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.

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.

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.

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.

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.

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.

Role of age, gender and marital status in prognosis for adults with depression: An individual patient data meta-analysis.

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.

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.

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 .

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).

Adapting IAPT services to support frontline NHS staff during the Covid-19 pandemic: the Homerton Covid Psychological Support (HCPS) pathway.

The Coronavirus (Covid-19) pandemic is exerting unprecedented pressure on NHS Health and Social Care provisions, with frontline staff, such as those of critical care units, encountering vast practical and emotional challenges on a daily basis. Although staff are being supported through organisational provisions, facilitated by those in leadership roles, the emergence of mental health difficulties or the exacerbation of existing ones amongst these members of staff is a cause for concern. Acknowledging this, academics and healthcare professionals alike are calling for psychological support for frontline staff, which not only addresses distress during the initial phases of the outbreak but also over the months, if not years, that follow. Fortunately, mental health services and psychology professional bodies across the United Kingdom have issued guidance to meet these needs. An attempt has been made to translate these sets of guidance into clinical provisions via the recently established Homerton Covid Psychological Support (HCPS) pathway delivered by Talk Changes (Hackney & City IAPT). This article describes the phased, stepped-care and evidence-based approach that has been adopted by the service to support local frontline NHS staff. We wish to share our service design and pathway of care with other Improving Access to Psychological Therapies (IAPT) services who may also seek to support hospital frontline staff within their associated NHS Trusts and in doing so, lay the foundations of a coordinated response. KEY LEARNING AIMS: (1)To understand the ways staff can be psychologically and emotionally impacted by working on the frontline of disease outbreaks.(2)To understand the ways in which IAPT services have previously supported populations exposed to crises.(3)To learn ways of delivering psychological support and interventions during a pandemic context based on existing guidance and research.

Infrared complex refractive index of N-containing astrophysical ices free of water processed by cosmic-ray simulated in laboratory.

Several nitrogen-containing molecules have been unambiguously identified in the Solar System and in the Interstellar Medium. It is believed that such a rich inventory of species is a result of the energetic processing of astrophysical ices during the interaction with ionizing radiation. An intrinsic parameter of matter, the complex refractive index, stores all the "chemical memory" triggered by energetic processing, and therefore might be used to probe ice observations in the infrared. In this study, four N-containing ices have been condensed in an ultra-high vacuum chamber and processed by heavy ions (O and Ni) with energies between 0.2 and 15.7 MeV at the Grand Accélérateur National d'Ions Lourds (GANIL), in Caen, France. All chemical changes were monitored in situ by Infrared Absorption Spectroscopy. The complex refractive index was calculated directly from the absorbance spectrum, by using the Lambert-Beer and Kramers-Kroning relations, and the values are available in an online database: https://www1.univap.br/gaa/nkabs-database/data.htm. As a result, other than the database, it was observed that non-polar ices are more destroyed by sputtering than polar ones. Such destruction and chemical evolution lead to variation in the IR albedo of samples addressed in this paper.

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.

Photochemistry and desorption induced by X-rays in water rich astrophysical ice analogs: implications for the moon Enceladus and other frozen space environments.

Soft X-rays are an important agent for chemical processing in the Solar System and in the interstellar medium. The photolysis and photodesorption processes of H2O-rich ices triggered by soft X-rays was, experimentally, addressed in this paper. The experiments were performed at the Brazilian synchrotron facility LNLS/CNPEN employing broadband radiation (from 6 to 2000 eV; mainly soft X-rays and a small fraction of VUV) in solid samples at temperatures of 20 and 80 K. The icy samples were monitored by infrared spectroscopy. We determined the effective destruction cross section (in the order 10-18 cm2) as well as the formation cross section for the new species produced after the irradiation. Among them, we list OCN-, CO, CO3, CH3OH, H2O2, HCOO-, NH4 +, HCONH2 and CH3HCO, mostly formed in the experiment at 80 K. The chemical equilibrium stage was characterized and molecular abundances were quantified. In addition, we discuss a methodology to estimate the amount of unknown species in the ice produced by photolysis. The samples reach chemical equilibrium at fluences around 2-3 × 1018 cm-2. Timescales for reaching chemical equilibrium in space environments illuminated by X-rays were given, as well as the desorption yields induced by X-rays. The astrophysical implication on the surface chemistry and desorption processes at the moon Enceladus are provided.

Depression is associated with enhanced aversive Pavlovian control over instrumental behaviour.

The dynamic modulation of instrumental behaviour by conditioned Pavlovian cues is an important process in decision-making. Patients with major depressive disorder (MDD) are known to exhibit mood-congruent biases in information processing, which may occur due to Pavlovian influences, but this hypothesis has never been tested directly in an unmedicated sample. To address this we tested unmedicated MDD patients and healthy volunteers on a computerized Pavlovian-Instrumental Transfer (PIT) task designed to separately examine instrumental approach and withdrawal actions in the context of Pavlovian appetitive and aversive cues. This design allowed us to directly measure the degree to which Pavlovian cues influence instrumental responding. Depressed patients were profoundly influenced by aversive Pavlovian stimuli, to a significantly greater degree than healthy volunteers. This was the case for instrumental behaviour both in the approach condition (in which aversive Pavlovian cues inhibited 'go' responses), and in the withdrawal condition (in which aversive Pavlovian cues facilitated 'go' responses). Exaggerated aversive PIT provides a potential cognitive mechanism for biased emotion processing in major depression. This finding also has wider significance for the understanding of disrupted motivational processing in neuropsychiatric disorders.

Risk factors for relapse and recurrence of depression in adults and how they operate: A four-phase systematic review and meta-synthesis.

PURPOSE: To review and synthesise prognostic indices that predict subsequent risk, prescriptive indices that moderate treatment response, and mechanisms that underlie each with respect to relapse and recurrence of depression in adults. RESULTS AND CONCLUSIONS: Childhood maltreatment, post-treatment residual symptoms, and a history of recurrence emerged as strong prognostic indicators of risk and each could be used prescriptively to indicate who benefits most from continued or prophylactic treatment. Targeting prognostic indices or their "down-stream" consequences will be particularly beneficial because each is either a cause or a consequence of the causal mechanisms underlying risk of recurrence. The cognitive and neural mechanisms that underlie the prognostic indices are likely addressed by the effects of treatments that are moderated by the prescriptive factors. For example, psychosocial interventions that target the consequences of childhood maltreatment, extending pharmacotherapy or adapting psychological therapies to deal with residual symptoms, or using cognitive or mindfulness-based therapies for those with prior histories of recurrence. Future research that focuses on understanding causal pathways that link childhood maltreatment, or cognitive diatheses, to dysfunction in the neocortical and limbic pathways that process affective information and facilitate cognitive control, might result in more enduring effects of treatments for depression.

Positive reinforcement targeting abstinence in substance misuse (PRAISe): Study protocol for a Cluster RCT & process evaluation of contingency management.

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

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.

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.