Childhood nephrotic syndrome and the clinical profile of thromboembolism: a systematic review and meta-analysis.

Nephrotic syndrome (NS) is a common kidney disease of childhood, affecting 2-7 children per 100,000. A potentially life-threatening complication affecting children with NS is thromboembolism (TE). However, there remains a paucity of information regarding the burden of TE and its associated risk factors in this population. A systematic review was performed on observational studies examining TE events in children with NS, published in Medline, Embase, CINAHL, and CENTRAL, until May 2021. Meta-analyses were separately conducted on the prevalence of TE within articles exclusively studying children with congenital NS and among articles including all forms of NS. Out of 13,626 articles, 22 were included (14,290 children). The pooled prevalence of symptomatic TE among articles including patients with all forms of NS was 3.60% (95% CI 1.95-5.63), which increased to 8.70% (95% CI 5.11-12.96) in articles with exclusively congenital NS patients. Children with steroid-resistant NS were at a higher risk of TE compared to steroid-sensitive children (OR 4.40, 95% CI 1.34-15.59, p = 0.013). Focal segmental glomerulosclerosis was the most common histology present in patients with TE (51.2%). Children diagnosed with NS have a significant risk of TE, particularly in patients with congenital NS and steroid resistance. IMPACT: The prevalence of symptomatic thromboembolic (TE) events in children with nephrotic syndrome (NS) was 3.60% (95% CI 1.95-5.63), which increased more than two-fold in children with congenital NS to 8.70% (95% CI 5.11-12.96). Potential risk factors for TE events in this population include congenital forms of NS and steroid resistance. This review provides a better estimate of the prevalence of TE in children with NS, while identifying potentially higher-risk populations who may benefit from TE screening and thromboprophylaxis.

Impact of SARS-CoV-2 pandemic on the mental and physical health of children enrolled in a paediatric weight management clinic.

Background: Obesity is a global public health concern. Given the widespread disruption caused by the SARS-CoV-2 pandemic, it is important to evaluate its impact on children with chronic health conditions. This study examines the health of paediatric patients with obesity enrolled in a tertiary hospital weight management program, before and 1 year into the COVID-19 pandemic. Methods: This is a retrospective chart review of patients aged 2 to 17 years enrolled in a paediatric weight management clinic. Mental health outcomes (i.e., new referrals to psychologist, social work, eating disorder program, incidence of dysregulated eating, suicidal ideation, and/or self-harm) and physical health (anthropometric measures) were compared before and 1 year into the pandemic. Results: Among the 334 children seen in either period, there was an increase in referrals to psychologist (12.4% versus 26.5%; P=0.002) and the composite mental health outcome (17.2% versus 30.2%; P=0.005) during the pandemic compared with pre-pandemic. In a subset of children (n=30) with anthropometric measures in both periods, there was a lower rate of decline in BMIz score (-1.5 [2.00] versus -0.3 [0.73]/year; P=0.002) and an increase in adiposity (-0.8 [4.64] versus 2.7 [5.54]%/year; P=0.043) during the pandemic. Discussion: The pandemic has impacted the mental and physical health of children with obesity engaged in a weight management clinic. While our study provides evidence of a negative impact on mental health outcomes and less improvement in anthropometric measures, future research when patients return to in-person care will enable further examination of our findings with additional objective measures.

Chronic stress and endothelial dysfunction: mechanisms, experimental challenges, and the way ahead.

Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiological complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. Therefore, this review article explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion, 2) discussing mechanistic links between chronic stress and endothelial dysfunction, and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. The data reveal that preclinical models play an important role in our efforts to gain an increased understanding of mechanisms underlying stress-mediated endothelial dysfunction. It is our understanding that this provides a good foundation going forward, and we propose that further efforts should be made to 1) more clearly define the concept of stress and 2) standardize protocols of animal models with specific guidelines to better indicate the mental complications that are simulated.

Type 1 Diabetes in Ontario Schools: Policy and Practice.

OBJECTIVES: Type 1 diabetes (T1D) is a challenging chronic condition. Young children with T1D require daily support to manage their condition while at school. In 2018, Ontario established a provincial policy to ensure safe and equitable school participation for children with diabetes. Despite this, children and parents describe very different school experiences. In this qualitative study we describe the interpretation and implementation of school board policy related to the care of children with T1D from the perspective of school educators (principals/teachers). METHODS: Policy documents were reviewed employing a qualitative descriptive research design using directed qualitative content analysis. Semistructured interviews were conducted with 13 teachers and principals from 10 publicly funded elementary schools across the Hamilton and Toronto District School Boards in 2021. RESULTS: There are major differences in how policies regarding T1D are being implemented in schools. This includes how school staff are educated about T1D, and how they interpret and act on blood glucose information. Although educators often play an active role in supporting children, many face barriers, including competing priorities, fear, lack of information, and lack of support. Facilitators include effective communication/collaboration, actionable information, time, and a diabetes "champion." In some instances, access to nursing support could help to resolve barriers or create care gaps. CONCLUSIONS: School board policy provides high-level guidance on how to support children with T1D in school, but gaps remain. We provide specific recommendations regarding policy, staff education/training, roles and responsibilities, and future research.

Factors Associated With the Development of Dyslipidemia Among Pediatric Patients With Diabetes: A Single-centre-based Study.

OBJECTIVES: The prevalence of pediatric diabetes is increasing. Dyslipidemia is an important modifiable cardiovascular disease risk factor often present in children with diabetes. In this study, we evaluated the adherence to Diabetes Canada 2018 lipid screening guidelines in a pediatric diabetes program to determine the prevalence of dyslipidemia in youth with diabetes and to identify risk factors related to dyslipidemia. METHODS: This retrospective chart review included patients at McMaster Children's Hospital with diabetes (types 1 and 2), who were at least 12 years of age as of January 1, 2019. Extracted data included age, sex, family history of diabetes or dyslipidemia, date of diagnosis, body mass index, glycemia monitoring system used, lipid profile, glycated hemoglobin (A1C), and thyroid-stimulating hormone values at the time the lipid profile was measured. Statistical methods included descriptive statistics and logistic regression modelling. RESULTS: Of the 305 patients included, 61% had a lipid profile measured according to guidelines, 29% had lipid screening completed outside of the recommended window, and 10% had no lipid profile on record. Among screened patients, 45% had dyslipidemia, most commonly hypertriglyceridemia (35%). Dyslipidemia was highest amongst those with type 2 diabetes, obesity, older age, short duration of diabetes, higher A1C, and those who used capillary blood glucose for monitoring (p<0.05). CONCLUSIONS: A high proportion of patients were screened for dyslipidemia, but many outside the recommended window. Dyslipidemia is highly prevalent in this patient population and was associated with the presence of obesity, but 44% of patients without obesity also had dyslipidemia.

The impact of chronic stress on intracellular redox balance: A systems level analysis.

Chronic psychosocial stress is implicated in the onset and progression of noncommunicable diseases, and mechanisms underlying this relationship include alterations to the intracellular redox state. However, such changes are often investigated in isolation, with few studies adopting a system level approach. Here, male Wistar rats were exposed to 9.5 weeks of chronic unpredictable mild stress and redox status assays were subsequently performed on cardiac, hepatic, and brain tissues versus matched controls. The stressed rats displayed an anxious phenotype, with lowered plasma corticosterone levels (p = 0.04 vs. Controls) and higher plasma epinephrine concentrations (p = 0.03 vs. Controls). Our findings showed organ-specific redox profiles, with stressed rats displaying increased myocardial lipid peroxidation (p = 0.04 vs. Controls) in the presence of elevated nonenzymatic antioxidant capacity (p = 0.04 vs. Controls). Conversely, hepatic tissues of stressed rats exhibited lowered nonenzymatic antioxidant capacity (p < 0.001 vs. Controls) together with increased superoxide dismutase (SOD) activity (p = 0.05 vs. Controls). The brain displayed region-specific antioxidant perturbations, with increased SOD activity (p = 0.01 vs. Controls) in the prefrontal cortex of the stressed rats. These findings reveal distinct stress-related organ-specific vulnerability to redox perturbations and may provide novel insights into putative therapeutic targets.

Insulin Edema Associated With Newly Diagnosed Type 1 Diabetes and High Glycated Hemoglobin: A Case and Review of the Pediatric Literature.

Insulin edema is a rare and poorly understood complication of insulin therapy. It has been associated with the initiation of insulin in patients with newly diagnosed diabetes or the intensification of insulin therapy in those with poor glycemic control. This condition is rarely reported in pediatric patients. We describe a case of insulin edema in a 14-year-old boy with potential risk factors of highly elevated glycated hemoglobin at diagnosis and history of unilateral renal atrophy. We also present a discussion of the pathophysiology of this condition and a review of the pediatric literature.

A prospective multiple case study of the impact of emerging scientific evidence on established colorectal cancer screening programs: a study protocol.

BACKGROUND: Health-policy decision making is a complex and dynamic process, for which strong evidentiary support is required. This includes scientifically produced research, as well as information that relates to the context in which the decision takes place. Unlike scientific evidence, this "contextual evidence" is highly variable and often includes information that is not scientifically produced, drawn from sources such as political judgement, program management experience and knowledge, or public values. As the policy decision-making process is variable and difficult to evaluate, it is often unclear how this heterogeneous evidence is identified and incorporated into "evidence-based policy" decisions. Population-based colorectal cancer screening poses an ideal context in which to examine these issues. In Canada, colorectal cancer screening programs have been established in several provinces over the past five years, based on the fecal occult blood test (FOBT) or the fecal immunochemical test. However, as these programs develop, new scientific evidence for screening continues to emerge. Recently published randomized controlled trials suggest that the use of flexible sigmoidoscopy for population-based screening may pose a greater reduction in mortality than the FOBT. This raises the important question of how policy makers will address this evidence, given that screening programs are being established or are already in place. This study will examine these issues prospectively and will focus on how policy makers monitor emerging scientific evidence and how both scientific and contextual evidence are identified and applied for decisions about health system improvement. METHODS: This study will employ a prospective multiple case study design, involving participants from Ontario, Alberta, Manitoba, Nova Scotia, and Quebec. In each province, data will be collected via document analysis and key informant interviews. Documents will include policy briefs, reports, meeting minutes, media releases, and correspondence. Interviews will be conducted in person with senior administrative leaders, government officials, screening experts, and high-level cancer system stakeholders. DISCUSSION: The proposed study comprises the third and final phase of an Emerging Team grant to address the challenges of health-policy decision making and colorectal cancer screening decisions in Canada. This study will contribute a unique prospective look at how policy makers address new, emerging scientific evidence in several different policy environments and at different stages of program planning and implementation. Findings will provide important insight into the various approaches that are or should be used to monitor emerging evidence, the relative importance of scientific versus contextual evidence for decision making, and the tools and processes that may be important to support challenging health-policy decisions.