Identifying patients with chronic widespread pain in primary care.

Chronic widespread pain (CWP) is common in the general population. It is unclear how people reporting this problem present in primary care; they may regularly consult for regional pains without being recognized as having a generalized condition. Our objectives were to determine the prevalence of people consulting in primary care for musculoskeletal conditions in different body regions on different occasions (recurrent regional pain consultation), the proportion with diagnosed generalized pain and survey-reported widespread pain, and if they have features characteristic of CWP. Phase 1 used electronic records from 12 general practices in North Staffordshire (Consultations in Primary Care Archive) from 2005 to 2009. Phase 2 used linked self-reported health and primary healthcare data from 8,286 people aged 50 plus in eight general practices (North Staffordshire Osteoarthritis Project) between 2002 and 2005. In Phase 1, 11% of registered patients fulfilled criteria for recurrent regional pain consultation. Three-quarters had no recorded CWP-related generalized pain condition (e.g. fibromyalgia). In Phase 2, 53% of recurrent regional pain consulters had survey-reported widespread pain and 88% had consulted for somatic symptoms. Self-reported general health was worse in recurrent regional pain consulters than in single-region consulters, and poorest in those who also reported persistent widespread pain. Recurrent regional pain consulters are a heterogeneous group of frequent consulters sharing features with CWP (e.g. somatic symptoms) but including those less severely affected. They lie on the spectrum of polysymptomatic distress characteristic of CWP and represent a group whose needs may be better met by earlier diagnosis of multi-site pain.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Risk of fractures in half a million survivors of 20 cancers: a population-based matched cohort study using linked English electronic health records.

BACKGROUND: A history of multiple myeloma, prostate cancer, and breast cancer has been associated with adverse bone health, but associations across a broader range of cancers are unclear. We aimed to compare the risk of any bone fracture and major osteoporotic fractures in survivors of a wide range of cancers versus cancer-free individuals. METHODS: In this population-based matched cohort study, we used electronic health records from the UK Clinical Practice Research Datalink linked to hospital data. We included adults (aged ≥18 years) eligible for linkage, and we restricted the study start to Jan 2, 1998, onwards and applied administrative censoring on Jan 31, 2020. The cancer survivor group included survivors of the 20 most common cancers. Each individual with cancer was matched (age, sex, and general practice) to up to five controls (1:5) who were cancer-free. The primary outcomes were any bone fracture and any major osteoporotic fracture (pelvic, hip, wrist, spine, or proximal humeral fractures) occurring more than 1 year after index date (ie, the diagnosis date of the matched individual with cancer). We used Cox regression models, adjusted for shared risk factors, to estimate associations between cancer survivorship and bone fractures. FINDINGS: 578 160 adults with cancer diagnosed in 1998-2020 were matched to 3 226 404 cancer-free individuals. Crude incidence rates of fractures in cancer survivors ranged between 8·39 cases (95% CI 7·45-9·46) per 1000 person-years for thyroid cancer and 21·62 cases (20·18-23·18) per 1000 person-years for multiple myeloma. Compared with cancer-free individuals, the risk of any bone fracture was increased in 15 of 20 cancers, and of major osteoporotic fractures in 17 of 20 cancers. Effect sizes varied: adjusted hazard ratios (HRs) were largest for multiple myeloma (1·94, 95% CI 1·77-2·13) and prostate cancer (1·43, 1·39-1·47); HRs in the range 1·20-1·50 were seen for stomach, liver, pancreas, lung, breast, kidney, and CNS cancers; smaller associations (HR <1·20) were observed for malignant melanoma, non-Hodgkin lymphoma, leukaemia, and oesophageal, colorectal, and cervical cancers. Increased risks of major osteoporotic fracture were noted most substantially in multiple myeloma (2·25, 1·96-2·58) and CNS (2·12, 1·56-2·87), liver (1·62, 1·01-2·61), prostate (1·60, 1·53-1·67), and lung cancers (1·60, 1·44-1·77). Effect sizes tended to reduce over time since diagnosis but remained elevated for more than 5 years in several cancers, such as multiple myeloma and stomach, lung, breast, prostate, and CNS cancers. INTERPRETATION: Survivors of most types of cancer were at increased risk of bone fracture for several years after cancer, with variation by cancer type. These findings can help to inform mitigation and prevention strategies. FUNDING: Wellcome Trust

Severe mental illness and chronic kidney disease: a cross-sectional study in the United Kingdom

OBJECTIVE: We investigated the burden of chronic kidney disease (CKD) among patients with severe mental illness (SMI). METHODS: We identified patients with SMI among all those aged 25–74 registered in the UK Clinical Practice Research Datalink as on March 31, 2014. We compared the prevalence of CKD (two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥3 months) and renal replacement therapy between patients with and without SMI. For patients with and without a history of lithium prescription separately, we used logistic regression to examine the association between SMI and CKD, adjusting for demographics, lifestyle characteristics, and known CKD risk factors. RESULTS: The CKD prevalence was 14.6% among patients with SMI and a history of lithium prescription (n = 4,295), 3.3% among patients with SMI and no history of lithium prescription (n = 24,101), and 2.1% among patients without SMI (n = 2,387,988; P < 0.001). The prevalence of renal replacement therapy was 0.23%, 0.15%, and 0.11%, respectively (P = 0.012). Compared to patients without SMI, the fully adjusted odds ratio for CKD was 6.49 (95% CI 5.84–7.21) for patients with SMI and a history of lithium prescription and 1.45 (95% CI 1.34–1.58) for patients with SMI and no history of lithium prescription. The higher prevalence of CKD in patients with SMI may, in part, be explained by more frequent blood testing as compared to the general population. CONCLUSION: CKD is identified more commonly among patients with SMI than in the general population

Identifying patients with chronic widespread pain in primary care.

Chronic widespread pain (CWP) is common in the general population. It is unclear how people reporting this problem present in primary care; they may regularly consult for regional pains without being recognized as having a generalized condition. Our objectives were to determine the prevalence of people consulting in primary care for musculoskeletal conditions in different body regions on different occasions (recurrent regional pain consultation), the proportion with diagnosed generalized pain and survey-reported widespread pain, and if they have features characteristic of CWP. Phase 1 used electronic records from 12 general practices in North Staffordshire (Consultations in Primary Care Archive) from 2005 to 2009. Phase 2 used linked self-reported health and primary healthcare data from 8,286 people aged 50 plus in eight general practices (North Staffordshire Osteoarthritis Project) between 2002 and 2005. In Phase 1, 11% of registered patients fulfilled criteria for recurrent regional pain consultation. Three-quarters had no recorded CWP-related generalized pain condition (e.g. fibromyalgia). In Phase 2, 53% of recurrent regional pain consulters had survey-reported widespread pain and 88% had consulted for somatic symptoms. Self-reported general health was worse in recurrent regional pain consulters than in single-region consulters, and poorest in those who also reported persistent widespread pain. Recurrent regional pain consulters are a heterogeneous group of frequent consulters sharing features with CWP (e.g. somatic symptoms) but including those less severely affected. They lie on the spectrum of polysymptomatic distress characteristic of CWP and represent a group whose needs may be better met by earlier diagnosis of multi-site pain.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Atopic eczema in adulthood and mortality: UK population–based cohort study, 1998-2016

BACKGROUND: Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death. OBJECTIVE: We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity. METHODS: The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016. RESULTS: A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes. CONCLUSION: The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority

Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK

BACKGROUND: Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk. METHODS: We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids). RESULTS: We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry. CONCLUSIONS: Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management

Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care

BACKGROUND: Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI – ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults. METHODS: We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥ 18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis. RESULTS: We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12– 1.22; psoriasis: HR=1.26,95% CI=1.18– 1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93– 1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05– 1.23). CONCLUSION: Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis

Inflammatory skin diseases and the risk of chronic kidney disease: population-based case-control and cohort analyses.

BACKGROUND: Emerging evidence suggests an association between common inflammatory skin diseases and chronic kidney disease (CKD). OBJECTIVES: To explore the association between CKD stages 3-5 (CKD3-5) and atopic eczema, psoriasis, rosacea and hidradenitis suppurativa. METHODS: We undertook two complementary analyses; a prevalent case-control study and a cohort study using routinely collected primary care data [UK Clinical Practice Research Datalink (CPRD)]. We matched individuals with CKD3-5 in CPRD in March 2018 with up to five individuals without CKD for general practitioner practice, age and sex. We compared the prevalence of CKD3-5 among individuals with and without each inflammatory skin disease. We included individuals in CPRD with diabetes mellitus (2004-2018) in a cohort analysis to compare the incidence of CKD3-5 among people with and without atopic eczema and psoriasis. RESULTS: Our study included 56 602 cases with CKD3-5 and 268 305 controls. Cases were more likely than controls to have a history of atopic eczema [odds ratio (OR) 1·14, 99% confidence interval (CI) 1·11-1·17], psoriasis (OR 1·13, 99% CI 1·08-1·19) or hidradenitis suppurativa (OR 1·49, 99% CI 1·19-1·85), but were slightly less likely to have been diagnosed with rosacea (OR 0·92, 99% CI 0·87-0·97), after adjusting for age, sex, practice (matching factors), index of multiple deprivation, diabetes, smoking, harmful alcohol use and obesity. Results remained similar after adjusting for hypertension and cardiovascular disease. In the cohort with diabetes (N = 335 827), there was no evidence that CKD3-5 incidence was associated with atopic eczema or psoriasis. CONCLUSIONS: Atopic eczema, psoriasis and hidradenitis suppurativa are weakly associated with CKD3-5. Future research is needed to elucidate potential mechanisms and the clinical significance of our findings

Long-term effects of bariatric surgery on acute kidney injury: a propensity-matched cohort in the UK Clinical Practice Research Datalink.

OBJECTIVE: Bariatric surgery is an effective method of weight reduction and has been associated with acute kidney injury (AKI) as a perioperative event. However, the long-term effects of the weight reduction after surgery on AKI are unknown. The objective of this study is to quantify the association of bariatric surgery with later risk of AKI. DESIGN: This study uses a propensity score-matched cohort of patients from the UK Clinical Practice Research Datalink database with and without bariatric surgery to compare rates of AKI episodes derived from linkage to the Hospital Episode Statistics. SETTING: England, UK. PARTICIPANTS: We included 2643 patients with bariatric surgery and 2595 patients without. RESULTS: Results were compatible with an increased risk of AKI in the first 30 days following surgery compared with patients without surgery, but AKI incidence was substantially decreased in patients with bariatric surgery during long-term follow-up (rate ratio 0.37, 95% CI 0.23 to 0.61) even after accounting for chronic kidney disease status at baseline. Over the whole period of follow-up, bariatric surgery had a net protective effect on risk of AKI (rate ratio 0.45, 95% CI 0.28 to 0.72). CONCLUSIONS: Bariatric surgery was associated with protective effects on AKI incidence during long-term follow-up. While the risk of AKI may be increased within the first 30 days, the net effect seen was beneficial.RM is supported by a Sir Henry Wellcome Postdoctoral Fellowship from the Wellcome Trust (201375/Z/16/Z). KB holds a Sir Henry Dale fellowship jointly funded by the Wellcome Trust and the Royal Society (107731/Z/15/Z). RLB is an NIHR Research Professor and supported by funding from the Rosetrees Trust and the Sir Jules Thorn Charitable Trust. LS is supported by a senior clinical fellowship from the Wellcome Trust (098504/Z/12/Z). IJD is funded by an unrestricted grant from GlaxoSmithKline

Social health and subsequent cognitive functioning in people aged 50 years and older:examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies

Background: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. Methods: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). Findings: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001–0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000–0·002]) and in delayed recall (PIE 0·001 [0·000–0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000–0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. Interpretation: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. Funding: EU Joint Programme—Neurodegenerative Disease Research (JPND) and Alzheimer's Society. Translation: For the Swedish translation of the abstract see Supplementary Materials section.</p