Retinoblastoma caused by an RB1 variant with unusually low penetrance in a Danish family.

Retinoblastoma is the most common eye cancer in children. It is caused by pathogenic alterations of both alleles of the tumor suppressor gene RB1. In heritable retinoblastoma, a constitutional RB1 variant predisposes the cells to tumor formation, and loss of the other allele is a prerequisite for the development of retinoblastoma. Heritable retinoblastoma is inherited in an autosomal dominant manner; however, the majority of cases are the result of a de novo pathogenic RB1 variant. Penetrance is usually high (>90%), but with marked inter-familial variability. In some families, penetrance is incomplete and family members who develop tumors tend to remain unilaterally affected. Moreover, some families with low penetrance also show a parent-of-origin effect. We describe a patient with unilateral retinoblastoma caused by a previously unreported likely pathogenic RB1 variant (c.1199T>C) that disrupts a highly conserved amino acid residue within the A-box functional domain. Segregation analysis showed that the variant had unusually low penetrance as nine non-affected family members carried the same variant. We emphasize the use of genetic analysis on tumor DNA for classifying the RB1 variant, and underline the challenges in clinical management and counseling of families carrying the specific RB1 variant.

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part I. Practice Preparation, Identification, Assessment, and Initial Management.

OBJECTIVES: To update clinical practice guidelines to assist primary care (PC) clinicians in the management of adolescent depression. This part of the updated guidelines is used to address practice preparation, identification, assessment, and initial management of adolescent depression in PC settings. METHODS: By using a combination of evidence- and consensus-based methodologies, guidelines were developed by an expert steering committee in 2 phases as informed by (1) current scientific evidence (published and unpublished) and (2) draft revision and iteration among the steering committee, which included experts, clinicians, and youth and families with lived experience. RESULTS: Guidelines were updated for youth aged 10 to 21 years and correspond to initial phases of adolescent depression management in PC, including the identification of at-risk youth, assessment and diagnosis, and initial management. The strength of each recommendation and its evidence base are summarized. The practice preparation, identification, assessment, and initial management section of the guidelines include recommendations for (1) the preparation of the PC practice for improved care of adolescents with depression; (2) annual universal screening of youth 12 and over at health maintenance visits; (3) the identification of depression in youth who are at high risk; (4) systematic assessment procedures by using reliable depression scales, patient and caregiver interviews, and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria; (5) patient and family psychoeducation; (6) the establishment of relevant links in the community, and (7) the establishment of a safety plan. CONCLUSIONS: This part of the guidelines is intended to assist PC clinicians in the identification and initial management of adolescents with depression in an era of great clinical need and shortage of mental health specialists, but they cannot replace clinical judgment; these guidelines are not meant to be the sole source of guidance for depression management in adolescents. Additional research that addresses the identification and initial management of youth with depression in PC is needed, including empirical testing of these guidelines.

Guidelines for Adolescent Depression in Primary Care (GLAD-PC): Part II. Treatment and Ongoing Management.

OBJECTIVES: To update clinical practice guidelines to assist primary care (PC) in the screening and assessment of depression. In this second part of the updated guidelines, we address treatment and ongoing management of adolescent depression in the PC setting. METHODS: By using a combination of evidence- and consensus-based methodologies, the guidelines were updated in 2 phases as informed by (1) current scientific evidence (published and unpublished) and (2) revision and iteration among the steering committee, including youth and families with lived experience. RESULTS: These updated guidelines are targeted for youth aged 10 to 21 years and offer recommendations for the management of adolescent depression in PC, including (1) active monitoring of mildly depressed youth, (2) treatment with evidence-based medication and psychotherapeutic approaches in cases of moderate and/or severe depression, (3) close monitoring of side effects, (4) consultation and comanagement of care with mental health specialists, (5) ongoing tracking of outcomes, and (6) specific steps to be taken in instances of partial or no improvement after an initial treatment has begun. The strength of each recommendation and the grade of its evidence base are summarized. CONCLUSIONS: The Guidelines for Adolescent Depression in Primary Care cannot replace clinical judgment, and they should not be the sole source of guidance for adolescent depression management. Nonetheless, the guidelines may assist PC clinicians in the management of depressed adolescents in an era of great clinical need and a shortage of mental health specialists. Additional research concerning the management of depressed youth in PC is needed, including the usability, feasibility, and sustainability of guidelines, and determination of the extent to which the guidelines actually improve outcomes of depressed youth.

Comparison of discrimination and prognostic value of two US Doppler scoring systems in rheumatoid arthritis patients: a prospective cohort study.

OBJECTIVES: The aim of this paper is to investigate sensitivity to change (SRM), predictive validity and discriminative ability of a quantitative (QS) and a semi-quantitative (SQS) Doppler ultrasound scoring systems in patients with rheumatoid arthritis (RA) treated with anti-TNF-α therapy. METHODS: RA patients with wrist joint affection treated with TNF-α inhibitor were followed for one year. The wrist was examined with Doppler before initiating therapy and after one year. DAS28 was determined at both visits. One person trained in the SQS system and one in the QS system evaluated the anonymised images. The SRM, predictive validity and discriminative ability for both systems were calculated using DAS28 as the measure of disease improvement. RESULTS: Fourty-six patients with RA (80% females) were included. The mean Doppler activity at baseline was QS:24.4% (SD=17.7%) and SQS:2.0 (SD=0.6). A decrease in Doppler activity was seen for both systems after anti-TNF-α therapy. Sensitivity to change was seen, SRM=-0.52 (95%CI; -0.83 to -0.21; QS) and -0.24 (-0.53 to -0.05; SQS). Predictive value was poor (QS rs=-0.24; SQS rs=-0.05). Construct validity was; QS: rs=0.29, SQS: rs=0.23. CONCLUSIONS: Both systems were to some extent sensitive to change. Predictive validity and discriminate capacity of both systems showed only a weak association to DAS 28 in the study population. The QS was a little superior to the SQS. The results do not necessarily reflect Doppler evaluation as being ineffective, but may be caused by DAS28 not being a perfect marker of inflammation.

Does a one-day educational training session influence primary care pediatricians' mental health practice procedures in response to a community disaster? Results from the reaching children initiative (RCI).

Although many children and adolescents need assessment and treatment for psychological problems, few get such treatment from mental health specialists after a community disaster Research suggests that a very large proportion of children are seen in pediatric primary care settings and that pediatricians can provide appropriate care for many social and emotional problems in children. However few pediatricians have received training in providing this help. The focus of this study was to assess whether brief training to increase the capacity of primary care pediatricians (PCPs) to respond to the social or emotional problems of children after the World Trade Center terrorist attacks improved the quality of services to disaster-affected children. Pediatricians (N = 137) attended a one-day training workshop covering best practice treatments for mental health problems with an emphasis on trauma, bereavement, and medication use. We surveyed attendees prior to training, immediately post-intervention, and 1- and 6-months later. At 6-months post-intervention, 64% of the primary care clinicians reported instituting practice changes recommended during training. Reported use of formal mental health screening instruments increased, but greater use of medications was more limited. Although participants in the immediate post-intervention survey indicated strong agreement with the desirability to implement specific practice changes, the perceived desirability of such changes declined substantially at the 6-month follow-up. Changes in PCPs 'mental health related practice procedures can be facilitated by brief educational interventions, but continued training and support may be needed. We discuss these results relative to preparedness for community disasters.

No difference in striatal dopamine transporter availability between active smokers, ex-smokers and non-smokers using [123I]FP-CIT (DaTSCAN) and SPECT.

BACKGROUND: Mesolimbic and nigrostriatal dopaminergic pathways play important roles in both the rewarding and conditioning effects of drugs. The dopamine transporter (DAT) is of central importance in regulating dopaminergic neurotransmission and in particular in activating the striatal D2-like receptors. Molecular imaging studies of the relationship between DAT availability/dopamine synthesis capacity and active cigarette smoking have shown conflicting results. Through the collaboration between 13 SPECT centres located in 10 different European countries, a database of FP-CIT-binding in healthy controls was established. We used the database to test the hypothesis that striatal DAT availability is changed in active smokers compared to non-smokers and ex-smokers. METHODS: A total of 129 healthy volunteers were included. Subjects were divided into three categories according to past and present tobacco smoking: (1) non-smokers (n = 64), (2) ex-smokers (n = 39) and (3) active smokers (n = 26). For imaging of the DAT availability, we used [123I]FP-CIT (DaTSCAN) and single photon emission computed tomography (SPECT). Data were collected in collaboration between 13 SPECT centres located in 10 different European countries. The striatal measure of DAT availability was analyzed in a multiple regression model with age, SPECT centre and smoking as predictor. RESULTS: There was no statistically significant difference in DAT availability between the groups of active smokers, ex-smokers and non-smokers (p = 0.34). Further, we could not demonstrate a significant association between striatal DAT and the number of cigarettes per day or total lifetime cigarette packages in smokers and ex-smokers. CONCLUSION: Our results do not support the hypothesis that large differences in striatal DAT availability are present in smokers compared to ex-smokers and healthy volunteers with no history of smoking.

Ultrasound Doppler measurements predict success of treatment with anti-TNF-α drug in patients with rheumatoid arthritis: a prospective cohort study.

OBJECTIVE: To investigate the predictive ability of core outcomes applied in RA trials, including ultrasound (US) Doppler (USD) measurements differentiating patients who remain on anti-TNF-α therapy following 1 year. METHODS: Patients with RA in anti-TNF-α therapy were followed 1 year after therapy initiation. All patients had wrist involvement. At baseline, 2 weeks, 26 weeks and 1 year a USD examination, clinical examination including tender and swollen joint count, visual analogue scale (VAS) global and HAQ, biochemical measures and 28-joint DAS (DAS28) were collected for all patients. The amount of USD signal in the synovium was quantified by measuring the percentage of colour pixels-the colour fraction (CF). Predictive validity for patients who remain on anti-TNF-α therapy after 1 year was assessed for both USD measurements and other disease measures. Baseline values of disease measures of patients who remained on treatment after 1 year was compared with those who stopped therapy. RESULTS: The study cohort consisted of 109 patients. In this study, the baseline CF was the only measure predicting which patients would stay on the initial anti-TNF-α therapy for 1 year, evaluated using the square-root of CF (P = 0.024). The other disease markers could not significantly differentiate between the two groups of patients, with P-values of 0.86 and 0.98 for tender and swollen joint count, respectively, 0.86 for CRP, 0.24 for VAS, 0.10 for HAQ and 0.38 for DAS28. CONCLUSION: There is now evidence to support that baseline USD, in contrast to clinical measures, can predict which patients will remain on anti-TNF-α 1 year after initiating therapy.

Mental health services for children placed in foster care: an overview of current challenges.

Given the evidence from studies indicating that children in care have significant developmental, behavioral, and emotional problems, services for these children are an essential societal investment. Youth in foster care and adults who formerly were placed in care (foster care alumni) have disproportionately high rates of emotional and behavioral disorders. Among the areas of concern has been the lack of comprehensive mental health screening of all children entering out-of-home care, the need for more thorough identification of youth with emotional and behavioral disorders, and insufficient youth access to high-quality mental health services. In 2001, the American Academy of Child and Adolescent Psychiatry (AACAP) and the Child Welfare League of America (CWLA) formed a foster care mental health values subcommittee to establish guidelines on improving policy and practices in the various systems that serve foster care children (AACAP and CWLA, 2002). Because of the excellent quality and comprehensiveness of these statements, the Casey Clinical Foster Care Research and Development Project undertook consensus development work to enhance and build upon these statements. This article presents an overview of mental health functioning of youth and alumni of foster care, and outlines a project that developed consensus guidelines.

Best practices for mental health in child welfare: screening, assessment, and treatment guidelines.

The Best Practices for Mental Health in Child Welfare Consensus Conference focused on developing guidelines in five key areas (screening and assessment, psychosocial interventions, psychopharmacologic treatment, parent engagement, and youth empowerment) related to children's mental health. This paper provides an overview of issues related to the first three areas, presents the guidelines developed in these areas, and discusses the implications these guidelines have for the field of child welfare.

Establishing ongoing, early identification programs for mental health problems in our schools: a feasibility study.

OBJECTIVE: To investigate the feasibility of establishing ongoing, early identification services for mental health problems in school settings. METHOD: School counselors and other mental health professionals (N = 41) in middle, junior, and high schools (N= 23) were given training and supervision in the administration of an evidence-based mental health assessment tool, the Voice Diagnostic Interview Schedule for Children IV (DISC-IV), over the course of 1 1/2 school years. RESULTS: During the study, 530 students were selected to be assessed with the DISC, and 72% were confirmed to be at risk for a mental health problem (DISC+). Among DISC+ cases, 71% had never been in treatment before. The most common problems identified by the DISC were symptoms related to suicide (28%), social phobia (20%), attention-deficit/ hyperactivity disorder (19%), and oppositional defiant disorder (19%). Based on schools' recommendations, 82% of parents with DISC+ children agreed to make an appointment for a follow-up evaluation. Of DISC+ children whose parents agreed to seek further evaluation, 65% of them were evaluated by a health or mental health professional within 2 weeks. CONCLUSIONS: Use of a computerized, evidence-based mental health assessment tool is a feasible strategy for providing early mental health identification services in schools and can help to bridge the gap between mental health providers and the unmet needs of children who are at risk for mental health problems within the community.

Implementation of evidence-based practices for children in four countries: a project of the World Psychiatric Association / Implementação de práticas baseadas em evidências para o tratamento de crianças em quatro países: um projeto da Associação Mundial de Psiquiatria

OBJETIVE: The present study examined implementation issues in adopting cognitive-behavioral therapies in routine clinical settings in four countries reflecting diverse cultures, languages, settings, and traditions. METHOD: A Director's Systems Survey was administered prior to program implementation and one year later. Therapist ratings on attitudes about evidence-based practices and satisfaction were also gathered. RESULTS: All sites reported successful adoption of the program, although significant variations existed in fiscal support, family involvement, prior experience with cognitive-behavioral therapies, and plans for sustainability. Therapists' ratings indicated overall satisfaction with the implementation of the project. Findings from the Director's Systems Survey pointed to five factors facilitating implementation: 1) early adoption and guidance by innovative leaders (i.e., the Directors); 2) attention to the "fit" between the intervention model and local practices; 3) attention to front-end implementation processes (e.g., cultural adaptation, translation, training, fiscal issues); 4) attention to back-end processes early in the project (e.g., sustainability); and 5) establishing strong relationships with multiple stakeholders within the program setting. CONCLUSIONS: The implementation issues here mirror those identified in other studies of evidence-based practices uptake. Some of the obstacles to implementation of evidence-based practices may be generic, whereas issues such as the impact of political/economic instability, availability of translated materials, constitute unique stressors that differentially affect implementation efforts within specific countries.

OBJETIVO: Este estudo visa a examinar problemas na implementação de técnicas psicoterápicas cognitivo-comportamentais em ambientes clínicos de atendimento primário em quatro países que refletem diversas culturas, línguas, ambientes e tradições. MÉTODO: Uma pesquisa foi aplicada aos diretores de Sistemas Clínicos antes da implementação do programa e um ano após. Também foram coletados dados sobre como os terapeutas avaliavam as ações relativas à prática baseada em evidências e qual seu grau de satisfação com essa prática. RESULTADOS: Todos os locais de implementação relataram a adoção bem sucedida do programa, ainda que com significativas variações no apoio fiscal, envolvimento familiar, experiência prévia com terapias cognitivo-comportamentais e planos de sustentação em longo prazo. As avaliações dos terapeutas indicaram uma satisfação generalizada com a implementação do projeto. Achados da pesquisa com os diretores dos Sistemas Clínicos apontaram cinco fatores que facilitaram a implementação: 1) rápida adoção e orientação por líderes inovadores (i.e., os diretores); 2) atenção à adequação entre o modelo de intervenção e as práticas locais; 3) atenção desde o início à relação entre os processos de implementação e os usuários finais (e.g., adaptação cultural, tradução, treinamento, problemas fiscais); 4) atenção precoce aos processos de retaguarda do projeto (e.g., sustentação); e 5) estabelecimento de relações estreitas com múltiplos financiadores da instalação do programa. CONCLUSÕES: Os problemas de implementação encontrados neste estudo se assemelham aos identificados em outros estudos sobre a aquisição de práticas baseadas em evidência. Alguns dos obstáculos para a implementação de práticas baseadas em evidência podem ser generalizados, ao passo que problemas como o impacto da instabilidade político-econômica e disponibilidade de materiais traduzidos constituem estressores peculiares que afetam de forma diferenciada os esforços de implementação em cada país.

Development of adaptable and flexible treatment manuals for externalizing and internalizing disorders in children and adolescents / Desenvolvimento de manuais adaptáveis e flexíveis para transtornos de externalização e internalização em crianças e adolescentes

In this paper we describe the process used to develop treatment manuals for internalizing and externalizing disorders in children and adolescents. These manuals were developed to offer health care providers and others working in child mental health a flexible intervention that could be adapted to different countries and localities based on: 1) the amount of health care and school resources that are available; 2) the nature and severity of the types of problems children have; and 3) the preferences and cultural factors that are important within these communities. We also discuss the experiences and cultural issues faced by sites in Egypt, Lebanon, Israel, and Brazil who volunteered to implement the manualized treatment programs. The feedback received from these sites indicates that the manuals can be implemented to help children with internalizing and externalizing problems.

Neste artigo, descrevemos o processo utilizado para elaborar manuais de tratamento para transtornos de externalização e intrnalização em crianças e adolescentes. Esses manuais foram elaborados para oferecer uma intervenção flexível para provedores de atenção à saúde e demais profissionais que trabalham com a saúde mental da criança, podendo ser adaptados a diferentes países e localidades, com base: 1) no nível de atenção médica e de recursos educacionais disponíveis; 2) na natureza e na gravidade dos tipos de problemas que as crianças apresentam; e 3) nas preferências e fatores culturais que são importantes nessas comunidades. Discutimos, também, as experiências e os problemas culturais enfrentados pelas localidades no Egito, Líbano, Israel e Brasil que foram voluntárias em implementar os programas de tratamento especificados nos manuais. O retorno recebido dessas localidades indica que os manuais podem ser implementados para auxiliar as crianças com problemas de externalização e internalização.

Training of evidence-based assessment and intervention approaches in cross-cultural contexts: challenges and solutions / Treinamento de estratégias de intervenção e avaliação baseadas em evidências em contextos transculturais: desafios e soluções

Dissemination of evidence-based assessment and intervention approaches for child and adolescent with behavioral and/or emotional problems is now a priority in the field worldwide. However, developing staff competence in evidence-based assessment and intervention approaches in different countries is complicated by some environmental and economic constraints. In this paper a distance training/supervision model is discussed. We describe seven specific challenges encountered and solutions used for overcoming the obstacles in order to implement evidence-based assessment and intervention approaches in different sites in Brazil, Egypt, Israel, and Lebanon.

A disseminação de estratégias de intervenção e avaliação baseadas em evidências para crianças e adolescentes com problemas comportamentais e/ou emocionais é hoje uma prioridade mundial. No entanto, o desenvolvimento de equipes capacitadas para implementação de estratégias de intervenção e avaliação baseadas em evidências nos diferentes países é limitado por restrições ambientais e econômicas. Neste artigo, discute-se um modelo de treinamento/supervisão à distância. Em seguida, são descritos sete desafios específicos encontrados e as soluções utilizadas para superar os obstáculos para implementação de estratégias de intervenção e avaliação baseadas em evidências em diferentes localidades no Brasil, Egito, Israel e Líbano.

An examination of cross-cultural systems implementing evidence-based assessment and intervention approaches / Exame dos sistemas transculturais que implementam estratégias de intervenção e avaliação baseadas em evidências

Implementation of evidence-based assessment and intervention approaches for youth with behavioral and/or emotional problems is rising to recognition worldwide. Feasibility research is critical to examine what characteristics of systems allow for success or barriers to the implementation of evidence-based practices into real-world settings, especially when working cross-culturally. This paper briefly reviews the experience of 4 international sites to understand how the overall structure and specific site variables directed the implementation of the World Health Organization and the World Psychiatry Association project. Discussion includes a thematic summary of the successes and challenges experienced by the sites, and future directions of feasibility studies.

A implementação de estratégias de intervenção e avaliação baseadas em evidências para jovens com problemas comportamentais e/ou emocionais está assumindo reconhecimento internacional. Estudos de praticabilidade são críticos para examinar quais características dos sistemas permitem êxito ou se constituem em barreiras para a implementação de práticas baseadas em evidências em instituições do mundo real, especialmente quando trabalhando de forma transcultural. Este estudo revisa brevemente a experiência de quatro localidades internacionais para compreender como a estrutura geral e as variáveis específicas da localidade orientaram a implementação do projeto da Organização Mundial de Saúde e da Associação Mundial de Psiquiatria. A discussão inclui um resumo temático dos êxitos e desafios vivenciados pelas localidades e os caminhos futuros de estudos de praticabilidade.

Mental health assessments in juvenile justice: report on the consensus conference.

OBJECTIVE: At national, state, and local levels, there is increasing recognition of the importance of identifying and responding to the mental health needs of youths in the juvenile justice system, as policymakers and practitioners struggle to find ways to address causes and correlates of juvenile crime and delinquency. The proposed guidelines for mental health assessment provide explicit information about how, why, and when to obtain mental health information on justice youths at each important juncture in processing. METHOD: A national group of expert researchers and practitioners convened in April 2002. Experts derived six recommendations, following the expert consensus method, for conducting mental health assessments in juvenile justice settings. Experts had broad experience creating collaborations between juvenile justice, mental health, and child welfare systems and understood the policy and health implications of conducting such assessments in juvenile justice settings. RESULTS: Consensus Conference recommendations regarding screening for emergent risk, screening and assessment of mental health service needs, comprehensive mental health assessment components, assessment before community re-entry, need for periodic reassessment, and staff training are presented. CONCLUSION: Deriving specific recommendations that can be implemented systematically is a necessary first step toward policy changes that will optimize the standard of care for this vulnerable population.