Detecting early signs of depressive and manic episodes in patients with bipolar disorder using the signature-based model

Recurrent major mood episodes and subsyndromal mood instability cause substantial disability in patients with bipolar disorder. Early identification of mood episodes enabling timely mood stabilisation is an important clinical goal. Recent technological advances allow the prospective reporting of mood in real time enabling more accurate, efficient data capture. The complex nature of these data streams in combination with challenge of deriving meaning from missing data mean pose a significant analytic challenge. The signature method is derived from stochastic analysis and has the ability to capture important properties of complex ordered time series data. To explore whether the onset of episodes of mania and depression can be identified using self-reported mood data.Comment: 12 pages, 3 tables, 10 figure

BFKL approach and 2->5 MHV amplitude

We study MHV amplitude for the 2 -> 5 scattering in the multi-Regge kinematics. The Mandelstam cut correction to the BDS amplitude is calculated in the leading logarithmic approximation (LLA) and the corresponding remainder function is given to any loop order in a closed integral form. We show that the LLA remainder function at two loops for 2 -> 5 amplitude can be written as a sum of two 2 -> 4 remainder functions due to recursive properties of the leading order impact factors. We also make some generalizations for the MHV amplitudes with more external particles. The results of the present study are in agreement with all leg two loop symbol derived by Caron-Huot as shown in a parallel paper of one of the authors with collaborators.Comment: 24 pages, 17 figure

Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data

Objectives: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. // Methods: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008–16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. // Results: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03–0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses. // Conclusions: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia

Identifying predictors of suicide in severe mental illness : a feasibility study of a clinical prediction rule (Oxford Mental Illness and Suicide tool or OxMIS)

Background: Oxford Mental Illness and Suicide tool (OxMIS) is a brief, scalable, freely available, structured risk assessment tool to assess suicide risk in patients with severe mental illness (schizophrenia-spectrum disorders or bipolar disorder). OxMIS requires further external validation, but a lack of large-scale cohorts with relevant variables makes this challenging. Electronic health records provide possible data sources for external validation of risk prediction tools. However, they contain large amounts of information within free-text that is not readily extractable. In this study, we examined the feasibility of identifying suicide predictors needed to validate OxMIS in routinely collected electronic health records. Methods: In study 1, we manually reviewed electronic health records of 57 patients with severe mental illness to calculate OxMIS risk scores. In study 2, we examined the feasibility of using natural language processing to scale up this process. We used anonymized free-text documents from the Clinical Record Interactive Search database to train a named entity recognition model, a machine learning technique which recognizes concepts in free-text. The model identified eight concepts relevant for suicide risk assessment: medication (antidepressant/antipsychotic treatment), violence, education, self-harm, benefits receipt, drug/alcohol use disorder, suicide, and psychiatric admission. We assessed model performance in terms of precision (similar to positive predictive value), recall (similar to sensitivity) and F1 statistic (an overall performance measure). Results: In study 1, we estimated suicide risk for all patients using the OxMIS calculator, giving a range of 12 month risk estimates from 0.1-3.4%. For 13 out of 17 predictors, there was no missing information in electronic health records. For the remaining 4 predictors missingness ranged from 7-26%; to account for these missing variables, it was possible for OxMIS to estimate suicide risk using a range of scores. In study 2, the named entity recognition model had an overall precision of 0.77, recall of 0.90 and F1 score of 0.83. The concept with the best precision and recall was medication (precision 0.84, recall 0.96) and the weakest were suicide (precision 0.37), and drug/alcohol use disorder (recall 0.61). Conclusions: It is feasible to estimate suicide risk with the OxMIS tool using predictors identified in routine clinical records. Predictors could be extracted using natural language processing. However, electronic health records differ from other data sources, particularly for family history variables, which creates methodological challenges

Personalised treatment for cognitive impairment in dementia : development and validation of an artificial intelligence model

Background Donepezil, galantamine, rivastigmine and memantine are potentially effective interventions for cognitive impairment in dementia, but the use of these drugs has not been personalised to individual patients yet. We examined whether artificial intelligence-based recommendations can identify the best treatment using routinely collected patient-level information. Methods Six thousand eight hundred four patients aged 59–102 years with a diagnosis of dementia from two National Health Service (NHS) Foundation Trusts in the UK were used for model training/internal validation and external validation, respectively. A personalised prescription model based on the Recurrent Neural Network machine learning architecture was developed to predict the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores post-drug initiation. The drug that resulted in the smallest decline in cognitive scores between prescription and the next visit was selected as the treatment of choice. Change of cognitive scores up to 2 years after treatment initiation was compared for model evaluation. Results Overall, 1343 patients with MMSE scores were identified for internal validation and 285 [21.22%] took the drug recommended. After 2 years, the reduction of mean [standard deviation] MMSE score in this group was significantly smaller than the remaining 1058 [78.78%] patients (0.60 [0.26] vs 2.80 [0.28]; P = 0.02). In the external validation cohort (N = 1772), 222 [12.53%] patients took the drug recommended and reported a smaller MMSE reduction compared to the 1550 [87.47%] patients who did not (1.01 [0.49] vs 4.23 [0.60]; P = 0.01). A similar performance gap was seen when testing the model on patients prescribed with AChEIs only. Conclusions It was possible to identify the most effective drug for the real-world treatment of cognitive impairment in dementia at an individual patient level. Routine care patients whose prescribed medications were the best fit according to the model had better cognitive performance after 2 years

Maximizing the use of social and behavioural information from secondary care mental health electronic health records

Purpose The contribution of social and behavioural factors in the development of mental health conditions and treatment effectiveness is widely supported, yet there are weak population level data sources on social and behavioural determinants of mental health. Enriching these data gaps will be crucial to accelerating precision medicine. Some have suggested the broader use of electronic health records (EHR) as a source of non-clinical determinants, although social and behavioural information are not systematically collected metrics in EHRs, internationally. Objective In this commentary, we highlight the nature and quality of key available structured and unstructured social and behavioural data using a case example of value counts from secondary mental health data available in the UK from the UK Clinical Record Interactive Search (CRIS) database; highlight the methodological challenges in the use of such data; and possible solutions and opportunities involving the use of natural language processing (NLP) of unstructured EHR text. Conclusions Most structured non-clinical data fields within secondary care mental health EHR data have too much missing data for adequate use. The utility of other non-clinical fields reported semi-consistently (e.g., ethnicity and marital status) is entirely dependent on treating them appropriately in analyses, quantifying the many reasons behind missingness in consideration of selection biases. Advancements in NLP offer new opportunities in the exploitation of unstructured text from secondary care EHR data particularly given that clinical notes and attachments are available in large volumes of patients and are more routinely completed by clinicians. Tackling ways to re-use, harmonize, and improve our existing and future secondary care mental health data, leveraging advanced analytics such as NLP is worth the effort in an attempt to fill the data gap on social and behavioural contributors to mental health conditions and will be necessary to fulfill all of the domains needed to inform personalized interventions

Glauber - Gribov approach for DIS on nuclei in N=4 SYM

In this paper the Glauber-Gribov approach for deep-inelastic scattering (DIS) with nuclei is developed in N=4 SYM. It is shown that the amplitude displays the same general properties, such as geometrical scaling, as is the case in the high density QCD approach. We found that the quantum effects leading to the graviton reggeization, give rise to an imaginary part of the nucleon amplitude, which makes the DIS in N=4 SYM almost identical to the one expected in high density QCD. We concluded that the impact parameter dependence of the nucleon amplitude is very essential for N=4 SYM, and the entire kinematic region can be divided into three regions which are discussed in the paper. We revisited the dipole description for DIS and proposed a new renormalized Lagrangian for the shock wave formalism which reproduces the Glauber-Gribov approach in a certain kinematic region. However the saturation momentum turns out to be independent of energy, as it has been discussed by Albacete, Kovchegov and Taliotis. We discuss the physical meaning of such a saturation momentum $Q_s(A)$ and argue that one can consider only $Q>Q_s(A)$ within the shock wave approximation.Comment: 40pp.,9 figures in eps file

Real-world effectiveness, its predictors and onset of action of cholinesterase inhibitors and memantine in dementia: retrospective health record study

Background The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline. Aims To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date. Method We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling. Results The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2–5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment. Conclusions This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate