Prevalence of chronic kidney disease among young people living with HIV in Sub Saharan Africa: A systematic review and meta-analysis.

BACKGROUND: Globally, the prevalence of chronic kidney disease (CKD) is increasing among young people living with HIV (YPLHIV), with inconsistent estimates. Aggregated data on the prevalence of CKD are needed in sub-Saharan Africa (SSA) to inform strategies for early diagnosis and management. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of CKD among YPLHIV in SSA. METHODS: We searched Medline/PubMed, EMBASE, African Index Medicus, and African Journals Online for articles reporting the prevalence of CKD among YPLHIV in SSA using predefined search strategies up to 15th January 2024. The reference lists of identified articles were checked for additional eligible studies. The eligibility criteria were studies among YPLHIV aged 10-24 years reporting CKD prevalence defined by either glomerular filtration rate (GFR), albumin-to-creatinine ratio (ACR) or proteinuria. We used a narrative synthesis to report differences between the included studies. The DerSimonian-Laird random effects model was used to pool the CKD prevalence, and heterogeneity was assessed using the Cochrane Q-test and I-squared values. We assessed the risk of bias in each article using the Joanna Briggs Institute checklist and publication bias in a funnel plot and Egger's test. RESULTS: Of 802 retrieved articles, 15 fulfilled the eligibility criteria and were included in the meta-analysis. Of these, 12 (80%) were cross-sectional studies that used estimated GFR to diagnose CKD. Only one study followed the standard definition of CKD. The pooled CKD prevalence from 15 studies was 12% (95% CI 6.0-19.5%), ranging from 0.8% to 53.1% according to the definition used, with a high degree of heterogeneity (I2 = 97.7%, p<0.001). The included studies were of moderate quality, with no evidence of publication bias. Sensitivity analysis showed that the findings were robust to the methodological and analytic approach. CONCLUSION: CKD prevalence among YPLHIV is moderately high and highly heterogeneous across SSA. The standard definition of CKD should be used to enable estimation of CKD prevalence in different studies and settings. HIV programs enrolling YPLHIV should routinely screen for CKD to ensure early diagnosis and management. TRIAL REGISTRATION: PROSPERO registration number: CRD42022347588.

Impacts of the COVID-19 pandemic on deprivation-level differences in cardiovascular hospitalisations: a comparison of England and Denmark using the OpenSAFELY platform and National Registry Data.

OBJECTIVES: To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021. DESIGN: Time-series studies in England and Denmark. SETTING: With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data. PARTICIPANTS: We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria. PRIMARY OUTCOME MEASURES: Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE). RESULTS: We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile. CONCLUSIONS: Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries.

Comparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda.

Introduction: Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population. Methods: A cross-sectional study with YPLHIV aged 10 to 24 years was conducted in seven HIV clinics. Participants provided a urine and blood sample to measure urinary albumin, proteinuria, serum creatinine and cystatin C levels at baseline and after three months. The estimated glomerular filtration rate (eGFR) was calculated using CKDEPI 2021, Cockroft-Gault and bedside Schwartz equations using creatinine or cystatin C. The albumin creatinine ratio (ACR) and proteinuria were measured. CKD was defined as either eGFR <60ml/min/1.73m2 or <90ml/min/1.73m2 or ACR above 30mg/g on two separate occasions. Univariable and multivariable logistic regression were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with CKD. Results: A total of 500 participants were enrolled. Most were female (56%; n=280) and aged 10 to 17 years (66.9%; n=335). CKD prevalence ranged from 0-23% depending on the criteria, equation and biomarker used. Cystatin C-based equations estimated higher prevalence of CKD compared to creatinine-based ones. Prevalence of ACR above 30mg/g was 10.1% and of proteinuria 29%. Factors independently associated with CKD were age (aOR=1.42; 95% CI:1.30-1.51) and male sex (aOR=3.02; 95% CI:1.68-5.43). Conclusion: CKD prevalence among YPLHIV varied substantially depending on definitions used and the current definition would likely lead to missed cases of CKD among YPLHIV. Estimating equations should be validated against measured GFR in YPLHIV and the optimal definition of CKD in this vulnerable population should be revised to optimise detection and opportunities for reducing disease progression.

Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.

BACKGROUND: Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. METHODS AND FINDINGS: We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. CONCLUSIONS: These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Impact of COVID-19 on recorded blood pressure screening and hypertension management in England: an analysis of monthly changes in the quality and outcomes framework indicators in OpenSAFELY.

BACKGROUND: The COVID-19 pandemic disrupted cardiovascular disease management in primary care in England. OBJECTIVE: To describe the impact of the pandemic on blood pressure screening and hypertension management based on a national quality of care scheme (Quality and Outcomes Framework, QOF) across key demographic, regional and clinical subgroups. METHODS: With NHS England approval, a population-based cohort study was conducted using OpenSAFELY-TPP on 25.2 million NHS patients registered at general practices (March 2019 to March 2023). We examined monthly changes in recorded blood pressure screening in the preceding 5 years in patients aged ≥45 years and recorded the hypertension prevalence and the percentage of patients treated to target (≤140/90 mmHg for patients aged ≤79 years and ≤150/90 mmHg for patients aged ≥80 years) in the preceding 12 months. RESULTS: The percentage of patients aged ≥45 years who had blood pressure screening recorded in the preceding 5 years decreased from 90% (March 2019) to 85% (March 2023). Recorded hypertension prevalence was relatively stable at 15% throughout the study period. The percentage of patients with a record of hypertension treated to target in the preceding 12 months reduced from a maximum of 71% (March 2020) to a minimum of 47% (February 2021) in patients aged ≤79 years and from 85% (March 2020) to a minimum of 58% (February 2021) in patients aged ≥80 years before recovery. Blood pressure screening rates in the preceding 5 years remained stable in older people, patients with recorded learning disability or care home status. CONCLUSIONS: The pandemic substantially disrupted hypertension management QOF indicators, which is likely attributable to general reductions of blood pressure measurement including screening. OpenSAFELY can be used to continuously monitor changes in national quality-of-care schemes to identify changes in key clinical subgroups early and support prioritisation of recovery from care disrupted by COVID-19.

Diagnostic performance of an albuminuria point-of-care test in screening for chronic kidney disease among young people living with HIV in Uganda: a cross-sectional study.

OBJECTIVES: The main aim was to determine the diagnostic performance of an albuminuria point-of-care test (POC) for diagnosis of chronic kidney disease among young people living with HIV (YPLHIV) in Uganda. DESIGN: We conducted a cross-sectional study comparing the diagnostic performance of MicroalbuPHAN (Erba Lachema, Czech Republic), an albuminuria POC test against the laboratory-measured albumin and creatinine as the reference standard. SETTING: The study was set in seven HIV clinics in Kampala, Uganda that provide antiretroviral therapy to adults and children living with HIV. The study took place from April to August 2023. PARTICIPANTS: 497 YPLHIV aged 10-24 years who were diagnosed with HIV before 10 years of age were randomly selected from the HIV clinics. Pregnant YPLHIV were excluded. PROCEDURES: Participants provided a spot urine sample that was tested for albumin and creatinine using the POC and in the laboratory and proteinuria using urine dipstick. The sensitivity, specificity, negative and positive predictive values (NPV, PPV) of the POC versus the laboratory test were calculated, and factors associated with having a positive POC test were estimated using logistic regression. OUTCOME MEASURES: The primary outcome was a diagnosis of albuminuria defined as an albumin creatinine ratio above 30 mg/g. RESULTS: Of the 497 participants enrolled, 278 (55.9%) were female and 331 (66.8%) were aged 10-17 years. The POC test had a sensitivity of 74.5% (95% CI 70.6% to 78.4%) and specificity of 68.1% (95% CI 63.9% to 72.3%). The PPV was 21.5% (95% CI 17.8% to 25.1%) and the NPV was 95.8% (95% CI 94.0% to 97.6%), with an accuracy of 68.8%. There was strong evidence that a positive POC test was associated with having proteinuria (OR 2.82; 95% CI 1.89 to 4.22, p<0.001); body mass index <19.5 (OR 1.69 95% CI 1.17 to 2.45, p=0.005) and being male (OR 1.48; 95% CI 1.02 to 2.14, p=0.04). CONCLUSIONS: The albuminuria POC test had low sensitivity and specificity. However, it can be used to exclude kidney disease given its high NPV. It should be validated against the 24-hour urinary excretion rate to further determine its diagnostic performance.

Changes in sick notes associated with COVID-19 from 2020 to 2022: a cohort study in 24 million primary care patients in OpenSAFELY-TPP.

OBJECTIVES: Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called 'fit notes') are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19. DESIGN: Cohort study. SETTING: With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database. PARTICIPANTS: People 18-64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673). PRIMARY OUTCOME MEASURE: Receipt of a sick note in primary care. RESULTS: Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia. CONCLUSIONS: Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Consistency, completeness and external validity of ethnicity recording in NHS primary care records: a cohort study in 25 million patients' records at source using OpenSAFELY.

BACKGROUND: Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients' ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. METHODS: We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. RESULTS: 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). CONCLUSIONS: Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.

Healthcare utilisation in people with long COVID: an OpenSAFELY cohort study.

BACKGROUND: Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined. METHODS: This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records. RESULTS: We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74-8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48-1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58-29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73-16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20-8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39-1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60-£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33-1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group. CONCLUSIONS: Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID.

Cardiorenal effects of Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people underrepresented in trials: analysis of routinely collected data with emulation of a reference trial (ONTARGET).

Cardiovascular disease (CVD) is a leading cause of death globally. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), compared in the ONTARGET trial, each prevent CVD. However, trial results may not be generalisable and their effectiveness in underrepresented groups is unclear. Using trial emulation methods within routine-care data to validate findings, we explored generalisability of ONTARGET results. For people prescribed an ACEi/ARB in the UK Clinical Practice Research Datalink GOLD from 1/1/2001-31/7/2019, we applied trial criteria and propensity-score methods to create an ONTARGET trial-eligible cohort. Comparing ARB to ACEi, we estimated hazard ratios for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure), and secondary outcomes. As the pre-specified criteria were met confirming trial emulation, we then explored treatment heterogeneity among three trial-underrepresented subgroups: females, those aged ≥75 years and those with chronic kidney disease (CKD). In the trial-eligible population (n=137,155), results for the primary outcome demonstrated similar effects of ARB and ACEi, (HR 0.97 [95% CI: 0.93, 1.01]), meeting the pre-specified validation criteria. When extending this outcome to trial-underrepresented groups, similar treatment effects were observed by sex, age and CKD. This suggests that ONTARGET trial findings are generalisable to trial-underrepresented subgroups.

OpenSAFELY: A platform for analysing electronic health records designed for reproducible research.

Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY's reproducibility-by-design approach in detail.

Clinical coding of long COVID in primary care 2020-2023 in a cohort of 19 million adults: an OpenSAFELY analysis.

Background: Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England. Methods: With the approval of NHS England we used routine clinical data from over 19 million adults in England linked to SARS-COV-2 test result, hospitalisation and vaccination data to describe trends in the recording of 16 clinical codes related to long COVID between November 2020 and January 2023. Using OpenSAFELY, we calculated rates per 100,000 person-years and plotted how these changed over time. We compared crude and adjusted (for age, sex, 9 NHS regions of England, and the dominant variant circulating) rates of recorded long COVID in patient records between different key demographic and vaccination characteristics using negative binomial models. Findings: We identified a total of 55,465 people recorded to have long COVID over the study period, which included 20,025 diagnoses codes and 35,440 codes for further assessment. The incidence of new long COVID records increased steadily over 2021, and declined over 2022. The overall rate per 100,000 person-years was 177.5 cases in women (95% CI: 175.5-179) and 100.5 in men (99.5-102). The majority of those with a long COVID record did not have a recorded positive SARS-COV-2 test 12 or more weeks before the long COVID record. Interpretation: In this descriptive study, EHR recorded long COVID was very low between 2020 and 2023, and incident records of long COVID declined over 2022. Using EHR diagnostic or referral codes unfortunately has major limitations in identifying and ascertaining true cases and timing of long COVID. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Impact of long COVID on health-related quality-of-life: an OpenSAFELY population cohort study using patient-reported outcome measures (OpenPROMPT).

Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems. Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72-5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37-30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

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.

Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.

Background: Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves. Methods: With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups. Findings: A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n = 5704) and sotrovimab (n = 3322) were included in the main analysis. The mean age was 52.7 (SD = 14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR = 0.89, 95% CI: 0.48-1.63; P = 0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR = 0.82, 95% CI: 0.45-1.52; P = 0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR = 0.45, 95% CI: 0.22-0.94; P = 0.033). Interpretation: In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant. Funding: UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in patients on kidney replacement therapy: observational study using the OpenSAFELY-UKRR and SRR databases.

Background: Due to limited inclusion of patients on kidney replacement therapy (KRT) in clinical trials, the effectiveness of coronavirus disease 2019 (COVID-19) therapies in this population remains unclear. We sought to address this by comparing the effectiveness of sotrovimab against molnupiravir, two commonly used treatments for non-hospitalised KRT patients with COVID-19 in the UK. Methods: With the approval of National Health Service England, we used routine clinical data from 24 million patients in England within the OpenSAFELY-TPP platform linked to the UK Renal Registry (UKRR) to identify patients on KRT. A Cox proportional hazards model was used to estimate hazard ratios (HRs) of sotrovimab versus molnupiravir with regards to COVID-19-related hospitalisations or deaths in the subsequent 28 days. We also conducted a complementary analysis using data from the Scottish Renal Registry (SRR). Results: Among the 2367 kidney patients treated with sotrovimab (n = 1852) or molnupiravir (n = 515) between 16 December 2021 and 1 August 2022 in England, 38 cases (1.6%) of COVID-19-related hospitalisations/deaths were observed. Sotrovimab was associated with substantially lower outcome risk than molnupiravir {adjusted HR 0.35 [95% confidence interval (CI) 0.17-0.71]; P = .004}, with results remaining robust in multiple sensitivity analyses. In the SRR cohort, sotrovimab showed a trend toward lower outcome risk than molnupiravir [HR 0.39 (95% CI 0.13-1.21); P = .106]. In both datasets, sotrovimab had no evidence of an association with other hospitalisation/death compared with molnupiravir (HRs ranged from 0.73 to 1.29; P > .05). Conclusions: In routine care of non-hospitalised patients with COVID-19 on KRT, sotrovimab was associated with a lower risk of severe COVID-19 outcomes compared with molnupiravir during Omicron waves.

Forgotten but not gone in rural South Africa: Urinary schistosomiasis and implications for chronic kidney disease screening in endemic countries.

Background: Urinary schistosomiasis caused by infection with Schistosoma haematobium ( S. haematobium) remains endemic in Africa and is associated with haematuria and albuminuria/proteinuria. Kidney Disease Improving Global Outcomes clinical guidelines recommend evaluating proteinuria/albuminuria and glomerular filtration rate for chronic kidney disease (CKD) diagnosis. The guidelines are informed by population data outside of Africa but have been adopted in many African countries with little validation. Our study aimed to characterise the burden of urinary schistosomiasis in rural South Africa (SA) and evaluate its relationship with markers of kidney dysfunction with implications for CKD screening. Methods: In this population-based cohort study, we recruited 2021 adults aged 20 - 79 years in the Mpumalanga Province, SA. Sociodemographic data were recorded, urinalysis performed, and serum creatinine and urine albumin and creatinine measured. Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m 2 and/or urine albumin-creatinine ratio >3.0mg/mmol. S . haematobium infection was determined by urine microscopy. Multivariable analyses were performed to determine relationships between S. haematobium and markers of kidney dysfunction. Results: Data were available for 1226 of 2021 participants. 717 (58.5%) were female and the median age was 35 years (IQR 27 - 47). Prevalence of kidney dysfunction and S. haematobium was 20.2% and 5.1% respectively. S. haematobium was strongly associated with kidney dysfunction (OR 8.66; 95% CI 4.10 - 18.3) and related to albuminuria alone (OR 8.69; 95% CI 4.11 - 18.8), with no evidence of an association with eGFR <90ml/min/1.73m 2 (OR 0.43; 95% CI 0.05 - 3.59). Discussion: The strong association between urinary schistosomiasis and albuminuria requires careful consideration when screening for CKD. Screening for, and treatment of, schistosomiasis should be a routine part of initial work-up for CKD in S. haematobium endemic areas. Urinary schistosomiasis, a neglected tropical disease, remains a public health concern in the Mpumulanga province of SA.

The risk of acute kidney injury in colorectal cancer survivors: an english population-based matched cohort study.

BACKGROUND: Colorectal cancer survival has improved in recent decades but there are concerns that survivors may develop kidney problems due to adverse effects of cancer treatment or complications of the cancer itself. We quantified the risk of acute kidney injury (AKI) in colorectal cancer survivors compared to people with no prior cancer. METHODS: Retrospective matched cohort study using electronic health record primary care data from the Clinical Practice Research Datalink GOLD linked to hospital data in England (HES-APC). Individuals with colorectal cancer between 1997-2018 were individually matched on age, sex, and GP practice to people with no prior cancer. We used Cox models to estimate hazard ratios for an incident hospital diagnosis of AKI in colorectal cancer survivors compared to individuals without cancer, overall and stratified by time since diagnosis adjusted for other individual-level factors (adj-HR). RESULTS: Twenty thousand three hundred forty colorectal cancer survivors were matched to 100,058 cancer-free individuals. Colorectal cancer survivors were at increased risk of developing AKI compared to people without cancer (adj-HR = 2.16; 95%CI 2.05-2.27). The HR was highest in the year after diagnosis (adj-HR 7.47, 6.66-8.37), and attenuated over time, but there was still increased AKI risk > 5 years after diagnosis (adj-HR = 1.26, 1.17-1.37). The association between colorectal cancer and AKI was greater for younger people, men, and those with pre-existing chronic kidney disease. CONCLUSIONS: Colorectal cancer survivors were at increased risk of AKI for several years after cancer diagnosis, suggesting a need to prioritise monitoring, prevention, and management of kidney problems in this group of cancer survivors.

Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.

BACKGROUND: People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic. OBJECTIVE: To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic. METHODS: Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP. FINDINGS: In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic. CONCLUSIONS: People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use. CLINICAL IMPLICATIONS: Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.