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Objectives. To examine temporal trends in the classification of opioid-involved overdose deaths (OODs) and racial variation in the classification of specific types of opioids used. Methods. We analyzed OODs coded as other or unspecified narcotics from 1999 to 2018 in the United States using data from the National Vital Statistics System and the Centers for Disease Control and Prevention. Results. The total proportion of OODs from unspecified narcotics decreased from 32.4% in 1999 to 1.9% in 2018. The proportion of OODs from unspecified narcotics among African American persons was approximately 2-fold greater than that of non-Hispanic White persons until 2012. Similarly, the proportion of OODs from unspecified narcotics among Hispanic persons was greater than that of White persons until 2015. After we controlled for death investigation system, African American persons had a higher incidence rate of OODs from unspecified narcotics compared with White persons. Conclusions. There have been significant improvements in the specification OODs over the past 20 years, and there has been significant racial disparity in the classification of OODs until about 2015. The findings suggest a health data disparity; the excessive misclassification of OODs is likely attributable to the race/ethnicity of the decedent.

Background: The emergence of coronavirus SARS-CoV-2, and the subsequent global epidemic of COVID-19, brought with it innumerable new clinical experiences across all medical specialties, and psychiatry is no exception. Individuals with serious mental illness, in particular schizophrenia and related disorders, may be especially susceptible to coronavirus infection given the overlapping risk factors of vulnerable sociodemographic status, increased challenges with quarantining requirements, and limited compliance with “respiratory etiquette.” The case presented here describes a patient with schizophrenia who was being managed on clozapine and who developed symptomatic COVID-19 infection. Special care was taken to ensure that potential interactions between clozapine and the associated COVID-19 treatments were safe for the patient’s mental and physical wellbeing. Case Presentation: A 71-year-old schizophrenic Caucasian male is being managed with clozapine. While hospitalized, the patient was screened positive for COVID-19 and was admitted to the ICU due to his declining respiratory status. He was treated with both remdesivir and prednisone. He was able to fully recover from his COVID-19 infection. Conclusion: The authors review the clinical characteristics of the case, highlighting both the overlapping synergistic effects and antagonistic influences of clozapine therapy in combination with COVID-19 and its associated treatments. A review of the literature offers an opportunity to examine various frameworks for individualized clinical decision-making while making the case for greater epidemiologic research into the optimal management of individuals with a psychotic disorder who are diagnosed with COVID-19 infection.

Purpose To report a case of bilateral sequential, CRVO in a man with newly diagnosed hemoglobin C trait. Methods A 67-year-old man presented with a one-month history of declining visual acuity. He was diagnosed with left CRVO. Bilateral temporal retinal ischemia and arteriovenous anastomoses on fluorescein angiography suggestive of sickle cell retinopathy prompted a systemic work-up. Hemoglobin electrophoresis revealed an underlying hemoglobin C trait. Six-months after his initial presentation, the patient developed symptomatic right CRVO. Results The initial left CRVO was complicated by optic disc swelling and macular edema. Intravitreal anti-angiogenic therapy was initiated and the macular edema resolved. The left eye subsequently developed an epiretinal membrane which was surgically removed. Macular edema in the right eye also resolved after intravitreal anti-angiogenic therapy. Conclusion This is the first reported case of bilateral CRVO in a case of hemoglobin C trait. It is possible that erythrocyte inflexibility, caused by hemoglobin C induced dehydration and crystallization, acted concomitantly with hypertension to produce occlusive microangiopathy. This case highlights the need for further investigation in patients presenting with central retinal vein occlusion, especially when bilateral, or when retinal angiography reveals bilateral pathology.

Background Major depressive disorder (MDD) is a common and highly heterogeneous psychiatric disorder but little is known about the genetic characterisation of this heterogeneity. Understanding the genetic etiology of MDD can be challenging as large sample sizes are needed for gene discovery – often achieved with a trade-off in the depth phenotyping. Methods The Australian Genetics of Depression Study is the largest stand-alone depression cohort with both genetic data and in-depth phenotyping and comprises a total of 15,792 participants of European ancestry, 92% of whom, met diagnostic criteria for MDD. We leveraged the unique nature of this cohort to conduct a meta-analysis with the largest depression GWAS to date and subsequently used polygenic scores (PGS) to investigate genetic heterogeneity across various clinical subtypes of MDD. Results We increased the number of known genome-wide significant variants associated with depression from 103 to 126 and found evidence of association of novel genes implicated in neuronal development. We show that a PGS for depression explains 5.7% of variance in MDD liability in our sample. Lastly, we find strong support for genetic heterogeneity in depression with differential associations of multiple psychiatric and comorbid traits with age of onset, longitudinal course and various subtypes of MDD. Conclusions Until now, this degree of detailed phenotyping in such a large sample of MDD cases has not been possible. Along with discovery of novel loci, we provide support for differential pathways to illness models that recognize both the overlap with other common psychiatric disorders, as well as pathophysiological differences.

Background Intravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary. Methods Ninety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data. Results Interleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = −0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029). Conclusion IL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.

Hypothesis Shoulder arthroplasty is a safe and durable procedure that provides pain relief, improved range of motion (ROM), and minimal complications for shoulder pain and dysfunction in patients with ipsilateral hemiparesis. Methods This is a retrospective review of all adult patients who underwent primary reverse total shoulder arthroplasty (RSA) or total shoulder arthroplasty (TSA) in the hemiparetic upper extremity at a single quaternary care academic medical center from 1988 to 2019. Patients were excluded if their neurologic insult was secondary to a spinal-cord injury, cerebral palsy, or inflammatory arthritis, if they underwent a hemiarthroplasty, if they exhibited mild hemiparesis (Medical Research Council Scale of ≥4), or if they had less than 30 days of radiographic follow-up. The primary clinical outcome was revision surgery for any reason. The secondary clinical outcomes included pain using the visual analog scale, ROM via active-assisted manual muscle testing (AAROM), and postoperative complications. The primary radiographic outcome was implant lucency using a standard scale. Results A total of 5 shoulders in 5 patients were included, 4 RSAs and 1 TSA with a mean clinical follow-up of 6.2 years (range: 1.42-14.2 years) and mean radiographic follow-up of 3.7 years (range: 31 days-13.5 years). No patient underwent revision surgery. The mean visual analog scale score significantly improved from 7.6 to 1.4 at the last follow-up (P = .005). The mean forward elevation AAROM improved from 27° preoperatively to 88° at the last follow-up (P = .015). There was no significant difference in external rotation at the last follow-up (P = .105). One patient had asymptomatic grade 1 glenoid component lucency with superior subluxation of the humerus after undergoing TSA at a final follow-up of 4.5 years. No other complications were reported. Conclusion Shoulder arthroplasty is a durable procedure that provides pain relief, improved AAROM, and minimal complications in patients with ipsilateral hemiparesis. The increase in active-assisted forward elevation ROM can improve caregiver ease with hygiene and dressing. Patients in this study who underwent RSA did not have subsequent glenohumeral dislocation. Larger numbers of patients would be required for adequate power analysis regarding instability in this cohort of patients who may be at risk; our small series did not identify any instability events. Level of evidence Level IV; Treatment Study

Rationale: The objective was to assess the cost-effectiveness of staging positron emission tomography/computed tomography (PET/CT) in early-stage follicular lymphoma from the Canadian health care system perspective. Methods: The study population was FL patients staged as early-stage using conventional CT imaging and planned for curative-intent radiation therapy (RT). A decision analytic model simulated the management after adding a staging PET/CT vs. using staging CT alone. In the no-PET/CT strategy, all patients proceeded to curative-intent RT as planned. In the PET/CT strategy, PET/CT information could result in an increased RT volume, switching to a non-curative approach, or no change in RT treatment as planned. Subsequent disease course was described using a state-transition cohort model over a 30-year time horizon. Diagnostic characteristics, probabilities, utilities and costs were derived from the literature. Baseline analysis was performed using quality-adjusted life years (QALYs), costs (2019 Canadian dollars, CAD$) and the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were conducted, evaluating net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Probabilistic sensitivity analysis using 10,000 simulations was performed. Costs and QALYs were discounted at a rate of 1.5%. Results: In the reference case scenario, staging PET/CT was the dominant strategy, resulting in an average lifetime cost saving of $3,165 and a gain of 0.32 QALYs. In deterministic sensitivity analyses, the PET/CT strategy remained the preferred strategy for all scenarios supported by available data. In probabilistic sensitivity analysis, the PET/CT strategy was strongly dominant in 77% of simulations (i.e., reduced cost and increased QALYs), and was cost-effective in 89% of simulations (i.e., either cost-saving or with an incremental cost-effectiveness ratio below $100,000/QALY). Conclusion: Our analysis shows that the use of PET/CT to stage early-stage FL patients reduces cost and improves QALYs. Patients with early-stage FL should undergo PET/CT prior to curative-intent RT.

Antibody tests for SARS-CoV-2, the virus that causes COVID-19, are widely available. These practice points help clinicians, patients, and public health professionals understand how to use and interpret these results on the basis of the available evidence. The practice points will be updated as more evidence becomes available., Description: The widespread availability of SARS-CoV-2 antibody tests raises important questions for clinicians, patients, and public health professionals related to the appropriate use and interpretation of these tests. The Scientific Medical Policy Committee (SMPC) of the American College of Physicians developed these rapid, living practice points to summarize the current and best available evidence on the antibody response to SARS-CoV-2 infection, antibody durability after initial infection with SARS-CoV-2, and antibody protection against reinfection with SARS-CoV-2. Methods: The SMPC developed these rapid, living practice points based on a rapid and living systematic evidence review done by the Portland VA Research Foundation and funded by the Agency for Healthcare Research and Quality. Ongoing literature surveillance is planned through December 2021. When new studies are identified and a full update of the evidence review is published, the SMPC will assess the new evidence and any effect on the practice points. Practice Points: Practice Point 1: Do not use SARS-CoV-2 antibody tests for the diagnosis of SARS-CoV-2 infection. Practice Point 2: Antibody tests can be useful for the purpose of estimating community prevalence of SARS-CoV-2 infection. Practice Point 3: Current evidence is uncertain to predict presence, level, or durability of natural immunity conferred by SARS-CoV-2 antibodies against reinfection (after SARS-CoV-2 infection).

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

PURPOSE CD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes. PATIENTS AND METHODS We conducted a multicenter, retrospective review of children and young adults with relapsed or refractory ALL who received CD19-CAR between 2012 and 2019. Primary objectives addressed 6-month relapse-free survival (RFS) and event-free survival (EFS), stratified by blinatumomab use. Secondary objectives included comparison of longer-term survival outcomes, complete remission rates, CD19 modulation, and identification of factors associated with EFS. RESULTS Of 420 patients (median age, 12.7 years; interquartile range, 7.1-17.5) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR constructs, 77 (18.3%) received prior blinatumomab. Blinatumomab-exposed patients more frequently harbored KMT2A rearrangements and underwent a prior stem-cell transplant than blinatumomab-naïve patients. Among patients evaluable for CD19-CAR response (n = 412), blinatumomab nonresponders had lower complete remission rates to CD19-CAR (20 of 31, 64.5%) than blinatumomab responders (39 of 42, 92.9%) or blinatumomab-naive patients (317 of 339, 93.5%), P < .0001. Following CD19-CAR, blinatumomab nonresponders had worse 6-month EFS (27.3%; 95% CI, 13.6 to 43.0) compared with blinatumomab responders (66.9%; 95% CI, 50.6 to 78.9; P < .0001) or blinatumomab-naïve patients (72.6%; 95% CI, 67.5 to 77; P < .0001) and worse RFS. High-disease burden independently associated with inferior EFS. CD19-dim or partial expression (preinfusion) was more frequently seen in blinatumomab-exposed patients (13.3% v 6.5%; P = .06) and associated with lower EFS and RFS. CONCLUSION With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high-disease burden were independently associated with worse RFS and EFS, identifying important indicators of long-term outcomes following CD19-CAR.

BACKGROUND: The enhanced recovery after surgery (ERAS) protocol is a multidisciplinary, multimodal approach which has been shown to facilitate recovery of physiological function, and reduce postoperative pain, complication rates, and length of stay without adversely affecting readmission rates. Design and implementation of ERAS protocols in the recent spine surgery literature has primarily focused on patients undergoing minimally invasive lumbar surgery. However, conventional open transforaminal lumbar interbody fusion (TLIF) remains a common procedure and to date there are no studies assessing an ERAS protocol in this patient population. PURPOSE: This study presents a single surgeon experience implementing an ERAS protocol in patients undergoing 1- or 2-level open TLIF. STUDY DESIGN/SETTING: Retrospective consecutive patient cohort with controls propensity-matched for age, body mass index, sex, and smoking status. PATIENT SAMPLE: Consecutive patients that underwent 1- or 2-level open TLIF for degenerative disease from 12/2018 – 02/2021 and controls from 12/2011–12/2017 by a single surgeon. ERAS was implemented in December 2018. OUTCOME MEASURES: Primary: length of stay; Secondary: first day to ambulate, first day to bowel movement, first day to void, daily average and maximum pain scores, opioid use, discharge disposition, 30-day readmission rate, and re-operations. METHODS: Demographic, perioperative, clinical, radiographic data were collected. Multivariate mixed-linear regression models were developed for length of stay, physiological function, pain scales, and opiate use. RESULTS: There were 114 patients included with 57 in each cohort. After propensity matching, patient characteristics were similar between groups. Operative time decreased significantly after institution of ERAS (170±44 vs. 141±37 minutes, p

PURPOSE: To examine the impact of global risk, a measure comprising age, comorbidities, function, and cognitive statuses, on treatment selection and outcomes among older home care recipients with diffuse large B-cell lymphoma. METHODS: From SEER-Medicare, we selected home care recipients diagnosed with diffuse large B-cell lymphoma in 2011-2015, who had pretreatment Outcome and Assessment Information Set (OASIS) evaluations. We created a global risk indicator categorizing patients as low-, moderate-, or high-risk on the basis of OASIS assessments. We examined the association of global risk with receipt of therapy and among chemotherapy recipients, with mortality, emergency department visits, hospitalization, and intensive care unit admission within 30 days from first treatment in logistic models, reporting adjusted odds ratios (OR) with 95% CI. We compared overall survival across risk groups estimating adjusted hazard ratios. RESULTS: Of the 1,232 patients (median age, 80 years), 65% received chemotherapy. High-risk patients ( v moderate-risk) were less likely to receive any chemotherapy (OR, 0.50; 95% CI, 0.39 to 0.64) and curative regimens (OR, 0.59; 95% CI, 0.40 to 0.86) if treated, although even in the moderate-risk group, only 61% received curative regimens. High-risk patients were more likely to experience acute mortality (OR, 2.24; 95% CI, 1.43 to 3.52), emergency department visits (OR, 1.35; 95% CI, 1.00 to 1.83), hospitalization (OR, 1.60; 95% CI, 1.19 to 2.17), or intensive care unit admission (OR, 1.52; 95% CI, 1.04 to 2.22) and had inferior overall survival (hazard ratio, 1.41; 95% CI, 1.11 to 1.78). CONCLUSION: Global risk on the basis of OASIS is easily available, suggesting a potential way to improve patient selection for curative treatment and institution of preventive measures.

Background Despite improvement in implant design, total elbow arthroplasty (TEA) failures remain a common occurrence with significant patient morbidity. Recent literature points to aseptic loosening as the most common cause of failure. However, investigations of the location of failure are conflicting, and most studies to date have been retrospective reports from single institutions. The aim of this study was to use a national database to investigate the distribution of TEA adverse events according to failure mode and location, with the hypothesis that the aseptic loosening would be the most common cause of TEA failure, and there would be no significant difference between rates of humeral-sided and ulnar-sided failures. Methods The US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is a federally mandated reporting system for implant failures. The MAUDE database was searched for TEA adverse event reports among all loosely linked TEA constructs from 2008 to 2019. TEA failure reports were individually analyzed for failure mode and categorized according to anatomic location. The chi-square test was used to statistically assess differences in categorical data between groups. Results A total of 869 TEA failure reports were included in this study. The most common mode of failure was aseptic loosening (26.8%) followed by component mechanical failure (23.9%), infection (16.1%), and periprosthetic fracture (11.5%). When evaluating TEA failure reports by anatomic location, the majority of aseptic loosening failures occurred at the humeral component as compared to the ulnar component (71.7% vs. 28.3%; P Conclusion TEA failure reports in the large and nationally representative FDA MAUDE database differed from what is represented in current literature, with higher rates of humeral component aseptic loosening than has been previously reported. Understanding TEA failure mechanisms will help direct future design and surgical technical improvements. Level of Evidence Level IV

Although revision to new components is favored after shoulder periprosthetic joint infections (PJIs), implant exchange is not always feasible. In certain cases, definitive treatment may be retainment of an antibiotic spacer or resection arthroplasty. The purpose of this investigation was to systematically review the literature for studies reporting on outcomes after resection arthroplasty or permanent antibiotic spacer for salvage treatment of shoulder PJIs.A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for Level I-IV studies that reported on the final treatment of periprosthetic shoulder infections using resection arthroplasty or a permanent antibiotic spacer. Data recorded included study demographics, causative infectious organism, shoulder-specific range of motion and outcome measures, and infection eradication rate. Study methodological quality was analyzed using the Methodological Index for Non-Randomized Studies score. Forest plots of proportions and meta-analyses of single means were generated for infection eradication rates and outcomes, respectively. Heterogeneity was quantified using the IThe initial search yielded 635 articles (211 duplicates, 424 screened, 57 full-text review). Twenty-three articles (126 resection arthroplasty and 177 retained antibiotic spacer patients, 51% females, mean age range 37-78.5 years, mean Methodological Index for Non-Randomized Studies score 9.6 ± 0.7) were included and analyzed. The pooled infection eradication rate was 82% (72%-89%) after resection arthroplasty and 85% (79%-90%) after permanent antibiotic spacer. The pooled mean forward flexion (71.5° vs. 48.7°; P.001) and mean American Shoulder and Elbow Surgeons score (53.5 vs. 31.0; P.001) were significantly higher for patients treated with a permanent antibiotic spacer compared with resection arthroplasty. No significant differences were found for mean external rotation (13.5° vs. 20.5°; P = .07), abduction (58.2° vs. 50.3°; P = .27), or visual analog scale pain (3.7 vs. 3.4; P = .24) between groups. There was a statistically significant, but not clinically significant, difference in mean Constant score between permanent antibiotic spacer and resection arthroplasty patients (33.6 vs. 30.0; P.001).When implant exchange after shoulder PJI is not feasible, permanent antibiotic spacers and resection arthroplasty are both salvage procedures that provide similar rates of infection eradication. Although both can decrease pain levels, the permanent antibiotic spacer may result in better functional outcomes compared with resection arthroplasty.

Congenital hydrocephalus (CH), characterized by incomplete clearance of CSF and subsequent enlargement of brain ventricles, is the most common congenital brain disorder. The lack of curative strategies for CH reflects a poor understanding of the underlying pathogenesis. Herein, the authors present an overview of recent findings in the pathogenesis of CH from human genetic studies and discuss the implications of these findings for treatment of CH. Findings from these omics data have the potential to reclassify CH according to a molecular nomenclature that may increase precision for genetic counseling, outcome prognostication, and treatment stratification. Beyond the immediate patient benefits, genomic data may also inform future clinical trials and catalyze the development of nonsurgical, molecularly targeted therapies. Therefore, the authors advocate for further application of genomic sequencing in clinical practice by the neurosurgical community as a diagnostic adjunct in the evaluation and management of patients diagnosed with CH.

The purpose of this study was to assess the performance and limitations of low-voltage zones (LVZ) localization by optimized late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) scar imaging in patients with cardiac implantable electronic devices (CIEDs).Scar evaluation by LGE-CMR can assist ventricular tachycardia (VT) ablation, but challenges with electroanatomical maps coregistration and presence of imaging artefacts from CIED limit accuracy.A total of 10 patients underwent VT ablation and preprocedural LGE-CMR using wideband imaging. Scar was segmented from CMR pixel signal intensity maps using commercial software (ADAS-VT, Galgo Medical) with bespoke tools and compared with detailed electroanatomical maps (CARTO). Coregistration of EP and imaging-derived scar was performed using the aorta as a fiducial marker, and the impact of coregistration was determined by assessing intraobserver/interobserver variability and using computer simulations. Spatial smoothing was applied to assess correlation at different spatial resolutions and to reduce noise.Pixel signal intensity maps localized low-voltage zones (V 1.5 mV) with area under the receiver-operating characteristic curve: 0.82 (interquartile range [IQR]: 0.76-0.83), sensitivity 74% (IQR: 71%-77%), and specificity 78% (IQR: 73%-83%) and correlated with bipolar voltage (r = -0.57 [IQR: -0.68 to -0.42]) across patients. In simulations, small random shifts and rotations worsened LVZ localization in at least some cases. The use of the full aortic geometry ensured high reproducibility of LVZ localization (r0.86 for area under the receiver-operating characteristic curve). Spatial smoothing improved localization of LVZ. Results for LVZ with V 0.5 mV were similar.In patients with CIEDs, novel wideband CMR sequences and personalized coregistration strategies can localize LVZ with good accuracy and may assist VT ablation procedures.

Treatment of malignant biliary strictures with endoscopic retrograde cholangiopancreatography (ERCP) guided stent placement is highly effective. Our objective was to compare the efficacy and adverse outcomes between plastic stents (PS) and self-expandable metallic stents (SEMS).A cohort study was performed of all consecutive patients who underwent ERCP with stent placement for the management of malignant biliary stricture. Comparisons on clinical success, patency duration, stent dysfunction, unplanned reintervention and adverse outcomes were performed. Univariate and multivariable analyses were performed to identify factors associated with clinical success, need for reintervention, and stent dysfunction.From 2012 to 2019, 1139 patients underwent ERCP with PS placement while 1008 patients received SEMS for the management of malignant biliary stricture. In distal strictures, SEMS reported a significantly higher rate of clinical success compared with PS (94.1% vs 87.4%, P0.001) and a lower rate of unplanned reintervention (17.1% vs 27.4%, P0.001). In hilar strictures, the rates of clinical success and unplanned intervention were comparable. The patency duration and time to unplanned reintervention were significantly longer with SEMS than PS, irrespective of stricture location. In distal stricture, PS was associated with a significantly higher rate of cholangitis than SEMS (6.9% vs 2.4%; P.001) but a lower rate of pancreatitis (3.6% vs 6%; P = 0.021).Given superior efficacy, durability and lower rates of cholangitis, SEMS should be offered as the first line endoscopic treatment option for malignant distal biliary stricture. For malignant hilar stricture, SEMS is an attractive alternative to PS in some cases by offering a comparable efficacy with a superior durability.

Background: Hypoglossal and masseteric nerve transfer are currently the most popular cranial nerve transfer techniques for patients with facial paralysis. The authors performed a systematic review and meta-analysis to compare functional outcomes and adverse effects of these procedures. Methods: A review of online databases was performed to include studies with four or more patients undergoing hypoglossal or masseter nerve transfer without muscle transfer or other cranial nerve transposition. Facial nerve outcomes, time to reinnervation, and adverse events were pooled and studied. Results: A total of 71 studies were included: 15 studies included 220 masseteric-facial transfers, and 60 studies included 1312 hypoglossal-facial transfers. Oral commissure symmetry at rest was better for hypoglossal transfer (2.22 ± 1.6 mm vs. 3.62 ± 2.7 mm, p = 0.047). The composite Sunnybrook Facial Nerve Grading Scale was better for masseteric transfer (47.7 ± 7.4 vs. 33.0 ± 6.4, p < 0.001). Time to first movement (in months) was significantly faster in masseteric transfer (4.6 ± 2.6 vs. 6.3 ± 1.3, p < 0.001). Adverse effects were rare (

Context: The Dynavision D2™ Mode A test (ModeA) is a 1-minute reaction time (RT) test commonly used in sports science research and clinical rehabilitation. However, there is limited data regarding the effect of repeated testing (ie, training) or subsequent periods of no testing (ie, detraining) on test–retest reliability and RT performance. Therefore, the purpose of this study was to examine the test–retest reliability, training, and detraining effects associated with the D2™ ModeA test. Design: Repeated measures/reliability. Methods: Twenty-four recreationally active men and women completed 15 training sessions consisting of 2 ModeA tests per session (30 tests). The participants were then randomized to either 1 or 2 weeks of detraining prior to completing 15 retraining sessions (30 tests). The training and retraining periods were separated into 10 blocks for analysis (3 tests per block). The number of hits (hits) and the average RT per hit (AvgRT) within each block were used to determine RT performance. Intraclass correlation coefficients, SEM, and minimum difference were used to determine reliability. Repeated-measures analysis of variance/analysis of covariance were used to determine training and detraining effects, respectively. Results: The ModeA variables demonstrated excellent test–retest reliability (intraclass correlation coefficient2,3 > .93). Significant improvements in hits and AvgRT were noted within training blocks 1 to 5 (P Conclusions: It appears that 15 tests are necessary to overcome the training effect and establish reliable baseline performance for the ModeA test. Detraining for 1 to 2 weeks did not impact RT performance. The authors recommend that investigators and clinicians utilize the average of 3 tests when assessing RT performance using the D2 ModeA test.

Bony stabilization procedures are a reliable solution for recurrent shoulder instability, but have a steep learning curve due to technical difficulties. Meticulous capsular closure is critical, and can be augmented with suture anchor constructs. Additionally, while fracture or fragmentation of the coracoid graft is a relatively uncommon, it is devastating. Here, we describe the use of additional circumferential suture fixation to Improve compression across the graft/glenoid interface, and help mitigate the risk of fracture bony augmentation procedures

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

BACKGROUND: Understanding the relationship between patterns of peripheral artery disease patterns and outcomes is an essential step towards improving care and outcomes. We hypothesized that clinician specialty would be associated with occurrence of major adverse vascular events (MAVE). METHODS: Patients with at least 1 peripheral artery disease-related encounter in our health system and fee-for-service Medicare were divided into groups based on the specialty of the clinician (cardiologist, surgeon, podiatrist, primary care, or other) providing a plurality of peripheral artery disease-coded care in the year prior to index encounter. The primary outcome was MAVE (a composite of all-cause mortality, myocardial infarction, stroke, lower extremity revascularization, and lower extremity amputation). RESULTS: The cohort included 1,768 patients, of whom 30.0% were Black, 23.9% were Medicaid dual-enrollment eligible, and 31.1% lived in rural areas. Patients receiving a plurality of their care from podiatrists had the highest 1-year rates of MAVE (34.4%, p

Detecting radioactive materials in mixtures is challenging due to low concentration, environmental factors, sensor noise, and others. This paper presents new results on nuclear material identification and mixing ratio estimation for mixtures of materials in which there are multiple isotopes present. Conventional and deep learning-based machine learning algorithms were compared. Both simulated and actual experimental data were used in the comparative studies. It was observed that some newly developed machine learning and deep learning methods have better performance than a conventional method based on region of interest (ROI). Extensive experiments also demonstrated that trained models using low signal-to-background ratio (SBR) data can better generalize to other SBR conditions.

Background Superficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long‐term remissions might be more common than previously believed and linked to treatment regimens. Hypothesis/Objectives Evaluate treatments and associated outcomes in dogs with hepatocutaneous‐associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES). Animals Forty‐one dogs of various breeds and ages diagnosed with ACHES. Methods Retrospective study. Electronic surveys, medical records (2014‐2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV‐AA) infusions (≥2 vs 1783 days, P = .02) than variably treated dogs (MST, 214 days). Conclusions and Clinical Importance Optimized ACHES management can resolve SND and HCH and confer long‐term survival.

Up to 93% of the human immunodeficiency virus (HIV) latent reservoir comprised defective proviruses, suggesting that a functional cure is possible through the elimination of a small population of cells containing intact virus, instead of the entire reservoir. Cyclophosphamide (Cy) is an established chemotherapeutic agent for immune cell cancers. In high doses, Cy is a nonselective cytoreductor, used in allogeneic stem-cell transplantation, while in a low dose, metronomic schedule, Cy selectively depletes regulatory T cells (Tregs). We administered low and high doses to simian immunodeficiency virus (SIV)-infected rhesus macaques (RM) to assess their effects on the SIV reservoirs. As a Treg-depleting agent, Cy unselectively depleted Treg and total lymphocytes, resulting in minimal immune activation and no viral reactivation. As a cytoreductive agent, Cy induced massive viral reactivation in elite controller RMs without ART. However, when administered with antiretroviral therapy (ART), Cy had substantial adverse effects, including mortality. Our study thus dissuades further investigation of Cy as an HIV cure agent.

To provide a systematic review and meta-analysis of the quantitative literature on homesickness in children, including how it is assessed and relationship to other negative states.A literature search was conducted using Medline, PsychINFO and Scopus databases. Studies were included if they assessed homesickness in children under eighteen years of age and were published in peer reviewed journals in the English language between 1990 and December 2020. A total of 176 studies were screened for relevance and 17 met the inclusion criteria for the systematic review with five studies included in the meta-analysis.The primary outcome measure was homesickness severity, and it was examined in relation to measures of depression and anxiety. The literature in relation to known risk and protective factors was also reviewed.Homesickness was reported in the majority of children who were separated from their home. It was associated with negative emotional states. A total of seventeen studies were included in the quantitative review. The meta-analysis showed a significant relationship between homesickness and depression r=0.431 (95% CI 0.344-0.510; p0.001) and homesickness and anxiety r=0.426 (95% CI 0.369-0.479; p0.001). Age was not a significant moderator of homesickness severity. Consideration of effective interventions to address homesickness was limited.Homesickness significantly impacts children's well-being regardless of age and is associated with overall distress, depression and anxiety. Future studies are required to examine homesickness interventions and supports to improve well-being in children.

Background Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with ‘pneumonia’ the year previously. Methods We conducted a medical record review of patients admitted with Covid-19 and a pulmonary infiltrate and compared them with patients diagnosed with pneumonia admitted in the prior year before the pandemic. Data abstracted included baseline demographics, comorbidities, signs and symptoms, laboratory and microbiological results, and imaging findings. Outcomes were bacterial infections and mortality. Patients presenting with and without Covid-19 were compared using univariable and multivariable analyses. Results There were 1398 and 1001 patients admitted through the emergency department (ED) with and without Covid-19 respectively. Compared with non-Covid-19 patients, those with Covid-19 were younger (61±18 vs. 65±25 years, P

PURPOSE Increased CD123 surface expression has been associated with high-risk disease characteristics in adult acute myeloid leukemia (AML), but has not been well-characterized in childhood AML. In this study, we defined CD123 expression and associated clinical characteristics in a uniformly treated cohort of pediatric patients with newly diagnosed AML enrolled on the Children's Oncology Group AAML1031 phase III trial ( NCT01371981 ). MATERIALS AND METHODS AML blasts within diagnostic bone marrow specimens (n = 1,040) were prospectively analyzed for CD123 protein expression by multidimensional flow cytometry immunophenotyping at a central clinical laboratory. Patients were stratified as low-risk or high-risk on the basis of (1) leukemia-associated cytogenetic and molecular alterations and (2) end-of-induction measurable residual disease levels. RESULTS The study population was divided into CD123 expression–based quartiles (n = 260 each) for analysis. Those with highest CD123 expression (quartile 4 [Q4]) had higher prevalence of high-risk KMT2A rearrangements and FLT3-ITD mutations ( P < .001 for both) and lower prevalence of low-risk t(8;21), inv(16), and CEBPA mutations ( P < .001 for all). Patients in lower CD123 expression quartiles (Q1-3) had similar relapse risk, event-free survival, and overall survival. Conversely, Q4 patients had a significantly higher relapse risk (53% v 39%, P < .001), lower event-free survival (49% v 69%, P < .001), and lower overall survival (32% v 50%, P < .001) in comparison with Q1-3 patients. CD123 maintained independent significance for outcomes when all known contemporary high-risk cytogenetic and molecular markers were incorporated into multivariable Cox regression analysis. CONCLUSION CD123 is strongly associated with disease-relevant cytogenetic and molecular alterations in childhood AML. CD123 is a critical biomarker and promising immunotherapeutic target for children with relapsed or refractory AML, given its prevalent expression and enrichment in patients with high-risk genetic alterations and inferior clinical outcomes with conventional therapy.

Background Selective dental clearance before total joint arthroplasty (TJA) has been proposed; however, effective strategies of carrying out this practice are lacking. This study aims to determine the positive predictive value (PPV) of a novel oral examination performed by an orthopedic surgeon to better direct limited resources for marginalized patients in a safety net hospital system. Methods A retrospective review was conducted on 105 consecutive patients who had an oral examination performed by a single surgeon before elective TJA. Patients who screened negative proceeded to surgery without further formal dental clearance. Patients who screened positive underwent formal examination/intervention by a dentist before surgery. The rate of correct referral that resulted in patients undergoing an oral surgical intervention was determined. Complications during a minimum 90-day postoperative follow-up period were collected and compared. Results Thirty patients (28.6%) screened positive while 75 patients (71.4%) screened negative and proceeded to surgery without referral. The PPV of the screening test was high, with 73.3% of patients receiving a major surgical oral intervention before TJA. Patients sent for formal referral required 89.1 more days to receive their surgery than those that screened negative (54.9 days ± 4.24 vs 144.0 days ± 82.4, P Conclusion An orthopedic surgeon’s oral examination demonstrates a high PPV to identify high-risk patients in need of an oral surgical intervention before TJA. This provides a unique solution regarding over-referral for preoperative dental clearance and avoids delays for marginalized patients considering elective TJA in a safety net hospital system.

Key Points The NGS-MRD assay detected clonotypic DNA in 100% of CSF samples from patients who had lymphoma with parenchymal CNS involvement.Clonotypic DNA in CSF was present in 36% of newly diagnosed aggressive lymphomas and was associated with a 29% risk of CNS recurrence., Visual Abstract, The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)–based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. They included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at a median of 39 months before accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive assay of CSF was associated with a 29% cumulative risk of CNS recurrence within 12 months of diagnosis, in contrast with a 0% risk among patients with negative CSF (P = .045). These observations suggest that detection of clonotypic DNA can aid in the diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay may enhance clinical risk assessment for CNS recurrence among patients with newly diagnosed lymphomas and help select those who may benefit most from novel approaches to CNS-directed prophylaxis.

As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN. The association between flares and HBsAg and HBV RNA changes were examined. On-treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4–12], 7.6 × ULN [IQR 6.2–10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no-flare group. More flares were observed on PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de novo combination (24%) vs. PEG-IFN-α add-on (2%) or NA monotherapy (1%) (p 10 at the final visit declines started shortly before the flare, progressing towards 24 weeks thereafter. On-treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG-IFN-α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG-IFN-α add-on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising.

This study aimed to investigate the impact of race on hospital length of stay (LOS) and hospital complications among pediatric patients with cervical/thoracic injury.A retrospective cohort was performed using the 2017 admission year from 753 facilities utilizing the National Trauma Data Bank. All pediatric patients with cervical/thoracic spine injuries were identified using the ICD-10-CM diagnosis coding system. These patients were segregated by their race, non-Hispanic white (NHW), non-Hispanic black (NHB), non-Hispanic Asian (NHA), and Hispanic (H). Demographic, hospital variable, hospital complications, and LOS data were collected. A linear and logistic multivariate regression analysis was performed to determine the risk ratio for hospital LOS as well as complication rate, respectively.A total of 4,125 pediatric patients were identified. NHB cohort had a greater prevalence of cervical-only injuries (NHW: 37.39% vs. NHB: 49.93% vs. NHA: 34.29% vs. H: 38.71%, P0.001). While transport accident was most common injury etiology for both cohorts, NHB cohort had a greater prevalence of assault (NHW: 1.53% vs. NHB: 17.40% vs. NHA: 2.86% vs. H: 6.58%, P0.001) than the other cohorts. Overall complication rates were significantly higher among NHB patients (NHW: 9.39% vs. NHB: 15.12% vs. NHA: 14.29% vs. H: 13.60%, P0.001). Compared with the NHW cohort, NHB, NHA, and H had significantly longer hospital LOS (NHW: 6.15 ± 9.03 days vs. NHB: 9.24 ± 20.78 days vs. NHA: 9.09 ± 13.28 days vs. H: 8.05 ± 11.45 days, P0.001). NHB race was identified as a significant predictor of increased LOS on multivariate regression analysis (risk ratio: 1.14, 95% confidence interval: 0.46, 1.82; P = 0.001) but not hospital complications (P = 0.345).Race may significantly impact health care resource utilization following pediatric cervical/thoracic spinal trauma.

Background Socioeconomic disparities have been associated with outcomes in many medical conditions. The association of socioeconomic status (SES) with readmissions after ventral and inguinal hernia repair has not been well studied on a national level. This study aims to evaluate the association of SES with readmission as a significant outcome in patients undergoing ventral and inguinal hernia repair. Methods A retrospective cohort study was performed evaluating patients undergoing ventral hernia and inguinal hernia repair with 1:1 propensity score matching using the Nationwide Readmissions Database (2016-2017). Both 30- and 90-day readmissions were examined. After matching, a multivariate logistic regression analysis was performed using confounding variables including hospital setting, comorbidities, urgency of repair, sociodemographic status, and payer. Likelihood of readmission was reported in odds ratio form. Results Readmission rates were 11.56% (24,323 out of 210,381) and 17.94% (30,893 out of 172,210) for 30- and 90-day readmissions, respectively. Patients with Medicaid and in the lower income quartile were more likely to present in an emergent fashion for hernia repair. After matching, a multivariate logistic regression analysis showed socioeconomic status (OR 1.250 and 1.229) was a statistically significant independent predictor of readmission at 30 and 90 days, respectively. Inversely, factors associated with the least likely chance of readmission were a laparoscopic approach (OR 0.646 and 0.641), elective admission (OR 0.824 and 0.779), and care in a teaching hospital (OR 0.784 and 0.798). Conclusion SES is an independent predictor of readmission at 30 and 90 days following open and laparoscopic ventral and inguinal hernia repair. Patients with a lower socioeconomic status were more likely to undergo hernia repair in the emergent setting. Efforts toward mitigating SES disparities by potentially promoting MIS techniques, enhancing access to elective cases, and systematic approaches to perioperative care for this disadvantaged population can potentially enhance overall hernia outcomes.

Over the last 50 years, nuclear energy has reduced US energy-related CO2 emissions by over 30 gigatons compared to if the same electricity were produced by fossil fuels such as coal and natural gas. However, many kilotons of spent nuclear fuel have accumulated at different sites across the country, and sociopolitical factors have frustrated efforts to address the challenge of nuclear waste disposal. Presently, a consolidated interim storage facility in Andrews, Texas, provides a promising temporary solution. In this paper, we compare the technical and policy risks of the project to continued storage at independent spent fuel storage installations. Our results indicate that the cost of the radiological risk is low (

Due to the high prevalence of opioid prescription following orthopedic procedures, there is a growing need to establish an animal model system to evaluate the effects of opioids on bone remodeling. Rabbits have been employed as model organisms in orthopedic research as they exhibit well-defined cortical bone remodeling similar to humans. Existing research in rabbits has been limited to modes of opioid administration that are short-acting and require repeated application. Here, we present data from a proof-of-principle longitudinal study employing two opioid analgesic administration routes (subcutaneous injection and transdermal patch) to evaluate the efficacy of studying chronic opioid exposure in a rabbit model. Skeletally mature male New Zealand White rabbits (Oryctolagus cuniculus) were divided into three groups of seven animals: morphine, fentanyl, and control. Experimental treatments were conducted for eight weeks. Preparation of the skin at the fentanyl patch site and subsequent patch removal presented experimental difficulties including consistent skin erythema. Though noninvasive, the patches further caused acute stress in fentanyl animals. We conclude that though transdermal fentanyl patches may be preferred in an acute clinical setting, this method is not feasible as a means of long-term pain relief or opioid delivery in a laboratory context.

In the United States, attaining the orthopedic certified specialist (OCS) credential or the orthopedic subspecialty credential of Fellow of the American Academy of Orthopedic Manual Physical Therapists (FAAOMPT), may lead to a higher level of orthopedic practice. It is unknown whether attaining these credentials influences physical therapist confidence in and frequency of engagement in prescription opioid medication misuse (POMM) management practices. A national cross-sectional web-based survey of PTs identified whether respondents had an OCS or FAAOMPT credential. Self-report confidence in POMM-related management practices and the frequency of engaging in these practices were assessed. Logistic regression evaluated association between credential status and confidence in, and frequency of, engagement in POMM-related management practices. The analysis included 402 respondents with a mean age of 41.0 (SD = 11.2) and 203 (50.4%) females. There were 91 (22.6%) PTs with a FAAOMPT credential, 143 (35.6%) with an OCS but with no FAAOMPT credential and 168 (41.8%) had neither credential. Compared to those with an OCS credential, FAAOMPTs reported greater confidence in, and greater frequency of engagement in, POMM-related management practices (p

This retrospective cohort study of cancer decedents during 2004–2015 examined end-of-life cancer care quality indicators (QIs) in the provinces of British Columbia (BC), Ontario, and Nova Scotia (NS). These included: emergency department use, in-patient hospitalization, intensive care unit admissions, physician house calls, home care visits, and death experienced in hospital. Ontario saw the greatest 12-year decrease in in-hospital deaths from 52.8% to 41.1%. Hospitalization rates within 30 days of death decreased in Ontario, increased in NS, and remained the same in BC. Ontario’s usage of aggressive end-of-life measures changed very little, while BC increased their utilization rates. Supportive care use increased in both NS and Ontario. Those who were male or living in a lower income/smaller community (in Ontario) were associated with a decreased likelihood of receiving supportive care. Despite the shift in focus to providing hospice and home care services, approximately 50% of oncology patients are still dying in hospital and 11.7% of patients overall are subject to aggressive care measures that may be out of line with their desire for comfort care. Supportive care use is increasing, but providers must ensure that Canadians are connected to palliative services, as its utilization improves a wide variety of outcomes.

In under-resourced settings, general surgeons may be called upon to perform emergency operations within other specialties. Accordingly, we aimed to characterise patient outcomes after emergency neurosurgery performed by a general surgeon or general surgery trainee. PubMed, Embase and the Cochrane Library were searched to 30 May 2021 for observational studies reporting outcomes after emergency neurosurgery performed by a general surgeon. Study screening, data extraction, and risk of bias using the Downs and Black checklist were performed in duplicate. Data on setting, operation undertaken, mortality rates and complications were extracted. Meta-analysis was planned but not possible due to heterogeneity. This study is registered with PROSPERO, CRD42021258097. From 632 records, 14 retrospective observational studies were included, covering a total sample of 1,988 operations. Four studies were from Australia, and the remaining 10 were, respectively, from 10 other countries. Most common operations performed were decompressive surgery with burr holes or craniectomy for head trauma and insertion of intracranial pressure monitors. Rural hospitals were the most common settings. Mortality rates for procedures performed by general surgeons at latest follow-up were heterogenous, ranging from 5% for evacuation of chronic subdural haematoma in Kenya to 81% in head injured patients in a Hong Kong study. This is the first systematic review that synthesises the literature to characterise patient outcomes after neurosurgical operations performed by a general surgeon. Findings from this study may benefit global surgery performed in rural, remote, military or humanitarian settings.