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Cognitive impairment is common after critical illness and persists beyond the period of acute illness. Clinicians caring for this patient population are encouraged to screen for cognitive impairment and provide supportive measures to mitigate its distressing effects. Further research is needed to evaluate the laboratory and neuroimaging correlates of post-intensive care unit (ICU) cognitive impairment, which may in turn lead to personalized interventions to address this debilitating complication of critical illness. Further research is needed to evaluate the laboratory and neuroimaging correlates of post-ICU cognitive impairment, which may, in turn, lead to personalized interventions to address this debilitating complication of critical illness., Competing Interests: Disclosures K. Honarmand have no conflicts of interest to declare. J.G. Boyd has a CIHR Project Grant (CONFOCAL-2 Study), has received a Clinician-Scientific Award from the Southeastern Ontario Academic Medical Association, and receives a stipend from the Ontario Health - Trillium Gift of Life for his role as Regional Medical Lead., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine the impact of point-of-care ultrasound (POCUS)-guided resuscitation on clinical outcomes in adult patients with shock., Data Source: We searched MEDLINE, Embase, and unpublished sources from inception to December 2023., Study Selection: We included randomized controlled trials (RCTs) that examined the use of POCUS to guide resuscitation in patients with shock., Data Extraction: We collected data regarding study and patient characteristics, POCUS protocol, control group interventions, and outcomes., Data Synthesis: We identified 18 eligible RCTs. POCUS slightly influences physicians' plans for IV fluid (IVF) and vasoactive medication prescription (moderate certainty), but results in little to no changes in the administration of IVF (low to high certainty) or inotropes (high certainty). POCUS may result in no change in the number of CT scans performed (low certainty) but probably reduces the number of diagnostic echocardiograms performed (moderate certainty). POCUS-guided resuscitation probably reduces 28-day mortality (relative risk [RR] 0.88; 95% CI, 0.78-0.99), the duration of vasoactive medication (mean difference -0.73 d; 95% CI, -1.16 to -0.30), and the need for renal replacement therapy (RRT) (RR 0.80; 95% CI, 0.63-1.02) (low to moderate certainty evidence), and lactate clearance (high certainty evidence). POCUS-guided resuscitation may results in little to no difference in ICU or hospital admissions, ICU and hospital length of stay, and the need for mechanical ventilation (MV) (low to moderate certainty evidence). There is an uncertain effect on the risk of acute kidney injury and the duration of MV or RRT (very low certainty evidence)., Conclusions: POCUS-guided resuscitation in shock may yield important patient and health system benefits. Due to lack of sufficient evidence, we were unable to explore how the thresholds of operator competency, frequency, and timing of POCUS scans impact patient outcomes., Competing Interests: Dr. Slessarev’s institution received funding from the Canadian Institutes of Health Research (CIHR) project grant for randomized controlled trial related to ICU sedation; he received support for article research from the CIHR. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs)., Methods: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing., Results: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care., Conclusions: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients., (© 2024. Canadian Anesthesiologists' Society.)

Objective: To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline., Design: Systematic review., Data Sources: We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020., Study Selection: Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome., Data Abstraction and Synthesis: 4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials., Results: We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005)., Conclusions: Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials., Prospero Registration Number: CRD42022282565., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/. EB-C has received investigator-initiated grant funding from Bayer, BMS-Pfizer and Roche Diagnostics and consulting honoraria from Trimedic Therapeutics, which were unrelated to the current work. JR is a co-methodologist on the Society of Critical Care Medicine Guideline Committee–End of Life Care in the ICU Guidelines. VP is a member of the Canadian Critical Care Society–Equity, Diversity, Decolonisation and Inclusion Committee. KEAB is President of the Canadian Critical Care Society and an Ex-officio member of the Canadian Critical Care Trials Group Executive Committee. There are no other relationships or activities that could appear to have influenced the submitted work., (© 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.)

Competing Interests: Dr. Umpierrez’s institution received funding from Dexcom, Abbott, Bayer, and Astra Zeneca. Dr. Sirimaturos’ institution received funding from Grifols; he received funding from Astra Zeneca. Dr. Mechanick received funding from Abbott Nutrition, Aveta.Life, and Twin Health. Dr. Irving disclosed that she is an American Society of Parenteral and Enteral Nutrition (ASPEN) board member and author on Society of Critical Care Medicine/ASPEN guidelines for pediatric nutrition support. Dr. Preiser received funding from Edwards, Glysure, Medtronic, and Optiscan. Dr. Krinsley received funding from Dexcom. Dr. Sands received funding from BioXcel Therapeutics. Dr. Jacobi disclosed that she is an Advisory Board Member of the Pfizer Hospital Business Unit. Dr. Agus’ institution received funding from the National Institutes of Health; he disclosed that Dexcom is providing in kind support with continuous glucose monitors for a clinical trial in children. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Rationale: Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods., Objectives: The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians., Panel Design: The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting., Methods: We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research., Results: This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available., Conclusions: The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics., Competing Interests: Dr. Umpierrez’s institution received funding from Dexcom, Abbott, Bayer, and Astra Zeneca. Dr. Sirimaturos’ institution received funding from Grifols; he received funding from Astra Zeneca. Dr. Mechanick received funding from Abbott Nutrition, Aveta.Life, and Twin Health. Dr. Irving disclosed that she is a board member of the American Society for Parenteral and Enteral Nutrition and a member of American Society for Parenteral and Enteral Nutrition/Society of Critical Care Medicine Pediatric Critical Care Nutrition Guideline. Dr. Preiser received funding from Edwards, Glysure, Medtronic, and Optiscan. Dr. Krinsley received funding from Dexcom. Dr. Sands received funding from BioXcel Therapeutics. Dr. Jacobi disclosed that she was an Advisory Board Member of the Pfizer Hospital Business Unit. Dr. Agus’ institution received funding from the National Institutes of Health; he disclosed that Dexcom is providing in kind support with continuous glucose monitors for a clinical trial in children. The remaining authors have disclosed that they do not have any potential conflicts of interest. The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients., Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients., Panel Design: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines., Methods: We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs)., Results: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system., Conclusions: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU., Competing Interests: Funding for these guidelines was provided solely by the Society of Critical Care Medicine. Panel members disclosed all potential financial and intellectual conflicts of interest according to the American College of Critical Care Medicine/Society of Critical Care Medicine Standard Operating Procedures. Refer to Supplemental Digital Contents 1 and 2 (http://links.lww.com/CCM/H434) for details. Dr. Penoyer received funding from Ivenix, Inc, Avanos, ICU Medical, and BD. Dr. Davis disclosed he is a consultant for Zoll and Healthstream and is Chief Executive Officer of Medical X Technologies. Dr. Edelson disclosed that she is president and co-founder of AgileMD and received equity interest, she is an employee of the National Institutes of Health, and received a research grant from BARDA (ARCD.P0535US). Dr. Rowley received funding from Draeger, STIMIT, and Vyaire. Dr. DeVita disclosed that he is a consultant for Hill Rom. Dr. Welch disclosed that he is an advisor in a one-off Becton, Dickinson and Co. Adult and Specialist Critical Care Advisory Board. Dr. Kellett disclosed that he is the founder and major shareholder of Tapa Healthcare DAC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients., Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients., Panel Design: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based clinical practice guidelines., Methods: We generated actionable questions using the Population, Intervention, Control, and Outcomes format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs)., Results: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among "unselected" patients due to the absence of data regarding the benefit and the potential harms of false positive alarms, the risk of alarm fatigue, and cost. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system (GPS)., Conclusions: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU., Competing Interests: Panel members disclosed all potential financial and intellectual conflicts of interest according to the American College of Critical Care Medicine/Society of Critical Care Medicine Standard Operating Procedures. For details, please refer to Supplemental Digital Contents 1 and 2 (http://links.lww.com/CCM/H433). Dr. Penoyer received funding from Ivenix, Avanos, ICU Medical, and BD. Dr. Davis disclosed he is a consultant for Zoll and Healthstream and is Chief Executive Officer of Medical X Technologies. Dr. Edelson disclosed that she is president and co-founder of AgileMD and received equity interest, she is an employee of the National Institutes of Health, and she received a research grant from BARDA (ARCD.P0535US). Dr. Rowley received funding from Draeger, STIMIT, and Vyaire. Dr. DeVita disclosed that he is a consultant for Hill Rom. Dr. Welch disclosed that he is an advisor in a one-off Becton, Dickinson and Co. Adult and Specialist Critical Care Advisory Board. Dr. Kellett disclosed that he is the founder and major shareholder of Tapa Healthcare DAC. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Source Citation: Gunst J, Debaveye Y, Güiza F, et al; TGC-Fast Collaborators. Tight blood-glucose control without early parenteral nutrition in the ICU. N Engl J Med. 2023;389:1180-1190. 37754283., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0109.

Importance: Blood collection for laboratory testing in intensive care unit (ICU) patients is a modifiable contributor to anemia and red blood cell (RBC) transfusion. Most blood withdrawn is not required for analysis and is discarded., Objective: To determine whether transitioning from standard-volume to small-volume vacuum tubes for blood collection in ICUs reduces RBC transfusion without compromising laboratory testing procedures., Design, Setting, and Participants: Stepped-wedge cluster randomized trial in 25 adult medical-surgical ICUs in Canada (February 5, 2019 to January 21, 2021)., Interventions: ICUs were randomized to transition from standard-volume (n = 10 940) to small-volume tubes (n = 10 261) for laboratory testing., Main Outcomes and Measures: The primary outcome was RBC transfusion (units per patient per ICU stay). Secondary outcomes were patients receiving at least 1 RBC transfusion, hemoglobin decrease during ICU stay (adjusted for RBC transfusion), specimens with insufficient volume for testing, length of stay in the ICU and hospital, and mortality in the ICU and hospital. The primary analysis included patients admitted for 48 hours or more, excluding those admitted during a 5.5-month COVID-19-related trial hiatus., Results: In the primary analysis of 21 201 patients (mean age, 63.5 years; 39.9% female), which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference in RBC units per patient per ICU stay (relative risk [RR], 0.91 [95% CI, 0.79 to 1.05]; P = .19; absolute reduction of 7.24 RBC units/100 patients per ICU stay [95% CI, -3.28 to 19.44]). In a prespecified secondary analysis (n = 27 411 patients), RBC units per patient per ICU stay decreased after transition from standard-volume to small-volume tubes (RR, 0.88 [95% CI, 0.77 to 1.00]; P = .04; absolute reduction of 9.84 RBC units/100 patients per ICU stay [95% CI, 0.24 to 20.76]). Median decrease in transfusion-adjusted hemoglobin was not statistically different in the primary population (mean difference, 0.10 g/dL [95% CI, -0.04 to 0.23]) and lower in the secondary population (mean difference, 0.17 g/dL [95% CI, 0.05 to 0.29]). Specimens with insufficient quantity for analysis were rare (≤0.03%) before and after transition., Conclusions and Relevance: Use of small-volume blood collection tubes in the ICU may decrease RBC transfusions without affecting laboratory analysis., Trial Registration: ClinicalTrials.gov Identifier: NCT03578419.

This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society., (© 2023. The Author(s).)

Purpose: We aimed to describe the Canadian public's understanding and perception of how death is determined in Canada, their level of interest in learning about death and death determination, and their preferred strategies for informing the public., Methods: We conducted a nationwide cross-sectional survey of a representative sample of the Canadian public. The survey presented two scenarios of a man who met current criteria for neurologic death determination (scenario 1) and a man who met current criteria for circulatory death determination (scenario 2). Survey questions evaluated understanding of how death is determined, acceptance of death determination by neurologic and circulatory criteria, and interest and preferred strategies in learning more about the topic., Results: Among 2,000 respondents (50.8% women; n = 1,015), nearly 67.2% believed that the man in scenario 1 was dead (n = 1,344) and 81.2% (n = 1,623) believed that the man in scenario 2 was dead. Respondents who believed that the man was not dead or were unsure endorsed several factors that may increase their agreement with the determination of death, including requiring more information about how death was determined, seeing the results of brain imaging/tests, and a third doctor's opinion. Predictors of disbelief that the man in scenario 1 is dead were younger age, being uncomfortable with the topic of death, and subscribing to a religion. Predictors of disbelief that the man in scenario 2 is dead were younger age, residing in Quebec (compared with Ontario), having a high school education, and subscribing to a religion. Most respondents (63.3%) indicated interest in learning more about death and death determination. Most respondents preferred to receive information about death and death determination from their health care professional (50.9%) and written information provided by their health care professional (42.7%)., Conclusion: Among the Canadian public, the understanding of neurologic and circulatory death determination is variable. More uncertainty exists with death determination by neurologic criteria than with circulatory criteria. Nevertheless, there is a high level of general interest in learning more about how death is determined in Canada. These findings provide important opportunities for further public engagement., (© 2023. The Author(s).)

Purpose: We sought to explore the lived experiences of a professionally diverse sample of healthcare workers (HCWs) in a single intensive care unit (ICU) serving a large and generalizable Canadian population. We aimed to understand how working during the COVID-19 pandemic affected their professional and personal lives, including their perceptions of institutional support, to inform interventions to ameliorate impacts of the COVID-19 and future pandemics., Methods: In this qualitative descriptive study, 23 ICU HCWs, identified using convenience purposive sampling, took part in individual semistructured interviews between July and November 2020, shortly after the first wave of the pandemic in Ontario. We used inductive thematic analysis to identify major themes., Results: We identified five major themes related to the COVID-19 pandemic: 1) communication and informational needs (e.g., challenges communicating policy changes); 2) adjusting to restricted visitation (e.g., spending less time interacting with patients); 3) staffing and workplace supports (e.g., importance of positive team dynamics); 4) permeability of professional and personal lives (e.g., balancing shift work and childcare); and 5) a dynamic COVID-19 landscape (e.g., coping with constant change). The COVID-19 pandemic contributed to HCWs in the ICU experiencing varied negative repercussions on their work environment, including staffing and institutional support, which carried into their personal lives., Conclusion: Healthcare workers in the ICU perceived that the COVID-19 pandemic had negative repercussions on their work environment, including staffing and institutional support, as well as their professional and personal lives. Understanding both the negative and positive experiences of all ICU HCWs working during the COVID-19 pandemic is critical to future pandemic preparedness. Their perspectives will help to inform the development of mental health and wellbeing interventions to support staff during the COVID-19 pandemic and beyond., (© 2023. The Author(s).)

Background: Medical assistance in dying (MAID) was legislatively enacted in Canada in June 2016. Most studies of patients who received MAID grouped patients with cancer and non-cancer diagnoses. Our goal was to analyze the characteristics of oncology patients who received MAID in a Canadian tertiary care hospital., Methods: We conducted a retrospective review of all patients with cancer who received MAID between June 2016 and July 2020 at London Health Sciences Centre (LHSC). We describe patients' demographics, oncologic characteristics, symptoms, treatments, and palliative care involvement., Results: Ninety-two oncology patients received MAID. The median age was 72. The leading cancer diagnoses among these patients were lung, colorectal, and pancreatic. At the time of MAID request, 68% of patients had metastatic disease. Most patients (90%) had ECOG performance status of 3 or 4 before receiving MAID. Ninety-nine percent of patients had distressing symptoms at time of MAID request, most commonly pain. One-third of patients with metastatic or recurrent cancer received early palliative care. The median time interval between the first MAID assessment and receipt of MAID was 7 days., Interpretation: Most oncology patients who received MAID at LHSC had poor performance status and almost all had distressing symptoms. The median time interval between first MAID assessment and receipt of MAID was shorter than expected. Only one-third of patients with metastatic or recurrent cancer received early palliative care. Improving access to early palliative care is a priority in patients with advanced cancer., Study Registration: We received research approval from Western University's Research Ethics Board (REB) with project ID number 115367, and from Lawson's Research Database Application (ReDA) with study ID number 9579.

BACKGROUND: Inflammation and oxidative damage caused by severe infections may be attenuated by vitamin C. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) of parenteral vitamin C as combined therapy or monotherapy versus no parenteral vitamin C administered to adults hospitalized with severe infection. The primary outcome was mortality. We performed random-effects meta-analyses and assessed certainty in effect estimates. RESULTS: Of 1547 citations, 41 RCTs (n = 4915 patients) were eligible for inclusion. Low-certainty evidence suggested that vitamin C may reduce in-hospital mortality (21 RCTs, 2762 patients; risk ratio, 0.88 [95% confidence interval (CI), 0.73 to 1.06]), 30-day mortality (24 RCTs, 3436 patients; risk ratio, 0.83 [95% CI, 0.71 to 0.98]), and early mortality (before hospital discharge or 30 days; 34 RCTs, 4366 patients; risk ratio, 0.80 [95% CI, 0.68 to 0.93]). Effects were attenuated in sensitivity analyses limited to published blinded trials at low risk-of-bias (in-hospital mortality: risk ratio, 1.07 [95% CI, 0.92 to 1.24], moderate certainty; 30-day mortality: risk ratio, 0.88 [95% CI, 0.71 to 1.10], low certainty; and early mortality: risk ratio, 0.88 [95% CI, 0.73 to 1.06], low certainty). For 90-day mortality, all trials had low risk-of-bias; moderate-certainty evidence suggested harm (five RCTs, 1722 patients; risk ratio, 1.07 [95% CI, 0.94 to 1.21]). Moderate-certainty evidence suggested an increased risk of hypoglycemia (risk ratio, 1.20 [95% CI, 0.69 to 2.08]). Effects on other secondary outcomes were mixed and informed by low-certainty evidence. No credible subgroup effects were observed for mortality related to cointerventions (monotherapy vs. combined therapy), dose, or type of infection (Covid-19 vs. other). CONCLUSIONS: Overall, evidence from RCTs does not establish a survival benefit for vitamin C in patients with severe infection. (PROSPERO number, CRD42020209187.)

Background: Characterizing the multiorgan manifestations and outcomes of patients hospitalized with COVID-19 will inform resource requirements to address the long-term burden of this disease. We conducted a descriptive analysis using prospectively collected data to describe the clinical characteristics and spectrum of organ dysfunction, and in-hospital and longer-term clinical outcomes of patients hospitalized with COVID-19 during the first wave of the pandemic at a Canadian centre., Methods: We conducted a prospective case series involving adult patients (aged ≥ 18 yr) with COVID-19 admitted to 1 of 2 hospitals in London, Ontario, from Mar. 17 to June 18, 2020, during the first wave of the pandemic. We recorded patients' baseline characteristics, physiologic parameters, measures of organ function and therapies administered during hospitalization among patients in the intensive care unit (ICU) and in non-ICU settings, and compared the characteristics of hospital survivors and nonsurvivors. Finally, we recorded follow-up thoracic computed tomography (CT) and echocardiographic findings after hospital discharge., Results: We enrolled 100 consecutive patients (47 women) hospitalized with COVID-19, including 32 patients who received ICU care and 68 who received treatment in non-ICU settings. Respiratory sequelae were common: 23.0% received high-flow oxygen by nasal cannula, 9.0% received noninvasive ventilation, 24.0% received invasive mechanical ventilation and 2.0% received venovenous extracorporeal membrane oxygenation. Overall, 9.0% of patients had cerebrovascular events (3.0% ischemic stroke, 6.0% intracranial hemorrhage), and 6.0% had pulmonary embolism. After discharge, 11 of 19 patients had persistent abnormalities on CT thorax, and 6 of 15 had persistent cardiac dysfunction on echocardiography., Interpretation: This study provides further evidence that COVID-19 is a multisystem disease involving neurologic, cardiac and thrombotic dysfunction, without evidence of hepatic dysfunction. Patients have persistent organ dysfunction after hospital discharge, underscoring the need for research on long-term outcomes of COVID-19 survivors., Competing Interests: Competing interests: Ian Ball declares a research grant from the Lawson Health Research Institute Internal Research Fund. He is the critical care lead for Ontario West and sits on the Ontario Critical Care COVID-19 Command Table. Mike Nicholson received teaching honoraria unrelated to acute COVID-19 from AstraZeneca, Horizon Therapeutics and Vertex Pharmaceuticals, and has served on a cystic fibrosis drug efficacy advisory board for Horizon and as a moderator for cystic fibrosis gene modulator launch educational seminars for Vertex Pharmaceuticals. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI  - 2.89 to  - 0.71; low certainty), and ICU length of stay (MD  - 0.32 days, 95% CI  - 0.42 to  - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Concerns that medical assistance in dying (MAiD) may harm vulnerable groups unable to access medical treatments and social supports have arisen since the legalization of MAiD on June 17, 2016; however, there is little research on the topic. The purpose of this study is to investigate the socioeconomic status (SES) of patients who request MAiD at the London Health Sciences Centre (LHSC). Methods: A retrospective analysis of patients from the LHSC MAiD database between June 6, 2016 and December 20, 2019 was conducted. Patients were linked to income data from the 2016 Canadian Census, and their corresponding income quintile was a proxy for SES. Geographic information system (GIS) mapping software was used to visualize the distribution of income and MAiD requests. Results: 39.4% of the LHSC catchment area was classified as low SES. Two hundred thirty-seven (58.1%) MAiD requests came from low SES patients and 171 (41.9%) requests came from high SES patients. Two hundred fifty-nine (63.5%) patients who requested a MAiD assessment did not receive MAiD following their request. Of the 237 lower SES patients, 150 (63.3% [95% CI 57.2-69.3]) did not receive MAiD. Of the 171 higher SES patients, 109 (63.7% [95% CI 56.5-70.9]) did not receive MAiD. Conclusion: A disproportionate number of requests for a MAiD assessment at LHSC came from lower SES patients; however, similar proportions of patients who requested MAiD from each SES group received aid in dying. Future research should explore why a disproportionately high number of low SES patients request MAiD at LHSC.

Introduction: We explored associations between sociodemographic factors and public beliefs, behaviors, and information acquisition related to the coronavirus disease 2019 (COVID-19) to identify how the experiences of subpopulations in Canada may vary., Methods: We administered a national online survey through Ipsos Incorporated to adults residing in Canada. Sampling was stratified by population age, sex, and regional distributions. We used descriptive statistics to summarize responses and test for differences based on gender, age, educational attainment, and household income using chi-squared tests, followed by weighted logistic regression., Results: We collected 1996 eligible questionnaires between April 26th and May 1st, 2020. Respondents mean age was 50 years, 51% were women, 56% had a post-secondary degree, and 72% had a household income <$100,000. Our analysis found differences within the four demographic groups, with age effects most acutely evidenced. Respondents 65 years and older were more likely to perceive the pandemic as very serious, less likely to report declines in overall health, and more likely to intend to get vaccinated, compared to 18-29 year olds. Women overall were more likely to report negative outcomes than men, including stress due to the pandemic, and worsening social, mental/emotional, and spiritual health. Respondents 45 and older were more likely to seek and trust information from traditional Canadian news sources, while 18-29 year olds were more likely to seek and trust information on social media; overall, women and respondents with a post-secondary degree were more likely to access and trust online information from public health sites., Conclusion: This study found important demographic differences in how adults living in Canada perceived the COVID-19 pandemic, the impacts on their health, and their preferences for information acquisition. Our results highlight the need to consider demographic characteristics in tailoring the format and information medium to improve large scale acceptance and uptake of mitigation and containment measures., (© 2022. The Author(s).)

Purpose: To evaluate the impact of the COVID-19 pandemic on Canadian intensive care unit (ICU) workers., Methods: Between June and August 2020, we distributed a cross-sectional online survey of ICU workers evaluating the impact of the pandemic, coping strategies, symptoms of post-traumatic stress disorder (PTSD; Impact of Events Scale-Revised), and psychological distress, anxiety, and depression (Kessler Psychological Distress Scale). We performed regression analyses to determine the predictors of psychological symptoms., Results: We analyzed responses from 455 ICU workers (80% women; 67% from Ontario; 279 nurses, 69 physicians, and 107 other healthcare professionals). Respondents felt that their job put them at great risk of exposure (60%), were concerned about transmitting COVID-19 to family members (76%), felt more stressed at work (67%), and considered leaving their job (37%). Overall, 25% had probable PTSD and 18% had minimal or greater psychological distress. Nurses were more likely to report PTSD symptoms (33%) and psychological distress (23%) than physicians (5% for both) and other health disciplines professionals (19% and 14%). Variables associated with PTSD and psychological distress included female sex (beta-coefficient [B], 1.59; 95% confidence interval [CI], 1.20 to 2.10 and B, 3.79; 95% CI, 1.79 to 5.78, respectively; P < 0.001 for differences in scores across groups) and perceived increased risk due to PPE shortage or inadequate PPE training (B, 1.87; 95% CI, 1.51 to 2.31 and B, 4.88; 95% CI, 3.34 to 6.43, respectively). Coping strategies included talking to friends/family/colleagues (80%), learning about COVID-19 (78%), and physical exercise (68%). Over half endorsed the following workplace strategies as valuable: hospital-provided scrubs, clear communication and protocols by hospitals, knowing their voice is heard, subsidized parking, and gestures of appreciation from leadership., Conclusions: This survey study shows that ICU workers have been impacted by the COVID-19 pandemic with high levels of stress and psychological burden. Respondents endorsed communication, protocols, and appreciation from leadership as helpful mitigating strategies., (© 2021. Canadian Anesthesiologists' Society.)

Objectives: We aimed to evaluate the personal, professional, and psychological impact of the COVID-19 pandemic on hospital workers and their perceptions about mitigating strategies., Design: Cross-sectional web-based survey consisting of (1) a survey of the personal and professional impact of the COVID-19 pandemic and potential mitigation strategies, and (2) two validated psychological instruments (Kessler Psychological Distress Scale [K10] and Impact of Events Scale Revised [IES-R]). Regression analyses were conducted to identify the predictors of workplace stress, psychological distress, and post-traumatic stress., Setting and Participants: Hospital workers employed at 4 teaching and 8 non-teaching hospitals in Ontario, Canada during the COVID-19 pandemic., Results: Among 1875 respondents (84% female, 49% frontline workers), 72% feared falling ill, 64% felt their job placed them at great risk of COVID-19 exposure, and 48% felt little control over the risk of infection. Respondents perceived that others avoided them (61%), reported increased workplace stress (80%), workload (66%) and responsibilities (59%), and 44% considered leaving their job. The psychological questionnaires revealed that 25% had at least some psychological distress on the K10, 50% had IES-R scores suggesting clinical concern for post-traumatic stress, and 38% fulfilled criteria for at least one psychological diagnosis. Female gender and feeling at increased risk due to PPE predicted all adverse psychological outcomes. Respondents favoured clear hospital communication (59%), knowing their voice is heard (55%), expressions of appreciation from leadership (55%), having COVID-19 protocols (52%), and food and beverages provided by the hospital (50%)., Conclusions: Hospital work during the COVID-19 pandemic has had important personal, professional, and psychological impacts. Respondents identified opportunities to better address information, training, and support needs., Competing Interests: The authors have declared that no competing interests exist.

Background: Severe infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature., Objective: We aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19., Methods: We searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available., Results: Among the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses., Conclusions: The results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review., Trial Registration: PROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=209187., International Registered Report Identifier (irrid): RR1-10.2196/33989., (©Arnav Agarwal, John Basmaji, Shannon M Fernando, Fang Zhou Ge, Yingqi Xiao, Haseeb Faisal, Kimia Honarmand, Mathieu Hylands, Vincent I Lau, Kimberley Lewis, Rachel Couban, François Lamontagne, Neill KJ Adhikari. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.01.2022.)

Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: (1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted., Competing Interests: E.B.-C. reports grants from Bayer and Roche, outside the submitted work. I.M.B. received a stipend for administrative work, Trillium Gift of Life ODO 2014-2019, Motivational Speaker for Gaia Insight. M.O.M. receives salary from the Trillium Gift of Life Network of Ontario for her work as a hospital donation physician. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The COVID-19 pandemic created the need for rapid and urgent guidance for clinicians to manage COVID-19 among patients and prevent transmission., Objective: To appraise the quality of clinical practice guidelines (CPGs) using the National Academy of Medicine (NAM) criteria., Evidence Review: A search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to December 14, 2020, and a search of related articles to February 28, 2021, that included CPGs developed by societies or by government or nongovernment organizations that reported pharmacologic treatments of hospitalized patients with COVID-19. Teams of 2 reviewers independently abstracted data and assessed CPG quality using the 15-item National Guideline Clearinghouse Extent of Adherence to Trustworthy Standards (NEATS) instrument., Findings: Thirty-two CPGs were included in the review. Of these, 25 (78.1%) were developed by professional societies and emanated from a single World Health Organization (WHO) region. Overall, the CPGs were of low quality. Only 7 CPGs (21.9%) reported funding sources, and 12 (37.5%) reported conflicts of interest. Only 5 CPGs (15.6%) included a methodologist, described a search strategy or study selection process, or synthesized the evidence. Although 14 CPGs (43.8%) made recommendations or suggestions for or against treatments, they infrequently rated confidence in the quality of the evidence (6 of 32 [18.8%]), described potential benefits and harms (6 of 32 [18.8%]), or graded the strength of the recommendations (5 of 32 [15.6%]). External review, patient or public perspectives, or a process for updating were rare. High-quality CPGs included a methodologist and multidisciplinary collaborations involving investigators from 2 or more WHO regions., Conclusions and Relevance: In this review, few COVID-19 CPGs met NAM standards for trustworthy guidelines. Approaches that prioritize engagement of a methodologist and multidisciplinary collaborators from at least 2 WHO regions may lead to the production of fewer, high-quality CPGs that are poised for updates as new evidence emerges., Trial Registration: PROSPERO Identifier: CRD42021245239.

Background: The coronavirus disease 19 (covid-19) pandemic has underscored the need to expedite clinical research, which may lead investigators to shift away from measuring patient-important outcomes (PIO), limiting research applicability. We aim to investigate if randomized controlled trials (RCTs) of covid-19 pharmacological therapies include PIOs., Methods: We will perform a meta-epidemiological study of RCTs that included people at risk for, or with suspected, probable, or confirmed covid-19, examining any pharmacological treatment or blood product aimed at prophylaxis or treatment. We will obtain data from all RCTs identified in a living network metanalysis (NMA). The main data sources are the living WHO covid-19 database up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Two reviewers independently will review each citation, full-text article, and abstract data. To categorize the outcomes according to their importance to patients, we will adapt a previously defined hierarchy: a) mortality, b) quality of life/ functional status/symptoms, c) morbidity, and d) surrogate outcomes. Outcomes within the category a) and b) will be considered critically important to patients, and outcomes within the category c) will be regarded as important. We will use descriptive statistics to assess the proportion of studies that report each category of outcomes. We will perform univariable and multivariable analysis to explore associations between trial characteristics and the likelihood of reporting PIOs., Discussion: The findings from this meta-epidemiological study will help health care professionals and researchers understand if the current covid-19 trials are effectively assessing and reporting the outcomes that are important to patients. If a deficiency in capturing PIOs is identified, this information may help inform the development of future RCTs in covid-19., Systematic Review Registrations: Open Science Framework registration: osf.io/6xgjz ., (© 2021. The Author(s).)

Objective: To describe the characteristics of Covid-19 randomized clinical trials (RCTs) and examine the association between trial characteristics and the likelihood of finding a significant effect., Study Design: We conducted a systematic review to identify RCTs (up to October 21, 2020) evaluating drugs or blood products to treat or prevent Covid-19. We extracted trial characteristics (number of centers, funding sources, and sample size) and assessed risk of bias (RoB) using the Cochrane RoB 2.0 tool. We performed logistic regressions to evaluate the association between RoB due to randomization, single vs. multicentre, funding source, and sample size, and finding a statistically significant effect., Results: We included 91 RCTs (n = 46,802); 40 (44%) were single-center, 23 (25.3%) enrolled <50 patients, 28 (30.8%) received industry funding, and 75 (82.4%) had high or probably high RoB. Thirty-eight trials (41.8%) reported a statistically significant effect. RoB due to randomization and being a single-center trial were associated with increased odds of finding a statistically significant effect., Conclusions: There is high variability in RoB among Covid-19 trials. Researchers, funders, and knowledge-users should be cognizant of the impact of RoB due to randomization and single-center trial status in designing, evaluating, and interpreting the results of RCTs., Registration: CRD42020192095., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The 3 Wishes Project (3WP) promotes holistic end-of-life care in the intensive care unit (ICU) to honor dying patients, support families, and encourage clinician compassion. Organ donation is a wish that is sometimes made by, or on behalf of, critically ill patients. Our objective was to describe the interface between the 3WP and organ donation as experienced by families, clinicians, and organ donation coordinators., Methods: In a multicenter evaluation of the 3WP in 4 Canadian ICUs, we conducted a thematic analysis of transcripts from interviews and focus groups with clinicians, organ donation coordinators, and families of dying or died patients for whom donation was considered., Results: We analyzed transcripts from 26 interviews and 2 focus groups with 18 family members, 17 clinicians, and 6 organ donation coordinators. The central theme describes the mutual goals of the 3WP and organ donation-emphasizing personhood and agency across the temporal continuum of care. During family decision-making , conversations encouraged by the 3WP can facilitate preliminary discussions about donation. During preparation for donation , memory-making activities supported by the 3WP redirect focus toward personhood. During postmortem family care , the 3WP supports families, including when donation is unsuccessful, and highlights aspirational pursuits of donation while encouraging reflections on other fulfilled wishes., Conclusions: Organ donation and the 3WP provide complementary opportunities to engage in value-based conversations during the dying process. The shared values of these programs may help to incorporate organ donation and death into a person's life narrative and incorporate new life into a person's death narrative.

Objectives: SARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear., Design: Systematic review., Data Sources: We searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020., Eligibility Criteria: All comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing., Results: Of 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified., Conclusions: There is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Providing optimal care to patients with acute respiratory illness while preventing hospital transmission of COVID-19 is of paramount importance during the pandemic; the challenge lies in achieving both goals simultaneously. Controversy exists regarding the role of early intubation versus use of non-invasive respiratory support measures to avoid intubation. This review summarizes available evidence and provides a clinical decision algorithm with risk mitigation techniques to guide clinicians in care of the hypoxemic, non-intubated, patient during the COVID-19 pandemic. Although aerosolization of droplets may occur with aerosol-generating medical procedures (AGMP), including high flow nasal oxygen and non-invasive ventilation, the risk of using these AGMP is outweighed by the benefit in carefully selected patients, particularly if care is taken to mitigate risk of viral transmission. Non-invasive support measures should not be denied for conditions where previously proven effective and may be used even while there is suspicion of COVID-19 infection. Patients with de novo acute respiratory illness with suspected/confirmed COVID-19 may also benefit. These techniques may improve oxygenation sufficiently to allow some patients to avoid intubation; however, patients must be carefully monitored for signs of increased work of breathing. Patients showing signs of clinical deterioration or high work of breathing not alleviated by non-invasive support should proceed promptly to intubation and invasive lung protective ventilation strategy. With adherence to these principles, risk of viral spread can be minimized.

Purpose: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products., Source: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology., Principal Findings: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density., Conclusions: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

Introduction: Cardiac transplantation remains the best treatment for patients with end-stage heart disease that is refractory to medical or device therapies, however, a major challenge for heart transplantation is the persistent discrepancy between the number of patients on waiting lists and the number of available hearts. While other countries (eg, UK, Australia and Belgium) have explored and implemented alternative models of transplantation, such as cardiac donation after circulatory determination of death (DCDD) to alleviate transplantation wait times, ethical concerns have hindered implementation in some countries. This study aims to explore the attitudes and opinions of healthcare providers and the public about cardiac DCDD in order to identify and describe opportunities and challenges in ensuring that proposed cardiac DCDD procedures in Canada are consistent with Canadian values and ethical norms., Methods and Analysis: This study will include two parts that will be conducted concurrently. Part 1 is a qualitative study consisting of semi-structured interviews with Canadian healthcare providers who routinely care for organ donors and/or transplant recipients to describe their perceptions about cardiac DCDD. Part 2 is a convergent parallel mixed-methods design consisting of a series of focus groups and follow-up surveys with members of the Canadian general public to describe their perceptions about cardiac DCDD., Ethics and Dissemination: This study has been approved by the Research Ethics Board at Western University. The findings will be presented at regional and national conferences and reported in peer-reviewed publications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long-term cognitive impairment is common among ICU survivors, but its natural history remains unclear. In this systematic review, we report the frequency of cognitive impairment in ICU survivors across various time points after ICU discharge that were extracted from 46 of the 3,350 screened records. Prior studies used a range of cognitive instruments, including subjective assessments (10 studies), single or screening cognitive test such as Mini-Mental State Examination or Trail Making Tests A and B (23 studies), and comprehensive cognitive batteries (26 studies). The mean prevalence of cognitive impairment was higher with objective rather than subjective assessments (54% [95% confidence interval (CI), 51-57%] vs. 35% [95% CI, 29-41%] at 3 months after ICU discharge) and when comprehensive cognitive batteries rather than Mini-Mental State Examination were used (ICU discharge: 61% [95% CI, 38-100%] vs. 36% [95% CI, 15-63%]; 12 months after ICU discharge: 43% [95% CI, 10-78%] vs. 18% [95% CI, 10-20%]). Patients with acute respiratory distress syndrome had higher prevalence of cognitive impairment than mixed ICU patients at ICU discharge (82% [95% CI, 78-86%] vs. 48% [95% CI, 44-52%]). Although some studies repeated tests at more than one time point, the time intervals between tests were arbitrary and dictated by operational limitations of individual studies or chosen cognitive instruments. In summary, the prevalence and temporal trajectory of ICU-related cognitive impairment varies depending on the type of cognitive instrument used and the etiology of critical illness. Future studies should use modern comprehensive batteries to better delineate the natural history of cognitive recovery across ICU patient subgroups and determine which acute illness and treatment factors are associated with better recovery trajectories.

Objectives: Numerous risk factors for sleep disruption in critically ill adults have been described. We performed a systematic review of all risk factors associated with sleep disruption in the ICU setting., Data Sources: PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central Register for Controlled Trials, and Cochrane Database of Systematic Reviews., Study Selection: English-language studies of any design published between 1990 and April 2018 that evaluated sleep in greater than or equal to 10 critically ill adults (> 18 yr old) and investigated greater than or equal to 1 potential risk factor for sleep disruption during ICU stay. We assessed study quality using Newcastle-Ottawa Scale or Cochrane Risk of Bias tool., Data Extraction: We abstracted all data independently and in duplicate. Potential ICU sleep disruption risk factors were categorized into three categories based on how data were reported: 1) patient-reported reasons for sleep disruption, 2) patient-reported ratings of potential factors affecting sleep quality, and 3) studies reporting a statistical or temporal association between potential risk factors and disrupted sleep., Data Synthesis: Of 5,148 citations, we included 62 studies. Pain, discomfort, anxiety/fear, noise, light, and ICU care-related activities are the most common and widely studied patient-reported factors causing sleep disruption. Patients rated noise and light as the most sleep-disruptive factors. Higher number of comorbidities, poor home sleep quality, home sleep aid use, and delirium were factors associated with sleep disruption identified in available studies., Conclusions: This systematic review summarizes all premorbid, illness-related, and ICU-related factors associated with sleep disruption in the ICU. These findings will inform sleep promotion efforts in the ICU and guide further research in this field.

Purpose: The number of patients on cardiac transplant waitlists exceeds the number of available donor organs. Cardiac donation is currently limited to those declared dead by neurologic criteria in all but three countries. Cardiac donation after circulatory determination of death (cardiac DCDD) can be conducted using direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP). Implementation of cardiac DCDD in many countries has been slowed by ethical debates within the donation and transplantation community. We conducted a national survey to determine the perceptions of healthcare providers regarding cardiac DCDD., Methods: We conducted an electronic survey of 398 healthcare providers who are involved in the management of heart donors and/or heart transplant recipients in Canada (226 nurses, 82 critical care physicians, 31 donation specialists, and 59 transplant specialists). Our primary outcomes were their attitudes towards and concerns regarding cardiac DCDD protocols and their implementation in Canada. We distributed the survey electronically through several Canadian donation and transplantation organizations., Results: We identified that 361 of 391 respondents (92.3%; 95% confidence interval [CI], 89.6 to 95.1) believed that DPP is acceptable, and 329 of 377 respondents (87.3%; 95% CI, 83.9 to 90.7) supported its implementation in Canada. We found that 301 of 384 respondents (78.4%; 95% CI, 74.2 to 82.6) believed that NRP is acceptable and 266 of 377 respondents (70.6%; 95% CI, 66.0 to 75.2) supported its implementation in Canada., Conclusion: This is the first survey describing the attitudes of healthcare providers towards cardiac DCDD. We identified widespread support for cardiac DCDD and its implementation in Canada among Canadian healthcare providers within the organ donation and transplantation community in Canada.

Purpose: Cardiac transplantation is a definitive therapy for end-stage heart failure, but demand exceeds supply. Cardiac donation after circulatory determination of death (cardiac DCDD) can be performed using direct procurement and perfusion (DPP), where cardiac activity is restored after heart recovery, or (NRP), where brain blood supply is surgically interrupted, circulation to the thoraco-abdominal organs is restored within the donor's body, followed by heart recovery. While cardiac DCDD would increase the number of heart donors, uptake of programs has been slowed in part because of ethical concerns within the medical community. These debates have been largely devoid of discussion regarding public perceptions. We conducted a national survey of public perceptions regarding cardiac DCDD., Methods: We surveyed 1,001 Canadians about their attitudes towards cardiac DCDD using a rigorously designed and pre-tested survey., Results: We found that 843 of 1,001 respondents (84.2%; 95% confidence interval [CI], 81.8 to 86.3) accepted the DPP approach, 642 (64.1%; 95% CI, 61.1 to 67.0) would agree to donate their heart using DPP, and 696 (69.5%; 95% CI, 66.6 to 72.3) would consent to the same for a family member. We found that 779 respondents of 1,001 respondents (77.8%; 95% CI, 75.1 to 80.3) accepted the NRP approach, 587 (58.6%; 95% CI, 55.5 to 61.6) would agree to donate their heart using NRP, and 636 (63.5%; 95% CI, 60.5 to 66.4) would consent to the same for a family member. Most respondents supported the implementation of DPP (738 respondents or 73.7%; 95% CI, 70.9 to 76.3) and NRP (655 respondents or 65.4%; 95% CI, 62.4 to 68.3) in Canada., Conclusion: The results of this national survey of public attitudes towards cardiac DCDD will inform the implementation of cardiac DCDD programs in a manner that is consistent with public values.

Purpose: Hemodynamic management of adults with distributive shock often includes the use of catecholamine-based vasoconstricting medications. It is unclear whether adding vasopressin or vasopressin analogues to catecholamine therapy is beneficial in the management of patients with distributive shock. The purpose of this guideline was to develop an evidence-based recommendation regarding the addition of vasopressin to catecholamine vasopressors in the management of adults with distributive shock., Methods: We summarized the evidence informing this recommendation by updating a recently published meta-analysis. Then, a multidisciplinary panel from the Canadian Critical Care Society developed the recommendation using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology., Results: The updated systematic review identified 25 randomized controlled trials including a total of 3,737 patients with distributive shock. Compared with catecholamine therapy alone, the addition of vasopressin or its analogues was associated with a reduced risk of mortality (relative risk [RR], 0.91; 95% confidence interval [CI], 0.85 to 0.99; low certainty), reduced risk of atrial fibrillation (RR, 0.77; 95% CI, 0.67 to 0.88; high certainty), and increased risk of digital ischemia (RR, 2.56; 95% CI, 1.24 to 5.25; moderate certainty)., Conclusions: After considering certainty in the evidence, values and preferences, cost, and other factors, the expert guideline panel suggests using vasopressin or vasopressin analogues in addition to catecholamines over catecholamine vasopressors alone for the management of distributive shock (conditional recommendation, low certainty evidence).

Purpose: Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients., Methods: Patients admitted to participating intensive care units during the one-month enrolment period were eligible. We excluded cardiac surgical patients and patients who were admitted and either died or were discharged within 12 hr. In enrolled patients, we measured high-sensitivity cardiac troponin I (hs-cTnI) and obtained electrocardiograms to ascertain the incidence of myocardial infarction (MI) and isolated troponin elevation. Our feasibility objectives were to measure recruitment rate, the proportion of patients who consented under a deferred consent model, and time required for data collection and study procedures., Results: Over a four-week enrolment period, 280 patients were enrolled using a deferred consent model. We obtained subsequent consent from 81% of patients. Study procedures and data collection required 1.7 hr per participant. Overall, 86 (38%) suffered a MI, 23 (10%) had an isolated hs-cTnI elevation, and 117 (52%) had no hs-cTnI elevation. The crude hospital mortality rate was 10% without an hs-cTnI elevation, 29% with an isolated hs-cTnl elevation (relative risk [RR]) 2.2; 95% confidence interval [CI], 1.0 to 6.0) and 29% with an MI (RR, 2.6; 95% CI, 1.4 to 5.1)., Conclusion: Myocardial injury with elevated hs-cTnI concentrations and MIs occur frequently during critical illness. This pilot study has established the feasibility of conducting a large-scale investigation addressing this issue.

Purpose: To assess the feasibility of using a widely validated, web-based neurocognitive test battery (Cambridge Brain Sciences, CBS) in a cohort of critical illness survivors., Methods: We conducted a prospective observational study in two intensive care units (ICUs) at two tertiary care hospitals. Twenty non-delirious ICU patients who were mechanically ventilated for a minimum of 24 hours underwent cognitive testing using the CBS battery. The CBS consists of 12 cognitive tests that assess a broad range of cognitive abilities that can be categorized into three cognitive domains: reasoning skills, short-term memory, and verbal processing. Patients underwent cognitive assessment while still in the ICU (n = 13) or shortly after discharge to ward (n = 7). Cognitive impairment on each test was defined as a raw score that was 1.5 or more standard deviations below age- and sex-matched norms from healthy controls., Results: We found that all patients were impaired on at least two tests and 18 patients were impaired on at least three tests. ICU patients had poorer performance on all three cognitive domains relative to healthy controls. We identified testing related fatigue due to battery length as a feasibility issue of the CBS test battery., Conclusions: Use of a web-based patient-administered cognitive test battery is feasible and can be used in large-scale studies to identify domain-specific cognitive impairment in critical illness survivors and the temporal course of recovery over time., Competing Interests: Competing Interests: I have read the journal’s policy and can confirm our previously submitted Competing Interests as follows: Dr. Adrian M. Owen holds shares in Cambridge Brain Sciences Inc, which markets the Cambridge Brain Sciences battery of tests. As the tests are made available to all members of the Western academic community through a free-licensing agreement, the current study involved no financial compensation to any party. The other authors report no conflicts of interest. In addition to the aforementioned Competing Interests, I can confirm that this does not alter our adherence to all PLOS ONE policies on sharing data and materials.

Aim of the Study: Identifying modifiable factors associated with survival following in-hospital cardiac arrest is crucial. The purpose of this study was to determine the extent to which adherence to the 2010 American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) guidelines in their entirety affects patient outcomes. In addition, we explored the role of code leader training level on patient outcomes., Methods: We conducted a retrospective review of records for cardiac arrests that occurred on hospital wards and were run by the hospital code team, at three tertiary care centres over 2 to 4 years. Deviations from the ACLS guidelines were quantified using a standardized checklist. Primary outcomes included return of spontaneous circulation (ROSC) and survival to hospital discharge., Results: Of 160 resuscitation events, ROSC was achieved in 75 events (46.9%) and survival to hospital discharge in 20 patients (13.1%). On average, there were 2.3 deviations from ACLS guidelines during events that led to ROSC and 3.9 deviations during events that did not lead to ROSC (p < 0.0001). There were fewer deviations during events that led to survival to hospital discharge (2.1) compared to those where the patient did not survive to hospital discharge (3.1; p = 0.016). Code leader training level was not associated with patient outcomes. Multivariable logistic regression analysis confirmed an association between deviations from ACLS guidelines and ROSC, but not for survival to hospital discharge. The latter finding may reflect a very low survival rate., Conclusion: We found that higher numbers of deviations from ACLS guidelines were associated with a lower likelihood of ROSC and survival to hospital discharge. These findings emphasize the importance of adherence to ACLS guidelines and the need for training healthcare personnel in resuscitation guidelines in order to improve outcomes for victims of in-hospital cardiac arrest., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Informed consent is a hallmark of ethical clinical research. An inherent challenge in critical care research is obtaining consent when patients lack decision-making capacity. One solution is deferred consent, which is often used for studies that are low risk or involve emergency interventions. Our objective was to describe a deferred consent model in a low-risk critical care study., Methods: Prognostic Value of Elevated Troponins in Critical Illness Study was a prospective, pilot observational study of critically ill patients in 3 intensive care units, involving serial electrocardiograms and cardiac biomarkers. Newly admitted patients were enrolled over 1 month. When possible, informed consent was obtained a priori from the patient or substitute decision maker (SDM); otherwise, consent was deferred until the patient regained consent capacity or until their SDM was available. Logistic regression analysis was used to determine the association between patient's sex, Acute Physiology and Chronic Health Evaluation II score, study center, person providing consent (patient vs SDM), method of consent (telephone vs in person), and the provision or not of informed consent., Results: The overall consent rate was 80.1% (213 of 266 persons approached). Of the 53 persons declining consent, 37 (69.8%) agreed to the use of data collected up until that point. Over half of all consent encounters were with patients rather than SDMs. Median interval delay between enrollment and the consent encounter was 1 day. On multivariate analysis, the only variable associated with consent was male sex of the patient (odds ratio for males 2.59, confidence interval: 1.19-5.63)., Conclusion: Deferred consent facilitates implementation of time-sensitive research protocols until a consent encounter is possible. As a feasible alternative to exclusive a priori consent, the deferred consent model can be useful in low-risk studies in critically ill patients.

Problem Gambling (PG) represents a serious problem for affected individuals, their families and society in general. Previous approaches to understanding PG have been confined to only a subset of the psychobiological factors influencing PG. We present a model that attempts to integrate potential causal factors across levels of organization, providing empirical evidence from the vast literature on PG and complimentary literatures in decision-making and addiction. The model posits that components are arranged systematically to bias decisions in favor of either immediately approaching or avoiding targets affording the opportunity for immediate reward. Dopamine, Testosterone and Endogenous Opioids favor immediate approach, while Serotonin and Cortisol favor inhibition. Glutamate is involved in associative learning between stimuli and promotes the approach response through its link to the DA reward system. GABA functions to monitor performance and curb impulsive decision-making. Finally, while very high levels of Norepinephrine can induce arousal to an extent that is detrimental to sound decision-making, the reactivity of the Norepinephrine system and its effects of Cortisol levels can shift the focus towards long-term consequences, thereby inhibiting impulsive decisions. Empirical evidence is provided showing the effects of each component on PG and decision-making across behavioural, neuropsychological, functional neuroimaging and genetic levels. Last, an effect size analysis of the growing pharmacotherapy literature is presented. It is hoped that this model will stimulate multi-level research to solidify our comprehension of biased decision-making in PG and suggest pharmacological and psychological approaches to treatment.

Objective: : To investigate the role of personality and anxiety to self-report measures of cognition in patients with multiple sclerosis (MS)., Background: : Self-report measures of cognition have consistently been shown to correlate better with depressed mood than neuropsychological test performance in patients with MS, with few studies focusing on the role of anxiety and personality., Method: : One hundred eight MS patients completed the following: (a) patient and informant report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ); (b) Hospital Anxiety and Depression Scale; (c) cognitive assessment with the Brief Repeatable Battery of Neuropsychological Tests; and (d) personality assessment using the self-report NEO Five-Factor Inventory., Results: : Higher patient MSNQ (P-MSNQ) scores (greater reported cognitive dysfunction) were significantly correlated with lower scores on the Paced Auditory Serial Addition Test (PASAT; r=-0.20, P<0.05), increased depression (r=0.45, P<0.01) and anxiety (r=0.54, P<0.01), higher neuroticism (r=0.51, P<0.01), and lower conscientiousness (r=-0.35, P<0.01). After controlling for demographic variables, significant predictors of P-MSNQ scores were anxiety (ΔR=0.272, P<0.001), conscientiousness (ΔR=0.067, P=0.002), and performance on the PASAT (ΔR=0.050, P=0.005). Depression and neuroticism did not contribute significant variance in comparison to anxiety., Conclusions: : Overall, patient self-reports of cognition did not correspond well to neuropsychological performance. Anxiety and conscientiousness contributed significantly to patients' perceptions of their cognitive failings and thus should be taken into account when addressing these complaints.

Background: While neuropsychological deficits have been reported in healthy individuals who use street cannabis, data in patients with multiple sclerosis (MS) are lacking. Given that MS is associated with cognitive deterioration, the aim of this study was to determine the neuropsychological effects of cannabis use in this population., Methods: Two groups, each of 25 patients with MS (cannabis users and nonusers), were administered the Minimal Assessment of Cognitive Function in MS battery of neuropsychological tests, the Hospital Anxiety and Depression Scale (HADS), and the Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID-I). Group-matching and regression analysis were used to control for the effects of age, sex, education, premorbid intelligence, disability, and disease course and duration on cognitive function., Results: Cannabis users performed significantly more poorly than nonusers on measures of information processing speed, working memory, executive functions, and visuospatial perception. They were also twice as likely as nonusers to be classified as globally cognitively impaired. There were no between-group differences on the HADS measures of depression and anxiety or lifetime SCID-I psychiatric diagnoses., Conclusion: This cross-sectional study provides empirical evidence that prolonged use of inhaled or ingested street cannabis in patients with MS is associated with poorer performance on cognitive domains commonly affected in this population. Whatever subjective benefits patients may derive from using street cannabis (e.g., pain and spasticity relief) should be weighed against the associated cognitive side effects.

The Symbol Digit Modalities Test (SDMT) is a particularly sensitive measure of cognitive dysfunction in patients with multiple sclerosis (MS). While computerized versions have been developed for use in functional magnetic resonance imaging (fMRI), none has been validated in MS patients. The aim of this study was to validate a new computerized version of the SDMT for use in MS patients. We developed a novel computerized version of the SDMT (c-SDMT) which was completed by 119 MS patients and 38 healthy controls. Our version consisted of eight timed trials of nine symbols. Both groups also underwent cognitive testing with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) which included the 90-s paper SDMT (p-SDMT) scored according to the number of correct responses per each 15-s interval. The sensitivity and specificity of the c-SDMT and p-SDMT to detect overall cognitive impairment on the BRB-N was determined. MS patients performed significantly worse than controls on both the c-SDMT (t = -6.1, p < 0.001) and p-SDMT (t = 5.7, p < 0.001). More MS patients were impaired on the c-SDMT than the p-SDMT (37% vs. 29%). The sensitivity and specificity of the SDMT was as follows: 71% and 84%, respectively, for the c-SDMT, and 67% and 95%, respectively, for the p-SDMT. Both versions detected a significant group × time effect over the course of the individual trials, although the pattern of responses differed between them. Good test-retest reliability for the c-SDMT was shown (ICC = 0.94). The results support the validity of this version of the c-SDMT as a sensitive measure of cognitive dysfunction in MS. The methodology is also fMRI compatible.

As many as two-thirds of multiple sclerosis (MS) patients are unable to retain employment. Neurological and cognitive status are known to be significant predictors of unemployment, but the relationship between the two is unclear. Furthermore, the association between employment status and depression, anxiety, and personality has not been adequately explored in MS patients. This study examined the demographic, neurological, neuropsychological, and personality factors associated with unemployment in MS. We also sought to determine the utility of the Multiple Sclerosis Functional Composite (MSFC), a measure of MS-related disability incorporating physical and cognitive measures, in predicting employment status. A consecutive sample of 106 MS patients (61.3% unemployed) completed the Brief Repeatable Battery of Neuropsychological Tests (BRBN), Hospital Anxiety and Depression Scale (HADS), and NEO Five-Factor Personality Inventory. The MSFC emerged as the most robust predictor of employment status in MS patients, exceeding the predictive value of the EDSS. Together with NEO "Agreeableness" and HADS Depression subscore, the MSFC accounted for 49.8% of the variance in employment status. Unemployment was also associated with a progressive disease course, longer disease duration, and being female. While Global Cognitive Impairment did not differentiate between groups, unemployed patients scored significantly lower on three of five BRBN indices: Symbol Digit Modality Test, Paced Auditory Serial Addition Test, and Word List Generation. The findings highlight the utility of the MSFC as a predictor of unemployment in MS. Furthermore, a strong association was found between unemployment and the personality construct "Agreeableness", and severity of depression.

Background: Neuropsychological batteries are long and require expertise to administer. For this reason, the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) was developed as it is quick and easy to complete. The informant version of the scale has proven to be a useful screen for cognitive impairment in multiple sclerosis (MS)., Objective: The objective was to validate an Internet version of the MSNQ., Methods: The following psychometric data were collected at home over the Internet in 82 MS patients: (a) patient self-report version MSNQ (P-MSNQ), (b) informant version MSNQ (I-MSNQ), and (c) Center for Epidemiological Studies Depression Scale (CES-D). Thereafter patients underwent in-office testing with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). The sensitivity and specificity of the Internet MSNQ to detect cognitive impairment relative to the BRB-N was determined using receiver operating characteristic (ROC) curve analysis., Results: Thirty-five percent of the sample was cognitively impaired. The P-MSNQ was correlated with depression and two tests of the BRB-N. The I-MSNQ was correlated with depression and all five tests of the BRB-N. A cut-off score of 26 on the I-MSNQ gave a sensitivity and specificity of 72% and 60% respectively. Test-retest and internal reliability analyses were strong for both the P-MSNQ and I-MSNQ., Conclusion: This is the first attempt at an Internet validation of the MSNQ. The modest sensitivity and specificity values suggest that further research is needed before either the patient or informant version of the MSNQ can be used for neuropsychological screening purposes over the Internet.