Jörg Assmus

Importance of motor vs. non-motor symptoms for health-related quality of life in early Parkinson's disease

BACKGROUND The relative impact of motor- and non-motor symptoms on health-related quality of life in early Parkinsons disease is poorly documented. METHODS 188 patients with incident Parkinsons disease from a population-based study were examined at the time of diagnosis, before initiation of dopaminergic treatment, with follow-up of 166 patients three years later. Health-related quality of life was assessed by the 36-item Short-form Health Survey (SF-36). Motor and non-motor variables were derived from the Unified Parkinsons disease rating scale and other established scales. RESULTS Multiple regression analyses showed that the non-motor symptoms strongest associated with reduced SF-36 scores at diagnosis and three years later were depression, fatigue and sensory complaints. The motor symptoms most related to impaired SF-36 scores were problems with gait and activities of daily living that cover personal needs. The variance of SF-36 mental summary scores was much better explained by non-motor vs. motor symptoms, both at baseline (R(2) = 0.384 vs. 0.095) and 3 years later (R(2) = 0.441 vs. 0.195). Also SF-36 physical summary scores were better explained by non-motor vs. motor symptoms with R(2) = 0.372 vs. 0.322 at baseline and R(2) = 0.468 vs. 0.315 after 3 years. CONCLUSION In early PD, including the phase before dopaminergic treatment is initiated, non-motor symptoms are more important for reduced health-related quality of life than motor symptoms. Fatigue, depression, sensory complaints and gait disturbances emerge as the most relevant symptoms and should be given corresponding attention in the management of patients with early PD.

Neurofeedback for the treatment of children and adolescents with ADHD: a randomized and controlled clinical trial using parental reports

BackgroundA randomized and controlled clinical study was performed to evaluate the use of neurofeedback (NF) to treat attention-deficit/hyperactivity disorder (ADHD) in children and adolescents.MethodsThe ADHD population was selected from an outpatient clinic for Child and Adolescent Mental Health in Norway. Ninety-one of the 275 children and adolescents ranging in age from 6 to 18 years (10.5 years) participated in 30 sessions of an intensive NF program. The reinforcement contingency was based on the subjects’ production of cortical beta1 activity (15–18 Hz). The ADHD participants were randomized into three groups, with 30 in the NF group, 31 controls in a group that was given methylphenidate, and 30 in a group that received NF and methylphenidate. ADHD core symptoms were reported by parents using the parent form of the Clinician’s Manual for Assessment by Russell A. Barkley.ResultsNinety-one children and adolescents were effectively randomized by age, sex, intelligence and distribution of ADHD core symptoms. The parents reported significant effects of the treatments, but no significant differences between the treatment groups were observed.ConclusionsNF was as effective as methylphenidate at treating the attentional and hyperactivity symptoms of ADHD, based on parental reports.Trial registrationCurrent Controlled Trials NCT01252446

Paternal Mental Health and Socioemotional and Behavioral Development in Their Children

OBJECTIVE: To examine the association between symptoms of psychological distress in expectant fathers and socioemotional and behavioral outcomes in their children at age 36 months. METHODS: The current study is based on data from the Norwegian Mother and Child Cohort Study on 31 663 children. Information about fathers’ mental health was obtained by self-report (Hopkins Symptom Checklist) in week 17 or 18 of gestation. Information about mothers’ pre- and postnatal mental health and children’s socioemotional and behavioral development at 36 months of age was obtained from parent-report questionnaires. Linear multiple regression and logistic regression models were performed while controlling for demographics, lifestyle variables, and mothers’ mental health. RESULTS: Three percent of the fathers had high levels of psychological distress. Using linear regression models, we found a small positive association between fathers’ psychological distress and children’s behavioral difficulties, B = 0.19 (95% confidence interval [CI] = 0.15–0.23); emotional difficulties, B = 0.22 (95% CI = 0.18–0.26); and social functioning, B = 0.12 (95% CI = 0.07–0.16). The associations did not change when adjusted for relevant confounders. Children whose fathers had high levels of psychological distress had higher levels of emotional and behavioral problems. CONCLUSIONS: This study suggests that some risk of future child emotional, behavioral, and social problems can be identified during pregnancy. The findings are of importance for clinicians and policy makers in their planning of health care in the perinatal period because this represents a significant opportunity for preventive intervention.

Individual Music Therapy for Mental Health Care Clients with Low Therapy Motivation: Multicentre Randomised Controlled Trial

Background: Music therapy (MT) has been shown to be efficacious for mental health care clients with various disorders such as schizophrenia, depression and substance abuse. Referral to MT in clinical practice is often based on other factors than diagnosis. We aimed to examine the effectiveness of resource-oriented MT for mental health care clients with low motivation for other therapies. Method: This was a pragmatic parallel trial. In specialised centres in Norway, Austria and Australia, 144 adults with non-organic mental disorders and low therapy motivation were randomised to 3 months of biweekly individual, resource-oriented MT plus treatment as usual (TAU) or TAU alone. TAU was typically intensive (71% were inpatients) and included the best combination of therapies available for each participant, excluding MT. Blinded assessments of the Scale for the Assessment of Negative Symptoms (SANS) and 15 secondary outcomes were collected before randomisation and after 1, 3 and 9 months. Changes were analysed on an intention-to-treat basis using generalised estimating equations in longitudinal linear models, controlling for diagnosis, site and time point. Results: MT was superior to TAU for total negative symptoms (SANS, d = 0.54, p < 0.001) as well as functioning, clinical global impressions, social avoidance through music, and vitality (all p < 0.01). Conclusion: Individual MT as conducted in routine practice is an effective addition to usual care for mental health care clients with low motivation.

IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy

OBJECTIVES Biomarkers for diagnosis and therapy efficacy in tuberculosis (TB) are requested. We have studied biomarkers that may differentiate between active and latent TB infection (LTBI), the influence of HIV infection and changes during anti-TB chemotherapy. METHODS Thirty-eight plasma cytokines, assessed by multiplex and enzyme immunoassays, were analyzed in patients with active TB before and during 24 weeks of anti-TB chemotherapy (n = 65), from individuals with LTBI (n = 34) and from QuantiFERON-TB (QFT) negative controls (n = 65). The study participants were grouped according to HIV status. RESULTS Plasma levels of the CXC chemokine IP-10 and soluble TNF receptor type 2 (sTNFr2) significantly differentiated active TB from the LTBI group, irrespective of HIV status. In the HIV-infected group the sensitivity and specificity was 100% for IP-10 with a cut-off of 2547 pg/mL. Plasma IP-10 declined gradually during anti-TB chemotherapy (12-24 weeks, p = 0.002) to a level comparable to LTBI and QFT negative control groups. sTNFr2 fluctuated throughout therapy, but was decreased after 12-24 weeks (p = 0.006). CONCLUSIONS IP-10 distinguished with high accuracy active TB from LTBI irrespective of HIV infection and declined during anti-TB chemotherapy. Plasma IP-10 may serve as a diagnostic biomarker to differentiate between the stages of TB infection and for monitoring therapy efficacy.

Autonomic symptoms and dopaminergic treatment in de novo Parkinson's disease

Autonomic symptoms are present in early stages of Parkinsons disease (PD), but evidence on how they are influenced by dopaminergic treatment remains unclear. The aim of this study was to investigate the impact of dopaminergic treatment on autonomic symptoms in early PD in a population‐based cohort.

Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial

The discovery of the blue lightsensitive retinal photoreceptor responsible for signaling daytime to the brain suggested that light to the circadian system could be inhibited by using blue‐blocking orange tinted glasses. Blue‐blocking (BB) glasses are a potential treatment option for bipolar mania. We examined the effectiveness of BB glasses in hospitalized patients with bipolar disorder in a manic state.

Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial

BACKGROUND Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. METHODS This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. FINDINGS Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64-79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2-8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84-1·38; p=0·52). By 3 months, 29 (5%) patients had died in the tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). INTERPRETATION Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether tenecteplase is non-inferior to alteplase. FUNDING Research Council of Norway.

Music Therapy for Prisoners: Pilot Randomised Controlled Trial and Implications for Evaluating Psychosocial Interventions

Mental health problems are common among prison inmates. Music therapy has been shown to reduce mental health problems. It may also be beneficial in the rehabilitation of prisoners, but rigorous outcome research is lacking. We compared group music therapy with standard care for prisoners in a pilot randomised controlled trial that started with the establishment of music therapy services in a prison near Bergen in 2008. In all, 113 prisoners agreed to participate. Anxiety (STAI-State [State–Trait Anxiety Inventory], STAI-Trait), depression (HADS-D [Hospital Anxiety and Depression Scale]), and social relationships (Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q]) were assessed at baseline; every 2 weeks in the experimental group; after 1, 3, and 6 months in the control group; and at release. No restrictions were placed on the frequency, duration, or contents of music therapy. Duration of stay in the institution was short (62% stayed less than 1 month). Only a minority reached clinical cutoffs for anxiety and depression at baseline. Between-group analyses of effects were not possible. Music therapy was well accepted and attractive among the prisoners. Post hoc analysis of within-group changes suggested a reduction of state anxiety after 2 weeks of music therapy (d = 0.33, p = .025). Short sentences and low baseline levels of psychological disturbance impeded the examination of effects in this study. Recommendations for planning future studies are given, concerning the careful choice of participants, interventions and settings, comparison condition and design aspects, choice of outcomes, and integration of research approaches. Thus, the present study has important implications for future studies evaluating interventions for improving prisoners’ mental health. Trial registration: ISRCTN22518605

Decay in chest compression quality due to fatigue is rare during prolonged advanced life support in a manikin model

BackgroundThe aim of this study was to measure chest compression decay during simulated advanced life support (ALS) in a cardiac arrest manikin model.Methods19 paramedic teams, each consisting of three paramedics, performed ALS for 12 minutes with the same paramedic providing all chest compressions. The patient was a resuscitation manikin found in ventricular fibrillation (VF). The first shock terminated the VF and the patient remained in pulseless electrical activity (PEA) throughout the scenario. Average chest compression depth and rate was measured each minute for 12 minutes and divided into three groups based on chest compression quality; good (compression depth ≥ 40 mm, compression rate 100-120/minute for each minute of CPR), bad (initial compression depth < 40 mm, initial compression rate < 100 or > 120/minute) or decay (change from good to bad during the 12 minutes). Changes in no-flow ratio (NFR, defined as the time without chest compressions divided by the total time of the ALS scenario) over time was also measured.ResultsBased on compression depth, 5 (26%), 9 (47%) and 5 (26%) were good, bad and with decay, respectively. Only one paramedic experienced decay within the first two minutes. Based on compression rate, 6 (32%), 6 (32%) and 7 (37%) were good, bad and with decay, respectively. NFR was 22% in both the 1-3 and 4-6 minute periods, respectively, but decreased to 14% in the 7-9 minute period (P = 0.002) and to 10% in the 10-12 minute period (P < 0.001).ConclusionsIn this simulated cardiac arrest manikin study, only half of the providers achieved guideline recommended compression depth during prolonged ALS. Large inter-individual differences in chest compression quality were already present from the initiation of CPR. Chest compression decay and thereby fatigue within the first two minutes was rare.