Validation of the University of São Paulo's Sensory Phenomena Scale -- English version.

INTRODUCTION: Sensory phenomena (SP) are disturbing sensations, feelings or urges. Although such feelings are often found in obsessive-compulsive disorder (OCD) and Tourette's Syndrome (TS) patients, sensory phenomena are usually not addressed in assessment measures. The University of São Paulo's Sensory Phenomena Scale (USP-SPS) was designed to measure sensory phenomena among all ages of patients with OCD and TS, and it was validated in Portuguese. OBJECTIVES: The aim of this study is to validate the English version of the USP-SPS and to examine its psychometric properties. MATERIAL AND METHODS: Sixty subjects, between the ages of 7 and 60 years, completed the USP-SPS, Y-BOCS or CY-BOCS and YGTSS. An expert clinician also performed a Clinical Inquiry about SP. Inter-rater reliability, sensitivity, specificity, convergent and divergent validity were evaluated. RESULTS: The USP-SPS symptom checklist showed good sensitivity in all ages, however its severity scale did not show good validity results for the pediatric population.

Development of a Transparent Transgenic Zebrafish Cellular Phenotype Tg(6xNF-kB:EGFP); Casper(roy-/-, nacre-/-) to Study NF-kB Activity.

NF-κB signaling has broad effects on cell survival, tissue growth, and proliferation activities. It controls many genes that are involved in inflammation and thus is a key player in many inflammatory diseases. The elevation of NF-κB activators is associated with elevated mortality, especially in cancer and cardiovascular diseases. The zebrafish has emerged as an important model for whole-organism in vivo modeling in translational research. In vertebrates, in-vivo spatial resolution is limited due to normal opacification of skin and subdermal structure. For in vivo imaging, skin transparency by blocking the pigmentation via chemical inhibition is required and the maintenance of this transparency is vital. The Casper(roy-/-, nacre-/-) mutant of zebrafish maintains this transparency throughout its life and serves as an ideal combination of sensitivity and resolution for in vivo stem cell analyses and imaging. We developed an NF-kB:GFP/Casper transparent transgenic zebrafish cellular phenotype to study inflammatory processes in vivo. We outline the experimental setup to generate a transparent transgenic NF-kB/Casper strain of zebrafish through the cross-breeding of Casper and NF-kB transgenic adult fish and have generated F01 in the form of heterozygous progeny. The transgenic F01 progeny was further inbred to generate heterozygous progenies from F1 to F4 generations. Furthermore, it continued to successfully develop the homozygous strain Tg(6xNF-kB:EGFP); Casper(roy-/-, nacre-/-) in the F05 generation. This novel strain of F05 generation showed 100% homozygosity in the transgenic transparent progeny of Tg(6xNF-kB:EGFP); Casper(roy-/-, nacre-/-). The strain has been confirmed by generating the F06 generation of homozygous progeny and again verified and validated for its homogeneity in the F07 generation. The newly developed novel transparent transgenic strain of the NF-kB reporter line has been coined as "Tg(6xNF-kB:EGFP); Casper(roy-/-, nacre-/-)gmc1". We have established a newly generated phenotype of transparent transgenic zebrafish for time-lapse in vivo confocal microscopy to study the cellular phenotype and pathologies at the cellular level over time. This will allow for quantifying the changes in the NF-kB functional activities over time and allow the comparison of control and cardiac-oncology experimental therapeutics. We validated the newly developed Tg(6xNF-kB:EGFP); Casper(roy-/-, nacre-/-)gmc1 homozygous strain of zebrafish by studying the inflammatory response to bacterial lipopolysaccharide (LPS) exposure, tolerance, and the inhibitory role of a potential novel drug candidate against LPS-induced inflammation. The results establish the unique application of newly developed strains by identifying hit and lead drug candidates for experimental therapeutics.

Identification and Characterization of a High-Need, High-Cost Group Among Hospitalized Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To identify a high-need, high-cost (HNHC) group among hospitalized lupus patients and to compare clinical and social factors of the HNHC group with those of other patients with lupus. METHODS: All hospitalizations for lupus in a tertiary care center over a 3-year period were recorded. The number of admissions, 30-day readmissions, length of stay (LOS), and cost of admissions were compared for high-risk patients with those of all other hospitalized lupus patients (OHLP) during this period. We then compared clinical measures (double-stranded DNA [dsDNA] levels, complement proteins, body mass index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] scores, and Case Mix Index [CMI] scores) for the HNHC cohort with those of the OHLP group. We additionally differentiated social factors (age, race and ethnicity, poverty, and medication adherence) between the 2 groups. RESULTS: A total of 202 patients with lupus accounted for 467 hospitalizations over the study period. The total cost of admissions was $13,192,346. Forty-four patients had significantly higher admissions, 30-day readmissions, and LOS. Furthermore, the cost for this group was 6-fold that for the OHLP group, confirming the presence of an HNHC cohort. The HNHC group had significantly higher dsDNA levels, SDI scores, and CMI scores compared with the OHLP group. Infections were the most common cause of admission for both groups. Patients in the HNHC group were more likely to be African American, younger, diagnosed with lupus at an earlier age, to have lower medication adherence, and to be significantly more likely to live in areas of poverty. CONCLUSION: A small group of patients with lupus (the HNHC group) accounts for most of the hospitalizations and cost. The HNHC group has both social and clinical factors significantly different from other patients with lupus.

Development and preliminary psychometric evaluation of the Children's Saving Inventory.

This study reports on the development and initial psychometric properties of the Children's Saving Inventory (CSI), a parent-rated measure designed to assess child hoarding behaviors. Subjects included 123 children and adolescents diagnosed with primary Obsessive-Compulsive Disorder (OCD) and their parents. Trained clinicians administered the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS), items assessing Family Accommodation and the Clinical Global Impressions--Severity index. Parents completed the CSI, Child Obsessive-Compulsive Impact Scale (COIS)--Parent Version and Child Behavior Checklist. Youth completed the COIS--Child Version, Obsessive-Compulsive Inventory Child Version (OCI-CV), Multidimensional Anxiety Scale for Children, and Children's Depression Inventory--Short Form. A four factor solution was identified; factors were named Discarding, Clutter, Acquisition, and Distress/Impairment. Internal consistency for the CSI Total and factor scores were good. One-week test-retest reliability (n = 31) from a random subsample was excellent. Known groups validity was supported vis-à-vis higher CSI scores for those endorsing hoarding on the CY-BOCS Symptom Checklist. Convergent and discriminant validity was evidenced by weak relationships with OCI-CV Checking and Contamination factors but strong relationships with the OCI-CV Hoarding factor and with hoarding obsession/compulsions on the CY-BOCS. These findings provide initial support for the reliability and validity of the CSI for the assessment of hoarding behaviors among youth with OCD. Future studies are needed to extend these findings to non-OCD samples of youth.

How often do community-based mental health providers educate and initiate PTSD treatment following training? Answering the question of reach.

Background: Posttraumatic stress disorder (PTSD) is a significant problem. Clinical practice guidelines recommend evidence-based treatments (EBTs) including cognitive processing therapy (CPT) and prolonged exposure (PE) as first-line treatments. Training in EBTs for PTSD has often been limited to large-scale systems (e.g., U.S. Department of Veterans Affairs). Research has shown that veteran-serving community-based mental health providers have low rates of training and supervision in EBTs for PTSD, suggesting that training initiatives for these community providers are critical to increase accessibility. This study aimed to examine the reach of education about EBTs for PTSD and the initiation of EBT for PTSD treatment among veteran-serving community-based providers participating in a large-scale training initiative. Methods: Participants (N = 280) were community-based, licensed mental health providers who received training in CPT (67%) or PE (33%). Provider attitudes toward EBTs were measured with the Perceived Characteristics of Intervention Scale. Reach was calculated from provider self-reported follow-up survey data, including caseload total number of patients with PTSD, number of patients provided education on EBTs for PTSD, and patient initiation of EBT for PTSD. Reach was calculated for both education and EBT initiation. Results: Providers reported positive attitudes toward CPT and PE. Rates of education reach for EBTs for PTSD ranged from 30% to 76%, and rates of EBTs for PTSD initiation ranged from 11% to 35% over the 5-month follow-up period. CPT providers had higher rates of education and initiation earlier in the follow-up period, although differences in initiation rates diminished after 3 months posttraining. Conclusion: Overall, this study examined how large-scale, training programs can be used to increase the education reach and initiation reach of EBTs for PTSD among veteran-serving community-based providers. Future work should examine how best to augment these training programs to reduce the gap between education and implementation of EBTs for PTSD. Plain Language Summary: Posttraumatic stress disorder (PTSD) is a significant problem among veterans. Although there are effective treatments for PTSD, mental health providers in community settings rarely have access to training in these treatments. Training programs are designed to offer providers the necessary training and support to deliver the most effective therapies to their clients. In evaluating these programs, it is important to determine whether they increase the likelihood that providers will deliver the interventions in which they were trained. Valuable outcomes include the percentage of patients who were educated on the specific intervention and who began to receive it. The (STRONG STAR) Training stron Initiative is a large-scale, community-based program that specializes in training providers in two leading PTSD therapies: cognitive processing therapy and prolonged exposure. Participants received a 2-day workshop, online resources, and weekly consultation calls to aid in the delivery of the intervention in which they were trained. Consequently, a large number of clients on provider caseloads are now aware of these PTSD treatments, and many have chosen to receive them. It is clear that the components within the (STRONG STAR) Training Initiative increase providers' competency in delivering therapies that have been widely studied. Therefore, more community members with PTSD will have access to gold-standard care. More funding should be devoted toward competency-based training programs to increase the number of people who receive education about and who engage in delivering effective therapies. This approach will ensure high-quality care and increased quality of life for those seeking treatment from community providers.

Resident assistant secondary trauma and burnout associated with student nonsuicidal self-injury.

Objective: To determine whether or not encountering students struggling with nonsuicidal self-injury (NSSI) put resident assistants (RAs) at greater risk of burnout or secondary traumatic stress. Participants: One hundred and fifty-five RAs at three Midwest public university campuses between March and April 2016. Methods: RAs participated in an anonymous online survey that collected demographics, information on RAs' experiences and thoughts related to their work, RAs' exposure to NSSI struggle of a resident, and measurements of compassion satisfaction, burnout, and secondary traumatic stress. Results: RAs who encountered resident NSSI demonstrated significantly higher levels of burnout and secondary traumatic stress than RAs who did not encounter resident NSSI. Conclusion: College students struggle with NSSI can significantly affect the people around them. Residence life administration and college counseling centers should provide training, support, and supervision to RAs in a way that addresses and reduces the RAs' potential distress.

Behavioral outcomes in children exposed prenatally to lamotrigine, valproate, or carbamazepine.

OBJECTIVES: To evaluate adaptive behavior outcomes of children prenatally exposed to lamotrigine, valproate, or carbamazepine, and to determine if these outcomes were dose-dependent. METHODS: Data were collected from women enrolled in the North American Anti epileptic Drug (AED) Pregnancy Registry who had taken lamotrigine, valproate, or carbamazepine monotherapies throughout pregnancy to suppress seizures. The adaptive behavior of 252 exposed children (including 104 lamotrigine-exposed, 97 carbamazepine-exposed, and 51 valproate-exposed), ages 3- to 6-years-old, was measured using the Vineland-II Adaptive Behavior Scales, administered to each mother by telephone. Mean Adaptive Behavior Composite (ABC), domain standard scores for communication, daily living, socialization and motor skills, and adaptive levels were analyzed and correlated with first trimester drug dose. RESULTS: After adjusting for maternal age, education, folate use, cigarette and alcohol exposure, gestational age, and birth weight by propensity score analysis, the mean ABC score for valproate-exposed children was 95.6 (95% CI [91, 101]), versus 100.8 (95% CI [98, 103]) and 103.5 (95% CI [101, 106]) for carbamazepine- and lamotrigine-exposed children, respectively (ANOVA; p=0.017). Significant differences were observed among the three drug groups in the ABC (p=0.017), socialization (p=0.026), and motor (p=0.018) domains, with a trend toward significance in the communication domain (p=0.053). Valproate-exposed children scored lowest and lamotrigine-exposed children scored highest in every category. Valproate-exposed children were most likely to perform at a low or moderately low adaptive level in each category. Higher valproate dose was associated with significantly lower ABC (p=0.020), socialization (p=0.009), and motor (p=0.041) scores before adjusting for confounders. After adjusting for the above variables, increasing VPA dose was associated with decreasing Vineland scores in all domains, but the relationships were not statistically significant. No dose effect was observed for carbamazepine or lamotrigine. CONCLUSIONS: Unlike carbamazepine and lamotrigine, prenatal valproate exposure was associated with adaptive behavior impairments with specific deficits in socialization and motor function, along with a relative weakness in communication. Increasing valproate dose was associated with a decline in adaptive functioning. This finding of a linear dose-dependent teratogenic effect suggests that valproate should be avoided at any dose during pregnancy. However, some women with epilepsy controlled only by valproate will decide, in consultation with their provider, that the benefits of continuing valproate during pregnancy outweigh the fetal risks. Faced with difficult choices, clinicians should be supportive as these patients consider their options.

Latino Adolescent Reproductive and Sexual Health Behaviors and Outcomes: Research Informed Guidance for Agency-based Practitioners.

Latinos are the largest and fastest growing minority youth group in the United States. Currently, Latino adolescents experience higher rates of teen pregnancy compared to any other racial or ethnic group and have disproportionately high levels of sexually transmitted infections and HIV. Latino teens are also affected by a number of social problems such as school dropout, poverty, depression and limited access to healthcare, which contributes to disparities in reproductive health outcomes for this population. Relatively few intervention research studies and programs have been dedicated to reducing sexual risk among Latino youth, despite their particular vulnerabilities in experiencing negative reproductive health outcomes. We provide recommendations for identifying the unique reproductive health needs of Latino youth and specific applied strategies so that agency-based social workers and other providers can develop family-based interventions that improve adolescent Latino sexual and reproductive health.

Traumatic events and obsessive compulsive disorder in children and adolescents: is there a link?

BACKGROUND: The extant literature supports an association between psychological trauma and development of OCD in adults, and this link is a plausible mediator for environment-gene interactions leading to phenotypic expression of OCD. OBJECTIVE: To explore the relationship between OCD and traumatic life events in children and adolescents. METHODS: We examined the prevalence of traumatic life events and PTSD in a large sample of systematically assessed children with OCD. OCD symptoms and severity were assessed using the Children's Yale Brown Obsessive Compulsive Scale (CY-BOCS) in those with and without concurrent PTSD. RESULTS: Rate of PTSD and trauma exposure was higher in children with OCD than in a comparable control group of non-OCD youth matched for age, gender and SES. Children with concurrent PTSD had more intrusive fears and distress and less control over their rituals than children with OCD but without PTSD. Total CY-BOCS scores were higher in those with concurrent PTSD. Specific type of OCD symptoms was not altered by a PTSD diagnosis. CONCLUSIONS: A history of psychologically traumatic events may be over-represented in children with OCD. Given the need to search for non-genetic factors that may lead to onset of OCD, better and more systematic methods to obtain and quantify psychologically traumatic life events are needed in clinical populations.

Atomoxetine for the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a review.

OBJECTIVE: This review examines and summarizes the pharmacodynamic and pharmacokinetic properties, short- and longer-term efficacy, the moderating effect of comorbid disorders, as well as short- and long-term safety and tolerability of atomoxetine for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD). METHODS: A systematic literature search was performed to review the extant literature on articles pertaining to the pharmacological treatment with atomoxetine in pediatric and/or adolescent ADHD. RESULTS: There is an extensive literature on atomoxetine; over 4000 children have participated in clinical trials of atomoxetine, demonstrating its short- and longer-term efficacy. In addition, studies have examined the moderating effect of comorbid disorders on atomoxetine response, as well as atomoxetine's therapeutic potential for other psychiatric conditions. Short- and longer-term safety and tolerability continue to be reported. CONCLUSIONS: Atomoxetine is indicated for both acute and maintenance/extended treatment of pediatric ADHD. Clinicians and families must be familiar with atomoxetine's evidence base, including its profile of clinical response and its possible effectiveness in the presence of comorbidity.

Innovative approaches in drug development.

This is the white paper on Innovative Approaches in Drug Development developed by the Biotechnology Industry Organization's (BIO) Clinical Trial Designs Workgroup. As recognized by the Food and Drug Administration's Critical Path Opportunities Report, the need to develop and apply innovative approaches to create new trial designs and clinical development programs is rapidly on the rise. Such novel approaches hold tremendous potential in the ability to refine mechanisms lying at the fundamental core of product safety and efficacy. The paper addresses the opportunities, challenges in pre-clinical and clinical trial design innovations; emphasizes the importance of safety database; and makes recommendations for carrying out the innovative approaches. The views expressed here in are solely those of the authors and do not reflect the official views of the Biotechnology Industry Organization.