, findings were confirmed with wider confidence intervals and the rate of prospective total falls was significantly predicted by baseline HRQoL (IRR = 0.025; 95% CI [0.001-0.909]; p = .044)., Conclusion: These findings suggest the ShortForm-6D should be considered as part of falls prevention screening strategies within a Falls Prevention Clinic setting. Trial Registrations ClinicalTrials.gov Protocol Registration System. Identifier: NCT01029171; URL: https://clinicaltrials.gov/ct2/show/NCT01029171 . Identifier: NCT00323596; URL: https://clinicaltrials.gov/ct2/show/NCT00323596 ., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Establish the minimal clinically important difference (MCID) of a health-related quality of life (HRQoL) measure-the EuroQol EQ-5 Dimensions-3 Level (EQ-5D-3L)-in older adults with a history of falls., Methods: This study is a secondary analysis of 255 complete cases who were enrolled in a 12-month randomized controlled trial (NCT01029171; NCT00323596); participants were randomized to the Otago Exercise Program (OEP; n = 126/172; Age:81.2 ± 6.2 years; 60.3% Female) or control (CON; n = 129/172; Age:81.7 ± 5.7 years; 70.5% Female). Participants completed the EQ-5D-3L and Visual Analogue Scale (VAS) at baseline and 1-year. The VAS was associated with HRQoL and was the health status anchor (VAS minimal improvement = 7 to 17, maximal improvement ≥ 18, minimal decline =  - 7 to - 17, maximal decline ≤  - 18 points). We used four distinct approaches to estimate MCID ranges: (1) anchor-based change differences of the EQ-5D-3L (1-year minus baseline); (2) anchor-based beta coefficients from ordinary least squares regressions (OLS); (3) anchor-based receiver operating characteristic (ROC), and 4) distribution-based standard deviation and standardized effect size of 0.5., Results: EQ-5D-3L MCID ranges for minimal improvements (OEP = 0.028 to 0.059; CON = 0.007 to 0.051), maximal improvements (OEP = 0.059 to 0.090; CON = 0.051 to 0.090), minimal declines (OEP =  - 0.029 to - 0.105; CON =  - 0.015 to - 0.051), and maximal declines (OEP =  - 0.018 to - 0.072; CON =  - 0.018 to - 0.082) were established using change difference, OLS, and distribution-based methods. The ROC area under the curve was poor, thus, it was not used to estimate the MCID., Conclusions: Our results will assist in the interpretation of changes in HRQoL, as measured by the EQ-5D-3L, in older adults with a history of falls., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Functional independence limitations restrict older adult self-sufficiency and can reduce quality of life. This systematic review and cost of impairment study examined the costs of functional independence limitations among community dwelling older adults to society, the health care system, and the person., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines this systematic review included community dwelling older adults aged 60 years and older with functional independence limitations. Databases (Cochrane Database of Systematic Reviews, EconLit, NHS EED, Embase, CINAHL, AgeLine, and MEDLINE) were searched between 1990 and June 2020. Two reviewers extracted information on study characteristics and cost outcomes including mean annual costs of functional independence limitations per person for each cost perspective (2020 US prices). Quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist., Results: 85 studies were included. The mean annual total costs per person (2020 US prices) were: $27,380.74 (95% CI: [$4075.53, $50,685.96]) for societal, $24,195.52 (95% CI: [$9679.77, $38,711.27]) for health care system, and $7455.49 (95% CI: [$2271.45, $12,639.53]) for personal. Individuals with cognitive markers of functional independence limitations accounts for the largest mean costs per person across all perspectives. Variations across studies included: cost perspective, measures quantifying functional independence limitations, cost items reported, and time horizon., Conclusions: This study sheds light on the importance of targeting cognitive markers of functional independence limitations as they accounted for the greatest costs across all economic perspectives., (© 2022. The Author(s).)

Importance: A stroke doubles one's risk for dementia. How to promote cognitive function among persons with chronic stroke is unclear., Objective: To evaluate the effect of exercise (EX) or cognitive and social enrichment activities (ENRICH) on cognitive function in adults with chronic stroke., Design, Setting, and Participants: This was a 3-group parallel, single-blinded, single-site, proof-of-concept randomized clinical trial at a research center in Vancouver, British Columbia, Canada. Participants included community-dwelling adults with chronic stroke, aged 55 years and older, able to walk 6 meters, and without dementia. The trial included a 6-month intervention and a 6-month follow-up. Randomization occurred from June 6, 2014, to February 26, 2019. Measurement occurred at baseline, 6 months, and 12 months. Data were analyzed from January to November 2021., Interventions: Participants were randomly allocated to twice-weekly supervised classes of: (1) EX, a multicomponent exercise program; (2) ENRICH, a program of cognitive and social enrichment activities; or (3) balance and tone (BAT), a control group that included stretches and light-intensity exercises., Main Outcomes and Measures: The primary outcome was the Alzheimer Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus), which included the 13-item ADAS-Cog, Trail Making Test Parts A and B, Digit Span Forward and Backward, Animal Fluency, and Vegetable Fluency., Results: One-hundred and twenty participants, with a mean (range) of 1.2 (1-4) strokes, a mean (SD) of 66.5 (53.8) months since the most recent stroke, mean (SD) baseline age of 70 (8) years, mean (SD) baseline ADAS-Cog-Plus of 0.22 (0.81), and 74 (62%) male participants, were randomized to EX (34 participants), ENRICH (34 participants), or BAT (52 participants). Seventeen withdrew during the 6-month intervention and another 7 during the 6-month follow-up. Including all 120 participants, at the end of the 6-month intervention, EX significantly improved ADAS-Cog-Plus performance compared with BAT (estimated mean difference: -0.24; 95% CI, -0.43 to -0.04; P = .02). This difference did not persist at the 6-month follow-up (estimated mean difference: -0.08; 95% CI, -0.29 to 0.12; P = .43). For the 13-item ADAS-Cog, the EX group improved by 5.65 points over the 6-month intervention (95% CI, 2.74 to 8.57 points; P < .001), exceeding the minimally clinical difference of 3.0 points., Conclusions and Relevance: These findings suggest that exercise can induce clinically important improvements in cognitive function in adults with chronic stroke. Future studies need to replicate current findings and to understand training parameters, moderators, and mediators to maximize benefits., Trial Registration: ClinicalTrials.gov identifier: NCT01916486.

Background: Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms., Methods: Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer's Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up)., Discussion: Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as "medicine" to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health., Trial Registration: ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016., (© 2022. The Author(s).)

Background: Aberrant RON signaling is present in numerous cancers including breast cancer. Evidence suggests that the ligand, hepatocyte growth factor-like (HGFL), is also overexpressed in breast cancer. RON ( MST1R ) and HGFL ( MST1 ) genes are located on human chromosome 3 and mouse chromosome 9 respectively and are found near each other in both species. Based on co-expression patterns, we posited that RON and HGFL are co-regulated and that coordinate upregulation drives aggressive tumorigenesis., Methods: Mouse models were used to establish the functional significance of RON and HGFL co-overexpression on the activation of tumor cells and tumor-associated macrophages in breast cancer. TCGA and METABRIC gene expression and alteration data were used to query the relationships between MST1R and MST1 in breast cancer., Results: In tumor models, physiologic sources of HGFL modestly improve Arginase-1 + (M2) macrophage recruitment to the tumor proper. Tumor-cell produced HGFL functions in autocrine to sustain tumor cell RON activation and MAPK-dependent secretion of chemotactic factors and in paracrine to activate RON on macrophages and to promote breast cancer stem cell self-renewal. In silico analyses support that RON and HGFL are co-expressed across virtually all cancer types including breast cancer and that common genomic alterations do not appear to be drivers of RON/HGFL co-overexpression., Conclusions: Co-overexpression of RON and HGFL in breast cancer cells (augmented by physiologic sources of HGFL) promotes tumorigenesis through autocrine-mediated RON activation/RON-dependent secretome changes and paracrine activation of macrophage RON to promote breast cancer stem cell self-renewal.

Objectives: To assess the effect of exercise training on the cognitive function of older adults living with different types of dementia, as well as potential moderators of exercise efficacy., Design: Systematic review and meta-analysis., Data Sources: Cochrane Central, PsycINFO, Embase, Medline and CINAHL., Eligibility Criteria: Peer-reviewed, randomised controlled trials, in English (1990-present), which examined the effects of exercise training on the cognitive function of older adults living with dementia., Study Appraisal and Synthesis: Risk of bias and study quality were assessed (Cochrane Risk of Bias Tool 2.0 and Physiotherapy Evidence Database Scale). We performed random-effects models using robust variance estimation and tested moderators using the approximate Hotelling-Zhang test., Results: Twenty-eight studies (n=2158) were included in the qualitative review and 25 in the meta-analysis. For all-cause dementia, a small effect of exercise training on cognitive function was observed ( g =0.19; 95% CI 0.05 to 0.33; p=0.009). Type of dementia and exercise training characteristics did not moderate the effects of exercise training on cognitive function (p>0.05). Adherence to the intervention moderated the cognitive outcome effect size such that greater mean adherence was associated with greater cognitive outcome effect sizes ( b =0.02; SE =0.01; p=0.005)., Conclusion: Exercise training showed small benefits for the cognitive function of older adults living with all-cause dementia. More research and standardised reporting of exercise training characteristics can strengthen the evidence for what works best for which types of dementia., Prospero Registration Number: CRD42020198716., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The novel coronavirus 2019 (COVID-19) pandemic caused the abrupt curtailment of on-campus research activities that amplified impacts experienced by female and racialized faculty. In this mixed-method study, we systematically and strategically unpack the impact of the shift of academic work environments to remote settings on tenured and tenure-track faculty in Canada. Our quantitative analysis demonstrated that female and racialized faculty experienced higher levels of stress, social isolation and lower well-being. Fewer women faculty felt support for health and wellness. Our qualitative data highlighted substantial gender inequities reported by female faculty such as increased caregiving burden that affected their research productivity. The most pronounced impacts were felt among pre-tenured female faculty. The present study urges university administration to take further action to support female and racialized faculty through substantial organizational change and reform. Given the disproportionate toll that female and racialized faculty experienced, we suggest a novel approach that include three dimensions of change: (1) establishing quantitative metrics to assess and evaluate pandemic-induced impact on research productivity, health and well-being, (2) coordinating collaborative responses with faculty unions across the nation to mitigate systemic inequities, and (3) strategically implementing a storytelling approach to amplify the experiences of marginalized populations such as women or racialized faculty and include those experiences as part of recommendations for change., Competing Interests: All authors have no conflict of interest to declare., (© 2022 The Authors. Gender, Work & Organization published by John Wiley & Sons Ltd.)

Objective: Using stratified analyses, we examined the cost-effectiveness of the Otago Exercise Programme (OEP), from a health care system perspective, among older women and men who have previously fallen., Methods: This study was a secondary stratified analysis (by women and men), of a 12-month prospective economic evaluation of a randomized clinical trial (OEP compared with usual care). Three hundred and forty four community-dwelling older adults (≥70; 172 OEP (110 women; 62 men), 172 usual care (119 women; 53 men)) who sustained a fall in the past 12 months and received a baseline assessment at the Vancouver Falls Prevention Clinic, Canada were included. A gender by OEP/usual care interaction was examined for the falls incidence rate ratio (IRR). Outcome measures stratified by gender included: falls IRR, incremental cost-per fall prevented (ICER), incremental cost per quality adjusted life year (QALY, ICUR) gained, and mean total health care resource utilization costs., Results: Men were frailer than women at baseline. Men incurred higher mean total healthcare costs $6794 (SD: $11906)). There was no significant gender by OEP/usual care interaction on falls IRR. The efficacy of the OEP did not vary by gender. The adjusted IRR for the OEP group demonstrated a 39% (IRR: 0.61, CI: 0.40-0.93) significant reduction in falls among men but not women (32% reduction (IRR: 0.69, CI: 0.47-1.02)). The ICER showed the OEP was effective in preventing falls and less costly for men, while it was costlier for women by $42. The ICUR showed the OEP did not impact quality of life., Conclusion: Future studies should explore gender factors (i.e., health seeking behaviours, gender related frailty) that may explain observed variation in the cost-effectiveness of the OEP as a secondary falls prevention strategy., Trial Registrations: ClinicalTrials.gov Protocol Registration System Identifier: NCT01029171; URL: https://clinicaltrials.gov/ct2/show/NCT01029171 Identifier: NCT00323596; URL: https://clinicaltrials.gov/ct2/show/NCT00323596., Competing Interests: The authors have declared that no competing interests exist.

Background: In preparation for surgery, patients being treated with disease-modifying antirheumatic drugs (DMARDs) are recommended to either continue or withhold therapy perioperatively. Some of these drugs have known effects against bone healing, hence the importance of adequately managing them before and after surgery., Objective: We aim to assess the current evidence for managing conventional synthetic and/or biologic DMARDs in the perioperative period for elective spine surgery., Methods: A systematic review of four databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The included manuscripts were methodically scrutinized for quality, postoperative infections, wound healing characteristics, bone fusion rates, and clinical outcomes., Results: Six studies were identified describing the management of conventional synthetic and/or biologic DMARDs. There were 294 DMARD-treated patients described undergoing various spine surgeries such as craniovertebral junction fusions. Three of the studies involved exclusive continuation of DMARDs in the perioperative window; one study involved exclusive discontinuation of DMARDs in the perioperative window; and two studies involved continuation or discontinuation of DMARDs perioperatively. Of patients that continued DMARDs in the perioperative period, 13/50 patients (26.0%) had postoperative surgical site infections or wound dehiscence, 2/19 patients (10.5%) had delayed wound healing, and 32/213 patients (15.0%) had secondary revision surgeries. A fusion rate of 14/19 (73.6%) was described in only one study for patients continuing DMARDs perioperatively., Conclusions: The available published data may suggest a higher risk of wound healing concerns and lower than average bone fusion, although this may be under-reported given the current state of the literature., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is unclear whether cardiometabolic risk shares an interactive relationship with age-associated differences in cognition, and whether this relationship varies by biological sex. We conducted a cross-sectional analysis using baseline data from the Canadian Longitudinal Study on Aging (CLSA; 2010-2015) to examine whether 1) cardiometabolic risk has an interactive relationship with age-associated cognition; and 2) interactive effects are sex-dependent. We measured memory, executive function, and verbal fluency in the Comprehensive cohort ( N  = 25 830; 45-86 years). Each cognitive domain was modeled using restricted cubic splines for age and each cardiometabolic risk factor (HbA1c, HSCRP, TG, and LDL and HDL cholesterol). Sex was included as a predictor in all models. Wald χ 2 statistics were used to determine the relative importance of age, cardiometabolic risk, sex, and their interactive effects on cognition. Age was the most important variable in each model (proportion χ 2  = 34%-48%). Biological sex was the second most important variable for memory (proportion χ 2  = 26%) but was unimportant for executive function and verbal fluency (proportion χ 2  = 3%-5%). Cardiometabolic risk factors were unimportant predictors in each model (proportion χ 2  = 1%-3%). Two- and 3-way interactions between cardiometabolic risk, age, and sex were also unimportant (proportion χ 2  = 0%-2%). Thus, cardiometabolic risk factors did not meaningfully account for age-associated differences in cognition, and these associations (or lack thereof) did not vary by sex. Novelty: Males have poorer age-associated cognitive performance than females. Females and males differ in cardiometabolic risk across middle and older adulthood. Cardiometabolic risk has a small association with age-associated cognition, and there are no sex differences in this relationship.

Seizures are common presenting symptoms of intracranial arteriovenous malformations (AVMs). This systematic review and meta-analysis aims to assess the current evidence regarding complete seizure freedom rates following surgical resection, stereotactic radiosurgery (SRS), and/or endovascular embolization of intracranial AVMs. A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality, spontaneous AVM-associated or hemorrhage-associated seizures, complete seizure-free rates following each interventional treatment, follow-up duration; determination methods of seizure outcomes, and average time-to-onset of recurrent seizures after each treatment. Manuscripts that described patients with nondisabling seizures or reduced seizure frequency in their seizure-free calculations were excluded. Seizure freedom rates following surgical resection, SRS, and endovascular embolization were compared via random-effect analysis. Thirty-four studies with a total of 1765 intracranial AVM patients presenting with spontaneous AVM-associated seizures and 408 patients presenting with hemorrhage-associated seizures were qualitatively analyzed. For patients presenting with AVM-associated seizures, the complete seizure-free rates were 73.0% (321/440 patients; 95% CI 68.8-77.1%) following surgical resection, 60.5% (376/622 patients; 95% CI 56.6-64.3%) following SRS, and 44.6% (29/65 patients; 95% CI 32.5-56.7%) following endovascular embolization alone. For patients presenting with either AVM-associated or hemorrhage-associated seizures, the complete seizure-free rates were 73.0% (584/800 patients; 95% CI 69.9-76.1%) following surgical resection, 46.4% (572/1233 patients; 95% CI 43.6-49.2%) following SRS, and 44.6% (29/65 patients; 95% CI 32.5-56.7%) following embolization. For patients presenting with either AVM-associated or hemorrhage-associated seizures, the overall improvements in seizure outcomes regardless of complete seizure freedom were 82.6% (661/800 patients; 95% CI 80.0-85.3%), 70.6% (870/1233 patients; 95% CI 68.0-73.1%), and 70.8% (46/65 patients; 95% CI 59.7-81.1%) following surgical resection, SRS, and embolization, respectively. No study reported information about the time-to-onset for recurrent seizures in any patient following treatment, as seizure outcomes were only described at the last follow-up visit. The available data suggests that surgical resection results in the highest rate of complete seizure freedom. The rate of seizure improvement following surgery increased further to 82.3% when including patients who had improved seizure frequency without achieving true seizure freedom. Complete seizure-free rates following SRS or embolization were more ambiguous and lower when compared to surgical resection. There is a need for high quality studies evaluating AVM treatment modalities and clearly defined seizure outcomes, as the current literature consists mostly of heterogenous patient populations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate clinical applications of dual-energy computed tomography (DECT) in pediatric-specific lung diseases and compare ventilation and perfusion findings with those from single-photon emission computed tomography (SPECT-CT) V/Q., Methods: All patients at our institution who underwent exams using both techniques within a 3-month period were included in this study. Two readers independently described findings for DECT, and two other readers independently analyzed the SPECT-CT V/Q scan data. All findings were compared between readers and disagreements were reassessed and resolved by consensus. Inter-modality agreements are described throughout this study., Results: Eight patients were included for evaluation. The median age for DECT scanning was 3.5 months (IQR = 2). Five of these patients were scanned for both DECT and SPECT-CT V/Q studies the same day, and three had a time gap of 7, 65, and 94 days between studies. The most common indications were chronic lung disease (5/8; 63%) and pulmonary hypertension (6/8; 75%). DECT and SPECT-CT V/Q identified perfusion abnormalities in concordant lobes in most patients (7/8; 88%). In one case, atelectasis limited DECT perfusion assessment. Three patients ultimately underwent lobectomy with corresponding perfusion abnormalities identified by all reviewers on both DECT and SPECT-CT V/Q in all resected lobes., Conclusion: DECT is a feasible technique that could be considered as an alternative for SPECT-CT V/Q for lung perfusion evaluation in infants., (© 2021 Wiley Periodicals LLC.)

Human milk enriches members of the genus Bifidobacterium in the infant gut. One species, Bifidobacterium pseudocatenulatum, is found in the gastrointestinal tracts of adults and breastfed infants. In this study, B. pseudocatenulatum strains were isolated and characterized to identify genetic adaptations to the breastfed infant gut. During growth on pooled human milk oligosaccharides (HMOs), we observed two distinct groups of B. pseudocatenulatum, isolates that readily consumed HMOs and those that did not, a difference driven by variable catabolism of fucosylated HMOs. A conserved gene cluster for fucosylated HMO utilization was identified in several sequenced B. pseudocatenulatum strains. One isolate, B. pseudocatenulatum MP80, which uniquely possessed GH95 and GH29 α-fucosidases, consumed the majority of fucosylated HMOs tested. Furthermore, B. pseudocatenulatum SC585, which possesses only a single GH95 α-fucosidase, lacked the ability to consume the complete repertoire of linkages within the fucosylated HMO pool. Analysis of the purified GH29 and GH95 fucosidase activities directly on HMOs revealed complementing enzyme specificities with the GH95 enzyme preferring 1-2 fucosyl linkages and the GH29 enzyme favoring 1-3 and 1-4 linkages. The HMO-binding specificities of the family 1 solute-binding protein component linked to the fucosylated HMO gene cluster in both SC585 and MP80 are similar, suggesting differential transport of fucosylated HMO is not a driving factor in each strain's distinct HMO consumption pattern. Taken together, these data indicate the presence or absence of specific α-fucosidases directs the strain-specific fucosylated HMO utilization pattern among bifidobacteria and likely influences competitive behavior for HMO foraging in situ . IMPORTANCE Often isolated from the human gut, microbes from the bacterial family Bifidobacteriaceae commonly possess genes enabling carbohydrate utilization. Isolates from breastfed infants often grow on and possess genes for the catabolism of human milk oligosaccharides (HMOs), glycans found in human breast milk. However, catabolism of structurally diverse HMOs differs between bifidobacterial strains. This study identifies key gene differences between Bifidobacterium pseudocatenulatum isolates that may impact whether a microbe successfully colonizes an infant gut. In this case, the presence of complementary α-fucosidases may provide an advantage to microbes seeking residence in the infant gut. Such knowledge furthers our understanding of how diet drives bacterial colonization of the infant gut.