Frailty in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma Receiving Curative-Intent Therapy: A Population-Based Study.

BACKGROUND: The objectives of this study were to determine whether frailty is associated with survival in a population-based sample of patients with diffuse large B-cell lymphoma (DLBCL) and to describe the healthcare utilization patterns of frail versus nonfrail patients during treatment. METHODS: A retrospective cohort study was conducted using population-based data in Ontario, Canada. Patients aged ≥66 years diagnosed between 2006 and 2017 with DLBCL or transformed follicular lymphoma who received first-line curative-intent chemoimmunotherapy were included. Frailty was defined using a modified version of a generalizable frailty index developed for use with Ontario administrative data. Cox regression was performed to examine the association between frailty and 1-year mortality. RESULTS: A total of 5,527 patients were included (median age, 75 years [interquartile range, 70-80 years]; 48% female), of whom 2,699 (49%) were classified as frail. Within 1 year of first-line treatment, 32% (n=868) of frail patients had died compared with 20% (n=553) of nonfrail patients (unadjusted hazard ratio, 1.8; 95% CI, 1.6-2.0; P<.0001). Frail patients had higher healthcare utilization during treatment, with most hospitalizations related to infection and/or lymphoma. In multivariable modeling controlling for age, inpatient diagnosis, number of chemoimmunotherapy cycles received, comorbidity burden, and healthcare utilization, frailty remained independently associated with 1-year mortality (adjusted hazard ratio, 1.5; 95% CI, 1.3-1.7; P<.0001). CONCLUSIONS: In a population-based sample of older adult patients with DLBCL receiving front-line curative-intent therapy, half were classified as frail, and their adjusted relative rate of death in the first year after starting treatment was 50% higher than that of nonfrail patients. Frailty seems to be associated with poor treatment tolerance and a higher likelihood of requiring acute hospital-based care.

Comparative Effectiveness and Safety of Pertuzumab and Trastuzumab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy for Treatment of Metastatic Breast Cancer.

IMPORTANCE: To date, limited studies have examined the comparative outcomes of pertuzumab treatment in the real-world setting. End-of-study analyses of the CLEOPATRA trial found median overall survival (OS) of 57.1 months in patients receiving pertuzumab compared with 40.8 months in control patients, a benefit of 16.3 months. However, studies examining the real-world use of pertuzumab have found conflicting results. OBJECTIVE: To assess the real-world comparative effectiveness and safety of pertuzumab, trastuzumab, and chemotherapy for patients with metastatic breast cancer in Ontario, Canada. DESIGN, SETTING, AND PARTICIPANTS: A population-based retrospective comparative effectiveness research study was conducted. Patients receiving first-line treatments for metastatic breast cancer from January 1, 2008, to March 31, 2018, in Ontario were identified. Data analysis was performed from November 13, 2019, to August 1, 2021. Thirteen patients had received treatment before diagnosis or were not Ontario residents and were excluded from the analysis. Of the remaining 1823 patients identified, 912 received pertuzumab and 911 were control patients. Using propensity-score methods, 579 pairs of patients receiving pertuzumab were matched to those in the control group, resulting in a total of 1158 patients in the final cohort. EXPOSURES: Patients in the case group received pertuzumab with trastuzumab and chemotherapy and those in the control group received trastuzumab and chemotherapy. MAIN OUTCOMES AND MEASURES: Overall survival (the primary outcome) and hazard ratios (HRs) were calculated using Kaplan-Meier and Cox proportional hazards regression methods. Secondary outcomes included cumulative incidence of safety end points including resource use and adverse events. Follow-up duration was up to 5 years from the start of therapy, with maximum follow-up to March 31, 2019. RESULTS: Of the 1158 matched patients (579 pairs) receiving pertuzumab and controls, 1151 (99%) were women (mean [SD] age, 58.2 [12.97] years). The median OS was higher in patients receiving pertuzumab (40.2; 95% CI, 35.6-47.8 months) than in the control patients (25.3; 95% CI, 22.8-27.6 months), a median OS improvement of 14.9 months. Pertuzumab was associated with reduced mortality (HR, 0.66; 95% CI, 0.57-0.79). The cumulative incidence of direct hospitalization at 1 year was lower among patients receiving pertuzumab (11.7%) compared with the control patients (19.0%) (P < .001). CONCLUSIONS AND RELEVANCE: Although the median OS in both the pertuzumab and control groups were shorter in this study than those observed in the CLEOPATRA trial, there appears to be a similar significant OS benefit with pertuzumab in the real-world setting.

Cost-effectiveness Analysis of Pertuzumab With Trastuzumab in Patients With Metastatic Breast Cancer.

IMPORTANCE: The initial assessment of pertuzumab use for treatment of metastatic breast cancer by health technology assessment agencies suggested that pertuzumab was not cost-effective. In Ontario, Canada, pertuzumab became funded in November 2013 based on the substantial clinical benefit. To date, there is a paucity of analysis of pertuzumab using real-world data for cost-effectiveness. OBJECTIVE: To assess the cost-effectiveness of pertuzumab, trastuzumab, and chemotherapy vs trastuzumab and chemotherapy for patients with metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS: A population-based retrospective economic evaluation was conducted in Ontario, Canada. Patients who received first-line treatments for metastatic breast cancer from January 1, 2008, to March 31, 2018, were identified. Patients were followed up from the start of treatment up to 5 years, with maximum follow-up to March 31, 2019. Patients were identified from the Ontario Cancer Registry and linked to the New Drug Funding Program database to identify receipt of first-line treatment (N = 1158). INTERVENTIONS: Treatment with pertuzumab, trastuzumab, and chemotherapy after public funding (November 25, 2013) compared with treatment with trastuzumab and chemotherapy before funding. MAIN OUTCOMES AND MEASURES: Cost-effectiveness, from a public payer perspective, was estimated from administrative data with a 5-year time horizon, adjusted for censoring, and discounted (1.5%). Incremental cost-effectiveness ratios for life-years gained and quality-adjusted life year (QALY) with bootstrapped 95% CIs were calculated. Sensitivity analysis with price reduction of pertuzumab alone or in combination with trastuzumab was conducted. RESULTS: A total of 579 pairs of matched patients receiving pertuzumab and controls were included. The mean (SD) age of the matched study cohort was 58 (12.97) years; 1151 were women (99.4%). Pertuzumab resulted in 0.61 life-years gained and 0.44 QALYs gained at an incremental cost of $192 139 (all costs measured in Canadian dollar values, CAD) with an incremental cost-effectiveness ratio of $316 203 per life-year gained and $436 679 per QALY. The main factors associated with cost included the cost of pertuzumab (60%), outpatient cancer treatment delivery (24%), and trastuzumab (15%). With 100% price reduction of pertuzumab, the incremental cost-effectiveness ratio was $174 027 per QALY. When the price of pertuzumab and trastuzumab were both reduced by more than 71%, the incremental cost-effectiveness ratio decreased below $100 000 per QALY. CONCLUSIONS AND RELEVANCE: The findings of this population-based study suggest that pertuzumab may increase survival for patients with metastatic breast cancer but would not be considered cost-effective, even after 100% price reduction, under conventional thresholds.

Risk of COVID-19 Infections and of Severe Complications Among Survivors of Childhood, Adolescent, and Young Adult Cancer: A Population-Based Study in Ontario, Canada.

PURPOSE: Survivors of childhood, adolescent, and young adult cancer are at risk of late effects, including pulmonary and infectious complications. Whether survivors are at increased risk of COVID-19 infection and severe complications is unknown. METHODS: Population-based registries in Ontario, Canada, identified all 5-year survivors of childhood cancer diagnosed age 0-17 years between 1985 and 2014, and of six common adolescent and young adult cancers diagnosed age 15-21 years between 1992 and 2012. Each survivor alive on January 1, 2020, was randomly matched by birth year, sex, and residence to 10 cancer-free population controls. Individuals were linked to population-based laboratory and health care databases to identify COVID-19 tests, vaccinations, infections, and severe outcomes (emergency department [ED] visits, hospitalizations, intensive care unit admissions, and death within 60 days). Demographic, disease, and treatment-related variables were examined as possible predictors of outcomes. RESULTS: Twelve thousand four hundred ten survivors were matched to 124,100 controls. Survivors were not at increased risk of receiving a positive COVID-19 test (386 [3.1%] v 3,946 [3.2%]; P = .68) and were more likely to be fully vaccinated (hazard ratio, 1.23; 95 CI, 1.20 to 1.37). No increase in risk among survivors was seen in emergency department visits (adjusted odds ratio, 1.2; 95 CI, 0.9 to 1.6; P = .19) or hospitalization (adjusted odds ratio, 1.8; 95 CI, 1.0 to 3.5; P = .07). No survivor experienced intensive care unit admission or died after COVID-19 infection. Pulmonary radiation or chemotherapies associated with pulmonary toxicity were not associated with increased risk. CONCLUSION: Cancer survivors were not at increased risk of COVID-19 infections or severe sequelae. These results can inform risk-counseling of survivors and their caregivers. Further study is warranted to determine risk in older survivors, specific subsets of survivors, and that associated with novel COVID-19 variants.

Obstetrical and Perinatal Outcomes in Female Survivors of Childhood and Adolescent Cancer: A Population-Based Cohort Study.

BACKGROUND: The likelihood of pregnancy and risk of obstetrical or perinatal complications is inadequately documented in female survivors of pediatric cancer. METHODS: We assembled a population-based cohort of female survivors of cancer diagnosed at age 21 years and younger in Ontario, Canada, between 1985 and 2012. Survivors were matched 1:5 to women without prior cancer. Multivariable Cox proportional hazards and modified Poisson models assessed the likelihood of a recognized pregnancy and perinatal and maternal complications. RESULTS: A total of 4062 survivors were matched to 20 308 comparisons. Median (interquartile range) age was 11 (4-15) years at cancer diagnosis and 25 (19-31) years at follow-up. By age 30 years, the cumulative incidence of achieving a recognized pregnancy was 22.3% (95% confidence interval [CI] = 20.7% to 23.9%) among survivors vs 26.6% (95% CI = 25.6% to 27.3%) among comparisons (hazard ratio = 0.80, 95% CI = 0.75 to 0.86). A lower likelihood of pregnancy was associated with a brain tumor, alkylator chemotherapy, cranial radiation, and hematopoietic stem cell transplantation. Pregnant survivors were as likely as cancer-free women to carry a pregnancy >20 weeks (relative risk [RR] = 1.01, 95% CI = 0.98 to 1.04). Survivors had a higher relative risk of severe maternal morbidity (RR = 2.31, 95% CI = 1.59 to 3.37), cardiac morbidity (RR = 4.18, 95% CI = 1.89 to 9.24), and preterm birth (RR = 1.57, 95% CI = 1.29 to 1.92). Preterm birth was more likely in survivors treated with hematopoietic stem cell transplantation (allogenic: RR = 8.37, 95% CI = 4.83 to 14.48; autologous: RR = 3.72, 95% CI = 1.66 to 8.35). CONCLUSIONS: Survivors of childhood or adolescent cancer are less likely to achieve a pregnancy and, once pregnant, are at higher risk for severe maternal morbidity and preterm birth.

Impact of locus of care on outcomes in adolescents and young adults with osteosarcoma and Ewing sarcoma treated at pediatric versus adult cancer centers: An IMPACT cohort study.

BACKGROUND: Location of cancer care (LOC; pediatric vs. adult center) impacts outcomes in adolescents and young adults (AYA) with some cancer types. Data on the impact of LOC on survival in AYA with osteosarcoma (OSS) and Ewing sarcoma (EWS) are limited OBJECTIVES: To compare differences in demographics, disease/treatment characteristics, and survival in a population-based cohort of AYA with OSS or EWS treated at pediatric versus adult centers METHODS: The Initiative to Maximize Progress in Adolescent Cancer Therapy (IMPACT) cohort captured demographic, disease, and treatment data for all AYA (15-21 years old) diagnosed with OSS and EWS in Ontario, Canada between 1992 and 2012. Patients were linked to provincial administrative health care databases. Outcomes were compared between patients treated in pediatric versus adult centers. RESULTS: One hundred thirty-seven AYA were diagnosed with OSS (LOC: 47 pediatric, 90 adult) and 84 with EWS (38 pediatric, 46 adult). AYA treated at pediatric centers were more likely to be enrolled in a clinical trial (OSS 55% vs. 1%, p < .001; EWS 53% vs. 2%, p < .001) and received higher cumulative chemotherapy doses. Five-year event-free survival (EFS ± standard error) in OSS and EWS were 47% ± 4% and 43% ± 5%, respectively. In multivariable analysis, the impact of LOC (pediatric vs. adult center) on EFS in OSS (adjusted hazard ratio [HR] 1.15, 95% confidence interval [CI]: 0.58-2.27, p = .69) and EWS (adjusted HR 1.82, 95% CI: 0.97-3.43, p = .06) was not statistically significant. CONCLUSION: Despite disparities in trial participation and chemotherapy doses, outcomes did not differ by LOC suggesting that AYA with bone tumors can be treated at either pediatric or adult centers.

Locus-of-care disparities in end-of-life care intensity among adolescents and young adults with cancer: A population-based study using the IMPACT cohort.

BACKGROUND: Adolescents and young adults (AYAs) with cancer may experience elevated rates of high-intensity end-of-life (HI-EOL) care. Locus-of-care (LOC) disparities (pediatric vs adult) in AYA end-of-life (EOL) care are unstudied. METHODS: A decedent population-based cohort of Ontario AYAs diagnosed between 1992 and 2012 at the ages of 15 to 21 years was linked to administrative data. The authors determined the prevalence and associations of a composite outcome of HI-EOL care that included any of the following: intravenous chemotherapy within 14 days of death, more than 1 emergency department visit, more than 1 hospitalization, or an intensive care unit (ICU) admission within 30 days of death. Secondary outcomes included measures of the most invasive EOL care (ventilation within 14 days of death and ICU death) and in-hospital death. RESULTS: There were 483 decedents: 60.5% experienced HI-EOL care, 20.3% were ventilated, and 22.8% died in the ICU. Compared with patients with solid tumors, patients with hematological malignancies had the greatest odds of HI-EOL care (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.5-3.4), ventilation (OR, 4.7; 95% CI, 2.7-8.3), and ICU death (OR, 4.4; 95% CI, 2.6-4.4). Subjects treated in pediatric centers versus adult centers near death (OR, 2.4; 95% CI, 1.2-4.8) and those living in rural areas (OR, 2.1; 95% CI, 1.1-3.9) were more likely to experience ICU death. CONCLUSIONS: AYAs with cancer experience high rates of HI-EOL care, with patients in pediatric centers and those living in rural areas having the highest odds of ICU death. This study is the first to identify LOC-based disparities in EOL care for AYAs, and it highlights the need to explore the mechanisms underlying these disparities.

Superior outcomes with paediatric protocols in adolescents and young adults with aggressive B-cell non-Hodgkin lymphoma.

Survival disparities by locus of care (LOC; paediatric versus adult) among adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) are well documented. Whether similar disparities exist among AYA with aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is unknown. We identified all Ontario, Canada AYA aged 15-21 years at diagnosis of B-NHL between 1992 and 2012. Demographic, disease, treatment and outcome data were chart abstracted. The impact of LOC on event-free (EFS) and overall survival (OS) were determined, adjusted for patient and disease covariates. Among 176 AYA with B-NHL, 62 (35·2%) received therapy at paediatric centres. The 5-year EFS and OS [± standard error (SE)] for the overall cohort were 72·2 [3·4]% and 76·1 [3·2]% respectively. Both EFS and OS were superior among paediatric centre AYA [EFS (± SE) 82·2 (4·9)% vs. 66·7 (4·4)%, P = 0·02; OS 85·5 (4·5)% vs. 71·1 (4·3)%, P = 0·03]. Adjusted for histology, stage and time period, adult centre AYA had inferior EFS [hazard ratio (HR) 2·4, 95% confidence interval (CI) 1·1-4·9, P = 0·02] and OS (HR 2·5, 95% CI 1·1-5·7, P = 0·03). Sensitivity analyses restricted to the latest time period, when most adult centre AYA received rituximab, demonstrated similar disparities. Similar to AYA with ALL, AYA with B-NHL may benefit from being treated with paediatric protocols. Studies prospectively validating these results are warranted.

Healthcare cost attributable to bronchiolitis: A population-based cohort study.

OBJECTIVE: To determine 1-year attributable healthcare costs of bronchiolitis. METHODS: Using a population-based matched cohort and incidence-based cost analysis approach, we identified infants <12 months old diagnosed in an emergency department (ED) or hospitalized with bronchiolitis between April 1, 2003 and March 31, 2014. We propensity-score matched infants with and without bronchiolitis on sex, age, income quintile, rurality, co-morbidities, gestational weeks, small-for-gestational-age status and pre-index healthcare cost deciles. We calculated mean attributable 1-year costs using a generalized estimating equation model and stratified costs by age, sex, income quintile, rurality, co-morbidities and prematurity. RESULTS: We identified 58,375 infants with bronchiolitis (mean age 154±95 days, 61.3% males, 4.2% with comorbidities). Total 1-year mean bronchiolitis-attributable costs were $4,313 per patient (95%CI: $4,148-4,477), with $2,847 (95%CI: $2,712-2,982) spent on hospitalizations, $610 (95%CI: $594-627) on physician services, $562 (95%CI: $556-567)] on ED visits, $259 (95%CI: $222-297) on other healthcare costs and $35 ($27-42) on drugs. Attributable bronchiolitis costs were $2,765 (95%CI: $2735-2,794) vs $111 (95%CI: $102-121) in the initial 10 days post index date, $4,695 (95%CI: $4,589-4,800) vs $910 (95%CI: $847-973) in the initial 180 days and $1,158 (95%CI: $1,104-1213) vs $639 (95%CI: $599-679) during days 181-360. Mean 1-year bronchiolitis costs were higher in infants <3 months old [$5,536 (95%CI: $5,216-5,856)], those with co-morbidities [$17,530 (95%CI: $14,683-20,377)] and with low birthweight [$5,509 (95%CI: $4,927-6,091)]. CONCLUSIONS: Compared to no bronchiolitis, bronchiolitis incurs five-time and two-time higher healthcare costs within the initial and subsequent six-months, respectively. Most expenses occur in the initial 10 days and relate to hospitalization.

Shorter Diagnosis-to-Treatment Interval in Diffuse Large B-Cell Lymphoma is Associated With Inferior Overall Survival in a Large, Population-Based Registry.

BACKGROUND: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. RESULTS: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8-13), and median DTI was 37 days (IQR, 22-61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4-2.8 years). Shorter DTI was a significant predictor of mortality (P<.001). Compared with the shortest DTI period of 0-18 days, those who commenced therapy at 19-29 days (hazard ratio [HR], 0.75; 95% CI, 0.68-0.84), 30-41 days (HR, 0.70; 95% CI, 0.63-0.78), 42-57 days (HR, 0.52; 95% CI, 0.46-0.58), and 58-180 days (HR, 0.52; 95% CI, 0.47-0.58) had improved survival. Increasing age (HR, 1.03; 95% CI, 1.03-1.04), male sex (HR, 1.23; 95% CI, 1.14-1.32), and increasing number of comorbidities (HR, 1.12; 95% CI, 1.11-1.13) were associated with inferior survival. CONCLUSIONS: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.

Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study.

BACKGROUND: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. OBJECTIVE: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. METHODS: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63-0.88). CONCLUSIONS: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.

Adolescents and young adult acute myeloid leukemia outcomes at pediatric versus adult centers: A population-based study.

BACKGROUND: Adolescents and young adult (AYA) acute myeloid leukemia (AML) outcomes remain poor. The impact of locus of care (LOC; adult vs pediatric) in this population is unknown. PROCEDURE: The IMPACT cohort comprises detailed data for all Ontario, Canada, AYA aged 15-21 years diagnosed with AML between 1992 and 2012, linked to population-based health administrative data. We determined the impact of LOC on event-free survival (EFS) and overall survival (OS), treatment-related mortality (TRM), and relapse/progression. RESULTS: Among 140 AYA, 51 (36.4%) received therapy at pediatric centers. The five-year EFS and OS for the whole cohort were 35.0% ± 4.0% and 53.6% ± 4.2%. Cumulative doses of anthracycline were higher among pediatric center AYA [median 355 mg/m2 , interquartile range (IQR) 135-492 vs 202 mg/m2 , IQR 140-364; P = 0.003]. In multivariable analyses, LOC was not predictive of either EFS [adult vs pediatric center hazard ratio (HR) 1.3, 95% confidence interval (CI) 0.8-2.2, P = 0.27] or OS (HR 1.0, CI 0.6-1.6, P = 0.97). However, patterns of treatment failure varied; higher two-year incidence of TRM in pediatric centers (23.5% ± 6.0% vs.10.1% ± 3.2%; P = 0.046) was balanced by lower five-year incidence of relapse/progression (33.3% ± 6.7% vs 56.2% ± 5.3%; P = 0.002). CONCLUSIONS: AYA AML survival outcomes did not vary between pediatric and adult settings. Causes of treatment failure were different, with higher intensity pediatric protocols associated with higher TRM but lower relapse/progression. Careful risk stratification and enhanced supportive care may be of substantial benefit to AYA with AML by allocating maximal treatment intensity to patients who most benefit while minimizing the risk of TRM.

Mortality among patients with frequent emergency department use for alcohol-related reasons in Ontario: a population-based cohort study.

BACKGROUND: Little is known about the risk of death among people who visit emergency departments frequently for alcohol-related reasons, including whether mortality risk increases with increasing frequency of visits. Our primary objective was to describe the sociodemographic and clinical characteristics of this high-risk population and examine their 1-year overall mortality, premature mortality and cause of death as a function of emergency department visit frequency in Ontario, Canada. METHODS: We conducted a population-based retrospective cohort study using linked health administrative data (Jan. 1, 2010, to Dec. 31, 2016) in Ontario for people aged 16-105 years who made at least 2 emergency department visits for mental or behavioural disorders due to alcohol within 1 year. We subdivided the cohort based on visit frequency (2, 3 or 4, or ≥ 5). The primary outcome was 1-year mortality, adjusted for age, sex, income, rural residence and presence of comorbidities. We examined premature mortality using years of potential life lost (YPLL). RESULTS: Of the 25 813 people included in the cohort, 17 020 (65.9%) had 2 emergency department visits within 1 year, 5704 (22.1%) had 3 or 4 visits, and 3089 (12.0%) had 5 or more visits. Males, people aged 45-64 years, and those living in urban centres and lower-income neighbourhoods were more likely to have 3 or 4 visits, or 5 or more visits. The all-cause 1-year mortality rate was 5.4% overall, ranging from 4.7% among patients with 2 visits to 8.8% among those with 5 or more visits. Death due to external causes (e.g., suicide, accidents) was most common. The adjusted mortality rate was 38% higher for patients with 5 or more visits than for those with 2 visits (adjusted hazard ratio 1.38, 95% confidence interval 1.19-1.59). Among 25 298 people aged 16-74 years, this represented 30 607 YPLL. INTERPRETATION: We observed a high mortality rate among relatively young, mostly urban, lower-income people with frequent emergency department visits for alcohol-related reasons. These visits are opportunities for intervention in a high-risk population to reduce a substantial mortality burden.

Treatment patterns and outcomes in adolescents and young adults with Hodgkin lymphoma in pediatric versus adult centers: An IMPACT Cohort Study.

Hodgkin lymphoma (HL) is a common adolescent and young adult (AYA) cancer. While outcome disparities between pediatric vs. adult centers [locus of care (LOC)] have been demonstrated in other AYA cancers such as acute lymphoblastic leukemia, they have not been well studied in HL. We therefore compared population-based treatment patterns and outcomes in AYA HL by LOC. The IMPACT Cohort includes data on all Ontario, Canada AYA (15-21 years) diagnosed with HL between 1992 and 2012. Linkage to population-based health administrative data identified late effects. We examined LOC-based differences in treatment modalities, cumulative doses, event-free survival (EFS), overall survival (OS), and late effects. Among 954 AYA, 711 (74.5%) received therapy at adult centers. Pediatric center AYA experienced higher rates of radiation therapy but lower cumulative doses of doxorubicin and bleomycin. 10-year EFS did not differ between pediatric vs. adult cancer vs. community centers (83.8% ± 2.4% vs. 82.8% ± 1.6% vs. 82.7%±3.0%; P = .71); LOC was not significantly associated with either EFS or OS in multivariable analyses. Higher incidences of second malignancies in pediatric center AYA and of cardiovascular events in adult center AYA were observed, but were not significant. In conclusion, while pediatric and adult centers used different treatment strategies, outcomes were equivalent. Differences in treatment exposures are however likely to result in different late-effect risks. Protocol choice should be guided by individual late-effect risk.

Statin and cyclooxygenase-2 inhibitors improve survival in newly diagnosed diffuse large B-cell lymphoma: a large population-based study of 4913 subjects.

Preclinical data suggests anti-lymphoma potential for statins, metformin and cyclooxygenase-2 (COX-2) inhibitors. We performed a retrospective population-based study of all adults aged ≥66 years diagnosed with diffuse large B-cell lymphoma (DLBCL) or transformed lymphoma treated with a rituximab containing regimen, between 2005 and 2015 in Ontario, Canada. Using administrative databases, we assessed the impact of medication exposures, prior to chemo-immunotherapy, on lymphoma survival. Cox regression analyses, controlling for sociodemographic factors and comorbidities, examined the relationship between medication exposure and survival. In total, 4913 patients were treated with curative intent (median age 75 years, 51% male) and 52·2% died at a median of 1 year from treatment initiation (67% due to DLBCL). In the year prior to commencing treatment, 45·7% received statins, 16·3% metformin, and 25·0% a COX-2 inhibitor. Adjusting for confounders, exposure to statin and COX-2 inhibitors prior to chemo-immunotherapy independently conferred a survival advantage: statin exposure for 30 days (hazard ratio [HR] 0·97, 95% confidence interval [CI] 0·96-0·98), 180 days (HR 0·84, 95% CI 0·80-0·89) and 365 days (HR 0·71, 95% CI 0·63-0·79) and COX-2 inhibitor exposure for 30 days (HR 0·95, 95% CI 0·95-0·98), 180 days (HR 0·76, 95% CI 0·66-0·86) and 365 days (HR 0·57, 95% CI 0·43-0·74). Metformin had no significant impact. This population-based study found a dose-related survival benefit of exposure to statins and COX-2 inhibitors prior to chemo-immunotherapy for newly diagnosed DLBCL.

The effect of adopting pediatric protocols in adolescents and young adults with acute lymphoblastic leukemia in pediatric vs adult centers: An IMPACT Cohort study.

BACKGROUND: Retrospective studies have shown adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have superior survival when treated in pediatric versus adult centers (locus of care; LOC). Several adult centers recently adopted pediatric protocols. Whether this has narrowed LOC disparities in real-world settings is unknown. METHODS: The IMPACT Cohort is an Ontario population-based cohort that captured demographic, disease and treatment (treatment protocol, chemotherapy doses) data for all 15-21 year olds diagnosed with ALL 1992-2011. Cancer outcomes were determined by chart abstraction and linkage to provincial healthcare databases. Treatment protocols were classified as pediatric- or adult-based. We examined predictors of outcome, including LOC, protocol, disease biology, and time period. RESULTS: Of 271 patients, 152 (56%) received therapy at adult centers. 5-year event-free survival (EFS ± SE) among AYA at pediatric vs adult centers was 72% ± 4% vs 56% ± 4% (P = 0.03); 5-year overall survival (OS) was 82% ± 4% vs 64% ± 4% (P < 0.001). After adjustment, OS remained inferior at adult centers (hazard ratio 2.5; 95% confidence interval 1.1-6.1; P = 0.04). In the most recent period (2006-2011), 39/59 (66%) AYA treated at adult centers received pediatric protocols. These AYA had outcomes superior to the 20 AYA treated on adult protocols, but inferior to the 44 AYA treated at pediatric centers (EFS 72% ± 5% vs 60% ± 9% vs 81% ± 6%; P = 0.02; OS 77% ± 7% vs 65% ± 11% vs 91% ± 4%; P = 0.004). Induction deaths and treatment-related mortality did not vary by LOC. CONCLUSIONS: Survival disparities between AYA with ALL treated in pediatric vs adult centers have persisted over time, partially attributable to incomplete adoption of pediatric protocols by adult centers. Although pediatric protocol use has improved survival, residual disparities remain, perhaps due to other differences in care between adult and pediatric centers.

Leveraging Quick Response Code Technology to Facilitate Simulation-Based Leaderboard Competition.

INTRODUCTION: Leaderboards provide feedback on relative performance and a competitive atmosphere for both self-guided improvement and social comparison. Because simulation can provide substantial quantitative participant feedback, leaderboards can be used, not only locally but also in a multidepartment, multicenter fashion. Quick Response (QR) codes can be integrated to allow participants to access and upload data. We present the development, implementation, and initial evaluation of an online leaderboard employing principles of gamification using points, badges, and leaderboards designed to enhance competition among healthcare providers. METHOD: This article details the fundamentals behind the development and implementation of a user-friendly, online, multinational leaderboard that employs principles of gamification to enhance competition and integrates a QR code system to promote both self-reporting of performance data and data integrity. An open-ended survey was administered to capture perceptions of leaderboard implementation. RESULTS: Conceptual step-by-step instructions detailing how to apply the QR code system to any leaderboard using simulated or real performance metrics are outlined using an illustrative example of a leaderboard that employed simulated cardiopulmonary resuscitation performance scores to compare participants across 17 hospitals in 4 countries for 16 months. The following three major descriptive categories that captured perceptions of leaderboard implementation emerged from initial evaluation data from 10 sites: (1) competition, (2) longevity, and (3) perceived deficits. CONCLUSIONS: A well-designed leaderboard should be user-friendly and encompass best practices in gamification principles while collecting and storing data for research analyses. Easy storage and export of data allow for longitudinal record keeping that can be leveraged both to track compliance and to enable social competition.

Canadian brain cancer survival rates by tumour type and region: 1992-2008.

OBJECTIVES: To investigate patterns of survival among brain cancer patients in Canada. METHODS: Canadian Cancer Registry data were obtained for all patients with first-ever primary malignant brain tumours diagnosed between 1992 and 2008 (n = 38,095). Follow-up ended with patient death or December 31, 2008, whichever occurred first. Crude Kaplan-Meier estimates were calculated at one, two and five years post-diagnosis. Cox proportional hazard models were used to obtain adjusted hazard ratios by region for major histology types. A time-specific generalized linear model was used to obtain 5-year survival estimates for specific age group, sex and region for major histology types. RESULTS: The overall five-year survival rate was 27%. No significant difference in survival rate over time is observed. The highest 5-year survival rate was 65% (95% CI: 62.5%-67.4%) for oligodendrogliomas and the lowest was 4.0% (95% CI: 3.7%-4.3%) for glioblastomas. Compared to Ontario, the adjusted 5-year glioblastoma survival estimates were lower in British Columbia, Alberta and the Prairie provinces (Manitoba and Saskatchewan), while the survival estimates were lower in all other regions for diffuse astrocytoma, and lower in Manitoba and Saskatchewan for anaplastic astrocytomas. Estimates were significantly higher for oligodendrogliomas in Alberta, and for anaplastic oligodendrogliomas in Alberta and Quebec (p < 0.05). CONCLUSION: These data are consistent with previous literature in observing higher survival rates at younger ages, in female patients and for tumours with mixed oligo components. There is a need to further explore the underlying reasons for the observed variation in survival rates by region in an effort to improve the prognosis of brain cancer in the Canadian patient population.

Current Status of Brain Tumor Surveillance in Canada and Why it Matters.

The Brain Tumor Foundation of Canada has identified developing a pan-Canadian report on all primary brain tumors as a priority. The objective of this report is to present the history and rationale underlying reporting of brain tumors and to summarize the current status of brain tumor data collection and reporting in Canadian registries. We reviewed the literature on reporting history and rationale, conducted a survey of cancer registries across Canada, and reviewed cancer registry websites and Canadian Cancer Statistics Reports for publicly available descriptive statistics. A brain tumor surveillance system that includes data on both malignant and benign brain tumors is feasible within Canada and will include approximately twice the number of malignant cases currently reported. Once patterns of brain tumors become available, clinicians, researchers, and policy makers will have a clearer understanding of disease burden and how Canadian survival outcomes fare across regions and against other nations. Collaborative efforts on the part of cancer registry and neurooncology stakeholders will serve to enhance the quality and utility of this information for improving the overall patient experience.