UK Primary Care Database Research Articles

Body mass index and risk of obesity-related conditions in a cohort of 2.9 million people: Evidence from a UK primary care database.

ObjectiveObesity rates in the United Kingdom are some of the highest in Western Europe, with considerable clinical and societal impacts. Obesity is associated with type 2 diabetes (T2D), osteoarthritis, cardiovascular disease, and increased mortality; however, relatively few studies have examined the occurrence of multiple obesity‐related outcomes in the same patient population. This study was designed to examine the associations between body mass index (BMI) and a broad range of obesity‐related conditions in the same large cohort from a UK‐representative primary care database.MethodsDemographic data and diagnosis codes were extracted from the Clinical Practice Research Datalink GOLD database in January 2019. Adults registered for ≥ 3 years were grouped by BMI, with BMI 18.5–24.9 kg/m2 as reference group. Associations between BMI and 12 obesity‐related outcomes were estimated using Cox proportional hazard models, adjusted for age, sex, and smoking.ResultsMore than 2.9 million individuals were included in the analyses and were followed up for occurrence of relevant outcomes for a median of 11.4 years during the study period. Generally, there was a stepwise increase in risk of all outcomes with higher BMI. Individuals with BMI 40.0–45.0 kg/m2 were at particularly high risk of sleep apnea (hazard ratio [95% confidence interval] vs. reference group: 19.8 [18.9–20.8]), T2D (12.4 [12.1–12.7]), heart failure (3.46 [3.35–3.57]), and hypertension (3.21 [3.15–3.26]).ConclusionsThis study substantiates evidence linking higher BMI to higher risk of a range of serious health conditions, in a large, representative UK cohort. By focusing on obesity‐related conditions, this demonstrates the wider clinical impact and the healthcare burden of obesity, and highlights the vital importance of management, treatment approaches, and public health programs to mitigate the impact of this disease.

Primary care consultations after hospitalisation for pneumonia: a large population-based cohort study.

Up to 70% of patients report ongoing symptoms 4 weeks after hospitalisation for pneumonia; the impact on primary care is poorly understood. To investigate the frequency of primary care consultations after hospitalisation for pneumonia, and the reasons for consultation. A population-based cohort study in England using a UK primary care database of anonymised medical records (Clinical Practice Research Datalink [CPRD]) linked to Hospital Episode Statistics (HES). Adults with the first International Classification of Diseases, 10th Revision (ICD-10) code for pneumonia (J12-J18) recorded in HES between July 2002 and June 2017 were included. Primary care consultation within 30 days of discharge was identified as the recording of any medical Read code (excluding administration-related codes) in CPRD. Competing-risks regression analyses were conducted to determine the predictors of consultation and antibiotic use at consultation; death and readmission were competing events. Reasons for consultation were examined. Of 56 396 adults, 55.9% (n = 31 542) consulted primary care within 30 days of hospital discharge. The rate of consultation was highest within 7 days (4.7 per 100 person-days). The strongest predictor for consultation was a higher number of primary care consultations in the year before index admission (adjusted subhazard ratio [sHR] 8.98, 95% confidence interval [CI] = 6.42 to 12.55). The most common reason for consultation was for a respiratory disorder (40.7%, n = 12 840), 11.8% for pneumonia specifically. At consultation, 31.1% (n = 9823) received further antibiotics. Penicillins (41.6%, n = 5753/13 829) and macrolides (21.9%, n = 3029/13 829) were the most common antibiotics prescribed. Following hospitalisation for pneumonia, a significant proportion of patients consulted primary care within 30 days, highlighting the morbidity experienced by patients during recovery from pneumonia.

COVID-19 death in people with HIV: interpret cautiously

COVID-19 death in people with HIV: interpret cautiously

Aspirin reduces cardiovascular events in patients with pneumonia: a prior event rate ratio analysis in a large primary care database.

Ischaemic stroke and myocardial infarction (MI) are common after pneumonia and are associated with long-term mortality. Aspirin may attenuate this risk and should be explored as a therapeutic option. We extracted all patients with pneumonia (aged over 50 years) from the Clinical Practice Research Datalink (CPRD), a large UK primary care database, from inception until January 2019. We then performed a prior event rate ratio (PERR) analysis with propensity score matching (PSM), an approach that allows for control of measured and unmeasured confounding, with aspirin usage as the exposure and ischaemic events as the outcome. The primary outcome was the combined outcome of ischaemic stroke and MI. Secondary outcomes were ischaemic stroke and MI individually. Relevant confounders (smoking, comorbidities, age and gender) were included in the analysis. 48 743 patients were eligible for matching. Of these, 9864 were aspirin users who were matched to 9864 non-users. Aspirin users had a reduced risk of the primary outcome (adjusted hazard ratio 0.64, 95% CI 0.52-0.79) in the PERR analysis. For both secondary outcomes, aspirin use was also associated with a reduced risk for MI (hazard ratio 0.46, 95% CI 0.30-0.72) and stroke (hazard ratio 0.70, 95% CI 0.55-0.91), respectively. This study provides supporting evidence that aspirin use is associated with reduced ischaemic events after pneumonia in a primary care setting. This drug may have a future clinical role in preventing this important complication.

The use of UK primary care databases in health technology assessments carried out by the National Institute for health and care excellence (NICE)

BackgroundReal world evidence (RWE) is becoming more frequently used in technology appraisals (TAs). This study sought to explore the use and acceptance of evidence from primary care databases, a key source of RWE in the UK, in National Institute for Health and Care Excellence (NICE) technology assessments and to provide recommendations regarding their use in future submissions.MethodsA keyword search was conducted relating to the main primary care databases in the UK on the NICE website. All NICE TAs identified through this search were screened, assessed for duplication and information on the data source and the way the data was used in the submission were extracted. Comments by the evidence review group (ERG) and the appraisal committee were also extracted and reviewed. All data extraction was performed by two independent reviewers and all decisions were reached by consensus with an additional third reviewer.ResultsA total of 52 NICE TAs were identified, 47 used the General Practice Research Database /Clinical Practice Research Datalink (GPRD/CPRD) database, 10 used The Health Improvement Network (THIN) database and 3 used the QResearch databases. Data from primary care databases were used to support arguments regarding clinical need and current treatment in 33 NICE TAs while 36 were used to inform input parameters for economic models. The databases were sometimes used for more than one purpose. The data from the three data sources were generally well received by the ERGs/committees. Criticisms of the data typically occurred where the results had been repurposed from a published study or had not been applied appropriately.ConclusionsThe potential of UK primary care databases in NICE submissions is increasingly being realised, particularly in informing the parameters of economic models. Purpose conducted studies are less likely to receive criticism from ERGs/committees, particularly when providing clinical input into cost effectiveness models.

The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes.

Background: Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure.Methods: A retrospective population based open cohort study using the UK primary care database, ‘The Health Improvement Network,’ between 1st January 1995-31st December 2018. 80,657 adult patients who had experienced childhood maltreatment or maltreatment related concerns (exposed patients) were matched to 161,314 unexposed patients by age and sex. Outcomes of interest were the development of CSS: either somatic (Fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic headache, myofascial pain syndrome and restless leg syndrome) or visceral (Interstitial cystitis, vulvodynia, chronic prostatitis and irritable bowel syndrome) in nature. Effect sizes are presented as adjusted incidence rate ratios (aIRR) with confidence intervals (CI). Models were adjusted for the following covariates at cohort entry: age, sex, deprivation, anxiety, depression and serious mental ill health.Results: The average age at cohort entry was 23.4 years and the median follow was 2.2 years. There was an increased risk of developing fibromyalgia (aIRR 2.06; 95% CI 1.71–2.48), chronic fatigue syndrome (1.47; 1.08–2.00), chronic lower back pain (1.99; 1.68–2.35), restless leg syndrome (1.82; 1.41–2.35) and irritable bowel syndrome (1.15; 1.08–1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88–1.13), chronic headache (1.04; 0.59–1.86), interstitial cystitis (1.19; 0.51–2.74), vulvodynia (0.65; 0.34–1.26), chronic prostatitis (0.34; 0.07–1.77) and myofascial pain syndrome (0.88; 0.36–2.14). Outcome numbers were low, most likely, due to the rarity of visceral conditions (aside from irritable bowel syndrome). The association between a history of childhood maltreatment and CSS were mainly observed in somatic CSS.Interpretation: The debilitating effects of CSS carry a substantial physical, psychological and economic burden to both the individuals who are diagnosed with them and the health services who serve them. Primary prevention approaches targeting childhood maltreatment as well as secondary preventative approaches should be considered to minimise the associated burden of CSS.

Increased Cardiometabolic and Mortality Risk Following Childhood Maltreatment in the United Kingdom.

BackgroundChildhood 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 ResultsUsing 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.ConclusionsConsidering 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.

Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation

IntroductionTo identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i).Research design and methodsWe assessed the relationship between baseline characteristics and genital...

Trends in the Incidence of Parkinson’s disease diagnosis between 2006 and 2016: Analysis of a large UK Primary care database. (5205)

Trends in the Incidence of Parkinson’s disease diagnosis between 2006 and 2016: Analysis of a large UK Primary care database. (5205)

Comorbidity phenotypes and risk of mortality in patients with ischaemic heart disease in the UK

ObjectivesThe objective of this study is to use latent class analysis of up to 20 comorbidities in patients with a diagnosis of ischaemic heart disease (IHD) to identify clusters of...

Effect of Bariatric Surgery on Diagnosed Chronic Kidney Disease and Cardiovascular Events in Patients with Insulin-treated Type 2 Diabetes: a Retrospective Cohort Study from a Large UK Primary Care Database

AimsTo 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).MethodsA 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.ResultsFor the matched cohort at baseline: mean age 52 ± 13 years (60% female); weight 116 ± 25 kg, body mass index (BMI) 41 ± 9kg/m2, estimated glomerular filtration rate (eGFR); 70.4 ± 20 mL/min/1.73 m2, 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 m2; P < 0.05), especially at 5-year point (74.2 vs 67.8 mL/min/1.73 m2; 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.ConclusionBariatric 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.

Epidemiology, morbidity and mortality in Behçet's disease: a cohort study using The Health Improvement Network (THIN).

The epidemiology of Behçet's disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). The prevalence of BD was 14.61 (95% CI 13.35-15.88) per 100000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28-7.44)], venous thrombosis [aHR 4.80 (2.42-9.54)] and mortality [aHR 1.40 (1.07-1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66-8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

Predictors of Bleeding in Patients with Symptomatic Peripheral Artery Disease: A Cohort Study Using the Health Improvement Network (THIN) in the UK

Introduction: Cardiovascular risk reduction guidelines recommend antiplatelets and statins for all individuals with symptomatic peripheral artery disease (PAD), and antihypertensives for those with concomitant hypertension. Antiplatelet use is associated with an increased bleeding risk. We aimed to assess potential risk factors for intracranial bleeding (ICB) and gastrointestinal bleeding (GIB) in patients with symptomatic PAD. Methods: Patients aged 50–89 years diagnosed with symptomatic PAD in 2000–2010 were identified using The Health Improvement Network (THIN) UK primary care database (N = 28 484). The main exclusion criteria were: dementia; ischaemic stroke; anticoagulant or dual antiplatelet therapy (past 3 months); and previous ICB or GIB (past 6 months). Patients were followed up until they reached an endpoint (ICB or GIB), death or end of follow-up (ICB: June 2013; GIB: March 2012). Follow-up for GIB was restricted to THIN practices linked to hospital episode statistics data. Potential comorbid, demographic and therapeutic risk factors for ICB (153 cases) and GIB (506 cases) were assessed using a nested case–control analysis, with 1000 controls for ICB and 5000 controls for GIB, case-matched by age, sex and calendar year. Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders, were calculated. Results: The incidence of ICB was 7.9 (95% CI: 6.8–9.3) per 10 000 person-years (median follow-up: 6.4 years). Previous ICB was a major predictor of ICB (OR: 3.85; 95% CI: 1.33–11.13). Regarding other potential risk factors for ICB, the OR (95% CI) was 0.90 (0.61–1.34) for treated hypertension, 1.59 (0.65–3.87) for untreated hypertension, 1.38 (0.80–2.36) for current smoking, 0.73 (0.40–1.33) for body mass index (BMI) ≥ 30 kg/m2 and 2.20 (1.12–4.34) for BMI 15–19 kg/m2. Compared with patients not using acetylsalicylic acid (ASA), clopidogrel or warfarin in the previous year (49 patients), the OR (95% CI) for ICB was 0.78 (0.50–1.21) with ASA monotherapy (55 patients), 0.40 (0.09–1.82) with clopidogrel monotherapy (2 patients) and 1.27 (0.47–3.47) with warfarin monotherapy (8 patients). The incidence of GIB was 9.6 (95% CI: 8.8–10.5) per 1000 person-years (median follow-up: 6.0 years). Major predictors (OR; 95% CI) of GIB were peptic ulcer disease (1.40; 1.05–1.86), dual antiplatelet therapy (3.20; 1.81–5.64) and use of non-steroidal anti-inflammatory drugs (1.96; 1.46–2.64). Regarding other potential risk factors for GIB, the OR (95% CI) was 1.32 (1.05–1.65) for treated hypertension, 1.35 (0.77–2.35) for untreated hypertension, 0.98 (0.72–1.33) for smoking, 1.26 (0.92–1.72) for BMI ≥ 30 kg/m2 and 0.67 (0.44–1.01) for BMI 15–19 kg/m2. Compared with individuals not using ASA, clopidogrel or warfarin in the previous year (124 patients), the OR (95% CI) for GIB was 1.78 (1.39–2.30) with ASA monotherapy (245 patients), 2.03 (1.05–3.93) with clopidogrel monotherapy (15 patients) and 1.25 (0.72–2.16) with warfarin monotherapy (19 patients). Conclusion: Incidence of GIB was about 10-fold higher than incidence of ICB in patients with symptomatic PAD in UK primary care. Antiplatelet therapy increased the risk of GIB.

PMU108 LEVERAGING ELECTRONIC HEALTH RECORDS TO MEET THE REAL-WORLD EVIDENCE NEEDS OF HTA: A UK PERSPECTIVE

Review the use of UK primary care databases in NICE technology assessments (TAs) and provide recommendations regarding their use in future submissions. The NICE website was searched for keywords relating to the main primary care databases in the UK. All NICE TAs identified through this search were screened and information on the data source and the way the data was used in the submission were extracted. Comments by the evidence review group (ERG) and committee were also extracted and reviewed. All data extraction was performed by two independent reviewers and all decisions were reached by consensus with an additional third reviewer. A total of 52 NICE TAs were identified, 47 used the GPRD/CPRD database, 10 used the THIN database and 3 used the QResearch databases. Data from primary care databases were used to support arguments regarding clinical need and current treatment in 33 NICE TAs while 36 were used to inform input parameters for economic models. The databases were sometimes used for more than one purpose. The data from the three data sources were generally well received by the ERGs/committees. Criticisms of the data typically occurred where the results had been repurposed from a published study or had not been applied appropriately. The potential of UK primary care databases in NICE submissions is increasingly being realised, particularly in informing the parameters of economic models. Purpose conducted studies are less likely to receive criticism from ERGs/committees, particularly when providing clinical input into cost effectiveness models.

Sleep problems and psychological symptoms as predictors of musculoskeletal conditions in children and adolescents.

Population-based studies show that sleep problems and psychological symptoms may increase the risk of musculoskeletal pain onset in children/adolescents. However, there is no evidence of these associations within primary care settings, where interventions can take place. This study investigated whether children/adolescents who consulted their general practitioner for sleep problems or psychological symptoms are at higher risk of subsequent consultations for musculoskeletal conditions. This prospective matched-cohort study used electronic medical records of children/ adolescents (aged 6-19years) from a UK primary care database. Associations between a consultation for sleep problems or psychological symptoms at baseline and a subsequent consultation for musculoskeletal conditions within the 2-year follow-up were investigated using survival analysis, producing hazard ratio (HR) and 95% confidence interval (CI) with adjustment for confounders. Children/adolescents who consulted for sleep problems had a significant increased risk of consultation for musculoskeletal conditions (HR=1.72; 95% CI 1.14, 2.60), which became nonsignificant after adjustment for confounders (HR=1.49; 95% CI 0.98, 2.27). Children/adolescents who consulted for psychological symptoms had a significant increased risk of consultation for musculoskeletal conditions (HR=1.59; 95% CI 1.31, 1.93), which was attenuated after adjustment (HR=1.39; 95% CI 1.14, 1.70). Children and adolescents who visit primary care for sleep problems or psychological symptoms have increased risk of future musculoskeletal consultations. Further work is needed to understand the causal mechanisms that explain these associations, before designing interventions strategies within primary care settings. Population-based studies showed that sleep problems and psychological symptoms may be important precursors of musculoskeletal pain in children and adolescents. By investigating these associations in primary care settings, this study showed that children and adolescents with consultations for sleep problems or psychological symptoms were at increased risk of subsequent consultations for musculoskeletal conditions. These findings support results from population-based studies, and identify potential areas for further research and potential intervention within primary care.

Trends in the incidence of Parkinson's disease between 2006 and 2016: Analysis of a large primary care database

Objective To investigate trends in the incidence of Parkinson’s disease (PD) between 2006 and 2016. Design Cohort study in The Health Improvement Network (THIN): a large UK primary care database. Study participants Individuals actively registered with a practice within THIN aged 50 years and over. Measures of outcome The incidence of Parkinson’s disease between 2006 and 2016 using different case definitions: 1) PD diagnostic Read code; 2) PD diagnostic Read code OR symptom Read code; 3) PD diagnostic Read code OR symptom Read code and OR at least 1 antiparkinsonian drug prescription; 4) PD diagnostic Read code OR symptom Read code plus at least 2 antiparkinsonian drug prescription. The effect of age and sex on these measures were investigated. Results The overall crude incidence of PD for people over 50 years has increased in recent years. The rates increased with increasing age and as expected, higher in men. Using the broadest case definition (3), incidence rate of PD between 2006 and 2016 in men was 190 per 100,000 person years (95% CI 187–193) and in women was 176 per 100,000 person years (95% CI 173–178). Incidence of PD was highest at age 90 (496 per 100,000 95% CI 471–522). Conclusion There is increasing diagnosis of PD in primary care setting.

Non-linear associations of 25-hydroxyvitamin D concentrations with risk of cardiovascular disease and all-cause mortality: Results from The Health Improvement Network (THIN) database

BackgroundThere is increasing evidence that vitamin D supplementation may only be beneficial in people with vitamin D deficiency, and the lack of sufficient people with very low vitamin D levels could explain the lack of protection against cardiovascular disease (CVD) reported in recent clinical trials of vitamin D supplementation. The aim of this study was to assess associations of low to moderate circulating concentrations of 25-hydroxyvitamin D (25(OH)D with risk of incident CVD and all-cause mortality, as well as the risk of ischaemic heart disease (IHD), cerebrovascular disease, and heart failure separately. Methods and ResultsLongitudinal analysis of electronic health records in The Health Improvement Network (THIN), a UK primary care database. The analysis included 180,263 patients age 18 years and older without a history of CVD and with circulating concentrations of 25(OH)D. After a mean follow-up of 2.2 (SD 1.7) years, there were 3747 patients diagnosed with CVD and 3912 patients died. Compared to patients in the highest quintile of 25(OHD) (≥ 67.5 nmol/L), those in the lowest 25(OH)D quintile (<23.1 nmol/L) had a hazard ratio (HR) of 1.24 (95% CI 1.12–1.38, P < 0.001) for CVD and 1.71 (1.55–1.88, P < 0.001) for mortality. The HR for both outcomes associated with 25(OH)D concentration was non-linear, being significantly increased in patients with 25(OH)D <35 nmol/L, and highest in those with 25(OH)D <25 nmol/L, although increased for mortality at 25(OH)D ≥100 nmol/L. The increased CVD HR in the lowest 25(OH)D quintile was more from IHD (1.35, 95% CI 1.13–1.60) and heart failure (1.38, 95% CI 1.08–1.77), than from cerebrovascular disease (1.13, 95% CI 0.97–1.31). ConclusionLow 25(OH)D are associated with highest risk of CVD and mortality, and are consistent with accumulating evidence that increased risk of these diseases occurs primarily in people with vitamin D deficiency.

Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records

IntroductionIn the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011,...

Risk of Nephrotic Syndrome for Non-Steroidal Anti-Inflammatory Drug Users.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with AKI. Their association with nephrotic syndrome has not been systematically studied. This study aimed to assess the risk of nephrotic syndrome associated with NSAID use. A matched case-control study was performed in the UK primary care database. Cases were patients with a first diagnosis of nephrotic syndrome and controls were those without nephrotic syndrome. NSAID exposure (grouped either based on cyclooxygenase enzyme selectivity and chemical groups) was classified as either current (use at the nephrotic syndrome diagnosis date and corresponding date in the control group), recent, or past use. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. We included 2620 cases and 10,454 controls. Compared with non-use, current use of 15-28 days and >28 days of conventional NSAIDs was associated with a higher relative risk of nephrotic syndrome: adjusted OR, 1.34; 95% CI, 1.06 to 1.70, and OR, 1.42; 95% CI, 0.79 to 2.55, respectively. Also, recent use (discontinuation 1-2 months before nephrotic syndrome diagnosis date; OR, 1.55; 95% CI, 1.11 to 2.15) and past use (discontinuation 2 months-2 years; OR, 1.24; 95% CI, 1.07 to 1.43), but not current use of <15 days (OR, 0.78; 95% CI, 0.46 to 1.31) nor past use (discontinuation >2 years; OR, 0.96; 95% CI, 0.85 to 1.09) were associated with a higher relative risk of nephrotic syndrome as well as past use of selective COX-2 inhibitors (discontinuation 2-24 months; OR, 1.24; 95% CI, 0.98 to 1.58). Categorization based on chemical groups showed that acetic acid and propionic acid derivatives were associated with a higher risk of nephrotic syndrome. The use of conventional NSAIDs was associated with a higher risk of nephrotic syndrome starting from at least 2 weeks of exposure, as well as for recent and past exposure up to 2 years before the diagnosis of nephrotic syndrome. This higher risk appeared mainly attributable to acetic acid and propionic acid derivatives.

Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis

The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns. This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters. 782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old. The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.