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Background: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes., Methods: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings., Results: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8-16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08-2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92-11.57) and 5.25 (95% CI, 2.05-13.40) of later osteochondral changes on MRI., Discussion: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objective: Ankylosing spondylitis, the most common spondyloarthritis, fuses individual spinal vertebrae into long segments. The unique biomechanics of the ankylosed spine places patients at unusually high risk for unstable fractures secondary to low-impact mechanisms. These injuries are unique within the spine trauma population and necessitate thoughtful management. Therefore, the authors aimed to present a richly annotated data set of operative AS spine fractures with a significant portion of patients with simultaneous dual noncontiguous fractures., Methods: Patients with ankylosing spondylitis with acute fractures who received operative management between 2012 and 2020 were reviewed. Demographic, admission, surgical, and outcome parameters were retrospectively collected and reviewed., Results: In total, 29 patients were identified across 30 different admissions. At admission, the mean age was 71.7 ± 11.8 years. The mechanism of injury in 77% of the admissions was a ground-level fall; 30% also presented with polytrauma. Of admissions, 50% were patient transfers from outside hospitals, whereas the other half presented primarily to our emergency departments. Fifty percent of patients sustained a spinal cord injury, and 35 operative fractures were identified and treated in 32 surgeries. The majority of fractures clustered around the cervicothoracic (C4-T1, 48.6%) and thoracolumbar (T8-L3, 37.11%) junctions. Five patients (17.2%) had simultaneous dual noncontiguous operative fractures; these patients were more likely to have presented with a higher-energy mechanism of injury such as a bicycle or motor vehicle accident compared with patients with a single operative fracture (60% vs 8%, p = 0.024). On preoperative MRI, 56.3% of the fractures had epidural hematomas (EDHs); 25% were compressive of the underlying neural elements, which dictated the number of laminectomy levels performed (no EDH, 2.1 ± 2.36; noncompressive EDH, 2.1 ± 1.85; and compressive EDH, 7.4 ± 4 [p = 0.003]). The mean difference in instrumented levels was 8.7 ± 2.6 with a mean estimated blood loss (EBL) of 1183 ± 1779.5 mL. Patients on a regimen of antiplatelet therapy had a significantly higher EBL (2635.7 mL vs 759.4 mL, p = 0.015). Overall, patients had a mean hospital length of stay of 15.2 ± 18.5 days; 5 patients died during the same admission or after transfer to an outside hospital. Nine of 29 patients (31%) had died by the last follow-up (the mean follow-up was 596.3 ± 878.9 days)., Conclusions: Patients with AS who have been found to have unstable spine fractures warrant a thorough diagnostic evaluation to identify secondary fractures as well as compressive EDHs. These patients experienced prolonged inpatient hospitalizations with significant morbidity and mortality.

Background: In March 2020, COVID-19 assessment centres were launched across the province of Ontario to facilitate COVID-19 testing outside of emergency departments. We aimed to study the degree to which assessment centres provide education and follow-up care for patients with suspected COVID-19., Methods: We conducted an online survey of Ontario COVID-19 assessment centre directors between September 15 and October 15, 2020. The primary outcomes studied were the types of educational modalities employed and information conveyed, methods and frequency of test result communication, and any follow-up care that was offered. Survey respondents were also asked to provide descriptions of barriers to patient education and test communication., Results: A total of 56 directors (representing 73 assessment centres) completed the survey. The most frequent educational modalities employed were educational handouts (92%), direct in-person counselling (89%), and referral to website (72%). Seventy-one percent of respondents indicated patients with positive test results would be notified, and 61% of respondents indicated that follow-up care would be offered. The most frequently reported barriers to patient education were insufficient time and high volume of tests, while the most frequently reported barriers to communication of test results were difficulty accessing online health portals and high volume of tests., Conclusion: The ability of many assessment centres to provide patient education is limited by both individual patient and system-level factors. Assessment centres may benefit from standardization of educational materials, improved accessibility to test results for patients in marginalized groups, and virtual pathways to facilitate additional counselling and care for individuals who test positive., Competing Interests: Dr Andany reports participation as a site investigator for HIV clinical trials sponsored by Gilead, Janssen and GlaxoSmithKline, outside the submitted work., (Copyright © 2021, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

Objective: Reduction of Meyerding grade is often performed during fusion for spondylolisthesis. Although radiographic appearance may improve, correlation with patient-reported outcomes (PROs) is rarely reported. In this study, the authors' aim was to assess the impact of spondylolisthesis reduction on 24-month PRO measures after decompression and fusion surgery for Meyerding grade I degenerative lumbar spondylolisthesis., Methods: The Quality Outcomes Database (QOD) was queried for patients undergoing posterior lumbar fusion for spondylolisthesis with a minimum 24-month follow-up, and quantitative correlation between Meyerding slippage reduction and PROs was performed. Baseline and 24-month PROs, including the Oswestry Disability Index (ODI), EQ-5D, Numeric Rating Scale (NRS)-back pain (NRS-BP), NRS-leg pain (NRS-LP), and satisfaction (North American Spine Society patient satisfaction questionnaire) scores were noted. Multivariable regression models were fitted for 24-month PROs and complications after adjusting for an array of preoperative and surgical variables. Data were analyzed for magnitude of slippage reduction and correlated with PROs. Patients were divided into two groups: < 3 mm reduction and ≥ 3 mm reduction., Results: Of 608 patients from 12 participating sites, 206 patients with complete data were identified in the QOD and included in this study. Baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts except for depression, listhesis magnitude, and the proportion with dynamic listhesis (which were accounted for in the multivariable analysis). One hundred four (50.5%) patients underwent lumbar decompression and fusion with slippage reduction ≥ 3 mm (mean 5.19, range 3 to 11), and 102 (49.5%) patients underwent lumbar decompression and fusion with slippage reduction < 3 mm (mean 0.41, range 2 to -2). Patients in both groups (slippage reduction ≥ 3 mm, and slippage reduction < 3 mm) reported significant improvement in all primary patient reported outcomes (all p < 0.001). There was no significant difference with regard to the PROs between patients with or without intraoperative reduction of listhesis on univariate and multivariable analyses (ODI, EQ-5D, NRS-BP, NRS-LP, or satisfaction). There was no significant difference in complications between cohorts., Conclusions: Significant improvement was found in terms of all PROs in patients undergoing decompression and fusion for lumbar spondylolisthesis. There was no correlation with clinical outcomes and magnitude of Meyerding slippage reduction.

The diagnostic role of Isocitrate Dehydrogenase (IDH) mutation status in adult lower grade astrocytomas was first formally presented within the WHO Classification of Tumours of the Central Nervous System (2016). IDH-mutant astrocytomas are not as common as IDH-wildtype astrocytomas but are of better prognosis. Our previous study provided an evident that IDH-mutant lower grade astrocytomas is not a homogeneous group and could be further stratified by PDGFRA amplification, CDK4 amplification and CDKN2A deletion. In this study, we detected the expressions of DNA mismatch repair (MMR) proteins (PMS2, MLH1, MSH2, MSH6) and PD-L1 by immunohistochemistry in 147 IDH-mutant lower grade astrocytomas and explored their clinical relevance. The loss of was identified in 28.6%, 1.4%, 8.8% and 13.6%, respectively. PD-L1 expression was detected in 1.4% of this cohort. Survival analysis revealed that loss of PMS2 was correlated with shorter OS (p < 0.001) and PFS (p = 0.005). Loss of PMS2 or MLH1 was associated with shorter OS (p < 0.001) and PFS (p = 0.008). In IDH-mutant lower grade astrocytomas without CDKN2A deletion, loss of PMS2 was associated with poorer OS (p < 0.001) and PFS (p = 0.001). Furthermore, among IDH-mutant lower grade astrocytomas lacking the three biomarkers (PDGFRA, CDK4 and CDKN2A), loss of PMS2 was also associated with a poorer OS (p < 0.001) and PFS (p = 0.003). Our data illustrated the potential application of MMR genes in stratification of IDH-mutant lower grade astrocytomas without PDGFRA, CDK4 and CDKN2A copy number alterations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Traditional iliac screws and S2-alar iliac (S2-AI) screws are common methods used for pelvic fixation, and many surgeons advocate pelvic fixation for long-segment fixation to the sacrum. However, in patients without severe deformities and only degenerative conditions, many surgeons may choose S1 screws only. Moreover, even with S2-AI screws, there is more muscular dissection than with using S1 screws, and the rod connection can be cumbersome in both S2-AI fixation and placing iliac screws. Using a surgical video, artist's illustration, and intraoperative photographs, the authors describe the S1-AI screw fixation technique that allows for single-screw sacral and iliac fixation, requires less distal dissection of the sacrum, allows for easier rod connection, and may be an option in degenerative conditions needing pelvic fixation. However, this is a preliminary feasibility study, and in long fusion constructs, this type of fixation has only been used in conjunction with L5-S1 anterior lumbar interbody fusion (ALIF), and there are no long-term data on the use of this screw fixation technique without ALIF. In short-segment revision fusions, this technique may be considered for salvage in cases of large halos in the sacrum from loosened S1 screw fixation.

Objective: Anterior lumbar interbody fusion (ALIF) is an effective surgical modality for many lumbar degenerative pathologies, but a rare and infrequently reported complication is postoperative lymphocele. The goals of the present study were to review a large consecutive series of patients who underwent ALIF at a high-volume institution, estimate the rate of lymphocele occurrence after ALIF, and investigate the outcomes of patients who developed lymphocele after ALIF., Methods: A retrospective review of the electronic medical record was completed, identifying all patients (≥ 18 years old) who underwent at a minimum a single-level ALIF from 2012 through 2019. Postoperative spinal and abdominal images, as well as radiologist reports, were reviewed for mention of lymphocele. Clinical data were collected and reported., Results: A total of 1322 patients underwent a minimum 1-level ALIF. Of these patients, 937 (70.9%) had either postoperative abdominal or lumbar spine images, and the resulting lymphocele incidence was 2.1% (20/937 patients). The mean ± SD age was 67 ± 10.9 years, and the male/female ratio was 1:1. Patients with lymphocele were significantly older than those without lymphocele (66.9 vs 58.9 years, p = 0.006). In addition, patients with lymphocele had a greater number of mean levels fused (2.5 vs 1.8, p < 0.001) and were more likely to have undergone ALIF at L2-4 (95.0% vs 66.4%, p = 0.007) than patients without lymphocele. On subsequent multivariate analysis, age (OR 1.07, 95% CI 1.01-1.12, p = 0.013), BMI (OR 1.10, 95% CI 1.01-1.18, p = 0.021), and number of levels fused (OR 1.82, 95% CI 1.05-3.14, p = 0.032) were independent prognosticators of postoperative lymphocele development. Patients with symptomatic lymphocele were successfully treated with either interventional radiology (IR) drainage and/or sclerosis therapy and achieved radiographic resolution. The mean ± SD length of hospital stay was 9.1 ± 5.2 days. Ten patients (50%) were postoperatively discharged to a rehabilitation center: 8 patients (40%) were discharged to home, 1 (5%) to a skilled nursing facility, and 1 (5%) to a long-term acute care facility., Conclusions: After ALIF, 2.1% of patients were diagnosed with radiographically identified postoperative lymphocele and had risk factors such as increased age, BMI, and number of levels fused. Most patients presented within 1 month postoperatively, and their clinical presentations included abdominal pain, abdominal distension, and/or wound complications. Of note, 25% of identified lymphoceles were discovered incidentally. Patients with symptomatic lymphocele were successfully treated with either IR drainage and/or sclerosis therapy and achieved radiographic resolution.

Competing Interests: Intérêts concurrents: Adrienne Chan est membre du conseil de Partners in Health Canada. Mackenzie Hamilton est actuellement en stage chez AstraZeneca Canada afin de soutenir les initiatives de recherche en santé en lien avec le lupus et la forme grave de l’asthme. Aucun autre intérêt concurrent n’a été déclaré.

Background: An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for <14 days compared with those on ART for >14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described., Methods: Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation., Results: Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6-1.2; P  = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8-1.32; P  = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART., Conclusions: In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To assess implementation and to identify barriers and facilitators to implementation, sustainability and scalability of an implementation strategy to provide lay health workers (LHWs) with the knowledge, skills and tools needed to implement an intervention to support patient tuberculosis (TB) treatment adherence., Design: Mixed-methods design including a cluster randomised controlled trial and process evaluation informed by the RE-AIM framework., Setting: Forty-five health centres (HCs) in four districts in the south east zone of Malawi, who had an opportunity to receive cascade training., Participants: Forty-five peer-trainers (PTs), 23 patients and 20 LHWs., Intervention: Implementation strategy employing peer-led educational outreach, a clinical support tool and peer support network to implement a TB treatment adherence intervention., Outcome Measures: Process data were collected from study initiation to the end-of-study PT meeting, and included: LHW and patient interviews, quarterly PT meeting notes, training logs and study team observations and meeting notes. Data sources were first analysed in isolation, followed by method, data source and analyst triangulation. Analyses were conducted independently by two study team members, and themes revised through discussion and involvement of additional study team members as needed., Results: Forty-one HCs (91%) trained at least one LHW. Of 256 LHWs eligible to participate at study start 152 (59%) completed training, with the proportion trained per HC ranging from 0% to 100% at the end of initial cascade training. Lack of training incentives was the primary barrier to implementation, with intrinsic motivation to improve knowledge and skills, and to improve patient care and outcomes the primary facilitators of participation., Conclusion: We identified important challenges to and potential facilitators of implementation, scalability and sustainability, of the TB treatment adherence intervention. Findings provide guidance to scale-up, and use of the implementation strategies employed, to address LHW training and supervision in other areas., Trial Registration Number: NCT02533089., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: With the advent of minimally invasive techniques, minimally invasive spine surgery (MISS) has become a realistic option for many spine cases. This study aims to evaluate the operative and clinical outcomes of MISS for total versus subtotal tumor resection from current evidence., Methods: A literature search was performed using the search term (Minimally invasive surgery OR MIS) AND (spine tumor OR spinal tumor). Studies including both minimally invasive total and subtotal resection cases with operative or clinical data were included., Results: Seven studies describing 159 spinal tumor cases were included. Compared with total resection, subtotal resection showed no significant differences in surgical time (mean difference (MD), 9.44 minutes; 95% confidence interval [CI], -47.66 to 66.55 minutes; P = 0.37), surgical blood loss (MD, -84.72 mL; 95% CI, -342.82 to 173.39 mL; P = 0.34), length of stay (MD, 1.38 days; 95% CI, -0.95 to 3.71 days; P = 0.17), and complication rate (odds ratio, 9.47; 95% CI, 0.34-263.56; P = 0.12). Pooled analyses with the random-effects model showed that neurologic function improved in 89% of patients undergoing total resection, whereas neurologic function improved in 61% of patients undergoing subtotal resection., Conclusions: Our analyses show that there is no significant difference in operative outcomes between total and subtotal resection. Patients undergoing total resection showed slightly better improvement in neurologic outcomes compared with patients undergoing subtotal resection. Overall, this study suggests that both total and subtotal resection may result in comparable outcomes for patients with spinal tumors. However, maximal safe resection remains the ideal treatment because it provides the greatest chance of long-term benefit., (Copyright © 2021. Published by Elsevier Inc.)

COVID-19 poses an infectious risk to healthcare workers especially during airway management. We compared the impact of early versus late intubation on infection control and performance in a randomised in situ simulation, using fluorescent powder as a surrogate for contamination. Twenty anaesthetists and intensivists intubated a simulated patient with COVID-19. The primary outcome was the degree of contamination. The secondary outcomes included the use of bag-valve-mask ventilation, the incidence of manikin cough, intubation time, first attempt success and heart rate variability as a measure of stress. The contamination score was significantly increased in the late intubation group, mean (standard deviation, SD) 17.20 (6.17), 95% confidence intervals (CI) 12.80 to 21.62 versus the early intubation group, mean (SD) 9.90 (5.13), 95% CI 6.23 to 13.57, P  = 0.005. The contamination score was increased after simulated cough occurrence (mean (SD) 18.0 (5.09) versus 5.50 (2.10) in those without cough; P <0.001), and when first attempt laryngoscopy failed (mean (SD) of 17.1 (6.41) versus 11.6 (6.20) P  = 0.038). The incidence of bag-mask ventilation was higher in the late intubation group (80% versus 30%; P =0.035). There was no significant difference in intubation time, incidence of failed first attempt laryngoscopy or heart rate variability between the two groups. Late intubation in patients with COVID-19 may be associated with greater laryngoscopist contamination and potential aerosol-generating events compared with early intubation. There was no difference in performance measured by intubation time and incidence of first attempt success. Late intubation, especially when resources are limited, may be a valid approach. However, strict infection control and appropriate personal protective equipment usage is recommended in such cases.

WHO 2016 classified glioblastomas into IDH-mutant and IDH-wildtype with the former having a better prognosis but there was no study on IDH-mutant primary glioblastomas only, as previous series included secondary glioblastomas. We recruited a series of 67 IDH-mutant primary glioblastomas/astrocytoma IV without a prior low-grade astrocytoma and examined them using DNA-methylation profiling, targeted sequencing, RNA sequencing and TERT promoter sequencing, and correlated the molecular findings with clinical parameters. The median OS of 39.4 months of 64 cases and PFS of 25.9 months of 57 cases were better than the survival data of IDH-wildtype glioblastomas and IDH-mutant secondary glioblastomas retrieved from datasets. The molecular features often seen in glioblastomas, such as EGFR amplification, combined +7/-10, and TERT promoter mutations were only observed in 6/53 (11.3%), 4/53 (7.5%), and 2/67 (3.0%) cases, respectively, and gene fusions were found only in two cases. The main mechanism for telomere maintenance appeared to be alternative lengthening of telomeres as ATRX mutation was found in 34/53 (64.2%) cases. In t-SNE analyses of DNA-methylation profiles, with an exceptional of one case, a majority of our cases clustered to IDH-mutant high-grade astrocytoma subclass (40/53; 75.5%) and the rest to IDH-mutant astrocytoma subclass (12/53; 22.6%). The latter was also enriched with G-CIMP high cases (12/12; 100%). G-CIMP-high status and MGMT promoter methylation were independent good prognosticators for OS (p = 0.022 and p = 0.002, respectively) and TP53 mutation was an independent poor prognosticator (p = 0.013) when correlated with other clinical parameters. Homozygous deletion of CDKN2A/B was not correlated with OS (p = 0.197) and PFS (p = 0.278). PDGFRA amplification or mutation was found in 16/59 (27.1%) of cases and was correlated with G-CIMP-low status (p = 0.010). Aside from the three well-known pathways of pathogenesis in glioblastomas, chromatin modifying and mismatch repair pathways were common aberrations (88.7% and 20.8%, respectively), the former due to high frequency of ATRX involvement. We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.

Study Design: Retrospective analysis of a prospective registry., Objective: We utilized the Quality Outcomes Database (QOD) registry to investigate the "July Effect" at QOD spondylolisthesis module sites with residency trainees., Summary of Background Data: There is a paucity of investigation on the long-term outcomes following surgeries involving new trainees utilizing high-quality, prospectively collected data., Methods: This was an analysis of 608 patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis at 12 high-enrolling sites. Surgeries were classified as occurring in July or not in July (non-July). Outcomes collected included estimated blood loss, length of stay, operative time, discharge disposition, complications, reoperation and readmission rates, and patient-reported outcomes (Oswestry Disability Index [ODI], Numeric Rating Scale [NRS] Back Pain, NRS Leg Pain, EuroQol-5D [EQ-5D] and the North American Spine Society [NASS] Satisfaction Questionnaire). Propensity score-matched analyses were utilized to compare postoperative outcomes and complication rates between the July and non-July groups., Results: Three hundred seventy-one surgeries occurred at centers with a residency training program with 21 (5.7%) taking place in July. In propensity score-matched analyses, July surgeries were associated with longer operative times ( average treatment effect = 22.4 minutes longer, 95% confidence interval 0.9-449.0, P = 0.041). Otherwise, July surgeries were not associated with significantly different outcomes for the remaining perioperative parameters (estimated blood loss, length of stay, discharge disposition, postoperative complications), overall reoperation rates, 3-month readmission rates, and 24-month ODI, NRS back pain, NRS leg pain, EQ-5D, and NASS satisfaction score (P > 0.05, all comparisons)., Conclusion: Although July surgeries were associated with longer operative times, there were no associations with other clinical outcomes compared to non-July surgeries following lumbar spondylolisthesis surgery. These findings may be due to the increased attending supervision and intraoperative education during the beginning of the academic year. There is no evidence that the influx of new trainees in July significantly affects long-term patient-centered outcomes.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations., Methods: We identified a 12-member panel composed of spine surgeons, fellows, and senior residents at a single institution. We created an initial telehealth strength examination protocol based on published data and developed 10 agree/disagree statements summarizing the protocol. A blinded Delphi method was utilized to build consensus for each statement, defined as > 80% agreement and no significant disagreement using a 2-way binomial test (significance threshold of p < 0.05). Any statement that did not meet consensus was edited and iteratively resubmitted to the panel until consensus was achieved. In the final round, the panel was unblinded and the protocol was finalized., Results: After the first round, 4/10 statements failed to meet consensus ( < 80% agreement, and p = 0.031, p = 0.031, p = 0.003, and p = 0.031 statistical disagreement, respectively). The disagreement pertained to grading of strength of the upper (3/10 statements) and lower extremities (1/10 statement). The amended statements clarified strength grading, achieved consensus ( > 80% agreement, p > 0.05 disagreement), and were used to create the final telehealth strength examination protocol., Conclusion: The resulting protocol was used in our clinic to standardize the telehealth strength examination. This protocol, as well as our summary of telehealth clinical practice, should aid neurosurgical clinics in integrating telemedicine modalities into their practice.

Background: There are many alternatives to direct journal access, such as podcasts, blogs, and news sites, that allow physicians and the general public to stay up to date with medical literature. However, there is a scarcity of literature that investigates the readership characteristics of open-access medical news sites and how these characteristics may have shifted during the COVID-19 pandemic., Objective: This study aimed to assess readership and survey data to characterize open-access medical news readership trends related to the COVID-19 pandemic and overall readership trends regarding pandemic-related information delivery., Methods: Anonymous, aggregate readership data were obtained from 2 Minute Medicine, an open-access, physician-run medical news organization that has published over 8000 original, physician-written texts and visual summaries of new medical research since 2013. In this retrospective observational study, the average number of article views, number of actions (defined as the sum of the number of views, shares, and outbound link clicks), read times, and bounce rates (probability of leaving a page in <30 s) were compared between COVID-19 articles published from January 1 to May 31, 2020 (n=40) and non-COVID-19 articles (n=145) published in the same time period. A voluntary survey was also sent to subscribed 2 Minute Medicine readers to further characterize readership demographics and preferences, which were scored on a Likert scale., Results: COVID-19 articles had a significantly higher median number of views than non-COVID-19 articles (296 vs 110; U=748.5; P<.001). There were no significant differences in average read times (P=.12) or bounce rates (P=.12). Non-COVID-19 articles had a higher median number of actions than COVID-19 articles (2.9 vs 2.5; U=2070.5; P=.02). On a Likert scale of 1 (strongly disagree) to 5 (strongly agree), our survey data revealed that 65.5% (78/119) of readers agreed or strongly agreed that they preferred staying up to date with emerging literature about COVID-19 by using sources such as 2 Minute Medicine instead of journals. A greater proportion of survey respondents also indicated that open-access news sources were one of their primary sources for staying informed (86/120, 71.7%) compared to the proportion who preferred direct journal article access (61/120, 50.8%). The proportion of readers indicating they were reading one or less full-length medical studies a month were lower following introduction to 2 Minute Medicine compared to prior (21/120, 17.5% vs 38/120, 31.6%; P=.005)., Conclusions: The readership significantly increased for one open-access medical literature platform during the pandemic. This reinforces the idea that open-access, physician-written sources of medical news represent an important alternative to direct journal access for readers who want to stay up to date with medical literature., (©Alex K Chan, Constance Wu, Andrew Cheung, Marc D Succi. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.05.2021.)

Background: Optimizing the public health response to reduce the burden of COVID-19 necessitates characterizing population-level heterogeneity of risks for the disease. However, heterogeneity in SARS-CoV-2 testing may introduce biased estimates depending on analytic design. We aimed to explore the potential for collider bias in a large study of disease determinants, and evaluate individual, environmental and social determinants associated with SARS-CoV-2 testing and diagnosis among residents of Ontario, Canada., Methods: We explored the potential for collider bias and characterized individual, environmental and social determinants of being tested and testing positive for SARS-CoV-2 infection using cross-sectional analyses among 14.7 million community-dwelling people in Ontario, Canada. Among those with a diagnosis, we used separate analytic designs to compare predictors of people testing positive versus negative; symptomatic people testing positive versus testing negative; and people testing positive versus people not testing positive (i.e., testing negative or not being tested). Our analyses included tests conducted between Mar. 1 and June 20, 2020., Results: Of 14 695 579 people, we found that 758 691 were tested for SARS-CoV-2, of whom 25 030 (3.3%) had a positive test result. The further the odds of testing from the null, the more variability we generally observed in the odds of diagnosis across analytic design, particularly among individual factors. We found that there was less variability in testing by social determinants across analytic designs. Residing in areas with the highest household density (adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 1.75-1.98), highest proportion of essential workers (adjusted OR 1.58, 95% CI 1.48-1.69), lowest educational attainment (adjusted OR 1.33, 95% CI 1.26-1.41) and highest proportion of recent immigrants (adjusted OR 1.10, 95% CI 1.05-1.15) were consistently related to increased odds of SARS-CoV-2 diagnosis regardless of analytic design., Interpretation: Where testing is limited, our results suggest that risk factors may be better estimated using population comparators rather than test-negative comparators. Optimizing COVID-19 responses necessitates investment in and sufficient coverage of structural interventions tailored to heterogeneity in social determinants of risk, including household crowding, occupation and structural racism., Competing Interests: Competing interests: Adrienne Chan is a member of the board of Partners in Health Canada. Mackenzie Hamilton is currently serving an internship at AstraZeneca Canada in support of health research initiatives in lupus and severe asthma. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Posterior cervical decompression and fusion (PCF) is a common procedure used to treat various cervical spine pathologies, but the 90-d outcomes following PCF surgery continue to be incompletely defined., Objective: To identify risk factors associated with 90-d readmission and reoperation following PCF surgery., Methods: Adults undergoing PCF from 2012 to 2020 were identified. Demographic and radiographic data, surgical characteristics, and 90-d outcomes were collected. Univariate analysis was performed using Student's t-test, chi square, and Fisher exact tests as appropriate. Multivariable logistic regression models with lasso penalty were used to analyze various risk factors., Results: A total of 259 patients were included. The 90-d readmission and reoperation rates were 9.3% and 4.6%, respectively. The most common reason for readmission was surgical site infection (SSI) (33.3%) followed by new neurological deficits (16.7%). Patients who smoked tobacco had 3-fold greater odds of readmission compared to nonsmokers (odds ratio [OR]: 3.48; 95% CI 1.87-6.67; P = .0001). Likewise, the most common reason for reoperation was SSI (33.3%) followed by seroma and implant failure (25.0% each). Smoking was also an independent risk factor for reoperation, associated with nearly 4-fold greater odds of return to the operating room (OR: 3.53; 95% CI 1.53-8.57; P = .003)., Conclusion: Smoking is a significant predictor of 90-d readmission and reoperation in patients undergoing PCF surgery. Smoking cessation should be strongly considered preoperatively in elective PCF cases to minimize the risk of 90-d readmission and reoperation., (© Congress of Neurological Surgeons 2021.)

Introduction: This study aimed to assess the impact of hemophilia on families, in the context of current and emerging hemostatic therapies, and explore the need for a hemophilia-specific tool targeted at parents of boys aged <4 years. A secondary aim was to develop and validate the new tool., Methods: Focus groups were conducted with parents of boys with hemophilia and hemophilia health care providers at Canadian hemophilia treatment centers (HTCs) to review the relevance of the Pediatric Quality of Life Family Impact Module (PedsQL-FIM); a novel questionnaire was developed by identifying core themes expressed. This questionnaire, the Hemophilia Family Impact Tool (H-FIT) was validated in a sample of parents of boys with hemophilia relative to the PedsQL-FIM., Results: Seven focus groups were conducted at four HTCs, generating themes specific to hemophilia not covered by the PedsQL-FIM, suggesting that a new tool be developed (the H-FIT). In the validation phase, 54 parents completed the H-FIT and PedsQL-FIM. The H-FIT had a strong correlation with the PedsQL-FIM across all ages (r = 0.79; P  < .0001) and a moderate correlation for parents of boys aged <7 years (r = 0.64; P  = .0007). There was a significant difference between the mean H-FIT scores for parents of boys using extended half-life factor (68.1; standard deviation [SD]=14.2) compared to standard half-life factor (54.7; SD=18.4; P  = .04)., Conclusion: A novel, disease-specific tool, the H-FIT, has been developed to measure the impact of hemophilia on families. The H-FIT has good preliminary measurement properties and may be responsive to changes in therapy associated with a decreased burden of administration., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objective: Optimizing patient discharge after surgery has been shown to impact patient recovery and hospital/physician workflow and to reduce healthcare costs. In the current study, the authors sought to identify risk factors for nonroutine discharge after surgery for cervical myelopathy by using a national spine registry., Methods: The Quality Outcomes Database cervical module was queried for patients who had undergone surgery for cervical myelopathy between 2016 and 2018. Nonroutine discharge was defined as discharge to postacute care (rehabilitation), nonacute care, or another acute care hospital. A multivariable logistic regression predictive model was created using an array of demographic, clinical, operative, and patient-reported outcome characteristics., Results: Of the 1114 patients identified, 11.2% (n = 125) had a nonroutine discharge. On univariate analysis, patients with a nonroutine discharge were more likely to be older (age ≥ 65 years, 70.4% vs 35.8%, p < 0.001), African American (24.8% vs 13.9%, p = 0.007), and on Medicare (75.2% vs 35.1%, p < 0.001). Among the patients younger than 65 years of age, those who had a nonroutine discharge were more likely to be unemployed (70.3% vs 36.9%, p < 0.001). Overall, patients with a nonroutine discharge were more likely to present with a motor deficit (73.6% vs 58.7%, p = 0.001) and more likely to have nonindependent ambulation (50.4% vs 14.0%, p < 0.001) at presentation. On multivariable logistic regression, factors associated with higher odds of a nonroutine discharge included African American race (vs White, OR 2.76, 95% CI 1.38-5.51, p = 0.004), Medicare coverage (vs private insurance, OR 2.14, 95% CI 1.00-4.65, p = 0.04), nonindependent ambulation at presentation (OR 2.17, 95% CI 1.17-4.02, p = 0.01), baseline modified Japanese Orthopaedic Association severe myelopathy score (0-11 vs moderate 12-14, OR 2, 95% CI 1.07-3.73, p = 0.01), and posterior surgical approach (OR 11.6, 95% CI 2.12-48, p = 0.004). Factors associated with lower odds of a nonroutine discharge included fewer operated levels (1 vs 2-3 levels, OR 0.3, 95% CI 0.1-0.96, p = 0.009) and a higher quality of life at baseline (EQ-5D score, OR 0.43, 95% CI 0.25-0.73, p = 0.001). On predictor importance analysis, baseline quality of life (EQ-5D score) was identified as the most important predictor (Wald χ2 = 9.8, p = 0.001) of a nonroutine discharge; however, after grouping variables into distinct categories, socioeconomic and demographic characteristics (age, race, gender, insurance status, employment status) were identified as the most significant drivers of nonroutine discharge (28.4% of total predictor importance)., Conclusions: The study results indicate that socioeconomic and demographic characteristics including age, race, gender, insurance, and employment may be the most significant drivers of a nonroutine discharge after surgery for cervical myelopathy.

Background: Incidental or intentional durotomy in spine surgery is associated with a risk of cerebrospinal fluid (CSF) leakage and reoperation. Several strategies have been introduced, but the incomplete closure is still relatively frequent and troublesome. In this study, we review current evidence on spinal dural repair strategies and evaluate their efficacy., Methods: PubMed, Web of Science, and Scopus were used to search primary studies about the repair of the spinal dura with different techniques. Of 265 articles found, 11 studies, which specified repair techniques and postoperative outcomes, were included for qualitative and quantitative analysis. The primary outcomes were CSF leakage and postoperative infection., Results: The outcomes of different dural repair techniques were available in 776 cases. Pooled analysis of 11 studies demonstrated that the most commonly used technique was a combination of primary closure, patch or graft, and sealant (22.7%, 176/776). A combination of primary closure and patch or graft resulted in the lowest rate of CSF leakage (5.5%, 7/128). In this study, sealants as an adjunct to primary closure (13.7%, 18/131) did not significantly reduce the rate of CSF leakage compared with primary closure alone (17.6%, 18/102). The rates of infection and postoperative neurologic deficit were similar regardless of the repair techniques., Conclusions: Although the use of sealants has become prevalent, available sealants as an adjunct to primary closure did not reduce the rate of CSF leakage compared with primary closure. The combination of primary closure and patches or grafts could be effective in decreasing postoperative CSF leakage., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Surgical site infection (SSI) is a complication linked to increased costs and length of hospital stay. Prevention of SSI is important to reduce its burden on individual patients and the healthcare system. The authors aimed to assess the efficacy of preoperative chlorhexidine gluconate (CHG) showers on SSI rates following cranial surgery., Methods: In November 2013, a preoperative CHG shower protocol was implemented at the authors' institution. A total of 3126 surgical procedures were analyzed, encompassing a time frame from April 2012 to April 2016. Cohorts before and after implementation of the CHG shower protocol were evaluated for differences in SSI rates., Results: The overall SSI rate was 0.6%. No significant differences (p = 0.11) were observed between the rate of SSI of the 892 patients in the preimplementation cohort (0.2%) and that of the 2234 patients in the postimplementation cohort (0.8%). Following multivariable analysis, implementation of preoperative CHG showers was not associated with decreased SSI (adjusted OR 2.96, 95% CI 0.67-13.1; p = 0.15)., Conclusions: This is the largest study, according to sample size, to examine the association between CHG showers and SSI following craniotomy. CHG showers did not significantly alter the risk of SSI after a cranial procedure.

Objective: The ideal surgical management of grade I lumbar spondylolisthesis has not been determined despite extensive prior investigations. In this cohort study, the authors used data from the large, multicenter, prospectively collected Quality Outcomes Database to bridge the gap between the findings in previous randomized trials and those in a more heterogeneous population treated in a typical practice. The objective was to assess the difference in patient-reported outcomes among patients undergoing decompression alone or decompression plus fusion., Methods: The primary outcome measure was change in 24-month Oswestry Disability Index (ODI) scores. The minimal clinically important difference (MCID) in ODI score change and 30% change in ODI score at 24 months were also evaluated. After adjusting for patient-specific and clinical factors, multivariable linear and logistic regressions were employed to evaluate the impact of fusion on outcomes. To account for differences in age, sex, body mass index, and baseline listhesis, a sensitivity analysis was performed using propensity score analysis to match patients undergoing decompression only with those undergoing decompression and fusion., Results: In total, 608 patients who had grade I lumbar spondylolisthesis were identified (85.5% with at least 24 months of follow-up); 140 (23.0%) underwent decompression alone and 468 (77.0%) underwent decompression and fusion. The 24-month change in ODI score was significantly greater in the fusion plus decompression group than in the decompression-only group (-25.8 ± 20.0 vs -15.2 ± 19.8, p < 0.001). Fusion remained independently associated with 24-month ODI score change (B = -7.05, 95% CI -10.70 to -3.39, p ≤ 0.001) in multivariable regression analysis, as well as with achieving the MCID for the ODI score (OR 1.767, 95% CI 1.058-2.944, p = 0.029) and 30% change in ODI score (OR 2.371, 95% CI 1.286-4.371, p = 0.005). Propensity score analysis resulted in 94 patients in the decompression-only group matched 1 to 1 with 94 patients in the fusion group. The addition of fusion to decompression remained a significant predictor of 24-month change in the ODI score (B = 2.796, 95% CI 2.228-13.275, p = 0.006) and of achieving the 24-month MCID ODI score (OR 2.898, 95% CI 1.214-6.914, p = 0.016) and 24-month 30% change in ODI score (OR 2.300, 95% CI 1.014-5.216, p = 0.046)., Conclusions: These results suggest that decompression plus fusion in patients with grade I lumbar spondylolisthesis may be associated with superior outcomes at 24 months compared with decompression alone, both in reduction of disability and in achieving clinically meaningful improvement. Longer-term follow-up is warranted to assess whether this effect is sustained.

Introduction: The purpose of this study was to review and update the content of the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool version 2.0 (CHO-KLAT), in the context of extended half-life (EHL) factor concentrates (FCs) and to establish the validity and reliability of the updated CHO-KLAT., Methods: Focus groups were conducted with boys with hemophilia, their parents, and health care providers across Canada to review the CHO-KLAT v2.0 and determine if any modifications were required. The validity of the revised CHO-KLAT (version 3.0) was then determined in a sample of boys with hemophilia and their parents by calculating its correlation with the Pediatric Quality of Life Core Module (PedsQL-Core). Test-retest reliability was assessed using an intraclass correlation coefficient (ICC)., Results: Thirteen focus groups at 5 pediatric hemophilia treatment centers (HTCs) (n = 71) resulted in 19 changes to the CHO-KLAT v2.0, generating a revised 40-item CHO-KLAT, the CHO-KLAT v3.0. Thirty-five boys with hemophilia (median age, 14; range, 7-17 years) and 47 parents participated in the validation of the CHO-KLAT v3.0. There was a moderate correlation between the CHO-KLAT v3.0 child self-report and PedsQL-Core ( r  = 0.56, P  = .01), and a strong correlation between the CHO-KLAT v3.0 parent-proxy and PedsQL-Core ( r  = .79, P  = .0007). The test-retest reliability ICC was 0.90 for the child self-report CHO-KLAT v3.0 and 0.68 for the parent-proxy CHO-KLAT v3.0., Conclusion: The CHO-KLAT v3.0 is a reliable and valid child-centric tool that effectively measures health-related quality of life in boys with hemophilia who are receiving standard half-life or EHL FCs., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Obstructive sleep apnoea syndrome (OSAS) is defined as the intermittent reduction or cessation of airflow due to partial or complete obstruction of the upper airway during sleep. Paediatric OSAS has specific contributing factors, presenting symptoms and management strategies in various age groups. Untreated OSAS can lead to detrimental effects on neurocognitive development and cardiovascular and metabolic functions of a growing child. In the past decade, practice guidelines have been developed to guide the evaluation and management of OSAS. This article provides a narrative review on the current diagnostic and treatment options for paediatric OSAS. Alternative diagnostic tools other than the standard polysomnography are discussed. Adenotonsillectomy is considered the first-line therapy yet it is not suitable for treatment of all OSAS cases. Nocturnal non-invasive positive airway pressure ventilation is effective and could be the priority treatment for patients with complex comorbidities, residual OSAS post-adenotonsillectomy or obesity. However, intolerance and non-adherence are major challenges of positive airway pressure therapy especially in young children. There is increasing evidence for watchful waiting and other gentler alternative treatment options in mild OSAS. The role of anti-inflammatory drugs as the primary or adjunctive treatment is discussed. Other treatment options, including weight reduction, orthodontic procedures and myofunctional therapy, are indicated for selected patients. Nevertheless, the successful management of paediatric OSAS often requires a multidisciplinary team approach., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2021/02/dic.2020-12-5-COI.pdf, (Copyright © 2021 Leung TNH, Cheng JWCH, Chan AKC.)

Background: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case., Methods: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p 0 ) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p 0 , ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment., Discussion: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection., Trial Registration: This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.

Background: Topical nitroglycerin (TNG) ointment has been used for almost 3 decades to treat neonatal peripheral tissue ischemia, but this product is now no longer being produced by its Canadian manufacturer. Our aim was to investigate the efficacy and safety of TNG products in newborns in neonatal intensive care units., Methods: In this systematic review we searched Embase, CINAHL, MEDLINE, PubMed and Web of Science from inception to April 2020 for studies on the use of TNG products (TNG ointment, TNG spray, glyceryl trinitrate [GTN] patch) for the treatment of neonatal tissue ischemia. We did not apply language or study design limitations. Animal studies and duplicate records were excluded. Two reviewers screened and extracted data. The Tool for Evaluating the Methodological Quality of Case Reports and Case Series was used to assess the risk of bias of individual studies., Results: We included 23 articles (20 case reports, 2 case series and 1 retrospective audit) describing the use of TNG ointment, TNG spray or GTN patch in the treatment of 39 tissue ischemia events in 37 newborns. Twenty-three (62.2%), 12 (32.4%), 1 (2.7%) and 1 (2.7%) infants received TNG ointment, GTN patch, both TNG ointment and GTN patch, and TNG spray, respectively. Nineteen (76.0%) and 7 (53.8%) injuries treated with TNG ointment and GTN patch showed complete recovery, respectively. Two (16.7%) infants treated with GTN patch experienced adverse events (i.e., methemoglobinemia) requiring treatment discontinuation., Interpretation: TNG ointment presents a safe therapeutic modality for salvage therapy of neonatal tissue ischemia. Engagement of stakeholders is essential to address its recent commercial inaccessibility in Canada., Competing Interests: Competing interests: None declared., (© 2021 Joule Inc. or its licensors.)

Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm 2 ) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient ( D ) and perfusion fraction ( f ) maps; ADC was calculated using the natural logarithm of b  = 1000 over b  = 0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMT PMS ), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, "Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma", published in Radiotherapy and Oncology [1]., Competing Interests: Arjun Sahgal: Advisor/consultant: AbbVie, Merck, Roche, Varian, Elekta, BrainLAB, VieCure Board Member: International Stereotactic Radiosurgery Society Co-Chair: AO Spine Knowledge Forum Tumor Past educational seminars: Elekta AB, Accuray Inc., Varian, BrainLAB, Medtronic Kyphon Research support: Elekta AB Travel support: Elekta, Varian, BrainLAB Consortia: Elekta MR Linac Research Consortium, Elekta Spine, Oligometastases and Linac Based SRS Consortia. Sten Myrehaug: Research support: Novartis AG Honoraria: Novartis AG, Ipsen Travel support: Elekta Chia-Lin Tseng: Honoraria: Elekta Travel support: Elekta Consortia: Elekta MR Linac Research Consortium Hany Soliman: Horaria: Elekta AB Travel support: Elekta AB Sunit Das: Advisor/consultant: AbbVie, Xpan Medical, Synaptive Board member: Subcortical Surgery Group Past educational seminars: AbbVie, Congress of Neurological Surgeons, American Association of Neurological Surgeons, Society for NeuroOncology Research supports: Alkerme, Medicenna Travel support: Subcortical Surgery Group, Congress of Neurological Surgeons, American Association of Neurological Surgeons, Society for NeuroOncology, Integra All other authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2021 The Author(s). Published by Elsevier Inc.)

Objectives: The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnoea is challenging to assess remotely, and the accuracy of subjective dyspnoea measures in capturing hypoxaemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnoea in diagnosing hypoxaemia in COVID-19 patients., Methods: This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from 3 April 2020 to 13 September 2020. Dyspnoea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV) and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxaemia. In the primary analysis, hypoxaemia was defined by oxygen saturation <95%; the diagnostic accuracy of subjective dyspnoea was also assessed across a range of oxygen saturation cutoffs from 92% to 97%., Results: During the study period, 89/501 (17.8%) of patients met criteria for home oxygen saturation monitoring, and of these 17/89 (19.1%) were diagnosed with hypoxaemia. The presence/absence of dyspnoea had limited accuracy for diagnosing hypoxaemia, with SN 47% (95% CI 24% to 72%), SP 80% (95% CI 68% to 88%), NPV 86% (95% CI 75% to 93%), PPV 36% (95% CI 18% to 59%), +LR 2.4 (95% CI 1.2 to 4.7) and -LR 0.7 (95% CI 0.4 to 1.1). The SN of dyspnoea was 50% (95% CI 19% to 81%) when a cut-off of < 92% was used to define hypoxaemia. A modified Medical Research Council dyspnoea score >1 (SP 98%, 95% CI 88% to 100%), Roth maximal count <12 (SP 100%, 95% CI 75% to 100%) and Roth counting time <8 s (SP 93%, 95% CI 66% to 100%) had high SP that could be used to rule in hypoxaemia, but displayed low SN (≤50%)., Conclusions: Subjective dyspnoea measures have inadequate accuracy for ruling out hypoxaemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this direct replication of Mueller and Oppenheimer's (2014) Study 1, participants watched a lecture while taking notes with a laptop ( n = 74) or longhand ( n = 68). After a brief distraction and without the opportunity to study, they took a quiz. As in the original study, laptop participants took notes containing more words spoken verbatim by the lecturer and more words overall than did longhand participants. However, laptop participants did not perform better than longhand participants on the quiz. Exploratory meta-analyses of eight similar studies echoed this pattern. In addition, in both the original study and our replication, higher word count was associated with better quiz performance, and higher verbatim overlap was associated with worse quiz performance, but the latter finding was not robust in our replication. Overall, results do not support the idea that longhand note taking improves immediate learning via better encoding of information.

The incidence of thrombotic disorders in neonates and children is increasing with advances in diagnostic modalities, supportive care, and management of many health conditions. The developing coagulation system, need for intensive care, including catheterization, and co-morbid conditions are responsible for the relatively high risk of thrombosis in neonates compared to older children. This review addresses the advances over the last 3 years in neonatal thrombosis, with a focus on epidemiology, cerebral sinovenous thrombosis (CSVT), renal vein thrombosis (RVT), and portal vein thrombosis (PVT). The incidence of neonatal thrombosis in the contemporary era is reported to be 6.9-15 per 1,000 neonatal intensive care unit (NICU) admissions, compared to 2.4 per 1,000 NICU admissions reported in older registry data. The majority of recently published studies are small, retrospective, and from single centers, albeit they emphasize the need for definitive data to support the efficacy and safety of anticoagulation therapy (ACT) in the management of CSVT, RVT, and PVT. We highlight two important international initiatives geared towards improving the evidence base for these conditions. The International Pediatric Thrombosis Network (IPTN) is a collaboration of 74 centers across 27 countries (as of January 2021) which has started important projects like the international neonatal RVT registry, while the International Pediatric Stroke Study (IPSS) group is in the planning stages of a randomized controlled trial to evaluate the utility of ACT in the management of neonatal CSVT., Competing Interests: The authors declare that they have no competing interests.Shoshana Revel-Vilk has collaborated with the authors on one consortium paper in 2020.No competing interests were disclosed., (Copyright: © 2021 Bhatt MD et al.)

Study Design: An experimental animal study., Objective: The aim of this study was to investigate the effect of pulsed electromagnetic fields (PEMF) on recovery of sensorimotor function in a rodent model of disc herniation (DH)., Summary of Background Data: Radiculopathy associated with DH is mediated by proinflammatory cytokines. Although we have demonstrated the anti-inflammatory effects of PEMF on various tissues, we have not investigated the potential therapeutic effect of PEMF on radiculopathy resulting from DH., Methods: Nineteen rats were divided into three groups: positive control (PC; left L4 nerve ligation) (n = 6), DH alone (DH; exposure of left L4 dorsal root ganglion [DRG] to harvested nucleus pulposus and DRG displacement) (n = 6), and DH + PEMF (n = 7). Rodents from the DH + PEMF group were exposed to PEMF immediately postoperatively and for 3 hours/day until the end of the study. Sensory function was assessed via paw withdrawal thresholds to non-noxious stimuli preoperatively and 1 and 3 days postoperatively, and every 7 days thereafter until 7 weeks after surgery. Motor function was assessed via DigiGait treadmill analysis preoperatively and weekly starting 7 days following surgery until 7 weeks following surgery., Results: All groups demonstrated marked increases in the left hindlimb response threshold postoperatively. However, 1 week following surgery, there was a significant effect of condition on left hindlimb withdrawal thresholds (one-way analysis of variance: F = 3.82, df = 2, P = 0.044) where a more rapid recovery to baseline threshold was evident for DH + PEMF compared to PC and DH alone. All groups demonstrated gait disturbance postoperatively. However, DH + PEMF rodents were able to regain baseline gait speeds before DH and PC rodents. When comparing gait parameters, DH + PEMF showed consistently less impairment postoperatively suggesting that PEMF treatment was associated with less severe gait disturbance., Conclusion: These data demonstrate that PEMF accelerates sensorimotor recovery in a rodent model of DH, suggesting that PEMF may be reasonable to evaluate for the clinical management of patients with herniation-associated radiculopathy.Level of Evidence: N/A., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Among 472 patients with human immunodeficiency virus-associated cryptococcal meningitis, 16% had severe visual loss at presentation, and 46% of these were 4-week survivors and remained severely impaired. Baseline cerebrospinal fluid opening pressure ≥40 cmH 2 O (adjusted odds ratio [aOR], 2.56; 95% confidence interval [CI], 1.36-4.83; P = .02) and fungal burden >6.0 log 10 colonies/mL (aOR, 3.01; 95% CI, 1.58-5.7; P = .003) were independently associated with severe visual loss., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Importance: Nursing home residents have been disproportionately affected by coronavirus disease 2019 (COVID-19). Prevention recommendations emphasize frequent testing of health care personnel and residents, but additional strategies are needed., Objective: To develop a reproducible index of nursing home crowding and determine whether crowding was associated with COVID-19 cases and mortality in the first months of the COVID-19 epidemic., Design, Setting, and Participants: This population-based retrospective cohort study included more than 78 000 residents across more than 600 nursing homes in Ontario, Canada, and was conducted from March 29 to May 20, 2020., Exposures: The nursing home crowding index equaled the mean number of residents per bedroom and bathroom., Main Outcomes and Measures: The cumulative incidence of COVID-19 cases confirmed by a validated nucleic acid amplification assay and mortality per 100 residents; the introduction of COVID-19 into a home (≥1 resident case) was a negative tracer., Results: Of 623 homes in Ontario, we obtained complete information on 618 homes (99%) housing 78 607 residents (women, 54 160 [68.9%]; age ≥85 years, 42 919 [54.6%]). A total of 5218 residents (6.6%) developed COVID-19 infection, and 1452 (1.8%) died of COVID-19 infection as of May 20, 2020. COVID-19 infection was distributed unevenly across nursing homes; 4496 infections (86%) occurred in 63 homes (10%). The crowding index ranged across homes from 1.3 (mainly single-occupancy rooms) to 4.0 (exclusively quadruple occupancy rooms); 308 homes (50%) had a high crowding index (≥2). Incidence in high crowding index homes was 9.7% vs 4.5% in low crowding index homes (P < .001), while COVID-19 mortality was 2.7% vs 1.3%, respectively (P < .001). The likelihood of COVID-19 introduction did not differ (high = 31.3% vs low = 30.2%; P = .79). After adjustment for regional, nursing home, and resident covariates, the crowding index remained associated with an increased incidence of infection (relative risk [RR] = 1.73, 95% CI, 1.10-2.72) and mortality (RR, 1.69; 95% CI, 0.99-2.87). A propensity score analysis yielded similar conclusions for infection (RR, 2.09; 95% CI, 1.30-3.38) and mortality (RR, 1.83; 95% CI, 1.09-3.08). Simulations suggested that converting all 4-bed rooms to 2-bed rooms would have averted 998 COVID-19 cases (19.1%) and 263 deaths (18.1%)., Conclusions and Relevance: In this cohort of Canadian nursing homes, crowding was common and crowded homes were more likely to experience larger and deadlier COVID-19 outbreaks.

As the COVID-19 pandemic continues to affect the international community, very little is known about its impact on the health and day-to-day activities of people with Parkinson's disease (PwPD). To better understand the emotional and behavioral consequences of the public health policies implemented to mitigate the spread of SARS-CoV-2 in PwPD, and to explore the factors contributing to accessing alternative health care mechanisms, such as telehealth, we administered an anonymous knowledge, attitude, and practice survey to PwPD and care partners, via the mailing lists of the Parkinson's Foundation and Columbia University Parkinson's Disease Center of Excellence with an average response rate of 19.3%. Sufficient information was provided by 1,342 PwPD to be included in the final analysis. Approximately half of respondents reported a negative change in PD symptoms, with 45-66% reporting mood disturbances. Telehealth use increased from 9.7% prior to the pandemic to 63.5% during the pandemic. Higher income and higher education were associated with telehealth use. Services were more often used for doctor's appointment than physical, occupational, speech, or mental health therapies. Almost half (46%) of PwPD preferred to continue using telehealth always or sometimes after the coronavirus outbreak had ended. Having received support/instruction for telehealth and having a care partner, friend, or family member to help them with the telehealth visit increased the likelihood of continuous use of telehealth after the pandemic ended. Taken together, PD symptoms and management practices were markedly affected by COVID-19. Given the observed demographic limitations of telehealth, expanding its implementation to include additional physical, occupational, psychological, and speech therapies, increasing support for telehealth, as well as reaching underserved (low income) populations is urgently required.

Arachnoid webs of the spine are a relatively rare entity with unique radiological findings, most notably the scalpel-sign on sagittal magnetic resonance imaging (MRI).1-4 To date there have been no videographic descriptions of the surgical treatment for this clinical entity. We present the case of a patient with progressive myelopathy and MRI showing a cervical and thoracic syrinx with a sharp transition point at the level of the T5 vertebral body. On computed tomography myelogram, there was preserved cerebrospinal fluid (CSF) in the ventral subarachnoid space-this space is often interrupted in ventral cord herniation, and preserved in dorsal arachnoid webs.5 A laminectomy with intradural excision of arachnoid web was offered and the patient consented for the procedure. Preoperatively, a fiducial screw was placed at T5. A T4-6 laminectomy was performed. A clearly compressive arachnoid web was encountered on exposure. Bands were dissected under an operating microscope, restoring normal CSF flow. Ventral dural defect was ruled out by passing a delicot beneath the cord and withdrawing it on the contralateral side. The patient did well and has shown improvement in myelopathic symptoms at 1- and 3-mo follow-up. Arachnoid webs of the spine can be treated effectively with a prudent, stepwise approach, and careful microsurgical technique. The neurosurgeon should consult closely with their neuroradiology colleagues to rule out other entities prior to the operation, such as ventral cord herniations, which can mimic dorsal arachnoid webs radiologically and clinically. We have received informed consent of the patient to submit this video., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Routinely collected health administrative data can be used to efficiently assess disease burden in large populations, but it is important to evaluate the validity of these data. The objective of this study was to develop and validate International Classification of Disease 10th revision (ICD -10) algorithms that identify laboratory-confirmed influenza or laboratory-confirmed respiratory syncytial virus (RSV) hospitalizations using population-based health administrative data from Ontario, Canada., Study Design and Setting: Influenza and RSV laboratory data from the 2014-15, 2015-16, 2016-17 and 2017-18 respiratory virus seasons were obtained from the Ontario Laboratories Information System (OLIS) and were linked to hospital discharge abstract data to generate influenza and RSV reference cohorts. These reference cohorts were used to assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ICD-10 algorithms. To minimize misclassification in future studies, we prioritized specificity and PPV in selecting top-performing algorithms., Results: 83,638 and 61,117 hospitalized patients were included in the influenza and RSV reference cohorts, respectively. The best influenza algorithm had a sensitivity of 73% (95% CI 72% to 74%), specificity of 99% (95% CI 99% to 99%), PPV of 94% (95% CI 94% to 95%), and NPV of 94% (95% CI 94% to 95%). The best RSV algorithm had a sensitivity of 69% (95% CI 68% to 70%), specificity of 99% (95% CI 99% to 99%), PPV of 91% (95% CI 90% to 91%) and NPV of 97% (95% CI 97% to 97%)., Conclusion: We identified two highly specific algorithms that best ascertain patients hospitalized with influenza or RSV. These algorithms may be applied to hospitalized patients if data on laboratory tests are not available, and will thereby improve the power of future epidemiologic studies of influenza, RSV, and potentially other severe acute respiratory infections., Competing Interests: The authors have declared that no competing interests exist.

Background: The role of the lipidome as a biomarker for Parkinson's disease (PD) is a relatively new field that currently only focuses on PD diagnosis., Objective: To identify a relevant lipidome signature for PD severity markers., Methods: Disease severity of 149 PD patients was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Montreal Cognitive Assessment (MoCA). The lipid composition of whole blood samples was analyzed, consisting of 517 lipid species from 37 classes; these included all major classes of glycerophospholipids, sphingolipids, glycerolipids, and sterols. To handle the high number of lipids, the selection of lipid species and classes was consolidated via analysis of interrelations between lipidomics and disease severity prediction using the random forest machine-learning algorithm aided by conventional statistical methods., Results: Specific lipid classes dihydrosphingomyelin (dhSM), plasmalogen phosphatidylethanolamine (PEp), glucosylceramide (GlcCer), dihydro globotriaosylceramide (dhGB3), and to a lesser degree dihydro GM3 ganglioside (dhGM3), as well as species dhSM(20:0), PEp(38:6), PEp(42:7), GlcCer(16:0), GlcCer(24:1), dhGM3(22:0), dhGM3(16:0), and dhGB3(16:0) contribute to PD severity prediction of UPDRS III score. These, together with age, age at onset, and disease duration, also contribute to prediction of UPDRS total score. We demonstrate that certain lipid classes and species interrelate differently with the degree of severity of motor symptoms between men and women, and that predicting intermediate disease stages is more accurate than predicting less or more severe stages., Conclusion: Using machine-learning algorithms and methodologies, we identified lipid signatures that enable prediction of motor severity in PD. Future studies should focus on identifying the biological mechanisms linking GlcCer, dhGB3, dhSM, and PEp with PD severity.

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. In this study, we investigated human T cell recall responses to fully glycosylated spike trimer, recombinant N protein, as well as to S, N, M, and E peptide pools in the early convalescent phase and compared them with influenza-specific memory responses from the same donors. All subjects showed SARS-CoV-2-specific T cell responses to at least one Ag. Both SARS-CoV-2-specific and influenza-specific CD4 + T cell responses were predominantly of the central memory phenotype; however SARS-CoV-2-specific CD4 + T cells exhibited a lower IFN-γ to TNF ratio compared with influenza-specific memory responses from the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. Most SARS-CoV-2-convalescent subjects also produced IFN-γ in response to seasonal OC43 S protein. We observed granzyme B + /IFN-γ + , CD4 + , and CD8 + proliferative responses to peptide pools in most individuals, with CD4 + T cell responses predominating over CD8 + T cell responses. Peripheral T follicular helper (pTfh) responses to S or N strongly correlated with serum neutralization assays as well as receptor binding domain-specific IgA; however, the frequency of pTfh responses to SARS-CoV-2 was lower than the frequency of pTfh responses to influenza virus. Overall, T cell responses to SARS-CoV-2 are robust; however, CD4 + Th1 responses predominate over CD8 + T cell responses, have a more inflammatory profile, and have a weaker pTfh response than the response to influenza virus within the same donors, potentially contributing to COVID-19 disease., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Background: With the global shortage of skilled health workers estimated at 7.2 million, outpatient tuberculosis (TB) care is commonly task-shifted to lay health workers (LHWs) in many low- and middle-income countries where the shortages are greatest. While shown to improve access to care and some health outcomes including TB treatment outcomes, lack of training and supervision limit the effectiveness of LHW programs. Our objective was to refine and evaluate an intervention designed to address common causes of non-adherence to TB treatment and LHW knowledge and skills training needs., Methods: We employed a pragmatic cluster randomized controlled trial. Participants included 103 health centres (HCs) providing TB care in four districts in Malawi, randomized 1:1 stratified by district and HC funding (Ministry of Health, non-Ministry funded). At intervention HCs, a TB treatment adherence intervention was implemented using educational outreach, a point-of-care reminder tool, and a peer support network. Clusters in the control arm provided usual care. The primary outcome was the proportion of patients with successful TB treatment (i.e., cure or treatment completion). We used a generalized linear mixed model, with district as a fixed effect and HC as a random effect, to compare proportions of patients with treatment success, among the trial arms, with adjustment for baseline differences., Results: We randomized 51 HCs to the intervention group and 52 HCs to the control group. Four intervention and six control HCs accrued no eligible patients, and 371 of 1169 patients had missing outcome, HC, or demographic data, which left 74 HCs and 798 patients for analysis. Randomization group was not related to missing outcome, however, district, age, and TB type were significantly related and included in the primary analysis model. Among the 1153 patients with HC and demographic data, 297/605 (49%) and 348/548 (64%) in the intervention and control arms, respectively, had treatment success. The intervention had no significant effect on treatment success (adjusted odds ratio 1.35 [95% confidence interval 0.93-1.98])., Conclusion: We found no significant effect of the intervention on TB treatment outcomes with high variability in implementation quality, highlighting important challenges to both scale-up and sustainability., Trial Registration: ClinicalTrials.gov NCT02533089 . Registered August 20, 2015.

Background: The factors driving the best outcomes following minimally invasive surgery (MIS) for grade 1 degenerative lumbar spondylolisthesis are not clearly elucidated., Objective: To investigate the factors that drive the best 24-mo patient-reported outcomes (PRO) following MIS surgery for grade 1 degenerative lumbar spondylolisthesis., Methods: A total of 259 patients from the Quality Outcomes Database lumbar spondylolisthesis module underwent single-level surgery for degenerative grade 1 lumbar spondylolisthesis with MIS techniques (188 fusions, 72.6%). Twenty-four-month follow-up PROs were collected and included the Oswestry disability index (ODI) change (ie, 24-mo minus baseline value), numeric rating scale (NRS) back pain change, NRS leg pain change, EuroQoL-5D (EQ-5D) questionnaire change, and North American Spine Society (NASS) satisfaction questionnaire. Multivariable models were constructed to identify predictors of PRO change., Results: The mean age was 64.2 ± 11.5 yr and consisted of 148 (57.1%) women and 111 (42.9%) men. In multivariable analyses, employment was associated with superior postoperative ODI change (β-7.8; 95% CI [-12.9 to -2.6]; P = .003), NRS back pain change (β -1.2; 95% CI [-2.1 to -0.4]; P = .004), EQ-5D change (β 0.1; 95% CI [0.01-0.1]; P = .03), and NASS satisfaction (OR = 3.7; 95% CI [1.7-8.3]; P < .001). Increasing age was associated with superior NRS leg pain change (β -0.1; 95% CI [-0.1 to -0.01]; P = .03) and NASS satisfaction (OR = 1.05; 95% CI [1.01-1.09]; P = .02). Fusion surgeries were associated with superior ODI change (β -6.7; 95% CI [-12.7 to -0.7]; P = .03), NRS back pain change (β -1.1; 95% CI [-2.1 to -0.2]; P = .02), and NASS satisfaction (OR = 3.6; 95% CI [1.6-8.3]; P = .002)., Conclusion: Preoperative employment and surgeries, including a fusion, were predictors of superior outcomes across the domains of disease-specific disability, back pain, leg pain, quality of life, and patient satisfaction. Increasing age was predictive of superior outcomes for leg pain improvement and satisfaction., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Competing Interests: Intérêts concurrents: Aucun déclaré.

Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.

Objective: Spine surgery is especially susceptible to malpractice claims. Critics of the US medical liability system argue that it drives up costs, whereas proponents argue it deters negligence. Here, the authors study the relationship between malpractice claim density and outcomes., Methods: The following methods were used: 1) the National Practitioner Data Bank was used to determine the number of malpractice claims per 100 physicians, by state, between 2005 and 2010; 2) the Nationwide Inpatient Sample was queried for spinal fusion patients; and 3) the Area Resource File was queried to determine the density of physicians, by state. States were categorized into 4 quartiles regarding the frequency of malpractice claims per 100 physicians. To evaluate the association between malpractice claims and death, discharge disposition, length of stay (LOS), and total costs, an inverse-probability-weighted regression-adjustment estimator was used. The authors controlled for patient and hospital characteristics. Covariates were used to train machine learning models to predict death, discharge disposition not to home, LOS, and total costs., Results: Overall, 549,775 discharges following spinal fusions were identified, with 495,640 yielding state-level information about medical malpractice claim frequency per 100 physicians. Of these, 124,425 (25.1%), 132,613 (26.8%), 130,929 (26.4%), and 107,673 (21.7%) were from the lowest, second-lowest, second-highest, and highest quartile states, respectively, for malpractice claims per 100 physicians. Compared to the states with the fewest claims (lowest quartile), surgeries in states with the most claims (highest quartile) showed a statistically significantly higher odds of a nonhome discharge (OR 1.169, 95% CI 1.139-1.200), longer LOS (mean difference 0.304, 95% CI 0.256-0.352), and higher total charges (mean difference [log scale] 0.288, 95% CI 0.281-0.295) with no significant associations for mortality. For the machine learning models-which included medical malpractice claim density as a covariate-the areas under the curve for death and discharge disposition were 0.94 and 0.87, and the R2 values for LOS and total charge were 0.55 and 0.60, respectively., Conclusions: Spinal fusion procedures from states with a higher frequency of malpractice claims were associated with an increased odds of nonhome discharge, longer LOS, and higher total charges. This suggests that medicolegal climate may potentially alter practice patterns for a given spine surgeon and may have important implications for medical liability reform. Machine learning models that included medical malpractice claim density as a feature were satisfactory in prediction and may be helpful for patients, surgeons, hospitals, and payers.

Background: For laminectomy and posterior spinal fusion (LPSF) surgery for cervical spondylotic myelopathy (CSM), the evidence is unclear as to whether fusions should cross the cervicothoracic junction (CTJ)., Objective: To compare LPSF outcomes between those with and without lower instrumented vertebrae (LIV) crossing the CTJ., Methods: A consecutive series of adults undergoing LPSF for CSM from 2012 to 2018 with a minimum of 12-mo follow-up were identified. LPSF with subaxial upper instrumented vertebrae and LIV between C6 and T2 were included. Clinical and radiographic outcomes were compared., Results: A total of 79 patients were included: 46 crossed the CTJ (crossed-CTJ) and 33 did not. The mean follow-up was 22.2 mo (minimum: 12 mo). Crossed-CTJ had higher preoperative C2-7 sagittal vertical axis (cSVA) (33.3 ± 16.0 vs 23.8 ± 12.4 mm, P = .01) but similar preoperative cervical lordosis (CL) and CL minus T1-slope (CL minus T1-slope) (P > .05, both comparisons). The overall reoperation rate was 3.8% (crossed-CTJ: 2.2% vs not-crossed: 6.1%, P = .37). In adjusted analyses, crossed-CTJ was associated with superior cSVA (β = -9.7; P = .002), CL (β = 6.2; P = .04), and CL minus T1-slope (β = -6.6; P = .04), but longer operative times (β = 46.3; P = .001). Crossed- and not-crossed CTJ achieved similar postoperative patient-reported outcomes [Visual Analog Scale (VAS) neck pain, VAS arm pain, Nurick Grade, Modified Japanese Orthopedic Association Scale, Neck Disability Index, and EuroQol-5D] in adjusted multivariable analyses (adjusted P > .05). For the entire cohort, higher postoperative CL was associated with lower postoperative arm pain (adjusted Pearson's r -0.1, P = .02). No postoperative cervical radiographic parameters were associated with neck pain (P > .05)., Conclusion: Subaxial LPSF for CSM that crossed the CTJ were associated with superior radiographic outcomes for cSVA, CL, and CL minus T1-slope, but longer operative times. There were no differences in neck pain or reoperation rate., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Anticoagulant treatment of pediatric central venous catheter-related venous thromboembolism (CVC-VTE) has not been specifically evaluated. In EINSTEIN-Jr, 500 children with any VTE received rivaroxaban or standard anticoagulants. A predefined analysis of the CVC-VTE cohort was performed. Children with CVC-VTE (age, birth to 17 years) were administered rivaroxaban or standard anticoagulants during the 1-month (children <2 years) or 3-month (all other children) study period. Predefined outcomes were recurrent VTE, change in thrombotic burden on repeat imaging, and bleeding. Predictors for continuation of anticoagulant therapy beyond the study period were evaluated. One hundred twenty-six children with symptomatic (n = 76, 60%) or asymptomatic (n = 50, 40%) CVC-VTE received either rivaroxaban (n = 90) or standard anticoagulants (n = 36). There was no recurrent VTE (0%; 95% confidence interval [CI], 0.0%-2.8%). Three children had the principal safety outcome: none had major bleeding and 3 children had clinically relevant nonmajor bleeding (2.4%; 95% CI, 0.7%-6.5%), all in the rivaroxaban arm. Complete or partial vein recanalization occurred in 57 (55%) and 38 (37%) of 103 evaluable children, respectively. Results were similar for symptomatic and asymptomatic CVC-VTE. Continuation of anticoagulant therapy beyond the study period occurred in 61 (48%) of children and was associated with residual VTE but only in children <2 years (odds ratio [OR], 20.9; P = .003) and continued CVC use (OR, 6.7; P = .002). Anticoagulant therapy appeared safe and efficacious and was associated with reduced clot burden in most children with symptomatic or asymptomatic CVC-VTE. Residual VTE and continued CVC use were associated with extended anticoagulation. This trial was registered at www.clinicaltrials.gov as #NCT02234843., (© 2020 by The American Society of Hematology.)

Background: Congregate settings have been disproportionately affected by coronavirus disease 2019 (COVID-19). Our objective was to compare testing for, diagnosis of and death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across 3 settings (residents of long-term care homes, people living in shelters and the rest of the population)., Methods: We conducted a population-based prospective cohort study involving individuals tested for SARS-CoV-2 in the Greater Toronto Area between Jan. 23, 2020, and May 20, 2020. We sourced person-level data from COVID-19 surveillance and reporting systems in Ontario. We calculated cumulatively diagnosed cases per capita, proportion tested, proportion tested positive and case-fatality proportion for each setting. We estimated the age- and sex-adjusted rate ratios associated with setting for test positivity and case fatality using quasi-Poisson regression., Results: Over the study period, a total of 173 092 individuals were tested for and 16 490 individuals were diagnosed with SARS-CoV-2 infection. We observed a shift in the proportion of cumulative cases from all cases being related to travel to cases in residents of long-term care homes (20.4% [3368/16 490]), shelters (2.3% [372/16 490]), other congregate settings (20.9% [3446/16 490]) and community settings (35.4% [5834/16 490]), with cumulative travel-related cases at 4.1% (674/16490). Cumulatively, compared with the rest of the population, the diagnosed cases per capita was 64-fold and 19-fold higher among long-term care home and shelter residents, respectively. By May 20, 2020, 76.3% (21 617/28 316) of long-term care home residents and 2.2% (150 077/6 808 890) of the rest of the population had been tested. After adjusting for age and sex, residents of long-term care homes were 2.4 (95% confidence interval [CI] 2.2-2.7) times more likely to test positive, and those who received a diagnosis of COVID-19 were 1.4-fold (95% CI 1.1-1.8) more likely to die than the rest of the population., Interpretation: Long-term care homes and shelters had disproportionate diagnosed cases per capita, and residents of long-term care homes diagnosed with COVID-19 had higher case fatality than the rest of the population. Heterogeneity across micro-epidemics among specific populations and settings may reflect underlying heterogeneity in transmission risks, necessitating setting-specific COVID-19 prevention and mitigation strategies., Competing Interests: Competing interests: None declared., (Copyright 2020, Joule Inc. or its licensors.)