Study protocol for leaving care-A comparison study of implementation, change mechanisms and effectiveness of transition services for youth.

INTRODUCTION: Youth placed in out-of-home care is a large and highly vulnerable group at high risk of negative developmental outcomes. Given the size and extent of negative developmental outcomes for youth placed in out-of-home care, interventions to help this vulnerable group navigate successfully towards independent living and promote wellbeing across a spectrum of outcome areas are needed. To date, there is a lack of such interventions, particularly in Sweden. Importing interventions from other societies and cultures is associated with difficulties. The aim of the research project is to implement, test, and evaluate interventions that have been recently developed in Swedish practice to close this gap. METHODS: The project has an ambitious and complex data collection and analysis strategy using qualitative, quantitative, and multiple information methods (hybrid effectiveness-implementation study) over the course of two years. Both the implementation and effectiveness of the interventions will be evaluated. The recently developed My Choice-My Way! leaving care program for youth aged 15+ will be the primary focus of the project and will be compared to usual services. CONCLUSIONS: The project has the potential to offer novel insights into how society can promote wellbeing across a spectrum of outcome areas for the high-risk group of youth transitioning from out-of-home care to independent living. As such, the project will have important implications for both research and practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05813197.

Safety and pharmacodynamics of a single infusion of danavorexton in adults with obstructive sleep apnea experiencing excessive daytime sleepiness despite adequate use of CPAP.

BACKGROUND: Sleep disruptions experienced by patients with obstructive sleep apnea (OSA) can lead to excessive daytime sleepiness (EDS) and significantly impact patients' quality of life. EDS may persist despite use of continuous positive airway pressure (CPAP) therapy. Small molecules that target the orexin system, which has a known role in sleep-wake regulation, show therapeutic potential for the treatment of EDS in patients with hypersomnia. This randomized, placebo-controlled, phase 1b study aimed to investigate the safety of danavorexton, a small-molecule orexin-2 receptor agonist, and its effects on residual EDS in patients with OSA. METHODS: Adults with OSA aged 18-67 years with adequate CPAP use were randomized to one of six treatment sequences of single IV infusions of danavorexton 44 mg, danavorexton 112 mg, and placebo. Adverse events were monitored throughout the study. Pharmacodynamic assessments included maintenance of wakefulness test (MWT), Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance test (PVT). RESULTS AND CONCLUSION: Among 25 randomized patients, 16 (64.0%) had treatment-emergent adverse events (TEAEs) and 12 (48.0%) had TEAEs considered related to treatment, all mild or moderate. Seven patients (28.0%) had urinary TEAEs: three, seven, and none while taking danavorexton 44 mg, danavorexton 112 mg, and placebo, respectively. There were no deaths or TEAEs leading to discontinuation. Improvements in mean MWT, KSS, and PVT scores were observed with danavorexton 44 mg and 112 mg vs placebo. These findings show that danavorexton can improve subjective and objective measures of EDS in patients with OSA and residual EDS despite adequate CPAP use.

Study protocol for a non-randomized controlled trial of the effects of internet-based parent training as a booster to the preschool edition of PATHS®: Universal edition of the Parent Web.

Well implemented, universal parental support is often effective in families with younger children, but research on their effects on families with adolescent children is scarce. In this study, a trial of the universal parent training intervention "Parent Web" in early adolescence is added to the social emotional learning intervention Promoting Alternative Thinking Strategies (PATHS®), completed in early childhood. The Parent Web is a universal online parenting intervention based on social learning theory. The intervention aims to promote positive parenting and family interaction through five weekly modules completed over 6-8 weeks. The main hypothesis is that participants in the intervention group will exhibit significant pre- to post- intervention-related benefits relative participants in the comparison group. The aims of this study are: 1) provide Parent Web as a booster aimed at improving parenting support and practices at the transition into adolescence to a cohort of parents whose children have previously participated in preschool PATHS, and 2) examine the effects of the universal edition of Parent Web. The study has a quasi-experimental design with pre- and post-testing. The incremental effects of this internet-delivered parent training intervention are tested in parents of early adolescents (11-13 years) who participated in PATHS when 4-5 years old compared to a matched sample of adolescents with no prior experience of PATHS. The primary outcomes are parent reported child behavior and family relationships. Secondary outcomes include self-reported parent health and stress. The proposed study is one of the few trials to test the effects of universal parental support in families of early adolescents and will therefore contribute to the understanding of how mental health in children and young people can be promoted across developmental periods through a continuum of universal measures. Trial registration: Clinical trials.gov (NCT05172297), prospectively registered on December 29, 2021.

TalkingMats as a decision aid to promote involvement in choice and decision-making around home care services for older people with mild to moderate dementia - study protocol for a randomized controlled trial.

BACKGROUND: In Sweden, 72% of people with dementia live in ordinary housing. Of these, 50% receive home care services. Older people with dementia may benefit from developments in decision-making support which aim to facilitate their ability to communicate their personal needs and preferences with care managers and staff in home care services. In this study, we will test and evaluate the use of TalkingMats in Swedish municipal home care services for older people with mild to moderate dementia. TalkingMats is a low-technology communication tool, to help people with communication difficulties express their views. It uses a simple system of picture symbols which are placed on a textured mat. This study will provide insight into the extent to which TalkingMats benefits older people with dementia to feel more involved in decisions related to home care services. In addition, this study will assess the extent to which the use of TalkingMats promotes service providers' efforts to involve service recipients in decision making. The implementation of TalkingMats in home care services will also be studied. METHODS: A parallel group, two-armed randomized controlled trial design in which TalkingMats and Usual Conversation Method will be compared. Two specific situations where older people with dementia must make decisions about home care services will be studied. First, a follow-up needs-assessment conversation between study participants and care managers will be studied. Second, a conversation between participants and home care staff regarding the delivery of the decided home care services will be studied. In addition, a qualitative approach will be used to gain an understanding of study participant and service provider experiences of the impact and implementation of TalkingMats. DISCUSSION: The combined exploratory, descriptive, and experimental study design is considered an important strength which will facilitate multi-facetted knowledge production concerning the involvement and communication needs of older people with dementia generally and within the context of home care services specifically. Combining qualitative and quantitative methods will maximize our ability to assess the effects of TalkingMats. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05561998 . Registered in September 28, 2022.

Safety and pharmacodynamics of a single infusion of danavorexton in adults with idiopathic hypersomnia.

STUDY OBJECTIVES: Idiopathic hypersomnia (IH) is a chronic disorder characterized by excessive daytime sleepiness unexplained by another disorder or drug/medication use. Although the orexin system plays a role in sleep-wake regulation, orexin A levels in the cerebrospinal fluid are normal in people with IH. This phase 1b, randomized, placebo-controlled, crossover study aimed to investigate the safety, pharmacokinetics, and pharmacodynamics of danavorexton, a small-molecule orexin-2 receptor agonist, in adults with IH. METHODS: Adults with IH aged 18-75 years were randomized to one of two treatment sequences of single intravenous infusions of danavorexton 112 mg and placebo. Pharmacodynamic endpoints included the maintenance of wakefulness test (MWT), the Karolinska Sleepiness Scale (KSS), and the psychomotor vigilance task (PVT). Adverse events were monitored throughout the study period. RESULTS: Of 28 randomized participants, 12 (44.4%) had a treatment-emergent adverse event (TEAE) and 10 (37.0%) had a TEAE considered related to study drug, most of which were mild or moderate. Four participants (18.2%) had urinary TEAEs while receiving danavorexton, all of which were mild in severity. There were no deaths or TEAEs leading to discontinuation. Improvements in MWT, KSS, and PVT scores were observed with danavorexton compared to placebo. Following drug administration, a mean sleep latency of 40 min (maximum value) was observed during the MWT within 2 h of danavorexton infusion in most participants. CONCLUSIONS: A single infusion of danavorexton improves subjective and objective excessive daytime sleepiness in people with IH with no serious TEAEs, indicating orexin-2 receptor agonists are promising treatments for IH. Clinical Trial: Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT04091438.

Publication bias, time-lag bias, and place-of-publication bias in social intervention research: An exploratory study of 527 Swedish articles published between 1990-2019.

Publication and related biases constitute serious threats to the validity of research synthesis. If research syntheses are based on a biased selection of the available research, there is an increased risk of producing misleading results. The purpose fo this study is to explore the extent of positive outcome bias, time-lag bias, and place-of-publication bias in published research on the effects of psychological, social, and behavioral interventions. The results are based on 527 Swedish outcome trials published in peer-reviewed journals between 1990 and 2019. We found no difference in the number of studies reporting significant compared to non-significant findings or in the number of studies reporting strong effect sizes in the published literature. We found no evidence of time-lag bias or place-of-publication bias in our results. The average reported effect size remained constant over time as did the proportion of studies reporting significant effects.

Neighborhood conditions in a Swedish context-Two studies of reliability and validity of virtual systematic social observation using Google Street View.

Introduction: The goal of these studies was to investigate the reliability and validity of virtual systematic social observation (virtual SSO) using Google Street View in a Swedish neighborhood context. Methods: This was accomplished in two studies. Study 1 focused on interrater reliability and construct validity, comparing ratings conducted in-person to those done using Google Street View, across 24 study sites within four postal code areas. Study 2 focused on criterion validity of virtual SSO in terms of neighborhoods with low versus high income levels, including 133 study sites within 22 postal code areas in a large Swedish city. In both studies, assessment of the neighborhood context was conducted at each study site, using a protocol adapted to a Swedish context. Results: Scales for Physical Decay, Neighborhood Dangerousness, and Physical Disorder were found to be reliable, with adequate interrater reliability, high consistency across methods, and high internal consistency. In Study 2, significantly higher levels of observed Physical Decay, Neighborhood Dangerousness, and signs of garbage or litter were observed in postal codes areas (site data was aggregated to postal code level) with lower as compared to higher income levels. Discussion: We concluded that the scales within the virtual SSO with Google Street View protocol that were developed in this series of studies represents a reliable and valid measure of several key neighborhood contextual features. Implications for understanding the complex person-context interactions central to many theories of positive development among youth were discussed in relation to the study findings.

The devil is in the details: Unpackaging the systematic in systematic reviews: Short reply to reconsidering the effectiveness of mentoring for prevention of juvenile criminal recidivism.

Replies to a comment made by DuBois (see record 2022-98051-005). The systematic review is an important tool for decision makers, intervention researchers, and practitioners to gain a clear and comprehensive overview of the available evidence on a given topic. We would, in this short reply, like to raise the two additional issues of critical appraisal and research synthesis. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Systematic review and meta-analysis of noninstitutional psychosocial interventions to prevent juvenile criminal recidivism.

OBJECTIVE: To assess the effectiveness of noninstitutional psychosocial interventions in preventing recidivism among criminal adolescents. METHOD: We performed a systematic review and meta-analysis of randomized and nonrandomized controlled trials assessing the impact on recidivism among juveniles aged 12-17. The included studies had a low to medium risk of bias and were published between 2000 and 2019. Standardized mean differences or risk differences were calculated. RESULTS: We included 35 (20 randomized, 15 nonrandomized) studies evaluating 17 unique, noninstitutional psychosocial interventions. A meta-analysis found no significant reductions in recidivism for studied interventions compared to control conditions. Although single studies suggested some positive effects, the evidence provided by these studies was found to have very low certainty. Post hoc analyses indicated that studies including a low-intensity control condition might have stronger relative intervention effects compared to studies with medium or high-intensity control conditions. CONCLUSION: This systematic review did not find any one noninstitutional psychosocial intervention to be more effective than control treatments in reducing future criminality among juvenile offenders aged 12-17. We discuss the implications of the present findings for social work and child and adolescent psychiatry practices. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Cluster Randomized Trial of Promoting Alternative Thinking Strategies (PATHS®) With Swedish Preschool Children.

The preschool edition of Promoting Alternative THinking Strategies (PATHS®) is a school-based, teacher implemented universal intervention developed in the United States designed to promote social emotional competence (SEC) in children as a foundation for improved mental health. PATHS is delivered as a curriculum and it is based on theories and research regarding SEC, brain development, and optimal school environments. A majority of children in Sweden attend preschool, which is government-subsidized and follows a national curriculum focusing on both academic and social emotional learning. However, there is not so much focus on formal instruction nor manual-based lessons. The purpose of this study was to assess the short-term (pre- to post-test) effects of PATHS in the Swedish preschool setting. Using a two-wave cluster randomized trial with multi-method and informant assessment (N = 285 4 and 5-year-old Swedish children; n = 145 wait-list control; n = 140 intervention; K = 26 preschools; k = 13 intervention; k = 13 control) we assessed changes in child emotional knowledge, emotional awareness, social problem solving, prosocial play, inhibitory control, and working memory using structural equation modeling (SEM). We included schools with at least one classroom of 4-5-year-old children from three municipalities. We excluded open preschools, parent cooperative preschools, and family day homes. After random assignment, schools were informed of condition assignment. Research team members were not blind to assignment. We hypothesized that relative to children in control schools, children in intervention schools would evidence improvements in social emotional competence as well as other outcomes. Children in PATHS, relative to children in the control, evidenced improvements in working memory and prosocial play, but also showed an increase in hyperactive behaviors. Girls in PATHS, relative to girls in the control, showed improvement in emotional knowledge and reduced anxiety. These results are considered in light of efforts to promote positive development and mental health. The trial registration number at ClinicalTrials.gov is NCT04512157. Main funding was from Swedish Council for Working Life and Social Research, the Swedish Research Council, Formas, and VINNOVA (dnr: 259-2012-71).

Reliability and construct validity of five life domains in the adolescent drug abuse diagnosis instrument in a sample of Swedish adolescent girls in special residential care.

Aim: This cross-sectional study investigates the psychometric properties of the Swedish edition of the Adolescent Drug Abuse Diagnosis (ADAD), and specifically examines the internal consistency and construct validity of five life domains reported by female adolescents in special residential care in Sweden (N = 780; M age = 16 years old). Methods: Principal component analysis and entropy-based analysis were used to test construct validity. Conclusion: Results indicate that ADAD may be able to reliably distinguish between areas that are important targets for intervention.

Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial.

BACKGROUND: Progressive supranuclear palsy is a rare neurodegenerative disease associated with dysfunctional tau protein. BIIB092 is a humanised monoclonal antibody that binds to N-terminal tau and is thus being assessed as a potential novel treatment for progressive supranuclear palsy. We aimed to investigate the safety and tolerability of BIIB092 in individuals with progressive supranuclear palsy. METHODS: This 12-week, double-blind, randomised, placebo-controlled, multiple ascending dose, phase 1b trial was done at 13 outpatient sites in the USA. Participants aged 41-86 years with probable or possible progressive supranuclear palsy with a score of 20 or greater on the Mini-Mental State Examination (MMSE) were enrolled. Three BIIB092 dose escalation cohorts (150 mg, 700 mg, or 2100 mg; eight participants per cohort) were tested sequentially. For each dose cohort, the first two participants were randomly assigned by a computer-generated scheme to receive either BIIB092 or placebo intravenously every 4 weeks for 57 days. After 2 days, the six remaining participants in each cohort were randomly assigned (5:1) to receive BIIB092 or placebo for 57 days. An additional expansion panel of 24 patients was randomly assigned (3:1) to receive 2100 mg or placebo every 4 weeks for 57 days. All participants were followed up to day 85. The primary outcome was safety, which was analysed in the treated population (all enrolled participants who received at least one dose of the study drug). This trial is registered with ClinicalTrials.gov, NCT02460094. FINDINGS: Between Oct 2, 2015, and Oct 19, 2016, 48 participants were enrolled and randomly assigned to the BIIB092 (n=36) and placebo (n=12) groups. No apparent demographic differences were observed between the two groups at baseline. All 48 participants completed the treatment phase of the study. Adverse events were generally mild to moderate in severity; the most common in the placebo and BIIB092 groups were falls (in two [17%] of 12 patients and in ten [28%] of 36 patients), urinary tract infections (in one [8%] of 12 and in six [17%] of 36), contusions (in one [8%] of 12 and in five [14%] of 36), and headaches (in none and in five [14%] of 36). Four serious adverse events resulting in admission to hospital were reported in three participants who received BIIB092 2100 mg: two severe adverse events of urinary tract infection, one severe adverse event of change in mental status, and one moderate adverse event of aspiration pneumonia. None was considered to be related to the study drug, all were resolved, and no deaths were reported. INTERPRETATION: Repeated administration of the anti-tau monoclonal antibody BIIB092, at doses of up to 2100 mg, appears to be well tolerated in participants with progressive supranuclear palsy. Results of this phase 1b trial have informed the design of the ongoing phase 2 PASSPORT (NCT03068468) study to examine the efficacy and safety of BIIB092. FUNDING: Bristol-Myers Squibb, Biogen.

The five-year costs and benefits of extended psychological and psychiatric assessment versus standard intake interview for women with comorbid substance use disorders treated in compulsory care in Sweden.

BACKGROUND: Women with comorbid substance use disorders are an extremely vulnerable group having an increased relative risk of negative outcomes such as incarceration, morbidity and mortality. In Sweden, women with comorbid substance use disorders may be placed in compulsory care for substance abuse treatment. Clinical intake assessment procedures are a distinct aspect of clinical practice and are a foundation upon which client motivation and continued treatment occurs. METHOD: The current study is a naturalistic quasi-experiment and aims to assess the five-year costs and benefits of a standard intake interview versus an extended psychological and psychiatric assessment for a group of chronic substance abusing women placed in compulsory care in Sweden between 1997 and 2000. Official register data on criminal activity, healthcare use, compulsory care stays and other services was retrieved and all resources used by study participants from date of index care episode was valued. In addition, the cost of providing the intake assessment was estimated. RESULTS: Results show that the extended assessment resulted in higher net costs over five years of between 256,000 and 557,000 SEK per person for women placed in care via the Law on Compulsory Care for Substance Abusers (LVM). Higher assessment costs made up a portion of this cost. The majority of this cost (47-57%) falls on the local municipality (social welfare) and 11.6-13.7% falls on the individual patient. CONCLUSIONS: Solid evidence supporting the clinical utility or incremental validity of assessment for improving treatment outcomes in this setting was not confirmed.

In-vivo microbiologic evaluation of polytetrafluoroethylene and cotton as endodontic spacer materials.

OBJECTIVE: Spacers are commonly placed between the canal orifice and the temporary material between endodontic treatment appointments. This prevents the temporary restoration material from obstructing the canal orifices and allows for easy removal. Various endodontic spacers are currently used, including polytetrafluoroethylene (PTFE) tape. Previous in-vitro studies have demonstrated the advantages of using PTFE over using cotton; however, no in-vivo studies have demonstrated this. Hence, the purpose of this study was to evaluate which spacer showed less bacterial leakage between endodontic treatments. METHOD AND MATERIALS: Fifty patients participated in the study and were randomly assigned to either the cotton or the PTFE group. Root canal treatments were completed in two appointments. Cotton and PTFE spacers were collected after a 2- to 4- week time interval between the first and second appointments. Samples were incubated on agar plates for 48 hours and then evaluated for presence of microbial growth. Colony forming units (CFUs) were counted for each of the samples. The results were analyzed using nonparametric statistical tests. RESULTS: Fifteen of the 24 cotton spacers and two of the 24 PTFE spacers were positive for bacterial growth. CONCLUSION: Cotton fibers exposed to the oral environment could potentially wick contaminants into the pulp chamber. The tendency of cotton to distort under masticatory forces may allow disruption of the temporary material's marginal seal. Based on the results of this study, the use of PTFE is strongly recommended over cotton as an endodontic spacer material. PTFE performed better than cotton in this in-vivo microbial study.

AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer's Disease.

AZD3293 (LY3314814) is a promising new potentially disease-modifying BACE1 (ß-secretase) inhibitor in Phase III clinical development for the treatment of Alzheimer's disease. Reported here are the first two Phase I studies: (1) a single ascending dose study evaluating doses of 1-750 mg with a food-effect component (n = 72), and (2) a 2-week multiple ascending dose study evaluating doses of 15 or 50 mg once daily (QD) or 70 mg once weekly (QW) in elderly subjects (Part 1, n = 31), and 15, 50, or 150 mg QD in patients with mild to moderate Alzheimer's disease (Part 2, n = 16). AZD3293 was generally well tolerated up to the highest doses given. No notable food effects were observed. PK following multiple doses (Part 2) were tmax of 1 to 3 h and mean t1/2 of 16 to 21 h across the 15 to 150 mg dose range. For single doses of ≥5 mg, a ≥70% reduction was observed in mean plasma Aß40 and Aß42 concentrations, with prolonged suppression for up to 3 weeks at the highest dose level studied. Following multiple doses, robust reductions in plasma (≥64% at 15 mg and ≥78% at ≥50 mg) and cerebrospinal fluid (≥51% at 15 mg and ≥76% at ≥50 mg) Aß peptides were seen, including prolonged suppression even with a QW dosing regimen. AZD3293 is the only BACE1 inhibitor for which prolonged suppression of plasma Aß with a QW dosing schedule has been reported. Two Phase III studies of AZD3293 (AMARANTH, NCT02245737; and DAYBREAK-ALZ, NCT02783573) are now ongoing.

Research that Guides Practice: Outcome Research in Swedish PhD Theses Across Seven Disciplines 1997-2012.

The core of evidence-based practice (EBP) as advocated for within the practice arms of the health and social sciences is to promote the routine incorporation of the best available research evidence into practice efforts. This requires discipline-specific education that is not only grounded in professional practice but also prepares would-be scientists in the application of the sophisticated techniques that characterize today's high research standards. Doctoral-level education is an important primer for future scientific endeavors across disciplines. This study examined 2334 theses published across Sweden in public health, criminology, nursing, psychiatry, psychology, social work, and sociology during the period 1997-2012. Of the theses reviewed, 13% aimed to investigate the effects of interventions. The highest percentage of effectiveness studies was found in nursing, public health, and psychology. The percentage of outcome research increased during the period. Controlled studies (with comparison group and pre- and post-test) occurred primarily within public health, nursing, psychiatry, and psychology. Of the 296 theses that included an intervention effectiveness study, 131 (44%), or 5.6% of all theses reviewed, met all four assessment criteria for quality. PhD education across seven disciplines in Sweden may be producing a professional core of scientists that is ill prepared to produce the type of research that is necessary to inform practice of the effects of its interventions as exposure to the rigors of quality effectiveness research is all but non-existent. This has implications for the advancement of an evidence-based practice and intervention science more broadly.

Women with comorbid substance dependence and psychiatric disorders in Sweden: a longitudinal study of hospital care utilization and costs.

BACKGROUND: Substance use disorders are regarded as one of the most prevalent, deadly and costly of health problems. Research has consistently found that the prevalence of other psychiatric disorders among those with substance related disorders is substantial. Combined, these disorders lead to considerable disability and health years lost worldwide as well as extraordinary societal costs. Relatively little of the literature on substance dependence and its impact on healthcare utilization and associated costs has focused specifically on chronic drug users, adolescents or women. In addition, the research that has been conducted relies largely on self-reported data and does not provide long-term estimates of hospital care utilization. The purpose of this study is to describe the long-term (24-32 year) healthcare utilization and it's associated costs for a nationally representative cohort of chronic substance abusing women (adults and adolescents) remanded to compulsory care between 1997-2000 (index episode). As such, this is the first study investigating healthcare costs for women in compulsory treatment in Sweden. METHODS: Women (n = 227) remanded to compulsory care for substance abuse were assessed at intake and their hospital care utilization was retrieved 5-years post compulsory care from national records. Unit costs for ICD-10 diagnoses were applied to all hospital care used from 1975-2006. Attempts are made to estimate productivity losses associated with hospitalization and premature death. RESULTS: Upon clinical assessment it was found that a majority of these women had a comorbid psychiatric disorder (primarily personality disorder). The women followed in this study were admitted to hospital five to six times that of the general population and had stays six to eight times that of the general population. Total direct healthcare costs per person over the study period averaged approximately $173,000 and was primarily the result of psychiatric department visits (71 %) and inpatient treatment (98.5 %; detoxification and short-term rehabilitation). CONCLUSIONS: Women placed in compulsory care use more hospital resources than that of the general Swedish population and when compared to international research of hospital care use and substance abuse. Direct hospital costs vary greatly over the life course. Effective services can have significant economic benefit.

Advancing adolescent health and health services in Saudi Arabia: exploring health-care providers' training, interest, and perceptions of the health-care needs of young people.

BACKGROUND: Adolescent health is regarded as central to global health goals. Investments made in adolescent health and health services protect the improvements witnessed in child health. Though Saudi Arabia has a large adolescent population, adolescent health-care only began to emerge in recent years, yet widespread uptake has been very limited. Health-care providers are key in addressing and providing the necessary health-care services for adolescents, and so this study was conducted with the aim of identifying opportunities for the advancement of knowledge transfer for adolescent health services in Saudi Arabia. METHODS: This Web-based, cross-sectional study was carried out at four hospitals in Saudi Arabia. Physicians and nurses were invited to participate in an online survey addressing their contact with adolescent patients, and training, knowledge, and attitudes towards adolescent health-care. RESULTS: A total of 232 professionals participated. The majority (82.3%) reported sometimes or always coming into contact with adolescent patients. Less than half (44%), however, had received any sort of training on adolescent health during their undergraduate or postgraduate education, and only 53.9% reported having adequate knowledge about the health-care needs of adolescents. Nurses perceived themselves as having more knowledge in the health-care needs of adolescents and reported feeling more comfortable in communicating with adolescents as compared with physicians. The majority of participants were interested in gaining further skills and knowledge in adolescent health-care and agreed or strongly agreed that adolescents have specific health-care needs that are different than children or adults (82.3% and 84.0%, respectively). With respect to health services, the majority (85.8%) believed that adolescents should be hospitalized in adolescent-specific wards. Only 26.7% of health-care providers believed that patients should be transferred from child to adult health-care services at 12-13 years of age, as is currently practiced in the country. CONCLUSION: A gap exists between the training, knowledge and skills of health-care providers, and the needs to address health-care issues of adolescents in Saudi Arabia. This coupled with the fact that health-care providers are interested in gaining more knowledge and skills and are supportive of changes in the health-care system provides an opportunity for building local capacity and instituting medical and nursing education and health-care reform that can better serve the needs of the country's young population.

Advancing school-based interventions through economic analysis.

Commentators interested in school-based prevention programs point to the importance of economic issues for the future of prevention efforts. Many of the processes and aims of prevention science are dependent upon prevention resources. Although economic analysis is an essential tool for assessing resource use, the attention given economic analysis within school-based prevention remains cursory. Largely, economic analyses of school-based prevention efforts are undertaken as secondary research. This limits these efforts to data that have been collected previously as part of epidemiological and outcomes research. Therefore, economic analyses suffer from gaps in the knowledge generated by these studies. This chapter addresses the importance of economic analysis for the future of school-based substance abuse prevention programs and highlights the role of prevention research in the development of knowledge that can be used for economic analysis.

Population pharmacokinetic and pharmacodynamic analysis of plasma Aß40 and Aß42 following single oral doses of the BACE1 inhibitor AZD3839 to healthy volunteers.

Modulating deposition of Aß-containing plaques in the brain may be beneficial in treating Alzheimer's disease. ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors have been shown to reduce Aß in plasma and CSF in healthy volunteers. In this study safety, pharmacokinetics and pharmacodynamics that is reduction of the plasma biomarkers Aß40 and Aß42 , of the BACE1 inhibitor AZD3839 were evaluated. Single oral ascending doses (1-300 mg) of AZD3839 were administered to 54 young healthy volunteers in a randomized, double-blind, placebo-controlled study. The data was analyzed using non-linear mixed effects modeling. AZD3839 reduced Aß40 and Aß42 in plasma with estimated potencies (EC50 ) of 46 and 59 nM, respectively, and a maximum effect of approximately 55%. This was in excellent agreement with the concentration-response relationships obtained in mouse and guinea pig. AZD3839 exposure displayed non-linear kinetics, described by a three-compartment model with a saturated binding compartment and an increase in bioavailability with dose. AZD3839 was safe, although, a dose-dependent QTcF prolongation was observed (mean 20 milliseconds at 300 mg). In conclusion, AZD3839 reduced plasma Aß40 and Aß42 , demonstrating clinical peripheral proof of mechanism. Pre-clinical models were predictive for the effect of AZD3839 on the human plasma biomarker in a strictly quantitative manner.