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.
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.
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.
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).
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.
Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only ...in free text clinical notes.
To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.
We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.
We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.
Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.
Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory ...that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs).
Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications.
Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42).
SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.
Anxiety is a prevalent condition with a substantial associated burden of morbidity. Previous literature investigating effects of anxiety on mortality rates has found conflicting results. This is in ...part due to inadequate consideration of comorbid depression as a confounder and analysing sub-types of anxiety together. The objective of this study was to compare mortality risks in people diagnosed with anxiety.
We undertook a retrospective cohort study using the 'The Health Improvement Network' database (a UK primary care dataset) between 1st January 2005 to 1st January 2018. 345 903 patients with anxiety (exposed group) were matched to 691 449 unexposed patients. Cox regression analyses were used to adjusted hazard ratios (HRs) for mortality risk.
During the study period 18 962 patients (5·5%) died in the exposed group compared to 32 288 (4·7%) in the unexposed group. This translated into a crude HR for all of 1·14 (95% CI 1·12 - 1·16), which remained significant after adjustment for key co-variates (including depression) giving a final HR of 1·05 (95% CI 1·03 - 1·07). When broken down by sub-type of anxiety (10·3% (35, 581) had phobias, 82·7% (385,882) has 'other' types, and 7·0% (24,262) had stress related anxiety) there were markedly different effect sizes. The adjusted model for the stress-related anxiety sub-type demonstrated a HR of 0·88 (95% CI 0·80 - 0·97). Conversely, the HR was increased in 'other' sub-types to 1·07 (95% CI 1·05 - 1·09) and non-significant in phobia types of anxiety.
A complex relationship is found between anxiety and mortality. The presence of anxiety slightly increased the risk of death, but this risk varies depending on the type of anxiety diagnosed.
Miscarriages affect up to a fifth of all pregnancies and are associated with substantial psychological morbidity. However, their relationship with cardiometabolic risk factors is not well known. ...Therefore, in this study we aimed to estimate the burden of cardiovascular risk factors including diabetes mellitus (type 1 or 2) and hypertension in women with miscarriage compared to women without a record of miscarriage.
A population-based retrospective cohort study was conducted using IVQIA Medical Research Data UK (IMRD-UK) between January 1995 and May 2016, an anonymised electronic health records database that is representative of the UK population. A total of 86,509, 16-50-year-old women with a record of miscarriage (exposed group) were matched by age, smoking status, and body mass index to 329,865 women without a record of miscarriage (unexposed group). Patients with pre-existing hypertension and diabetes were excluded. Adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI) for diabetes and hypertension were estimated using multivariable Poisson regression models offsetting for person-years follow-up.
The mean age at cohort entry was 31 years and median follow up was 4.6 (IQR 1.7-9.4) years. During the study period, a total of 792 (IR 1.44 per 1000 years) and 2525 (IR 1.26 per 1000 years) patients developed diabetes in the exposed and unexposed groups, respectively. For hypertension, 1995 (IR 3.73 per 1000 years) and 1605 (IR 3.39 per 1000 years) new diagnoses were recorded in the exposed and unexposed groups, respectively. Compared to unexposed individuals, women with a record miscarriage were more likely to develop diabetes (aIRR = 1.25, 95% CI: 1.15-1.36; p<0.001) and hypertension (aIRR = 1.07, 95% CI: 1.02-1.12; p = 0.005).
Women diagnosed with miscarriage were at increased risk of developing diabetes mellitus and hypertension. Women with history of miscarriage may benefit from periodic monitoring of their cardiometabolic health.
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 (+ or - 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. Keywords: Polycystic ovary syndrome, PCOS, Preterm, Birthweight, Stillbirth, Delivery
Summary
Objective
Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex‐specific link between circulating androgens and risk of type 2 ...diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study.
Design
A retrospective cohort study in a UK primary care database.
Patients
We included men and women with available serum testosterone and sex hormone‐binding globulin (SHBG) results.
Measurements
We categorized serum concentrations according to clinically relevant cut‐off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs).
Results
Serum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34‐3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55‐2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively.
Conclusions/Interpretation
In this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively.
This study aimed to investigate the level of guideline adherence for cardiometabolic health monitoring for patients prescribed antipsychotic medicines in UK primary care.
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.
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%).
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.
•Cardiometabolic monitoring in patients prescribed antipsychotics is suboptimal.•Monitoring frequency did not seem to improve when using antipsychotics with higher known metabolic side effects.•Suboptimal monitoring suggests non-compliance with the monitoring guidelines.•Monitoring of central obesity needs more attention in patients prescribed antipsychotics.•There is a need to promote guideline adherence to promote safe and effective use of antipyschotics.
The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study ...aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.
A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.
During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57), belonging to an ethnic minority group aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women and smoking or previously smoking aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06). Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.
The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.
PDF
