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Using natural language processing, it is possible to extract structured information from raw text in the electronic health record (EHR) at reasonably high accuracy. However, the accurate distinction between negated and non-negated mentions of clinical terms remains a challenge. EHR text includes cases where diseases are stated not to be present or only hypothesised, meaning a disease can be mentioned in a report when it is not being reported as present. This makes tasks such as document classification and summarisation more difficult. We have developed the rule-based EdIE-R-Neg, part of an existing text mining pipeline called EdIE-R (Edinburgh Information Extraction for Radiology reports), developed to process brain imaging reports, (https://www.ltg.ed.ac.uk/software/edie-r/) and two machine learning approaches; one using a bidirectional long short-term memory network and another using a feedforward neural network. These were developed on data from the Edinburgh Stroke Study (ESS) and tested on data from routine reports from NHS Tayside (Tayside). Both datasets consist of written reports from medical scans. These models are compared with two existing rule-based models: pyConText (Harkema et al. 2009. Journal of Biomedical Informatics42(5), 839–851), a python implementation of a generalisation of NegEx, and NegBio (Peng et al. 2017. NegBio: A high-performance tool for negation and uncertainty detection in radiology reports. arXiv e-prints, p. arXiv:1712.05898), which identifies negation scopes through patterns applied to a syntactic representation of the sentence. On both the test set of the dataset from which our models were developed, as well as the largely similar Tayside test set, the neural network models and our custom-built rule-based system outperformed the existing methods. EdIE-R-Neg scored highest on F1 score, particularly on the test set of the Tayside dataset, from which no development data were used in these experiments, showing the power of custom-built rule-based systems for negation detection on datasets of this size. The performance gap of the machine learning models to EdIE-R-Neg on the Tayside test set was reduced through adding development Tayside data into the ESS training set, demonstrating the adaptability of the neural network models.
In the NHS Forth Valley (Central Scotland) substance misuse service (SMS), there is an arrangement whereby the details of individuals administered naloxone for overdose via the ambulance service are passed to the SMS. Each patient has an allocated keyworker (nurse). It is accepted that near fatal overdoses (NFOs) are possible precursors to fatal overdose and drug-related deaths.
– if the information is being disseminated appropriately;
– service response and follow-up for individuals;
– patterns which might influence prescribing practice.
A list of NFOs of known patients for the previous two years was acquired from the ambulance service. There was a retrospective review of the SMS prescribing database and clinical casenotes.
– 81% male;
– 53% aged < 40;
– 14% of NFO's involved those in titration phase;
– 86% were prescribed methadone. Methadone average dose 57 mg (20–80 mg) and 54% were prescribed > 60 mg/day.
Receipts of information:
– sixty-one percent of keyworkers were notified.
– in most cases when the keyworkers was informed, there was prompt action to contact and review patients (0–21 days). However, only 21% had a timely review (within 1 month) by a doctor following NFO.
There needs to be an improvement in the dissemination of information between the ambulance service, administrative staff and keyworkers. Most NFO patients were prescribed > 60 mg of methadone. There needs to better identification of “harm-reduction” prescribing whereby methadone doses should be reduced at times of ongoing drug use. Fourteen percent of NFO's involved those in titration phase (twice weekly reviews) which provides an opportunity to screen and intervene for potential NFOs.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.
Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.
Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).
Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
The Reinforcement Sensitivity Theory of Personality has as its main foundation a Behavioural Inhibition System (BIS), defined by anxiolytic drugs, in which high trait sensitivity should lead to internalising, anxiety, disorders. Conversely, it has been suggested that low BIS sensitivity would be a characteristic of externalising disorders. BIS output should lead to increased arousal and attention as well as behavioural inhibition. Here, therefore, we tested whether an externalising disorder, Attention Deficit Hyperactivity Disorder (ADHD), involves low BIS sensitivity. Goal-Conflict-Specific Rhythmicity (GCSR) in an auditory Stop Signal Task is a right frontal EEG biomarker of BIS function. We assessed children diagnosed with ADHD-I (inattentive) or ADHD-C (combined) and healthy control groups for GCSR in: a) an initial smaller study in Dunedin, New Zealand (population ~120,000: 15 control, 10 ADHD-I, 10 ADHD-C); and b) a main larger one in Tehran, Iran (population ~9 [city]-16 [metropolis] million: 27 control, 18 ADHD-I, 21 ADHD-C). GCSR was clear in controls (particularly at 6–7 Hz) and in ADHD-C (particularly at 8–9 Hz) but was reduced in ADHD-I. Reduced attention and arousal in ADHD-I could be due, in part, to BIS dysfunction. However, hyperactivity and impulsivity in ADHD-C are unlikely to reflect reduced BIS activity. Increased GCSR frequency in ADHD-C may be due to increased input to the BIS. BIS dysfunction may contribute to some aspects of ADHD (and potentially other externalising disorders) and to some differences between the ADHD subtypes but other prefrontal systems (and, e.g. dopamine) are also important.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy.
A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25–40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment.
Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up.
The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder.
The aims of the study were to describe the patterning and persistence of anxiety and depressive symptoms from adolescence to young adulthood and to examine long-term developmental relationships with earlier patterns of internalizing behaviours in childhood.
We used parallel processes latent growth curve modelling to build trajectories of internalizing from adolescence to adulthood, using seven waves of follow-ups (ages 11–27 years) from 1406 participants of the Australian Temperament Project. We then used latent factors to capture the stability of maternal reported child internalizing symptoms across three waves of early childhood follow-ups (ages 5, 7 and 9 years), and examined relationships among these patterns of symptoms across the three developmental periods, adjusting for gender and socio-economic status.
We observed strong continuity in depressive symptoms from adolescence to young adulthood. In contrast, adolescent anxiety was not persistent across the same period, nor was it related to later depressive symptoms. Anxiety was, however, related to non-specific stress in young adulthood, but only moderately so. Although childhood internalizing was related to adolescent and adult profiles, the associations were weak and indirect by adulthood, suggesting that other factors are important in the development of internalizing symptoms.
Once established, adolescent depressive symptoms are not only strongly persistent, but also have the potential to differentiate into anxiety in young adulthood. Relationships with childhood internalizing symptoms are weak, suggesting that early adolescence may be an important period for targeted intervention, but also that further research into the childhood origins of internalizing behaviours is needed.
The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.
To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.
Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.
There were significant associations between mood disorder features and ‘any cardiovascular disease’ (depression odds ratio (OR) = 1.15, 95% CI 1.12–1.19; bipolar OR = 1.28, 95% CI 1.14–1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13–1.18; bipolar OR = 1.26, 95% CI 1.12–1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24–1.73; bipolar OR = 2.23, 95% CI 1.53–3.57) and stroke (depression OR = 2.46, 95% CI 2.10–2.80; bipolar OR = 2.31, 95% CI 1.39–3.85).
Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder.
Impaired neuropsychological functioning is a feature of major depression. Previous studies have suggested that at least some aspects of neuropsychological functioning improve with successful treatment of major depression. The extent to which medications may affect the degree of normalization of these functions is unclear. The aim of the current study was to examine the course of neuropsychological functioning during treatment of major depression with cognitive–behaviour therapy (CBT) or schema therapy (ST).
A total of 69 out-patients with a primary diagnosis of major depression and 58 healthy controls completed mood ratings, neuropsychological measures, and measures of emotional processing at baseline and after 16 weeks. Participants were randomized after baseline assessment to a year-long course of CBT or ST. Patients reassessed at 16 weeks were medication-free throughout the study.
Significant neuropsychological impairment was evident at baseline in depressed participants compared with healthy controls. After 16 weeks of psychotherapy, mean depression rating scores fell more than 50%. However, no neuropsychological measures showed convincing evidence of significant improvement and emotional processing did not change.
Persisting impairment in neuropsychological functioning after the first 16 weeks of CBT or ST suggests a need to modify psychological treatments to include components targeting cognitive functioning.