Differences in Drowning Rates between Rural and Non-Rural Residents of Ontario, Canada

The objective of our study was to determine if rural residence was associated with an increased risk of drowning in Ontario, Canada. We conducted a retrospective cohort study of all unintentional drowning deaths in Ontario Canada from 2004 to 2008. Age-adjusted mortality rates for males and females living in rural and non-rural areas were calculated using direct standardization, with non-rural residents as the reference population. We identified a total of 564 unintentional drowning deaths. The majority (89%) of fatal drowning victims were male, and 75% percent of victims were from non-rural area. Excluding bathtub drowning deaths, the age-adjusted drowning mortality rate was significantly higher for both males (rate ratio 2.8; 95% CI, 2.3- 3.4) and females (rate ratio 2.8; 95% CI 1.5- 5.0) from rural compared to non-rural areas. In Ontario, rural residence was associated with an increased risk of unintentional drowning

Severe Erosive Pill Esophagitis Induced by Crizotinib Therapy: A Case Report and Literature Review

Previous case reports have described esophagitis thought to be secondary to crizotinib, an oral tyrosine-kinase inhibitor used in the treatment of anaplastic lymphoma kinase- (ALK-) positive non-small cell lung cancer (NSCLC). In those reports, the interval development of esophagitis was between two days and three months after initiating or reinitiating crizotinib therapy. We present a woman who developed ulcerative esophagitis ten months after beginning crizotinib therapy, which is highly unusual. We believe the provoking factor was a change in her medication administration routine, done to accommodate religious practices during the period of Ramadan. This case illustrates the mechanism of pill esophagitis and reinforces the importance of patient education when it comes to medication administration. Clinicians may consider early imaging or investigations in patients with concerning symptomatology in the context of crizotinib therapy or other offending medications. Future research may help to uncover additional risk factors for this exceedingly rare diagnosis in this patient population. Most importantly, this case highlights nonpharmacologic ways to improve tolerability and decrease adverse effects of a highly effective chemotherapeutic agent.Peer Reviewe

Severe Erosive Pill Esophagitis Induced by Crizotinib Therapy: A Case Report and Literature Review

Previous case reports have described esophagitis thought to be secondary to crizotinib, an oral tyrosine-kinase inhibitor used in the treatment of anaplastic lymphoma kinase- (ALK-) positive non-small cell lung cancer (NSCLC). In those reports, the interval development of esophagitis was between two days and three months after initiating or reinitiating crizotinib therapy. We present a woman who developed ulcerative esophagitis ten months after beginning crizotinib therapy, which is highly unusual. We believe the provoking factor was a change in her medication administration routine, done to accommodate religious practices during the period of Ramadan. This case illustrates the mechanism of pill esophagitis and reinforces the importance of patient education when it comes to medication administration. Clinicians may consider early imaging or investigations in patients with concerning symptomatology in the context of crizotinib therapy or other offending medications. Future research may help to uncover additional risk factors for this exceedingly rare diagnosis in this patient population. Most importantly, this case highlights nonpharmacologic ways to improve tolerability and decrease adverse effects of a highly effective chemotherapeutic agent

Rare ATGL Haplotypes Are Associated with Increased Plasma Triglyceride Concentrations in the Greenland Inuit

Objectives. To genotype common genetic variants found in the adipose triglyceride lipase (ATGL) gene and test them for association with cardiovascular disease risk factors in the Greenland Inuit. Study design. Candidate gene association study of discrete and quantitative traits related to cardiovascular health. Methods. ATGL was sequenced in 10 European subjects to identify DNA sequence variants. The identified polymorphisms were subsequently genotyped in a population-based cohort of 1,218 unrelated Greenland Inuit subjects, ascertained from the Greenland Population Study. Genotypes and reconstructed haplotypes were tested for association with cardiovascular disease risk factors using additive, dominant or recessive models, corrected for age, sex and body mass index. Results. Five single nucleotide polymorphisms and one 4-base pair deletion were identified in the European sample and were similarly polymorphic in the Greenland Inuit. Independently, variants were not associated with any cardiovascular traits. However, reconstructed rare ATGL haplotypes were associated with increased plasma triglyceride (TG) concentrations compared to the major haplotype under a dominant model (1.21 +/-0.7 mmol/L and 1.11 +/-0.6 mmol/L, respectively, p=0.006). Conclusions. Rare ATGL haplotypes are associated with increased plasma TG concentrations in the Greenland Inuit

Red Blood Cell Transfusions and Iron Therapy for Patients Presenting with Acute Upper Gastrointestinal Bleeding: A Survey of Canadian Gastroenterologists and Hepatologists

Introduction. There is limited data evaluating physician transfusion practices in patients with acute upper gastrointestinal bleeding (UGIB). Methods. A web-based survey was sent to 500 gastroenterologists and hepatologists across Canada. The survey included clinical vignettes where physicians were asked to choose transfusion thresholds. Results. The response rate was 41% (N=203). The reported hemoglobin (Hgb) transfusion trigger differed by up to 50 g/L. Transfusions were more liberal in hemodynamically unstable patients compared to stable patients (mean Hgb of 86.7 g/L versus 71.0 g/L; p<0.001). Many clinicians (24%) reported transfusing a hemodynamically unstable patient at a Hgb threshold of 100 g/L and the majority (57%) are transfusing two units of RBCs as initial management. Patients with coronary artery disease (mean Hgb of 84.0 g/L versus 71.0 g/L; p<0.01) or cirrhosis (mean Hgb of 74.4 g/L versus 71.0 g/L; p<0.01) were transfused more liberally than healthy patients. Fewer than 15% would prescribe iron to patients with UGIB who are anemic upon discharge. Conclusions. The transfusion practices of gastroenterologists in the management of UGIB vary widely and more high-quality evidence is needed to help assess the efficacy and safety of selected transfusion thresholds in varying patients presenting with UGIB

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were &lt; 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were &lt; 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so