Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

From Traditional Typing to Intelligent Insights: A Narrative Review of Directions Toward Targeted Therapies in Delirium.

Delirium is a heterogeneous syndrome characterized by an acute change in level of consciousness that is associated with inattention and disorganized thinking. Delirium affects most critically ill patients and is associated with poor patient-oriented outcomes such as increased mortality, longer ICU and hospital length of stay, and worse long-term cognitive outcomes. The concept of delirium and its subtypes has existed since nearly the beginning of recorded medical literature, yet robust therapies have yet to be identified. Analogous to other critical illness syndromes, we suspect the lack of identified therapies stems from patient heterogeneity and prior subtyping efforts that do not capture the underlying etiology of delirium. The time has come to leverage machine learning approaches, such as supervised and unsupervised clustering, to identify clinical and pathophysiological distinct clusters of delirium that will likely respond differently to various interventions. We use sedation in the ICU as an example of how precision therapies can be applied to critically ill patients, highlighting the fact that while for some patients a sedative drug may cause delirium, in another cohort sedation is the specific treatment. Finally, we conclude with a proposition to move away from the term delirium, and rather focus on the treatable traits that may allow precision therapies to be tested.

Cerebral autoregulation-based mean arterial pressure targets and delirium in critically ill adults without brain injury: a retrospective cohort study.

PURPOSE: Cerebral autoregulation (CA) is a mechanism that acts to maintain consistent cerebral perfusion across a range of blood pressures, and impaired CA is associated with delirium. Individualized CA-derived blood pressure targets are poorly characterized in critically ill patients and the association with intensive care unit (ICU) delirium is unknown. Our objectives were to characterize optimal mean arterial pressure (MAPopt) ranges in critically ill adults without brain injury and determine whether deviations from these targets contribute to ICU delirium. METHODS: We performed a retrospective cohort analysis of patients with shock of any etiology and/or respiratory failure requiring invasive mechanical ventilation, without a neurologic admitting diagnosis. Patients were screened daily for delirium. Cerebral oximetry and mean arterial pressure data were captured for the first 24 hr from enrolment. RESULTS: Forty-two patients with invasive blood pressure monitoring data were analyzed. Optimal mean arterial pressure targets ranged from 55 to 100 mm Hg. Optimal mean arterial pressure values were not significantly different based on history of hypertension or delirium status, and delirium was not associated with deviations from MAPopt. Nevertheless, the majority (69%) of blood pressure targets exceeded the current 65 mm Hg Surviving Sepsis guidelines. CONCLUSION: We observed that MAPopt targets across patients were highly variable, but did not observe an association with the incidence of delirium. Studies designed to evaluate the impact on neurologic outcomes are needed to understand the association with individualized mean arterial pressure targets in the ICU. STUDY REGISTRATION: ClinicalTrials.gov (NCT02344043); first submitted 22 January 2015.

RéSUMé: OBJECTIF: L'autorégulation cérébrale (AC) est un mécanisme qui agit pour maintenir une perfusion cérébrale constante pour une gamme de tensions artérielles, et une altération de l'AC est associée au delirium. Les cibles de tension artérielle individualisées dérivées de l'AC sont mal caractérisées chez les patient·es gravement malades et l'association avec le delirium à l'unité de soins intensifs (USI) est inconnue. Nos objectifs étaient de caractériser la tension artérielle moyenne optimale (TAMopt) chez les adultes gravement malades sans lésion cérébrale et de déterminer si les écarts par rapport à ces cibles contribuaient au delirium à l'USI. MéTHODE: Nous avons réalisé une analyse de cohorte rétrospective de patient·es présentant un choc de toute étiologie et/ou une insuffisance respiratoire nécessitant une ventilation mécanique invasive, et n'ayant pas reçu de diagnostic d'atteinte neurologique à l'admission. Les patients ont été dépistés quotidiennement pour le delirium. Les données d'oxymétrie cérébrale et de tension artérielle moyenne ont été saisies pendant les 24 premières heures suivant le recrutement. RéSULTATS: Quarante-deux patient·es pour qui des données de monitorage invasif de la tension artérielle étaient disponibles ont été analysé·es. Les cibles optimales de tension artérielle moyenne variaient de 55 à 100 mm Hg. Les valeurs optimales de tension artérielle moyenne n'étaient pas significativement différentes en fonction des antécédents d'hypertension ou de delirium, et le delirium n'était pas associé à des écarts par rapport à la TAMopt. Néanmoins, la majorité (69 %) des cibles de tension artérielle dépassaient celle de 65 mm Hg préconisée par les lignes directrices Surviving Sepsis. CONCLUSION: Nous avons observé que les cibles de TAMopt étaient très variables chez les patient·es, mais nous n'avons pas observé d'association avec l'incidence de delirium. Des études conçues pour évaluer l'impact sur les issues neurologiques sont nécessaires pour comprendre l'association avec les cibles de tension artérielle moyenne individualisées à l'USI. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02344043); soumis pour la première fois le 22 janvier 2015.

Feasibility and Cost Analysis of Portable MRI Implementation in a Remote Setting in Canada.

OBJECTIVE: To conduct feasibility and cost analysis of portable MRI implementation in a remote setting where MRI access is otherwise unavailable. METHODS: Portable MRI (ultra-low field, 0.064T) was installed in Weeneebayko General Hospital, Moose Factory, Ontario. Adult patients, presenting with any indication for neuroimaging, were eligible for study inclusion. Scanning period was from November 14, 2021, to September 6, 2022. Images were sent via a secure PACS network for Neuroradiologist interpretation, available 24/7. Clinical indications, image quality, and report turnaround time were recorded. A cost analysis was conducted from a healthcare system's perspective in 2022 Canadian dollars, comparing cost of portable MRI implementation to transporting patients to a center with fixed MRI. RESULTS: Portable MRI was successfully implemented in a remote Canadian location. Twenty-five patients received a portable MRI scan. All studies were of diagnostic quality. No clinically significant pathologies were identified on any of the studies. However, based on clinical presentation and limitations of portable MRI resolution, it is estimated that 11 (44%) of patients would require transfer to a center with fixed MRI for further imaging workup. Cost savings were $854,841 based on 50 patients receiving portable MRI over 1 year. Five-year budget impact analysis showed nearly $8 million dollars saved. CONCLUSIONS: Portable MRI implementation in a remote setting is feasible, with significant cost savings compared to fixed MRI. This study may serve as a model to democratize MRI access, offer timely care and improved triaging in remote areas where conventional MRI is unavailable.

Infratentorial brain injury and death by neurologic criteria in Canada: a narrative review.

There are two anatomic formulations of death by neurologic criteria accepted worldwide: whole-brain death and brainstem death. As part of the Canadian Death Definition and Determination Project, we convened an expert working group and performed a narrative review of the literature. Infratentorial brain injury (IBI) with an unconfounded clinical assessment consistent with death by neurologic criteria represents a nonrecoverable injury. The clinical determination of death cannot distinguish between IBI and whole-brain cessation of function. Current clinical, functional, and neuroimaging assessments cannot reliably confirm the complete and permanent destruction of the brainstem. No patient with isolated brainstem death has been reported to recover consciousness and all patients have died. Studies suggest a significant majority of isolated brainstem death will evolve into whole-brain death, influenced by time/duration of somatic support and impacted by ventricular drainage and/or posterior fossa decompressive craniectomy. Acknowledging variability in intensive care unit (ICU) physician opinion on this matter, a majority of Canadian ICU physicians would perform ancillary testing for death determination by neurologic criteria in the context of IBI. There is currently no reliable ancillary test to confirm complete destruction of the brainstem; ancillary testing currently includes evaluation of both infratentorial and supratentorial flow. Acknowledging international variability in this regard, the existing evidence reviewed does not provide sufficient confidence that the clinical exam in IBI represents a complete and permanent destruction of the reticular activating system and thus the capacity for consciousness. On this basis, IBI consistent with clinical signs of death by neurologic criteria without significant supratentorial involvement does not fulfill criteria for death in Canada and ancillary testing is required.

RéSUMé: Il existe deux formulations anatomiques du décès selon des critères neurologiques acceptés dans le monde entier : la mort du cerveau entier et la mort du tronc cérébral. Dans le cadre du Projet canadien de définition et de détermination du décès, nous avons réuni un groupe de travail composé d'experts et réalisé un compte rendu narratif de la littérature. Une lésion cérébrale infratentorielle (LCI) avec une évaluation clinique sans facteur confondant et compatible avec un décès selon des critères neurologiques représente une atteinte irrécupérable. La détermination clinique du décès ne permet pas de faire la distinction entre une LCI et l'arrêt de la fonction dans le cerveau entier. Les évaluations cliniques, fonctionnelles et de neuroimagerie actuelles ne peuvent pas confirmer de manière fiable la destruction complète et permanente du tronc cérébral. La récupération de la conscience n'a jamais été signalée chez aucun patient présentant une mort isolée du tronc cérébral, et tous les patients sont décédés. Des études suggèrent qu'une majorité significative des morts isolées du tronc cérébral évolueront vers la mort cérébrale entière, étant influencées par le temps et la durée de l'assistance somatique et impactées par le drainage ventriculaire et/ou la craniectomie décompressive de la fosse postérieure. Compte tenu de la variabilité des opinions des médecins intensivistes à ce sujet, la majorité des médecins intensivistes canadiens réaliseraient des examens auxiliaires pour déterminer le décès selon des critères neurologiques dans le contexte d'une LCI. Il n'existe actuellement aucun examen auxiliaire fiable pour confirmer la destruction complète du tronc cérébral; les examens auxiliaires comprennent actuellement l'évaluation de la circulation infratentorielle et supratentorielle. Reconnaissant la variabilité internationale à cet égard, les données probantes existantes passées en revue ne sont pas suffisamment fiables pour affirmer que l'examen clinique en cas de LCI représente une destruction complète et permanente du système d'activation réticulaire et donc de la capacité de conscience. En se fondant sur cette base, une LCI compatible avec les signes cliniques d'un décès selon des critères neurologiques sans atteinte supratentorielle significative ne répond pas aux critères de décès au Canada et un examen auxiliaire est requis.

Ancillary investigations for death determination in infants and children: a systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis to determine the diagnostic test accuracy of ancillary investigations for declaration of death by neurologic criteria (DNC) in infants and children. SOURCE: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases from their inception to June 2021 for relevant randomized controlled trials, observational studies, and abstracts published in the last three years. We identified relevant studies using Preferred Reporting Items for Systematic Reviews and Meta-Analysis methodology and a two-stage review. We assessed the risk of bias using the QUADAS-2 tool, and applied Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the certainty of evidence. A fixed-effects model was used to meta-analyze pooled sensitivity and specificity data for each ancillary investigation with at least two studies. PRINCIPAL FINDINGS: Thirty-nine eligible manuscripts assessing 18 unique ancillary investigations (n = 866) were identified. The sensitivity and specificity ranged from 0.00 to 1.00 and 0.50 to 1.00, respectively. The quality of evidence was low to very low for all ancillary investigations, with the exception of radionuclide dynamic flow studies for which it was graded as moderate. Radionuclide scintigraphy using the lipophilic radiopharmaceutical 99mTc-hexamethylpropyleneamine oxime (HMPAO) with or without tomographic imaging were the most accurate ancillary investigations with a combined sensitivity of 0.99 (95% highest density interval [HDI], 0.89 to 1.00) and specificity of 0.97 (95% HDI, 0.65 to 1.00). CONCLUSION: The ancillary investigation for DNC in infants and children with the greatest accuracy appears to be radionuclide scintigraphy using HMPAO with or without tomographic imaging; however, the certainty of the evidence is low. Nonimaging modalities performed at the bedside require further investigation. STUDY REGISTRATION: PROSPERO (CRD42021278788); registered 16 October 2021.

RéSUMé: OBJECTIF: Nous avons réalisé une revue systématique et une méta-analyse pour déterminer la précision des tests diagnostiques des examens auxiliaires pour la déclaration du décès selon des critères neurologiques (DCN) chez les nourrissons et les enfants. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, EMBASE, Web of Science et Cochrane de leur création jusqu'en juin 2021 pour trouver des études randomisées contrôlées, des études observationnelles et des résumés pertinents publiés au cours des trois dernières années. Nous avons identifié les études pertinentes utilisant la méthodologie PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) et une revue en deux étapes. Nous avons évalué le risque de biais en utilisant l'outil QUADAS-2 et appliqué la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation) afin d'évaluer la certitude des données probantes. Un modèle à effets fixes a été utilisé pour méta-analyser les données de sensibilité et de spécificité regroupées pour chaque examen auxiliaire avec au moins deux études. CONSTATATIONS PRINCIPALES: Trente-neuf manuscrits admissibles évaluant 18 examens auxiliaires uniques (n = 866) ont été identifiés. La sensibilité et la spécificité variaient de 0,00 à 1,00 et de 0,50 à 1,00, respectivement. La qualité des données probantes était faible à très faible pour tous les examens auxiliaires, à l'exception des études de circulation nucléaire dynamique, pour lesquelles elle a été classée comme modérée. La scintigraphie nucléaire à l'aide du produit radiopharmaceutique lipophile 99mTc- hexa-méthyl-propylène amine oxime (HMPAO) avec ou sans imagerie tomographique était à la base des examens auxiliaires les plus précis, avec une sensibilité combinée de 0,99 (intervalle de densité le plus élevé [IDE] à 95 %, 0,89 à 1,00) et une spécificité de 0,97 (IDE à 95 %, 0,65 à 1,00). CONCLUSION: L'examen auxiliaire pour un DCN chez les nourrissons et les enfants offrant la plus grande précision semble être la scintigraphie nucléaire utilisant le HMPAO avec ou sans imagerie tomographique; cependant, la certitude des données probantes est faible. Les modalités sans imagerie réalisées au chevet du patient nécessitent un examen plus approfondi. Enregistrement de l'étude: PROSPERO (CRD42021278788); enregistrée le 16 octobre 2021.

A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline.

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.

RéSUMé: Ces Lignes directrices de pratique clinique 2023 Lignes directrices de pratique clinique dicale du décès basée sur l'arrêt permanent de la fonction cérébrale qui s'applique à toute personne, ainsi que des recommandations pour la détermination du décès par des critères circulatoires pour des donneurs d'organes potentiels et des recommandations pour la détermination du décès par des critères neurologiques pour tous les patients sous ventilation mécanique, indépendamment de leur potentiel de donneur d'organes. Les présentes Lignes directrices sont approuvées par la Société canadienne de soins intensifs, l'Association médicale canadienne, l'Association canadienne des infirmiers/infirmières en soins intensifs, la Société canadienne des anesthésiologistes, la Fédération des sciences neurologiques du Canada (représentant la Société canadienne de neurologie, la Société canadienne de neurochirurgie, la Société canadienne de neurophysiologie clinique, l'Association canadienne de neurologie pédiatrique, la Société canadienne de neuroradiologie et le Consortium neurovasculaire canadien), la Société canadienne du sang, le Programme de recherche en don et transplantation du Canada, l'Association canadienne des médecins d'urgence, l'Association des infirmières et infirmiers praticiens du Canada, et la Société canadienne de soins intensifs cardiovasculaires (CANCARE) et la Société canadienne de pédiatrie.

Informed consent practices in clinical research: present and future.

Clinical research must balance the need for ambitious recruitment with protecting participants' autonomy; a requirement of which is informed consent. Despite efforts to improve the informed consent process, participants are seldom provided sufficient information regarding research, hindering their ability to make informed decisions. These issues are particularly pervasive among patients experiencing acute illness or neurological impairment, both of which may impede their capacity to provide consent. There is a critical need to understand the components, requirements, and methods of obtaining true informed consent to achieve the vast numbers required for meaningful research. This paper provides a comprehensive review of the tenets underlying informed consent in research, including the assessment of capacity to consent, considerations for patients unable to consent, when to seek consent from substitute decision-makers, and consent under special circumstances. Various methods for obtaining informed consent are addressed, along with strategies for balancing recruitment and consent.

Tools for assessing health research partnership outcomes and impacts: a systematic review.

OBJECTIVE: To identify and assess the globally available valid, reliable and acceptable tools for assessing health research partnership outcomes and impacts. METHODS: We searched Ovid MEDLINE, Embase, CINAHL Plus and PsycINFO from origin to 2 June 2021, without limits, using an a priori strategy and registered protocol. We screened citations independently and in duplicate, resolving discrepancies by consensus and retaining studies involving health research partnerships, the development, use and/or assessment of tools to evaluate partnership outcomes and impacts, and reporting empirical psychometric evidence. Study, tool, psychometric and pragmatic characteristics were abstracted using a hybrid approach, then synthesized using descriptive statistics and thematic analysis. Study quality was assessed using the quality of survey studies in psychology (Q-SSP) checklist. RESULTS: From 56 123 total citations, we screened 36 027 citations, assessed 2784 full-text papers, abstracted data from 48 studies and one companion report, and identified 58 tools. Most tools comprised surveys, questionnaires and scales. Studies used cross-sectional or mixed-method/embedded survey designs and employed quantitative and mixed methods. Both studies and tools were conceptually well grounded, focusing mainly on outcomes, then process, and less frequently on impact measurement. Multiple forms of empirical validity and reliability evidence was present for most tools; however, psychometric characteristics were inconsistently assessed and reported. We identified a subset of studies (22) and accompanying tools distinguished by their empirical psychometric, pragmatic and study quality characteristics. While our review demonstrated psychometric and pragmatic improvements over previous reviews, challenges related to health research partnership assessment and the nascency of partnership science persist. CONCLUSION: This systematic review identified multiple tools demonstrating empirical psychometric evidence, pragmatic strength and moderate study quality. Increased attention to psychometric and pragmatic requirements in tool development, testing and reporting is key to advancing health research partnership assessment and partnership science. PROSPERO CRD42021137932.

A Pregnant Pause: System-Level Barriers to Perinatal Mental Health Care.

Perinatal mood and anxiety disorders, defined as mood and anxiety disorders during pregnancy and the year following birth, affect one in five pregnant and postpartum individuals in the United States and are associated with substantial morbidity and mortality for both pregnant individuals and their infants. Despite this tremendous prevalence and associated disease burden, the overwhelming majority of those affected do not receive treatment. Although prior research has identified several patient-level barriers to effective treatment, the contributions of system-level factors have been underappreciated. We present a pilot study using a simulated patient approach to describe the accessibility and affordability of mental health care through the 18 clinics affiliated with U.S. reproductive psychiatry fellowship programs. Based on our experience, a prospective patient seeking care from these 18 clinics without a prior referral would only have been successful half of the time-and even then may have to wait as long as 2 months for an initial appointment. These data underscore the need for clinicians, public health professionals, and institutions to address system-level barriers that undermine effective referrals for care, including implementing "warm-handoffs" to mental health providers and ending practices that restrict appointments to existing patients within a health care system. They also reinforce the importance of contemporary federal policy efforts to address maternal health, particularly among low-income and racially minoritized communities. Key policies include expanding postpartum insurance coverage, which plays a critical role in reducing insurance disruptions that can undermine the accessibility of mental health care and other vital health services.

New Measurements of the Beam-Normal Single Spin Asymmetry in Elastic Electron Scattering over a Range of Spin-0 Nuclei.

We report precision determinations of the beam-normal single spin asymmetries (A_{n}) in the elastic scattering of 0.95 and 2.18 GeV electrons off ^{12}C, ^{40}Ca, ^{48}Ca, and ^{208}Pb at very forward angles where the most detailed theoretical calculations have been performed. The first measurements of A_{n} for ^{40}Ca and ^{48}Ca are found to be similar to that of ^{12}C, consistent with expectations and thus demonstrating the validity of theoretical calculations for nuclei with Z≤20. We also report A_{n} for ^{208}Pb at two new momentum transfers (Q^{2}) extending the previous measurement. Our new data confirm the surprising result previously reported, with all three data points showing significant disagreement with the results from the Z≤20 nuclei. These data confirm our basic understanding of the underlying dynamics that govern A_{n} for nuclei containing ≲50 nucleons, but point to the need for further investigation to understand the unusual A_{n} behavior discovered for scattering off ^{208}Pb.

Precision Determination of the Neutral Weak Form Factor of

We report a precise measurement of the parity-violating (PV) asymmetry A_{PV} in the elastic scattering of longitudinally polarized electrons from ^{48}Ca. We measure A_{PV}=2668±106(stat)±40(syst) parts per billion, leading to an extraction of the neutral weak form factor F_{W}(q=0.8733 fm^{-1})=0.1304±0.0052(stat)±0.0020(syst) and the charge minus the weak form factor F_{ch}-F_{W}=0.0277±0.0055. The resulting neutron skin thickness R_{n}-R_{p}=0.121±0.026(exp)±0.024(model) fm is relatively thin yet consistent with many model calculations. The combined CREX and PREX results will have implications for future energy density functional calculations and on the density dependence of the symmetry energy of nuclear matter.

Acute kidney injury is associated with subtle but quantifiable neurocognitive impairments.

BACKGROUND: Acute kidney injury (AKI) is associated with long-term morbidity and mortality. The effects of AKI on neurocognitive functioning remain unknown. Our objective was to quantify neurocognitive impairment after an episode of AKI. METHODS: Survivors of AKI were compared with age-matched controls, as well as a convenience sample of patients matched for cardiovascular risk factors with normal kidney function (active control group). Patients with AKI completed two assessments, while the active control group completed one assessment. The assessment included a standardized test: the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and a robotic assessment: Kinarm. RESULTS: The cohort consisted of 21 patients with AKI, 16 of whom completed both assessments, and 21 active control patients. The majority of patients with AKI had Kidney Disease: Improving Global Outcomes Stage 3 AKI (86%), 57% received dialysis and 43% recovered to ≤25% of their baseline serum creatinine by their first assessment. Compared with the RBANS, which detected little impairment, the Kinarm categorized patients as impaired in visuomotor (10/21, 48%), attention (10/20, 50%) and executive tasks (11/21, 52%) compared with healthy controls. Additionally, patients with AKI performed significantly worse in attention and visuomotor domains when compared with the active controls. Neurocognitive performance was generally not impacted by the need for dialysis or whether kidney function recovered. CONCLUSIONS: Robotic technology identified quantifiable neurocognitive impairment in survivors of AKI. Deficits were noted particularly in attention, visuomotor and executive domains. Further investigation into the downstream health consequences of these neurocognitive impairments is warranted.

The Use of Near-Infrared Spectroscopy and/or Transcranial Doppler as Non-Invasive Markers of Cerebral Perfusion in Adult Sepsis Patients With Delirium: A Systematic Review.

BACKGROUND: Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear. METHODS: We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (≥18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science. RESULTS: Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis. CONCLUSION: The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAPOPT), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis.

Evaluation of an alternative skeletal muscle index for skeletal muscle mass assessment in a group of Australian women.

BACKGROUND: Sarcopenia is assessed by several methods, including dual energy X-ray absorptiometry (DEXA), which provide a height-adjusted skeletal muscle index (H-SMI). A SMI 2 standard deviation below the young adult reference [1] combined with low muscle strength or performance is used to identify sarcopenia. As height declines with age, H-SMI may underestimate low skeletal muscle mass in the older population. Our study aims to evaluate an alternative SMI and to examine its relationship to grip strength in a group of Australian women. METHODS: Women from two cohorts were analysed. 2041 women had body composition data (112 had calf circumference, 137 had leg length measurements) without grip strength, and 49 women had grip strength measured (40 had body composition data).The relationship between leg length-adjusted SMI (LL-SMI) to grip strength and anthropometric variables to skeletal muscle mass by DEXA were examined by linear regression analysis. RESULTS: Cohort 1: Older women were compared to younger women. Older women were shorter but leg length did not differ between different age groups. H-SMI was not different between groups (P = 0.528). LL-SMI was lower in older women (P = 0.002). Cohort 2: LL-SMI was significantly associated with grip strength (P = 0.048) after adjustment for age. CONCLUSION: Older women were shorter, while leg length did not differ from the younger group. H-SMI may obscure and may underestimate low muscle mass in older individuals. LL-SMI may be a better measure of skeletal muscle mass in older individuals. These alternate SMI would benefit from further exploration in older individuals.

Outcomes of critically ill COVID-19 survivors and caregivers: a case study-centred narrative review.

PURPOSE: Critical illness is a transformative experience for both patients and their family members. For COVID-19 patients admitted to the intensive care unit (ICU), survival may be the start of a long road to recovery. Our knowledge of the post-ICU long-term sequelae of acute respiratory distress syndrome (ARDS) and severe acute respiratory syndrome (SARS) may inform our understanding and management of the long-term effects of COVID-19. SOURCE: We identified international and Canadian epidemiologic data on ICU admissions for COVID-19, COVID-19 pathophysiology, emerging ICU practice patterns, early reports of long-term outcomes, and federal support programs for survivors and their families. Centred around an illustrating case study, we applied relevant literature from ARDS and SARS to contextualize knowledge within emerging COVID-19 research and extrapolate findings to future long-term outcomes. PRINCIPAL FINDINGS: COVID-19 is a multisystem disease with unknown long-term morbidity and mortality. Its pathophysiology is distinct and unique from ARDS, SARS, and critical illness. Nevertheless, based on initial reports of critical care management for COVID-19 and the varied injurious supportive practices employed in the ICU, patients and families are at risk for post-intensive care syndrome. The distinct incremental risk of COVID-19 multiple organ dysfunction is unknown. The risk of mood disorders in family members may be further exacerbated by imposed isolation and stigma. CONCLUSION: Emerging literature on COVID-19 outcomes suggests some similarities with those of ARDS/SARS and prolonged mechanical ventilation. The pathophysiology of COVID-19 is presented here in the context of early outcome data and to inform an agenda for longitudinal research for patients and families.

RéSUMé: OBJECTIF: Les maladies au stade critique constituent une expérience bouleversante tant pour les patients que pour leurs proches. Pour les patients atteints de la COVID-19 admis aux soins intensifs (USI), la survie peut être le début d'un long parcours vers la guérison. Notre connaissance des séquelles à long terme post-USI d'un syndrome de détresse respiratoire aiguë (SDRA) ou d'un syndrome respiratoire aigu sévère (SRAS) pourrait éclairer notre compréhension et notre prise en charge des effets à long terme de la COVID-19. SOURCES: Nous avons identifié des données épidémiologiques internationales et canadiennes sur les admissions aux soins intensifs pour la COVID-19, la physiopathologie de la COVID-19, les schémas de pratique émergents en soins intensifs, les premiers rapports sur les issues à long terme et les programmes de soutien fédéraux pour les survivants et leurs familles. En nous centrant autour d'une étude de cas pour illustrer notre propos, nous avons appliqué la littérature pertinente à propos du SDRA et du SRAS afin de contextualiser les connaissances de la recherche émergente sur la COVID-19 et extrapoler les conclusions aux futures issues à long terme. CONSTATATIONS PRINCIPALES: La COVID-19 est une maladie multisystémique dont la morbidité et la mortalité à long terme sont inconnues. Sa physiopathologie est unique et distincte du SDRA, du SRAS et des maladies graves. Néanmoins, en nous fondant sur les rapports initiaux de prise en charge aux soins intensifs de la COVID-19 et sur les diverses pratiques de support préjudiciables utilisées aux soins intensifs, les patients et les familles sont à risque de syndrome post-soins intensifs. Le risque distinct supplémentaire de dysfonctionnement multiviscéral de la COVID-19 est inconnu. Le risque de troubles de l'humeur chez les proches peut être encore exacerbé par l'isolement imposé et la stigmatisation. CONCLUSION: La littérature émergente sur les issues de la COVID-19 suggère certaines similitudes avec celles du SDRA/SRAS et de la ventilation mécanique prolongée. La physiopathologie de la COVID-19 est présentée ici dans le contexte des premières données sur les issues et pour éclairer un programme de recherche longitudinale pour les patients et leurs familles.

Overview and Diagnostic Accuracy of Near Infrared Spectroscopy in Carotid Endarterectomy: A Systematic Review and Meta-analysis.

OBJECTIVE: Carotid endarterectomy is recommended for the prevention of ischaemic stroke due to carotid stenosis. However, the risk of stroke after carotid endarterectomy has been estimated at 2% - 5%. Monitoring intra-operative cerebral oxygenation with near infrared spectroscopy (NIRS) has been assessed as a strategy to reduce intra- and post-operative complications. The aim was to summarise the diagnostic accuracy of NIRS to detect intra-operative ischaemic events, the values associated with ischaemic events, and the relative contribution of external carotid contamination to the NIRS signal in adults undergoing carotid endarterectomy. DATA SOURCES: EMBASE, MEDLINE, Cochrane Centre Register of Controlled Trials, and reference lists through May 2019 were searched. REVIEW METHODS: Non-randomised and randomised studies assessing NIRS as an intra-operative monitoring tool in carotid endarterectomy were included. Studies using NIRS as the reference were excluded. Risk of bias was assessed using the Newcastle Ottawa Scale, RoB-2, and QUADAS-2. RESULTS: Seventy-six studies were included (n = 8 480), under local (n = 1 864) or general (n = 6 582) anaesthesia. Seven studies were eligible for meta-analysis (n = 524). As a tool for identifying intra-operative ischaemia, specificity increased with more stringent NIRS thresholds, while there was unpredictable variation in sensitivity across studies. A Δ20% threshold under local anaesthesia resulted in pooled estimates for sensitivity and specificity of 70.5% (95% confidence interval, CI, 54.1 - 82.9) and 92.4% (95% CI 85.5 - 96.1) compared with awake neurological monitoring. These studies had low or unclear risk of bias. NIRS signal consistently dropped across clamping and recovered to pre-clamp values upon de-clamp in most studies, and larger decreases were observed in patients with ischaemic events. The contribution of extracranial signal to change in signal across clamp varied from 3% to 50%. CONCLUSION: NIRS has low sensitivity and high specificity to identify intra-operative ischaemia compared with awake monitoring. Extracranial signal contribution was highly variable. Ultimately, data from high quality studies are desperately needed to determine the utility of NIRS.

Physician Scientists Of Yesterday, Today And Tomorrow.

While the separate roles of physicians and scientists are well defined, the role of a physician scientist is broad and variable. In today's society, physician scientists are seen as a hybrid between the two fields and they are, therefore, expected to be key to the translation of biomedical research into clinical care. This article offers a narrative review on physician scientists and endeavours to answer whether there is an ongoing need for physician scientists today. The historical role of physician scientists is discussed and compared with physician scientists of the 21st century. Fundamental differences and similarities between the separate roles of physicians and scientists are examined as well as the current state of bench to bedside research. Finally, the ability of 21st century physician scientists to impact their respective medical and scientific fields in comparison to non-physician scientists will be discussed. This paper speculates as to why numbers of physician scientists are dwindling and uses the COVID-19 pandemic as an example of rapid translational research. Ultimately, we suggest that physician scientists are important and may have the most impact on their field by working to connect bedside and bench rather than simply working separately in the bedside and bench. To do this, physician scientists may need to lead clinical research teams composed of individuals from diverse training backgrounds.

Race, Power, and COVID-19: A Call for Advocacy within Bioethics.

Events in 2020 have sparked a reimagination of how both individuals and institutions should consider race, power, health, and marginalization in society. In a response to these developments, we examine the current and past limitations of the ways in which bioethicists have considered race and, more generally, discourses of marginalization. We argue that the foundational principle of justice necessitates that bioethics, as an institution, maintain an active voice against systemic injustice. To carry out this charge, bioethics as a field should promote alternative narratives-"counter storytelling"-to the mainstream voices that have traditionally been heard and accepted, largely without opposition. Additionally, we engage with both Post-Colonial and Critical Race Theory, which we believe are important tools for bioethics in pursuit of equity. Ultimately, we advocate for a proactive form of bioethics that actively resists and denounces injustice and which considers a much wider variety of voices about justice than bioethics has historically considered.