Identification of patients undergoing chronic kidney replacement therapy in primary and secondary care data: validation study based on OpenSAFELY and UK Renal Registry.

Objective: To validate primary and secondary care codes in electronic health records to identify people receiving chronic kidney replacement therapy based on gold standard registry data. Design: Validation study using data from OpenSAFELY and the UK Renal Registry, with the approval of NHS England. Setting: Primary and secondary care electronic health records from people registered at 45% of general practices in England on 1 January 2020, linked to data from the UK Renal Registry (UKRR) within the OpenSAFELY-TPP platform, part of the NHS England OpenSAFELY covid-19 service. Participants: 38 745 prevalent patients (recorded as receiving kidney replacement therapy on 1 January 2020 in UKRR data, or primary or secondary care data) and 10 730 incident patients (starting kidney replacement therapy during 2020), from a population of 19 million people alive and registered with a general practice in England on 1 January 2020. Main outcome measures: Sensitivity and positive predictive values of primary and secondary care code lists for identifying prevalent and incident kidney replacement therapy cohorts compared with the gold standard UKRR data on chronic kidney replacement therapy. Agreement across the data sources overall, and by treatment modality (transplantation or dialysis) and personal characteristics. Results: Primary and secondary care code lists were sensitive for identifying the UKRR prevalent cohort (91.2% (95% confidence interval (CI) 90.8% to 91.6%) and 92.0% (91.6% to 92.4%), respectively), but not the incident cohort (52.3% (50.3% to 54.3%) and 67.9% (66.1% to 69.7%)). Positive predictive values were low (77.7% (77.2% to 78.2%) for primary care data and 64.7% (64.1% to 65.3%) for secondary care data), particularly for chronic dialysis (53.7% (52.9% to 54.5%) for primary care data and 49.1% (48.0% to 50.2%) for secondary care data). Sensitivity decreased with age and index of multiple deprivation in primary care data, but the opposite was true in secondary care data. Agreement was lower in children, with 30% (295/980) featuring in all three datasets. Half (1165/2315) of the incident patients receiving dialysis in UKRR data had a kidney replacement therapy code in the primary care data within three months of the start date of the kidney replacement therapy. No codes existed whose exclusion would substantially improve the positive predictive value without a decrease in sensitivity. Conclusions: Codes used in primary and secondary care data failed to identify a small proportion of prevalent patients receiving kidney replacement therapy. Codes also identified many patients who were not recipients of chronic kidney replacement therapy in UKRR data, particularly dialysis codes. Linkage with UKRR kidney replacement therapy data facilitated more accurate identification of incident and prevalent kidney replacement therapy cohorts for research into this vulnerable population. Poor coding has implications for any patient care (including eligibility for vaccination, resourcing, and health policy responses in future pandemics) that relies on accurate reporting of kidney replacement therapy in primary and secondary care data.

Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.

OBJECTIVE: To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England. DESIGN: Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England. SETTING: Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR). PARTICIPANTS: A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR. MAIN OUTCOME MEASURES: Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models. RESULTS: 992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake. CONCLUSION: Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.

Exploring the relationship between environmental enteric dysfunction and oral vaccine responses.

Oral vaccines significantly underperform in low-income countries. One possible contributory factor is environmental enteric dysfunction (EED), a subclinical disorder of small intestinal structure and function among children living in poverty. Here, we review studies describing oral vaccine responses and EED. We identified eight studies evaluating EED and oral vaccine responses. There was substantial heterogeneity in study design and few consistent trends emerged. Four studies reported a negative association between EED and oral vaccine responses; two showed no significant association; and two described a positive correlation. Current evidence is therefore insufficient to determine whether EED contributes to oral vaccine underperformance. We identify roadblocks in the field and future research needs, including carefully designed studies those can investigate this hypothesis further.

Causes of impaired oral vaccine efficacy in developing countries.

Oral vaccines are less immunogenic when given to infants in low-income compared with high-income countries, limiting their potential public health impact. Here, we review factors that might contribute to this phenomenon, including transplacental antibodies, breastfeeding, histo blood group antigens, enteric pathogens, malnutrition, microbiota dysbiosis and environmental enteropathy. We highlight several clear risk factors for vaccine failure, such as the inhibitory effect of enteroviruses on oral poliovirus vaccine. We also highlight the ambiguous and at times contradictory nature of the available evidence, which undoubtedly reflects the complex and interconnected nature of the factors involved. Mechanisms responsible for diminished immunogenicity may be specific to each oral vaccine. Interventions aiming to improve vaccine performance may need to reflect the diversity of these mechanisms.

Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame.

The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio.

Advances in enteric disease vaccines: from innovation to implementation.

The Seventh International Conference on Vaccines for Enteric Diseases Bangkok, Thailand, 6-8 November 2013 Hosting 222 participants from more than 25 countries, the Seventh International Conference on Vaccines for Enteric Diseases (VED 2013) displayed the considerable progress that has been made in recent years towards unraveling the burden and etiology of enteric infections, alongside advances in the development, testing and implementation of vaccines that target them. The pervasive nature of enteric diseases, and the significant morbidity and mortality they account for, underscore the substantial public health benefits achievable through the use of enteric vaccines. A number of key talking points raised during the conference are discussed here, including early experiences with the use of double-mutant heat-labile enterotoxin as an antigen and adjuvant, progress and challenges associated with the implementation of oral cholera vaccines, and the issue of impaired rotavirus vaccine immunogenicity in lower-income countries.