Real-World Investigation of Eosinophilic-Associated Disease Overlap (REVEAL): Analysis of a US Claims Database.

PURPOSE: The epidemiology of eosinophil-associated diseases (EADs) is not yet fully understood. While some studies have been conducted on stand-alone eosinophilic diseases, there is scarce evidence on the degree of overlap among rarer conditions. METHODS: The retrospective Real-world inVestigation of Eosinophilic-Associated disease overLap (REVEAL) study used data from the Optum® Clinformatics® insurance claims database to describe and characterize disease overlap among 11 EADs: allergic bronchopulmonary aspergillosis, atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic gastritis/gastroenteritis, eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis, bullous pemphigoid, chronic obstructive pulmonary disorder, chronic spontaneous urticaria, and non-cystic fibrosis bronchiectasis. Patient records with EADs of interest were identified between January 1, 2015, and June 30, 2018. RESULTS: Overall, 1,326,645 patients were included; 74.4% had 1 EAD, 20.5% had ≥ 2 EADs, and 5.1% had ≥ 3 EADs. Higher rates of disease overlap were associated with older age. Higher blood eosinophil counts were also observed in patients with a greater number of overlapping conditions, suggesting a common role for eosinophilic inflammation in the pathogenesis of multiple diseases. Furthermore, greater disease overlap was associated with higher disease severity in most cohorts. CONCLUSIONS: Results from this study have implications for quantifying unmet needs and can be used to inform treatment guidelines and raise the awareness of eosinophilic inflammation and EAD overlap among healthcare professionals from a range of disease specialties.

Association of Patient Mental Health Status With the Level of Agreement Between Patient and Physician Ratings of Psoriasis Severity.

Importance: The emerging paradigm of treat-to-target in psoriasis requires accurate monitoring of treatment response. The commonly used physician global assessment tool does not capture the patient's perception of their disease. Patient assessments facilitate shared decision-making and foster patient-centered care; however, recent research reports a discordance between patient- and physician-reported psoriasis severity. Understanding the factors underlying this discordance may improve treatment satisfaction and disease outcomes. Objectives: To evaluate the discordance between patient- and physician-reported measures of psoriasis severity and assess the association with patient mental health status. Design, Setting, and Participants: A cohort study using repeated cross-sectional analysis of real-world longitudinal data was conducted at a large specialist psoriasis service serving London and Southeast England. A total of 502 patients attending the psoriasis service between May 12, 2016, and November 1, 2018, were included. Data analysis was conducted July 22 to October 22, 2019. Main Outcomes and Measures: Psoriasis severity was assessed on each visit with identical 5-point physician and patient global assessment scales (clear/nearly clear, mild, moderate, severe, and very severe). Each patient completed validated self-report screens for depression and anxiety on each visit. Results: Longitudinal data from 502 individuals with psoriasis (1985 total observations) were available. A total of 339 patients (68%) were men, 396 (79%) were White, mean (SD) age was 47 (13) years, and 197 patients (39%) had concurrent psoriatic arthritis, 43 (9%) screened positive for depression, and 49 (10%) screened positive for anxiety. There was discordance between physician and patient measures of disease severity in 768 of 1985 office appointments (39%); on 511 visits (26%) patients rated their psoriasis as less severe and on 257 visits (13%) patients rated their psoriasis as more severe compared with their physician. Individuals who screened positive for depression or anxiety were more likely to overestimate their psoriasis severity compared with their physician (relative risk ratio: depression, 2.7; 95% CI, 1.6-4.5; anxiety, 2.1; 95% CI, 1.3-3.4). These findings remained statistically significant after adjustment for age, ethnicity, sex, body mass index, smoking, number of comorbidities, treatment modality, and presence of psoriatic arthritis. Conclusions and Relevance: The findings of this cohort study suggest that discordance between patient and physician assessments of psoriasis severity is associated with patients' mental health status. Recognition of anxiety and depression in individuals with psoriasis appears to be important when interpreting patient-reported outcome measures and informing appropriate treatment decisions.

Characteristics, comorbidities, and correlates of atypical depression: evidence from the UK Biobank Mental Health Survey.

BACKGROUND: Depression is a heterogeneous disorder with multiple aetiological pathways and multiple therapeutic targets. This study aims to determine whether atypical depression (AD) characterized by reversed neurovegetative symptoms is associated with a more pernicious course and a different sociodemographic, lifestyle, and comorbidity profile than nonatypical depression (nonAD). METHODS: Among 157 366 adults who completed the UK Biobank Mental Health Questionnaire (MHQ), N = 37 434 (24%) met the DSM-5 criteria for probable lifetime major depressive disorder (MDD) based on the Composite International Diagnostic Interview Short Form. Participants reporting both hypersomnia and weight gain were classified as AD cases (N = 2305), and the others as nonAD cases (N = 35 129). Logistic regression analyses were conducted to examine differences between AD and nonAD in depression features, sociodemographic and lifestyle factors, lifetime adversities, psychiatric and physical comorbidities. RESULTS: Persons with AD experienced an earlier age of depression onset, longer, more severe and recurrent episodes, and higher help-seeking rates than nonAD persons. AD was associated with female gender, unhealthy behaviours (smoking, social isolation, low physical activity), more lifetime deprivation and adversity, higher rates of comorbid psychiatric disorders, obesity, cardiovascular disease (CVD), and metabolic syndrome. Sensitivity analyses comparing AD persons with those having typical neurovegetative symptoms (hyposomnia and weight loss) revealed similar results. CONCLUSIONS: These findings highlight the clinical and public health significance of AD as a chronic form of depression, associated with high comorbidity and lifetime adversity. Our findings have implications for predicting depression course and comorbidities, guiding research on aetiological mechanisms, planning service use and informing therapeutic approaches.

The Genetic Links to Anxiety and Depression (GLAD) Study: Online recruitment into the largest recontactable study of depression and anxiety.

BACKGROUND: Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors, but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety and broad assessment of risks to facilitate future research. METHODS: The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact. RESULTS: Online recruitment was effective; 42,531 participants consented and 27,776 completed the questionnaire by end of July 2019. Participants' questionnaire data identified very high rates of recurrent depression, severe anxiety, and comorbidity. Participants reported high rates of treatment receipt. The age profile of the sample is biased toward young adults, with higher recruitment of females and the more educated, especially at younger ages. DISCUSSION: This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes, and treatment for anxiety and depression.

Indicators of mental disorders in UK Biobank-A comparison of approaches.

OBJECTIVES: For many research cohorts, it is not practical to provide a "gold-standard" mental health diagnosis. It is therefore important for mental health research that potential alternative measures for ascertaining mental disorder status are understood. METHODS: Data from UK Biobank in those participants who had completed the online Mental Health Questionnaire (n = 157,363) were used to compare the classification of mental disorder by four methods: symptom-based outcome (self-complete based on diagnostic interviews), self-reported diagnosis, hospital data linkage, and self-report medication. RESULTS: Participants self-reporting any psychiatric diagnosis had elevated risk of any symptom-based outcome. Cohen's κ between self-reported diagnosis and symptom-based outcome was 0.46 for depression, 0.28 for bipolar affective disorder, and 0.24 for anxiety. There were small numbers of participants uniquely identified by hospital data linkage and medication. CONCLUSION: Our results confirm that ascertainment of mental disorder diagnosis in large cohorts such as UK Biobank is complex. There may not be one method of classification that is right for all circumstances, but an informed and transparent use of outcome measure(s) to suit each research question will maximise the potential of UK Biobank and other resources for mental health research.

Common mental disorders within chronic inflammatory disorders: a primary care database prospective investigation.

OBJECTIVE: There is inconsistent evidence about the association between inflammatory disorders and depression and anxiety onset in a primary care context. The study aimed to evaluate the risk of depression and anxiety within multisystem and organ-specific inflammatory disorders. METHODS: This is a prospective cohort study with primary care patients from the UK Clinical Practice Research Datalink diagnosed with an inflammatory disorder between 1 January 2001 and 31 December 2016. These patients were matched on age, gender, practice and index date with patients without an inflammatory disorder. The study exposures were seven chronic inflammatory disorders. Clinical diagnosis of depression and anxiety represented the outcome measures of interest. RESULTS: Among 538 707 participants, the incidence of depression ranged from 14 per 1000 person-years (severe psoriasis) to 9 per 1000 person-years (systemic vasculitis), substantively higher compared with their comparison group (5-7 per 1000 person-years). HRs of multiple depression and anxiety events were 16% higher within inflammatory disorders (HR, 1.16, 95% CI 1.12 to 1.21, p<0.001) compared with the matched comparison group. The incidence of depression and anxiety was strongly associated with the age at inflammatory disorder onset. The overall HR estimate for depression was 1.90 (95% CI 1.66 to 2.17, p<0.001) within early-onset disorder (<40 years of age) and 0.93 (95% CI 0.90 to 1.09, p=0.80) within late-onset disorder (≥60 years of age). CONCLUSIONS: Primary care patients with inflammatory disorders have elevated rates of depression and anxiety incidence, particularly those patients with early-onset inflammatory disorders. This finding may reflect the impact of the underlying disease on patients' quality of life, although the precise mechanisms require further investigation.

Are subjective memory complaints indicative of objective cognitive decline or depressive symptoms? Findings from the English Longitudinal Study of Ageing.

Older adults often complain about their memory ability, but it is not clear to what extent subjective memory complaints accurately reflect objective cognitive dysfunctions. The concordance between objective and subjective cognitive performance may be affected by depressive symptoms and by declining insight into cognitive deficits. This study aims to examine longitudinal associations between subjective memory complaints, objective cognitive performance and depressive symptoms. 11,092 participants aged 50 years and above from the English Longitudinal Study of Ageing were followed-up every 2 years over a 6-year period. Two processes latent growth curve models (LGCM) examined associations between levels and changes in several cognitive abilities and subjective memory complaints, unadjusted for depression symptoms. Then three processes LGCM examined associations between levels and changes in depressive symptoms, subjective memory complaints and objective cognitive abilities in the overall sample, and separately among persons with mild cognitive impairment at baseline. More subjective memory complaints were associated with poorer performance in all cognitive domains at baseline. Steeper decline in immediate recall, verbal fluency and processing speed performance was associated increasing subjective memory complaints both in the overall sample and among persons with mild cognitive impairment. Increasing depressive symptoms were associated with both objective and subjective cognitive decline in the overall sample, and only with subjective memory decline among cognitively impaired persons. Self-reported memory complaints may have the potential to identify decline in objective cognitive performance that cannot be explained by depressive symptoms. Among cognitively impaired persons depressive symptoms may amplify subjective but not objective cognitive decline.

Cohort Differences in Cognitive Aging in the Longitudinal Aging Study Amsterdam.

Objectives: This study aims to examine cohort differences in cognitive performance and rates of change in episodic memory, processing speed, inductive reasoning, and general cognitive performance and to investigate whether these cohort effects may be accounted for by education attainment. Method: The first cohort (N = 705) was born between 1920 and 1930, whereas the second cohort (N = 646) was born between 1931 and 1941. Both birth cohorts were aged 65 to 75 years at baseline and were followed up 3 and 6 years later. Data were analyzed using linear mixed models. Results: The later born cohort had better general cognitive performance, inductive reasoning, and processing speed at baseline, but cohort differences in inductive reasoning and general cognitive performance disappeared after adjusting for education. The later born cohort showed steeper decline in processing speed. Memory decline was steeper in the earlier born cohort but only from Time 1 to Time 3 when the same memory test was administered. Education did not account for cohort differences in cognitive decline. Discussion: The later born cohort showed better initial performance in certain cognitive abilities, but no better preservation of cognitive abilities overtime compared with the earlier born cohort. These findings carry implications for healthy cognitive aging.

Late-life depression symptom dimensions and cognitive functioning in the Longitudinal Aging Study Amsterdam (LASA).

BACKGROUND: Depression often co-occurs in late-life in the context of declining cognitive functions, but it is not clear whether specific depression symptom dimensions are differentially associated with cognitive abilities. METHODS: The study sample comprised 3107 community-dwelling older adults from the Longitudinal Aging Study Amsterdam (LASA). We applied a Multiple Indicators Multiple Causes (MIMIC) model to examine the association between cognitive abilities and latent dimensions of the Center for Epidemiologic Studies Depression Scale (CES-D), while accounting for differential item functioning (DIF) due to age, gender and cognitive function levels. RESULTS: A factor structure consisting of somatic symptoms, positive affect, depressed affect, and interpersonal difficulties fitted the data well. Higher levels of inductive reasoning were significantly associated with lower levels of depressed affect and somatic symptoms, whereas faster processing speed was significantly associated with lower levels of somatic symptoms. DIF due to age and gender was found, but the magnitude of the effects was small and did not alter substantive conclusions. LIMITATIONS: Due to the cross-sectional context of this investigation, the direction of influence between depression symptom levels and cognitive function levels cannot be established. Furthermore, findings are relevant to non-clinical populations, and they do not clarify whether certain DIF effects may be found only at high or low levels of depression. CONCLUSIONS: Our findings suggest differential associations between late-life depression dimensions and cognitive abilities in old age, and point towards potential etiological mechanisms that may underline these associations. These findings carry implications for the prognosis of cognitive outcomes in depressed older adults.

A multiple indicators multiple causes model of late-life depression in Latin American countries.

BACKGROUND: The Euro-D depression scale consists of symptom clusters that may be differentially related to demographic and cognitive characteristics in older adults. This hypothesis needs further investigation and the role of measurement bias on substantive conclusions remains to be established. METHOD: The study sample comprised 10,405 community-dwelling older adults from six Latin American countries. We applied a Multiple Indicators Multiple Causes (MIMIC) model for a concurrent investigation of measurement bias and of the association between Euro-D symptom clusters and background variables. RESULTS: The factorial validity of Euro-D, with a two-dimensional structure--affective suffering and motivation disturbance, was consistently supported in all countries. Although complete measurement invariance could not be assumed across countries, measurement bias was minor. Both Euro-D factors were unrelated to age, but related to gender, as well as to impairment in memory and verbal fluency. Gender differences were larger for affective suffering than for motivation disturbance, whereas differences in verbal fluency impairment were more strongly related to motivation disturbance. LIMITATIONS: Our analytic strategies could only examine invariance at the level of indicator thresholds. The generalisability of current findings needs to be examined in clinical populations. A wider set of cognitive tests is needed. We did not examine the compositional factors that could have accounted for the variation in Euro-D scores across countries, as this was beyond the aims of the paper. CONCLUSION: The current study adds evidence for the construct validity of Euro-D and for the possible differential association of depression symptom-clusters with gender and verbal fluency in older adults. An understanding of the heterogeneity of late-life depression may carry clinical implications for the diagnosis and treatment of depression in old age.