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Lecanemab and donanemab are monoclonal antibody therapies that remove amyloid-beta from the brain. They are the first therapies that alter a fundamental mechanism, amyloid-beta deposition, in Alzheimer disease (AD). To inform Canadian decisions on approval and use of these drugs, the Canadian Consortium on Neurodegeneration in Aging commissioned Work Groups to review evidence on the efficacy and safety of these new therapies, as well as their projected impacts on Canadian dementia systems of care. We included persons with lived experience with Alzheimer disease in the discussion about the benefits and harms. Our review of the trial publications found high quality evidence of statistically significant group differences, but also recognized that there are mixed views on the clinical relevance of the observed differences and the value of therapy for individual patients. The drugs are intended for persons with early AD, at a stage of mild cognitive impairment or mild dementia. If patients are treated, then confirmation of AD by positron emission tomography or cerebrospinal fluid analysis and monitoring for risk of amyloid-related imaging abnormalities was recommended, as done in the clinical trials, although it would strain Canadian resource capacity. More data are needed to determine the size of the potentially eligible treatment population in Canada., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Howard Cherkow reports financial support was provided by Canadian Institutes of Health Research. Howard Chertkow reports financial support was provided by Alberta Prion Research Institute. Howard Chertkow reports financial support was provided by Alberta Innovates. Howard Chertkow reports financial support was provided by Alzheimer Research UK. Alzheimer Society of Canada reports financial support was provided by Alzheimer Society of Canada. Alzheimer Society of Canada reports financial support was provided by Brain Canada Foundation. Howard Chertkow reports financial support was provided by Canadian Nurses Foundation. Howard Chertkow reports financial support was provided by Eli Lilly and Company. Howard Chertkow reports financial support was provided by Quebec Health Research Fund. Howard Chertkow reports financial support was provided by Hypertension Canada. Howard Chertkow reports financial support was provided by Michael Smith Foundation for Health Research. Howard Chertkow reports financial support was provided by New Brunswick Health Research Foundation. Howard Chertkow reports financial support was provided by Nova Scotia Health Research Foundation. Howard Chertkow reports financial support was provided by Ontario Brain Institute. Howard Chertkow reports financial support was provided by Pfizer Canada Inc. Howard Chertkow reports financial support was provided by Robin and Barry Picov Family Foundation. Howard Chertkow reports financial support was provided by Sanofi. Howard Chertkow reports financial support was provided by Saskatchewan Health Research Foundation. AmanPreet Badhwar reports a grant from the Alzheimer Society of Canada, paid to her institution. Laura Barlow reports no disclosures. Robert Bartha reports no disclosures. Sarah Best reports honoraria from Eisai pharmaceuticals, paid to her. Jennifer Bethell reports no disclosures. Jaspreet Bhangu reports a contract from Eisai for site PI, paid to his institution; consulting for Eisai, unpaid; and consulting for Eli Lilly, paid to him. Sandra Black reports contracts with Genentech, Optina, Roche, Eli Lilly, Eisai/Biogen Idec, Novo Nordisk, Lilly Avid, and ICON, paid to her institution; grants from the Ontario Brain Institute, CIHR, Leducq Foundation, Heart and Stroke Foundation of Canada, NIH, Alzheimers Drug Discovery Foundation, Brain Canada, Weston Brain Institute, Canadian Partnership for Stroke Recovery, Canadian Foundation for Innovation, Focused Ultrasound Foundation, Alzheimers Association US, Queens University, Compute Canada Resources for Research Groups, CANARIE, and Networks of Centres of Excellence of Canada, paid to her institution; consulting for Novo Nordisk, Eisai, Eli Lilly, Roche, and Cpd network, paid to her; consulting for DSR: Diagnosis, Solutions & Results Inc., Conference Board Canada, World Dementia Council, University of Rochester Contribution to the Mission and Scientific Leadership of the Small Vessel VCID Biomarker Validation Consortium, National Institute of Neurological Disorders and Stroke, and Ontario Dementia Care Alliance (ODCA), paid to her institution; honoraria from Biogen, Roche, and Eisai, paid to her; and honoraria from Roche, unpaid. Christian Bocti reports stock in Imeka. Michael Borrie reports consulting for Eisai, Eli Lilly, Biogen, and Hoffmann-La Roche, paid to him; and contracts with Eisai, Eli Lilly, Biogen, Hoffmann-La Roche, and Alector, paid to his institution. Susan Bronskill reports grants from the Alzheimer Society of Canada, Brain Canada Foundation, Evaluative Clinical Sciences Research Platform of Sunnybrook Research Institute, Canadian Consortium on Neurodegeneration in Aging (CCNA), Canadian Institutes of Health Research, and Ontario Brain Institute, paid to her institution; and a contract with the Public Health Agency of Canada, paid to her institution. Amer Burhan reports a contract with the Toronto Memory Program (Headland Research), paid to him; consulting for Eisai, Avanir, Otsuka-Lundbeck, Boehringer-Ingelheim, and Roche Pharma, paid to him; and grants from the National Institute of Aging, Brain Canada Foundation, Alzheimer Drug Discovery Foundation, National Research Council, Weston Foundation, and Canada Institute for Health Research, paid to his institution. Frederic Calon reports meeting expenses from Eli Lilly, paid to him. Richard Camicioli reports grants from the Canadian Institutes of Health Research, National Institute of Health, Weston Foundation, paid to him; and support for attending meetings from Parkinson Canada, Canadian Movement Disorders Group, and the Canadian Consortium on Neurodegeneration in Aging, paid to him; and advisory boards for Ambroxal trial and Parkinson Canada, unpaid. Barry Campbell reports no disclosures. Howard Chertkow reports contracts as site PI for clinical trials with Hoffmann-La Roche Limited, TauRx, Eli Lilly Corp., Anavex Life Sciences, Alector LLC, Biogen MA Inc., IntelGenX Corp., and Immunocal, paid to his institution; and consulting for Eisai, Biogen, and Lilly Inc. in Canada, paid to his institution. D. Louis Collins reports no disclosures. Mahsa Dadar reports no disclosures. Mari DeMarco reports consulting for Roche and Eisai, paid to her; honoraria from Roche, paid to her; and a grant from Roche, paid to her institution. Philippe Desmarais reports consulting for Eisai, paid to him. Simon Ducharme reports contracts for clinical trials with Biogen, Janssen, Novo Nordisk, Alnylam, Passage Bio, and Innodem Neurosciences, paid to his institution; consulting for QuRALIS, Eisai, and Eli Lilly, paid to him; honoraria from Eisai, paid to him; and participation in a Data Safety Monitoring Board or Advisory Board for Aviado Bio and IntelGenX, paid to him. Simon Duchesne reports stock or stock options for True Positive Medical Devices Inc., paid to him; honoraria from Novo Nordisk, paid to him; and travel expenses from Eisai, paid to him. Gillian Einstein reports no disclosures. Howard Feldman reports consulting for Eisai Inc., Biogen, LuMind, and Novo Nordisk, paid to his institution; grants from Allyx Therapeutics, Vivoryon Therapeutics, Biohaven Pharmaceuticals, and LuMind Foundation, paid to his institution; royalties from the University of British Columbia, paid to him; a patent held by the University of British Columbia, paid to him; consulting for Axon Neuroscience, Arrowhead Pharmaceuticals, and Biosplice Therapeutics, paid to his institution; support for attending meetings or travel from Novo Nordisk Inc., Royal Society of Canada, Translating Research in Elder Care (TREC), and the Association for Frontotemporal Dementia (AFTD), with payments made to his institution; participation in a Data Safety Monitoring Board or Advisory Board for the Tau Consortium and Janssen Research & Development LLC, paid to his institution; and philanthropic support from the Epstein Family Alzheimers Research Collaboration, paid to his institution. John Fisk reports no disclosures. Andrew Frank reports consulting for Eli Lilly Canada, Eisai Canada, and Novo Nordisk, paid to him. Aravind Ganesh reports grants from the Alzheimer Society of Canada and Alzheimer Society of Alberta and Northwest Territories, paid to his institution; and consulting for Biogen and Eisai, paid to him. Jodie Gawryluk reports no disclosures. Linda Grossman reports no disclosures. Arthur Harrison reports no disclosures. Alexandre Henri-Bhargava reports consulting for Eisai Canada and Eli Lilly, paid to him; contracts for clinical trials with Novo Nordisk, Cerevel, Anavex, IntelGenX, and Green Valley (Shanghai), paid to his institution; honoraria from the Canadian Coalition for Seniors Mental Health, paid to him; leadership in the Consortium of Canadian Centres for Clinical Cognitive Research and the Canadian Neurological Society, unpaid; and other financial or non-financial interests through the Neil and Susan Manning Cognitive Health Initiative, paid to his institution. Zahinoor Ismail reports consulting for CADTH, Eisai, Lilly, Lundbeck, Novo Nordisk, Otsuka, and Roche, paid to him. Inbal Itzhak reports no disclosures. Manish Joshi reports consulting for Eisai, Biogen, Eli Lilly, and Clario, paid to him. Edeltraut Kroger reports no disclosures. Sanjeev Kumar reports no disclosures. Robert Laforce reports consulting for Eisai and Eli Lilly, paid to him. Krista Lanctot reports grants from the Canadian Institutes of Health Research, Alzheimers Drug Discovery Foundation, Weston Foundation, Alzheimers Association (US), and Pooler Charitable Fund, paid to her institution; contracts with Cerevel and BioXcel, paid to her institution; consulting for Boehringer Ingelheim, Bright Minds, Bristol Myers Squibb, Cerevel, Eisai Co. Ltd, Exciva, Ironshore Pharmaceuticals, Kondor Pharma, H Lundbeck A/S, Novo Nordisk, and Praxis Therapeutics, paid to her; honoraria from Novo Nordisk, H Lundbeck, and Eisai, paid to her; support for attending meetings or travel from H Lundbeck and Eisai, paid to her institution; participation in a Data Safety Monitoring Board or advisory board for the PAS-MCI Study, unpaid; leadership in the American Association of Geriatric Psychiatry, unpaid; and receipt of equipment, materials, drugs, gifts, or services from PBG, paid to her institution. Meghan Lau reports no disclosures. Linda Lee reports consulting for Eisai, Lilly, Novo Nordisk, Lundbeck, and Roche, paid to her. Mario Masellis reports grants from the Canadian Institutes of Health Research, Weston Brain Institute, Ontario Brain Institute, Washington University, Women's Brain Health Initiative, Brain Canada, and EU Joint Program for Neurodegenerative Disease Research, paid to him; contracts for clinical trials with Roche and Alector, paid to his institution; consulting fees from Ionis, Alector, Biogen Canada, Wave Life Science, Eisai Canada, and Novo Nordisk Canada, paid to him; royalties from the Henry Stewart Talks, paid to him; honoraria from MINT Memory Clinics and ECHO Dementia Series, paid to him; and membership in Scientific Advisory Boards of the Alzheimer's Society Canada and Parkinson Canada, unpaid. Fadi Massoud reports honoraria from Astellas and Pfizer, paid to him; and consulting for Eisai and Novo Nordisk, paid to him. Sara Mitchell reports consulting for Eisai, paid to her; honoraria from Eisai and Eli Lilly, paid to her; support for attending meetings or travel from Eli Lilly, paid to her; and leadership in the Novo Nordisk Advisory Board, paid to her. Manuel Montero-Odasso reports no disclosures. Karen Myers Barnett reports no disclosures. Haakon Nygaard reports consulting for Eisai, paid to him; and participation in advisory boards for Biogen and Hoffmann-La Roche, paid to him. Stephen Pasternak reports a grant from Zywie Bio LLC and the Weston Foundation, paid to his institution; site investigator for contracts with Cassava and AriBio, paid to his institution; consulting for Eisai, unpaid; an advisory board role for Zywie Bio LLC, unpaid; stock in Zywie Bio LLC; a patent through Zywie Bio LLC, unpaid; and leadership in the C5R Board, unpaid. Jody Peters reports no disclosures. Natalie Phillips reports no disclosures. M. Natasha Rajah reports no disclosures. Julie Robillard reports no disclosures. Kenneth Rockwood reports royalties from The Clinical Frailty Scale and the Pictorial Fit-Frail Scale, paid to his institution; honoraria from the Burnaby Family Practice, Chinese Medical Association, University of Nebraska-Omaha, the Australia New Zealand Society of Geriatric Medicine, the Atria Institute, University of British Columbia, McMaster University, and Fraser Health Authority, paid to him; a US patent application submitted for Electronic Goal Attainment Scaling (patent number US20230402138A1); consulting for EIP Pharma Inc., the ADMET-2 advisory board (Johns Hopkins), and the Wake Forest University Medical School Centre advisory board, unpaid; advisory board roles with Ardea Outcomes, Danone, Hollister, INmune, Novartis, Takeda, and Nutricia, unpaid. Pedro Rosa-Neto reports no disclosures. Dallas Seitz reports a grant from the University Health Foundation - Alberta Roche Collaboration in Health, Alzheimers Association, and Alzheimer Society of Canada, paid to his institution; honoraria from the Canadian Coalition for Seniors Mental Health, Alberta Health Services, and Recovery Alberta, paid to him; and leadership on the Board of Directors for the Alzheimer Society of Alberta and Northwest Territories, unpaid. Eric Smith reports grants from the Canadian Institutes of Health Research, Weston Family Foundation, and Weston Brain Institute, paid to his institution; contracts for clinical trials from Biogen, paid to his institution; contracts with Sense Diagnostics and SFJ Pharmaceuticals, paid to his institution; royalties from UpToDate and UTI Limited Partnership, paid to him; consulting for Eisai, Eli Lilly, and Alnylam, unpaid; and participation in a Data Safety and Monitoring Board for NINDS, paid to him. Jean-Paul Soucy reports grants from the Weston Foundation and Canadian Institutes of Health Research, paid to his institution; a contract with Charles River, paid to his institution; and consulting for Biogen, paid to him. Shanna Trenaman reports being a patient advisor for a Delphi panel developing best practices for antipsychotic use in long-term care, unpaid. Cheryl Wellington reports grants from the Heart and Stroke Foundation of Canada, BrightFocus Foundation, and Cure Alzheimer Fund, paid to her institution. Aicha Zadem reports no disclosures. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Masson SAS.)

Objective: Around 400,000 cataract operations are performed annually in the UK, with a complication rate of 1.95% and the associated financial costs at over £13 million. Cataract operations are occasionally cancelled when patients cannot attend. To fully utilize theatre time, agreeable patients may be directly sent for surgery from assessment clinics. This study investigates the validity of "Murphy's Law" in ophthalmology, namely, whether there is an increase in complication rates amongst these 'add-on' cases., Design & Participants: Retrospective study to compare data of add-on phacoemulsification operations against the departmental baseline., Methods: Chi-square test was used to determine whether the complication rates differed significantly. 1-sided p -value of <0.05 was considered to be significant., Results: 227 'add-on' cases were identified, of which 3 complications occurred. Departmental baseline of 4289 operations resulted in 44 complications. These represented complication rates of 1.32% and 1.03%, respectively. The level of surgical difficulty between the two groups were comparable. Statistical comparison of these complication rates demonstrated a p -value of 0.67, indicating that Murphy's Law is not significant., Conclusions: This is the first study of its kind to examine the rates of adverse outcomes in unscheduled 'add-on' cataract surgeries, a commonly deployed method to maximize eye theatre time usage. Our data suggested no significant difference in complication rates between the add-on operations and local baseline. Thus, we demonstrated that the practice of same day proceeding from pre-operative assessment clinic to the operating table is a safe option to optimize theatre time use, should a surgery cancellation arise., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The Canadian Stroke Best Practice Recommendations (CSPR) 7th edition includes this new module on the diagnosis and management of vascular cognitive impairment (VCI) with or without neurodegenerative disease. An expert writing group and people with VCI lived experience (PWLE) reviewed current evidence. Existing recommendations were reviewed and revised, and new recommendations added. Sections include definitions, signs and symptoms, screening, assessment, diagnosis, pharmacological and non-pharmacological management, secondary prevention, rehabilitation, and end-of-life care. PWLE were actively involved in all aspects of the development, ensuring their experiences are integrated. A unique VCI journey map, developed by PWLE, is included, and helped to motivate and anchor the recommendations. We encourage it to be displayed across healthcare settings to raise awareness and support persons with VCI. These VCI CSBPRs emphasize the need for integrated multidisciplinary care across the continuum. Evidence for the diagnosis and management of VCI continues to emerge and gaps in knowledge should drive future research. HIGHLIGHTS: This Canadian Stroke Best Practice Recommendations module focuses specifically on VCI using a structured framework and validated methodology. A comprehensive set of evidence-based recommendations is presented that addresses the continuum from symptom onset to diagnosis, management, and end of life. The recommendations consider individuals who experience VCI because of stroke or because of other vascular pathologies such as atrial fibrillation or heart failure. A journey map of an individual's experience with VCI has been developed by individuals with lived experience. It is a valuable guide to inform educational content, approaches to caring for individuals and families with VCI, and systems planning., (© 2025 Heart and Stroke Foundation of Canada. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: There is a projected and growing gap of geriatricians in Canada. Geriatricians play a crucial role in addressing the health needs of older adults. We aimed to understand the factors that influence the choice of first-practice location for new geriatricians in the context of an aging Canadian population., Methods: We distributed an online survey to geriatric medicine subspecialty residents and recently licensed geriatricians in Canada. The survey was developed through expert opinions, career planning sessions, and a literature review. There were nine survey sections: general characteristics, location determinants, practice determinants, colleague determinants, support and space, non-clinical opportunities, income models, lifestyle factors, and recruitment determinants. The data were analyzed descriptively., Results: A total of 61 respondents (51 English, 10 French) completed the survey. The respondents were new practicing geriatricians (37) and geriatric medicine residents (24). Most planned to practice in Ontario (26.2%) or Quebec (27.9%), and 75.4% were women. Flexibility in work-life balance (95.1%), collegiality (93.4%) and reasonable call schedules (93.4%) were the most important factors influencing first practice location. Income did not rank among the highest priorities for choosing the first practice location relative to other factors but was mentioned in open-ended responses to recruitment questions., Conclusions: This is the first survey identifying the determinants of first practice location in geriatric medicine in Canada. Work-life balance and collegial support are a priority for new geriatricians and may be the strongest incentives a program can provide. For recruitment, income incentives may be beneficial to building new specialized geriatric services. Future research will examine determinants of first practice location among Care of the Elderly clinicians., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure and declare there are none., (© 2024 Author(s).)

Given their sudden onset and life-threatening consequences, strokes and transient ischemic attacks (TIAs) can trigger posttraumatic stress disorder (PTSD). To gain a deeper understanding of the potential influence of factors in patients' descriptions of these medical events on PTSD, we conducted a standardized trauma interview with a convenience sample of patients hospitalized for suspected stroke/TIA (N = 98) to assess the details and emotional experience of the stroke/TIA event. Three researchers reviewed the interviews and the research literature on risk and protective factors for PTSD. From this analysis, a codebook with descriptions, examples, and scoring protocols for eight Likert scale, two categorical, and four binary codes was developed. Upon demonstrating sufficient interrater reliability, the research team scored all narratives. Three superordinate themes were identified in the analysis: distress (e.g., fear, helplessness), potential protective factors (e.g., positive expectancies, concern for loved ones), and level of detail (e.g., somatic detail, emotional detail). Differences in perceptions, themes, and expectations emerged in the narratives, indicating a wide range of responses following stroke/TIA. Additionally, patient age was negatively correlated with scores for the fear, r = -.34, p < .001, and negative consequences, r = -.24, p = .018, codes and positively associated with the likelihood of having positive expectancies, OR = 1.05, 95% CI [1.00, 1.10], p = .039. These findings provide a more comprehensive understanding of how patients reflect on their experiences post-stroke/TIA and can inform future research on the contributions of trauma narrative characteristics and emotional responses to PTSD risk., (© 2024 The Author(s). Journal of Traumatic Stress published by Wiley Periodicals LLC on behalf of International Society for Traumatic Stress Studies.)

Upright posture challenges the cerebrovascular system, leading to changes in middle cerebral artery velocity (MCAv) dynamics which are less evident at supine rest. Chronic alterations in MCAv have been linked to hypoperfusion states and the effect that this may have on cognition remains unclear. This study aimed to determine if MCAv and oscillatory metrics of MCAv (ex. pulsatility index, PI) during upright posture are i) associated with cognitive function and gait speed (GS) to a greater extent than during supine rest, and ii) are different between sexes. Beat-by-beat MCAv (transcranial Doppler ultrasound) and mean arterial pressure (MAP, plethysmography) were averaged for 30-seconds during supine-rest through a transition to standing for 53 participants (73±6yrs, 17 females). While controlling for age, multiple linear regressions predicting MoCA scores and GS from age, supine MCAv metrics, and standing MCAv metrics, were completed. Simple linear regressions predicting Montreal Cognitive Assessment (MoCA) score and GS from MCAv metrics were performed separately for females and males. Significance was set to p <0.05. Lower standing diastolic MCAv was a significant ( p  = 0.017) predictor of lower MoCA scores in participants with mild cognitive impairment, and this relationship only remained significant for males. Lower standing PI was associated with slower GS ( p  = 0.027, r =-0.306) in both sexes. Our results indicate a relationship between blunted MCAv and altered oscillatory flow profiles during standing, with lower MoCA scores and GS. These relationships were not observed in the supine position, indicating a unique relationship between standing measures of MCAv with cognitive and physical functions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the severity of renal insufficiency; this will determine treatment options at the beginning and throughout the management of pain in CKD patients. The dosage of hydrophilic drugs and drugs with active metabolites should be adjusted according to the severity of CKD, and the process of treatment should be monitored by modifying drug dosages as necessary for background and breakthrough pain. Patients with CKD may benefit from opioid analgesics that are lipophilic, such as methadone, fentanyl, and buprenorphine, as the first line; however, fentanyl is inappropriate for patients undergoing hemodialysis. Opioid prescription in CKD patients is the subject of this systematic review, which aims to compare their safety and efficacy. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Using three databases (PubMed, ScienceDirect, and Google Scholar), we collected and reviewed articles, including literature reviews, randomized control trials (RCTs), and systematic reviews published between 1980 and 2022, to enable us to gather enough valuable data on this rare topic. After applying appropriate filters, a total of 109 results were obtained. They were further screened and subjected to quality assessment tools, which finally yielded 11 studies included in this systematic review. This consisted of two RCTs, two systematic reviews, and seven narrative reviews. This review focused on the safety and appropriate use of opioids in patients with CKD. The accumulation of morphine and codeine metabolites may result in neurotoxic side effects. Hydromorphone and oxycodone are considered safe to administer but require careful adjustments in dosage. Common comorbidities among patients with CKD may amplify opioid-related adverse effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Odoma et al.)

Background and Aims: Systemic chemotherapy followed by hepatic resection is the treatment of choice for patients with colorectal cancer liver metastasis (CRCLM) but reliable biomarkers predicting response to therapy are needed. Spontaneous apoptosis of single tumour cells is common in CRCLM. We explored the potential of circulating apoptosis markers to predict treatment response., Materials and Methods: Fifty-eight patients with CRCLM or hepatocellular carcinoma (HCC) were included in this study. Tumour tissue and blood samples were obtained before and after initiation of chemotherapy. Immunohistochemistry and ELISA assays were utilized to quantify the apoptosis marker caspase-cleaved cytokeratin 18 (M30) in tissue and circulation., Results: CRCLM tissues showed more apoptotic tumour cells than HCC, or healthy liver. This was associated with elevated levels of circulating M30 (median = 244 U/l vs. 37 U/l in healthy controls, p = 0.009) which correlated with tumour volume (r 2  = 0.92). Patients with progressive disease during chemotherapy showed higher M30 levels before therapy than responders (745 U/l vs. 136 U/l, p = 0.016). The predictive potential of M30 was higher than that of the tumour markers CA19-9 or CEA (AUC: 0.93, 0.63, and 0.78, respectively)., Conclusions: Apoptotic tumour cells release cellular debris into the circulation, which provides information about tumour size and vitality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cognitive reserve may protect against the effects of brain pathology, but few studies have looked at whether cognitive reserve modifies the adverse effects of vascular brain pathology., Objective: We determined if cognitive reserve attenuates the associations of vascular brain lesions with worse cognition in persons with subjective concerns or mild impairment., Methods: We analyzed 200 participants aged 50-90 years from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study. Cognition was measured using the Montreal Cognitive Assessment and a neuropsychological test battery. High vascular lesion burden was defined as two or more supratentorial infarcts or beginning confluent or confluent white matter hyperintensity. Cognitive reserve proxies included education, occupational attainment, marital status, social activities, physical activity, household income, and multilingualism., Results: Mean age was 72.8 years and 48% were female; 73.5% had mild cognitive impairment and 26.5% had subjective concerns. Professional/managerial occupations, annual household income≥$60,000 per year, not being married/common law, and high physical activity were independently associated with higher cognition. Higher vascular lesion burden was associated with lower executive function, but the association was not modified by cognitive reserve., Conclusion: Markers of cognitive reserve are associated with higher cognition. Vascular lesion burden is associated with lower executive function. However, cognitive reserve does not mitigate the effects of vascular lesion burden on executive function. Public health efforts should focus on preventing vascular brain injury as well as promoting lifestyle factors related to cognitive reserve, as cognitive reserve alone may not mitigate the effects of vascular brain injury., Competing Interests: Romella Durrani, Aravind Ganesh, Jaspreet Bhangu, Sandra Black, and Vladimir Hachinski report no disclosures. Philip Barber reports research grant funding from the Heart and Stroke Foundation of Canada. Thalia Field reports a research grant from Bayer (in-kind study medication) and consulting fees from HLS Therapeutics. Rick Swartz received salary support for research from Heart and Stroke Foundation Clinician-Scientist Phase II Award, the Sunnybrook Department of Medicine and the SE Black Centre for Brain Resilience and Recovery, and research grant funding from CIHR, Heart and Stroke Foundation, National Institute of Health, and the Ontario Brain Institute. Mukul Sharma reports research support from Bayer, Bristol Myers Squibb and Janssen, and consulting fees from Bayer, Bristol Myers Squibb, Alexion, and HLS Therapeutics. Eric Smith reports consulting fees from Bayer, Biogen, and Cyclerion, and royalties from UpToDate., (© 2022 – The authors. Published by IOS Press.)

Circadian rhythms are maintained by a complex "system of systems" that continuously coordinates biological processes with each other and the environment. Although humans predominantly entrain to solar time, individual persons vary in their precise behavioral timing due to endogenous and exogenous factors. Endogenous differences in the timing of individual circadian rhythms relative to a common environmental cue are known as chronotypes, ranging from earlier than average (Morningness) to later than average (Eveningness). Furthermore, individual behavior is often constrained by social constructs such as the 7-day week, and the "sociogenic" impact our social calendar has on our behavioral rhythms is likely modified by chronotype. Our aim in this study was to identify and characterize differences in sleep and rest-activity rhythms (RAR) between weekends and weekdays and between-chronotypes. Male volunteers (n = 24, mean age = 23.46 y) were actigraphically monitored for 4 weeks to derive objective behavioral measures of sleep and RARs. Chronotype was assessed through self-report on the Morningness-Eveningness Questionnaire. Sleep characteristics were derived using Actiware; daily rest-activity rhythms were modeled using a basic 3-parameter cosinor function. We observed that both Eveningness and Morningness Chronotypes were more active and slept later on the weekends than on weekdays. Significant between-chronotype differences in sleep timing and duration were observed within individual days of the week, especially during transitions between weekends and the workweek. Moreover, chronotypes significantly varied in their weekly rhythms: e.g. Morningness Chronotypes generally shifted their sleep duration, timing and quality across work/rest transitions quicker than Eveningness Chronotypes. Although our results should be interpreted with caution due to the limitations of our cosinor model and a homogenous cohort, they reinforce a growing body of evidence that day of the week, chronotype and their interactions must be accounted for in observational studies of human behavior, especially when circadian rhythms are of interest.

Patients with atopic dermatitis experience increased nocturnal pruritus which leads to scratching and sleep disturbances that significantly contribute to poor quality of life. Objective measurements of nighttime scratching and sleep quantity can help assess the efficacy of an intervention. Wearable sensors can provide novel, objective measures of nighttime scratching and sleep; however, many current approaches were not designed for passive, unsupervised monitoring during daily life. In this work, we present the development and analytical validation of a method that sequentially processes epochs of sample-level accelerometer data from a wrist-worn device to provide continuous digital measures of nighttime scratching and sleep quantity. This approach uses heuristic and machine learning algorithms in a hierarchical paradigm by first determining when the patient intends to sleep, then detecting sleep-wake states along with scratching episodes, and lastly deriving objective measures of both sleep and scratch. Leveraging reference data collected in a sleep laboratory (NCT ID: NCT03490877), results show that sensor-derived measures of total sleep opportunity (TSO; time when patient intends to sleep) and total sleep time (TST) correlate well with reference polysomnography data (TSO: r = 0.72, p < 0.001; TST: r = 0.76, p < 0.001; N = 32). Log transformed sensor derived measures of total scratching duration achieve strong agreement with reference annotated video recordings (r = 0.82, p < 0.001; N = 25). These results support the use of wearable sensors for objective, continuous measurement of nighttime scratching and sleep during daily life.

Purpose : Spontaneous eye-blink rate is the number of involuntary blinks performed during a certain period of time. Assessing blink rate in humans provides valuable physiological and behavioral data for studying neuropathology and emotional states. Cognitive states, including awareness on the part of the subject that his or her blinks are being counted, may influence blink activity and confound blink rate measurements. The goal of this study was to provide direct experimental evaluation of the hypothesis that subject awareness affects tasked-based blink activity. Materials and methods : 30 young healthy adult males with normal vision underwent a series of tasks - viewing images, talking, sitting quietly, and cross fixation - while being video recorded. Each subject completed the tasks naively, then repeated them after being explicitly told their blink rate was being measured. Blink rate was measured through minute-by-minute blink counts by human raters. Results : We found a transitory impact on blink count during the first and third minute of a passive image-viewing task that occurred immediately after subjects were informed of their eye blinks being counted. However, the overall blink rate across the 7-min passive image-viewing task was not influenced. In three other tasks - fixation, silence, and conversation - we observed no statistically significant difference in minute-by-minute blink count or overall blink rate. Conclusions : We conclude that informing a subject that his eye blinks are being counted exerts a modest but significant acute influence on blinking activity, but critically does not appear to confound blink rate over prolonged tasks.

Bioorthogonal click reactions yielding stable and irreversible adducts are in high demand for in vivo applications, including in biomolecular labeling, diagnostic imaging, and drug delivery. Previously, we reported a novel bioorthogonal "click" reaction based on the coupling of ortho-acetyl arylboronates and thiosemicarbazide-functionalized nopoldiol. We now report that a detailed structural analysis of the arylboronate/nopoldiol adduct by X-ray crystallography and 11 B NMR reveals that the bioorthogonal reactants form, unexpectedly, a tetracyclic adduct through the cyclization of the distal nitrogen into the semithiocarbazone leading to a strong B-N dative bond and two new 5-membered rings. The cyclization adduct, which protects the boronate unit against hydrolytic breakdown, sheds light on the irreversible nature of this polycondensation. The potential of this reaction to work in a live animal setting was studied through in vivo capture of fluorescently labeled molecules in vivo . Arylboronates were introduced into tissues through intradermal injection of their activated NHS esters, which react with amines in the extracellular matrix. Fluorescently labeled nopoldiol molecules were administered systemically and were efficiently captured by the arylboronic acids in a location-specific manner. Taken together, these in vivo proof-of-concept studies establish arylboronate/nopoldiol bioorthogonal chemistry as a candidate for wide array of applications in chemical biology and drug delivery.

This study describes the design and synthesis of arylboronic acid 2, the first example of a permanently open "frustrated" benzoxaborole, along with an exploration of its application in bioconjugation. An efficient and high yielding seven-step synthesis was optimized. NMR experiments confirmed that compound 2 exists in the open ortho-hydroxyalkyl arylboronic acid structure 2-I, a form that is effectively prevented to undergo a dehydrative cyclization as a result of unfavorable geometry. Compound 2-I conjugates effectively with amines to form stable hemiaminal ether structures, including a highly effective reaction with lysozyme. Complexation with cysteine induces an open structure containing a free hydroxymethyl arm, with the amino and thiol groups reacting preferentially with the formyl group to form a N,S-acetal.

The continuous, longitudinal nature of accelerometry monitoring is well-suited to capturing the regular 24-hour oscillations in human activity across the day, the cumulative effect of our circadian rhythm and behavior. Disruption of the circadian rhythm in turn disrupts rest-activity rhythms. Although circadian disruption is a major feature of Parkinson's disease (PD), rest-activity rhythms and their relationship with disease severity have not been well characterized in PD. 13 PD participants (Hoehn & Yahr Stage [H&Y] 1-3) wore a Philips Actiwatch Spectrum PRO continuously for two separate weeks. Rest-activity rhythms were quantified by fitting an oscillating 24-hour cosinor model to each participant-day of activity data. One-way ANOVAs adjusted for demographics revealed significant variation in the amount (MESOR, F = 12.76, p < .01), range (Amplitude, F = 9.62, p < .01), and timing (Acrophase, F = 2.7, p = .05) of activity across H&Y Stages. Those with higher H&Y Stages were significantly more likely to be active later in the day, where-as those who shifted between H&Y Stages during the study were significantly more active than those who did not change H&Y Stage. Being active later in the day was also significantly associated with higher scores on the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Section III (motor symptom severity, p = .02), Section II (self-reported impact of motor symptoms on daily living, p = .01), and Total Score ( p = .01) in an adjusted linear regression model; significant associations between MDS-UPDRS scores and activity levels were observed only in the unadjusted model. These findings demonstrate that continuous actigraphy is capable of detecting rest-activity disruption in PD, and provides preliminary evidence that rest-activity rhythms are associated with motor symptom severity and H&Y Stage.

Objectives: In 2010, South Africa (SA) hosted the Fédération Internationale de Football Association (FIFA) World Cup (soccer). Emergency Medical Services (EMS) used the SA mass gathering medicine (MGM) resource model to predict resource allocation. This study analyzed data from the World Cup and compared them with the resource allocation predicted by the SA mass gathering model., Methods: Prospectively, data were collected from patient contacts at 9 venues across the Western Cape province of South Africa. Required resources were based on the number of patients seeking basic life support (BLS), intermediate life support (ILS), and advanced life support (ALS). Overall patient presentation rates (PPRs) and transport to hospital rates (TTHRs) were also calculated., Results: BLS services were required for 78.4% (n = 1279) of patients and were consistently overestimated using the SA mass gathering model. ILS services were required for 14.0% (n = 228), and ALS services were required for 3.1% (n = 51) of patients. Both ILS and ALS services, and TTHR were underestimated at smaller venues., Conclusions: The MGM predictive model overestimated BLS requirements and inconsistently predicted ILS and ALS requirements. MGM resource models, which are heavily based on predicted attendance levels, have inherent limitations, which may be improved by using research-based outcomes.

Introduction: Health literacy can create barriers for ED staff attempting to communicate important information to patients. Video discharge instructions may address some of these barriers by improving patients' comprehension of medical information and addressing health literacy challenges., Methods: One hundred ninety-six patients diagnosed with either hypertension, asthma, congestive heart failure, or diabetes were randomly assigned to 1 of 2 interventions: watching video medical information followed by reviewing written discharge instructions or written instructions first, followed by video education. After the interventions, patients from both groups completed surveys assessing their preferences for receiving medical information., Results: We found that 44% (n = 86/196) of ED patients preferred receiving medical information in video format, whereas 18% (n = 35/196) favored the written format, and 38% (n = 75/196) of the sample preferred receiving both formats. Fifty-five percent of men (n = 38/69) preferred the video format, whereas 42% (n = 51/122) of women indicated a preference for both video and written formats. Learning something new from the video was associated with patient preference for receiving medical instructions, (χ2 [1] = 9.39, P = 0.01) and the desire to watch medical videos or read information at home via the Internet (χ2 [1] = 18.46, P < 0.001)., Discussion: The majority of ED patients in this study preferred medical information in video or video plus written formats, compared with written-only format., (Copyright © 2019 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Background: Returning to driving after stroke is one of the key goals in stroke rehabilitation, and fitness to drive guidelines must be informed by evidence pertaining to risk of motor vehicle collision (MVC) in this population., Objectives: The purpose of the present study was to determine whether stroke and/or transient ischemic attack (TIA) are associated with an increased MVC risk., Methods: We searched MEDLINE, CINAHL, EMBASE, PsycINFO, and TRID through December 2016. Pairs of reviewers came to consensus on inclusion, based on an iterative review of abstracts and full-text manuscripts, on data extraction, and on the quality of evidence., Results: Reviewers identified 5,605 citations, and 12 articles met inclusion criteria. Only one of three case-control studies showed an association between stroke and MVC (OR 1.9, 95% CI 1.0-3.9). Of five cohort reports, only one study, limited to self-report, found an increased risk of MVC associated with stroke or TIA (RR 2.71, 95% CI 1.11-6.61). Two of four cross-sectional studies using computerized driving simulators identified a more than two-fold risk of MVCs among participants with stroke compared with controls. The difference in one of the studies was restricted to those with middle cerebral artery stroke., Conclusions: The evidence does not support a robust increase in risk of MVCs. While stroke clearly prevents some patients from driving at all and impairs driving performance in others, individualized assessment and clinical judgment must continue to be used in assessing and advising those stroke patients who return to driving about their MVC risk.

Aim: There is growing evidence of an overlap between unexplained falls and syncope in older adults. Our aim was to examine the prevalence and associated resource utilization of these conditions in an urban emergency department (ED)., Patients and Methods: A single-centre, prospective, observational study was carried out over a 6-month period. Consecutive patients older than 50 years who presented to the ED because of a fall, collapse or syncope were included. Univariate analysis of demographic data is presented as percentages, mean (SD), 95% confidence intervals (CIs) and medians (interquartile range). Logistic regression modelling was used to examine the association between falls and resource utilization., Results: A total of 561 patients fulfilled the inclusion criteria during the study period. Unexplained fallers accounted for 14.3% (n=80; 95% CI: 13.3-15.3) and syncope for 12.7% (n=71; 95% CI: 11.7-13.6) of all fall presentations. Overall, 50% (n=282; 95% CI: 48.20-52.34) of patients required admission to hospital. Patients with syncope [odds ratio (OR)=2.48, 95% CI: 1.45-4.23], and unexplained falls (OR=2.36, 95% CI: 1.37-4.08) were more likely to require admission than those with an explained falls. Unexplained fallers were nearly five times more likely to suffer recurrent falls (OR=4.97, 95% CI: 2.89-8.56)., Conclusion: One in four older fallers presenting to ED have symptoms suggestive of syncope or an unexplained fall. There are significant biological consequences of recurrent falls including greater rates of cognitive decline, gait and mobility disturbances, depression and frailty. Recognition that syncope can present as an unexplained fall in older adults is important to ensure that appropriate early modifiable interventions are initiated.

Introduction: The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the current gold standard means of assessing disease state in Parkinson's disease (PD). Objective measures in the form of wearable sensors have the potential to improve our ability to monitor symptomology in PD, but numerous methodological challenges remain, including integration into the MDS-UPDRS. We applied a structured video coding scheme to temporally quantify clinical, scripted, motor tasks in the MDS-UPDRS for the alignment and integration of objective measures collected in parallel., Methods: 25 PD subjects completed two video-recorded MDS-UPDRS administrations. Visual cues of task performance reliably identifiable in video recordings were used to construct a structured video coding scheme. Postural transitions were also defined and coded. Videos were independently coded by two trained non-expert coders and a third expert coder to derive indices of inter-rater agreement., Results: 50 videos of MDS-UPDRS performance were fully coded. Non-expert coders achieved a high level of agreement (Cohen's κ > 0.8) on all postural transitions and scripted motor tasks except for Postural Stability (κ = 0.617); this level of agreement was largely maintained even when more stringent thresholds for agreement were applied. Durations coded by non-expert coders and expert coders were significantly different (p < 0.05) for only Postural Stability and Rigidity, Left Upper Limb., Conclusions: Non-expert coders consistently and accurately quantified discrete behavioral components of the MDS-UPDRS using a structured video coding scheme; this represents a novel, promising approach for integrating objective and clinical measures into unified, longitudinal datasets., (Copyright © 2018. Published by Elsevier Ltd.)

In this account, we describe the synthesis of a series of BINOL-based bis- and trisphosphoric acids 11d/e/f, which commonly feature an unusual phosphoric acid monoester motif. This motif is generated by an acid-catalyzed 5- endo- dig cyclization of the 3-alkynyl-substituted BINOL precursors to give the corresponding Furan-annelated derivatives, followed by phosphorylation of the remaining phenolic alcohols. In the cyclization reaction, we observed an unexpected partial racemization in the bis- and tris-BINOL scaffolds, leading to mixtures of diastereomers that were separated and characterized spectroscopically and by X-ray crystal structure analyses. The cyclization and racemization processes were investigated both experimentally and by DFT-calculations, showing that although the cyclization proceeds faster, the barrier for the acid-catalyzed binaphthyl-racemization is only slightly higher.

Objective: This study aimed to evaluate the nature and type of communication and workflow arrangements between nurses and doctors out-of-hours (OOH). Effective communication and workflow arrangements between nurses and doctors are essential to minimize risk in hospital settings, particularly in the out-of-hour's period. Timely patient flow is a priority for all healthcare organizations and the quality of communication and workflow arrangements influences patient safety., Design: Qualitative descriptive design and data collection methods included focus groups and individual interviews., Setting: A 500 bed tertiary referral acute hospital in Ireland., Participants: Junior and senior Non-Consultant Hospital Doctors, staff nurses and nurse managers., Results: Both nurses and doctors acknowledged the importance of good interdisciplinary communication and collaborative working, in sustaining effective workflow and enabling a supportive working environment and patient safety. Indeed, issues of safety and missed care OOH were found to be primarily due to difficulties of communication and workflow. Medical workflow OOH is often dependent on cues and communication to/from nursing. However, communication systems and, in particular the bleep system, considered central to the process of communication between doctors and nurses OOH, can contribute to workflow challenges and increased staff stress. It was reported as commonplace for routine work, that should be completed during normal hours, to fall into OOH when resources were most limited, further compounding risk to patient safety., Conclusion: Enhancement of communication strategies between nurses and doctors has the potential to remove barriers to effective decision-making and patient flow., (© The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Mesiodentes are the most frequently encountered supernumerary teeth. Recently, reports of double mesiodens have increased, which may be due to the availability of better diagnostic methods. This article discusses 2 cases of double mesiodens with varying clinical presentations. In addition, the literature related to the etiology, clinical presentation, diagnosis, and management of mesiodentes is reviewed.

Objectives: To calculate the prevalence of all falls, non-accidental falls and syncope in an older population and characterize cardiovascular risk profiles., Design: Prospective, longitudinal cohort study., Setting: The first two waves of data from the Irish Longitudinal Study on Ageing (TILDA)., Participants: 8172 community-dwelling adults aged 50 years and older resident in the Republic of Ireland., Measurements: Self-reported history of all falls, non-accidental falls and syncope in the year preceding the first two waves of data collection. Demographic factors and self-reported cardiovascular conditions were used to characterize cardiovascular risk profiles., Results: The prevalence of all falls in the past year was 19.2% or 192 per thousand persons and increased with age (50-64 years 17.5%; 65-74 years 19.4%; 75+ years 24.4%). Non-accidental falls had an estimated prevalence of 5.1% or 51 falls per thousand persons and accounted for 26.5% of all falls reported and also increased with age (50-64 years 4.0%; 65-74 years 5.5%; 75+ years 8.0%). The prevalence for syncope was estimated to be 4.4% or 44per thousand persons but did not show a similar age gradient. Participants with at least 5 cardiovascular conditions were more likely to report all falls (OR = 2.07, 95% CI 1.18-3.64, p<0.05) and NAF (OR = 2.89, 95%CI 1.28-6.52, p<0.05)., Conclusions: The prevalence of all falls and non-accidental falls increases with age but the same pattern was not consistently observed for syncope. There is an increased odds of reporting all three outcomes with increasing number of self-reported cardiovascular conditions. Further work is needed to uncover the interplay between cardiovascular disease and subsequent falls.

Aims: Unexplained falls account for 20% of falls in older cohorts. The role of the implantable loop recorder (ILR) in the detection of arrhythmias in patients with unexplained falls is unknown. We aimed to examine the diagnostic utility of the ILR in detection of arrhythmogenic causes of unexplained falls in older patients., Methods: A single centre, prospective, observational cohort study of recurrent fallers over the age of 50 years with two or more unexplained falls presenting to an emergency department. Insertion of an ILR (Reveal, Medtronic, Minnesota, USA) was used to detect arrhythmia. The primary outcome was detection of cardiac arrhythmia associated with a fall or syncope. The secondary outcome was detection of cardiac arrhythmia independent of falls or syncope, and falls or syncope without associated arrhythmia., Results: Seventy patients, mean age 70 years (51-85 years) received an ILR. In 70% of patients cardiac arrhythmias were detected at a mean time of 47.3 days (SD 48.25). In 20%, falls were attributable to a modifiable cardiac arrhythmia; 10 (14%) received a cardiac pacemaker, 4 (6%) had treatment for supraventricular tachycardia. Patients who had a cardiac arrhythmia detected were more likely to experience a further fall., Conclusions: 14 (20%) patients demonstrated an arrhythmia which was attributable as the cause of their fall. Patients who have cardiac arrhythmia are significantly more likely to experience future falls. Further research is important to investigate if early detection of arrhythmogenic causes of falls using the ILR prevents future falls in older patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: Cardiovascular disorders are recognized as risk factors for falls in older adults. The aim of this systematic review was to identify cardiovascular disorders that are associated with falls, thus providing angles for optimization of fall-preventive care., Design: Systematic review., Data Sources: Medline and Embase., Eligibility Criteria for Selecting Studies: studies addressing persons aged 50 years and older that described cardiovascular risk factors for falls. Key search terms for cardiovascular abnormalities included all synonyms for the following groups: structural cardiac abnormalities, cardiac arrhythmia, blood pressure abnormalities, carotid sinus hypersensitivity (CSH), orthostatic hypotension (OH), vasovagal syncope (VVS), postprandial hypotension (PPH), arterial stiffness, heart failure, and cardiovascular disease. Quality of studies was assed using the Newcastle-Ottawa Scale., Results: Eighty-six studies were included. Of studies that used a control group, most consistent associations with falls were observed for low blood pressure (BP) (4/5 studies showing a positive association), heart failure (4/5), and cardiac arrhythmia (4/6). Higher prevalences of CSH (4/6), VVS (2/2), and PPH (3/4) were reported in fallers compared with controls in most studies, but most of these studies failed to show clear association measures. Coronary artery disease (6/10), orthostatic hypotension (9/25), general cardiovascular disease (4/9), and hypertension (7/25) all showed inconsistent associations with falls. Arterial stiffness was identified as an independent predictor for falls in one study, as were several echocardiographic abnormalities., Conclusion: Several cardiovascular associations with falls were identified, including low BP, heart failure, and arrhythmia. These results provide several angles for optimizing fall-preventive care, but further work on standard definitions, as well as the exact contribution of individual risk factors on fall incidence is now important to find potential areas for preventive interventions., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Syncope is a common problem which can be remarkably debilitating and associated with high health care costs; its true incidence is difficult to estimate due to variation in definition, differences in population prevalence and under reporting in the general population. The median peak of first syncope is around 15 years with a sharp increase after 70 years. Vasovagal syncope is the commonest cause of syncope for all age groups, but cardiac causes become more common with advancing age. The cumulative incidence of syncope ranges from 5% in females aged 20 to 29, up to 50% in females aged 80 and above. One-third of medical students report at least one syncopal episode in their life-time. The life-time cumulative incidence of syncope in women is almost twice that of men. Syncope accounts for up to 1-3% of hospital admissions and Emergency Room (ER) visits and in these settings is associated with cardiovascular co-morbidity and cardiovascular pharmacotherapy. In older adults syncope is a major cause of morbidity and mortality with enormous personal and wider health economic costs. Prevalence and incidence figures for syncope in older adults are confounded by an overlap with presentations classified as falls. In addition to injury and increasing dependency, quality-of-life studies consistently show that functional impairment in persons with recurrent syncope is similar to other chronic diseases., (Copyright © 2013 Elsevier Inc. All rights reserved.)