Venous Thromboembolism in Surgically Treated Esophageal Cancer Patients: A Provincial Population-Based Study.

Objective Venous thromboembolism (VTE) is a major cause of morbidity and mortality in surgical patients. Surgery for esophageal cancer carries a high risk of VTE. This study identifies the risk factors and associated mortality of thrombotic complications among patients undergoing esophageal cancer surgery. Methods All patients in the province of Ontario undergoing esophageal cancer surgery from 2007 to 2017 were identified. Logistic regression identified VTE risk factors at 90 days and 1 year postoperatively. A flexible parametric survival analysis compared mortality and survival up to 5 years after surgery for patients with and without a postoperative VTE. Results Overall 9,876 patients with esophageal cancer were identified; 2,536 (25.7%) underwent surgery. VTE incidence at 90 days and 1 year postoperatively were 4.1 and 6.3%, respectively. Patient factors including age, sex, performance status, and comorbidities were not associated with VTE risk. VTE risk peaked at 1 month after surgery, with a subsequent decline, plateauing after 6 months. Adenocarcinoma was strongly associated with VTE risk compared with squamous cell carcinoma (SCC) (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.38-4.63, p = 0.003). VTE risk decreased with adjuvant chemotherapy (OR = 0.58, 95% CI 0.36-0.94, p = 0.028). Postoperative VTE was associated with decreased survival at 1 and 5 years (hazard ratio = 1.57, 95% CI 1.23-2.00, p < 0.001). Conclusion Esophageal cancer patients with postoperative VTE have worse long-term survival compared with those without thrombotic complications. Adenocarcinoma carries a higher VTE risk compared with SCC. Strategies to reduce VTE risk should be considered to reduce the negative impacts on survival conferred by thrombotic events.

Survival effects of time to surgery for Stage I lung cancer: A population-based study.

OBJECTIVES: To examine the impact of time to surgery (TTS) on survival among patients with stage I non-small cell lung cancer (NSCLC). METHODS: All patients in the Canadian province of Ontario with stage I NSCLC from 2007 to 2017 were included. A logistic regression identified the predictors of TTS and a flexible parametric model estimated survival rates based on TTS. RESULTS: Over the study period, 6428 patients with stage I NSCLC undergoing surgical resection were identified, of which 62.5% had TTS >28 days. Less than half these patients (40.8%) underwent open resection, with 19.3% undergoing open sublobar and 21.5% undergoing open lobectomy. Adenocarcinoma and squamous cell carcinoma tumors accounted for 33.3% and 22.0% of cases, respectively. The majority (85.6%) of patients lived in urban areas within 50 km of a regional cancer center (76.9%). Variables that predicted TTS >28 days include age and extent of resection. After adjustment for VATS vs. open resection, age, sex, frailty, year of diagnosis, histology of tumor, and extent of resection, the hazard ratio for TTS >28 days was 1.26 (95%CI:1.13-1.40), indicating a 26% increased risk of all-cause mortality (p < 0.0001). The highest 5-year survival was observed for patients with stage I disease undergoing resection within 28 days. CONCLUSIONS: The present study found age and extent of resection to be associated with increased TTS. Importantly, patients with TTS >28 days had reduced long-term survival.

Venous Thromboembolism in Surgical Lung Cancer Patients: A Provincial Population-Based Study.

BACKGROUND: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in surgical patients. Thoracic surgery patients are at increased risk due to inherent technical and disease-specific factors. Other surgical specialties have adopted postdischarge extended VTE prophylaxis; however evidence is scarce in thoracic surgery. This study aims to identify VTE risk factors and associated mortality among surgical lung cancer patients. METHODS: Using administrative databases all patients in the province of Ontario undergoing lung cancer surgery from 2007 to 2017 were identified. Logistic regression identified VTE risk factors at 90 days and 1 year postoperatively. A flexible parametric survival analysis compared mortality and survival up to 5 years after surgery between patients with and without VTE. RESULTS: Of 65,513 patients diagnosed with lung cancer, 12,626 (19.3%) underwent surgery. VTE incidence at 90 days and 1 year postoperatively was 1.3% and 2.7%, respectively. Open and more extensive resections carried an increased VTE risk, with pneumonectomy conferring the highest risk (odds ratio, 2.36; P < .001). Stage III and IV disease carried a 3.19 and 4.97 times higher risk of VTE, respectively, compared with stage I (P < .001). The hazard ratio for mortality at 1 year for patients with VTE was 2.01 (P < .001). Patients suffering a VTE had reduced 5-year survival. CONCLUSIONS: Patients undergoing pneumonectomy and those with advanced stage have an increased VTE risk. Patients suffering a thrombotic complication have an increased risk of mortality and decreased 5-year survival. Accordingly strategies to reduce VTE risk should be considered in patients undergoing high-risk operations to reduce the mortality of VTEs.

Uptake of minimally invasive surgery for early stage colorectal cancer and its effect on survival: A population-based study.

PURPOSE: The uptake of minimally invasive surgery (MIS) for colorectal cancer (CRC) varies between jurisdictions. We aimed to identify the factors associated with the uptake of MIS for early-stage CRC and its oncologic outcomes in the Canadian province of Ontario. METHODS: This study includes all patients with CRC in Ontario from 2007 to 2017. A logistic regression analysis was used to identify the predictors of MIS and a flexible parametric survival model to estimate survival rates based on MIS versus open surgery. RESULTS: In total, 14,675 patients with CRC were identified of which 29.5% had MIS resections. The likelihood of undergoing MIS decreased with age, disease stage, and distance to the regional cancer center, and increased with year of diagnosis. The likelihood of mortality for MIS was significantly lower compared to open surgery (p < 0.001). In terms of survival, MIS was most beneficial to older patients with stage II disease, despite their lower likelihood of receiving MIS. CONCLUSIONS: Despite the lower uptake of MIS among older patients and patients with stage II disease, these patients had the greatest long-term survival benefit from MIS. This suggests further use of laparoscopy to patient populations that are often excluded.

Change in treatment modality and trends in survival among stage I non-small cell lung cancer patients: a population-based study.

BACKGROUND: A number of treatment modalities are available to patients with early non-small cell lung cancer (NSCLC) but there is inconsistency regarding their effects on survival. The associated survival of each treatment modality is crucial for patients in making informed treatment decisions. We aimed to examine the change in treatment modality and trends in survival for patients with stage I NSCLC and assess the association between treatment modality and survival. METHODS: All patients diagnosed with stage I NSCLC in the Canadian province of Ontario between 2007 and 2015 were included in this population-based study. We used a flexible parametric model to estimate the trends in survival rate. RESULTS: Overall, 11,910 patients were identified of which 7,478 patients (62.8%) received surgical resection and 2,652 (22.3%) radiation only. The proportion of patients who received radiation only increased from 13.2% in 2007 to 28.0% in 2015 (P-for-trend <0.001). Survival increased for all treatment modalities from 2007 to 2015. The increase in 5-year survival was more than 20% for all surgical groups and more than 35% for radiation-only group. CONCLUSIONS: The survival of patients with stage I NSCLC increased for all treatment modalities over the study period, most distinctly in elderly patients, which coincided with a rise in the use of radiation therapy. While surgical resection was associated with the best chance of 5-year survival, radiation therapy is a safe and effective treatment for medically inoperable patients with early disease.

The TRAAGIC score: early predictors of inpatient mortality in adult trauma patients

Background: Scoring systems are important in prognostication and decision-making in the management of trauma patients. However, they often include an extensive list of factors not easily recalled by clinicians on admission. Additionally, multivariable analyses examining predictors of mortality in these patients is lacking. This study aimed to develop and validate a mortality prediction score for adult trauma inpatients. The intention was to create a scoring tool that could be easily remembered and implemented by clinicians. Methods: This is a retrospective analysis of 5175 adult trauma patients treated at a level 1 trauma centre in Hamilton, Ontario, from 2002 to 2013. For derivation of the score, logistic regression was applied to data collected from 2002 to 2006 to identify potential predictors. Variables with p ≤ 0.10 identified from univariable analysis were entered in the multivariable logistic regression. Statistical significance was set at a value of 0.05. The prediction performance of the score was then assessed and validated on data for trauma patients treated from 2007 to 2013. The discrimination ability and calibration of the validation model were assessed. Frequencies, odds ratios with 95% confidence intervals (CIs) and C-statistics were reported. Results: The TRAAGIC prediction score (transfusion, age, airway, hyperglycemia, international normalized ratio, creatinine) showed a C-index of 0.85 (95% CI 0.83­0.87) in the derivation cohort. The TRAAGIC score had high discrimination and good calibration when applied to the validation cohort. Conclusion: The TRAAGIC score is an easily remembered and straightforward toolthat can reasonably predict inpatient mortality for adult trauma patients.

Contexte: Les systèmes de classification sont importants pour le pronostic et le processus décisionnel relatifs à la prise en charge des patients de traumatologie. Par contre, ces systèmes incluent souvent une longue liste de facteurs dont les cliniciens peuvent difficilement se rappeler quand un patient est admis. De plus, on déplore l'absence d'analyses multivariées sur les prédicteurs de mortalité chez ces patients. La présente étude visait à concevoir et valider un score de prédiction de la mortalité pour les polytraumatisés adultes hospitalisés. L'intention était de créer pour les médecins un outil de classification facile à retenir et simple à utiliser. Méthodes: Il s'agit d'une analyse rétrospective de 5175 polytraumatisés adultes traités dans un centre de traumatologie de niveau 1 de Hamilton, en Ontario, de 2002 à 2013. Le score est dérivé de l'analyse de régression logistique appliquée aux données recueillies de 2002 à 2006 pour dégager les prédicteurs potentiels. Les variables identifiées à partir d'analyses univariées dont p ≤ 0,10 ont été incluses dans l'analyse de régression logistique multivariée. La portée statistique a été fixée à 0,05. Le rendement prédictif du score a alors été évalué et validé pour les polytraumatisés traités de 2007 à 2013. On a évalué le pouvoir discriminant et l'étalonnage du modèle de validation, et on a fait état des fréquences, des rapports des cotes avec intervalles de confiance (IC) de 95 % et de la statistique C. Résultats: Le score de prédiction TRAAGIC (transfusion, âge, voies aériennes, hyperglycémie, ratio international normalisé, créatinine) a produit un indice de concordance de 0,85 (IC de 95 % 0,83­0,87) dans la cohorte de dérivation. Le score TRAAGIC s'est révélé doté d'un important pouvoir discriminant et d'un bon étalonnage lorsqu'on l'a appliqué à la cohorte de validation. Conclusion: Le score TRAAGIC est un outil facile à retenir et simple à utiliser qui permet de prédire raisonnablement le risque de mortalité chez les polytraumatisés adultes hospitalisés.

Geographic and socioeconomic predictors of perforated appendicitis: A national Canadian cohort study.

BACKGROUND/PURPOSE: Appendiceal perforation significantly impacts the outcomes of pediatric appendicitis. While socioeconomic status affects perforation risk in the United States, these effects should dissipate in a universal healthcare system. The specific spatial patterns associated with perforation have also never been delineated. This study examined the effect of geography and SES on appendiceal perforation in Canada's universal healthcare system. METHODS: Using administrative databases, Canadian children with appendicitis from 2008 to 2015 were identified. Perforation rates were examined based on rurality, distance from treating hospital, and SES. A spatial analysis identified neighborhoods with high perforation rates. Predictors of high perforation clusters were determined using logistic regression. RESULTS: Over the study period, 43,055 children with appendicitis were identified. The overall perforation rate was 31.5%. Rural neighborhoods and those >125 km from the treating hospital were more likely to be within a high perforation cluster (OR 2.39, 95%CI 1.31-4. 02, p = 0.001; and OR 2.55, 95%CI 1.35-4.47, p = 0.001, respectively). Children in high perforation clusters were more likely to suffer complications. SES was not associated with perforation rates. CONCLUSIONS: In this population-based study, appendiceal perforation was not a function of SES, but a spatial phenomenon. These findings highlight disparities in access to surgical care in Canada. LEVEL OF EVIDENCE: Prognosis study, level II.

A population-based cohort examining factors affecting all-cause morbidity and cost after pediatric appendectomy: Does annual adult procedure volume matter?

BACKGROUND: The purpose of this study was to examine factors affecting morbidity and cost after pediatric appendectomy and particularly the role of adult surgical volume. MATERIALS AND METHODS: This was population-based study including all pediatric patients who underwent appendectomy for appendicitis in Canada (excluding Quebec) from 2008 to 2015. All-cause morbidity was the main outcome of interest. Cost of the index admission (in 2014 Canadian dollars) was a secondary outcome. Hierarchal linear and logistic regressions were used to model the outcomes. RESULTS: Overall, 41,512 patients were identified. After adjustment, younger patients (OR = 0.98/year, 95%CI 0.97-0.99, p < 0.001), patients with comorbidities (OR = 2.20, 95%CI 1.96-2.46, p < 0.001), and those with perforated appendicitis (OR = 5.95, 95%CI 5.44-6.50, p < 0.001) were more susceptible to morbidity. Annual pediatric appendectomy volume was a significant predictor of reduced morbidity (OR = 0.85/20 cases, 95%CI 0.76-0.93, p < 0.001) as was the use of laparoscopy (OR = 0.81, 95%CI 0.72-0.91, p = 0.001). Conversely, annual adult appendectomy volume conferred no benefit nor did pediatric surgery specialty training. CONCLUSION: Outcomes after pediatric appendectomy are influenced by pediatric case volume, regardless of specialty training, but extra adult surgical volume confers no benefit.

Factors Associated With Outcomes and Costs After Pediatric Laparoscopic Cholecystectomy.

Importance: The prevalence of pediatric cholelithiasis is increasing with the epidemic of childhood obesity. With this rise, the outcomes and costs of pediatric laparoscopic cholecystectomy become an important public health and economic concern. Objective: To assess patient and health system factors associated with the outcomes and costs after laparoscopic cholecystectomy among Canadian children. Design, Setting, and Participants: This was a retrospective, population-based study of children 17 years and younger undergoing laparoscopic cholecystectomy from April 1, 2008, until March 31, 2015. The data source was the Canadian Institute for Health Information. The Canadian Institute for Health Information Discharge Abstract Database includes data from all Canadian hospitals. The analysis was limited to inpatient cholecystectomies. All Canadian children undergoing laparoscopic cholecystectomy were included. Exposure: The exposure in this study was laparoscopic cholecystectomy. Main Outcomes and Measures: The primary outcome was all-cause morbidity, a composite outcome of any complication that prolonged length of stay by 24 hours or required a second, unplanned procedure. The cost of the index admission was also calculated as a secondary outcome. These outcomes of interest were determined before data analysis. Odds ratios and 95% CIs were estimated using multilevel logistic regression models. Results: During the study period, 3519 laparoscopic cholecystectomies were performed; of these, 79.1% (n = 2785) were in girls, and 98.0% (n = 3450) were for gallstone disease. The overall morbidity rate was 3.9% (n = 137). After adjustment, patients with comorbidities were more susceptible to morbidity (odds ratio, 2.68; 95% CI, 1.78-3.86; P < .001). Operations for gallstones were less morbid. High-volume general surgeons had lower morbidity rates compared with low-volume pediatric surgeons (odds ratio, 0.32; 95% CI, 0.12-0.69; P = .005) independent of pediatric volumes. The mean (SD) unadjusted cost of a laparoscopic cholecystectomy was $4115 ($7273). Operative indication, complications, comorbidities, emergency admission, and surgeon volume were associated with cost. Conclusions and Relevance: The high-volume nature of adult general surgery translated to lower morbidity and cost after pediatric laparoscopic cholecystectomy, suggesting that adult volume is associated with pediatric outcomes. As the rate of pediatric gallstone disease increases, surgeon volume, rather than specialty training, should be considered when pursuing operative management.

Long-term trends in the incidence and relative survival of pancreatic cancer in Canada: A population-based study.

BACKGROUND/OBJECTIVE: The poor survival among pancreatic cancer patients accounts for a disproportionate number of cancer deaths, and there has been little or no improvement in the long-term survival of these patients. This study examines the long-term trends in incidence and relative survival of patients diagnosed with pancreatic cancer in Canada between 1992 and 2008. METHODS: We used pancreatic cancer data from the Canadian Cancer Registry. Incidence rate per age group was estimated over the aforementioned period. A flexible parametric model was used to estimate trends in one- and five-year relative survival for each age group and sex. Excess mortality rate was estimated to illustrate additional mortality due to a cancer diagnosis. RESULTS: In total, 34,577 patients with pancreatic cancer were identified, of which 49.3% were male. Mean age at diagnosis was 70.1 (SD = 12.3) years. Approximately 60.0% of patients were older than 70 years at diagnosis. There has been no change in the incidence rate of pancreatic cancer in Canada; however, it significantly decreased for men (80+) (p = 0.011). Although one-year relative survival increased over time for all patients, five-year relative survival increased only 5% for the youngest age group (<50 years). CONCLUSIONS: Overall survival of patients with pancreatic cancer remains low, although advances in chemotherapy and palliative care may have provided some improvement. Excess mortality remains highest shortly after diagnosis, which is likely attributable to the late diagnosis of pancreatic cancer.

Quality of life in children with epilepsy: How does it compare with the quality of life in typical children and children with cerebral palsy?

Our objective was to compare the quality of life (QoL) of children with epilepsy to that of typical children and children with cerebral palsy (CP). We measured self- and proxy-reported QoL of children with epilepsy and contrasted that with data for typical children (European KIDSCREEN project) and children with CP (SPARCLE study). Children ages 8-12 years with epilepsy were recruited from six Canadian sites. Same-aged children with CP and children in the general population aged 8-11 years came from several European countries. All participants completed the KIDSCREEN-52 questionnaire. Our results showed no clinically important differences (>0.5 SD) between self-reported QoL in 345 children with epilepsy compared with 489 children with CP or 5950 children in the general population. However, parents reported clinically important differences between the epilepsy and the other groups in five KIDSCREEN-52 domains. Compared with the CP group, parents of children with epilepsy reported better QoL in physical well-being (Cohen d=0.81), social support (d=0.80), and autonomy (d=0.72). Parents reported poorer QoL in the domains of mood and emotions compared with both contrast groups (d=-0.72 and d=-0.53), and in the domain of bullying compared with the CP group (d=-0.51). Families should find comfort in the results, which indicate that children with epilepsy do not perceive any important differences in QoL compared with their typical peers. The comparisons of parental reports detect their group-specific observations and worries that need to be addressed by the health-care providers and may require specifically designed assessment batteries followed by appropriate interventions.

Genetic markers of inflammation and their role in cardiovascular disease.

Atherosclerosis and associated cardiovascular diseases (CVD) are multifaceted disorders, influenced by environmental and heritable risk factors. Inflammation plays a significant role in each stage of atherosclerosis and as such, discovery and characterization of inflammatory biomarkers associated with risk of CVD is an active area of research. Because of the strong predicted genetic components of both CVD and inflammatory biomarkers, there is interest in identifying genetic determinants of inflammatory markers and characterizing their role in CVD. Recent developments in the methodological approaches of genetic epidemiology, especially genome-wide association studies and Mendelian randomization studies, have been effective in identifying novel gene associations and determining the causality of these genes with CVD. In this review, we will summarize the current understanding of the genetic architecture of inflammatory markers. The markers selected for this review include C-reactive protein, soluble intercellular adhesion molecule-1, interleukin-6, and P-selectin.