Registry versus publication: discrepancy of primary outcomes and possible outcome reporting bias in child and adolescent mental health.

Outcome reporting bias is one of the fundamental forms of publication bias. It implies publishing only outcomes that have positive results. The aim of this observational study was to explore primary outcome discrepancies between registry of clinical trials and their corresponding publications, since these can indicate outcome reporting bias in child mental health. Data were extracted from completed interventional clinical trials from ClinicalTrial.gov registry and its Archive site. Trials were registered under "Behaviours and Mental Disorders" category, and conducted on underage participants (0-17 years). Their primary outcomes were compared to those published in publication which had a corresponding NCT number stated in the text. Sixteen percent of trials did not have the minimum information on primary outcome stated in the registry-neither the measure used nor the measurement time points; 38.9% of trials had the minimum information stated to describe primary outcome, while only 3.3% of trials had all the necessary elements stated in the registry. Most of the publication in our sample had positive results (66.4%). Half of the trials registered before completion had non-matching primary outcomes in the registry and publication; 85.4% of trials with non-matching outcomes indicated possible outcome reporting bias for some of the primary outcome. Middle-sized trials and industry-funded trials were related with higher quality of primary outcome registration. Industry funding was related with positive findings in publication. Non-industry funding proved to be the only significant predictor of discrepancy between registered and published primary outcomes, and possible outcome reporting bias. Journal impact factor was not related with any of the outcome measures. The main limitation of the study is that it primarily offers an insight into discrepancy of registered and published outcomes. The methodology does not imply an access to results of unpublished outcomes - therefore, it was not possible to determine the presence of the bias with sufficient certainty in large number of trials. Further research should be done with improved methodology and additional data.

Cohort profile: demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe.

PURPOSE: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. PARTICIPANTS: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be 'markedly ill', 'severely ill' or 'among the most extremely ill' by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. FUTURE PLANS: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. TRIAL REGISTRATION NUMBER: NCT03013595.

Posttraumatic stress disorder symptoms among trauma-exposed adolescents from low- and middle-income countries.

BACKGROUND: Exposure to traumatic events in childhood is associated with the development and maintenance of various psychiatric disorders, but most frequently with posttraumatic stress disorder (PTSD). The aim of this study was to evaluate the types of traumatic events experienced and the presence and predictors of PTSD symptoms among adolescents from the general population from ten low- and middle-income countries (LMICs). METHODS: Data were simultaneously collected from 3370 trauma-exposed adolescents (mean age = 15.41 [SD = 1.65] years, range 12-18; 1465 (43.5%) males and 1905 (56.5%) females) in Brazil, Bulgaria, Croatia, Indonesia, Montenegro, Nigeria, the Palestinian Territories, the Philippines, Romania, and Serbia, with Portugal, a high-income country, as a reference point. The UCLA PTSD Reaction Index for the DSM-5 (PTSD-RI-5) was used for the assessment of traumatic events and PTSD symptoms. RESULTS: The most frequently reported traumatic events were death of a close person (69.7%), witnessing violence other than domestic (40.5%), being in a natural disaster (34.4%) and witnessing violent death or serious injury of a close person (33.9%). In total, 28.5% adolescents endorsed two to three DSM-5 PTSD criteria symptoms. The rates of adolescents with symptoms from all four DSM-5 criteria for PTSD were 6.2-8.1% in Indonesia, Serbia, Bulgaria, and Montenegro, and 9.2-10.5% in Philippines, Croatia and Brazil. From Portugal, 10.7% adolescents fall into this category, while 13.2% and 15.3% for the Palestinian Territories and Nigeria, respectively. A logistic regression model showed that younger age, experiencing war, being forced to have sex, and greater severity of symptoms (persistent avoidance, negative alterations in cognitions and mood, and alterations in arousal and reactivity) were significant predictors of fulfilling full PTSD criteria. CONCLUSIONS: Nearly every third adolescent living in LMICs might have some PTSD symptoms after experiencing a traumatic event, while nearly one in ten might have sufficient symptoms for full DSM-5 PTSD diagnosis. The findings can inform the generation of PTSD burden estimates, allocation of health resources, and designing and implementing psychosocial interventions for PTSD in LMICs.

External locus-of-control partially mediates the association between cumulative trauma exposure and posttraumatic stress symptoms among adolescents from diverse background.

Locus of control (LOC) is a modifiable mediator of symptoms of posttraumatic stress disorder (PTSD) among traumatized individuals and a potential target of intervention. Compared with studies involving adults, the potential mediation effect of LOC on PTSD symptoms among trauma-exposed children and adolescents is relatively under-explored. This study, therefore, assessed the mediation effects of LOC on the association between lifetime cumulative trauma and PTSD symptoms among a large cohort of adolescents from different cultural background.Cross-sectional study.LOC was determined using the Multi-Dimension Locus of Control Scale; Posttraumatic stress symptoms using the UCLA PTSD Reaction Index; and other significant negative life events using the Life Events Checklist.Among 3826 adolescents who completed the study, external LOC explained 24% of variance (R2 = .24; F2,3823 = 619.01; p < .01) in PTSD symptoms and had significant indirect effect on the relationship between self-reported cumulative traumatic event exposure and PTSD symptoms (ß = .14; 95% BC CI [.10, .20]). Moderated mediation results showed significant potentiation of the moderation effects among older adolescents; boys; and those from more affluent families.The study further strengthened the hitherto limited evidence that external LOC partially mediate the relationship between cumulative trauma exposure and PTSD symptoms among adolescents.

Validation of the Transition Readiness and Appropriateness Measure (TRAM) for the Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare in Europe (MILESTONE) study.

OBJECTIVE: Young people moving from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) are faced with significant challenges. To improve this state of affairs, there needs to be a recognition of the problem and initiatives and an urgent requirement for appropriate tools for measuring readiness and outcomes at the transfer boundary (16-18 years of age in Europe). The objective of this study was to develop and validate the Transition Readiness and Appropriateness Measure (TRAM) for assessing a young person's readiness for transition, and their outcomes at the transfer boundary. DESIGN: MILESTONE prospective study. SETTING: Eight European Union (EU) countries participating in the EU-funded MILESTONE study. PARTICIPANTS: The first phase (MILESTONE validation study) involved 100 adolescents (pre-transition), young adults (post-transition), parents/carers and both CAMHS and AMHS clinicians. The second phase (MILESTONE cohort study and nested cluster randomised trial) involved over 1000 young people. RESULTS: The development of the TRAM began with a literature review on transitioning and a review of important items regarding transition by a panel of 34 mental health experts. A list of 64 items of potential importance were identified, which together comprised the TRAM. The psychometric properties of the different versions of the TRAM were evaluated and showed that the TRAM had good reliability for all versions and low-to-moderate correlations when compared with other established instruments and a well-defined factor structure. The main results of the cohort study with the nested cluster randomised trial are not reported. CONCLUSION: The TRAM is a reliable instrument for assessing transition readiness and appropriateness. It highlighted the barriers to a successful transition and informed clinicians, identifying areas which clinicians on both sides of the transfer boundary can work on to ease the transition for the young person. TRIAL REGISTRATION NUMBER: ISRCTN83240263 (Registered 23 July 2015), NCT03013595 (Registered 6 January 2017); Pre-results.

A cross-cultural qualitative study of the ethical aspects in the transition from child mental health services to adult mental health services.

BACKGROUND: Transitioning from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) raises novel ethical aspects for healthcare professionals, as well as for young people, their parents and carers. METHOD: Focus groups were conducted in Croatia, Ireland and the United Kingdom with youth mental health groups and youth representatives with no mental health (MH) remit. One hundred and eleven participants, aged from 16 to 60 years, contributed to discussions. RESULTS: Perpetuation of stigma, autonomy and decision-making were central themes as both enablers and deterrents of successful transition. The tension between professional (and at times parental) paternalism and young persons' growing autonomy was well captured in the themes; (a) desired practice, (b) who should decide, (c) the process of decision-making and (d) potential harm(s). CONCLUSIONS: This study provides insight into the ethical values, particularly autonomy and collaboratively working, which people expect to underpin the transition between CAMHS and AMHS. KEY PRACTITIONER MESSAGE: Engaging young people early in making decisions about their future care can enhance trust between practitioner and the young person. In addition to diagnosis, a number of factors (such as moving home; waiting lists and stigma) may need to be taken into account when considering the direction of future health care. When possible, alternatives to AMHS should be considered if considered by the young person to be a less-stigmatising treatment option.

Low dissemination rates, non-transparency of trial premature cessation and late registration in child mental health: observational study of registered interventional trials.

The aim of this observational study was to explore trial premature cessation, non-publication and trial registration time in child mental health. Data were extracted for "closed" trials in Clinicaltrials.gov registry and European Union Clinical Trial Register (EUCTR) and corresponding publications of completed trials indexed in three data bases (PubMed, Scopus and Google Scholar). We restricted the extraction to the 'Behaviours and Mental Disorders' category and participants' age of 0-17 years. Outcome measures were trial completion, results reporting within a year after the trial completion, publishing an article in a peer-reviewed journal within an average time to publish (729 days), and registration time. The number of EUCTR trials was relatively small (n = 35) and with many inconsistencies. Out of 827 "closed" trials extracted from ClinicalTrials.gov, 69% were completed, 24.2% of prematurely ceased trials did not report reasons for early termination, 12.2% of the completed trials had results reported within a year, and 29.3% had an article published within 24 months after completion. Middle-sized (100-499 participants) and behavioural trials had higher chances of being successfully completed. Middle-sized and industry-funded trials were associated with results reporting. Chances for publishing an article were lower for industry-funded trials. Industry funding and drug interventions were related to timely registration. Large sample and non-industry funding were related to retrospective registration, which was recorded more often in recent years than before (we observed trials registered from 2002 until 2017). This study found low dissemination rates in the field of child mental health, with worrying under-reporting of premature termination causes. These findings indicate that more children are being subjected to unnecessary risk that comes with trial participation.

ESSENCE-Q: Slavic language versions for developmental screening in young children.

PURPOSE: The Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - Questionnaire (ESSENCE-Q) was developed as a brief screener to identify children with developmental concerns who might have neurodevelopmental disorders (NDDs). This study aimed to translate the ESSENCE-Q into south Slavic languages, namely, Bosnian, Bulgarian, Croatian, Macedonian, Montenegrin, Serbian, and Slovenian, and to evaluate its psychometric properties for screening purposes in clinical settings. PATIENTS AND METHODS: In the study, the ESSENCE-Q was completed for 251 "typically developing" children and 200 children with 1 or more diagnosed NDDs, all aged 1-6 years. Internal consistency and construct validity were tested first, followed by generating receiver operating characteristic curves and the area under the curve. Optimal cutoff values were then explored. RESULTS: The Cronbach's α coefficients were 0.91, 0.88, and 0.86 for ESSENCE-Q parent-completed form, and the telephone and direct interview forms administered by trained nurse or specialist, respectively. The 3 versions produced area under the curve values (95% confidence interval): 0.96 (0.93-0.99), 0.91 (0.86-0.95), and 0.91 (0.86-0.97), respectively. An optimal cutoff for ESSENCE-Q parent-completed form was found to be ≥3 points, while for the telephone and direct interviews, it was ≥5 points. CONCLUSION: We found adequate measurement properties of the south Slavic languages versions of the ESSENCE-Q as a screener for NDDs in clinical settings. This study provided additional data supporting sound psychometric properties of the ESSENCE-Q.

Protocol for a cohort study of adolescent mental health service users with a nested cluster randomised controlled trial to assess the clinical and cost-effectiveness of managed transition in improving transitions from child to adult mental health services (the MILESTONE study).

INTRODUCTION: Disruption of care during transition from child and adolescent mental health services (CAMHS) to adult mental health services may adversely affect the health and well-being of service users. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare) study evaluates the longitudinal course and outcomes of adolescents approaching the transition boundary (TB) of their CAMHS and determines the effectiveness of the model of managed transition in improving outcomes, compared with usual care. METHODS AND ANALYSIS: This is a cohort study with a nested cluster randomised controlled trial. Recruited CAMHS have been randomised to provide either (1) managed transition using the Transition Readiness and Appropriateness Measure score summary as a decision aid, or (2) usual care for young people reaching the TB. Participants are young people within 1 year of reaching the TB of their CAMHS in eight European countries; one parent/carer and a CAMHS clinician for each recruited young person; and adult mental health clinician or other community-based care provider, if young person transitions. The primary outcome is Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) measuring health and social functioning at 15 months postintervention. The secondary outcomes include mental health, quality of life, transition experience and healthcare usage assessed at 9, 15 and 24 months postintervention. With a mean cluster size of 21, a total of 840 participants randomised in a 1:2 intervention to control are required, providing 89% power to detect a difference in HoNOSCA score of 0.30 SD. The addition of 210 recruits for the cohort study ensures sufficient power for studying predictors, resulting in 1050 participants and an approximate 1:3 randomisation. ETHICS AND DISSEMINATION: The study protocol was approved by the UK National Research Ethics Service (15/WM/0052) and equivalent ethics boards in participating countries. Results will be reported at conferences, in peer-reviewed publications and to all relevant stakeholder groups. TRIAL REGISTRATION NUMBER: ISRCTN83240263; NCT03013595 (pre-results).

Can we really use available scales for child and adolescent psychopathology across cultures? A systematic review of cross-cultural measurement invariance data.

In this systematic review, we assessed available evidence for cross-cultural measurement invariance of assessment scales for child and adolescent psychopathology as an indicator of cross-cultural validity. A literature search was conducted using the Medline, PsychInfo, Scopus, Web of Science, and Google Scholar databases. Cross-cultural measurement invariance data was available for 26 scales. Based on the aggregation of the evidence from the studies under review, none of the evaluated scales have strong evidence for cross-cultural validity and suitability for cross-cultural comparison. A few of the studies showed a moderate level of measurement invariance for some scales (such as the Fear Survey Schedule for Children-Revised, Multidimensional Anxiety Scale for Children, Revised Child Anxiety and Depression Scale, Revised Children's Manifest Anxiety Scale, Mood and Feelings Questionnaire, and Disruptive Behavior Rating Scale), which may make them suitable in cross-cultural comparative studies. The remainder of the scales either showed weak or outright lack of measurement invariance. This review showed only limited testing for measurement invariance across cultural groups of scales for pediatric psychopathology, with evidence of cross-cultural validity for only a few scales. This study also revealed a need to improve practices of statistical analysis reporting in testing measurement invariance. Implications for future research are discussed.

Risk factors associated with postoperative pain after ophthalmic surgery: a prospective study.

BACKGROUND: Risk factors associated with postoperative pain intensity and duration, as well as consumption of analgesics after ophthalmic surgery are poorly understood. METHODS: A prospective study was conducted among adults (N=226) who underwent eye surgery at the University Hospital Split, Croatia. A day before the surgery, the patients filled out questionnaires assessing personality, anxiety, pain catastrophizing, sociodemographics and were given details about the procedure, anesthesia, and analgesia for each postoperative day. All scales were previously used for the Croatian population. The intensity of pain was measured using a numerical rating scale from 0 to 10, where 0 was no pain and 10 was the worst imaginable pain. The intensity of pain was measured before the surgery and then 1 hour, 3 hours, 6 hours, and 24 hours after surgery, and then once a day until discharge from the hospital. Univariate and multivariate analyses were performed. RESULTS: A multivariate analysis indicated that independent predictors of average pain intensity after the surgery were: absence of premedication before surgery, surgery in general anesthesia, higher pain intensity before surgery and pain catastrophizing level. Independent predictors of postoperative pain duration were intensity of pain before surgery, type of anesthesia, and self-assessment of health. Independent predictors of pain intensity ≥5 during the first 6 hours after the procedure were the type of procedure, self-assessment of health, premedication, and the level of pain catastrophizing. CONCLUSION: Awareness about independent predictors associated with average postoperative pain intensity, postoperative pain duration, and occurrence of intensive pain after surgery may help health workers to improve postoperative pain management in ophthalmic surgery.