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Objective: This study assessed longer-term outcomes of low-income patients with cancer (predominantly female and Hispanic) after treatment in a collaborative model of depression care or in enhanced usual care.Methods: The randomized controlled trial, conducted in safety-net oncology clinics, recruited 472 patients with major depression symptoms. Patients randomly assigned to a 12-month intervention (a depression care manager and psychiatrist provided problem-solving therapy, antidepressants, and symptom monitoring and relapse prevention) or enhanced usual care (control group) were interviewed at 18 and 24 months after enrollment.Results: At 24 months, 46% of patients in the intervention group and 32% in the control group had a ≥50% decrease in depression score over baseline (odds ratio=2.09, 95% confidence interval=1.13-3.86; p=.02); intervention patients had significantly better social (p=.03) and functional (p=.01) well-being. Treatment receipt among intervention patients declined (72%, 21%, and 18% at 12, 18, and 24 months, respectively); few control group patients reported treatment receipt (10%, 6%, and 13%, respectively). Significant differences in receipt of counseling or antidepressants disappeared at 24 months. Depression recurrence was similar between groups (intervention, 36%; control, 39%). Among patients with depression recurrence, intervention patients were more likely to receive treatment after 12 months (34% versus 10%; p=.03). At 24 months, attrition (262 patients, 56%) did not vary by group; 22% were deceased, 20% declined further participation, and 14% could not be located.Conclusions: Collaborative care reduced depression symptoms and enhanced quality of life; however, results call for ongoing depression symptom monitoring and treatment for low-income cancer survivors. [ABSTRACT FROM AUTHOR]

Objective: To determine whether evidence-based socioculturally adapted collaborative depression care improves receipt of depression care and depression and diabetes outcomes in low-income Hispanic subjects.Research Design and Methods: This was a randomized controlled trial of 387 diabetic patients (96.5% Hispanic) with clinically significant depression recruited from two public safety-net clinics from August 2005 to July 2007 and followed over 18 months. Intervention (INT group) included problem-solving therapy and/or antidepressant medication based on a stepped-care algorithm; first-line treatment choice; telephone treatment response, adherence, and relapse prevention follow-up over 12 months; plus systems navigation assistance. Enhanced usual care (EUC group) included standard clinic care plus patient receipt of depression educational pamphlets and a community resource list.Results: INT patients had significantly greater depression improvement (> or =50% reduction in Symptom Checklist-20 depression score from baseline; 57, 62, and 62% vs. the EUC group's 36, 42, and 44% at 6, 12, and 18 months, respectively; odds ratio 2.46-2.57; P < 0.001). Mixed-effects linear regression models showed a significant study group-by-time interaction over 18 months in diabetes symptoms; anxiety; Medical Outcomes Study Short-Form Health Survey (SF-12) emotional, physical, and pain-related functioning; Sheehan disability; financial situation; and number of social stressors (P = 0.04 for disability and SF-12 physical functioning, P < 0.001 for all others) but no study group-by-time interaction in A1C, diabetes complications, self-care management, or BMI.Conclusions: Socioculturally adapted collaborative depression care improved depression, functional outcomes, and receipt of depression treatment in predominantly Hispanic patients in safety-net clinics. [ABSTRACT FROM AUTHOR]

Adenomatoid tumor of the epididymis is a rare benign neoplasm of mesothelial origin, mostly localized in the epididymis. It is usually presented as an indolent, painless scrotal enlargement. Immunohistochemically it is characterized by strong positivity for calretinin and epithelial markers, while tumor marker values are within the reference ranges. In this paper, two cases of 28- and 37-year-old men with adenomatoid tumors of the epididymis are described. In both, the tumor was presented as an indolent, slowly growing palpable mass in the epididymis. Tumor markers were in the normal range, digital examination found painless scrotal enlargement, while ultrasound showed a nonhomogeneous tumor. Immunohistochemically, they were characterized by strong positivity for calretinin and epithelial markers. If a localized epididymal mass is found, it is necessary to conduct an adequate diagnostic examination to differentiate inflammatory process from the neoplasm. An excision of the lesion is the most recommended option that also preserves testicular function and fertility. Histological and immunohistochemical evaluation are mandatory for a definitive diagnosis.

Background: Screen time among children and adolescents has increased dramatically, raising concerns about its impact on development and mental health. While research highlights both potential benefits and risks, excessive use has been linked to issues like anxiety, depression, and gaming addiction. Despite growing concern, effective interventions are scarce. Recognizing the importance of family dynamics in child development, we propose a family-centered program to address problematic gaming and excessive screen use in a clinical population. By involving both children and parents, we aim to create a more comprehensive approach to prevention and treatment., Objective: This study aims to determine the possibility of distributing and evaluating a family-centered group program for problematic gaming and excessive screen use (FAME) in a clinical child and adolescent psychiatry (CAP) population. We will monitor the recruitment rate; track the retention and attendance rates of both parents and children; and assess whether each session's objectives are met, the content is delivered within the allotted time, and the necessary resources (eg, facilitators and materials) are available. Additionally, we will gather qualitative and quantitative feedback from participants through postprogram surveys and individual interviews with both children and parents., Methods: A total of 10 families with ongoing contact with CAP in Skåne, Sweden, will be recruited and offered participation in a family-centered group program targeting children aged 10-18 years with reported difficulties regarding screen gaming or screen use. The intervention to be tested is a newly developed, family-centered, psychoeducational, cognitive behavioral therapy-based intervention addressing both positive and negative aspects of screen use; setting boundaries; the connection between thoughts, feelings, and behaviors; conflict triggers; and sleep hygiene. The primary goal of the pilot study is to test the feasibility of the program, as well as recruitment and the analysis of participants' experiences with the program., Results: A total of 11 children and their parents were enrolled during first quarter of 2024. A 4-session pilot was delivered in first quarter of 2024, and the first results are expected in the third quarter of 2024., Conclusions: The overarching goal of this pilot study is to determine the possibility of distributing and evaluating a family-centered group program for problematic gaming and excessive screen use (FAME) in a clinical CAP population. The insights gained from this study will guide our future research, which will focus on conducting a larger-scale evaluation of the intervention's impact on family screen time conflicts and inform future strategies for the implementation of family-centered interventions in child and youth clinics., Trial Registration: ClinicalTrials.gov NCT06098807; https://clinicaltrials.gov/study/NCT06098807., International Registered Report Identifier (irrid): DERR1-10.2196/56387., (©Marie Werner, Sabina Kapetanovic, Emma Claesdotter-Knutsson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 08.10.2024.)

Background and Objectives: Immune-mediated necrotizing myopathy (IMNM) caused by antibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is an inflammatory myopathy that has been epidemiologically correlated with previous statin exposure. We characterized in detail a series of 11 young statin-naïve patients experiencing a chronic disease course mimicking a limb-girdle muscular dystrophy. With the hypothesis that HMGCR upregulation may increase immunogenicity and trigger the production of autoantibodies, our aim was to expand pathophysiologic knowledge of this distinct phenotype., Methods: Clinical and epidemiologic data, autoantibody titers, creatine kinase (CK) levels, response to treatment, muscle imaging, and muscle biopsies were assessed. HMGCR expression in patients' muscle was assessed by incubating sections of affected patients with purified anti-HMGCR+ serum. Whole-exome sequencing (WES) with a special focus on cholesterol biosynthesis-related genes and high-resolution human leukocyte antigen (HLA) typing were performed., Results: Patients, aged 3-25 years and mostly female (90.9%), presented with subacute proximal weakness progressing over many years and high CK levels (>1,000 U/L). Diagnostic delay ranged from 3 to 27 years. WES did not reveal any pathogenic variants. HLA-DRB1*11:01 carrier frequency was 60%, a significantly higher proportion than in the control population. No upregulation or mislocalization of the enzyme in statin-exposed or statin-naïve anti-HMGCR+ patients was observed, compared with controls., Discussion: WES of a cohort of patients with dystrophy-like anti-HMGCR IMNM did not reveal any common rare variants of any gene, including cholesterol biosynthesis-related genes. HLA analysis showed a strong association with HLA-DRB1*11:01, previously mostly described in statin-exposed adult patients; consequently, a common immunogenic predisposition should be suspected, irrespective of statin exposure. Moreover, we were unable to conclusively demonstrate muscle upregulation/mislocalization of HMGCR in IMNM, whether or not driven by statins.

Background: Sustaining multiple concussions over one's lifetime may be associated with behavioral and mood changes beyond the acute phase of injury. The present cross-sectional study examined the relationship between concussion history, the incidence of current moderate-severe psychological distress, and lifetime adolescent hazardous gambling in high school students., Methods: Four-hundred fifty-nine high school students from southern Sweden (age: 16.81 ± 0.83, 58.2% male) completed a survey assessing concussion history (0,1,2…>8), psychological distress using the Kessler-6 scale, and lifetime hazardous gambling using the NODS-CLiP scale., Results: Participants who self-reported three or more concussions were more likely to endorse moderate-severe symptoms of psychological distress than those with no concussion history while controlling for covariates, OR = 2.71, 95% CI [1.19, 6.18]. In contrast, concussion history was not associated with hazardous gambling after controlling for confounding variables., Conclusions: Self-reporting three or more concussions was associated with increased current psychological distress beyond the acute phase of injury among high school students. Adolescents who have sustained multiple concussions should undergo mental health evaluations beyond the acute phase of injury to identify and treat psychological distress, but probing for hazardous gambling may not be clinically relevant in this previously concussed adolescent population., (© 2024. The Author(s).)

Intrapersonal parental factors play a significant role in the development of problematic gaming in children. However, few studies have explored parental perspectives on their relationship with a child engaged in problematic gaming, as well as the need for support parents perceive in relation to the child's gaming. We conducted semi-structured interviews with 12 parents (83.3% women) of 11 children (81.8% boys, Mage = 15 ± 2) to examine how parents of children with problematic gaming behavior perceive the parent-child relationship and their need for additional support. We analyzed qualitative accounts using thematic analysis to identify themes and subthemes while drawing on the theoretical frameworks of Aaron Antonovsky's theory of sense of coherence (SOC) and Jürgen Habermas' theory of logic. Participants described difficulties regarding all three components of SOC (meaningfulness, comprehensibility, and manageability) in relation to their child's gaming, with the most significant challenge being manageability. Parents primarily sought assistance from institutions and organizations, such as mental health services, to enhance manageability. The findings emphasize parents' need for relational and practical support tailored to their unique context, as well as their wish to be more involved in the treatment of their children.

Objectives: To evaluate the effectiveness of relapse prevention (RP) as a treatment for internet gaming disorder (IGD)., Design: Randomized controlled trial., Setting: Three child and adolescent psychiatry (CAP) units in Region Skåne, Sweden., Participants: Children aged 13-18 years, coming for their first visit to CAP during 2022, were screened for gaming behavior. Those who met the proposed DSM-5 criteria for IGD were offered participation in the trial, if they had the capacity to provide written informed consent and if they spoke Swedish. A total of 111 CAP patients agreed to participate. Out of those, 11 patients were excluded due to incorrect inclusion such as young age ( n  = 1), or due to the absence of responses to follow-up measures ( n  = 9). After exclusion, 102 participants remained (intervention = 47, control = 55)., Interventions: The intervention, RP, is based on cognitive behavioral treatment (CBT) and was provided individually, comprising of five to seven 45-min sessions over a period of 5 to 7 weeks versus treatment as usual., Outcome Measures: Participants were assessed with Game Addiction Scale for Adolescents pre-treatment (GASA) (baseline), post-treatment (treatment group only), and 3 months after baseline (follow-up)., Results: The repeated measures ANOVA showed a significant interaction effect between treatment and time. Both the control group and treatment group lowered their mean GASA score from baseline to follow-up significantly, but the improvement was greater in the treatment group (mean difference in control group -5.1, p  < 0.001, 95% CI = - 3.390 to -6.755, mean difference in treatment group -9.9, p  < 0.001, 95% CI = -11.746 to -8.105)., Conclusion: RP was found to be superior to treatment as usual in terms of reduction of IGD symptoms. Future research should address which aspects within a given treatment are effective, who benefits from treatment, in what aspects, and why., Trial Registration Number: ClinicalTrials.gov, NCT05506384 https://clinicaltrials.gov/ct2/show/NCT05506384., Competing Interests: AH has an employment at Lund University, sponsored by the state-owned Swedish gambling operator Svenska Spel. AH also has research funding from the research council of the Swedish state monopoly for alcohol, Systembolaget AB. EC has funding from the research council of Svenska Spel. None of these bodies had any role in, or influence on, the present study. The authors alone are responsible for the content and writing of the paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 André, Kapetanovic, Einarsson, Trebbin Harvard, Franzén, Möttus, Håkansson and Claesdotter Knutsson.)

Given the increasing prevalence of problematic gaming, in 2013, the diagnosis "Internet gaming disorder (IGD)" was included in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) as a potential diagnosis. With a new diagnosis, it is important to determine treatment options. The importance of the parent-child relationship has been emphasised in problematic gaming and its treatment. This study aims to provide more knowledge about adolescents' perceptions of a treatment for problematic gaming and understand whether such treatment may have a bearing on the parent-child relationship. We conducted individual interviews with nine adolescents who completed a treatment for problematic gaming. The interviews were analysed using thematic analysis. The analysis revealed three themes. Theme 1: adolescents' experiences of the new treatment; Theme 2: adolescents' perceptions of the effect of the treatment on their gaming behaviour; and Theme 3: adolescents' perceptions of changes in their parent-child relationships. The adolescents viewed the treatment as a way of gaining control of their gaming, a process in which a therapist played an integral part. For the majority of the adolescents in our study, the main effects of treatment were gaining insight into how their gaming and gaming-related behaviours affected other parts of their lives. The participants felt that the treatment improved their relationship with their parents through reducing everyday conflicts. This new knowledge can be used for the development of future interventions involving children and adolescents.

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests:Pia Enebrink is co-developer of the Parent Web intervention that is tested in this protocol., (Copyright: © 2023 Olsson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Deep Acute pancreatitis (AP) is an urging cause of hospitalization in the gastroenterology due to different causes and an unpredictable outcome. Known causes are grouped into four main groups: metabolic, mechanical, vascular and infectious., Objective: To determine the role of certain biochemical or radiological parameters as predictors of an involvement of other organs in AP different pathological staging and the surgical outcome in the treatment of AP., Methods: Ninety-seven AP patients hospitalized in General Hospital "Prim.dr Abdulah Nakaš" Sarajevo, in a period between 2016 and 2021 for both sexes, were divided according to the etiological factors of AP into four groups: nutritional factors, biliary concernments, alcohol and morphological changes of the pancreas. Beside laboratory tests, the imaging methods of abdomen (transabdominal ultrasound, abdominal computed tomography) used in determining morphological changes in the pancreas and other organs were analyzed in relation to parameters that predict the need for surgical outcomes., Results: AP etiological factors of patients differ significantly by gender and showed the dominance of dietary factors in female subjects (51%), followed by the presence of concernments in the biliary tract in 36% of cases, and alcohol consumption in male subjects in 28% of cases. The only variable correlated with the indicator of necessity for surgery is the existence of pleural effusion (coefficient of correlation was 0.38; risk ratio was 5.5) resulting that patients with pleural effusion have a 5.5 times higher chance of surgery indication than other patients., Conclusion: The application of simple parameters such as creatinine value with the values of amylases in serum and urine and the presence of pleural effusion confirmed by radiological imaging of the lungs opens the possibility of a simple and effective selection of patients for surgical treatment with a more severe form of AP., Competing Interests: There are no conflicts of interest., (© 2023 Azra Husic - Selimovic, Nina Bijedic, Amela Sofic, Amir Selimagic, Nedim Vanis, Rijad Jahic, Sanja Kapetanovic.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Clausén Gull, Kapetanovic, Norman, Ferrer-Wreder, Olsson and Eninger.)

Background: Although gaming is a common arena where children socialize, an increasing number of children are exhibiting signs of problem gaming or internet gaming disorder. An important factor to the development of problem gaming is parent-child relationships. A cognitive behavioral therapy-based form of treatment, labeled relapse prevention, has been developed as a treatment for child and adolescent problem gaming or internet gaming disorder. However, no study has evaluated the effect of this treatment among Swedish children and youth nor the role of the parent-child relationships in this treatment., Objective: This study aims (1) to evaluate a relapse prevention treatment for patients showing signs of problem gaming or internet gaming disorder recruited from child and youth psychiatric clinics and (2) to test whether the quality of parent-child relationships plays a role in the effect of relapse prevention treatment and vice versa-whether the relapse prevention treatment has a spillover effect on the quality of parent-child relationships. Moreover, we explore the carer's attitudes about parent-child relationships and child gaming, as well as experiences of the treatment among the children, their carers, and the clinicians who carried out the treatment., Methods: This study is a 2-arm, parallel-group, early-stage randomized controlled trial with embedded qualitative components. Children aged 12-18 years who meet the criteria for problem gaming or internet gaming disorder will be randomized in a 1:1 ratio to either intervention (relapse prevention treatment) or control (treatment as usual), with a total of 160 (80 + 80) participants. The primary outcomes are measures of gaming and gambling behavior before and after intervention, and the secondary outcomes include child ratings of parent-child communication and family functioning. The study is supplemented with a qualitative component with semistructured interviews to capture participants' and clinicians' experiences of the relapse prevention, as well as attitudes about parent-child relationships and parenting needs in carers whose children completed the treatment., Results: The trial started in January 2022 and is expected to end in December 2023. The first results are expected in March 2023., Conclusions: This study will be the first randomized controlled trial evaluating relapse prevention as a treatment for child and adolescent problem gaming and internet gaming disorder in Sweden. Since problem behaviors in children interact with the family context, investigating parent-child relationships adjacent to the treatment of child problem gaming and internet gaming disorder is an important strength of the study. Further, different parties, ie, children, carers, and clinicians, will be directly or indirectly involved in the evaluation of the treatment, providing more knowledge of the treatment and its effect. Limitations include comorbidity in children with problem gaming and internet gaming disorder and challenges with the recruitment of participants., Trial Registration: ClinicalTrials.gov NCT05506384 (retrospectively registered); https://clinicaltrials.gov/ct2/show/NCT05506384., International Registered Report Identifier (irrid): DERR1-10.2196/44318., (©Sabina Kapetanovic, Sevtap Gurdal, Isak Einarsson, Marie Werner, Frida André, Anders Håkansson, Emma Claesdotter-Knutsson. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.01.2023.)

Objective: We investigated dynamics of inflammatory biomarkers in children with perinatally acquired HIV (PHIV) who started antiretrovirals at age less than 3 years and achieved sustained virologic control (HIV plasma RNA <400 copies/ml)., Design: This was a retrospective analysis of inflammatory biomarkers in children enrolled in a randomized trial of early (<3 years of age) PI-based versus NNRTI-based regimens (P1060), who achieved sustained virologic control and participated in a neurodevelopmental follow-up study (P1104s) between ages 5 and 11 years., Methods: We measured 20 inflammatory biomarkers using ELISA or chemiluminescence at onset of sustained virologic control (Tc) and at P1104s entry (Te)., Results: The 213 participants had median ages of 1.2, 1.9, and 7 years at antiretroviral initiation, Tc, and Te, respectively, with 138 on protease inhibitor-based and 74 on NNRTI-based regimens at Tc. Eighteen markers decreased and two increased from Tc to Te (Te-Tc). Biomarker subsets, particularly cytokines, the chemokine IP-10, and adhesion molecules sICAM-1 and sVCAM-1, correlated at Tc, Te, and Te-Tc. At Tc, higher biomarker levels were associated with younger age, female sex, HIV plasma RNA at least 750 000 copies/ml, lower nadir CD4 + %, lower nadir weight z scores, and NNRTI-based treatment. Greater Te-Tc biomarker declines were associated with younger age, male sex, higher Tc biomarker levels, lower nadir CD4 + %, and NNRTI-based treatment. Duration of controlled viremia and nadir height z scores showed mixed associations., Conclusion: Biomarker expression showed substantial coordination. Most markers decreased after virologic control. Demographic and clinical variables associated with biomarker patterns were identified. Mechanistic studies of these biomarker patterns are needed to inform interventions to control inflammation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Immigrant parents of adolescents experience challenges in their role as parents in the new country and express a need for parental support. Still, they are underrepresented in existing parenting programs and when they do attend, their parenting practices improve less than what they do among native parents. Self-assured parents (SAP; Swe . Trygga Föräldrar) targets immigrant parents living in deprived areas in Sweden who worry about their adolescents' adjustment. This study's purposes are to examine if SAP is a feasible intervention in Swedish municipalities and if SAP is effective in reaching its aims, namely to promote parental self-efficacy and parent-adolescent communication and to reduce parents' worries in the target group., Methods: SAP will be evaluated when implemented by social workers in three Swedish municipalities using a culturally-informed mixed design procedure. Parents will be recruited to the program by local social workers. Groups leaders will be interviewed, observed, and they will fill out self-reports to measure implementation quality, including fidelity and acceptability. A group of parents will be interviewed to better understand their perceived challenges and needs in their parenting in Sweden and their experience of participating in SAP. An interrupted time series design with three measurements before, two measurements during, and two measurements after the intervention has ended will be employed using self-reports of parental self-efficacy, parent-child communication, and parents' worries. Informed consent will be collected from all study participants., Discussion: Immigrant parents living in deprived areas is an understudied and marginalized population. There is a lack of culturally-informed, evidence-based parenting programs aimed at this group in Sweden. The need for specifically developed programs for immigrant parents living in deprived areas with teenage children, has been voiced by both immigrant parents themselves and the Swedish government. Thus, this study will contribute not only to the scientific literature, but also to social service practice and potentially policy making., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors.)

Background: The aim of the study was to investigate how general family relations, reported changes in family interaction and involvement with peers during the Covid-19 pandemic, and following rules and recommendations during the pandemic relate to adolescent smoking, alcohol use, inebriation, and use of narcotics during Covid-19., Methods: An online national survey of Swedish adolescents (n = 1818) aged 15-19 years was conducted in June 2020. Hierarchical regression analysis was used to predict adolescents' reported change in substance use during the pandemic. Person-oriented analyses, were used to identify clusters of participants characterized by similar patterns of substance use following ANOVA analysis with Scheffe post hoc tests testing differences between clusters in terms of family relations, reported changes in family interaction and involvement with peers during the Covid-19 pandemic, and following rules and recommendations during the pandemic., Results: Higher general family conflict, increased involvement with peers, a strained relationship with parents, and less compliance with rules and restrictions during the pandemic predicted a reported increase in adolescent substance use during this period. The grouping of scores for adolescent smoking, alcohol use, inebriation, and use of narcotics resulted in a six-cluster solution. One cluster (n = 767) either did not use or had decreased use of substances during the Covid-19 pandemic. Five other clusters, thus risk clusters, had retained or increased use of substances during the pandemic. Poor general family relations, increased peer involvement, and difficulties to conform to the rules and restrictions during the covid-19 pandemic were characteristics of risk clusters., Conclusions: Most of adolescents in our study did not increase their substance use during the pandemic. However, adolescents with poor family relations who turn to peers during stressful times and who have difficulty following the government's rules and restrictions, are at risk of increased substance use during the pandemic. This is a potential threat both to adolescents themselves and others in their surroundings which is why at-risk adolescents and their families need more attention from public health and social services during this time of crisis., (© 2022. The Author(s).)

Objective: To report the clinical, neuroimaging, and antibody associations in patients with autoimmune encephalitis (AE) and thymoma., Methods: A retrospective cohort study of 43 patients was conducted. Antibody determination and immunoprecipitation to characterize novel antigens were performed using reported techniques., Results: Patients' median age was 52 years (range: 23-88 years). Forty (93%) had neuronal surface antibodies: gamma-aminobutyric acid receptor A (GABA A R) (15), amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) (13), contactin-associated protein-like 2 (CASPR2) (4), leucine-rich, glioma inactivated 1 (LGI1) (3), glycine receptor (GlyR) (3), and unknown antigens (2). Concurrent antibodies against intracellular antigens occurred in 13 (30%; 9 anti-collapsin response mediator protein 5 [CRMP5]) and were more frequent in anti-AMPAR encephalitis (54% vs 20%; p = 0.037). The most common clinical presentation was encephalitis with multiple T2/fluid-attenuated inversion recovery hyperintense lesions in 23 (53%) patients (15 GABA A R, 5 AMPAR, and 1 unknown neuropil antibody), followed by encephalitis with peripheral nerve hyperexcitability in 7 (16%; 4 CASPR2, 2 LGI1, and 1 unknown antibody), limbic encephalitis in 6 (14%; 4 AMPAR, 1 LGI1, and 1 antibody negative), progressive encephalomyelitis with rigidity and myoclonus in 4 (9%; 3 GlyR and 1 AMPAR antibodies), and encephalitis with normal MRI in 3 (7%; AMPAR antibodies). Anti-GABA A R encephalitis was more prevalent in Japanese patients compared with Caucasians and other ethnicities (61% vs 16%; p = 0.003). In anti-AMPAR encephalitis, 3/4 patients with poor and 0/6 with good outcome had concurrent CRMP5 antibodies ( p = 0.033). Immunoprecipitation studies identified metabotropic glutamate receptor 3 antibodies that were additionally found in 5 patients (3 with and 2 without encephalitis)., Conclusions: AE in patients with thymoma include several clinical-radiologic syndromes that vary according to the associated antibodies. Anti-GABA A R encephalitis was the most frequent AE and occurred more frequently in Japanese patients., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: We examined relationships between plasma biomarkers and neurodevelopment in children from sub-Saharan Africa with perinatal HIV (PHIV) with controlled viremia on antiretroviral therapy (ART)., Design: Longitudinal retrospective cohort study of children with controlled blood HIV replication., Methods: Children (N = 213; 57% girls) started ART at less than 3 years of age, had neurodevelopmental assessments (cognition, attention/impulsivity, motor proficiency, global executive functions) at 5-11 years, and achieved controlled viremia (HIV-1 RNA <400 copies/ml for ≥9 months before initial assessment). Twenty-three plasma biomarkers were measured at onset of controlled viremia, week 0 (first neurodevelopmental assessment), and week 48 (second neurodevelopmental assessment). Factor analysis was conducted at each time point. Multivariable linear regressions assessed associations between factors and neurodevelopmental scores., Results: Median age at week 0 was 7.0 years. Eighteen biomarkers loaded on six factors: a (L-10, IFNγ, IFNα2, IL-1β, IL-6, IP-10, TNFα); B (sCD163, sICAM-1, sVCAM-1, CRP); C (sE-selectin, sP-selectin); D [MIP-1β, vascular endothelial growth factor (VEGF)-A]; E (sCD14, CRP); and F (CX3CL1, MCP-1). Higher factor B scores were consistently associated with worse cognition and attention/impulsivity, and higher factor D scores with better attention/impulsivity., Conclusion: These results suggest a detrimental effect of increased endothelial cell activation (sICAM-1, sVCAM-1) and monocyte/macrophage scavenger function (sCD163) and a beneficial effect of increased CCR5 ligand and HIV entry blocker MIP-1β and angiogenesis stimulant-VEGF concentrations on the neurodevelopment of children with PHIV. The model that emerges is of vascular inflammation leading to neurodevelopmental deficits. The role of persistent HIV replication in the central nervous system also needs to be further explored., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Uptake of evidence-based interventions for adolescents and young adults living with HIV (AYA-LWH) in sub-Saharan Africa (SSA) is complex, and cultural differences necessitate local adaptations to enhance effective implementation. Few models exist to guide intervention tailoring, yet operationalizing strategies is critical to inform science and implementation outcomes, namely acceptability, appropriateness, feasibility, fidelity, and sustainability. This paper describes operationalizing the ADAPT-ITT framework applied to a manualized trauma-informed cognitive behavioral therapy (TI-CBT) intervention addressing mental and sexual health for AYA-LWH in SSA in preparation for a randomized controlled trial (RCT). Methods: Phase 1 of the RCT focused on operationalizing ADAPT-ITT steps 3-7 to tailor the intervention for use in eight sites across Botswana, Malawi, South Africa, and Zimbabwe. Well-defined processes were developed to supplement the general guidelines for each step to provide clear, consistent direction on how to prepare and conduct each step, including documenting, assessing, and determining adaptations, while maintaining intervention fidelity. The processes provided efficient standardized step-by-step progression designed for future replication. All sites participated in Phase 1 using the created tools and strategies to translate and present the TI-CBT to community stakeholders for feedback informing local adaptations. Results: The research team developed and operationalized materials guiding adaptation. A translation review process verified local adaptability, maintained core concepts, and revealed differing interpretations of words, idioms, and culturally acceptable activities. Strategically designed tools comprised of feedback and translation verification forms resulted in meticulous management of adaptations. Robust collaborations between investigators, research managers, site personnel, and topical experts maximized multidisciplinary expertise, resulting in ~10-15 personnel per site facilitating, collecting, assessing, and integrating local feedback. Processes and tools operationalized in steps 3-7 effectively addressed implementation outcomes during community engagements ( n = 108), focus groups ( n = 5-8 AYA-LWH and caregivers per group), and strategic training of youth leaders. Discussion: This paper offers a novel generalizable approach using well-defined processes to guide intervention adaptation building on the ADAPT-ITT framework. The processes strengthen the science of implementation and provide much-needed specificity in adaptation steps to optimize and sustain real-world impact and help researchers and community stakeholders maximize existing infrastructure, culture, and resources to inform implementation strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Libous, Montañez, Dow, Kapetanovic, Buckley, Kakhu, Kamthunzi, Maliwichi, Vhembo, Chawana, Nematadzira and Donenberg.)

Background: With maturity and development, complexity in demands and roles change. As participation is often restricted in children with disabilities, this process might be delayed in adolescents. Investigating profiles of participation for adolescents with and without neurodevelopmental impairments could provide an understanding of which factors relate to high level of participation. The aim is to investigate trajectories of participation in everyday activities across clusters based on self-rated participation patterns in frequency of participation and perceived importance of activities related to domestic life and peer-related activities for adolescents with and without self-reported neurodevelopmental impairments., Methods and Procedures: A prospective person-based cohort study design., Outcomes and Results: Five typical trajectories were identified. Trajectories between clusters with high perceived involvement in peer relations were associated with sibling support and family communication. Self-reported neurodevelopmental impairments did not predict participation profiles at certain time points, nor movements between clusters when measuring self-reported attendance and importance in domestic life and in peer-related activities., Conclusion and Implications: Perceived sibling support and family communication are important for predicting typical trajectories across clusters in frequency of attendance and the perceived importance of domestic life and peer relations. Type of impairment was less important in predicting typical trajectories., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Background: An increasing number of neurologic problems are being described in coronavirus disease 2019 (COVID-19) disease, but their frequency and type have not been defined. In this study, we sought to determine the extent of neurologic manifestations of COVID-19 in a prospective series of unselected patients admitted to the general medicine wards of our hospitals due to COVID-19 and who were examined by a team of neurologists., Methods: Eight neurologists provided medical attention to patients hospitalized for COVID-19 to provide medical support to other hospital units tasked with the care of an increasingly larger influx of patients with COVID-19. A series of 100 consecutive, unselected patients were evaluated systematically, including a questionnaire that collected medical information derived from the initial examination and the medical history., Results: Eighty-eight percent of the patients had 1 neurologic manifestation associated with COVID-19 during hospitalization. Most common were anosmia-dysgeusia and headache (44% each), myalgias (43%), and dizziness (36%). Less frequent were encephalopathy (8%), syncope (7%), seizures (2%), and ischemic stroke during the period of hospitalization (2%). Anosmia and headache associated with younger patients with less severe disease, and both were associated with each other and with serum inflammatory markers. Encephalopathy was associated with fever and syncope and with markers of inflammation., Conclusions: Neurologic disturbances are common in patients with COVID-19, particularly if patients are evaluated by neurologists. There is a wide variety of neurologic conditions, some of them severe, in the spectrum of COVID-19 disease that will benefit from an evaluation by practicing neurologists., (© 2020 American Academy of Neurology.)

Background: Interpersonal trauma (IPT) is highly prevalent among HIV-positive (HIV+) individuals, but its relationship with brain morphology and function is poorly understood., Setting: This cross-sectional analysis evaluated the associations of IPT with cognitive task performance, daily functioning, magnetic resonance imaging (MRI) brain cortical thickness, and bilateral volumes of 4 selected basal ganglia regions in a US-based cohort of aviremic HIV+ individuals, with (HIV+ IPT+) and without IPT exposure (HIV+ IPT-), and sociodemographically matched HIV-negative controls with (HIV- IPT+) and without IPT exposure (HIV- IPT-)., Methods: Enrollees completed brain MRI scans, a semistructured psychiatric interview, a neurocognitive battery, and 3 measures of daily functioning. Demographic and clinical characteristics of the 4 groups were described, and pairwise between-group comparisons performed using χ tests, analysis of variance, or t-tests. Linear or Poisson regressions evaluated relationships between group status and the outcomes of interest, in 6 pairwise comparisons, using Bonferroni correction for statistical significance., Results: Among 187 participants (mean age 50.0 years, 63% male, 64% non-white), 102 were HIV+ IPT+, 35 were HIV+ IPT-, 26 were HIV- IPT-, and 24 were HIV- IPT+. Compared with the remaining 3 groups, the HIV+ IPT+ group had more activities of daily living declines, higher number of impaired Patient's Assessment of Own Functioning Inventory scores, and lower cortical thickness in multiple cerebral regions. Attention/working memory test performances were significantly better in HIV- IPT- compared with the HIV+ IPT+ and HIV+ IPT- groups. Basal ganglia MRI volumes were not significantly different in any between-group comparisons., Conclusion: IPT exposure and HIV infection have a synergistic effect on daily functioning and cortical thickness in aviremic HIV+ individuals.

Introduction: Acute appendicitis (AA) is the most common surgical condition of the abdomen in children. The aim of this study was to analyse the possible use of the neutrophil-to-lymphocyte ratio (NLR) in the diagnosis and prediction of AA complications in children., Material and Methods: We included 170 AA patients under 15 years of age, who were divided into the following groups: Group 1 - non-operated patients with AA, and Group 2 - patients who underwent appendectomy. Based on pathologic grades of AA, Group 2 was subdivided into: Group A - phlegmonous, Group B - gangrenous, and Group C - perforated AA. NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count., Results: In Group 2 NLR was significantly higher than in Group 1 (5.5 (1.9-9.9) vs. 2.3 (1.2-3.7); p < 0.001). A significant difference in NLR was found between Group C and Group A ( p < 0.001), and as well as between Group B and Group A ( p = 0.001). The determined optimal cut-off value of NLR in differentiating Group 1 vs. Group 2 was ≥ 3.48 ( p < 0.001). In differentiating Group A from Group C the optimal cut-off value of NLR was ≥ 5.61 ( p < 0.001). Furthermore, optimal cut-off value of NLR in differentiating Group A from Group B was ≥ 5.45 ( p = 0.001)., Conclusions: The obtained results suggest that NLR could be used as a simple and reliable test in the diagnosis and prediction of AA complications in children. However, to draw definite conclusions on the predictive power of NLR as a marker of AA large multicentric studies are required., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG) exp ] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG) 11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth. Methods: IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(-)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan. Results: Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5-118.2) kg, 21.8 (9.1-24.7) years, and 75.0 (12.5-150.0) mg once daily. Sertraline exposure was highest for HIV(-) and lowest for EFV cohorts; median dose-normalized AUC 0-24 was 1176 (HIV(-)), 791 (PI/r) and 473 (EFV) ng * hr/mL, and C 24 was 32.7 (HIV(-)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(-) vs. PI/r cohorts ( p = 0.01). Four HIV(-) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5). Conclusions: HIV(-) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(-); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants.

Objective: To evaluate the safety of in-utero exposure to atazanavir and neurodevelopment in perinatally HIV-exposed but uninfected (PHEU) infants., Design: Prospective cohort study of mother-PHEU infant pairs in the Surveillance Monitoring for ART Toxicities protocol of the Pediatric HIV/AIDS Cohort Study., Methods: Pregnant women living with HIV who initiated an antiretroviral regimen during pregnancy were followed from the date of antiretroviral initiation. Women were classified according to whether the antiretroviral regimen contained atazanavir and the trimester of antiretroviral initiation. Neurodevelopment at 9-15 months was evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). We estimated mean differences for the five Bayley-III domains for atazanavir-containing regimens versus all other regimens. Models included baseline covariates and adjustment for failure to complete the Bayley-III using inverse probability weighting., Results: PHEU infants were exposed in utero to atazanavir-containing (n = 167) and nonatazanavir-containing (n = 750) antiretroviral regimens. The adjusted mean differences (95% confidence interval) in Bayley-III domain scores for initiating an atazanavir-containing regimen in the first trimester were: cognitive, -1.5 (-6.2, 3.2); language, -3.3 (-7.6, 1.0); motor, -2.9 (-7.7, 1.9); social-emotional, 0.1 (-6.2, 6.4); and adaptive behavior, -0.1 (-4.3, 4.0). The mean differences for the second or third trimester were: cognitive, 0.4 (-3.2, 4.0); language, -3.4 (-6.2, -0.5); motor, 0.3 (-2.9, 3.4); social-emotional, -5.9 (-9.4, -2.3); and adaptive behavior, -2.5 (-5.9, 0.8)., Conclusion: In-utero exposure to atazanavir-containing regimens compared with non-atazanavir-containing regimens may adversely affect language and social-emotional development in PHEU infants during the first year of life, but the absolute difference is small.

Aim: To determine if efforts to improve antiretroviral therapy (ART) adherence minimizes the negative impact of depression on human immunodeficiency virus (HIV) outcomes., Methods: A cross-sectional study of a clinic-based cohort of 158 HIV seropositive (HIV+) African Americans screened for major depressive disorder (MDD) in 2012. CD4 T lymphocyte (CD4+) counts were obtained from these individuals. Self-report on adherence to ART was determined from questionnaire administered during clinic visits. The primary outcome measure was conditional odds of having a poorer CD4+ count (< 350 cells/mm(3)). Association between CD4+ count and antidepressant-treated or untreated MDD subjects was examined controlling for self-reported adherence and other potential confounders., Results: Out of 147 individuals with available CD4+ T lymphocyte data, 31% hadCD4+ count < 350 cells/mm(3) and 28% reported poor ART adherence. As expected the group with > 350 cells/mm(3) CD4+ T lymphocyte endorsed significantly greater ART adherence compared to the group with < 350 cells/mm(3) CD4+ T lymphocyte count (P < 0.004). Prevalence of MDD was 39.5% and 66% of individuals with MDD took antidepressants. Poor CD4+ T lymphocyte count was associated with poor ART adherence and MDD. Adjusting for ART adherence, age, sex and education, which were potential confounders, the association between MDD and poor CD4+ T lymphocyte remained significant only in the untreated MDD group., Conclusion: Therefore, CD4+ count could be a clinical marker of untreated depression in HIV+. Also, mental health care may be relevant to primary care of HIV+ patients.

Background: We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study., Methods: Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry., Results: Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets., Conclusions: In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.

Objective: To evaluate prevalence, incidence, remission, and persistence of psychiatric and substance use disorders among HIV-infected mothers and identify biopsychosocial correlates., Methods: HIV-infected mothers (n = 1223) of HIV-exposed uninfected children enrolled in a prospective cohort study; HIV-uninfected mothers (n = 128) served as a comparison group. Mothers provided sociodemographic and health information and completed the Client Diagnostic Questionnaire (CDQ). Prevalence of any psychiatric or substance use disorder at initial evaluation was compared between the 2 groups. Incident, remitting, and persisting disorders were identified for 689 mothers with HIV who completed follow-up CDQs. We used logistic regression to evaluate adjusted associations of biopsychosocial characteristics with presence, incidence, remission, and persistence of disorders., Results: Thirty-five percent of mothers screened positive for any psychiatric or substance use disorder at initial evaluation, with no difference by maternal HIV status (P = 1.00). Among HIV-infected mothers, presence of any disorder was associated with younger age [adjusted odds ratio (aOR): 1.39; 95% CI: 1.09 to 1.75], single parenthood (aOR: 1.35; 95% CI: 1.08 to 1.68), and functional limitations (aOR: 2.29; 95% CI: 1.81 to 2.90). Incident disorders were associated with functional limitations (aOR: 1.92; 95% CI: 1.10 to 3.30). Among HIV-infected mothers with a disorder at initial evaluation (n = 238), 61% had persistent disorders. Persistent disorders were associated with lower income (aOR: 2.44; 95% CI: 1.33 to 4.76) and functional limitations (aOR: 3.19; 95% CI: 1.87 to 5.48). Receipt of treatment for any disorder was limited: 4.5% at study entry, 7% at follow-up, 5.5% at both entry and follow-up., Conclusions: Psychiatric and substance use disorders remain significant comorbid conditions among HIV-infected mothers and require accessible evidence-informed treatment.

Objective: To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth., Design: Cross-sectional design within a prospective, 15-site US-based cohort study., Methods: Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores., Results: Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs., Conclusion: Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.

Objective: To evaluate baseline T-cell activation and neurodevelopmental outcomes over time in a cohort of perinatally HIV-infected (PHIV-infected) children with severe disease., Design: Pediatric AIDS Clinical Trials Group protocol 366 (PACTG 366) was a partially randomized, open-label, multicenter 96-week antiretroviral treatment-algorithm study. Neurodevelopmental status, measured by age-dependent evaluations (Bayley scales of infant development-II; Wechsler preschool and primary scale of intelligence-revised; Wechsler intelligence scale for children-III), was a secondary outcome., Methods: Linear mixed models were used to assess the baseline and follow-up neurodevelopmental outcomes in relation to immune activation, measured by CD38 and human leukocyte antigen (HLA) DR expression on peripheral CD4(+) and CD8(+) T cells at study baseline. Models were adjusted for age, sex, race/ethnicity, baseline viral load, baseline CD4%, cytomegalovirus (CMV) infection status at entry, study treatment arms, central nervous system penetrance score of antiretroviral regimen at entry, and viral load response 16 weeks postentry., Results: Among 126 PACTG 366 enrollees who were at least 1 year old and had both immune activation and age-appropriate neurodevelopmental assessments at baseline, 80 (63%) were black non-Hispanic, 71 (56%) males, 122 (97%) were on antiretrovirals, and 45 (36%) were in Centers for Disease Control and Prevention (CDC) disease category C at entry. CD4(+)CD38(+)HLADR(+)%, CD4(+)CD38(-)HLADR(+)%, and CD8(+)CD38(+)HLADR(+)% were positively associated with full-scale Intelligence Quotient scores (FSIQ) (slope = 0.18, 0.70, and 0.15, respectively; P = 0.02, 0.03, and 0.04, respectively). CD4(+)CD38(+)HLADR(-)% was negatively associated with FSIQ (slope =  -0.16, P = 0.01)., Conclusion: Contrary to HIV-infected adults, in PHIV-infected children higher CD4(+)CD38(+)HLADR(+)% may be associated with a neuroprotective effect and higher percentage of CD4(+)CD38(+) but HLADR(-) T cells may be deleterious.

PURPOSE: Perinatally HIV-infected children, who are increasingly aging into adolescence and early adulthood, have significant rates of psychiatric co-morbidities, some of which are treated with second-generation antipsychotics (SGAs). SGAs have been associated with elevated total cholesterol (TC) in youth, but no studies have examined this association in perinatally HIV-infected youth. This study examined changes in TC levels of youth with perinatally acquired HIV infection and co-morbid psychiatric conditions treated with SGAs. PATIENTS AND METHODS: Long-term changes in TC levels were examined using data from the US multisite prospective Pediatric AIDS Clinical Trials Group 219C cohort study. The change in TC levels from baseline to 12 months after initiating SGA use was compared between 52 SGA-exposed and 148 matched SGA-unexposed perinatally HIV-infected youth, using generalized estimating equation models adjusting for other covariates. The prevalence and time to incident hypercholesterolemia were also compared between these 2 groups. RESULTS: After adjustment for confounders, 52 youth with prescriptions for SGAs had a larger increase in TC levels than 148 matched youth without antipsychotic prescriptions (mean difference = 9 mg/dL, z = 1.96, df = 1, P = 0.0496). Among youth with TC below 220 mg/dL at baseline, 27% of SGA-exposed youth developed hypercholesterolemia (defined as two consecutive TC measurements ≥220 mg/dL), compared with 13% of SGA-unexposed patients (Fisher's exact test, P = 0.046). CONCLUSIONS: Caution should be used in prescribing SGAs to perinatally HIV-infected youth with psychiatric co-morbidities due to increased risk of hypercholesterolemia. Patients should be monitored, and alternative evidence-based treatments considered when available.

Objective: To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease., Design: A cross-sectional design within a prospective, 15-site cohort study conducted in the United States., Methods: Nine vascular biomarkers were examined in 89 HIV-infected children: soluble P-selectin/sCD62P, fibrinogen, adiponectin, monocyte chemoattractant protein-1/CCL-2, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1/sCD106, sE-selectin/sCD62E, and soluble intercellular adhesion molecule-1/sCD54. The Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) was administered yielding indices for verbal comprehension, perceptual reasoning, working memory and processing speed, and overall composite Full-Scale IQ score. Linear regression models were used to evaluate neurodevelopmental status (measured by WISC-IV scores) as a function of each biomarker while adjusting for demographics, disease severity, and receipt of HAART. Biomarker levels were evaluated in quartiles to evaluate trends in WISC-IV responses., Results: Among the 89 HIV-infected children (median age = 12 years), 56% were girls, 71% black, 16% Hispanic, and 43% had yearly household income below US $20,000. Log (soluble P-selectin) was significantly correlated with all WISC-IV scores; adjusted slopes showed 6-11-point average decrease in scores for each one log unit increase in soluble P-selectin. Final linear regression models for log (fibrinogen) adjusted for sociodemographic and disease characteristics also indicated a negative correlation with all WISC-IV scores (13-30-point decrease for each one log unit increase in fibrinogen); these decreases were significant in the verbal comprehension, perceptual reasoning, and Full-Scale IQ scores., Conclusion: Proinflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally acquired HIV disease.