Epidemiology and microbiology of recurrent UTI in women in the community in Oxfordshire, UK.

Background: Recurrent urinary tract infection (rUTI) contributes to significant morbidity and antibiotic usage. Objectives: To characterize the age of women experiencing rUTI, the microbiology of rUTIs, and the risk of further rUTIs in Oxfordshire, UK. Patients and methods: We retrospectively analysed de-identified linked microbiology and hospital admissions data (Infections in Oxfordshire Research Database), between 2008 and 2019, including positive urine cultures from women aged ≥16 years in community settings. We defined rUTI as ≥2 positive urine cultures within 6 months or ≥3 within 12 months. Results: Of 201 927 women with urine culture performed, 84 809 (42%) had ≥1 positive culture, and 15 617 (18%) of these experienced ≥1 rUTI over a median (IQR) follow-up of 6 (3-9) years. Women with rUTI were 17.0 (95% CI: 16.3-17.7) years older on average. rUTI was commonest (6204; 40%) in those aged 70-89 years. Post-rUTI, the risk of further UTI within 6 months was 29.4% (95% CI: 28.7-30.2). Escherichia coli was detected in 65% of positive cultures. Among rUTIs where the index UTI was E. coli associated, the second UTI was also E. coli associated in 81% of cases. Conclusions: rUTIs represent a substantial healthcare burden, particularly in women >60 years. One-third of women experiencing rUTI have a further microbiologically confirmed UTI within 6 months.

Risk of death by suicide following self-harm presentations to healthcare: development and validation of a multivariable clinical prediction rule (OxSATS).

BACKGROUND: Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes. OBJECTIVE: We developed and validated a predictive model for suicide following self-harm. METHODS: We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work. FINDINGS: An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS). CONCLUSIONS: OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility. CLINICAL IMPLICATIONS: Using a clinical prediction score may assist clinical decision-making and resource allocation.

Modifiable risk factors for inpatient violence in psychiatric hospital: prospective study and prediction model.

BACKGROUND: Violence perpetrated by psychiatric inpatients is associated with modifiable factors. Current structured approaches to assess inpatient violence risk lack predictive validity and linkage to interventions. METHODS: Adult psychiatric inpatients on forensic and general wards in three psychiatric hospitals were recruited and followed up prospectively for 6 months. Information on modifiable (dynamic) risk factors were collected every 1-4 weeks, and baseline background factors. Data were transferred to a web-based monitoring system (FOxWeb) to calculate a total dynamic risk score. Outcomes were extracted from an incident-reporting system recording aggression and interpersonal violence. The association between total dynamic score and violent incidents was assessed by multilevel logistic regression and compared with dynamic score excluded. RESULTS: We recruited 89 patients and conducted 624 separate assessments (median 5/patient). Mean age was 39 (s.d. 12.5) years with 20% (n = 18) female. Common diagnoses were schizophrenia-spectrum disorders (70%, n = 62) and personality disorders (20%, n = 18). There were 93 violent incidents. Factors contributing to violence risk were a total dynamic score of ⩾1 (OR 3.39, 95% CI 1.25-9.20), 10-year increase in age (OR 0.67, 0.47-0.96), and female sex (OR 2.78, 1.04-7.40). Non-significant associations with schizophrenia-spectrum disorder were found (OR 0.50, 0.20-1.21). In a fixed-effect model using all covariates, AUC was 0.77 (0.72-0.82) and 0.75 (0.70-0.80) when the dynamic score was excluded. CONCLUSIONS: In predicting violence risk in individuals with psychiatric disorders, modifiable factors added little incremental value beyond static ones in a psychiatric inpatient setting. Future work should make a clear distinction between risk factors that assist in prediction and those linked to needs.

UMBRELLA protocol: systematic reviews of multivariable biomarker prognostic models developed to predict clinical outcomes in patients with heart failure.

BACKGROUND: Heart failure (HF) is a chronic and common condition with a rising prevalence, especially in the elderly. Morbidity and mortality rates in people with HF are similar to those with common forms of cancer. Clinical guidelines highlight the need for more detailed prognostic information to optimise treatment and care planning for people with HF. Besides proven prognostic biomarkers and numerous newly developed prognostic models for HF clinical outcomes, no risk stratification models have been adequately established. Through a number of linked systematic reviews, we aim to assess the quality of the existing models with biomarkers in HF and summarise the evidence they present. METHODS: We will search MEDLINE, EMBASE, Web of Science Core Collection, and the prognostic studies database maintained by the Cochrane Prognosis Methods Group combining sensitive published search filters, with no language restriction, from 1990 onwards. Independent pairs of reviewers will screen and extract data. Eligible studies will be those developing, validating, or updating any prognostic model with biomarkers for clinical outcomes in adults with any type of HF. Data will be extracted using a piloted form that combines published good practice guidelines for critical appraisal, data extraction, and risk of bias assessment of prediction modelling studies. Missing information on predictive performance measures will be sought by contacting authors or estimated from available information when possible. If sufficient high quality and homogeneous data are available, we will meta-analyse the predictive performance of identified models. Sources of between-study heterogeneity will be explored through meta-regression using pre-defined study-level covariates. Results will be reported narratively if study quality is deemed to be low or if the between-study heterogeneity is high. Sensitivity analyses for risk of bias impact will be performed. DISCUSSION: This project aims to appraise and summarise the methodological conduct and predictive performance of existing clinically homogeneous HF prognostic models in separate systematic reviews.Registration: PROSPERO registration number CRD42019086990.

Prognostic models for newly-diagnosed chronic lymphocytic leukaemia in adults: a systematic review and meta-analysis.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common cancer of the lymphatic system in Western countries. Several clinical and biological factors for CLL have been identified. However, it remains unclear which of the available prognostic models combining those factors can be used in clinical practice to predict long-term outcome in people newly-diagnosed with CLL. OBJECTIVES: To identify, describe and appraise all prognostic models developed to predict overall survival (OS), progression-free survival (PFS) or treatment-free survival (TFS) in newly-diagnosed (previously untreated) adults with CLL, and meta-analyse their predictive performances. SEARCH METHODS: We searched MEDLINE (from January 1950 to June 2019 via Ovid), Embase (from 1974 to June 2019) and registries of ongoing trials (to 5 March 2020) for development and validation studies of prognostic models for untreated adults with CLL. In addition, we screened the reference lists and citation indices of included studies. SELECTION CRITERIA: We included all prognostic models developed for CLL which predict OS, PFS, or TFS, provided they combined prognostic factors known before treatment initiation, and any studies that tested the performance of these models in individuals other than the ones included in model development (i.e. 'external model validation studies'). We included studies of adults with confirmed B-cell CLL who had not received treatment prior to the start of the study. We did not restrict the search based on study design. DATA COLLECTION AND ANALYSIS: We developed a data extraction form to collect information based on the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). Independent pairs of review authors screened references, extracted data and assessed risk of bias according to the Prediction model Risk Of Bias ASsessment Tool (PROBAST). For models that were externally validated at least three times, we aimed to perform a quantitative meta-analysis of their predictive performance, notably their calibration (proportion of people predicted to experience the outcome who do so) and discrimination (ability to differentiate between people with and without the event) using a random-effects model. When a model categorised individuals into risk categories, we pooled outcome frequencies per risk group (low, intermediate, high and very high). We did not apply GRADE as guidance is not yet available for reviews of prognostic models. MAIN RESULTS: From 52 eligible studies, we identified 12 externally validated models: six were developed for OS, one for PFS and five for TFS. In general, reporting of the studies was poor, especially predictive performance measures for calibration and discrimination; but also basic information, such as eligibility criteria and the recruitment period of participants was often missing. We rated almost all studies at high or unclear risk of bias according to PROBAST. Overall, the applicability of the models and their validation studies was low or unclear; the most common reasons were inappropriate handling of missing data and serious reporting deficiencies concerning eligibility criteria, recruitment period, observation time and prediction performance measures. We report the results for three models predicting OS, which had available data from more than three external validation studies: CLL International Prognostic Index (CLL-IPI) This score includes five prognostic factors: age, clinical stage, IgHV mutational status, B2-microglobulin and TP53 status. Calibration: for the low-, intermediate- and high-risk groups, the pooled five-year survival per risk group from validation studies corresponded to the frequencies observed in the model development study. In the very high-risk group, predicted survival from CLL-IPI was lower than observed from external validation studies. Discrimination: the pooled c-statistic of seven external validation studies (3307 participants, 917 events) was 0.72 (95% confidence interval (CI) 0.67 to 0.77). The 95% prediction interval (PI) of this model for the c-statistic, which describes the expected interval for the model's discriminative ability in a new external validation study, ranged from 0.59 to 0.83. Barcelona-Brno score Aimed at simplifying the CLL-IPI, this score includes three prognostic factors: IgHV mutational status, del(17p) and del(11q). Calibration: for the low- and intermediate-risk group, the pooled survival per risk group corresponded to the frequencies observed in the model development study, although the score seems to overestimate survival for the high-risk group. Discrimination: the pooled c-statistic of four external validation studies (1755 participants, 416 events) was 0.64 (95% CI 0.60 to 0.67); 95% PI 0.59 to 0.68. MDACC 2007 index score The authors presented two versions of this model including six prognostic factors to predict OS: age, B2-microglobulin, absolute lymphocyte count, gender, clinical stage and number of nodal groups. Only one validation study was available for the more comprehensive version of the model, a formula with a nomogram, while seven studies (5127 participants, 994 events) validated the simplified version of the model, the index score. Calibration: for the low- and intermediate-risk groups, the pooled survival per risk group corresponded to the frequencies observed in the model development study, although the score seems to overestimate survival for the high-risk group. Discrimination: the pooled c-statistic of the seven external validation studies for the index score was 0.65 (95% CI 0.60 to 0.70); 95% PI 0.51 to 0.77. AUTHORS' CONCLUSIONS: Despite the large number of published studies of prognostic models for OS, PFS or TFS for newly-diagnosed, untreated adults with CLL, only a minority of these (N = 12) have been externally validated for their respective primary outcome. Three models have undergone sufficient external validation to enable meta-analysis of the model's ability to predict survival outcomes. Lack of reporting prevented us from summarising calibration as recommended. Of the three models, the CLL-IPI shows the best discrimination, despite overestimation. However, performance of the models may change for individuals with CLL who receive improved treatment options, as the models included in this review were tested mostly on retrospective cohorts receiving a traditional treatment regimen. In conclusion, this review shows a clear need to improve the conducting and reporting of both prognostic model development and external validation studies. For prognostic models to be used as tools in clinical practice, the development of the models (and their subsequent validation studies) should adapt to include the latest therapy options to accurately predict performance. Adaptations should be timely.

Prevalence of chronic kidney disease in the community using data from OxRen: a UK population-based cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a largely asymptomatic condition of diminished renal function, which may not be detected until advanced stages without screening. AIM: To establish undiagnosed and overall CKD prevalence using a cross-sectional analysis. DESIGN AND SETTING: Longitudinal cohort study in UK primary care. METHOD: Participants aged ≥60 years were invited to attend CKD screening visits to determine whether they had reduced renal function (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 or albumin:creatinine ratio ≥3 mg/mmol). Those with existing CKD, low eGFR, evidence of albuminuria, or two positive screening tests attended a baseline assessment (CKD cohort). RESULTS: A total of 3207 participants were recruited and 861 attended the baseline assessment. The CKD cohort consisted of 327 people with existing CKD, 257 people with CKD diagnosed through screening (CKD prevalence of 18.2%, 95% confidence interval [CI] = 16.9 to 19.6), and 277 with borderline/transient decreased renal function. In the CKD cohort, 54.4% were female, mean standard deviation (SD) age was 74.0 (SD 6.9) years, and mean eGFR was 58.0 (SD 18.4) ml/min/1.73 m2. Of the 584 with confirmed CKD, 44.0% were diagnosed through screening. Over half of the CKD cohort (51.9%, 447/861) fell into CKD stages 3-5 at their baseline assessment, giving an overall prevalence of CKD stages 3-5 of 13.9% (95% CI = 12.8 to 15.1). More people had reduced eGFR using the Modification of Diet in Renal Disease (MDRD) equation than with CKD Epidemiology Collaboration (CKD-EPI) equation in the 60-75-year age group and more had reduced eGFR using CKD-EPI in the ≥80-year age group. CONCLUSION: This study found that around 44.0% of people living with CKD are undiagnosed without screening, and prevalence of CKD stages 1-5 was 18.2% in participants aged >60 years. Follow-up will provide data on annual incidence, rate of CKD progression, determinants of rapid progression, and predictors of cardiovascular events.

Prediction of violent reoffending in prisoners and individuals on probation: a Dutch validation study (OxRec).

Scalable and transparent methods for risk assessment are increasingly required in criminal justice to inform decisions about sentencing, release, parole, and probation. However, few such approaches exist and their validation in external settings is typically lacking. A total national sample of all offenders (9072 released from prisoners and 6329 individuals on probation) from 2011-2012 in the Netherlands were followed up for violent and any reoffending over 2 years. The sample was mostly male (n = 574 [6%] were female prisoners and n = 784 [12%] were female probationers), and median ages were 30 in the prison sample and 34 in those on probation. Predictors for a scalable risk assessment tool (OxRec) were extracted from a routinely collected dataset used by criminal justice agencies, and outcomes from official criminal registers. OxRec's predictive performance in terms of discrimination and calibration was tested. Reoffending rates in the Dutch prisoner cohort were 16% for 2-year violent reoffending and 44% for 2-year any reoffending, with lower rates in the probation sample. Discrimination as measured by the c-index was moderate, at 0.68 (95% CI: 0.66-0.70) for 2-year violent reoffending in prisoners and between 0.65 and 0.68 for other outcomes and the probation sample. The model required recalibration, after which calibration performance was adequate (e.g. calibration in the large was 1.0 for all scenarios). A recalibrated model for OxRec can be used in the Netherlands for individuals released from prison and individuals on probation to stratify their risk of future violent and any reoffending. The approach that we outline can be considered for external validations of criminal justice and clinical risk models.

Control charts for monitoring mood stability as a predictor of severe episodes in patients with bipolar disorder.

BACKGROUND: Recurrent mood episodes and subsyndromal mood instability cause substantial disability in patients with bipolar disorder. Early identification of mood episodes enabling timely mood stabilization is an important clinical goal. This study investigates the ability of control chart methodology to predict manic and/or depressive episodes by applying Shewhart's control rules to weekly self-reported scores from mania and depression questionnaires. METHODS: Shewhart's control rules were applied to weekly self-reported scores from the Altman Self-Rating Mania Scale (ASRM) and the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS) collected from 2001 to 2012 as part of the OXTEXT programme. Manic and depressive episodes were defined as an ASRM score ≥ 10 or a QIDS score ≥ 15, respectively. An episode-free run-in period of eight consecutive weeks without an episode of either type was used to calibrate control charts. Shewhart's rules were then applied to follow-up data. Their sensitivity and positive predictive value for predicting manic or depressive episodes within the next 4 weeks were calculated focusing on the first episode. Secondary analyses varying control chart type, length of episode-free run-in period, time frames to evaluate diagnostic accuracy, thresholds defining either manic or depressive episodes, and missing data methods were performed. RESULTS: Data from 146 participants (37% men) were included. The mean age was 43.4 (SD = 13.3) years. The median follow-up was 10 (IQR 5-40) weeks for mania and 10 (IQR 5-23) weeks for depression. A total of 53 (36%) participants had a manic episode and 67 (46%) had a depressive episode. For manic episodes, the sensitivity and positive predictive value of Shewhart's control rules were 30% (95% CI 19-45%) and 7% (95% CI 5-9%), and for depressive episodes, 33% (95% CI 22-46%) and 9% (95% CI 6-12%), respectively. Results from secondary analyses were similar to these. CONCLUSIONS: Tele-monitoring with control rules has the potential to predict about one-third of manic or depressive episodes before they occur, at the cost of a high false positive rate. Given the severe consequences of manic and depressive episodes, this trade-off may be desirable.

Use of risk assessment instruments to predict violence in forensic psychiatric hospitals: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Violent behaviour by forensic psychiatric inpatients is common. We aimed to systematically review the performance of structured risk assessment tools for violence in these settings. METHODS: The nine most commonly used violence risk assessment instruments used in psychiatric hospitals were examined. A systematic search of five databases (CINAHL, Embase, Global Health, PsycINFO and PubMed) was conducted to identify studies examining the predictive accuracy of these tools in forensic psychiatric inpatient settings. Risk assessment instruments were separated into those designed for imminent (within 24 hours) violence prediction and those designed for longer-term prediction. A range of accuracy measures and descriptive variables were extracted. A quality assessment was performed for each eligible study using the QUADAS-2. Summary performance measures (sensitivity, specificity, positive and negative predictive values, diagnostic odds ratio, and area under the curve value) and HSROC curves were produced. In addition, meta-regression analyses investigated study and sample effects on tool performance. RESULTS: Fifty-two eligible publications were identified, of which 43 provided information on tool accuracy in the form of AUC statistics. These provided data on 78 individual samples, with information on 6,840 patients. Of these, 35 samples (3,306 patients from 19 publications) provided data on all performance measures. The median AUC value for the wider group of 78 samples was higher for imminent tools (AUC 0.83; IQR: 0.71-0.85) compared with longer-term tools (AUC 0.68; IQR: 0.62-0.75). Other performance measures indicated variable accuracy for imminent and longer-term tools. Meta-regression indicated that no study or sample-related characteristics were associated with between-study differences in AUCs. INTERPRETATION: The performance of current tools in predicting risk of violence beyond the first few days is variable, and the selection of which tool to use in clinical practice should consider accuracy estimates. For more imminent violence, however, there is evidence in support of brief scalable assessment tools.

Factorial structure and long-term stability of the Autonomy Preference Index.

The autonomy preference index scale (API) has been designed to measure patient preference for 2 dimensions of autonomy: Their desire to take part in making medical decisions (decision making, [DM]) and their desire to be informed about their illness and the treatment (information seeking; [IS]). The DM dimension is measured by 6 general items together with 9 items related to 3 clinical vignettes (3 × 3 items). The IS dimension is measured by 8 items. While the API is widely used, a review of literature has identified several inconsistencies in the way it is scored. The first aim of this study was to determine the best scoring structure of the API on the basis of validity and reliability evidence. The second aim was to investigate the long-term stability of API scores. Two-hundred and 85 patients with a diagnosis of psychosis were assessed as they were about to be discharged from involuntary psychiatric hospitalization and they were reassessed after 6 and 12 months. Confirmatory factor analysis (CFA) revealed that a 3-factor solution was most adequate and that 2 distinct DM subscales should be preferred to 1 total DM score. While internal consistency estimates of the 3 subscales were good, the long-term stability of API scores was only modest. Multigroup-CFA revealed scalar invariance indicating API scores kept the same meaning longitudinally. In conclusion, a 3-factor structure seemed to be most adequate for the API scale. Long-term stability estimates suggested that clinicians should regularly assess patients' preferences for autonomy because API scores fluctuate over time. (PsycINFO Database Record

Is supervision necessary? Examining the effects of internet-based CBT training with and without supervision.

OBJECTIVE: To investigate the effect of Internet-based training (IBT), with and without supervision, on therapists' (N = 61) cognitive-behavioral therapy (CBT) skills in routine clinical practice. METHOD: Participants were randomized into 3 conditions: (1) Internet-based training with use of a consultation worksheet (IBT-CW); (2) Internet-based training with CBT supervision via Skype (IBT-S); and (3) "delayed-training" controls (DTs), who did not receive the training until all data collection was completed. The IBT participants received access to training over a period of 3 months. CBT skills were evaluated at pre-, mid- and posttraining/wait using assessor competence ratings of recorded therapy sessions. RESULTS: Hierarchical linear analysis revealed that the IBT-S participants had significantly greater CBT competence at posttraining than did IBT-CW and DT participants at both the mid- and posttraining/wait assessment points. There were no significant differences between IBT-CW and the delayed (no)-training DTs. CONCLUSIONS: IBT programs that include supervision may be a scalable and effective method of disseminating CBT into routine clinical practice, particularly for populations without ready access to more-traditional "live" methods of training. There was no evidence for a significant effect of IBT without supervision over a nontraining control, suggesting that merely providing access to IBT programs may not be an effective method of disseminating CBT to routine clinical practice.

GPs' adherence to guidelines for structured assessments of stroke survivors in the community and care homes.

BACKGROUND: Clinical practice guidelines recommend that stroke survivors' needs be assessed at regular intervals after stroke. The extent to which GPs comply with national guidance particularly for patients in care homes who have greatest clinical complexity is unknown. OBJECTIVES: This study aimed to establish the current clinical practice in the UK of needs assessment by GPs for stroke survivors after hospital discharge for acute stroke. METHODS: Cross-sectional online survey of current practice of GPs, using the national doctors.net network. RESULTS: The survey was completed by 300 GPs who had on average been working for 14 years. The structured assessment of stroke survivors' needs was not offered by 31% of GPs, with no significant difference for level of provision in community or care home settings. The outputs of reviews were added to patients' notes by 89% of GPs and used to change management by 57%. Only half the GPs reported integrating the information obtained into care plans and only a quarter of GPs had a protocol for follow-up of identified needs. Analysis of free-text comments indicated that patients in some care homes may receive more regular and structured reviews. CONCLUSIONS: This survey suggests that at least one-third of GPs provide no formal review of the needs of stroke patients and that in only a minority are identified needs addressed in a structured way. Standardization is required for what is included in reviews and how needs are being identified and met.

Effect of increased compulsion on readmission to hospital or disengagement from community services for patients with psychosis: follow-up of a cohort from the OCTET trial.

BACKGROUND: Community treatment orders (CTOs) have not been shown in randomised trials to reduce readmission to hospital in patients with psychosis, but these trials have been short (11-12 months). We previously investigated the effect of CTOs on readmission rates over 12 months in a randomised trial (OCTET). Here, we present follow-up data for a cohort of individuals recruited to our original trial to examine the long-term effect of CTOs on readmissions and the risk of patients disengaging from mental health services temporarily or enduringly. METHODS: For OCTET, an open-label, parallel, randomised controlled trial, we recruited patients aged 18-65 years involuntarily admitted to mental health hospitals in 32 trusts in England, with a diagnosis of psychosis and deemed suitable for CTOs by their clinicians. Between Nov 10, 2008, and Feb 22, 2011, we recruited and randomly assigned 336 eligible patients (1:1) to be discharged on either a CTO (n=167) or to voluntary status via Section 17 leave (control group; n=169). For the analysis presented in this report, we assessed data at 36 months for 330 of these patients. We tested rates of readmission to hospital, time to first readmission, number of readmissions, and duration of readmission in patients assigned to CTO versus those assigned to control, and in all patients with CTO experience at any time in the 36 months versus those without. We also tested whether duration of CTO affected readmission outcomes in patients with CTO experience. We examined discontinuation (≥60 days between clinical contacts) and disengagement from services (no clinical contact for ≥90 days with no return to contact) in the whole cohort. OCTET is registered with isrctn.com, number ISRCTN73110773. FINDINGS: We obtained data for 330 patients in the relevant period between Nov 10, 2008 and Feb 22, 2014 (36 months after the last patient was randomly assigned to OCTET). We identified no difference between the randomised groups in the numbers of patients readmitted (100 [61%] of 165 CTOs vs 113 [68%] of 165 controls; relative risk 0·88 [95% CI 0·75-1·03]), number of readmissions (mean 2·4 readmissions [SD 1·91] vs 2·2 [1·43]; incident density ratio [IDR] 0·97 [95% CI 0·76-1·24]), duration of readmissions (median 117·5 days [IQR 63-303] vs 139·5 days [63·0-309·5]; IDR 0·84 [95% CI 0·51-1·38]), or time to first readmission (median 601·0 days [95% CI 387·0-777·0] vs 420·0 days [352·0-548·0]; hazard ratio [HR] 0·81 [95% CI 0·62-1·06]). The CTO experience group had significantly more readmissions than the group without (IDR 1·39 [95% CI 1·07-1·79]) and we noted no significant difference between groups in readmission rates, duration of readmission, or time to first readmission. We did not identify a linear relationship between readmission outcomes and duration of CTO. 19 (6%) patients disengaged from services (12 [7%] of 165 CTOs vs 7 [4%] of 165 controls). Longer duration of compulsion was associated with later disengagement (HR 0·946 [95% CI 0·90-0·99, p=0·023). 187 (57%) experienced no discontinuities, and we noted no significant difference between the CTO and control groups for time to disengagement or number of discontinuities. Levels of discontinuity were associated with compulsion (IDR 0·973 [95% CI 0·96-0·99, p<0·0001]. We identified no effect of baseline characteristics on the associations between compulsion and disengagement. INTERPRETATION: We identified no evidence that increased compulsion leads to improved readmission outcomes or to disengagement from services in patients with psychosis over 36 months. The level of persisting clinical follow-up was much higher than expected, irrespective of CTO status, and could partly account for the absence of CTO effect. The findings from our 36-month follow-up support our original findings that CTOs do not provide patient benefits, and the continued high level of their use should be reviewed. FUNDING: National Institute for Health Research.

Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: relevance to the diagnosis of neuroblastoma.

BACKGROUND: Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. PROCEDURE: We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. RESULTS: We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. CONCLUSIONS: A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients.

The clinical profile of high-risk mentally disordered offenders.

PURPOSE: High-risk mentally disordered offenders present a diverse array of clinical characteristics. To contain and effectively treat this heterogeneous population requires a full understanding of the group's clinical profile. This study aimed to identify and validate clusters of clinically coherent profiles within one high-risk mentally disordered population in the UK. METHODS: Latent class analysis (a statistical technique to identify clustering of variance from a set of categorical variables) was applied to 174 cases using clinical diagnostic information to identify the most parsimonious model of best fit. Validity analyses were performed. RESULTS: Three identified classes were a 'delinquent' group (n = 119) characterised by poor educational history, strong criminal careers and high recidivism risk; a 'primary psychopathy' group (n = 38) characterised by good educational profiles and homicide offences and an 'expressive psychopathy' group (n = 17) presenting the lowest risk and characterised by more special educational needs and sexual offences. CONCLUSIONS: Individuals classed as high-risk mentally disordered offenders can be loosely segregated into three discrete subtypes: 'delinquent', 'psychopathic' or 'expressive psychopathic', respectively. These groups represent different levels of risk to society and reflect differing treatment needs.

Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial.

BACKGROUND: Compulsory supervision outside hospital has been developed internationally for the treatment of mentally ill people following widespread deinstitutionalisation but its efficacy has not yet been proven. Community treatment orders (CTOs) for psychiatric patients became available in England and Wales in 2008. We tested whether CTOs reduce admissions compared with use of Section 17 leave when patients in both groups receive equivalent levels of clinical contact but different lengths of compulsory supervision. METHODS: OCTET is a non-blinded, parallel-arm randomised controlled trial. We postulated that patients with a diagnosis of psychosis discharged from hospital on CTOs would have a lower rate of readmission over 12 months than those discharged on the pre-existing Section 17 leave of absence. Eligible patients were those involuntarily admitted to hospital with a diagnosis of psychosis, aged 18-65 years, who were deemed suitable for supervised outpatient care by their clinicians. Consenting patients were randomly assigned (1:1 ratio) to be discharged from hospital either on CTO or Section 17 leave. Randomisation used random permuted blocks with lengths of two, four, and six, and stratified for sex, schizophrenic diagnosis, and duration of illness. Research assistants, treating clinicians, and patients were aware of assignment to randomisation group. The primary outcome measure was whether or not the patient was admitted to hospital during the 12-month follow-up period, analysed with a log-binomial regression model adjusted for stratification factors. We did all analyses by intention to treat. This trial is registered, number ISRCTN73110773. FINDINGS: Of 442 patients assessed, 336 patients were randomly assigned to be discharged from hospital either on CTO (167 patients) or Section 17 leave (169 patients). One patient withdrew directly after randomisation and two were ineligible, giving a total sample of 333 patients (166 in the CTO group and 167 in the Section 17 group). At 12 months, despite the fact that the length of initial compulsory outpatient treatment differed significantly between the two groups (median 183 days CTO group vs 8 days Section 17 group, p<0·001) the number of patients readmitted did not differ between groups (59 [36%] of 166 patients in the CTO group vs 60 [36%] of 167 patients in the Section 17 group; adjusted relative risk 1·0 [95% CI 0·75-1·33]). INTERPRETATION: In well coordinated mental health services the imposition of compulsory supervision does not reduce the rate of readmission of psychotic patients. We found no support in terms of any reduction in overall hospital admission to justify the significant curtailment of patients' personal liberty. FUNDING: National Institute of Health Research.

The reliability, validity, and applicability of an English language version of the Mini-ICF-APP.

PURPOSE: This study aimed at establishing the validity and reliability of an English language version of the Mini-ICF-APP. METHODS: One hundred and five patients under the care of secondary mental health care services were assessed using the Mini-ICF-APP and several well-established measures of functioning and symptom severity. 47 (45 %) patients were interviewed on two occasions to ascertain test-retest reliability and 50 (48 %) were interviewed by two researchers simultaneously to determine the instrument's inter-rater reliability. Occupational and sick leave status were also recorded to assess construct validity. RESULTS: The Mini-ICF-APP was found to have substantial internal consistency (Chronbach's α 0.869-0.912) and all 13 items correlated highly with the total score. Analysis also showed that the Mini-ICF-APP had good test-retest (ICC 0.832) and inter-rater (ICC 0.886) reliability. No statistically significant association with length of sick leave was found, but the unemployed scored higher on the Mini ICF-APP than those in employment (mean 18.4, SD 9.1 vs. 9.4, SD 6.4, p < 0.001). The Mini-ICF-APP correlated highly with the other measures of illness severity and functioning considered in the study. CONCLUSIONS: The English version of the Mini-ICF-APP is a reliable and valid measure of disorders of capacity as defined by the International Classification of Functioning. Further work is necessary to establish whether the scale could be divided into sub scales which would allow the instrument to more sensitively measure an individual's specific impairments.

A randomized clinical trial of mindfulness-based cognitive therapy versus unrestricted services for health anxiety (hypochondriasis).

OBJECTIVE: The efficacy and acceptability of existing psychological interventions for health anxiety (hypochondriasis) are limited. In the current study, the authors aimed to assess the impact of mindfulness-based cognitive therapy (MBCT) on health anxiety by comparing the impact of MBCT in addition to usual services (unrestricted services) with unrestricted services (US) alone. METHOD: The 74 participants were randomized to either MBCT in addition to US (n = 36) or US alone (n = 38). Participants were assessed prior to intervention (MBCT or US), immediately following the intervention, and 1 year postintervention. In addition to independent assessments of diagnostic status, standardized self-report measures and assessor ratings of severity and distress associated with the diagnosis of hypochondriasis were used. RESULTS: In the intention-to-treat (ITT) analysis (N = 74), MBCT participants had significantly lower health anxiety than US participants, both immediately following the intervention (Cohen's d = 0.48) and at 1-year follow-up (d = 0.48). The per-protocol (PP) analysis (n = 68) between groups effect size was d = 0.49 at postintervention and d = 0.62 at 1-year follow-up. Mediational analysis showed that change in mindfulness mediated the group changes in health anxiety symptoms. Significantly fewer participants allocated to MBCT than to US met criteria for the diagnosis of hypochondriasis, both immediately following the intervention period (ITT 50.0% vs. 78.9%; PP 47.1% vs. 78.4%) and at 1-year follow-up (ITT 36.1% vs. 76.3%; PP 28.1% vs. 75.0%). CONCLUSIONS: MBCT may be a useful addition to usual services for patients with health anxiety.

Pressures to adhere to treatment ('leverage') in English mental healthcare.

BACKGROUND: Coercion has usually been equated with legal detention. Non-statutory pressures to adhere to treatment, 'leverage', have been identified as widespread in US public mental healthcare. It is not clear if this is so outside the USA. AIMS: To measure rates of different non-statutory pressures in distinct clinical populations in England, to test their associations with patient characteristics and compare them with US rates. METHOD: Data were collected by a structured interview conducted by independent researchers supplemented by data extraction from case notes. RESULTS: We recruited a sample of 417 participants from four differing clinical populations. Lifetime experience of leverage was reported in 35% of the sample, 63% in substance misusers, 33% and 30% in the psychosis samples and 15% in the non-psychosis sample. Leverage was associated with repeated hospitalisations, substance misuse diagnosis and lower insight as measured by the Insight and Treatment Attitudes Questionnaire. Housing leverage was the most frequent form (24%). Levels were markedly lower than those reported in the USA. CONCLUSIONS: Non-statutory pressure to adhere to treatment (leverage) is common in English mental healthcare but has received little clinical or research attention. Urgent attention is needed to understand its variation and place in community practice.