Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.

BACKGROUND: People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population. METHODS: People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership. RESULTS: The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters. CONCLUSION: The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.

How is nicotine vaping product (e-cigarette) use monitored in primary care electronic health records in the United Kingdom? An exploratory analysis of Clinical Practice Research Datalink (CPRD).

BACKGROUND: Electronic health records (EHRs) could identify long-term health effects of nicotine vaping. We characterised the extent to which vaping is recorded in primary care EHRs in the UK, on a population level. METHODS: We performed descriptive analysis of Clinical Practice Research Datalink (CPRD), primary care electronic health records of 25% of the UK population (~ 16 million patients). Patients aged ≥ 18 years whose vaping status was recorded using medical codes between 2006 and 2022 were identified. We reported the frequency of vaping codes; their distribution by patient age, gender, and ethnicity; trends in vaping recording over time (including interrupted time series analyses); and transitions in patient smoking status. RESULTS: Seven medical codes indicated current or former vaping, from 150,114 patients. When their vaping status was first recorded, mean patient age was 50.2 years (standard deviation: 15.0), 52.4% were female, and 82.1% were White. Of those recorded as currently vaping, almost all (98.9%) had records of their prior smoking status: 55.0% had been smoking, 38.3% had stopped smoking, 5.6% had never smoked. Of those who were smoking prior to being recorded as vaping, more than a year after the vaping record, over a third (34.2%) were still smoking, under a quarter (23.7%) quit smoking, 1.7% received a 'never smoked' status, and there was no smoking status for 40.4%. The 'e-cigarette or vaping product use-associated lung injury' (EVALI) outbreak was significantly associated with a declining trend in new records of current vaping between September 2019 and March 2020; and an immediate significant increase in new records of former vaping, followed by a declining trend. CONCLUSIONS: Few patients are being asked about vaping. Most who vape had smoked, and many quit smoking after starting vaping. To enable electronic health records to provide stronger evidence on health effects, we recommend improved completeness, accuracy and consistency.

Frailty in individuals with depression, bipolar disorder and anxiety disorders: longitudinal analyses of all-cause mortality.

BACKGROUND: Frailty is a medical syndrome that is strongly associated with mortality risk and an emerging global health burden. Mental disorders are associated with reduced life expectancy and elevated levels of frailty. In this study, we examined the mortality risk associated with frailty in individuals with a lifetime history of mental disorders compared to individuals without a history of mental disorders. METHODS: The UK Biobank study recruited > 500,000 adults, aged 37-73, between 2006 and 2010. We derived the two most common albeit distinctive measures of frailty, the frailty phenotype and the frailty index. Individuals with lifetime depression, bipolar disorder or anxiety disorders were identified from multiple data sources. The primary outcome was all-cause mortality. We have also examined differences in frailty, separately by sex and age. RESULTS: Analyses included up to 297,380 middle-aged and older adults with a median follow-up of 12.19 (interquartile range = 1.31) years, yielding 3,516,706 person-years of follow-up. We observed higher levels of frailty in individuals with mental disorders for both frailty measures. Standardised mean differences in the frailty index ranged from 0.66 (95% confidence interval [CI] 0.65-0.67) in individuals with anxiety disorders to 0.94 (95% CI 0.90-0.97) in individuals with bipolar disorder, compared to people without mental disorders. For key comparisons, individuals with a mental disorder had greater all-cause mortality hazards than the comparison group without mental disorders. The highest hazard ratio (3.65, 95% CI 2.40-5.54) was observed among individuals with bipolar disorder and frailty, relative to non-frail individuals without mental disorders. CONCLUSIONS: Our findings highlight elevated levels of frailty across three common mental disorders. Frailty and mental disorders represent potentially modifiable targets for prevention and treatment to improve population health and life expectancy, especially where both conditions coexist.

Prospective associations between vitamin D and depression in middle-aged adults: findings from the UK Biobank cohort.

BACKGROUND: A possible role of vitamin D in the pathophysiology of depression is currently speculative, with more rigorous research needed to assess this association in large adult populations. The current study assesses prospective associations between vitamin D status and depression in middle-aged adults enrolled in the UK Biobank. METHODS: We assessed prospective associations between vitamin D status at the baseline assessment (2006-2010) and depression measured at the follow-up assessment (2016) in 139 128 adults registered with the UK Biobank. RESULTS: Amongst participants with no depression at baseline (n = 127 244), logistic regression revealed that those with vitamin D insufficiency [adjusted odds ratio (aOR) = 1.14, 95% confidence interval (CI) = 1.07-1.22] and those with vitamin D deficiency (aOR = 1.24, 95% CI 1.13-1.36) were more likely to develop new-onset depression at follow-up compared with those with optimal vitamin D levels after adjustment for a wide range of relevant covariates. Similar prospective associations were reported for those with depression at baseline (n = 11 884) (insufficiency: aOR = 1.11, 95% CI 1.00-1.23; deficiency: aOR = 1.30, 95% CI 1.13-1.50). CONCLUSIONS: The prospective associations found between vitamin D status and depression suggest that both vitamin D deficiency and insufficiency might be risk factors for the development of new-onset depression in middle-aged adults. Moreover, vitamin D deficiency (and to a lesser extent insufficiency) might be a predictor of sustained depressive symptoms in those who are already depressed. Vitamin D deficiency and insufficiency is very common, meaning that these findings have significant implications for public health.

Prospective associations between depression and risk of hospitalisation for infection: Findings from the UK Biobank.

BACKGROUND: Associations between depression and non-communicable disease have been well-described. However, the evidence for its role in the development of infectious disease is less understood. We aimed to examine prospective associations between depression and risk of hospitalisation for infection in middle-aged adults from the UK Biobank (linked with Hospital Episode Statistics) and assessed the role of several depression-related factors. METHODS: We assessed prospective associations between depression status at the baseline assessment (2006-2010) and hospitalisations for infection up to the end of March 2016 in 460,418 middle-aged adults enrolled in the UK Biobank (mean age = 56.23 ± 8.11 years, 53.5% female). Cox regression was used to assess associations between depression and subsequent hospitalisations for any infections, as well as infection subtypes, viral infections, and bacterial infections. Amongst those with depression, we also examined the role of depression duration, the age of onset, and the use of antidepressants in hospitalisation risk. RESULTS: Depression at baseline was prospectively associated with an increased risk of hospitalisation for infection (adjusted hazard ration (aHR) = 1.20, 95% confidence interval (CI) = 1.16 to 1.25). This association was found for all infection subtypes apart from infections of the central nervous system (p = 0.911) and the skin (p = 0.313). Receipt of a depression diagnosis in late adulthood and use of antidepressants (but only in those with none/mild depressive symptoms at baseline) increased the risk of hospitalisation for infection amongst those with depression. CONCLUSIONS: These findings suggest that depression might be a risk factor which could be used to identify those at risk of hospitalisation for infection. Future research is required to understand the underlying factors that might result in this increased risk, so that targeted interventions can be developed. FUNDING: AD and AR are funded by Guy's Charity grant number EIC180702 (MLTC Challenge Fund); AD and JAT are co-funded by MRC and NIHR through grant number MR/S028188/1. IB is supported by the NIHR Maudsley BRC and by the NIHR Collaboration for Leadership in Applied Health Research and Care South Londnoo at King's College Hospital NHS Foundation Trust, King's College London. The views expressed are those of the author[s] and not necessarily those of the ESRC, NIHR, the Department of Health and Social Care or King's College London.

Diagnostic promiscuity: the use of real-world data to study multimorbidity in mental health.

Mental health-related multimorbidity can be considered as multimorbidity in the presence of a mental disorder. Some knowledge gaps on the study of mental health-related multimorbidity were identified. These knowledge gaps could be potentially addressed with real-world data.

Association of macro-level determinants with adolescent overweight and suicidal ideation with planning: A cross-sectional study of 21 Latin American and Caribbean Countries.

BACKGROUND: Adolescents and young people (10-24 years old) in the Latin America and the Caribbean (LAC) region represent approximately 25% of the region's population. Since the 2008 global economic crisis, the pace of reduction in poverty and income inequality in the LAC region has stalled. The region is characterised by high levels of inequities and is also vulnerable to many natural disasters. Food systems are changing with increased availability and marketing of packaged and fast foods and sugar-sweetened drinks. Adolescence is a formative phase of the life course with multiple physical, emotional and social changes which can make them vulnerable to health problems. We assess the potential impact of macro-determinants, human and economic development as well as income inequality, on 2 top-ranking regional priorities for adolescent nutrition and mental health, using measures of overweight and suicidal ideation and planning which some have shown to be associated. METHODS AND FINDINGS: The Global School-based Health Survey (GSHS) is a nationally representative self-administered, school-based survey. We examined overweight/obesity and suicidal ideation with planning by gross domestic product (GDP) per capita or human development index (HDI) in 10-19-year-old adolescents from 21 LAC countries between 2009 and 2013. Sample sizes varied from 943 in Anguilla to 27,988 in Argentina. A total of 55,295 adolescents had a measure of overweight/obesity status, and 59,061 adolescents reported about suicidal ideation with planning. There was equal representation by sex in the surveys (52% girls and 48% boys). A total of 28.8% of boys and 28.1% of girls had overweight/obesity, and 7.5% of boys and 17.5% of girls reported suicidal ideation with planning over the last 12 months. Adjusted for individual socioeconomic and risk behaviours, and relative to the highest GDP per capita tertile, the middle tertile was associated with 42% (95% confidence interval (CI) 59% to 17%, p = 0.003) and 32% (95% CI 60% to 5%, p = 0.023), and the lowest tertile with 40% (95% CI 55% to 19%, p = 0.001) and 46% (95% CI 59% to 29%, p < 0.001) lower chances of overweight/obesity for girls and boys, respectively. A similar positive effect was seen with HDI, with lowest chances of overweight in the lowest tertile compared with the highest tertile for both sexes. Overweight/obesity was positively related with suicidal ideation with planning for girls (odds ratio (OR) 1.12, 95% CI 1.02 to 1.22, p = 0.009) and weakly related for boys (OR 1.09, 95% CI 0.96 to 1.24, p = 0.182). In contrast to overweight/obesity status, suicidal ideation with planning was not related to macro-level indices despite both outcomes sharing common individual socioeconomic and risk behaviour correlates. Limitations include the dominance of Argentinians in the sample (40%), the exclusion of vulnerable adolescents who dropped out of school, and reporting bias due to stigma of mental health-related issues. CONCLUSIONS: This study shows that economic and human development were positively associated with adolescent overweight/obesity but not with suicidal ideation with planning. We also observed an interconnectedness between overweight/obesity and suicide ideation with planning among girls. These findings highlight the importance of strategies that engage with both upstream and downstream determinants to improve adolescent nutrition and mental health.

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.

Demographic variation in fit note receipt and long-term conditions in south London.

OBJECTIVES: Introduced in the UK in 2010, the fit note was designed to address the problem of long-term sickness absence. We explored (1) associations between demographic variables and fit note receipt, 'maybe fit' use and long-term conditions, (2) whether individuals with long-term conditions receive more fit notes and are more likely to have the 'maybe fit' option selected and (3) whether long-term conditions explained associations between demographic variables and fit note receipt. METHODS: Data were extracted from Lambeth DataNet, a database containing electronic medical records of all 45 general practitioner (GP) practices within the borough of Lambeth. Individual-level anonymised data on GP consultations, prescriptions, Quality and Outcomes Framework diagnostic data and demographic information were analysed using survival analysis. RESULTS: In a sample of 326 415 people, 41 502 (12.7%) received a fit note. We found substantial differences in fit note receipt by gender, age, ethnicity and area-level deprivation. Chronic pain (HR 3.7 (95% CI 3.3 to 4.0)) and depression (HR 3.4 (95% CI 3.3 to 3.6)) had the highest rates for first fit note receipt. 'Maybe fit' recommendations were used least often in patients with epilepsy and serious mental illness. The presence of long-term conditions did not explain associations between demographic variables and fit note use. CONCLUSIONS: For the first time, we show the relationships between fit note use and long-term conditions using individual-level primary care data from south London. Further research is required in order to evaluate this relatively new policy and to understand the needs of the population it was designed to support.

Weight misperception and psychological symptoms from adolescence to young adulthood: longitudinal study of an ethnically diverse UK cohort.

BACKGROUND: To evaluate the association between weight misperception and psychological symptoms in the Determinants of young Adults Social well-being and Health (DASH) longitudinal study. METHODS: A longitudinal sample of 3227 adolescents, in 49 secondary schools in London, aged 11-16 years participated in 2002/2003 and were followed up in 2005/2006. A sub-sample (N = 595) was followed up again at ages 21-23 years in 2012/2013. An index of weight misperception was derived from weight perception and measured weight. Psychological well- being was measured using the Strengths and Difficulties Questionnaire at 11-16 years and the General Health Questionnaire at 21-23 years. Associations with weight misperception was assessed using regression models, adjusted for socio-economic and lifestyle factors. RESULTS: White British males and females were more likely than ethnic minority peers to report accurate perceptions of measured weight. At 11-13y, 46% females and 38% males did not have an accurate perception of their measured weight. The comparable figures at 14-16y were 42 and 40%. Compared with male adolescents, more females perceived themselves as overweight or were unsure of their weight but measured normal weight, and this was more pronounced among Indians, Pakistanis and Bangladeshis. At 14-16y, more males perceived themselves as underweight but measured normal weight, and this was more pronounced among Indians. Compared with those who had an accurate perception of their normal weight, a higher likelihood of probable clinically-relevant psychological symptoms was observed among those who measured normal weight but perceived themselves to be underweight (females Odds Ratio (OR) = 1.87 95% CI 1.03-3.40; males OR = 2.34 95% CI 1.47-3.71), overweight (females only OR = 2.06 95% CI 1.10-3.87), or unsure of their weight (males only OR = 1.61 95% CI 1.04-2.49). Among females, the association was driven by internalising rather than externalising symptoms. An accurate perception of overweight was associated with higher psychological symptoms in adolescence and early 20s. Ethnic specific effects were not evident. CONCLUSION: Weight misperception may be an important determinant of psychological symptoms in young people, with an accurate perception of normal weight status being protective. Culturally targeted interventions should be considered to promote healthy perceptions of body image.

Impact of comorbidity on the short- and medium-term risk of revision in total hip and knee arthroplasty.

BACKGROUND: The impact of comorbidity on the risk of revision in patients undergoing Total Knee arthroplasty (TKA) and Total Hip Arthroplasty (THA) is not currently well known. The aim of this study was to analyze the impact of comorbidity on the risk of revision in TKA and THA. METHODS: Patients recorded in the Catalan Arthroplasty Register (RACat) between 01/01/2005 and 31/12/2016 undergoing TKA (n = 49,701) and THA (n = 17,923) caused by osteoarthritis were included. As main explanatory factors, comorbidity burden was assessed by the Elixhauser index, categorized, and specific comorbidities from the index were taken into account. Descriptive analyses for comorbidity burden and specific conditions were done. Additionally, incidence at 1 and 5 years' follow-up was calculated, and adjusted Competing Risks models were fitted. RESULTS: A higher incidence of revision was observed when the number of comorbidities was high, both at 1 and 5 years for THA, but only at 1 year for TKA. Of the specific conditions, only obesity was related to the incidence of revision at 1 year in both joints, and at 5 years in TKA. The risk of revision was related to deficiency anemia and liver diseases in TKA, while in THA, it was related to peripheral vascular disorders, metastatic cancer and psychoses. CONCLUSIONS: Different conditions, depending on the joint, might be related to higher revision rates. This information could be relevant for clinical decision-making, patient-specific information and improving the results of both TKA and THA.

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.

National disparities in the relationship between antimicrobial resistance and antimicrobial consumption in Europe: an observational study in 29 countries.

BACKGROUND: Antimicrobial resistance in invasive infections is driven mainly by human antimicrobial consumption. Limited cross-national comparative evidence exists about variation in antimicrobial consumption and effect on resistance. METHODS: We examined the relationship between national community antimicrobial consumption rates (2013) and national hospital antimicrobial resistance rates (2014) across 29 countries in the European Economic Area (EEA). Consumption rates were obtained from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). Resistance data were obtained from the European Antimicrobial Resistance Surveillance Network (EARS-Net), based on 196480 invasive isolates in 2014. RESULTS: Data availability and consistency were good. Some countries did not report figures for each strain of resistant bacteria. National antimicrobial consumption rates (2013) varied from ≤ 13 DDD (Estonia, the Netherlands and Sweden) to ≥ 30 DDD (France, Greece and Romania) per 1000 inhabitants per day. National antimicrobial resistance rates (hospital isolates, 15 species) also varied from <6.1% (Finland, Iceland and Sweden) to > 37.2% (Bulgaria, Greece, Romania and Slovakia). National antimicrobial consumption rates (2013) showed strong to moderate correlation with national hospital antimicrobial resistance rates (2014) in 19 strains of bacteria (r = 0.84 to r = 0.39). Some countries defied the trend with high consumption and low resistance (France, Belgium and Luxembourg) or low consumption and high resistance (Bulgaria, Hungary and Latvia). CONCLUSIONS: We found associations between national community antimicrobial consumption and national hospital antimicrobial resistance across a wide range of bacteria. These associations were not uniform. Different mechanisms may drive resistance in hospital-based invasive infections. Future research on international variations in antimicrobial resistance should consider environmental factors, agricultural use, vaccination policies and prescribing quality.

Determinants of multimorbidity in low- and middle-income countries: A systematic review of longitudinal studies and discovery of evidence gaps.

Multimorbidity-the coexistence of at least two chronic health conditions within the same individual-is an important global health challenge. In high-income countries (HICs), multimorbidity is dominated by non-communicable diseases (NCDs); whereas, the situation may be different in low- and middle-income countries (LMICs), where chronic communicable diseases remain prominent. The aim of this systematic review was to identify determinants (including risk and protective factors) and potential mechanisms underlying multimorbidity from published longitudinal studies across diverse population-based or community-dwelling populations in LMICs. We systematically searched three electronic databases (Medline, Embase, and Global Health) using pre-defined search terms and selection criteria, complemented by hand-searching. All titles, abstracts, and full texts were independently screened by two reviewers from a pool of four researchers. Data extraction and reporting were according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality and risk of bias assessment was performed using the Newcastle-Ottawa Scale for cohort studies. Data were summarized using narrative synthesis. The search yielded 1782 records. Of the 52 full-text articles included for review, 8 longitudinal population-based studies were included for final data synthesis. Almost all studies were conducted in Asia, with only one from South America and none from Africa. All studies were published in the last decade, with half published in the year 2021. The definitions used for multimorbidity were heterogeneous, including 3-16 chronic conditions per study. The leading chronic conditions were heart disease, stroke, and diabetes, and there was a lack of consideration of mental health conditions (MHCs), infectious diseases, and undernutrition. Prospectively evaluated determinants included socio-economic status, markers of social inequities, childhood adversity, lifestyle behaviors, obesity, dyslipidemia, and disability. This review revealed a paucity of evidence from LMICs and a geographical bias in the distribution of multimorbidity research. Longitudinal research into epidemiological aspects of multimorbidity is warranted to build up scientific evidence in regions beyond Asia. Such evidence can provide a detailed picture of disease development, with important implications for community, clinical, and interventions in LMICs. The heterogeneity in study designs, exposures, outcomes, and statistical methods observed in the present review calls for greater methodological standardisation while conducting epidemiological studies on multimorbidity. The limited evidence for MHCs, infectious diseases, and undernutrition as components of multimorbidity calls for a more comprehensive definition of multimorbidity globally.

Comparison of a sleep item from the General Health Questionnaire-12 with the Jenkins Sleep Questionnaire as measures of sleep disturbance.

BACKGROUND: The objective of this study was to examine whether a widely available single-item measure of sleep disturbances is an acceptable alternative to a multi-item sleep questionnaire. METHODS: Data were derived from Finnish Helsinki Health Study postal questionnaires administered in 2000-2002 (n = 7777, response rate 67%). The measures were the 4-item Jenkins Sleep Questionnaire (JSQ) on difficulties initiating and maintaining sleep, and nonrestorative sleep, and an item on sleep loss due to worry, from the General Health Questionnaire-12 (GHQ-12). Receiver operating characteristics (ROC) curve analyses were done to compare the predictive performance of the GHQ-12 item with the JSQ scale. Using the above 2 measures of sleep, logistic regression models were used to examine associations between sociodemographic factors, working conditions, health-related factors, and sleep disturbance. RESULTS: The estimated area under the ROC curve was 0.68 among both women and men, which suggests that the ability of the GHQ-12 item to discriminate true positives from false positives was modest. However, the associations of sleep disturbance with its key determinants were largely similar using the GHQ-12 and the JSQ. CONCLUSIONS: A widely available, GHQ-12-based, single-item sleep measure was not an adequate substitute for a multi-item measure of overall sleep disturbance. Although the measures produced largely similar associations for key determinants of poor sleep, the discrepancies between responses must be considered when analyzing data from a measure that uses a single sleep item.

Vitamin D and the risk of treatment-resistant and atypical depression: A Mendelian randomization study.

Observational evidence has implicated vitamin D levels as a risk factor in major depressive disorder (MDD). Confounding or reverse causation may be driving these observed associations, with studies using genetics indicating little evidence of an effect. However, genetic studies have relied on broad definitions of depression. The genetic architecture of different depression subtypes may vary since MDD is a highly heterogenous condition, implying potentially diverging requirements in therapeutic approaches. We explored the associations between vitamin D and two subtypes of MDD, for which evidence of a causal link could have the greatest clinical benefits: treatment-resistant depression (TRD) and atypical depression (AD). We used a dual approach, combining observational data with genetic evidence from polygenic risk scores (PRS) and two-sample Mendelian randomization (MR), in the UK Biobank. There was some evidence of a weak association between vitamin D and both incident TRD (Ncases = 830) and AD (Ncases = 2366) in observational analyses, which largely attenuated when adjusting for confounders. Genetic evidence from PRS and two-sample MR, did not support a causal link between vitamin D and either TRD (Ncases = 1891, OR = 1.01 [95%CI 0.78, 1.31]) or AD (Ncases = 2101, OR = 1.04 [95%CI 0.80, 1.36]). Our comprehensive investigations indicated some evidence of an association between vitamin D and TRD/AD observationally, but little evidence of association when using PRS and MR, mirroring findings of genetic studies of vitamin D on broad depression phenotypes. Results do not support further clinical trials of vitamin D in these MDD subtypes but do not rule out that small effects may exist that require larger samples to detect.

Associations between physical multimorbidity patterns and common mental health disorders in middle-aged adults: A prospective analysis using data from the UK Biobank.

BACKGROUND: We aimed to identify specific patterns of physical multimorbidity, defined as the presence of two or more physical long-term conditions, and to examine the extent to which these specific patterns could predict future incident and persistent common mental health disorders (CMDs) in middle-aged adults enrolled in the UK Biobank. METHODS: We assessed prospective associations between physical multimorbidity status at the baseline assessment (2006-2010) and depression and anxiety 'caseness' according to the Patient Health Questionnaire (PHQ)-9 and the Generalised Anxiety Disorder Assessment (GAD)-7 at the follow-up assessment (2016) in 154,367 middle-aged adults enrolled in the UK Biobank (median age: 57 years, interquartile range = 50-62 years, 56.5% female, mean duration of follow-up: 7.6 years, standard deviation = 0.87). Patterns of physical multimorbidity were identified using exploratory factor analysis. Logistic regression was used to assess prospective associations between physical multimorbidity patterns at baseline and both incident and persistent depression and anxiety at follow-up. FINDINGS: Compared to those with no physical multimorbidity, having two (adjusted odds ratio (aOR) =1.41, 95%CI 1.32 to 1.53), three (aOR = 1.94, 95%CI 1.76 to 2.14), four (aOR = 2.38, 95%CI 2.07 to 2.74), and five or more (aOR = 2.89, 95%CI 2.42 to 3.45) physical conditions was prospectively associated with incident depression at follow-up in a dose response manner. Similar trends emerged for incident anxiety, persistent depression, and persistent anxiety, but associations were strongest for incident CMDs. Regarding specific patterns of physical MM, the respiratory pattern (aOR = 3.23, 95%CI 2.44 to 4.27) and the pain/gastrointestinal pattern (aOR = 2.19, 95%CI 1.92 to 2.50) emerged as the strongest predictors of incident depression. Similar results emerged for incident anxiety. INTERPRETATION: These findings highlight patterns of physical multimorbidity with the poorest prognosis for both emerging and persisting depression and anxiety. These findings might have significant implications for the implementation of integrated mental and physical healthcare and facilitate the development of targeted preventative interventions and treatment for those with physical multimorbidity. FUNDING: AR is supported by Guy's Charity grant number EIC180702; JAT is funded by Medical Research Council (MRC) number MR/SO28188/1; AD is funded by Guy's Charity grant number EIC180702 and MRC grant number MR/SO28188/1. JD is part supported by the ESRC Centre for Society and Mental Health at King's College London (ES/S012567/1), grants from the ESRC (ES/S002715/1), by the Health Foundation working together with the Academy of Medical Sciences, for a Clinician Scientist Fellowship, and by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and the National Institute for Health Research (NIHR) Applied Research Collaboration South London (NIHR ARC South London) at King's College Hospital NHS Foundation Trust. The views expressed are those of the author[s] and not necessarily those of the ESRC, NIHR, the Department of Health and Social Care or King's College London.

Multimorbidity patterns, all-cause mortality and healthy aging in older English adults: Results from the English Longitudinal Study of Aging.

AIM: This study aimed to investigate the relationships between multimorbidity, healthy aging and mortality. METHODS: Using data from 9171 individuals aged ≥50 years at wave 2 and mortality data at wave 5 of the English Longitudinal Study of Aging, a multiple linear regression model and a Cox proportional hazards model were used to investigate how multimorbidity patterns (identified as cardiorespiratory/arthritis/cataracts, metabolic and relatively healthy) were associated with a composite index of healthy aging (derived from 41 intrinsic capacity and functional ability items) and with mortality. RESULTS: A total of 60% of the sample with multimorbidity had a moderate or high level of healthy aging. Both the cardiorespiratory/arthritis/cataracts group (n = 1826) and the metabolic group (n = 844) were negatively associated with healthy aging. The expected healthy aging index score decreased by 5.81 points (95% CI -6.69, -4.92) for the first group, and by 2.39 points (95% CI -3.54, -1.24) for the latter group. Only the cardiorespiratory/arthritis/cataracts group was positively associated with mortality. The risk of death for this group was 1.27-fold (95% CI: 1.14, 1.43) than the relatively healthy group. The relationship between multimorbidity patterns and mortality did not differ when considering levels of healthy aging. CONCLUSIONS: Although it is not impossible for people with multimorbidity to age healthily, those with the most complex combination of diseases are at higher risk of death and have lower levels of healthy aging. Geriatr Gerontol Int 2020; 20: 1126-1132.