Longitudinal Clinical Features of Post-COVID-19 Patients-Symptoms, Fatigue and Physical Function at 3- and 6-Month Follow-Up.

Post-COVID-19 syndrome (PCS) has been described as 'the pandemic after the pandemic' with more than 65 million people worldwide being affected. The enormous range of symptoms makes both diagnosis complex and treatment difficult. In a post-COVID rehabilitation outpatient clinic, 184 patients, mostly non-hospitalized, received a comprehensive, interdisciplinary diagnostic assessment with fixed follow-up appointments. At baseline, three in four patients reported more than 10 symptoms, the most frequent symptoms were fatigue (84.9%), decreased physical capacity (83.0%), tiredness (81.1%), poor concentration (73.6%), sleeping problems (66.7%) and shortness of breath (67.3%). Abnormalities were found in the mean values of scores for fatigue (FAS = 34.3), cognition (MoCA = 25.5), psychological alterations (anxiety, depression, post-traumatic stress disorder), limitation of lung function (CAT) and severity scores for PCS (PCFS, MCRS). Clinical abnormalities were found in elevated values of heart rate, breathing rate at rest, blood pressure and NT-proBNP levels. As the frequency of the described symptoms decreases only slowly but most often significantly over the course, it is important to monitor the patients over a longer period of time. Many of them suffer from an immense symptom burden, often without pre-existing clinical correlates. Our results show a clear association with objectifiable assessments and tests as well as pronounced symptoms.

Effects of Sensorimotor Training on Transversus Abdominis Activation in Chronic Low Back Pain Patients.

(1) Background: The aim of this study was to investigate and compare the effect of sensorimotor training on transversus abdominis activation. (2) Methods: Seventy-five patients with chronic low back pain were randomly assigned to one of three groups (whole body vibration training using Galileo®, coordination training using Posturomed®, or physiotherapy (control)). Transversus abdominis activation was measured by using sonography pre- and post-intervention. Second, changes in clinical function tests and their correlation with the sonographic measurements were determined. (3) Results: All three groups showed an improvement in activation of the transversus abdominis post-intervention, with the Galileo® demonstrating the largest improvement. There were no relevant (r > 0.5) correlations between activation of the transversus abdominis muscle and any clinical tests. (4) Conclusions: The present study provides evidence that sensorimotor training on the Galileo® significantly improves the activation of the transversus abdominis muscle.

Effects of Different Forms of Sensorimotor Training on Postural Control and Functional Status in Patients with Chronic Low Back Pain.

The aim of this study was to compare three sensorimotor training forms in patients with chronic low back pain to determine their effects on the reduction of pain-related impairment and changes in posturography. Over two weeks, during the multimodal pain therapy (MMPT) period, six sessions of sensorimotor physiotherapy or training in the Galileo® or Posturomed® (n = 25 per group) were performed. A significant reduction in pain-related impairment after the intervention phase was shown across all groups (time effect: p < 0.001; ηp2 = 0.415). There was no change in postural stability (time effect: p = 0.666; ηp2 = 0.003), but there was a significant improvement in the peripheral vestibular system (time effect: p = 0.014; ηp2 = 0.081). An interaction effect was calculated for the forefoot-hindfoot ratio (p = 0.014; ηp2 = 0.111). Only the Posturomed® group showed an improvement in anterior-posterior weight distribution (heel load: 47% vs. 49%). These findings suggest that these forms of sensorimotor training in the context of MMPT are suitable for reducing pain-related impairment. Posturography demonstrated stimulation of a subsystem, but no improvement in postural stability.

Pressure Pain Thresholds and Central Sensitization in Relation to Psychosocial Predictors of Chronicity in Low Back Pain.

(1) Background: Peripheral, as well as central, sensitization have been described in chronic low back pain (cLBP). The purpose of this study is to investigate the influence of psychosocial factors on the development of central sensitization. (2) Methods: This prospective study investigated local and peripheral pressure pain thresholds and their dependence on psychosocial risk factors in patients with cLBP receiving inpatient multimodal pain therapy. Psychosocial factors were assessed using the Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ). (3) Results: A total of 90 patients were included in the study, 61 (75.4% women, 24.6% men) of whom had significant psychosocial risk factors. The control group consisted of 29 patients (62.1% women, 37.9% men). At baseline, patients with psychosocial risk factors showed significantly lower local and peripheral pressure pain thresholds, suggesting central sensitization, compared to the control group. Sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), was also correlated with altered PPTs. After multimodal therapy, all participants reported increased local pain thresholds compared to at admission, independent of psychosocial chronification factors. (4) Conclusions: Psychosocial chronicity factors measured using the ÖMPSQ have a significant influence on pain sensitization in cLBP. A 14-day multimodal pain therapy increased local, but not peripheral, pressure pain thresholds.

The Greifswald Post COVID Rehabilitation Study and Research (PoCoRe)-Study Design, Characteristics and Evaluation Tools.

(1) Background: COVID-19 is often associated with significant long-term symptoms and disability, i.e., the long/post-COVID syndrome (PCS). Even after presumably mild COVID-19 infections, an increasing number of patients seek medical help for these long-term sequelae, which can affect various organ systems. The pathogenesis of PCS is not yet understood. Therapy has so far been limited to symptomatic treatment. The Greifswald Post COVID Rehabilitation Study (PoCoRe) aims to follow and deeply phenotype outpatients with PCS in the long term, taking a holistic and comprehensive approach to the analysis of their symptoms, signs and biomarkers. (2) Methods: Post-COVID outpatients are screened for symptoms in different organ systems with a standardized medical history, clinical examination, various questionnaires as well as physical and cardiopulmonary function tests. In addition, biomaterials are collected for the analysis of immunomodulators, cytokines, chemokines, proteome patterns as well as specific (auto)antibodies. Patients are treated according to their individual needs, adhering to the current standard of care. PoCoRe's overall aim is to optimize diagnostics and therapy in PCS patients.

[Orofacial and musculoskeletal disorders of professional musicians - Frequency and therapy principles]. / Orofaziale und muskuloskelettale Schmerzsyndrome bei professionellen Musikern ­ Häufigkeiten und Therapieprinzipien.

Playing-related musculoskeletal disorders are frequently found in the upper extremety and the spine. Moreover, orofacial pain syndromes and craniomandibular dysfunctions are important in upper string players and wind players. The treatment of musicians is based on a diagnostic process including the evaluation of specific musical aspects, a functional manual medicine examination and an evaluation of postural and movement characteristics while playing the musical instrument.

Back pain treatment: a new perspective.

This article aims to provide new perspectives for the treatment of low back pain (LBP). A narrative literature review highlights the treatment strategies currently anchored in the guidelines as well as the extensive attempts to identify subgroups within the non-specific low back pain (NSLBP) classification. A variety of multimodal approaches exist for both diagnostic assessments and therapy approaches. Nonetheless, there are often gaps in the classification systems as well as in published treatment concepts with regard to the implementation of musculoskeletal functional disorders. Indeed, a growing body of evidence shows that more holistic and flexible approaches are needed to individually diagnose and target the complexity of LBP. As an example, both a diagnostic and a (independently developed) therapeutic LBP concept will be presented and discussed. Ultimately, guidelines and subgroup classification systems can only reflect the complexity of LBP, if they capture its entire multidimensional and biopsychosocial character in both the diagnostic and therapeutic processes. Furthermore, the expansion of the pain definition to include the nociplastic pain mechanism, as an important driver of LBP, has the potential to provide important impulses for further necessary research. In conclusion, the implementation of a functional musculoskeletal approach along with the emerging nociceptive pain concept in individually targeted holistic approaches seems to be the successful way to deal with the complexity of LBP.

Aerosol emission from playing wind instruments and related COVID-19 infection risk during music performance.

The pandemic of COVID-19 led to restrictions in all kinds of music activities. Airborne transmission of SARS-CoV-2 requires risk assessment of wind instrument playing in various situations. Previous studies focused on short-range transmission, whereas long-range transmission risk has not been assessed. The latter requires knowledge of aerosol emission rates from wind instrument playing. We measured aerosol concentrations in a hermetically closed chamber of 20 m3 in an operating theatre as resulting from 20 min standardized wind instrument playing (19 flute, 11 oboe, 1 clarinet, 1 trumpet players). We calculated aerosol emission rates showing uniform distribution for both instrument groups. Aerosol emission from wind instrument playing ranged from 11 ± 288 particles/second (P/s) up to 2535 ± 195 P/s, expectation value ± uncertainty standard deviation. The analysis of aerosol particle size distributions shows that 70-80% of emitted particles had a size of 0.25-0.8 µm and thus are alveolar. Masking the bell with a surgical mask did not reduce aerosol emission. Aerosol emission rates were higher from wind instrument playing than from speaking or breathing. Differences between instrumental groups could not be found but high interindividual variance, as expressed by uniform distribution of aerosol emission rates. Our findings indicate that aerosol emission depends on physiological factors and playing techniques rather than on the type of instrument, in contrast to some previous studies. Based on our results, we present transmission risk calculations for long-range transmission of COVID-19 for three typical woodwind playing situations.

Neuromodulation through brain stimulation-assisted cognitive training in patients with post-COVID-19 cognitive impairment (Neuromod-COV): study protocol for a PROBE phase IIb trial.

INTRODUCTION: A substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments. METHODS AND ANALYSIS: This study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings). ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04944147.

Safe Polycationic Dendrimers as Potent Oral In Vivo Inhibitors of Mycobacterium tuberculosis: A New Therapy to Take Down Tuberculosis.

The long-term treatment of tuberculosis (TB) sometimes leads to nonadherence to treatment, resulting in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. Inadequate bioavailability of the drug is the main factor for therapeutic failure, which leads to the development of drug-resistant cases. Therefore, there is an urgent need to design and develop novel antimycobacterial agents minimizing the period of treatment and reducing the propagation of resistance at the same time. Here, we report the development of original and noncytotoxic polycationic phosphorus dendrimers essentially of generations 0 and 1, but also of generations 2-4, with pyrrolidinium, piperidinium, and related cyclic amino groups on the surface, as new antitubercular agents active per se, meaning with intrinsic activity. The strategy is based on the phenotypic screening of a newly designed phosphorus dendrimer library (generations 0-4) against three bacterial strains: attenuated Mycobacterium tuberculosis H37Ra, virulent M. tuberculosis H37Rv, and Mangora bovis BCG. The most potent polycationic phosphorus dendrimers 1G0,HCl and 2G0,HCl are active against all three strains with minimum inhibitory concentrations (MICs) between 3.12 and 25.0 µg/mL. Both are irregularly shaped nanoparticles with highly mobile branches presenting a radius of gyration of 7 Å, a diameter of maximal 25 Å, and a solvent-accessible surface area of dominantly positive potential energy with very localized negative patches arising from the central N3P3 core, which steadily interacts with water molecules. The most interesting is 2G0,HCl, showing relevant efficacy against single-drug-resistant (SDR) M. tuberculosis H37Rv, resistant to rifampicin, isoniaid, ethambutol, or streptomycin. Importantly, 2G0,HCl displayed significant in vivo efficacy based on bacterial counts in lungs of infected Balb/C mice at a dose of 50 mg/kg oral administration once a day for 2 weeks and superior efficacy in comparison to ethambutol and rifampicin. This series of polycationic phosphorus dendrimers represents first-in-class drugs to treat TB infection, could fulfill the clinical candidate pipe of this high burden of infectious disease, and play a part in addressing the continuous demand for new drugs.

Datasets and analyses of molecular dynamics simulations of covalent binary and ternary complexes of MHC class I-related molecule/T-cell receptor (MR1/TCR) agonists to understand complex formation and conditions of fluorescent labelling.

Data of molecular dynamics (MD) simulations were obtained for mucosal-associated invariant T (MAIT) cell ligands complexed with MR1 or MR1/TCR. Ligands included in the simulations were natural ligands 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), 5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracil (5-OP-RU), their C5' ethinylated analogs in S or R configuration, as well as the corresponding fluorophore-reacted products. All-atom models of the binary and ternary complexes were constructed using PDB entry 4NQE and docked poses [1]. Missing loops, N- and C-termini were completed by homology modelling, the loop conformations optimized, and the models energy minimized prior to setup for MD simulations. A standard pre-equilibration protocol was applied before the production phase of 120 ns simulation as NPT ensemble at 300 K and 1 atm applying an explicit solvent model with OPLS3 force field parameters. Atomic coordinates and energies were recorded every 60 ps and 12 ps, respectively. The corresponding raw data files of the MD simulations are part of this dataset. All simulations were analysed with respect to root mean square deviations (rmsd) and root mean square fluctuations (rmsf) of the coordinates of protein and ligand atoms, stability of protein secondary structure, protein-ligand contacts, ligand torsion profiles, and ligand properties. More detailed statistics of non-covalent interaction counts were also collected. Radial distribution functions (rdf) were calculated when relevant. Visualization of the trajectories permits appreciation of the molecular dynamics of both, ligands and proteins and their interactions, thereby supporting drug design of MAIT cell ligands; furthermore, additional analysis of e.g. conformational changes or interactions not reported in the primary publication [1] can be performed on the data. The raw data may also be used as starting point for extension of the simulations or more sophisticated MD techniques.

Multivalent Copper(II)-Conjugated Phosphorus Dendrimers with Noteworthy In Vitro and In Vivo Antitumor Activities: A Concise Overview.

Dendrimers are macromolecules with well-defined, homogeneous, and monodispersed structures that form a branch-like structure. In general, they have a symmetric core, inner shells, and an outer shell. Over the past decade, metallodendritic architectures have developed into a new area in nanomedicine. Due to their versatility and facile customization, phosphorus dendrimers represent interesting platforms for biomedical applications. Metallo-conjugated phosphorus dendrimers have been developed within the dendrimer space, an important part of the chemical space. The first investigation was made using phosphorus dendrimers bearing copper(II) groups on their surface as the original anticancer drug candidates. The aim of this minireview is to present our powerful strategy to find and develop original multivalent copper(II)-conjugated phosphorus dendrimers. The most potent of them is G3 dendrimers with N-(pyridine-2-ylmethylene)ethanamine as the chelating motif complexed with Cu(II) (1G3-Cu), showing very good in vitro and in vivo antiproliferative efficacy. On the basis of these results, 1G3-Cu is a potential clinical candidate having progressed from hit to preclinical candidate status.

Synthesis, biological evaluation and molecular modelling of new potent clickable analogues of 5-OP-RU for their use as chemical probes for the study of MAIT cell biology.

MAIT cells are preset αß T lymphocytes that recognize a series of microbial antigens exclusively derived from the riboflavin biosynthesis pathway, which is present in most bacteria. The most active known antigen is unstable 5-(2-oxopropylideneamino)-6-(d-ribitylamino)uracil (5-OP-RU) which is stabilized when bound and presented to MAIT cells by MHC-related protein 1 (MR1). Here we describe the chemical synthesis and biological evaluation of new chemical probes for the study of MAIT cell biology. The two probes were ethinyl functionalized analogues of 5-OP-RU able to react through CuAAC also called "click chemistry". The molecules up-regulated more MR1 than 5-OP-RU and they efficiently activated iVα19 Vß8 TCR transgenic murine MAIT cells but not iVα19 TCRα transgenic MAIT cells indicating a surprisingly strong impact of the TRCß chain. Moreover, the use of these molecules as chemical probes was validated in vitro by efficient and selective binding to MR1 revealed via fluorescence microscopy. This study was also complemented by molecular modelling investigation of the probes and the binary/ternary complexes they form with MR1 and the TCR. These new probes will be crucial to delineate the dynamics of 5-OP-RU at the cellular or whole organism level and to identify the cells presenting 5-OP-RU to MAIT cells in vivo.

Tetravalent Bispecific Tandem Antibodies Improve Brain Exposure and Efficacy in an Amyloid Transgenic Mouse Model.

Most antibodies display very low brain exposure due to the blood-brain barrier (BBB) preventing their entry into brain parenchyma. Transferrin receptor (TfR) has been used previously to ferry antibodies to the brain by using different formats of bispecific constructs. Tetravalent bispecific tandem immunoglobulin Gs (IgGs) (TBTIs) containing two paratopes for both TfR and protofibrillar forms of amyloid-beta (Aß) peptide were constructed and shown to display higher brain penetration than the parent anti-Aß antibody. Additional structure-based mutations on the TfR paratopes further increased brain exposure, with maximal enhancement up to 13-fold in wild-type mice and an additional 4-5-fold in transgenic (Tg) mice harboring amyloid plaques, the main target of our amyloid antibody. Parenchymal target engagement of extracellular amyloid plaques was demonstrated using in vivo and ex vivo fluorescence imaging as well as histological methods. The best candidates were selected for a chronic study in an amyloid precursor protein (APP) Tg mouse model showing efficacy at reducing brain amyloid load at a lower dose than the corresponding monospecific antibody. TBTIs represent a promising format for enhancing IgG brain penetration using a symmetrical construct and keeping bivalency of the payload antibody.

Effect of subgroup-specific multimodal therapy on chronic spinal back pain and function-a prospective inpatient multicentre clinical trial in Germany.

Treatment modalities of spinal pain patients are discussed diversely, and different multimodal therapy programs have been developed. Purpose of the present study was to evaluate therapy outcome and effectiveness of an inpatient interdisciplinary and multimodal treatment program.This prospective multicentre clinical trial has been performed with patients from orthopedic hospitals receiving a functional musculoskeletal therapy pathway. Outcome measures were pain intensity and back-specific function (Oswestry Disability Index) before (T1) and after the intervention (T2) as well as after 6 and 12 months (T3, T4). Statistical approach included parametric (t test) and nonparametric (Wilcoxon-test) tests and the calculation of effect sizes. Additionally, a statistical subgroup analysis based on selected parameters (degree of pain chronicity, gender, and age) was performed using linear mixed models.In total, 249 patients (42.6% men, 57.4% women) with spinal pain were included, 133 patients were accessible for follow-up at T3 and 106 patients at T4.Average pain (AP) reduced significantly (P <.001) from T1 to T4 with an effect size of 0.99. Back-specific function also improved (P <.001) over all measuring time points (TP) (effect size: 0.63). Furthermore, the statistical subgroup analysis demonstrated the efficacy of the treatment concept within the subgroup parameters chronicity degree and age.A functional musculoskeletal therapy pathway including treatment of musculoskeletal dysfunctions appears to be beneficial in terms of treating pain and function. Pain chronicity and age seems to be factors influencing therapy outcome. Further studies are needed to examine the superiority of these inpatient programs for back pain including control groups.

Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators.

A multivalent phosphorus dendrimer 1G3 and its corresponding Cu-complex, 1G3-Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis. To get insight in their mode of action, cell death pathways have been examined in human cancer cell lines: early apoptosis was followed by secondary necrosis after multivalent phosphorus dendrimers exposure. The multivalent plain phosphorus dendrimer 1G3 moderately activated caspase-3 activity, in contrast with the multivalent Cu-conjugated phosphorus dendrimer 1G3-Cu which strikingly reduced the caspase-3 content and activity. This decrease of caspase activity is not related to the presence of copper, since inorganic copper has no or little effect on caspase-3. Conversely the potent apoptosis activation could be related to a noticeable translocation of Bax to the mitochondria, resulting in the release of AIF into the cytosol, its translocation to the nucleus and a severe DNA fragmentation, without alteration of the cell cycle. The multivalent Cu-conjugated phosphorus dendrimer is more efficient than its non-complexed analog to activate this pathway in close relationship with the higher antiproliferative potency. Therefore, this multivalent Cu-conjugated phosphorus dendrimer 1G3-Cu can be considered as a new and promising first-in-class antiproliferative agent with a distinctive mode of action, inducing apoptosis tumor cell death through Bax activation pathway.

CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications.

Bispecific immunoglobulins (Igs) typically contain at least two distinct variable domains (Fv) that bind to two different target proteins. They are conceived to facilitate clinical development of biotherapeutic agents for diseases where improved clinical outcome is obtained or expected by combination therapy compared to treatment by single agents. Almost all existing formats are linear in their concept and differ widely in drug-like and manufacture-related properties. To overcome their major limitations, we designed cross-over dual variable Ig-like proteins (CODV-Ig). Their design is akin to the design of circularly closed repeat architectures. Indeed, initial results showed that the traditional approach of utilizing (G4S)x linkers for biotherapeutics design does not identify functional CODV-Igs. Therefore, we applied an unprecedented molecular modeling strategy for linker design that consistently results in CODV-Igs with excellent biochemical and biophysical properties. CODV architecture results in a circular self-contained structure functioning as a self-supporting truss that maintains the parental antibody affinities for both antigens without positional effects. The format is universally suitable for therapeutic applications targeting both circulating and membrane-localized proteins. Due to the full functionality of the Fc domains, serum half-life extension as well as antibody- or complement-dependent cytotoxicity may support biological efficiency of CODV-Igs. We show that judicious choice in combination of epitopes and paratope orientations of bispecific biotherapeutics is anticipated to be critical for clinical outcome. Uniting the major advantages of alternative bispecific biotherapeutics, CODV-Igs are applicable in a wide range of disease areas for fast-track multi-parametric drug optimization.

Neck muscle function in violinists/violists with and without neck pain.

Neck pain is associated with changes in neuromuscular control of cervical muscles. Violin and viola playing requires good function of the flexor muscles to stabilize the instrument. This study investigated the flexor muscle behaviour in violin/viola players with and without neck pain using the craniocervical flexion test (CCFT). In total, 12 violin/viola players with neck pain, 21 violin/viola players without neck pain in the preceding 12 weeks and 21 pain-free non-musicians were included. Activity of the sternocleidomastoid muscles (SCM) was measured with surface electromyography (EMG) during the CCFT. Violin/viola players with neck pain displayed greater normalised SCM EMG amplitudes during CCFT than the pain-free musicians and non-musicians (P < 0.05). Playing-related neck pain in violinists/violists is associated with altered behaviour of the superficial neck flexor muscles consistent with neck pain, despite the specific use of the deep and superficial neck flexors during violin playing.

From embouchure problems to embouchure dystonia? A survey of self-reported embouchure disorders in 585 professional orchestra brass players.

OBJECTIVES: Data concerning embouchure problems in professional brass players are scarce. Embouchure problems can potentially lead to focal dystonia. The aim of this study was to investigate the frequency of distinct embouchure problems in professional brass players. Furthermore, the frequency of "cramping", a distinct symptom of embouchure dystonia, was evaluated in the context of established embouchure dystonia risk factors. METHODS: Five hundred and eighty-five professional brass players participated in a cross-sectional study concerning embouchure problems. A self-administered questionnaire was developed to evaluate embouchure fatigue, embouchure disorders and their consequences. To study the association between risk factors and cramping (a symptom of embouchure dystonia), a log-binomial regression analysis was conducted, enabling estimation of prevalence ratios (PR) and 95 % confidence intervals (95 % CI). RESULTS: Thirty percent (95 % CI 25.9-33.3) reported embouchure fatigue. The relative frequency of embouchure disorders was 59 % (95 % CI 54.6-63.6), with 26 % (95 % CI 22.4-29.5) reporting embouchure cramping. Embouchure disorders resulted in sick leave in 16 % (95 % CI 12.7-20.6). Female brass players (PR 2.0, 95 % CI 0.98-3.98) and musicians with a prior change in their embouchure (PR 2.4, 95 % CI 1.38-4.05) or breathing technique (PR 2.2, 95 % CI 1.25-3.72) and musicians with embouchure fatigue (PR 1.9, 95 % CI 1.18-2.93) presented more frequently with embouchure cramping than musicians with other or without risk factors. CONCLUSION: This study shows a high relative frequency of embouchure problems in professional brass players. Given that embouchure dystonia is often preceded by embouchure problems, these findings may assist in gaining further insight into the characteristics of embouchure dystonia and the development of preventive strategies.

Sensory and sensorimotor features in violinists and violists with neck pain.

OBJECTIVE: To investigate sensory and sensorimotor function in violin and viola players with and without neck pain. DESIGN: Prospective, cross-sectional study. SETTING: University laboratory. PARTICIPANTS: Convenience sample of violin players with playing-related neck pain (n=22), violinists without neck pain (n=21), and healthy nonmusician comparison subjects (n=21). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measures include thermal pain thresholds (cold and heat) and pressure pain thresholds (PPTs) over the cervical spine and over a remote region (tibialis anterior muscle). Motor performance tests including reaction times, speed of movement, accuracy, coordination, and tapping speed assessed with a special upper-limb test battery. RESULTS: Musicians with neck pain had significantly lower heat and elevated cold pain thresholds as well as lower PPTs over C5-6 (P<.01) and over the tibialis anterior (P<.05). Motor performance tests revealed no differences between the symptomatic and asymptomatic musicians and nonmusician comparison groups (P>.05). CONCLUSIONS: Violin players with neck pain demonstrated signs of sensory impairment, suggesting that playing-related neck pain may be associated with augmented central pain processing consistent with findings in other neck pain groups. No differences were evident in the motor performance tests. Fine motor skills of violin players may be better assessed in the context of playing their musical instruments before definitive conclusions can be drawn about the presence or not of sensorimotor impairments in this group of musicians with playing-related neck pain.