Effectiveness of trauma-focused cognitive behavioral therapy compared to psychosocial counseling in reducing HIV risk behaviors, substance use, and mental health problems among orphans and vulnerable children in Zambia: a community-based randomized controlled trial.

Orphans and vulnerable children (OVC) in sub-Saharan Africa are at high risk for HIV infection and transmission. HIV prevention and treatment efforts with OVC are hindered by mental health and substance use problems. This randomized controlled trial compared a mental health intervention, Trauma Focused Cognitive Behavioral Therapy (TF-CBT), to an enhanced version of an existing HIV Psychosocial Counseling (PC+) program among 610 adolescents who met PEPFAR criteria for OVC and had HIV risk behaviors in Lusaka, Zambia. Outcomes included HIV risk behaviors (e.g., risky sexual behaviors), mental health (internalizing symptoms, externalizing behaviors, PTSD) and substance use. At 12-month follow-up, there were significant within group reductions in both groups for all outcomes, with the only significant between group difference being for substance use, in which OVC who received TF-CBT had significantly greater reductions than OVC who received PC+. In a subgroup analysis of OVC with high levels of PTSD symptoms, TF-CBT was superior to PC + in reducing internalizing symptoms, functional impairment, and substance use. Findings support TF-CBT for reducing substance use among OVC. Subgroup analysis results suggest that a robust intervention such as TF-CBT is warranted for OVC with significant mental and behavioral health comorbidities. The similar performance of TF-CBT and PC + in the overall sample for risky sexual behavior and mild mental health problems indicates that enhancing existing psychosocial programs, such as PC, with standard implementation factors like having a defined training and supervision schedule (as was done to create PC+) may improve the efficacy of HIV risk reduction efforts.Clinical Trials Number: NCT02054780.

Two chemically similar stellar overdensities on opposite sides of the plane of the Galactic disk.

Our Galaxy is thought to have an active evolutionary history, dominated over the past ten billion years or so by star formation, the accretion of cold gas and, in particular, the merging of clumps of baryonic and dark matter. The stellar halo-the faint, roughly spherical component of the Galaxy-reveals rich 'fossil' evidence of these interactions, in the form of stellar streams, substructures and chemically distinct stellar components. The effects of interactions with dwarf galaxies on the content and morphology of the Galactic disk are still being explored. Recent studies have identified kinematically distinct stellar substructures and moving groups of stars in our Galaxy, which may have extragalactic origins. There is also mounting evidence that stellar overdensities (regions with greater-than-average stellar density) at the interface between the outer disk and the halo could have been caused by the interaction of a dwarf galaxy with the disk. Here we report a spectroscopic analysis of 14 stars from two stellar overdensities, each lying about five kiloparsecs above or below the Galactic plane-locations suggestive of an association with the stellar halo. We find that the chemical compositions of these two groups of stars are almost identical, both within and between these overdensities, and closely match the abundance patterns of stars in the Galactic disk. We conclude that these stars came from the disk, and that the overdensities that they are part of were created by tidal interactions of the disk with passing or merging dwarf galaxies.

A randomised controlled trial to assess the clinical effectiveness and safety of the endometrial scratch procedure prior to first-time IVF, with or without ICSI.

STUDY QUESTION: What is the clinical-effectiveness and safety of the endometrial scratch (ES) procedure compared to no ES, prior to usual first time in vitro fertilisation (IVF) treatment? SUMMARY ANSWER: ES was safe but did not improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF cycle, with or without intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ES is an 'add-on' treatment that is available to women undergoing a first cycle of IVF, with or without ICSI, despite a lack of evidence to support its use. STUDY DESIGN, SIZE, DURATION: This pragmatic, superiority, open-label, multi-centre, parallel-group randomised controlled trial involving 1048 women assessed the clinical effectiveness and safety of the ES procedure prior to first time IVF, with or without ICSI, between July 2016 and October 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants aged 18-37 years undergoing their first cycle of IVF, with or without ICSI, were recruited from 16 UK fertility clinics and randomised (1:1) by a web-based system with restricted access rights that concealed allocation. Stratified block randomisation was used to allocate participants to TAU or ES in the mid-luteal phase followed by usual IVF with or without ICSI treatment. The primary outcome was live birth after completing 24 weeks gestation within 10.5 months of egg collection. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1048 women randomised to TAU (n = 525) and ES (n = 523) were available for intention to treat analysis. In the ES group, 453 (86.6%) received the ES procedure. IVF, with or without ICSI, was received in 494 (94.1%) and 497 (95.0%) of ES and TAU participants respectively. Live birth rate was 37.1% (195/525) in the TAU and 38.6% (202/523) in the ES: an unadjusted absolute difference of 1.5% (95% CI -4.4% to 7.4%, P = 0.621). There were no statistical differences in secondary outcomes. Adverse events were comparable across groups. LIMITATIONS, REASONS FOR CAUTION: A sham ES procedure was not undertaken in the control group, however, we do not believe this would have influenced the results as objective fertility outcomes were used. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest trial that is adequately powered to assess the impact of ES on women undergoing their first cycle of IVF. ES was safe, but did not significantly improve pregnancy outcomes when performed in the mid-luteal phase prior to the first IVF or ICSI cycle. We recommend that ES is not undertaken in this population. STUDY FUNDING/COMPETING INTEREST(S): Funded by the National Institute of Health Research. Stephen Walters is an National Institute for Health Research (NIHR) Senior Investigator (2018 to present) and was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2011-2017), NIHR HTA Commissioning Strategy Group (2012 to 2017); NIHR Programme Grants for Applied Research Committee (2020 to present); NIHR Pre doctoral Fellowship Committee (2019 to present). Dr. Martins da Silva reports grants from AstraZeneca, during the conduct of the study; and is Associate editor of Human Reproduction and Editorial Board member of Reproduction and Fertility. Dr. Bhide reports grants from Bart's Charity and grants and non-financial support from Pharmasure Pharmaceuticals outside the submitted work. TRIAL REGISTRATION NUMBER: ISRCTN number: ISRCTN23800982. TRIAL REGISTRATION DATE: 31 May 2016. DATE OF FIRST PATIENT'S ENROLMENT: 04 July 2016.

Changes in Brain Volume Associated with Trauma-Focused Cognitive Behavioral Therapy Among Youth with Posttraumatic Stress Disorder.

This study investigated group differences and longitudinal changes in brain volume before and after trauma-focused cognitive behavioral therapy (TF-CBT) in 20 unmedicated youth with maltreatment-related posttraumatic stress disorder (PTSD) and 20 non-trauma-exposed healthy control (HC) participants. We collected MRI scans of brain anatomy before and after 5 months of TF-CBT or the same time interval for the HC group. FreeSurfer software was used to segment brain images into 95 cortical and subcortical volumes, which were submitted to optimal scaling regression with lasso variable selection. The resulting model of group differences at baseline included larger right medial orbital frontal and left posterior cingulate corticies and smaller right midcingulate and right precuneus corticies in the PTSD relative to the HC group, R2 = .67. The model of group differences in pre- to posttreatment change included greater longitudinal changes in right rostral middle frontal, left pars triangularis, right entorhinal, and left cuneus corticies in the PTSD relative to the HC group, R2 = .69. Within the PTSD group, pre- to posttreatment symptom improvement was modeled by longitudinal decreases in the left posterior cingulate cortex, R2 = .45, and predicted by baseline measures of a smaller right isthmus (retrosplenial) cingulate and larger left caudate, R2 = .77. In sum, treatment was associated with longitudinal changes in brain regions that support executive functioning but not those that discriminated PTSD from HC participants at baseline. Additionally, results confirm a role for the posterior/retrosplenial cingulate as a correlate of PTSD symptom improvement and predictor of treatment outcome.

Epidemiology of Childhood Uveitis in a Tertiary Care Center: A 20-Year Study.

PURPOSE: To investigate demographics and causes of pediatric uveitis in a Swiss tertiary reference center over a 20-year period. MATERIALS AND METHODS: Retrospective cohort study on patients with uveitis aged less than 16 years seen at Jules-Gonin Eye Hospital between 1 January 2000 and 31 December 2019. RESULTS: Out of 2846 patients with uveitis seen in the Jules-Gonin Eye Hospital Ocular Immune-Infectiology Department, 317 (11.1%) were under 16 years of age and were included in this study. Median age at onset of the uveitis was 8.9 years (range 0 - 16). Anterior uveitis was the most frequent presentation (45.1%) followed by posterior uveitis in 26.2%, intermediate uveitis in 23.3%, and panuveitis in 5.4%. The inflammation was most frequently bilateral and non-granulomatous. A systemic inflammatory disease was found in 34% of the cases and an infectious cause in 24%. CONCLUSION: The repartition of the location of the uveitis was similar to previous reports from Western countries. Uveitis in juvenile idiopathic arthritis is the most frequent etiology related to a systemic disease in children. An infectious cause was found in 24% of our patients, which is a greater proportion than in adult cohorts.

"Like a huge weight lifted off my shoulders": Exploring young peoples' experiences of treatment in a pilot trial of trauma-focused cognitive behavioral therapy.

Background: The efficacy of trauma-focused cognitive behavioral therapy (TF-CBT) is well-established, yet little work has been done to understand how young people experience this intervention.Method: Semi-structured interviews were conducted with 13 young people aged 17-25 years (M = 20.0, SD = 2.61) who received TF-CBT as part of a pilot trial. Transcripts were analyzed via interpretative phenomenological analysis.Results: Four super-ordinate themes were identified: (i) experience of authentic care, (ii) personal role in therapy and recovery, (iii) talking about trauma is difficult but important, and (iv), transformative change. Young people described authenticity on behalf of the therapist, which seemed to foster emotional connection and comfort discussing trauma. They emphasized the importance of retaining autonomy and control during therapy, and a degree of personal responsibility in their recovery. Talking about trauma was described as difficult and potentially distressing, but also as critical for recovery. Transformative life changes were noted, which had a significant impact on young peoples' future outlook and self-perception.Conclusions: This study suggests that therapists should be attuned to the interpersonal needs of clients, attempt to foster self-determination throughout therapy, and simultaneously recognize the difficulty and importance of trauma work for young people when delivering TF-CBT.

Sexual Violence in Sport: Expanding Awareness and Knowledge for Sports Medicine Providers.

ABSTRACT: Athletes are vulnerable to sexual violence. Perpetrators of sexual violence may be a trusted coach, a member of the health care team, or a peer. The consequences of sexual violence are wide ranging, resulting in immediate and long-term physical and mental health outcomes that require recognition and comprehensive, multidisciplinary care. Sports medicine providers need to have specific knowledge and skill to care for athletes who experience sexual violence. Several sports organizations (e.g., International Olympic Committee, United States Olympic and Paralympic Committee, the National Collegiate Athletic Association, and the National Athletic Trainers' Association) have developed policies and procedures to prevent sexual violence and help sports medicine specialists provide care and services for athletes affected by sexual violence. Nevertheless, there remains a need for clinical guidelines, screening tools, and education, as well as clinical best practices to address sexual violence in sports medicine.

Trauma-focused cognitive behavioral therapy for children and families.

OBJECTIVE: This article provides information about trauma-focused cognitive behavioral therapy (TF-CBT), an evidence-based treatment for traumatized children, adolescents, and families. METHOD: The evolution of the TF-CBT model is described from the perspective of the treatment developers, including population of focus, conceptual and methodological features of the research, critical challenges and design issues that have been confronted, and how they have been addressed. Major research findings and their implications for clinical practice are also described, as well as future research challenges and directions for young researchers starting out in this field. RESULTS: The TF-CBT model has been been tested in a variety of challenging research settings and has strong evidence for improving trauma symptoms across diverse populations of traumatized children. CONCLUSIONS: TF-CBT is an effective and widely used treatment for addressing childhood trauma.

A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities In Utero.

OBJECTIVES: This systematic review was undertaken to define the diagnostic performance of in utero MR (iuMR) imaging when attempting to confirm, exclude or provide additional information compared with the information provided by prenatal ultrasound scans (USS) when there is a suspicion of foetal brain abnormality. METHODS: Electronic databases were searched as well as relevant journals and conference proceedings. Reference lists of applicable studies were also explored. Data extraction was conducted by two reviewers independently to identify relevant studies for inclusion in the review. Inclusion criteria were original research that reported the findings of prenatal USS and iuMR imaging and findings in terms of accuracy as judged by an outcome reference diagnosis for foetal brain abnormalities. RESULTS: 34 studies met the inclusion criteria which allowed diagnostic accuracy to be calculated in 959 cases, all of which had an outcome reference diagnosis determined by postnatal imaging, surgery or autopsy. iuMR imaging gave the correct diagnosis in 91 % which was an increase of 16 % above that achieved by USS alone. CONCLUSION: iuMR imaging makes a significant contribution to the diagnosis of foetal brain abnormalities, increasing the diagnostic accuracy achievable by USS alone. KEY POINTS: • Ultrasound is the primary modality for monitoring foetal brain development during pregnancy • iuMRI used together with ultrasound is more accurate for detecting foetal brain abnormalities • iuMR imaging is most helpful for detecting midline brain abnormalities • The moderate heterogeneity of reviewed studies may compromise findings.

Stepped care versus standard trauma-focused cognitive behavioral therapy for young children.

BACKGROUND: To compare the effectiveness and cost of stepped care trauma-focused cognitive behavioral therapy (SC-TF-CBT), a new service delivery method designed to address treatment barriers, to standard TF-CBT among young children who were experiencing posttraumatic stress symptoms (PTSS). METHODS: A total of 53 children (ages 3-7 years) who were experiencing PTSS were randomly assigned (2:1) to receive SC-TF-CBT or TF-CBT. Assessments by a blinded evaluator occurred at screening/baseline, after Step One for SC-TF-CBT, posttreatment, and 3-month follow-up. TRIAL REGISTRATION: ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01603563. RESULTS: There were comparable improvements over time in PTSS and secondary outcomes in both conditions. Noninferiority of SC-TF-CBT compared to TF-CBT was supported for the primary outcome of PTSS, and the secondary outcomes of severity and internalizing symptoms, but not for externalizing symptoms. There were no statistical differences in comparisons of changes over time from pre- to posttreatment and pre- to 3-month follow-up for posttraumatic stress disorder diagnostic status, treatment response, or remission. Parent satisfaction was high for both conditions. Costs were 51.3% lower for children in SC-TF-CBT compared to TF-CBT. CONCLUSIONS: Although future research is needed, preliminary evidence suggests that SC-TF-CBT is comparable to TF-CBT, and delivery costs are significantly less than standard care. SC-TF-CBT may be a viable service delivery system to address treatment barriers.

Moderators of treatment response to trauma-focused cognitive behavioral therapy among youth in Zambia.

BACKGROUND: The effectiveness of mental health interventions such as trauma-focused cognitive behavioral therapy (TF-CBT) may vary by client, caregiver, and intervention-level variables, but few randomized trials in low- and middle-income countries (LMIC) have conducted moderation analyses to investigate these characteristics. This study explores moderating factors to TF-CBT treatment response among a sample of orphans and vulnerable children (OVC) in Zambia. METHODS: Data were obtained from a completed randomized trial of TF-CBT among 257 OVC in Zambia. Trauma symptoms and functioning were measured at baseline and following the end of treatment. Mixed effects regression models were estimated for each moderator of interest: gender, age, number of trauma types experienced, history of sexual abuse, orphan status, primary caretaker, school status, and parental involvement in treatment. RESULTS: Treatment effectiveness was moderated by history of sexual abuse with greater reductions in both outcomes (trauma, p < .05; functioning, p < .01) for those that experienced sexual abuse. Primary caretaker was also a moderator with greater trauma reductions in those who identified their mother as the primary caretaker (p < .01), and better functioning in those that identified their father as the primary caretaker (p < .05). Nonorphans and single orphans (mother alive) showed greater reduction in functional impairment (p < .01) compared with double orphans. There was no significant moderator effect found by gender, age, number of trauma types, school status, or caregiver participation in treatment. CONCLUSIONS: This study suggests that TF-CBT was effective in reducing trauma symptoms and functional impairment among trauma-affected youth overall and that it may be particularly effective for survivors of child sexual abuse and children whose primary caretaker is a biological parent. Scale-up of TF-CBT is warranted given the wide range of effectiveness and prevalence of child sexual abuse. Future randomized trials of interventions in LMIC should power for moderation analyses in the study design phase when feasible.

The PXDLS linear motif regulates circadian rhythmicity through protein-protein interactions.

The circadian core clock circuitry relies on interlocked transcription-translation feedback loops that largely count on multiple protein interactions. The molecular mechanisms implicated in the assembly of these protein complexes are relatively unknown. Our bioinformatics analysis of short linear motifs, implicated in protein interactions, reveals an enrichment of the Pro-X-Asp-Leu-Ser (PXDLS) motif within circadian transcripts. We show that the PXDLS motif can bind to BMAL1/CLOCK and disrupt circadian oscillations in a cell-autonomous manner. Remarkably, the motif is evolutionary conserved in the core clock protein REV-ERBα, and additional proteins implicated in the clock's function (NRIP1, CBP). In this conjuncture, we uncover a novel cross talk between the two principal core clock feedback loops and show that BMAL/CLOCK and REV-ERBα interact and that the PXDLS motif of REV-ERBα participates in their binding. Furthermore, we demonstrate that the PXDLS motifs of NRIP1 and CBP are involved in circadian rhythmicity. Our findings suggest that the PXDLS motif plays an important role in circadian rhythmicity through regulation of protein interactions within the clock circuitry and that short linear motifs can be employed to modulate circadian oscillations.

Diagnóstico y tratamiento de la esofagitis eosinofílica en niños. Revisión de la literatura y recomendaciones basadas en la evidencia. Grupo de trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición pediátrica (SLAGHNP).

During the last twenty years Eosinophilic Esophagitis has become one the most important causes of esophageal disfunction in children, food impactation in adolescents and young adults, therapeutic failure in patients with gastroesophageal reflux disease (GERD) and the most frecuent eosinophilic disease of the gastrointestinal tract. We present recommendations for the diagnosis and treatment of the disease based in a systematic review of the literature.

Addressing mRNAs to the ER: cis sequences act up!

Translation-coupled protein translocation requires that mRNAs encoding secreted and membrane proteins (mSMPs) reach the ER membrane. The classical view is that the signal recognition particle (SRP) pathway delivers translating signal sequence-containing proteins to the SRP receptor present on the ER surface and engages the translocation machinery. However, recent studies demonstrate both SRP- and translation-independent mRNA recruitment to the ER, and that mRNAs encoding non-signal sequence-containing cytosolic proteins (mCPs) might be full-time residents of ER membranes. Furthermore, translation-independent cis-acting sequence elements present in both mCPs and mSMPs appear to govern the ability of mRNAs to associate with ER. Thus, a more complex picture of how and why mRNAs target the ER is emerging.

World Health organization guidelines for management of acute stress, PTSD, and bereavement: key challenges on the road ahead.

Wietse Tol and colleagues discuss some of the key challenges for implementation of new WHO guidelines for stress-related mental health disorders in low- and middle-income countries. Please see later in the article for the Editors' Summary.

Treating maladaptive grief and posttraumatic stress symptoms in orphaned children in Tanzania: group-based trauma-focused cognitive-behavioral therapy.

This study was designed to test the feasibility and child clinical outcomes for group-based trauma-focused cognitive behavior therapy (TF-CBT) for orphaned children in Tanzania. There were 64 children with at least mild symptoms of grief and/or traumatic stress and their guardians who participated in this open trial. The TF-CBT for Child Traumatic Grief protocol was adapted for use with a group, resulting in 12 weekly sessions for children and guardians separately with conjoint activities and 3 individual visits with child and guardian. Using a task-sharing approach, the intervention was delivered by lay counselors with no prior mental health experience. Primary child outcomes assessed were symptoms of grief and posttraumatic stress (PTS); secondary outcomes included symptoms of depression and overall behavioral adjustment. All assessments were conducted pretreatment, posttreatment, and 3 and 12 months after the end of treatment. Results showed improved scores on all outcomes posttreatment, sustained at 3 and 12 months. Effect sizes (Cohen's d) for baseline to posttreatment were 1.36 for child reported grief symptoms, 1.87 for child-reported PTS, and 1.15 for guardian report of child PTS.

Counselor and client perspectives of Trauma-focused Cognitive Behavioral Therapy for children in Zambia: a qualitative study.

This study examined Zambian counselors, children, and caregivers' perceptions of an evidence-based treatment (EBT) for trauma (Trauma-Focused Cognitive Behavioral Therapy [TF-CBT]) utilized in Zambia to address mental health problems in children. Semistructured interviews were conducted with local counselors trained in TF-CBT (N = 19; 90% of those trained; 12 female) and children/caregivers who had received TF-CBT in a small feasibility study (N = 18; 86% of the children and N = 16; 76% of the caregivers) who completed TF-CBT (total completed; N = 21). Each client was asked six open-ended questions, and domain analysis was used to explore the data. Counselors were positive about the program, liked the structure and flexibility, reported positive changes in their clients, and discussed the cultural adaptation around activities and language. Counselors stated the training was too short, and the supervision was necessary. Challenges included client engagement and attendance, availability of location, funding, and a lack of community understanding of "therapy." Children and caregivers stated multiple positive changes they attributed to TF-CBT, such as better family communication, reduction of problem behaviors, and ability to speak about the trauma. They recommended continuing the program. This study brings a critical examination of providers' and clients' perspectives of the implementation of an EBT for children in a low-resource setting. Clinical implications include changing implementation methods based on responses. Research implications include future study directions such as an effectiveness trial of TF-CBT and an examination of implementation factors.

Prediction of unsuccessful treatment in patients with severe acute asthma.

BACKGROUND: Clinical assessment can be used to identify which patients with acute asthma are at risk of unsuccessful initial treatment. OBJECTIVE: To determine which elements of clinical assessment predict unsuccessful treatment, defined as needing critical care or any unplanned additional treatment. METHODS: We analysed data from a large multicentre trial (the 3Mg trial). Adults with severe acute asthma underwent standardised clinical assessment, including peak expiratory flow rate (PEFR), up to 2 h after initiation of treatment. Standard care was provided other than blinded random allocation to trial treatment or placebo. Patients were followed up by record review up to 30 days. Unsuccessful treatment was defined as needing (1) critical care or (2) critical care or any unplanned additional treatment within 7 days of presentation. Logistic regression was used to identify predictors and derive a prediction model for each outcome. RESULTS: Out of 1084 patients analysed, 81 (7%) received critical care and 157 (14%) received critical care or unplanned additional treatment. Baseline PEFR (p=0.017), baseline heart rate (p<0.001), other serious illness (p=0.019), PEFR change (p=0.015) and heart rate change (p<0.001) predicted need for critical care. Baseline PEFR (p=0.010), baseline heart rate (p<0.001), baseline respiratory rate (p=0.017), other serious illness (p=0.023), PEFR change (p=0.003) and heart rate change (p=0.001) predicted critical care or additional treatment. Models based on these characteristics had c-statistics of 0.77 and 0.69, respectively. CONCLUSIONS: PEFR, heart rate and other serious illnesses are the best predictors of unsuccessful treatment, but models based on these variables provide modest predictive value.