Incidence of childhood cancer in Canada during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years. METHODS: We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [ß], level 4.98, 95% CI -15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2]). INTERPRETATION: We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada.

Chronic and acute melatonin effects in gerbil global forebrain ischemia: long-term neural and behavioral outcome.

Melatonin attenuates the short-term consequences of brain ischemia in several animal models. However, there is scant information regarding its efficacy for improving the long-term outcome. To further address that issue, we subjected gerbils to 5-min bilateral carotid occlusion. Some gerbils received acute peri-surgical administration of melatonin while others received continuous melatonin in their water. The gerbils' brains were histologically assessed at 20 wk postsurgery. Chronic but not acute melatonin attenuated ischemia-induced hyperactivity at 3 days postsurgery. Twenty weeks postsurgery, the ischemic gerbils showed varying degrees of bilateral loss of hippocampal CA1 pyramidal cells and elevation of glial fibrillary acidic protein immunoreactivity there. Both the cell loss and the immunoreactivity were markedly asymmetrical for some gerbils. Neither acute nor chronic melatonin altered this pattern of CA1 cell loss and glial immunoreactivity increase. Ischemia increased the number of CA1 cells that were immunoreactive for doublecortin (DCX), a marker for newborn neurons. This increase in CA1 DCX expression was not affected by either melatonin treatment. However, both acute and chronic melatonin reduced the number of DCX immunoreactive neurons in the dentate gyrus. Thus, neither acute nor chronic melatonin altered the long-term neural outcome of forebrain ischemia, although chronic administration seemed to attenuate the short-term behavioral effect. It is suggested that persistently high brain levels of melatonin may be essential for long-term neuroprotection against ischemia. The possibility that melatonin may modulate hippocampal neurogenesis merits further exploration both in normal animals and in models of brain insult.

Use of diagnostic imaging in the emergency department for cervical spine injuries in Kingston, Ontario.

OBJECTIVES: This study assessed the use and clinical yield of diagnostic imaging (radiography, computed tomography, and medical resonance imaging) ordered to assist in the diagnosis of acute neck injuries presenting to emergency departments (EDs) in Kingston, Ontario, from 2002-2003 to 2009-2010. METHODS: Acute neck injury cases were identified using records from the Kingston sites of the Canadian National Ambulatory Care Reporting System. Use of radiography was analyzed over time and related to proportions of cases diagnosed with clinically significant cervical spine injuries. RESULTS: A total of 4,712 neck injury cases were identified. Proportions of cases referred for diagnostic imaging to the neck varied significantly over time, from 30.4% in 2002-2003 to 37.6% in 2009-2010 (ptrend  =  0.02). The percentage of total cases that were positive for clinically significant cervical spine injury ("clinical yield") also varied from a low of 5.8% in 2005-2006 to 9.2% in 2008-2009 (ptrend  =  0.04), although the clinical yield of neck-imaged cases did not increase across the study years (ptrend  =  0.23). Increased clinical yield was not observed in association with higher neck imaging rates whether that yield was expressed as a percentage of total cases positive for clinically significant injury (p  =  0.29) or as a percentage of neck-imaged cases that were positive (p  =  0.77). CONCLUSIONS: We observed increases in the use of diagnostic images over time, reflecting a need to reinforce an existing clinical decision rule for cervical spine radiography. Temporal increases in the clinical yield for total cases may suggest a changing case mix or more judicious use of advanced types of diagnostic imaging.

Injuries in the North--analysis of 20 years of surveillance data collected by the Canadian Hospitals Injury Reporting and Prevention Program.

BACKGROUND: Injury is a major public health concern, particularly for Canadians living in Arctic regions where the harsh physical and social conditions pose additional challenges. Surveillance data collected over the past 2 decades through the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) provide insights into the burden of injuries in certain parts of Canada. OBJECTIVES: This study aims to summarize and compare patterns of injuries in the Northwest Territories (NWT) and Nunavut to other southern communities across Canada. METHODS: Analysis was based on CHIRPP data covering the period 1991-2010. Proportionate injury ratio (PIR) and its 95% confidence interval were used to summarize and compare the injury experience of Canadians living in the Arctic regions to other CHIRPP sites across Canada. RESULTS: Between 1991 and 2010, there were 65,116 reported injuries. Approximately 83% of the cases were unintentional in nature; however, significantly higher proportions were observed for assaults and maltreatment (PIR = 2.80, 95% CI: 2.72-2.88) among Canadians living in northern communities. Significantly higher proportions were also observed for crushing/amputations (PIR = 2.28, 95% CI: 2.14-2.44), poison/toxic effects (PIR = 1.21, 95% CI: 1.15-1.28), drowning/asphyxiations (PIR = 1.52, 95% CI: 1.33-1.74) and frostbites (PIR = 7.39, 95% CI: 6.60-8.28). The use of all-terrain vehicles or snowmobiles also resulted in significantly higher proportions of injuries (PIR = 1.93, 95% CI: 1.79-2.09). CONCLUSIONS: This study contributes to the limited literature describing injuries in northern communities where the harsh physical and social climates pose additional challenges. Excesses in the proportions identified in this study could be useful in identifying strategies needed to minimize injury risks in northern communities within Canada.

The effects of neonatal forebrain cholinergic lesion on adult hippocampal neurogenesis.

Previous work in our laboratory indicated that cholinergic denervation by intraventricular infusion of 192-IgG-saporin on postnatal day 7 (N192S) reduced the number of cells in the dentate gyrus expressing doublecortin, a marker for immature neuroblasts. In addition, there was a suggestion that N192S impaired the neurogenic response to environmental enrichment (EE). The purpose of the present study was to further characterize the impact of N192S on the proliferation, differentiation and survival of newborn cells in the dentate gyrus. After 42 days in EE or standard housing, all rats received injections of 5-bromo-2-deoxyuridine (BrdU) to label dividing cells. They were sacrificed either one day (to assess cell proliferation) or 28 days later (to assess survival and differentiation of BrdU-labelled cells). EE failed to increase neurogenesis, thereby preventing determination of the effects of N192S on EE-induced neurogenesis. However, N192S by itself reduced the number of BrdU(+) cells 1 day after BrdU exposure, but did not alter the number of cells expressing the cell cycle marker Ki-67. The number of BrdU(+) cells 28 days after BrdU exposure was not affected by N192S. Confocal analysis of BrdU(+) cells double-immunofluorescently stained to detect NeuN or S100B indicated that N192S did not alter the proportion of new cells that adopted a neuronal or glial identity. The most plausible explanation for these results is that N192S accelerates the death of newborn cells, but does not change their overall survival rate or phenotypic differentiation.

Developmental forebrain cholinergic lesion and environmental enrichment: behaviour, CA1 cytoarchitecture and neurogenesis.

Intraventricular injections of 192 IgG saporin in 7-day-old rat severely reduced hippocampal cholinergic innervation as reflected by both decreased acetylcholinesterase staining and immunoreactivity for the p75 neurotrophin receptor. It was determined if this altered the effects of environmental enrichment on spatial learning, hippocampal CA1 cell cytoarchitecture as reflected by the Golgi stain, and neurogenesis in the dentate gyrus as indicated by doublecortin immunoreactivity. At weaning, lesioned and control rats were either group housed in large, environmentally enriched cages or housed two per standard cage for 42 days. When subsequently assessed with a working-memory spatial navigation task, both lesioned and control rats showed enhanced learning as a result of enrichment. Quantitative analysis of Golgi stained sections indicated that enrichment did not affect CA1 dendritic branching, total dendritic length or dendritic spine density. However, the lesion reduced the number of apical branches, spine density on intermediate to distal apical dendrites, and the length of basal branches. It also reduced the number of doublecortin immunoreactive neurons in the dentate gyrus and appeared to prevent their increase due to environmental enrichment. It is concluded that developmental cholinergic lesioning does not attenuate neurobehavioral plasticity, at least as reflected by the behavioral consequences of enrichment. It does, however, attenuate neurogenesis in the dentate gyrus, like adult-inflicted cholinergic lesions. As previously found for cortical neurons, it also reduces CA1 pyramidal cell dendritic complexity and spine density in adulthood. The results have implications for the loss of synapses that occurs in both developmental and aging-related brain disorders involving cholinergic dysfunction.