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Background: In effort to improve post-operative outcomes, enhanced recovery after surgery (ERAS) protocols have gained popularity. The objective of this systematic review was to assess the reporting and methodological quality of plastic surgery ERAS studies., Methods: All plastic surgery ERAS implementation studies, published between January 1, 2020, to November 20, 2023, were included. The primary outcome was reporting quality based on "The Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOvER) checklist" (40 points). Secondary outcomes included methodology quality as per ERAS® Society endorsed guidelines (Breast 18 points; Head and Neck (H&N) 24 points)., Results: Fifty ERAS studies were included (breast reconstruction: 29, 58%; head and neck: 7, 14%; craniofacial: 6, 12%; aesthetic: 5, 10%; other: 3, 6%). Average reporting quality was 22.6/40 (56.7%). ERAS protocol elements least adhered to included: patient warming strategy (8/50, 16%), management of post-operative fluids (14/50, 28%), and post-discharge outcome tracking (14/50, 28%). Evaluation of breast methodological quality revealed average compliance of 9.2/18 (51.3%). The least complied with elements included preoperative computed tomography angiography (4/23, 17.4%), intraoperative warming (6/23, 26.1%), and post-operative wound management (2/23, 8.7%). For head and neck studies, average compliance was 9.1/23 (39.6%). The least complied with elements included pre-anesthesia pain medications (1/7, 14.3%), post-operative wound care (0/7, 0%), and urinary catheterization removal (1/7, 14.3%)., Conclusions: ERAS implementation studies in plastic surgery are highly variable, with overall low reporting and methodology quality. Plastic surgeons should be cautious when adopting published ERAS protocols that do not adhere to the recommended and official ERAS® Society guidelines., Competing Interests: Conflict of interest statement The authors declare that there are no relevant conflicts of interest. Dr. Thoma is an Editor of the book Evidence-Based Surgery: A Guide for Understanding and Interpreting the Surgical Literature and receives royalties from SPRINGER., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Recreational cannabis legalization marked a significant policy shift in Canada, but has been difficult to evaluate because of the absence of a control group. Although it is unfeasible to evaluate legalization using a randomized controlled trial design, sophisticated statistical techniques can employ quasi-experimental designs using natural experiments. This study evaluates the impact of cannabis legalization in a longitudinal cohort of Canadian emerging adults by comparing changes in cannabis use frequency and related consequences over time to changes in a similar cohort in a United States jurisdiction where no policy change took place., Methods: Two samples of emerging adults from Hamilton, Ontario, and Memphis, Tennessee, were followed longitudinally in 4-month intervals from March 16, 2018 to March 11, 2020, with three pre-legalization and four post-legalization assessments. Doubly robust difference-in-difference (DiD) estimation was used to assess whether cannabis legalization impacted cannabis use frequency or cannabis-related consequences in the Canadian sample over time. The impact of cannabis legalization on alcohol use and alcohol-related consequences was also assessed as a control form of substance use for which no policy change took place. Cohort differences were adjusted within DiD estimation using propensity score balancing., Results: Against a general trend of decreasing use over time, the DiD estimation revealed significantly greater cannabis use frequency approximately 6-months post legalization (ATT (95% CI): 0.2245 (0.0154, 0.4336)) and approximately one year post legalization (ATT (95% CI):0.3091 (0.0473, 0.5709)) in the Canadian sample compared to the American sample. Cannabis-related consequences were also greater in the Canadian sample at both of these time points (ATT (95% CI): 0.0.7610 (0.0797, 1.4423)), (ATT (95% CI): 1.0396 (0.1864, 1.8928)). These higher levels reflected less steep declines over time (i.e., attenuated 'aging out'). Alcohol changes showed no impact of legalization at any time point, as expected., Conclusions: Findings suggest that cannabis legalization was associated with smaller reductions in cannabis use frequency and adverse consequences than expected in the Canadian sample compared to the American control sample. Although the magnitude of these impacts was small, these findings suggest the start of diverging cannabis trajectories. Given that effects of legalization are hypothesized to be long-term rather than immediate, further monitoring of the impacts of cannabis legalization on developmental trends in cannabis use and related consequences is warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM is a principal in Beam Diagnostics, Inc. and a consultant to Clairvoyant Therapeutics, Inc. All other authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to determine whether magnetic resonance imaging (MRI) biomarkers are associated with visual prognosis in myelin oligodendrocyte protein (MOG)-associated optic neuritis (ON)., Design: Cross-sectional analysis., Participants: Patients meeting 2023 international diagnostic criteria for MOG antibody-associated disease who were seen for first episodes of MOG-associated ON at 3 tertiary neuro-ophthalmology practices between January 2017 and July 2023 were enrolled. Patients who received < 3 months of neuro-ophthalmic follow-up and did not demonstrate visual recovery (visual acuity [VA] ≥ 20/20 and visual field mean deviation [VFMD] > -5.0 dB) during this time were excluded., Methods: Patients underwent contrast-enhanced, fat-suppressed MRI of the brain and orbits within 1 month of symptom onset., Main Outcome Measures: The associations between radiologic biomarkers and poor VA outcome (< 20/40), incomplete VA recovery (< 20/20), and poor VFMD outcome (VFMD < -5.0 dB) were assessed using multivariable logistic regression adjusting for time from symptom onset to treatment and nadir VA or VFMD. Radiologic biomarkers included length of optic nerve enhancement (> 25% vs. < 25%; > 50% vs. < 50%; and > 75% vs. < 75%); degree of orbital, canalicular, and intracranial or chiasmal optic nerve enhancement (mild vs. moderate to severe compared with the lacrimal gland); and absence versus presence of optic nerve sheath enhancement on baseline T1-weighted MRI., Results: A total of 129 eyes of 92 patients (median age, 37.0 years [interquartile range, 20.8-51.3 years]; 65.2% female) were included. Poor VA outcome was seen in 6.2% of patients, incomplete VA recovery was seen in 19.4% of patients, and poor VFMD outcome was seen in 16.9% of patients. Compared with eyes with moderate to severe enhancement, eyes with mild orbital optic nerve enhancement were more likely to have poor VA outcome (odds ratio [OR], 8.57; 95% confidence interval [CI], 1.85-51.14; P = 0.009), incomplete VA recovery (OR, 7.31, 95% CI, 2.42-25.47; P = 0.001), and poor VFMD outcome (adjusting for time to treatment: OR, 6.81; 95% CI, 1.85-28.98; P = 0.005; adjusting for nadir VFMD: OR, 11.65; 95% CI, 1.60-240.09; P = 0.04). Lack of optic nerve sheath enhancement additionally was associated with incomplete VA recovery (OR, 3.86; 95% CI, 1.19-12.85; P = 0.02) compared with the presence of enhancement. These associations remained consistent in subgroup logistic regression analysis of MRIs performed before initiation of treatment but were not seen in pairwise analysis of MRIs performed after treatment., Conclusions: In eyes with first MOG-associated ON episodes, milder enhancement in the orbital optic nerve was associated with poorer VA and visual field recovery. Prospective and mechanistic studies are needed to confirm the prognostic usefulness of MRI in MOG-associated ON., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: Anemia in pregnancy has negative impacts on maternal and neonatal morbidity and mortality and has been described as an issue of health equity. The primary aim of our study was to describe the rates of anemia near delivery and assess whether this correlates with neighbourhood-level income status., Methods: We conducted a retrospective cohort study of pregnant persons delivering from January 2012 through December 2022 at 2 large academic centres. We used log-binomial regression to estimate the association between neighbourhood-level income quintile and anemia near delivery, defined as a hemoglobin <110 g/L within 30 days of delivery, controlling for maternal age, parity, thalassemia trait, number of fetuses, blood group, and service provider type. Secondary maternal and fetal outcomes were analyzed descriptively., Results: A total of 51 782 deliveries were included; the majority were singleton (97%) pregnancies delivered vaginally (61%). Although 77% of patients had a complete blood count done within 30 days of delivery, only 13% had a ferritin value checked within 9 months of delivery. Approximately 30% of all patients were anemic near delivery, with higher rates of anemia in lower income quintiles; patients in the lowest income quintile were 18% more likely to be anemic than those in the highest income quintile (relative risk 1.18; 95% CI 1.12-1.25)., Conclusions: Even within a high-resource academic setting, anemia in pregnancy is common. Given the high rates of anemia in our study, particularly, amongst patients in lower income quintiles, widespread targeted educational and system interventions are required to ensure equitable patient care., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common after noncardiac surgery. Postsurgical pain is frequent and can persist as chronic postsurgical pain (CPSP). The association between postsurgical pain and POD or POCD is biologically plausible. We conducted this systematic review to evaluate the association between acute postsurgical pain or CPSP and POD or POCD in adults undergoing noncardiac surgery., Methods: We followed Preferred Reporting Items for Systematic Review and Meta-Analyses. We searched MEDLINE, EMBASE, Cochrane, CINAHL and PSYCHINFO up to May 2023. We included cohort, case-control, and cross-sectional studies of any language. Pairs of reviewers independently screened studies, extracted data and assessed the risk of bias using the CLARITY tool and the Joanna Briggs Institute checklist. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where possible, we conducted random-effects meta-analyses to summarise our findings., Results: We analysed 30 studies (>9000 participants) that assessed the association between acute postoperative pain and POD/POCD. Dose-response meta-analyses found that postoperative pain intensity was associated with occurrence of POD (adjusted relative risk [aRR]/unit of pain intensity: 1.26; 95% confidence interval [CI]: 1.17-1.35; low certainty of evidence) and risk of developing POD (aRR/unit of pain intensity: 1.18; 95% CI: 1.08-1.30; low certainty of evidence). There was very low certainty of evidence regarding the association between postoperative pain and POCD. No studies assessed the association between CPSP and POCD. Residual confounding and substantial methodological variability between studies prevented pooling data from many of the included studies and lowered certainty of evidence., Conclusions: Dose-response meta-analyses found that postoperative pain intensity was associated with occurrence of and risk of developing POD., Systematic Review Protocol: PROSPERO-CRD42021192105., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

A 56-year-old woman required urgent cardiac surgery for Streptococcus mitis mitral valve infective endocarditis complicated by severe autoimmune heparin-induced thrombocytopenia (aHIT). We reasoned that the combination of high-dose intravenous immunoglobulin G (IVIG; to mitigate aHIT antibody-mediated platelet activation in the presence of heparin) together with the high concentrations of heparin attained during cardiac surgery (which typically produces less platelet activation in vitro vs usual therapeutic heparin concentrations) might prove effective. Accordingly, our patient underwent cardiac surgery with heparin following high-dose IVIG (1 g/kg × 2) without intra- or postoperative thrombosis. Serial serotonin release assays, using blood obtained pre-/post-IVIG, showed minimal platelet activation (∼30% serotonin release) post-IVIG at heparin concentrations typically obtained during cardiac surgery (2-5 U/mL) and significantly less than pre-IVIG serum in heparin's absence (∼85% serotonin release). In the setting of urgent cardiac surgery, preoperative high-dose IVIG appears to be a reasonable strategy to reduce platelet-activating effects of heparin-induced thrombocytopenia (including aHIT) antibodies, permitting safe use of standard intraoperative heparin dosing., Competing Interests: Declaration of Competing Interests There are no competing interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Despite numerous studies linking prenatal vaping to adverse perinatal outcomes, a systematic assessment for critical comparison remains absent. To investigate these associations, we conducted a systematic search of studies assessing perinatal outcomes in mothers and/or neonates exposed to vaping during pregnancy compared to those in women without prenatal vaping exposure through MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, PROSPERO, and Google Scholar until July 5, 2024. We performed inverse-variance random-effects meta-analyses for maternal and neonatal outcomes of 23 studies with a total of 924,376 participants with 7552 reporting vaping-only use during pregnancy. Prenatal vaping was associated with 53 % higher odds of an adverse maternal outcome (OR: 1.53; 95 % CI: 1.27-1.85; I 2 = 80 %), particularly with decreased breastfeeding (OR: 0.53; 95 % CI: 0.38-0.72; I 2 = 45 %) and reduced prevalence of adequate prenatal care (OR: 0.69; 95 % CI: 0.56-0.86; I 2 = 82 %). Prenatal vaping was also associated with a similarly 53 % higher odds of an adverse neonatal outcome (OR: 1.53; 95 % CI: 1.34-1.76; I 2 = 45 %), such as low birth weight (OR: 1.56; 95 % CI: 1.28-1.93; I 2 : 15 %), preterm birth (OR: 1.49; 955 CI: 1.27-1.76; I 2 : 0 %), and small for gestational age (OR: 1.48; 955 CI: 1.16-1.89; I 2 : 70 %). This is the first comprehensive systematic review and meta-analysis demonstrating vaping during pregnancy as a risk factor for increased odds of both maternal and neonatal outcomes and underscores the urgency to address awareness and regulations of vaping and its potential harms to both humans and the environment. REGISTRATION: PROSPERO CRD42023446266., Competing Interests: Declaration of Competing Interest Nicola Murgia reports non-financial support from GSK, AstraZeneca, Chiesi Farmaceutici, and Menarini outside the submitted work. Margie H Davenport reports grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), Social Sciences and Humanities Research Council (SSHRC), International Olympic Committee (IOC), and Women and Children’s Health Research Institute outside the submitted work. She is the Christenson Professor in Active Healthy Living. Padma Kaul holds a Canadian Institute of Health Research (CIHR) Sex and Gender Science Chair and a Heart & Stroke Chair in Cardiovascular Research. Paige Lacy reports grants from the Wellness of Workers (WoW) Program, Local 110 Heat & Frost Insulators & Allied Workers, Synergy Respiratory and Cardiac Care, AstraZeneca Canada, and the Natural Sciences and Engineering Research Council of Canada (NSERC) during the conduct of the study and personal fees from AstraZeneca Canada and GSK Canada outside the submitted work. Subhabrata Moitra reports personal fees from Elsevier (USA), Synergy Respiratory and Cardiac Care (Canada) and Permanyer Inc. (Spain), and lecture fees from Apollo Multispeciality Hospitals (India) and the Institute of Allergy – Kolkata (India) outside the submitted work. All other authors do not have any disclosures to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objective: GRADE and other evidence to decision (EtD) frameworks are widely used by guideline development groups (GDG) and other decision-makers. When GDGs judge the magnitude of desirable and undesirable health outcomes on EtDs, they typically categorize them as trivial, small, moderate, or large. However, generic judgment or decision thresholds (DTs) that could guide the user about such estimates of effect size or serve as references for interpretation of findings are not yet available. The objective of this study was to empirically derive DTs for EtD judgments about the magnitude of dichotomously assessed health benefits and harms., Methods: We conducted a methodological randomized controlled trial to derive empirical DTs across conditions and health outcomes. We invited stakeholders, including clinicians, epidemiologists, decision scientists, health research methodologists, experts in health technology assessment (HTA), members of GDGs, patient representatives, and the public to participate in the trial. We employed randomly assigned case scenarios to elicit ranges of absolute risk differences judged as small and moderate effects from study participants. We then used the collected data to derive empirical DTs. We also investigated the validity of our DTs by measuring the agreement between judgments that were made by GDGs in the past and the judgments that our DTs approach would suggest if applied to the same guideline data., Results: A total of 445 stakeholders accessed the survey of which 409 were randomised and 288 rated at least one case scenario. Based on these participants, the study findings support our a priori hypothesis of a difference in the DTs for trivial, small, moderate, and large effects and are suggestive of a relation between raters' judgments and the joint measure of absolute effects and outcome values. The results permit the use and calculation of DTs for a variety of scenarios and we present three ways of how to use the results practically., Conclusions: In this trial we confirmed that empirically derived DTs discriminate between judgments on the EtDs. These DTs can be used for judgments about desirable and undesirable health effects in systematic reviews or to initiate and inform a discussion with a GDG. This ensures consistency in judgments across different guideline questions and promotes transparency in judgments., Plain Language Summary: Decision thresholds (DTs) help with determining if effects of interventions should be considered absent, small, moderate or large. In this study we derived an overarching approach for these thresholds across conditions and outcomes. The results of this study, a randomized experiment, will help guideline developers and other decision-makers to make these judgments objectively. They will be particularly relevant for the use in Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence to decision (EtD) frameworks., Competing Interests: Declaration of competing interest The authors declare no direct financial conflicts of interest related to the content of this manuscript. They are GRADE Working Group members or contributors to the work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to artificial light-at-night (ALAN) has been linked to cancer risk. Few meta-analyses on this topic have reviewed only breast cancer. This study aimed to systematically review and meta-analyze existing studies on ALAN exposure and cancer incidence, thoroughly evaluating exposure assessment quality. We considered observational studies (cohort, case-control, cross-sectional) on ALAN exposure (indoor and outdoor) and cancer incidence, measured by relative risk, hazard ratio, and odds ratio. We searched six databases, two registries, and Google Scholar from inception until April 17, 2024. Quality of studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. Random-effects meta-analysis was used to estimate relative risks (RR) and 95 % confidence intervals (CI) for ALAN exposures. We identified 9835 studies and included 28 for qualitative synthesis with 2,508,807 individuals (15 cohort, 13 case-control). Out of the included studies, 20 studies on breast cancer (731,493 individuals) and 2 studies on prostate cancer (53,254 individuals) were used for quantitative synthesis. Higher levels of outdoor ALAN were associated with breast cancer risk (meta-estimate = 1.12, 95 % CI 1.03-1.23 (I 2  = 69 %)). We observed a non-significant positive association between indoor ALAN levels and breast cancer risk (meta-estimate = 1.07, 0.95-1.21, I 2  = 60 %), and no differences by menopausal status. The meta-analysis for prostate cancer suggested a non-statistically significant increased risk for higher levels of outdoor ALAN (meta-estimate = 1.43, 0.75-2.72, I 2  = 90 %). In the qualitative synthesis, we observed positive associations with non-Hodgkin lymphoma and colorectal, pancreatic and thyroid cancer. We found an association between outdoor ALAN and breast cancer risk. However, most studies relied on satellite-images with a very low resolution (1 to 5 km, from the Defense Meteorological Program [DMSP]) and without information on color of light. Future studies with better exposure assessment should focus on investigating other cancer sites., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The PANELVIEW questionnaire identifies the strengths and weaknesses of the process and methods used for developing health guidelines from the guideline development group's perspective. To expand its use, PANELVIEW ideally should be available in different languages. We aimed to cross-culturally adapt PANELVIEW into Spanish and assess its acceptability, validity, and reliability., Study Design and Setting: To translate and culturally adapt PANELVIEW to Spanish, we followed International Society for Pharmacoeconomics and Outcomes Research's Translation and Cultural Adaptation Good Practice Principles guidelines. The process consisted of 1) forward and back translation, 2) input from an expert panel, and 3) cognitive debriefing interviews. We assessed the content validity with experts in guideline development who rated instrument items for relevance to determine the item content validity index and scale content validity index (I-CVI and S-CVI). We tested the reliability with health guidelines panels from Spanish-speaking countries and measured internal consistency (Cronbach's alpha). We examined acceptability through the number of missing responses for each item., Results: The content comparison between the back-translation and the original version showed that most items (24/34) were conceptually equivalent but with grammatical differences. Through the cognitive interviews, we identified six items with wording issues, ten with clarity issues, and two with applicability issues. I-CVI ranged from 0.77 to 1.00, with two items needing revision. S-CVI was 0.92, showing excellent content validity. The PANELVIEW Spanish version demonstrated very good reliability (Cronbach's alpha coefficient of 0.96). Panel members responded to all items, showing good acceptability., Conclusion: The PANELVIEW Spanish version was conceptually equivalent to the original version and provided satisfactory evidence of acceptability, validity and reliability., Competing Interests: Declaration of competing interest W.W., Elie Akl and H.S. will retain the copyright of the PANELVIEW tool through McMaster University (Technology ID 20-031), and the tool may be licensed in the future. There are no competing interests for any other author., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. Despite the devastating effect of this disease on atherosclerotic cardiovascular health, the disease phenotype and severity are more heterogeneous than previously thought. The predictors of atherosclerotic cardiovascular disease (ASCVD) in HoFH patients have never been systematically studied., Objective: To investigate the univariate and multivariate predictors of ASCVD in HoFH patients., Methods: Patients from the Canadian HoFH Registry were included in the present retrospective longitudinal study. Data for these patients were collected using a standardized questionnaire between 2019 and 2022 in 19 academic sites across Canada. Predictors of ASCVD were evaluated using Cox proportional hazards models., Results: Among 48 HoFH patients, 26 (54 %) of them had at least one ASCVD event. The average age at baseline was 19 ± 15 years and women represented 56 % of the cohort. The independent predictors of ASCVD events were male sex (HR 2.57 (1.13-5.84)), diabetes (HR 16.22 (3.38-77.97)), and LDL-C above the median of 14.45 mmol/L [559 mg/dL] (HR 3.10 (1.24-7.76)). When performing subgroup analysis according to sex, the presence of LDL-C above median was associated with a significantly higher probability of ASCVD (88 % vs. 43 %, p = 0.005) in women, but not in men (100 % at age 40 in both groups, p = 0.98)., Conclusion: This study reported for the first time the univariate and multivariate predictors of ASCVD in HoFH patients. We demonstrate that predictors of ASCVD in HoFH differ in males and females with respect to LDL-C levels., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objective: Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT is widely applied to efficiently use existing credible guidelines and contextualize them to a target setting. To highlight the experiences of a Latin American Guideline Development Group (GDG) applying GRADE-ADOLOPMENT to adapt the American Society of Hematology's clinical practice guideline on managing venous thromboembolisms (VTEs) in Latin America., Study Design and Setting: We employed a mixed-method postevaluation using self-administered surveys and semistructured interviews. We assessed the Latin American GDG (1) general satisfaction and confidence using the approach, (2) their ratings on the usefulness, appropriateness, and importance of GRADE-ADOLOPMENT and its tools to inform their judgements, and (3) any additional facilitators and barriers to refine the process., Results: Eleven of the 14 GDG members, including nine panelists and two methodologists, provided survey responses and eight participated in the interview. Respondents felt "mostly" or "completely" satisfied with the adapted guideline. Eight panelists who were surveyed agree that GRADE-ADOLOPMENT is useful in countries with limited resources. Although panelists expressed initial apprehensions in their understanding of the process, they demonstrated enhanced confidence in their capacity to apply GRADE after completing workshop training and by acquiring experience. Panelists reiterated the importance of considering evidence-to-decision (EtD) criteria (ie, resources, feasibility, and cost-effectiveness) when adapting recommendations. The GDG encountered challenges with collecting local and regional data, prioritizing recommendations while considering intraregional diversity, and the lengthy publication period, although the latter stemmed from procedures not related to GRADE-ADOLOPMENT., Conclusions: GRADE-ADOLOPMENT is an important tool to facilitate the adaptation and uptake of clinical practice guidelines in novel settings. The GDG felt satisfied with their overall experience using the GRADE-ADOLOPMENT approach. However, their experience could have been optimized if they had access to robust regional evidence, more recommendations to adapt from, and worked with more efficient guideline production timelines., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hip fractures carry a substantial risk of complications and death. This study aimed to report the 90-day incidence of mortality, major perioperative complications and in-hospital timelines after a hip fracture in the Spanish HIP ATTACK-1 trial cohort, comparing with the non-Spanish cohort., Methods: Prospective cohort study of Spanish patients nested in the HIP ATTACK-1 trial. The HIP ATTACK-1 was an international, randomized, controlled trial (17 countries, 69 hospitals, 7 in Spain, highest recruiting country). Patients were randomized to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. Participants were ≥45 years of age who presented with a low-energy hip fracture requiring surgery., Results: Among 534 patients in the Spanish cohort, 69 (12.9 %) patients died at 90 days follow-up, compared to 225 (9.2 %) in the non-Spanish cohort (p = 0.009), mostly due to higher nonvascular related mortality. A composite of major postoperative complication occurred in 126 patients (23.6 %). The most common perioperative complications were myocardial injury (189 patients, 35.4 %), infection with no sepsis (86 patients, 16.1 %) and perioperative delirium (84 patients, 15.7 %); all these complication rates in Spain were significantly higher than the non-Spanish patients (29.2 % p = 0.005; 11.9 % p = 0.008 and 9.2 % p < 0.0001, respectively). Spanish cohort patients were older and had more comorbidities than the non-Spanish cohort, evidencing their greater frailty at baseline. Among Spanish patients, the median time from hip fracture diagnosis to surgery was 30.0 h (IQR 21.1-53.9) in the standard-care group, with 68.8 % of patients receiving surgery within 48 h of diagnosis. This median time was lower in the non-Spanish cohort (22.8 h, IQR 9.5-37.0), where 82.1 % of patients were operated within 48 h., Conclusions: In the HIP ATTACK-1 trial, 1 in 8 patients died 90 days after a hip fracture in Spain. The most common complication after a hip fracture was myocardial injury, followed by infection and delirium. Spanish patients had worse outcomes than non-Spanish patients. Research needs to focus on new interventions such as accelerated surgery and perioperative troponin measurement with the appropriate investment of resources, to prevent and identify early these complications with a goal of improving mortality for this high-risk population., Level of Evidence: II., Competing Interests: Declaration of competing interest Dr. Ernesto Guerra-Farfán and Dr. PJ Devereaux received research grants from Smith & Nephew for this investigator-initiated trial. Based on study questions Dr. PJ Devereaux originated and grants he has written, he has received grants from Abbott Diagnostics, Roche Diagnostics, and Siemens. Dr. Flavia K Borges received investigator-initiated research grants from Roche diagnostics and SIEMENS. Mohit Bhandari (g), Yaiza Garcia-Sanchez (h), Jorge H. Nuñez (c,i), Jaume Mestre-Torres (j), Jordi Tomas-Hernandez (a), Jordi Teixidor-Serra (a), Mariano Balaguer-Castro (k), Pablo Castillón (i), Alfred Dealbert (l), Julio De Caso Rodriguez (m), Hector J. Aguado (n), Enrique Guerado (o), Ekaterine Popova(m), Ana Claudia Tonelli (p), Kumar Balasubramanian (e), Jessica Vincent (e), Valerie Harvey (e), Etri Kocaqi (q) and Gerard Slobogean (r s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Objective: The Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-ADOLOPMENT methodology has been widely used to adopt, adapt, or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. The objective of this guidance is to refine the operationalization for applying GRADE-ADOLOPMENT., Methods: Through iterative discussions, online meetings, and email communications, the GRADE-ADOLOPMENT project group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE working group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people), and twice in September 2023 (approximately 60 and 90 people) for approval., Results: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by doing the following: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing evidence-to-decision (EtDs), when available or developing new EtDs, if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others., Conclusion: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over 6 years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources., Competing Interests: Declaration of competing interest The authors are members or contributors to the GRADE working group. Zachary Munn is supported by an NHMRC investigator grant APP 1195676. Alexander G. Mathioudakis was supported by the National Institute for Health and Care Research Manchester Biomedical Research Centre (NIHR Manchester BRC, NIHR203308) and by an NIHR Clinical Lectureship in Respiratory Medicine. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics., Objectives: To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis., Methods: Systematic review and meta-analysis., Data Sources: MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023., Study Eligibility Criteria: Prospective and retrospective studies with 1-group and 2-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis., Participants: Adult and/or paediatric patients with CNS aspergillosis., Test(s): Galactomannan testing on CSF specimens., Reference Standard: European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent., Assessment of Risk of Bias: QUADAS-2 assessment in duplicate., Methods of Data Synthesis: Bivariate restricted maximum likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver operating characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none)., Results: We included eight studies (n = 342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI, 57.2-78.7%) and 94.4% (95% CI, 82.8-98.3%), respectively. Using meta-regression, galactomannan cut-off (p = 0.38), EORTC/MSGERC criteria version (p = 0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p = 0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analysing the EORTC/MSGERC criteria reference standard used (e.g. 2002 vs. 2008 definitions) or whether paediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and 1-group design studies., Discussion: CSF galactomannan is a highly specific but insensitive test for use as a component of CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Study Objective: Depression is a common cause of long-lasting disability and preoperative mental health state that has important implications for optimizing recovery in the perioperative period. In older elective surgical patients, the prevalence of preoperative depression and associated adverse pre- and postoperative outcomes are unknown. This systematic review and meta-analysis aimed to determine the prevalence of preoperative depression and the associated adverse outcomes in the older surgical population., Design: Systematic review and meta-analysis., Setting: MEDLINE, MEDLINE Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations, Embase/Embase Classic, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews, ClinicalTrials.Gov, the WHO ICTRP (International Clinical Trials Registry Platform) for relevant articles from 2000 to present., Patients: Patients aged ≥65 years old undergoing non-cardiac elective surgery with preoperative depression assessed by tools validated in older adults. These validated tools include the Geriatric Depression Scale (GDS), Hospital Depression and Anxiety Scale (HADS), Beck Depression Inventory-II (BDI), Patient Health Questionnaire-9 (PHQ-9), and the Centre for Epidemiological Studies Depression Scale (CESD)., Interventions: Preoperative assessment., Measurement: The primary outcome was the prevalence of preoperative depression. Additional outcomes included preoperative cognitive impairment, and postoperative outcomes such as delirium, functional decline, discharge disposition, readmission, length of stay, and postoperative complications., Main Results: Thirteen studies (n = 2824) were included. Preoperative depression was most assessed using the Geriatric Depression Scale-15 (GDS-15) (n = 12). The overall prevalence of preoperative depression was 23% (95% CI: 15%, 30%). Within non-cancer non-cardiac mixed surgery, the pooled prevalence was 19% (95% CI: 11%, 27%). The prevalence in orthopedic surgery was 17% (95% CI: 9%, 24%). In spine surgery, the prevalence was higher at 46% (95% CI: 28%, 64%). Meta-analysis showed that preoperative depression was associated with a two-fold increased risk of postoperative delirium than those without depression (32% vs 23%, OR: 2.25; 95% CI: 1.67, 3.03; I 2 : 0%; P ≤0.00001)., Conclusions: The overall prevalence of older surgical patients who suffered from depression was 23%. Preoperative depression was associated with a two-fold higher risk of postoperative delirium. Further work is needed to determine the need for depression screening and treatment preoperatively., Competing Interests: Declaration of competing interest Frances Chung: Reports research support from the Ontario Ministry of Health Innovation Fund, ResMed Foundation, University Health Network Foundation, Up-to-date royalties, consultant to Takeda Pharma, STOP-Bang proprietary to University Health Network. Linda Ma: Reports grant funding from Brain Canada, Centre for Aging and Brain Health Innovation, MOHLTC AFP Innovation Fund. Carmela Tartaglia: reports grand funding from NIH, Weston Brain Foundation, consultant to EISAI, Eli Lilly, and clinical trials work with Passage Bio, Janssen, Biogen, Avanex, Green Valley, Roche, GSK, BMS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To quantify post-cataract surgery health care utilization caused by dry eye symptoms (DES) and identify preoperative risk factors and mediators of postoperative DES., Setting: An outpatient surgical centre in Toronto, Canada., Design: Retrospective cohort study., Participants: Included patients had cataract surgery between April 2019 and January 2020, completed a preoperative Dry Eye Questionnaire 5 (DEQ5), and were over age 18., Methods: Data collected included DES risk factors, prophylaxis, and intraoperative and postoperative details. DES health care utilization and prevalence were reported as percentages. Risk of DES follow-up with DES prophylaxis use, and within each DEQ5 severity group, were analyzed with χ 2 -square test of independence and odds ratios. Binomial logistic regression assessed for significance of multiple preoperative and intraoperative risk factors, controlling for one another., Results: Of 1074 patients (46% male, mean age: 71, mean DEQ5: 5.12), 18.1% had at least one nonroutine postoperative appointment due to DES. Patients with moderate/severe DEQ5 scores were 1.843 times likelier to have postoperative DES concerns than those with no/mild scores (CI = 1.307-2.599). Preoperative DES prophylaxis did not reduce DES risk in any severity group. Higher DEQ5 score, female sex, bilateral sequential surgeries, and femtosecond laser-assisted cataract surgery had higher likelihood of postoperative DES (B = 0.054; p < 0.001; B = -0.351; p = 0.037; B = 0.695; p = 0.003; B = 0.491; p = 0.003, respectively)., Conclusion: Nearly 1 in 5 patients had DES postcataract surgery, with 1 in 12 requiring one or more nonroutine follow-ups for DES, suggesting substantial health care burden. Current standard preoperative DES treatment may not reduce postoperative DES, and further studies are needed to elucidate why., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: The suitability of ambulatory surgery for patients with obstructive sleep apnea (OSA) remains controversial. This systematic review and meta-analysis aimed to evaluate the odds of perioperative adverse events in patients with OSA undergoing ambulatory surgery, compared to patients without OSA., Methods: Four electronic databases were searched for studies published between January 1, 2011 and July 11, 2023. The inclusion criteria were: adult patients with diagnosed or high-risk of OSA undergoing ambulatory surgery; perioperative adverse events; control group included; general and/or regional anesthesia; and publication on/after February 1, 2011. We calculated effect sizes as odds ratios using a random effects model, and additional sensitivity analyses were conducted., Results: Seventeen studies (375,389 patients) were included. OSA was associated with an increased odds of same-day admission amongst all surgery types (OR 1.94, 95% CI 1.46-2.59, I 2 :79%, P < 0.00001, 11 studies, n = 347,342), as well as when only orthopedic surgery was considered (OR 2.68, 95% CI 2.05-3.48, I 2 :41%, P < 0.00001, 6 studies, n = 132,473). Three studies reported that OSA was strongly associated with prolonged post anesthesia care unit (PACU) length of stay (LOS), while one study reported that the association was not statistically significant. In addition, four studies reported that OSA was associated with postoperative respiratory depression/hypoxia, with one large study on shoulder arthroscopy reporting an almost 5-fold increased odds of pulmonary compromise, 5-fold of myocardial infarction, 3-fold of acute renal failure, and 5-fold of intensive care unit (ICU) admission., Conclusions: Ambulatory surgical patients with OSA had almost two-fold higher odds of same-day admission compared to non-OSA patients. Multiple large studies also reported an association of OSA with prolonged PACU LOS, respiratory complications, and/or ICU admission. Clinicians should screen preoperatively for OSA, optimize comorbidities, adhere to clinical algorithm-based management perioperatively, and maintain a high degree of vigilance in the postoperative period., Competing Interests: Declaration of competing interest This research did not receive any grants or funding., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general., Study Design and Setting: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met prespecified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions., Results: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with 3 (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation and 6 (23.1%) used Confidence In Network Meta-analysis. Surface Under the Cumulative Ranking Curve was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%)., Conclusion: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms; those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice., Competing Interests: Declaration of competing interest T.A. reports a relationship with MAGIC Evidence Ecosystem Foundation that includes: board membership and employment. P.O.V. reports a relationship with MAGIC Evidence Ecosystem Foundation that includes: board membership and employment. P.O.V. and T.A. are CEO and deputy CEO of the nonprofit organization MAGIC Evidence Ecosystem Foundation (https://www.magicevidence.org). In collaboration with P.O.L. at Lovisenberg Diaconal Hospital, MAGIC is conducting the research project Making Alternative Treatment Choices Intuitive and Trustworthy (MATCH-IT). The overarching aim of MATCH-IT is to develop a new interactive SoF table and decision support tool, displaying multiple structured evidence summaries from NMAs. The tool may be integrated as part of MAGICapp (https://app.magicapp.org/#/guidelines), an online author and publication platform for guidelines, evidence summaries and decision aids. A.A.V. is Statistical Associate Editor for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. A.C.T. is Coeditor-in-Chief for the Journal of Clinical Epidemiology, but had no involvement with the peer review process or decision for publication. X.W., T.P., M.Ø., and C.L. 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Anterior uveitis presents a diagnostic challenge due to its wide array of etiologies and clinical manifestations. This narrative review aims to equip general ophthalmologists with a comprehensive understanding of anterior uveitis epidemiology, diagnosis, and treatment. Particular emphasis is placed on developing a tailored and stepwise strategy, rather than a one-size-fits-all approach, for the workup and treatment of anterior uveitis. Chest radiography and serologic testing for syphilis, human leukocyte antigen B27, and angiotensin-converting enzyme are appropriate routine investigations in cases of severe, bilateral, recurrent, or chronic anterior uveitis. Additional testing should be guided by clinical findings and regional epidemiology, especially when considering expensive and invasive modalities. Investigations that are obtained in the absence of clinical and epidemiologic orientation are of limited utility and incur significant costs to patients and health care systems. Most cases of anatomically isolated anterior uveitis resolve with topical corticosteroids, but some patients require escalation to systemic immunomodulatory therapy (IMT). IMT should be considered in patients who respond poorly to corticosteroids, develop side effects related to corticosteroids that limit their use, require high doses to maintain disease remission, or have concomitant systemic inflammatory disease. Comprehensive ophthalmologists should feel comfortable comanaging patients that require conventional disease-modifying antirheumatic drugs/antimetabolite therapy (i.e., methotrexate, azathioprine, and mycophenolate mofetil) with rheumatologists and providing guidance on ocular dosing. When uveitis quiescence cannot be achieved despite maximally tolerated antimetabolite therapy, patients should be referred to a uveitis specialist for consultation and consideration of IMT escalation. The timing of uveitis referral may depend on local factors specific to health care jurisdictions., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Vascular dementia (VaD) is a prevalent form of cognitive impairment with underlying vascular etiology. In this review, we examine recent genetic advancements in our understanding of VaD, encompassing a range of methodologies including genome-wide association studies, polygenic risk scores, heritability estimates, and family studies for monogenic disorders revealing the complex and heterogeneous nature of the disease. We report well known genetic associations and highlight potential pathways and mechanisms implicated in VaD and its pathological risk factors, including stroke, cerebral small vessel disease, and cerebral amyloid angiopathy. Moreover, we discuss important modifiable risk factors such as hypertension, diabetes, and dyslipidemia, emphasizing the importance of a multifactorial approach in prevention, treatment, and understanding the genetic basis of VaD. Last, we outline several areas of scientific advancements to improve clinical care, highlighting that large-scale collaborative efforts, together with an integromics approach can enhance the robustness of genetic discoveries. Indeed, understanding the genetics of VaD and its pathophysiological risk factors hold the potential to redefine VaD on the basis of molecular mechanisms and to generate novel diagnostic, prognostic, and therapeutic tools., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The COVID-19 pandemic prompted the scientific community to collaborate in an unprecedented way, with the rapid and urgent generation and translation of new knowledge about the disease and its causative agent. Iteratively, and at different levels of government and globally, population-level guidance was created and updated, resulting in the need for a living catalog of guidelines, the eCOVID-19 Recommendations Map and Gateway to Contextualization (RecMap). This article focuses on the approach that was used to analyze barriers and opportunities associated with using the RecMap in public health in Canada., Study Design and Setting: A mixed qualitative and quantitative approach data were used to inform this knowledge mobilization project and inform feedback on implementation of the eCOVID-19 RecMap. This approach involved surveying 110 attendees from a public health webinar. Following this webinar, an evidence brief and series of case studies were created and disseminated to 24 Canadian public health practitioners who attended a virtual workshop. This workshop identified barriers and opportunities to improve RecMap use., Results: This study helped to shed light on the needs that public health practitioners have when finding, using, and disseminating public health guidelines. Through the workshop that was conducted, opportunities for public health guidelines can be categorized into 4 categories: 1) information access, 2) awareness, 3) public health development, and 4) usability. Barriers that were identified can also be categorized into 4 categories: 1) usability, 2) information maintenance, 3) public health guidance, 4) awareness., Conclusion: This work will help to inform the development and organization of future public health guidelines, and the needs that public health practitioners have when engaging with them., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin., Objectives: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context., Methods: The ability of F(ab')2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4., Results: A strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition., Conclusion: A simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible., Competing Interests: Declaration of competing interests C.V. reports honorarium from Viatris. J.R. reports research grant from Stago. H.G. reports transport fees from Stago. F.M. reports speaker fees from Fresenius, Technoclone, and Werfen, all outside the submitted work. Y.G. reports research grant and symposium fees from Stago. C.P. reports research grant from Stago. All other authors of this paper have no conflicts of interest., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR). Five recommendations had the LOE upgraded to A and 2 new recommendations on antithrombotic treatment for patients with COVID-19 were added. Furthermore, a section was added to answer questions about COVID-19 vaccination and vaccine-induced immune thrombotic thrombocytopenia (VITT), for which studies have provided some evidence. We only included recommendations with LOE A or B. Panelists agreed on 19 recommendations, 4 for nonhospitalized, 5 for noncritically ill hospitalized, 3 for critically ill hospitalized, and 2 for postdischarge patients, as well as 5 for vaccination and VITT. A strong recommendation (COR 1) was given for (a) use of prophylactic dose of low-molecular-weight heparin or unfractionated heparin in noncritically ill patients hospitalized for COVID-19, (b) for select patients in this group, use of therapeutic-dose low-molecular-weight heparin/unfractionated heparin in preference to prophylactic dose, and (c) for use of antiplatelet factor 4 enzyme immunoassays for diagnosing VITT. A strong recommendation was given against (COR 3) the addition of an antiplatelet agent in hospitalized, noncritically ill patients. These international guidelines provide recommendations for countries with diverse healthcare resources and COVID-19 vaccine availability., Competing Interests: Declaration of competing interests S.S. has received a research grant from Octapharma; served on data safety monitoring boards for Alexion, Bayer, Boehringer-Ingelheim, and Sanofi; served on event adjudication for Daiichi Sankyo; and served on an advisory board for Servier. D.M.A. received research grants from Rigel Pharmaceuticals and the Public Health Agency of Canada and is a consultant for Amgen, Paradigm, Sobi, Alpine, Novartis, and Argenx. C.A.B. has received a research grant from Amgen, honoraria from BMS-Pfizer, Janssen, and Sanofi, and served on the advisory board for Novartis. L.B. currently owns a stock portfolio with Johnson & Johnson and Pfizer. J.M.C. has received a research grant from CSL Behring and has served on scientific advisory boards for Abbott, Anthos, Bristol Myers Squibb, Pfizer, and Werfen. A.F. has received honoraria from Kedrion and Rovi and served on an advisory board for Sanofi. S.K. has received research grants from Bayer and is a consultant for Inari and Janssen. J.H.L. has served on a data safety monitoring board with Merck, a research study steering committee with Octapharma, and the advisory board for Werfen. S.M. has received research grants from Bayer, Abbvie, Hemab, Viatris, and Sanofi and honoraria from AstraZeneca, Norgine, and Alveron. I.N. has received research grants from Paradigm Pharmaceuticals, Janssen/Johnson & Johnson, UCB Biopharma, AstraZeneca, and the Public Health Agency of Canada and is a consultant for Paradigm Pharmaceuticals, Janssen/Johnson & Johnson, UCB Biopharma, and AstraZeneca. E.R. has received research grants from Bayer, Pfizer, and Novartis and honoraria from Sanofi, Bayer, Ache, Daiichi Sankyo, and Pfizer. C.M.S. served on an advisory board for Norgine Pharma. M.S. has received research grants from Pfizer, Amgen, and Sanofi; received honoraria from Pfizer, Octapharma, Amgen, and Novartis; and served on advisory boards for Amgen and Novartis. A.C.S. has received a research grant from AstraZeneca and honoraria from Janssen, Regeneron, and AstraZeneca. J.T. received honoraria from Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. R.Z. has received research grants from the Canadian Institute of Health Research, LifeArc, Nation Institute of Health, Research Manitoba, CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, Thistledown Foundation, and Manitoba Medical Services Foundation. The remaining authors have no conflicts of interest to declare. S.S. has been primary author and coauthor on review articles on COVID-19. D.M.A. has been coauthor and senior author on articles on diagnosis and treatment of VITT. C.A.B. has been primary author and co-author on articles on heparins and antiplatelet agents for treatment of COVID-19. J.M.C. has been primary author and coauthor on articles on antiplatelet agents, apixaban, and heparin for treatment of COVID-19. A.F. has been coauthor on review articles on treatment of COVID-19, including with heparin. T.I. has been primary author and coauthor on articles on coagulopathy in COVID-19 and in VITT. S.K. has been coauthor on articles on heparin and antiplatelet agents for treatment of COVID-19. J.H.L. has been primary author and coauthor on articles on coagulopathy in COVID-19 and in VITT and on heparin for treatment of COVID-19. S.M. has been coauthor on articles on heparin and oral anticoagulants for the treatment of COVID-19. I.N. has been primary author, senior author, and coauthor on articles on coagulopathy and laboratory diagnosis in VITT and COVID-19. C.M.S. has been coauthor on articles on coagulopathy in COVID-19. M.S. has been primary author on articles on heparin for treatment of COVID-19. A.C.S. has been primary author and senior author on articles on heparin and coauthor on articles on rivaroxaban for treatment of COVID-19. J.T. has been primary author and coauthor on articles on coagulopathy in COVID-19. R.Z. has been primary author and coauthor on articles on heparin and antiplatelet agents, respectively, for treatment of COVID-19. The remaining authors have no intellectual conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human immunodeficiency virus-1 remains a major global health threat. Since the virus is often transmitted through sexual intercourse and women account for the majority of new infections within the most endemic regions, research on mucosal immunity at the female reproductive tract (FRT) is of paramount importance. At the FRT, there are intrinsic barriers to HIV-1 infection, such as epithelial cells and the microbiome, and immune cells of both the innate and adaptive arms are prepared to respond in case the virus overcomes the first line of defense. In this review, we discuss recent findings on FRT mucosal mechanisms of HIV-1 defense and highlight research gaps. While defense from HIV-1 infection at the FRT has been understudied, current and future research is essential to develop new therapeutics and vaccines that can protect this unique mucosal site from HIV-1., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Given the key role that pilot and feasibility (PAF) trials play in addressing the challenges of surgical trials, adequate reporting completeness is essential. Our aim was to assess completeness of reporting and evaluate if the items of the Consolidated Standards of Reporting Trials (CONSORT) extension for PAF trials have been reported in surgical PAF trials., Study Design: This is a metaresearch study reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they were pilot or feasibility randomized trials evaluating a surgical intervention. The primary outcome was overall adherence to the CONSORT statement extension to randomized PAF trials checklist. A Poisson regression was performed to explore the association between research factors and reporting completeness., Setting: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from January 1-December 31, 2011 and 2021., Results: After screening 1991 citations, 38 studies from 2011 to 34 studies from 2021 were included. The mean CONSORT reporting score across all included studies was 21.5 (standard deviation 6.3). After excluding items that were not applicable to all studies, a mean of 20.1 (standard deviation 6.1) of 34 items (0.59) were reported. Studies published in 2021 (vs 2011) did not have a greater number of CONSORT items reported (incidence rate ratio [IRR] 1.01, 95% confidence interval [CI] 0.89-1.15). Studies registered in a clinical trial registry (IRR 1.29, 95% CI 1.12-1.48) and randomizing more than 50 patients (IRR 1.16, 95% CI 1.04-1.30) were associated with more CONSORT items reported., Conclusion: The reporting completeness of surgical PAF trials is poor and has not improved after the publication of the CONSORT extension., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The Eyesi Surgical Simulator (VRmagic, Mannheim, Germany) is the most commonly used ophthalmic virtual reality surgical simulator. While studies have demonstrated improved trainee skill acquisition with simulation-based training tools, a systematic review and meta-analysis evaluating Eyesi specifically has yet to be conducted. The aim of this study was to meta-analyze studies comparing Eyesi with other methods of technical skill teaching for trainees., Methods: MEDLINE, Embase, and CENTRAL databases were searched. Articles included compared Eyesi Surgical Simulator use with alternative methods of technical skill training for medical students or residents. A pairwise meta-analysis using inverse variance random effects was performed. Standardized mean differences (SMDs) were used as the primary outcome measure to account for differences in surgical skill evaluation tools., Results: From 207 citations, 8 studies with 108 learners using Eyesi and 123 learners not using Eyesi were included. Improvements in technical skill scores were significantly greater with the use of Eyesi (3 studies; SMD = 2.02; 95% CI, 1.47-2.57; p < 0.001; I 2  = 0%). There was a significant reduction in the number of learners experiencing post-training technical errors in the Eyesi group (5 studies: odds ratio = 0.43; 95% CI, 0.20-0.90; p = 0.03; I 2  = 30%). There were no significant differences in post-training time to task completion between groups (3 studies; SMD = 1.96; 95% CI, -1.96-5.88; p = 0.33; I 2  = 97%)., Conclusions: The Eyesi Surgical Simulator may improve technical skill acquisition (grade: low certainty of evidence) and decrease technical errors (grade: very low certainty of evidence) during cataract surgery among trainees. Further prospective studies evaluating Eyesi modules with standardized scoring systems is warranted., Competing Interests: Footnotes and Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize the neuro-ophthalmology publishing trends of the top general clinical ophthalmology and neurology journals and to report (i) the proportion of articles that are neuro-ophthalmology focused and (ii) the correlation between annual proportion of neuro-ophthalmology-focused articles and annual proportion of neuro-ophthalmologist journal editors., Design: Retrospective database review., Materials: Articles in the top 5 general clinical ophthalmology and neurology journals., Methods: Publications from 2012 through 2021 were retrieved from Embase and classified as teaching or nonteaching articles based on journal indexing. Duplicate screening was conducted to further categorize articles as either focused or not focused on neuro-ophthalmology., Results: The titles, abstracts, and (or) full texts of 34,660 articles were reviewed. The total proportions of nonteaching articles and teaching articles focused on neuro-ophthalmology were 3.4% and 13.8%, respectively. Neuro-ophthalmology contributions to nonteaching and teaching publications were greater among the ophthalmology journals (4.0% and 15.2%) than among the neurology journals (2.6% and 13.3%). There were no clear trends in the annual proportion of neuro-ophthalmology-focused articles across the 10-year period. The annual proportion of neuro-ophthalmologist journal editors was positively correlated with annual neuro-ophthalmology output for teaching articles (Pearson's r = 0.541; p < 0.001) but not articles unrelated to teaching (Pearson's r = 0.067; p = 0.598)., Conclusions: Our study found that there was a lower prevalence of neuro-ophthalmology papers in high-impact-factor general clinical ophthalmology and neurology journals over the last 10 years. It is important to have good representation of neuro-ophthalmology studies in such journals to promote best neuro-ophthalmic practices among all clinicians., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery., Methods: We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis., Results: From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3-2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%-23.2%) at 3 months, 24.4% (17.7%-30.6%) at 6 months, 30.1% (22.8%-36.7%) at 12 months and 35.3% (27.6%-42.2%) at 18 months., Conclusions: In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Assessment of the certainty of evidence (CoE) from network meta-analysis is critical to convey the strength of inferences for clinical decision-making. Both the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group (GWG) and the Confidence in Network Meta-Analysis (CINeMA) framework have been designed to assess the CoE of treatment effects informed by network meta-analysis; however, the concordance of results is uncertain., Study Design and Setting: We assessed the CoE for treatment effects of individual opioids on pain relief and physical functioning from a network meta-analysis for chronic noncancer pain using the GWG approach and the CINeMA framework. Both approaches evaluate the CoE as high, moderate, low or very low. We quantified the number of discrepant CoE ratings between approaches and the magnitude of the difference (ie, one level, two levels, or three levels)., Results: Across 105 comparisons among individual opioids for pain relief, the GWG and CINeMA approaches provided different CoE ratings in 34% of cases (36 of 105). Across 66 comparisons for physical functioning, there was discordance in 17% of cases (11 of 66). All discrepancies were separated by one level. The CINeMA framework typically provided lower CoE ratings compared to the GWG approach, predominantly because of differences in the assessment of transitivity and heterogeneity., Conclusion: Our findings suggest there are differences between the CoE ratings provided by the GWG and CINeMA approaches when applied to network meta-analyses. Further research is needed to replicate or refute our findings in other network meta-analyses and assess the implications for clinical decision-making., Competing Interests: Declaration of competing interest BS and GHG are members of the GRADE working group. GHG is a member of the JCE Editorial Board. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the tumor microenvironment, and improve effectiveness of other therapies. Observational studies have demonstrated variable effects from statin therapy on oncologic outcomes in these patients. As such, we aimed to pool previous data via a systematic review and meta-analysis to elucidate the impact of concurrent statin use on oncologic outcomes for patients with TNBC. Medline, EMBASE, CENTRAL, and PubMed were systematically searched from inception through to June 2022. Studies were included if they compared patients with TNBC receiving and not receiving statin therapy concurrently with oncologic treatment for curative intent in terms of recurrence and survival in a non-metastatic setting. The primary outcomes were 5-year disease-free survival (DFS) and 5-year overall survival (OS). A pairwise meta-analyses was performed using inverse variance random effects. Risk of bias was assessed with the ROBINS-I and the GRADE approach was conducted to assess quality of evidence. From 4014 citations, 5 studies with 625 patients on statin therapy and 2707 patients not on statin therapy were included. There was a significant increase in 5-year DFS for patients on statin therapy compared to patients not on statin therapy (OR 1.44, 95% CI 1.04-1.98, P = .03). No significant difference was noted in 5-year OS between the 2 groups (OR 1.12, 95% CI 0.86-1.47, P = .40). Included studies were at moderate-to-high risk of bias. The GRADE quality of evidence was very low. This review presents very low-quality evidence that concurrent use of statins with oncologic treatment may potentially improve long-term DFS for patients with TNBC undergoing curative intent therapy. Future research by way of large, prospective study is required to further clarify the clinical utility of statins on patients undergoing treatment for TNBC., Competing Interests: Disclosures 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 © 2023 Elsevier Inc. All rights reserved.)

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic disorder associated with a severe deficiency of ADAMTS-13-the protease that cleaves von Willebrand factor. Plasma therapy is the current standard of care for managing acute episodes of TTP, which involves removing patient plasma and replacing it with donor plasma to raise the level of ADAMTS-13 activity. Recently, therapies aimed at replacing ADAMTS-13 have been investigated as possible substitutes or add-ons to plasma therapy for congenital and immune-mediated TTP. Enzyme replacement therapy provides recombinant ADAMTS-13 via intravenous (i.v.) infusion to restore enzyme activity. Recombinant ADAMTS-13-loaded platelets localize to the site of thrombus formation in a more concentrated manner than enzyme replacement or plasma therapy. ADAMTS-13-encoding messenger RNA aims to induce a steady supply of secreted protein and gene therapy is a potentially curative strategy. Overall, targeted ADAMTS-13 replacement therapies may provide better outcomes than plasma therapy by achieving higher levels of ADAMTS-13 activity and a more sustained response with fewer adverse events. Herein, we describe targeted ADAMTS-13 replacement therapies for the treatment of TTP and discuss the advantages and limitations of each approach., Competing Interests: Declaration of competing interests None of the authors have any competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Reporting bias refers to the phenomenon in which the reporting of research findings is influenced by the nature of the results. Without the totality of evidence, clinical practice may be misguided. The objective of this work was to examine the extent of reporting bias in clinical trials of breast reconstruction surgery., Methods: We searched and extracted data from all completed breast reconstruction clinical trials published in ClinicalTrials.gov from database inception to August 2020. Investigators sought to identify published full manuscripts of the registered trials. The primary outcome was classified as positive or nonpositive and trials were classified as industry or nonindustry funded. Time to publication in a peer-reviewed journal was computed and compared using time-to-event analysis. Trial characteristics associated with publication were evaluated using logistic regression., Results: A total of 156 clinical trials were identified, of which, 53 trials were published. The median time to publication was 22 months (IQR, 13-35 months). Industry-funded studies were associated with a longer time to publication (HR = 2.4, p = 0.023) and publication in lower-impact journals (OR = 3.7, p = 0.048). Randomized clinical trials were associated with faster times to publication than nonrandomized studies (aHR = 3.2, p = 0.030). Statistical significance and the effect size were not associated with time to publication., Conclusions: We found no evidence that industry-funded trials were more likely to report a positive primary outcome. However, industry-funded trials were associated with a longer time to publication and publication in lower-impact journals., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: Gender and racial diversity in academic Canadian departments of obstetrics and gynecology (OBGYN) have not been previously described. We examined gender representation in leadership in academic OBGYN departments and gynecologic oncology (GO) divisions, and determined factors predictive of leadership and promotion including racialized status., Methods: This cross-sectional study of Canadian residency-affiliated academic OBGYN departments queried institutional websites in January 2021 to compile a list of academic faculty. Subjective gender was assessed using photographs and pronouns, and racialized status was determined using photographs. Logistic regression analyses determined predictive factors for leadership roles. Fassiotto et al. rank equity indices (REI) and Hofler et al. representation ratios were calculated., Results: Within 16 Canadian institutions there were 354 (33.6%) men and 699 (66.4%) women, with 18.3% racialized faculty. Men were more likely to reach full professorship (P < 0.00001) and leadership positions of department chair, vice-chair or division head (P = 0.01). Representation ratios for women in OBGYN were <1 for all administrative leadership positions, and pairwise comparisons of the probability of promotion for women OBGYNs using REI reveal significant disparities between senior and junior administrative leadership and professorial ranks. Racialized physicians were less likely to have attained full professorship (P = 0.002). Ninety-seven academic GOs were identified: 68 (70.1%) were women, 17 (17.5%) racialized. Seven GO divisions (44%) had no racialized members. On multivariate analysis, only year of completion of fellowship was predictive of leadership., Conclusion: In academic Canadian OBGYN departments women are underrepresented in leadership and full professor positions. Racialized faculty are underrepresented in full professorship., (Copyright © 2024 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer., Objectives: To describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status., Methods: We conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge., Results: Patients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor., Conclusions: Active cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures., Competing Interests: Declaration of competing interests J.R. Shaw has received in-kind laboratory support from Diagnostica Stago. T-F. Wang reports research funding from Leo Pharma and advisory honoraria from Valeo Pharma. Dr. Spyropoulos has received research support from Boehringer Ingelheim and Janssen, and consulting fees from Janssen, Bristol-Meyer Squibb/Pfizer Alliance, Sanofi, Alexion, Boehringer Ingelheim, Bayer, Roche Diagnostics. M. Carrier has received research funding from Leo Pharma and Pfizer, in addition to honoraria from BMS, Valeo Pharma, Leo Pharma, Sanofi, and Servier. J. Douketis has conducted consultancy/advisory board work for AstraZeneca, Cytosorb, PhaseBio, Servier, Leo Pharma and Pfizer. N. Li, J. Abdulrehman, S. Frosi Stella, M. St John, J. Nixon and S. Schulman declare no relevant conflicts of interest., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal semi-dominant lipid metabolism disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. The objective of this study was to investigate sex-differences in the treatment and outcomes of patients with HoFH., Methods: We examined clinical characteristics, lipid-lowering therapy (LLT), and cardiovascular events using descriptive statistics of patients in the Canadian HoFH registry. Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, non-fatal myocardial infarction, and stroke. Sex differences between continuous and categorical variables were analyzed using Mann-Whitney U test and Fisher's Exact test, respectively., Results: This study included 48 patients (27 (56%) female). The median age at diagnosis in females was 14.0 (interquartile range (IQR) 9.0-30.0) and in males was 8.0 (IQR 2.0-23.0) (p = 0.07). Baseline clinical characteristics were comparable between both sexes. The median baseline LDL-C was 12.7 mmol/L (10.0-18.3) in females and 15.3 (10.5-20.0) in males (p = 0.51). Follow up LDL-C levels were 7.6 mmol/L (IQR 4.8-11.0) in females and 6.3 (IQR 4.6-7.5) in males (p = 0.1). Most patients were taking 3 or more LLTs, with comparable proportions in both sexes (p = 0.26). Apheresis was similar in both sexes, 14 (51.8%) vs. 10 (47.6%) (p = 0.2). Over a mean of 10 years of follow-up, MACE occurred in 3 females (11.1%) and 4 males (19.1%) (p = 0.2)., Conclusion: Lipid levels and treatment were similar between sexes. MACE occurred in similar proportions between sexes, indicating that HoFH offsets the inherently lower cardiovascular risk in pre-menopausal females. Further investigation into sex-differences in HoFH in larger sample sizes is warranted., (Copyright © 2024. Published by Elsevier Inc.)

Background: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications., Methods: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates., Results: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty)., Conclusion: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Solution NMR spectroscopy of large protein systems is hampered by rapid signal decay, so most multidimensional studies focus on long-lived 1 H- 13 C magnetization in methyl groups and/or backbone amide 1 H- 15 N magnetization in an otherwise perdeuterated environment. Herein we demonstrate that it is possible to biosynthetically incorporate additional 1 H- 12 C groups that possess long-lived magnetization using cost-effective partially deuterated or unlabeled amino acid precursors added to Escherichia coli growth media. This approach is applied to the outer membrane enzyme PagP in membrane-mimetic dodecylphosphocholine micelles. We were able to obtain chemical shift assignments for a majority of side chain 1 H positions in PagP using nuclear Overhauser enhancements (NOEs) to connect them to previously assigned backbone 1 H- 15 N groups and newly assigned 1 H- 13 C methyl groups. Side chain methyl-to-aromatic NOEs were particularly important for confirming that the amphipathic α-helix of PagP packs against its eight-stranded β-barrel, as indicated by previous X-ray crystal structures. Interestingly, aromatic NOEs suggest that some aromatic residues in PagP that are buried in the membrane bilayer are highly mobile in the micellar environment, like Phe138 and Phe159. In contrast, Tyr87 in the middle of the bilayer is quite rigid, held in place by a hydrogen bonded network extending to the surface that resembles a classic catalytic triad: Tyr87-His67-Asp61. This hydrogen bonded arrangement of residues is not known to have any catalytic activity, but we postulate that its role is to immobilize Tyr87 to facilitate packing of the amphipathic α-helix against the β-barrel., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Hwang reports financial support was provided by NSERC., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Although cognitive dysfunction is associated with depression in adults, the link in children and adolescents is unclear. This systematic review and meta-analysis quantifies the association between depression and cognitive function in children and adolescents. Systematic searches were conducted in six databases: Child Development and Adolescent Studies, Ovid MEDLINE, Ovid Embase, Ovid APA PsycINFO, EBSCO CINAHL Plus, Scopus (last search: April 2023). Studies including measures of cognitive outcomes (memory, attention, executive function, processing speed, language) among children (≤18 years) with depression were included. The Joanna Briggs Institute Critical Appraisal Tools were used to determine study risk of bias. Random-effects meta-analyses of study outcomes were performed. Seventeen studies were included (15 were cross-sectional, 1 prospective, 1 randomized control trial). Participants (N = 13,567) were 10 to 17 years old (mean 13.8 ± 2.2 years; 60 % female). Compared with healthy controls, depressed participants had lower performance on tests of working memory (g = -0.40; 95 % CI: -0.67, -0.13), long-term memory (g = -0.48; 95 % CI: -0.72, -0.25), attention (g = -0.15; 95 % CI: -0.26, -0.04), executive function (g = -0.16; 95 % CI: -0.24, -0.08), and language (g = -0.23; 95 % CI: -0.36, -0.09). No performance differences were observed on tests of short-term memory or processing speed. Children and adolescents with depression demonstrated lower performance on tests of working and long-term memory, attention, executive function and language. These findings emphasize the importance of considering cognitive functioning among children with depression, and greater understanding of the effect of treatment on these outcomes. PROSPERO (CRD42022332064)., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)