Periprocedural Anticoagulation Management of Patients Undergoing Colonoscopy with Polypectomy.

Introduction/Objective Colonoscopy with polypectomy is an integral component of colorectal cancer screening. There are limited data and consensus on periprocedural anticoagulation management, especially regarding bleeding risk with uninterrupted anticoagulation and thromboembolic risk with interruption. Our aim was to determine the incidence of bleeding and thromboembolic complications among colon screening participants undergoing colonoscopy following implementation of a novel patient care pathway for standardized periprocedural anticoagulation management. Methods We conducted a retrospective study including all participants (age 50-74) on an oral anticoagulant (e.g., vitamin K antagonists, direct oral anticoagulants) referred to the British Columbia Colon Screening Program for colonoscopy following abnormal fecal immunochemical test in a 6-month period (March-August 2022). Data relating to their specific periprocedural anticoagulant management and colonoscopy results including method of polypectomy were obtained. Primary outcomes were major bleeding and arterial or venous thromboembolic events from time of oral anticoagulant interruption until 14 days of postcolonoscopy. Secondary outcomes included nonmajor and minor bleeding, acute coronary syndrome, emergency room visit, hospital admission, and death due to any cause. Results Over the 6-month period, 162 participants completed standardized periprocedural anticoagulation management, colonoscopy ± polypectomy, and 14-day follow-up. One (0.6%) had a major bleeding event and one (0.6%) had an arterial thromboembolic event. Conclusions A novel patient care pathway for standardized periprocedural anticoagulation management with a multidisciplinary team is associated with low rates of major bleeding and thrombotic complications after colonoscopy with polypectomy.

Anticoagulation stewardship: Improving adherence to clinical guidelines and reducing overuse of venous thromboembolism prophylaxis in hospitalized medical patients.

Adherence to guideline recommendations for venous thromboembolism prophylaxis (VTE) in hospitalized medical patients is suboptimal despite national policies and institutional interventions. The aim of this quality improvement project was to improve adherence to guidelines and decrease the overuse of VTE prophylaxis in order to reduce the institutional cost for heparins. A multidisciplinary anticoagulation stewardship program (ACSP) using the audit and feedback strategy was implemented on the medicine inpatient units at a teaching hospital in Canada. The primary outcome measure was a comparison, pre and post introduction of the ACSP, of the costs per 6-month period for prophylactic dose enoxaparin and unfractionated heparin on the medicine units. The balancing measures were the 90-day VTE rate and major bleeding rate during the hospitalization. Six months after the implementation of the ACSP, the cost was decreased by >50 % without any observed negative impact on patient safety. This study demonstrates the potential for anticoagulation stewardship programs to optimize the use of VTE prophylaxis and reduce the associated costs and risks.

Synthetic BZLF1-targeted transcriptional activator for efficient lytic induction therapy against EBV-associated epithelial cancers.

The unique virus-cell interaction in Epstein-Barr virus (EBV)-associated malignancies implies targeting the viral latent-lytic switch is a promising therapeutic strategy. However, the lack of specific and efficient therapeutic agents to induce lytic cycle in these cancers is a major challenge facing clinical implementation. We develop a synthetic transcriptional activator that specifically activates endogenous BZLF1 and efficiently induces lytic reactivation in EBV-positive cancer cells. A lipid nanoparticle encapsulating nucleoside-modified mRNA which encodes a BZLF1-specific transcriptional activator (mTZ3-LNP) is synthesized for EBV-targeted therapy. Compared with conventional chemical inducers, mTZ3-LNP more efficiently activates EBV lytic gene expression in EBV-associated epithelial cancers. Here we show the potency and safety of treatment with mTZ3-LNP to suppress tumor growth in EBV-positive cancer models. The combination of mTZ3-LNP and ganciclovir yields highly selective cytotoxic effects of mRNA-based lytic induction therapy against EBV-positive tumor cells, indicating the potential of mRNA nanomedicine in the treatment of EBV-associated epithelial cancers.

Factors that modulate platelet reactivity as measured by 5 assay platforms in 3429 individuals.

Background: Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing "one-size-fits-all" approach in the interpretation of measures of platelet reactivity, with arbitrary cutoffs often derived from healthy volunteer responses. Objectives: Our aim was to compare well-used platelet reactivity assays. Methods: Blood and platelet-rich plasma obtained from the Framingham Heart Study (N = 3429) were assayed using a range of agonists in 5 platelet assays: light transmission aggregometry, Optimul aggregometry, Multiplate impedance aggregometry (Roche Diagnostics), Total Thrombus-Formation Analysis System, and flow cytometry. Using linear mixed-effect models, we determined the contribution of preanalytical and technical factors that modulated platelet reactivity traits. Results: A strong intra-assay correlation of platelet traits was seen in all assays, particularly Multiplate velocity (r = 0.740; ristocetin vs arachidonic acid). In contrast, only moderate interassay correlations were observed (r = 0.375; adenosine diphosphate Optimul Emax vs light transmission aggregometry large area under the curve). As expected, antiplatelet drugs strongly reduced platelet responses, with aspirin use primarily targeting arachidonic acid-induced aggregation, and explained substantial variance (ß = -1.735; P = 4.59 × 10-780; variance proportion = 46.2%) and P2Y12 antagonists blocking adenosine diphosphate responses (ß = -1.612; P = 6.75 × 10-27; variance proportion = 2.1%). Notably, female sex and older age were associated with enhanced platelet reactivity. Fasting status and deviations from standard venipuncture practices did not alter platelet reactivity significantly. Finally, the agonist batch, phlebotomist, and assay technician (more so for assays that require additional sample manipulation) had a moderate to large effect on measured platelet reactivity. Conclusion: Caution must be exercised when extrapolating findings between assays, and the use of standard ranges must be medication-specific and sex-specific at a minimum. Researchers should also consider preanalytical and technical variables when designing experiments and interpreting platelet reactivity measures.

MFGE8 in exosomes derived from mesenchymal stem cells prevents esophageal stricture after endoscopic submucosal dissection in pigs.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the current standard treatment for early-stage esophageal neoplasms. However, the postoperative esophageal stricture after extensive mucosal dissection remains a severe challenge with limited effective treatments available. In this study, we introduced a chitosan/gelatin (ChGel) sponge encapsulating the adipose mesenchymal stem cells (ADMSCs)-derived exosomes (ChGelMSC-Exo) for the prevention of esophageal stenosis after ESD in a porcine model. RESULTS: Pigs were randomly assigned into (1) ChGelMSC-Exo treatment group, (2) ChGelPBS group, and (3) the controls. Exosome treatments were applied immediately on the day after ESD as well as on day 7. Exosome components crucial for wound healing were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and small RNA sequencing. ChGelMSC-Exo treatment significantly reduced mucosal contraction on day 21, with less fiber accumulation and inflammatory infiltration, and enhanced angiogenesis when compared with the control and ChGelPBS groups. The anti-fibrotic effects following MSC-Exo treatment were further found to be associated with the anti-inflammatory M2 polarization of the resident macrophages, especially within the M2b subset characterized by the reduced TGFß1 secretion, which sufficiently inhibited inflammation and prevented the activation of myofibroblast with less collagen production at the early stage after ESD. Moreover, the abundant expression of exosomal MFGE8 was identified to be involved in the transition of the M2b-macrophage subset through the activation of MFGE8/STAT3/Arg1 axis. CONCLUSIONS: Our study demonstrates that exosomal MFGE8 significantly promotes the polarization of the M2b-macrophage subset, consequently reducing collagen deposition. These findings suggest a promising potential for MSC-Exo therapy in preventing the development of esophageal stricture after near-circumferential ESD.

Walking the talk for dementia: A unique immersive, embodied, and multi-experiential initiative.

Coping with dementia requires an integrated approach encompassing personal, health, research, and community domains. Here we describe "Walking the Talk for Dementia," an immersive initiative aimed at empowering people with dementia, enhancing dementia understanding, and inspiring collaborations. This initiative involved 300 participants from 25 nationalities, including people with dementia, care partners, clinicians, policymakers, researchers, and advocates for a 4-day, 40 km walk through the Camino de Santiago de Compostela, Spain. A 2-day symposium after the journey provided novel transdisciplinary and horizontal structures, deconstructing traditional hierarchies. The innovation of this initiative lies in its ability to merge a physical experience with knowledge exchange for diversifying individuals' understanding of dementia. It showcases the transformative potential of an immersive, embodied, and multi-experiential approach to address the complexities of dementia collaboratively. The initiative offers a scalable model to enhance understanding, decrease stigma, and promote more comprehensive and empathetic dementia care and research.

Normative reference values, determinants and regression equations for the incremental shuttle walk test (ISWT) in healthy Asian population aged 21 to 80 years.

BACKGROUND: The validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population. OBJECTIVES: This study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT. METHODS: This cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE). RESULTS: 199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population. CONCLUSIONS: This study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation.

Trends among platelet function, arterial calcium, and vascular function measures.

Arterial tonometry and vascular calcification measures are useful in cardiovascular disease (CVD) risk assessment. Prior studies found associations between tonometry measures, arterial calcium, and CVD risk. Activated platelets release angiopoietin-1 and other factors, which may connect vascular structure and platelet function. We analyzed arterial tonometry, platelet function, aortic, thoracic and coronary calcium, and thoracic and abdominal aorta diameters measured in the Framingham Heart Study Gen3/NOS/OMNI-2 cohorts (n = 3,429, 53.7% women, mean age 54.4 years ±9.3). Platelet reactivity in whole blood or platelet-rich plasma was assessed using 5 assays and 7 agonists. We analyzed linear mixed effects models with platelet reactivity phenotypes as outcomes, adjusting for CVD risk factors and family structure. Higher arterial calcium trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity. Characteristic impedance (Zc) and central pulse pressure positively trended with various platelet traits, while pulse wave velocity and Zc negatively trended with collagen, ADP, and epinephrine traits. All results did not pass a stringent multiple test correction threshold (p < 2.22e-04). The diameter trends were consistent with lower shear environments invoking less platelet reactivity. The vessel calcium trends were consistent with subclinical atherosclerosis and platelet activation being inter-related.

What is the context? Prior research has reported that measures of vascular system-influencing proteins such as angiopoietin-2, arterial calcium plaque formation, and arterial stiffness assessed by tonometry are associated with CVD risk.Since activated platelets produce and release vascular proteins like angiopoietin when activated, and microparticles that interact with endothelium, release of the foregoing mediators could provide one way in which vascular structure and platelet function influence each other.To our knowledge, no prior studies have directly investigated associations between these measures in a large sample. This investigation relates platelet function to arterial tonometry, aortic and arterial diameter, and arterial calcium measures in the Framingham Heart Study (FHS) Gen3/NOS/OMNI-2 cohorts (n = 3,429).What's new? Generally, higher arterial calcium measures trended with higher platelet reactivity, whereas larger aortic diameters trended with lower platelet reactivity.Arterial tonometry measures had positive and negative trends with platelet functions, including platelet measures with opposite relations to negative-inverse carotid-femoral pulse wave velocity (niCFPWV) and characteristic impedance (Zc). All tonometry, calcium, and diameter results did not reach a more stringent multiple testing threshold (p < 2.22e-04).What's the impact? The aortic diameter trends are consistent with lower shear stress invoking less platelet reactivity.The vessel calcium trends are consistent with increased vascular calcium buildup that could provoke platelet activation, thereby contributing to increased blood clot risk. Conversely, increased platelet activation could contribute to increased inflammation and thrombosis, leading to calcification in the arterial wall.

Technology Affordance in an Information and Communication Technology Delivered Group Psychotherapy and Exercise Program for Older People With Depressive Symptoms: A Multiple Triangulation Qualitative Study.

Background and Objectives: Health and mental health interventions, such as psychotherapy and exercise programs, delivered via information and communication technology (ICT) may improve service access. However, adjustment among older people and in synchronous group interventions is more challenging. Technology affordance concerns the possibilities engendered by technology for various users and purposes and can help understand challenges in ICT-delivered groups and identify possible solutions. Research Design and Methods: Adopting a multiple triangulation approach, we observed ICT-delivered groups of acceptance and commitment therapy and exercise for older people with depressive symptoms, conducted focus groups with older people who had received group psychotherapy with or without an exercise component, and obtained clinical notes from interventionists. We conducted a thematic analysis of the observation notes, focus group transcriptions, and clinical notes. Results: Four focus groups were conducted with 22 participants (mean age = 72.6 years, standard deviation = 7.2, 86% female). We identified 3 challenges: (1) seeing-be seen dilemma, (2) speaking-hearing dilemma, and (3) blurred therapy-home boundary, and 2 solutions: (1) maneuvering layouts and collaborative tools, and (2) cross-platform mediated strategies. Participants struggled to observe the interventionist while simultaneously demonstrating their posture in front of a camera. Remaining silent and moderated turn-taking allowed for clearer hearing but limited interactions. Interruptions from the background environment and intersections of family living spaces disrupted audio-visual communication and jeopardized the sense of security. As a solution, interventionists maneuvered layouts and collaborative tools on teleconferencing applications to achieve intervention goals and provided support through different media. Discussion and Implications: The identified challenges and potential solutions can be understood from interactivity, portability, temporality, persistence, and multimediality. Technology affordance can guide ICT-delivered group design by matching the affordance of various technologies and communication media with the characteristics of the intervention and users to enhance efficacy and avoid an unnecessary digital divide.

Alcohol intake including wine drinking is associated with decreased platelet reactivity in a large population sample.

BACKGROUND: Alcohol consumption is linked to decreased platelet function. Whether this link is dependent on sex or type of beverage remains unclear. METHODS: Cross-sectional data were obtained from the Framingham Heart Study (N = 3427). Alcohol consumption was assessed by using standardized medical history and Harvard semi-quantitative food frequency questionnaires. Five bioassays measured 120 platelet reactivity traits across agonists in whole-blood and platelet-rich plasma samples. Linear mixed-effects models adjusted for age, sex and aspirin use, hypertension, body mass index, cholesterol, high-density lipoprotein, triglycerides, smoking and diabetes evaluated associations between platelet reactivity and alcohol consumption. Beta effects, the regression coefficients that estimate the amount of change in each unit of the predictor variable whereas all other predictor variables remain fixed, for heavy alcohol consumption were compared with effects of aspirin use. RESULTS: Alcohol consumption was associated with decreased platelet reactivity, with more associations among wine and liquor compared with beer. Many platelet-alcohol associations in the full sample (86%, P < 0.01) had larger effect sizes in females. Lower light transmission aggregometry adenosine diphosphate (1.82 µM) maximum aggregation (P = 2.6E-3, 95% CI = -0.07, -0.02, ß = -0.042) and area under the curve (P = 7.7E-3, 95% CI = -0.07, -0.01, ß = -0.039) were associated with white wine consumption; however, red wine had no associations with platelet reactivity. The effect of aspirin use was on average 11.3 (±4.0) times greater than that of heavy drinking in our full sample. CONCLUSIONS: We confirm associations between alcohol consumption and decreased platelet reactivity. Effects appeared larger for liquor and wine intake and in our female cohort. Red wine consumption is not associated with lower platelet function, contrasting with prior population studies. Although we report an inhibitory relationship between alcohol intake and platelet function, these effects appear much smaller than that of aspirin use.

Renal Function Underpins the Cyclooxygenase-2: Asymmetric Dimethylarginine Axis in Mouse and Man.

Introduction: Through the production of prostacyclin, cyclooxygenase (COX)-2 protects the cardiorenal system. Asymmetric dimethylarginine (ADMA), is a biomarker of cardiovascular and renal disease. Here we determined the relationship between COX-2/prostacyclin, ADMA, and renal function in mouse and human models. Methods: We used plasma from COX-2 or prostacyclin synthase knockout mice and from a unique individual lacking COX-derived prostaglandins (PGs) because of a loss of function mutation in cytosolic phospholipase A2 (cPLA2), before and after receiving a cPLA2-replete transplanted donor kidney. ADMA, arginine, and citrulline were measured using ultra-high performance liquid-chromatography tandem mass spectrometry. ADMA and arginine were also measured by enzyme-linked immunosorbent assay (ELISA). Renal function was assessed by measuring cystatin C by ELISA. ADMA and prostacyclin release from organotypic kidney slices were also measured by ELISA. Results: Loss of COX-2 or prostacyclin synthase in mice increased plasma levels of ADMA, citrulline, arginine, and cystatin C. ADMA, citrulline, and arginine positively correlated with cystatin C. Plasma ADMA, citrulline, and cystatin C, but not arginine, were elevated in samples from the patient lacking COX/prostacyclin capacity compared to levels in healthy volunteers. Renal function, ADMA, and citrulline were returned toward normal range when the patient received a genetically normal kidney, capable of COX/prostacyclin activity; and cystatin C positively correlated with ADMA and citrulline. Levels of ADMA and prostacyclin in conditioned media of kidney slices were not altered in tissue from COX-2 knockout mice compared to wildtype controls. Conclusion: In human and mouse models, where renal function is compromised because of loss of COX-2/PGI2 signaling, ADMA levels are increased.

Assessment of Platelet Function by High-Throughput Screening Light Transmission Aggregometry: Optimul Assay.

Platelet function testing is critical in the diagnosis of bleeding disorders and allows monitoring of antiplatelet therapy. The gold standard assay, light transmission aggregometry (LTA), was developed 60 years ago and remains widely used worldwide. It requires, however, access to expensive equipment and is time-consuming, and the interpretation of results requires evaluation by an experienced investigator. It also suffers from a lack of standardization, resulting in widely variable results between laboratories. 96-well plate-based Optimul aggregometry utilizes the same principles of LTA and aims to standardize agonist concentrations with the development of 96-well plates which are precoated with 7 concentrations of each lyophilized agonist (arachidonic acid, adenosine diphosphate, collagen, epinephrine, TRAP-6 amide, and U46619) and stored at ambient room temperature (20-25 °C) for up to 12 weeks. For platelet function testing, 40 µL of platelet-rich plasma is added to each well, and the plate is placed onto a plate shaker, after which platelet aggregation is determined by changes in light absorbance. This method reduces the blood volume required and allows for in-depth platelet function analysis without specialist training, or the need to purchase expensive, dedicated equipment.

The association between platelet reactivity and lipoprotein levels in Framingham Heart Study participants.

BACKGROUND: Hypertriglyceridemia is an independent risk factor for major adverse cardiovascular events, though the mechanisms linking triglycerides and platelet function with thrombosis, remain elusive. The aim of this study was to assess the association between platelet function and triglyceride levels. METHODS: We included participants from the Framingham Heart Study Third Generation cohort, OMNI, and New Offspring Spouse cohort who attended the third examination cycle (2016-2019). Eligible participants were categorized into four triglyceride subgroups. RESULTS: The study comprised a total of 1897 (55.53 %) participants with normal TG levels; 883 (25.85 %) participants with high-normal TGs; 378 (11.07 %) with borderline high TGs; and 258 (7.55 %) participants with hypertriglyceridemia. After adjusting for age, sex, alcohol consumption, aspirin, statin and P2Y12 inhibitors, the levels of ADP-induced platelet aggregation were inversely associated with total cholesterol levels (P < 0.0001). Platelet disaggregation was associated with low-density lipoprotein and high-density lipoprotein cholesterol levels (P < 0.0001). Lastly, in a shear-stress chamber assay mimicking arterial flow velocities, TG levels in the normal-high group were associated with increased levels of collagen-dependent thrombogenicity (ß = 24.16, SE = 6.65, P < 0.0001). CONCLUSION: Triglyceride levels are associated with altered platelet activation and aggregation. Furthermore, increased platelet-driven thrombogenicity is directly associated with triglyceride levels after adjusting for medications and other covariates.

Innovative Care for Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Use of Bedside Intestinal Ultrasound to Optimize Management.

Background: The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods: We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results: A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn's disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion: Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.

Examination Under Anesthesia May Not Be Universally Required Prior to Anti-TNF Therapy in Perianal Crohn's Disease: A Comparative Cohort Study.

BACKGROUND: Multidisciplinary care involving exam under anesthesia (EUA) and tumor necrosis factor (TNF) inhibitors is recommended for perianal Crohn's disease. However, the impact of this combined approach is not well established. METHODS: We performed a comparative cohort study between 2009 and 2019. Patients with perianal Crohn's disease treated with EUA before anti-TNF therapy (combined modality therapy) were compared with anti-TNF alone. The primary outcome was fistula closure assessed clinically. Secondary outcomes included subsequent local surgery and fecal diversion. Multivariable analysis adjusted for abscesses, concomitant immunomodulators, and time to anti-TNF initiation was performed. RESULTS: Anti-TNF treatment was initiated 188 times in 155 distinct patients: 66 (35%) after EUA. Abscesses (50% vs 15%; P < .001) and concomitant immunomodulators (64% vs 50%; P = .07) were more common in the combined modality group, while age, smoking status, disease duration, and intestinal disease location were not significantly different. Combined modality therapy was not associated with higher rates of fistula closure at 3 (adjusted odds ratio [aOR], 0.7; 95% confidence interval [CI], 0.3-1.8), 6 (aOR, 0.8; 95% CI, 0.4-2.0) and 12 (aOR, 1.0; 95% CI, 0.4-2.2) months. After a median follow-up of 4.6 (interquartile range, 5.95; 2.23-8.18) years, combined therapy was associated with subsequent local surgical intervention (adjusted hazard ratio, 2.2; 95% CI, 1.3-3.6) but not with fecal diversion (adjusted hazard ratio, 1.3; 95% CI, 0.45-3.9). Results remained consistent when excluding patients with abscesses and prior biologic failure. CONCLUSIONS: EUA before anti-TNF therapy was not associated with improved clinical outcomes compared with anti-TNF therapy alone, suggesting that EUA may not be universally required. Future prospective studies controlling for fistula severity are warranted.

This comparative cohort study found that an exam under anesthesia before initiation of anti-tumor necrosis factor therapy in perianal Crohn's disease was not associated with higher rates of fistula closure, suggesting that an exam under anesthesia may not be universally required in patients with perianal Crohn's disease.

Empathy as a crucial skill in disrupting disparities in global brain health.

Brain health refers to the state of a person's brain function across various domains, including cognitive, behavioral and motor functions. Healthy brains are associated with better individual health, increased creativity, and enhanced productivity. A person's brain health is intricately connected to personal, social and environmental factors. Racial, ethnic, and social disparities affect brain health and on the global scale these disparities within and between regions present a hurdle to brain health. To overcome global disparities, greater collaboration between practitioners and healthcare providers and the people they serve is essential. This requires cultural humility driven by empathy. Empathy is a core prosocial value, a cognitive-emotional skill that helps us understand ourselves and others. This position paper aims to provide an overview of the vital roles of empathy, cooperation, and interdisciplinary partnerships. By consciously integrating this understanding in practice, leaders can better position themselves to address the diverse challenges faced by communities, promote inclusivity in policies and practices, and further more equitable solutions to the problem of global brain health.

How safe are paediatric emergency departments? A national prospective cohort study.

BACKGROUND: Despite the high number of children treated in emergency departments, patient safety risks in this setting are not well quantified. Our objective was to estimate the risk and type of adverse events, as well as their preventability and severity, for children treated in a paediatric emergency department. METHODS: Our prospective, multicentre cohort study enrolled children presenting for care during one of 168 8-hour study shifts across nine paediatric emergency departments. Our primary outcome was an adverse event within 21 days of enrolment which was related to care provided at the enrolment visit. We identified 'flagged outcomes' (such as hospital visits, worsening symptoms) through structured telephone interviews with patients and families over the 21 days following enrolment. We screened admitted patients' health records with a validated trigger tool. For patients with flags or triggers, three reviewers independently determined whether an adverse event occurred. RESULTS: We enrolled 6376 children; 6015 (94%) had follow-up data. Enrolled children had a median age of 4.3 years (IQR 1.6-9.8 years). One hundred and seventy-nine children (3.0%, 95% CI 2.6% to 3.5%) had at least one adverse event. There were 187 adverse events in total; 143 (76.5%, 95% CI 68.9% to 82.7%) were deemed preventable. Management (n=98, 52.4%) and diagnostic issues (n=36, 19.3%) were the most common types of adverse events. Seventy-nine (42.2%) events resulted in a return emergency department visit; 24 (12.8%) resulted in hospital admission; and 3 (1.6%) resulted in transfer to a critical care unit. CONCLUSION: In this large-scale study, 1 in 33 children treated in a paediatric emergency department experienced an adverse event related to the care they received there. The majority of events were preventable; most were related to management and diagnostic issues. Specific patient populations were at higher risk of adverse events. We identify opportunities for improvement in care.

Guidance for Cardiopulmonary Resuscitation of Children With Suspected or Confirmed COVID-19.

This article aims to provide guidance to health care workers for the provision of basic and advanced life support to children and neonates with suspected or confirmed coronavirus disease 2019 (COVID-19). It aligns with the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular care while providing strategies for reducing risk of transmission of severe acute respiratory syndrome coronavirus 2 to health care providers. Patients with suspected or confirmed COVID-19 and cardiac arrest should receive chest compressions and defibrillation, when indicated, as soon as possible. Because of the importance of ventilation during pediatric and neonatal resuscitation, oxygenation and ventilation should be prioritized. All CPR events should therefore be considered aerosol-generating procedures. Thus, personal protective equipment (PPE) appropriate for aerosol-generating procedures (including N95 respirators or an equivalent) should be donned before resuscitation, and high-efficiency particulate air filters should be used. Any personnel without appropriate PPE should be immediately excused by providers wearing appropriate PPE. Neonatal resuscitation guidance is unchanged from standard algorithms, except for specific attention to infection prevention and control. In summary, health care personnel should continue to reduce the risk of severe acute respiratory syndrome coronavirus 2 transmission through vaccination and use of appropriate PPE during pediatric resuscitations. Health care organizations should ensure the availability and appropriate use of PPE. Because delays or withheld CPR increases the risk to patients for poor clinical outcomes, children and neonates with suspected or confirmed COVID-19 should receive prompt, high-quality CPR in accordance with evidence-based guidelines.

A pilot study assessing the implementation of 96-well plate-based aggregometry (Optimul) in Australia.

Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k2)=0.84], supporting its role as a useful screening tool in the assessment of platelet function. Optimul assay performance was quick and the methodology simple, requiring no specialised training or resources to be implemented at either the regional or metropolitan laboratory. Widespread implementation, particularly in regional laboratories within Australia where specialised platelet function testing is unavailable, has the potential to drastically improve the inequity of access to such services.

A year of COVID-19 GWAS results from the GRASP portal reveals potential genetic risk factors.

Host genetic variants influence the susceptibility and severity of several infectious diseases, and the discovery of genetic associations with coronavirus disease 2019 (COVID-19) phenotypes could help to develop new therapeutic strategies to decrease its burden. Between May 2020 and June 2021, we used COVID-19 data released periodically by UK Biobank and performed 65 genome-wide association studies in up to 18 releases of COVID-19 susceptibility (n = 18,481 cases in June 2021), hospitalization (n = 3,260), severe outcomes (n = 1,244), and deaths (n = 1,104), stratified by sex and ancestry. In coherence with previous studies, we observed two independent signals at the chr3p21.31 locus (rs73062389-A, odds ratio [OR], 1.21 (P = 4.26 × 10-15) and rs71325088-C, OR, 1.62 [P = 2.25 × 10-9]) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A; OR, 1.10; P = 3.30 × 10-12), suggesting an increased risk of infection in non-O blood groups carriers. Additional signals at the APOE (associated with severity and death) LRMDA (susceptibility in non-European) and chr2q32.3 (susceptibility in women) loci were also identified, but did not replicate in independent datasets. We then devised an approach to extract variants suggestively associated (P < 10-5), exhibiting an increase in significance over time. When applied to the susceptibility, hospitalization and severity analyses, this approach revealed the known RPL24, DPP9, and MAPT loci, respectively, among hundreds of other signals. These results, freely available on the GRASP portal, provide insights on the genetic mechanisms involved in COVID-19 phenotypes.