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Rationale: Hospitals are increasingly utilising allied-health professionals to provide clinical triage to patients. While these positions are routinely implemented, and several observational studies have reported positive outcomes, the effectiveness of this intervention has been rarely tested in a clinical trial., Aims and Objectives: The objectives of this study were to (i) evaluate a podiatry-led orthopaedic triage service using patient-reported outcome measures (PROMs), and (ii) determine if it is cost-effective in terms of incremental cost/quality-adjusted life years (QALYs)., Methods: This pragmatic, randomised, wait-list-control trial recruited participants referred to an orthopaedic foot and ankle clinic at a tertiary-level health service. Trial registration was 31 March 2020. Participants were randomised to either immediate clinical triage (intervention) or to remain on the waiting-list (control). The primary outcome measure was change in foot pain as measured by the Manchester-Oxford Foot and Ankle Questionnaire (MOxFQ) at 6-months. Core outcome measures for chronic musculoskeletal pain were also measured and cost-effectiveness calculated., Results: One hundred and forty-eight participants were recruited, randomising 73 people to the intervention and 75 people to the control. No between-group differences in pain or demographics were detected at baseline. Foot pain as measured by the MOxFQ improved in both groups at 6-months follow-up, but no significant between-group differences were identified. Significant between-group differences, however, were detected in the patient global impression of change. Additionally, the intervention resulted in a 30% discharge rate, and is considered cost-effective, with each QALY gain costing < $30,000 in real-world scenarios., Conclusion: A clinical triage service has minimal impact on PROMS for foot and ankle pain or chronic musculoskeletal pain, but it is generally well-received, is cost-effective, and participants were more likely to report global improvement if they attended., (© 2024 John Wiley & Sons Ltd.)

Background: This systematic review aims to update and extend the findings of an earlier review on the suicidogenic impact of natural disasters., Methods: A systematic search of research published in 17 bibliographic databases was conducted (PROSPERO CRD42020216722). The review following PRISMA checklist identified 64 primary studies, published between 2012 and 2022, investigating the association between natural disasters and suicidal behaviour and ideation., Results: The majority of studies related to natural disasters in Japan, China, USA, India and Australia. Over half the studies (n = 39) investigated the impact of earthquakes. Other disasters included hurricanes, floods, tsunamis, droughts, wildfires, tornadoes and multiple disasters. Concerning suicide mortality (the most studied suicide-related outcome), there was variability in the suicidogenic impact of earthquakes depending on location, age, sex and time elapsed since the event. While suicide mortality appeared to increase following drought, investigations of hurricanes/tornadoes and floods found no evidence of a similar association. Findings relating to other suicide-related outcomes are more consistent, suggesting that exposure to droughts, hurricanes, tsunamis, floods, and other natural disasters is associated with increased risk of suicidal ideation and non-fatal suicidal behaviour. This association, however, is dependent on other factors, including the level of structural adversity in the exposed population (e.g., unemployment, poverty, food insecurity), individual vulnerabilities (e.g., physical and mental health), local resources, and availability of support., Limitations: Publications in languages other than English, French, Spanish, Italian and Portuguese may have been missed. The heterogeneity and methodological weakness of primary studies limited our ability to provide definitive responses to our research questions., Conclusions: The considerable inconsistency in the findings reported across these studies, particularly relating to suicide mortality, is noteworthy. While this may be an artefact of methodological limitations, it is possible that there are substantive ('real') differences in the impact of natural disasters on suicidal behaviour linked to the type of disaster, the socioeconomic and sociocultural context, the type of suicidal behaviour, or other explanatory factors., Competing Interests: Declaration of competing interest None., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Carbonaceous aerosols (CA), composed of black carbon (BC) and organic matter (OM), significantly impact the climate. Light absorption properties of CA, particularly of BC and brown carbon (BrC), are crucial due to their contribution to global and regional warming. We present the absorption properties of BC (b Abs,BC ) and BrC (b Abs,BrC ) inferred using Aethalometer data from 44 European sites covering different environments (traffic (TR), urban (UB), suburban (SUB), regional background (RB) and mountain (M)). Absorption coefficients showed a clear relationship with station setting decreasing as follows: TR > UB > SUB > RB > M, with exceptions. The contribution of b Abs,BrC to total absorption (b Abs ), i.e. %Abs BrC , was lower at traffic sites (11-20 %), exceeding 30 % at some SUB and RB sites. Low AAE values were observed at TR sites, due to the dominance of internal combustion emissions, and at some remote RB/M sites, likely due to the lack of proximity to BrC sources, insufficient secondary processes generating BrC or the effect of photobleaching during transport. Higher b Abs and AAE were observed in Central/Eastern Europe compared to Western/Northern Europe, due to higher coal and biomass burning emissions in the east. Seasonal analysis showed increased b Abs , b Abs,BC , b Abs,BrC in winter, with stronger %Abs BrC , leading to higher AAE. Diel cycles of b Abs,BC peaked during morning and evening rush hours, whereas b Abs,BrC , %Abs BrC , AAE, and AAE BrC peaked at night when emissions from household activities accumulated. Decade-long trends analyses demonstrated a decrease in b Abs , due to reduction of BC emissions, while b Abs,BrC and AAE increased, suggesting a shift in CA composition, with a relative increase in BrC over BC. This study provides a unique dataset to assess the BrC effects on climate and confirms that BrC can contribute significantly to UV-VIS radiation presenting highly variable absorption properties in Europe., 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. Griša Močnik, Asta Gregorič, Matic Ivančič and Martin Rigler were or are employed by the manufacturer of the instruments used in this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To analyze endophthalmitis characteristics and risks following a 25-gauge vitrectomy or microincision vitrectomy surgery (MIVS)., Design: Retrospective., Subjects: Post-MIVS endophthalmitis patients., Methods: The records of a private, retina practice and an ambulatory surgery center (ASC) were searched from January 2010-April 2024, for post-MIVS endophthalmitis cases. Data collected were age, sex, surgeon, first assistant, procedure, surgery date, surgical platform, symptom onset date, preoperative visual acuity (VA), infection presentation VA, 90-day postoperative VA, case length, vitreous substitute (balanced salt solution (BSS), gas, air, or oil), sclerotomy suture use, surgical complications, vitreous sampling culture growth, and endophthalmitis treatment. LogMar converted VAs were analyzed from preoperative to 90-day postoperative endophthalmitis. Procedures included pars plana vitrectomy (PPV) for macular pucker, vitreous opacity or hemorrhage, with endolaser, for retinal detachment (RD), and macular hole (MH). An all MIVS cohort to analyze patient sex, surgeon case load, platforms, and procedure was created for incidence and statistical calculations. A secondary comparison, April-May 2023, was performed analyzing endophthalmitis per vitreous substitute via chi-square test for independence., Main Outcome Measures: Endophthalmitis post-MIVS., Results: The ASC saw 27/24,987 (0.11%) post-MIVS endophthalmitis cases. None of the surgeries recorded intraoperative complications. Average time between surgery and presentation was 2.88+/-2.66 days. Mean VA preoperatively and 90-day postoperatively were calculated, 0.630+/-0.717 and 1.041+/-0.895 respectively (0.286+/-0.437 mean difference). Individual surgeon incidence of endophthalmitis was not found to be significant in this study. Endophthalmitis incidence per PPV is 13/5545 (0.23%) post-macular pucker, 7/4619 (0.15%) vitreous opacity or hemorrhage, 4/2350 (0.17%) endolaser, 3/9834 (0.03%) RD, and 0 (0.0%) MH (p=0.0004). Of 435 PPVs performed April-May 2023, vitreous substitutes were: 183 (42%) gas-filled, 169 (38.9%) BSS-filled, 45 (10.3%) oil-filled, and 38 (8.7%) air-filled. Of the 27 endophthalmitis cases, 23 (85.2%) used BSS, 1 (3.7%) oil-filled, and 2 (7.4%) air-filled. A significant statistical association between vitreous substitute and endophthalmitis incidence via chi-square testing (p<0.0001) was found., Conclusion: This study found a 1/910 (0.11%) incidence of endophthalmitis post-25-gauge MIVS. Both vitreous substitute and procedure type showed significant risk of endophthalmitis. While endophthalmitis risk is low overall, the potential for severe vision loss warrants further examination into contributing characteristics and risks., (Copyright © 2024. Published by Elsevier Inc.)

The prevention and treatment of fracture-related infections (FRIs) pose significant challenges in orthopaedic trauma care, with current practices predominantly relying on systemic antibiotic administration. However, locally delivered antibiotics achieve substantially higher tissue concentrations and minimise systemic side effects. Whilst extensively researched in periprosthetic joint infections (PJIs), the use of local delivery methods is increasingly prevalent in FRI prevention and treatment. Various local delivery methods such as powders, aqueous injections and carriers such as cement, bone graft, bioceramics, polymers and hydrogels have been explored. Biodegradable antibiotic carriers offer a promising alternative to non-absorbable carriers (i.e., cement), which necessitate surgical removal. There is good evidence for the use of local antibiotics in preventing and treating FRI, particularly in high-risk fractures or in treating more severe, resistant infections. Despite theoretical concerns, reports of adverse events in human studies are rare. To enhance our understanding of the safety and efficacy of these methods across various fracture patterns, further prospective randomised controlled trials are warranted. This article describes the current strategies and methodologies for FRI prevention and treatment and reviews the existing evidence base., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mills et al.)

Competing Interests: Declaration of Competing Interest None.

The prevalence of hemorrhagic diseases of the central nervous system of dogs and cats is low compared to other diseases such as neoplasia and inflammation. However, the clinical consequences can be devastating. Several etiological and localization-based classification systems have been reported for intracerebral and spinal cord hemorrhage or hematomyelia in humans but similar systems do not exist in veterinary medicine. The authors propose an etiologic classification system for both intraparenchymal hemorrhagic encephalopathy and myelopathy following a review of the literature detailing the presentation, diagnosis, therapy, and prognosis of these diseases. A summary of the investigative and therapeutic approach to these cases is also provided., Competing Interests: SP was employed by Vet Oracle Teleradiology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Santifort and Platt.)

Objective: This study evaluated changes in best-corrected visual acuity and submacular hemorrhage (SMH) resolution in eyes after a single rapid subretinal displacement surgery using subretinal balanced saline solution and sterile air without tissue plasminogen activator (tPA)., Design: A retrospective comparative interventional analysis., Participants: Twenty-six eyes with thick SMH who underwent pars plana vitrectomy and subretinal fluid displacement without tPA from 2015 and 2021 and at least 1-year of follow-up., Methods: Surgical intervention included a standard small-gauge pars plana vitrectomy with subretinal displacement using balanced saline solution with subretinal sterile air and partial gas-air fluid exchange. Main outcome measures included degree of subfoveal SMH displacement, best and final postoperative visual acuities, and adverse events. Snellen acuity was converted to logMARs for statistical analysis., Results: The most common etiology associated with thick SMH (92.3%) was neovascular age-related macular degeneration. Within 1 month postoperatively, 21 patients (80.8%) saw complete subfoveal blood displacement. Most of the SMH surgical displacements were done within 1 week of presenting symptoms. Average preoperative duration of SMH was 3.60 ± 2.78 days (range, 1-12 days). Mean logMAR best-corrected visual acuity improved from 1.63 ± 0.58 (Snellen 20/800 baseline) to 0.90 ± 0.42 letters (Snellen 20/160) at last follow-up (p = 0.001). This study's visual acuity improvement is comparable with that of prior studies using tPA. Early postoperative complications included 1 retinal detachment, 1 vitreous hemorrhage, and 1 macular hole., Conclusion: Rapid surgery with subretinal balanced saline solution-sterile air injection without tPA was found to be effective for displacement of thick SMH with retinal function, visual acuity, and corneal refractive therapy improvement., (Published by Elsevier Inc.)

The hair follicle and nail unit develop and regenerate through epithelial-mesenchymal interactions. Here, we review some of the key signals and molecular interactions that regulate mammalian hair follicle and nail formation during embryonic development and how these interactions are reutilized to promote their regeneration during adult homeostasis and in response to skin wounding. Finally, we highlight the role of some of these signals in mediating human hair follicle and nail conditions., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study of protein function and dynamics in their native cellular environment is essential for progressing fundamental science. To overcome the requirement of genetic modification of the protein or the limitations of dissociable fluorescent ligands, ligand-directed (LD) chemistry has most recently emerged as a complementary, bioorthogonal approach for labeling native proteins. Here, we describe the rational design, development, and application of the first ligand-directed chemistry approach for labeling the A 1 AR in living cells. We pharmacologically demonstrate covalent labeling of A 1 AR expressed in living cells while the orthosteric binding site remains available. The probes were imaged using confocal microscopy and fluorescence correlation spectroscopy to study A 1 AR localization and dynamics in living cells. Additionally, the probes allowed visualization of the specific localization of A 1 ARs endogenously expressed in dorsal root ganglion (DRG) neurons. LD probes developed here hold promise for illuminating ligand-binding, receptor signaling, and trafficking of the A 1 AR in more physiologically relevant environments.

Granuloprival degeneration is an uncommon form of cerebellar cortical degeneration (CCD). A 3-month-old Yorkshire Terrier and a 7-month-old Lagotto Romagnolo dog were presented with a history of progressive cerebellar dysfunction including wide-based stance, cerebellar ataxia, intention tremors, and loss of menace response despite normal vision. Magnetic resonance imaging of the brain identified marked diffuse decrease of the cerebellum size. Euthanasia was performed in both cases because of progression of clinical signs. Histopathological examination identified marked diffuse thinning of the granular cell layer with almost complete loss of the granular cell neurons, providing a definitive diagnosis of granuloprival CCD. Granuloprival CCD should be considered as a differential diagnosis in Yorkshire Terrier and Lagotto Romagnolo dogs with post-natal progressive clinical signs of cerebellar dysfunction., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

National suicide prevention strategies have been identified as evidence-informed interventions that require multisectoral efforts by governments. This article reviews the rationale for national strategies, the need for a whole-of-government approach, and current progress on national strategies worldwide, including successes and challenges regarding implementation. We highlight the limitations of existing evidence and describe how future research may help to address knowledge gaps. We conclude that national strategies are an important tool for suicide prevention worldwide. However, a more robust evidence base evaluating the impact of strategies on suicide-related outcomes is needed.

Open reduction and internal fixation are the standard of care to stabilize tibial plafond fractures. However, it remains uncertain as to whether fixation of the fibula affects the outcome. This study aimed to review the evidence base for comparable outcomes in tibial plafond fractures when undergoing open reduction and internal fixation of ipsilateral fibula fractures compared with open reduction and internal fixation of the tibia alone. A systematic review and meta-analysis of the literature was completed; 4 studies were included for analysis. This study demonstrated no statistically significant differences in the incidence of nonunion (p = .784) or mal-union (p = .416). There was a greater rate of removal of metalwork in the fibula operative group compared to the tibia alone group (p < .001). The current evidence demonstrates that open reduction and internal fixation of ipsilateral fibula fractures in tibial plafond fractures is not necessarily routinely indicated for all fractures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The concept of agonist-independent signalling that can be attenuated by inverse agonists is a fundamental element of the cubic ternary complex model of G protein-coupled receptor (GPCR) activation. This model shows how a GPCR can exist in two conformational states in the absence of ligands; an inactive R state and an active R* state that differ in their affinities for agonists, inverse agonists, and G-protein alpha subunits. The proportion of R* receptors that exist in the absence of agonists determines the level of constitutive receptor activity. In this study we demonstrate that mechanical stimulation can induce β 2 -adrenoceptor agonist-independent Gs-mediated cAMP signalling that is sensitive to inhibition by inverse agonists such as ICI-118551 and propranolol. The size of the mechano-sensitive response is dependent on the cell surface receptor expression level in HEK293G cells, is still observed in a ligand-binding deficient D113A mutant β 2 -adrenoceptor and can be attenuated by site-directed mutagenesis of the extracellular N-glycosylation sites on the N-terminus and second extracellular loop of the β 2 -adrenoceptor. Similar mechano-sensitive agonist-independent responses are observed in HEK293G cells overexpressing the A 2A -adenosine receptor. These data provide new insights into how agonist-independent constitutive receptor activity can be enhanced by mechanical stimulation and regulated by inverse agonists., (© 2024. The Author(s).)

Single-cell RNA sequencing has been widely used to investigate cell state transitions and gene dynamics of biological processes. Current strategies to infer the sequential dynamics of genes in a process typically rely on constructing cell pseudotime through cell trajectory inference. However, the presence of concurrent gene processes in the same group of cells and technical noise can obscure the true progression of the processes studied. To address this challenge, we present GeneTrajectory, an approach that identifies trajectories of genes rather than trajectories of cells. Specifically, optimal transport distances are calculated between gene distributions across the cell-cell graph to extract gene programs and define their gene pseudotemporal order. Here we demonstrate that GeneTrajectory accurately extracts progressive gene dynamics in myeloid lineage maturation. Moreover, we show that GeneTrajectory deconvolves key gene programs underlying mouse skin hair follicle dermal condensate differentiation that could not be resolved by cell trajectory approaches. GeneTrajectory facilitates the discovery of gene programs that control the changes and activities of biological processes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Infection with Sars-CoV-2 is known to cause cardiac injury and coronary artery changes in moderate to severe acute COVID-19 and post-acute multisystem inflammatory syndrome in children (MIS-C). However, little is known about the potential for cardiac involvement, in particular coronary artery dilation, in asymptomatic or mild cases of COVID-19., Methods: A retrospective review of children ≤ 18 years of age with a history of asymptomatic or mild COVID-19 disease who underwent echocardiography after Sars-CoV-2 infection is conducted. Patients were excluded if they had been hospitalised for COVID-19/MIS-C or had a history of cardiac disease that could affect coronary artery dimension. Coronary artery dilation was defined as the Boston Z-score greater than 2.0., Results: One hundred and fifty-seven patients met inclusion criteria with a mean age of 9.4 years (+/- 5.4 years). Eighty-four (54%) patients were identified as having COVID-19 through positive antibody testing. All patients underwent electrocardiogram and echocardiogram as part of their cardiology evaluation. One hundred and thirty-five (86%) patients had a normal evaluation or only a minor variant on electrocardiogram, while 22 patients had abnormalities on echocardiogram, 4 of which demonstrated coronary artery dilation based on the Boston Z-score., Conclusions: Much of the literature for post-infectious screening and follow-up focuses on patients with a history of moderate to severe COVID-19 disease, emphasising the need for surveillance for the potential development of myocarditis. In this study, 4 out of 157 (2.5%) children with a history of asymptomatic or mild COVID-19 disease without MIS-C were found to have some degree of coronary artery dilation. The significance of this finding currently remains unknown.

CXCL17 is a chemokine principally expressed by mucosal tissues, where it facilitates chemotaxis of monocytes, dendritic cells, and macrophages and has antimicrobial properties. CXCL17 is also implicated in the pathology of inflammatory disorders and progression of several cancers, and its expression is increased during viral infections of the lung. However, the exact role of CXCL17 in health and disease requires further investigation, and there is a need for confirmed molecular targets mediating CXCL17 functional responses. Using a range of bioluminescence resonance energy transfer (BRET)-based assays, here we demonstrated that CXCL17 inhibited CXCR4-mediated signaling and ligand binding. Moreover, CXCL17 interacted with neuropillin-1, a VEGFR2 coreceptor. In addition, we found that CXCL17 only inhibited CXCR4 ligand binding in intact cells and demonstrated that this effect was mimicked by known glycosaminoglycan binders, surfen and protamine sulfate. Disruption of putative GAG binding domains in CXCL17 prevented CXCR4 binding. This indicated that CXCL17 inhibited CXCR4 by a mechanism of action that potentially required the presence of a glycosaminoglycan-containing accessory protein. Together, our results revealed that CXCL17 is an endogenous inhibitor of CXCR4 and represents the next step in our understanding of the function of CXCL17 and regulation of CXCR4 signaling.

Aims The purpose of this study was to attempt to quantify the impact of skateboarding-related injuries on our local orthopaedic service. Method Every presentation to the emergency departments of Gold Coast health public hospitals was retrospectively reviewed to determine whether these were skateboarding-related injuries. Between 2008 and 2018, 5,026 injuries were identified. Patient demographics, mechanism of injury, anatomic location of the injury, treatment, and medical specialty providing treatment were collected and analysed. Results Our investigation demonstrated that skateboarding injuries are common and cause significant trauma in a large percentage of cases. These injuries place a high demand on orthopaedic and emergency departments. This cohort demonstrated a male-to-female ratio of over 4:1. The most common injury type was fracture (44%), of which the upper limb (56%) was the most commonly affected anatomical region. Injuries to the wrist and hand account for 57% of all upper limb injuries, and ankle injuries account for 45% of lower limb injuries. Traumatic brain injuries and concussions account for 62% of all head injuries in this cohort. The mean age was 19 years, with a predominance of 18-25 years old. Only 14% of injuries occurred in those 30 and older. Definitive orthopaedic care, involving inpatient admissions and/or outpatient clinic follow-up, was required in at least 48% of cases, whilst 50% were able to be treated in the emergency department. Additionally, 86% of head injuries were able to be managed in the emergency department, and 11% required specialist neurosurgical management. Conclusion Skateboard-related injuries represent a significant burden of trauma to the local community, predominantly musculoskeletal injuries within the adolescent and young male adult population. This research may direct future strategies for harm minimization, specifically targeted at this demographic of patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Quinn et al.)

Objectives: To identify independent predictors of and derive a risk score for acute hematogenous osteomyelitis (AHO) in children., Methods: We conducted a retrospective matched case-control study of children >90 days to <18 years of age undergoing evaluation for a suspected musculoskeletal (MSK) infection from 2017 to 2019 at 23 pediatric emergency departments (EDs) affiliated with the Pediatric Emergency Medicine Collaborative Research Committee. Cases were identified by diagnosis codes and confirmed by chart review to meet accepted diagnostic criteria for AHO. Controls included patients who underwent laboratory and imaging tests to evaluate for a suspected MSK infection and received an alternate final diagnosis., Results: We identified 1135 cases of AHO matched to 2270 controls. Multivariable logistic regression identified 10 clinical and laboratory factors independently associated with AHO. We derived a 4-point risk score for AHO using (1) duration of illness >3 days, (2) history of fever or highest ED temperature ≥38°C, (3) C-reactive protein >2.0 mg/dL, and (4) erythrocyte sedimentation rate >25 mm per hour (area under the curve: 0.892, 95% confidence interval [CI]: 0.881 to 0.901). Choosing to pursue definitive diagnostics for AHO when 3 or more factors are present maximizes diagnostic accuracy at 84% (95% CI: 82% to 85%), whereas children with 0 factors present are highly unlikely to have AHO (sensitivity: 0.99, 95% CI: 0.98 to 1.00)., Conclusions: We identified 10 predictors for AHO in children undergoing evaluation for a suspected MSK infection in the pediatric ED and derived a novel 4-point risk score to guide clinical decision-making., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Fibrocartilaginous embolic myelopathy (FCE) is a well-documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined., Objectives: Define the association of the chondrodystrophy-associated FGF4L2 retrogene with histopathologically confirmed cases of FCE., Animals: Ninety-eight dogs with a histopathologic diagnosis of FCE., Methods: Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin-fixed, paraffin-embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies., Results: FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2-segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P < .001) and negatively associated with FCE relative to predicted hospital-population dogs. FCE was overrepresented in Boxer, Great Dane, Yorkshire Terrier, Bernese Mountain Dog, Miniature Schnauzer, Rottweiler, and Shetland Sheepdog breeds., Conclusions and Clinical Importance: Study data based on genotypically and histopathologically defined cases support the historical observation that FCE is uncommon in chondrodystrophic dog breeds. FGF4 plays an important role in angiogenesis and vascular integrity; anatomical studies comparing chondrodystrophic and non-chondrodystrophic dogs might provide insight into the pathogenesis of FCE., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: The lasting effects of the coronavirus disease 2019 pandemic are likely to be significant., Aims: This study tracked worry and rumination levels during the pandemic and investigated whether periods with higher COVID-related worry and rumination were associated with more negative mental health and loneliness., Methods: A quota survey design and a sampling frame that permitted recruitment of a national sample were employed. Findings for waves 1 (March 2020) to 6 (November 2020) are reported ( N  = 1943)., Results: Covid-related worry and rumination levels were highest at the beginning of the first lockdown, then declined but increased when the UK returned to lockdown. Worry levels were higher than rumination levels throughout. High levels of COVID-related worry and rumination were associated with a five- and ten-fold increase in clinically meaningful rates of depression and anxiety (respectively) together with lower well-being and higher loneliness. The effects of COVID-related worry on depression and anxiety levels were most marked and clinically meaningful in individuals living with a pre-existing mental health condition., Conclusions: Psychological interventions should include components that specifically target COVID-related worry and rumination. Individuals with pre-existing mental health conditions should be prioritised as we emerge from the current pandemic and in any future public health crises.

Background: Femoral neck fractures are a common cause of morbidity and mortality in the community. Minimally displaced subcapital necks of femoral fractures are usually managed with internal fixation, although there is debate as to which method is superior. This systematic review aimed to compare the outcomes of different fixation methods in the management of this common fracture., Methods: This systematic review was conducted in accordance with PRISMA statement guidelines. The databases searched were MEDLINE (Ovid), Cochrane Central Register of Controlled Trials, and EMBASE (Ovid). The study quality and risk of bias were assessed using the Newcastle-Ottawa Quality Assessment Scale, and relevant data were extracted and synthesised., Results: Nine articles met the inclusion criteria. A total of 819 patients were included in this study. Eight of the nine studies were case series, and one was a randomised control trial. The mean risk of bias was 7.4/9 for non-randomised articles. The fixation methods used in the included studies were dynamic hip screw (DHS), cannulated screws, Smith-Peterson nail, hooknail, Moore's pins, and Knowle's pins. DHS was found to be a superior method of fixation and was supported by a clinical trial. It has high rates of union (99 %), low rates of avascular necrosis (<1 %), and low rates of fixation failure (<1 %)., Conclusions: Based on the available data, DHS appears to be the superior method of fixation for the minimally displaced subcapital neck of femoral fractures. Given the general low level of evidence currently available, additional clinical trials are needed in this area., Competing Interests: There are no acknowledgements, conflicts of interest and this research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors by any of the authors., (© 2023 Published by Elsevier B.V. on behalf of Professor P K Surendran Memorial Education Foundation.)

A 1.5-year-old female entire French bulldog was referred for neurological evaluation, further diagnostic tests, and treatment 24 h after a road traffic accident. Initial emergency treatment, diagnostic tests, and stabilization had been performed by the referring veterinarian. Neurological examination revealed severe spastic non-ambulatory tetraparesis and was consistent with a C1-5 myelopathy. A magnetic resonance imaging (MRI) study revealed an irregular to elongated ovoid intramedullary lesion centered over the body of C2. The lesion showed marked signal heterogeneity with a central T2W and T2* hyperintense region, surrounded by a hypointense rim on both sequences. The lesion appeared heterogeneously T1W hypointense. The lesion was asymmetric (right-sided), affecting both white and gray matter. The C2-3 intervertebral disk appeared moderately degenerate with a Pfirrmann grade of 3. No evidence of vertebral fracture or luxation was found on radiographs or MRI of the vertebral column. Additional soft tissue abnormalities in the area of the right brachial plexus were suggestive of brachial plexus and muscle injury. A diagnosis of traumatic hemorrhagic myelopathy at the level of C2 and concurrent brachial plexus injury was formed. Conservative treatment was elected and consisted of physiotherapy, bladder care with an indwelling urinary catheter, repeated IV methadone based on pain scoring (0.2 mg/kg), oral meloxicam 0.1 mg/kg q24h, and oral gabapentin 10 mg/kg q8h. The dog was discharged after 4 days, with an indwelling urinary catheter and oral medication as described. The catheter was replaced two times by the referring veterinarian and finally removed after 10 days. Thereafter, voluntary urination was seen. During the 2 months after the road traffic accident, slow recovery of motor function was seen. The right thoracic limb recovery progressed more slowly than the left limb, also showing some lower motor neuron signs during follow-up. This was judged to be consistent with a right-sided brachial plexus injury. The dog was reported ambulatory with mild residual ataxia and residual monoparesis of the right thoracic limb at the last follow-up 3 months post-injury. This case report highlights the MRI-based diagnosis of traumatic hemorrhagic myelopathy in a dog. A fair short-term outcome was achieved with conservative treatment in this case., Competing Interests: IC and SP were employed by Vet Oracle Teleradiology. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Santifort, Carrera and Platt.)

A 3.5-year-old male intact Staffordshire terrier crossbreed dog was presented with a one-week history of progressive paraparesis with fecal and urinary incontinence. Neurological examination was consistent with a T3-L3 myelopathy. A magnetic resonance imaging study revealed the presence of a well-circumscribed hemorrhagic space-occupying lesion at the level of T12, suspected to be a vascular malformation, such as cavernoma or arteriovenous fistula, primary hematoma or hamartoma; less likely considerations included hemorrhagic inflammation or hemorrhagic primary or secondary neoplasia. A dorsal laminectomy, durotomy, and midline dorsal myelotomy were performed with a surgical microscope, and the vascular lesion was identified and removed. Histological examination of surgical samples yielded fibrin, hemorrhage, hematoidin pigment, and some neural tissue. Although a lining wall was visualized during surgery consistent with a vascular malformation, there was no histological confirmation of such a structure, hampering definitive classification of the lesion. There was no gross or histopathological evidence that would support a diagnosis of a hamartoma or benign neoplasia. The dog was paraplegic with intact nociception the day following surgery. Ambulation was recovered within 2 weeks. Progressive and complete recovery of neurological function was seen over the next 12 weeks. No recurrence of neurological dysfunction was seen over a 12-month follow-up period. Surgical treatment should be considered in dogs with spinal intramedullary vascular lesions which can have a successful long-term outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Santifort, Plonek, Grinwis, Carrera and Platt.)

Background: The second Multicenter Medication Reconciliation Quality Improvement Study demonstrated a marked reduction in medication discrepancies per patient. The aim of the current analysis was to determine the association of patient exposure to each system-level intervention and receipt of each patient-level intervention on these results., Methods: This study was conducted at 17 North American Hospitals, the study period was 18 months per site, and sites typically adopted interventions after 2-5 months of preintervention data collection. We conducted an on-treatment analysis (ie, an evaluation of outcomes based on patient exposure) of system-level interventions, both at the category level and at the individual component level, based on monthly surveys of implementation site leads at each site (response rate 65%). We then conducted a similar analysis of patient-level interventions, as determined by study pharmacist review of documented activities in the medical record. We analysed the association of each intervention on the adjusted number of medication discrepancies per patient in admission and discharge orders, based on a random sample of up to 22 patients per month per site, using mixed-effects Poisson regression with hospital site as a random effect. We then used a generalised linear mixed-effects model (GLMM) decision tree to determine which patient-level interventions explained the most variance in discrepancy rates., Results: Among 4947 patients, patient exposure to seven of the eight system-level component categories was associated with modest but significant reductions in discrepancy rates (adjusted rate ratios (ARR) 0.75-0.97), as were 15 of the 17 individual system-level intervention components, including hiring, reallocating and training personnel to take a best possible medication history (BPMH) and training personnel to perform discharge medication reconciliation and patient counselling. Receipt of five of seven patient-level interventions was independently associated with large reductions in discrepancy rates, including receipt of a BPMH in the emergency department (ED) by a trained clinician (ARR 0.40, 95% CI 0.37 to 0.43), admission medication reconciliation by a trained clinician (ARR 0.57, 95% CI 0.50 to 0.64) and discharge medication reconciliation by a trained clinician (ARR 0.64, 95% CI 0.57 to 0.73). In GLMM decision tree analyses, patients who received both a BPMH in the ED and discharge medication reconciliation by a trained clinician experienced the lowest discrepancy rates (0.08 per medication per patient)., Conclusion and Relevance: Patient-level interventions most associated with reductions in discrepancies were receipt of a BPMH of admitted patients in the ED and admission and discharge medication reconciliation by a trained clinician. System-level interventions were associated with modest reduction in discrepancies for the average patient but are likely important to support patient-level interventions and may reach more patients. These findings can be used to help hospitals and health systems prioritise interventions to improve medication safety during care transitions., Competing Interests: Competing interests: JLS and ASM received remuneration from American Society of Health-System Pharmacists (ASHP) to develop their best possible medication history training curriculum. JLS received funding from Synapse Medicine for an investigator-initiated study to evaluate the effects of their medication decision support software on hospital pharmacists’ medication recommendations., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: National suicide prevention strategies support development of suicide prevention activities and their evaluation. Aims: To describe components included in national suicide prevention strategies and analyze the potential contribution of individual components to reduce suicide rates. Method: We conducted a narrative review and statistical analysis of national suicide prevention strategies. The narrative review was based on a framework of 12 components and included 29 countries (14 lower middle-income countries [LMICs] and 15 high-income countries [HICs]) with a national suicide prevention strategy. The statistical analyses covered suicide mortality data for 24 countries with a national strategy (9 LMICs and 15 HICs). Results: The number of components adopted in national strategies ranged from 4 to 11, and training and education were included in 96.5% of strategies. Estimated period effects for total suicide rates in individual countries ranged from a significant decrease in the yearly suicide rate (RR = 0.80; 95% CI 0.69-0.93) to a significant increase (RR = 1.12; 95% CI 1.05-1.19). There were no changes in suicide mortality associated with individual components of national strategies. Limitations: The limitations of existing suicide mortality data apply to our study. Conclusion: Further detailed evaluations will help identify the specific contribution of individual components to the impact national strategies. Until then, countries should be encouraged to implement and evaluate comprehensive national suicide prevention strategies.

Background: Befriending is one of many strategies with the potential to reduce suicidal ideation and decrease the risk of suicide. Aims: To measure change in suicidal ideation and behavior among visitors (service users) supported at The Listening Place (TLP), a charity which offers volunteer-run, face-to-face befriending to people who are suicidal. Method: This study was peer reviewed and preregistered on the Open Science Framework prior to data extraction. Anonymized data were extracted for visitors at the point of referral and after 3 months of receiving support. Paired-sample tests were used to test whether self-reported suicidal ideation and behaviors changed after 3 months of support from TLP. Multivariable regressions were used to test whether change in suicidal feelings was associated with demographic characteristics or baseline self-reported suicidality. Results: TLP received 13,938 referrals from July 2016 to February 2022. Self-reported suicidal ideation, suicidal behavior, and feelings of distress decreased after 3 months, while feelings of support increased. Only self-reported suicidal behavior prior to referral was associated with a lesser reduction in self-reported suicidality after 3 months. Limitations: In the absence of a control group, it cannot be concluded that TLP causes the reduction in self-reported suicidality. Conclusions: An empathetic, nonjudgmental, listening service for people who are feeling suicidal was well received by users, who experienced a reduction in suicidality.

E-selectin is expressed on endothelial cells in response to inflammatory cytokines and mediates leukocyte rolling and extravasation. However, studies have been hampered by lack of experimental approaches to monitor expression in real time in living cells. Here, NanoLuc Binary Technology (NanoBiT) in conjunction with CRISPR-Cas9 genome editing was used to tag endogenous E-selectin in human umbilical vein endothelial cells (HUVECs) with the 11 amino acid nanoluciferase fragment HiBiT. Addition of the membrane-impermeable complementary fragment LgBiT allowed detection of cell surface expression. This allowed the effect of inflammatory mediators on E-selectin expression to be monitored in real time in living endothelial cells. NanoBiT combined with CRISPR-Cas9 gene editing allows sensitive monitoring of real-time changes in cell surface expression of E-selectin and offers a powerful tool for future drug discovery efforts aimed at this important inflammatory protein., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Introduction: Interpretation of high-resolution CT images plays an important role in the diagnosis and management of interstitial lung diseases. However, interreader variation may exist due to varying levels of training and expertise. This study aims to evaluate interreader variation and the role of thoracic radiology training in classifying interstitial lung disease (ILD)., Methods: This is a retrospective study where seven physicians (radiologists, thoracic radiologists, and a pulmonologist) classified the subtypes of ILD of 128 patients from a tertiary referral center, all selected from the Interstitial Lung Disease Registry which consists of patients from November 2014 to January 2021. Each patient was diagnosed with a subtype of interstitial lung disease by a consensus diagnosis from pathology, radiology, and pulmonology. Each reader was provided with only clinical history, only CT images, or both. Reader sensitivity and specificity and interreader agreements using Cohen's κ were calculated., Results: Interreader agreement based only on clinical history, only on radiologic information, or combination of both was most consistent amongst readers with thoracic radiology training, ranging from fair (Cohen's κ: 0.2-0.46), moderate to almost perfect (Cohen's κ: 0.55-0.92), and moderate to almost perfect (Cohen's κ: 0.53-0.91) respectively. Radiologists with any thoracic training showed both increased sensitivity and specificity for NSIP as compared to other radiologists and the pulmonologist when using only clinical history, only CT information, or combination of both (p < 0.05)., Conclusions: Readers with thoracic radiology training showed the least interreader variation and were more sensitive and specific at classifying certain subtypes of ILD., Summary Sentence: Thoracic radiology training may improve sensitivity and specificity in classifying ILD based on HRCT images and clinical history., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus interna (GPi) have differential therapeutic effects for Parkinson's disease (PD) that drive patient selection. For example, GPi DBS is preferred for dystonic features and dyskinesia, whereas STN DBS has shown faster tremor control and medication reduction. Connectivity studies comparing these two targets, using patient-specific data, are still lacking. The objective was to find STN and GPi structural connectivity patterns in order to better understand differences in DBS-activated brain circuits between these two stimulation targets and to guide optimal contact selection., Methods: The authors simulated DBS activation along the main axis of both the STN and GPi by using volume of activated tissue (VAT) modeling with known average stimulation parameters (2.8 V and 60 μsec for STN; 3.3 V and 90 μsec for GPi). The authors modeled VATs in the anterior, middle, and posterior STN and the anterior, midanterior, midposterior, and posterior GPi. The authors generated maps of the connections shared by the patients for each VAT by using probabilistic tractography of diffusion-weighted imaging data obtained in 46 PD patients who underwent DBS (26 with STN and 20 with GPi targeting), and differences between VATs for whole-brain and distal regions of interest (prefrontal cortex, supplementary motor area, primary motor cortex, primary sensory cortex, caudate, motor thalamus, and cerebellum) were generated from structural atlases. Differences between maps were quantified and compared., Results: VATs across the STN and GPi had different structural connectivity patterns. The authors found significant connectivity differences between VATs for all regions of interest. Posterior and middle STN showed stronger connectivity to the primary motor cortex and supplementary motor area (SMA) (p < 0.001). Posterior STN had the strongest connectivity to the primary sensory cortex and motor thalamus (p < 0.001). Posterior GPi showed stronger connectivity to the primary motor cortex (p < 0.001). Connectivity to the SMA was similar for the posterior and midposterior GPi (p > 0.05), which was greater than that for the anterior GPi (p < 0.001). When both nuclei were compared, posterior and middle STN had stronger connectivity to the SMA, cerebellum, and motor thalamus than GPi (all p < 0.001). Posterior GPi and STN had similar connectivity to the primary sensory cortex., Conclusions: On patient-specific imaging, structural connectivity differences existed between GPi and STN DBS, as measured with standardized electrical field modeling of the DBS targets. These connectivity differences may correlate with the differential clinical benefits obtained by targeting each of the two nuclei with DBS for PD. Prospective work is needed to relate these differences to clinical outcomes and to inform targeting and programming.

For accurate diagnosis of interstitial lung disease (ILD), a consensus of radiologic, pathological, and clinical findings is vital. Management of ILD also requires thorough follow-up with computed tomography (CT) studies and lung function tests to assess disease progression, severity, and response to treatment. However, accurate classification of ILD subtypes can be challenging, especially for those not accustomed to reading chest CTs regularly. Dynamic models to predict patient survival rates based on longitudinal data are challenging to create due to disease complexity, variation, and irregular visit intervals. Here, we utilize RadImageNet pretrained models to diagnose five types of ILD with multimodal data and a transformer model to determine a patient's 3-year survival rate. When clinical history and associated CT scans are available, the proposed deep learning system can help clinicians diagnose and classify ILD patients and, importantly, dynamically predict disease progression and prognosis., (© 2023. The Author(s).)

Background: Many women, and other females, with epithelial ovarian cancer (EOC) develop resistance to conventional chemotherapy drugs. Drugs that inhibit angiogenesis (development of new blood vessels), essential for tumour growth, control cancer growth by denying blood supply to tumour nodules., Objectives: To compare the effectiveness and toxicities of angiogenesis inhibitors for treatment of epithelial ovarian cancer (EOC)., Search Methods: We identified randomised controlled trials (RCTs) by searching CENTRAL, MEDLINE and Embase (from 1990 to 30 September 2022). We searched clinical trials registers and contacted investigators of completed and ongoing trials for further information., Selection Criteria: RCTs comparing angiogenesis inhibitors with standard chemotherapy, other types of anti-cancer treatment, other angiogenesis inhibitors with or without other treatments, or placebo/no treatment in a maintenance setting, in women with EOC.  DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our outcomes were overall survival (OS), progression-free survival (PFS), quality of life (QoL), adverse events (grade 3 and above) and hypertension (grade 2 and above)., Main Results: We identified 50 studies (14,836 participants) for inclusion (including five studies from the previous version of this review): 13 solely in females with newly-diagnosed EOC and 37 in females with recurrent EOC (nine studies in platinum-sensitive EOC; 19 in platinum-resistant EOC; nine with studies with mixed or unclear platinum sensitivity). The main results are presented below.  Newly-diagnosed EOC Bevacizumab, a monoclonal antibody that binds vascular endothelial growth factor (VEGF), given with chemotherapy and continued as maintenance, likely results in little to no difference in OS compared to chemotherapy alone (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.88 to 1.07; 2 studies, 2776 participants; moderate-certainty evidence). Evidence is very uncertain for PFS (HR 0.82, 95% CI 0.64 to 1.05; 2 studies, 2746 participants; very low-certainty evidence), although the combination results in a slight reduction in global QoL (mean difference (MD) -6.4, 95% CI -8.86 to -3.94; 1 study, 890 participants; high-certainty evidence). The combination likely increases any adverse event (grade ≥ 3) (risk ratio (RR) 1.16, 95% CI 1.07 to 1.26; 1 study, 1485 participants; moderate-certainty evidence) and may result in a large increase in hypertension (grade ≥ 2) (RR 4.27, 95% CI 3.25 to 5.60; 2 studies, 2707 participants; low-certainty evidence). Tyrosine kinase inhibitors (TKIs) to block VEGF receptors (VEGF-R), given with chemotherapy and continued as maintenance, likely result in little to no difference in OS (HR 0.99, 95% CI 0.84 to 1.17; 2 studies, 1451 participants; moderate-certainty evidence) and likely increase PFS slightly (HR 0.88, 95% CI 0.77 to 1.00; 2 studies, 2466 participants; moderate-certainty evidence). The combination likely reduces QoL slightly (MD -1.86, 95% CI -3.46 to -0.26; 1 study, 1340 participants; moderate-certainty evidence), but it increases any adverse event (grade ≥ 3) slightly (RR 1.31, 95% CI 1.11 to 1.55; 1 study, 188 participants; moderate-certainty evidence) and may result in a large increase in hypertension (grade ≥ 3) (RR 6.49, 95% CI 2.02 to 20.87; 1 study, 1352 participants; low-certainty evidence).  Recurrent EOC (platinum-sensitive) Moderate-certainty evidence from three studies (with 1564 participants) indicates that bevacizumab with chemotherapy, and continued as maintenance, likely results in little to no difference in OS (HR 0.90, 95% CI 0.79 to 1.02), but likely improves PFS (HR 0.56, 95% CI 0.50 to 0.63) compared to chemotherapy alone. The combination may result in little to no difference in QoL (MD 0.8, 95% CI -2.11 to 3.71; 1 study, 486 participants; low-certainty evidence), but it increases the rate of any adverse event (grade ≥ 3) slightly (RR 1.11, 1.07 to 1.16; 3 studies, 1538 participants; high-certainty evidence). Hypertension (grade ≥ 3) was more common in arms with bevacizumab (RR 5.82, 95% CI 3.84 to 8.83; 3 studies, 1538 participants).  TKIs with chemotherapy may result in little to no difference in OS (HR 0.86, 95% CI 0.67 to 1.11; 1 study, 282 participants; low-certainty evidence), likely increase PFS (HR 0.56, 95% CI 0.44 to 0.72; 1 study, 282 participants; moderate-certainty evidence), and may have little to no effect on QoL (MD 6.1, 95% CI -0.96 to 13.16; 1 study, 146 participants; low-certainty evidence). Hypertension (grade ≥ 3) was more common with TKIs (RR 3.32, 95% CI 1.21 to 9.10). Recurrent EOC (platinum-resistant) Bevacizumab with chemotherapy and continued as maintenance increases OS (HR 0.73, 95% CI 0.61 to 0.88; 5 studies, 778 participants; high-certainty evidence) and likely results in a large increase in PFS (HR 0.49, 95% CI 0.42 to 0.58; 5 studies, 778 participants; moderate-certainty evidence). The combination may result in a large increase in hypertension (grade ≥ 2) (RR 3.11, 95% CI 1.83 to 5.27; 2 studies, 436 participants; low-certainty evidence). The rate of bowel fistula/perforation (grade ≥ 2) may be slightly higher with bevacizumab (RR 6.89, 95% CI 0.86 to 55.09; 2 studies, 436 participants). Evidence from eight studies suggest TKIs with chemotherapy likely result in little to no difference in OS (HR 0.85, 95% CI 0.68 to 1.08; 940 participants; moderate-certainty evidence), with low-certainty evidence that it may increase PFS (HR 0.70, 95% CI 0.55 to 0.89; 940 participants), and may result in little to no meaningful difference in QoL (MD ranged from -0.19 at 6 weeks to -3.40 at 4 months). The combination increases any adverse event (grade ≥ 3) slightly (RR 1.23, 95% CI 1.02 to 1.49; 3 studies, 402 participants; high-certainty evidence). The effect on bowel fistula/perforation rates is uncertain (RR 2.74, 95% CI 0.77 to 9.75; 5 studies, 557 participants; very low-certainty evidence)., Authors' Conclusions: Bevacizumab likely improves both OS and PFS in platinum-resistant relapsed EOC. In platinum-sensitive relapsed disease, bevacizumab and TKIs probably improve PFS, but may or may not improve OS. The results for TKIs in platinum-resistant relapsed EOC are similar. The effects on OS or PFS in newly-diagnosed EOC are less certain, with a decrease in QoL and increase in adverse events. Overall adverse events and QoL data were more variably reported than were PFS data. There appears to be a role for anti-angiogenesis treatment, but given the additional treatment burden and economic costs of maintenance treatments, benefits and risks of anti-angiogenesis treatments should be carefully considered., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The Knosp criteria have been the historical standard for predicting cavernous sinus invasion, and therefore extent of surgical resection, of pituitary macroadenomas. Few studies have sought to reappraise the utility of this tool after recent advances in visualization and modeling of tumors in complex endoscopic surgery., Objective: To evaluate our proposed alternative method, using 3-dimensional (3D) volumetric imaging, and whether it can better predict extent of resection in nonfunctional pituitary adenomas., Methods: Patients who underwent endoscopic transsphenoidal resection of pituitary macroadenomas at our institution were reviewed. Information was collected on neurological, endocrine, and visual function. Volumetric segmentation was performed using 3D Slicer software. Relationship of tumor volume, clinical features, and Knosp grade on extent of resection was examined., Results: One hundred forty patients were identified who had transsphenoidal resection of nonfunctional pituitary adenomas. Macroadenomas had a median volume of 6 cm 3 (IQR 3.4-8.7), and 17% had a unilateral Knosp grade of at least 3B. On multiple logistic regression, only smaller log-transformed preoperative tumor volume was independently associated with increased odds of gross total resection (GTR; odds ratio: 0.27, 95% CI: 0.07-0.89, P < .05) when controlling for tumor proliferative status, age, and sex (area under the curve 0.67). The Knosp criteria did not independently predict GTR in this cohort ( P > .05, area under the curve 0.46)., Conclusion: Increasing use of volumetric 3D imaging may better anticipate extent of resection compared with the Knosp grade metric and may have a greater positive predictive value for GTR. More research is needed to validate these findings and implement them using automated methods., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: BI-RADS 0 screening mammograms require follow-up diagnostic imaging, optimally within 60 days. Our study aims to identify risk factors for delayed follow-up., Methods: We conducted a retrospective case-control study of individuals who had a nondiagnostic BI-RADS 0 screening mammogram between March 19, 2018, and March 19, 2020. Sociodemographic information was collected from a self-reported questionnaire. We aimed to identify factors associated with <60-day follow-up, >60-day follow-up, or no follow-up outcomes. The χ 2 test and univariate logistic regressions were performed. Significant variables were included in multinomial logistic regression. We also aimed to identify risk factors that lead to delayed follow-up times among individuals with follow-up. Spearman's correlation and Mann-Whitney Wilcoxon tests and Kruskal-Wallis tests were performed., Results: Review returned 5,034 screening mammograms. Of 4,552 individuals included, 904 (19.9%) had no follow-up. Of the 3,648 (80.1%) with follow-up, 2,797 (76.7%) had a follow-up <60 days (median 20 days) and 851 (23.3%) had follow-up >60 days (median 176 days). Multinomial regression found that Asian (P = .022), Black (P < .0001), and individuals who identified their race as other (P < .0001) were independently more likely to have no or >60-day follow-up. Individuals who did not report their race (P = .001) or completed the questionnaire in Spanish (P = .025) were more likely to have no or >60-day follow-up. Among individuals with follow-up, Black individuals (P < .0001), those who identified their race as other (P < .0001), Hispanic individuals (P = .04), and those who completed the questionnaire in Spanish (P < .0001) had follow-up delays. BRCA-positive individuals had shorter follow-up times (P = .021)., Discussion: Follow-up time is affected by cancer risk factors such as BRCA status in addition to race, preferred language, and Hispanic ethnicity., (Published by Elsevier Inc.)

The blood-brain barrier (BBB) presents a formidable obstacle to the effective delivery of systemically administered pharmacological agents to the brain, with ~5% of candidate drugs capable of effectively penetrating the BBB. A variety of biomaterials and therapeutic delivery devices have recently been developed that facilitate drug delivery to the brain. These technologies have addressed many of the limitations imposed by the BBB by: (1) designing or modifying the physiochemical properties of therapeutic compounds to allow for transport across the BBB; (2) bypassing the BBB by administration of drugs via alternative routes; and (3) transiently disrupting the BBB (BBBD) using biophysical therapies. Here we specifically review colloidal drug carrier delivery systems, intranasal, intrathecal, and direct interstitial drug delivery methods, focused ultrasound BBBD, and pulsed electrical field induced BBBD, as well as the key features of BBB structure and function that are the mechanistic targets of these approaches. Each of these drug delivery technologies are illustrated in the context of their potential clinical applications and limitations in companion animals with naturally occurring intracranial diseases., Competing Interests: Authors ML, CA, RD, and JR have issued patents and/or patents pending in the area of irreversible electroporation induced blood-brain barrier disruption and may receive royalties. CR and JR have issued patents for convection enhanced delivery catheter systems and may receive royalties. AM has issued and pending patents in focused ultrasound blood-barrier disruption and may receive royalties. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Partridge, Eardley, Morales, Campelo, Lorenzo, Mehta, Kani, Mora, Campbell, Arena, Platt, Mintz, Shinn, Rylander, Debinski, Davalos and Rossmeisl.)

Suicide is an increasing contributing cause of mortality in middle-aged adults; however, knowledge to guide prevention is limited. This first systematic review and meta-analysis of studies on midlife suicide has provided an overview of published research on this issue and synthesized the evidence on socioeconomic and physical and mental health factors associated with this mortality. Using PRISMA guidelines MEDLINE, Embase, PsycINFO, Scopus and Web of Science were searched for English-language publications that involved persons aged 35 to 65, used individual-level data, and reported prevalence of exposure(s) or relative risks. The search identified 62 studies on midlife suicides and associated factors (28 for SES, 22 for psychiatric disorder and 23 for physical illness). All studies were from high income countries, and most (80.6%) used data from population registries. Meta-analyses showed that the pooled prevalence of exposure in suicide decedents was 57.8% for psychiatric disorder, 56.3% for low income, 43.2% for unemployment, and 27.3% for physical illness. The associated pooled risk ratio was 11.68 (95% confidence intervals: 5.82-23.47) for psychiatric illness of any type, 12.59 (8.29-19.12) for mood disorders, 3.91 (2.72-5.59) for unemployment, 3.18 (2.72-3.72) for being separated or divorced, 2.64 (2.26-3.10) for cancer, 2.50 (0.96-6.38) for central nervous system illness, and 2.26 (1.16-4.41) for low income. In conclusion, midlife suicide is strongly associated with socioeconomic difficulties and physical and psychiatric illnesses that are common in this age population. Future investigations should consider the interactions between risk factors, the intersectionality of sex and ethnicity, and include data from low- and middle-income countries., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally., Methods: We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age- and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation., Findings: We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well., Interpretation: Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue., Funding: None., Competing Interests: JP is funded by a National Health and Medical Research Council Investigator Grant (GNT1173126). DG receives funding support from the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust. He is an unpaid member of the UK Government's Department of Health and Social Care National Suicide Prevention Strategy Advisory Group, England and the COVID-19 response sub-group, an unpaid member of the Samaritan's Policy, Partnerships and Research Committee, and an unpaid member of the Movember Global Advisory Committee. LA has a research grant to Manchester University from Health Quality Improvement Partnership, on behalf of NHS England and devolved UK governments. He is also Chair, National Suicide Prevention Strategy Advisory Group, Department of Health and Social Care. SF was Special Advisor to a Coroner for a specific investigation and is Chairperson, New Zealand Mortality Review Committee. AB is supported by the EU Erasmus+ Strategic Partnership Programme (2019-1-SE01-KA203-060571). LFC is Primary Investigator for pesticide suicide research in Malaysia funded by the Centre of Pesticide Suicide Prevention Malaysia, University of Edinburgh (Oct 2020-31 March 2022). NK is Member, National Suicide Prevention Strategy Advisory Group (England) and Topic Advisor for NICE self-harm guidelines. NK also declares research grants paid to his institution by NIHR, HQIP and DHSC for work related to the treatment and prevention of suicidal behaviour (but not directly related to the current work). OJK is supported by a Senior Postdoctoral Fellowship from Research Foundation Flanders (FWO 1257821N); payment made to institution (KU Leuven). OJK reports grants from UCB Community Health Fund, outside the submitted work. The UCB Community Health funds in this case are managed and disbursed by the King Baudouin Foundation (Belgium). Selection is by an independent jury and UCB is not involved. Payment is to the institution (KU Leuven). OJK received a waived registration fee for the 2021 International Academy of Suicide Research (IASR) Summit in Barcelona (held online), as an invited speaker (unrelated to the current work). No payment was received directly. Fee was automatically waived at registration. OJK is a member of the Samaritans Research Ethics Board (SREB); this is an unpaid role. OJK is co-chair of the Early Career Group of the International Association for Suicide Prevention (IASP). This role is unpaid, but yearly IASP membership fee is covered in return for this service role. No funds are exchanged, but membership fee is covered directly by IASP. DK reports that the Wellcome Trust has supported the Elizabeth Blackwell Institute with a ISSF grant. DK also declares a grant from the Centre for Pesticide Suicide Prevention to conduct COVID-19 related work on self-harm in Sri Lanka, and panel fees from the Department of Health and Social Care for assessing grants. She also declares a leadership or fiduciary role with Migration Health and Development Research Initiative; no fees received. SL declares a $75,000 grant from Queensland Health; payment will be made to institution when payment occurs. SL also declares project funding from the Queensland Government for the Queensland Suicide Register; made to his institution. SL is also on the Technical Advisory Group (unfunded role), NSW Suicide Monitoring System. HO declares registration for the online congress DGPPN (2020 and 2021) and for the DGPPN congress (2019). He also declares registration for the congress OGPP (2019). SP declares a personal consultancy for support and advice to the National Office for Suicide Prevention (Health Service Executive, Dublin, Ireland) and a personal consultancy for support and advice to the National Suicide Prevention Leadership Group and the Scottish Government. SP also declares support from the World Health Organization for attending a workshop on National Suicide Prevention Implementation and Evaluation, Geneva, November 2019. SP also holds unpaid roles as adviser and committee chairmanships with the International Association for Suicide Prevention. GP is supported by the Flemish Government – Department of Health, Wellbeing and Family. AR and CR-L declare support by the Federal Health Ministry of Germany (BMG), grant number ZMVI1-2517FSB136. CR-L also declares payment or honoraria and participation on a Data Safety Monitoring Board or Advisory Board with Janssen and LivaNova. NR-V declares she is the designated representative of the Puerto Rico Department of Health in the Puerto Rico Administration of Mental Health and Anti-Addiction Services’ Mental Health and Addiction Council. It is not a paid position; she attends meetings as part of her responsibilities at the Puerto Rico Department of Health and is the Coordinator of the Public Policy Committee within this advisory council. The aforementioned council is a requisite with which the Puerto Rico Administration of Mental Health and Anti-Addiction Services must comply with because this Administration receives federal funding from the Substance Abuse and Mental Health Services Administration of the United States of America., (© 2022 The Authors.)

Organic aerosol (OA) is a key component of total submicron particulate matter (PM 1 ), and comprehensive knowledge of OA sources across Europe is crucial to mitigate PM 1 levels. Europe has a well-established air quality research infrastructure from which yearlong datasets using 21 aerosol chemical speciation monitors (ACSMs) and 1 aerosol mass spectrometer (AMS) were gathered during 2013-2019. It includes 9 non-urban and 13 urban sites. This study developed a state-of-the-art source apportionment protocol to analyse long-term OA mass spectrum data by applying the most advanced source apportionment strategies (i.e., rolling PMF, ME-2, and bootstrap). This harmonised protocol was followed strictly for all 22 datasets, making the source apportionment results more comparable. In addition, it enables quantification of the most common OA components such as hydrocarbon-like OA (HOA), biomass burning OA (BBOA), cooking-like OA (COA), more oxidised-oxygenated OA (MO-OOA), and less oxidised-oxygenated OA (LO-OOA). Other components such as coal combustion OA (CCOA), solid fuel OA (SFOA: mainly mixture of coal and peat combustion), cigarette smoke OA (CSOA), sea salt (mostly inorganic but part of the OA mass spectrum), coffee OA, and ship industry OA could also be separated at a few specific sites. Oxygenated OA (OOA) components make up most of the submicron OA mass (average = 71.1%, range from 43.7 to 100%). Solid fuel combustion-related OA components (i.e., BBOA, CCOA, and SFOA) are still considerable with in total 16.0% yearly contribution to the OA, yet mainly during winter months (21.4%). Overall, this comprehensive protocol works effectively across all sites governed by different sources and generates robust and consistent source apportionment results. Our work presents a comprehensive overview of OA sources in Europe with a unique combination of high time resolution (30-240 min) and long-term data coverage (9-36 months), providing essential information to improve/validate air quality, health impact, and climate models., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Educational environments that are structured by race perpetuate poor mental health for Black adolescents. This empirical relationship is pronounced when it is examined through Racial Battle Fatigue theory, which provides a framework that links educational environments and poor psychological health of Black students. School police have a major effect on Black adolescents' educational and health experiences and trajectories. The purpose of this person-centered study was to assess the risk of Black students' depressive symptoms who were stopped by school police, saw other students stopped by school police, or experienced school discipline., Method: Data on Black student youths from the Fragile Families Study Year 15 wave (N = 1,601) were used to conduct a latent class analysis to identify subgroups of school policing (ie, being stopped by school police, seeing other students stopped by school police) and school discipline on the distal outcome of depressive symptoms. Covariates included demographic and school attachment., Results: We identified 4 distinct Black student subgroups: (1) unscathed [no school policing or discipline reported]; (2) school disciplined; (3) combined school policing; and (4) school policed [arrested by police]. Each subgroup had an incremental increase in mean depressive symptom scores. Compared to the unscathed subgroup, each subgroup also had lower school attachment., Conclusion: This study disrupts the notion that education environments are a social determinant of health and a great equalizer. This study critically exposes how educational institutions complicit with school policing are associated with racism-related mental health conditions of Black youths., (Copyright © 2022. Published by Elsevier Inc.)

Iran is one of the few countries in the Eastern Mediterranean Region (EMR) to have developed a national suicide prevention program (NSPP). This report introduces Iran's NSPP to policy planners and researchers working in suicide prevention, and is intended to encourage other low- and middle-income countries to develop, implement, and evaluate their own NSPPs. Background and Aims: Iran is one of the few countries in the Eastern Mediterranean Region (EMR) to have developed a national suicide prevention program (NSPP). This report introduces Iran's NSPP to policy planners and researchers working in suicide prevention, and is intended to encourage other low- and middle-income countries to develop, implement, and evaluate their own NSPPs. Method: While the national incidence of suicide is low, there are higher rates among young adults, particularly women, in western regions. In 2010, Iran's NSPP was integrated into primary health care. A rigorous evaluation of Iran's suicide prevention program concluded that Iran has the potential to take a leadership role in suicide prevention within the EMR, although several challenges were identified. Results: While the national incidence of suicide is low, there are higher rates among young adults, particularly women, in western regions. In 2010, Iran's NSPP was integrated into primary health care. A rigorous evaluation of Iran's suicide prevention program concluded that Iran has the potential to take a leadership role in suicide prevention within the EMR, although several challenges were identified. Limitation: Given Iran's unstable situation, the NSPP needs to be monitored, evaluated, and adjusted according to evidence and ongoing changing national and local needs.Conclusion: Given Iran's unstable situation, the NSPP needs to be monitored, evaluated, and adjusted according to evidence and ongoing changing national and local needs.

Background: Waves 1 to 3 (March 2020 to May 2020) of the UK COVID-19 Mental Health and Wellbeing study suggested an improvement in some indicators of mental health across the first 6 weeks of the UK lockdown; however, suicidal ideation increased., Aims: To report the prevalence of mental health and well-being of adults in the UK from March/April 2020 to February 2021., Method: Quota sampling was employed at wave 1 (March/April 2020), and online surveys were conducted at seven time points. Primary analyses cover waves 4 (May/June 2020), 5 (July/August 2020), 6 (October 2020) and 7 (February 2021), including a period of increased restrictions in the UK. Mental health indicators were suicidal ideation, self-harm, suicide attempt, depression, anxiety, defeat, entrapment, loneliness and well-being., Results: A total of 2691 (87.5% of wave 1) individuals participated in at least one survey between waves 4 and 7. Depressive symptoms and loneliness increased from October 2020 to February 2021. Defeat and entrapment increased from July/August 2020 to October 2020, and remained elevated in February 2021. Well-being decreased from July/August 2020 to October 2020. Anxiety symptoms and suicidal ideation did not change. Young adults, women, those who were socially disadvantaged and those with a pre-existing mental health condition reported worse mental health., Conclusions: The mental health and well-being of the UK population deteriorated from July/August 2020 to October 2020 and February 2021, which coincided with the second wave of COVID-19. Suicidal thoughts did not decrease significantly, suggesting a need for continued vigilance as we recover from the pandemic.

Introduction: Australia is one of the largest surfing nations with over 10% of the population participating; yet there is a paucity of literature analysing the injuries from surfing participation, particularly injuries requiring orthopaedic care. This study retrospectively analyses surfing injuries presenting to a tertiary hospital Emergency Department over a ten-year period with aims of quantifying surfing injuries and investigating injury characteristics requiring orthopaedic input., Methods: A retrospective clinical audit of presentations to Gold Coast Public Hospital Emergency Departments over a ten-year period was conducted using electronic hospital databases. Broad search teams were used to identify presentations, followed by exclusion based on relevance. Subsequent analysis of data was performed to investigate patient demographics and injury characteristics., Results: A total of 2680 surfing related injury presentations were analysed. The median age was 30 years (range 2-77), with 455 females (17%) and 2225 males (83%). Lacerations were the most common injury type (37.9%), followed by ligament injury (21.3%), fractures (12.2%), and contusions (11.4%). The most common areas for lacerations were head/face (59.2%), lower limb (30%), and upper limb (26.5%). Dislocation rate was 4.9%, with shoulder dislocation (76.5%), and patella dislocation (12.1%) being the most common types. 1512 presentations (56.4%) required orthopaedic management. 93.5% did not require admission and were discharged., Conclusion: Over half (56.4%) of surfing injuries were orthopaedic in nature; requiring orthopaedic advice or management. Lacerations, ligament injury, fractures and dislocations were the most commonly managed injuries. This emphasises the importance of understanding the prevalence and characteristics of surfing injuries for an orthopaedic service., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Status epilepticus (SE) can be effectively resolved if diagnosis and treatment are addressed at an early stage, although this is not always possible in clinical practice. If untreated, continuous seizure activity leads to refractory SE which does not respond to antiseizure medication. Although refractory SE is a life-threatening emergency, there is a lack of veterinary consensus on its appropriate management. Classical therapeutic approaches often fail to prevent the progression of SE. One of the main reasons for failure or inadequate response, is a lack of understanding of the fundamental progressive pathophysiology occurring during SE. If the therapeutic approach is focussed on the specific pathophysiologic alterations responsible for initiating and maintaining continuous seizure activity, SE could be successfully resolved during its early stages, preventing progression to a refractory state. The aim of this review is to detail the underlying pathophysiology of SE at its different temporal stages in order to determine a more effective therapeutic approach., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: while physician burnout has been studied in high-income countries, more research is necessary on burnout in lesser-income regions such as Tanzania. This study aimed to determine levels of burnout in Tanzanian physicians and to understand the contributing risk factors for burnout in this region., Methods: the Maslach Burnout Inventory (MBI-HSS) was adapted to assess burnout in Tanzanian physicians. Utilizing a cross-sectional design, we studied two distinct cohorts: 1) Emergency Medicine (EM) trained physicians in Tanzania and; 2) specialists at Bugando Medical Centre. We surveyed demographic, personal, and workplace data to identify risk factors for burnout., Results: seventy-seven percent (30/39) of Tanzanian EM providers and 39% (37/94) of Bugando specialists completed the survey. We identified burnout in 67% of Tanzanian EM providers and in 70% of specialists at Bugando. Burnout risk factors in EM physicians included dissatisfaction with career choice, considering switching institutions, working in an urban setting, inadequate coverage for emergencies/leave, and financial housing responsibilities. In Bugando specialists, risk factors were unnecessary administrative paperwork, working overnight shifts, pressure to achieve patient satisfaction or decrease length of stay, meaningful mentorship, and not having a close friend/family member die., Conclusion: this study reports a high prevalence of burnout in Tanzanian physicians. Risk factors for burnout were multifactorial but mainly related to institutional and workplace constituents. Targeting these risk factors provides opportunities to boost physician wellness and guides important areas for future research in this African region., Competing Interests: The authors declare no competing interest., (Copyright: Shweta Iyer et al.)

Background: The first Multicenter Medication Reconciliation Quality Improvement (QI) Study (MARQUIS1) demonstrated that mentored implementation of a medication reconciliation best practices toolkit decreased total unintentional medication discrepancies in five hospitals, but results varied by site. The objective of this study was to determine the effects of a refined toolkit on a larger group of hospitals., Methods: We conducted a pragmatic quality improvement study (MARQUIS2) at 18 North American hospitals or hospital systems from 2016 to 2018. Incorporating lessons learnt from MARQUIS1, we implemented a refined toolkit, offering 17 system-level and 6 patient-level interventions. One of eight physician mentors coached each site via monthly calls and performed one to two site visits. The primary outcome was number of unintentional medication discrepancies in admission or discharge orders per patient. Time series analysis used multivariable Poisson regression., Results: A total of 4947 patients were sampled, including 1229 patients preimplementation and 3718 patients postimplementation. Both the number of system-level interventions adopted per site and the proportion of patients receiving patient-level interventions increased over time. During the intervention, patients experienced a steady decline in their medication discrepancy rate from 2.85 discrepancies per patient to 0.98 discrepancies per patient. An interrupted time series analysis of the 17 sites with sufficient data for analysis showed the intervention was associated with a 5% relative decrease in discrepancies per month over baseline temporal trends (adjusted incidence rate ratio: 0.95, 95% CI 0.93 to 0.97, p<0.001). Receipt of patient-level interventions was associated with decreased discrepancy rates, and these associations increased over time as sites adopted more system-level interventions., Conclusion: A multicentre medication reconciliation QI initiative using mentored implementation of a refined best practices toolkit, including patient-level and system-level interventions, was associated with a substantial decrease in unintentional medication discrepancies over time. Future efforts should focus on sustainability and spread., Competing Interests: Competing interests: JLS has received funding from Mallinckrodt Pharmaceuticals for an investigated-initiated study of opioid-related adverse drug events. JLS and AM received remuneration from American Society of Health-System Pharmacists (ASHP) to develop their best possible medication history training curriculum., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Translation of acute ischemic stroke research to the clinical setting remains limited over the last few decades with only one drug, recombinant tissue-type plasminogen activator, successfully completing the path from experimental study to clinical practice. To improve the selection of experimental treatments before testing in clinical studies, the use of large gyrencephalic animal models of acute ischemic stroke has been recommended. Currently, these models include, among others, dogs, swine, sheep, and nonhuman primates that closely emulate aspects of the human setting of brain ischemia and reperfusion. Species-specific characteristics, such as the cerebrovascular architecture or pathophysiology of thrombotic/ischemic processes, significantly influence the suitability of a model to address specific research questions. In this article, we review key characteristics of the main large animal models used in translational studies of acute ischemic stroke, regarding (1) anatomy and physiology of the cerebral vasculature, including brain morphology, coagulation characteristics, and immune function; (2) ischemic stroke modeling, including vessel occlusion approaches, reproducibility of infarct size, procedural complications, and functional outcome assessment; and (3) implementation aspects, including ethics, logistics, and costs. This review specifically aims to facilitate the selection of the appropriate large animal model for studies on acute ischemic stroke, based on specific research questions and large animal model characteristics.

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement., (© 2022. The Author(s).)