Whole-exome sequencing has revealed novel genetic characteristics in intracranial germ cell tumours in the Chinese.

AIMS: Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. METHODS AND RESULTS: In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression-free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance. CONCLUSION: This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.

Disproportionate Rates of COVID-19 Among Black Canadian Communities: Lessons from a Cross-Sectional Study in the First Year of the Pandemic.

BACKGROUND: Racialized communities, including Black Canadians, have disproportionately higher COVID-19 cases. We examined the extent to which SARS-CoV-2 infection has affected the Black Canadian community and the factors associated with the infection. METHODS: We conducted a cross-sectional survey in an area of Ontario (northwest Toronto/Peel Region) with a high proportion of Black residents along with 2 areas that have lower proportions of Black residents (Oakville and London, Ontario). SARS-CoV-2 IgG antibodies were determined using the EUROIMMUN assay. The study was conducted between August 15, 2020, and December 15, 2020. RESULTS: Among 387 evaluable subjects, the majority, 273 (70.5%), were enrolled from northwest Toronto and adjoining suburban areas of Peel, Ontario. The seropositivity values for Oakville and London were comparable (3.3% (2/60; 95% CI 0.4-11.5) and 3.9% (2/51; 95% CI 0.5-13.5), respectively). Relative to these areas, the seropositivity was higher for the northwest Toronto/Peel area at 12.1% (33/273), relative risk (RR) 3.35 (1.22-9.25). Persons 19 years of age or less had the highest seropositivity (10/50; 20.0%, 95% CI 10.3-33.7%), RR 2.27 (1.23-3.59). There was a trend for an interaction effect between race and location of residence as this relates to the relative risk of seropositivity. INTERPRETATION: During the early phases of the pandemic, the seropositivity within a COVID-19 high-prevalence zone was threefold greater than lower prevalence areas of Ontario. Black individuals were among those with the highest seroprevalence of SARS-CoV-2.

Cardiac sarcoma presenting as paraneoplastic arthritis and clubbing: a case report and literature review.

BACKGROUND: Cardiac tumours are rare, and clinical manifestations depend on the anatomical location. Symptoms can be the result of cardiac outflow anomalies, constitutional features such as fever, loss of weight, and/or paraneoplastic manifestations such as arthritis. To date, there has only been one other case report in the literature of cardiac sarcoma presenting as paraneoplastic arthropathy. CASE PRESENTATION: A 52-year-old woman presented with acute onset corticosteroid-resistant inflammatory polyarthralgia, clubbing and a systolic murmur. Transthoracic echocardiogram revealed a dilated left atrium with an echogenic mass and brain magnetic resonance imaging revealed multiple embolic infarcts. Histopathology following emergency resection showed a Grade 3 left atrial intimal sarcoma. The polyarthralgia and clubbing resolved soon after tumour removal. The patient went on to receive chemotherapy and remains in remission. CONCLUSIONS: This case highlights the rare paraneoplastic association of cardiac sarcoma and arthropathy.

Outcome of Absence Epilepsy With Onset at 8-11 Years of Age: Watershed Ages When Syndromes Overlap.

Introduction: Absence seizures occur in various epilepsy syndromes, including childhood and juvenile absence epilepsy and juvenile myoclonic epilepsy. When children present with absence seizures at ages when syndromes overlap, initial syndrome designation is not always possible, making early prognostication challenging. For these children, the study objective is to determine clinical and initial electroencephalograph (EEG) findings to predict the development of generalized tonic-clonic seizures, which is a factor that affects outcome. Methods: Children with new-onset absence seizures between 8 and 11 years of age with at least 5 years of follow-up data were studied through the review of medical records and initial EEG tracings. Results: Ninety-eight patients were included in the study. The median age of absence seizure onset was 9 years (interquartile range [IQR] = 8.00, 10.00) and follow-up was 15 years (IQR = 13.00, 18.00). Forty-six percent developed generalized tonic-clonic seizures and 20% developed myoclonic seizures. On multiple regression analysis, a history of myoclonic seizures, anxiety, as well as bifrontal slowing and mild background slowing on initial EEG (P < .05) were associated with generalized tonic-clonic seizures. Although not statistically significant, a shorter duration of shortest EEG burst on baseline EEG was also associated with generalized tonic-clonic seizures. Conclusion: On initial EEG, bifrontal and background slowing and myoclonic seizures and anxiety are associated with developing generalized tonic-clonic seizures, which is of prognostic significance when early syndrome designation is difficult.

Challenges implementing recent recommendations of daily formula supplementation for allergy prevention and practical real-world options.

The Canadian Paediatric Society's Position statement 'Dietary exposures and allergy prevention in high-risk infants' December 2021 provides recommendations for regular ingestion of cow's milk protein (CMP) once introduced in early infancy. These recommendations are based on evidence from randomized controlled trials (RCTs) where researchers supported participants in adhering to diet recommendations. Real-life dilemmas that relate to dietary adherence including cost, food wastage, and practicality are not addressed and are the crux of where -evidence-based recommendations fail. This commentary highlights the difficulties in carrying out the proposed recommendation for regular ingestion of CMP in practice and offers three practical real-world options instead.

Enhancing BIM security in emergency construction projects using lightweight blockchain-as-a-service.

Rapid design and construction of mobile cabin hospitals (MCHs) have become imperative in the COVID-19 response. However, due to unique design specifications (e.g., parallel design and model pre-revision), collaboration in emergency construction projects (ECPs) like MCHs presents data security vulnerabilities, including a lack of traceability and transparency. These hazards invariably reduce design effectiveness, leading to undesirable rework and project delay. Blockchain technology is a potential solution to address the aforementioned security issues in ECPs because it offers immutable and traceable data storage. Nevertheless, directly implementing blockchain in ECPs is impractical, for the blockchain has a complex deployment process and provides limited functions supporting BIM-based design. Therefore, this paper develops a lightweight blockchain-as-a-service (LBaaS) prototype to enhance the ECPs design efficiency by securing and automating information exchange while eliminating the difficulties of deploying and using blockchain. This paper contributes three elements: (1) Security vulnerabilities of design in ECP are identified. Taking an MCH in Hong Kong as an example, this paper investigates its design process and determines two design characteristics and associated security flaws. (2) Key technologies to support easy deployment and usage of blockchain in ECPs are developed. New technical elements, including a Multi-to-One mapping (MtOM) kit for easy blockchain registration, an integrated workflow retaining existing design practices, and smart contracts for secure interaction with blockchain, are developed to support LBaaS functionality. (3) An LBaaS prototype is validated and evaluated. The prototype is illustrated and evaluated using design examples based on actual MCH project data. Results show that the LBaaS is a feasible and secure approach for ECPs collaboration. This paper deepens the understanding of data security issues in ECPs and offers technical guidance in establishing blockchain solutions.

Factors associated with research participation in a large primary care practice-based pediatric cohort: Results from the TARGet Kids! longitudinal cohort study.

BACKGROUND: All longitudinal cohort studies strive for high participant retention, although attrition is common. Understanding determinants of attrition is important to inform and develop targeted strategies to improve study participation. We aimed to identify factors associated with research participation in a large children's primary care cohort study. METHODS: In this longitudinal cohort study between 2008 and 2020, all children who participated in the Applied Research Group for Kids (TARGet Kids!) were included. TARGet Kids! is a large primary care practice-based pediatric research network in Canada with ongoing data collection at well-child visits. Several sociodemographic, health, and study design factors were examined for their associations with research participation. The primary outcome was attendance of eligible research follow-up visits. The secondary outcome was time to withdrawal from the TARGet Kids! study. Generalized linear mixed effects models and Cox proportional hazard models were fitted. We have engaged parent partners in all stages of this study. RESULTS: A total 10,412 children with 62,655 total eligible research follow-up visits were included. Mean age at enrolment was 22 months, 52% were male, and 52% had mothers of European ethnicity. 68.4% of the participants attended at least 1 research follow-up visit. Since 2008, 6.4% of the participants have submitted a withdrawal request. Key factors associated with research participation included child age, ethnicity, maternal age, maternal education level, family income, parental employment, child diagnosis of chronic health conditions, certain study sites, and missingness in questionnaire data. CONCLUSIONS: Socioeconomic status, demographic factors, chronic conditions, and missingness in questionnaire data were associated with research participation in this large primary care practice-based cohort study of children. Results from this analysis and input from our parent partners suggested that retention strategies could include continued parent engagement, creating brand identity and communication tools, using multiple languages and avoiding redundancy in the questionnaires.

Dual-energy x-ray absorptiometry assessment of bone health in Australian men with prostate cancer commencing androgen deprivation therapy.

OBJECTIVE: To determine the prevalence in Australia of bone health assessment of men with prostate cancer by dual-energy x-ray absorptiometry (DXA), from six months before to twelve months after initiation of androgen deprivation therapy (ADT). DESIGN, SETTING: Cross-sectional national study; linkage of de-identified Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data. PARTICIPANTS: Men (18 years or older) first dispensed PBS-subsidised ADT during 1 May 2017 - 31 July 2020. MAIN OUTCOME MEASURES: Prevalence of MBS-subsidised DXA assessments undertaken from six months before to twelve months after first ADT prescription. RESULTS: Of 33 836 men with prostate cancer commencing ADT therapy during 2017-20, 6683 (19.8%) underwent DXA bone heath assessments between six months before and twelve months after commencing ADT; the mean time from first ADT dispensing to DXA scanning was +90 days (standard deviation, 134 days). The proportion of men aged 54 years or younger who had scans (66 of 639, 10%) was smaller than that of men aged 70-84 years (4528 of 19 378, 23.4%; adjusted odds ratio, 0.36; 95% CI, 0.28-0.47). CONCLUSIONS: For about 80% of men with prostate cancer commencing ADT in Australia, therapy initiation was not accompanied by DXA assessment of bone health. Given the excellent long term prognosis for men with prostate cancer and the availability of bone protective therapy, bone health monitoring should be a routine component of prostate cancer care for men receiving ADT.

The disproportionately large contribution of the Maori and Pacific Islander community to the healthcare burden of gout in Western Sydney.

BACKGROUND: Gout is a common chronic inflammatory disorder due to monosodium urate deposition, which results in severe inflammatory arthritis. It is particularly common in those of Maori or Pacific Islander heritage. There is a significant number of this at-risk ethnic group in western Sydney. AIMS: To determine the healthcare burden of gout in Western Sydney. METHODS: We characterised patients managed in the emergency departments (EDs) of the four Western Sydney Local Health District (WSLHD) hospitals and those admitted for gout as the primary or secondary diagnosis from 1 January 2017 to 31 December 2018. RESULTS: There were 472 patients managed in ED on 552 occasions at a direct cost to the LHD of A$367 835. Those of Maori or Pacific Islander ethnicity comprised 25.2% (n = 119/472), while half (n = 39/80) of those managed in ED for gout on two or more occasions were of Maori or Pacific Islander ethnicity. Overall, 310 patients were admitted with gout as the principal diagnosis on 413 occasions at a cost of A$1.73 million. Seventy-five (24.2%) of the 310 patients were of Maori or Pacific Islander heritage. A total of 584 WSLHD inpatients had gout as a secondary diagnosis. This was associated with 714 admissions. CONCLUSIONS: The disproportionately large healthcare burden of gout in Western Sydney from the relatively small Maori and Pacific Islander population needs attention. Urgent culturally appropriate interventions to address gout are required to address this inequality.

Development of a Novel Prospective Model to Predict Unplanned 90-Day Readmissions After Total Hip Arthroplasty.

BACKGROUND: For hospitals participating in bundled payment programs, unplanned readmissions after surgery are often termed "bundle busters." The aim of this study was to develop the framework for a prospective model to predict 90-day unplanned readmissions after elective primary total hip arthroplasty (THA) at a macroscopic hospital-based level. METHODS: A national, all-payer, inpatient claims and cost accounting database was used. A mixed-effect logistic regression model measuring the association of unplanned 90-day readmissions with a number of patient-level and hospital-level characteristics was constructed. RESULTS: Using 427,809 unique inpatient THA encounters, 77 significant risk factors across 5 domains (ie, comorbidities, demographics, surgical history, active medications, and intraoperative factors) were identified. The highest frequency domain was comorbidities (64/100) with malignancies (odds ratio [OR] 2.26), disorders of the respiratory system (OR 1.75), epilepsy (OR 1.5), and psychotic disorders (OR 1.5), being the most predictive. Other notable risk factors identified by the model were the use of opioid analgesics (OR 7.3), Medicaid coverage (OR 1.8), antidepressants (OR 1.6), and blood-related medications (OR 1.6). The model produced an area under the curve of 0.715. CONCLUSION: We developed a novel model to predict unplanned 90-day readmissions after elective primary THA. Fifteen percent of the risk factors are potentially modifiable such as use of tranexamic acid, spinal anesthesia, and opioid medications. Given the complexity of the factors involved, hospital systems with vested interest should consider incorporating some of the findings from this study in the form of electronic medical records predictive analytics tools to offer clinicians with real-time actionable data.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Bone health assessment with dual energy X-ray absorptiometry in men with high-risk prostate carcinoma commencing adjuvant androgen deprivation therapy.

Background: Androgen deprivation therapy (ADT) is a key component of therapy for patients with high-risk prostate carcinoma, but it may be deleterious for bone health. We sought to determine the frequency of dual energy x-ray absorptiometry (DXA) scanning in patients commencing adjuvant ADT for treatment of high-risk prostate cancer at a large integrated regional cancer centre. Material and methods: The electronic medical records (EMR) of all patients with high-risk prostate carcinoma commenced on adjuvant ADT between January 1, 2016 and December 31, 2017 at the Mid-North Coast Cancer Institute, Coffs Harbour, Australia were reviewed. Patients commenced on neoadjuvant ADT and long-term suppressive ADT for metastatic disease were excluded. The following data were obtained: socio-demographic information, prostate cancer data, ADT details and DXA results. Results: 188 men (mean age ± SD, 75.4 ± 7 years) were commenced on adjuvant ADT for a total duration (mean ± SD) of 23.4 ± 7 months. Most (n = 155/188, 82%) were commenced on leuprorelin acetate. While only 26/188 (14%) had a DXA scan performed prior to ADT, another 133 (71%) had a DXA scan at a median of 20 days (interquartile range 7-98), later. Of the 159 men with DXA readings, 76 (48%) were osteopaenic and 38 (24%) were osteoporotic by DXA criteria. Conclusion: A high level (85%) of DXA scanning in men commencing ADT for prostate cancer can be achieved at a regional centre. The high prevalence (72%) of low bone mass in our unselected cohort underscores the importance of routine DXA scanning to guide bone health management during ADT.

Hiding and seeking: Children's lived experiences during COVID-19.

A qualitative study explored the perspectives and lived experiences of school-age children during COVID-19 using a child rights lens. Twenty children between the ages of 7 and 12 participated in open-ended, virtual interviews. Our hermeneutic analysis found children's right to play and education were severely compromised leaving children to navigate between two worlds: the adult world of public health restrictions and that of their childhood. Despite challenges and lost childhood opportunities, children emerged as competent social agents and responsible citizens. Planning for future pandemics should include policies and practices that balance public health needs with the protection of children's rights.

The Detection, Evaluation, and Management of Dyslipidemia in Children and Adolescents: A Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Clinical Practice Update.

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth.

The exercise in pulmonary arterial hypertension (ExPAH) study: A randomized controlled pilot of exercise training and multidisciplinary rehabilitation in pulmonary arterial hypertension.

Pulmonary hypertension (PH) is characterized by progressive dyspnea, fatigue, and reduced exercise capacity. Despite medical treatment, outcomes remain poor. While exercise training is well established in patients with heart failure, it is less established in patients with PH. This single-blind, randomized controlled pilot study examined the feasibility and effect of 12-week outpatient exercise (multidisciplinary rehabilitation or home walking program) on hemodynamics using cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH), a subset of PH. Sixteen participants were randomized to either multidisciplinary outpatient rehabilitation or a home walking program for 12 weeks. Primary outcome measures were changes in right ventricular ejection fraction and stroke volume index on cMRI. Secondary outcome measures included hemodynamics on RHC, quality of life (QOL), muscle strength (handgrip and vital capacity) and 6-min walk test. This preliminary, pilot study suggests that outpatient exercise interventions may be associated with improved hemodynamic function (mean pulmonary artery wedge pressure, stroke volume, and stroke volume index), QOL (PH symptoms, depression, and anxiety), and muscular strength (vital capacity and handgrip strength) for people with PAH, but was not adequately powered to make any formal conclusions. However, our outpatient programs were feasible, safe, and acceptable to participants. Future studies are required to further explore the potential hemodynamic benefits of exercise in PAH.

An 11-year longitudinal analysis of refracture rates and public hospital service utilisation in Australia's most populous state.

This detailed 11-year longitudinal analysis calculated the public health cost of managing refractures in people aged ≥ 50 years in Australia's most populous state. It provides current and projected statewide health system costs associated with managing osteoporosis and provides a foundation to evaluate a novel statewide model of fracture prevention. PURPOSE: The purpose of this longitudinal analysis was to calculate current and projected refracture rates and associated public hospital utilisation and costs in New South Wales (NSW), Australia. These results will be used to inform scaled implementation and evaluation of a statewide Osteoporotic Refracture Prevention (ORP) model of care. METHODS: Linked administrative data (inpatient admissions, outpatient attendances, Emergency Department presentations, deaths, cost) were used to calculate annual refracture rates and refracture-related service utilisation between 2007 and 2018 and healthcare costs between 2008 and 2019. Projections for the next decade were made using 'business-as-usual' modelling. RESULTS: Between 2007 and 2018, 388,743 people aged ≥ 50 years experienced an index fracture and 81,601 had a refracture. Refracture was more common in older people (rising from a cumulative refracture rate at 5 years of 14% in those aged 50-64 years, to 44% in those aged > 90 years), women with a major index fracture (5-year cumulative refracture rate of 26% in females, compared to 19% for males) or minimal trauma index fracture and those with an osteoporosis diagnosis (5-year cumulative refracture rate of 36% and 22%, respectively in those with and without an osteoporosis diagnosis). Refractures increased from 8774 in 2008 to 14,323 in 2018. The annual cost of refracture to NSW Health increased from AU$130 million in 2009 to AU$194 million in 2019. It is projected that, over the next decade, if nothing changes, 292,537 refracture-related hospital admissions and Emergency Department presentations and 570,000 outpatient attendances will occur, at an estimated total cost to NSW Health of AU$2.4 billion. CONCLUSION: This analysis provides a detailed picture of refractures and associated projected service utilisation and costs over the next decade in Australia's most populous state. Understanding the burden of refracture provides a foundation for evaluation of a novel statewide ORP model of care to prevent refractures in people aged ≥ 50 years.