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Introduction: Early mid-life is marked by accumulating risks for cardiometabolic illness linked to health-risk behaviors like nicotine use. Identifying polygenic indices (PGI) has enriched scientific understanding of the cumulative genetic contributions to behavioral and cardiometabolic health, though few studies have assessed these associations alongside socioeconomic (SES) and lifestyle factors., Aims and Methods: Drawing on data from 2337 individuals from the United States participating in the National Longitudinal Study of Adolescent to Adult Health, the current study assesses the fraction of variance in five related outcomes-use of conventional and electronic cigarettes, body mass index (BMI), waist circumference, and glycosylated hemoglobin (A1c)-explained by PGI, SES, and lifestyle., Results: Regression models on African ancestry (AA) and European ancestry (EA) subsamples reveal that the fraction of variance explained by PGI ranges across outcomes. While adjusting for sex and age, PGI explained 3.5%, 2.2%, and 0% in the AA subsample of variability in BMI, waist circumference, and A1c, respectively (in the EA subsample these figures were 7.7%, 9.4%, and 1.3%). The proportion of variance explained by PGI in nicotine-use outcomes is also variable. Results further indicate that PGI and SES are generally complementary, accounting for more variance in the outcomes when modeled together versus separately., Conclusions: PGI are gaining attention in population health surveillance, but polygenic variability might not align clearly with health differences in populations or surpass SES as a fundamental cause of health disparities. We discuss future steps in integrating PGI and SES to refine population health prediction rules., Implications: Study findings point to the complementary relationship of PGI and socioeconomic indicators in explaining population variance in nicotine outcomes and cardiometabolic wellness. Population health surveillance and prediction rules would benefit from the combination of information from both polygenic and socioeconomic risks. Additionally, the risk for electronic cigarette use among users of conventional cigarettes may have a genetic component tied to the cumulative genetic propensity for heavy smoking. Further research on PGI for vaping is needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Although ventilation/perfusion (V/Q) scintigraphy is a widely used imaging test, different options are possible for the acquisition and interpretation of the scan. The aim of this study was to assess current practices regarding the use and interpretation of lung scintigraphy in various clinical indications., Patients and Methods: An online survey comprising 25 questions was sent to nuclear medicine departments in Australia, Canada, France, Germany, and United States between 2022 and 2023. A single response per department was consolidated., Results: Four hundred nineteen responses were collected (Australia: 32, Canada: 58, France: 149, Germany: 92, and United States: 88). For acute pulmonary embolism (PE) diagnosis, 82.8% of centers reported using SPECT acquisitions (Australia: 93.3%, Canada: 91.8%, France: 99.2%, Germany: 96.2%, and United States: 32.1%). Among them, SPECT images were combined with a CT scan in 70.5% of centers. A total of 10.6% of centers reported not using ventilation for acute PE diagnosis. SPECT acquisition was used in 97.8% of centers using 99m Tc carbon particles, 97.1% 81m Kr gas, 58.7% 99m Tc-DTPA, and 19.4% 133 Xe gas, respectively. For V/Q SPECT interpretation, the EANM criteria were used in 65.0% of departments. A very wide variety of practices were observed in pregnant women and in COVID-19 patients. SPECT acquisition was widely used in the follow-up of PE and for the screening of chronic thromboembolic pulmonary hypertension (>90% of centers), with inconsistency regarding the interpretation of matched perfusion defects in this setting., Conclusions: This survey shows the strong adoption of SPECT in the various clinical indications of lung scintigraphy, except in the United States, where planar imaging is still mostly used. The survey also shows variability in interpretation criteria both for PE diagnosis and screening for chronic thromboembolic pulmonary hypertension, highlighting the need for further standardizations of practices., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cluster randomized trials (CRTs) are increasingly important for evaluating interventions embedded in health care systems. An essential parameter in sample size calculation to detect both overall and heterogeneous treatment effects for CRTs is the intra-cluster correlation coefficient (ICC) of both outcome and covariates of interest. However, obtaining advance estimates for the ICC can be challenging. When trial outcomes will be obtained from routinely collected data sources, there is an opportunity to obtain reliable ICC estimates in advance of the trial. Using USA national Medicare data, we estimated ICCs for a range of outcomes to inform the design of CRTs for people living with Alzheimer's and related dementias (ADRD)., Method: Data from 2018 Medicare Fee-for-Service beneficiaries, specifically, 1,898,812 individuals (≥ 65 years) with diagnosis of ADRD within 3436 hospital service areas (treated as clusters) and 306 hospital referral regions (treated as fixed strata), were used to calculate unadjusted and adjusted ICC estimates for three outcomes: death, any hospitalizations, and any emergency department (ED) visits and three covariates: age, race and sex. We present both overall and stratum-specific ICC estimates. We illustrate their use in sample size calculations for overall treatment effects as well as detecting treatment effect heterogeneity., Results: The unadjusted overall ICCs for death, hospitalizations, and ED visits were 0.001, 0.010, and 0.017 respectively. Stratum-specific ICCs varied widely across the 306 HRRs: median 0.001, 0.010 and 0.025 for death, hospitalizations, and ED visits respectively and 0.007, 0.001, and 0.080 for age, sex and race. An interactive R Shiny app is provided that allows users to retrieve estimates overlayed on a map of the USA., Conclusions: We presented both adjusted and unadjusted ICCs for outcomes as well as unadjusted ICCs for covariates of potential interest from population-level data in the USA and demonstrated how the estimates may be used in sample size calculations for CRTs in ADRD., (© 2024. The Author(s).)

Objective: Physicians vary in their computed tomography (CT) scan usage. It remains unclear how physician gender relates to clinical practice or patient outcomes. The aim of this study was to assess the association between physician gender and decision to order head CT scans for older emergency patients who had fallen., Methods: This was a secondary analysis of a prospective observational cohort study conducted in 11 hospital emergency departments (EDs) in Canada and the United States. The primary study enrolled patients who were 65 years and older who presented to the ED after a fall. The analysis evaluated treating physician gender adjusted for multiple clinical variables. Primary analysis used a hierarchical logistic regression model to evaluate the association between treating physician gender and the patient receiving a head CT scan. Secondary analysis reported the adjusted odds ratio (OR) for diagnosing intracranial bleeding by physician gender., Results: There were 3663 patients and 256 physicians included in the primary analysis. In the adjusted analysis, women physicians were no more likely to order a head CT than men (OR 1.26, 95% confidence interval 0.98-1.61). In the secondary analysis of 2294 patients who received a head CT, physician gender was not associated with finding a clinically important intracranial bleed., Conclusions: There was no significant association between physician gender and ordering head CT scans for older emergency patients who had fallen. For patients where CT scans were ordered, there was no significant relationship between physician gender and the diagnosis of clinically important intracranial bleeding., (© 2024 Society for Academic Emergency Medicine.)

Accurate weight predictions are essential for weight management program patients. The freely available National Institutes of Health Body Weight Planner (NIH-BWP) returns expected weights over time but overestimates weight when patients consume a low-calorie diet. This study sought to increase the accuracy of NIH-BWP predicted weights for people on low-calorie diets. People enrolled in a weight management program were included if they received meal replacements with defined caloric content for the 3 months of the weight loss phase of the program. The Ottawa Weight Loss Prediction Model (OWL-PM) modelled the relative difference between observed and NIH-BWP predicted weights using longitudinal analysis methods based on patient factors. OWL-PM was externally validated. 1761 people were included (mean age 46 years, 73.3% women) with a mean (SD) baseline weight in pounds and body mass index of 271.9 (55.6) and 43.9 (7.4), respectively. At the end of the program's weight loss phase, people lost a median (IQR) of 17.1% (14.8-19.5) of their baseline weight. Observed weight relative to NIH-BWP predicted weights had a median value of - 4.9% but ranged from - 32.1% to + 28.5%. After adjustment, weight overestimation by NIH-BWP was most pronounced in male patients, people without diabetes and with increased observation time. OWL-PM returned expected weights at 3 months that were significantly more accurate than those from NIH-BWP alone (mean difference observed vs. expected [95% CI] 6.7lbs [6.4-7.0] vs. 12.6lbs [12.1-13.0]). In the external validation cohort (n = 106), OWL-PM was significantly more accurate than NIH-BWP (mean squared error 24.3 vs. 40.0, p = 0.0018). OWL-PM incorporated patient-level covariates to significantly increase weight prediction accuracy of NIH-BWP in patients consuming a low-calorie diet., (© 2024. The Author(s).)

Objective: To evaluate the reporting of race/ethnicity data in randomized controlled trials (RCTs) of attention-deficit/hyperactivity disorder (ADHD) medications. Secondary objectives were to estimate temporal trends in the reporting, and to compare the pooled prevalence of racial/ethnic groups in RCTs conducted in the US to national estimates., Method: We drew on, adapted, and updated the search of a network meta-analysis by Cortese et al. (2018) up to March 2022. We calculated the percentage of RCTs reporting data on race/ethnicity of participants in the published article or in related unpublished material. Temporal trends were estimated with logistic regression. The pooled prevalence of each racial/ethnic group across US RCTs was calculated using random-effects model meta-analyses., Results: We retained 310 RCTs (including 44,447 participants), of which 231 were conducted in children/adolescents, 78 in adults, and 1 in both. Data on race/ethnicity were reported in 59.3% of the RCTs (75% of which were conducted in children/adolescents and 25% in adults) in the published article, and in unpublished material in an additional 8.7% of the RCTs. Reporting improved over time. In the US RCTs, Asian and White individuals were under- and overrepresented, respectively, compared to national estimates in the most recent time period considered., Conclusion: More than 30% of the RCTs of ADHD medications retained in this review did not include data on race/ethnicity in their published or unpublished reports, and more than 40% in their published articles, even though reporting improved over time. Results should inform investigators, authors, editors, regulators, and study participants in relation to efforts to tackle inequalities in ADHD research., Plain Language Summary: A systematic review of 310 randomized controlled trials for attention-deficit/hyperactivity disorder (ADHD) medications found that race/ethnicity were reported in only 30% of trials. Compared to national estimates, Asian individuals were underrepresented and non-Hispanic Whites individuals were overrepresented, drawing attention to the inequities in participation in ADHD research., Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work., Study Preregistration Information: Reporting and representation of race/ethnicity in double blind randomised controlled trials of medications for ADHD; https://osf.io/; hfgz8., (Copyright © 2024. Published by Elsevier Inc.)

Background: Policy initiatives have attempted to reduce healthcare inequalities in the USA, but evidence on whether these initiatives have reduced racial and ethnic disparities in pain treatment in primary care is lacking., Objective: To determine whether racial and ethnic disparities in medication prescribed for pain in primary care settings have diminished over a 21-year period from 1999 to 2019., Design: An annual, representative cross-sectional probability sample of visits to US primary care physicians, taken from the National Ambulatory Medical Care Survey., Patients: Pain-related visits to primary care physicians., Main Measures: Prescriptions for opioid and non-opioid analgesics., Key Results: Of 599,293 (16%) sampled visits, 94,422 were pain-related, representing a population-weighted estimate of 143 million visits made annually to primary care physicians for pain. Relative risk analysis controlling for insurance, pain type, and other potential confounds showed no difference in pain medication prescribed between Black and White patients (p = .121). However, White patients were 1.61 (95% CI 1.32-1.97) and Black patients 1.57 (95% CI 1.26-1.95) times more likely to be prescribed opioids than a more underrepresented group consisting of Asian, Native-Hawaiian/Pacific-Islander, and American-Indian/Alaska-Natives (ps < .001). Non-Hispanic/Latino patients were 1.32 (95% CI 1.18-1.45) times more likely to receive opioids for pain than Hispanic/Latino patients (p < .001). Penalized cubic spline regression found no substantive narrowing of disparities over time., Conclusions: These findings suggest that additional intervention strategies, or better implementation of existing strategies, are needed to eliminate ethnic and racial disparities in pain treatment towards the goal of equitable healthcare., (© 2024. The Author(s).)

Preterm birth (PTB) is the leading cause of morbidity and mortality in children globally, yet its prevalence has been difficult to accurately estimate due to unreliable methods of gestational age dating, heterogeneity in counting, and insufficient data. The estimated global PTB rate in 2020 was 9.9% (95% confidence interval: 9.1, 11.2), which reflects no significant change from 2010, and 81% of prematurity-related deaths occurred in Africa and Asia. PTB prevalence in the United States in 2021 was 10.5%, yet with concerning racial disparities. Few effective solutions for prematurity prevention have been identified, highlighting the importance of further research., Competing Interests: Disclosure The authors have no disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Four sphingosine 1-phosphate (S1P) receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are approved by the US Food and Drug Administration for the treatment of multiple sclerosis. This review summarizes efficacy and safety data on these S1P receptor modulators, with an emphasis on similarities and differences. Efficacy data from the pivotal clinical trials are generally similar for the four agents. However, because no head-to-head clinical studies were conducted, direct efficacy comparisons cannot be made. Based on the adverse event profile of S1P receptor modulators, continued and regular monitoring of patients during treatment will be instructive. Notably, the authors recommend paying attention to the cardiac monitoring guidelines for these drugs, and when indicated screening for macular edema and cutaneous malignancies before starting treatment. To obtain the best outcome, clinicians should choose the drug based on disease type, history, and concomitant medications for each patient. Real-world data should help to determine whether there are meaningful differences in efficacy or side effects between these agents., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR., Methods: This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard., Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β 2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%., Conclusion: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research., (© 2023 American College of Rheumatology.)

Objectives: To investigate scientific collaboration and citation metrics of reporting guidelines for health research., Study Design and Setting: A cross-sectional analysis of published articles of reporting guidelines for health research. A search of the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network Library (from inception to January 21, 2021) was supplemented by searching websites of guideline developers. For each article, metadata (e.g., authors, institutions, countries, citations) were extracted from the Web of Science and Scopus (up to October 25, 2021). Descriptive analyses were conducted. Network analyses of collaborations were presented., Results: We included 662 articles published in 332 journals. The BMJ (n = 50 articles; 8%), Annals of Internal Medicine (n = 29; 4%), and Journal of Clinical Epidemiology (n = 24; 4%) published the largest number of articles. Four thousand seven hundred twenty two authors, 1,647 institutions, and 83 countries were involved. The global productivity was led by the United States (n = 456 articles), the United Kingdom (n = 414), and Canada (n = 306). We found eight clusters of authors (e.g., one major group with 337 members) and three clusters of institutions (e.g., one major group with 256 members). The most prolific authors were affiliated with the Ottawa Hospital Research Institute (Canada), the University of Ottawa (Canada), the University of Oxford (the United Kingdom), and Stanford University (the United States)., Conclusion: Our analysis identified key actors producing reporting guidelines, most intense collaborations, and 'citation classics' in the field. These results could potentially be used to strengthen collaborations for developing and disseminating reporting guidelines for health research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The challenges of conducting hyperacute stroke research and obtaining informed consent have been increasingly recognized within the stroke research community in recent years. Deferral of consent, in which a patient is enrolled in a trial and then provides consent at some point thereafter, is increasingly used to enroll patients into hyperacute stroke trials in Canada and Europe, although it is not permitted in the United States. Deferral of consent offers several potential advantages-quicker door-to-randomization, increased enrolment, decreased selection bias-but these must be balanced against the risk of enrolling patients against their wishes. We seek to minimize the attendant risks of deferral of consent by offering practical guidance regarding how to conduct acute stroke trials using deferral of consent. Building on existing guidelines and recent experiences with deferral of consent in acute stroke trials, we have developed a protocol for the use of deferral of consent that aims to maximize patient involvement while minimizing ethical and scientific risks., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Children today are conceived and live in a sea of wireless radiation that did not exist when their parents were born. The launch of the digital age continues to transform the capacity to respond to emergencies and extend global communications. At the same time that this increasingly ubiquitous technology continues to alter the nature of commerce, medicine, transport and modern life overall, its varied and changing forms have not been evaluated for their biological or environmental impacts. Standards for evaluating radiation from numerous wireless devices were first set in 1996 to avoid heating tissue and remain unchanged since then in the U.S. and many other nations. A wide range of evidence indicates that there are numerous non-thermal effects from wireless radiation on reproduction, development, and chronic illness. Many widely used devices such as phones and tablets function as two-way microwave radios, sending and receiving various frequencies of information-carrying microwave radiation on multiple simultaneously operating antennas. Expert groups advising governments on this matter do not agree on the best approaches to be taken. The American Academy of Pediatrics recommends limited screen time for children under the age of two, but more than half of all toddlers regularly have contact with screens, often without parental engagement. Young children of parents who frequently use devices as a form of childcare can experience delays in speech acquisition and bonding, while older children report feelings of disappointment due to 'technoference'-parental distraction due to technology. Children who begin using devices early in life can become socially, psychologically and physically addicted to the technology and experience withdrawal upon cessation. We review relevant experimental, epidemiological and clinical evidence on biological and other impacts of currently used wireless technology, including advice to include key questions at pediatric wellness checkups from infancy to young adulthood. We conclude that consistent with advice in pediatric radiology, an approach that recommends that microwave radiation exposures be As Low As Reasonably Achievable (ALARA) seems sensible and prudent, and that an independently-funded training, research and monitoring program should be carried out on the long term physical and psychological impacts of rapidly changing technological milieu, including ways to mitigate impacts through modifications in hardware and software. Current knowledge of electrohypersensitivity indicates the importance of reducing wireless exposures especially in schools and health care settings., (Copyright © 2023. Published by Elsevier Inc.)

Background: Non-specific low back pain (LBP) commonly presents to primary care, where inappropriate use of imaging remains common despite guideline recommendations against its routine use. Little is known about strategies to enhance intervention fidelity (i.e., whether interventions were implemented as intended) for interventions developed to reduce non-indicated imaging for LBP., Objectives: We aim to inform the development of an intervention to reduce non-indicated imaging among general practitioners (GPs) and chiropractors in Newfoundland and Labrador (NL), Canada. The study objectives are: [1] To explore perceived barriers and enablers to enhancing fidelity of training of GPs and chiropractors to deliver a proposed intervention to reduce non-indicated imaging for LBP and [2] To explore perceived barriers and enablers to enhancing fidelity of delivery of the proposed intervention., Methods: An exploratory, qualitative study was conducted with GPs and chiropractors in NL. The interview guide was informed by the National Institutes of Health Behavior Change Consortium fidelity checklist; data analysis was guided by the Theoretical Domains Framework (TDF). Participant quotes were coded into TDF domains, belief statements were generated at each domain, and domains relevant to enhancing fidelity of provider training or intervention delivery were identified., Results: The study included five GPs and five chiropractors from urban and rural settings. Barriers and enablers to enhancing fidelity to provider training related to seven TDF domains: [1] Beliefs about capabilities, [2] Optimism, [3] Reinforcement, [4] Memory, attention, and decision processes, [5] Environmental context and resources, [6] Emotion, and [7] Behavioural regulation. Barriers and enablers to enhancing fidelity to intervention delivery related to seven TDF domains: [1] Beliefs about capabilities, [2] Optimism, [3] Goals, [4] Memory, attention, and decision processes, [5] Environmental context and resources, [6] Social influences, and [7] Behavioural regulation., Conclusion: The largest perceived barrier to attending training was time; perceived enablers were incentives and flexible training. Patient pressure, time, and established habits were perceived barriers to delivering the intervention as intended. Participants suggested enhancement strategies to improve their ability to deliver the intervention as intended, including reminders and check-ins with researchers. Most participants perceived intervention fidelity as important. These results may aid in the development of a more feasible and pragmatic intervention to reduce non-indicated imaging for GPs and chiropractors in NL., (© 2023. The Author(s).)

Background: Age-related complex medical conditions have been commonly reported among adolescents and young adults with advanced life-limiting illness. There is increasing interest in exploring their palliative care needs and end-of-life experiences., Aim: This scoping review aimed to explore the available literature about providing palliative and end-of-life care to adolescents and young adults with advanced life-limiting illnesses., Design: Scoping review. This review was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/SPTD7)., Data Sources: Electronic databases (MEDLINEALL, Embase, Emcare, Cochrane Central Register of Controlled Trial CENTRAL, Scopus, PsycINFO, Cochrane Database of Systematic Reviews), Google Scholar and reference lists were searched up to October 2021. We included studies reporting on adolescents and/or young adults with advanced life-limiting illnesses. There were no limitations concerning location, type of illness or study design., Results: We identified 51 studies published between 2002 and 2021. Most studies were published in the United States ( n  = 34, 67%), and nine studies (18%) reported exclusively on patients with non-malignant illnesses. Two thirds of the identified studies were case reports and retrospective chart reviews ( n  = 33). Three main topics were identified: Physical symptom burden ( n  = 26, 51%), Psychological and social needs ( n  = 33, 65%), and end-of-life care ( n  = 30, 59%). Twenty-six studies (51%) were focused only on one topic, and the age range used to identify adolescents and young adults varied based on the study location., Conclusion: The findings of this review shed light on the different palliative care experiences and knowledge gaps related to adolescents and young adults as an underserved and vulnerable patient population. Further research needs to be dedicated toward palliative care programs tailored for adolescents and young adults.

Background: Premature and sick neonates may require weeks of hospitalization in a noisy neonatal intensive care unit (NICU) environment with sound levels that may reach 120 decibels. The American Academy of Pediatrics recommends a maximum sound level of 45 decibels., Purpose: To measure sound levels in a level III NICU and to describe contributing environmental factors., Methods: Descriptive quantitative study. Sound levels were measured using a portable sound meter in an open-bay level III NICU. Contributing environmental factors were recorded and analyzed., Results: Mean sound levels for day, evening, and night shifts were 83.5, 83, and 80.9 decibels, respectively. Each period of time exceeded the recommended guidelines 90% of the time and was almost double the American Academy of Pediatrics' recommendation. Multiple linear regression findings demonstrated significant factors associated with elevated sound levels including number of neonates, number of people, number of alarms, acuity level, and shift type. Observational data explain 14.5% of elevated sound levels., Implications for Practice: An understanding of baseline sound levels and contributing environmental factors is the first step in developing strategies to mitigate excessive noise in the NICU., Implications for Research: Research should focus on effective and sustainable ways to reduce sound levels in the NICU, including inside the isolette, in order to provide an environment that is conducive to optimal growth and neurodevelopment for preterm and sick infants., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the National Association of Neonatal Nurses.)

Background: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19., Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines., Results: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk., Conclusions: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19-related critical illness., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines from the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation in patients with COVID-19., Methods: ASH formed a multidisciplinary guideline panel that included patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process and performed systematic evidence reviews (through November 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 as part of the living phase of these guidelines., Results: The panel made one additional recommendation. The panel issued a conditional recommendation in favor of therapeutic-intensity over prophylactic-intensity anticoagulation in patients with COVID-19-related acute illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of risk of thrombosis and bleeding. The panel also noted that heparin (unfractionated or low molecular weight) may be preferred because of a preponderance of evidence with this class of anticoagulants., Conclusion: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation in patients with COVID-19-related acute illness., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We established a split nanoluciferase complementation assay to rapidly screen for inhibitors that interfere with binding of the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein with its target receptor, angiotensin-converting enzyme 2 (ACE2). After a screen of 1,200 US Food and Drug Administration (FDA)-approved compounds, we identified bifonazole, an imidazole-based antifungal agent, as a competitive inhibitor of RBD-ACE2 binding. Mechanistically, bifonazole binds ACE2 around residue K353, which prevents association with the RBD, affecting entry and replication of spike-pseudotyped viruses as well as native SARS-CoV-2 and its variants of concern (VOCs). Intranasal administration of bifonazole reduces lethality in K18-hACE2 mice challenged with vesicular stomatitis virus (VSV)-spike by 40%, with a similar benefit after live SARS-CoV-2 challenge. Our screen identified an antiviral agent that is effective against SARS-CoV-2 and VOCs such as Omicron that employ the same receptor to infect cells and therefore has high potential to be repurposed to control, treat, or prevent coronavirus disease 2019 (COVID-19)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Context is recognized as important to successful knowledge translation (KT) in health settings. What is meant by context, however, is poorly understood. The purpose of the current study was to elicit tacit knowledge about what is perceived to constitute context by conducting interviews with a variety of health system stakeholders internationally so as to compile a comprehensive list of contextual attributes and their features relevant to KT in healthcare., Methods: A descriptive qualitative study design was used. Semi-structured interviews were conducted with health system stakeholders (change agents/KT specialists and KT researchers) in four countries: Australia, Canada, the United Kingdom, and the United States. Interview transcripts were analyzed using inductive thematic content analysis in four steps: (1) selection of utterances describing context, (2) coding of features of context, (3) categorizing of features into attributes of context, (4) comparison of attributes and features by: country, KT experience, and role., Results: A total of 39 interviews were conducted. We identified 66 unique features of context, categorized into 16 attributes. One attribute, Facility Characteristics, was not represented in previously published KT frameworks. We found instances of all 16 attributes in the interviews irrespective of country, level of experience with KT, and primary role (change agent/KT specialist vs. KT researcher), revealing robustness and transferability of the attributes identified. We also identified 30 new context features (across 13 of the 16 attributes)., Conclusion: The findings from this study represent an important advancement in the KT field; we provide much needed conceptual clarity in context, which is essential to the development of common assessment tools to measure context to determine which context attributes and features are more or less important in different contexts for improving KT success., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: Hysterectomy is a common gynaecological procedure, and therefore online information is highly valuable to patients. Our objective was to evaluate the quality, readability, and comprehensiveness of online patient information on hysterectomy., Methods: The first 25 patient-directed websites on hysterectomy, identified using 5 online search engines (Google, Yahoo, AOL, Bing, Ask.com) as well as clinical professional societies, were assessed using validated tools for quality (DISCERN, JAMA benchmark), readability (Flesch-Kincaid Grade Level [FKGL], Gunning Fog, Simple Measure of Gobbledygook [SMOG], Flesch Reading Ease Score [FRES]), and completeness of information., Results: We identified 50 websites for inclusion. Overall, websites were of good quality (median DISCERN score 53/80 [interquartile range {IQR} 47-61]; median JAMA score 3/4 [IQR 1-4]). Most websites described surgical risks (39, 78%), benefits (45, 90%), and types of hysterectomy (48, 96%). Content readability corresponded to grade 11 using FKGL (median 11.1 [IQR 10.2-13.0]) and SMOG (median 10.9 [IQR 10.2-12.4]), or 15 years education using Gunning Fog (median 14.7 [IQR 13.8-16.4]). Websites were assessed as difficult to read using FRES (median 45.6/100 [IQR 37.9-50.9]). No differences were observed in readability scores when we compared websites from clinical professional societies, government, health care, or academic organizations with other websites (P > 0.05)., Conclusion: Online patient information on hysterectomy is of good quality and comprehensive. However, the content is above the American Medical Association's recommended grade 6 reading level. Website authors should consider readability to make their content more accessible to patients., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

The staging and surveillance of testicular cancer is a complex topic, which integrates clinical, biochemical, and imaging components. The use of imaging for staging and surveillance of testicular cancer is individually tailored to each patient by considering tumor histology and prognosis. This document discusses the rationale for use of imaging by imaging modality during the initial staging of testicular seminoma and nonseminoma tumors and during the planned surveillance of stage IA and IB testicular cancer by histological subtype integrating clinical suspicion for disease recurrence in surveillance protocols. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2022 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Modern health surveillance and planning requires an understanding of how preventable risk factors impact population health, and how these effects vary between populations. In this study, we compare how smoking, alcohol consumption, diet and physical activity are associated with all-cause mortality in Canada and the United States using comparable individual-level, linked population health survey data and identical model specifications., Methods: The Canadian Community Health Survey (CCHS) (2003-2007) and the United States National Health Interview Survey (NHIS) (2000, 2005) linked to individual-level mortality outcomes with follow up to December 31, 2011 were used. Consistent variable definitions were used to estimate country-specific mortality hazard ratios with sex-specific Cox proportional hazard models, including smoking, alcohol, diet and physical activity, sociodemographic indicators and proximal factors including disease history., Results: A total of 296,407 respondents and 1,813,884 million person-years of follow-up from the CCHS and 58,232 respondents and 497,909 person-years from the NHIS were included. Absolute mortality risk among those with a 'healthy profile' was higher in the United States compared to Canada, especially among women. Adjusted mortality hazard ratios associated with health behaviours were generally of similar magnitude and direction but often stronger in Canada., Conclusion: Even when methodological and population differences are minimal, the association of health behaviours and mortality can vary across populations. It is therefore important to be cautious of between-study variation when aggregating relative effect estimates from differing populations, and when using external effect estimates for population health research and policy development., (© 2022. The Author(s).)

Objective: We sought to map the landscape of trials investigating hydroxychloroquine (HCQ) for SARS-CoV-2 in order to draw conclusions about how clinical trials have been conducted in the pandemic environment and offer potential regulatory recommendations., Study Design and Setting: We identified and captured data related to registered studies using HCQ to treat SARS-CoV-2 registered with the publicly available National Institutes of Health (NIH) Clinical Trials Registry between February and November 2020., Results: Between February and November 2020, 206 studies investigating HCQ in SARS-CoV-2 were registered with the NIH Clinical Trials Registry. As of November 2020, 135 studies were listed as ongoing, 22 have been completed, and 46 are either suspended or have been terminated. Reasons for suspension or termination included difficulties with patient recruitment (n = 9), emerging evidence showing a lack of benefit of HCQ (n = 7), and recommendations by regulatory boards to discontinue (n = 10)., Conclusion: Many clinical trials of HCQ were launched in the first months of the pandemic, and a significant proportion of them remained active as of November 2020. The medical community appears to have responded very quickly to political interest in HCQ, while responding much more slowly to the evolving medical evidence of its lack of efficacy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: COVID-19-related acute illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19 who do not have confirmed or suspected VTE., Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the grading of recommendations assessment, development, and evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment., Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation against the use of outpatient anticoagulant prophylaxis in patients with COVID-19 who are discharged from the hospital and who do not have suspected or confirmed VTE or another indication for anticoagulation., Conclusions: This recommendation was based on very low certainty in the evidence, underscoring the need for high-quality randomized controlled trials assessing the role of postdischarge thromboprophylaxis. Other key research priorities include better evidence on assessing risk of thrombosis and bleeding outcomes in patients with COVID-19 after hospital discharge., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Alongside the growing concerns regarding predatory journal growth, other questionable editorial practices have gained visibility recently. Among them, we explored the usefulness of the Percentage of Papers by the Most Prolific author (PPMP) and the Gini index (level of inequality in the distribution of authorship among authors) as tools to identify journals that may show favoritism in accepting articles by specific authors. We examined whether the PPMP, complemented by the Gini index, could be useful for identifying cases of potential editorial bias, using all articles in a sample of 5,468 biomedical journals indexed in the National Library of Medicine. For articles published between 2015 and 2019, the median PPMP was 2.9%, and 5% of journal exhibited a PPMP of 10.6% or more. Among the journals with the highest PPMP or Gini index values, where a few authors were responsible for a disproportionate number of publications, a random sample was manually examined, revealing that the most prolific author was part of the editorial board in 60 cases (61%). The papers by the most prolific authors were more likely to be accepted for publication within 3 weeks of their submission. Results of analysis on a subset of articles, excluding nonresearch articles, were consistent with those of the principal analysis. In most journals, publications are distributed across a large number of authors. Our results reveal a subset of journals where a few authors, often members of the editorial board, were responsible for a disproportionate number of publications. To enhance trust in their practices, journals need to be transparent about their editorial and peer review practices., Competing Interests: The authors have declared that no competing interests exist.

The antimicrobial medication malarone (atovaquone/proguanil) is used as a fixed-dose combination for treating children and adults with uncomplicated malaria or as chemoprophylaxis for preventing malaria in travelers. It is an inexpensive, efficacious, and safe drug frequently prescribed around the world. Following anecdotal evidence from 17 patients in the provinces of Quebec and Ontario, Canada, suggesting that malarone/atovaquone may present some benefits in protecting against COVID-19, we sought to examine its antiviral potential in limiting the replication of SARS-CoV-2 in cellular models of infection. In VeroE6 expressing human TMPRSS2 and human lung Calu-3 epithelial cells, we show that the active compound atovaquone at micromolar concentrations potently inhibits the replication of SARS-CoV-2 and other variants of concern including the alpha, beta, and delta variants. Importantly, atovaquone retained its full antiviral activity in a primary human airway epithelium cell culture model. Mechanistically, we demonstrate that the atovaquone antiviral activity against SARS-CoV-2 is partially dependent on the expression of TMPRSS2 and that the drug can disrupt the interaction of the spike protein with the viral receptor, ACE2. Additionally, spike-mediated membrane fusion was also reduced in the presence of atovaquone. In the United States, two clinical trials of atovaquone administered alone or in combination with azithromycin were initiated in 2020. While we await the results of these trials, our findings in cellular infection models demonstrate that atovaquone is a potent antiviral FDA-approved drug against SARS-CoV-2 and other variants of concern in vitro.

Cerebrovascular disease is a broad topic. This document focuses on the imaging recommendations for the varied clinical scenarios involving intracranial aneurysms, vascular malformations, and vasculitis, which all carry high risk of morbidity and mortality. Additional imaging recommendations regarding complications of these conditions, including subarachnoid hemorrhage and vasospasm, are also covered. While each variant presentation has unique imaging recommendations, the major focus of this document is neurovascular imaging techniques. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2021 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: Intravenous immune globulin (IVIG) may improve survival in people with septic shock. Current utilization patterns of IVIG are unknown. We sought to characterize adult patients with septic shock requiring vasopressors who received IVIG, describes IVIG regimens, and evaluate determinants of IVIG use in patients with septic shock., Methods: We conducted a retrospective database study of adult patients with septic shock admitted to US hospitals in the Premier Healthcare Database (from July 2010 to June 2013). We described the proportion of patients with septic shock receiving IVIG, examined IVIG regimens across sites and employed random-effects multivariable regression techniques to identify predictors of IVIG use., Results: Intravenous immune globulin was administered to 0.3% (n = 685) of patients with septic shock; with a median [interquartile range (IQR)] dose of 1 [0.5-1.8] g·kg -1 for a median [IQR] of 1 [1-2] day. Receipt of IVIG was less likely for Black patients (odds ratio [OR], 0.54; 95% confidence interval [CI] 0.41 to 0.72) and patients without private insurance (Medicare OR, 0.73; 95% CI 0.59 to 0.90; Medicaid OR, 0.41; 95% CI 0.30 to 0.57) and more likely for patients with immunocompromise (OR, 6.83; 95% CI 5.47 to 8.53), necrotizing fasciitis (OR, 9.78; 95% CI 6.97 to 13.72), and toxic shock (OR, 56.9; 95% CI 38.7 to 83.7)., Conclusions: Intravenous immune globulin is used infrequently across the US in patients with septic shock. Regimens of IVIG in septic shock may be less intensive than those associated with a survival benefit in meta-analyses. Observed infrequent use supports apparent clinical equipoise, perhaps secondary to limitations of the primary literature. A clinical trial evaluating the role of IVIG in septic shock is needed., (© 2021. Canadian Anesthesiologists' Society.)

Importance: Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials., Objective: To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period., Design: We performed post hoc descriptive analyses of data from five trials conducted under EFIC., Setting: Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada., Participants: Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury., Exposures: Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study's enrollment period., Outcomes: TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification., Results: Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew., Conclusions and Relevance: There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care., (© 2021. The Author(s).)

Background: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE)., Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE., Methods: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process by performing systematic evidence reviews (up to 5 March 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021., Results: The panel agreed on 1 additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE., Conclusions: This recommendation was based on low certainty in the evidence, which underscores the need for additional high-quality, randomized, controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence regarding predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of nonanticoagulant therapies (eg, antiviral agents, corticosteroids) on thrombotic risk., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: It is unknown how frequently damage control (DC) laparotomy is used across trauma centers in different countries. We conducted a cross-sectional survey of trauma centers in the United States, Canada, and Australasia to study variations in use of the procedure and predictors of more frequent use of DC laparotomy., Methods: A self-administered, electronic, cross-sectional survey of trauma centers in the United States, Canada, and Australasia was conducted. The survey collected information about trauma center and program characteristics. It also asked how often the trauma program director estimated DC laparotomy was performed on injured patients at that center on average over the last year. Multivariable logistic regression was used to identify predictors of a higher reported frequency of use of DC laparotomy., Results: Of the 366 potentially eligible trauma centers sent the survey, 199 (51.8%) trauma program directors or leaders responded [United States = 156 (78.4%), Canada = 26 (13.1%), and Australasia = 17 (8.5%)]. The reported frequency of use of DC laparotomy was highly variable across trauma centers. DC laparotomy was used more frequently in level-1 than level-2 or -3 trauma centers. Further, high-volume level-1 centers used DC laparotomy significantly more often than lower volume level-1 centers (p = 0.02). Nearly half (48.4%) of high-volume volume level-1 trauma centers reported using the procedure at least once weekly. Significant adjusted predictors of more frequent use of DC laparotomy included country of origin [odds ratio (OR) for the United States vs. Canada = 7.49; 95% confidence interval (CI) 1.39-40.27], level-1 verification status (OR = 6.02; 95% CI 2.01-18.06), and the assessment of a higher number of severely injured (Injury Severity Scale score > 15) patients (OR per-100 patients = 1.62; 95% CI 1.20-2.18) and patients with penetrating injuries (OR per-5% increase = 1.27; 95% CI 1.01-1.58) in the last year., Conclusions: The reported frequency of use of DC laparotomy was highly variable across trauma centers. Those centers that most need to evaluate the benefit-to-risk ratio of using DC laparotomy in different scenarios may include high-volume, level-1 trauma centers, particularly those that often manage penetrating injuries., (© 2021. The Author(s).)

Importance: Several studies have estimated the financial inputs for successful drug development. Such analyses do not capture the large investment that patient study participants commit to drug development., Objective: To estimate the volume of patients required to achieve a first US Food and Drug Administration (FDA) approval for a new anticancer drug or biologic therapy., Design, Setting, and Participants: This cohort study included a random sample of prelicense oncology drugs and biologics with a trial site in the United States that were launched into clinical efficacy testing between January 1, 2006, and December 31, 2010. Drugs and biologics were identified using ClinicalTrials.gov registration records. Total patient enrollment was captured over an 8-year span, and each intervention was classified based on whether it received FDA approval and was deemed as having intermediate or substantial value according to the American Society of Clinical Oncology Value Framework (ASCO-VF) score. Secondarily, the association between patient numbers and intervention characteristics was tested. Data were analyzed in February 2020., Main Outcomes and Measure: The prespecified primary outcome was the number of patients enrolled in prelicense trials per FDA approval., Results: A total of 120 drugs and biologics were included in our study, with 84 (70.0%) targeted agents, 20 (16.7%) immunotherapies, and 71 (59.2%) novel agents. A total of 13 drugs and biologics (10.8%; 95% CI, 5.3%-16.8%) in our sample gained FDA approval within 8 years, of which 1 (7.7%) was deemed of intermediate value and 3 (23.1%) were deemed of substantial value using ASCO-VF scoring. Overall, 158 810 patients were enrolled in 1335 trials testing these drugs and biologics, 47 913 (30.2%) in trials that led to FDA approval and 110 897 (69.8%) in trials that did not. An estimated 12 217 (95% CI, 7970-22 215) patient study participants contributed to prelicense trials per FDA approval. The estimated number of patients needed to produce a single FDA-approved drug or biologic of intermediate or substantial ASCO-VF clinical value was 39 703 (95% CI, 19 391-177 991)., Conclusions and Relevance: The results of this cohort study make visible the substantial patient investment required for prelicense oncology drug development. Such analyses can be used to devise policies that maximize the clinical impact of research on a per-patient basis.

Head trauma (ie, head injury) is a significant public health concern and is a leading cause of morbidity and mortality in children and young adults. Neuroimaging plays an important role in the management of head and brain injury, which can be separated into acute (0-7 days), subacute (<3 months), then chronic (>3 months) phases. Over 75% of acute head trauma is classified as mild, of which over 75% have a normal Glasgow Coma Scale score of 15, therefore clinical practice guidelines universally recommend selective CT scanning in this patient population, which is often based on clinical decision rules. While CT is considered the first-line imaging modality for suspected intracranial injury, MRI is useful when there are persistent neurologic deficits that remain unexplained after CT, especially in the subacute or chronic phase. Regardless of time frame, head trauma with suspected vascular injury or suspected cerebrospinal fluid leak should also be evaluated with CT angiography or thin-section CT imaging of the skull base, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Published by Elsevier Inc.)

Objectives: The objective of the study was to assess the impact of narrative review (NR) vs. systematic review (SR) on expert assessments of a clinical trial., Study Design and Setting: Experts in colon and rectal surgery were randomized to read an NR or SR for an ongoing clinical trial involving surgery for colorectal cancer. Experts from the United States and Canada completed online or paper surveys between December 2018 and June 2019. After reading the NR or SR, experts predicted the trial's outcome and evaluated the trial under a hypothetical ethical review., Results: Experts who read the NR (n = 55) compared with those who read the SR (n = 56) were more likely to predict a higher absolute risk reduction, 58% vs. 33%, P = 0.018, mean predictions 10.6% vs. 6.6%, mean difference 4.0% [95% confidence interval: 0.3%, 7.8%]. Experts who read the NR were more likely to evaluate the trial more favorably under a hypothetical ethical review, 48% vs. 26%, P = 0.039, 20.0% vs. 8.9% "strongly in favor" of trial being pursued., Conclusion: An NR and an SR for the same trial led to different judgments of likely outcomes and ethical appropriateness. These differences point to a potential source of unaddressed bias in ethical review., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Venous thromboembolism (VTE) is a common complication among patients with cancer. Patients with cancer and VTE are at a markedly increased risk for morbidity and mortality., Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the prevention and treatment of VTE in patients with cancer., Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The guideline development process was supported by updated or new systematic evidence reviews. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence and make recommendations., Results: Recommendations address mechanical and pharmacological prophylaxis in hospitalized medical patients with cancer, those undergoing a surgical procedure, and ambulatory patients receiving cancer chemotherapy. The recommendations also address the use of anticoagulation for the initial, short-term, and long-term treatment of VTE in patients with cancer., Conclusions: Strong recommendations include not using thromboprophylaxis in ambulatory patients receiving cancer chemotherapy at low risk of VTE and to use low-molecular-weight heparin (LMWH) for initial treatment of VTE in patients with cancer. Conditional recommendations include using thromboprophylaxis in hospitalized medical patients with cancer, LMWH or fondaparinux for surgical patients with cancer, LMWH or direct oral anticoagulants (DOAC) in ambulatory patients with cancer receiving systemic therapy at high risk of VTE and LMWH or DOAC for initial treatment of VTE, DOAC for the short-term treatment of VTE, and LMWH or DOAC for the long-term treatment of VTE in patients with cancer., (© 2021 by The American Society of Hematology.)

Purpose: Choosing Wisely (CW)® was created by the American Board of Internal Medicine (ABIM) to promote patient-physician conversations about unnecessary medical interventions. Similarly, other countries created their own panels of experts called "CW® campaigns" which review recommendations submitted by that country's oncology societies. We performed a scoping review to consolidate CW® recommendations from different groups with respect to breast cancer care., Methods: A systematic search of Medline and Embase was designed by an information specialist for publications presenting CW® recommendations for breast cancer care practices from 2011-2020. We also reviewed the websites of all CW® campaigns and reference sections of each CW® recommendation. Two reviewers independently screened studies for inclusion and performed data extraction. Findings were summarized narratively., Results: Review of ABIM CW® recommendations showed 19 breast cancer-related recommendations pertaining to; screening (n = 4), radiological staging (n = 2), treatment (n = 10), surveillance (n = 2), and miscellaneous (genetic testing; n = 1). Of 22 countries with CW® campaigns, 10 published recommendations for breast cancer. Over half (57%) of recommendations were supported by more than one country. No recommendations were refuted between campaigns. Two campaigns developed 3 novel recommendations on new topics, including chemotherapy in ductal carcinoma in situ (Italy) and comparison of screening imaging modalities (Portugal)., Conclusions: CW® recommendations focus on reducing overutilization of investigations and treatments. There was a high rate of consensus between different CW® campaigns. As health care systems globally move attention to reduce low-value care, further studies are required to address adherence to these current recommendations and develop new recommendations.

Background: Acute kidney injury (AKI) is a key risk factor for chronic kidney disease in the general population, but has not been investigated in detail among renal transplant recipients (RTRs). We investigated the incidence, severity and risk factors for AKI following cardiac surgery among RTRs compared with non-RTRs with otherwise similar clinical characteristics., Methods: We conducted a retrospective cohort study of RTRs (n = 83) and non-RTRs (n = 83) who underwent cardiac surgery at two major academic medical centers. Non-RTRs were matched 1:1 to RTRs by age, preoperative (preop) estimated glomerular filtration rate and type of cardiac surgery. We defined AKI according to Kidney Disease: Improving Global Outcomes criteria., Results: RTRs had a higher rate of AKI following cardiac surgery compared with non-RTRs [46% versus 28%; adjusted odds ratio 2.77 (95% confidence interval 1.36-5.64)]. Among RTRs, deceased donor (DD) versus living donor (LD) status, as well as higher versus lower preop calcineurin inhibitor (CNI) trough levels, were associated with higher rates of AKI (57% versus 33% among DD-RTRs versus LD-RTRs; P = 0.047; 73% versus 36% among RTRs with higher versus lower CNI trough levels, P = 0.02). The combination of both risk factors (DD status and higher CNI trough level) had an additive effect (88% AKI incidence among patients with both risk factors versus 25% incidence among RTRs with neither risk factor, P = 0.004)., Conclusions: RTRs have a higher risk of AKI following cardiac surgery compared with non-RTRs with otherwise similar characteristics. Among RTRs, DD-RTRs and those with higher preop CNI trough levels are at the highest risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Decision aids are patient-focused tools that have the potential to reduce the overuse of head computed tomography (CT) scans., Objective: The objective of this study was to create a consensus among Canadian mild traumatic brain injury and emergency medicine experts on modifications required to adapt two American decision aids about head CT use for adult and paediatric mild traumatic brain injury to the Canadian context., Methods: We invited 21 Canadian stakeholders and the two authors of the American decision aids to a Nominal Group Technique consensus meeting to generate suggestions for adapting the decision aids. This method encourages idea generation and sharing between team members. Each idea was discussed and then prioritised using a voting system. We collected data using videotaping, writing material and online collaborative writing tools. The modifications proposed were analysed using a qualitative thematic content analysis., Results: Twenty-one participants took part in the meeting, including researchers and clinician researchers (n = 9; 43%), patient partners (n = 3; 14%) and decision makers (n = 2; 10%). A total of 84 ideas were generated. Participants highlighted the need to clarify the purpose of the decision aids, the nature of the problem being addressed and the target population. The tools require sociocultural adaptations, better identification of their target population, better description of head CT utility, advantages and related risks, modification of the visual and written representation of the risk of brain injury and head CT use, and locally adapted, patient follow-up plans., Conclusions: This study based on a Nominal Group Technique identified several adaptations for two American decision aids about head CT use for mild traumatic brain injury to support their use in Canada's different healthcare, social, cultural and legal context. These adaptations concerned the target users of the decision aids, the information presented, and how the benefits and risks were communicated in the decision aids. Future steps include prototyping the two adapted decision aids, conducting formative evaluations with actual emergency department patients and clinicians, and measuring the impact of the adapted tools on CT scan use.

Background: Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood., Aims: To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19., Sources: We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection., Content: Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4-6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6-18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3-9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3-13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%)., Implications: Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Critical drug shortages have been widely documented during the coronavirus disease 2019 (COVID-19) pandemic, particularly for IV sedatives used to facilitate mechanical ventilation. Surges in volume of patients requiring mechanical ventilation coupled with prolonged ventilator days and the high sedative dosing requirements observed quickly led to the depletion of "just-in-time" inventories typically maintained by institutions. This manuscript describes drug shortages in the context of global, manufacturing, regional and institutional perspectives in times of a worldwide crisis such as a pandemic. We describe etiologic factors that lead to drug shortages including issues related to supply (eg, manufacturing difficulties, supply chain breakdowns) and variables that influence demand (eg, volatile prescribing practices, anecdotal or low-level data, hoarding). In addition, we describe methods to mitigate drug shortages as well as conservation strategies for sedatives, analgesics and neuromuscular blockers that could readily be applied at the bedside. The COVID-19 pandemic has accentuated the need for a coordinated, multi-pronged approach to optimize medication availability as individual or unilateral efforts are unlikely to be successful., (Copyright © 2020 American College of Chest Physicians. All rights reserved.)