Inter- and intra-rater-reliability of a clinical framework for spine-related neck-arm pain.

OBJECTIVE: A mechanism-based clinical framework for spine-related pain differentiates (i) somatic referred pain, ii) heightened nerve mechanosensitivity, iii) radicular pain, iv) radiculopathy and mixed-pain. This study aimed to determine the reliability of proposed framework. METHOD: Fifty-one people with unilateral spine-related neck-arm pain were assessed and categorized by examiner-1. The classifications were compared to those made by two other examiners, based on written documentation of examiner-1. Cohens kappa was calculated between examiner-pairs; Fleiss Kappa among all examiners to assess agreement in classifying subgroups and entire framework. RESULT: Inter-rater-reliability showed moderate to almost perfect reliability (somatic: no variation, mechanosensitivity: 0.96 (95% CI 0.87-1.0) to 1.0 (95% CI: 1.0-1.0), radicular pain: 0.46 (95% CI: 0.19-0.69) to 0.62 (95% CI: 0.42-0.81), radiculopathy: 0.65 (95% CI: 0.43-0.84) to 0.80 (95% CI: 0.63-0.96) mixed-pain: 0.54 (95% CI: 0.21-0.81) to 0.75 (95% CI: 0.48-0.94). There was almost perfect to moderate reliability among all examiners (somatic: no variation, mechanosensitivity: 0.97 (95% CI: 0.82-1.0), radicular pain: 0.56 (95% CI: 0.40-0.71), radiculopathy: 0.74 (95% CI: 0.58-0.90), mixed-pain: 0.63 (95% CI: 0.47-0.79), entire framework: 0.64 (95% CI: 0.57-0.71)). Intra-rater-reliability showed substantial to almost perfect reliability (somatic: no variation, mechanosensitivity: 0.96 (95% CI: 0.87-1.0), radicular pain: 0.76 (95% CI: 0.57-0.92), radiculopathy: 0.84 (95% CI: 0.67-0.96), mixed-pain: 0.83 (95% CI: 0.60-1.0), entire framework: 0.80 (95% CI: 0.61-0.92). CONCLUSION: Moderate to almost perfect reliability in subgrouping people with spine-related neck-arm pain and substantial reliability for entire framework support this classification's reliability.

Psychometric evaluation of a motor control test battery of the craniofacial region.

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.

Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based sensitization pattern.

BACKGROUND: Increased serum IgE levels are characteristic but not specific for allergic diseases. Particularly, severe atopic dermatitis (AD) overlaps with hyper-IgE syndromes (HIES) regarding eczema, eosinophilia, and increased serum IgE levels. HIES are primary immunodeficiencies due to monogenetic defects such as in the genes DOCK8 and STAT3. As it is not known to date why allergic manifestations are not present in all HIES entities, we assessed the specificity of serum IgE of AD and HIES patients in the context of clinical and immunological findings. METHODS: Clinical data, skin prick tests, specific IgE to aero- and food allergens, and T helper (Th) subpopulations were compared in AD and molecularly defined HIES patients. RESULTS: Total serum IgE levels were similarly increased in STAT3-HIES, DOCK8-HIES, and AD patients. The ratio of aeroallergen-specific IgE to total IgE was highest in AD, whereas DOCK8-HIES patients showed the highest specific serum IgE against food allergens. Overall, clinical allergy and skin prick test results complied with the specific IgE results. Th2-cell numbers were significantly increased in DOCK8-HIES and AD patients compared to STAT3-HIES patients and controls. AD patients showed significantly higher nTreg-cell counts compared to STAT3-HIES and control individuals. High Th17-cell counts were associated with asthma. Specific IgE values, skin prick test, and T-cell subsets of STAT3-HIES patients were comparable with those of healthy individuals except decreased Th17-cell counts. CONCLUSION: Hyper-IgE syndromes and atopic dermatitis patients showed different sensitization pattern of serum IgE corresponding to the allergic disease manifestations and Th-cell subset data, suggesting a key role of DOCK8 in the development of food allergy.

STAT6 polymorphisms are associated with neonatal regulatory T cells and cytokines and atopic diseases at 3 years.

BACKGROUND: The transcription factor STAT6 is crucial for activation of the interleukin (IL)-4/IL-13 pathway and has been linked to regulatory T cells (Tregs). Associations of STAT6 polymorphisms with IgE levels were described; however, their impact on neonatal immune responses and early disease development is unknown. METHODS: STAT6 polymorphisms were genotyped in cord blood mononuclear cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene expression was assessed by real-time polymerase chain reaction (PCR) and cytokines by Multiplex. At age 3 years, atopic diseases were assessed by questionnaires. RESULTS: STAT6 rs324011 but not rs1059513 polymorphism was associated with significant or borderline significant decreased mRNA expression of Treg-associated genes (FOXP3, GITR, LAG3). Heterozygotes and minor allele homozygotes of rs324011 had low levels of tumor necrosis factor alpha (TNF-α) and increased interferon gamma (IFN-γ) (P ≤ 0.04), while heterozygotes and minor allele homozygotes of rs1059513 had increased TNF-α and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (P ≤ 0.05). In minor allele homozygotes of rs324011, expression of Treg-associated genes was strongly inverse correlated with IFN-γ (unstimulated, r = -0.7, P = 0.111; LpA stimulation, r = -0.8, P = 0.011), but not in heterozygotes or major allele homozygotes. Heterozygotes and minor allele homozygotes of rs324011 presented a lower risk of atopic dermatitis and obstructive bronchitis until age 3 years. CONCLUSIONS: Two STAT6 polymorphisms were associated with altered immune responses already at birth. STAT6 rs324011 was associated with lower neonatal Treg and increased Th1 response. Those neonates had a lower risk of atopic dermatitis and obstructive bronchitis until 3 years. Our data suggest a role for STAT6 polymorphisms in early immune regulation and implications on early atopic disease development.