Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes

BACKGROUND: Paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS) have a very poor prognosis: more than half of the patients become bedridden and median survival is less than 12 months. Several lines of evidence suggest a pathogenic T cell-mediated immune response. Therefore, we conducted a prospective open-label phase II trial with natalizumab. METHODS: Twenty Hu-PNS patients with progressive disease were treated with a maximum of three monthly natalizumab cycles (300 mg). The primary outcome measure was functional improvement, this was defined as at least one point decrease in modified Rankin Scale (mRS) score at the last treatment visit. In addition, treatment response was assessed wherein a mRS score ≤3 after treatment was defined as treatment responsive. RESULTS: The median age at onset was 67.8 years (SD 8.4) with a female predominance (n = 17, 85%). The median time from symptom onset to Hu-PNS diagnosis was 5 months (IQR 2–11). Most patients had subacute sensory neuronopathy (n = 15, 75%), with a median mRS of 4 at baseline. Thirteen patients had a tumor, all small cell lung cancer. After natalizumab treatment, two patients (10%) showed functional improvement. Of the remaining patients, 60% had a stable functional outcome, while 30% showed further deterioration. Treatment response was classified as positive in nine patients (45%). CONCLUSIONS: Natalizumab may ameliorate the disease course in Hu-PNS, but no superior effects above other reported immunosuppressive and immunomodulatory were observed. More effective treatment modalities are highly needed. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000675-13/N

Association of ethnicity with multisystem inflammatory syndrome in children related to SARS-CoV-2 infection: an international case-referent study

Background: It has been suggested that children and infants can develop multisystem inflammatory syndrome in children (MIS-C) in response to a SARS-CoV-2 infection and that Black children are overrepresented among cases. The aim of the current study was to quantify the association between Black, Asian, or other non-White genetic background and COVID-19-related MIS-C in children and infants.Methods: Eight different research groups contributed cases of MIS-C, potentially related to SARS-CoV-2 infection. Several sensitivity analyses were performed, including additional data available from the literature. Analyses were stratified by geographical region.Results: Seventy-three cases from nine distinct geographical regions were included in the primary analyses. In comparison to White children, the relative risk for developing MIS-C after SARS-CoV-2 infection was 15 [95% confidence interval (CI): 7.1 to 32] for Black children, 11 (CI: 2.2 to 57) for Asian, and 1.6 (CI: 0.58 to 4.2) for other ethnic background.Conclusion: Pediatricians should be aware of the fact that the risk of COVID-19-related MIS-C is severely increased in Black children.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Emotional problems in preadolescents in Norway: the role of gender, ethnic minority status, and home- and school-related hassles

<p>Abstract</p> <p>Background</p> <p>"The gender gap" refers to a lifelong higher rate of emotional problems in girls, as compared to boys, that appears during adolescence. The gender gap is a well-replicated finding among older adolescents and is assumed to be a cross-cultural phenomenon. However, these cross-cultural studies have not investigated the gender gap in ethnic minorities but sampled ethnic majority adolescents in different countries. Some studies that investigated the gender gap across ethnic groups indirectly (by presenting emotional problem scores stratified by gender and ethnic group) indicate that the gender gap is less prominent or even absent among minorities. The aims of this study were to assess whether the gender gap is found in both majority and minority preadolescents, and to investigate whether a possible (gender and ethnic) group difference can be accounted for by differences in home or school hassles.</p> <p>Methods</p> <p>Participants were 902 preadolescent students (aged 10 to 12) from two cities in Norway. We collected self-report measures of emotional problems and home and school hassles. Using mediated moderation analysis we tested whether the interaction effect between gender and ethnic minority background on emotional problems was mediated by home or school hassles.</p> <p>Results</p> <p>The gender gap in emotional problems was restricted to ethnic majority preadolescents. School hassles but not home hassles accounted in part for this effect.</p> <p>Conclusions</p> <p>The absence of the gender gap among minority as opposed to majority preadolescents may indicate that social circumstances may postpone or hamper the emergence and magnitude of the gender gap in ethnic minority preadolescents. In this study, school hassles partly accounted for the combined gender and ethnic group differences on emotional problems. This indicates that school hassles may play a role in the higher levels of emotional problems in preadolescent minority boys and consequently the absence of a gender gap found in our minority sample.</p

Use of the Pediatric Symptom Checklist for the detection of psychosocial problems in preventive child healthcare

BACKGROUND: Early detection and treatment of psychosocial problems by preventive child healthcare may lead to considerable health benefits, and a short questionnaire could support this aim. The aim of this study was to assess whether the Dutch version of the US Pediatric Symptom checklist (PSC) is valid and suitable for the early detection of psychosocial problems among children. METHODS: We included 687 children (response 84.3%) aged 7–12 undergoing routine health assessments in nine Preventive Child Health Services across the Netherlands. Child health professionals interviewed and examined children and parents. Before the interview, parents completed an authorised Dutch translation of the PSC and the Child Behavior Checklist (CBCL). The CBCL and data on the child's current treatment status were used as criteria for the validity of the PSC. RESULTS: The consistency of the Dutch PSC was good (Cronbach alpha 0.89). The area under the ROC curve using the CBCL as a criterion was 0.94 (95% confidence interval 0.92 to 0.96). At the US cut-off (28 and above), the prevalence rate of an increased score and sensitivity were lower than in the USA. At a lower cut-off (22 and above), sensitivity and specificity were similar to that of the US version (71.7% and 93.0% respectively). Information on the PSC also helped in the identification of children with elevated CBCL Total Problems Scores, above solely clinical judgment. CONCLUSION: The PSC is also useful for the early detection of psychosocial problems in preventive child healthcare outside the USA, especially with an adjusted cut-off

European youth care sites serve different populations of adolescents with cannabis use disorder. Baseline and referral data from the INCANT trial

Background: MDFT (Multidimensional Family Therapy) is a family based outpatient treatment programme for adolescent problem behaviour. MDFT has been found effective in the USA in adolescent samples differing in severity and treatment delivery settings. On request of five governments (Belgium, France, Germany, the Netherlands, and Switzerland), MDFT has now been tested in the joint INCANT trial (International Cannabis Need of Treatment) for applicability in Western Europe. In each of the five countries, study participants were recruited from the local population of youth seeking or guided to treatment for, among other things, cannabis use disorder. There is little information in the literature if these populations are comparable between sites/countries or not. Therefore, we examined if the study samples enrolled in the five countries differed in baseline characteristics regarding demographics, clinical profile, and treatment delivery setting.Methods: INCANT was a multicentre phase III(b) randomized controlled trial with an open-label, parallel group design. It compared MDFT with treatment as usual (TAU) at and across sites in Berlin, Brussels, Geneva, The Hague and Paris.Participants of INCANT were adolescents of either sex, from 13 through 18 years of age, with a cannabis use disorder (dependence or abuse), and at least one parent willing to take part in the treatment. In total, 450 cases/families were randomized (concealed) into INCANT.Results: We collected data about adolescent and family demographics (age, gender, family composition, school, work, friends, and leisure time). In addition, we gathered data about problem behaviour (substance use, alcohol and cannabis use disorders, delinquency, psychiatric co-morbidity).There were no major differences on any of these measures between the treatment conditions (MDFT and TAU) for any of the sites. However, there were cross-site differences on many variables. Most of these could be explained by variations in treatment culture, as reflected by referral policy, i.e., participants' referral source. We distinguished 'self-determined' referral (common in Brussels and Paris) and referral with some authority-related 'external' coercion (common in Geneva and The Hague). The two referral types were more equally divided in Berlin. Many cross-site baseline differences disappeared when we took referral source into account, but not all.Conclusions: A multisite trial has the advantage of being efficient, but it also carries risks, the most important one being lack of equivalence between local study populations. Our site populations differed in many respects. This is not a problem for analyses and interpretations if the differences somehow can be accounted for. To a major extent, this appeared possible in INCANT. The most important factor underlying the cross-site variations in baseline characteristics was referral source. Correcting for referral source made most differences disappear. Therefore, we will use referral source as a covariate accounting for site differences in future INCANT outcome analyses

Parents' concerns about children are highly prevalent but often not confirmed by child doctors and nurses

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the prevalence in the general population of parents' concerns about the development of their child, to identify groups at risk and to assess the association between parents' concerns and professional judgement.</p> <p>Methods</p> <p>We obtained cross-sectional data on a Dutch nationally representative sample of children aged 14 months, 3 3/4, 5–6 and 8–12 years within the setting of routine well-child visits provided to the entire population. A total of 4,107 participated (response rate 85.3%). Data were about concerns that parents reported by questionnaire before the visit regarding behavioural and emotional problems, developmental delay, consequences of disease and contact with peers that needed professional assistance, and about the assessment of these domains by doctors and nurses during the visit. Moreover, we obtained data on parent-reported psychosocial problems using the Infant-Toddler Social and Emotional Assessment and the Child Behavior Checklist.</p> <p>Results</p> <p>Of all parents, 49.3% reported some concerns and 8.7% reported frequent concerns, most frequently on child behaviour. Frequent concerns were most likely to refer to young children, children from labour immigrant families, with fathers of medium educational level and in low-income families. The prevalence rates of professional-assessed parenting problems were much lower than parent-reported ones. The rates of psychosocial problems were highest in the case of shared concerns, but also higher if parents expressed concerns that were not confirmed by professionals.</p> <p>Conclusion</p> <p>A very large proportion of parents of young children have concerns regarding their child, but agreement on these concerns with child health professionals is relatively low.</p

Addressing risk factors for child abuse among high risk pregnant women: design of a randomised controlled trial of the nurse family partnership in Dutch preventive health care

<p>Abstract</p> <p>Background</p> <p>Low socio-economic status combined with other risk factors affects a person's physical and psychosocial health from childhood to adulthood. The societal impact of these problems is huge, and the consequences carry on into the next generation(s). Although several studies show these consequences, only a few actually intervene on these issues. In the United States, the Nurse Family Partnership focuses on high risk pregnant women and their children. The main goal of this program is primary prevention of child abuse. The Netherlands is the first country outside the United States allowed to translate and culturally adapt the Nurse Family Partnership into VoorZorg. The aim of the present study is to assess whether VoorZorg is as effective in the Netherland as in the United States.</p> <p>Methods</p> <p>The study consists of three partly overlapping phases. Phase 1 was the translation and cultural adaptation of Nurse Family Partnership and the design of a two-stage selection procedure. Phase 2 was a pilot study to examine the conditions for implementation. Phase 3 is the randomized controlled trial of VoorZorg compared to the care as usual. Primary outcome measures were smoking cessation during pregnancy and after birth, birth outcomes, child development, child abuse and domestic violence. The secondary outcome measure was the number of risk factors present.</p> <p>Discussion</p> <p>This study shows that the Nurse Family Partnership was successfully translated and culturally adapted into the Dutch health care system and that this program fulfills the needs of high-risk pregnant women. We hypothesize that this program will be effective in addressing risk factors that operate during pregnancy and childhood and compromise fetal and child development.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN16131117">ISRCTN16131117</a></p

Trajectories of peer nominated aggression: Risk status, predictors and outcomes

Developmental trajectories of peer-nominated aggression, risk factors at baseline, and outcomes were studied. Peer nominations of aggression were obtained annually from grades 1 to 3. Three developmental trajectories were identified: an early-onset/increasers trajectory with high levels of peer-nominated aggression at elementary school entry and increasing levels throughout follow-up; a moderate-persistent trajectory of aggression in which children were characterized by moderate levels of physical aggression at baseline; and a third trajectory with stable low levels of aggression. Children following the early-onset/increasers trajectory showed physical forms of aggression at baseline. Male gender and comorbid attention deficit/hyperactivity problems, oppositional defiant problems and poor prosocial behavior plus negative life events predicted which children would follow the early-onset/increasers trajectory of aggression. The outcomes associated with the early-onset/increaser children suggest high risk for chronically high levels of aggressive behavior. © 2005 Springer Science+Business Media, Inc

Anti-NMDAR Encephalitis in the Netherlands, Focusing on Late-Onset Patients and Antibody Test Accuracy

BACKGROUND AND OBJECTIVES: To describe the clinical features of anti-NMDAR encephalitis, emphasizing on late-onset patients and antibody test characteristics in serum and CSF. METHODS: Nationwide observational Dutch cohort study, in patients diagnosed with anti-NMDAR encephalitis between 2007 and 2019. RESULTS: One hundred twenty-six patients with anti-NMDAR encephalitis were included with a median age of 24 years (range 1-86 years). The mean annual incidence was 1.00/million (95% CI 0.62-1.59). Patients ≥45 years of age at onset (19%) had fewer seizures (46% vs 71%, p = 0.021), fewer symptoms during disease course (3 vs 6 symptoms, p = 0.020), and more often undetectable serum antibodies compared with younger patients (p = 0.031). In the late-onset group, outcome was worse, and all tumors were carcinomas (both p < 0.0001). CSF was more accurate than serum to detect anti-NMDAR encephalitis (sensitivity 99% vs 68%, p < 0.0001). Using cell-based assay (CBA), CSF provided an unconfirmed positive test result in 11/2,600 patients (0.4%); 6/11 had a neuroinflammatory disease (other than anti-NMDAR encephalitis). Patients with anti-NMDAR encephalitis, who tested positive in CSF only, had lower CSF antibody titers (p = 0.003), but appeared to have an equally severe disease course. DISCUSSION: Anti-NMDAR encephalitis occurs at all ages and is less rare in the elderly patients than initially anticipated. In older patients, the clinical phenotype is less outspoken, has different tumor association, and a less favorable recovery. Detection of antibodies in CSF is the gold standard, and although the CBA has very good validity, it is not perfect. The clinical phenotype should be leading, and confirmation in a research laboratory is recommended, when in doubt

Better mental health in children of Vietnamese refugees compared with their Norwegian peers - a matter of cultural difference?

<p>Abstract</p> <p>Background</p> <p>There are conflicting results on whether immigrant children are at a heightened risk of mental health problems compared with native youth in the resettlement country.</p> <p>The objective of the study</p> <p>To compare the mental health of 94 Norwegian-born children from a community cohort of Vietnamese refugees, aged 4 - 18 years, with that of a Norwegian community sample.</p> <p>Methods</p> <p>The SDQ was completed by two types of informants; the children's self-reports, and the parents' reports, for comparison with Norwegian data from the Health Profiles for Children and Youth in the Akershus study.</p> <p>Results</p> <p>The self-perceived mental health of second-generation Vietnamese in Norway was better than that of their Norwegian compatriots, as assessed by the SDQ. In the Norwegian-Vietnamese group, both children and parents reported a higher level of functioning.</p> <p>Conclusion</p> <p>This surprising finding may result from the lower prevalence of mental distress in Norwegian-Vietnamese children compared with their Norwegian peers, or from biased reports and cultural differences in reporting emotional and behavioural problems. These findings may represent the positive results of the children's bi-cultural competencies.</p