Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study.

BACKGROUND: The risk of skin cancer associated with antihypertensive medication use is unclear, although thiazides have been implicated in regulatory safety warnings. We aimed to assess whether use of thiazides and other antihypertensives is associated with increased rates of keratinocyte carcinoma and melanoma. METHODS: We conducted a population-based inception cohort study using linked administrative health data from Ontario, 1998-2017. We matched adults aged ≥ 66 years with a first prescription for an antihypertensive medication (thiazides, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, ß-blockers) by age and sex to 2 unexposed adults who were prescribed a non-antihypertensive medication within 30 days of the index date. We evaluated each antihypertensive class in a separate cohort study. Our primary exposure was the cumulative dose within each class, standardized according to the World Health Organization's Defined Daily Dose. Outcomes were time to first keratinocyte carcinoma, advanced keratinocyte carcinoma and melanoma. RESULTS: The inception cohorts included a total of 302 634 adults prescribed an antihypertensive medication and 605 268 unexposed adults. Increasing thiazide exposure was associated with an increased rate of incident keratinocyte carcinoma (adjusted hazard ratios [HRs] per 1 Defined Annual Dose unit 1.08, 95% confidence interval [CI] 1.03-1.14), advanced keratinocyte carcinoma (adjusted HR 1.07, 95% CI 0.93-1.23) and melanoma (adjusted HR 1.34, 95% CI 1.01-1.78). We found no consistent evidence of association between other antihypertensive classes and keratinocyte carcinoma or melanoma. INTERPRETATION: Higher cumulative exposure to thiazides was associated with increased rates of incident skin cancer in people aged 66 years and older. Consideration of other antihypertensive treatments in patients at high risk of skin cancer may be warranted.

Association between diabetes and haematological malignancies: a population-based study.

AIMS/HYPOTHESIS: Contemporary data for the association of diabetes with haematological malignancies are lacking. We evaluated the risk of developing haematological malignancies and subsequent mortality in individuals with diabetes compared with those without diabetes. METHODS: We conducted a population-based observational study using healthcare databases from Ontario, Canada. All Ontario residents 30 years of age or older free of cancer and diabetes between 1 January 1996 and 31 December 2015 were eligible for inclusion. Using Cox regression analyses, we explored the association between diabetes and the risk and mortality of haematological malignancies (leukaemia, lymphoma, multiple myeloma). The impact of timing on associations was evaluated with analyses stratified by time since diabetes diagnosis (<3 months, 3 months to 1 year, ≥1 year). RESULTS: We identified 1,003,276 individuals with diabetes and age and sex matched these to 2,006,552 individuals without diabetes. Compared with individuals without diabetes, those with diabetes had a modest but significantly higher risk of a haematological malignancy (adjusted HR 1.10 [95% CI 1.08, 1.12] p < 0.0001). This association persisted across all time periods since diabetes diagnosis. Among those with haematological malignancies, diabetes was associated with a higher all-cause mortality (HR 1.36 [95% CI 1.31, 1.41] p < 0.0001) compared with no diabetes, as well as cause-specific mortality. CONCLUSIONS/INTERPRETATION: Diabetes is associated with a higher risk of haematological malignancies and is an independent risk factor of all-cause and cause-specific mortality. Greater efforts for lifestyle modification may not only reduce diabetes burden and its complications but may also potentially lower risk of malignancy and mortality. Graphical abstract.

Temporal Trends and Factors Associated with Home Hemodialysis Technique Survival in Canada.

BACKGROUND AND OBJECTIVES: The last 15 years has seen growth in home hemodialysis (HD) utilization in Canada owing to reports of improved outcomes relative to patients on conventional in-center HD. What effect growth has had on home HD technique and patient survival during this period is not known. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We compared the risk of home HD technique failure, mortality, and the composite outcome among three incident cohorts of patients on home HD in Canada: 1996-2002, 2003-2007, and 2008-2012. A multivariable piece-wise exponential model was used to evaluate all outcomes using inverse probability of treatment and censoring weights. RESULTS: A total of 1869 incident patients on home HD were identified from the Canadian Organ Replacement Register. Relative to those treated between 2003 and 2007 (n=568), the risk of home HD technique failure was similar between patients treated between 1996 and 2002 (n=233; adjusted hazard ratio [AHR], 1.39; 95% confidence interval [95% CI], 0.78 to 2.46) but higher among incident patients on home HD treated between 2008 and 2012 (n=1068; AHR, 1.51; 95% CI, 1.06 to 2.15). Relative to patients treated between 2003 and 2007, adjusted mortality was similar among those treated between 2008 and 2012 (AHR, 0.83; 95% CI, 0.58 to 1.19) and those treated between 1996 and 2002 (AHR, 0.67; 95% CI, 0.38 to 1.21). The risk of the composite outcome of death and technique failure was similar across cohorts, as was the risk of receiving a kidney transplant. Increasing age, diabetes as a comorbidity, and smoking status were associated with an increased risk of death as well as the composite outcome. Medium-sized facilities had a lower risk of death, technique failure, and the composite outcome compared with larger facilities. CONCLUSIONS: A higher risk of technique failure was seen in the most contemporary era. Further characterization of the risk factors for, and causes of technique failure is needed to develop strategies to improve patient retention on home HD.

Increased hemodialysis catheter use in Canada and associated mortality risk: data from the Canadian Organ Replacement Registry 2001-2004.

BACKGROUND AND OBJECTIVES: The 1999 Canadian vascular access guidelines recommend the fistula as the access of choice. The study describes the trends in hemodialysis access use, variation among provinces, and the association with mortality from 2001 to 2004. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: An observational study of adult patients registered in Canadian Organ Replacement Registry on hemodialysis. Access trends were examined among incident and prevalent hemodialysis patients adjusted for age, sex, body mass index, late referral, race, smoking status, province, etiology of end-stage renal disease, and comorbidities. Cox proportional hazard regression analysis was used to analyze risk for death for patients followed to December 31, 2005. RESULTS: From 2001 to 2004, incident catheter use increased from 76.8% to 79.1%, fistulas decreased from 21.6% to 18.6%, and grafts remained between 2.1% to 2.6%. Prevalent catheter use increased from 41.8% to 51.7%, and fistulas and grafts decreased from 46.8% to 41.6% and 11.4% to 6.7%, respectively. There was significant variation in incident and prevalent fistulae use among the provinces. Adjustment for differences in patient characteristics did not change these trends. Incident catheter use was associated with a 6 times greater risk of death compared with fistula or graft use combined. CONCLUSIONS: In Canada there has been a decrease in fistulae and grafts with a subsequent increase in catheters that is not explained by changes in patient characteristics. Vascular access use varied by province, suggesting differences in practice patterns. Because incident catheter use was associated with increased mortality, urgent measures are needed to develop strategies to decrease catheter use.