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We evaluate the utility of the National Surveys of Attitudes and Sexual Lifestyles (Natsal) undertaken in 2000 and 2010, before and after the introduction of the National Chlamydia Screening Programme, as an evidence source for estimating the change in prevalence of Chlamydia trachomatis (CT) in England, Scotland and Wales. Both the 2000 and 2010 surveys tested urine samples for CT by Nucleic Acid Amplification Tests (NAATs). We examined the sources of uncertainty in estimates of CT prevalence change, including sample size and adjustments for test sensitivity and specificity, survey non-response and informative non-response. In 2000, the unadjusted CT prevalence was 4.22% in women aged 18-24 years; in 2010, CT prevalence was 3.92%, a non-significant absolute difference of 0.30 percentage points (95% credible interval -2.8 to 2.0). In addition to uncertainty due to small sample size, estimates were sensitive to specificity, survey non-response or informative non-response, such that plausible changes in any one of these would be enough to either reverse or double any likely change in prevalence. Alternative ways of monitoring changes in CT incidence and prevalence over time are discussed. [ABSTRACT FROM AUTHOR]

Background Early detection could reduce the duration of untreated psychosis. GPs are a vital part of the psychosis care pathway but find it difficult to detect the early features. An accurate risk prediction tool (P Risk) was developed to detect these. Aim The external validation of P Risk. Methods A retrospective cohort study using a validation dataset of 1,647,934 UK Clinical Practice Research Datalink primary care records linked to secondary care records. The same predictors (age, sex, ethnicity, social deprivation, consultations for suicidal behaviour, depression/anxiety and substance abuse, history of consultations for suicidal behaviour, smoking history and substance abuse and prescribed medications for depression/anxiety/PTSD/OCD and total number of consultations) were used as for P Risk development. Predictive risk, sensitivity, specificity, and likelihood ratios were calculated for various risk thresholds. Discrimination (Harrell's C) and calibration were calculated. Results were compared between the development (GOLD) and validation (AURUM) datasets. Findings Psychosis risk increased with values of the P Risk prognostic index. Incidence was highest in younger age groups and mainly higher in males. Harrell's C was 0.79 (95% CI 0.78, 0.79) in the validation dataset and 0.77 in the development dataset. A risk threshold of 1% gave sensitivity of 65.9% and specificity of 86.6%. Interpretation Further testing is required but P Risk has the potential to be used in primary care to detect future risk of psychosis., (Copyright © 2024, The Authors.)

Background: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes., Methods: In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months)., Discussion: This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths., Trial Registration: ISRCTN ISRCTN14957538. Registered in October 2022., (© 2024. The Author(s).)

Background: An accurate risk prediction algorithm could improve psychosis outcomes by reducing duration of untreated psychosis., Objective: To develop and validate a risk prediction model for psychosis, for use by family doctors, using linked electronic health records., Methods: A prospective prediction study. Records from family practices were used between 1/1/2010 to 31/12/2017 of 300,000 patients who had consulted their family doctor for any nonpsychotic mental health problem. Records were selected from Clinical Practice Research Datalink Gold, a routine database of UK family doctor records linked to Hospital Episode Statistics, a routine database of UK secondary care records. Each patient had 5-8 years of follow up data. Study predictors were consultations, diagnoses and/or prescribed medications, during the study period or historically, for 13 nonpsychotic mental health problems and behaviours, age, gender, number of mental health consultations, social deprivation, geographical location, and ethnicity. The outcome was time to an ICD10 psychosis diagnosis., Findings: 830 diagnoses of psychosis were made. Patients were from 216 family practices; mean age was 45.3 years and 43.5 % were male. Median follow-up was 6.5 years (IQR 5.6, 7.8). Overall 8-year psychosis incidence was 45.8 (95 % CI 42.8, 49.0)/100,000 person years at risk. A risk prediction model including age, sex, ethnicity, social deprivation, consultations for suicidal behaviour, depression/anxiety, substance abuse, history of consultations for suicidal behaviour, smoking history and prescribed medications for depression/anxiety/PTSD/OCD and total number of consultations had good discrimination (Harrell's C = 0.774). Identifying patients aged 17-100 years with predicted risk exceeding 1.0 % over 6 years had sensitivity of 71 % and specificity of 84 %., Funding: NIHR, School for Primary Care Research, Biomedical Research Centre., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists., Methods: A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a 'global rating of change' scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R)., Results: For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) -26.7 to -14.9) on the PHQ-9; 23% (95% CI -27.8 to -18.0) on the BDI-II and 26.8% (95% CI -33.5 to -20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were -1.7, -3.5 and -1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement., Conclusions: An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit., Funding: Funding. National Institute for Health Research.

Background: Psychotic experiences are reported by 5-10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance., Aims: To investigate how longitudinal profiles of psychotic experiences, created from assessments at three different time points, are influenced by early life and co-occurring factors., Method: Using data from 8045 individuals from a birth cohort study, longitudinal profiles of psychotic experiences based on semi-structured interviews conducted at 12, 18 and 24 years were defined. Environmental, cognitive, psychopathological and genetic determinants of these profiles were investigated, along with concurrent changes in psychopathology and cognition., Results: Following multiple imputations, the distribution of longitudinal profiles of psychotic experiences was none (65.7%), transient (24.1%), low-frequency persistent (8.4%) and high-frequency persistent (1.7%). Individuals with high-frequency persistent psychotic experiences were more likely to report traumatic experiences, other psychopathology, a more externalised locus of control, reduced emotional stability and conscientious personality traits in childhood, compared with those with transient psychotic experiences. These characteristics also differed between those who had any psychotic experiences and those who did not., Conclusions: These findings indicate that the same risk factors are associated with incidence as with persistence of psychotic experiences. Thus, it might be that the severity of exposure, rather than the presence of specific disease-modifying factors, is most likely to determine whether psychotic experiences are transient or persist, and potentially develop into a clinical disorder over time.

Background: Self-administered questionnaires are widely used in primary care and other clinical settings to assess the severity of depressive symptoms and monitor treatment outcomes. Qualitative studies have found that changes in questionnaire scores might not fully capture patients' experience of changes in their mood but there are no quantitative studies of this issue. We examined the extent to which changes in scores from depression questionnaires disagreed with primary care patients' perceptions of changes in their mood and investigated factors influencing this relationship., Methods: Prospective cohort study assessing patients on four occasions, 2 weeks apart. Patients (N = 554) were recruited from primary care surgeries in three UK sites (Bristol, Liverpool and York) and had reported depressive symptoms or low mood in the past year [68% female, mean age 48.3 (s.d. 12.6)]. Main outcome measures were changes in scores on patient health questionnaire (PHQ-9) and beck depression inventory (BDI-II) and the patients' own ratings of change., Results: There was marked disagreement between clinically important changes in questionnaire scores and patient-rated change, with disagreement of 51% (95% CI 46-55%) on PHQ-9 and 55% (95% CI 51-60%) on BDI-II. Patients with more severe anxiety were less likely, and those with better mental and physical health-related quality of life were more likely, to report feeling better, having controlled for depression scores., Conclusions: Our results illustrate the limitations of self-reported depression scales to assess clinical change. Clinicians should be cautious in interpreting changes in questionnaire scores without further clinical assessment.

Objective: The authors investigated the incidence, course, and outcome of psychotic experiences from childhood through early adulthood in the general population and examined prediction of psychotic disorder., Methods: This was a population-based cohort study using the semistructured Psychosis-Like Symptoms Interview at ages 12, 18, and 24 (N=7,900 with any data). Incidence rates were estimated using flexible parametric modeling, and positive predictive values (PPVs), sensitivity, specificity, and area under the curve were estimated for prediction., Results: The incidence rate of psychotic experiences increased between ages 13 and 24, peaking during late adolescence. Of 3,866 participants interviewed at age 24, 313 (8.1%, 95% CI=7.2, 9.0) had a definite psychotic experience since age 12. A total of 109 individuals (2.8%) met criteria for a psychotic disorder up to age 24, of whom 70% had sought professional help. Prediction of current psychotic disorder at age 24 (N=47, 1.2%), by both self-report and interviewer-rated measures of psychotic experiences at age 18 (PPVs, 2.9% and 10.0%, respectively), was improved by incorporating information on frequency and distress (PPVs, 13.3% and 20.0%, respectively), although sensitivities were low. The PPV of an at-risk mental state at age 18 predicting incident disorder at ages 18-24 was 21.1% (95% CI=6.1, 45.6) (sensitivity, 14.3%, 95% CI=4.0, 32.7)., Conclusions: The study results show a peak in incidence of psychotic experiences during late adolescence as well as an unmet need for care in young people with psychotic disorders. Because of the low sensitivity, targeting individuals in non-help-seeking samples based only on more severe symptom cutoff thresholds will likely have little impact on population levels of first-episode psychosis.

Background: Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response., Methods: The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants., Findings: Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication., Interpretation: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder., Funding: National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Seroprevalence surveys of Chlamydia trachomatis (CT) antibodies are promising for estimating age-specific CT cumulative incidence, however accurate estimates require improved understanding of antibody response to CT infection., Methods: We used GUMCAD, England's national sexually transmitted infection (STI) surveillance system, to select sera taken from female STI clinic attendees on the day of or after a chlamydia diagnosis. Serum specimens were collected from laboratories and tested anonymously on an indirect and a double-antigen ELISA, both of which are based on the CT-specific Pgp3 antigen. We used cross-sectional and longitudinal descriptive analyses to explore the relationship between seropositivity and a) cumulative number of chlamydia diagnoses and b) time since most recent chlamydia diagnosis., Results: 919 samples were obtained from visits when chlamydia was diagnosed and 812 during subsequent follow-up visits. Pgp3 seropositivity using the indirect ELISA increased from 57.1% (95% confidence interval: 53.2-60.7) on the day of a first-recorded chlamydia diagnosis to 89.6% (95%CI: 79.3-95.0) on the day of a third or higher documented diagnosis. With the double-antigen ELISA, the increase was from 61.1% (95%CI: 53.2-60.7) to 97.0% (95%CI: 88.5-99.3). Seropositivity decreased with time since CT diagnosis on only the indirect assay, to 49.3% (95%CI: 40.9-57.7) two or more years after a first diagnosis and 51.9% (95%CI: 33.2-70.0) after a repeat diagnosis., Conclusion: Seropositivity increased with cumulative number of infections, and decreased over time after diagnosis on the indirect ELISA, but not on the double-antigen ELISA. This is the first study to demonstrate the combined impact of number of chlamydia diagnoses, time since diagnosis, and specific ELISA on Pgp3 seropositivity. Our findings are being used to inform models estimating age-specific chlamydia incidence over time using serial population-representative serum sample collections, to enable accurate public health monitoring of chlamydia., Competing Interests: The authors have declared that no competing interests exist.

Background: Depressive symptoms are usually managed within primary care and antidepressant medication constitutes the first-line treatment. It remains unclear at present which people are more likely to benefit from antidepressant medication. This paper describes the protocol for a randomised controlled trial (PANDA) to investigate the severity and duration of depressive symptoms that are associated with a clinically significant response to sertraline compared to placebo, in people presenting to primary care with depression., Methods/design: PANDA is a randomised, double blind, placebo controlled trial in which participants are individually randomised to sertraline or placebo. Eligible participants are those who are between the ages of 18 to 74; have presented to primary care with depression or low mood during the past 2 years; have not received antidepressant or anti-anxiety medication in the 8 weeks prior to enrolment in the trial and there is clinical equipoise about the benefits of selective serotonin reuptake inhibitor (SSRI) medication. Participants who consent to participate in the trial are randomised to receive either sertraline or matching placebo, starting at 50 mg daily for 1 week, increasing to 100 mg daily for up to 11 weeks (with the option of increasing to 150 mg if required). Participants, general practitioners (GPs) and the research team will be blind to treatment allocation. The primary outcome will be depressive symptoms measured by the Patient Health Questionnaire-9 (PHQ-9) at 6 weeks post randomisation, measured as a continuous outcome. Secondary outcomes include depressive symptoms measured with the PHQ-9 at 2 and 12 weeks as a continuous outcome and at 2, 6 and 12 weeks as a binary outcome; follow-up scores on depressive symptoms measured with the Beck Depression Inventory-II, anxiety symptoms measured by the Generalized Anxiety Disorder-7 and quality of life measured with the Euroqol-5D-5L and Short Form-12; emotional processing task scores measured at baseline, 2 and 6 weeks; and costs associated with healthcare use, time off work and personal costs., Discussion: The PANDA trial uses a simple self-administered measure to establish the severity and duration of depressive symptoms associated with a clinically significant response to sertraline. The evidence from the trial will inform primary care prescribing practice by identifying which patients are more likely to benefit from antidepressants., Trial Registration: Controlled Trials ISRCTN Registry, ISRCTN84544741 . Registered on 20 March 2014. EudraCT Number: 2013-003440-22; Protocol Number: 13/0413 (version 6.1).

Purpose: To investigate the longitudinal associations between social cognitive ability an external locus of control (externality) and adolescent psychopathology., Methods: 7058 participants from a prospective population-based cohort provided data on externality, social communication, and emotion perception between 7 and 16 years and psychotic experiences and depressive symptoms at 12 and 18 years. Bivariate probit modelling was used to investigate associations between these risk factors and psychopathological outcomes., Results: Externality was associated with psychopathology at 12 (psychotic experiences OR 1.23 95% CI 1.14, 1.33; depression OR 1.12 95% CI 1.02, 1.22) and 18 years (psychotic experiences OR 1.38 95% CI 1.23, 1.55; depression OR 1.40 95% CI 1.28, 1.52). Poor social communication was associated with depression at both ages (12 years OR 1.22 95% CI 1.11, 1.34; 18 years OR 1.21 95% CI 1.10, 1.33) and marginally associated with psychotic experiences. There was marginal evidence of a larger association between externality and psychotic experiences at 12 years (p = 0.06) and between social communication and depression at 12 years (p = 0.03)., Conclusions: Externality was more strongly associated with psychotic experiences. At 18 years change in externality, between 8 and 16 years were associated with a larger increase in the risk of depression. Poor social communication was more strongly associated with depression.

Purpose: To investigate whether low parental socioeconomic position (SEP) at birth is associated only with early-onset depressive symptoms in offspring., Methods: This prospective cohort study used data on 9193 individuals (4768 females, 4425 males) from the Avon Longitudinal Study of Parents and Children. Depressive symptoms during three age periods (10-12, 12-16, 16-20 years) were assessed using the Short Mood and Feelings Questionnaire, and ICD-10 depression at age 18 was assessed using the Clinical Interview Schedule-Revised., Results: Low SEP was associated with increased incidence rates of depressive symptoms in all age periods, with indicators of low standard of living showing the strongest associations. For instance, incidence rate ratios for material hardship were 1.75 (95% CI [1.42-2.15]) at 10-12 years, 1.36 (1.16-1.61) at 12-16 years and 1.39 (1.21-1.59) at 16-20 years. Low SEP was also associated with increased odds of ICD-10 depression at 18 years, ranging from OR = 1.20 (95% CI [0.94-1.52]) for manual social class to 1.74 (1.35-2.24) for material hardship., Conclusions: There was no evidence that depressive symptoms can be "subtyped" by the age of onset, because the association with low SEP was evident for early- and later-onset symptoms. If socioeconomic inequalities in early life have long-term adverse impacts on mental health, policies addressing these inequalities could benefit the mental health of the population., Competing Interests: Compliance with ethical standards Ethical standards The study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. Conflicts of interest The authors declare that they have no conflict of interest.

Background: Positive self-bias is thought to be protective for mental health. We previously found that the degree of positive bias when learning self-referential social evaluation decreases with increasing social anxiety. It is unclear whether this reduction is driven by differences in state or trait anxiety, as both are elevated in social anxiety; therefore, we examined the effects on the state of anxiety induced by the 7.5% carbon dioxide (CO2) inhalation model of generalised anxiety disorder (GAD) on social evaluation learning., Methods: For our study, 48 (24 of female gender) healthy volunteers took two inhalations (medical air and 7.5% CO2, counterbalanced) whilst learning social rules (self-like, self-dislike, other-like and other-dislike) in an instrumental social evaluation learning task. We analysed the outcomes (number of positive responses and errors to criterion) using the random effects Poisson regression., Results: Participants made fewer and more positive responses when breathing 7.5% CO2 in the other-like and other-dislike rules, respectively (gas × condition × rule interaction p = 0.03). Individuals made fewer errors learning self-like than self-dislike, and this positive self-bias was unaffected by CO2. Breathing 7.5% CO2 increased errors, but only in the other-referential rules (gas × condition × rule interaction p = 0.003)., Conclusions: Positive self-bias (i.e. fewer errors learning self-like than self-dislike) seemed robust to changes in state anxiety. In contrast, learning other-referential evaluation was impaired as state anxiety increased. This suggested that the previously observed variations in self-bias arise due to trait, rather than state, characteristics., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2016.)

Chlamydia trachomatis (Ct) serological studies in populations could help monitor changes in lifetime cumulative risk of infection. We developed a double-antigen sandwich ELISA based on the Ct-specific Pgp3 antigen, then tested blind stored sera from over 800 participants in a New Zealand birth cohort from Dunedin at ages 26, 32 and 38. The double-antigen sandwich ELISA was more sensitive than our previously characterised indirect Pgp3 ELISA. Pgp3 antibody was detected more often in women compared to men and correlated with increasing numbers of sexual partners, self-reported Ct, and younger age at sexual debut in both women and men. At age 26, 24.1% (99/411) of women were Pgp3 seropositive, as were 79.5% (35/44) of those reporting Ct infection; Pgp3 antibody persisted to age 38 in 96.5% (83/86). In men at age 26, the figures were 10.7% (47/442) and 25.0% (6/24), respectively, with high (83.9%) antibody persistence to age 38. At age 38, among those Pgp3 seropositive, 63.3% of women and 83.1% of men had not reported Ct infection. Thus, Ct-specific Pgp3 antibody was detected in most women reporting Ct infection and correlated with risk of infection in those who did not, with most infections remaining undetected. As this antibody persisted for at least twelve years in 96% of these women, serology could be used to evaluate Ct prevention programmes among women.

Background: Cognitive behavioural therapy (CBT) is an effective treatment for people whose depression has not responded to antidepressants. However, the long-term outcome is unknown. In a long-term follow-up of the CoBalT trial, we examined the clinical and cost-effectiveness of cognitive behavioural therapy as an adjunct to usual care that included medication over 3-5 years in primary care patients with treatment-resistant depression., Methods: CoBalT was a randomised controlled trial done across 73 general practices in three UK centres. CoBalT recruited patients aged 18-75 years who had adhered to antidepressants for at least 6 weeks and had substantial depressive symptoms (Beck Depression Inventory [BDI-II] score ≥14 and met ICD-10 depression criteria). Participants were randomly assigned using a computer generated code, to receive either usual care or CBT in addition to usual care. Patients eligible for the long-term follow-up were those who had not withdrawn by the 12 month follow-up and had given their consent to being re-contacted. Those willing to participate were asked to return the postal questionnaire to the research team. One postal reminder was sent and non-responders were contacted by telephone to complete a brief questionnaire. Data were also collected from general practitioner notes. Follow-up took place at a variable interval after randomisation (3-5 years). The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0-63), analysed by intention to treat. Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs). This study is registered with isrctn.com, number ISRCTN38231611., Findings: Between Nov 4, 2008, and Sept 30, 2010, 469 eligible participants were randomised into the CoBalT study. Of these, 248 individuals completed a long-term follow-up questionnaire and provided data for the primary outcome (136 in the intervention group vs 112 in the usual care group). At follow-up (median 45·5 months [IQR 42·5-51·1]), the intervention group had a mean BDI-II score of 19·2 (SD 13·8) compared with a mean BDI-II score of 23·4 (SD 13·2) for the usual care group (repeated measures analysis over the 46 months: difference in means -4·7 [95% CI -6·4 to -3·0, p<0·001]). Follow-up was, on average, 40 months after therapy ended. The average annual cost of trial CBT per participant was £343 (SD 129). The incremental cost-effectiveness ratio was £5374 per QALY gain. This represented a 92% probability of being cost effective at the National Institute for Health and Care Excellence QALY threshold of £20 000., Interpretation: CBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective., Funding: National Institute for Health Research Health Technology Assessment., (Copyright © 2016 Wiles et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: Fear of negative evaluation (FNE) defines social anxiety yet the process of inferring social evaluation, and its potential role in maintaining social anxiety, is poorly understood. We developed an instrumental learning task to model social evaluation learning, predicting that FNE would specifically bias learning about the self but not others., Methods: During six test blocks (3 self-referential, 3 other-referential), participants (n = 100) met six personas and selected a word from a positive/negative pair to finish their social evaluation sentences "I think [you are / George is]…". Feedback contingencies corresponded to 3 rules, liked, neutral and disliked, with P[positive word correct] = 0.8, 0.5 and 0.2, respectively., Results: As FNE increased participants selected fewer positive words (β = -0.4, 95% CI -0.7, -0.2, p = 0.001), which was strongest in the self-referential condition (FNE × condition 0.28, 95% CI 0.01, 0.54, p = 0.04), and the neutral and dislike rules (FNE × condition × rule, p = 0.07). At low FNE the proportion of positive words selected for self-neutral and self-disliked greatly exceeded the feedback contingency, indicating poor learning, which improved as FNE increased., Conclusions: FNE is associated with differences in processing social-evaluative information specifically about the self. At low FNE this manifests as insensitivity to learning negative self-referential evaluation. High FNE individuals are equally sensitive to learning positive or negative evaluation, which although objectively more accurate, may have detrimental effects on mental health.

Objective: Trials often may report several similar outcomes measured on different test instruments. We explored a method for synthesising treatment effect information both within and between trials and for reporting treatment effects on a common scale as an alternative to standardisation, Study Design: We applied a procedure that simultaneously estimates a pooled treatment effect and the "mapping" ratios between the treatment effects on test instruments in a connected network. Standardised and non-standardised treatment effects were compared. The methods were illustrated in a dataset of 22 trials of selective serotonin reuptake inhibitors against placebo for social anxiety disorder, each reporting treatment effects on between one and six of a total nine test instruments., Results: Ratios of treatment effects on different test instruments varied from trial to trial, with a coefficient of variation of 18% (95% credible interval 11-29%). Standardised effect models fitted the data less well, and standardised treatment effects were estimated with less relative precision than non-standardised effects and with greater relative heterogeneity., Conclusion: Simultaneous synthesis of treatment effects and mapping to a common scale make fewer assumptions than standardising by dividing effects by the sample standard deviation, allow results to be reported on a common scale, and deliver estimates with superior relative precision., (© 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd.)

Background: Psychotic experiences are prevalent in community samples and are highly correlated with depressive symptoms. This study aimed to investigate the longitudinal associations between psychotic experiences and depressive symptoms between adolescence and young adulthood., Method: Prospective cohort study with a 6 year follow-up in a community sample of 7632 adolescents and young adults. Depressive symptoms were assessed with the Short Moods and Feelings Questionnaire and psychotic experiences with a semi-structured clinical interview at 12 and 18 years. Longitudinal and cross-sectional associations were investigated with regression and structural equation models., Results: Depressive symptoms and psychotic experiences were associated at each time-point (12 years r = 0.486 [95% CI 0.457, 0.515]; 18 years r = 0.286 [95% CI 0.233, 0.339]) and there were longitudinal within-phenotype associations (depressive symptoms r = 0.252 [95% CI 0.205, 0.299]; psychotic experiences r = 0.662 [95% CI 0.595, 0.729]). There was an across-phenotype association between psychotic experiences at 12 and depressive symptoms at 18 r = 0.139 [95% CI 0.086, 0.192; p<0.001], but no association between depressive symptoms at 12 and psychotic experiences at 18 r = -0.022 [95% CI -0.032, 0.077; p = 0.891]., Conclusions: Longitudinal across-phenotype associations were substantially weaker than cross-sectional associations or within-phenotype longitudinal associations. Whilst psychotic experiences at 12 years were associated with a small increase in depression at 18 years, depression at 12 years was not associated with psychotic experiences at 18 years once across-phenotype cross-sectional and within-phenotype longitudinal associations were accounted for. This suggests that the biological mechanisms underlying depression at this age do not increase subsequent risk of psychotic experiences once they resolve.

Objectives: A new method is presented for both synthesizing treatment effects on multiple outcomes subject to measurement error and estimating coherent mapping coefficients between all outcomes. It can be applied to sets of trials reporting different combinations of patient- or clinician-reported outcomes, including both disease-specific measures and generic health-related quality-of-life measures. It is underpinned by a structural equation model that includes measurement error and latent common treatment effect factor. Treatment effects can be expressed on any of the test instruments that have been used., Methods: This is illustrated in a synthesis of eight placebo-controlled trials of TNF-α inhibitors in ankylosing spondylitis, each reporting treatment effects on between two and five of a total six test instruments., Results: The method has advantages over other methods for synthesis of multiple outcome data, including standardization and multivariate normal synthesis. Unlike standardization, it allows synthesis of treatment effect information from test instruments sensitive to different underlying constructs. It represents a special case of previously proposed multivariate normal models for evidence synthesis, but unlike the former, it also estimates mappings. Combining synthesis and mapping as a single operation makes more efficient use of available data than do current mapping methods and generates treatment effects that are consistent with the mappings. A limitation, however, is that it can only generate mappings to and from those instruments on which some trial data exist., Conclusions: The method should be assessed in a wide range of data sets on different clinical conditions, before it can be used routinely in health technology assessment., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Importance: Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention., Objective: To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression., Design, Setting, and Participants: Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring., Main Outcomes and Measures: Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision., Results: Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression., Conclusions and Relevance: The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

OBJECTIVE The authors examined the development of psychotic experiences and psychotic disorders in a large population-based sample of young adults and explored their relationship to psychotic phenomena earlier in childhood. METHOD The authors conducted a longitudinal birth cohort study of individuals assessed with the semistructured Psychosis-Like Symptom Interviews at ages 12 and 18 years. RESULTS Of the 4,724 individuals interviewed at age 18, 433 (9.2%) had either suspected (N=203 [4.3%]) or definite (N=230 [4.9%]) psychotic experiences. Of these, 79 (1.7%) met criteria for a psychotic disorder, and of those, only 50% sought professional help. All psychotic outcomes were more likely in young women and in those from socioeconomically disadvantaged backgrounds. Of the participants who had psychotic experiences at age 12, 78.7% had remitted by age 18. The risk of psychotic disorders at age 18 was greater in those with suspected (odds ratio=5.6, 95% CI=2.6-12.1) and especially in those with definite (odds ratio=12.7, 95% CI=6.2-26.1) psychotic experiences at age 12, and also among those with psychotic experiences at age 12 attributed to sleep or fever or with nonpsychotic experiences such as depersonalization. The positive predictive values for increasing frequency of experiences at age 12 predicting psychotic disorders at age 18 ranged from 5.5% to 22.8%. CONCLUSIONS Despite evidence for a continuum of psychotic experiences from as early as age 12, positive predictive values for predicting psychotic disorders were too low to offer real potential for targeted interventions. Psychotic disorders in young adults are relatively uncommon, but they constitute an important unmet need for care given that half of the individuals in this study who met criteria for a psychiatric disorder had not sought help for these problems despite high levels of associated distress and impairment.

The purpose of this study was to evaluate the use of rectal gluten challenge in the diagnosis of coeliac disease. A total of 103 patients with features suggestive of this diagnosis were prospectively enrolled into the study; a diagnosis of coeliac disease was based on strictly defined criteria used in judging the proximal jejunal biopsy. On that basis, 45 out of the 103 patients were deemed to have coeliac disease. A slurry of gluten powder in physiological saline was introduced into the rectum, and biopsies taken before and at 2 h or 4 h after the challenge were examined immunohistochemically by computerized image analysis. Cell counts were analysed by logistic regression, and the best equations were obtained for each challenge group. The 2 h challenge yielded diagnostic sensitivity and specificity of 69.6% and 78.6% respectively. The 4 h challenge provided sensitivity and specificity of 100% and 100% respectively. These results were compared with other clinical diagnostic predictors,including anti-endomysial antibodies, which yielded diagnostic sensitivity and specificity of 70% and 98% respectively. It is concluded that a 4 h rectal challenge is a highly sensitive means of identifying gluten-sensitized individuals, and would be of particular value in cases showing negative antibody screening or equivocal biopsy appearances.

Objective: A pilot study to explore diet-related atherogenic patterns in continuous ambulatory peritoneal dialysis (CAPD) patients on the island of Crete. Cretans are well known for their high olive consumption and low atherosclerotic heart disease mortality, in general., Design: Case-control study., Setting: This was a hospital-based study initiated in 1991. Catchment area was the island of Crete, Greece., Participants: Seventeen patients admitted for treatment to the General State Hospital of Rethimnon. Controls were selected from the general population of the island and consisted of a random sample of 27 subjects from a total of 168 healthy subjects who visited the Preventive Medicine Clinic of the University Hospital for routine check-up. The control group was age- and sex-matched with patients. Both CAPD patients and controls had been residents of Crete for at least the last 10 years., Main Outcome Measures: Adipose tissue was aspirated, and a 12-hour fasting blood sample was collected for determination of serum lipid parameters and serum alpha-tocopherol levels; dietary data from a 3-day recall were recorded., Results: No significant differences between the two groups were observed with respect to the mean macronutrient intake. The mean levels of serum triglycerides (p = 0.016) and serum alpha-tocopherol (p = 0.001) were significantly higher in CAPD patients compared to controls. Mean levels of total serum cholesterol, high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol were not significantly different. In CAPD patients the mean total percentage of monounsaturated fatty acids (MUFA) was significantly higher (p = 0.006) than in controls. The mean total percentage of saturated fatty acids (p = 0.004), along with the mean percentage of omega-6 (p = 0.002), the mean value of the ratio omega-6/omega-3 (p < 0.0001), and the percentage of linoleic acid (p = 0.001) were significantly lower in CAPD patients than in the controls. Among subjects with higher levels of MUFA in the adipose tissue, the CAPD patients were twice as likely to have high serum alpha-tocopherol (p < 0.001), and 2.6 times more likely to be in high risk of high total cholesterol (TC)/HDL (p = 0.08) compared to the controls. However, CAPD patients with high levels of MUFA in the adipose tissue (above the average of 65%) were unlikely [odds ratio (OR) = 0.001, p < 0.001] to be at risk of high TC/HDL (above the average of 4.1), and maybe unlikely (OR = 0.08, but p = 0.1) to have low serum alpha-tocopherol, when compared with the CAPD patients with low levels of MUFA. CAPD patients with high TC/HDL are 0.15 times less likely (p = 0.1) to have high levels of serum alpha-tocopherol compared to those with low TC/HDL., Conclusion: Cretan CAPD patients demonstrate an interesting profile consisting of unexpectedly positive aspects when atherogenesis-related factors such as those of adipose tissue fatty acid composition, serum lipids, and serum antioxidant alpha-tocopherol are considered.

Spectral analysis of heart rate variability (HRV) was used to assess changes in autonomic function before and during postural tilt in 28 syncopal patients: 14 (group A) with positive and 14 (group B) with negative tilting test, and 14 normal controls (group C). Frequency-domain measurements of the high (HF) and low (LF) frequency bands and the ratio LF/HF were derived from Holter recordings, computed by Fast Fourier analysis for 4-minute intervals immediately before tilt testing, immediately after tilting, and just before the end of the test. In group A, the mean values of LF and HF decreased slightly in response to tilting while the LF/HF ratio increased, though these changes were not statistically significant. All parameters showed a statistically significant increase just before the onset of syncope. In group B, there were no significant changes in the parameters measured throughout the test. In group C, there was an increase in the LF and LF/HF ratio and a decrease in the HF immediately after tilting. There were no further significant changes in any of the parameters during the test. Syncopal patients have a different pattern of response to the orthostatic stimulus, in that they do not show the increase in sympathetic tone observed in normal individuals immediately after tilting. In the patients with a positive tilt test, there is a shift in the balance of ANS activity towards the sympathetic system shortly before the onset of syncope.