Study protocol: multimodal physiotherapy as an add-on treatment to botulinum neurotoxin type A therapy for patients with cervical dystonia: DysPT-multi-a prospective, multicentre, single-blind, randomized, controlled study.

BACKGROUND: Botulinum neurotoxin (BoNT) is currently the best therapeutic option in the treatment for cervical dystonia (CD). Additional treatments like physiotherapy (PT) may even improve the results of the BoNT injection with type A (BoNT-A), but there are no definite recommendations. In the last few years, some studies showed tendencies for PT as an adjuvant therapy to benefit. However, high-quality studies are required. METHODS: This study is a multicentre, randomized, single-blind, controlled trial to demonstrate the effectiveness of a multimodal PT program compared to a nonspecific cupping therapy, additionally to the BoNT-A therapy. Two hundred participants will be assigned into the multimodal PT plus BoNT intervention arm or the BoNT plus cupping arm using randomization. Primary endpoint is the total Score of Toronto Western Spasmodic Rating Scale (TWSTRS). Secondary endpoints are the mobility of the cervical spine (range of motion, ROM), the TWSTRS subscales, and the quality of life (measured by questionnaires: CDQ-24 and SF-36). Patients will be single-blind assessed every 3 months according to their BoNT injection treatment over a period of 9 months. DISCUSSION: The study aims to determine the effectiveness and therefore potential benefit of an additional multimodal physiotherapy for standardized treatment with BoNT-A in patients with CD, towards the BoNT-therapy alone. This largest randomized controlled trial in this field to date is intended to generate missing evidence for therapy guidelines. TRIAL REGISTRATION: The study was registered in the German Clinical Study Register before the start of the patient recruitment ( DRKS00020411 ; date: 21.01.2020).

Psychosocial factors, mental health, and coordination capacity in patients with heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction.

AIMS: Patients with heart failure (HF) suffer from reduced quality-of-life (QoL). We aimed to compare QoL, depression, and anxiety scores among outpatients with preserved (HFpEF) and reduced (HFrEF) ejection fraction and non-HF controls and its relationship to coordination capacity. METHODS AND RESULTS: Fifty-five participants were recruited prospectively at the University Hospital Jena, Germany (17 HFpEF, 18 HFrEF, and 20 non-HF controls). All participants underwent echocardiography, cardiopulmonary exercise testing (CPET), 10 m walking test (10-MWT), isokinetic muscle function and coordination tests, and QoL assessments using the short form of health survey (SF-36), and hospital anxiety and depression scale (HADS). Furthermore, inflammatory biomarkers such as growth differentiation factor-15 (GDF-15) were assessed. Patients with HFpEF showed compared with HFrEF and non-HF controls reduced QoL [mental component score (MCS): 43.6 ± 7.1 vs. 50.2 ± 10.0 vs. 50.5 ± 5.0, P = 0.03), vitality (VT): 47.5 ± 8.4 vs. 53.6 ± 8.6 vs. 57.1 ± 5.2, P = 0.004), and elevated anxiety (6.5 ± 3.2 vs. 3.3 ± 2.8 vs. 3.8 ± 2. 8, P = 0.02) and depression scores (6.5 [3.5-10.0] vs. 3.0 [1.0-6.5] vs. 2.0 [0.75-3.0], P = 0.01)]. After adjusting to multiple comparisons, anxiety remained higher in HFpEF patients compared with HFrEF (ppost-hoc  = 0.009). HFpEF and HFrEF patients showed reduced coordination capacity compared with non-HF controls (P < 0.05). In a logistic regression, the presence of depression score ≥8 remained an independent factor for predicting reduced coordination capacity after adjusting for peak VO2 , GDF-15, 10-MWT, physical component score (PCS), and peak torque of the leg [odds ratio (OR): 0.1, 95% confidence interval (CI): 0.004-0.626, P = 0.02]. CONCLUSION: Outpatients with HFpEF had worse QoL and higher anxiety and depression scores compared with HFrEF and non-HF controls. Depression is associated with reduced QoL and is an independent predictor for reduced coordination capacity.

Skeletal Muscle Function, Structure, and Metabolism in Patients With Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Reduced exercise capacity in patients with heart failure (HF) could be partially explained by skeletal muscle dysfunction. We compared skeletal muscle function, structure, and metabolism among clinically stable outpatients with HF with preserved ejection fraction, HF with reduced ejection fraction, and healthy controls (HC). Furthermore, the molecular, metabolic, and clinical profile of patients with reduced muscle endurance was described. METHODS: Fifty-five participants were recruited prospectively at the University Hospital Jena (17 HF with preserved ejection fraction, 18 HF with reduced ejection fraction, and 20 HC). All participants underwent echocardiography, cardiopulmonary exercise testing, 6-minute walking test, isokinetic muscle function, and skeletal muscle biopsies. Expression levels of fatty acid oxidation, glucose metabolism, atrophy genes, and proteins as well as inflammatory biomarkers were assessed. Mitochondria were evaluated using electron microscopy. RESULTS: Patients with HF with preserved ejection fraction showed compared with HF with reduced ejection fraction and HC reduced muscle strength (eccentric extension: 13.3±5.0 versus 18.0±5.9 versus 17.9±5.1 Nm/kg, P=0.04), elevated levels of MSTN-2 (myostatin-2), FBXO-32 (F-box only protein 32 [Atrogin1]) gene and protein, and smaller mitochondrial size (P<0.05). Mitochondrial function and fatty acid and glucose metabolism were impaired in HF-patients compared with HC (P<0.05). In a multiple regression analysis, GDF-15 (growth and differentiation factor 15), CPT1B (carnitine palmitoyltransferase IB)-protein and oral anticoagulation were independent factors for predicting reduced muscle endurance after adjusting for age (log10 GDF-15 [pg/mL] [B, -54.3 (95% CI, -106 to -2.00), P=0.043], log10 CPT1B per fold increase [B, 49.3 (95% CI, 1.90-96.77), P=0.042]; oral anticoagulation present [B, 44.8 (95% CI, 27.90-61.78), P<0.001]). CONCLUSIONS: Patients with HF with preserved ejection fraction have worse muscle function and predominant muscle atrophy compared with those with HF with reduced ejection fraction and HC. Inflammatory biomarkers, fatty acid oxidation, and oral anticoagulation were independent factors for predicting reduced muscle endurance.

Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen.

BACKGROUND: The antisense oligonucleotide Nusinersen recently became the first approved drug against spinal muscular atrophy (SMA). It was approved for all ages, albeit the clinical trials were conducted exclusively on children. Hence, clinical data on adults being treated with Nusinersen is scarce. In this case series, we report on drug application, organizational demands, and preliminary effects during the first 10 months of treatment with Nusinersen in seven adult patients. METHODS: All patients received intrathecal injections with Nusinersen. In cases with severe spinal deformities, we performed computed tomography (CT)-guided applications. We conducted a total of 40 administrations of Nusinersen. We evaluated the patients with motor, pulmonary, and laboratory assessments, and tracked patient-reported outcome. RESULTS: Intrathecal administration of Nusinersen was successful in most patients, even though access to the lumbar intrathecal space in adults with SMA is often challenging. No severe adverse events occurred. Six of the seven patients reported stabilization of motor function or reduction in symptom severity. The changes in the assessed scores did not reach a significant level within this short time period. CONCLUSIONS: Treating adult SMA patients with Nusinersen is feasible and most patients consider it beneficial. It demands a complex organizational and interdisciplinary effort. Due to the slowly decreasing motor functions in adult SMA patients, long observation phases for this recently approved treatment are needed to allow conclusions about effectiveness of Nusinersen in adults.

Corrigendum to "Development of a Symmetry Score for Infantile Postural and Movement Asymmetries: Preliminary Results of a Pilot Study" [Journal of Chiropractic Medicine 17 (2018) 206-216].

[This corrects the article DOI: 10.1016/j.jcm.2018.03.006.].

Development of a Symmetry Score for Infantile Postural and Movement Asymmetries: Preliminary Results of a Pilot Study.

OBJECTIVE: The purpose of this study was to develop and verify a quantifiable symmetry score for infantile postural and movement asymmetries. METHODS: Three studies were conducted. For reliability, 6 test items examining postural and movement asymmetries, which came under consideration, were investigated in 24 infants with postural abnormality (range: 14-24 weeks). The inter-rater reliability was chosen as the primary endpoint. Furthermore, intrarater reliability and test-retest reliability were determined. Analysis and weighting of the items were performed by calculating the intraclass correlation coefficient. The validity was reviewed by expert opinion and by using a study with 26 infants (range: 12-28 weeks) of a cross-section population. The pilot study involved 38 infants, aged 14 to 24 weeks, who were examined using video. Their autonomic symptoms were recorded, and subsequently, they were treated once by means of manual medicine. The parents were instructed to a daily home program that focused on "tummy time." RESULTS: The reliability tests led to a 4-item symmetry score with a point value between 4 points (very symmetrical) and 17 points (very asymmetrical). The chosen items achieved an intraclass correlation coefficient >0.8 and Cohen's κ >0.6, respectively. The experts' opinions matched mainly to a majority agreement (>50%). Furthermore, a comparison between the outcome of clinical testing and the symmetry score applied to 26 children without diagnosed abnormalities displayed an agreement of 84.6%. The pilot study showed a good reduction of the postural and movement abnormalities because 63% of the manual treated children were assessed as being symmetric afterward. CONCLUSION: The reliable and valid 4-item symmetry score served for the diagnosis, evaluation, and follow-up of infants aged 3 to 6 months with infantile postural and movement asymmetries. The results of a pilot study showed the positive effect of a single manual medical treatment session along with a home program focusing on "tummy time."

Results of an Interdisciplinary Day Care Approach for Chronic Tinnitus Treatment: A Prospective Study Introducing the Jena Interdisciplinary Treatment for Tinnitus.

Objective: Considering the heterogeneity of the symptoms shown by patients suffering from chronic tinnitus, there are surprisingly few interdisciplinary treatments available, and mostly available only for inpatients. In order to provide an interdisciplinary treatment, we developed a day care concept in which each patient was treated by an ENT doctor, a cognitive behavioral therapist, a specialist for medical rehabilitation and an audiologist (Jena Interdisciplinary Treatment for Tinnitus, JITT). The aim of this study was to observe the changes of tinnitus related distress due to interdisciplinary day care treatment and to determine which factors mediate this change. Subjects and Methods: Tinnitus annoyance was measured using the Tinnitus Questionnaire on 308 patients with chronic tinnitus. They were treated in the day care unit over five consecutive days between July 2013 and December 2014. Data were collected before treatment when screened (T0), at the beginning (T1) and at the end of the 5 day treatment (T2), as well as 20 days (T3) and 6 months after treatment (T4). Results: Overall, tinnitus annoyance improved significantly from the screening day to the beginning of treatment, and to a much larger degree from the beginning to the end of treatment. The treatment outcome remained stable 6 months after treatment. Patients with the following symptoms displayed higher tinnitus annoyance at T0: dizziness at tinnitus onset, tinnitus sound could not be masked with background noise, tinnitus worsening during physical stress, comorbid psychiatric diagnosis, higher age and higher hearing loss. Loudness of tinnitus perceived in the right ear correlated with tinnitus annoyance significantly. Demographic, tinnitus and strain variables could only explain 12.8% of the variance of the change in tinnitus annoyance from T0 to T4. Out of 39 predictors, the only significant ones were "sick leave 6 months before treatment" and "tinnitus annoyance at T0." Conclusion: The newly developed JITT represents a valuable treatment for chronic tinnitus patients with improvement remaining stable for at least 6 months after treatment. Using a large number of variables did not allow predicting treatment outcome which underlines the heterogeneity of tinnitus.

Potential effect of physiotherapeutic treatment on mortality rate in patients with severe sepsis and septic shock: a retrospective cohort analysis.

PURPOSE: The aim of the study was to examine the onset and frequency of physiotherapeutic interventions (PTI) and their potential effects on the intensive care unit (ICU) mortality rate in patients with severe sepsis or septic shock. MATERIAL AND METHODS: Retrospective data analysis. Univariate and multivariate Cox proportional-hazards regression analyses were performed. RESULTS: About 6.2% of all patients (n = 999, length of ICU stay 12 days, averaged SOFA score 14) developed sepsis within three years. Of these, 77% received at least once PTI. The relative number of PTI (RNPTI index, individually calculated by the number of PTI/length of stay) in patients with sepsis was 42%. The first physiotherapeutic treatment was five days after ICU admission. Cox regression multivariate analysis adjusted by disease severity scores, sedation state and other clinical variables found RNPTI index as significant risk factor for the ICU mortality rate (hazard ratio, 0.982; 95% confidence interval, 0.974-0.990; P < .001). CONCLUSIONS: Physiotherapists routinely assess and treat patients with sepsis. The frequency of PTI was associated with an improved outcome. Prospective studies are necessary to confirm the potential favorable impact.

Measurement of mandible movements using a vernier caliper--an evaluation of the intrasession-, intersession- and interobserver reliability.

The aim of this study was to evaluate the intrasession-, intersession-, and interrater reliability of a vernier caliper measurement of mandible movements. The authors calculated the intrasession, intersession-, and interrater reliability using a plastic caliper for important mandibular parameters. All intraclass-correlation-coefficients (ICC) are at least moderately accurate, especially the values for intrasession- and intersession reliability, which were excellent. Only the interrater reliability shows greater fluctuations. Whereas the mouth opening, protrusion, and the tooth positions are reliably correct, the same was not applicable to the side movements. The lateral movement measurements were highly variable. This did not apply to other movements. Patient compliance is important along with a different mouth-opening angle. It is possible to generate a variable laterotrusion to both sides. The caliper investigated is a fast, simple, and inexpensive tool for daily work.