A transdiagnostic prodrome for severe mental disorders: an electronic health record study.

Effective prevention of severe mental disorders (SMD), including non-psychotic unipolar mood disorders (UMD), non-psychotic bipolar mood disorders (BMD), and psychotic disorders (PSY), rely on accurate knowledge of the duration, first presentation, time course and transdiagnosticity of their prodromal stages. Here we present a retrospective, real-world, cohort study using electronic health records, adhering to RECORD guidelines. Natural language processing algorithms were used to extract monthly occurrences of 65 prodromal features (symptoms and substance use), grouped into eight prodromal clusters. The duration, first presentation, and transdiagnosticity of the prodrome were compared between SMD groups with one-way ANOVA, Cohen's f and d. The time course (mean occurrences) of prodromal clusters was compared between SMD groups with linear mixed-effects models. 26,975 individuals diagnosed with ICD-10 SMD were followed up for up to 12 years (UMD = 13,422; BMD = 2506; PSY = 11,047; median[IQR] age 39.8[23.7] years; 55% female; 52% white). The duration of the UMD prodrome (18[36] months) was shorter than BMD (26[35], d = 0.21) and PSY (24[38], d = 0.18). Most individuals presented with multiple first prodromal clusters, with the most common being non-specific ('other'; 88% UMD, 85% BMD, 78% PSY). The only first prodromal cluster that showed a medium-sized difference between the three SMD groups was positive symptoms (f = 0.30). Time course analysis showed an increase in prodromal cluster occurrences approaching SMD onset. Feature occurrence across the prodromal period showed small/negligible differences between SMD groups, suggesting that most features are transdiagnostic, except for positive symptoms (e.g. paranoia, f = 0.40). Taken together, our findings show minimal differences in the duration and first presentation of the SMD prodromes as recorded in secondary mental health care. All the prodromal clusters intensified as individuals approached SMD onset, and all the prodromal features other than positive symptoms are transdiagnostic. These results support proposals to develop transdiagnostic preventive services for affective and psychotic disorders detected in secondary mental healthcare.

Cognitive bias modification for paranoia (CBM-pa): a randomised controlled feasibility study in patients with distressing paranoid beliefs.

BACKGROUND: Cognitive Bias Modification for paranoia (CBM-pa) is a novel, theory-driven psychological intervention targeting the biased interpretation of emotional ambiguity associated with paranoia. Study objectives were (i) test the intervention's feasibility, (ii) provide effect size estimates, (iii) assess dose-response and (iv) select primary outcomes for future trials. METHODS: In a double-blind randomised controlled trial, sixty-three outpatients with clinically significant paranoia were randomised to either CBM-pa or an active control (text reading) between April 2016 and September 2017. Patients received one 40 min session per week for 6 weeks. Assessments were given at baseline, after each interim session, post-treatment, and at 1- and 3-months post-treatment. RESULTS: A total of 122 patients were screened and 63 were randomised. The recruitment rate was 51.2%, with few dropouts (four out of 63) and follow-up rates were 90.5% (1-month) and 93.7% (3-months). Each session took 30-40 min to complete. There was no statistical evidence of harmful effects of the intervention. Preliminary data were consistent with efficacy of CBM-pa over text-reading control: patients randomised to the intervention, compared to control patients, reported reduced interpretation bias (d = -0.48 to -0.76), improved symptoms of paranoia (d = -0.19 to -0.38), and lower depressed and anxious mood (d = -0.03 to -0.29). The intervention effect was evident after the third session. CONCLUSIONS: CBM-pa is feasible for patients with paranoia. A fully powered randomised control trial is warranted.

Clinical prediction models in psychiatry: a systematic review of two decades of progress and challenges.

Recent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progress towards clinical implementation of prediction modeling for psychiatric outcomes. We searched MEDLINE, PubMed, Embase, and PsychINFO databases from inception to September 30, 2020, for English-language articles that developed and/or validated multivariable models to predict (at an individual level) onset, course, or treatment response for non-organic psychiatric disorders (PROSPERO: CRD42020216530). Individual prediction models were evaluated based on three key criteria: (i) mitigation of bias and overfitting; (ii) generalizability, and (iii) clinical utility. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used to formally appraise each study's risk of bias. 228 studies detailing 308 prediction models were ultimately eligible for inclusion. 94.5% of developed prediction models were deemed to be at high risk of bias, largely due to inadequate or inappropriate analytic decisions. Insufficient internal validation efforts (within the development sample) were also observed, while only one-fifth of models underwent external validation in an independent sample. Finally, our search identified just one published model whose potential utility in clinical practice was formally assessed. Our findings illustrated significant growth in precision psychiatry with promising progress towards real-world application. Nevertheless, these efforts have been inhibited by a preponderance of bias and overfitting, while the generalizability and clinical utility of many published models has yet to be formally established. Through improved methodological rigor during initial development, robust evaluations of reproducibility via independent validation, and evidence-based implementation frameworks, future research has the potential to generate risk prediction tools capable of enhancing clinical decision-making in psychiatric care.

Influence of cannabis use on incidence of psychosis in people at clinical high risk.

AIMS: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome. METHODS: Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale. RESULTS: During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome. CONCLUSIONS: These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis.

BACKGROUND: Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. METHODS: In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. RESULTS: There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. CONCLUSIONS: In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BACKGROUND: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. METHODS: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. RESULTS: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. CONCLUSIONS: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.

SITAgliptin for Depressive Symptoms in Type 2 Diabetes: A Feasibility Randomized Controlled Trial.

OBJECTIVE: We tested the feasibility of using sitagliptin-a dipeptidyl peptidase-IV inhibitor-for depressive symptoms in type 2 diabetes (T2D). METHODS: In a feasibility, double-blind, randomized controlled trial, we recruited people aged 18 to 75 years with T2D (glycated hemoglobin A1c levels ≥53 and ≤86 mmol/mol prescribed oral hypoglycemic therapy) and comorbid depressive symptoms (Patient Health Questionnaire-9 score ≥10) from family practices in South London. Eligible patients were randomized to sitagliptin 100 mg per day or matched placebo for 12 weeks. The primary feasibility outcomes were participation rates, attrition rates, and adverse events. The primary clinical outcomes were depressive symptoms (Patient Health Questionnaire-9 and 16-item Quick Inventory of Depressive Symptomatology scores) at 12 weeks as assessed using analyses of covariance. Ranges of treatment effects were estimated using Cohen d and associated 95% confidence intervals, where negative values favored sitagliptin over placebo. RESULTS: Of 153 people screened across 32 practices, 44 were randomized (22 to each arm). The mean (standard deviation) age was 58.8 (8.3) years, 46% were female, and 52% were of non-white ethnicity. Of those treated, 1 patient (4.5%) in each arm withdrew, and there were no group differences in adverse events. Despite improving 12-week glycated hemoglobin A1c (d = -1.19 [95% confidence interval = -1.90 to -0.48), improvement in 12-week Quick Inventory of Depressive Symptomatology score with sitagliptin was inferior to placebo across the range of estimated treatment effects (d = 0.71 [0.13 to 1.30]). Effects of sitagliptin on inflammation were inconsistent (d = -0.32 [-0.81 to 0.17] for high-sensitivity C-reactive protein). CONCLUSIONS: Repositioning of oral hypoglycemic therapy for depressive symptoms in T2D is feasible. However, in this unpowered feasibility study, we did not detect evidence of superiority of sitagliptin over placebo. The results are cautioned by the small sample size and limited treatment duration.Trial Registration: EudraCT: 2015-004527-32.

Development and validation of prediction model to estimate 10-year risk of all-cause mortality using modern statistical learning methods: a large population-based cohort study and external validation.

BACKGROUND: In increasingly ageing populations, there is an emergent need to develop a robust prediction model for estimating an individual absolute risk for all-cause mortality, so that relevant assessments and interventions can be targeted appropriately. The objective of the study was to derive, evaluate and validate (internally and externally) a risk prediction model allowing rapid estimations of an absolute risk of all-cause mortality in the following 10 years. METHODS: For the model development, data came from English Longitudinal Study of Ageing study, which comprised 9154 population-representative individuals aged 50-75 years, 1240 (13.5%) of whom died during the 10-year follow-up. Internal validation was carried out using Harrell's optimism-correction procedure; external validation was carried out using Health and Retirement Study (HRS), which is a nationally representative longitudinal survey of adults aged ≥50 years residing in the United States. Cox proportional hazards model with regularisation by the least absolute shrinkage and selection operator, where optimisation parameters were chosen based on repeated cross-validation, was employed for variable selection and model fitting. Measures of calibration, discrimination, sensitivity and specificity were determined in the development and validation cohorts. RESULTS: The model selected 13 prognostic factors of all-cause mortality encompassing information on demographic characteristics, health comorbidity, lifestyle and cognitive functioning. The internally validated model had good discriminatory ability (c-index=0.74), specificity (72.5%) and sensitivity (73.0%). Following external validation, the model's prediction accuracy remained within a clinically acceptable range (c-index=0.69, calibration slope ß=0.80, specificity=71.5% and sensitivity=70.6%). The main limitation of our model is twofold: 1) it may not be applicable to nursing home and other institutional populations, and 2) it was developed and validated in the cohorts with predominately white ethnicity. CONCLUSIONS: A new prediction model that quantifies absolute risk of all-cause mortality in the following 10-years in the general population has been developed and externally validated. It has good prediction accuracy and is based on variables that are available in a variety of care and research settings. This model can facilitate identification of high risk for all-cause mortality older adults for further assessment or interventions.

Supported discharge service versus inpatient care evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm, functional impairment, and educational and clinical outcomes.

Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. The aim of this study is to undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. 106 patients aged 12-18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomisation, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (five or more) of self-harm (OR = 0.18, 95% CI: 0.05-0.64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28.2-208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment.

Feasibility randomized controlled trial of a one-day CBT workshop ('DISCOVER') for 15- to 18-year-olds with anxiety and/or depression in clinic settings.

BACKGROUND: 'DISCOVER' one-day cognitive behavioural therapy (CBT) workshops have been developed to provide accessible, developmentally sensitive psychological support for older adolescents experiencing emotional difficulties. Previous school-based evaluations of the DISCOVER model have shown positive outcomes. AIMS: The current study aimed to test the model for clinically referred adolescents, in real-world settings. METHOD: A randomized controlled trial (RCT) assessed feasibility, acceptability and preliminary outcomes of the DISCOVER intervention, in comparison with usual care, for 15- to 18-year-olds with emotional difficulties. Participants were recruited from outpatient clinic waiting lists in UK child and adolescent mental health services (CAMHS). Research feasibility indicators included rates of recruitment, randomization, intervention participation (group workshops and individualized follow-up telephone calls), and data collection (at baseline and 8-week follow-up). Intervention acceptability was assessed using a structured service satisfaction questionnaire and semi-structured qualitative interviews with intervention participants. Preliminary clinical outcomes were explored using adolescent-reported validated measures of depression, anxiety and well-being. RESULTS: n = 24 participants were randomized to intervention and usual care groups. Workshop attendance was good and high levels of treatment satisfaction were reported, although feasibility challenges emerged in recruitment and randomization. Trends were found towards potential improvements in anxiety and well-being for the intervention group, but the effect estimate for depression was imprecise; interpretability was also limited due to the small sample size. CONCLUSIONS: DISCOVER appears to be a feasible and acceptable intervention model for clinically referred 15- to 18-year-olds with emotional difficulties. A full-scale RCT is warranted to evaluate effectiveness; protocol modifications may be necessary to ensure feasible recruitment and randomization procedures.

Changes in care costs associated with cognitive behavioural therapy for psychosis delivered in routine clinical practice.

Background: Schizophrenia spectrum disorders are long-term disabling conditions placing high economic demands on health services.Aim: To investigate whether cognitive behavioural therapy for psychosis (CBTp), delivered in a specialist psychological therapies service, was associated with a reduction in intensive care costs.Methods: Days using inpatient care and out of hours crisis support were recorded (N = 69). Costs associated with high intensity care use in the 12 months pre-referral were compared to during, and 12 months following cessation of therapy.Results: Despite the majority of participants incurring £0 at all time periods, costs of intensive mental health care more than halved with CBTp delivery, with a significant decrease during therapy, and at trend level after therapy (p = 0.07). Post hoc analysis revealed that offsetting the cost of therapy for those who utilised intensive care services at any time point (N = 18) resulted in therapy being cost neutral during therapy and cost effective (at trend level) 12 months following cessation of therapy.Conclusion: CBTp may reduce costs associated with intensive psychiatric care, even in a population where the minority use these services. Investment in therapy may lead to both clinical and financial benefits.

The Association Between Selective Serotonin Reuptake Inhibitors and Glycemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Individual studies have reported conflicting effects of selective serotonin reuptake inhibitors (SSRIs) on glycemia. We systematically reviewed the effects of SSRIs on glycemia and whether metabolic and psychological factors moderated these effects. METHODS: We systematically searched for placebo-controlled randomized controlled trials investigating the effect of SSRIs on glycemia (fasting blood glucose or HbA1c) as a primary or secondary outcome. Random effects meta-analysis was conducted to compute an overall treatment effect. Meta-regression tested whether depression, type 2 diabetes, insulin resistance, treatment duration, and weight loss moderated treatment effects. RESULTS: Sixteen randomized controlled trials (n = 835) were included and glycemia was usually a secondary outcome. Overall, SSRIs improved glycemia versus placebo (pooled effect size (ES) = -0.34, 95% confidence interval (CI) = -0.48 to -0.21; p < .001, I = 0%). Individually, fluoxetine (ES = -0.29, 95% CI = -0.54 to -0.05; p = .018) and escitalopram/citalopram (ES = -0.33, 95% CI = -0.59 to -0.07; p = .012) outperformed placebo, but paroxetine (ES = -0.19, 95% CI = -0.58 to 0.19; p = .33) did not. Results were similar in populations selected for depression as those not. Across studies, baseline insulin resistance (p = .46), treatment duration (p = .47), diabetes status (p = .41), and weight loss (p = .93) did not moderate changes. Heterogeneity for all analyses was nonsignificant. CONCLUSIONS: SSRIs seem to have an association with improvement in glycemia, which is not moderated by depression status, diabetes status, or change in weight across studies. Future powered trials with longer treatment duration are needed to confirm these findings. REGISTRATION: PROSPERO ID: CRD4201809239.

Effect of lifestyle, medication and ethnicity on cardiometabolic risk in the year following the first episode of psychosis: prospective cohort study.

BACKGROUND: The first episode of psychosis is a critical period in the emergence of cardiometabolic risk. AIMS: We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis. METHOD: This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months. RESULTS: Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol). CONCLUSIONS: Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

School-based early intervention for anxiety and depression in older adolescents: A feasibility randomised controlled trial of a self-referral stress management workshop programme ("DISCOVER").

INTRODUCTION: Schools may provide a convenient intervention setting for young people with mental health problems generally, as well as for those who are unwilling or unable to access traditional clinic-based mental health services. However, few studies focus on older adolescents, or those from ethnic minority groups. This study aims to assess the feasibility of a brief school-based psychological intervention for self-referred adolescents aged 16-19 years. METHODS: A two-arm cluster randomised controlled trial was conducted in 10 inner-city schools with block randomisation of schools. The intervention comprised a one-day CBT Stress management programme with telephone follow-up (DISCOVER) delivered by 3 psychology (2 clinical and 1 assistant) staff. The control was a waitlist condition. Primary outcomes were depression (Mood and Feelings Questionnaire; MFQ) and anxiety (Revised Child Anxiety and Depression Scale; RCADS-anxiety subscale). Data were analysed descriptively and quantitatively to assess feasibility. RESULTS: 155 students were enrolled and 142 (91.6%) followed up after 3 months. Participants were predominantly female (81%) and the mean age was 17.3 years, with equal numbers enrolled from Year 12 and Year 13. Over half (55%) of students were from ethnic minority groups. Intraclass correlations were low. Variance estimates were calculated to estimate the sample size for a full RCT. Preliminary outcomes were encouraging, with reductions in depression (d = 0.27 CI-0.49 to -0.04, p = 0.021) and anxiety (d = 0.25, CI-0.46 to -0.04, p = 0.018) at follow-up. CONCLUSIONS: Results support the feasibility of a school-based, self-referral intervention with older adolescents in a definitive future full-scale trial (Trial no. ISRCTN88636606).

Interpersonal processes in paranoia: a systematic review.

Paranoid ideation is a core feature of psychosis, and models of paranoia have long proposed that it arises in the context of disturbances in the perception of the self. However, to develop targeted interventions, there is a benefit in clarifying further, which aspects of self-perception are implicated. Interpersonal sensitivity is a personality trait which has been associated with the risk of paranoid thinking in the general population. However, not all studies have found this link. We aimed to review the empirical literature assessing the association between interpersonal sensitivity and paranoia in both general population and clinical samples; and to explore if associations found differed depending on whether state or trait paranoia was assessed. The review followed PRISMA guidelines. Articles were identified through a literature search in OVID (PsychINFO, MEDLINE) and Web of Science up to December 2016. Fourteen studies with a total of 12 138 participants were included. All studies were of 'fair' or 'good' quality. A robust association was found between interpersonal sensitivity and paranoia in clinical and general population samples alike, regardless of the method of assessment of both paranoia and interpersonal sensitivity. Although this finding was more pronounced in studies of trait paranoia, it is likely that differences in study purpose, measurement, and power explain these differences. Findings from this review support the hypothesis that feelings of personal vulnerability and exaggerated socially evaluative concerns are central for both onset and maintenance of paranoid symptoms, suggesting avenues for future research in targeted interventions.

Diabetes and TelecommunicationS (DATES) study to support self-management for people with type 2 diabetes: a randomized controlled trial.

BACKGROUND: The increasing prevalence of type 2 diabetes and suboptimal glycaemic control in Kuwait requires novel, wide-reaching, low-cost interventions to motivate and mobilise individuals towards more effective self-management. More than 2 million people in Kuwait own mobile phones. We will test whether automated personalised health text messages based on principles of motivational interviewing and are responsive to biodata delivered remotely is potentially effective in improving glycaemic control compared to usual care. METHODS: This is a two-arm parallel single-blind randomised controlled trial of 572 individuals with type 2 diabetes in Kuwait. We will develop a culturally appropriate database of text messages supporting positive lifestyle changes in type 2 diabetes. A computer programme will deliver over 400 text messages over a 12-month period using algorithms which provide participants with information on diet and physical activity as well as personalised messages regarding motivators to change behaviours. Individuals aged 18-75 years with established type 2 diabetes who are fluent in Arabic or English and officially resident in Kuwait will be identified via screening of hospital diabetes clinic and primary care practices and invited to participate. A sample of 572 participants will be randomised to usual care or usual care plus the DATES text message intervention. Randomisation will be conducted by an independent Clinical Trials Unit and researchers collecting baseline and outcome data will be blinded to treatment allocation. The primary outcome is change in HbA1c and weight at 12 months in both study arms. Secondary outcomes will include changes in physical activity, fasting lipids and quality of life in both study arms. DISCUSSION: The potential of mobile phones in improving diabetes self-care in settings with a high prevalence of diabetes and widespread mobile phone usage has face validity. Mobile phones and text messaging are an understudied virtual communication media which can deliver discrete focused psychological support to motivate and enable diabetes self-care changes. TRIAL REGISTRATION: ISRCTN10342151 . 11/03/2015.

Response bias to a randomised controlled trial of a lifestyle intervention in people at high risk of cardiovascular disease: a cross-sectional analysis.

BACKGROUND: Research evaluating lifestyle interventions for prevention of cardiovascular disease (CVD) may not reach those most at risk. We compared the response rate to a randomised controlled trial (RCT) of a lifestyle intervention by CVD risk, ethnicity and level of deprivation. METHODS: Primary care patients with a QRisk2 score ≥ 20% were invited to participate in a RCT of an intensive lifestyle intervention versus usual care. This cross-sectional analysis compares anonymised data of responders and non-responders with multiple logistic regression, using adjusted odds ratios (AORs) for QRisk2 score, ethnicity, Index of Multiple Deprivation (IMD 2010) quintile, age and sex. RESULTS: From 60 general practices, 8902 patients were invited and 1489 responded. The mean age was 67.3 years and 21.0% were female. Of all patients invited, 69.9% were of white ethnic background, 13.9% ethnic minority backgrounds and 16.2% had no ethnicity data recorded in their medical records. Likelihood of response decreased as QRisk2 score increased (AOR 0.82 per 5 percentage points, 95% CI 0.77-0.88). Black African or Caribbean patients (AOR 0.67; 95% CI 0.45-0.98) and those with missing ethnicity data (AOR 0.55; 95% CI 0.46-0.66) were less likely to respond compared to participants of white ethnicity, but there was no difference in the response rates between south Asian and white ethnicity (AOR 1.08; 95% CI 0.84-1.38). Patients residing in the fourth (AOR 0.70; 95% CI 0.56-0.87) and fifth (AOR 0.52; 95% CI 0.40-0.68) most deprived IMD quintile were less likely to respond compared to the least deprived quintile. CONCLUSIONS: Evaluations of interventions intended for those at high risk of CVD may fail to reach those at highest risk. Hard to reach patient groups may require different recruitment strategies to maximise participation in future trials. Improvements in primary care ethnicity data recording is required to aid understanding of how successfully study samples represent the target population. TRIAL REGISTRATION: ISRCTN, ISRCTN84864870. Registered 15 May 2012, https://doi.org/10.1186/ISRCTN84864870 .

The Coping with Unusual Experiences for Children Study (CUES): A pilot randomized controlled evaluation of the acceptability and potential clinical utility of a cognitive behavioural intervention package for young people aged 8-14 years with unusual experiences and emotional symptoms.

OBJECTIVES: Health care guidelines recommend psychological interventions for childhood unusual experiences that are associated with distress or adverse functional impact (UEDs), based on adult, rather than child-specific, evidence. We report the first randomized controlled evaluation of the acceptability and potential clinical utility of cognitive behavioural therapy for childhood UEDs (CBT-UED). DESIGN: Pilot randomized controlled trial. METHODS: Participants aged 8-14 years were recruited from referrals to community services for children with emotional/behavioural problems and screened for self-reported UEDs. RESULTS: Of around 1,000 referrals over 36 months, 304 (30%) were identified to the research team, 174 (57%) were successfully contacted, 110 (63%) consented to screening, 96 (87%) attended a screening assessment, and 51 (53%) reported UEDs. Forty-nine (96%) consented to randomization to either CBT-UED (9-12 weekly sessions of 40-50 min, adjunctive to usual care, n = 24) or treatment-as-usual/waitlist control (TAU/WL, n = 25). Childhood internalizing emotional symptoms (e.g., feeling 'nervous'/'scared'/'tearful'/'worried'/'sick'; proposed primary outcome), UEDs, depression, anxiety, and childhood psychopathology (secondary outcomes) were measured at baseline, at 12 weeks, and, where therapy was ongoing but incomplete (<12 sessions) at 12 weeks, at end-of-treatment (EOT). Twenty-two CBT-UED participants (92%) attended ≥5 sessions. Forty-four participants (90%) completed 12-week assessments (CBT-UED, n = 21/24, 88%; TAU/WL, n = 23/25, 92%). Preliminary findings were encouraging for emotional symptoms and UEDs, but otherwise mixed. CONCLUSIONS: Retention, screening, and consent rates were as anticipated; recruitment took longer than planned. Trial procedures were acceptable to young people, their families, and clinicians. Therapy exceeded 12 weeks, but was well-received, with no serious adverse events attributed to participation. Further evaluation is needed. PRACTITIONER POINTS: Around half of 8- to 14-year-olds in Child and Adolescent Mental Health Services reported distressing unusual experiences. An age-adapted cognitive behavioural intervention appears feasible, and safe to deliver, with the potential to augment standard care. This is a pilot study, and further evaluation is needed. Longer term outcomes should be a focus of future evaluation.

The association of depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years in newly diagnosed type 2 diabetes: a prospective cohort study.

AIMS/HYPOTHESIS: We examined the associations between depressive symptoms and diabetes distress with glycaemic control and diabetes complications over 2 years, after diagnosis of type 2 diabetes. METHODS: In a multi-ethnic, primary care cohort (n = 1735) of adults, all with recent (<6 months) diagnosis of type 2 diabetes, we measured the associations between depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) and diabetes distress (Problem Areas in Diabetes [PAID] score ≥40), with change in 2 year HbA1c as the primary outcome and with incident rates of diabetes complications as secondary outcomes. Multivariate models were used to account for potential confounders. RESULTS: Of the 1651 participants (95.2%) of the total primary care cohort with available baseline PHQ-9 and PAID scores, mean ± SD age was 56.2 ± 11.1 years, 55.1% were men and 49.1% were of non-white ethnicity; 232 (14.1%) and 111 (6.7%) had depressive symptoms and diabetes distress, respectively. After adjustment for confounders, depressive symptoms were not associated with worsening HbA1c. After adjustment for age, sex, ethnicity, vascular risk factors and diabetes treatments, depressive symptoms were associated with increased risk of incident macrovascular complications (OR 2.78 [95% CI 1.19, 6.49], p = 0.018) but not microvascular complications. This was attenuated (p = 0.09) after adjustment for IL-1 receptor antagonist concentration. Diabetes distress was not associated with worsening HbA1c or incident complications. CONCLUSIONS/INTERPRETATION: In the first 2 years of type 2 diabetes, the effect of depressive symptoms and diabetes distress on glycaemic control is minimal. There was, however, an association between depressive symptoms and incidence of macrovascular complications. Elevated innate inflammation may be common to both depression and macrovascular diabetes complications, but these findings require replication.

Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. Real-time functional magnetic resonance neurofeedback (rtfMRI-NF) allows participants to gain self-control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological-NF on ADHD symptoms, no study has applied the spatially superior rtfMRI-NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI-NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region-specificity, an active control group received rtfMRI-NF of the left parahippocampal gyrus (lPHG). Thirty-one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI-NF runs over 2 weeks. Feedback was provided through a video-clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11-month follow-up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof-of-concept study demonstrates for the first time feasibility, safety, and shorter- and longer-term efficacy of rtfMRI-NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190-3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.