Donation after circulatory death (DCD) donors are an important source of kidneys for transplantation, but DCD donor transplantation is less common in the United States than in other countries. In this study of national data obtained between 2008 and 2015, recovery of DCD kidneys varied substantially among the country's 58 donor service areas, and 25% of DCD kidneys were recovered in only four donor service areas. Overall, 20% of recovered DCD kidneys were discarded, varying from 3% to 33% among donor service areas. Compared with kidneys from neurologically brain dead (NBD) donors, DCD kidneys had a higher adjusted odds ratio of discard that varied from 1.25 (95% confidence interval [95% CI], 1.16 to 1.34) in kidneys with total donor warm ischemic time (WIT) of 10-26 minutes to 2.67 (95% CI, 2.34 to 3.04) in kidneys with total donor WIT >48 minutes. Among the 12,831 DCD kidneys transplanted, kidneys with WIT≤48 minutes had survival similar to that of NBD kidneys. DCD kidneys with WIT>48 minutes had a higher risk of allograft failure (hazard ratio, 1.23; 95% CI, 1.07 to 1.41), but this risk was limited to kidneys with cold ischemia time (CIT) >12 hours. We conclude that donor service area-level variation in the recovery and discard of DCD kidneys is large. Additional national data collection is needed to understand the potential to increase DCD donor transplantation in the United States. Strategies to minimize cold ischemic injury may safely allow increased use of DCD kidneys with WIT>48 minutes.

The factors underlying the decline in living kidney donation in the United States since 2005 must be understood to inform strategies to ensure access to this option for future patients. Population-based estimates provide a better assessment of donation activity than do trends in the number of living donor transplants. Using data from the Scientific Registry of Transplant Recipients and the United States Census, we determined longitudinal changes in living kidney donation between 2005 and 2015, focusing on the effect of sex and income. We used multilevel Poisson models to adjust for differences in age, race, the incidence of ESRD, and geographic factors (including population density, urbanization, and daily commuting). During the study period, the unadjusted rate of donation was 30.1 and 19.3 per million population in women and men, respectively, and the adjusted incidence of donation was 44% higher in women (incidence rate ratio [IRR], 1.44; 95% confidence interval [95% CI], 1.39 to 1.49). The incidence of donation was stable in women (IRR, 0.95; 95% CI, 0.84 to 1.07) but declined in men (IRR, 0.75; 95% CI, 0.68 to 0.83). Income was associated with longitudinal changes in donation in both sexes, yet donation was stable in the highest two population income quartiles in women but only in the highest income quartile in men. In both sexes, living related donations declined, irrespective of income. In conclusion, living donation declined in men but remained stable in women between 2005 and 2015, and income appeared to have a greater effect on living donation in men.

C haracterizing mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome has led to the identifi cation of variants of concern (VOCs) on the basis of such criteria as increased transmissibility, clinical severity, effect on diagnostic testing, and reduced vaccine effi cacy (1-5). Globally, the B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma) lineages represented the 3 main actively circulating VOCs in late 2020 and early 2021 (6). B.1.1.7 was fi rst detected in England in September 2020 and progressed to become the dominant lineage in this setting within months (4,7). By early January 2021, >40 countries had documented B.1.1.7 cases, demonstrating rapid international spread (8). This lineage has been associated with an estimated 40%-90% increase in transmissibility (4,7), variable effects on clinical severity and mortality rates (5,9,10), and limited effect on vaccine effectiveness (11). In contrast, whereas B.1.351 and P.1 also emerged in fall 2020 and spread rapidly locally, initial evidence of international transmission beyond South Africa and Brazil was limited (8,12,13). The P.1 lineage poses concern given its associations with an estimated 70%-240% increase in transmissibility ( 12), decreased neutralization capacity by monoclonal and serum-derived polyclonal antibodies ( 14), and increased risk for reinfection (12). Limited evidence from Italy, where B.1.1.7 and P.1 lineages have cocirculated, has shown the potential for B.1.1.7 to surpass P.1 for dominant VOC status in a short timeframe (15; P. Stefanelli et al., unpub. data, https://www.medrxiv.org/content/10.1101/ 2021.04.06.21254923v1). However, recent evidence from the United States suggests that infection after vaccination might be attributed to variants characterized by such mutations as E484K, T95I, del142-144, and D614G (16). The SARS-CoV-2 spike E484K mutation, which is present in the P. 1 and B.1.351 lineages,

In living donor transplantation, cold ischemia time is a concern in transplants involving kidney paired donation. The impact of cold ischemia time over eight hours is unknown. Here we examined the association of cold ischemia time with delayed graft function and allograft loss among 48,498 living recipients in the Scientific Registry of Transplant Recipients registry. The incidence of delayed graft function was low but significantly higher among patients with longer cold ischemia times (0-2.0 hours: 3.3%; 2.1-4.0 hours: 3.9%; 4.1-8.0 hours: 4.3%; 8.1-16.0 hours: 5.5%). In multivariate analyses, only those with cold ischemia times of 8.1-16.0 hours had increased odds of delayed graft function (odds ratio 1.47; 95% confidence interval 1.05-2.05) compared to patients with times of 0-2.0 hours. In multivariate time-to-event analyses, cold ischemia times of 16 hours or less were not associated with allograft loss from any cause including death or death-censored graft loss with hazard ratios for cold ischemia times between 8.0-16.0 hours of 0.97 (95% confidence interval 0.74-1.26) and 1.09 (0.81-1.48) compared to patients with times of 0-2.0 hours). The results were consistent in paired and non-kidney paired donation transplants and in those with living donors over 50 years of age. In subgroup analysis restricted to kidney paired donation recipients, there was no difference in the risk of delayed graft function with an odds ratio of 1.40 (0.88, 2.40) or all-cause graft loss with a hazard ratio of 0.89 (0.62, 1.30) in transplant recipients who received kidneys that were shipped versus not shipped. Thus, a cold ischemia time up to 16 hours has limited impact on living donor outcomes. These findings may help expand living donor transplantation through kidney paired donation.

Background: Obsessive-compulsive disorder (OCD) has complex genetic underpinnings, particularly in its earlyonset form, which places siblings at a 10-fold increased risk of developing the disorder. Examination for neurocognitive markers preceding pediatric OCD onset has not been conducted, although markers have been identified in adult OCD. This study compared neurocognition across groups of OCD-affected youth (n = 87), unaffected siblings of those with early-onset OCD (n = 67), and healthy controls (HC; n = 79). Methods: A total of 233 participants aged 6-18 years old completed standardized neurocognitive tests of cognitive flexibility, decision making, planning, response inhibition, spatial working memory, attention, recognition nonverbal memory, and intelligence. They were administered the Anxiety Disorders Interview Schedule-Parent version (ADIS-P) and completed self-report anxiety and OCD questionnaires. Linear mixed-effects models tested for differences between groups, adjusting for age, gender, IQ, state anxiety, and ethnicity, and accounting for random effects of family membership. Results: OCD-affected youth and unaffected siblings performed significantly worse on planning in comparison to HCs (Cohen's d = 0.74; 95% CI = [0.11, 1.36]; Cohen's d = 0.75; 95% CI = [0.12, 1.38], respectively; omnibus group effect p = .007). No other significant between-group differences were identified. Conclusions: Neurocognitive performance differences between groups identified planning as a preexisting trait marker of pediatric OCD, while no other domain presented as a preceding marker of pediatric OCD. This differs from adult OCD, which is associated with broader cognitive impairments. Investigating longitudinal trajectories and predictive significance of neurocognition in those affected by, and at risk for, early-onset OCD is warranted. Ideally, this will enhance individualized risk stratification and inform future prevention and early intervention strategies.

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Area-based socio-economic indicators, such as the Canadian Index of Multiple Deprivation (CIMD), have been used in equity analyses to inform strategies to improve needs-based, timely, and effective patient care and public health services to communities. The CIMD comprises four dimensions of deprivation: residential instability, economic dependency, ethno-cultural composition, and situational vulnerability. Using the CIMD methodology, the British Columbia Index of Multiple Deprivation (BCIMD) was developed to create indexes at the Community Health Services Area (CHSA) level in British Columbia (BC). BCIMD indexes are reported by quintiles, where quintile 1 represents the least deprived (or ethno-culturally diverse), and quintile 5 is the most deprived (or diverse). Distinctive characteristics of a community can be captured using the BCIMD, where a given CHSA may have a high level of deprivation in one dimension and a low level of deprivation in another. The utility of this data as a surveillance tool to monitor population demography has been used to inform decision making in healthcare by stakeholders in the regional health authorities and governmental agencies. The data have also been linked to health care data, such as COVID-19 case incidence and vaccination coverage, to understand the epidemiology of disease burden through an equity lens.

BackgroundCOVID-19 vaccination is a key public health measure in the pandemic response. The rapid evolution of SARS-CoV-2 variants introduce new groups of spike protein mutations. These new mutations are thought to aid in the evasion of vaccine-induced immunity and render vaccines less effective. However, not all spike mutations contribute equally to vaccine escape. Previous studies associate mutations with vaccine breakthrough infections (BTI), but information at the population level remains scarce. We aimed to identify spike mutations associated with SARS-CoV-2 vaccine BTI in a community setting during the emergence and predominance of the Delta-variant.MethodsThis case-control study used both genomic, and epidemiological data from a provincial COVID-19 surveillance program. Analyses were stratified into two periods approximating the emergence and predominance of the Delta-variant, and restricted to primary SARS-CoV-2 infections from either unvaccinated individuals, or those infected ≥14 days after their second vaccination dose in a community setting. Each sample's spike mutations were concatenated into a unique spike mutation profile (SMP). Penalized logistic regression was used to identify spike mutations and SMPs associated with SARS-CoV-2 vaccine BTI in both time periods.Results and DiscussionThis study reports population level relative risk estimates, between 2 and 4-folds, of spike mutation profiles associated with BTI during the emergence and predominance of the Delta-variant, which comprised 19,624 and 17,331 observations, respectively. The identified mutations cover multiple spike domains including the N-terminal domain (NTD), receptor binding domain (RBD), S1/S2 cleavage region, fusion peptide and heptad regions. Mutations in these different regions imply various mechanisms contribute to vaccine escape. Our profiling method identifies naturally occurring spike mutations associated with BTI, and can be applied to emerging SARS-CoV-2 variants with novel groups of spike mutations.