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Importance Keratinocyte carcinoma (KC), also known as nonmelanoma skin cancer, is the most common malignancy after solid organ transplant. Epidemiologic data on posttransplant KC in North America are limited by a lack of KC capture in cancer and transplant registries. Objective To estimate the incidence and identify risk factors for posttransplant KC. Design, Setting, and Participants This population-based inception cohort study in Ontario, Canada, used linked administrative databases and a health insurance claims–based algorithm. Participants were adult recipients of a first kidney, liver, heart, or lung transplant from January 1, 1994, to December 31, 2012. The cohort (n = 10 198) was followed up to December 31, 2013. Data were analyzed from May 31, 2016, to April 21, 2017. Exposures Solid organ transplant with functioning graft. Main Outcomes and Measures Age- and sex-adjusted standardized incidence ratio for KC in the transplant cohort was compared with that in the general population. Cumulative incidence of posttransplant KC was estimated using cumulative incidence functions, accounting for the competing risks of death or kidney graft loss. The association between KC and patient-, transplant-, and health services–related factors was evaluated with a multivariable cause-specific hazards model. Results A total of 10 198 transplant recipients were included in the study. The median (interquartile range [IQR]) age at transplant was 51 (41-59) years, with most recipients being male (6608 [64.8%]) and white (5964 [58.5%]). Posttransplant KC was diagnosed in 1690 patients (16.6%) after a median (IQR) of 3.96 (1.94-7.09) years, with an incidence rate of 2.63 per 100 patient-years (95% CI, 2.51-2.76). The rate of KC was significantly higher after transplant compared with the general population (standardized incidence ratio, 6.61; 95% CI, 6.31-6.93). The highest 10-year cumulative incidence was in the subsets of patients with a history of pretransplant skin cancer (66.5%), older than 50 years at transplant (27.5% for 51-65 years; 40.5% for >65 years), and of the white race (24.1%). The strongest independent risk factors for KC included older age at transplant (adjusted hazard ratio [aHR], 9.27; 95% CI, 7.08-12.14 for >65 years vs 18-35 years), white vs black race (aHR, 8.50; 95% CI, 4.03-17.91), pretransplant invasive skin cancer (aHR, 4.30; 95% CI, 3.72-4.98), and posttransplant precancerous skin lesions (aHR, 4.32; 95% CI, 3.77-4.95). Conclusions and Relevance The incidence of KC appeared to be substantially increased after transplant, particularly in patients who were older at transplant, were white, and had a history of cancerous or precancerous skin tumors; intensified skin cancer screening, education, and early use of chemopreventive interventions may be warranted for these high-risk patient subsets.

This study characterizes the exclusion of patients with chronic kidney disease (CKD) in randomized clinical trials of drug treatment for bladder, breast, colorectal, lung, and prostate cancer.

Importance Observational studies have associated patent ductus arteriosus (PDA) ligation among preterm infants with adverse neonatal outcomes and neurodevelopmental impairment in early childhood, with a resultant secular trend away from surgical treatment. However, to our knowledge, studies have inadequately addressed sources of residual bias, including survival bias and major neonatal morbidities arising before exposure to ligation. Objective Evaluate the association between PDA ligation vs medical management and neonatal and neurodevelopmental outcomes. Design, Setting, and Participants This retrospective cohort study of preterm infants younger than 28 weeks gestational age born between January 1, 2006, and December 31, 2012, with clinical and echocardiography diagnoses of hemodynamically significant PDA was conducted at 3 tertiary neonatal intensive care units and affiliated follow-up programs. Exposure Surgical ligation vs medical management. Main Outcomes and Measures The primary outcome was a composite of death or neurodevelopmental impairment (NDI) at 18 to 24 months corrected age. Secondary outcomes included death before discharge, NDI, moderate-severe chronic lung disease, and severe retinopathy of prematurity. Multivariable logistic regression analysis was used to adjust for perinatal and postnatal confounders. Results Of 754 infants with hemodynamically significant PDA (mean [standard deviation] gestational age 25.7 [1.2] weeks and birth weight 813 [183] grams), 184 (24%) underwent ligation. Infants who underwent ligation had a higher frequency of morbidities before PDA closure, including sepsis, necrotizing enterocolitis, and a dependence on mechanical ventilation. After adjusting for perinatal characteristics and preligation morbidities, there was no difference in the odds of death or NDI (adjusted odds ratio (aOR), 0.83; 95% CI, 0.52-1.32), NDI (aOR, 1.27; 95% CI, 0.78-2.06), chronic lung disease (aOR, 1.36; 95% CI, 0.78-2.39) or severe retinopathy of prematurity (aOR, 1.61; 95% CI, 0.85-3.06). Ligation was associated with lower odds of mortality (aOR, 0.09; 95% CI, 0.04-0.21). Conclusions and Relevance Patent ductus arteriosus ligation among preterm neonates younger than 28 weeks gestational age was not associated with the composite outcome of death or NDI, and there were no differences in chronic lung disease, retinopathy of prematurity, or NDI among survivors. Mortality was lower among infants who underwent ligation, though residual survival bias could not be excluded. Previously reported associations of ligation with increased morbidity may be because of bias from confounding by indication.

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.

A shortage of organs for transplant has prompted many countries to encourage citizens to register (“opt in”) to donate their organs and tissues when they die.1 However, less than 40% of the public is registered for organ donation in most countries with a registry.1 One common fear is that physicians will not take all measures to save the life of a registered citizen at a time of illness.2 Showing that many physicians are registered for organ donation themselves could help dispel this myth. Although most physicians in surveys support organ donation,3 whether they are actually registered remains unknown.