The medical and functional burden of surviving childhood ependymoma: A population-based study in Ontario, Canada.

BACKGROUND: Few studies have characterized the burden of late effects among childhood ependymoma survivors. To address this gap, we examined these sequelae using real-world health services data in a population-based ependymoma survivor cohort. METHODS: All individuals younger than 18 years diagnosed with an ependymoma in Ontario, Canada between 1987 and 2015 who had survived at least 5 years from their latest pediatric cancer event (index date) were matched 1:5 with population controls. Following linkage with provincial health services data, the cumulative incidences of multiple medical and functional outcomes between survivors and controls were compared. RESULTS: Among 96 survivors, 77.1% had been irradiated and 9.4% had received cisplatin. At 10 years post-index, survivors were at significantly higher risk of all-cause mortality (7.1%, 95% confidence interval [CI]: 1.0-13.3 vs. 0.3%, 95% CI: 0.0-1.0; p = .0002), non-obstetric hospitalization (45.1%, 95% CI: 32.6-56.7 vs. 10.6%, 95% CI: 7.6-14.1; p < .0001), stroke (6.5%, 95% CI: 2.3-13.7 vs. 0%; p < .0001), severe hearing loss requiring an amplification device (7.5%, 95% CI: 2.7-15.7 vs. 0%; p < .0001), receiving homecare service (27.6%, 95% CI: 18.5-37.5 vs. 7.7%, 95% CI: 5.3-10.7; p < .0001), and submitting a disability support prescription claim (24.0%, 95% CI: 14.8-34.3 vs. 5.4%, 95% CI: 3.5-7.8; p < .0001) compared to controls. CONCLUSIONS: Pediatric ependymoma survivors are highly vulnerable to severe late sequelae, including death, stroke, severe hearing loss, and disability. Urgent efforts are needed to improve risk-stratification approaches that mitigate exposure to toxic therapies for children with lower risk disease. Interventions to prevent or decrease the risk of developing late sequelae are critical to optimizing survivor long-term health.

Internal and external validation of an updated ICD-10-CA to AIS-2005 update 2008 algorithm.

BACKGROUND: Administrative data are a powerful tool for population-level trauma research but lack the trauma-specific diagnostic and injury severity codes needed for risk-adjusted comparative analyses. The objective of this study was to validate an algorithm to derive Abbreviated Injury Scale (AIS-2005 update 2008) severity scores from Canadian International Classification of Diseases (ICD-10-CA) diagnostic codes in administrative data. METHODS: This was a retrospective cohort study using data from the 2009 to 2017 Ontario Trauma Registry for the internal validation of the algorithm. This registry includes all patients treated at a trauma center who sustained a moderate or severe injury or were assessed by a trauma team. It contains both ICD-10-CA codes and injury scores assigned by expert abstractors. We used Cohen's kappa (𝜅) coefficient to compare AIS-2005 Update 2008 scores assigned by expert abstractors to those derived using the algorithm and the intraclass correlation coefficient to compare assigned and derived Injury Severity Scores. Sensitivity and specificity for detection of a severe injury (AIS score, ≥ 3) were then calculated. For the external validation of the algorithm, we used administration data to identify adults who either died in an emergency department or were admitted to hospital in Ontario secondary to a traumatic injury (2009-2017). Logistic regression was used to evaluate the discriminative ability and calibration of the algorithm. RESULTS: Of 41,869 patients in the Ontario Trauma Registry, 41,793 (99.8%) had at least one diagnosis matched to the algorithm. Evaluation of AIS scores assigned by expert abstractors and those derived using the algorithm demonstrated a high degree of agreement in identification of patients with at least one severe injury (𝜅 = 0.75; 95% confidence interval [CI], 0.74-0.76). Likewise, algorithm-derived scores had a strong ability to rule in or out injury with AIS ≥ 3 (specificity, 78.5%; 95% CI, 77.7-79.4; sensitivity, 95.1; 95% CI, 94.8-95.3). There was strong correlation between expert abstractor-assigned and crosswalk-derived Injury Severity Score (intraclass correlation coefficient, 0.80; 95% CI, 0.80-0.81). Among the 130,542 patients identified using administrative data, the algorithm retained its discriminative properties. CONCLUSION: Our ICD-10-CA to AIS-2005 update 2008 algorithm produces reliable estimates of injury severity and retains its discriminative properties with administrative data. Our findings suggest that this algorithm can be used for risk adjustment of injury outcomes when using population-based administrative data. LEVEL OF EVIDENCE: Diagnostic Tests/Criteria; Level II.

A population-based study of the direct longitudinal health care costs of upper extremity trauma in patients aged 18-65 years.

BACKGROUND: Upper extremity (UE) trauma represents a common reason for emergency department visits, but the longitudinal economic burden of this public health issue is unknown. This study assessed the 3-year attributable health care use and expenditure after UE trauma requiring acute surgical intervention, with specific focus on injuries that affect function of the hand and wrist. METHODS: We conducted an incidence-based, propensity score-matched cohort study (2006-2014) in Ontario, Canada, using linked administrative health care data to identify case patients and matched control patients. We matched adults with hand, wrist and UE nerve trauma requiring surgery 1:4 to control patients. We compared total direct health care costs, including 1-year pre-index costs, between case and control patients using a differences-in-difference methodology. The primary outcome was attributable health care costs within 3 years of injury. RESULTS: We matched patients with trauma (n = 26 123) to noninjured patients (n = 104 353). Mean direct health care costs attributable to UE trauma were $9210 (95% confidence interval [CI] 8880 to 9550) within 3 years. Patients with trauma had significantly more emergency department visits (≥ 3 visits: 25% v. 12%; p < 0.001), mental health visits (34% v. 28%; p < 0.05) and secondary surgeries (25% v. 5%; p < 0.001). Specific patient populations had significantly greater attributable costs: patients requiring post-traumatic mental health visits ($11 360 v. $7090; p < 0.001), inpatient surgery ($14 060 v. $5940, p < 0.001) and complex injuries ($13 790 v. $7930; p < 0.001). INTERPRETATION: Health care expenditure increased more than fivefold in the year after UE trauma surgery and remained greater than the matched cohort for the subsequent 2 years. Those with more serious injuries and post-injury visits for mental health were associated with higher costs, requiring further study for this public health issue. The mean 1-year pre-injury and 1-year post-injury total costs were $1710 and $9350, respectively.

The Burden of Surviving Childhood Medulloblastoma: A Population-Based, Matched Cohort Study in Ontario, Canada.

PURPOSE: Survivors of childhood medulloblastoma suffer from substantial late effects. We characterized these sequelae using real-world health services data in a population-based cohort of medulloblastoma survivors. METHODS: All 5-year medulloblastoma survivors diagnosed age < 18 years between 1987 and 2015 in Ontario, Canada, were identified and matched 1:5 with population controls. Index date was 5 years from latest pediatric cancer event. Linkage to provincial administrative health data allowed for comparison of cumulative incidences of several adverse outcomes. RESULTS: Two hundred thirty survivors, 81.3% of whom had received craniospinal irradiation, were matched with 1,150 controls. The 10-year postindex cumulative incidence of all-cause mortality was 7.9% (95% CI, 3.9 to 11.8) in survivors versus 0.6% (95% CI, 0.1 to 1.1) in controls (hazard ratio [HR], 21.5; 95% CI, 9.8 to 54.0). The cumulative incidence of stroke was higher in survivors (4.8%; 95% CI, 2.2 to 9.0) compared with controls (0.1; 95% CI, 0.01 to 0.7; HR, 45.6; 95% CI, 12.8 to 289.8). Hearing loss requiring an amplification device was present in 24.9% (95% CI, 18.8 to 31.4) of survivors versus 0.3% (95% CI, 0.1 to 1.0) of controls (HR, 96.3; 95% CI, 39.7 to 317.3). Disability support prescription claims were submitted by 44.5% (95% CI, 37.1 to 51.6) of survivors versus 5.5% (95% CI, 4.2 to 7.1) of controls (HR, 10.0; 95% CI, 7.3 to 13.6). Female survivors were significantly less likely to deliver a liveborn child compared with controls (HR, 0.2; 95% CI, 0.1 to 0.7). CONCLUSION: Survivors of medulloblastoma have significant long-term medical sequelae, increased all-cause mortality, and are frequently dependent on disability supports. Efforts to reduce the toxicity of current therapy, specifically incorporating molecularly informed risk stratification to spare low- and intermediate-risk survivors the toxicity of treatment, are urgently needed. These findings should prompt a re-evaluation of our current treatment approaches where research focused on late-effect interventions should be prioritized.

Development of algorithms to identify individuals with Neurofibromatosis type 1 within administrative data and electronic medical records in Ontario, Canada.

BACKGROUND: There is limited population-based data on Neurofibromatosis type 1 (NF1) in North America. We aimed to develop and validate algorithms using administrative health data and electronic medical records (EMRs) to identify individuals with NF1 in Ontario, Canada. METHODS: We conducted an electronic free-text search of 15 commonly-used terms related to NF1 in the Electronic Medical Records Primary Care Database. Records were reviewed by two trained abstractors who classified them as confirmed, possible, and not NF1. An investigator with clinical expertise performed final NF1 classification. Patients were classified as confirmed if there was a documented diagnosis, meeting NIH criteria. Patients were classified as possible if (1) NF1 was recorded in the cumulative patient profile, but no clinical information to support the diagnosis; (2) only one criterion for diagnosis (e.g. child of confirmed case) but no further data to confirm or rule out. We tested different combinations of outpatient and inpatient billing codes, and applied a free-text search algorithm to identify NF1 cases in administrative data and EMRs, respectively. RESULTS: Of 273,440 eligible patients, 2,058 had one or more NF1 terms in their medical records. The terms "NF", "café-au-lait", or "sheath tumour" were constrained to appear in combination with another NF1 term. This resulted in 837 patients: 37 with possible and 71 with confirmed NF1. The population prevalence ranged from 1 in 3851 (confirmed NF1) to 1 in 2532 (possible and confirmed NF1). Billing code algorithms had poor performance, with overall low PPV (highest being 71%). The accuracy of the free-text EMR algorithm in identifying patients with NF1 was: sensitivity 85% (95% CI 74-92%), specificity 100% (95% CI 100-100%), positive predictive value 80% (95% CI 69-88%), negative predictive value 100% (95% CI 100-100%), and false positive rate 20% (95% CI 11-33%). Of false positives, 53% were possible NF1. CONCLUSIONS: A free-text search algorithm within the EMR had high sensitivity, specificity and predictive values. Algorithms using billing codes had poor performance, likely due to the lack of NF-specific codes for outpatient visits. While NF1 ICD-9 and 10 codes are used for hospital admissions, only ~ 30% of confirmed NF1 cases had a hospitalization associated with an NF1 code.

Quantifying cancer risk from exposures to medical imaging in the Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study: research methods and cohort profile.

PURPOSE: The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. METHODS: The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages. RESULTS: The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine. CONCLUSION: The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.

Risks of late mortality and morbidity among survivors of childhood acute leukemia with Down syndrome: A population-based cohort study.

BACKGROUND: Children with leukemia and Down syndrome (DS) are at higher risk of acute treatment toxicities than those without DS. Whether late toxicity risks are also elevated is unknown. METHODS: The authors identified all patients diagnosed with leukemia before the age of 18 years in Ontario, Canada between 1987 and 2013 and who survived greater than 5 years since their last pediatric cancer event. Survivors were divided into those with and without DS, matched by birth year, sex, leukemia type, and receipt of radiation. DS survivors were matched to individuals with DS without childhood cancer (DS controls) in a 1:10 ratio. Outcomes were identified through linkage to population-based health services databases. RESULTS: DS survivors (n = 79) experienced inferior overall survival compared to non-DS survivors (n = 231) (20-year overall survival, 81.7% ± 6.8% vs 98.3% ± 1.2%; hazard ratio [HR], 12.8; P < .0001) and to DS controls (n = 790; 96.3% ± 1.2%; HR, 5.4 P < .0001). Pulmonary and infectious deaths were noted among DS survivors. There was no difference in the incidence of congestive heart failure between DS survivors and either control cohort, nor of hearing loss or dementia between DS survivors and DS controls. CONCLUSIONS: DS survivors were at substantially higher risk of late mortality than non-DS survivors or DS controls. This excess risk was not attributable to cardiac- or subsequent malignant neoplasm-related late effects, historically main causes of premature death among non-DS survivors. Chronic morbidities associated with DS were not increased compared to DS controls. DS-specific surveillance guidelines may be warranted.

Morbidity and mortality associated with prescription cannabinoid drug use in COPD.

INTRODUCTION: Respiratory-related morbidity and mortality were evaluated in relation to incident prescription oral synthetic cannabinoid (nabilone, dronabinol) use among older adults with chronic obstructive pulmonary disease (COPD). METHODS: This was a retrospective, population-based, data-linkage cohort study, analysing health administrative data from Ontario, Canada, from 2006 to 2016. We identified individuals aged 66 years and older with COPD, using a highly specific, validated algorithm, excluding individuals with malignancy and those receiving palliative care (n=185 876 after exclusions). An equivalent number (2106 in each group) of new cannabinoid users (defined as individuals dispensed either nabilone or dronabinol, with no dispensing for either drug in the year previous) and controls (defined as new users of a non-cannabinoid drug) were matched on 36 relevant covariates, using propensity scoring methods. Cox proportional hazard regression was used. RESULTS: Rate of hospitalisation for COPD or pneumonia was not significantly different between new cannabinoid users and controls (HR 0.87; 95% CI 0.61-1.24). However, significantly higher rates of all-cause mortality occurred among new cannabinoid users compared with controls (HR 1.64; 95% CI 1.14-2.39). Individuals receiving higher-dose cannabinoids relative to controls were observed to experience both increased rates of hospitalisation for COPD and pneumonia (HR 2.78; 95% CI 1.17-7.09) and all-cause mortality (HR 3.31; 95% CI 1.30-9.51). CONCLUSIONS: New cannabinoid use was associated with elevated rates of adverse outcomes among older adults with COPD. Although further research is needed to confirm these observations, our findings should be considered in decisions to use cannabinoids among older adults with COPD.

Predictors of Opioid-related Adverse Pulmonary Events among Older Adults with Chronic Obstructive Pulmonary Disease.

Rationale: Although opioids are frequently prescribed in chronic obstructive pulmonary disease (COPD), there is poor understanding regarding which individuals will experience pulmonary harm upon exposure.Objectives: We sought to identify patient characteristics and opioid drug properties predictive of opioid-related adverse pulmonary events among older adults with chronic COPD.Methods: A retrospective, population-based, cohort study design was used, analyzing Ontario heath administrative data. Individuals aged 66 years and older, with validated, physician-diagnosed COPD receiving a new opioid drug were included. Adverse pulmonary events (defined as an emergency room visit, hospitalization, or death related to either COPD or pneumonia) occurring within 30 days following new opioid receipt were considered. Multivariable-adjusted, cause-specific hazard modeling was used to identify predictors of adverse pulmonary events.Results: Out of 169,517 older adults with COPD receiving a new opioid, 4,861 (2.9%) experienced an adverse pulmonary event within 30 days. Factors independently predisposing to adverse pulmonary events included older age (≥85 yr old: hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.26-1.49), long-term-care home residence (HR, 1.32; 95% CI, 1.21-1.44), severe COPD exacerbation within the preceding year (HR, 2.96; 95% CI, 2.77-3.17), comorbidities (including non-COPD lung disease [HR, 1.16; 95% CI, 1.09-1.23], congestive heart failure [HR, 1.22; 95% CI, 1.14-1.30], sleep disorder [HR, 1.22; 95% CI, 1.15-1.30], and dementia [HR, 1.14; 95% CI, 1.05-1.24]); other psychoactive medication receipt, including benzodiazepines (HR, 1.27; 95% CI, 1.19-1.35) and serotonergic antidepressants (HR, 1.10; 95% CI, 1.03-1.19), and receipt of an opioid-only agent (HR, 1.35; 95% CI, 1.26-1.46). Factors that independently protected from adverse pulmonary events included female sex (HR, 0.78; 95% CI, 0.73-0.82), surgery within the preceding year (HR, 0.70; 95% CI, 0.64-0.77), and musculoskeletal disease (HR, 0.75; 95% CI, 0.70-0.80). No significant associations were observed between adverse pulmonary events and opioid half-life duration or opioid daily dosage.Conclusions: Patient and opioid drug factors predictive of opioid-related adverse pulmonary events among older adults with COPD were identified, which may assist with safer opioid prescribing.

Hospital resources do not predict accuracy of secondary trauma triage: A population-based analysis.

BACKGROUND: The identification of patients who require transfer from non-trauma centers to trauma centers (secondary triage) is complicated by high rates of undertriage and overtriage. The objective of this study was to evaluate variations in secondary triage accuracy across non-trauma centers and identify factors associated with highly accurate secondary triage. METHODS: We performed a population-based study of injured patients who presented to non-trauma centers in a large regional trauma system. Patients were categorized as undertriaged, overtriaged, or appropriately triaged based on transfer status and presence of a severe injury (Injury Severity Score >15, death within 24 hours, or critical injury as defined by the American College of Surgeons). Mixed-effect models, adjusted for case mix and hospital resource, were used to compare triage accuracy across hospitals and identify factors associated with high-performing centers. RESULTS: Among 118,973 patients identified at 182 non-trauma centers, 37,528 (31.5%) had severe injuries. The majority (76.9%) of severely injured patients were not transferred to a trauma center (undertriaged), while 9.6% of nonseverely injured patients were transferred to a trauma center (overtriaged). Mixed-effect models demonstrated that at the average hospital severely injured patients were 3.76 times more likely to be transferred than nonseverely injured patients (diagnostic odds ratio, 3.76; 95% confidence interval, 3.20-4.31). Despite significant variation in triage accuracy across hospitals, adjusted analyses suggested that local resources bore no relationship to triage accuracy. CONCLUSION: Triage accuracy varies significantly across non-trauma centers, after adjusting for hospital resources. These findings suggest that other potentially modifiable factors play a key role in transfer decisions. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.