Rinku Sutradhar

Bleeding and Perforation After Outpatient Colonoscopy and Their Risk Factors in Usual Clinical Practice

BACKGROUND & AIMS The most widely quoted complication rates for colonoscopy are from case series performed by expert endoscopists. Our objectives were to evaluate the rates of bleeding, perforation, and death associated with outpatient colonoscopy and their risk factors in a population-based study. METHODS We identified all individuals 50 to 75 years old who underwent an outpatient colonoscopy during April 1, 2002, to March 31, 2003, in British Columbia, Alberta, Ontario, and Nova Scotia, Canada. Using administrative data, we identified all individuals who were admitted to hospital with bleeding or perforation within 30 days following the colonoscopy in each province. We calculated the pooled rates of bleeding and perforation from the 4 provinces. In Ontario, we abstracted the hospital charts of all deaths that occurred within 30 days following the procedure. We used generalized estimating equations models to evaluate factors associated with bleeding and perforation. RESULTS We identified 97,091 persons who had an outpatient colonoscopy. The pooled rates of colonoscopy-related bleeding and perforation were 1.64/1000 and 0.85/1000, respectively. The death rate was 0.074/1000 or approximately 1/14,000. Older age, male sex, having a polypectomy, and having the colonoscopy performed by a low-volume endoscopist were associated with increased odds of bleeding or perforation. CONCLUSIONS Although colonoscopy has established benefits for the detection of colorectal cancer and adenomatous polyps, the procedure is associated with risks of serious complications, including death. Older age, male sex, having a polypectomy, and having the procedure done by a low-volume endoscopist were independently associated with colonoscopy-related bleeding and perforation.

Analysis of Administrative Data Finds Endoscopist Quality Measures Associated With Postcolonoscopy Colorectal Cancer

BACKGROUND & AIMS Most quality indicators for colonoscopy measure processes; little is known about their relationship to patient outcomes. We investigated whether characteristics of endoscopists, determined from administrative data, are associated with development of postcolonoscopy colorectal cancer (PCCRC). METHODS We identified individuals diagnosed with colorectal cancer in Ontario from 2000 to 2005 using the Ontario Cancer Registry. We determined performance of colonoscopy using Ontario Health Insurance Plan data. Patients who had complete colonoscopies 7 to 36 months before diagnosis were defined as having a PCCRC. Patients who had complete colonoscopies within 6 months of diagnosis had detected cancers. We determined if endoscopist factors (volume, polypectomy and completion rate, specialization, and setting) were associated with PCCRC using logistic regression, controlling for potential covariates. RESULTS In the study, 14,064 patients had a colonoscopy examination within 36 months of diagnosis; 584 (6.8%) with distal and 676 (12.4%) with proximal tumors had PCCRC. The endoscopists specialty (nongastroenterologist/nongeneral surgeon) and setting (non-hospital-based colonoscopy) were associated with PCCRC. Those who underwent colonoscopy by an endoscopist with a high completion rate were less likely to have a PCCRC (distal: odds ratio [OR], 0.73; 95% confidence interval [CI], 0.54-0.97; P = .03; proximal: OR, 0.72; 95% CI, 0.53-0.97; P = .002). Patients with proximal cancers undergoing colonoscopy by endoscopists who performed polypectomies at high rates had a lower risk of PCCRC (OR, 0.61; 95% CI, 0.42-0.89; P < .0001). Endoscopist volume was not associated with PCCRC. CONCLUSIONS Endoscopist characteristics derived from administrative data are associated with development of PCCRC and have potential use as quality indicators.

Impact of Androgen Deprivation Therapy on Cardiovascular Disease and Diabetes

PURPOSE Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort. METHODS Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined. Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio [HR], 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes. CONCLUSION Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.

Symptom burden and performance status in a population‐based cohort of ambulatory cancer patients

For ambulatory cancer patients, Ontario has standardized symptom and performance status assessment population‐wide, using the Edmonton Symptom Assessment System (ESAS) and Palliative Performance Scale (PPS). In a broad cross‐section of cancer outpatients, the authors describe the ESAS and PPS scores and their relation to patient characteristics.

Multiple superoxide dismutase 1/splicing factor serine alanine 15 variants are associated with the development and progression of diabetic nephropathy: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics study

BACKGROUND— Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes. RESEARCH DESIGN AND METHODS— We performed an individual-based genetic association study with time to renal and retinal outcomes in 1,362 white probands with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Specifically, we genotyped 1,411 SNPs that capture common variations in 212 candidate genes for long-term complications and analyzed them for association with the time from DCCT baseline to event for renal and retinal outcomes using multivariate Cox proportion hazards models. To address multiple testing and assist interpretation of the results, false discovery rate q values were calculated separately for each outcome. RESULTS— We observed association between rs17880135 in the 3′ region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64–4.18], P = 5.6 × 10−5, q = 0.06) and persistent microalbuminuria (1.82 [1.29–2.57], P = 6.4 × 10−4, q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P < 10−3) with persistent microalbuminuria, whereas rs17880135 and rs17881180 were similarly associated with the development of severe nephropathy. Attempts to replicate the findings in three cross-sectional case-control studies produced equivocal results. We observed no striking differences between risk genotypes in serum SOD activity, serum SOD1 mass, or SOD1 mRNA expression in lymphoblastoid cell lines. CONCLUSIONS— Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT/EDIC study.

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis

BackgroundSurgery is the fundamental curative option for gastric cancer patients. Imaging scans are routinely prescribed in an attempt to stage the disease prior to surgery. Consequently, the correlation between radiology exams and pathology is crucial for appropriate treatment planning.MethodsSystematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009. We calculated the accuracy, overstaging rate, understaging rate, Kappa statistic, sensitivity, and specificity for abdominal ultrasound (AUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) with respect to the gold standard (pathology). We also compared the performance of CT by detector number and image type. A meta-analysis was performed.ResultsFor pre-operative T staging MRI scans had better performance accuracy than CT and AUS; CT scanners using ≥4 detectors and multi-planar reformatted (MPR) images had higher staging performances than scanners with <4 detectors and axial images only. For pre-operative N staging PET had the lowest sensitivity, but the highest specificity among modalities; CT performance did not significantly differ by detector number or addition of MPR images. For pre-operative M staging performance did not significantly differ by modality, detector number, or MPR images.ConclusionsThe agreement between pre-operative TNM staging by imaging scans and post-operative staging by pathology is not perfect and may affect treatment decisions. Operator dependence and heterogeneity of data may account for the variations in staging performance. Physicians should consider this discrepancy when creating their treatment plans.

Fracture Types and Risk Factors in Men With Prostate Cancer on Androgen Deprivation Therapy: A Matched Cohort Study of 19,079 Men

PURPOSE Accumulating evidence shows that androgen deprivation therapy is associated with osteoporosis and fragility fractures of the spine, hip and wrist. One study suggested that androgen deprivation therapy may also be associated with nonfragility fractures in older men. Whether other clinical risk factors independently increase the risk of fractures is not certain. MATERIALS AND METHODS Using linked administrative databases in Ontario, Canada, we matched 19,079 men 66 years old or older with prostate cancer with at least 6 months of continuous androgen deprivation therapy or bilateral orchiectomy with men with prostate cancer who had never received androgen deprivation. Matching variables were age, prior cancer treatment, diagnosis year, comorbidity, medication, prior fractures and socioeconomic variables. Primary outcomes were a typical fragility fracture of the spine, hip or wrist and any fracture. Independent predictors of fracture outcomes were assessed with Cox proportional hazards models. RESULTS At a mean 6.47-year followup androgen deprivation therapy was associated with an increased risk of fragility fracture (HR 1.65, 95% CI 1.53-1.78) and any fracture (HR 1.46, 95% CI 1.39-1.54). Independent predictors of fragility and any fracture were increasing age, prior bone thinning medications, chronic kidney disease, prior dementia, prior fragility fracture and prior osteoporosis diagnosis or treatment (p <0.05). CONCLUSIONS Continuous androgen deprivation therapy for at least 6 months is associated with an increased risk of fracture. Increasing age, prior osteoporotic fracture and dementia are important clinical factors that may warrant greater consideration of anti-osteoporotic therapy in these men.

Multiple SOD1/SFRS15 variants are associated with the development and progression of diabetic nephropathy: The DCCT/EDIC Genetics study

BACKGROUND— Despite familial clustering of nephropathy and retinopathy severity in type 1 diabetes, few gene variants have been consistently associated with these outcomes. RESEARCH DESIGN AND METHODS— We performed an individual-based genetic association study with time to renal and retinal outcomes in 1,362 white probands with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Specifically, we genotyped 1,411 SNPs that capture common variations in 212 candidate genes for long-term complications and analyzed them for association with the time from DCCT baseline to event for renal and retinal outcomes using multivariate Cox proportion hazards models. To address multiple testing and assist interpretation of the results, false discovery rate q values were calculated separately for each outcome. RESULTS— We observed association between rs17880135 in the 3′ region of superoxide dismutase 1 (SOD1) and the incidence of both severe nephropathy (hazard ratio [HR] 2.62 [95% CI 1.64–4.18], P = 5.6 × 10−5, q = 0.06) and persistent microalbuminuria (1.82 [1.29–2.57], P = 6.4 × 10−4, q = 0.46). Sequencing and fine-mapping identified additional SOD1 variants, including rs202446, rs9974610, and rs204732, which were also associated (P < 10−3) with persistent microalbuminuria, whereas rs17880135 and rs17881180 were similarly associated with the development of severe nephropathy. Attempts to replicate the findings in three cross-sectional case-control studies produced equivocal results. We observed no striking differences between risk genotypes in serum SOD activity, serum SOD1 mass, or SOD1 mRNA expression in lymphoblastoid cell lines. CONCLUSIONS— Multiple variations in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy in the DCCT/EDIC study.

Cancer Mortality Among Recipients of Solid-Organ Transplantation in Ontario, Canada

IMPORTANCE Solid-organ transplant recipients (SOTRs) are at greater risk of developing some cancers than the general population; however, because they are also at increased risk of mortality from noncancer causes, the effect of transplantation on cancer mortality is unclear. OBJECTIVE To describe cancer mortality in SOTRs and to assess whether SOTRs are at increased risk of cancer mortality compared with the general population. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of patients who underwent solid-organ transplantation in Ontario, Canada, between 1991 and 2010 with 85 557 person-years of follow-up through December 31, 2011. Solid-organ transplantation was identified using the national transplant register and linked to the provincial cancer registry and administrative databases. The analysis was conducted between November 2013 and February 2015. EXPOSURE Solid-organ transplantation. MAIN OUTCOMES AND MEASURES Cancer mortality for SOTRs was compared with that of the general population using standardized mortality ratios (SMRs). Mortality and cause of death were ascertained by record linkage between the Canadian Organ Replacement Register, the Ontario Cancer Registry, and the Office of the Registrar General of Ontario death database. RESULTS A total of 11 061 SOTRs were identified, including 6516 kidney, 2606 liver, 929 heart, and 705 lung transplantations. Recipients had a median (interquartile range) age of 49 (37-58) years, and 4004 (36.2%) were women. Of 3068 deaths, 603 (20%) were cancer related. Cancer mortality in SOTRs was significantly elevated compared with the Ontario population (SMR, 2.84 [95% CI, 2.61-3.07]). The risk remained elevated when patients with pretransplant malignant neoplasms (n = 1124) were excluded (SMR, 1.93 [95% CI, 1.75-2.13]). The increased risk was observed irrespective of transplanted organ. The SMR for cancer death after solid-organ transplantation was higher in children (SMR, 84.61 [95% CI, 52.00-128.40]) and lower in patients older than 60 years (SMR, 1.88 [95% CI, 1.62-2.18]) but remained elevated compared with the general population at all ages. CONCLUSIONS AND RELEVANCE Cancer death rate in SOTRs was increased compared with that expected in the general population; cancer was the second leading cause of death in these patients. Advances in prevention, clinical surveillance, and cancer treatment modalities for SOTRs are needed to reduce the burden of cancer mortality in this population.

Assessing the Volume-Outcome Hypothesis and Region-Level Quality Improvement Interventions: Pancreas Cancer Surgery in Two Canadian Provinces

BackgroundThe volume-outcome hypothesis suggests that if increased provider procedure volume is associated with improved patient outcomes, then greater regionalization to high-volume providers should improve region-level outcomes. Quality improvement interventions for pancreas cancer surgery implemented in year 1999 in Ontario, Canada were designed to regionalize surgery to high-volume hospitals and decrease operative mortality. Similar interventions were not used in Quebec, Canada. We assessed the volume-outcome hypothesis and the impact of the Ontario quality improvement interventions.Materials and MethodsAdministrative databases helped identify pancreatic resections from years 1994 to 2004 and relevant patient and hospital characteristics. Hospitals were high-volume if they provided ≥10 procedures in a given calendar year. Outcomes were regionalization of surgery to high-volume providers and rates of operative mortality.ResultsFrom 1994 to 2004 the percentage of cases in high-volume hospitals increased from 33 to 71% in Ontario and from 36 to 76% in Quebec. Annual rates of operative mortality dropped in Ontario (10.4–2.2% or less) and changed little in Quebec (7.2–9.8%). Changes in measures over time in both provinces were similar before and after year 1999.ConclusionsRegionalization was associated with improved operative mortality in Ontario but not in Quebec, undermining the volume-outcome hypothesis. The Ontario quality improvement interventions likely were of little influence since patterns in regionalization and operative mortality were similar before and after year 1999.