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ImportancePrenatal exposure to benzodiazepines is reported to be associated with neurodevelopmental disorders among children, but associations of maternal genetic confounding with neurodevelopmental disorders among children have not been taken into consideration.ObjectiveTo ascertain whether prenatal benzodiazepine exposure was associated with development of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD).Design, Setting, and ParticipantsThis cohort study used linked data from birth certificate registration and the Taiwan National Health Insurance Research Database from January 1, 2004, to December 31, 2017, on 1 138 732 mothers with 1 516 846 live births between January 1, 2004, and December 31, 2017. Data were analyzed between February 20, 2021, and September 19, 2022.ExposureBenzodiazepine exposure during pregnancy (first trimester to third trimester) was defined as having at least one benzodiazepine prescription dispensed.Main Outcomes and MeasuresThe main outcomes were ADHD and ASD.ResultsThere were 1 516 846 children (mean [SD] gestational age, 38.5 [1.8] years; 789 455 boys [52.0%]) born full term who were younger than 14 years of age and followed up to 2017; 5.0% of the children (n = 76 411) were exposed to a benzodiazepine during pregnancy. Benzodiazepine exposure during pregnancy was associated with increased risks of ADHD (first trimester exposure: hazard ratio [HR], 1.24 [95% CI, 1.20-1.28]; second trimester exposure: HR, 1.27 [95% CI, 1.21-1.34]; third trimester exposure: HR, 1.25 [95% CI, 1.14-1.37]) and ASD (first trimester exposure: HR, 1.13 [95% CI, 1.05-1.21]; second trimester exposure: HR, 1.10 [95% CI, 0.98-1.22]; third trimester exposure: HR, 1.21 [95% CI, 1.00-1.47]). However, no differences were found with unexposed sibling controls during the same time frame for ADHD (first trimester exposure: HR, 0.91 [95% CI, 0.83-1.00]; second trimester exposure: HR, 0.89 [95% CI, 0.78-1.01]; third trimester exposure: HR, 1.08 [95% CI, 0.83-1.41]) or ASD (first trimester exposure: HR, 0.92 [95% CI, 0.75-1.14]; second trimester exposure: HR, 0.97 [95% CI, 0.71-1.33]; third trimester exposure: HR, 1.07 [95% CI, 0.53-2.16]). Similar findings were also noted in the stratification analysis of short-acting and long-acting benzodiazepines.Conclusions and RelevanceThis cohort study suggests that previously described adverse neurodevelopmental outcomes associated with benzodiazepine exposure during pregnancy were likely to be accounted for by maternal genetic confounding.

Background Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. Methods Patients with treatment-resistant schizophrenia commenced on clozapine between January 2007 and December 2014 by the United Kingdom’s largest mental health trust were identified from electronic patient records. Hematological data from these patients were obtained from a monitoring registry. White blood cell, neutrophil, and platelet count were assessed at baseline and during the early phase of clozapine treatment. Clozapine response at 3 months was defined as “much,” or “very much” improved on the seven-point Clinical Global Impression—Improvement (CGI-I) subscale. Results In the total sample (n = 188), clozapine initiation was associated with a significant transient increase (peaking in weeks 3 to 4) in white blood cell, neutrophil, and platelet count (P < 0.001). There were 112 (59.6%) patients that responded to treatment; however, none of the hematological factors assessed at baseline, nor changes in these factors, were directly associated with treatment response. Implications Clozapine treatment is associated with transient hematological changes during the first month of treatment; however, there was no evidence that these were related to the therapeutic response.

Introduction: Routine crossmatch of packed red blood cells (pRBCs) is completed preoperatively at many centers despite conflicting evidence on the incidence of blood transfusions with renal transplantation. In the current economic climate, resource adjudication should be judicious and medically appropriate. The objective of this study was to determine the incidence, timing, and predictors of early postoperative pRBC transfusion in patients undergoing renal transplantation. Methods: A retrospective review of all patients undergoing renal transplantation at our institution from January 2013 to May 2016 was performed. Demographic, biochemical, and clinical parameters were recorded. The primary outcome was early postoperative transfusion, defined as an intraoperative transfusion or within 2 days of surgery. Multivariable logistic regression was performed to identify associations with early postoperative transfusion. Results: We identified 428 patients during the study period (average age 55 years, 60% male, 30% obese, 67% deceased donor, and 43% preoperative antithrombotic use). Forty (9.3%) patients required early postoperative transfusion (mean: 2.8 pRBCs/transfusion) and most did not require blood urgently. Only 20 (4.7%) patients required a transfusion intraoperatively or on the same day of surgery. Lower preoperative hemoglobin (per g/L unit: odds ratio [OR]: 0.943), female gender (OR: 2.752), and preoperative antithrombotic use (OR 2.369) were associated with a need for early postoperative transfusion. Conclusion: Transfusion in the early postoperative period following renal transplantation was less than 10%, suggesting that routine crossmatch may not be necessary for all patients. Preoperative hemoglobin, female gender, and preoperative antithrombotic use were associated with increased risk and may be useful to risk-stratify patients who require crossmatch.

Objectives The effects of sleep disturbance and its treatment on the prognosis of patients with acute coronary syndrome (ACS) are not well understood. This study investigated the impact of sleep disturbance on long-term all-cause mortality, according to depression comorbidity and treatment, in patients with ACS. Methods A cross-sectional baseline study and a nested 24-week double-blind escitalopram–placebo controlled trial were carried out from May 2007 to March 2013; 5–12-year follow-up for all-cause mortality was conducted. A total of 1152 patients with ACS were stratified by baseline depression comorbidity and treatment allocation into four groups: no depression (N = 706), depression on escitalopram (N = 149), depression on placebo (N = 151), and depression on medical care as usual (CAU; N = 146). Sleep disturbance was evaluated by the Leeds Sleep Evaluation Questionnaire. During the 5–12-year follow-up, Kaplan–Meyer event rates for all-cause mortality were calculated; hazard ratios (HRs) using Cox regression models were estimated after adjustment for a range of covariates. Results Worse sleep states at baseline increased long-term all-cause mortality in all patients (HRs 1.08–1.59). The associations between worse sleep states and long-term all-cause mortality were significant in patients without depression and in patients with depression who received CAU, but not in patients with depression who participated in the 24-week trial. Conclusions Routine evaluations of sleep disturbance in ACS and further treatment allocation may contribute to reducing long-term mortality associated with the disease. Trial registration ClinicalTrials.gov Identifier for the 24 week drug trial, NCT00419471 .

Antipsychotic treatments are associated with safety concerns in people with dementia. The authors aimed to investigate whether risk of adverse outcomes related to antipsychotic prescribing differed according to major neuropsychiatric syndromes—specifically psychosis, agitation, or a combination. A cohort of 10,106 patients with a diagnosis of dementia was assembled from a large dementia care database in South East London. Neuropsychiatric symptoms closest to first dementia diagnosis were determined according to the Health of the Nation Outcome Scales’ mental and behavioural problem scores and the sample was divided into four groups: ‘agitation and psychosis’, ‘agitation, but no psychosis’, ‘psychosis, but no agitation’, and ‘neither psychosis nor agitation’. Antipsychotic prescription in a one-year window around first dementia diagnosis was ascertained as exposure variable through natural language processing from free text. Cox regression models were used to analyse associations of antipsychotic prescription with all-cause and stroke-specific mortality, emergency hospitalisation and hospitalised stroke adjusting for sixteen potential confounders including demographics, cognition, functioning, as well as physical and mental health. Only in the group ‘psychosis, but no agitation’ (n = 579), 30% of whom were prescribed an antipsychotic, a significant antipsychotic-associated increased risk of hospitalised stroke was present after adjustment (adjusted hazard ratio (HR) 2.16; 95% confidence interval (CI) 1.09–4.25). An increased antipsychotic-related all-cause (adjusted HR 1.14; 95% CI 1.04–1.24) and stroke-specific mortality risk (adjusted HR 1.28; 95% CI 1.01–1.63) was detected in the whole sample, but no interaction between the strata and antipsychotic-related mortality. In conclusion, the adverse effects of antipsychotics in dementia are complex. Stroke risk may be highest when used in patients presenting with psychosis without agitation, indicating the need for novel interventions for this group. Electronic supplementary material The online version of this article (10.1007/s10654-020-00643-2) contains supplementary material, which is available to authorized users.

Background hospitalisations are sentinel events for people with dementia. How patterns of unplanned hospital admissions change among people with dementia after diagnosis is relatively unknown. Objective to describe patterns of unplanned hospital admissions of people with dementia from diagnosis until death/study end. Methods retrospective cohort study using mental healthcare provider data of people diagnosed with dementia in London, UK (1995–2017), linked to mortality and hospital data. The primary outcome was the rate of unplanned hospital admissions after diagnosis until death/study end. We calculated the cumulative incidence of unplanned hospital admissions. The rates of unplanned hospital admissions and the percentage of time spent as an inpatient were stratified by time from first dementia diagnosis. Results for 19,221 people with dementia (61.4% female, mean age at diagnosis 81.0 years (standard deviation, SD 8.5)), the cumulative incidence of unplanned hospital admissions (n = 14,759) was 76.8% (95% CI 76.3%–77.3%). Individuals remained in the study for mean 3.0 (SD 2.6) years, and 12,667 (65.9%) died. Rates and lengths of unplanned hospital admissions remained relatively low and short in the months after the dementia diagnosis, increasing only as people approached the end of life. Percentage of time spent as an inpatient was Conclusions the steep rise in hospitalisations before death highlights the need for improved community care and services for people with dementia who are approaching the end of life.

Current criteria for depression are imprecise and do not accurately characterize its distinct clinical presentations. As a result, its diagnosis lacks clinical utility in both treatment and research settings. Data-driven efforts to refine criteria have typically focused on a limited set of symptoms that do not reflect the disorder’s heterogeneity. By contrast, clinicians often write about patients in depth, creating descriptions that may better characterize depression. However, clinical text is not commonly used to this end. Here we show that clinically relevant depressive subtypes can be derived from unstructured electronic health records. Five subtypes were identified amongst 18,314 patients with depression treated at a large mental healthcare provider by using unsupervised machine learning: severe-typical, psychotic, mild-typical, agitated, and anergic-apathetic. Subtypes were used to place patients in groups for validation; groups were found to be associated with future outcomes and characteristics that were consistent with the subtypes. These associations suggest that these categorizations are actionable due to their validity with respect to disease prognosis. Moreover, they were derived with automated techniques that might theoretically be widely implemented, allowing for future analyses in more varied populations and settings. Additional research, especially with respect to treatment response, may prove useful in further evaluation.

Increased prevalence of sleep disorders has been found in patients with functional dyspepsia; however, direction of causality remains unclear. Our aim was to compare the risk of incident functional dyspepsia between patients with and without sleep disturbance from a large population-based sample. Utilizing a nation-wide health insurance administrative dataset, we assembled an 11-year historic cohort study to compare subsequent incidence of diagnosed functional dyspepsia between adult patients with any diagnosis of sleep disturbance and age- and gender-matched controls. Hazard ratios adjusted for other relevant comorbidities and medications were calculated using Cox regression models. 45,310 patients with sleep disorder and 90,620 controls were compared. Patients with sleep apnea had a 3.3-fold (95% confidence interval: 2.82 ~ 3.89) increased hazard of functional dyspepsia compared with controls. This increased risk persisted regardless of previously diagnosed depression coexisted. Sleep disturbance was associated with an increased risk of subsequent functional dyspepsia. Potential mechanisms are discussed.

Purpose: To investigate whether a significant difference exists between the calcification of the common iliac arteries (CIAs) and the external iliac arteries (EIAs) and test for associations between clinical factors and the distribution of calcification. Methods: A retrospective review of renal transplant candidates who underwent a routine preoperative unenhanced computed tomography yielded 214 patients. Agatston scores for the patients’ left CIA, left EIA, right CIA, and right EIA were assigned. A retrospective search of patient records screened for 5 clinical factors (diabetes, hypertension, coronary artery disease [CAD], smoking, and dialysis). Data were assessed using a 2-sided t test, odds ratio, and a multivariate linear regression calculated through generalized estimating equation (GEE). Results: The log-transformed Agatston scores in the CIA were found to be significantly greater than that in the EIA ( t = 9.57, P < .0001), with a mean difference of 1.5078 (95% confidence interval: 1.1962-1.8194), indicating relative EIA sparing. There were no significant differences in calcification between the right and left sides. Generalized estimating equation found that CAD and smoking demonstrated independent positive associations with EIA sparing (GEE = 2.6464 [ P = .0197] and 1.9092 [ P = .0470], respectively). Age was also significantly associated and indicated that EIA sparing remained relatively constant throughout patients’ lives (GEE = 1.0711 [ P < .0001]). Conclusion: This study has demonstrated statistically significant EIA sparing in end-stage renal disease patients and identified CAD and smoking as associated factors. This phenomenon warrants further investigation into its biological mechanisms and the impact of EIA sparing on outcomes following transplants.

ObjectiveSuicide attempts requiring hospitalization are known to be common in patients who are diagnosed with eating disorders. Attempting suicide is a major indicator for those at risk of completed suicide. Both the specific eating disorder diagnosis and the influence of psychiatric comorbidities on suicide attempts requiring hospitalization were investigated, with demographic and socioeconomic variables as confounders, over a 10‐year observation period from January 2007 to March 2017.MethodsAnonymized health‐record data from the South London and Maudsley NHS Foundation Trust (SLaM) were retrieved through the Clinical Record Interactive Search (CRIS) data resource; this is linked to national Hospital Episode Statistics (HES) data. These data include all diagnoses for inpatient admissions. Hazard ratios, with 95% confidence intervals (CIs), were calculated from cox regression analyses and the effects of a number of confounders were estimated by performing multivariable analyses.ResultsIn total, 4,895 patients were diagnosed with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorder otherwise not specified (EDNOS). Of these, 331 (6.7%) had attempted suicide requiring hospitalization and 21 (0.04%) completed suicide. The eating disorder category associated with the highest risk of a suicide attempt was AN (HR: 1.43, 95%CI: 1.08–1.89, p = .01). The risk was significantly increased further if the patient had a comorbid diagnosis of personality disorder, depression, bipolar affective disorder, and substance misuse.DiscussionSuicide attempts requiring hospitalization have a high incidence rate among patients with eating disorders, and the risk is significantly increased in AN. Comorbid psychiatric illness and suicidal ideation should be carefully assessed in all eating disorder patients.

BackgroundTo investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS).MethodsProspective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5–12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M).ResultsCumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63–2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline.ConclusionsRoutine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.

Background Depression has been associated with worse cardiac outcomes in patients with acute coronary syndrome, while no study has investigated trajectory of depression and ACS prognosis. This study investigated associations of depressive disorder within 2 weeks (early) and at 1 year (late) after ACS with major adverse cardiac event (MACE). Method In 757 ACS patients recruited in 2007–2012 and evaluated for depressive disorder at the two time-points, 5–12 year follow-up for MACE was conducted. Results MACE incidence was significantly higher in patients with depressive disorder at early or late phase of ACS than those without, regardless of status at the other time point; however, highest incidence was found following depression at both time points. Limitation The follow-up for depressive disorder was made at only one point. Conclusion Depression evaluation thus needs consideration both early and late post-ACS.

BackgroundDepressive symptoms are associated with higher cancer mortality, whereas anxiety symptoms are associated with lower than expected risk.AimsThis study aimed to investigate the prospective association between depressive/anxiety symptoms and the extent of disease (EOD) of first cancer at diagnosis.MethodProspective population-based study conducted from the second wave of the Nord-Trøndelag Health (HUNT) study. Of 65 000 residents comprehensively interviewed and examined for health status, 407 received first lifetime cancer diagnoses 1–3 years later, ascertained from the Cancer Registry of Norway, and had EOD recorded. Patients with localised disease or regional/distant spread at cancer diagnosis were analysed for earlier depressive/anxiety symptoms ascertained by the Hospital Anxiety and Depression Scale in HUNT.ResultsBeyond-local EOD was present in 59.8% of those with neither anxiety nor depression, in 76.6% of those with depression alone (odds ratio, 2.20; 1.08–4.49), in 39.3% of those with anxiety alone (odds ratio, 0.44; 0.20–0.96) and in 57.7% of those with both anxiety and depression (odds ratio, 0.92; 0.41–2.06). After adjustment for demographic and health status, and cancer type, these associations were marginally stronger, but no longer statistically significant (odds ratios, 2.26; 0.84–6.11; 0.43; 0.15–1.26; and 1.00; 0.98–1.03, respectively).ConclusionsIn people who develop cancer, beyond-local EOD at diagnosis was more common in people with previous depression and less common in people with previous anxiety; however, independence from confounding factors could not be concluded.

Background transitions between care settings near the end-of-life for people with dementia can be distressing, lead to physical and cognitive deterioration, and may be avoidable. Objective to investigate determinants of end-of-life hospital transitions, and association with healthcare use, among people with dementia. Design retrospective cohort study. Setting electronic records from a mental health provider in London, linked to national mortality and hospital data. Subjects people with dementia who died in 2007–2016. Methods end-of-life hospital transitions were defined as: multiple admissions in the last 90 days (early), or any admission in the last three days of life (late). Determinants were assessed using logistic regression. Results of 8,880 people, 1,421 (16.0%) had at least one end-of-life transition: 505 (5.7%) had early, 788 (8.9%) late, and 128 (1.5%) both types. Early transitions were associated with male gender (OR 1.33, 95% CI 1.11–1.59), age (>90 vs Conclusions in contrast to late transitions, early transitions are associated with higher healthcare use and characteristics that are predictable, indicating potential for prevention.

Background: There is inconsistent evidence about the association between inflammatory disorders with depression and anxiety onset in a primary care context. The study aimed evaluate the risk of depression and anxiety within multisystem and organ-specific inflammatory disorders. Methods: Prospective cohort study with primary care patients from the UK Clinical Practice Research Datalink diagnosed with an inflammatory disorder between 1st of January 2001 and 31st of 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. Findings: 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 to their comparison group (5 to 7 per 1000 person-years). Hazard ratios (HR) of multiple depression and anxiety events were 16% higher within inflammatory disorders (HR, 1·16, 95%CI 1·12-1·21, p

Background Robust quality indicators (QIs) are essential for monitoring and improving the quality of care and learning from good practice. We aimed to identify and assess QIs for the care of older people and people with dementia who are nearing the end of life and recommend QIs for use with routinely collected electronic data across care settings. Methods A systematic review was conducted, including five databases and reference chaining. Studies describing the development of QIs for care of older people and those with dementia nearing the end of life were included. QIs were categorized as relating to processes or outcomes, and mapped against six care domains. The psychometric properties (acceptability, evidence base, definition, feasibility, reliability, and validity) of each QI were assessed; QIs were categorized as robust, moderate, or poor. Results From 12,980 titles and abstracts screened, 37 papers and 976 QIs were included. Process and outcome QIs accounted for 780 (79.7%) and 196 (20.3%) of all QIs, respectively. Many of the QIs concerned physical aspects of care (n = 492, 50.4%), and very few concerned spiritual and cultural aspects of care (n = 19, 1.9%). Three hundred and fifteen (32.3%) QIs were robust and of those 220 were measurable using routinely collected electronic data. The final shortlist of 71 QIs came from seven studies. Conclusions Of the numerous QIs developed for care of older adults and those with dementia nearing the end of life, most had poor or moderate psychometric properties or were not designed for use with routinely collected electronic datasets. Infrastructure for data availability, combined with use of robust QIs, is important for enhancing understanding of care provided to this population, identifying unmet needs, and improving service provision.

Despite the recognized antidepressant role of serotonin (5-hydroxytryptamine [5-HT]) signaling pathways in the central nervous system, the association between baseline peripheral 5-HT level and the antidepressant treatment response in clinical studies remains debatable. We investigated the interaction effects of baseline serum 5-HT level and age on the 12-week remission in outpatients with depressive disorders who received stepwise antidepressant treatment. Baseline serum serotonin levels were measured and the age of 1094 patients recorded. The patients received initial antidepressant monotherapy; then, patients with an insufficient response or who experienced uncomfortable side effects received alternative treatments every 3 weeks (3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. Individual and interaction effects of serum 5-HT level (as a binary [low vs. high, based on the median value of 72.6 ng/mL] or continuous variable) and age (as a binary [vs. ≥ 60 years] or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. High 5-HT (≥ 72.6 ng/mL) and age ≥ 60 years were associated with the highest 12-week remission rates and a significant multiplicative interaction effect. The interaction effect of the two variables on the 12-week remission rate was significant even when analyzed as a continuous variable. Our study suggests that the association between baseline serum 5-HT level and 12-week antidepressant treatment outcomes differs according to patient age.

In people with mental disorders, adverse general health is well recognized but dental diseases remain underinvestigated. The objective of this study was to investigate risk factors for hospital admissions for dental disorders in patients with severe mental illness (SMI) and/or depressive disorder. De‐identified electronic mental health records from the South London and Maudsley NHS Foundation Trust (SLaM) were linked to national Hospital Episode Statistics (HES) data for analysis. Data were extracted for adults with a diagnosis of SMI (schizophrenia, schizoaffective disorder, bipolar disorder) and/or depression, who had received care at SLaM between 1 January 2010 and 31 March 2017. In the cohort of 18,999 patients thus obtained, the following factors were independently associated with hospital admission for dental disorders: female gender [odds ratio (OR) = 1.48, 95% CI: 1.31–1.68)], Health of the Nation Outcome Scales (HoNOS) problem drinking/drug taking (OR = 1.12, 95% CI: 1.05–1.19), HoNOS physical illness/disability (OR = 1.18, 95% CI: 1.12–.25), diabetes (OR = 1.24, 95% CI: 1.06–1.43), recorded current/past smoking (OR = 1.35, 95% CI: 1.06–1.43), treatment with antidepressant medication (OR = 1.48, 95% CI: 1.31–1.68), and depressive disorder (OR = 1.36, 95% CI: 1.11–1.68). Building on previous research in this population, which indicated a relatively high risk of acute care hospitalizations with dental disorders as discharge diagnoses, a number of demographic and clinical characteristics were found to be independent predictors over a 7‐yr period. Further research into these predictors would facilitate a better understanding of how adverse dental outcomes might be prevented.

Background Symptoms may be more useful prognostic markers for mental illness than diagnoses. We sought to investigate symptom domains in women with pre-existing severe mental illness (SMI; psychotic and bipolar disorder) as predictors of relapse risk during the perinatal period. Methods Data were obtained from electronic health records of 399 pregnant women with SMI diagnoses from a large south London mental healthcare provider. Symptoms within six domains characteristically associated with SMI (positive, negative, disorganization, mania, depression, and catatonia) recorded in clinical notes 2 years before pregnancy were identified with natural language processing algorithms to extract data from text, and associations investigated with hospitalization during pregnancy and 3 months postpartum. Results Seventy-six women (19%) relapsed during pregnancy and 107 (27%) relapsed postpartum. After adjusting for covariates, disorganization symptoms showed a positive association at borderline significance with relapse during pregnancy (adjusted odds ratio [aOR] = 1.36; 95% confidence interval [CI] = 0.99–1.87 per unit increase in number of symptoms) and depressive symptoms negatively with relapse postpartum (0.78; 0.62–0.98). Restricting the sample to women with at least one recorded symptom in any given domain, higher disorganization (1.84; 1.22–2.76), positive (1.50; 1.07–2.11), and manic (1.48; 1.03–2.11) symptoms were associated with relapse during pregnancy, and disorganization (1.54; 1.08–2.20) symptom domains were associated with relapse postpartum. Conclusions Positive, disorganization, and manic symptoms recorded in the 2 years before pregnancy were associated with increased risk of relapse during pregnancy and postpartum. The characterization of routine health records from text fields is relatively transferrable and could help inform predictive risk modelling.

Background Patients with functional dyspepsia (FD) are more likely to have persistent depression, yet whether depression and antidepressant treatments are associated with subsequent risk of FD remain unclear. Methods Using population-based insurance administrative data of Taiwan, an 11-year historic cohort study was assembled, comparing cases aged 18 and above with the diagnosis of depressive disorder, to a propensity score-matched sample of adults without depression. Incident FD as a primary diagnosis was ascertained. Hazard ratios of FD were calculated using Cox regression models by age, gender, other comorbidities, nonsteroidal anti-inflammatory medications, antidepressants and antidiabetic agents. Results A total of 20,197 people with depressive disorder and 20,197 propensity score-matched comparisons without depression were followed up. The incidence of FD was 1.7-fold greater in the depressive cohort than in comparisons (12.9 versus 7.57 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.16 (95% confidence interval (CI) 1.93~2.41). Increased risks were significant regardless of comorbidities or medication uses, the highest in the untreated depression group compared to the group without depression, with an aHR of 2.51(95% CI 2.15~2.93). Conclusions This population-based study showed that patients with depressive disorder are at elevated risk of FD. Antidepressant treatment could reduce the risk of FD.

Objectives(1) To explore the role of ethnicity in receiving cognitive–behavioural therapy (CBT) for people with psychosis or bipolar disorder while adjusting for differences in risk profiles and symptom severity. (2) To assess whether context of treatment (inpatient vs community) impacts on the relationship between ethnicity and access to CBT.DesignCohort study of case register data from one catchment area (January 2007–July 2017).SettingA large secondary care provider serving an ethnically diverse population in London.ParticipantsData extracted for 30 497 records of people who had diagnoses of bipolar disorder (International Classification of Diseases (ICD) code F30-1) or psychosis (F20–F29 excluding F21). Exclusion criteria were: Outcome assessmentsORs for receipt of CBT (single session or full course) as determined via multivariable logistic regression analyses.ResultsIn models adjusted for risk and severity variables, in comparison with White British people; Black African people were less likely to receive a single session of CBT (OR 0.73, 95% CI 0.66 to 0.82, pConclusionsThis study highlights disparity in receipt of CBT from a large provider of secondary care in London for Black African and Caribbean people and that the context of therapy (inpatient vs community settings) has a relationship with disparity in access to treatment.

Hospitalisation of people with dementia is associated with adverse outcomes and high costs. We aimed to examine general, i.e. non-psychiatric, hospitalisation rates, changes since 2008 and factors associated with admission. We also aimed to compare admission rates of people with dementia with age-matched people without dementia. We conducted a cohort study of adults ≥ 65 years, with dementia diagnosed during the 2008–2016 study window, derived from a large secondary mental healthcare database in South London, UK. We used national general hospital records to identify emergency and elective hospitalisations. We calculated the cumulative incidence and rate of hospitalisation and examined predictors of hospitalisation using negative binomial regression, with multiple imputation for missing covariate data. We calculated age-standardised admission ratio for people with dementia compared to those without. Of 10,137 people, 50.6% were admitted to hospital in the year following dementia diagnosis and 75.9% were admitted during median 2.5 years follow-up. Annual admission rate was 1.26/person-year of which 0.90/person-year were in emergency. Emergency hospitalisation rate increased throughout the study period. Compared to controls without diagnosed dementia in the catchment area, the age-standardised emergency admission ratio for people with dementia was 2.06 (95% CI 1.95, 2.18). Male, older, white and socio-economically deprived people and those with clinically significant comorbid physical illness, depressed mood, activity of daily living or living condition problems had more hospitalisations. Emergency hospitalisations of people with dementia are higher than those without, and increasing. Many factors associated with admission are social and psychological, and may be targets for future interventions that aim to reduce avoidable admissions. Electronic supplementary material The online version of this article (10.1007/s10654-019-00481-x) contains supplementary material, which is available to authorized users.

ObjectivesTo evaluate the risk and common causes of hospitalisation in patients with newly diagnosed dementia and variation by severity of cognitive impairment.SettingWe used data from a large London mental healthcare case register linked to a national hospitalisation database.ParticipantsIndividuals aged ≥65 years with newly diagnosed dementia with recorded cognitive function and the catchment population within the same geography.Outcome measuresWe evaluated the risk and duration of hospitalisation in the year following a dementia diagnosis. In addition we identified the most common causes of hospitalisation and calculated age-standardised and gender-standardised admission ratios by dementia severity (mild/moderate/severe) relative to the catchment population.ResultsOf the 5218 patients with dementia, 2596 (49.8%) were hospitalised in the year following diagnosis. The proportion of individuals with mild, moderate and severe dementia who had a hospital admission was 47.9%, 50.8% and 51.7%, respectively (p= 0.097). Duration of hospital stay increased with dementia severity (median 2 days in mild to 4 days in severe dementia, p 0.0001). After excluding readmissions for the same cause, the most common primary hospitalisation discharge diagnoses among patients with dementia were urinary system disorders, pneumonia and fracture of femur, accounting for 15%, 10% and 6% of admissions, respectively. Overall, patients with dementia were hospitalised 30% more than the catchment population, and this trend was observed for most of the discharge diagnoses evaluated. Standardised admission ratios for urinary and respiratory disorders were higher in those with more severe dementia at diagnosis.ConclusionsIndividuals with a dementia diagnosis were more likely to be hospitalised than individuals in the catchment population. The length of hospital stay increased with dementia severity. Most of the common causes of hospitalisation were more common than expected relative to the catchment population, but standardised admission ratios only varied by dementia stage for certain groups of conditions.

High levels of methylation in the GR gene (nuclear receptor subfamily 3, group C, member 1; NR3C1) have been associated with depression and cardiovascular risk. This study aimed to investigate whether NR3C1 methylation status was associated with the long-term prognosis of acute coronary syndrome (ACS) considering depression and cardiovascular status at the early phase of ACS. A total of 969 patients with recent ACS were recruited at a tertiary university hospital in Korea. Baseline evaluations were made from 2007 to 2012, including DSM-IV depressive disorder, NR3C1 methylation, and various demographic and clinical characteristics such as cardiovascular risk markers. Over a 5~12 year follow-up after the index ACS, time to major adverse cardiac event (MACE) was investigated using Cox regression models. Higher NR3C1 methylation status was associated with depression and several cardiovascular risk markers at baseline. NR3C1 hypermethylation predicted worse long-term prognosis of ACS only in the presence of depressive disorder with significant synergistic interaction terms and independent of potential confounding factors. Synergistic effects of depressive disorder and NR3C1 hypermethylation on long-term cardiac outcomes in ACS were found. NR3C1 methylation status represents a candidate prognostic biomarker for ACS in combination with a diagnosis of depressive disorder. Further research is needed to ascertain the generalisability of these findings.

Background The higher mortality rates in people with severe mental illness (SMI) may be partly due to inadequate integration of physical and mental healthcare. Accurate recording of SMI during hospital admissions has the potential to facilitate integrated care including tailoring of treatment to account for comorbidities. We therefore aimed to investigate the sensitivity of SMI recording within general hospitals, changes in diagnostic accuracy over time, and factors associated with accurate recording. Methods and findings We undertook a cohort study of 13,786 adults with SMI diagnosed during 2006–2017, using data from a large secondary mental healthcare database as reference standard, linked to English national records for 45,706 emergency hospital admissions. We examined general hospital record sensitivity across patients’ subsequent hospital records, for each subsequent emergency admission, and at different levels of diagnostic precision. We analyzed time trends during the study period and used logistic regression to examine sociodemographic and clinical factors associated with psychiatric recording accuracy, with multiple imputation for missing data. Sensitivity for recording of SMI as any mental health diagnosis was 76.7% (95% CI 76.0–77.4). Category-level sensitivity (e.g., proportion of individuals with schizophrenia spectrum disorders (F20-29) who received any F20-29 diagnosis in hospital records) was 56.4% (95% CI 55.4–57.4) for schizophrenia spectrum disorder and 49.7% (95% CI 48.1–51.3) for bipolar affective disorder. Sensitivity for SMI recording in emergency admissions increased from 47.8% (95% CI 43.1–52.5) in 2006 to 75.4% (95% CI 68.3–81.4) in 2017 (ptrend < 0.001). Minority ethnicity, being married, and having better mental and physical health were associated with less accurate diagnostic recording. The main limitation of our study is the potential for misclassification of diagnosis in the reference-standard mental healthcare data. Conclusions Our findings suggest that there have been improvements in recording of SMI diagnoses, but concerning under-recording, especially in minority ethnic groups, persists. Training in culturally sensitive diagnosis, expansion of liaison psychiatry input in general hospitals, and improved data sharing between physical and mental health services may be required to reduce inequalities in diagnostic practice., In a cohort study using linked registry data, Hassan Mansour and colleagues examine the factors related to and temporal trends in the accurate recording of severe mental illness diagnoses among individuals admitted to hospitals in England between 2006 and 2017., Author summary Why was this study done? People with severe mental illness (SMI) have increased mortality and morbidity, largely due to preventable medical conditions, and these disparities have the potential to be ameliorated through better healthcare integration. Accurate recognition of SMI during hospital admissions can be critical as it allows continuity of previous pharmacological and supportive treatments and tailoring of inpatient and discharge care to individual needs. What did the researchers do and find? We examined the hospital discharge records of 13,786 individuals with SMI diagnosis from a mental health service, who had 45,706 admissions to English general hospitals between 2006 and 2017. We found that a psychiatric condition is recorded in around two-thirds of general hospital admissions of people with SMI. Recording of SMI diagnosis increased between 2006 and 2017. However, people from ethnic minority and married backgrounds were less likely to have psychiatric diagnosis recorded. Similarly, those with less severe mental or physical health symptoms were also less likely to have diagnosis recorded. What do these findings mean? Despite improvements over the past decade, inequities related to ethnicity remain. Policy-makers and clinicians should endeavor to improve recognition and recording of SMI in general hospital settings to promote integrated physical and mental healthcare. A limitation of our study is that our use of electronic health records for the reference-standard means that some people with SMI may have been misclassified.

ObjectivesTo examine whether depressive symptoms predict receipt of cognitive–behavioural therapy for psychosis (CBTp) in individuals with psychosis.DesignRetrospective cross-sectional analysis of electronic health records (EHRs) of a clinical cohort.SettingA secondary National Health Service mental healthcare service serving four boroughs of south London, UK.Participants20 078 patients diagnosed with an International Classification of Diseases, version 10 (ICD-10) code between F20 and 29 extracted from an EHR database.Primary and secondary outcome measuresPrimary: Whether recorded depressive symptoms predicted CBTp session receipt, defined as at least one session of CBTp identified from structured EHR fields supplemented by a natural language processing algorithm. Secondary: Whether age, gender, ethnicity, symptom profiles (positive, negative, manic and disorganisation symptoms), a comorbid diagnosis of depression, anxiety or bipolar disorder, general CBT receipt prior to the primary psychosis diagnosis date or type of psychosis diagnosis predicted CBTp receipt.ResultsOf patients with a psychotic disorder, only 8.2% received CBTp. Individuals with at least one depressive symptom recorded, depression symptom severity and 12 out of 15 of the individual depressive symptoms independently predicted CBTp receipt. Female gender, White ethnicity and presence of a comorbid affective disorder or primary schizoaffective diagnosis were independently positively associated with CBTp receipt within the whole sample and the top 25% of mentioned depressive symptoms.ConclusionsIndividuals with a psychotic disorder who had recorded depressive symptoms were significantly more likely to receive CBTp sessions, aligning with CBTp guidelines of managing depressive symptoms related to a psychotic experience. However, overall receipt of CBTp is low and more common in certain demographic groups, and needs to be increased.

ObjectivesTo investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders.DesignCohort study.SettingThe South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register.ParticipantsA large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30–F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register.Primary and secondary outcome measuresFalls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures.ResultsOf 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures.ConclusionsOver a mean 5 years’ follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group.

Background: Computer-modelling approaches have the potential to predict the interactions between different antipsychotics and provide guidance for polypharmacy. Aims: To evaluate the accuracy of the quantitative systems pharmacology platform to predict parkinsonism side-effects in patients prescribed antipsychotic polypharmacy. Methods: Using anonymized data from South London and Maudsley NHS Foundation Trust electronic health records we applied quantitative systems pharmacology, a neurophysiology-based computer model of humanized neuronal circuits, to predict the risk for parkinsonism symptoms in patients with schizophrenia prescribed two concomitant antipsychotics. The performance of the quantitative systems pharmacology model was compared with the performance of simple parameters such as: combination of affinity constants (1/Ksum); sum of D2R occupancies (D2R) and chlorpromazine equivalent dose. Results: We identified 832 patients with schizophrenia who were receiving two antipsychotics for six or more months, between 1 January 2007 and 31 December 2014. The area under the receiver operating characteristic (AUROC) curve for the quantitative systems pharmacology model was 0.66 (p = 0.01), while AUROCs for D2R, 1/Ksum and chlorpromazine equivalent dose were 0.52 (p = 0.350), 0.53 (p = 0.347) and 0.52 (p = 0.330) respectively. Conclusion: Our results indicate that quantitative systems pharmacology has the potential to predict the risk of parkinsonism associated with antipsychotic polypharmacy from minimal source information, and thus might have potential decision-support applicability in clinical settings.

Purpose The predictive value of suicide risk assessment in secondary mental healthcare remains unclear. This study aimed to investigate the extent to which clinical risk assessment ratings can predict suicide among people receiving secondary mental healthcare. Methods Retrospective inception cohort study (n = 13,758) from the South London and Maudsley NHS Foundation Trust (SLaM) (London, UK) linked with national mortality data (n = 81 suicides). Cox regression models assessed survival from the last suicide risk assessment and ROC curves evaluated the performance of risk assessment total scores. Results Hopelessness (RR = 2.24, 95% CI 1.05–4.80, p = 0.037) and having a significant loss (RR = 1.91, 95% CI 1.03–3.55, p = 0.041) were significantly associated with suicide in the multivariable Cox regression models. However, screening statistics for the best cut-off point (4–5) of the risk assessment total score were: sensitivity 0.65 (95% CI 0.54–0.76), specificity 0.62 (95% CI 0.62–0.63), positive predictive value 0.01 (95% CI 0.01–0.01) and negative predictive value 0.99 (95% CI 0.99–1.00). Conclusions Although suicide was linked with hopelessness and having a significant loss, risk assessment performed poorly to predict such an uncommon outcome in a large case register of patients receiving secondary mental healthcare. Electronic supplementary material The online version of this article (10.1007/s00127-018-1536-8) contains supplementary material, which is available to authorized users.

ObjectivesTo investigate the association between long‐term antipsychotic polypharmacy use and mortality; and determine whether this risk varies by cause of death and antipsychotic dose.MethodsUsing data from a large anonymised mental healthcare database, we identified all adult patients with serious mental illness (SMI) who had been prescribed a single antipsychotic or polypharmacy, for six or more months between 2007 and 2014. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical factors and smoking, to examine the association between APP use and the risk of death.ResultsWe identified 10 945 adults with SMI who had been prescribed long‐term antipsychotic monotherapy (76.9%) or APP (23.1%). Patients on long‐term APP had a small elevated risk of mortality, which was significant in some but not all models. The adjusted hazard ratios for death from natural and unnatural causes associated with APP were 1.2 (0.9–1.4, P = 0.111) and 1.1 (0.7–1.9, P = 0.619) respectively. The strengths of the associations between APP and mortality outcomes were similar after further adjusting for % BNF antipsychotic dose (P = 0.031) or olanzapine equivalence (P = 0.088).ConclusionThe findings suggest that the effect of long‐term APP on mortality is not clear‐cut, with limited evidence to indicate an association, even after controlling for the effect of dose.

Longitudinal associations of cytokine levels with depression are unclear. This study aimed to investigate cross-sectional and prospective associations between five serum pro-inflammatory cytokine levels and late-life depression. 732 Korean people aged 65+ were evaluated at baseline. Of 631 without depression (Geriatric Mental State schedule) at baseline, 521 (83%) were followed over a 2 year period and incident depression was ascertained. Serum tumor necrosis factor-α, interleukin (IL)-1α, IL-1β, IL-6, and IL-8 levels were assayed at both baseline and follow-up. Associations between cytokine levels and depressive status were evaluated using linear regression models, considering potential covariates (demographics, cognitive function, disability, lifestyle factors, and vascular risk factors) and applying Bonferroni corrections. Prevalent depression at baseline was significantly associated with higher contemporaneous levels of IL-1β and IL-8, independent of relevant covariates and after applying Bonferroni corrections. In the analyses of the five cytokine levels in combination, independent associations were found between prevalent depression and increased numbers of cytokines at higher levels at baseline. Incident depression was significantly associated with increases in IL-1β, IL-6, and IL-8 levels during the follow-up independent of relevant covariates and after applying Bonferroni corrections. In combination analyses, incident depression was independently associated with higher numbers of cytokines showing increasing levels over the same follow-up period. However, incident depression was not predicted by higher baseline pro-inflammatory cytokine levels in any analysis. Our findings suggest that depression might affect serum cytokines alterations and lead to inflammatory processes in late-life.

BackgroundSerious mental illness (SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder) is associated with worse general health. However, admissions to general hospitals have received little investigation. We sought to delineate frequencies of and causes for non-psychiatric hospital admissions in SMI and compare with the general population in the same area.MethodsRecords of 18 380 individuals with SMI aged ⩾20 years in southeast London were linked to hospitalisation data. Age- and gender-standardised admission ratios (SARs) were calculated by primary discharge diagnoses in the 10th edition of the World Health Organization International Classification of Diseases (ICD-10) codes, referencing geographic catchment data.ResultsCommonest discharge diagnosis categories in the SMI cohort were urinary conditions, digestive conditions, unclassified symptoms, neoplasms, and respiratory conditions. SARs were raised for most major categories, except neoplasms for a significantly lower risk. Hospitalisation risks were specifically higher for poisoning and external causes, injury, endocrine/metabolic conditions, haematological, neurological, dermatological, infectious and non-specific (‘Z-code’) causes. The five commonest specific ICD-10 diagnoses at discharge were ‘chronic renal failure’ (N18), a non-specific code (Z04), ‘dental caries’ (K02), ‘other disorders of the urinary system’ (N39), and ‘pain in throat and chest’ (R07), all of which were higher than expected (SARs ranging 1.57–6.66).ConclusionA range of reasons for non-psychiatric hospitalisation in SMI is apparent, with self-harm, self-neglect and/or reduced healthcare access, and medically unexplained symptoms as potential underlying explanations.

Purpose Recalled experiences of parental bonding may be important in the aetiology of perinatal depression. We hypothesized that lower recalled parental bonding would be associated with perinatal depression. Method In a cohort study of perinatal depression in Turkey, 677 women were recruited in their third trimester. Parental Bonding Inventory (PBI) scores at baseline were investigated as predictors of depression on the Edinburgh Postnatal Depression Scale (EPDS) at 4, 14 and 21 months after childbirth in mothers without depression at baseline. Results Poor parental bonding scores, apart from paternal control and overprotection, were independently associated with antenatal depression. Incident postnatal depression at 4 months was predicted by parental overprotection, at 14 months by parental care and overprotection, and at 21 months by paternal control and overprotection. Conclusions Less satisfactory parenting recalled in the antenatal period was an independent predictor of postnatal depression; however, the different bonding subscales varied as predictors according to the timing of the depression assessment after childbirth.

Objectives The aim of this study was to determine if there was an association between being discharged on antipsychotic polypharmacy (APP) and risk of readmission into secondary mental health care. Methods Using data from the South London and Maudsley (SLAM) case register, service users with serious mental illness (SMI), discharged between 1st January 2007 and 31th December 2014, were followed up for 6 months. Patients were classified as receiving either monotherapy or polypharmacy at index discharge. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical and service use factors. Results We identified 5523 adults who had been admitted at least once to SLAM, of whom 1355 (24.5%) were readmitted into secondary mental health care. In total, 15% (n = 826) of patients were discharged on APP and 85% (n = 4697) on monotherapy. Of these, 30.9% (n = 255) and 23.4% (n = 1100) were readmitted respectively. Being discharged on APP was associated with a significantly increased risk of readmission, in comparison to patients discharged on monotherapy (HR = 1.4, 1.2–1.7, p

Introduction: A fall in hospital deaths in dementia has been interpreted as indicating an improvement in end-of-life care. Whether other indicators of quality of end-of-life care, such as emergency department (ED) attendance, show a similar trend is unclear. Methods: Retrospective cohort study using electronic medical records from a large mental health care provider, linked to national mortality and hospital use data (2008–2013). Results: Of 4867 patients, 78.6% (3824) had at least one ED attendance during their last year of life (mean 2.13, standard deviation 2.34, range 0–54). ED attendance increased over the time period (incidence rate ratio 1.62, 95% confidence interval 1.46–1.80 for 2012–2013 compared with 2008–2009). Discussion: ED attendance in the last year of life for people with dementia is common and is increasing. Policy makers must pay attention to a broader range of indicators of poor end-of-life care alongside the place of death.

Importance Previous research has linked a history of depression with arterial stiffness (AS) during midlife. Objective To assess the association of depression with elevated midlife AS and to investigate the extent to which this association is mediated via metabolic syndrome (MetS). Design, Settings, and Participants This population-based retrospective cohort study analyzed data collected between March 2006 and December 2010 from 124 445 participants aged 40 to 69 years from the UK Biobank. Participants without data on AS at baseline (n = 332 780) or who reported a previous diagnosis of cardiovascular disease (n = 45 374) were not eligible. Data analysis was performed from May to August 2019. Exposures Lifetime history of depression was assessed via verbal interview and linked hospital-based clinical depression diagnosis. Metabolic syndrome was defined as the presence of 3 or more of hypertension, dyslipidemia, hyperglycemia, hypertriglyceridemia, and unhealthy waist circumference. Main Outcomes and Measures Peripherally assessed AS index (ASI) using digital photoplethysmography. Results Of 124 445 included participants with ASI assessed, 71 799 (57.7%) were women, and the mean (SD) age was 56 (8) years. A total of 10 304 participants (8.3%) reported a history of depression. Study findings indicated a significant direct association between depression and ASI levels (β = 0.25; 95% CI, 0.17-0.32). A significant indirect association was also observed between depression and ASI levels (β = 0.10; 95% CI, 0.07-0.13), indicating that 29% of the association of depression with ASI was mediated by MetS. The proportion of mediation increased to 37% when C-reactive protein was added to the MetS criteria (direct association: β = 0.21; 95% CI, 0.15-0.28; indirect association: β = 0.13; 95% CI, 0.10-0.17). Concerning components of MetS, the strongest indirect association was for waist circumference, accounting for 25% of the association between depression and ASI levels (direct association: β = 0.26; 95% CI, 0.18-0.34; indirect association: β = 0.09; 95% CI, 0.06-0.11). Among men, hypertriglyceridemia accounted for 19% of the association between depression and ASI (direct association: β = 0.22; 95% CI, 0.05-0.40; indirect association: β = 0.05; 95% CI, 0.02-0.08). Conclusions and Relevance One-third of the association of depression with elevated ASI levels during midlife may be accounted for by combined MetS and inflammatory processes. Unhealthy waist circumference and hypertriglyceridemia emerged as the most important potential targets for preventive interventions within women and men, respectively.

Objective Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. Material and methods We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). Results Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. Conclusion A better understanding of how drugs work in the real world can complement clinical trials.

ObjectivesTo identify predictors of recurrent cerebrovascular morbidity in a cohort of patients with depression and a cerebrovascular disease (CBVD) history.MethodsWe used the Maudsley Biomedical Research Centre Case Register to identify patients aged 50 years or older with a diagnosis of depressive disorder between 2008 and 2017 and a previous history of hospitalised CBVD. Using depression diagnosis as the index date we followed patients until first hospitalised CBVD recurrence or death due to CBVD. Sociodemographic data, symptom and functioning scores of Health of the Nation Outcome Scales, medications and comorbidities were extracted and modelled in multivariate survival analyses to identify predictors of CBVD reoccurrence.ResultsOf 1292 patients with depression and CBVD (mean age 75.6 years; 56.6% female), 264 (20.4%) experienced fatal/non-fatal CBVD recurrence during a median follow-up duration of 1.66 years. In multivariate Cox regression models, a higher risk of CBVD recurrence was predicted by older age (HR, 1.02; 95% CI, 1.01 to 1.04) (p=0.002), physical health problems (moderate to severe HR, 2.47; 95% CI, 1.45 to 4.19) (p=0.001), anticoagulant (HR, 1.40; 95% CI, 1.01 to 1.93) (p=0.041) and antipsychotic medication (HR, 0.66; 95% CI 0.44 to 0.99) (p=0.047). Neither depression severity, mental health symptoms, functional status, nor antidepressant prescribing were significantly associated with CBVD recurrence.ConclusionsApproximately one in five patients with depression and CBVD experienced a CBVD recurrence over a median follow-up time of 20 months. Risk of CBVD recurrence was largely dependent on age and physical health rather than on severity of depressive symptoms, co-morbid mental health or functional problems, or psychotropic prescribing.

BACKGROUND: To estimate the potential gain in life expectancy from addressing modifiable risk factors for all-cause mortality (excluding suicide and deaths from accidents or violence) across specific serious mental illness (SMI) subgroups, namely schizophrenia, schizoaffective disorders, and bipolar disorders in a Western population.METHODS: We have used relative risks from recent meta-analyses to estimate the population attribution fraction (PAF) due to specific modifiable risk factors known to be associated with all-cause mortality within SMI. The potential gain in life expectancy at birth, age 50 and age 65 years were assessed by estimating the combined effect of modifiable risk factors from different contextual levels (behavioural, healthcare, social) and accounting for the effectiveness of existing interventions tackling these factors. Projections for annual gain in life expectancy at birth during a two-decade was estimated using the Annual Percentage Change (APC) formula. The predicted estimates were based on mortality rates for year 2014-2015.RESULTS: Based on the effectiveness of existing interventions targeting these modifiable risk factors, we estimated potential gain in life expectancy at birth of four (bipolar disorders), six (schizoaffective disorders), or seven years (schizophrenia). The gain in life expectancy at age 50 years was three (bipolar disorders) or five (schizophrenia and schizoaffective disorders) years. The projected gain in life expectancy at age 65 years was three (bipolar disorders) or four (schizophrenia and schizoaffective disorders) years.CONCLUSIONS: The implementation of existing interventions targeting modifiable risk factors could narrow the current mortality gap between the general and the SMI populations by 24% (men) to 28% (women). These projections represent ideal circumstances and without the limitation of overestimation which often comes with PAFs.

Objective: The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations. Design: Case-control study. Setting: Six European electronic health records databases. Participants: 291 780 cases at the date of first-recorded dementia diagnosis, compared with 29 170 549 controls randomly selected from the same databases, age matched and sex matched at this index date. Exposure: The following measures were extracted whenever recorded within each dataset: BMI (kg/m2), SBP and DBP (mm Hg) and serum total cholesterol (mmol/L). Levels for each of these variables were defined within six 2-year time intervals over the 12 years prior to the index date. Main outcomes: Case-control differences in exposures of interest were modelled for each time period and adjusted for demographic and clinical factors (ischaemic/unspecified stroke, type 2 diabetes mellitus, acute myocardial infarction, hypertension diagnosis, antihypertensive medication, cholesterol-lowering medication). Coefficients and interactions with time period were meta-analysed across the six databases. Results: Mean BMI (coefficient -1.16 kg/m2; 95% CI -1.38 to 0.93) and SBP (-2.83 mm Hg; 95% CI -4.49 to -1.16) were lower in cases at diagnosis, and case-control differences were greater in more recent time periods, as indicated by significant case-x-time interaction and case-x-time-squared interaction terms. Time variations in coefficients for cholesterol levels were less consistent between databases and those for DBP were largely not significant. Conclusion: Routine clinical data show emerging divergence in levels of BMI and SBP prior to the diagnosis of dementia but less evidence for DBP or total cholesterol levels. These divergences should receive at least some consideration in routine dementia risk screening, although underlying mechanisms still require further investigation. The research leading to these results has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. RS and GP are part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London.

BackgroundThe prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.MethodsA total of 611 patients with recent ACS were recruited at a university hospital in Korea. Baseline evaluations from 2007 to 2012 assessed BDNF val66met polymorphism and personality using the Big Five Inventory, which yielded two personality clusters (resilient and vulnerable) and five dimensions (extraversion, agreeableness, conscientiousness, neuroticism, and openness). Over a 5~12 year follow-up after the index ACS, times to MACE were investigated using Cox regression models after adjustment for a range of covariates.ResultsThe BDNF val66met polymorphism modified the associations between vulnerable personality type and worse long-term cardiac outcomes in ACS patients with significant interaction terms, in that the associations were statistically significant in the presence met allele. Similar findings were observed for the individual personality dimensions of agreeableness and neuroticism.ConclusionsGene (BDNF val66met polymorphism) x environment (personality traits) interactions on long-term cardiac outcomes were found in ACS.

Background Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. Methods A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. Results Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52–0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17–0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57–1.37). Conclusions Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.

Obsessive and Compulsive Symptoms (OCS) or Obsessive Compulsive Disorder (OCD) in the context of schizophrenia or related disorders are of clinical importance as these are associated with a range of adverse outcomes. Natural Language Processing (NLP) applied to Electronic Health Records (EHRs) presents an opportunity to create large datasets to facilitate research in this area. This is a challenging endeavour however, because of the wide range of ways in which these symptoms are recorded, and the overlap of terms used to describe OCS with those used to describe other conditions. We developed an NLP algorithm to extract OCS information from a large mental healthcare EHR data resource at the South London and Maudsley NHS Foundation Trust using its Clinical Record Interactive Search (CRIS) facility. We extracted documents from individuals who had received a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. These text documents, annotated by human coders, were used for developing and refining the NLP algorithm (600 documents) with an additional set reserved for final validation (300 documents). The developed NLP algorithm utilized a rules-based approach to identify each of symptoms associated with OCS, and then combined them to determine the overall number of instances of OCS. After its implementation, the algorithm was shown to identify OCS with a precision and recall (with 95% confidence intervals) of 0.77 (0.65–0.86) and 0.67 (0.55–0.77) respectively. The development of this application demonstrated the potential to extract complex symptomatic data from mental healthcare EHRs using NLP to facilitate further analyses of these clinical symptoms and their relevance for prognosis and intervention response.

Aims Brain-derived neurotrophic factor (BDNF) plays important roles in angiogenesis, inflammation, and neuronal plasticity. BDNF methylation has been extensively investigated in depression, but not in cardiac diseases. We asked whether BDNF methylation status is associated with a major adverse cardiac event (MACE), inflammation, and the association with depression comorbidity and its treatment in patients with acute coronary syndrome (ACS). Methods and results A cross-sectional baseline study and nested 24 week double-blind escitalopram placebo-controlled trial (ClinicalTrial.gov identifier NCT00419471) were performed from 2006 to 2012, with 5–12 year follow-up for MACE. Patients with recent ACS (969 total) were divided into four groups according to depression comorbidity at baseline and treatment allocation: 591, absent depression; 127, depression on escitalopram; 128, depression on placebo; 123, depression on care as usual (CAU). BDNF methylation was measured in leucocyte DNA, and multiple demographic and clinical characteristics including interleukin 6 were evaluated as covariates at baseline. The primary outcome, time to first MACE (a composite of all-cause mortality, myocardial infarction and percutaneous coronary intervention), was investigated using Cox regression models after adjustment for covariates. Interleukin 6 level was significantly higher in patients with higher BDNF methylation values. Higher BDNF methylation was associated with increased MACE independent of confounding factors [HR (95% CI) = 1.45 (1.17–1.78)]. This association was significant in patients without depression [HR (95% CI) = 1.39 (1.01–1.90)] and depressive patients on placebo [HR (95% CI) = 1.72 (1.02–3.02)] or CAU [HR (95% CI) = 1.53 (1.01–2.61)], but not in those treated with escitalopram [HR (95% CI) = 1.00 (0.51–1.95)]. Conclusion BDNF methylation was significantly associated with prognosis of ACS. Escitalopram may mitigate the deleterious effect of higher BDNF methylation in depressive patients with ACS. Further research is needed to elucidate the mechanistics and to assess the generalisability of these findings.

Objectives: The association between older-age bipolar disorder and cognitive impairments may be mediated by vascular burden. The aim of the study was to examine the difference of cognitive function between older people with late-onset bipolar disorder (LOBD) and early-onset bipolar disorder (EOBD) by considering rigorous vascular risk burden evaluation, comprehensive cognitive tests, and relevant biochemistry data. Methods: We recruited 95 outpatients aged over 55 with a DSM-IV-TR diagnosis of bipolar I disorder. Fifty had LOBD, defined by age of onset after 40. Cognitive function was evaluated through a battery of tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility. Vascular risk assessments included individual disorders, 10-year Framingham cardiovascular risk scores, and serum levels of homocysteine, vitamin B12, folate, and triiodothyronine. Results: No differences were observed between LOBD and EOBD on any cognitive test after adjusting for potential confounders. In addition to age and educational years, multiple linear regression analyses indicated significantly negative associations between serum homocysteine levels and cognitive performances in attention, psychomotor speed, verbal memory, and executive function. Conclusions: Among older people with bipolar disorder, LOBD is not associated with more cognitive dysfunction in this study. However, higher serum homocysteine levels were significantly associated with worse cognitive performance in this particular group. Clinicians therefore have to pay attention to the cognitive function in older bipolar patients with higher levels of homocysteine.

Objective: To synthesize the evidence across longitudinal studies comparing survival in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We conducted a systematic review and meta-analysis of studies comparing survival in clinically diagnosed DLB to AD. Longitudinal cohort studies were identified through a systematic search of major electronic databases from inception to May 2018. A random effects meta-analysis was performed to calculate survival time and relative risk of death. Results: Overall, 11 studies were identified including 22,952 patients with dementia: 2029 with DLB (mean diagnosis age 76.3; 47% female) compared with 20,923 with AD (mean diagnosis age 77.2; 65.1% female). Average survival time in DLB from diagnosis was 4.11 years (SD ± 4.10) and in AD 5.66 (SD ± 5.32) years, equating to a 1.60 (95% CI: -2.44 to -0.77) years shorter survival in DLB (p < 0.01). Relative risk of death was increased by 1.35 (95%CI: 1.17–1.55) in DLB compared to AD (p < 0.01). Differences in survival were not explained by follow-up time, age at diagnosis, gender, or cognitive score. Conclusions: There is consistent evidence for higher and earlier mortality in DLB compared to AD. This is important for all stakeholders and underlines the importance of expanding research into DLB. © 2019 Elsevier B.V.

Key Points Question Is attention-deficit/hyperactivity disorder (ADHD) associated with higher early mortality risk among patients in Taiwan? Findings In this Taiwan nationwide population-based cohort study, there were 275 980 patients with ADHD and 1 931 860 matched controls. After adjustment for potential confounders, patients with ADHD had significantly elevated early mortality risk for suicide, homicide, and unintentional injuries compared with the non-ADHD group. Meaning These findings suggest that ADHD may be associated with excess mortality from injury causes., This nationwide cohort study in Taiwan evaluates whether attention-deficit/hyperactivity disorder (ADHD) is associated with higher risk of mortality from all causes, suicide, unintentional injury, homicide, and natural causes., Importance Few studies have investigated levels of mortality in patients with attention-deficit/hyperactivity disorder (ADHD), and findings have been inconsistent and lacking information on specific causes of deaths. Objective To investigate the association between ADHD and causes of death in Taiwan. Design, Setting, and Participants A nationwide population-based cohort study was conducted using a cross-national Taiwanese registry. The ADHD group comprised 275 980 individuals aged 4 to 44 years with a new diagnosis between January 1, 2000, and December 31, 2012. All individuals with ADHD were compared with 1 931 860 sex- and age-matched controls without ADHD. Exposures The association between ADHD and mortality was analyzed using a Cox regression model that controlled for sex, age, residence, insurance premium, outpatient visits, congenital anomaly, intellectual disability, depression disorder, autism, substance use disorder, conduct disorder, and oppositional defiant disorder. The analysis of suicide, unintentional injury, homicide, and natural-cause mortality was performed by a competing risk adjusted Cox regression controlling for other causes of mortality and potential confounding factors. Main Outcomes and Measures Data on mortality from all causes, suicide, unintentional injury, homicide, and natural causes collected from a national mortality database. Results There were 275 980 individuals with ADHD and 1 931 860 comparison individuals without ADHD in this study. Sex and age at index date were matched. The mean (SD) age was 9.61 (5.74) years for both groups. Most of the participants were male (209 406 in the ADHD group; 1 465 842 in the non-ADHD group; 75.88% for both groups). A total of 4321 participants from both cohorts died during the follow-up period (15.1 million person-years), including 727 (0.26%) from the ADHD group and 3594 (0.19%) from the non-ADHD group. Of those who died, 546 (75.1%) in the ADHD group and 2852 (79.4%) in the non-ADHD group were male. After adjusting for potential confounders, compared with the non-ADHD group, patients with ADHD showed higher overall mortality (adjusted hazard ratio, 1.07; 95% CI, 1.00-1.17) and higher injury-cause mortality from suicide (adjusted hazard ratio, 2.09; 95% CI, 1.62-2.71), unintentional injury (adjusted hazard ratio, 1.30; 95% CI, 1.10-1.52), and homicide (adjusted hazard ratio, 2.00; 95% CI, 1.09-3.68). No increased risk of natural-cause mortality was observed after adjustment. Conclusions and Relevance In this study, ADHD was associated with higher injury-cause mortality, particularly that due to suicide, unintentional injury, and homicide. Although the risk of injury mortality was significantly higher in patients with ADHD than in the non-ADHD group, the absolute risk of mortality was low.

BackgroundDepression is associated with increased mortality, however, little is known about its variation by ethnicity.MethodsWe conducted a cohort study of individuals with ICD-10 unipolar depression from secondary mental healthcare, from an ethnically diverse location in southeast London, followed for 8 years (2007–2014) linked to death certificates. Age- and sex- standardised mortality ratios (SMRs), with the population of England and Wales as a standard population were derived. Hazard ratios (HRs) for mortality were derived through multivariable regression procedures.ResultsData from 20 320 individuals contributing 91 635 person-years at risk with 2366 deaths were used for analyses. SMR for all-cause mortality in depression was 2.55(95% CI 2.45–2.65), with similar trends by ethnicity. Within the cohort with unipolar depression, adjusted HR (aHRs) for all-cause mortality in ethnic minority groups relative to the White British group were 0.62(95% CI 0.53–0.74) (Black Caribbean), 0.53(95% CI 0.39–0.72) (Black African) and 0.69(95% CI 0.52–0.90) (South Asian). Male sex and alcohol/substance misuse were associated with an increased all-cause mortality risk [aHR:1.94 (95% CI 1.68–2.24) and aHR:1.18 (95% CI 1.01–1.37) respectively], whereas comorbid anxiety was associated with a decreased risk [aHR: 0.72(95% CI 0.58–0.89)]. Similar associations were noted for natural-cause mortality. Alcohol/substance misuse and male sex were associated with a near-doubling in unnatural-cause mortality risk, whereas Black Caribbean individuals with depression had a reduced unnatural-cause mortality risk, relative to White British people with depression.ConclusionsAlthough individuals with depression experience an increased mortality risk, marked heterogeneity exists by ethnicity. Research and practice should focus on addressing tractable causes underlying increased mortality in depression.

Polypharmacy, defined through the number of medications prescribed, has been linked to a range of adverse health outcomes in people with dementia. It is however unclear whether a numerical threshold of concurrently prescribed drugs is a suitable predictor for cognitive decline. We aimed to test associations between polypharmacy and both short-term (six months) and long-term (three years) cognitive trajectories in patients with incident dementia. Using data from a large mental health and dementia care database in South London, a cohort of 12,148 patients (mean age = 80.7 years, 61.1% female, mean MMSE = 18.6) clinically diagnosed with dementia was identified. We determined the number of medications prescribed at dementia diagnosis and defined two exposure groups: polypharmacy (5–9 medication) and excessive polypharmacy (≥10 medications), with 0–4 medications as reference group. All Mini Mental State Examination (MMSE) scores between one year before and three years after dementia diagnosis were ascertained. Effects of polypharmacy on cognitive decline were studied using Generalized Additive Models for Location, Scale and Shape and Linear Mixed Estimation Models. At the time of dementia diagnosis polypharmacy was present in 3503 (28.8%) patients and excessive polypharmacy in 1235 (10.2%) patients. In all three groups MMSE scores initially improved after dementia diagnosis and further decline was detected in the time interval from six months to three years after dementia diagnosis. No significant differences to the control group were found in relation to polypharmacy or excessive polypharmacy, neither in the initial cognitive improvement nor long-term decline. In conclusion, polypharmacy defined by the number of drugs does not appear to predict cognitive decline in a naturalistic cohort of patients with dementia. More sophisticated tools, considering appropriateness of prescribing and the clinical picture, might be better placed to evaluate cognitive outcomes in dementia and to make practice and research recommendations. © 2019 Elsevier Inc.