Dataset Information

Incidence of new-onset diabetes mellitus and association with mortality in childhood solid organ transplant recipients: a population-based study.

ABSTRACT:

Background

Precise estimates of the long-term risk of new-onset diabetes and its impact on mortality among transplanted children are not known.

Methods

We conducted a cohort study comparing children undergoing solid organ (kidney, heart, liver, lung and multiple organ) transplant (n?=?1020) between 1991 and 2014 with healthy non-transplanted children (n?=?7?134?067) using Ontario health administrative data. Outcomes included incidence of diabetes among transplanted and non-transplanted children, the relative hazard of diabetes among solid organ transplant recipients, overall and at specific intervals posttransplant, and mortality among diabetic transplant recipients.

Results

During 56 019 824 person-years of follow-up, the incidence rate of diabetes was 17.8 [95% confidence interval (CI) 15-21] and 2.5 (95% CI 2.5-2.5) per 1000 person-years among transplanted and non-transplanted children, respectively. The transplant cohort had a 9-fold [hazard ratio (HR) 8.9; 95% CI 7.5-10.5] higher hazard of diabetes compared with those not transplanted. Risk was highest within the first year after transplant (HR 20.7; 95% CI 15.9-27.1), and remained elevated even at 5 and 10?years of follow-up. Lung and multiple organ recipients had a 5-fold (HR 5.4; 95% CI 3.0-9.8) higher hazard of developing diabetes compared with kidney transplant recipients. Transplant recipients with diabetes had a three times higher hazard of death compared with those who did not develop diabetes (HR 3.3; 95% CI 2.3-4.8).

Conclusions

The elevated risk of diabetes in transplant recipients persists even after a decade, highlighting the importance of ongoing surveillance. Diabetes after transplantation increases the risk of mortality among childhood transplant recipients.

SUBMITTER: Chanchlani R

PROVIDER: S-EPMC6399486 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Incidence of new-onset diabetes mellitus and association with mortality in childhood solid organ transplant recipients: a population-based study.

Chanchlani Rahul R Kim Sang Joseph SJ Dixon Stephanie N SN Jassal Vanita V Banh Tonny T Borges Karlota K Vasilevska-Ristovska Jovanka J Paterson John Michael JM Ng Vicky V Dipchand Anne A Solomon Melinda M Hebert Diane D Parekh Rulan S RS

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20190301 3

<h4>Background</h4>Precise estimates of the long-term risk of new-onset diabetes and its impact on mortality among transplanted children are not known.<h4>Methods</h4>We conducted a cohort study comparing children undergoing solid organ (kidney, heart, liver, lung and multiple organ) transplant (n = 1020) between 1991 and 2014 with healthy non-transplanted children (n = 7 134 067) using Ontario health administrative data. Outcomes included incidence of diabetes among transplanted and non-transpl ...[more]

PMID: 30060206

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Project description:ImportanceLittle is known about the incidence and outcomes of Clostridioides difficile infection (CDI) in solid organ transplant (SOT) recipients.ObjectiveTo estimate the CDI incidence and outcomes in SOT recipients.Design, setting, and participantsA population-based cohort study was conducted using administrative health care data for all Ontario, Canada, residents who received organ allografts from April 1, 2003, to December 31, 2017; March 31, 2020, was the end of the study period.Main outcomes and measuresThe primary outcome was hospital admission with CDI diagnosis. The secondary outcomes included all-cause death, intensive care unit admission, acute kidney injury requiring dialysis, and fulminant CDI comprising any of the following: toxic megacolon, ileus, perforation, or colectomy. The association between short- vs long-term mortality (ie, death occurring within or after 90 days post-CDI) and the following variables was evaluated: age, sex, Deyo-Charlson Comorbidity Index, SOT type, early- vs late-onset CDI, fulminant CDI, intensive care unit admission, and acute kidney injury requiring acute dialysis.ResultsOverall, 10 724 SOT recipients (6901 [64.4%] men; median age, 54 [IQR, 44-62] years) were eligible. Kidney transplant was the most common SOT type (6453 [60.2%]). The median follow-up time was 5.0 (IQR, 2.3-8.8) years, resulting in 61 987 person-years of follow-up. A total of 726 patients (6.8%) were hospitalized with CDI. The 1-year CDI incidence significantly increased in annual cohorts (ie, from 23.1; 95% CI, 12.8-41.8 per 1000 person-years in 2004 to 46.7; 95% CI, 35.0-62.3 per 1000 person-years in 2017; P = .001). Clostridioides difficile was associated with a 16.8% rate (n = 122) of 90-day mortality. In patients who underwent kidney transplant, CDI was typically late-onset (median interval, 2.2; IQR, 0.4-6.0 years) compared with recipients of other organs. Acute kidney injury requiring dialysis was significantly associated with short-term (adjusted odds ratio [aOR], 1.86; 95% CI, 1.07-3.26) and long-term (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.29-2.78) mortality, and late-onset CDI was also significantly associated with a greater risk of short-term (aOR, 4.26; 95% CI, 2.51-7.22) and long-term (aHR, 2.49; 95% CI, 1.78-3.49) mortality.Conclusions and relevanceIn this study, increasing CDI trends in annual cohorts of SOT recipients were observed. Posttransplant CDI was associated with mortality, and late-onset CDI was associated with a greater risk of death than early-onset CDI. These findings suggest that preventive strategies should not be limited to the initial months following transplantation. Comprehensive therapeutic approaches targeting acute kidney injury risk factors in SOT recipients may reduce short- and long-term post-CDI mortality.

Project description:BackgroundSolid organ transplant recipients have an elevated risk of cancer. Quantifying deaths attributable to cancer can inform priorities to reduce cancer burden.MethodsLinked transplantation and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987-2014). Population-attributable fractions (PAFs) of deaths due to cancer and corresponding cancer-attributable mortality rates were estimated using Cox models.ResultsAmong 221,962 solid organ transplant recipients, 15,012 developed cancer. Approximately 13% of deaths (PAF, 13.2%) were attributable to cancer, corresponding to a cancer-attributable mortality rate of 516 per 100,000 person-years. Lung cancer was the largest contributor to mortality (PAF, 3.1%), followed by non-Hodgkin lymphoma (NHL; PAF, 1.9%), colorectal cancer (PAF, 0.7%), and kidney cancer (PAF, 0.5%). Cancer-attributable mortality rates increased with age at transplantation, reaching 1229 per 100,000 person-years among recipients aged ≥65 years. NHL was the largest contributor among children (PAF, 4.1%) and lung cancer was the largest contributor among recipients aged ≥50 years (PAFs, 3.7%-4.3%). Heart recipients had the highest PAF (16.4%), but lung recipients had the highest cancer-attributable mortality rate (1241 per 100,000 person-years). Overall, mortality attributable to cancer increased steadily with longer time since transplantation, reaching 15.7% of deaths (810 per 100,000 person-years) at ≥10 years after transplantation. Comparison of cancer-attributable mortality rates with specified causes of death indicated that some deaths recorded as other causes might instead be caused by cancer or its treatment.ConclusionsCancer is a substantial cause of mortality among solid organ transplant recipients, with major contributions reported from lung cancer and NHL. Cancer-attributable mortality increases with age and time since transplantation, and therefore cancer deaths will become an increasing burden as recipients live longer.

Project description:BACKGROUND:Immunosuppressed solid organ transplant recipients [SOTRs] have elevated rates of certain rare cancers caused by viruses. Evaluating risk of rare cancers among SOTRs may provide etiological clues for additional cancers linked to poor immunity and viral infections. METHODS:We performed a cohort study of 262,455 SOTRs (1987-2014) from the US SOTR registry linked to 17 population-based cancer registries. First cancers in SOTRs were categorized using an established classification scheme based on site and histology. Standardized incidence ratios (SIRs) compared risk in SOTRs to the general population. We used Poisson regression to calculate incidence rate ratios (IRRs) according to immune-related SOTR characteristics, including time since transplant (i.e., duration of immunosuppression). All statistical tests are two-sided. RESULTS:We examined 694 distinct cancer subtypes, with 33 manifesting statistically significantly elevated SIRs (Bonferroni p?<?7.2 x 10-5). All 33 are rare (incidence <6 per 100,000 person-years) and several have known viral etiology (e.g. Merkel cell carcinoma (SIR = 24.7, 95%CI = 20.8 to 29.1). Additional cancers that were increased include squamous cell carcinomas (SCCs) of the lip (SIR range = 18.3-19.8), eye/adnexa (SIR = 13.8, 95%CI = 7.9 to 22.3), salivary gland (SIR = 9.3, 95%CI = 6.1 to 13.5), and nasal cavity/sinuses (SIR = 4.5, 95%CI = 2.8 to 6.8); sebaceous adenocarcinoma (SIR = 34.3, 95%CI = 26.3 to 44.0); malignant fibrous histiocytoma (15.4); and subtypes of bladder, kidney, lung, and colon cancer (SIR range = 3.2-13.3). Incidence of several cancers increased over time since transplant (ptrend<0.05), including SCCs of the lip, salivary gland, and anogenital sites. CONCLUSIONS:SOTRs experience elevated rates of several rare cancers. Because some of these cancers exhibit aggressive behavior with poor outcomes, it is important to further characterize the role of immunity and the potential involvement of oncogenic viruses to improve prevention and treatment.

Project description:ImportanceRisk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights.ObjectiveTo assess SC incidence and patient survival after solid organ transplantation.Design, setting, and participantsThis cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals.Main outcomes and measuresSebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population.ResultsA total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P < .001), race/ethnicity (non-Hispanic Black vs non-Hispanic White, IRR, 0.28; 95% CI, 0.10-0.77; P = .01), older age (IRR, 7.85; 95% CI, 3.85-16.0; ≥65 vs 0-44 years; P < .001 for trend), use of thymoglobulin induction (IRR, 1.82; 95% CI, 1.16-2.86; P = .009), posttransplant cutaneous squamous cell carcinoma (IRR, 4.60; 95% CI, 2.67-7.94; P < .001), and longer time since transplant (IRR, 8.40; 95% CI, 3.94-17.90; ≥10 vs 0-1.9 years; P < .001 for trend). Muir-Torre syndrome-associated cancers were rare among both SOTRs and others with SC (3.3%-4.1%). Among patients with SC, prior transplantation was associated with increased overall mortality (adjusted hazard ratio, 2.09; 95% CI, 1.45-3.01), although few deaths were attributed to SC (4 of 92 SOTRs [4.3%]; 235 of 3585 non-SOTRs [6.6%]).Conclusions and relevanceAmong SOTRs, results of this large cohort study suggest that SC was associated with measures of immunosuppression, and overall survival was worse than for other patients with SC. Findings also suggest a possible role for UV radiation in carcinogenesis.

Dataset Information

Incidence of new-onset diabetes mellitus and association with mortality in childhood solid organ transplant recipients: a population-based study.

Background

Methods

Results

Conclusions

Publications

Incidence of new-onset diabetes mellitus and association with mortality in childhood solid organ transplant recipients: a population-based study.

Similar Datasets

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