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**Background:** Psoriasis is a chronic inflammatory skin condition that impacts quality of life and requires long-term treatment and effective symptom management. Interleukin-23 (IL-23) has emerged as a key player in the pathogenesis of psoriasis and tildrakizumab and guselkumab are both immunomodulatory agents that inhibit the p19 subunit of IL-23. In its pivotal Phase III trial, tildrakizumab demonstrated greater efficacy than etanercept in moderate-to-severe psoriasis. However, there are no head-to-head trials comparing tildrakizumab with guselkumab. **Methods:** We conducted a systematic literature review and Bucher indirect comparison of tildrakizumab and guselkumab, using placebo as a common comparator. We searched MEDLINE, MEDLINE In-Process, MEDLINE(R) Daily Epub Ahead of Print, and Cochrane Central Register of Controlled Trials for Phase III randomized controlled trials between 1946 and November 2018. Inclusion criteria were adult patients ≥18 years with moderate-to-severe chronic plaque psoriasis, and intervention with tildrakizumab or guselkumab compared to placebo or best supportive care. Outcomes included were severity of psoriasis as defined by the Psoriasis Area and Severity Index (PASI) 75 and PASI 90, frequency of serious adverse events (SAEs), and treatment discontinuations. Outcomes were evaluated at Weeks 12 to 16 and 24 to 28. Analysis was based on the intent-to-treat population and, for all outcomes, the number of events reported were analyzed as a proportion of the number of patients randomized to ensure consistency across trials. **Results:** Overall, 154 unique records were identified. Five studies met the eligibility criteria and were included in the analysis; two tildrakizumab trials (reSURFACE 1 and reSURFACE 2) and three guselkumab trials (VOYAGE 1, VOYAGE 2, and a Japanese study). There was no statistically significant difference between guselkumab and tildrakizumab for PASI 75, PASI 90, SAEs, and rate of discontinuations at either timepoint. **Conclusion:** This study assessed the comparative efficacy of tildrakizumab and guselkumab for the treatment of moderate-to-severe psoriasis. Limitations included the limited number of publications, imputation of placebo arm values for Weeks 24 to 28, and limited relevance of the Japanese study. This indirect comparison does not provide evidence that one treatment is superior to the other.

Objective School-age children with attention-deficit/hyperactivity disorder (ADHD) have reduced health-related quality of life (HRQoL), but it is unclear whether this is also true for preschool children. It is unknown whether parent training (PT) improves HRQoL. This study compared HRQoL in preschool children with ADHD with age-matched children from the general population; examined whether PT improves HRQoL; and tested if treatment-related changes in HRQoL were mediated by improvements in ADHD, parent efficacy, and family stress. Method Parents of 164 children age 3–7 years with an ADHD diagnosis participated in a randomized controlled trial comparing the New Forest Parenting Programme and treatment as usual. Measures of HRQoL, ADHD, parent efficacy, and family stress were completed at baseline, posttreatment, and 36-week follow-up. Child baseline HRQoL was compared with 2 general population-based reference groups. PT effects were analyzed using linear models and mediation analyses. Results Preschoolers with ADHD had lower HRQoL than the reference groups. The New Forest Parenting Programme, but not treatment as usual, was associated with improvement in psychosocial HRQoL at posttreatment (change 2.28, 95% CI [0.78, 3.77]) and at 36-week follow-up (change 2.05, 95% CI [0.56, 3.54]). This difference between treatment arms was not statistically significant. Parent efficacy and family stress scores at posttreatment significantly mediated improvements in HRQoL at 36-week follow-up; ADHD scores at posttreatment did not. Conclusion ADHD negatively impacts HRQoL in early childhood. PT for ADHD has the potential to improve HRQoL independently of its effects on ADHD symptoms. Clinical trial registration information A Controlled Study of Parent Training in the Treatment of ADHD in Young Children (D’SNAPP); http://clinicaltrial.gov/ ; NCT01684644.

BACKGROUND: A growing number of adults are receiving pharmacological treatment for ADHD but a sizable proportion also discontinues or have gaps in treatment. The primary aims of this study were to identify how many patients treated for ADHD in adulthood, have at least one event of discontinuation in treatment and to identify possible associated variables.METHODS: Within the Danish population aged 18-60 years on the 1st of January 2013, we identified the number of individuals who had been prescribed ADHD-medication at least once during the 1st of January 2002-31st of December 2013 using Danish register data. Among those who filed more than one prescription, treatment discontinuation was defined as having more than 211 days between two prescriptions. In crude and adjusted logistic regression analysis, we explored potential associations to discontinuation for variables such as gender and age at treatment initiation.RESULTS: In a population, if N = 3,165,844 individuals, n = 42,892 had received at least one prescription for ADHD medication. Among those with more than one prescription ( N = 38,289), 29.4% had discontinued their treatment at least once, according to our definition of treatment discontinuation. ADHD treatment discontinuation was associated with being male, unemployment, lower educational attainment, receiving incapacity benefits and younger age at treatment initiation ( p CONCLUSIONS: A large proportion of individuals treated for ADHD had at least one discontinuation of treatment according to our definition. Although the present study does not allow for investigating the direction of these effects, nor whether some patients later resumed treatment, having at least one discontinuation was associated with a range of variables relating to e.g. age and gender, and provides an emerging profile for clinicians of patients more likely to discontinue.

Aim Attention Deficit Hyperactivity Disorder (ADHD) is a lifespan disorder associated with considerable economic cost. While the economic burden of ADHD has been widely estimated, there is considerable variation in reported costs between studies, which typically focus on health outcomes only, lack adequate control and fail to correct for the influence of genetic and shared environmental factors. The aim of this study is to overcome these limitations to reach a fuller understanding of the economic burden of ADHD. Method Using the Danish National Registers 5269 adults with a diagnosis of ADHD in adulthood who had not received a diagnosis in childhood were identified. Excluding cases with missing data, comorbid diagnoses, and cases without a same sex sibling free of any diagnosed psychiatric diagnoses, a final cohort was formed consisting of 460 sibling dyads. Using a cross-sectional method focusing on the year 2010, cost differences between each adult with ADHD and their sibling were calculated from data retrieved from health, education, crime, employment and social care registers. Results Adults with ADHD had considerably lower disposable income and paid less tax than their siblings. They also received more state benefits, had higher costs for health, social care, and crime than their siblings. The total average costs difference for the year 2010 was 20,134 euros more than their sibling for each adult with ADHD. Conclusion ADHD is associated with considerable costs which are borne by both the individual and the state and underlines the need to consider the wider economic impact of ADHD beyond income and healthcare utilisation costs.

Objective: Parent training is recommended for attention-deficit/hyperactivity disorder (ADHD) in preschool children. Evidence-based interventions are important, but only if they produce better outcomes than usual care. Method: The authors conducted a multicenter, 2-arm, parallel-group, randomized controlled trial in routine specialist ADHD clinics in the Danish Child and Adolescent Mental Health Services. Children (N = 164, 3–7 years old) with ADHD received a well-established parent training program (New Forest Parenting Programme; n = 88) or treatment as usual (n = 76). The primary outcome was parent ratings of child ADHD symptoms. Secondary outcomes included teacher ratings and direct observations of ADHD symptoms. Outcomes were measured at baseline, after treatment, and at follow-up (36 weeks later). Representativeness of participants was evaluated against the total national cohort of children (N = 1,378, 3–7 years old) diagnosed with ADHD during the same period using the Danish Civil Registration System. Statistical analysis used a repeated measure model. Results: After treatment, the parent training program was superior to treatment as usual on parent-rated ADHD symptoms (p =.009; effect size d = 0.30) and on parenting self-efficacy and family strain. Effects persisted to 36 weeks after treatment. There were no effects on teacher ratings or direct observations of ADHD or on ratings of conduct problems or parenting. The clinical sample was similar to the national cohort of young children with ADHD. Conclusion: Evidence-based parent training has value as an intervention for preschool ADHD in routine clinical settings. As in previous trials, effects were restricted to parent-reported outcomes. Surprisingly, there were no effects on child conduct problems. Clinical trial registration information: A Controlled Study of Parent Training in the Treatment of ADHD in Young Children (D'SNAPP). http://clinicaltrial.gov/; NCT01684644.

Background ADHD is a debilitating disorder with symptoms often appearing in early childhood. To facilitate early identification, developmentally appropriate and validated assessment tools for the preschool-age are needed. Aims The current study aims to examine the psychometric properties of the ADHD Rating Scale (RS)-IV Preschool Version (-P) in a Danish community sample and provide national standardisation data. Methods and procedures Parents (n = 916) and kindergarten teachers (n = 275) of preschool children, aged 3–5 years, completed the ADHD RS-IV-P. Outcomes and results Confirmatory factor analysis indicated that a three-factor model (inattention, hyperactivity, and impulsivity) best fit the data regardless of rater. Scales generally showed acceptable internal consistency, test-retest reliability, inter-rater reliability, and criterion validity. Boys received higher ratings on the ADHD RS-IV-P than girls and younger preschool children were rated as more inattentive than older preschool children. Conclusions and implications Our findings support the reliability and validity of the ADHD RS-IV-P and a three-factor model of ADHD. However, high factor correlations and similarity in model fit suggest that more research is needed to clarify the organisation of ADHD symptoms in preschool children. Furthermore, the external validity of separate ADHD dimensions at this age should be examined.

The New Forest Parenting Programme (NFPP) is a parenting program developed for parents who have a child with attention-deficit hyperactivity disorder (ADHD). It is a manualized program that is delivered in a parent's home over 8 weeks, or in a group format, or through a self-help manual. Three randomized controlled trials have been carried out in the United Kingdom. The NFPP group has adapted the program according to feedback from parents and therapists, and for use with different populations, both within the United Kingdom and internationally. The first international trial took place in New York, United States. Trials in Denmark, Hong Kong, and Japan followed. More recently, a trial of the self-help manual has been carried out in mainland China. This paper will outline the adaptions that were needed in order to be able to deliver the program in different countries with their own expectations of parenting, culture, and language. Training had to be differently focused; manuals and handouts had to be revised, translated and back-translated; and supervision had to be delivered at a distance to maintain the fidelity of the program. The international group will outline their experience of running trials in their own countries with the NFPP in a face-to-face format (Denmark), a group format (Hong Kong and Japan), and a self-help format (mainland China).

Background: Parent training is recommended as the first-line treatment for attention-deficit/hyperactivity disorder (ADHD) in preschool children. The New Forest Parenting Programme (NFPP) is an evidence-based parenting program developed specifically to target preschool ADHD.Objective: The objective of this trial is to investigate whether the NFPP can be effectively delivered for children referred through official community pathways in everyday clinical practice.Methods: A multicenter randomized controlled parallel arm trial design is employed. There are two treatment arms, NFPP and treatment as usual. NFPP consists of eight individually delivered parenting sessions, where the child attends during three of the sessions. Outcomes are examined at three time points (T1, T2, T3): T1 (baseline), T2 (week 12, post intervention), and T3 (6 month follow/up). 140 children between the ages of 3-7, with a clinical diagnosis of ADHD, informed by the Development and Well Being Assessment, and recruited from three child and adolescent psychiatry departments in Denmark will take part. Randomization is on a 1:1 basis, stratified for age and gender.Results: The primary endpoint is change in ADHD symptoms as measured by the Preschool ADHD-Rating Scale (ADHD-RS) by T2. Secondary outcome measures include: effects on this measure at T3 and T2 and T3 measures of teacher reported Preschool ADHD-RS scores, parent and teacher rated scores on the Strength & Difficulties Questionnaire, direct observation of ADHD behaviors during Child’s Solo Play, observation of parent-child interaction, parent sense of competence, and family stress. Results will be reported using the standards set out in the Consolidated Standards of Reporting Trials Statement for Randomized Controlled Trials of nonpharmacological treatments.Conclusions: The trial will provide evidence as to whether NFPP is a more effective treatment for preschool ADHD than the treatment usually offered in everyday clinical practice.Trial Registration: ClinicalTrials.gov NCT01684644; https://clinicaltrials.gov/ct2/show/NCT01684644?term= NCT01684644&rank=1

The rapid increase in recent years in the number of children and adults accessing care for ADHD (Attention Deficit Hyperactivity Disorder), raises a number of questions. It is unclear whether the increase is due to an increased public and professional recognition and awareness of ADHD as a debilitating human condition or to an actual increase in the incidence of individuals suffering from ADHD. Depending on the reasons behind the increased burden on services, and whether more effective treatments can be found, the future costs to society could be enormous. The study presented in this book estimates the private and social costs of ADHD. The key focus of this book is to study the costs related to individuals with ADHD who have not been diagnosed and who have not received treatment. In this respect, the study makes a unique contribution to scientific knowledge by investigating the cost of untreated ADHD. The study investigates the extent to which individuals with undiagnosed ADHD in childhood fare differently compared to otherwise similar individuals without ADHD. A long list of important parameters in an individual's life, e.g. educational attainment, occupational status, income, family situation, criminal record, health is examined. The results of the study provide not just cost estimates of ADHD; per se, but also create a point of reference which will be highly relevant for the evaluation of any future treatment for ADHD. The clear picture emerging from this study is that ADHD is associated with considerable private and social costs, reflecting that Adults with ADHD exhibit weak performance across all applied measures. These findings remain even when adults with ADHD are compared to a control group of their own siblings Even though the study is performed for Denmark it is argued that generalizability of the established results beyond Denmark is valid. Contributors to this volume - Torben Tranaes Anders Sorensen

ObjectivesParent training is recommended as first-line treatment for ADHD in preschool children. The New Forest Parenting Programme (NFPP) is an evidence-based parenting program developed specifically to target preschool ADHD. This talk will present fresh results from a multicenter trial designed to investigate whether the NFPP can be delivered effectively for children who are referred through official community pathways in everyday clinical practice.MethodsA multicenter randomized controlled parallel arm trial design was incorporated. There were two treatment arms, NFPP and treatment as usual. NFPP consisted of eight individually delivered parenting sessions where the child attended three of the sessions. Outcomes were examined at three time points as follows: T1, baseline; T2, week 12, postintervention; and T3, 6-month follow-up. Children (N = 165; ages 3–7 years) with a clinical diagnosis of ADHD, informed by the Development and Well-Being Assessment (DAWBA), were recruited from three child and adolescent psychiatry departments in Denmark. Randomization was on a 1:1 basis and stratified for age and gender.ResultsThe primary endpoint showed a change in ADHD symptoms as measured by the Preschool ADHD-Rating Scale (Preschool ADHD-RS) by T2. Secondary outcome measures included the following: effects on this measure at T3; T2 and T3 measures of teacher-reported preschool ADHD-RS scores; parent- and teacher-rated scores on the Strength and Difficulties Questionnaire; direct observation of ADHD behaviors during child’s solo play; observation of parent–child interaction; parent sense of competence; and family stress.ConclusionsThis trial will provide evidence on whether NFPP is a more effective treatment for preschool ADHD than the treatment usually offered in everyday clinical practice.

This paper discusses the application of economic appraisal in pre-natal screening. In particular it examines the way in which economists to date have attempted to measure and value the benefits of pre-natal screening. The authors argue that there are problems with existing approaches particularly in terms of the nature of women's utility functions and which arguments are present in these utility functions. They suggest that policy makers are unlikely to take full account of the results of such analyses until economists better attempt to reflect measures of what women want from pre-natal screening.

Objective: The purpose of this study is to analyze the perception of the content of health technology assessment (HTA) among health professionals applying for a state grant of DKK 10 million. Methods: A total of 113 applications were received and analyzed. When conducting the analysis, it was assumed that the applicants' maximum five-page project description would reflect: a) the applicants' perception of what an HTA is; b) how the assessment was to be conducted; and c) what the results were going to be used for. Results: More than 40% of all applications focused on treatment; in 51% only one or two professional groups were to be involved (thus interdisciplinarity was questionable); only 22% of the HTA cases were intended to form the basis for political/administrative decisions; in general, the HTAs were planned far less comprehensively than was relevant; 76% of the projects did not include a formal synthesis phase; 41% intended to use diffusion as the only method for publication of the HTA result. Conclusions: The analysis reveals several areas where DIHTA has to make an effort in order to secure that HTA in fact constitutes a comprehensive and well-documented basis for decision making. These areas concern the following topics: multidisciplinarity, the objective of HTA, comprehensiveness, the synthesis phase, and publication and utilization of the HTA result.