Prodromal symptoms of rheumatoid arthritis in a primary care database: variation by ethnicity and socioeconomic status.

OBJECTIVES: To assess whether prodromal symptoms of rheumatoid arthritis (RA), as recorded in the Clinical Practice Research Datalink Aurum (CPRD) database of English primary care records, differ by ethnicity and socioeconomic status. METHODS: A cross-sectional study to determine the coding of common symptoms (≥0.1% in the sample) in the 24 months preceding RA diagnosis in CPRD Aurum, recorded between January 1st 2004 to May 1st 2022. Eligible cases were adults with a code for RA diagnosis. For each symptom, a logistic regression was performed with the symptom as dependent variable, and ethnicity and socioeconomic status as independent variables. Results were adjusted for sex, age, BMI, and smoking status. White ethnicity and the highest socioeconomic quintile were comparators. RESULTS: In total, 70115 cases were eligible for inclusion, of which 66.4% female. Twenty-one symptoms were coded in > 0.1% of cases so were included in the analysis. Patients of South Asian ethnicity had higher frequency of codes for several symptoms, with the largest difference by odds ratio being muscle cramps (OR 1.71, 1.44-2.57) and shoulder pain (1.44, 1.25-1.66). Patients of Black ethnicity had higher prevalence of several codes including unintended weight loss (2.02, 1.25-3.28) and ankle pain (1.51, 1.02-2.23). Low socioeconomic status was associated with morning stiffness (1.74, 1.08-2.80) and falls (1.37, 2.03-1.82). CONCLUSION: There are significant differences in coded symptoms between demographic groups, which must be considered in clinical practice in diverse populations and to avoid algorithmic bias in prediction tools derived from routinely collected healthcare data.

The association between menstrual cycle characteristics and cardiometabolic outcomes in later life: a retrospective matched cohort study of 704,743 women from the UK.

BACKGROUND: Female reproductive factors are gaining prominence as factors that enhance cardiovascular disease (CVD) risk; nonetheless, menstrual cycle characteristics are under-recognized as a factor associated with CVD. Additionally, there is limited data from the UK pertaining to menstrual cycle characteristics and CVD risk. METHODS: A UK retrospective cohort study (1995-2021) using data from a nationwide database (The Health Improvement Network). Women aged 18-40 years at index date were included. 252,325 women with history of abnormal menstruation were matched with up to two controls. Two exposures were examined: regularity and frequency of menstrual cycles; participants were assigned accordingly to one of two separate cohorts. The primary outcome was composite cardiovascular disease (CVD). Secondary outcomes were ischemic heart disease (IHD), cerebrovascular disease, heart failure (HF), hypertension, and type 2 diabetes mellitus (T2DM). Cox proportional hazards regression models were used to derive adjusted hazard ratios (aHR) of cardiometabolic outcomes in women in the exposed groups compared matched controls. RESULTS: During 26 years of follow-up, 20,605 cardiometabolic events occurred in 704,743 patients. Compared to women with regular menstrual cycles, the aHRs (95% CI) for cardiometabolic outcomes in women with irregular menstrual cycles were as follows: composite CVD 1.08 (95% CI 1.00-1.19), IHD 1.18 (1.01-1.37), cerebrovascular disease 1.04 (0.92-1.17), HF 1.30 (1.02-1.65), hypertension 1.07 (1.03-1.11), T2DM 1.37 (1.29-1.45). The aHR comparing frequent or infrequent menstrual cycles to menstrual cycles of normal frequency were as follows: composite CVD 1.24 (1.02-1.52), IHD 1.13 (0.81-1.57), cerebrovascular disease 1.43 (1.10-1.87), HF 0.99 (0.57-1.75), hypertension 1.31 (1.21-1.43), T2DM 1.74 (1.52-1.98). CONCLUSIONS: History of either menstrual cycle irregularity or frequent or infrequent cycles were associated with an increased risk of cardiometabolic outcomes in later life. Menstrual history may be a useful tool in identifying women eligible for periodic assessment of their cardiometabolic health.

Depression and anxiety in women with idiopathic intracranial hypertension compared to migraine: A matched controlled cohort study.

OBJECTIVE: To evaluate mental health burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls. BACKGROUND: Depression and anxiety are recognized comorbid conditions in those with IIH and lead to worse predicted medical outcomes. The mental health burden in IIH has not been previously evaluated in a large, matched cohort study. METHODS: We performed a population-based matched, retrospective cohort study to explore mental health outcomes (depression and anxiety). We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical records database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged ≥16 years were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls). RESULTS: A total of 3411 women with IIH, 30,879 migraine controls and 33,495 population controls were included. Of these, 237, 2372 and 1695 women with IIH, migraine controls and population controls, respectively, developed depression during follow-up, and 179, 1826 and 1197, respectively, developed anxiety. There was a greater hazard of depression and anxiety in IIH compared to population controls (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.20-1.58; and aHR 1.40, 95% CI 1.19-1.64, respectively), while hazards were similar to migraine controls (aHR 0.98, 95% CI 0.86-1.13; and aHR 0.98, 95% CI 0.83-1.14, respectively). CONCLUSION: Depression and anxiety burden in women with IIH is higher than in the general population, and comparable to that in matched women with migraine. This may indicate that presence of headache is a potential driver for comorbid depression and anxiety in IIH.

The risk of subsequent surgery following bowel resection for Crohn's disease in a national cohort of 19 207 patients.

AIM: Surgery is required for most patients with Crohn's disease (CD) and further surgery may be necessary if medical treatment fails to control disease activity. The aim of this study was to characterize the risk of, and factors associated with, further surgery following a first resection for Crohn's disease. METHODS: Hospital Episode Statistics from England were examined to identify patients with CD and a first recorded bowel resection between 2007 and 2016. Multivariable logistic regression was used to examine risk factors for further resectional surgery within 5 years. Prevalence-adjusted surgical rates for index CD surgery over the study period were calculated. RESULTS: In total, 19 207 patients (median age 39 years, interquartile range 27-53 years; 55% women) with CD underwent a first recorded resection during the study period. 3141 (16%) underwent a further operation during the study period. The median time to further surgery was 2.4 (interquartile range 1.2-4.6) years. 3% of CD patients had further surgery within 1 year, 14% by 5 years and 23% by 10 years. Older age (≥58), index laparoscopic surgery and index elective surgery (adjusted OR 0.65, 95% CI 0.54-0.77; 0.77, 0.67-0.88; and 0.77, 0.69-0.85; respectively) were associated with a reduced risk of further surgery by 5 years. Prior surgery for perianal disease (1.60, 1.37-1.87), an extraintestinal manifestation of CD (1.51, 1.22-1.86) and index surgery in a high-volume centre for CD surgery (1.20, 1.02-1.40) were associated with an increased risk of further surgery by 5 years. A 25% relative and 0.3% absolute reduction in prevalence-adjusted index surgery rates for CD was observed over the study period. CONCLUSIONS: Further surgery following an index operation is common in CD. This risk was particularly seen in patients with perianal disease, extraintestinal manifestations and those who underwent index surgery in a high-volume centre.

Cardiometabolic screening and monitoring in patients prescribed antipsychotic drugs in primary care: A population-based cohort study.

BACKGROUND: This study aimed to investigate the level of guideline adherence for cardiometabolic health monitoring for patients prescribed antipsychotic medicines in UK primary care. METHODS: In this population-based retrospective open cohort study, we used dataset of patients from the IQVIA Medical Research Data (IMRD) database between 1st January 2003 to 31st December 2018. Clinical Read codes were used to identify a cohort of adult patients with a diagnosis of Schizophrenia and at least four prescriptions of an anti-psychotic medication within 12 months of diagnosis. We then extracted data in relation to monitoring of cardiometabolic parameters (body compositions, lipids, and glucose outcomes) at baseline, then at six weeks, 12 weeks, and then 12 months. The frequency of outcome monitoring was described using descriptive statistics. FINDINGS: A total of 11,435 patients were eligible and of them (n = 9707; 84·8%) were prescribed second-generation antipsychotics (SGAs). Only a small portion of the cohort (≈2·0%) received complete monitoring (at time points) for certain outcomes. Just over half the patients (n = 6599, 52%) had evidence of any cardiometabolic baseline testing for any of the study outcomes and the high majority had at least one abnormal lab value at baseline (n = 4627, 96·7%). INTERPRETATION: In UK primary care, cardiometabolic monitoring practices among patients prescribed antipsychotics remain suboptimal. There is a need to promote guideline adherence to prevent adverse outcomes in antipsychotic users.

Risk of cardiometabolic outcomes among women with a history of pelvic inflammatory disease: a retrospective matched cohort study from the UK.

INTRODUCTION: To describe the incidence and prevalence of pelvic inflammatory disease (PID) and to estimate the risk of cardiometabolic outcomes among women with PID compared to women without PID. METHODS: A UK retrospective matched cohort study using data from The Health Improvement Network. To assess cardiometabolic risk, women (aged ≥ 16 years) with PID were compared to matched controls without PID. Annual prevalence and incidence of PID (1998-2017) were estimated among women aged 16-50 years using annual cross-sectional and cohort analyses, respectively. Adjusted hazard ratios (aHR) and 95% CI for cardiometabolic outcomes were estimated using Cox proportional hazards models. The primary outcome was composite cardiovascular disease (CVD) and its subtypes, including ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were hypertension, and type 2 diabetes mellitus (T2DM). RESULTS: Among the 715 recorded composite CVD events, the crude incidence rate per 1000 person-years was 1.5 among women with history of PID compared to 1.3 in matched controls. Compared to women without PID (N = 73,769), the aHRs for cardiometabolic outcomes among women with PID (N = 19,804) were: composite CVD 1.10 (95% CI 0.93-1.30); IHD 1.19 (95% CI 0.93-1.53); cerebrovascular disease 1.13 (95% CI 0.90-1.43); HF 0.92 (95% CI 0.62-1.35) hypertension 1.10 (95% CI 1.01-1.20); and T2DM 1.25 (95% CI 1.09-1.43). The prevalence (per 10,000 population) of PID was 396.5 in 1998 and 237 in 2017. The incidence (per 10,000 person-years) of PID was 32.4 in 1998 and 7.9 in 2017. CONCLUSION: There was no excess risk of composite CVD or its subtypes among women with history of PID compared to matched controls. Findings from our study suggest that history of PID was associated with an increased risk of hypertension and type 2 diabetes mellitus, two major risk factors for CVD. Additional studies are required to support these findings.

Co-morbid Polycystic Ovarian Syndrome with Idiopathic Intracranial Hypertension.

The link between polycystic ovarian syndrome (PCOS) and idiopathic intracranial hypertension (IIH) has long been debated. Historically, there is a wide range of reported occurrence of both conditions, being between 15% and 64%. Both conditions share a common phenotype. The awareness that in a new large data study that there is a 1.5-fold increased prevalence of diagnosed PCOS in participants with IIH as compared to the controls is important. Assessment for the potential of co-morbid PCOS in women with IIH is important as this may enable optimisation of weight and fertility management.

Risk of incident obstructive sleep apnoea in patients with type 1 diabetes: a population-based retrospective cohort study.

AIMS/HYPOTHESIS: People with type 2 diabetes are at increased risk of developing obstructive sleep apnoea. However, it is not known whether people with type 1 diabetes are also at an increased risk of obstructive sleep apnoea. This study aimed to examine whether people with type 1 diabetes are at increased risk of incident obstructive sleep apnoea compared with a matched cohort without type 1 diabetes. METHODS: We used a UK primary care database, The Health Improvement Network (THIN), to perform a retrospective cohort study between January 1995 and January 2018 comparing sleep apnoea incidence between patients with type 1 diabetes (exposed) and without type 1 diabetes (unexposed) (matched for age, sex, BMI and general practice). The outcome was incidence of obstructive sleep apnoea. Baseline covariates and characteristics were assessed at the start of the study based on the most recent value recorded prior to the index date. The Cox proportional hazards regression model was used to estimate unadjusted and adjusted hazard ratios, based on a complete-case analysis. RESULTS: In total, 34,147 exposed and 129,500 matched unexposed patients were included. The median follow-up time was 5.43 years ((IQR 2.19-10.11), and the mean BMI was 25.82 kg/m2 (SD 4.33). The adjusted HR for incident obstructive sleep apnoea in patients with type 1 diabetes vs those without type 1 diabetes was 1.53 (95% CI 1.25, 1.86; p<0.001). Predictors of incident obstructive sleep apnoea in patients with type 1 diabetes were older age, male sex, obesity, being prescribed antihypertensive or lipid-lowering drugs, atrial fibrillation and depression. CONCLUSIONS/INTERPRETATION: Individuals with type 1 diabetes are at increased risk of obstructive sleep apnoea compared with people without diabetes. Clinicians should suspect obstructive sleep apnoea in patients with type 1 diabetes if they are old, have obesity, are male, have atrial fibrillation or depression, or if they are taking lipid-lowering or antihypertensive drugs.

Polycystic ovary syndrome and risk of adverse obstetric outcomes: a retrospective population-based matched cohort study in England.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects up to one in five women of childbearing age. Observational studies assessing the association between maternal PCOS and adverse obstetric outcomes have reported varying results, depending on patient population, diagnostic criteria for PCOS and covariates accounted for in their analyses. We aimed to assess the risk of obstetric outcomes among a population-based representative cohort of women with PCOS compared to an age-matched cohort of women without PCOS. METHODS: A retrospective cohort study was conducted of pregnancies of women in England aged 15-49 years identified from the Clinical Practice Research Datalink (CPRD) GOLD pregnancy register and linked Hospital Episodes Statistic (HES) data between March 1997 and March 2020. Pregnancies from the register that had a linked HES delivery record were included. Linked CPRD primary care data was used to ascertain maternal PCOS exposure prior to pregnancy. To improve detection of PCOS, in addition to PCOS diagnostic codes, codes for (1) polycystic ovaries or (2) hyperandrogenism and anovulation together were also considered. Sensitivity analysis was limited to only pregnant women with a diagnostic code for PCOS. Primary outcomes ascertained from linked HES data were (1) preterm delivery (gestation < 37 weeks), (2) mode of delivery, (3) high (> 4000 g) or low birthweight (< 2500 g) and (4) stillbirth. Secondary outcomes were (1) very preterm delivery (< 32 weeks), (2) extremely preterm delivery (< 28 weeks), (3) small and (4) large for gestational age. Conditional logistic regression models were performed adjusting for age, ethnicity, deprivation, dysglycaemia, hypertension, thyroid disorders, number of babies born at index pregnancy, and pre-gravid BMI. Multiple imputation was performed for missing outcome data. RESULTS: 27,586 deliveries with maternal PCOS were matched for age (± 1 year) to 110,344 deliveries without PCOS. In the fully adjusted models, maternal PCOS was associated with an increased risk of (1) preterm birth [aOR: 1.11 (95% CI 1.06-1.17)], and (2) emergency caesarean, elective caesarean and instrumental vaginal compared to spontaneous delivery [aOR: 1.10 (1.05-1.15), 1.07 (1.03-1.12) and 1.04 (1.00-1.09), respectively]. There was absence of association with low birthweight, high birthweight and stillbirth. In the sensitivity analysis, the association with preterm birth [aOR: 1.31 (95% CI 1.13-1.52)], emergency caesarean [aOR: 1.15 (95% CI 1.02-1.30)], and elective caesarean [aOR: 1.03 (95% CI 1.02-1.03)] remained. While there was no significant association with any of the secondary outcomes in the primary analysis, in the sensitivity analysis maternal PCOS was associated with increased risk of extremely preterm delivery [aOR: 1.86 (95% CI 1.31-2.65)], and lower risk of small for gestational age babies [aOR: 0.74 (95% CI 0.59-0.94)]. CONCLUSIONS: Maternal PCOS was associated with increased risk of preterm and caesarean delivery. Association with low birthweight may be largely mediated by lower gestational age at birth.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.

AIMS: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. METHODS: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. RESULTS: During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively). CONCLUSION: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

Achalasia Is Associated With Atopy in Patients Younger Than 40 Years of Age.

INTRODUCTION: Case reports describe individuals with achalasia features subsequently diagnosed with eosinophilic esophagitis (an atopic disorder). We have examined associations between achalasia and atopic and autoimmune conditions. METHODS: This is a UK cohort study of 2,593 subjects with achalasia matched to 10,402 controls. RESULTS: At diagnosis, achalasia was associated with autoimmune conditions (odds ratio 1.39; 95% confidence interval 1.02-1.90) and atopic conditions (1.40; 1.00-1.95) in those aged younger than 40 years. DISSCUSSION: Our findings support an autoimmune etiology in achalasia but also suggest a possible atopic etiology in younger subjects.

Impact of diabetes specialist nurses on inpatient care: A systematic review.

BACKGROUND: People with diabetes have longer hospital stays and poorer clinical outcomes. Diabetes inpatient specialist nurses have been introduced to improve care. AIMS: To assess the evidence for the benefit of diabetes specialist nurses in the inpatient setting. METHODS: A systematic search of MEDLINE (ovid), Embase (ovid), CINAHL (EBSCO) and Web of Science core collection from January 1998 to September 2019 was performed using key terms for diabetes specialist nurses and hospital setting. Studies measuring patient care using any standardised or validated outcome measures after introduction of a dedicated diabetes specialist nurse or nursing team were eligible for inclusion and findings reported by narrative synthesis. RESULTS: There were 10 studies which met the inclusion criteria. One was a randomised controlled study and the remaining nine studies were before and after studies with three of them using a time series analysis methodology. The majority reported length of stay (LOS) and showed a reduction in median LOS by between 0.5 and 3 days. Reductions in bed occupancy ranged from 39% to 47%. There was a paucity of evidence for outcomes related to patient care with some measures limited to single studies. These included a 52% reduction in total drug errors, improved patient knowledge, higher patient satisfaction and improved glycaemic control post-discharge. There was no reduction of mortality observed. CONCLUSIONS: These studies suggest a reduction in LOS and improved clinical care for patients with diabetes after the introduction of diabetes inpatient specialist nurses. Future research should examine a range of benefits associated with diabetes inpatient specialist nurse delivered services, including reduction of inpatient complications such as infections and cardiovascular events.

Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.

Renin-angiotensin system inhibitors and susceptibility to COVID-19 in patients with hypertension: a propensity score-matched cohort study in primary care.

INTRODUCTION: Renin-angiotensin system (RAS) inhibitors have been postulated to influence susceptibility to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This study investigated whether there is an association between their prescription and the incidence of COVID-19 and all-cause mortality. METHODS: We conducted a propensity-score matched cohort study comparing the incidence of COVID-19 among patients with hypertension prescribed angiotensin-converting enzyme I (ACE) inhibitors or angiotensin II type-1 receptor blockers (ARBs) to those treated with calcium channel blockers (CCBs) in a large UK-based primary care database (The Health Improvement Network). We estimated crude incidence rates for confirmed/suspected COVID-19 in each drug exposure group. We used Cox proportional hazards models to produce adjusted hazard ratios for COVID-19. We assessed all-cause mortality as a secondary outcome. RESULTS: The incidence rate of COVID-19 among users of ACE inhibitors and CCBs was 9.3 per 1000 person-years (83 of 18,895 users [0.44%]) and 9.5 per 1000 person-years (85 of 18,895 [0.45%]), respectively. The adjusted hazard ratio was 0.92 (95% CI 0.68 to 1.26). The incidence rate among users of ARBs was 15.8 per 1000 person-years (79 out of 10,623 users [0.74%]). The adjusted hazard ratio was 1.38 (95% CI 0.98 to 1.95). There were no significant associations between use of RAS inhibitors and all-cause mortality. CONCLUSION: Use of ACE inhibitors was not associated with the risk of COVID-19 whereas use of ARBs was associated with a statistically non-significant increase compared to the use of CCBs. However, no significant associations were observed between prescription of either ACE inhibitors or ARBs and all-cause mortality.

Cardio-metabolic outcomes in South Asians compared to White Europeans in the United Kingdom: a matched controlled population-based cohort study.

BACKGROUND: There appears to be an inequality in the risk of cardio-metabolic disease between those from a South Asian (SA) background when compared to those of White Europeans (WE) descendance, however, this association has not been explored in a large European cohort. This population-based open retrospective cohort explores the incidence of cardio-metabolic disease in those without pre-existing cardiometabolic disease taken from a large UK primary care database from 1st January 2007 to 31st December 2017. METHODS: A retrospective open cohort matched population-based study using The Health Improvement Network (THIN) database. The outcomes of this study were the incidences of cardio-metabolic events (type 2 diabetes mellitus, hypertension, ischemic heart disease, stroke, heart failure, and atrial fibrillation). RESULTS: A total of 94,870 SA patients were matched with 189,740 WE patients. SA were at an increased risk of developing: T2DM (adjusted hazard ratio (aHR) 3.1; 95% CI 2.97-3.23); HTN (1.34; 95% CI: 1.29-1.39); ischaemic heart disease (IHD) (1.81; 95% CI: 1.68-1.93) and heart failure (HF) (1.11; 95% CI: 1.003-1.24). However, they were at a lower risk of atrial fibrillation (AF) (0.53; 95% CI: 0.48-0.59) when compared to WE. Of those of SA origin, the Bangladeshi community were at the greatest risk of T2DM, HTN, IHD and HF, but were at the lowest risk of AF in when compared to Indians and Pakistanis. CONCLUSION: Considering the high risk of cardio-metabolic diseases in the SA cohort, differential public health measures should be considered in these patients to reduce their risk of disease, which may be furthered tailored depending on their country of origin.

Bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: a systematic review and meta-analysis.

BACKGROUND: The role of bronchoalveolar lavage fluid (BALF) lymphocyte percentage in diagnosing chronic hypersensitivity pneumonitis (CHP) is unclear. We conducted a systematic review and meta-analysis of bronchoalveolar lavage (BAL) lymphocyte percentage in the diagnosis of CHP. METHODS: We searched Medline, Embase and the Cochrane Library from inception to August 2019. Individual patient data were obtained to test performance characteristics of BAL lymphocyte percentage at different thresholds. Random-effects models were used for pooled estimates, with comparisons made between CHP and non-CHP interstitial lung diseases (ILDs). RESULTS: Fifty-three studies were included in the systematic review and 42 in the meta-analysis. The pooled estimate for BAL lymphocyte percentage was 42.8% (95% CI 37.7-47.8, I2=95.3%) in CHP, 10.0% (95% CI 6.9-13.1, I2=91.2%) in idiopathic pulmonary fibrosis (IPF), 23.1% (95% CI 3.0-43.2, I2=85.2%) in non-IPF idiopathic interstitial pneumonia (IIP), 23.4% (95% CI 11.0-35.9, I2=45.7%) in connective-tissue disease associated ILD (CTD-ILD) and 31.2% (95% CI 17.6-44.8, I2=95.2%) in sarcoidosis. Results differed between CHP and IPF (p<0.0001), non-IPF IIP (p=0.0309) or CTD-ILD (p=0.0824), but not between CHP and sarcoidosis (p=0.0966). Using individual patient data from eight studies, a lymphocyte percentage threshold of >20% provided a sensitivity of 68.1% and a specificity of 64.8% for CHP. Higher thresholds provided lower sensitivity with higher specificity. Older age and ever having smoked were associated with lower lymphocyte percentage in CHP. CONCLUSIONS: BAL lymphocyte percentage is higher in CHP compared to IPF and other IIPs, with higher thresholds providing improved specificity at the cost of sensitivity. However, the parent studies are at risk of incorporation bias and prospective studies should evaluate the additive discriminate value of BAL lymphocyte percentage to accurately diagnose CHP.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cardiovascular, thromboembolic and renal outcomes in IgA vasculitis (Henoch-Schönlein purpura): a retrospective cohort study using routinely collected primary care data.

BACKGROUND: IgA vasculitis (IgAV, Henoch-Schönlein purpura) is a small-vessel vasculitis most common in children but also occurring in adults. Case series have suggested that IgAV may be associated with cardiovascular disease and venous thromboembolism, but this has not been evaluated in population-based studies. Renal disease and hypertension are possible complications of the disease with unknown incidence. METHODS: Using a large UK primary care database, we conducted an open retrospective matched cohort study of cardiovascular, venous thrombotic and renal outcomes in adult-onset and childhood-onset IgAV. Control participants were selected at a 2:1 ratio, matched for age and sex. Adjusted HRs (aHRs) were calculated using Cox proportional hazards models. RESULTS: 2828 patients with adult-onset IgAV and 10 405 patients with childhood-onset IgAV were compared with age-matched and sex-matched controls. There was significantly increased risk of hypertension (adult-onset aHR 1.42, 95% CI 1.19 to 1.70, p < 0.001; childhood-onset aHR 1.52, 95% CI 1.22 to 1.89, p < 0.001) and stage G3-G5 chronic kidney disease (adult-onset aHR 1.54, 95% CI 1.23 to 1.93, p < 0.001; childhood-onset aHR 1.89, 95% CI 1.16 to 3.07, p=0.010). There was no evidence of association with ischaemic heart disease, cerebrovascular disease or venous thromboembolism. All-cause mortality was increased in the adult-onset IgAV cohort compared with controls (aHR 1.27, 95% CI 1.07 to 1.50, p=0.006). CONCLUSIONS: Patients with IgAV are at increased risk of hypertension and chronic kidney disease (CKD) compared with individuals without IgAV; analysis restricted to adult-onset IgAV patients showed increased mortality. Appropriate surveillance and risk factor modification could improve long-term outcomes in these patients.