Predicting prognosis for adults with depression using individual symptom data: a comparison of modelling approaches.

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.

Committee experiences of using formal consensus in healthcare guidelines: a longitudinal qualitative study.

BACKGROUND: This feasibility study has the primary aim of capturing and comparing participant expectations and experiences of using a formal consensus method (FCM) and to explore whether these views change following participation within a guideline committee where FCM are used. METHODS: Twelve healthcare committee members and associated technical team members participated in semi-structured qualitative interviews before and after using FCM during guideline committee meetings. Interviews also focused on past experiences and expectations of informal consensus methods. RESULTS: Participants said formal consensus included a greater range of evidence. They described positive reactions and found it a useful way to encourage involvement by balancing group power dynamics. Group discussion time was identified as important to clarify ideas, supported by good group chairing. However, participants reported that undertaking FCM required additional resources and suggested targeting its use for low quality evidence, limited committee expertise, or where the evidence is controversial. CONCLUSIONS: FCM is an acceptable alternative to informal consensus methods that has qualities specifically helpful to healthcare guidelines such as encouraging participation, inclusivity of a broad range of evidence, and managing group dynamics. More research is required to better understand when using formal consensus is most appropriate and effective.

The importance of transdiagnostic symptom level assessment to understanding prognosis for depressed adults: analysis of data from six randomised control trials.

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.

A demonstration of using formal consensus methods within guideline development; a case study.

BACKGROUND: Recommendations within guidelines are developed by synthesising the best available evidence; when limited evidence is identified recommendations are generally based on informal consensus. However, there are potential biases in group decision making, and formal consensus methods may help reduce these. METHODS: We conducted a case study using formal consensus, to develop one set of recommendations within the Neonatal Parenteral Nutrition guideline being produced for the National Institute for Health and Care Excellence. Statements were generated through identification of published guidelines on several topics relating to neonatal parenteral nutrition. Ten high quality guidelines were included, and 28 statements were generated; these statements were rated by the committee via two rounds of voting. The statements which resulted in agreement were then used to develop the recommendations. RESULTS: The approach was systematic and provided transparency. Additionally, a number of lessons were learnt; including the value of selecting the appropriate topic, giving adequate time to the process, and ensuring methodologies are understood by the committee for their value and relevance. CONCLUSION: Formal consensus is a valuable option for use within guideline development when specific criteria are met. The approach provides transparent methodology, ensuring clarity on how recommendations are developed.

Photolysis of CH3CN Ices by Soft X-rays: Implications for the Chemistry of Astrophysical Ices at the Surroundings of X-ray Sources.

In this work, broad-band soft X-ray (6-2000 eV) was employed to irradiate frozen acetonitrile CH3CN, at the temperature 13 K, with different photon fluences up to 1.5 × 1018 photons cm-2. Here, acetonitrile is considered as a representative complex organic molecule (COM) present in astrophysical water-rich ices. The experiments were conduced at the Brazilian synchrotron facility (LNLS/CNPEM) employing infrared spectroscopy (FTIR) to monitor chemical changes induced by radiation. The effective destruction cross section of acetonitrile and effective formation cross section for daughter species formed inside the ice were obtained. The identified radiation products were HCN, CH4, H2CCNH, and CH3NC showing that fragmentation and rearrangement contribute to acetonitrile destruction. Chemical equilibrium and molecular abundances at this stage were determined, which also includes the abundance estimates of unknown molecules, produced but not directly detected, in the ice. The chemical equilibrium was reached at fluence around 1.5 × 1018 photons cm-2. Time scales for ices, at hypothetical snow line distances, to reach chemical equilibrium around compact objects, young stellar objects, and O/B stars and inside solar system were given. Among the obtained results are the time scales for reaching chemical equilibrium around different astronomical strong X-ray emitters, e.g., 14 days (for the Sun at 5 AU), 41 and 82 days (for O/B stars at 5 AU), 109-1011 years (for white dwarfs at 1 LY), 450 years (for Crab pulsar at 2.25 LY), around 107 years (for Vela pulsar at 2.25 LY), and 7.5 × 106 years (for Sagittarius A* at 3 LY).

Attentional Control as a Predictor of Response to Psychological Treatment for Depression and Relapse up to 1 year After Treatment: A Pilot Cohort Study.

BACKGROUND: Identifying depressed patients unlikely to reach remission and those likely to relapse after reaching remission is of great importance, but there are few pre-treatment factors that can help clinicians predict prognosis and together these explain relatively little variance in treatment outcomes. Attentional control has shown promise in studies to date, but has not been investigated prospectively in routine clinical settings with depressed patients. AIMS: This study aimed to pilot the use of a brief self-report measure of attentional control in routine care and investigate the associations between attentional control, psychological treatment response and relapse to depression up to 1 year post-treatment. METHOD: Depressed patients were recruited from two primary care psychological treatment (IAPT) services and completed the Attentional Control Scale (ACS) alongside routine symptom measures at every therapy session. Participants were tracked and followed up for 1 year post-treatment. RESULTS: Baseline ACS scores were associated with remission and residual depressive symptoms post-treatment, and relapse within 12 months of ending treatment, all independent of pre-treatment depressive symptom severity, and the latter also independent of residual symptoms. CONCLUSION: A self-report measure of attentional control can potentially be used to predict levels of depressive symptoms post-treatment and can contribute to predicting risk of relapse to depression in IAPT services, without affecting rates of therapy completion/drop-out or data completion of standard IAPT measures. However, this pilot study had a small overall sample size and a very small number of observed relapses, so replication in a larger study is needed before firm conclusions can be made.

Disrupted habenula function in major depression.

The habenula is a small, evolutionarily conserved brain structure that plays a central role in aversive processing and is hypothesised to be hyperactive in depression, contributing to the generation of symptoms such as anhedonia. However, habenula responses during aversive processing have yet to be reported in individuals with major depressive disorder (MDD). Unmedicated and currently depressed MDD patients (N=25, aged 18-52 years) and healthy volunteers (N=25, aged 19-52 years) completed a passive (Pavlovian) conditioning task with appetitive (monetary gain) and aversive (monetary loss and electric shock) outcomes during high-resolution functional magnetic resonance imaging; data were analysed using computational modelling. Arterial spin labelling was used to index resting-state perfusion and high-resolution anatomical images were used to assess habenula volume. In healthy volunteers, habenula activation increased as conditioned stimuli (CSs) became more strongly associated with electric shocks. This pattern was significantly different in MDD subjects, for whom habenula activation decreased significantly with increasing association between CSs and electric shocks. Individual differences in habenula volume were negatively associated with symptoms of anhedonia across both groups. MDD subjects exhibited abnormal negative task-related (phasic) habenula responses during primary aversive conditioning. The direction of this effect is opposite to that predicted by contemporary theoretical accounts of depression based on findings in animal models. We speculate that the negative habenula responses we observed may result in the loss of the capacity to actively avoid negative cues in MDD, which could lead to excessive negative focus.

ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in the decision-making process. METHODS: This guideline has been developed using the GRADE methodology and following the recently updated EAN recommendations for guideline development. Clinical questions were formulated in PICO format (patient, intervention, comparator, outcome) and outcomes were prioritized according to their relevance to clinical practice. An exhaustive literature search up to December 2016 was performed for each question and the evidence is presented narratively and, when possible, combined in a meta-analysis using a random-effects model. The quality of evidence for each outcome was rated into four categories - very high, high, low and very low - according to the risk of bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro) software (Version 3.6). The recommendations with assigned strength (strong, weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panellists was reached by use of the modified nominal group technique. RESULTS: A total of 10 questions have been agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency at the time of publication. A total of 20 recommendations were agreed by the guideline working group members after three rounds of consensus.

The Impact of Alcohol Use on Drop-out and Psychological Treatment Outcomes in Improving Access to Psychological Therapies Services: an Audit.

BACKGROUND: The impact of alcohol use disorders (AUD) on psychological treatments for depression or anxiety in primary care psychological treatment services is unknown. AIMS: To establish levels of alcohol misuse in an Improving Access to Psychological Therapies (IAPT) service, examine the impact of higher risk drinking on IAPT treatment outcomes and drop-out, and to inform good practice in working with alcohol misuse in IAPT services. METHOD: 3643 patients completed a brief questionnaire on alcohol use pre-treatment in addition to measures of depression, anxiety and functioning. Symptom and functioning measures were re-administered at all treatment sessions. RESULTS: Severity of alcohol misuse was not associated with treatment outcomes, although those scoring eight or more on the AUDIT-C were more likely to drop out from treatment. CONCLUSIONS: IAPT services may be well placed to offer psychological therapies to patients with common mental disorders and comorbid AUD. Patients with AUD can have equivalent treatment outcomes to those without AUD, but some higher risk drinkers may find accessing IAPT treatment more difficult as they are more likely to drop out. Alcohol misuse on its own should not be used as an exclusion criterion from IAPT services. Recommendations are given as to how clinicians can: adjust their assessments to consider the appropriateness of IAPT treatment for patients that misuse alcohol, consider the potential impact of alcohol misuse on treatment, and improve engagement in treatment for higher risk drinkers.

Radiolysis of N2-rich astrophysical ice by swift oxygen ions: implication for space weathering of outer solar system bodies.

In order to investigate the role of medium mass cosmic rays and energetic solar particles in the processing of N2-rich ice on frozen moons and cold objects in the outer solar system, the bombardment of an N2 : H2O : NH3 : CO2 (98.2 : 1.5 : 0.2 : 0.1) ice mixture at 16 K employing 15.7 MeV 16O5+ was performed. The changes in the ice chemistry were monitored and quantified by Fourier transformed infrared spectroscopy (FTIR). The results indicate the formation of azide radicals (N3), and nitrogen oxides, such as NO, NO2, and N2O, as well as the production of CO, HNCO, and OCN-. The effective formation and destruction cross-sections are roughly on the order of 10-12 cm2 and 10-13 cm2, respectively. From laboratory molecular analyses, we estimated the destruction yields for the parent species and the formation yields for the daughter species. For N2, this value was 9.8 × 105 molecules per impact of ions, and for the most abundant new species (N3), it was 1.1 × 105 molecules per impact of ions. From these yields, an estimation of how many species are destroyed or formed in a given timescale (108 years) in icy bodies in the outer solar system was calculated. This work reinforces the idea that such physicochemical processes triggered by cosmic rays, solar wind, and magnetospheric particles (medium-mass ions) in nitrogen-rich ices may play an important role in the formation of molecules (including pre-biotic species precursors such as amino acids and other "CHON" molecules) in very cold astrophysical environments, such as those in the outer region of the solar system (e.g. Titan, Triton, Pluto, and other KBOs).

Ion irradiation of pure and amorphous CH4 ice relevant for astrophysical environments.

This work presents a physicochemical study of frozen amorphous methane (at 16 K) under bombardment by medium-mass ions (15.7 MeV 16O5+) with implications for icy bodies in the outer Solar System exposed to the action of cosmic rays and energetic particles. The experiment was performed at the Grand Accélérateur National d'Ions Lourds (GANIL) located in Caen, France. The results demonstrate that irradiation of CH4-containing ices by swift medium mass ions with delivered energy covering both stopping power regimes until its implantation on ice (i.e. electronic and nuclear) leads to the production of many hydrocarbons, such as C2H2, C2H4, C2H6, and C3H8 (the most abundant daughter species produced). Values for the effective dissociation cross section of CH4 and the average value for the effective formation cross-sections of its daughter species were about 10-14 cm2 and 10-15 cm2, respectively. The half-life of methane ice in the presence of swift medium mass ions extrapolated to some outer Solar System environments is estimated to be around 106 years. The measured sputtering yield of methane due to incoming swift ions was about 7.30 × 105 molecules per impact. Such parameters can be used as models to estimate the amount of CH4 and other molecular species desorbed from the icy surfaces that are constantly being incorporated to the gaseous atmosphere in the vicinity of these outer Solar System bodies due to the presence of energetic particles and cosmic rays.

Group cognitive behavioural treatment for insomnia in primary care: a randomized controlled trial.

BACKGROUND: Insomnia disorder is common and often co-morbid with mental health conditions. Cognitive behavioural therapy (CBT) for insomnia is effective, but is rarely implemented as a discrete treatment. The aim of this study was to evaluate the effectiveness of brief CBT groups for insomnia compared to treatment as usual (TAU) for insomnia delivered by mental health practitioners in a primary-care mental health service. METHOD: A total of 239 participants were randomized to either a five-session CBT group or to TAU. Assessments of sleep and of symptoms of depression and anxiety were carried out at baseline, post-treatment and at 20 weeks. Primary outcome was sleep efficiency post-treatment. RESULTS: Group CBT participants had better sleep outcomes post-treatment than those receiving TAU [sleep efficiency standardized mean difference 0.63, 95% confidence interval (CI) 0.34-0.92]. The effect at 20 weeks was smaller with a wide confidence interval (0.27, 95% CI -0.03 to 0.56). There were no important differences between groups at either follow-up period in symptoms of anxiety or depression. CONCLUSIONS: Dedicated CBT group treatment for insomnia improves sleep more than treating sleep as an adjunct to other mental health treatment.

A systematic comparison of antimicrobial wound dressings using a planktonic cell and an immobilized cell model.

AIM: The aim of the study was to evaluate the ability of in vitro planktonic and immobilized cell models for determining the antimicrobial efficacy of common antimicrobial wound dressings. METHODS AND RESULTS: Five strains of Acinetobacter baumannii, Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus were tested against four antimicrobial wound dressings containing silver, honey or polyhexamethylene biguanide (PHMB), using both a planktonic and immobilized cell model. Across all species and models used, the nanocrystalline silver coated dressing demonstrated the best antimicrobial activity being as good if not better than all the other dressings. The planktonic cell model was less effective at differentiating the dressings on antimicrobial performance as the immobilized cell model indicating that a diffusion barrier had a significant impact on the performance of some dressings. In the presence of the diffusion barrier, antimicrobial impact of the Honey and PHMB dressings was significantly reduced, particularly in the case of A. baumannii. Activity was at least an order of magnitude lower in the immobilized cell model vs the planktonic cell model. CONCLUSIONS: The use of a planktonic cell model within standard tests may overestimate the efficacy of honey and PHMB. The use of an immobilized cell model provides a more demanding test for antimicrobial dressings allowing dressing to dressing and pathogen to pathogen differences to be more clearly quantified. SIGNIFICANCE AND IMPACT OF THE STUDY: The introduction of planktonic and immobilized cell models as part of testing regimens for wound dressings will provide a more thorough understanding of their antimicrobial and anti-biofilm properties.

Single and double ionization of the camphor molecule excited around the C 1s edge.

RATIONALE: An interesting class of volatile compounds, the monoterpenes, is present in some plants although their functions are not yet fully understood. We have studied the interaction of the camphor molecule with monochromatic high-energy photons (synchrotron radiation) using time-of-flight mass spectrometry and coincidence techniques. METHODS: A commercial sample of S-camphor was admitted into the vacuum chamber, without purification, through an inlet system. Monochromatic light with energy around the C 1s edge was generated by the TGM beamline at the Brazilian Synchrotron Facility. A Wiley-McLaren mass spectrometer was used to characterize and detect the ions formed by the camphor photoionization. The data analysis was supported by energy calculations. RESULTS: Although the fragmentation patterns were basically the same at 270 eV and 330 eV, it was observed that above the C 1s edge the contribution to the spectrum from lower mass/charge fragment ions increased, pointing to a higher degree of dissociation of the molecule. Projections of the PEPIPICO spectra demonstrated the existence of unstable doubly charged species. The Gibbs free energy was calculated using the Møller-Plesset perturbation theory (MP2) for the neutral, singly and doubly excited camphor molecule. CONCLUSIONS: Our PEPIPICO spectrum clearly demonstrated the formation of doubly ionic dissociative species. From a slope analysis, we propose a secondary decay after a deferred charge separation mechanism in which, after a few steps, the camphor dication dissociates into C2 H3 (+) and C3 H5 (+) . This is the main relaxation route observed at 270 eV and 330 eV. The large energy difference between the mono and the dication (of the order of 258.2 kcal/mol) may explain the experimentally observed absence of stable dications in the spectra, because their formation is disadvantaged energetically.

Measurement invariance and differential item functioning of the PHQ-9 and GAD-7 between working age and older adults seeking treatment for common mental disorders.

BACKGROUND: The nine-item Patient Health Questionnaire (PHQ-9) and seven-item Generalised Anxiety Disorder (GAD-7) scale are widely used clinically and within research, and so it is important to determine how the measures, and individual items within the measures, are answered by adults of differing ages. This study sought to evaluate measurement invariance and differential item functioning (DIF) of the PHQ-9 and GAD-7 between working age and older adults seeking routine psychological treatment. METHODS: Data of working age (18-64 years old) and older (≥65) adults in eight Improving Access to Psychological Therapies (IAPT) services were used. Confirmatory factor analysis (CFA) was used to establish unidimensionality of the PHQ-9 and GAD-7, with multiple-group CFA to test measurement invariance and The Multiple Indicators, Multiple Causes Models approach to assess DIF. The employed methods were applied to a propensity score matched (PSM) sample in sensitivity analyses to control for potential confounding. RESULTS: Data from 166,816 patients (159,325 working age, 7491 older) were used to show measurement invariance for the PHQ-9 and GAD-7, with limited evidence of DIF and similar results found with a PSM sample (n = 5868). LIMITATIONS: The localised sample creates an inability to detect geographical variance, and the potential effect of unmeasured confounders cannot be ruled out. CONCLUSIONS: The findings support the use of the PHQ-9 and GAD-7 measures for working age and older adults, both clinically and in research settings. This study validates using the measures for these age groups to assess clinically significant symptom thresholds, and monitor treatment outcomes between them.

Predicting post-treatment symptom severity for adults receiving psychological therapy in routine care for generalised anxiety disorder: a machine learning approach.

Approximately half of generalised anxiety disorder (GAD) patients do not recover from first-line treatments, and no validated prediction models exist to inform individuals or clinicians of potential treatment benefits. This study aimed to develop and validate an accurate and explainable prediction model of post-treatment GAD symptom severity. Data from adults receiving treatment for GAD in eight Improving Access to Psychological Therapies (IAPT) services (n=15,859) were separated into training, validation and holdout datasets. Thirteen machine learning algorithms were compared using 10-fold cross-validation, against two simple clinically relevant comparison models. The best-performing model was tested on the holdout dataset and model-specific explainability measures identified the most important predictors. A Bayesian Additive Regression Trees model out-performed all comparison models (MSE=16.54 [95 % CI=15.58; 17.51]; MAE=3.19; R²=0.33, including a single predictor linear regression model: MSE=20.70 [95 % CI=19.58; 21.82]; MAE=3.94; R²=0.14). The five most important predictors were: PHQ-9 anhedonia, GAD-7 annoyance/irritability, restlessness and fear items, then the referral-assessment waiting time. The best-performing model accurately predicted post-treatment GAD symptom severity using only pre-treatment data, outperforming comparison models that approximated clinical judgement and remaining within the GAD-7 error of measurement and minimal clinically important differences. This model could inform treatment decision-making and provide desired information to clinicians and patients receiving treatment for GAD.

Ionization and fragmentation of methane induced by 40 eV to 480 eV synchrotron radiation: from valence to beyond core electron ionization.

Photoionization and fragmentation of gaseous methane induced by tunable synchrotron radiation were investigated in a wide energy range, from 40 eV up to 480 eV. We report electron-ion coincidence experiments by measuring the relative partial-ion yields and precursor-specific relative yields for individual fragment ions and for ion fragment pairs as a function of photon energy. The fragmentation patterns are discussed with emphasis on the transition behavior of the bond breaking reactions and of the hydrogen rearrangements from valence to core electron ionization. Below the C 1s threshold, a comparison between photon induced dissociation and electron impact data showed that the ionic fragments formation depends for both projectiles on the same final electronic state reached upon ionization.

Examining bi-directional change in sleep and depression symptoms in individuals receiving routine psychological treatment.

BACKGROUND: Sleep disturbance is a common symptom of depression. There is conflicting evidence whether improvements in sleep might impact depressive symptoms, or whether treating the core depressive symptoms might improve sleep disturbance. This study explored the bi-directional impact of sleep and depressive symptom change among individuals receiving psychological treatment. METHODS: Session-by-session change in sleep disturbance and depressive symptom severity scores were explored in patients receiving psychological therapy for depression from Improving Access to Psychological Therapies services in England. Bi-directional change in sleep disturbance and depressive symptoms was modelled using random-intercept cross-lagged panel models with items from the PHQ-9. RESULTS: The sample included 17,732 adults that had received three or more treatment sessions. Both depressive symptoms and sleep disturbance scores decreased. Between initial timepoints, higher sleep disturbance was associated with lower depression scores, but after this point positive cross-lagged effects were observed for both the impact of sleep disturbance on later depressive symptoms, and depressive symptoms on later sleep disturbance scores. The magnitude of effects suggested depressive symptoms may have more impact on sleep than the reverse, and this effect was larger in sensitivity analyses. CONCLUSIONS: Findings provide evidence that psychological therapy for depression results in improvements in core depressive symptoms and sleep disturbance. There was some evidence that depressive symptoms may have more impact on sleep disturbance scores at the next therapy session, than sleep disturbance does on later depressive symptoms. Targeting the core symptoms of depression initially may optimise outcomes, but further research is needed to elucidate these relationships.

Transdiagnostic symptom dynamics during psychotherapy.

Psychotherapy is an effective treatment for many common mental health problems, but the mechanisms of action and processes of change are unclear, perhaps driven by the focus on a single diagnosis which does not reflect the heterogeneous symptom experiences of many patients. The objective of this study was to better understand therapeutic change, by illustrating how symptoms evolve and interact during psychotherapy. Data from 113,608 patients from psychological therapy services who completed depression and anxiety symptom measures across three to six therapy sessions were analysed. A panel graphical vector-autoregression model was estimated in a model development sample (N = 68,165) and generalizability was tested in a confirmatory model, fitted to a separate (hold-out) sample of patients (N = 45,443). The model displayed an excellent fit and replicated in the confirmatory holdout sample. First, we found that nearly all symptoms were statistically related to each other (i.e. dense connectivity), indicating that no one symptom or association drives change. Second, the structure of symptom interrelations which emerged did not change across sessions. These findings provide a dynamic view of the process of symptom change during psychotherapy and give rise to several causal hypotheses relating to structure, mechanism, and process.

Mobile telephone delivered contingency management for encouraging adherence to supervised methadone consumption: feasibility study for an RCT of clinical and cost-effectiveness (TIES).

BACKGROUND: Prescription methadone or buprenorphine enables people with opioid use disorder to stop heroin use safely while avoiding withdrawal. To ensure methadone is taken as prescribed and to prevent diversion onto the illicit market, people starting methadone take their daily dose under a pharmacist's supervision. Many patients miss their daily methadone dose risking withdrawal, craving for heroin and overdose due to loss of heroin tolerance. Contingency management (CM) can improve medication adherence, but remote delivery using technology may be resource-light and cost-effective. We developed an innovative way to deliver CM by mobile telephone. Software monitors patients' attendance and supervised methadone consumption through an internet self-login at the pharmacy and sends reinforcing text messages to patients' mobile telephones. A linked system sends medication adherence reports to prescribers and provides early warning alerts of missed doses. A pre-paid debit card system provides financial incentives. METHODS: A cluster randomised controlled trial design was used to test the feasibility of conducting a future trial of mobile telephone CM to encourage adherence to supervised methadone in community pharmacies. Each cluster (drug service/3 allied pharmacies) was randomly allocated to provide patient's presenting for a new episode of opiate agonist treatment (OAT) with either (a) mobile telephone text message CM, (b) mobile telephone text message reminders, or (c) no text messages. We assessed acceptability of the interventions, recruitment, and follow-up procedures. RESULTS: Four drug clinics were approached and three recruited. Thirty-three pharmacists were approached and 9 recruited. Over 3 months, 173 individuals were screened and 10 enrolled. Few patients presented for OAT and high numbers were excluded due to receiving buprenorphine or not attending participating pharmacies. There was 96% consistency in recording medication adherence by self-login vs. pharmacy records. In focus groups, CM participants were positive about using self-login, the text messages, and debit card. Prescribers found weekly reporting, time saving, and allowed closer monitoring of patients. Pharmacists reported that the tablet device was easy to host. CONCLUSION: Mobile telephone CM worked well, but a planned future trial will use modified eligibility criteria (existing OAT patients who regularly miss their methadone/buprenorphine doses) and increase the number of participating pharmacies. TRIAL REGISTRATION: The trial is retrospectively registered, ISRCTN 58958179 .