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Aims and hypothesisWe hypothesised that there would be an association between maintaining a routine during lockdown and both lower emotional and behavioural difficulties in children and lower parental anxiety. We also hypothesised that children of ‘keyworker’ parents would have fewer emotional and behavioural symptoms due to having maintained more normal routines.BackgroundThe Covid-19 pandemic and related public health measures have impacted on mental health of children.MethodsWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to explore associations between maintaining a routine, and emotional and behavioural difficulties in children, using linear regression models. We included measures of parental anxiety. We separately explored associations with having a keyworker parent. We used the Carey Infant Temperament Questionnaire and the Revised Rutter Parent Scale for Preschool Children to establish levels of emotional and behavioural difficulties.Results289 parents completed questionnaires about their 411 children. Keeping a routine was associated with emotional and behavioural difficulty scores 5.0 points lower (95% CI -10.0 to - 0.1), p=0.045 than not keeping a routine. Parents who reported keeping a routine had anxiety scores 4.3 points lower (95% CI -7.5 to -1.1), p=0.009 than those who did not. Children of keyworkers tended to have lower emotional and behavioural difficulty scores (−3.1 (95%CI -6.26 to 0.08), p=0.056) than children of non-keyworkers. All models were adjusted for relevant potential confounders.ConclusionMaintaining a routine may be beneficial for both child emotional wellbeing and parental anxiety, although it is also possible that lower parental anxiety levels made maintaining a routine easier. Being the child of a keyworker parent during lockdown may have been protective for child emotional wellbeing.

BackgroundPsychotic 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.AimsTo investigate how longitudinal profiles of psychotic experiences, created from assessments at three different time points, are influenced by early life and co-occurring factors.MethodUsing 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.ResultsFollowing 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.ConclusionsThese 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.

BackgroundDespite a growing number of prescriptions for antidepressants (over 70 million in 2018), there is uncertainty about when people with depression might benefit from antidepressant medication and concern that antidepressants are prescribed unnecessarily.ObjectivesThe main objective of the PANDA (What are the indications for Prescribing ANtiDepressAnts that will lead to a clinical benefit?) research programme was to provide more guidance about when antidepressants are likely to benefit people with depression. We aimed to estimate the minimal clinically important difference for commonly used self-administered scales for depression and anxiety, and to understand more about how patients respond to such assessments. We carried out an observational study of patients with depressive symptoms and a placebo-controlled randomised controlled trial of sertraline versus placebo to estimate the treatment effect in UK primary care. The hypothesis was that the severity and duration of symptoms were related to treatment response.DesignThe programme consisted of three phases. The first phase relied on the secondary analysis of existing data extracted from published trials. The second phase was the PANDA cohort study of patients with depressive symptoms who presented to primary care and were followed up 2, 4 and 6 weeks after a baseline assessment. Both quantitative and qualitative methods were used in the analysis. The third phase was a multicentre randomised placebo-controlled double-blind trial of sertraline versus placebo in patients presenting to primary care with depressive symptoms.SettingUK primary care in Bristol, London, Liverpool and York.ParticipantsPatients aged 18–74 years who were experiencing depressive symptoms in primary care. Eligibility for the PANDA randomised controlled trial included that there was uncertainty about the benefits about treatment with an antidepressant.InterventionsIn the PANDA randomised controlled trial, patients were individually randomised to 100 mg daily of sertraline or an identical placebo. The PANDA cohort study was an observational study.Main outcome measuresDepressive symptoms measured using the Patient Health Questionnaire were the primary outcome for the randomised controlled trial. Other outcomes included anxiety symptoms using the Generalised Anxiety Disorder-7; depressive symptoms using the Beck Depression Inventory, version 2; health-related quality of life; self-reported improvement; and cost-effectiveness.ResultsThe secondary analysis of existing randomised controlled trials [GENetic and clinical Predictors Of treatment response in Depression (GenPod), TREAting Depression with physical activity (TREAD) and Clinical effectiveness and cost-effectiveness of cognitive Behavioural Therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care (CoBalT)] found evidence that the minimal clinically important difference increased as the initial severity of depressive symptoms rose. Our estimates of minimal clinically important difference were a 17% and 18% reduction in Beck Depression Inventory scores for GenPod and TREAD, respectively. In CoBalT, a 32% reduction corresponded to the minimal clinically important difference but the participants in this study had depression that had not responded to antidepressants. In the PANDA study cohort, and from our analyses in existing data, we found that the minimal clinically important difference varies considerably with the initial severity of depressive and anxiety symptoms. Expressing the minimal clinically important difference as a percentage reduction reduces this variation at higher scores, but at low scores the percentage reduction increased substantially. The results from the qualitative studies pointed out many limitations of the Patient Health Questionnaire-9 items in assessing change and recovery from depression. In the PANDA randomised controlled trial, there was no evidence that sertraline resulted in a reduction in depressive symptoms within 6 weeks of randomisation, but there was some evidence of a reduction by 12 weeks. However, sertraline led to a reduction in anxiety symptoms, an improvement of mental health-related quality of life and an increased likelihood of reporting improvement. The mean Patient Health Questionnaire-9 items score at 6 weeks was 7.98 (standard deviation 5.63) in the sertraline group and 8.76 (standard deviation 5.86) in the placebo group (5% relative reduction, 95% confidence interval –7% to 15%;p = 0.41). Of the secondary outcomes, there was strong evidence that sertraline reduced anxiety symptoms (Generalised Anxiety Disorder-7 score reduced by 17% (95% confidence interval 9% to 25%;p = 0.00005). Sertraline had a high probability (> 90%) of being cost-effective at 12 weeks. The PANDA randomised controlled trial found no evidence that treatment response or cost-effectiveness was related to severity or duration of depressive symptoms. The minimal clinically important difference estimates suggested that sertraline’s effect on anxiety, but not on depression, was likely to be clinically important.LimitationsThe results from the randomised controlled trial and the estimates of minimal clinically important difference were not sufficiently precise to provide specific clinical guidance for individuals. We had low power in testing whether or not initial severity and duration of depressive symptoms are related to treatment response.ConclusionsThe results of the trial support the use of sertraline and probably other selective serotonin reuptake inhibitors because of their action in reducing anxiety symptoms and the likelihood of longer-term benefit on depressive symptoms. Sertraline could be prescribed for anxiety symptoms that commonly occur with depression and many patients will experience a clinical benefit. The Patient Health Questionnaire-9 items and similar self-administered scales should not be used on their own to assess clinical outcome, but should be supplemented with further clinical assessment.Future workWe need to examine the longer-term effects of antidepressant treatment. We need more precise estimates of the treatment effects and minimal clinically important difference at different severities to provide more specific guidance for individuals. However, the methods we have developed provide an approach towards providing such detailed guidance.Trial registrationCurrent Controlled Trials ISRCTN84544741 and EudraCT number 2013-003440-22.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full inProgramme Grants for Applied Research; Vol. 7, No. 10. See the NIHR Journals Library website for further project information.

Background: An accurate risk prediction algorithm could improve psychosis outcomes by reducing duration of untreated psychosis. The objective was 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 to 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 individual 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 incidence of psychosis 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 and substance abuse, a history of consultations for suicidal behaviour, smoking history and substance abuse and prescribed medications for depression/anxiety/PTSD/OCD and total number of consultations resulted in good discrimination (Harrell’s C=0.77 after internal validation). Identifying patients with predicted risk exceeding 1% over 6 years had sensitivity of 69% and specificity of 71%. Interpretation: An accurate prediction model for risk of psychosis developed from electronic health records could be used to facilitate early detection of psychosis by family doctors. Funding: NIHR, School for Primary Care Research. Declaration of Interest: None of the authors have any declarations of interest to declare. Ethical Approval: Approval was obtained from the CPRD’s Independent Scientific Advisory Committee.

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.

BackgroundSelf-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.MethodsProspective 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.ResultsThere 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.ConclusionsOur 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.

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.

Background Given the global burden of disease of psychotic disorders and the promise of benefit from early intervention, there is an imperative to understand the developmental trajectories from onset of psychotic experiences to clinical disorder and to improve identification of individuals at greatest risk. The aims of this study therefore were: 1) to describe, for the first time, the change in incidence of psychotic experiences in the general population from childhood through early adulthood; 2) to describe the prevalence and burden of unmet clinical need of at-risk mental states and psychotic disorder among young adults in the general population; 3) to examine the predictive ability of both self-reported and interviewer-rated measures of psychotic experiences during childhood and adolescence in identifying psychotic disorder by early adulthood; and 4) to describe longitudinal profiles of psychotic experiences from childhood through early adulthood and investigate a comprehensive range of childhood determinants of symptom persistence. Methods We used data from the ALSPAC birth cohort study. Psychotic experiences and disorder were assessed using semi-structured interviews 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. Longitudinal profiles were constructed based on interviewer ratings and frequency of experiences, with profiles describing no experiences (62.5%), episodic experiences (26.5%), persistent/recurrent low frequency (9.1%), and persistent/recurrent high frequency (1.9%) groups. Multinomial regression was used to examine risk factors for persistence, covering socio-demographic, genetic, behavioural, cognitive, and psychological characteristics during childhood. Results The incidence rate of psychotic experiences increased between ages 12 and 24, peaking during late adolescence. 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), and the sensitivity was 14.3% (95%CI 4.0, 32.7). Longitudinal profile analysis showed that persistence was highest in those with higher levels of emotional instability and borderline personality traits in childhood, whilst persistence was strongly related to concurrent and increasing levels of social isolation, anxiety, self-harm, and substance use over time. Discussion Our study results show a peak in incidence of psychotic experience during late adolescence just prior to the peak incidence rate for schizophrenia, and an unmet need for care in young people with psychotic disorders. Although we show the potential efficiency of self-report measures for prediction, 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. The primary characteristics indexing whether psychotic experiences are likely to persist over time is the presence of emotion regulation difficulties in childhood, providing evidence of a potentially modifiable target for prevention.

BackgroundSeroprevalence 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.MethodsWe 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.Results919 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.ConclusionSeropositivity 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.

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). Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2253-4) contains supplementary material, which is available to authorized users.

The potential effects of air pollution are a major concern both in terms of the environment and in relation to human health. In order to support environmental policy, there is a need for accurate measurements of the concentrations of pollutants at high geographical resolution over large regions. However, within such regions, there are likely to be areas where the monitoring information will be sparse and so methods are required to accurately predict concentrations. Set within a Bayesian framework, models are developed which exploit the relationships between pollution and geographical covariate information, such as land use, climate and transport variables together with spatial structure. Candidate models are compared based on their ability to predict a set of validation sites. The chosen model is used to perform large-scale prediction of nitrogen dioxide at a 1×1 km resolution for the entire EU. The models allow probabilistic statements to be made with regard to the levels of air pollution that might be e...

Objectives We present a meta-analytic method that combines information on treatment effects from different instruments from a network of randomized trials to estimate instrument relative responsiveness. Study Design and Setting Five depression-test instruments [Beck Depression Inventory (BDI I/II), Patient Health Questionnaire (PHQ9), Hamilton Rating for Depression 17 and 24 items, Montgomery-Asberg Depression Rating] and three generic quality of life measures [EuroQoL (EQ-5D), SF36 mental component summary (SF36 MCS), and physical component summary (SF36 PCS)] were compared. Randomized trials of treatments for depression reporting outcomes on any two or more of these instruments were identified. Information on the within-trial ratios of standardized treatment effects was pooled across the studies to estimate relative responsiveness. Results The between-instrument ratios of standardized treatment effects vary across trials, with a coefficient of variation of 13% (95% credible interval: 6%, 25%). There were important differences between the depression measures, with PHQ9 being the most responsive instrument and BDI the least. Responsiveness of the EQ-5D and SF36 PCS was poor. SF36 MCS performed similarly to depression instruments. Conclusion Information on relative responsiveness of several test instruments can be pooled across networks of trials reporting at least two outcomes, allowing comparison and ranking of test instruments that may never have been compared directly.

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.

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 checkup. 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 α-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 α-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 ω-6 ( p = 0.002), the mean value of the ratio ω-6/ω-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 α-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 α-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 α-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 α-tocopherol are considered.