A 12-month randomised pilot trial of the Alzheimer's and music therapy study: a feasibility assessment of music therapy and physical activity in patients with mild-to-moderate Alzheimer's disease.

BACKGROUND: The Alzheimer's and Music Therapy (ALMUTH) study is the first randomised controlled trial (RCT) design with 12 months of active non-pharmacological therapy (NPT) implementing music therapy (MT) and physical activity (PA) for participants with Alzheimer's disease (AD). The aim of the present article is to retrospectively examine the inclusion of mild-to-moderate Alzheimer's Disease patients into the main ALMUTH study protocol and to determine if continued inclusion of AD patients is warranted. METHODS: The randomised pilot trial was conducted as a parallel three-arm RCT, reflecting the experimental design of the ALMUTH study. The trial was conducted in Bergen, Norway, and randomisation (1:1:1) was performed by an external researcher. The study was open label and the experimental design features two active NPTs: MT and PA, and a passive control (no intervention, CON) in Norwegian speaking patients with AD who still live at home and could provide informed consent. Sessions were offered once per week (up to 90 min) up to 40 sessions over 12 months. Baseline and follow-up tests included a full neuropsychological test battery and three magnetic resonance imaging (MRI) measurements (structural, functional, and diffusion weighted imaging). Feasibility outcomes were assessed and were determined as feasible if they met the target criteria. RESULTS: Eighteen participants with a diagnosis of mild-to-moderate AD were screened, randomised, and tested once at baseline and once after 12-months. Participants were divided into three groups: MT (n = 6), PA (n = 6), and CON (n = 6). Results of the study revealed that the ALMUTH protocol in patients with AD was not feasible. The adherence to the study protocol was poor (50% attended sessions), with attrition and retention rates at 50%. The recruitment was costly and there were difficulties acquiring participants who met the inclusion criteria. Issues with study fidelity and problems raised by staff were taken into consideration for the updated study protocol. No adverse events were reported by the patients or their caregivers. CONCLUSIONS: The pilot trial was not deemed feasible in patients with mild-to-moderate AD. To mitigate this, the ALMUTH study has expanded the recruitment criteria to include participants with milder forms of memory impairment (pre-AD) in addition to expanding the neuropsychological test battery. The ALMUTH study is currently ongoing through 2023. TRIAL REGISTRATION: Norsk Forskningsråd (NFR) funded. Regional Committees for Medical and Health Research Ethics (REC-WEST: reference number 2018/206). CLINICALTRIALS: gov: NCT03444181 (registered retrospectively 23 February 2018, https://clinicaltrials.gov/ct2/show/NCT03444181 ).

Diffusion Tensor Imaging Shows Differences Between Myotonic Dystrophy Type 1 and Type 2.

BACKGROUND: Myotonic Dystrophies type 1 and type 2 are hereditary myopathies with dystrophic muscle degeneration in varying degrees. Differences in muscle diffusion between both diseases have not been evaluated yet. OBJECTIVE: To evaluate the ability of muscle diffusion tensor imaging (mDTI) and Dixon fat-quantification to distinguish between Myotonic Dystrophy (DM) type 1 and type 2 and if both diseases show distinct muscle involvement patterns. METHODS: We evaluated 6 thigh and 7 calf muscles (both legs) of 10 DM 1, 13 DM 2 and 28 healthy controls (HC) with diffusion tensor imaging, T1w and mDixonquant sequences in a 3T MRI scanner. The quantitative mDTI-values axial diffusivity (λ1), mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA) as well as fat-fraction were analysed. CTG-triplet repeat-length of DM 1 patients was correlated with diffusion metrics and fat-fraction. RESULTS: mDTI showed significant differences between DM 1 and DM 2 vs. healthy controls in diffusion parameters of the thigh (all p < 0.001) except for FA (p = 0.0521 / 0.8337). In calf muscles mDTI showed significant differences between DM 1 and DM 2 patients (all p < 0.0001) as well as between DM 1 patients and controls (all p = 0.0001). Thigh muscles had a significant higher fat-fraction in both groups vs. controls (p < 0.05). There was no correlation of CTG triplet length with mDTI values and fat-fraction. DISCUSSION: mDTI reveals specific changes of the diffusion parameters and fat-fraction in muscles of DM 1 and DM 2 patients. Thus, the quantitative MRI methods presented in this study provide a powerful tool in differential diagnosis and follow-up of DM 1 and DM 2, however, the data must be validated in larger studies.

Shell Filling and Trigonal Warping in Graphene Quantum Dots.

Transport measurements through a few-electron circular quantum dot in bilayer graphene display bunching of the conductance resonances in groups of four, eight, and twelve. This is in accordance with the spin and valley degeneracies in bilayer graphene and an additional threefold "minivalley degeneracy" caused by trigonal warping. For small electron numbers, implying a small dot size and a small displacement field, a two-dimensional s shell and then a p shell are successively filled with four and eight electrons, respectively. For electron numbers larger than 12, as the dot size and the displacement field increase, the single-particle ground state evolves into a threefold degenerate minivalley ground state. A transition between these regimes is observed in our measurements and can be described by band-structure calculations. Measurements in the magnetic field confirm Hund's second rule for spin filling of the quantum dot levels, emphasizing the importance of exchange interaction effects.

Pathological spontaneous activity as a prognostic marker in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Monitoring of the disease course of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) remains challenging because nerve conduction studies do not adequately correlate with functional disability. The prognostic value of pathological spontaneous activity (PSA) in needle electromyography (EMG) in different CIDP subgroups in a longitudinal context has, to date, not been analysed. We aimed to determine whether PSA was a prognostic marker or a marker of disease activity in a cohort of patients with CIDP. METHODS: A total of 127 patients with CIDP spectrum disorder were retrospectively analysed over 57 ± 47 months regarding the occurrence of PSA (fibrillations and positive sharp waves). The presence of PSA at diagnosis, newly occurring PSA, and continuously present PSA were longitudinally correlated with clinical disability using the Inflammatory Neuropathy Cause and Treatment Overall Disability Sum Score (INCAT-ODSS) and CIDP subtype. RESULTS: Pathological spontaneous activity occurred in 49.6% of all CIDP patients at first diagnosis. More frequent evidence of PSA was significantly associated with a higher INCAT-ODSS at the last follow-up. Continuous and new occurrence of PSA were associated with higher degree of disability at the last follow-up. The majority of patients with sustained evidence of PSA were characterized by an atypical phenotype, higher degree of disability, and the need for escalation of treatment. CONCLUSIONS: Pathological spontaneous activity was associated with a higher degree of disability and occurred more frequently in atypical CIDP variants according to the longitudinal data of a large cohort of patients with CIDP. Our results showed that EMG examination was an adequate marker for disease progression and should be evaluated during the disease course.

Measuring the Degeneracy of Discrete Energy Levels Using a GaAs/AlGaAs Quantum Dot.

We demonstrate an experimental method for measuring quantum state degeneracies in bound state energy spectra. The technique is based on the general principle of detailed balance and the ability to perform precise and efficient measurements of energy-dependent tunneling-in and -out rates from a reservoir. The method is realized using a GaAs/AlGaAs quantum dot allowing for the detection of time-resolved single-electron tunneling with a precision enhanced by a feedback control. It is thoroughly tested by tuning orbital and spin degeneracies with electric and magnetic fields. The technique also lends itself to studying the connection between the ground-state degeneracy and the lifetime of the excited states.

Electrographic Correlates of Plateau Waves in Patients With Leptomeningeal Metastases.

We describe video electroencephalography (video-EEG) correlates of transient neurological attacks due to plateau waves-paroxysmal elevations in intracranial pressure-in patients with leptomeningeal metastases. We identified 3 patients with leptomeningeal metastases, intracranial hypertension, and transient neurological attacks captured on video-EEG without evidence of seizures or epileptiform activity. We identified all clinical events on video and reviewed the corresponding EEG data for evidence of abnormalities. All 3 patients had mild to moderate slowing and 2 had frontal intermittent rhythmic delta activity during background EEG recording. There were 33 clinical events recorded and stereotyped for each patient. All 33 events were associated with an increase in delta range slowing of ≥30% compared to the background. This abnormality started ≤2 minutes before the onset of clinical symptoms and persisted for minutes after clinical resolution. This study is the first to carefully describe the electrographic correlates of transient neurological attacks due to plateau waves in patients with leptomeningeal metastasis. Clinical attacks were consistently associated with a possible EEG signature of diffuse delta range slowing. Future studies can validate the sensitivity and specificity of these EEG changes as a prognostic and/or response biomarker in patients with leptomeningeal metastases with or without intracranial hypertension.

[Radiation-Induced Radiculopathy with Paresis of the Neck and Autochthonous Back Muscles with Additional Myopathy]. / Parese der Nacken- und autochthonen Rückenmuskulatur durch strahleninduzierte zervikale Radikulopathie mit Begleitmyopathie.

Radiation-induced tissue damage is caused by ionizing radiation mainly affecting the skin, vascular, neuronal or muscle tissue. Early damages occur within weeks and months while late damages may occur months or even decades after radiation.Radiation-induced paresis of the spine or the trunk muscles with camptocormia or dropped-head syndrome are rare but have already been described as long-term sequelae after treatment of Hodgkin's lymphoma. The differential diagnosis includes limb-girdle muscular dystrophy, fascioscapulohumeral muscular dystrophy (FSHD) or lysosomal storage diseases (e. g. Acid Maltase Deficiency). We present the case of a patient with long lasting diagnostics over many months due to different inconclusive results.

Unplanned Transfers from Hospital Wards to the Neurological Intensive Care Unit.

BACKGROUND: The aim of this study is to evaluate the characteristics of unplanned transfers of adult patients from hospital wards to a neurological intensive care unit (NICU). METHODS: We retrospectively reviewed consecutive unplanned transfers from hospital wards to the NICU at our institution over a 3-year period. In-hospital mortality rates were compared between patients readmitted to the NICU ("bounce-back transfers") and patients admitted to hospital wards from sources other than the NICU who were then transferred to the NICU ("incident transfers"). We also measured clinical characteristics of transfers, including source of admission and indication for transfer. RESULTS: A total of 446 unplanned transfers from hospital wards to the NICU occurred, of which 39% were bounce-back transfers. The in-hospital mortality rate associated with all unplanned transfers to the NICU was 17% and did not differ significantly between bounce-back transfers and incident transfers. Transfers to the NICU within 24 h of admission to a floor service accounted for 32% of all transfers and were significantly more common for incident transfers than bounce-back transfers (39 vs. 21%, p = .0002). Of patients admitted via the emergency department who had subsequent incident transfers to the NICU, 50% were transferred within 24 h of admission. CONCLUSIONS: Unplanned transfers to an NICU were common and were associated with a high in-hospital mortality rate. Quality improvement projects should target the triage process and transitions of care to the hospital wards in order to decrease unplanned transfers of high-risk patients to the NICU.

[Participatory Quality Development: Engaging Community Members in All Phases of Project Planning and Implementation]. / Partizipative Qualitätsentwicklung: Zielgruppen in alle Phasen der Projektgestaltung einbeziehen.

Community participation, recognised as a central feature of successful health promotion and prevention, is often difficult to implement. In this research project internationally recognised methods of participatory health research were applied to demonstrate ways in which community members can be engaged. Participatory health research is characterised by a close collaboration between academic researchers, practitioners and community members in order to generate common knowledge. It is not a question of translating knowledge from research into practice, but rather a question of promoting a collective learning process on the part of all participants for the purpose of developing solutions which address the interests and needs of local people. The result of the project is a new approach for strengthening the quality of prevention and health promotion interventions: participatory quality development (PQD).

Group music therapy for severe mental illness: a randomized embedded-experimental mixed methods study.

OBJECTIVE: Music therapy is an innovative approach to support people with severe mental illness (SMI). The aim of the study was to determine whether group music therapy (GMT) positively impacted on quality of life (QoL), social enrichment, self-esteem, spirituality and psychiatric symptoms of participants with SMI and how they experienced the intervention. METHOD: The primary outcome was QoL; secondary measures assessed social enrichment, self-esteem, spirituality and psychiatric symptoms. The 13-week intervention comprised singing familiar songs and composing original songs recorded in a professional studio. Qualitative data were generated from focus group interviews and song lyric analysis. RESULTS: Ninety-nine adults (57 female) were recruited, with an initial cohort (n = 75) randomized to either: weekly GMT followed by standard care (SC) or SC followed by GMT. Crossover occurred after 13 weeks. Measures were conducted at baseline, 13, 26 and 39 weeks. A second cohort (n = 24) could not be randomized and were assigned to GMT followed by SC. Intention-to-treat analysis showed a significant difference between GMT and SC on QoL and spirituality. This was robust to different assumptions about missing data (listwise deletion, last observation carried forward or multiple imputation). Per-protocol analysis suggested greater benefit for those receiving more sessions. Focus group interview and song lyric analyses suggested that GMT was enjoyable; self-esteem was enhanced; participants appreciated therapists and peers; and although challenges were experienced, the programme was recommended to others. CONCLUSION: Group music therapy may enhance QoL and spirituality of persons with SMI.

Family-centred music therapy to promote social engagement in young children with severe autism spectrum disorder: a randomized controlled study.

BACKGROUND: Limited capacity for social engagement is a core feature of autism spectrum disorder (ASD), often evident early in the child's development. While these skills are difficult to train, there is some evidence that active involvement in music-making provides unique opportunities for social interaction between participants. Family-centred music therapy (FCMT) endeavours to support social engagement between child and parent within active music-making, yet the extent of benefits provided is unknown. AIM: This study investigated the impacts of FCMT on social engagement abilities. METHODS: Twenty-three children (36-60 months) with severe ASD received either 16 weeks of FCMT in addition to their early intervention programmes (n = 12), or their early intervention programme only (n = 11). Change in social engagement was measured with standardized parent-report assessments, parent interviews and clinician observation. RESULTS: Intention-to-treat analysis for the Vineland Social Emotional Early Childhood Scale indicated a significant effect in favour of FCMT. Thematic qualitative analysis of the parent interviews showed that the parent-child relationship grew stronger. CONCLUSION: FCMT improves social interactions in the home and community and the parent-child relationship, but not language skills or general social responsiveness. This study provides preliminary support for the use of FCMT to promote social engagement in children with severe ASD.

Shifting effects in randomised controlled trials of complex interventions: a new kind of performance bias?

OBJECTIVE: Randomised controlled trials (RCTs) aim to provide unbiased estimates of treatment effects. However, the process of implementing trial procedures may have an impact on the performance of complex interventions that rely strongly on the intuition and confidence of therapists. We aimed to examine whether shifting effects over the recruitment period can be observed that might indicate such impact. METHOD: Three RCTs investigating music therapy vs. standard care were included. The intervention was performed by experienced therapists and based on established methods. We examined outcomes of participants graphically, analysed cumulative effects and tested for differences between first vs. later participants. We tested for potential confounding population shifts through multiple regression models. RESULTS: Cumulative differences suggested trends over the recruitment period. Effect sizes tended to be less favourable among the first participants than later participants. In one study, effects even changed direction. Age, gender and baseline severity did not account for these shifting effects. CONCLUSION: Some trials of complex interventions have shifting effects over the recruitment period that cannot be explained by therapist experience or shifting demographics. Replication and further research should aim to find out which interventions and trial designs are most vulnerable to this new kind of performance bias.

[Memorandum - research funding of prevention]. / Memorandum - Forschungsförderung Prävention.

The memorandum of the research funding of prevention has been devised within the framework of the Prevention Research Funding Programme of the Federal Ministry of Education and Research. It consists not only of the obtained findings of the research-practice co-operation but also of recommendations for the implementation of prospective, innovational, effective, practice-oriented and sustainable research. The respective knowledge has been acquired from quantitative surveys on the experiences of scientists and practice partners within the prevention research funding project as well as from extensive qualitative methods of structured group evaluation. A participatory co-operation between research and practice based on mutual respect, trust and recognition is seen as mandatory for the further development of both prevention and health promotion research. Research and practice partners are required to engage in an ab initio collaboration starting from the conception phase, whereby it is advisable to encourage and fortify the communication between research, practice and funding partners by systematic surveillance in form of a meta-project. In addition, the inclusion of the target population from the outset and on a collaborative basis is considered as beneficial in order to ensure the practical application of the research findings. Furthermore, innovatory research designs which are able to provide a framework for internal flexibility, continuous re-assessment and adjustment are fundamental for the implementation of practice-oriented research. Moreover, a dynamic co-operation between different groups of interest not only depends on sharing responsibility but also on sufficient funding for both research and practice, which is particularly important for the transfer and communication of the attained findings. With regard to the evaluation of both effectiveness and sustainability of interventions, a research funding project is required which makes long-term results possible through the utilization of regulated monitoring and guarantees quality and continuous effectiveness. Furthermore, in order to stimulate progress within the basic theories of prevention and health promotion, it is also essential for a funding project to focus on elementary concepts. Additionally, for the efficient and sustainable development of health within a population it is advisable to apply both self-contained research and the involvement of primary prevention and health promotion to research projects concerning health, social affairs, education, work and environment.

Interplay between crystal field splitting and Kondo effect in CeNi9Ge(4-x)Si(x).

The pseudo-ternary solid solution CeNi(9)Ge(4-x)Si(x) (0 ≤ x ≤ 4) has been investigated by means of x-ray diffraction, magnetic susceptibility, specific heat, electrical resistivity, thermopower and inelastic neutron scattering studies. The isoelectronic substitution of germanium by silicon atoms causes a dramatic change of the relative strength of competing Kondo, RKKY and crystal field (CF) energy scales. The strongest effect is the continuous elevation of the Kondo temperature T(K) from approximately 3.5 K for CeNi(9)Ge(4) to about 70 K for CeNi(9)Si(4). This increase of the Kondo temperature is attended by a change of the CF level scheme of the Ce ions. The interplay of the different energy scales results in an incipient reduction of the ground state degeneracy from an effectively fourfold degenerate non-magnetic Kondo ground state with unusual non-Fermi-liquid features of CeNi(9)Ge(4) to a lower one, followed by an increase towards a sixfold, fully degenerate ground state multiplet in CeNi(9)Si(4) (T(K) ∼ Δ(CF)).

Side effects of anesthesia in DM2 as compared to DM1: a comparative retrospective study.

BACKGROUND AND PURPOSE: Myotonic dystrophy type 2 (DM2) is an adult-onset progressive multisystem disease. There have been no reported risks for anesthesia in DM2. METHODS: We assess the frequency, type, and severity of peri-operative complications under general and local anesthesia in genetically proven DM2. A retrospective multicenter study was conducted. RESULTS: Out of 320 DM2 patients, 134 participated by completing questionnaires (41, 88%), which were delivered by mail, and their clinical records were reviewed (class III evidence). A total of 121 patients had 340 operations in general anesthesia at an average age of 40.5 years (range 18-82); 132 (38.8%) general anesthesia were performed prior to DM2 onset, 187 (55.9%) after disease onset. A total of 212 (62.4%) of the interventions were performed without known DM2 diagnosis. In 120 (35.3%) interventions, DM2 was already diagnosed. The locations of surgery were lower abdomen (47%), peripheral extremities (46.8%), upper abdomen (3.8%), thorax (1.8%), and brain (0.6%). The overall frequency of severe complications was 0.6% (2 of 340). One incident was a post-operative development of rhabdomyolysis, hyperthermia, muscle weakness and renal failure; the others, prolonged muscular weakness and renal failure. Minor complications related to a general anesthesia were reported by 27 participants (20.2%). In 116 patients (86.6%), 342 interventions were performed in regional anesthesia. Minor complications were reported by 20.2% participants such as nausea (6.7%), muscular weakness and pain (5.9%), prolonged anesthesia (5.2%), circulatory insufficiency (2.9%), and shortness of breath (2.9%). CONCLUSION: The overall lower risk seems to be predominantly related to the minor respiratory involvement in DM2, than in myotonic dystrophy type 1 (DM1).

Evolution of quantum criticality in CeNi(9-x)Cu(x)Ge(4).

Crystal structure, specific heat, thermal expansion, magnetic susceptibility and electrical resistivity studies of the heavy fermion system CeNi(9-x)Cu(x)Ge(4) (0≤x≤1) reveal a continuous tuning of the ground state by Ni/Cu substitution from an effectively fourfold-degenerate non-magnetic Kondo ground state of CeNi(9)Ge(4) (with pronounced non-Fermi-liquid features) towards a magnetically ordered, effectively twofold-degenerate ground state in CeNi(8)CuGe(4) with T(N) = 175 ± 5 mK. Quantum critical behavior, [Formula: see text], is observed for [Formula: see text]. Hitherto, CeNi(9-x)Cu(x)Ge(4) represents the first system where a substitution-driven quantum phase transition is connected not only with changes of the relative strength of the Kondo effect and RKKY interaction, but also with a reduction of the effective crystal field ground state degeneracy.

Music therapy for depression.

BACKGROUND: Depression is a highly prevalent disorder associated with reduced social functioning, impaired quality of life, and increased mortality. Music therapy has been used in the treatment of a variety of mental disorders, but its impact on those with depression is unclear. OBJECTIVES: To examine the efficacy of music therapy with standard care compared to standard care alone among people with depression and to compare the effects of music therapy for people with depression against other psychological or pharmacological therapies. SEARCH STRATEGY: CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007, MEDLINE, PsycINFO, EMBASE, PsycLit, PSYindex, and other relevant sites were searched in November 2006. Reference lists of retrieved articles were hand searched, as well as specialist music and arts therapies journals. SELECTION CRITERIA: All randomised controlled trials comparing music therapy with standard care or other interventions for depression. DATA COLLECTION AND ANALYSIS: Data on participants, interventions and outcomes were extracted and entered onto a database independently by two review authors. The methodological quality of each study was also assessed independently by two review authors. The primary outcome was reduction in symptoms of depression, based on a continuous scale. MAIN RESULTS: Five studies met the inclusion criteria of the review. Marked variations in the interventions offered and the populations studied meant that meta-analysis was not appropriate. Four of the five studies individually reported greater reduction in symptoms of depression among those randomised to music therapy than to those in standard care conditions. The fifth study, in which music therapy was used as an active control treatment, reported no significant change in mental state for music therapy compared with standard care. Dropout rates from music therapy conditions appeared to be low in all studies. AUTHORS' CONCLUSIONS: Findings from individual randomised trials suggest that music therapy is accepted by people with depression and is associated with improvements in mood. However, the small number and low methodological quality of studies mean that it is not possible to be confident about its effectiveness. High quality trials evaluating the effects of music therapy on depression are required.

The additional therapeutic effect of group music therapy for schizophrenic patients: a randomized study.

OBJECTIVE: Schizophrenia is one of the most serious mental disorders. Music therapy has only recently been introduced as a form of treatment. The aim of this study was to examine the effect of music therapy for schizophrenic in-patients needing acute care. METHOD: Thirty-seven patients with psychotic disorders were randomly assigned to an experimental group and a control group. Both groups received medication and treatment indicated for their disorder. Additionally, the experimental group (n = 21) underwent group music therapy. RESULTS: Significant effects of music therapy are found in patients' self-evaluation of their psychosocial orientation and for negative symptoms. No differences were found in the quality of life. CONCLUSION: Musical activity diminishes negative symptoms and improves interpersonal contact. These positive effects of music therapy could increase the patient's abilities to adapt to the social environment in the community after discharge from the hospital.

Mitofusin 2 gene mutation (R94Q) causing severe early-onset axonal polyneuropathy (CMT2A).

Charcot-Marie-Tooth disease (CMT) has been classified into two types: demyelinating forms (CMT1) and axonal forms (CMT2). Mutations in the CMT2A locus have been linked to the KIF1B and the mitofusin 2 (MFN2) genes. Here, we report a German patient with CMT2 with an underlying spontaneous mutation (c.281G-->A) in the MFN2 gene. Clinically, the patient presented with early-onset CMT that was not associated with additional central nervous system pathology. The disease course was rapidly progressive in the first years and slowed afterwards. We also suggest that single patients with early-onset axonal polyneuropathies should be screened for MFN2 mutations.