The role of well-child visits in detecting developmental delay in preschool children.

BACKGROUND: Early detection of developmental delay (DD) in preschool children is crucial for counselling parents, initiating diagnostic work-up, and starting early intervention (EI). METHODS: We conducted a register study of all preschool children referred for EI in the Canton of Zurich, Switzerland, in 2017 (N = 1,785) and used an online survey among primary care physicians (PCPs, N = 271) to evaluate the care service of DD children. RESULTS: PCPs accounted for 79.5% of all referrals by physicians and had correctly referred over 90% of the children in need of EI at an average age of 39.3 months (SD 8.9). In the survey, which represents 59.2% of all pediatricians and 11.3% of all general practitioners in the Canton, PCPs reported performing a mean of 13.5 (range 0-50, SD 10.7) well-child visits per week to preschool children and estimated well-child visits to be the most frequent type of consultation (66.7%) for the identification of DD. Parents' hesitancy in accepting further evaluation or support were reported by 88.7%. CONCLUSIONS: Most preschool children with DD are identified in well-child visits. These visits represent an ideal opportunity for early detection of developmental impairment and initiation of EI. Carefully addressing parents' reservations could reduce the rate of refusal, thus improving early support for children with DD.

Diagnosis and management of ADHD: a pediatric perspective on practice and challenges in Switzerland.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in childhood. In Switzerland, the complex diagnosis and treatment are being carried out by adolescent-/child psychiatrists, and pediatricians. Guidelines recommend a multimodal therapy for patients with ADHD. However, it has been questioned whether health professionals follow this approach or favor drug therapy. This study aims to provide insights into the practice of pediatricians in Switzerland regarding diagnosis and treatment of ADHD and their perceptions of these processes. METHOD: An online survey (self-report) about current practices of diagnosis and management as well as challenges regarding ADHD was distributed to office-based pediatricians in Switzerland. One hundred fifty-one pediatricians participated. Results show that therapy options were almost always discussed with parents and older children. Exchange with parents (81%) and level of child's suffering (97%) were central when selecting therapy options. RESULTS: Therapies about which pediatricians informed most often were: pharmacological therapy, psychotherapy, and multimodal therapy. Challenges voiced were the subjectivity of diagnostic criteria and dependence on third parties, low availability of psychotherapy, and a rather negative public attitude towards ADHD. Needs that were expressed were further education for all professionals, support for coordination with specialists and schools as well as improvement of information on ADHD. CONCLUSIONS: Pediatricians do consider a multimodal approach when treating ADHD and take the families` and children's opinions into account. Improvements of the availability of child and youth psychotherapy, the strengthening of the interprofessional cooperation with therapists and schools, and efforts to increase public knowledge about ADHD are proposed.

[Retrospective evaluation of electronically recorded patient questionnaires of a university outpatient pain clinic with the painDETECT® questionnaire]. / Retrospektive Auswertung elektronisch erhobener Patientenfragebögen einer universitären Schmerzambulanz mit dem painDETECT®-Fragebogen.

BACKGROUND AND OBJECTIVE: Psychometric tests can provide important information for diagnostics and progression in chronic pain patients. Between 2008 and 2018, the electronic system painDETECT® was used in the outpatient pain clinic of the Hannover Medical School (MHH). The aim of this retrospective study was to evaluate the pain symptomatology data recorded using painDETECT® and the treatment procedures used in the patient cohort examined over a period of 15 months. MATERIAL AND METHODS: A statistical analysis of baseline and follow-up data was performed. The analysis comprised pain-related parameters recorded by use of the painDETECT® system as well as outpatient records. RESULTS: Baseline data of 459 patients (66% women) could be evaluated. The most common clinical pictures were spinal pain, headache, facial pain, and somatoform disorders, mostly with many years of previous treatment. Approximately 40% showed evidence of neuropathic pain components or central sensitization. With a mean pain intensity of VAS 6 (0-10), a predominantly high degree of chronicity was present. Approximately one third showed a high degree of pain-related functional impairment. Slightly more than half showed evidence of clinically relevant depression. Approximately 80% showed clinically relevant sleep disturbances. Follow-up data were available for 145 patients (31.6%). The proportion of patients receiving a nonpharmacological form of treatment increased by 44.1% (physical therapy) and by 24.1% (psychotherapeutic procedures) during the observation period. The use of co-analgesics increased by approximately 30% over the course. CONCLUSION: In the outpatient setting, an extension of treatment can be successful for high-grade chronic pain patients. Close structural networking with the clinics for rehabilitation medicine and for psychosomatics and psychotherapy at the MHH can be a favorable prerequisite for this.

Methylation and Expression of Mutant FUS in Motor Neurons Differentiated From Induced Pluripotent Stem Cells From ALS Patients.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease leading to degeneration of motor neurons (MNs). Epigenetic modification of gene expression is increasingly recognized as potential disease mechanism. In the present study we generated motor neurons from induced pluripotent stem cells from ALS patients carrying a mutation in the fused in sarcoma gene (FUS) and analyzed expression and promoter methylation of the FUS gene and expression of DNA methyltransferases (DNMTs) compared to healthy control cell lines. While mutant FUS neural progenitor cells (NPCs) did not show a difference in FUS and DNMT expression compared to healthy controls, differentiated mutant FUS motor neurons showed significantly lower FUS expression, higher DNMT expression and higher methylation of the proximal FUS gene promoter. Immunofluorescence revealed perceived proximity of cytoplasmic FUS aggregates in ALS MNs together with 5-methylcytosin (5-mC). Targeting disturbed methylation in ALS may therefore restore transcriptional alterations and represent a novel therapeutic strategy.

Leptin Expression and Gene Methylation Patterns in Alcohol-Dependent Patients with Ethyltoxic Cirrhosis-Normalization After Liver Transplantation and Implications for Future Research.

AIMS: Liver transplantation is the only curative treatment available for patients with end-stage alcoholic liver disease. As different studies showed a significant association between leptin plasma levels, gene methylation patterns and the extent of craving in alcohol-dependent patients, we investigated the effect of liver transplantation on leptin expression and promoter methylation. SHORT SUMMARY: The present study shows that in alcohol-dependent patients with liver cirrhosis leptin is significantly higher before liver transplantation and decreases significantly after transplantation. Alcohol-dependent patients on the waiting list had significantly higher leptin promoter methylation values than patients who underwent liver transplantation for other reasons than alcoholic liver disease. METHODS: Only plasma of 118 and peripheral blood mononuclear cells of 121 patients were used: healthy controls (C, n = 24/22), alcohol-dependent patients without ethyltoxic liver cirrhosis (AD, n = 24/22), patients after liver transplantation for other reasons than ethyltoxic liver cirrhosis (C-Tx, n = 18/21), alcohol-dependent patients suffering from ethyltoxic liver cirrhosis on the transplantation waiting list (Pre-Tx, n = 30/28) and patients with prior ethyltoxic liver cirrhosis after liver transplantation (Post-Tx, n = 22/28). RESULTS: Leptin protein was significantly elevated in the pre-transplantation cohort when compared to post-transplantation and alcohol-dependent cohorts. Furthermore, leptin promoter methylation was higher in ethyltoxic patients before transplantation compared to non-ethyltoxic patients after transplantation, but not when compared to ethyltoxic patients after transplantation. C-Tx had lower methylation values than all other groups except for Post-Tx. CONCLUSIONS: Our study outlines the role of leptin protein levels as a marker for AD-related liver damage, contrasting it from AD without severe liver damage. With regard to the results of the methylation analysis, inflammation of the liver appears to cause mechanisms of leptin regulation to deviate from transcriptional regulation. Our data also suggest that leptin regulation is altered in ethyltoxic liver disease when compared to liver cirrhosis caused by other pathologies.

Motor dysfunction and behavioural problems frequently coexist with congenital heart disease in school-age children.

AIM: Patients with congenital heart disease are at risk of neurodevelopmental deficits. Impairments in motor and behavioural function occur frequently, but no information is available concerning the coexistence of deficits in these two developmental domains. This study explored the occurrence of motor and behavioural deficits and their coexistence in children with surgically corrected congenital heart disease. METHODS: Outcome was assessed in 95 children with congenital heart disease who had undergone cardiopulmonary bypass surgery. Their mean age was 9.6 years (SD 2.5). Motor function was assessed with the Zurich Neuromotor Assessment and behaviour with the Strength and Difficulties Questionnaire. RESULTS: Children with congenital heart disease performed poorer in all motor domains compared with the reference population (all p ≤ 0.001). Behaviour was affected in the domains 'emotional symptoms' and 'hyperactivity/inattention' (both p < 0.01), and 54% of the children with motor abnormalities showed behavioural deficits. Children with coexistent abnormalities in behaviour and motor function had higher rates of remedial school services and therapeutic support. CONCLUSION: Children with congenital heart disease are at risk of long-term motor and behavioural problems, and there is a high rate of coexistence of problems in both domains. Early and longitudinal assessment of all developmental domains is necessary to provide adequate early support.

Neurocognition and its influencing factors in the treatment of schizophrenia-effects of aripiprazole, olanzapine, quetiapine and risperidone.

BACKGROUND: To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. METHODS: Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. RESULTS: A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. CONCLUSION: The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine.

Effect of aripiprazole on cognition in the treatment of patients with schizophrenia.

BACKGROUND: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.

Amygdala reduction in patients with ADHD compared with major depression and healthy volunteers.

OBJECTIVE: Results in adult attention deficit hyperactivity disorder (ADHD) on structural brain changes and the clinical relevance are contradictory. The aim of this study was to investigate whether in adult patients with ADHD hippocampal or amygdala volumes differs from that in healthy controls and patients with major depression (MD). METHOD: Twenty patients with ADHD, 20 matched patients with MD and 20 healthy controls were studied with high resolution magnetic resonance imaging. RESULTS: Amygdala volumes in patients with ADHD were bilaterally smaller than in patients with MD and healthy controls. In ADHD, more hyperactivity and less inattention were associated with smaller right amygdala volumes, and more symptoms of depression with larger amygdala volumes. CONCLUSION: This study supports findings that the amygdala plays an important role in the systemic brain pathophysiology of ADHD. Whether patients with ADHD and larger amygdala volumes are more vulnerable to affective disorders needs further investigation.

Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, deltaTrkA.

Neurotrophins and their receptors play a key role in neurogenesis and survival. However, we and others have recently obtained evidence for a potential involvement of this receptor system in leukemia. To investigate mechanisms underlying the leukemogenic potential of activated neurotrophin receptor signaling, we analyzed in vivo leukemogenesis mediated by deltaTrkA, a mutant of TRKA (tropomyosin-related kinase A) isolated from a patient with acute myeloid leukemia (AML). Retroviral expression of deltaTrkA in myeloid 32D cells induced AML in syngeneic C3H/Hej mice (n=11/11, latency approximately 4 weeks). C57Bl/6J mice transplanted with deltaTrkA-transduced primary lineage negative (Lin-) bone marrow cells died of a transient polyclonal AML (n=7/15, latency of <12 days). Serial transplantation of AML cells did not re-induce this disease but rather acute lymphoblastic leukemia (ALL, latency >78 days). All primary recipients surviving the early AML developed clonal ALL or myeloid leukemia (latency >72 days) that required additional genetic lesions. PI3K and mTOR-raptor were identified as the crucial mediators of leukemic transformation, whereas STAT and MAP kinase signaling pathways were not activated. Thus, our findings reveal potent and unique transforming properties of altered neurotrophin receptor signaling in leukemogenesis, and encourage further analyses of neurotrophin receptors and downstream signaling events in hematological malignancies.

A role for CD81 in early T cell development.

Early stages of T cell development are thought to include a series of coordinated interactions between thymocytes and other cells of the thymus. A monoclonal antibody specific for mouse CD81 was identified that blocked the appearance of alpha beta but not gamma delta T cells in fetal organ cultures initiated with day 14.5 thymus lobes. In reaggregation cultures with CD81-transfected fibroblasts, CD4-CD8- thymocytes differentiated into CD4+CD8+ T cells. Thus, interactions between immature thymocytes and stromal cells expressing CD81 are required and may be sufficient to induce early events associated with T cell development.

Reduction of deepwater formation in the greenland sea during the 1980s: evidence from tracer data.

Hydrographic observations and measurements of the concentrations of chlorofluorocarbons (CFCs) have suggested that the formation of Greenland Sea Deep Water (GSDW) slowed down considerably during the 1980s. Such a decrease is related to weakened convection in the Greenland Sea and thus could have significant impact on the properties of the waters flowing over the Scotland-Iceland-Greenland ridge system into the deep Atlantic. Study of the variability of GSDW formation is relevant for understanding the impact of the circulation in the European Polar seas on regional and global deep water characteristics. New long-term multitracer observations from the Greenland Sea show that GSDW formation indeed was greatly reduced during the 1980s. A box model of deepwater formation and exchange in the European Polar seas tuned by the tracer data indicates that the reduction rate of GSDW formation was about 80 percent and that the start date of the reduction was between 1978 and 1982.

Groups for bereaved parents-how they can help.

The authors wished to establish an organized approach for helping parents of patients who had died. Over a 14-month period, 81 people participated in a series of groups. A closed-group, eight-meeting format was used, under professional leadership. Main topics covered in discussion were: problems and feelings associated with the death of the child; problems of coping with everyday life; and philosophical issues. Conclusions emphasize the need for professional leadership and screening of potential members. The groups were found to be an effective way to help normal people with normal grief. Participants saw their experience as extremely valuable, and as something which could not be gained through conventional therapy.