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Health care providers like physiotherapists should address the needs of performing artists for a specific health care derived from physical and psychosocial (performance-related) complaints. The aims of this study were (1) to compose an algorithm including subjective outcome measures in order to suggest how to evaluate the physical and psychosocial health status of performing artists in its complexity in a manner as targeted and detailed as possible, and (2) to test the feasibility of applying this algorithm.

The primary objective of this study was to determine the structural and known-group validity as well as the inter-rater reliability of a test battery to evaluate the motor control of the craniofacial region. Seventy volunteers without TMD and 25 subjects with TMD (Axes I) per the DC/ TMD were asked to execute a test battery consisting of eight tests. The tests were video-taped in the same sequence in a standardised manner. Two experienced physical therapists participated in this study as blinded assessors. We used exploratory factor analysis to identify the underlying component structure of the eight tests. Internal consistency (Cronbach's α), inter-rater reliability (intra-class correlation coefficient) and construct validity (ie, hypothesis testing-known-group validity) (receiver operating curves) were also explored for the test battery. The structural validity showed the presence of one factor underlying the construct of the test battery. The internal consistency was excellent (0.90) as well as the inter-rater reliability. All values of reliability were close to 0.9 or above indicating very high inter-rater reliability. The area under the curve ( AUC) was 0.93 for rater 1 and 0.94 for rater two, respectively, indicating excellent discrimination between subjects with TMD and healthy controls. The results of the present study support the psychometric properties of test battery to measure motor control of the craniofacial region when evaluated through videotaping. This test battery could be used to differentiate between healthy subjects and subjects with musculoskeletal impairments in the cervical and oro-facial regions. In addition, this test battery could be used to assess the effectiveness of management strategies in the craniofacial region. [ABSTRACT FROM AUTHOR]

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Objective: The objective of this study was to investigate whether trigeminal somatosensory function and mechanosensitivity differ between groups with craniofacial neuropathic pain (CNP), non-neuropathic craniofacial pain (NNP), and healthy controls (HC)., Methods: Thirty-three participants were categorized into these groups, matched for age and sex. The study evaluated pain intensity, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), and various trigeminal somatosensory tests, including vibration, pressure pain, thermal detection, cold pain, and neurodynamic tests of the trigeminal nerve., Results: Cold pain thresholds differed significantly among the three groups CNP, NNP, and HC ( p  = .047). No difference was found in vibration detection, pressure pain threshold, and thermal detection. Trigeminal nerve mechanosensitivity was significantly different among the three groups ( p  = .03), particularly between groups CNP and HC ( p  = .01)., Conclusion: Differences in aspects of trigeminal somatosensory function, including cold pain and trigeminal mechanosensitivity, exist between subjects with chronic craniofacial pain and HC. This implies that a clinical classification system for neuromusculoskeletal rehabilitation could be valuable in evaluating patients.

Background: Although awake bruxism is associated with temporomandibular disorder (TMD) as well as head and neck pain, the effects of physical therapy and bruxism education to address these factors have not been investigated., Objective: The aim of this study was to evaluate the effects of oro-facial manual therapy and bruxism neuroscience education (BNE) on awake bruxism over a 3-week period with an open-ended follow-up questionnaire after 3 months., Methods: Subjects (n = 28) were randomly allocated to one of two groups, an intervention group and a control group. Data regarding disability, function and pain were collected pre- and post-assessment, with all measures administered in a single-blind fashion. Participants in both groups received six treatment sessions during this period. In addition to manual therapy, participants were provided with information on the neurophysiological mechanisms of bruxism and contributing factors. Individual behavioural guidelines and daily exercises were determined in consultation with the therapist. An introduction to a bruxism specific app (Brux.App) was also provided, which all participants used as an adjunct to their treatment., Results: The intervention group demonstrated notable improvement as indicated by their scores in the Neck Disability Index (NDI) (p = .008), Pain Disability Index (PDI) (p = .007) and Jaw Disability List (JDL) (p = .03). Furthermore, clinical assessments of the temporomandibular joint (TMJ) revealed a significant progress in terms of mouth opening (p = .03) and lateral jaw movement (laterotrusion) (p = .03). The mechanical pain threshold (PTT) of both the masseter (p = .02) and temporalis muscle (p = .05) also showed significant improvement. At 3-month follow-up, the questionnaire revealed that the majority of the intervention group (13/15, 87%) reported a benefit from the treatment., Conclusion: The reduction in pain and disability together with improvement in function and increased coping suggest a potential modification of awake bruxism through specialised musculoskeletal intervention and BNE tailored to the individual patient., (© 2024 The Author(s). Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Abstract: This review presents a comprehensive summary and critical evaluation of intention-to-treat analysis, with a particular focus on its application to randomized controlled trials within the field of rehabilitation. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a methodological review that encompassed electronic and manual search strategies to identify relevant studies. Our selection process involved two independent reviewers who initially screened titles and abstracts and subsequently performed full-text screening based on established eligibility criteria. In addition, we included studies from manual searches that were already cataloged within the first author's personal database. The findings are synthesized through a narrative approach, covering fundamental aspects of intention to treat, including its definition, common misconceptions, advantages, disadvantages, and key recommendations. Notably, the health literature offers a variety of definitions for intention to treat, which can lead to misinterpretations and inappropriate application when analyzing randomized controlled trial results, potentially resulting in misleading findings with significant implications for healthcare decision making. Authors should clearly report the specific intention-to-treat definition used in their analysis, provide details on participant dropouts, and explain upon their approach to managing missing data. Adherence to reporting guidelines, such as the Consolidated Standards of Reporting Trials for randomized controlled trials, is essential to standardize intention-to-treat information, ensuring the delivery of accurate and informative results for healthcare decision making., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cervical manipulations are widely used by physiotherapists, chiropractors, osteopaths, and medical doctors for musculoskeletal dysfunctions like neck pain and cervicogenic headache. The use of cervical manipulation remains controversial, since it is often considered to pose a risk for not only benign adverse events (AEs), such as aggravation of pain or muscle soreness, but also severe AEs such as strokes in the vertebrobasilar or carotid artery following dissections. Studies finding an association between cervical manipulation and serious AEs such as artery dissections are mainly case control studies or case reports. These study designs are not appropriate for investigating incidences and therefore do not imply causal relationships. Randomized controlled trials (RCTs) are considered the gold standard study designs for assessing the unconfounded effects of benefits and harms, such as AEs, associated with therapies., Objective: Due to the unclear risk level of AEs associated with high-velocity, low-amplitude (HVLA) cervical manipulation, the aim of this study was to extract available information from RCTs and thereby synthesize the comparative risk of AEs following cervical manipulation to that of various control interventions., Study Design: Systematic review and meta-analysis., Methods: A systematic literature search was conducted in the PubMed and Cochrane databases. This search included RCTs in which cervical HVLA manipulations were applied and AEs were reported. Two independent reviewers performed the study selection, the methodological quality assessment, and the GRADE approach. Incidence rate ratios (IRR) were calculated. The study quality was assessed by using the risk of bias 2 (RoB-2) tool, and the certainty of evidence was determined by using the GRADE approach., Results: Fourteen articles were included in the systematic review and meta-analysis. The pooled IRR indicates no statistically significant differences between the manipulation and control groups. All the reported AEs were classified as mild, and none of the AEs reported were serious or moderate., Limitations: The search strategy was limited to literature in English or German. Furthermore, selection bias may have occurred, since only PubMed and Cochrane were used as databases, and searching was done by hand. RCTs had to be excluded if the results did not indicate the group in which the AEs occurred. A mandatory criterion for inclusion in the meta-analysis was a quantitative reproduction of the frequencies of AEs that could be attributed to specific interventions., Conclusion: In summary, HVLA manipulation does not impose an increased risk of mild or moderate AEs compared to various control interventions. However, these results must be interpreted with caution, since RCTs are not appropriate for detecting the rare serious AEs. In addition, future RCTs should follow a standardized protocol for reporting AEs in clinical trials.

Purpose: Dysfunctional breathing patterns (DAM) are deviations from physiologic breathing patterns. DAM seem to be associated with lower asthma control. To date, it is unclear what effect inpatient rehabilitation can have on this problem. The aim of this work is to investigate the effect of pulmonary rehabilitation (PR) on DAM., Methods: The data are based on a randomized controlled trial with a waiting control group. The intervention group (IG) received PR 4 weeks after application approval and the control group (KG) after 5 months. Dysfunctional breathing was assessed by Nijmegen-Questionnaire (NQ). Values ≥ 23 points indicate an existing DAM. Values at the end of rehabilitation (T2) and after three months (T3) were compared (analysis of covariance). Supplemental moderator analysis was performed to examine whether the effect of PR was related to baseline NQ scores., Results: Significant differences in NQ score are found between IG (n=202) and KG (n=210) at T2 (AMD=10.5; 95%CI [9; 12]; d=1.4; p<0.001) and at T3 (AMD=5.8; 95%CI [4.3; 7.3]; d=0.8; p<0.001). There is an interaction effect between the difference in NQ score between the groups at T2 and baseline at T0 (b=5.6; 95%CI [2.2; 11.9]; p<0.001). At T3, this interaction effect was no longer detectable (b=4.5; 95%CI [-3.1; 14.1]; p=807)., Conclusion: Inpatient, multimodality, and interdisciplinary PR is associated with significant and clinically relevant improvement in DAM both at discharge and 3 months later. In the short term, patients with existing DAM benefit more from PR than patients without DAM., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Evidence concerning the development of musculoskeletal health complaints (MHCs) among music students is limited due to inappropriate study designs. We aimed to assess the occurrences of MHCs and associated risk factors in freshmen music students compared to students from other disciplines., Methods: A prospective cohort study was conducted. Risk factors such as pain-related, physical, and psychosocial variables were measured at baseline. Episodes of MHCs were recorded monthly., Results: A total of 146 music students and 191 students from other disciplines were analyzed. In the cross-sectional comparison, pain-related, physical, and psychosocial variables were significantly altered in music students compared to students from other disciplines. Furthermore, music students with current MHCs differed significantly from music students without current MHCs with respect to physical health, pain, and history of MHCs. Our longitudinal analysis showed that monthly MHCs were higher in music students compared to students from other disciplines. Independent predictors for monthly MHCs in music students were current MHCs and reduced physical function. Predictors for MHCs in students from other disciplines were a history of MHCs and stress., Conclusions: We provided insight into the development of MHCs and risk factors in music students. This may help in the creation of targeted, evidence-based prevention and rehabilitation.

Abstract: A thorough knowledge of biases in intervention studies and how they influence study results is essential for the practice of evidence-based medicine. The objective of this review was to provide a basic knowledge and understanding of the concept of biases and associated influence of these biases on treatment effects, focusing on the area of rehabilitation research. This article provides a description of selection biases, confounding, and attrition biases. In addition, useful recommendations are provided to identify, avoid, or control these biases when designing and conducting rehabilitation trials. The literature selected for this review was obtained mainly by compiling the information from several reviews looking at biases in rehabilitation. In addition, separate searches by biases and looking at reference lists of selected studies as well as using Scopus forward citation for relevant references were used. If not addressed appropriately, biases related to intervention research are a threat to internal validity and consequently to external validity. By addressing these biases, ensuring appropriate randomization, allocation concealment, appropriate retention techniques to avoid dropouts, appropriate study design and statistical analysis, among others, will generate more accurate treatment effects. Based on their impact on clinical results, a proper understanding of these concepts is central for researchers, rehabilitation clinicians, and other stakeholders working on this field., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recently, Wolf et al. proposed a novel, marker-based method to analyze the three-dimensional upper-body kinematics of high string players for clinical application. The method provides an objective evaluation of high string players' motor strategies, especially in the shoulder complex, by distinguishing between the scapulothoracic (ST) and glenohumeral (GH) joints, while minimizing skin movement artifacts, marker occlusions, and limitations due to instrument placement. Nevertheless, reproducibility of kinematic measurements is crucial for clinical applications. The aim of this study was to assess the method's reproducibility in terms of reliability and repeatability., Methods: One healthy professional violinist underwent a total of nine bowing trials in three different laboratory sessions. Each trial was conducted by one of two different examiners. A biomechanical model was applied to motion capture data of the pelvis, thorax, spine, and head, as well as both upper limbs (consisting of the scapula, upper arm, forearm and hand). Reproducibility was assessed by calculating inter- and intra-tester, inter-session, and intra-subject measurement errors for each rotational degree of freedom in the upper-body segments and joints., Findings: Small measurement errors were accepted to be good indicators for reproducibility. Intra- and inter-tester errors were found to be small (< 3° for the most part). Both inter-session and intra-subject repeatability were found to be larger (< 5° for the most part)., Interpretation: This study generally showed the novel, marker-based method to have good reproducibility for a healthy violinist. This indicates that the proposed method is a reliable tool for quantifying upper-body movements during violin playing across subjects, examiners, laboratories, and motion capture systems.

Abstract: Bias is a systematic error that can cause distorted results leading to incorrect conclusions. Intervention bias (i.e., contamination bias, cointervention bias, compliance bias, and performance bias) and detection bias are the most common biases in rehabilitation research. A better understanding of these biases is essential at all stages of research to enhance the quality of evidence in rehabilitation trials. Therefore, this narrative review aims to provide insights to the readers, clinicians, and researchers about contamination, cointervention, compliance, performance, and detection biases and ways of recognizing and mitigating them. The literature selected for this review was obtained mainly by compiling the information from several reviews looking at biases in rehabilitation. In addition, separate searches by biases and looking at reference lists of selected studies as well as using Scopus forward citation for relevant references were used.This review provides several strategies to guard against the impact of bias on study results. Clinicians, researchers, and other stakeholders are encouraged to apply these recommendations when designing and conducting rehabilitation trials., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Music-related physical and mental health conditions are common among post-secondary music students, with many studies reporting a prevalence greater than 70%. However, there is currently no consensus on appropriate, validated assessments for this population. The aim of this pilot study was to test the feasibility of an assessment protocol developed for a German longitudinal study with Canadian post-secondary music students, and to compare the health of music students to non-music students. Using a cross-sectional design, first-semester music and non-music control students were recruited at two campuses at the same university. Both groups completed questionnaires and physical testing, including range of motion, core strength, and pressure pain threshold. Nineteen music students and 50 non-music student controls participated in this study., Results: The German protocol is feasible in a Canadian post-secondary setting. Canadian music students demonstrated similar health outcomes to those in the parent study. All participants demonstrated poorer mental and physical quality of life than the Canadian norms, though this was not statistically significant. The results of this study should be confirmed in a larger study. Future studies with larger sample sizes can provide further insight into the health of Canadian music students, providing a basis for prevention and intervention., (© 2021. The Author(s).)

Background: The Craniofacial Pain and Disability Inventory (CF-PDI) is a cross-culturally adapted instrument designed from a biopsychosocial perspective to measure pain, disability, and function in orofacial head and neck pain with shown psychometric properties; however, the German cross-cultural adaption is lacking., Objectives: To carry out a transcultural translation of CF-PDI into German and assess its psychometric properties in patients with painful temporomandibular disorders (TMD) with respect to construct and clinical validity, internal consistency and reproducibility., Study Design: Multicenter, prospective, cross-sectional design., Setting: Patients (n = 398) were recruited from dental and physical therapy clinics in middle and south Germany., Methods: Structural validity was assessed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We investigated know-group validity by means of the scale's potential to discriminate between affected and unaffected subjects. Multiple linear regression analysis was used to estimate convergent validity. We tested test-retest reliability by the intraclass correlation coefficient and the Internal consistency by Cronbach's alpha, or each dimension separately, and the total score. Multiple linear regression analysis was used to estimate convergent validity., Results: Two hundred forty-six heterogeneous chronic craniofacial pain patients and 152 patients without complaints were recruited from the middle and south of Germany. The German version CF-PDI-G presents 21 items, 4 factors, and adequate psychometric properties. The test-retest reliability and internal consistency of the CF-PDI-G were both excellent for the entire instrument and also for all sub-scales (intraclass correlation coefficient [ICC] > 0.90) except for the comorbidities and interference with work which was acceptable (ICC = 0.69). Standard error of the measurement (SEM) and minimal detectable change values are sufficiently low. Assessment of clinical validity shows good potential of discrimination and classification into categories "no," "mild," "moderate," and "severe." The multiple linear regression model showed a strong association between neck disability index, Visual Analog Scale, and anamnestic questionnaire (supporting the scale's convergent validity)., Limitations: Our sample has a higher prevalence of women and the sample was not recruited consecutively, which may lead to a biased estimation of psychometric properties., Conclusions: The CF-PDI-G represents valid and reliable instrument to assess pain and disability in patients with orofacial pain and headache suitable for research and clinical practice.

Currently, the treatment of musicians is an interprofessional approach. Playing-related health complaints may impact the performance of a musician. In Germany, a medical consulting hour for musicians exists, but those for athletes in sports medicine are not so common. The diagnosing and treatment procedure within the physiotherapy consultation for musicians follows a specific concept-b and requires knowledge of instruments and musician-specific complaints. Based on the consulting hour in a clinic in Osnabrueck, 614 case reports were part of this sample, of which 558 data sets were complete. The focus of the analysis is the instrument and the primary complaint. Also, the type of therapy is characterized, and the amount is calculated. Primary complaints of musicians, in general, are found most frequently in the spine and upper extremity. Musician complaints are different between instruments. Instrumentalists have a significantly higher chance to suffer from a primary complaint in the area of the upper extremity. Furthermore, the groups without an instrument (e.g., singing or dancing) are developing complaints in the anatomical area which they primarily use. Therefore, these types of therapy were used: physiotherapy, manual therapy, and osteopathy with an average of 5.9 treatment units. This study underpinned the importance of musician-specific physiotherapy as a profession to treat musicians. Also, an interdisciplinary approach is necessary to treat all aspects of complaints., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zalpour, Ballenberger and Avermann.)

Background: The clinical presentation of neck-arm pain is heterogeneous with varying underlying pain types (nociceptive/neuropathic/mixed) and pain mechanisms (peripheral/central sensitization). A mechanism-based clinical framework for spinally referred pain has been proposed, which classifies into (1) somatic pain, (2) neural mechanosensitivity, (3) radicular pain, (4) radiculopathy and mixed pain presentations. This study aims to (i) investigate the application of the clinical framework in patients with neck-arm pain, (ii) determine their somatosensory, clinical and psychosocial profile and (iii) observe their clinical course over time., Method: We describe a study protocol. Patients with unilateral neck-arm pain (n = 180) will undergo a clinical examination, after which they will be classified into subgroups according to the proposed clinical framework. Standardized quantitative sensory testing (QST) measurements will be taken in their main pain area and contralateral side. Participants will have to complete questionnaires to assess function (Neck Disability Index), psychosocial factors (Tampa Scale of Kinesiophobia, Pain Catastrophizing Scale, Depression, anxiety and stress scale), neuropathic pain (Douleur Neuropathique 4 Questions, PainDETECT Questionnaire) and central sensitization features (Central Sensitization Inventory). Follow-ups at three, six and 12 months include the baseline questionnaires. The differences of QST data and questionnaire outcomes between and within groups will be analyzed using (M)AN(C)OVA and/or regression models. Repeated measurement analysis of variance or a linear mixed model will be used to calculate the differences between three, six, and 12 months outcomes. Multiple regression models will be used to analyze potential predictors for the clinical course., Conclusion: The rationale for this study is to assess the usability and utility of the proposed clinical framework as well as to identify possible differing somatosensory and psychosocial phenotypes between the subgroups. This could increase our knowledge of the underlying pain mechanisms. The longitudinal analysis may help to assess possible predictors for pain persistency., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Attrition, missing data, compliance, and related biases can influence the magnitude of treatment effects in randomized controlled trials (RCTs). It is unclear which items should be considered when reporting and evaluating the influence of these biases in trial reports in the rehabilitation field. The aim was to describe which individual items considering attrition, missing data, compliance, and related biases are included in quality tools used in rehabilitation research. In addition, we aimed to determine whether the existing reporting guidelines, such as the CONSORT and its extensions include all relevant items related to these biases when reporting RCTs in the area of rehabilitation., Evidence Acquisition: Comprehensive literature searches and a systematic approach to identify tools and items looking at attrition, missing data, compliance and related biases in rehabilitation were performed. We extracted individual items linked to these biases from all quality tools. We calculated the frequency of quality items used across tools and compared them to those found in the CONSORT statement and its extensions. A list of items to be potentially added to the CONSORT statement was generated., Evidence Synthesis: Three new tools to assess the conduct and reporting of trials in the rehabilitation field were found. From these tools, 28 items were used to evaluate the reporting as well as the conduct of trials considering attrition, missing data, compliance, and related biases in the rehabilitation field. However, our team found that some of these items lack specificity in the information required and therefore more research is needed to determine a core set of items used for reporting as well as assessing the risk of bias (RoB) of RCT in the rehabilitation field., Conclusions: Although many items have been described by existing tools and the CONSORT statement (and its extensions) that deal with attrition, missing data, compliance, and related biases, several gaps in reporting were identified. It is crucial that future research investigate a core set of items to be used in the field of rehabilitation to facilitate the reporting as well as the conduct of RCTs.

Despite normal neurological integrity tests, some patients with non-specific neck-arm pain (NSNAP) have heightened nerve mechanosensitivity upon neurodynamic testing. The aim of this study was to determine whether or not a nerve dysfunction is present in patients with positive neurodynamic tests compared to those with negative neurodynamic tests or healthy controls. Somatosensory profiling using quantitative sensory testing (QST) was established in 40 consecutive patients with unilateral NSNAP; 23 had positive upper limb neurodynamic tests (ULNT POS ) and 17 had negative neurodynamic tests (ULNT NEG ) and in 26 healthy controls. QST included measurement of thermal and mechanical detection and pain thresholds in the maximal pain area on the symptomatic side as well as the corresponding contralateral area. Fifty-seven percent of patients with NSNAP had positive neurodynamic tests. Somatosensory profiling revealed a loss of function phenotype in NSNAP patients compared to healthy controls both in the maximal pain area and asymptomatic side. Hyperalgesia (cold, heat and pressure) was present bilaterally in both NSNAP groups. Direct comparison between the patient groups revealed no significant differences in somatosensory profiles. However, the ULNT POS group demonstrated sensory loss compared to healthy controls in more parameters than the ULNT NEG group. The ULNT NEG subgroup represented an intermediate phenotype between ULNT POS patients and healthy controls in most detection thresholds as well as thermal and pressure pain thresholds. Even though patients with NSNAP present as a spectrum, it remains unclear whether the sensory changes are indicative of a nerve dysfunction/lesion or rather a marker of altered central pain processing., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Attrition, missing data, compliance, and related biases are three interrelated concepts. Previous research has found that these biases can affect the treatment estimates of randomized trials (RCTs). The extent to which the effects of attrition, missing data, compliance and related biases influence effect size estimates in rehabilitation as well as the effect of analytic strategies to mitigate these biases is unknown., Evidence Acquisition: To compile and synthetize the empirical evidence regarding the effects of attrition and compliance related biases on treatment effect estimates in rehabilitation RCTs. Electronic searches were conducted. Studies were included if they investigated the effects of attrition, missing data, compliance and related biases on treatment estimates. The seven studies meeting inclusion criteria were coded for type of biases and summarized using a narrative and/or quantitative approach when appropriate., Evidence Synthesis: Findings demonstrated that trials reporting higher levels of attrition (differences in ES: 0.18 [95%CI: 0.15, 0.22 ]), exclusion of participants from analyses (differences in ES: 0.13 [95% CI: -0.03, 0.29]), lack of good control of incomplete outcome data (differences in ES: 0.14 [95%CI: -0.02, 0.30]) and analysis by "as treated"(differences in ES:-0.39 [95%CI: -0.99, 0.2]) or "per protocol" (differences in ES:-0.46 [95%CI: -0.92, 0]) analyses were more likely to have higher effects than those that did not., Conclusions: These findings suggest that attrition, missing data, compliance, and related biases have an influence in treatment effect estimates in rehabilitation trials. Therefore, these results should be taken into consideration when designing, conducting and reporting trials in the rehabilitation field.

Objective: To identify assessment tools used to evaluate patients with temporomandibular disorders (TMD) considered to be clinically most useful by a panel of international experts in TMD physical therapy (PT)., Methods: A Delphi survey method administered to a panel of international experts in TMD PT was conducted over three rounds from October 2017 to June 2018. The initial contact was made by email. Participation was voluntary. An e-survey, according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES), was posted using SurveyMonkey for each round. Percentages of responses were analysed for each question from each round of the Delphi survey administrations., Results: Twenty-three experts (completion rate: 23/25) completed all three rounds of the survey for three clinical test categories: 1) questionnaires, 2) pain screening tools and 3) physical examination tests. The following was the consensus-based decision regarding the identification of the clinically most useful assessments. (1) Four of 9 questionnaires were identified: Jaw Functional Limitation (JFL-8), Mandibular Function Impairment Questionnaire (MFIQ), Tampa Scale for Kinesiophobia for Temporomandibular disorders (TSK/TMD) and the neck disability index (NDI). (2) Three of 8 identified pain screening tests: visual analog scale (VAS), numeric pain rating scale (NRS) and pain during mandibular movements. (3) Eight of 18 identified physical examination tests: physiological temporomandibular joint (TMJ) movements, trigger point (TrP) palpation of the masticatory muscles, TrP palpation away from the masticatory system, accessory movements, articular palpation, noise detection during movement, manual screening of the cervical spine and the Neck Flexor Muscle Endurance Test., Conclusion: After three rounds in this Delphi survey, the results of the most used assessment tools by TMD PT experts were established. They proved to be founded on test construct, test psychometric properties (reliability/validity) and expert preference for test clusters. A concordance with the screening tools of the diagnostic criteria of TMD consortium was noted. Findings may be used to guide policymaking purposes and future diagnostic research., (© 2020 John Wiley & Sons Ltd.)

Purpose: Bruxism is highly prevalent and defined as abnormal habitual mouth activity including clenching of the teeth and increased jaw muscle activity. The association between bruxism and temporomandibular dysfunction (TMD) is debated, in particular the association between cervical spine impairments, bruxism, and TMD. Hence the purpose of this study was to identify the relationship between bruxism, TMD, and cervical spine impairments., Methods: This observational study categorized 55 female volunteers suitable for evaluation to a bruxism (n = 33) or non-bruxism group (n = 22) based on comprehensive screening using questionnaires and visual observation of the mouth by 2 independent dentists. Following this, both groups were evaluated for TMD, severity and location of head/neck pain, neck disability index (NDI), cervical spine impairments, and tissue mechanosensitivity. Regression analysis was used to evaluate the relationship between bruxism, TMD severity, and cervical impairments., Results: Coefficients of pain and bruxism were significantly associated with NDI scores (0.43, p < 0.001; 3.24, p = 0.01) with large and medium sized effects. As a consequence, both severity of TMD and bruxism status are independently associated with cervical impairments. Having TMD is an independent predictor for head/neck pain and cervical impairments. Pain associated with movement tests and tissue mechanosensitivity was found to be an important factor in bruxism., Conclusion: Clinicians need to be aware that signs of cervical movement impairment are not likely to be associated with bruxism, rather they should focus on improving orofacial function and tissue mechanosensitivity., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Assessment of low back pain (LBP) includes segmental motion tests. Although often used in clinical practice, the validity, inter- and intra-rater reliability of such tests in individuals with LBP are not universally accepted, making it difficult to interpret findings in clinical practice., Objective: The purposes of this study were to determine the validity and reliability of segmental motion tests for patients with LBP and to give reasoned recommendations for their use in practice., Design: Systematic review., Methods: A systematic literature research was conducted of databases PubMed, LIVIVO and Cochrane library. The included studies were appraised for quality by using QUADAS-2 and an adapted version of QAREL tools. Results of studies were appraised to give reasoned recommendations taking quality criteria into account., Results: Thirteen studies were included covering passive accessory intervertebral motion testing (PAIVMs), passive physiological intervertebral motion testing (PPIVMs) and the prone instability test (PIT). The risk of bias of studies ranged from high to low. When used in isolation, specificity of PAIVMS and PPIVMs was generally high and sensitivity poor. Reliability was overwhelming poor for both. Reliability of the PIT was inconsistent. None of these assessments can be strongly recommended when used in isolation., Conclusion: The evidence regarding validity and reliability of segmental motion testing is poor and clinical use of stand-alone tests cannot be recommended. Superiority of the combination of tests as a test battery or with other clinical information needs further investigation., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: High string players (violin and viola) often suffer from musculoskeletal disorders. Although 3D motion analysis has proved helpful in diagnosing different musculoskeletal syndromes and identifying injurious movement patterns in violin and viola performance, more detailed analyses of upper body movement strategies and especially of the shoulder complex have not yet been recorded. The use of spherical surface markers on some anatomical landmarks is, however, inappropriate when an instrument is being played. The aim of this study was to develop and evaluate a novel marker-based method for analyzing upper body kinematics of high string players using conditions specific to violin and viola playing., Methods: A custom upper body marker set was developed and a biomechanical model applied to 3D motion capture data of the pelvis, thorax, spine, head, and both upper limbs (scapula, upper arm, forearm, hand) of 12 professional violinists, to assess its clinical feasibility., Findings: Lumbar and thoracic spine, thorax, neck, and left upper limb were quite static, while extensive motion occurred in the right upper limb. Most rotation angles showed a reasonable intersubject variability except for glenohumeral and wrist joints. Significant differences were observed between G- and D-string bowing, especially in the left wrist and right shoulder joints., Interpretation: This study suggests that the proposed method is a valid tool for quantifying upper body movements in violin and viola performance. With the extended upper body model, it will improve understanding of the motor strategies adopted by high string players and may contribute to injury prevention, diagnosis, and treatment.

Objectives: To develop a time-efficient motor control (MC) test battery while maximising diagnostic accuracy of both a two-level and three-level classification system for patients with non-specific low back pain (LBP)., Design: Case-control study., Setting: Four private physiotherapy practices in northern Germany., Participants: Consecutive males and females presenting to a physiotherapy clinic with non-specific LBP (n=65) were compared with 66 healthy-matched controls., Primary Outcome Measures: Accuracy (sensitivity, specificity, Youden index, positive/negative likelihood ratio, area under the curve (AUC)) of a clinically driven consensus-based test battery including the ideal number of test items as well as threshold values and most accurate items., Results: For both the two and three-level categorisation system, the ideal number of test items was 10. With increasing number of failed tests, the probability of having LBP increases. The overall discrimination potential for the two-level categorisation system of the test is good (AUC=0.85) with an optimal cut-off of three failed tests. The overall discrimination potential of the three-level categorisation system is fair (volume under the surface=0.52). The optimal cut-off for the 10-item test battery for categorisation into none, mild/moderate and severe MC impairment is three and six failed tests, respectively., Conclusion: A 10-item test battery is recommended for both the two-level (impairment or not) and three-level (none, mild, moderate/severe) categorisation of patients with non-specific LBP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction:  There have been controversial discussions in research regarding the mutual relationship between changes in dental occlusion and postural reorganisation. Particularly in professional sports, the application of dental splints has been studied increasingly. However, there is a lack of data regarding the effects of a dental splint on the motor function of the shoulder joint, although overhead athletes often have to deal with long-lasting shoulder problems and their consequences. This study aimed to investigate the influence of a change in dental occlusion by means of a dental splint on the rehabilitation of a glenohumeral internal rotation deficit (GIRD) among volleyball players., Method:  In this study, 22 professional female volleyball players with GIRD and a tROM larger than five degrees were included. Participants were randomised to a splint group (n = 11) and a non-splint group (n = 11). Range of motion and the isometric strength of the dominant shoulder were measured. Shoulder pain and function were investigated by the SPADI assessment, and the functional status of the temporomandibular joints was assessed through the DC/TMD classification. Over a period of eight weeks, both groups received an individual training program. The splint group completed the training program with a dental splint (1-2 mm thick), the non-splint group without a splint., Results:  Range of motion: There are no significant differences between the two groups in the range of motion (internal rotation U = 33 000, p = 0.36; external rotation U = 39 500, p = 0.66; GIRD U = 41 000, p = 0.78; tROM U = 41 000, p = 0.78). At the end of the study, none of the volleyball players in the splint or non-splint group had a GIRD > 20 degrees or a tROM difference > 5 degrees. Shoulder strength: No differences were detected between the two groups in force (internal rotation U = 36 000, p = 0.50; external rotation U = 44 000, p = 0.97; elbow flexion U = 28 000, p = 0.18). Only the force of the shoulder quadrant changed significantly (U = 20 500, p = 0.04). Shoulder pain and function (SPADI): No significant differences were found for the SPADI assessment (U = 31 000; p = 0.28). Functional status of the temporomandibular joint (DC/TMD): The DC/TMD assessments also did not change significantly., Conclusion:  Regarding the secondary hypothesis, a significant change in Q strength was detected. All other parameters (ROM: internal rotation, external rotation, GIRD, tROM; strength: internal rotation, external rotation, elbow flexion; shoulder pain and function: SPADI; TMJ: depression, palpation of masseter muscle and temporalis muscle, TMJ) revealed no significant changes between the two groups. In sum, it can be stated that the use of a dental splint does not significantly influence the rehabilitation of GIRD in volleyball players., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Tests to evaluate the integrity of the alar ligaments are important clinical tools for manual therapists, but there is limited research regarding their validity., Method: A single blinded examiner assessed alar ligament integrity using the lateral shear test (LST), rotation stress test (RST) and side-bending stress test (SBST) on a sample of convenience comprising 7 subjects with MRI confirmed alar ligament lesions and 11 healthy people. Alar ligament lesions were identified using both supine and high-field strength upright MRI., Results: The RST had a sensitivity of 80% and a specificity of 69.2%. The SBST and the LST both showed a sensitivity of 80% and a specificity of 76.9%. In cases where all three tests were positive, the specificity increased to 84.6%., Discussion: Tests of manual examination of alar ligament integrity have some diagnostic utility; however, these findings require further corroboration in a larger sample.

Many musicians suffer from playing-related musculoskeletal disorders (PRMDs) however many of the epidemiological surveys on PRMD do not utilize evaluated self-report instruments, especially as a tool to assess musculoskeletal pain intensity and pain interference in terms of function and psychosocial constructs. The aim of this study was to translate and cross-culturally adapt the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM) into German, and validate it among a population of professional orchestral musicians. The translated and cross-culturally adapted German version of the questionnaire was sent to a total of 367 professional orchestral musicians in Germany who were eligible for the study. Of this total, 124 musicians responded to the questionnaire. The psychometric evaluation showed a clear two dimensionality namely "pain intensity" and "pain interference". Internal consistency was very high for both the "pain intensity" and "pain interference" dimensions as well as for the complete scale. The values for the Intraclass Correlation Coefficient for the test-retest reliability indicated good to excellent repeatability. The subscales of MPIIQM showed strong correlation with the Brief Pain Inventory (BPI) and the shorter version of Disabilities of the Arm, Shoulder and Hand (QuickDash) and low correlation with the Fatigue Severity Scale (FSS). These results were as expected, confirming the good construct validity of the MPIIQM. The German Version of the MPIIQM (MPIIQM-G) and the original version have similarly high qualities and thus the MPIIQM-G represents a useful self-report instrument for the measurement and evaluation of musculoskeletal pain intensity and pain interference for professional orchestral musicians., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: In this prospective longitudinal study, the physical and psychological health status of music students is assessed at the beginning of their university music study and tracked over time. Analysis strategies and interim results from the first-year cohort, including 1-year incidences, monthly prevalences, and predictors of developing musculoskeletal health complaints (MHC), are presented., Methods: This prospective longitudinal study is calculated to enlist a total sample of 370 participants, including musicians and non-musicians, over 5 years. Baseline measurements include a self-designed questionnaire, core strength endurance, hypermobility, finger-floor-distance, motor control, mechanosensitivity, health-related quality of life (SF36), and stress and coping inventory (SCI). The occurrence of MHC is based on monthly online questionnaires., Results: The first-year subcohort enrolled 33 music students and 30 non-music control students. The mean monthly completion rate for the questionnaire was 55.7±8.7%. At baseline, music students showed significantly more stress symptoms, reduced physical function¬ing, and increased bodily pain compared to control students. The 1-year incidence of MHC was 59% for music students and 44% for controls. Risk factors for MHC included being a music student, previous pain, reduced physical functioning, stress symptoms, reduced emotional functioning, and mechanosensitivity. Being a music student, physical functioning, sleep duration, positive thinking, and general mechanosensitivity had a predictive ability of 0.77 (ROC curve) for MHC., Conclusion: A total of 63 students enrolled in the first cohort is in line with the precalculated sample size. This prospective study design enables the measurement of MHC incidence and provides insight into mechanisms in the development of MHC among music students, including the interaction of physical, psychological, and psychosocial factors.

Background: Muscle fatigue seems to be a risk factor in the development of performance-related musculoskeletal disorders (PRMDs) in musicians, but it is unclear how muscle activity characteristics change between musicians with and without PRMDs over a prolonged playing period., Purpose: To investigate muscle activity patterns in muscles of the arms, shoulder, and back of high string musicians during prolonged performance., Methods: Fifteen professional or university high string musicians were divided into PRMD and non-PRMD groups. All musicians played a chromatic scale, then an individual "heavy" piece for 1 hr, and finally the chromatic scale again. Surface electromyography (sEMG) data were recorded from 16 muscles of the arm, shoulder, and trunk on both sides of the body. Two parameters were analyzed: the percentage load in relation to the respective maximum force during the chromatic scale, and the low-frequency spectrum to determine the fatigue behavior of muscles during the 1-hr play., Results: Changes in muscle activation patterns were observed at the beginning and end of the trial duration; however, these varied depending on whether musicians had PRMDs or no PRMDs. In addition, low-frequency spectrum changes were observed after 1 hr of playing in the PRMD musicians, consistent with signs of muscular fatigue., Conclusion: Differences in muscle activity appear between high string musicians with and without PRMDs as well as altered frequency spectrum shifts, suggesting possible differential muscle fatigue effects between the groups. The applied sEMG analysis proved a suitable tool for detailed analysis of muscle activation characteristics over prolonged playing periods for musicians with and without PRMDs.

Objectives: To identify clinical patterns of impairment affecting the cervical spine and masticatory systems in different subcategories of temporomandibular disorder (TMD) by an explorative data-driven approach., Methods: For this observational study, 144 subjects were subdivided according to Research Diagnostic Criteria for TMDs into: Healthy controls, temporomandibular joint (TMJ) signs without symptoms, TMJ affected, temporomandibular muscles affected, or TMJ and muscles affected. Factor analysis and linear regression were applied to cervical spine and masticatory data to identify and characterize clinical patterns in subgroups., Results: Factor analysis identified five clinical dimensions, which explained 59% of all variance: Mechanosensitivity, cervical movement, cervical and masticatory dysfunction, jaw movement, and upper cervical movement. Regression analysis identified different clinical dimensions in each TMD subgroup., Conclusion: Distinct clinical patterns of cervical spine and masticatory function were found among subgroups of TMD, which has clinical implications for therapeutic management.

Background: There is preliminary evidence of cervical musculoskeletal impairment in some temporomandibular disorder (TMD) pain states., Objectives: To determine whether people with TMD, classified as either mild or moderate/severe TMD, have more cervical signs of dysfunction than healthy subjects., Design: Cross-sectional survey., Method: Based on the Conti Amnestic Questionnaire and examination of the temporomandibular joint (Axis I classification of the Research Diagnostic Criteria for TMD), of 144 people examined 59 were classified to a mild TMD group, 40 to a moderate/severe TMD group and 45 to an asymptomatic control group without TMD. Subjects were evaluated for signs of cervical musculoskeletal impairment and disability including the Neck Disability Index, active cervical range of motion, the Flexion-Rotation Test, mechanical pain threshold of the upper trapezius and obliquus capitis inferior muscles, Cranio-Cervical Flexion test and passive accessory movements of the upper 3 cervical vertebrae., Results: According to cervical musculoskeletal dysfunction, the control group without TMD were consistently the least impaired and the group with moderate/severe TMD were the most impaired. These results suggest, that the more dysfunction and pain is identified in the temporomandibular region, the greater levels of dysfunction is observable on a number of cervical musculoskeletal function tests. The pattern of cervical musculoskeletal dysfunction is distinct to other cervical referred pain phenomenon such as cervicogenic headache., Conclusion: These findings provide evidence that TMD in an acute/subacute pain state is strongly related with certain cervical spine musculoskeletal impairments which suggests the cervical spine should be examined in patients with TMD as a potential contributing factor., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Childhood asthma is classified into allergic asthma (AA) and nonallergic asthma (NA), yet both are treated identically, with only partial success., Objective: We sought to identify novel immune phenotypes for childhood AA and NA., Methods: The Clinical Asthma Research Association cohort study includes 275 steroid-naive 4- to 15-year-old German children (healthy control subjects [HCs], patients with AA, and patients with NA). In PBMCs both quantitative and functional analysis of regulatory T (Treg) and TH17 cells (flow cytometry/Treg cell suppression) before/after anti-CD3/CD28, lipid A, and peptidoglycan stimulation were performed. Cytokines and gene expression, as assessed by using Luminex or transcriptomics/quantitative real-time RT-PCR, were analyzed by means of regression analysis. Linear discriminant analysis was applied to discriminate between phenotypes., Results: The 3 phenotypes were immunologically well discriminated by means of microarray and protein analysis with linear discriminant analysis. Patients with AA were characterized by increased Treg cells compared with those in HCs but not those in patients with NA. Treg cells from patients with AA, but not patients with NA, significantly suppressed IL-5, IL-13, and IFN-γ secretion. Patients with AA had decreased expression of chloride intracellular channel 4 (CLIC4) and tuberous sclerosis 1 (TSC1), important innate immunity regulators. Patients with NA were characterized by increased proinflammatory IL-1β levels, neutrophil counts, and IL-17-shifted immunity. In parallel, expressions of anti-inflammatory IL37, proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2), and the neutrophil-associated genes CD93, triggering receptor expressed on myeloid cells 1 (TREM1), and regulator of G-protein signaling 13 (RGS13) were increased in patients with NA. A shared TH2 immunity was present in both asthma phenotypes., Conclusion: Novel immune-regulatory mechanisms in childhood asthma identified increased Treg cells in patients with AA compared with those in HCs but not those in NA and decreased innate immunity genes for patients with AA, the first potentially indicating a counterregulatory mechanism to suppress cytokines yet not sufficient to control allergic inflammation. Very distinctly, patients with NA showed an IL-17-shifted proinflammatory immunity, promoting neutrophil inflammation and less functional Treg cells. Identification of these unique pathways provides a profound basis for future strategies for individualized prediction of asthma development, disease course, and prevention., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by TH1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as TH17 cells, influenced by genetic predisposition., Objective: We examined the role of maternal farm exposure and genetic predisposition on TH17 cell responses to innate and adaptive immune stimulation in cord blood., Methods: Eighty-four pregnant mothers were recruited before delivery. Detailed questionnaires (60 nonfarming mother, 22 farming mothers, and 2 exclusions) assessed farming exposures. Cord blood was stimulated with lipid A, peptidoglycan (Ppg), or PHA. TH17 lineage (retinoic acid receptor-related orphan receptor C [RORC], retinoic acid receptor-related orphan receptor α [RORA], IL-23 receptor [IL23R], IL17, IL17F, and IL22) and Treg cell markers (forkhead box protein 3 [FOXP3], lymphocyte activation gene 3 [LAG3], and glucocorticoid-induced TNF receptor [GITR]) were assessed at the mRNA level. TH17/Treg/TH1/TH2 cytokines and 7 single nucleotide polymorphisms within the TH17 lineage (RORC, IL23R, and IL17) were examined., Results: TH17 lineage mRNA markers were expressed at birth at low concentrations independent of maternal farm exposure. A positive correlation between TH17 lineage markers and FOXP3 (mRNA) was observed on stimulation (nonfarming mothers: lipid A, Ppg, and PHA; farming mothers: Ppg and PHA), influenced by maternal farming. Specific single nucleotide polymorphisms within the TH17 lineage genes influenced gene expression of TH17 and Treg cell markers and cytokine secretion., Conclusions: Gene expression of TH17 lineage markers in cord blood was not influenced by maternal farming. Yet TH17 and Treg cell markers were positively correlated and influenced by maternal farm exposure. Our data suggest that prenatal exposures and genetic predisposition play a role during early TH17 immune maturation, potentially regulating the development of immune-mediated diseases, such as childhood asthma., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objective: The aim of this study was to determine the activity of the masseter and anterior temporalis muscles in relation to different positions of the upper cervical spine during maximal voluntary isometric clenching by surface electromyography (EMG)., Methods: This was a cross-sectional study with a repeated-measures design performed using 25 asymptomatic subjects (13 female and 12 male; mean age, 31 years; SD, 8.51). The EMG activity of the masseter and anterior temporalis muscles was recorded bilaterally during maximal clenching at neutral position and during extension, flexion, ipsilateral lateral flexion, contralateral lateral flexion, and ipsilateral and contralateral rotations in maximal flexion. In addition, the upper cervical range of motion and mandibular excursions were assessed. The EMG activity data were analyzed using a 3-way analysis of variance in which the factors considered were upper cervical position, sex (male and female), and side (right and left), and the hypothesis of importance was the interaction side x position., Results: The 3-way analysis of variance detected statistically significant differences between the several upper cervical positions (F = 13.724; P < .001) but found no significant differences for sex (F = 0.202; P = .658) or side (F = 0.86; P = .53) regarding EMG activity of the masseter muscle. Significant differences were likewise observed for interaction side x position for the masseter muscle (F = 12.726; P < .001). The analysis of the EMG activity of anterior temporalis muscle did not produce statistically significant differences (P > .05)., Conclusion: This preliminary study suggests that the upper cervical movements influence the surface EMG activity of the masseter muscle. These findings support a model in which there are interaction between the craniocervical and the craniomandibular system., (Copyright © 2012 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects., Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding., Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping., Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression., Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets.

Background: TBX21 (T cell specific T-box transcription factor) and HLX1 (H.20-like homeobox 1) are crucial transcription factors of T(H)1-cells, inducing their differentiation and suppressing T(H)2 commitment, particularly important for early life immune development. This study investigated the influence of TBX21 and HLX1 single nucleotide polymorphisms (SNPs), which have previously been shown to be associated with asthma, on T(H)1/T(H)2 lineage cytokines at birth., Methods and Findings: Cord blood mononuclear cells (CBMCs) of 200 neonates were genotyped for two TBX21 and three HLX1 SNPs. CBMCs were stimulated with innate (Lipid A, LpA; Peptidoglycan, Ppg), adaptive stimuli (house dust mite Dermatophagoides pteronyssinus 1, Derp1) or mitogen (phytohemagglutinin, PHA). Cytokines, T-cells and mRNA expression of T(H)1/T(H)2-related genes were assessed. Atopic diseases during the first 3 years of life were assessed by questionnaire answered by the parents. Carriers of TBX21 promoter SNP rs17250932 and HLX1 promoter SNP rs2738751 showed reduced or trendwise reduced (p≤0.07) IL-5, IL-13 and TNF-α secretion after LpA-stimulation. Carriers of HLX1 SNP rs2738751 had lower IL-13 levels following Ppg-stimulation (p = 0.08). Carriers of HLX1 exon 1 SNP rs12141189 showed increased IL-5 (LpA, p = 0.007; Ppg, p = 0.10), trendwise increased IL-13 (LpA), higher GM-CSF (LpA/Ppg, p≤0.05) and trendwise decreased IFN-γ secretion (Derp1+LpA-stimulation, p = 0.1). Homozygous carriers of HLX1 promoter SNP rs3806325 showed increased IL-13 and IL-6 (unstimulated, p≤0.03). In carriers of TBX21 intron 3 SNP rs11079788 no differences in cytokine secretion were observed. mRNA expression of T(H)1/T(H)2-related genes partly correlated with cytokines at protein level. TBX21 SNP rs11079788 carriers developed less symptoms of atopic dermatitis at 3 years of age (p = 0.03)., Conclusions: Polymorphisms in TBX21 and HLX1 influenced primarily IL-5 and IL-13 secretion after LpA-stimulation in cord blood suggesting that genetic variations in the transcription factors essential for the T(H)1-pathway may contribute to modified T(H)2-immune responses already early in life. Further follow-up of the cohort is required to study the polymorphisms' relevance for immune-mediated diseases such as childhood asthma.