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Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs. Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors. Design: A prospective cohort study. Methods: CanProCo is a national, prospective, observational cohort study that has recruited 944 individuals from 5 large academic MS centers in Canada. Participants include people with radiologically isolated syndrome (RIS), early relapsing-remitting and primary progressive MS (RRMS, PPMS), and healthy controls (HCs). Annually, participants complete self-reported questionnaires, undergo clinical evaluation and, if clinically indicated, magnetic resonance images (MRIs) of the brain and cervical spinal cord; in a subset of participants (n = 399), blood, and research MRIs of the brain and cervical spinal cord are collected. Linkages to health administrative databases are available at three sites. Results: Overall, 944 participants were recruited (53 HCs, 63 RIS, 751 RRMS, 77 PPMS). RIS and MS participants had a mean age of 39.0 years and 70.5% female. The mean time since diagnosis was 2.7 years. There were differences observed in the Expanded Disability Status Scale score and components of the MS performance test (walking speed test, manual dexterity test, processing speed test, and low-contrast visual acuity) between RIS and MS subtypes. Questionnaires revealed more symptoms of depression and anxiety and impaired physical and mental quality of life in people with RIS/MS versus HCs and differences across RIS/MS subtypes. Conclusion: Physical and mental neurological disability is prevalent even in the earliest stages of MS. Transdisciplinary approaches such as those used in CanProCo are needed to better characterize clinical progression in MS. Additional CanProCo results, including MRI, biological, and pharmaco-economic data will be forthcoming. Going forward, CanProCo's data sharing and collaborative vision will facilitate numerous global collaborations, which will inform the development and implementation of effective interventions for people with MS around the world. [ABSTRACT FROM AUTHOR]

Background: Different racial and ethnic groups have demonstrated heterogeneity in the clinical course of multiple sclerosis(MS)., Objective: We aimed to evaluate disease characteristics in African, Caribbean, and Black people with MS(ACB-MS) followed at a single centre in Toronto, Canada., Methods: ACB-MS were compared with age- and sex-matched people with MS (pwMS) of European descent(EUR-MS) identified through the clinic registry., Results: 344 PwMS were included(n = 172 ACB-MS, n = 172 EUR-MS; mean age 43 years, 68 % female). Baseline mean Expanded disability status scale (EDSS) scores (ACB-MS 2.3 ± 2.3 vs. EUR-MS 2.2 ± 2.0, p = 0.38) and subsequent clinical and radiological measures of disease activity were similar between groups, including annualized relapse rate (ARR)(ACB-MS 0.47 ± 0.47 vs. EUR-MS 0.41 ± 0.34, p = 0.2) and most recent EDSS (ACB-MS 2.7 ± 2.2 vs. EUR-MS 2.3 ± 2.1, p = 0.10). However, the proportion of MRI brain demonstrating new disease activity was higher(37% vs. 26 %, p < 0.05) and disability progression greater in ACB-MS vs. EUR-MS(43% vs. 33 %,p < 0.05) but measures of disease severity including MS Severity Score(3.17 vs. 2.58, p = 0.3) and Progression Index(PI) (0.27 vs. 0.30, p = 0.5) were comparable., Conclusion: Disability progression was seen more commonly in ACB-MS, though clinical disease activity and severity were generally comparable between ACB-MS and EUR-MS patients in Toronto, Canada. These findings partially differ from prior studies demonstrating more overtly aggressive MS disease courses in Black and African American PwMS, necessitating further studies to understand how structural determinants of health drive these disparities., Competing Interests: Declaration of competing interest A.M. Kuczynski reports no disclosures relevant to the manuscript A. Jones reports no disclosures relevant to the manuscript D. Kimbrough is a consultant for CVS Health A. Muccilli received personal compensation for consulting or speaking from Biogen, EMD-Serono, and Novartis C. Roy-Hewitson has received personal compensation for consulting from Biogen Idec, EMD Serono, Novartis, Sanofi Genzyme, and Horizon Idec D.T. Okuda received personal compensation for consulting and advisory services from Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, Janssen Pharmaceuticals, Novartis, Osmotica Pharmaceuticals, RVL Pharmaceuticals, Inc., TG Therapeutics, Viela Bio, Inc., and research support from Biogen, EMD Serono/Merck, and Novartis. D.T. Okuda has issued national and international patents along with pending patents related to this current work and other developed technologies. D.T. Okuda received royalties for intellectual property licensed by The Board of Regents of The University of Texas System S. Baral reports no relevant disclosures. J. Oh is supported by the Waugh Family Chair in MS Research at the University of Toronto, and the Barford and Love MS Fund of St. Michael's Hospital Foundation. J.Oh has received research funding from Biogen-Idec, EMD-Serono, Roche, and personal compensation for consulting or speaking from Biogen-Idec, Eli-Lilly, EMDSerono, Novartis, Roche, and Sanofi-Genzyme., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson's disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD. • STRAT-PARK: an initiative to stratify Parkinson's disease into biological subtypes. • Bottom-up, multidisciplinary biomarker-based and data-driven approach. • Unique focus on examining mitochondrial function. [ABSTRACT FROM AUTHOR]

Background: Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS). Although there are a handful of disease-modifying treatments approved for use in progressive phenotypes of MS, there are no treatments that substantially modify the course of clinical progression in MS. Characterizing the determinants of clinical progression can inform the development of novel therapeutic agents and treatment approaches that target progression in MS, which is one of the greatest unmet needs in clinical practice. Canada, having one of the world's highest rates of MS and a publicly-funded health care system, represents an optimal country to achieve in-depth analysis of progression. Accordingly, the overarching aim of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) is to evaluate a wide spectrum of factors associated with the clinical onset and rate of disease progression in MS, and to describe how these factors relate to one another to influence progression.Methods: CanProCo is a prospective, observational cohort study with investigators specializing in epidemiology, neuroimaging, neuroimmunology, health services research and health economics. CanProCo's study design was approved by an international review panel, comprised of content experts and key stakeholders. One thousand individuals with radiologically-isolated syndrome, relapsing-remitting MS, and primary-progressive MS within 10-15 years of disease onset will be recruited from 5 academic MS centres in Canada. Participants will undergo detailed clinical evaluation annually over 5 years (including advanced, app-based clinical data collection). In a subset of participants within 5-10 years of disease onset (n = 500), blood, cerebrospinal fluid, and research MRIs will be collected allowing an integrated, in-depth evaluation of factors contributing to progression in MS from multiple perspectives. Factors of interest range from biological measures (e.g. single-cell RNA-sequencing), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician-assessed, health-system based), and micro and macro-environmental factors.Discussion: Halting the progression of MS remains a fundamental need to improve the lives of people living with MS. Achieving this requires leveraging transdisciplinary approaches to better characterize why clinical progression occurs. CanProCo is a pioneering multi-dimensional cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions. [ABSTRACT FROM AUTHOR]

Recommendation 1: Multidisciplinary Approach To optimize treatment outcomes, the management of patients with recurrent glioblastoma should be individualized and should involve a multidisciplinary team approach, including neurosurgery, neuropathology, radiation oncology, neuro-oncology, and allied health professions. Recommendation 2: Imaging The standard imaging modality for assessment of recurrent glioblastoma is Gd-enhanced magnetic resonance imaging (MRI). Tumour recurrence should be assessed according to the criteria set out by the Response Assessment in Neuro-Oncology Working Group. The optimal timing and frequency of MRI after chemoradiation and adjunctive therapy have not been established. Recommendation 3: Pseudo-progression Progression observed by MRI after chemoradiation can be pseudo-progression. Accordingly, treated patients should not be classified as having progressive disease by Gd-enhancing MRI within the first 12 weeks after the end of radiotherapy unless new enhancement is observed outside the radiotherapy field or viable tumour is confirmed by pathology at the time of a required re-operation. Adjuvant temozolomide should be continued and follow-up imaging obtained. Recommendation 4: Repeat Surgery Surgery can play a role in providing symptom relief and confirming tumour recurrence, pseudo-progression, or radiation necrosis. However, before surgical intervention, it is essential to clearly define treatment goals and the expected impact on prognosis and the patient's quality of life. In the absence of level 1 evidence, the decision to re-operate should be made according to individual circumstances, in consultation with the multidisciplinary team and the patient. Recommendation 5: Re-irradiation Re-irradiation is seldom recommended, but can be considered in carefully selected cases of recurrent glioblastoma. Recommendation 6: Systemic Therapy Clinical trials, when available, should be offered to all eligible patients. In the absence of a trial, systemic therapy, including temozolomide rechallenge or antiangiogenic therapy, may be considered. Combination therapy is still experimental; optimal drug combinations and sequencing have not been established. [ABSTRACT FROM AUTHOR]

Purpose: Partial nephrectomy (PN) for early stage renal cancer preserves renal function better than radical nephrectomy (RN) and is generally considered oncologically similar. The Intergroup European Organisation for Research and Treatment of Cancer trial comparing outcomes after PN vs. RN, however, showed reduced overall survival in the PN group. Our aim was to evaluate recurrence, death, and renal function after PN vs. RN for T1 tumors in a Canadian population.Materials and Methods: From 2000 to 2015, 2,358 patients with a first occurrence of a clinical T1 renal cancer who underwent PN or RN were identified from the Canadian Kidney Cancer Information System. Clinical, surgical, and pathologic parameters were analyzed. Time to progression was compared after PN vs. RN using a Cox proportional hazards model, adjusted for pertinent variables.Results: Inclusion criteria were met in 1,615 PN and 743 RN. Preoperative characteristics appeared similar in both groups. Time to progression was not different after PN vs. RN, adjusted for potential confounders (hazard ratio = 1.17 [95% CI: 0.8-1.72, P = 0.42]). Postoperative estimated glomerular filtration rate at 1 and 3 years was significantly greater for PN vs. RN in a linear regression model, accounting for preoperative estimated glomerular filtration rate.Conclusions: These results suggest that progression-free survival after PN and RN in patients with T1 renal cancer was similar, but that there was better preservation of renal function after PN. This suggests that both PN and RN have similar oncological efficiency, and that selection of surgical approach should be based on other factors such as technical feasibility, potential complications, and preservation of renal function. [ABSTRACT FROM AUTHOR]

The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of hydrocephalus, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Evidence for risk factors was limited for both onset and progression. Two meta-analyses that examined a risk factor for onset met the inclusion criteria. One found a significant protective effect of prenatal vitamins among case control studies, but not cohort/randomized controlled trials (RCTs). The second found maternal obesity to be a significant risk factor for congenital hydrocephalus. Significant risk factors among 25 observational studies included: biological (multiple births, maternal parity, common cold with fever, maternal thyroid disease, family history, preterm birth, hypertension, ischemic heart disease, ischemic ECG changes, higher cerebrospinal fluid protein concentration following vestibular schwannoma); lifestyle (maternal obesity, high-density lipoprotein (HDL) cholesterol, maternal diabetes, maternal age), healthcare-related (caesarean section, interhospital transfer, drainage duration following subarachnoid hemorrhage, proximity to midline for craniectomy following traumatic brain injury); pharmaceutical (prenatal exposure to: tribenoside, metronidazole, anesthesia, opioids); and environmental (altitude, paternal occupation). Three studies reported on genetic risk factors: no significant associations were found. There are major gaps in the literature with respect to risk factors for the natural progression of hydrocephalus. Only two observational studies were included and three factors reported. Many risk factors for the onset of hydrocephalus have been studied; for most, evidence remains limited or inconclusive. More work is needed to confirm any causal associations and better inform policy., (Copyright © 2016. Published by Elsevier B.V.)

Background & Aims: Crohn's disease (CD) diagnosed in pediatric patients has been reported to have a more aggressive phenotype and course, with a greater prevalence of upper gastrointestinal involvement, than in adults. However, studies have not accounted for differences in diagnostic tests. We aimed to discern whether, in fact, CD diagnosed in childhood has a different outcome than CD diagnosed in adults., Methods: We performed comprehensive medical chart reviews of 571 patients with CD (451 with complete data) who were followed in a single referral inflammatory bowel disease clinic in Winnipeg, Canada, from 1993-2012. For specific time intervals, we determined types and numbers of imaging studies performed and parameters of disease phenotype, including age at diagnosis according to the Montreal classification (A1 diagnosed <17 years of age, A2 diagnosed 17-40 years, and A3 diagnosed >40 years)., Results: Within 1 year of diagnosis, a higher proportion of A1 patients had upper gastrointestinal involvement and ileocolonic (L3) disease than A2 or A3 patients. These differences could be partly accounted for by the diagnostic tests performed during this time period. Although A1 patients underwent more extensive imaging studies, they had a lower prevalence of complicated disease, particularly compared with A3 patients. After a median follow-up period of 11.1 years, complicated disease behavior (B2 [structuring] or B3 [penetrating]) was similar among the 3 groups. Nonetheless, at the end of the study period, rates of inflammatory bowel disease-related abdominal surgery were significantly lower for A1 than A2 patients (odds ratio, 0.63; 95% confidence interval, 0.41-0.98) but not for A3 patients (odds ratio, 0.71; 95% confidence interval, 0.40-1.27)., Conclusions: On the basis of a database analysis of different age groups of patients with CD, studies of disease phenotypes among different cohorts should account for different patterns of diagnostic imaging evaluation. Our data show that although children are at increased risk of panenteric disease, they are not more likely to have more complicated disease or undergo surgery than adults., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Among adults, lower socioeconomic status (SES) is a risk factor for chronic kidney disease (CKD), progression to end-stage renal disease, and poor health outcomes; but its impact on young people with CKD is not established., Study Design: Prospective cohort study., Settings & Participants: 572 children and adolescents aged 1-16 years with mild to moderate CKD residing in the United States and Canada who were enrolled in the Chronic Kidney Disease in Children (CKiD) Study., Predictor: Self-reported annual household income category as a proxy measure for SES: ≥$75,000 (high income), $30,000 to <$75,000 (middle income) and <$30,000 (low income)., Outcomes & Measurements: Clinical characteristics and CKD severity at baseline (glomerular filtration rate [GFR] and comorbid conditions related to disease severity and management) and longitudinally (GFR decline and changes in blood pressure z scores and height z scores per year)., Results: At baseline, low and middle household incomes, compared to high income, were associated with minority race (39% and 20% vs. 7%), lower maternal education (28% and 5% vs. 1%), abnormal birth history (34% and 32% vs. 21%), and having at least one clinical comorbid condition (66% and 64% vs. 55%). Baseline median GFRs were similar across income categories (43-45 mL/min/1.73 m2). After adjusting for baseline differences, average GFR declines per year for the low-, middle-, and high-income categories were -2.3%, -2.7%, and -1.9%, respectively, and were not statistically significantly different among groups. Blood pressure control tended to improve in all groups (z score, -0.10 to -0.04) but higher income was associated with a faster improvement. Each group showed similar deficits in height at baseline. Height deficits diminished over time for participants from high-income families, but not among those from low-income families (z scores for height per year, 0.05 and -0.004, respectively; P = 0.03 for comparison of high and low income)., Limitations: Income is an imperfect measure for SES; CKiD participants are not representative of children and adolescents with CKD who are uninsured or not receiving care; statistical power to detect associations by income level is limited., Conclusions: GFR decline was similar across income groups but better improvement in BP was observed among those with high income. Children and adolescents with CKD from lower income households are at higher risk of impaired growth., (Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.)