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Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.
Background: Pediatric inflammatory myopathies (PIM) are a rare, heterogenous group of disorders requiring prompt diagnosis and treatment to reduce complications and improve long-term outcome. This study reviews the clinical characteristics, management, and outcomes in PIM. Methods: A retrospective analysis of pediatric patients diagnosed with PIM at CHEO from January 2009 to December 2023 was performed. Patient data, including age at symptom onset, diagnostic testing performed, treatment, and follow-up durations, were evaluated. Results: A total of 25 patients with juvenile dermatomyositis (JDM), overlap syndromes, and necrotizing myopathy (HMG-CoA reductase and anti-SRP myositis) were identified. Symptoms began at an average age of 8.37 years (1.10-14.11), with formal diagnosis occurring at 8.57 years (2.02-16.11). Initial symptoms included skin changes, muscle weakness, joint pain, and fatigue. Diagnosis involved laboratory testing (CK, myositis antibodies), muscle MRI, electromyography, and/or muscle biopsy. Treatments included corticosteroids, IVIG, and steroid-sparing agents (methotrexate, mycophenolate mofetil, rituximab, hydroxychloroquine). Follow-up averaged 4.23 years (range: 0.5 to 13). Most patients displayed only mild residual symptoms with the exception of an anti-SRP myositis patient who became wheelchair-dependent, requiring ventilatory support. Conclusions: Inflammatory myopathies require prompt treatment to prevent complications. Most patients require multiple treatment modalities, however with early diagnosis and treatment the majority of patients’ symptoms resolve.
Background: LC-FAOD may be missed in neuromuscular (NM) clinics due to its rarity and absence from common NM genetic panels. The Canadian Neuromuscular Disease Registry (CNDR) collects real-world patient data and includes a network of clinician-investigators. Our objective was to inform future registry work by evaluating diagnosis pathways for LC-FAOD patients and estimating the number followed at Canadian NM clinics. Methods: A questionnaire was developed with an expert committee and circulated to 111 CNDR-affiliated NM neurologists. Results: 12 neurologists in 5 provinces, primarily adult-treating (n=8) completed the survey (10.8% response rate). Eleven (91.7%) practiced for >10 years. Agreement trends existed between definition of, and tests to evaluate, rhabdomyolysis. Four clinics routinely follow LC-FAOD patients. In the last 1-2 years, respondents diagnosed approximately 91 patients with LC-FAOD (mean=7.5 per clinic). 83.3% never received continuing education on LC-FAOD, though 75% indicated interest in expert-led webinars. Further data will be presented. Conclusions: Low sample size limits conclusions about LC-FAOD clinical trends. Results suggest LC-FAOD may be under-diagnosed or not routinely followed by NM specialists, limiting viability of an LC-FAOD registry. Practitioners may be interested in LC-FAOD-specific education. Future work could include collaboration with metabolic geneticists on education initiatives to raise awareness and improve care for these patients.
Background: Patient registries are an effective tool in tracking the natural history of rare diseases as well as post-marketing surveillance of novel therapies. The Canadian Neuromuscular Disease Registry (CNDR) is a pan-neuromuscular disease registry that prospectively collects Spinal Muscular Atrophy (SMA)-specific data in 28 clinics across Canada. The objective of this study is to describe real-world data from the CNDR-SMA patient population. Methods: We report cross-sectional data from Canadian SMA patients. Patients were included in analysis if they were active (alive and with follow-up within 24 months). Results: Of 171 SMA patients included in analyses, 37% currently use non-invasive ventilation, 2% invasive ventilation, and 61% no ventilation support. Feeding tubes are used by 27% of patients. and 28% of patients have a history of scoliosis surgery. Of the 171 patients, 137 have had disease-modifying therapy: 96 on nusinersen, 22 on risdiplam, and 19 on onasemnogene abeparvovec (OA). Median (min,max) years of age at therapy initiation was 7 (0,54), 20.5 (5,53), and 1 (0,6), respectively. At therapy initiation, functional status was 32% non-sitters, 38% sitters, and 30% walkers. Conclusions: The CNDR captures a comprehensive SMA dataset that prospectively evaluates real-world data, supporting post-marketing surveillance of novel therapies in Canada.
The COVID-19 pandemic has affected all our lives, not only through the infection itself but also through the measures taken to control the spread of the virus (e.g. lockdown).
Aims
Here, we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales.
Method
We compared the mental health symptoms of up to 4773 twins in their mid-20s in 2018 prior to the COVID-19 pandemic (T1) and during four-wave longitudinal data collection during the pandemic in April, July and October 2020, and in March 2021 (T2–T5) using phenotypic and genetic longitudinal designs.
Results
The average changes in mental health were small to medium and mainly occurred from T1 to T2 (average Cohen d = 0.14). Despite the expectation of catastrophic effects of the pandemic on mental health, we did not observe trends in worsening mental health during the pandemic (T3–T5). Young people with pre-existing mental health problems were disproportionately affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences in mental health symptoms did not change during the lockdown (average heritability 33%); the average genetic correlation between T1 and T2–T5 was 0.95, indicating that genetic effects before the pandemic were substantially correlated with genetic effects up to a year later.
Conclusions
We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.
A subcommittee of the Hawaii Governor's Joint Task Force on Rat Lungworm Disease developed preliminary guidelines for the diagnosis and treatment of neuroangiostrongyliasis (NAS) in 2018 (Guidelines, 2018). This paper reviews the main points of those guidelines and provides updates in areas where our understanding of the disease has increased. The diagnosis of NAS is described, including confirmation of infection by real-time polymerase chain reaction (RTi-PCR) to detect parasite DNA in the central nervous system (CNS). The treatment literature is reviewed with recommendations for the use of corticosteroids and the anthelminthic drug albendazole. Long-term sequelae of NAS are discussed and recommendations for future research are proposed.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Stars form in clusters, while planets form in gaseous disks around young stars. Cluster dissolution occurs on longer time scales than disk dispersal. Planet formation thus typically takes place while the host star is still inside the cluster. We explore how the presence of other stars affects the evolution of circumstellar disks. Our numerical approach requires multi-scale and multi-physics simulations where the relevant components and their interactions are resolved. The simulations start with the collapse of a turbulent cloud, from which stars with disks form, which are able to influence each other. We focus on the effect of extinction due to residual cloud gas on the early evolution of circumstellar disks. We find that this extinction protects circumstellar disks against external photoevaporation, but these disks then become vulnerable to dynamic truncation by passing stars. We conclude that circumstellar disk evolution is heavily affected by the early evolution of the cluster.
Depression in older adults is often under-diagnosed and consequently under-treated, despite association with higher rates of morbidity and mortality, increased healthcare utilisation and greater economic cost compared to younger populations. Better identification will be imperative in the future because of the estimated growth in the older adult population. Screening could improve identification; a well-known screening tool tis the Geriatric Depression Scale (GDS).
Objective
To evaluate the diagnostic accuracy of the brief GDS-15 and ultra-brief versions in the detection of major depression.
Method
Seven electronic databases and unpublished literature were searched, using predefined criteria, from 1982 to April 2014. Primary study quality was assessed using the QUADAS-2. Pooled diagnostic performance data was calculated using bivariate meta-analysis. Subgroup and sensitivity analyses were pre-planned. Heterogeneity was explored through meta-regression.
Results
Of 6635 records identified 32 studies were included. Meta-analyses were possible for the GDS-1, GDS-4 and GDS-15. For the GDS-15, at the recommended cut-off score of 5, the diagnostic odds ratio was highest in a community setting and for older adults aged ≤69 years. A cut-off score of 4, however, provided better diagnostic accuracy. Diagnostic data was less favourable when depression prevalence was ≥10%. Better diagnostic properties were found in non-Western countries. Meta-regression revealed country and language were predictive of diagnostic accuracy.
Conclusions
Further research is needed to explore diagnostic properties of ultra-brief GDS versions. GDS-15 findings suggest selective reporting of cut-off scores, which requires cautious interpretation and a need for greater methodological rigor in primary studies.
Navigating the research domain at an academic medical center can be challenging, even for seasoned investigators. To address this, Duke University launched two initiatives: (1) a research navigation “hotline” to provide brief assistance with a variety of research questions; and (2) researcher onboarding and consultation, a one-to-one tailored offering to ensure that researchers are equipped to navigate research resources and processes effectively. The services are provided by the myRESEARCHnavigators (MRN) team, funded by Duke’s CTSA. The diverse scientific backgrounds of the six team members align well with those of the research community, allowing for a good match between the researcher and MRN team member. The MRN team answers approximately 30 questions per month, and has provided consultations to almost 400 researchers. Both services receive high satisfaction ratings (4 or 5 stars [out of 5 stars] given to 90% of hotline answers, and 99% of researcher onboarding/consultation sessions). As of July 2019, the School of Medicine has determined that the consultations are critical to their mission and have made them a requirement for new research faculty. The team will continue marketing both services to encourage adoption.
In 2013, a task force was developed to discuss the future of the Canadian pediatric neurology workforce. The consensus was that there was no indication to reduce the number of training positions, but that the issue required continued surveillance. The current study provides a 5-year update on Canadian pediatric neurology workforce data.
Methods:
Names, practice types, number of weekly outpatient clinics, and dates of certification of all physicians currently practicing pediatric neurology in Canada were obtained. International data were used to compute comparisons between countries. National data sets were used to provide information about the number of residency positions available and the number of Canadian graduates per year. Models for future projections were developed based on published projected population data and trends from the past decade.
Results:
The number of pediatric neurologists practicing in Canada has increased 165% since 1994. During this period, wait times have not significantly shortened. There are regional discrepancies in access to child neurologists. The Canadian pediatric neurology workforce available to see outpatient consultations is proportionally less than that of USA. After accounting for retirements and emigrations, the number of child neurologists being added to the workforce each year is 4.9. This will result in an expected 10-year increase in Canadian pediatric neurologists from 151 to 200.
Conclusions:
Despite an increase in the number of Canadian child neurologists over the last two decades, we do not predict that there will be problems with underemployment over the next decade.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Commentary on the introduction of the Australian Curriculum (AC) has reflected a tension for educators of students with disabilities (SWD) between in-principle support for a curriculum that is inclusive of all students and the challenge of translating a general framework into relevant, individualised learning experiences appropriate for all SWD. In this paper, we report on findings from the second part of a national online survey in which we explored the perceptions and practices of 151 educators of SWD in specialist settings (special schools, disability units co-located at mainstream schools, special classes within mainstream schools) in relation to the AC. Specifically, these findings relate to the professional learning (PL) experiences and perceived needs of educators of SWD related to the AC and their advice to policymakers about the AC for SWD. Consistent with previous research, participants expressed a preference for PL experiences delivered on site, facilitated by content experts over extended periods, with opportunities for demonstration and targeted feedback, and in the context of collegial learning communities. In addition, participants raised concerns about the extent to which the AC is fully inclusive of all SWD. Implications for policy, practice, and future research are discussed.
Despite aspirations to be a world-class national curriculum, the Australian Curriculum (AC) has been criticised as ‘manifestly deficient’ (Australian Government Department of Education and Training, 2014 p. 5) as an inclusive curriculum, failing to meet the needs of all students with disabilities (SWD) and their teachers. There is a need for research into the daily attempts of educators to navigate the tension between a ‘top-down’ system-wide curriculum and a ‘bottom-up’ regard for individual student needs, with a view to informing both policy and practice. This article is the first of two research papers in which we report the findings from a national online Research in Special Education (RISE) Australian Curriculum Survey of special educators in special schools, classes, and units regarding their experience using the AC to plan for and teach SWD. Survey results indicated (a) inconsistent use of the AC as the primary basis for developing learning objectives and designing learning experiences, (b) infrequent use of the achievement standards to support assessment and reporting, and (c) considerable supplementation of the AC from other resources when educating SWD. Overall, participants expressed a lack of confidence in translating the AC framework into a meaningful curriculum for SWD. Implications for policy, practice, and future research are discussed.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Background: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Methods: Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. Results: The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. Conclusions: There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option.