Late first acute rejection in pediatric kidney transplantation: A North American Pediatric Renal Trials and Collaborative Studies special study.

Rates of early AR in pediatric kidney transplantation have declined in every era but the most recent NAPRTCS cohort has shown an increase in late first AR rates. We hypothesized this was due to an increased proportion of deceased donor utilization and early steroid taper utilization. Using the NAPRTCS database, we compared the most recent three cohorts of patients transplanted between 2002-2006, 2007-2011, and 2012-2017. To determine variables that predict late first AR, we used two multivariable models: a standard Cox regression model and LASSO model. From the LASSO model, deceased donor source (P = .002), higher recipient age (P = .019), black race (P = .010), and transplant cohort 2012-17 (P = .014) were all significant predictors of more late first AR. On standard Cox regression analysis, those same variables, minus donor source, were significant, in addition to mycophenolates usage (P = .007) and lower eGFR at 12 months (P = .02). The most recent 2012-2017 cohort remains an independently significant risk factor for late first AR, suggesting unmeasured variables. Further research is needed to determine whether these higher late first AR rates will impact long-term graft survival in the most recent cohort.

Participant-Directed Intervention Tailoring Is Associated With Improvements in Glycemic Control for South Asian Adults With Type 2 Diabetes.

OBJECTIVES: Our aim was to determine the impact of a 3-month diabetes self-management education and support (DSME/DSMS) intervention involving both professional and peer support on glycemic control and diabetes distress in South Asian adults with type 2 diabetes (T2D) living in Metro Vancouver. METHODS: We recruited 114 South Asian adults with T2D for a study conducted across 7 sites in Metro Vancouver. A previous DSME/DSMS intervention was modified using participant feedback. Participants attended the updated intervention involving 6 biweekly group-based DSME sessions co-led by a diabetes educator and peer leader and 6 biweekly DSMS sessions delivered by a peer leader. Assessments were conducted at baseline and 3 months. Primary outcomes were glycated hemoglobin (A1C) and diabetes distress. Secondary outcomes included apolipoprotein B, blood pressure (BP), height and weight, waist circumference, diabetes support and depressive symptoms. RESULTS: After the 3-month intervention, linear mixed-effects modelling demonstrated A1C decreased significantly from 8.2% (66 mmol/mol) to 7.8% (62 mmol/mol) (p<0.0001), as did body mass index (from 30.02 to 29.7 kg/m2; p=0.0005) and diastolic BP (from 75.86 to 70.78 mmHg; p<0.0001). These reductions persisted after adjusting for the fixed-effects of age, sex, intensification of diabetes and BP medication, as well as random effects for subject and location. CONCLUSIONS: Participation in a professional plus peer-led intervention tailored by South Asian adults with T2D is associated with improved glycemic control and other favourable health outcomes.

A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes.

OBJECTIVES: We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia. METHODS: We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: (i) 45 mg loading weeks 0/4/16, (ii) 45 mg maintenance weeks 0/4/16/28/40, (iii) 90 mg loading weeks 0/4/16, and (iv) 90 mg maintenance weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses. RESULTS: Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90 mg maintenance dosing cohort had the smallest mean decline in C-peptide area under the curve (AUC) (0.1 pmol/ml). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1, and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A. CONCLUSION: Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90 mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response.

Do Cultural and Psychosocial Factors Contribute to Type 2 Diabetes Risk? A Look Into Vancouver's South Asian Community.

OBJECTIVES: South Asian immigrants are generally healthy upon arrival, but precipitously develop diabetes after immigration. Whether cultural and psychosocial factors contribute to diabetes risk in this ethnic minority group remains unclear. Existing prediction models focus primarily on clinical and lifestyle factors. This study explored whether nontraditional risk factors are incrementally predictive beyond traditional risk factors in this South Asian community. METHODS: In this cross-sectional study, we recruited 425 South Asian adults attending Sikh and Hindu temples in Metro Vancouver between July 2013 and June 2014. We measured traditional risk factors, including glycated hemoglobin (A1C), apolipoprotein B, systolic and diastolic blood pressure (BP), waist circumference, weight, body mass index (BMI), dietary patterns and physical activity level. Self-report questionnaires assessed cultural and psychosocial factors, including acculturation, dinnertime (timing of the evening meal), religion and depressive symptoms. We constructed a penalized multivariable linear model with A1C level using the least absolute shrinkage and selection operator (LASSO) approach to overcome issues of overfitting and reduce prediction error of previous diabetes prediction models. RESULTS: The LASSO model selected 24 risk factors for the optimal model to predict glycemic control. Results revealed that higher degree of acculturation (p=0.007), later dinnertime (p=0.01) and greater depressive symptoms (p=0.038) are important factors in diabetes risk in addition to traditional risk factors (fruit/vegetable/fibre intake, BMI and systolic BP). CONCLUSIONS: Nontraditional factors, such as cultural practices and emotional functioning, are also important predictors of diabetes risk and should be considered when culturally tailoring diabetes prevention programs.

Quality of life and socioeconomic indicators associated with survival of myeloid leukemias in Canada.

Understanding how patient-reported quality of life (QoL) and socioeconomic status (SES) relate to survival of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) may improve prognostic information sharing. This study explores associations among QoL, SES, and survival through administration of the Euro-QoL 5-Dimension, 3-level and Functional Assessment of Cancer Therapy-Leukemia and financial impact questionnaires to 138 adult participants with newly diagnosed AML or MDS in a longitudinal, pan-Canadian study. Cox regression and lasso variable selection models were used to explore associations among QoL, SES, and established predictors of survival. Secondary outcomes were changes in QoL, performance of the QoL instruments, and lost income. We found that higher QoL and SES were positively associated with survival. The Lasso model selected the visual analog scale of the EQ-5D-3L as the most important predictor among all other variables (P = .03; 92% selection). Patients with AML report improved QoL after treatment, despite higher mean out-of-pocket expenditures compared with MDS (up to $599 CDN/month for AML vs $239 for MDS; P = .05), greater loss of productivity-related income (reaching $1786/month for AML vs $709 for MDS; P < .05), and greater caregiver effects (65% vs 35% caregiver productivity losses for AML vs MDS; P < .05). Our results suggest that including patient-reported QoL and socioeconomic indicators can improve the accuracy of survival models.

Measuring the impact of influenza vaccination on healthcare worker absenteeism in the context of a province-wide mandatory vaccinate-or-mask policy.

OBJECTIVES: In 2012, British Columbia (BC) implemented a province-wide vaccinate-or-mask influenza prevention policy for healthcare workers (HCWs) with the aim of improving HCW coverage, and reducing illness in patients and staff. We assess post-policy impacts of HCW vaccination status on their absenteeism. METHODS: We matched individual HCW payroll data from December 1, 2012 to March 31, 2017 with annually self-reported vaccination status for BC health authority employees to assess sick rates (sick time as a proportion of sick time and productive time). We modelled adjusted odds ratios (OR) of taking any sick time, relative rates (RR) of sick time taken, and predicted mean sick rates by vaccination status in influenza (December 1-March 31) and non-influenza seasons (April 1 to November 30). We used two methods to assess changes in influenza season sick rates for HCWs who had a change in their vaccination status over the five years. RESULTS: HCWs who reported 'early' vaccination (before December 1 when the policy is in effect) were less likely to take sick time (OR 0.874, 95%CI: 0.866-0.881) and took less sick time (RR 0.907, 95%CI: 0.901-0.912) in influenza season compared to HCWs who did not report vaccination; whereas HCWs who reported 'late' (between December 1 and March 31, and subject to masking until vaccinated) had similar sick rates to HCWs who did not report vaccination. These trends were also observed in non-influenza season. Influenza season sick rates were similar for HCWs that had at least one year of 'early' vaccination and one year where vaccination was not reported over the five year period. CONCLUSIONS: Overall absenteeism is lower among HCWs who report vaccination versus those who do not report. However, absenteeism behaviours appear to be influenced by individual level factors other than vaccination status.

Measuring the impact of a mandatory province-wide vaccinate-or-mask policy on healthcare worker absenteeism in British Columbia, Canada.

OBJECTIVES: Vaccinate-or-mask (VOM) policies aim to improve influenza vaccine coverage among healthcare workers (HCW) and reduce influenza-related illness among patients and staff. In 2012, British Columbia (BC) implemented a province-wide VOM influenza prevention policy. This study describes an evaluation of policy impacts on HCW absenteeism rates from before to after policy implementation. METHODS: Using payroll data from regional and provincial Health Authorities (HA), we assessed all-cause sick rates (sick time as a proportion of sick time and productive time) before (2007-2011, excluding 2009-2010) and after (2012-2017) policy implementation, and during influenza season (December 1-March 31) and non-influenza season (April 1-November 30). We used a two-part negative binomial hurdle model to calculate odds ratios (OR) of taking any sick time, relative rates (RR) of sick time taken, and predicted mean sick rates, adjusting for age group, sex, job type, job classification, HA, year and vaccine effectiveness. RESULTS: During influenza season, HCWs in the post-policy period were less likely to take any sick time (OR 0.989, 95%CI: 0.979-0.999) but had higher rates of sick time (RR 1.038, 95%CI: 1.030-1.045). However, during non-influenza season, HCWs in the post-policy period were more likely to take any sick time (OR 1.015, 95%CI: 1.008-1.022) but had lower rates of sick time (RR 0.971, 95%CI: 0.966-0.976). There was an overall increase in predicted mean sick rate from pre to post-policy in influenza season (4.392% to 4.508%) and non-influenza season (3.815% to 3.901%). CONCLUSIONS: The observed year-round increase in sick rates from pre-to-post policy was likely influenced by other factors; however, opposite trends in how HCWs took sick time in the influenza and non-influenza seasons may reflect policy influences and need further research to explore reasons for these differences.