Background. The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. Methods. We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals. Case fatality rate ratios were adjusted using a Cox proportional hazards model to generate hazard ratio (95% confidence interval). Results. On August 31, 2021, it was found that 3080 (7.1%) were unvaccinated, 1141 (2.6%) had 1 vaccine dose, and 39 260 (90.3%) had 2 vaccine doses. There were 4147 SARS-CoV-2 infections and 407 deaths (unadjusted case fatality rate 9.8%). The riskadjusted infection incidence rate ratio was 1.29 (1.03-1.61), implying that vaccination was not associated with reduction in risk of testing positive for SARS-CoV-2 RNA. Overall, the hazard ratio for death within 28 d of SARS-CoV-2 infection was 0.80 (0.63-1.00), a 20% reduction in risk of death in vaccinated patients (P = 0.05). Two doses of ChAdOx1-S were associated with a significantly reduced risk of death (hazard ratio, 0.69; 0.52-0.92), whereas vaccination with BNT162b2 was not (0.97; 0.71-1.31). Conclusions. Vaccination of SOT recipients confers some protection against SARS-CoV-2-related mortality, but this protection is inferior to that achieved in the general population. SOT recipients require additional protective measures, including further vaccine doses, antiviral drugs, and nonpharmaceutical interventions. (Transplantation 2022;106: 436-446).

ObjectivesTo determine the short-term impact of a soft opt-out organ donation system on consent rates and donor numbers.DesignBefore and after observational study using bespoke routinely collected data.SettingNational Health Service Blood and Transplant.Participants205 potential organ donor cases in Wales.InterventionsThe Act and implementation strategy.Primary and secondary outcomesConsent rates at 18 months post implementation compared with 3 previous years, and organ donor numbers 21 months before and after implementation. Changes in organ donor register activity post implementation for 18 months.ResultsThe consent rate for all modes of consent was 61.0% (125/205), showing a recovery from the dip to 45.8% in 2014/2015. 22.4% (46/205) were deemed consented donors: consent rate 60.8% (28/46). Compared with the 3 years before the switch there was a significant difference in Welsh consent rates (χ2 p value=0.009). Over the same time period, rest of the UK consent rates also significantly increased from 58.6% (5256/8969) to 63.1% (2913/4614) (χ2 p value<0.0001), therefore the Wales increase cannot be attributed to the Welsh legislation change. Deceased donors did not increase: 101 compared with 104. Organ donation registration increased from 34% to 38% with 6% registering to opt-out.ConclusionThis is the first rigorous initial evaluation with bespoke data collected on all cases. The longer-term impact on consent rates and donor numbers is unclear. Concerns about a potential backlash and mass opting out were not realised. The move to a soft opt-out system has not resulted in a step change in organ donation behaviour, but can be seen as the first step of a longer journey. Policymakers should not assume that soft opt-out systems by themselves simply need more time to have a meaningful effect. Ongoing interventions to further enhance implementation and the public’s understanding of organ donation are needed to reach the 2020 target of 80% consent rates. Further longitudinal monitoring is required.

Between 2013 and 2019, there was an increase in the consent rate for organ donation in the UK from 61% to 67%, but this remains lower than many European countries. Data on all family approaches (16,896) for donation in UK intensive care units or emergency departments between April 2014 and March 2019 were extracted from the referral records and the national potential donor audit held by NHS Blood and Transplant. Complete data were available for 15,465 approaches. Consent for donation after brain death was significantly higher than for donation after circulatory death, 70% (4260/6060) vs. 60% (5645/9405), (OR 1.58, 95%CI 1.47-1.69). Patient ethnicity, religious beliefs, sex and socio-economic status, and knowledge of a patient's donation decision were strongly associated with consent (p < 0.001). These factors should be addressed by medium-to long-term strategies to increase community interventions, encouraging family discussions regarding donation decisions and increasing registration on the organ donor register. The most readily modifiable factor was the involvement of an organ donation specialist nurse at all stages leading up to the approach and the approach itself. If no organ donation specialist nurse was present, the consent rates were significantly lower for donation after brain death (OR 0.31, 95%CI 0.23-0.42) and donation after cardiac death (OR 0.26, 95%CI 0.22-0.31) compared with if a collaborative approach was employed. Other modifiable factors that significantly improved consent rates included less than six relatives present during the formal approach; the time from intensive care unit admission to the approach (less for donation after brain death, more for donation after cardiac death); family not witnessing neurological death tests; and the relationship of the primary consenter to the patient. These modifiable factors should be taken into consideration when planning the best bespoke approach to an individual family to discuss the option of organ donation as an end-of-life care choice for the patient.

Background Co‐production of research into public health services has yet to demonstrate tangible benefits. Few studies have reported the impact of co‐production on research outcomes. The previous studies of organ donation have identified challenges in engaging with public organizations responsible, gaining ethical approval for sensitive studies with the recently bereaved and difficulty in recruiting bereaved family members who were approached about organ donation. Objective To address these challenges, we designed the first large co‐productive observational study to evaluate implementation of a new system of organ donation in Wales. This paper outlines the co‐productive strategies that were designed to overcome known methodological challenges and reports what impact they had on resolving these challenges. Design Two‐year co‐produced study with multiple stakeholders with the specific intention of maximizing engagement with the National Health Service arm in Wales responsible for organ donation, and recruitment of bereaved family members whose perspectives are essential but commonly absent from studies. Setting and participants NHS Blood and Transplant, Welsh Government and multiple patient and public representatives who served as co‐productive partners with the research team. Results Co‐productive strategies enabled a smooth passage through four different ethics processes within the 10‐week time frame, family member recruitment targets to be surpassed, sharing of routinely collected data on 100% of potential organ donor cases and development of further research capacity and capability in a critically under researched area. Discussion and conclusion Although expensive and time consuming, co‐production was effective and added value to research processes and study outcomes.

Background. The effectiveness of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 Omicron variant in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. Methods. National registries in England were linked to identify SARS-CoV-2 positive tests, noninjury hospitalization within 14 d, and deaths within 28 d between December 7, 2020, and March 31, 2022 in adult SOT recipients. Incidence rate ratios (IRRs) for infection, and hospitalization or death, were adjusted for recipient demographics and calendar month for the Omicron-dominant period (December 20, 2021, to March 31, 2022). Mortality risk following SARS-CoV-2 infection was adjusted for recipient demographics and dominant variant using a Cox proportional-hazards model for the entire time period. Results. During the Omicron-dominant period, infection IRRs (95% confidence intervals) were higher in those receiving 2, 3, and 4 vaccine doses than in unvaccinated patients (1.25 [1.08-1.45], 1.46 [1.28-1.67], and 1.79 [1.54-2.06], respectively). However, hospitalization or death IRRs during this period were lower in those receiving 3 or 4 vaccine doses than in unvaccinated patients (0.62 [0.45-0.86] and 0.39 [0.26-0.58], respectively). Risk-adjusted analyses for deaths after SARS-CoV-2 infection between December 7, 2020, and March 31, 2022, found hazard ratios (95% confidence intervals) of 0.67 (0.46-0.98), 0.46 (0.30-0.69), and 0.18 (0.09-0.35) for those with 2, 3, and 4 vaccine doses, respectively, when compared with the unvaccinated group. Conclusions. In immunosuppressed SOT recipients, vaccination is associated with incremental, dose-dependent protection against hospitalization or death after SARS-CoV-2 infection, including against the Omicron variant.

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Background. HLA incompatible renal transplantation still remains one of best therapeutic options for a subgroup of patients who are highly sensitized and difficult to match but not much is known about its long-term graft and patient survival. Methods. One hundred thirty-four HLA incompatible renal transplantation patients from 2003 to 2018 with a median follow of 6.93 y were analyzed retrospectively to estimate patient and graft survivals. Outcomes were compared with groups defined by baseline crossmatch status and the type and timings of rejection episodes. Results. The overall patient survival was 95%, 90%, and 81%; and graft survival was 95%, 85%, and 70% at 1, 5, and 10 y, respectively. This was similar to the first-time deceased donor transplant cohort. The graft survival for pretreatment cytotoxic-dependent crossmatch (CDC) positive crossmatch group was significantly low at 83%, 64%, and 40% at 1, 5, and 10 y, respectively, compared with other groups (Bead/CDC, P = 0.007; CDC/Flow, P = 0.001; and microbead assay/flow cytometry crossmatch, P = 0.837), although those with a low CDC titer (<1 in 2) have comparable outcomes to the CDC negative group. Female patients in general fared worse in both patient and graft survival outcomes in each of the 3 groups based on pretreatment crossmatch, although this did not reach statistical significance. Antibody-mediated rejection was the most frequent type of rejection with significant decline in graft survival by 10 y when compared with no rejection ( P < 0.001). Rejection that occurred or continued to occur after the first 2 wk of transplantation caused a significant reduction in graft survivals ( P < 0.001), whereas good outcomes were seen in those with a single early rejection episode. Conclusions. One-, 5-, and 10-y HLA incompatible graft and patient survival is comparable to deceased donor transplantation and can be further improved by excluding high-CDC titer cases. Antibody-positive female patients show worse long-term survival. Resolution of early rejection is associated with good long-term graft survival.

BackgroundThe UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry.MethodsWe performed Cox survival analysis on first kidney-only deceased brain-dead transplants in paediatric (&lt;18 years) recipients from 2000-2014. The primary outcome was death-censored allograft survival &gt;30 days post-transplant. The main study variable was UK-KDRI derived from seven donor risk-factors, categorised into four groups (D1-low risk, D2, D3 and D4-highest risk). Follow-up ended on 31-December-2021.Results319/908 patients experienced transplant loss with rejection as the main cause (55%). The majority of paediatric patients received donors from D1 donors (64%). There was an increase in D2-4 donors during the study period, whilst the level of HLA mismatching improved. The KDRI was not associated with allograft failure. In multi-variate analysis, increasing recipient age [adjusted HR and 95%CI: 1.05(1.03-1.08) per-year, p&lt;0.001], recipient minority ethnic group [1.28(1.01-1.63), p&lt;0.05), dialysis before transplant [1.38(1.04-1.81), p&lt;0.005], donor height [0.99 (0.98-1.00) per centimetre, p&lt;0.05] and level of HLA mismatch [Level 3: 1.92(1.19-3.11); Level 4: 2.40(1.26-4.58) versus Level 1, p&lt;0.01] were associated with worse outcomes. Patients with Level 1 and 2 HLA mismatches (0 DR +0/1 B mismatch) had median graft survival &gt;17 years regardless of UK-KDRI groups. Increasing donor age was marginally associated with worse allograft survival [1.01 (1.00-1.01) per year, p=0.05].SummaryAdult donor risk scores were not associated with long-term allograft survival in paediatric patients. The level of HLA mismatch had the most profound effect on survival. Risk models based on adult data alone may not have the same validity for paediatric patients and therefore all age-groups should be included in future risk prediction models.