No abstract

IntroductionThe 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.MethodsThis 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.Results782 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.ConclusionsThe 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.

Objective. To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.Methods. We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.Results. During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex. Conclusion.No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.

Objective To describe the prevalence and incidence of endometriosis and to estimate the risk of cardiovascular outcomes in women with endometriosis.Design Population-based cohort study using The Health Improvement Network database.Setting UK primary care.Population Women aged 16-50 years were followed from 1995 to 2018.Methods Adjusted hazard ratios (aHR) for cardiovascular outcomes comparing women with endometriosis with those without endometriosis were estimated using multivariable Cox regression models. Prevalence and incidence of endometriosis were estimated using annual (1998-2017) sequential crosssectional and cohort studies, respectively.Main outcome measure The primary outcome was composite cardiovascular disease (CVD) including, ischaemic heart disease (IHD), heart failure (HF) and cerebrovascular disease. Secondary outcomes were arrhythmia, hypertension and allcause mortality.Results In all, 56 090 women with endometriosis and 223 669 matched controls without endometriosis were included in the analysis of cardiovascular risk. Compared with women without endometriosis, the aHR for cardiovascular outcomes among women with endometriosis were: composite CVD 1.24 (95% CI 1.13-1.37); IHD 1.40 (95% CI 1.22-1.61); cerebrovascular disease 1.19 (95% CI 1.04-1.36); HF 0.76 (95% CI 0.54-1.07); arrhythmia 1.26 (95% CI 1.11-1.43); hypertension 1.12 (95% CI 1.07-1.17) and all-cause mortality 0.66 (95% CI 0.59-0.74). The incidence of endometriosis was 12.3 per 10 000 person-years in 1998 and 11.5 per 10 000 person-years in 2017. The prevalence of endometriosis increased from 119.7 per 10 000 population in 1998 to 201.3 per 10 000 population in 2017.Conclusion Endometriosis is associated with an increased risk of cardiovascular outcomes. Young women with endometriosis are a potential target for CVD risk assessment and prevention.

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 1.71À2.48), chronic fatigue syndrome (1.47; 1.08À2.00), chronic lower back pain (1.99; 1.68À2.35), restless leg syndrome (1.82; 1.41À2.35) and irritable bowel syndrome (1.15; 1.08À1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88À1.13), chronic headache (1.04; 0.59À1.86), interstitial cystitis (1.19; 0.51À2.74), vulvodynia (0.65; 0.34À1.26), chronic prostatitis (0.34; 0.07À1.77) and myofascial pain syndrome (0.88; 0.36À2.14). 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.

Objective Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. Research Design and Methods We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. Results There were 29,558 and 10,271 patients in the MF+ and MF- groups respectively who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratio for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19 related mortality were 0.85 (95%CI 0.67, 1.08), 0.80 (95%CI 0.49, 1.30), and 0.87 (95%CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. Conclusion Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19 related mortality. It is safe to continue prescribing metformin to improve glycaemic control in patients with diabetes, despite concerns about an impending second wave of COVID-19.

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 comorbidities and to examine the associations between these clusters and mortality.MethodsLongitudinal analysis of electronic health records in the health improvement network (THIN), a UK primary care database including 92 186 men and women aged ≥18 years with IHD and a median of 2 (IQR 1–3) comorbidities.ResultsLatent class analysis revealed five clusters with half categorised as a low-burden comorbidity group. After a median follow-up of 3.2 (IQR 1.4–5.8) years, 17 645 patients died. Compared with the low-burden comorbidity group, two groups of patients with a high-burden of comorbidities had the highest adjusted HR for mortality: those with vascular and musculoskeletal conditions, HR 2.38 (95% CI 2.28 to 2.49) and those with respiratory and musculoskeletal conditions, HR 2.62 (95% CI 2.45 to 2.79). Hazards of mortality in two other groups of patients characterised by cardiometabolic and mental health comorbidities were also higher than the low-burden comorbidity group; HR 1.46 (95% CI 1.39 to 1.52) and 1.55 (95% CI 1.46 to 1.64), respectively.ConclusionsThis analysis has identified five distinct comorbidity clusters in patients with IHD that were differentially associated with risk of mortality. These analyses should be replicated in other large datasets, and this may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters.

Background Back pain is a common and costly health problem worldwide. There is yet a lack of consistent methodologies to estimate the economic burden of back pain to society. Objective To systematically evaluate the methodologies used in the published cost of illness (COI) literature for estimating the direct and indirect costs attributed to back pain, and to present a summary of the estimated cost burden. Methods Six electronic databases were searched to identify COI studies of back pain published in English up to February 2021. A total of 1,588 abstracts were screened, and 55 full-text studies were subsequently reviewed. After applying the inclusion criteria, 45 studies pertaining to the direct and indirect costs of back pain were analysed. Results The studies reported data on 15 industrialised countries. The national cost estimates of back pain in 2015 USD ranged from $259 million ($29.1 per capita) in Sweden to $71.6 billion ($868.4 per capita) in Germany. There was high heterogeneity among the studies in terms of the methodologies used for analysis and the resulting costs reported. Most of the studies assessed costs from a societal perspective (n = 29). The magnitude and accuracy of the reported costs were influenced by the case definition of back pain, the source of data used, the cost components included and the analysis method. Among the studies that provided both direct and indirect cost estimates (n = 15), indirect costs resulting from lost or reduced work productivity far outweighed the direct costs. Conclusion Back pain imposes substantial economic burden on society. This review demonstrated that existing published COI studies of back pain used heterogeneous approaches reflecting a lack of consensus on methodology. A standardised methodological approach is required to increase credibility of the findings of COI studies and improve comparison of estimates across studies.