Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy (TAMDMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Drug repurposing could provide novel treatment options for Duchenne muscular dystrophy. Because tamoxifen-an oestrogen receptor regulator-reduced signs of muscular pathology in a Duchenne muscular dystrophy mouse model, we aimed to assess the safety and efficacy of tamoxifen in humans as an adjunct to corticosteroid therapy over a period of 48 weeks. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 12 study centres in seven European countries. We enrolled ambulant boys aged 6·5-12·0 years with a genetically confirmed diagnosis of Duchenne muscular dystrophy and who were on stable corticosteroid treatment for more than 6 months. Exclusion criteria included ophthalmological disorders, including cataracts, and haematological disorders. We randomly assigned (1:1) participants using an online randomisation tool to either 20 mg tamoxifen orally per day or matched placebo, stratified by centre and corticosteroid intake. Participants, caregivers, and clinical investigators were masked to treatment assignments. Tamoxifen was taken in addition to standard care with corticosteroids, and participants attended study visits for examinations every 12 weeks. The primary efficacy outcome was the change from baseline to week 48 in scores on the D1 domain of the Motor Function Measure in the intention-to-treat population (defined as all patients who fulfilled the inclusion criteria and began treatment). This study is registered with ClinicalTrials.gov (NCT03354039) and is completed. FINDINGS: Between May 24, 2018, and Oct 14, 2020, 95 boys were screened for inclusion, and 82 met inclusion criteria and were initially enrolled into the study. Three boys were excluded after initial screening due to cataract diagnosis or revoked consent directly after screening, but before randomisation. A further boy assigned to the placebo group did not begin treatment. Therefore, 40 individuals assigned tamoxifen and 38 allocated placebo were included in the intention-to-treat population. The primary efficacy outcome did not differ significantly between tamoxifen (-3·05%, 95% CI -7·02 to 0·91) and placebo (-6·15%, -9·19 to -3·11; 2·90% difference, -3·02 to 8·82, p=0·33). Severe adverse events occurred in two participants: one participant who received tamoxifen had a fall, and one who received placebo suffered a panic attack. No deaths or life-threatening serious adverse events occurred. Viral infections were the most common adverse events. INTERPRETATION: Tamoxifen was safe and well tolerated, but no difference between groups was reported for the primary efficacy endpoint. Slower disease progression, defined by loss of motor function over time, was indicated in the tamoxifen group compared with the placebo group, but differences in outcome measures were neither clinically nor statistically significant. Currently, we cannot recommend the use of tamoxifen in daily clinical practice as a treatment option for boys with Duchenne muscular dystrophy due to insufficient clinical evidence. FUNDING: Thomi Hopf Foundation, ERA-Net, Swiss National Science Foundation, Duchenne UK, Joining Jack, Duchenne Parent Project, Duchenne Parent Project Spain, Fondation Suisse de Recherche sur les Maladies Musculaires, Association Monegasque contre les Myopathies.

Metabolic markers of short and long-term exogenous DL-beta-hydroxybutyrate supplementation in episodic migraine patients: an exploratory analysis of a randomized-controlled-trial.

Background: Emerging findings propose that the pathophysiology of migraine may be associated with dysfunctional metabolic mechanisms. Recent findings suggest that migraine attacks are a response to the cerebral energy deficit, and ingestion of ketone bodies stabilizes the generation of a migraine attack. Based on these findings, ketone body supplementation is postulated as a prophylactic treatment approach to restore cerebral metabolism deficiency. Metabolic markers are unexplored after exogenous ketone body supplementation in episodic migraineurs. Therefore, the present single-arm uncontrolled explorative analysis evaluated blood ketone body and glucose concentration after short and long-term 6 g exogenous DL-Mg-Ca-beta-hydroxybutyrate (DL-ßHB) supplementation. Methods: The presented data are part of the MigraKet randomized-control cross-over clinical trial of 41 episodic migraineurs (Number NCT03132233). Patients were given a single dose of 6 g DL-ßHB. Ketone body and glucose blood concentration were assessed before intake, 20, and 40 min after DL-ßHB intake. Ketone body, glucose concentration and glycated hemoglobin values were evaluated after 12 weeks of 18 g DL-ßHB ingestion (total dose), taken three times daily (6g/dose; 3x/day). Linear models explored the association between the ketone body and glucose levels. Results: Ketone body concentration increased within-group to a mean of 0.46 (0.30) mmol/L after 40 min post- DL-ßHB supplementation [estimate = 0.24 mmol/L, CI = (0.20.0.27), p < 0.01]. This within-group increase of ketone body concentration did not change after repeated daily intake of DL-ßHB supplementation over 12 weeks [estimate = 0.00 mmol/L, CI = (-0.03.0.04), p = 0.794]. DL-ßHB intake significantly reduced blood glucose concentration within-group from a mean baseline of 4.91 (0.42) mmol/L to 4.75 (0.47) mmol/L 40 min post-DL-ßHB supplementation [estimate = -0.16 mmol/L, CI = (-0.15, 0.03), p < 0.01]. Repeated DL-ßHB supplementation for 12 weeks showed no change within-group in acute ketone bodies concentration [estimate = 0.00 mmol/L, CI = (-0.03.0.04), p = 0.794] and in the HbA1c value [estimate = 0.02, CI = (-0.07.0.11), p = 0.69]. Conclusion: A single dose of 6 g DL-ßHB significantly elevated blood ketone bodies and decreased blood glucose concentration within-group in episodic migraineurs. Long-term DL-ßHB supplementation for 12 weeks showed no effect within-group on acute ketone body concentration and had not impact on HbA1c. The elevation of the ketone body concentration was moderate, indicating that nutritional ketosis was not reached. Therefore, a dose higher than 6 g of DL-ßHB is required to reach the nutritional level of ketosis. ClinicalTrials.gov Identifier: NCT03132233.

Clinician perspectives on how digital phenotyping can inform client treatment.

This qualitative study explores mental health clinician perspectives on how information extracted from client interactions with digital devices such as smartphones and the Internet (their digital footprint data) can inform client treatment. The process of learning about an individual's behaviours and psychology from their digital footprint, what has been termed 'digital phenotyping', has emerged in recent years as a field of research with potential to offer insights of clinical value that could be used to predict/detect mental ill-health and inform treatment. This research agenda has largely consisted of quantitative studies exploring statistical associations between smartphone data and psychometric outcomes among relatively small participant cohorts. We on the other hand focus on how the data gathered from smartphones and other digital sources could be converted to pieces of meaningful information that clinicians could directly access and interpret to augment their practice and inform their treatment of clients. Through a reflexive thematic analysis of interviews involving clinical psychologists, this study presents ideas and a framework for understanding how digital phenotyping can inform, augment, and innovate client treatment. In total, five themes concerning the ethics, praxis, and value of digital phenotyping for client treatment are generated.

Validity of the Early Functional Ability scale (EFA) among critically ill patients undergoing early neurological rehabilitation.

BACKGROUND: A reliable assessment of the functional abilities of patients after severe brain damage is crucial for valid prognostication and treatment decisions, but most clinical scales are of limited use among this specific group of patients. AIM: The present study investigates the usefulness of the Early Functional Ability (EFA) scale, which determines the functional abilities of severely impaired patients. METHODS: Critically ill patients consecutively admitted to early neurological rehabilitation were screened for eligibility. We assessed the correlation between the EFA scale and (i) the Early Rehabilitation Barthel Index (ERBI), and (ii) the Coma Recovery Scale-Revised (CRS-R). The 1-year outcome on the Glasgow Outcome Scale-extended (GOSE) was used to examine the predictive validity. Demographical and medical variables were entered into univariate and multivariate binary regression models to identify independent predictors of 1-year outcome. RESULTS: Two hundred fifty-seven patients (168 men) with a median age of 62 years (IQR = 51-75) were enrolled. The correlation of the EFA scale with the CRS-R was high but low with the ERBI upon admission. Multivariate regression analysis yielded the vegetative subscale of the EFA scale as the only independent predictor for the 1-year outcome of patients admitted to early neurological rehabilitation. CONCLUSIONS: This study shows a high correlation of the EFA scale with the CRS-R but a weak correlation with the ERBI in patients with low functional abilities. With improving patient abilities, these correlations were partly reversed. Thus, the EFA scale is a useful tool to assess the functional abilities and the prognosis of critically ill patients adequately and may be more feasible than other scales.

The predictive validity of the Hessisch Oldendorf Risk of Falling Scale (HOSS) decreases during the course of rehabilitation.

BACKGROUND: Falls are highly frequent among neurological patients during rehabilitation and subsequent risk assessments are crucial to prevent falls. OBJECTIVE: This study aims to determine the predictive values of the Hessisch Oldendorf Risk of Falling Scale (HOSS, "Hessisch Oldendorfer Sturzrisiko Skala") for two timeframes: the first month of rehabilitation and from the second month to the end of rehabilitation. METHODS: Scale performances were assessed for 512 patients during inpatient neurological rehabilitation by calculating the sensitivity and the specificity. HOSS items were entered into a binary logistic regression model. Fall rates were calculated and used for correlation analyses and group comparisons. RESULTS: Initial HOSS assessment showed a sensitivity of 80.4% and a specificity of 60.7%. The HOSS re-assessment resulted in a sensitivity of 67.3% and a specificity of 69.5%. Only a non-somnolent state was identified to increase the risk of falling in both timeframes. Patients with a moderate impaired functional status (Barthel-Index between 20 and 50 points) showed the highest fall rates. CONCLUSION: The predictive validity of the HOSS decreases during the rehabilitation course. This might be caused by an altered relevance of the HOSS items during the re-assessment compared to the initial assessment for which the HOSS was developed for.

Spinal cord gray matter atrophy is associated with functional decline in post-polio syndrome.

OBJECTIVE: To determine if patients with post-polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient-reported functional decline. METHODS: Twenty patients diagnosed with PPS (March of Dimes criteria) and 20 age- and sex-matched healthy controls (HC) underwent 3T axial 2D-rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3-C6/C7, T9/T10 and the lumbar enlargement level (Tmax ) (0.5 × 0.5 mm2 in-plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self-reported fatigue, depression and pain measures were assessed. RESULTS: Post-polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p < 0.001), C5/C6 (p = 0.004) and Tmax (p = 0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain and depression. SCGM areaTmax together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS-related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity. CONCLUSIONS: Patients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS-related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases.

Thyroid Hormone Levels Help to Predict Outcome of Critically Ill Patients Undergoing Early Neurological Rehabilitation.

The present study was aimed at examining thyroid hormones and other clinical factors to improve the accuracy of outcome prediction among critically ill patients undergoing early neurological rehabilitation. Patients consecutively admitted to an intensive or intermediate care unit were screened for eligibility. Serum levels of free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) were collected during the first three days after admission. The Glasgow Outcome Scale (GOS) was defined as the primary outcome measure. Thyroid hormone levels and other clinical factors were entered into a binary logistic regression model to predict a good outcome at the end of early rehabilitative treatment. 395 patients (268 males) with a median age of 62 years (IQR = 52 - 76) and a median disease duration of 19 days (IQR = 13 - 28) were included in the study. Most patients (80%) had decreased fT3 values. Patients with low fT3 were admitted earlier to the rehabilitation facility and had more severe impairment upon admission compared to patients with fT3 values within the normal range. Both decreased fT3 and TSH levels were associated with an unfavorable outcome (GOS ≤ 3), but only TSH proved to be an independent predictor in multivariate analyses (OR = 1.11; 95%CI = 1.02 - 1.22). These data suggest that decreased fT3 and TSH levels upon admission may predict an unfavorable outcome at the end of early rehabilitative treatment. Thus, thyroid hormone levels are not only important during acute treatment but also in prolonged critical illness.

One-year outcome of brain injured patients undergoing early neurological rehabilitation: a prospective observational study.

BACKGROUND: The present study intended to analyze the outcome of patients with severe brain injury one-year after discharge from early rehabilitation. METHODS: Early neurological rehabilitation patients admitted to intensive or intermediate care units and discharged between June 2018 and May 2020 were screened for eligibility. The level of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R) upon admission and at discharge. At one-year follow-up, the outcome was assessed with the Glasgow Outcome Scale-extended (GOSE). Demographical and clinical data collected during inpatient rehabilitation were used to predict the outcome 1 year after discharge. RESULTS: Two hundred sixty-four patients (174 males, 90 females) with a median age of 62 years (IQR = 51-75) and a median duration of their disease of 18 days (IQR = 12-28) were included in the study. At follow-up, the mortality rate was 27% (n = 71). Age and discharge CRS-R total score were independent predictors in a Cox proportional hazards model with death (yes/no) as the dependent variable. According to the GOSE interviews, most patients were either dead (n = 71; 27%), in a vegetative state (n = 28; 11%) or had a severe disability (n = 124; 47%), whereas only a few patients showed a moderate disability (n = 18; 7%) or a good recovery (n = 23; 9%) 1 year after discharge. Age, non-traumatic etiology, discharge CRS-R total score and length of stay independently predicted whether the outcome was good or poor at follow-up. CONCLUSION: Age was an important predictor for outcome at one-year follow-up, which might be due to altered brain plasticity and more comorbidities in elderly subjects. In addition, the present study demonstrated that the CRS-R total score at discharge might be more important for the prediction of one-year outcome than the initial assessment upon admission.

[Relevance of the Clinical Ethics Committee (CEC) for Clinical Staff of a Specialized Neurological Clinic]. / Bedeutung des Klinischen Ethikkomitees (KEKs) für Klinikmitarbeiter einer neurologischen Fachklinik.

BACKGROUND: Clinical ethics committees (CECs) have been implemented in German clinics since the 1990s. Besides problems with the integration into clinical routines, CECs result in an enrichment and relief for employees and relatives. Investigating the current status of CECs in specialized neurological clinics is crucial because changes in therapy goals towards palliative care are often requested and the treatment team is sometimes overwhelmed with clarifying the presumed patient's wishes. So far, however, there have been no studies that have examined the work of the CEC and its importance for clinical staff in specialized neurological clinics. METHOD: In a single-center, prospective observational study, 161 clinic employees with contact to the patients and 10 members of the CEC were asked about their previous experiences and impressions with and in the CEC. At the same time, 31 patients were retrospectively identified for whom an ethical case consultation was carried out by the CEC in 2019. A qualitative evaluation was carried out for the protocols of the ethical case counseling. RESULTS: 56% of the clinic employees and 90% of the CEC members considered the CEC as enrichment for the clinic. Although more than a third of the clinic employees evaluated the CEC as a relief during difficult ethical decisions, the presence of the CEC in particular for relatives and employees is described as insufficient. In the majority, a reduction in the hierarchy by the CEC was confirmed by the members of the CEC (70%), whereas the majority of the clinic employees increasingly denied this (55%). The CEC recommendation was implemented in 94% of the cases. CONCLUSION: A central problem in working with and within a CEC is maybe the lack of presence and information for employees. Due to this lack of presence, the CEC is not sufficiently visible in everyday clinical practice.

Evaluation of the predictive validity of the Hessisch Oldendorf Risk of Falling Scale (HOSS).

OBJECTIVE: This study aims to further validate the Hessisch Oldendorf Risk of Falling Scale (HOSS) for neurological rehabilitation patients. DESIGN: The overall scale performance and fall rate was calculated in a retrospective data analysis. SETTING: The study was performed in a subacute care facility during inpatient neurological rehabilitation. SUBJECTS: The study population (n = 512) included neurological and neurosurgical patients with heterogeneous levels of disability. MAIN MEASURES: The HOSS total score and the suspected risk of falling were compared with the number of falls. Characteristics of fallers and non-fallers were compared using non-parametric group comparisons. Overall scale performance was assessed by calculating the area under the receiver operating characteristic curve of the HOSS as well as by calculating the sensitivity and specificity. RESULTS: A total of 82 (16%) patients experienced at least one fall. Fallers were characterized by an older age, a longer length of stay, a more severe impairment in the activities of daily living upon admission, a hemiparesis, an orientation disorder, a need of a walking aid device and an urinary incontinence. The number of falls was associated with the HOSS total score. Sixty-four fallers and two hundred seventy-four non-fallers were correctly categorized leading to a sensitivity of 78.0% and a specificity of 63.7%. The area under the receiver operating characteristic curve of the HOSS was 0.778 ± 0.25 (CI = 0.729-0.828, P < 0.001). CONCLUSION: The scale performance of the HOSS showed a good sensitivity and an adequate specificity to identify neurological patients who are at high risk of falling during inpatient rehabilitation.

Efficacy and safety of exogenous beta-hydroxybutyrate for preventive treatment in episodic migraine: A single-centred, randomised, placebo-controlled, double-blind crossover trial.

BACKGROUND: Several studies propose that brain energy deficit might be partially involved in the pathophysiology of migraine. Previously, studies demonstrated that ketogenic diet causes a substantial reduction in migraine frequency. Since the ketogenic diet is restricting and its adherence is difficult, we proposed to supplement ketone bodies exogenously to provide a prophylactic effect in migraineurs. AIM: To evaluate the prophylactic effect of exogenous DL-beta-hydroxybutyrate supplementation in episodic migraineurs. METHODS: A double-blind, placebo-controlled, randomised crossover trial was conducted, involving 41 patients with episodic migraine. Patients were randomised 1:1 into placebo or beta-hydroxybutyrate group before entering the first treatment period. Each treatment period was 12 weeks long, followed by four weeks of washout phase and four weeks of run-in phase before entering into the corresponding second treatment period. The primary endpoint was the number of migraine days in the last four weeks of treatment, adjusted for baseline. RESULTS: We observed no clinically significant amelioration of migraine frequency or intensity under DL-beta-hydroxybutyrate treatment as compared to placebo regarding number of migraine days (mean difference [95% CI]: -1.1[-5.07, 2.85]), migraine intensity (0-10 VAS: 1.5[-0.8, 3.7]). CONCLUSION: The selected dose of supplemented exogenous DL-beta-hydroxybutyrate did not demonstrate efficacy in episodic migraineurs.ClinicalTrials.gov Identifier: NCT03132233.

Implementation of Motor Function Measure score percentile curves - Predicting motor function loss in Duchenne muscular dystrophy.

The Motor Function Measure is a standardized scoring system to evaluate motor function and monitor disease progression in neuromuscular diseases such as Duchenne muscular dystrophy. There are no available reference percentile curves for this measure. The aim of this analysis was to generate Motor Function Measure percentile curves for ambulant and non-ambulant patients affected by Duchenne Muscular Dystrophy, providing the opportunity to better evaluate the status and progression of an individual patient compared to other patients in the same age group. Data of patients aged between 6 and 15 years (819 measurements) was obtained from the international Motor Function Measure database. Age-dependent percentile curves were estimated using a "Generalized additive model for location, scale and shape" as suggested by the World Health Organisation Multicentre Growth Reference Study Group. Percentile curves for the Motor Function Measure total score and its sub-scores for patients with and without treatment with glucocorticoids are presented. Mean scores decline with age. Patients treated with glucocorticoids have higher mean values compared to glucocorticoid-naïve patients at the same age. The percentile curves with the online tool extend the clinical utility of the Motor Function Measure by facilitating the interpretation of individual standing and disease progression.

Treatment with L-Citrulline in patients with post-polio syndrome: A single center, randomized, double blind, placebo-controlled trial.

This single-centered, randomized, double-blind, placebo-controlled study reports the results of L-Citrulline treatment for 24 weeks in patients with post-polio syndrome (PPS). Twenty-nine patients were randomized and assigned into receiving a treatment of 15 g L-Citrulline or placebo. The primary endpoint was the change of the 6 min walking distance test. Secondary endpoints included motor function measure, quantitative muscle strength, quantitative MRI and self-reported impairment questionnaires. Patients receiving L-Citrulline walked 17.5 longer in the 6 min walking distance test when compared to placebo group, however not statistically significant (95% CI = -14.69; 49.68, p = 0.298). None of the secondary endpoints showed a statistically significant change in the L-Citrulline group when compared to placebo group. The motor function measure showed a change of -0.78 (95% CI= [-3.39; 1.83] p = 0.563). Muscle degeneration of leg muscles assessed with quantitative MRI indicated no significant change (estimate= -0.01, 95% CI =-0.13; 0.11, p = 0.869). L-Citrulline was safe and well tolerated. In conclusion, administration of 15 g L-Citrulline daily for 24 weeks to patients with PPS showed no beneficial treatment effect in timed muscle function.

Treatment of upper limb spasticity with inhibitory repetitive transcranial magnetic stimulation: A randomized placebo-controlled trial.

BACKGROUND: Upper limb dysfunction is a frequent complication after stroke impairing outcome. Inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the contralesional hemisphere is supposed to enhance the positive effects of conventional rehabilitative treatment. OBJECTIVE: This double-blind randomized placebo-controlled trial investigated whether inhibitory rTMS as add-on to standard therapy improves upper limb spasticity. METHODS: Twenty-eight patients (aged 44 to 80 years) with unilateral stroke in the middle cerebral artery territory were analyzed. Participants were randomly assigned to inhibitory, low-frequency (LF-) rTMS (n = 14) or sham-rTMS (n = 14). The primary outcome measure was the spasticity grade, which was assessed with the Modified Ashworth Scale (MAS). In addition, the Fugl-Meyer-Assessment (FMA) for the upper extremity (UE) and a resting-state fMRI were performed to measure motor functions and the sensorimotor network, respectively. RESULTS: The MAS score was reduced in the LF-rTMS group only, whereas the FMA score improved in both groups over time. Regarding the fMRI data, both groups activated typical regions of the sensorimotor network. In the LF-rTMS group, however, connectivity to the left angular gyrus increased after treatment. CONCLUSION: Changes in functional connectivity in patients receiving inhibitory rTMS over the contralesional motor cortex suggest that processes of neuronal plasticity are stimulated.

Auditory Stimulation Modulates Resting-State Functional Connectivity in Unresponsive Wakefulness Syndrome Patients.

Passive listening to music is associated with several psychological and physical benefits in both, healthy and diseased populations. In this fMRI study, we examined whether preferred music has effects on the functional connectivity within resting-state networks related to consciousness. Thirteen patients in unresponsive wakefulness syndrome (UWS) and 18 healthy controls (HC) were enrolled. Both groups were exposed to different auditory stimulation (scanner noise, preferred music, and aversive auditory stimulation). Functional connectivity was analyzed using a seed-based approach. In HC, no differences were found between the three conditions, indicating that their networks are already working at high level. UWS patients showed impaired functional connectivity within all resting-state networks. In addition, functional connectivity of the auditory network was modulated by preferred music and aversive auditory stimulation. Hence, both conditions have the potential to modulate brain activity of UWS patients.

The influence of the CRS-R score on functional outcome in patients with severe brain injury receiving early rehabilitation.

BACKGROUND: The aim of the study was to determine the role of the Coma Recovery Scale-Revised (CRS-R) in the prediction of functional status at the end of neurological early rehabilitative treatment. METHODS: Patients consecutively admitted to intensive or intermediate care units of a neurological rehabilitation center were enrolled in the study. Consciousness and functional status were assessed with the Coma Recovery Scale-Revised (CRS-R) and the Early Rehabilitation Barthel Index (ERBI), respectively. Both assessments were carried out weekly within the first month and at the end of early rehabilitation. Patient and clinical data were entered into a binary logistic regression model to predict functional status at discharge. RESULTS: 327 patients (112 females, 215 males) with a median age of 63 years (IQR = 53-75) and a median disease duration of 18 days (IQR = 12-28) were included. Most patients suffered from stroke (59 %), followed by traumatic brain injury (31 %), and hypoxic ischemic encephalopathy (10 %). Upon admission, 12 % were diagnosed as comatose, 31 % as unresponsive wakefulness syndrome (UWS), 35 % as minimally conscious state (MCS) and 22 % already emerged from MCS (eMCS). Of all patients undergoing complete early rehabilitative treatment (n = 180), 72 % showed improvements in level of consciousness (LOC). In this group, age, initial CRS-R score and gains in CRS-R score after four weeks independently predicted functional outcome at discharge. CONCLUSIONS: The study confirms the relevance of the CRS-R score for functional outcome prediction. High CRS-R scores and young age facilitate functional improvements and increase the probability to continue treatment in subsequent rehabilitation phases. Moreover, results indicate that recovery might occur over a period of time that extends beyond acute care.

[Impact of occupational problems on employment status six months after inpatient neurological rehabilitation]. / Einfluss beruflicher Problemlagen auf den Beschäftigungsstatus sechs Monate nach stationärer neurologischer Rehabilitation.

BACKGROUND: By identifying occupational problems, job-related therapies may be included in rehabilitation at an early stage, increasing the return-to-work rate. The aim of the present study was to examine whether occupational problems that were identified were associated with the employment status six months after inpatient rehabilitation. METHODS: A total of 122 neurological patients undergoing neurological inpatient rehabilitation at the BDH-Clinic Hessisch Oldendorf were retrospectively analysed using clinical routine data from the database of the clinic. Occupational problems were identified with the help of a self-assessment (Wuerzburg Screening [WS]) and an ICF-compliant medical assessment (d850) at the beginning of neurological rehabilitation. In addition, data about the employment status six months after rehabilitation were collected. RESULTS: While the BPL identified in the WS was associated with the employment status at the time of follow-up (r=-0.288; p=.007), there was no relationship between the medical assessment of occupational impairment and the employment status. In binary logistic regression models for predicting the employment status, the duration of the incapacity to work, age, gender and an interdisciplinary assessment at the end of rehabilitation proved to be predictors for the employment status. CONCLUSION: Occupational problems are associated with occupational reintegration six months after discharge from neurological inpatient rehabilitation. Since occupational problems are taken into account in the treatment planning, the impact on the return to work rate may be underestimated in the current study.

Spread of Terbinafine-Resistant Trichophyton mentagrophytes Type VIII (India) in Germany-"The Tip of the Iceberg?"

Chronic recalcitrant dermatophytoses, due to Trichophyton (T.) mentagrophytes Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of T. mentagrophytes Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of T. mentagrophytes Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 T. mentagrophytes isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-α gene (TEF1-α)). All were identified as genotype VIII (India) of T. mentagrophytes. In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints ≥0.2 µg/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited Phe397Leu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined Phe397Leu and Ala448Thr amino acid substitutions, and one strain a single Leu393Phe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight Ala448Thr, and in one Ala448Thr +, new Val444 Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant T. mentagrophytes Type VIII are being increasingly isolated. In Germany, transmission of T. mentagrophytes Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.

Health-related quality of life, self-reported impairments and activities of daily living in relation to muscle function in post-polio syndrome.

BACKGROUND: The symptoms of post-polio syndrome (PPS) and its resulting disabilities can affect quality of life and the ability to perform daily activities. No study has comprehensively analysed how various patient-reported outcome measures (PROMs) are associated with objectively assessed physical function in patients with PPS. AIM: To investigate health-related quality of life (HRQOL), self-reported impairments and activities of daily living during 6 months and evaluate their association with clinical muscle function outcomes in individuals with PPS. METHODS: Twenty-seven patients with PPS were included in the study. At baseline and 6 months, patients were administered PROMs measuring HRQOL (WHOQOL-BREF), self-reported impairments related to PPS (SIPP-RS) and activities of daily living (IBM-FRS). Clinical muscle function outcomes included 6 min walking distance (6MWD) and motor function measure (MFM). RESULTS: There were no changes in self-reported impairments (25.52 to 24.93, p = 0.40), activities of daily living (33.89 to 33.30, p = 0.20), 6MWD (391.52 to 401.85, p = 0.30) and MFM (83.87 to 85.46, p = 0.14) during 6 months, while the HRQOL psychological health decreased during this period (76.85 to 72.38, p = 0.05). A strong association was found between activities of daily living and clinical muscle function outcomes (6MWD: ß = 0.02, 95% CI: 0.02;0.03, t = 6.88, p < 0.01; MFM: ß = 0.25, 95% CI: 0.17;0.33, t = 6.69, p < 0.01). Self-reported impairments and HRQOL domains were not associated with the clinical muscle outcomes. CONCLUSIONS: Study findings indicate that objectively measured walking and motor abilities do not reflect patient's perspectives of their HRQOL and impairment due to PPS. More research is needed to assess changes over time and capture clinically meaningful changes in individuals with PPS and to increase the understanding of how the patient's perspective of disability measured by PROMs is related to objectively measured walking and motor abilities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier ( NCT02801071 ) registered June 15, 2016.