NHS Greater Glasgow & Clyde

Pre-implantation biopsy may help select kidneys retrieved from elderly deceased donors for transplantation, but concerns persist that it may cause unnecessary discard of kidneys that would have provided acceptable transplant function. The PITHIA trial tested the hypothesis that introduction of a National Digital Pathology Service (NDPS) would increase the proportion of kidneys transplanted from elderly donors and/or improve their function.

A stepped-wedge cluster randomised controlled registry trial delivered the NDPS to 22 UK kidney transplant centres (clusters) in 5 sequences at four-monthly intervals, using a restricted randomisation technique to ensure similar cluster sizes in the intervention and control status. Upon access to the intervention, centres could request urgent pre-implantation biopsy on kidneys from deceased donors aged 60 years or older. Co-primary outcome measures were the proportion of kidneys transplanted upon first offer according to whether the centre had access or not to the biopsy service, and the 1-year eGFR of the kidneys that were transplanted. Analysis adjusts for clustering and underlying secular trends, with 97.5% Confidence Intervals (CI) reported to reflect the two co-primary outcomes. The trial is complete (Trial Registration Number: ISRCTN 11708741).

The trial commenced on 1st October 2018 and ended on 31st January 2022. Of the 2502 eligible kidneys offered, 1355 single and 67 dual transplants were performed. Regarding the first primary endpoint, a non-significantly lower proportion of those kidneys first offered to centres with access to the biopsy service were transplanted compared with those offered to centres without access (295 of 1241 (23.8%) vs. 377 of 1261 (29.9%): adjusted Odds Ratio (97.5% CI) 0.91 (0.60-1.39); p = 0.6083). For the second primary endpoint, the adjusted mean (SE) 1-year eGFR of the transplant kidneys was similar, irrespective of whether the implanting centre had access to the biopsy service or not (43.7 (1.3) ml/min/1.73 m² vs. 42.2 (1.3) ml/min/1.73 m²; adjusted mean difference (97.5% CI) 1.53 (-2.33 to 5.40); p = 0.37). Secondary outcome analysis of how the biopsy service was adopted revealed that biopsies were performed on 287 of the 1493 (19.2%) kidneys offered to at least one centre with access to the biopsy service, with marked variation between transplant centres in requests for biopsy, and in implantation rates of biopsied kidneys. Nevertheless, 191 (66.6%) of biopsied kidneys were transplanted, compared with 643 of the 1009 (63.7%) kidneys only ever offered to centres without biopsy access, and 588 of the 1206 (48.8%) kidneys that were not biopsied, despite being offered to at least one centre with biopsy access.

Implementation of the NDPS did not significantly increase transplantation rates of elderly deceased donor kidneys upon first offer, nor improve 1-year eGFR of the transplanted kidneys. This may reflect inter-centre variation in adoption and application of the biopsy service; such variations would need to be considered when designing future studies of pre-implantation biopsy analysis.

NIHR Research for Patient Benefit programme (RfPB PB-PG-1215-20033).

The COVID-19 pandemic led to changes in delivery of opioid-agonist treatment (OAT) and risk of drug-related harm in Scotland. This study aimed to (i) examine changes in drug-related death (DRD) rates and the protective effect of OAT during the COVID-19 pandemic in Scotland (2020-2022) compared with the previous decade (2011-2019); and (ii) describe trends in OAT prescribing over the same period.

We conducted a retrospective cohort study using data from the Scottish national Prescribing Information System linked to healthcare and administrative data from Public Health Scotland. The cohort included individuals prescribed OAT (methadone or buprenorphine). We examined trends in OAT prescribing, calculated crude DRD rates per 1000 person-years, and used multivariable quasi-Poisson regression to estimate adjusted incidence rate ratios (aIRR) for DRD risk across four time periods (2011-2013, 2014-2016, 2017-2019, and 2020-2022).

Between 2011 and 2022, 49,000 individuals accessed OAT, contributing 366,344 person years of follow-up, during which 5255 DRDs occurred. In the COVID-19 pandemic period (2020-2022), 34,241 people received OAT and there were 1825 DRDs. DRD rates increased steadily prior to 2020, but remained stable during the pandemic: the observed DRD rate during 2020-2022 was comparable to 2017-2019 (aIRR=0.96, 95 % CI=0.80, 1.15). Across all periods, being on OAT was consistently associated with a lower risk of DRD compared to being off treatment (aIRR=3.47, 95 % CI=2.98, 4.05).

During the COVID-19 pandemic in Scotland, DRD rates remained stable following a three-fold rise since 2011-13. The protective effect of OAT was sustained during the pandemic, which highlights the importance of maintaining access to OAT during public health crises.

Opportunistic premise plumbing pathogens occur naturally in water but can pose a health risk to hospital patients who are more vulnerable due to illness or treatment. Ward closure periods can lead to microbial proliferation within water systems, posing a challenge to hospital estates and infection control teams. Following the 3-year closure of our paediatric haemato-oncology ward, water testing showed high total viable counts (TVCs) in over 20 % of samples and elevated counts of numerous Gram negative bacterial species (GNBs) in 73 % of samples, despite daily flushing and continuous chlorine dioxide dosing. We aimed to determine the extent of microbial proliferation, measure the impact of three sequential interventions (system disinfections with chlorine, with silver stabilised hydrogen peroxide, and then tap replacement), and assess the long-term performance of this water system. By sampling systematically across spatial and temporal scales, and using a range of microbiological tests (TVCs, Legionella spp., Pseudomonas spp., Gram negative bacteria, atypical mycobacteria and fungi), we showed that microbial proliferation was confined to the closed ward. Chlorine treatment had no significant impact on TVCs, but both silver stabilised hydrogen peroxide and tap replacement resulted in significant decreases (p < 0.01). Similarly, the three Gram negative species that were enriched following the reconstruction period (Cupriavidus pauculus, Sphingomonas paucimobilis, and Acidovorax temperans) were less impacted by chlorine than by the other interventions. Following these interventions, fewer than 1 % of samples exceeded our strict local TVC threshold of 10 CFU/ml and GNBs were detected in 7 % of samples. Since the ward reopened to patients in 2022, there has been no return of the high microbiological counts observed immediately after reconstruction. Gram negative bacteria have been detected only sporadically, and the taxa found in samples collected through 0.2 μm point-of-use filters shifted towards species associated with humans. Our systematic approach was successful in returning this hospital water system to a safe state, and once microbial proliferation within the system itself was rectified, further positive results were likely attributable to the interactions of users with the outlets. Distinguishing between possible sources of microbial counts in water is crucial to selecting the most suitable interventions and helping ensure provision of safe water to patients.