Publications
scientifiques

BACKGROUND: Few studies have shown that an increased risk of dementia is associated with diabetes mellitus. OBJECTIVE: To estimate the prevalence and incidence of dementia in people with diabetes in primary care in the UK. METHODS: We conducted a descriptive study using the UK The Health Improvement Network (THIN) database. People diagnosed with diabetes from 2000 to 2016 were included in the study. Prevalence and incidence rates of dementia were calculated annually, stratified by age and gender. RESULTS: The prevalence of dementia was 0.424% [95% CI (0.420%-0.427%)] in 2000 and 2.508% [95% CI (2.501%-2.515%)] in 2016. The highest prevalence was in those aged 85+ from 2.9% [95% CI (2.890%-2.974%)] in 2000 to 11.3% [95% CI (11.285%-11.384%)] in 2016. The incidence of dementia increased 3.7 times, from 0.181 cases per 100 persons [95% CI (0.179-0.183)] in 2000 to 0.683 cases per 100 persons [95% CI (0.679-0.686)] in 2016, respectively. Women had a higher prevalence and incidence of dementia than men 3.138% [95% CI (3.127%-3.150%)] versus 2.014% [95% CI (2.006%-2.022%)] and 0.820 [95% CI (0.814-0.826)] versus 0.576 cases per 100 persons [95% CI (0.571-0.580)] in 2016, respectively. CONCLUSION: There was a trend of increasing prevalence and incidence of dementia in people with diabetes over the period of 2000 to 2016. This study adds to the evidence on dementia prevalence and incidence, particularly in the diabetic population.

BACKGROUND: Whether oral anticoagulation (OAC) can prevent dementia or cognitive impairment (CI) in patients with atrial fibrillation (AF) remains unclear. OBJECTIVE: The purpose of this study was to investigate the risk of dementia/CI among AF patients with and without OAC treatment. METHODS: We conducted a retrospective cohort study using United Kingdom (UK) primary care data (2000-2017). Participants with newly diagnosed AF without a history of dementia/CI were identified. Inverse probability of treatment weights based on propensity scores and Cox regression were used to compare the dementia outcomes. RESULTS: Among 84,521 patients with AF, 35,245 were receiving OAC treatment and 49,276 received no OAC treatment; of these patients, 29,282 were receiving antiplatelets. Over a mean follow-up of 5.9 years, 5295 patients developed dementia/CI. OAC treatment was associated with a lower risk of dementia/CI compared to no OAC treatment (hazard ratio [HR] 0.90; 95% confidence interval 0.85-0.95; P <.001) or antiplatelets (HR 0.84; 95% confidence interval 0.79-0.90; P <.001). No significant difference in dementia risk was observed for direct oral anticoagulants (DOACs) vs warfarin (HR 0.89; 95% confidence interval 0.70-1.14; P = .373), whereas dual therapy (OAC plus an antiplatelet agent) was associated with a higher risk of dementia/CI compared with no treatment (HR 1.17; 95% confidence interval 1.05-1.31; P = .006). CONCLUSION: OAC use was associated with a lower risk of dementia/CI compared to non-OAC and antiplatelet treatment among AF patients. The evidence for DOAC on cognitive function is insufficient, and further studies including randomized clinical trials are warranted.

Background Childhood maltreatment remains a significant public health issue associated with a number of poor health outcomes. This study explores the association between childhood maltreatment and the subsequent development of cardiometabolic disease and all-cause mortality. Methods and Results Using a UK primary care database between January 1, 1995 and December 31, 2018, we conducted a population-based open retrospective cohort study. We matched 80 657 adult patients with a historic recording of childhood maltreatment or maltreatment-related concerns (exposed group) to 161 314 unexposed patients. Outcomes of interest were the development of cardiovascular disease, hypertension, type 2 diabetes mellitus, and risk of all-cause mortality. During the study period there were 243 new diagnoses of cardiovascular disease (incidence rate 8.3 per 10 000 person-years) in the exposed group compared with 254 in the unexposed group (incidence rate 4.6 per 10 000 person-years). Following adjustment for key covariates, this translated to an adjusted incidence rate ratio of 1.71 (95% CI 1.42-2.06). Additionally, the exposed group had an increased risk of hypertension (adjusted incidence rate ratio 1.42; 95% CI, 1.26-1.59), type 2 diabetes mellitus (adjusted incidence rate ratio 2.13; 95% CI, 1.86-2.45) and all-cause mortality (adjusted incidence rate ratio 1.75; 95% CI, 1.52-2.02) during the study period compared with the unexposed group. Conclusions Considering the high prevalence of exposure to childhood maltreatment, we have demonstrated the substantial associated burden of preventable cardiometabolic disease. There is a clear need to ensure that public health approaches are implemented to prevent the adverse consequences following exposure to childhood maltreatment.

AIMS: To compare the effect of bariatric surgery on renal, chronic kidney disease (CKD) and cardiovascular (CV) outcomes among obese patients with insulin-treated type 2 diabetes (T2D) with and without microalbuminuria (i.e., uACR > 3.0 mg/mmol). METHODS: A retrospective cohort study was conducted among 11,125 active patients with T2D from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10 years (6487 person-years) to compare differences in risk of cardiovascular events and in renal outcomes. RESULTS: For the matched cohort at baseline: mean age 52 ± 13 years (60% female); weight 116 ± 25 kg, body mass index (BMI) 41 ± 9kg/m , estimated glomerular filtration rate (eGFR); 70.4 ± 20 mL/min/1.73 m , and median albumin-creatinine ratio (uACR) 2.0 mg/mmol (interquartile range (IQR): 0.9-5.2 mg/mmol). Bariatric surgery was associated with a 54% reduction in developing CKD compared to their matched non-bariatric cohort (adjusted hazard ratio [aHR]: 0.46; 95%CI: 0.24-0.85, P = 0.02). Among patients with microalbuminuria at baseline, bariatric surgery was protective against CKD (aHR: 0.42, 95%CI: 0.18-0.99, P = 0.050). eGFR was significantly increased from baseline favouring the bariatric group during 75% of the follow-up time (calculated mean difference between groups: 4.1 mL/min/1.73 m ; P < 0.05), especially at 5-year point (74.2 vs 67.8 mL/min/1.73 m ; P < 0.001). However, no significant change was observed with non-fatal CVD episodes (aHR: 0.36, 95%CI: 0.11-1.13, P = 0.079). Albumin levels were significantly reduced throughout the 2 years following the surgery (3.9 vs 4.1 g/dL, P < 0.001). uACR and total protein levels had little or no statistical association to the intervention. CONCLUSION: Bariatric surgery may protect patients with diabetes with or without microalbuminuria against the risk of CKD and with a modest protective effect on non-fatal CVD risk. Bariatric surgery is also associated with improvements in overall renal outcomes such as eGFR.

BACKGROUND: Data regarding incidence, prevalence and long-term outcomes of inflammatory bowel diseases in the UK are limited or outdated. AIMS: To investigate incidence and prevalence of Crohn's disease and ulcerative colitis and risk of colorectal cancer and all-cause mortality in these diseases. METHODS: Inflammatory bowel disease cases between 2000 and 2018 were identified from a national primary care database. Inflammatory bowel disease prevalence was forecast until 2025. The association between inflammatory bowel disease and colorectal cancer and all-cause mortality was investigated using age/sex-matched retrospective cohort studies. Hazard ratios were adjusted for age, sex, deprivation, comorbidity, smoking status and body mass index. RESULTS: Ulcerative colitis prevalence increased from 390 to 570 per 100 000 population from 2000 to 2017. Prevalence of Crohn's disease increased from 220 to 400 per 100 000. In 2017 male Crohn's disease prevalence was 0.35% (95% confidence interval 0.34-0.36); female prevalence was 0.44% (0.43-0.45). Prevalence of inflammatory bowel disease is predicted to be 1.1% by 2025. Incidence of ulcerative colitis and Crohn's disease was 23.2 (22.8-23.6) and 14.3 (14.0-14.7) per 100 000 person-years respectively. Subjects with ulcerative colitis were more likely to develop colorectal cancer than controls (adjusted Hazard Ratio 1.40 [1.23-1.59]). Colorectal cancer rates remained stable in inflammatory bowel diseases over time. Ulcerative colitis and Crohn's disease were associated with increased risk of all-cause mortality (1.17 [1.14-1.21] and 1.42 [1.36-1.48] respectively). CONCLUSIONS: The UK prevalence of inflammatory bowel disease is greater than previous reports suggest and we predict an 11% increase in prevalence by the year 2025. Mortality risk in inflammatory bowel disease and colorectal cancer risk in ulcerative colitis are increased compared to matched controls.

AIMS: Prevalence of the use of antipsychotics (APs) in the paediatric population is globally increasing. The aim of this study was to describe multinational trends and patterns in AP use in children and adolescents in Europe. METHODS: This was a dynamic retrospective cohort study comprising all children and adolescents (⩽18 years of age). Data were extracted from five population-based electronic healthcare databases in Europe (Denmark, Germany, Italy, the Netherlands and United Kingdom) from 2000 to 2010. Yearly prevalence and incidence of AP use was expressed per 1000 person-years (PYs). RESULTS: Prevalence increased from 1.44 to 3.41/1000 PYs (2008) in Denmark and from 2.07 to 4.35/1000 PYs in the NL (2009), moderately increased from 2.8 to 3.24/1000 in UK (2009) and from 1.53 to 1.74/1000 PYs in Germany (2008) and remained low from 0.61 to 0.34/1000 PYs in Italy (2010). Similarly, incidence rates increased from 0.69 to 1.52/1000 PYs in Denmark and from 0.86 to 1.49/1000 PYs in the NL, stabilised from 2.29 to 2.37/1000 PYs in the UK and from 0.79 to 0.80/1000 PYs in Germany and remained low from 0.32 to 0.2/1000 PYs in Italy. AP use was highest in 15-18 year olds and in boys compared to girls. Yet, the use observed in the 5-9 year olds was found to be comparatively high in the NL. Prescriptions of second generation APs, especially risperidone, were privileged but the first generation APs were still prescribed in the youngest. CONCLUSIONS: A steady increase in AP use in children and adolescents was observed essentially in the NL and Denmark. The use in Germany and Italy was lowest among countries. The use of APs under 9 years of age underlines their off-label use and should be carefully monitored as the risk/benefit ratio of these medications remains unclear in young children. AP use was altogether lower in Europe as compared to that reported in North America.

OBJECTIVE: To evaluate health outcomes, resource use and corresponding costs attributable to managing burns in clinical practice, from initial presentation, among a cohort of adults in the UK. DESIGN: Retrospective cohort analysis of the records of a randomly selected cohort of 260 patients from The Health Improvement Network (THIN) database who had 294 evaluable burns. SETTING: Primary and secondary care sectors in the UK. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients' characteristics, wound-related health outcomes, healthcare resource use and total National Health Service (NHS) cost of patient management. RESULTS: Diagnosis was incomplete in 63% of patients' records as the location, depth and size of the burns were missing. Overall, 70% of all the burns healed within 24 months and the time to healing was a mean of 7.8 months per burn. Sixty-six per cent of burns were initially managed in the community and the other 34% were managed at accident and emergency departments. Patients' wounds were subsequently managed predominantly by practice nurses and hospital outpatient clinics. Forty-five per cent of burns had no documented dressings in the patients' records. The mean NHS cost of wound care in clinical practice over 24 months from initial presentation was an estimated £16 924 per burn, ranging from £12 002 to £40 577 for a healed and unhealed wound, respectively. CONCLUSIONS: Due to incomplete documentation in the patients' records, it is difficult to say whether the time to healing was excessive or what other confounding factors may have contributed to the delayed healing. This study indicates the need for education of general practice clinicians on the management and care of burn wounds. Furthermore, it is beholden on the burns community to determine how the poor healing rates can be improved. Strategies are required to improve documentation in patients' records, integration of care between different providers, wound healing rates and reducing infection.

Exploring and combining results from more than one real-world data (RWD) source might be necessary in order to explore variability and demonstrate generalizability of the results or for regulatory requirements. However, the heterogeneous nature of RWD poses challenges when working with more than one source, some of which can be solved by analyzing databases converted into a common data model (CDM). The main objective of the study was to evaluate the implementation of the Observational Medical Outcome Partnership (OMOP) CDM on IQVIA Medical Research Data (IMRD)-UK data. A drug utilization study describing the prescribing of codeine for pain in children was used as a case study to be replicated in IMRD-UK and its corresponding OMOP CDM transformation. Differences between IMRD-UK source and OMOP CDM were identified and investigated. In IMRD-UK updated to May 2017, results were similar between source and transformed data with few discrepancies. These were the result of different conventions applied during the transformation regarding the date of birth for children younger than 15 years and the start of the observation period, and of a misclassification of two drug treatments. After the initial analysis and feedback provided, a rerun of the analysis in IMRD-UK updated to September 2018 showed almost identical results for all the measures analyzed. For this study, the conversion to OMOP CDM was adequate. Although some decisions and mapping could be improved, these impacted on the absolute results but not on the study inferences. This validation study supports six recommendations for good practice in transforming to CDMs.

Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

BACKGROUND: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk monitoring of vaccines using existing healthcare databases in Europe. We estimated vaccine coverage from electronic healthcare databases as part of a fit-for-purpose assessment for vaccine benefit-risk studies. METHODS: A retrospective dynamic cohort study was conducted through a distributed network approach. Coverage with measles-vaccine for birth year 2006, human papillomavirus (HPV)-vaccine for birth years 1990-2000 and influenza-vaccine for birth years 1920-1950 was estimated using period-prevalence and inverse probability weighting methods. Seven databases from four countries participated: Italy (Pedianet, Val Padana), Spain (BIFAP, SIDIAP), UK (RCGP-RSC, THIN), Denmark (SSI/AUH). Database access providers extracted the data, transformed it into a common structure and ran an R-script locally. The created output tables were shared and pooled at a central server. RESULTS: The total study population comprised 274,616 persons for measles-vaccine, 2,011,666 persons for HPV-vaccine and 14,904,033 persons for influenza-vaccine. Measles-vaccine coverage varied from 84.3% (Denmark) to 96.5% (Italy, Val Padana) for the first dose and from 82.8% (Italy, Val Padana) to 90.9% (UK) for the second dose at the age of 7 years. The HPV-vaccine coverage, aggregated over birth years 1997-2000, ranged from 60% (UK) to 88.3% (Denmark) at the age of 15 years. The influenza-vaccine coverage for the influenza seasons from 2009 to 2015 for persons aged 65 years and more was roughly stable around 43% in Denmark and around 68% in the UK while a decrease from 58 to 50% was observed in Catalonia (Spain). CONCLUSIONS: We obtained detailed, age-specific coverage estimates though a common procedure. We discussed between database comparability and comparability to published national estimates.

This study measured the exposure to different categories of medicinal products discussed by the European Union (EU) Pharmacovigilance Risk Assessment Committee from September to November 2018 in four electronic primary care health databases: IQVIA Medical Research Data-UK, IQVIA Medical Research Data-France, IQVIA Medical Research Data-Germany, and Clinical Practice Research Datalink Aurum, in the entire lifespan of each database until August 31, 2018. The assessment of 83 centrally authorized products and 45 nationally authorized products showed that coverage was better for products marketed for longer duration and worse for orphan drugs. The ability to detect associations against hypothetical comparators was better for more common events and for larger effect sizes. Coverage of advanced therapies was worse for those typically administered in a specialized rather than primary care setting. This study shows that to enable better informed regulatory decisions there is a need to access complementary data sources, particularly capturing secondary care prescribing.

BACKGROUND: Primary care is likely to see the highest number of Lyme disease patients. Despite this, there is limited published data regarding Lyme disease patients accessing primary care in the UK. We aim to describe trends in the incidence of a new diagnosis, and demographics of patients identified in a primary care electronic health database. METHODS: A descriptive epidemiological study of Lyme disease coded patients in UK primary care. 3725 patients coded for Lyme disease during 1998-2016 were identified within The Health Improvement Network (THIN). Incidence rates and the demographics of cases identified were described. Poisson regression was used to analyse socio-demographic characteristics of the cases. RESULTS: There was an increase in annual crude incidence rates, peaking in 2015 at 5.47 (95% CI 4.85-6.14) cases per 100,000 population per year. Multivariable analysis showed there were significant differences in the ages of those affected, incidence of a new diagnosis rose as deprivation levels improved, and that there was a higher incidence of cases living in rural areas compared to urban areas. There was no significant difference between sexes for the UK. Cases were significantly more likely to identify with being white compared to the national population. CONCLUSIONS: An increasing incidence of patients newly coded with Lyme disease related Read codes was identified using data from a UK national primary care database. By comparing these incidence figures with national laboratory-confirmed surveillance data, a multiplication factor of 2.35 (95%CI 1.81-2.88) can be calculated in order to estimate the annual number of cases seen in primary care. The significant socio-demographic variables associated with a Lyme disease diagnosis likely reflect a complex interplay of socio-economic issues, which needs to be further explored. Future work is needed to examine the treatment and management of patients within this database.

BACKGROUND: The database used for the NHS Bowel Cancer Screening Programme (BCSP) derives participant information from primary care records. Combining predictors with FOBTs has shown to improve referral decisions and accuracy. The richer data available from GP databases could be used to complement screening referral decisions by identifying those at greatest risk of colorectal cancer. We determined the availability of data for key predictors and whether this information could be used to inform more accurate screening referral decisions. METHODS: An English BCSP cohort was derived using the electronic notifications received from the BCSP database to GP records. The cohort covered a period between 13th May 2009 to 17th January 2017. Completeness of variables and univariable associations were assessed. Risk prediction models were developed using Cox regression and multivariable fractional polynomials with backwards elimination. Optimism adjusted performance metrics were reported. The sensitivity and specificity of a combined approach using the negative FOBT model plus FOBT positive patients was determined using a probability equivalent to a 3% PPV NICE guidelines level. RESULTS: 292,059 participants aged 60-74 were derived for the BCSP screening cohort. A model including the screening test result had a C-statistic of 0.860, c-slope of 0.997, and R of 0.597. A model developed for negative screening results only had a C-statistic of 0.597, c-slope of 0.940, and R of 0.062. Risk predictors included in the models included; age, sex, alcohol consumption, IBS diagnosis, family history of gastrointestinal cancer, smoking status, previous negatives and whether a GP had ordered a blood test. For the combined screening approach, sensitivity increased slightly from 53.90% (FOBT only) to 58.82% but at the expense of an increased referral rate. CONCLUSIONS: This research has identified several potential predictors for CRC in a BCSP population. A risk prediction model developed for BCSP FOBT negative patients was not clinically useful due to a low sensitivity and increased referral rate. The predictors identified in this study should be investigated in a refined algorithm combining the quantitative FIT result. Combining data from multiple sources enables fuller patient profiles using the primary care and screening database interface.

BACKGROUND: Albuminuria is a recognized diagnostic and prognostic marker of chronic kidney disease and cardiovascular (CV) risk but the well-known relationship between increments in urinary albumin:creatinine ratio (UACR) and CV outcomes and mortality has not been fully explored in insulin-treated patients with type 2 diabetes (T2D) in routine clinical care. METHODS: We investigated data for insulin users with T2D from UK general practices between 2007 and 2014. The UACR at the time of insulin initiation was measured and categorized as <10, 10- 29, 30-300 and >300 mg/g. Patients were followed up for 5 years or the earliest occurrence of all-cause mortality, non-fatal myocardial infarction or stroke. Cox proportional hazards models were fitted to estimate the risk of a composite of these events. RESULTS: A total of 12 725 patients with T2D (mean age 58.6 ± 13.8 years, mean haemoglobin A1c 8.7 ± 1.8%) initiating insulin therapy between 2007 and 2014 met the inclusion criteria. Compared with patients whose ACR levels at insulin initiation were <10 mg/g, the adjusted risk of the 3-point composite endpoint was 9, 30 and 98% higher in those with ACR levels between 10-29, 30-300 and >300 mg/g, respectively, after a follow-up period of 5 years. The ACR category on its own did not predict risk of all-cause mortality. CONCLUSIONS: This study shows that in patients with T2D on insulin therapy, increased urinary ACR is independently associated with an increased risk of major adverse CV events and all-cause mortality.

BACKGROUND: Cohort studies have shown that bariatric surgery may reduce the incidence of and mortality from cardiovascular disease (CVD), but studies using real-world data are limited. This study examined the impact of bariatric surgery on incident CVD, hypertension and atrial fibrillation, and all-cause mortality. METHODS: A retrospective, matched, controlled cohort study of The Health Improvement Network primary care database (from 1 January 1990 to 31 January 2018) was performed (approximately 6 per cent of the UK population). Adults with a BMI of 30 kg/m or above who did not have gastric cancer were included as the exposed group. Each exposed patient, who had undergone bariatric surgery, was matched for age, sex, BMI and presence of type 2 diabetes mellitus (T2DM) with two controls who had not had bariatric surgery. RESULTS: A total of 5170 exposed and 9995 control participants were included; their mean(s.d.) age was 45·3(10·5) years and 21·5 per cent (3265 of 15 165 participants) had T2DM. Median follow-up was 3·9 (i.q.r. 1·8- 6·4) years. Mean(s.d.) percentage weight loss was 20·0(13·2) and 0·8(9·5) per cent in exposed and control groups respectively. Overall, bariatric surgery was not associated with a significantly lower CVD risk (adjusted hazard ratio (HR) 0·80; 95 per cent c.i. 0·62 to 1·02; P = 0·074). Only in the gastric bypass group was a significant impact on CVD observed (HR 0·53, 0·34 to 0·81; P = 0·003). Bariatric surgery was associated with significant reduction in all-cause mortality (adjusted HR 0·70, 0·55 to 0·89; P = 0·004), hypertension (adjusted HR 0·41, 0·34 to 0·50; P < 0·001) and heart failure (adjusted HR 0·57, 0·34 to 0·96; P = 0·033). Outcomes were similar in patients with and those without T2DM (exposed versus controls), except for incident atrial fibrillation, which was reduced in the T2DM group. CONCLUSION: Bariatric surgery is associated with a reduced risk of hypertension, heart failure and mortality, compared with routine care. Gastric bypass was associated with reduced risk of CVD compared to routine care.

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75-300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case-control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB ( = 987), ORs (95% CIs) were 0.69 (0.54-0.88) for >1 month PPI use and 2.65 (1.62-4.3) for ≤1 month PPI use. Among the latter group, ORs (95% CIs) were 3.05 (1.75-5.33) for PPI initiation after start of aspirin therapy, and 1.66 (0.63-4.36) for PPI initiation on/before start of aspirin therapy. For LGIB ( = 1428), ORs (95% CIs) were 0.98 (0.81-1.17) for >1 month PPI use and 1.12 (0.73-1.71) for ≤1 month PPI use. Among low-dose aspirin users, maintaining PPI use (>1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk.

BACKGROUND: Understanding the outcomes and risks for live kidney donors (LD) is increasingly important; this study investigated all-cause mortality and morbidity outcomes of LD compared with a healthy cohort. METHODS: Live donor dataset was obtained from the UK Transplant Registry and a comparator nondonor cohort selected from The Health Improvement Network (THIN) database, a UK primary healthcare database. All LD from January 1, 2001, to December 31, 2013, were included, with follow-up until December 31, 2016. RESULTS: There were 9750 LD and 19 071 THIN participants. Median follow-up (interquartile range) for LD was 8.4 (6.0-11.3) years and for THIN was 5.4 (2.6-8.5) years. In up to 15 years, follow-up end-stage renal disease was observed in 1 LD versus 7 THIN (P = 0.280). Nine LD had estimated glomerular filtration rate of <30 mL/min/1.73 m versus 43 in THIN (P = 0.012), but no statistically significant difference in adjusted logistic regression analyses. Risk of diabetes mellitus, depression, and cardiovascular disease was significantly higher for THIN cohort in adjusted analyses. The risk of hypertension was higher for LD at 5 years but was not significantly different in fully adjusted analyses at 10 years. There were 68 deaths in LD and 485 in THIN over the follow-up period, with significant difference in mortality favoring LD (P < 0.001). CONCLUSIONS: The medium-term morbidity and mortality outcomes of live donors in comparison with a healthy cohort suggest that live donation is not associated with excess mortality, end-stage renal disease, or morbidity, in at least 10 years follow-up.