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Presents a letter to the editor in response to an article which discussed HIV tests, published in a July 2002 issue of the "Canadian Medical Association Journal."

Background: Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumor surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates., Methods: In this study, we analyzed postoperative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and pediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n = 427)., Results: Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the pediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to the prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviors., Conclusions: Our findings indicate that CMS-associated lesions may result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: New Zealand's public health response to the COVID-19 pandemic has largely been considered successful, although there have been concerns surrounding the potential harms of the lockdown restrictions enforced, including alteration of alcohol consumption. New Zealand utilised a four-tiered alert level system of lockdowns and restrictions, with Level 4 denoting strict lockdown. This study aimed to compare alcohol-related hospital presentations during these periods with corresponding calendar-matched dates from the preceding year., Methods: We conducted a retrospective case-controlled analysis of all alcohol-related hospital presentations between 1 January 2019 to 2 December 2021 and compared COVID-19 restriction periods to corresponding calendar-matched pre-pandemic periods., Results: A total of 3,722 and 3,479 alcohol-related acute hospital presentations occurred during the four COVID-19 restriction levels and corresponding control periods respectively. Alcohol-related presentations accounted for a greater proportion of all admissions during COVID-19 Alert Levels 3 and 1 than the respective control periods (both p⁢0.05), but not during Levels 4 and 2 (both p>0.30). Acute mental and behavioural disorders accounted for a greater proportion of alcohol-related presentations during Alert Levels 4 and 3 (both p≤0.02), although alcohol dependence was present in a lower proportion of presentations during Alert Levels 4, 3, and 2 (all p⁢0.01). There was no difference in acute medical conditions including hepatitis and pancreatitis during all alert levels (all p>0.05)., Conclusion: Alcohol-related presentations were unchanged compared to matched control periods during the strictest level of lockdown, although acute mental and behavioural disorders accounted for a greater proportion of alcohol-related admissions during this period. New Zealand appears to have avoided the general trend of increased alcohol-related harms seen internationally during the COVID-19 pandemic and its lockdown restrictions., Competing Interests: Nil, (© PMA.)

Background: Primary tumors involving the spine are relatively rare but represent surgically challenging procedures with high patient morbidity. En bloc resection of these tumors necessitates large exposures, wide tumor margins, and poses risks to functionally relevant anatomical structures. Augmented reality neuronavigation (ARNV) represents a paradigm shift in neuronavigation, allowing on-demand visualization of 3D navigation data in real-time directly in line with the operative field., Methods: Here, we describe the first application of ARNV to perform distal sacrococcygectomies for the en bloc removal of sacral and retrorectal lesions involving the coccyx in 2 patients, as well as a thoracic 9-11 laminectomy with costotransversectomy for en bloc removal of a schwannoma in a third patient., Results: In our experience, ARNV allowed our teams to minimize the length of the incision, reduce the extent of bony resection, and enhanced visualization of critical adjacent anatomy. All tumors were resected en bloc, and the patients recovered well postoperatively, with no known complications. Pathologic analysis confirmed the en bloc removal of these lesions with negative margins., Conclusions: We conclude that ARNV is an effective strategy for the precise, en bloc removal of spinal lesions including both sacrococcygeal tumors involving the retrorectal space and thoracic schwannomas., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ribonucleotide reductase (RNR) is an essential enzyme found in all organisms. The function of RNR is to catalyze the conversion of nucleotides to deoxynucleotides. RNRs rely on metallocofactors to oxidize a conserved cysteine in the active site of the enzyme into a thiyl radical, which then initiates nucleotide reduction. The proteins required for MnIII2-Y• cluster formation in class Ib RNRs are NrdF (β-subunit) and NrdI (flavodoxin). An oxidant is channeled from the FMN cofactor in NrdI to the dimanganese center in NrdF, where it oxidizes the dimanganese center and a tyrosyl radical (Y•) is formed. Both Streptococcus sanguinis and Escherichia coli MnII2-NrdF structures have a constriction in the channel immediately above the metal site. In E. coli, the constriction is formed by the side chain of S159, whereas in the S. sanguinis system it involves T158. This serine-to-threonine substitution was investigated using S. sanguinis and Streptococcus pneumoniae class Ib RNRs but it is also present in other pathogenic streptococci. Using stopped-flow kinetics, we investigate the role of this substitution in the mechanism of MnIII2-Y• cluster formation. In addition to different kinetics observed in the studied streptococci, we found that affinity constants of NrdF for MnII and FeII are about 1 µM and the previously reported preference for MnII could not be explained by affinity only., (© The Author(s) 2021. Published by Oxford University Press.)

Background: A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial., Objectives: We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders., Global Summit: The Global Summit took place on September 14-15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence., Systematic Review of the Literature: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus., Results: We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report., Conclusion: Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.

Background and Purpose: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification., Materials and Methods: The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons ( n = 122), medulloblastoma ( n = 272), pilocytic astrocytoma ( n = 135), and ependymoma ( n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists., Results: Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F 1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F 1 score were higher than those of 2 of the 4 radiologists., Conclusions: We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis., (© 2020 by American Journal of Neuroradiology.)

Background and Objective: Clinical guidelines recommend the use of beta-blockers and other cardiovascular prevention drugs in patients with acute coronary syndrome (ACS). Studies in several countries have found that beta-blockers are underused in patients with chronic obstructive pulmonary disease (COPD) and co-morbid heart disease, although most have only examined use in subgroups of patients. We undertook a nationwide follow-up study in New Zealand to describe the use of beta-blockers and other cardiovascular prevention drugs in patients with COPD and ACS., Methods: National health and pharmaceutical dispensing data were used to derive the study cohort, identify patients who were admitted to hospital with ACS and/or heart failure before cohort entry and during follow-up, and ascertain drug use., Results: The study cohort included 83 435 patients aged ≥45 years, with 290 400 person-years of follow-up. Among 2637 patients with ≥1 ACS admission during follow-up, only 56.6% received a beta-blocker in the 6 months following the first admission, while 87.7% and 81%, respectively, received aspirin and a statin. Patients with higher COPD severity were less likely to receive a beta-blocker than those with lower severity, as were those with no history of previous ACS and/or heart failure., Conclusion: Use of beta-blockers following an ACS admission was much lower than expected based on the findings of general audits of ACS management in New Zealand. Along with the higher proportions using aspirin and statins, and the differences in beta-blocker dispensing by COPD severity, this suggests a particular reluctance to prescribe beta-blockers to patients with COPD., (© 2019 Asian Pacific Society of Respirology.)

Aim: To describe the use of contraindicated and use-with-caution medicines among new users of simvastatin., Methods: We used information from Ministry of Health national datasets to establish a cohort of all patients aged >18 years who initiated simvastatin use between January 2006 and December 2013 (n=349,371). We estimated the cumulative incidences of the first dispensing of contraindicated and use-with-caution medicines during simvastatin use, and explored factors associated with co-prescription, using Kaplan-Meir and Cox regression methods, respectively., Results: Eleven percent and 16% of patients were dispensed a contraindicated and use-with-caution medicine, respectively, during the first two years of simvastatin use; by seven years, the figures were 17% and 26%. Thirty-six percent of patients were co-prescribed a contraindicated medicine on >1 occasion; the corresponding proportion for use-with-caution medicines was 84%. For a substantial proportion of those co-prescribed a use-with-caution medicine, the concomitant daily dose of simvastatin exceeded the maximum dose recommended at the time of prescribing. In the majority of cases, the prescriber of simvastatin and the contraindicated or use-with-caution medicine were the same. Co-prescribing of contraindicated medicines varied by sex, age, ethnicity and comorbidity., Conclusions: The prescription of contraindicated and use-with-caution drugs to patients taking simvastatin is not uncommon in New Zealand., Competing Interests: Nil.

Background: Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recently, endoscopic transsphenoidal approaches have been increasingly used; however, few case series exist in the pediatric population., Methods: A retrospective review of patients (aged <18 years) undergoing endoscopic transsphenoidal resection of craniopharyngiomas between 1995 and 2016 was performed. Preoperative data included presenting symptoms, tumor size, location, and components. Postoperative outcomes included symptom resolution, visual outcomes, endocrine outcomes, disease recurrence, and major complications., Results: Sixteen pediatric patients with mean age of 11.0 years (range, 5-15 years) were included. The median follow-up time was 56.2 months. Mean maximal tumor diameter was 3.98 cm. Most of the tumors had suprasellar (93.8%) and intrasellar (68.8%) components. The gross total resection rate was 93.8%. The most common presenting symptoms were vision changes (81.3%) and increased intracranial pressure (56.3%). Most patients (66.7%) had their presenting symptoms resolved by their first postoperative visit. Vision improved or remained normal in 69.2% of patients. Postoperatively, new incidence of panhypopituitarism or diabetes insipidus developed in 63.6% and 46.7% of patients, respectively. New hypothalamic obesity developed in 28.6% of patients. The postoperative cerebrospinal fluid leak rate was 18.8%. One patient died of intraventricular hemorrhage postoperatively. The major complication rate was 12.5%. Disease recurrence occurred in 1 patient with gross total resection (6.3%)., Conclusions: Endoscopic transsphenoidal resection for craniopharyngiomas can achieve high rates of total resection with low rates of disease recurrence in larger tumors than previously described. However, hypothalamic-pituitary dysfunction and cerebrospinal fluid leak remain significant postoperative morbidities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Control of crystal size and shape is crucially important for crystallization process development in the pharmaceutical industries. In general crystals of large size and low aspect ratio are desired for improved downstream manufacturability. It can be extremely challenging to design crystallization processes that achieve these targets for active pharmaceutical ingredients (APIs) that have very slow growth kinetics and needle-like morphology. In this work, a batch cooling crystallization process for a GlaxoSmithKline patented API, which is characterized by very slow growth rate and needle morphology, was studied and improved using process analytical technology (PAT) based feedback control techniques and in situ immersion milling. Four specific approaches were investigated: Supersaturation control (SSC), direct nucleation control (DNC), sequential milling-DNC, and simultaneous milling-DNC. This is the first time that immersion wet milling is combined with feedback control in a batch crystallization process. All four approaches were found to improve crystal size and/or shape compared to simple unseeded or seeded linear cooling crystallizations. DNC provided higher quality crystals than SSC, and sequential and simultanesou milling-DNC approaches could reduce particle 2D aspect ratio without generating too much fines. In addition, an ultra-performance liquid chromatography (UPLC) system was used online as a novel PAT tool in the crystallization study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose To determine if adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) is associated with postpublication citation rates. Materials and Methods A comprehensive search of PubMed, EMBASE, and Cochrane Library databases was performed to identify published articles that have evaluated adherence of diagnostic accuracy studies to the STARD statement. These were included if the number of STARD items reported ("STARD result") could be obtained for each evaluated study. The date of publication, journal impact factor, and citation rate (citations per day) were extracted for the diagnostic accuracy studies. Univariate correlations were performed to identify any association between STARD result, impact factor, and citation rate. Multivariate regression analysis was performed to explore the effect of impact factor on postpublication citation rates. Results The authors were able to obtain the STARD results for 1002 "original" diagnostic accuracy studies from eight different "STARD evaluation" articles. The median impact factor was 3.97 (interquartile range [IQR]: 2.32-6.21), the median STARD result was 15 of 25 items (IQR: 12-18), and the median citation rate was 0.007 citations per day (IQR: 0.0032-0.017). The authors identified a weak positive correlation between STARD result and citation rate (r = 0.096; 95% confidence interval [CI]: 0.034, 0.157), a moderate positive correlation between impact factor and citation rate (r = 0.58; 95% CI: 0.535, 0.617), and a weak positive correlation between impact factor and STARD result (r = 0.13; 95% CI: 0.064, 0.186). Multivariate analysis accounting for journal clustering effects revealed that, when impact factor is partialed out, the positive correlation between citation rate and STARD result does not persist (r = 0.029; 95% CI: -0.033, 0.091). Conclusion There is a positive correlation between completeness of reporting, as evaluated with STARD, and citation rate as well as impact factor. When adjusted for impact factor, the positive correlation between completeness of reporting and citation rate does not persist. (©) RSNA, 2016 Online supplemental material is available for this article.