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

The Doctor and the Law: A Practical Guide for the Canadian Physician, 3rd Edition

Book review of The Doctor and the Law: A Practical Guide for the Canadian Physician, 3rd Edition by H.E. Emson and published by Butterworths (Markham, Ont.), 1995. (282 pp.

Major depression and survival in people with cancer

OBJECTIVE: The question of whether depression is associated with worse survival in people with cancer remains unanswered because of methodological criticism of the published research on the topic. We aimed to study the association in a large methodologically robust study. METHODS: We analysed data on 20,582 patients with breast, colorectal, gynaecological, lung and prostate cancers who had attended cancer outpatient clinics in Scotland, UK. Patients had completed two-stage screening for major depression as part of their cancer care. These data on depression status were linked to demographic, cancer and subsequent mortality data from national databases. We estimated the association of major depression with survival for each cancer using Cox regression. We adjusted for potential confounders and interactions between potentially time-varying confounders and the interval between cancer diagnosis and depression screening, and used multiple imputation for missing depression and confounder data. We pooled the cancer-specific results using fixed-effects meta-analysis. RESULTS: Major depression was associated with worse survival for all cancers, with similar adjusted hazard ratios: breast cancer (HR 1.42, 95% CI 1.15-1.75), colorectal cancer (HR 1.47, 95% CI 1.11-1.94), gynaecological cancer (HR 1.36, 95% CI 1.08-1.71), lung cancer (HR 1.39, 95% CI 1.24-1.56), prostate cancer (HR 1.76, 95% CI 1.08-2.85). The pooled hazard ratio was 1.41 (95% CI 1.29-1.54, p<0.001, I2=0%). These findings were not materially different when we only considered the deaths (90%) that were attributed to cancer. CONCLUSIONS: Major depression is associated with worse survival in patients with common cancers. The mechanisms of this association and the clinical implications require further study

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

Association Between Atopic Eczema and Cancer in England and Denmark.

Importance: Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk. Objective: To investigate whether atopic eczema is associated with cancer. Design, Setting, and Participants: Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema. Exposure: Atopic eczema. Main Outcomes and Measures: Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema. Results: In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide. Conclusions and Relevance: The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk

Atopic-eczema-associated fracture risk and oral corticosteroids: a population-based cohort study

Background Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association. Objective To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures. Methods We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose). Results We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]). Conclusions Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use

Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.

OBJECTIVES: Visuospatial processing deficits have been reported in Huntington's disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. METHODS: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. RESULTS: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation ("same") was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. CONCLUSIONS: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595-608)

Patterns of Atopic Eczema Disease Activity From Birth Through Midlife in 2 British Birth Cohorts.

IMPORTANCE: Atopic eczema is characterized by a heterogenous waxing and waning course, with variable age of onset and persistence of symptoms. Distinct patterns of disease activity such as early-onset/resolving and persistent disease have been identified throughout childhood; little is known about patterns into adulthood. OBJECTIVE: This study aimed to identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, to examine whether early life risk factors and participant characteristics are associated with these subtypes, and to determine whether subtypes are associated with other atopic diseases and general health in mid-adulthood. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated members of 2 population-based birth cohorts, the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participant data were collected over the period between 1958 and 2016. Data were analyzed over the period between 2018 and 2020. MAIN OUTCOMES AND MEASURES: Subtypes of atopic eczema were identified based on self-reported atopic eczema period prevalence at multiple occasions. These subtypes were the outcome in models of early life characteristics and an exposure variable in models of midlife health. RESULTS: Latent class analysis identified 4 subtypes of atopic eczema with distinct patterns of disease activity among 15 939 individuals from the NCDS (51.4% male, 75.4% White) and 14 966 individuals from the BCS70 (51.6% male, 78.8% White): rare/no (88% to 91%), decreasing (4%), increasing (2% to 6%), and persistently high (2% to 3%) probability of reporting prevalent atopic eczema with age. Sex at birth and early life factors, including social class, region of residence, tobacco smoke exposure, and breastfeeding, predicted differences between the 3 atopic eczema subtypes and the infrequent/no atopic eczema group, but only female sex differentiated the high and decreasing probability subtypes (odds ratio [OR], 1.99; 95% CI, 1.66-2.38). Individuals in the high subtype were most likely to experience asthma and rhinitis, and those in the increasing subtype were at higher risk of poor self-reported general (OR, 1.29; 95% CI, 1.09-1.53) and mental (OR 1.45; 95% CI, 1.23-1.72) health in midlife. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that extending the window of observation beyond childhood may reveal clear subtypes of atopic eczema based on patterns of disease activity. A newly identified subtype with increasing probability of activity in adulthood warrants additional attention given observed associations with poor self-reported health in midlife

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

Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics.

Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies