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Background The impact of social determinants of health (SDoH) on survival outcomes is unclear in the universal Canadian health care system. We investigated the impact of distance to treatment center and income quintile on survival outcomes in pediatric extracranial solid tumors in Canada. Methods Children < 15 years old diagnosed with 7 common solid extracranial tumors from 2001 to 2020 were included using the Cancer in Young People in Canada (CYP‐C) data tool. We used logistic regression to examine the association of income quintile and distance on cancer outcomes. We used Cox proportional hazard models to examine associations with time‐to‐event outcomes (OS) and Fine–Gray competing risk regression (recurrence) adjusting for metastasis, age, region, and tumor location. Results The cohort included 3969 patients. Median age was 3.6 years (IQR: 1.3–8.9); 48.7% were female. Tumor diagnosis: 34% neuroblastoma, 21% Wilms tumor, 13% rhabdomyosarcoma, 11% osteosarcoma, 8% Ewing sarcoma, 7% hepatoblastoma, and 6% germ cell tumors. On multivariable analysis, income quintile and distance did not significantly or consistently impact survival across all tumors. In rhabdomyosarcoma, the second lowest income quintile had inferior survival compared to the highest income quintile (p = 0.0264, HR 1.91, 95% CI 1.08, 3.37). In neuroblastoma, the lowest income quintile had inferior survival compared to the highest (p = 0.0052, HR 1.82, 95% CI 1.20, 2.77). Patients diagnosed with hepatoblastoma living > 500 km from a pediatric treatment facility had inferior OS compared to those within 50 km (p = 0.0065, HR 3.29, 95% CI 1.40, 7.79). Conclusion Overall, distance and income did not show a consistent significant impact on survival outcomes for children with extracranial solid tumors. In this national analysis of Canadian children with solid extracranial tumors, our results do not demonstrate a consistent relationship between socioeconomic status or distance and survival outcomes across all solid tumors.

Background: Frailty is associated with hospitalization and mortality among dialysis patients. To now, few studies have considered the degree of frailty as a predictor of hospitalization. Objective: We evaluated whether frailty severity was associated with hospitalization after dialysis initiation. Design: Retrolective cohort study. Setting: Nova Scotia, Canada. Patients: Consecutive adult, chronic dialysis patients who initiated dialysis from January 1, 2009 to June 30, 2014, (last follow-up June, 2015). Methods: Frailty Severity, as determined by the 7-point Clinical Frailty Scale (CFS, ranging from 1 = very fit to 7 = severely frail), was measured at dialysis initiation and treated as continuous and in categories (CFS scores of 1-3, 4/5, and 6/7). Hospitalization was characterized by cumulative time admitted to hospital (proportion of days admitted/time at risk) and by the joint risk of hospitalization and death. Time at risk included time in hospital after dialysis initiation and patients were followed until transplantation or death. Results: Of 647 patients (mean age: 62 ± 15), 564 (87%) had CFS scores. The mean CFS score was 4 (“corresponding to “vulnerable”) ± 2 (“well” to “moderately frail”). In an adjusted negative binomial regression model, moderate-severely frail patients (CFS 6/7) had a >2-fold increased risk of cumulative time admitted to hospital compared to the lowest CFS category (IRR = 2.18, 95% confidence interval [CI] = 1.31-3.63). In the joint model, moderate-severely frail patients had a 61% increase in the relative hazard for hospitalization (hazard ratio [HR] = 1.61, 95% CI = 1.29-2.02) and a 93% increase in the relative hazard for death compared to the lowest CFS category (HR = 1.93, 95% CI = 1.16-3.22). Limitations: Potential unknown confounders may have affected the association between frailty severity and hospitalization given observational study design. The CFS is subjective and different clinicians may grade frailty severity differently or misclassify patients on the basis of limited availability. Conclusions: Among incident dialysis patients, a higher frailty severity as defined by the CFS is associated with both an increased risk of cumulative time admitted to hospital and joint risk of hospitalization and death.

ObjectiveCognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood–brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage.MethodsConsecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers.ResultsThere were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8–24 years) vs 15 (2–16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage.ConclusionsExtensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

ObjectiveCognitive impairment (CI) is the most frequent manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE), yet the mechanisms underlying it remain poorly understood. We have previously reported an association between enhanced permeability of the blood-brain barrier (BBB), loss of grey matter volume and cognitive impairment in SLE patients. This study examined the associations of brain functional connectivity (FC) with CI and BBB dysfunction among patients with SLE.MethodsCognitive function was assessed by neuropsychological testing (n=77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n=78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (DCE-MRI) (n=61). Differences in rsFC were compared between SLE patients with CI (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls.ResultsA whole-brain rsFC comparison found significant differences in intra-network and inter- network FC in SLE-CI versus SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared to SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared to SLE-NC (P=0.030) and healthy controls (P=0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P=0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and CI in SLE patients was mediated by alterations in FC.ConclusionSLE patients with CI had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and CI.

Background:Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment.Methods:Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls.Results:For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079).Conclusion:EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.

ObjectivesTo examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE).MethodsA total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage.ResultsPatients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cognitive scores (p=0.02), and with the presence of impairment on one or more cognitive tasks (p=0.01).ConclusionOur findings provide evidence for a link between extensive BBB leakage and changes in both brain structure and cognitive function in patients with SLE. Future studies should investigate the mechanisms underlying BBB-mediated cognitive impairment, validate the diagnostic utility of BBB imaging, and determine the potential of targeting the BBB as a therapeutic strategy in patients with SLE.

BackgroundCardiac assessment with multi-gated acquisition scan (MUGA) or echocardiography (ECHO) is commonly employed prior to adjuvant anthracycline-based chemotherapy (AA). However, the clinical utility of routine baseline cardiac assessments prior to AA for early-stage breast cancer (EBC) is unknown.ObjectivesTo determine: (i) the clinical utility of routine baseline cardiac assessments prior to AA for EBC and (ii) identify patients in whom baseline cardiac assessments may not be warranted.MethodsA systematic review of the literature was conducted to identify all relevant studies that met predefined criteria. The clinical utility was defined by: (i) the rates of abnormal baseline left ventricular ejection fraction (LVEF) and (ii) the rates of change in chemotherapy decisions prompted by baseline LVEF results.ResultsEight studies met our criteria, of whom six (n = 2545) reported rates of abnormal LVEF and six (n = 1713) reported rates of change in chemotherapy decision. Overall, 2.5% (95% CI 2.0–4.0%) of patients had abnormal baseline LVEF and 1.6% (95% CI 1.0–3.0%) had a change in chemotherapy decision. In subset analyses, the underlying imaging modality (ECHO vs. MUGA) or inclusion of patients with metastatic disease (YES vs. NO) did not significantly affect these rates. There were no consistently identified underlying predictors of abnormal baseline LVEF across studies.ConclusionsRoutine baseline cardiac assessments prior to AA in all EBC patients have low yield and infrequently affect clinical management. Future studies should further examine potential predictors of abnormal cardiac functions in an attempt to identify low risk patients in whom routine baseline LVEF assessment may not be warranted and prevent delay in chemotherapy administration.

Background: Low-dose computed tomography (LDCT) screening is recommended for heavy smokers (HS), but 15%40% of lung cancer patients are light-or-never smokers (LONS). The SCREEN study investigated whether survival differs between lung cancer patients who were eligible (HS) and ineligible (LONS) for LDCT screening to establish whether expanded screening criteria should be studied. SCREEN is a retrospective cohort study of 917 lung cancer cases from 2005 to 2020 at a tertiary Canadian institution. Methods: Proportional-hazards models were used to compare mortality risk between HS and LONS, defined by the National Lung Screening Trial (NSLT) criteria and sepa- rately by the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial criteria. One-year and 5-year survival rates were also compared between HS and LONS. Results: The median follow-up was 2.9 years. The cohort comprised 36.9% (NLST, n = 338) and 56.3% (NELSON, n = 516) HS. LONS had a higher proportion of stage 1 cancer than HS (NELSON: 58.7% [n = 216] v. 51.8% [n = 244], p = 0.047). The 5-year overall survival rate was similar between LONS and HS using NLST criteria (55.2% [n = 338] v. 58.5% [n = 529], p = 0.408; hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.80-1.40, p = 0.704) and NELSON criteria (57.6% [n = 401] v. 56.9% [n = 516], p = 0.855; HR 1.02, 95% CI 0.73-1.42, p = 0.925). Multivariate analysis showed males were at increased risk of mortality compared females in both the NLST (HR 2.00, 95% CI 1.57-2.54, p < 0.001) and NELSON models (HR 2.00, 95% CI 1.58-2.54, p < 0.001). Conclusion: Survival did not differ between HS and LONS, but there was a higher proportion of stage 1, potentially curable lung cancers among LONS. Smoking status and age alone may be insufficient predictors of lung cancer risk. Additional research is needed to refine lung cancer screening eligibility criteria through expanded risk factor analysis to ensure that screening is effective and equitable.

PurposePatients with ErbB2/Her2 oncoprotein-positive breast cancers often receive neoadjuvant therapies (NATs) containing the anti-ErbB2 antibody trastuzumab. Tumors that are still present after NATs are resected, and patients continue receiving trastuzumab. These cancers are associated with high relapse risk. Whether relapse will occur cannot be presently reliably predicted. The ability to make such predictions could improve disease management. We found previously that ErbB2 blocks breast tumor cell anoikis, apoptosis induced by cell detachment from the extracellular matrix, by downregulating the pro-apoptotic protein Irf6 and upregulating the anti-apoptotic protein Epidermal Growth Factor Receptor (EGFR) in the cells and, thus, promotes their three-dimensional growth. We now tested whether tumor levels of these proteins before and after NATs correlate with patients’ relapse-free survival (RFS) and overall survival (OS).MethodsWe selected archival breast tumor samples collected from 37 women with ErbB2-positive stages II and III breast cancer before and after NATs. We used immunohistochemistry to test whether levels of the indicated proteins in respective tumors correlate with RFS and OS.ResultsWe observed that the presence of high Irf6 levels in the tumors following NATs correlated with reduced RFS and OS. Perhaps not by coincidence, we noticed that trastuzumab-sensitive ErbB2-positive breast cancer cells selected for the ability to overproduce exogenous Irf6 in culture acquired trastuzumab resistance. Finally, EGFR presence in patients’ tumors before or after NATs was associated with decreased RFS and OS.ConclusionsThis study could help identify patients with ErbB2-positive tumors that are at increased risk of disease relapse following NATs.

INTRODUCTION: Urolithiasis is a common complication of primary hyperparathyroidism (PHPT). Parathyroidectomy has been shown to decrease the rate of stone formation. The purpose of this study was to evaluate healthcare resource utilization before and after parathyroidectomy and identify predictors of increased healthcare utilization. METHODS: A retrospective analysis of patients who had a parathyroidectomy for PHPT in Nova Scotia from 2013-2018 was performed. Data from five years before parathyroidectomy to three years after were included. Outcomes included emergency department (ED) visits and the number of urologic interventions. Random-effects Poisson regression models were used to calculate the primary outcomes, ED visits, and the number of urologic interventions while adjusting for prespecified characteristics. RESULTS: Fifty patients (62% female) with a mean age of 60[+ or -]11 years were identified. ED visits were 0.42 per year before parathyroidectomy and 0.20 per year after in a multivariate analysis (incidence rate ratio [IRR] 0.48, confidence interval [CI] 0.25-0.91, p=0.024). There was no statistical difference between male and female ED visits (p=0.6719). There was no difference in the rate of ED visits for non-urologic reasons after parathyroidectomy (p=0.0749). The incidence of urologic intervention for stones was 1.24 per year before parathyroidectomy and 0.53 per year after (IRR 0.42, CI 0.26-0.68, p=0.0005). CONCLUSIONS: Healthcare resource utilization, in terms of ED visits and urologic intervention, significantly decreased after parathyroidectomy. Sex showed no statistical difference in predicting healthcare utilization, while non-urologic ED visits remained the same after surgery. Expedited parathyroidectomy for PHPT patients may decrease urologic interventions and ED visits, resulting in less healthcare utilization.