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.
Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30-60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (n
= 25 453, n
= 58 113) ...and an additional analysis of Current Anxiety Symptoms (n
= 19 012, n
= 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.
There is increasing availability of data derived from diagnoses made routinely in mental health care, and interest in using these for research. Such data will be subject to both diagnostic (clinical) ...error and administrative error, and so it is necessary to evaluate its accuracy against a reference-standard. Our aim was to review studies where this had been done to guide the use of other available data.
We searched PubMed and EMBASE for studies comparing routinely collected mental health diagnosis data to a reference standard. We produced diagnostic category-specific positive predictive values (PPV) and Cohen's kappa for each study.
We found 39 eligible studies. Studies were heterogeneous in design, with a wide range of outcomes. Administrative error was small compared to diagnostic error. PPV was related to base rate of the respective condition, with overall median of 76 %. Kappa results on average showed a moderate agreement between source data and reference standard for most diagnostic categories (median kappa = 0.45-0.55); anxiety disorders and schizoaffective disorder showed poorer agreement. There was no significant benefit in accuracy for diagnoses made in inpatients.
The current evidence partly answered our questions. There was wide variation in the quality of source data, with a risk of publication bias. For some diagnoses, especially psychotic categories, administrative data were generally predictive of true diagnosis. For others, such as anxiety disorders, the data were less satisfactory. We discuss the implications of our findings, and the need for researchers to validate routine diagnostic data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Psychotic experiences, such as hallucinations and delusions, are reported by approximately 5% to 10% of the general population, although only a small proportion develop psychotic ...disorders such as schizophrenia. Studying the genetic causes of psychotic experiences in the general population, and its association with the genetic causes of other disorders, may increase the understanding of their pathologic significance. OBJECTIVES: To determine whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits and to identify genetic loci associated with psychotic experiences. DESIGN, SETTING AND PARTICIPANTS: Analyses of genetic correlation, polygenic risk scores, and copy number variation were performed using data from participants in the UK Biobank from April 1, 2018, to March 20, 2019, to assess whether genetic liability to psychotic experiences is shared with schizophrenia and/or other neuropsychiatric disorders and traits. Genome-wide association studies of psychotic experience phenotypes were conducted to identify novel genetic loci. Participants in the final analyses after exclusions included 6123 individuals reporting any psychotic experience, 2143 individuals reporting distressing psychotic experiences, and 3337 individuals reporting multiple occurrences of psychotic experiences. A total of 121 843 individuals who did not report a psychotic experience formed the comparator group. Individuals with a psychotic disorder were excluded from all analyses. MAIN OUTCOMES AND MEASURES: Genetic associations with psychotic experience phenotypes. RESULTS: The study included a total of 127 966 participants (56.0% women and 44.0% men; mean SD age, 64.0 7.6 years). Psychotic experiences were genetically correlated with major depressive disorder, schizophrenia, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Analyses of polygenic risk scores identified associations between psychotic experiences and genetic liability for major depressive disorder, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. Individuals reporting psychotic experiences had an increased burden of copy number variations previously associated with schizophrenia (odds ratio OR, 2.04; 95% CI, 1.39-2.98; P = 2.49 × 10−4) and neurodevelopmental disorders more widely (OR, 1.75; 95% CI, 1.24-2.48; P = 1.41 × 10−3). Genome-wide association studies identified 4 significantly associated loci, including a locus in Ankyrin-3 (ANK3 GenBank NM_020987) (OR, 1.16; 95% CI, 1.10-1.23; P = 3.06 × 10−8) with any psychotic experience, and a locus in cannabinoid receptor 2 gene (CNR2 GenBank NM_001841) (OR, 0.66; 95% CI, 0.56-0.78; P = 3.78 × 10−8) with distressing psychotic experiences. The genome-wide association study of any psychotic experience had a low single-nucleotide polymorphism–based heritability estimate (h2 = 1.71%; 95% CI, 1.02%-2.40%). CONCLUSIONS AND RELEVANCE: A large genetic association study of psychotic experiences from the population-based UK Biobank sample found support for a shared genetic liability between psychotic experiences and schizophrenia, major depressive disorder, bipolar disorder, and neurodevelopmental disorders.
Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and ...suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h
) estimates were ~10%, and both traits were highly genetically correlated (LDSC r
> 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES
More people with dementia also fall into the category of high vascular risk, for which a statin is usually prescribed. However, these recommendations are based on studies in people without ...dementia. We aimed to evaluate the evidence for the long‐term effectiveness and harm of statin therapy in patients with dementia.
DESIGN
Systematic review of randomized controlled trials and observational research.
SETTING
Publications from developed countries indexed in the PubMed, Web of Science, and Cochrane trial database between 2007 and 2019.
PARTICIPANTS
Trials including people with all types of dementia with a mean age older than 65 years.
INTERVENTION
Treatment with a statin for 6 months or longer.
MEASUREMENTS
Major adverse cardiovascular events, dementia progression, and general health at 2 years, or medication adverse events (AEs) at any time. Each article was assessed for bias using the Newcastle‐Ottawa or Cochrane Collaboration tools. A narrative synthesis and pooled analyses are reported.
RESULTS
Five articles met the inclusion criteria. They reported only on dementia of the Alzheimer's type. There was no evidence regarding cardiovascular events or general health. We made a very low confidence finding that statins reduce dementia progression based on three cohort studies of heterogeneous design. We made a very low confidence finding of no significant difference in AEs based on two randomized controlled trials of 18 months: odds ratios of any AE = 1.21 (95% confidence interval CI = .83‐1.77), serious AE = 1.03 (95% CI = .76‐1.87), and death = 1.69 (95% CI = .79‐3.62).
CONCLUSION
Evidence was insufficient to fully evaluate the efficacy of statins in people with dementia. We found that statins may have a small benefit delaying progression in Alzheimer's dementia, although this conflicted with previous findings from shorter randomized trials. For safety, the trial data lacked power to show clinically important differences between the groups. We recommend that clinical data be leveraged for further observational studies to inform prescribing decisions. J Am Geriatr Soc 68:650–658, 2020
Objectives
For many research cohorts, it is not practical to provide a “gold‐standard” mental health diagnosis. It is therefore important for mental health research that potential alternative ...measures for ascertaining mental disorder status are understood.
Methods
Data from UK Biobank in those participants who had completed the online Mental Health Questionnaire (n = 157,363) were used to compare the classification of mental disorder by four methods: symptom‐based outcome (self‐complete based on diagnostic interviews), self‐reported diagnosis, hospital data linkage, and self‐report medication.
Results
Participants self‐reporting any psychiatric diagnosis had elevated risk of any symptom‐based outcome. Cohen's κ between self‐reported diagnosis and symptom‐based outcome was 0.46 for depression, 0.28 for bipolar affective disorder, and 0.24 for anxiety. There were small numbers of participants uniquely identified by hospital data linkage and medication.
Conclusion
Our results confirm that ascertainment of mental disorder diagnosis in large cohorts such as UK Biobank is complex. There may not be one method of classification that is right for all circumstances, but an informed and transparent use of outcome measure(s) to suit each research question will maximise the potential of UK Biobank and other resources for mental health research.
Purpose
People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and ...benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and observational studies.
Methods
We searched three databases for research published between 2007 and 2020. Each eligible article was assessed for risk of bias, and confidence in findings was rated using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
Results
Four papers met inclusion criteria: one randomised controlled trial, two cohort studies, and one with pooled data. All looked only at dementia of Alzheimer’s type, and none addressed myocardial or cerebral infarction as outcomes. Dementia progression was reported by two studies, with conflicting results. The trial found no significant effect of aspirin on mortality (odds ratio aspirin vs. no aspirin 1.07, 95% confidence interval 0.58–1.97) but found more events of severe bleeding with aspirin (OR aspirin vs. no aspirin 6.9, 1.5–31.2). An excess in intracranial haemorrhage in the aspirin group was judged plausible based on two non-randomised studies.
Conclusions
The review findings are limited because studies include only people with Alzheimer’s-type dementia and lack confirmatory studies, although an increased risk of bleeding events is recognised. Further research that addresses the benefits and risks of aspirin in more representative groups of people with dementia is needed to guide prescribing decisions.
Abstract
Background
Researchers conducting cohort studies may wish to investigate the effect of episodes of COVID-19 illness on participants. A definitive diagnosis of COVID-19 is not always ...available, so studies have to rely on proxy indicators. This paper seeks to contribute evidence that may assist the use and interpretation of these COVID-indicators.
Methods
We described five potential COVID-indicators: self-reported core symptoms, a symptom algorithm; self-reported suspicion of COVID-19; self-reported external results; and home antibody testing based on a 'lateral flow' antibody (IgG/IgM) test cassette. Included were staff and postgraduate research students at a large London university who volunteered for the study and were living in the UK in June 2020. Excluded were those who did not return a valid antibody test result. We provide descriptive statistics of prevalence and overlap of the five indicators.
Results
Core symptoms were the most common COVID-indicator (770/1882 participants positive, 41%), followed by suspicion of COVID-19 (
n
= 509/1882, 27%), a positive symptom algorithm (
n
= 298/1882, 16%), study antibody lateral flow positive (
n
= 124/1882, 7%) and a positive external test result (
n
= 39/1882, 2%), thus a 20-fold difference between least and most common. Meeting any one indicator increased the likelihood of all others, with concordance between 65 and 94%. Report of a low suspicion of having had COVID-19 predicted a negative antibody test in 98%, but positive suspicion predicted a positive antibody test in only 20%. Those who reported previous external antibody tests were more likely to have received a positive result from the external test (24%) than the study test (15%).
Conclusions
Our results support the use of proxy indicators of past COVID-19, with the caveat that none is perfect. Differences from previous antibody studies, most significantly in lower proportions of participants positive for antibodies, may be partly due to a decline in antibody detection over time. Subsequent to our study, vaccination may have further complicated the interpretation of COVID-indicators, only strengthening the need to critically evaluate what criteria should be used to define COVID-19 cases when designing studies and interpreting study results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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