Eribulin in combination with bevacizumab as second-line treatment for HER2-negative metastatic breast cancer progressing after first-line therapy with paclitaxel and bevacizumab: a multicenter, phase II, single arm trial (GIM11-BERGI).

BACKGROUND: We evaluated the efficacy and safety of the nontaxane microtubule dynamics inhibitor eribulin plus the humanized anti-VEGF monoclonal antibody bevacizumab in a novel second-line chemotherapy scheme in HER2-negative metastatic breast cancer (MBC) patients progressing after first-line paclitaxel and bevacizumab. PATIENTS AND METHODS: This is a multicenter, single-arm, Simon's two-stage, phase II study. The primary endpoint was the overall response rate, considered as the sum of partial and complete response based on the best overall response rate (BORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate. RESULTS: A total of 58 of the 61 patients enrolled in the study were evaluable for efficacy. The BORR was 24.6% (95% CI 14.5-37.3). The clinical benefit rate was 32.8% (95% CI 21.3-46.0). The median PFS was 6.2 months (95% CI 4.0-7.8), and median OS was 14.8 months (95% CI 12.6-22.8). Overall, adverse events (AEs) were clinically manageable and the most common AEs were fatigue, paresthesia, and neutropenia. Quality of life was well preserved in most patients. CONCLUSIONS: The results of this study suggest that second-line therapy with bevacizumab in combination with eribulin has a meaningful clinical activity and may represent a potential therapeutic option for patients with HER2-negative MBC.

Biomechanical Effects of Different Auxiliary-Aligner Designs for the Extrusion of an Upper Central Incisor: A Finite Element Analysis.

Aim: To evaluate the biomechanical effects of four different auxiliary-aligner combinations for the extrusion of a maxillary central incisor and to define the most effective design through finite element analysis (FEA). Materials and Methods: A full maxillary arch (14 teeth) was modelled by combining two different imaging techniques: cone beam computed tomography and surface-structured light scan. The appliance and auxiliary element geometries were created by exploiting computer-aided design (CAD) procedures. The reconstructed digital models were imported within the finite element solver (Ansys® 17). For the extrusion movement, the authors compared the aligner without an attachment with three auxiliary-aligner designs: a rectangular palatal attachment, a rectangular buccal attachment, and an ellipsoid buccal attachment. The resulting force-moment (MF) system delivered by the aligner to the target tooth and the tooth displacement were calculated for each scenario. Results: The maximum tooth displacement along the z-axis (0.07 mm) was obtained with the rectangular palatal attachment, while the minimum (0.02 mm) was obtained without any attachments. With the ellipsoid attachment, the highest undesired moments M x and M y were found. The rectangular palatal attachment showed the highest F z (2.0 N) with the lowest undesired forces (F x = 0.4 N; F y = -0.2 N). Conclusions: FEA demonstrated that the rectangular palatal attachment can improve the effectiveness of the appliance for the extrusion of an upper central incisor.

Two repetitive bouts of intense eccentric-concentric jaw exercises reduce experimental muscle pain in healthy subjects.

High-intensity eccentric-concentric contractions of the jaw-closing muscles induce muscle soreness, fatigue and functional impairment of the jaw, resembling the symptoms of myalgia, according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). However, it is claimed that repetition of similar exercises can minimise these detrimental effects. This study aimed to evaluate the response of jaw-closing muscles following two series of intense eccentric-concentric exercises of the masticatory muscles in healthy subjects. Twelve pain-free participants underwent 2 sessions of intense eccentric-concentric jaw exercises, with 1-week interval in between. Each session of jaw exercises comprises 6 sets of 5-minute-long bouts of concentric-eccentric contractions. Self-reported muscle fatigue and pain, maximum mouth opening without pain (MMO), pain pressure thresholds (PPTs) of temporalis and masseter muscles and maximum voluntary bite force (MVBF) were recorded before, immediately after, 24 and 48 hours after each bout of exercises. ANOVA for repeated measurements was used to analyse the data. During session 2, muscle pain and fatigue were statistically significantly decreased (P < .05) as compared to session 1. Furthermore, statistically significant increases of MVBF (P < .005), MMO (P < .005) and PPTs (P < .005) were found at session 2 as compared to session 1. Within the limitations of the study, is can be concluded that the repetition of eccentric-concentric jaw-closing exercises results in signs of muscle training. Future studies can elucidate whether this motor training might be useful for the treatment of myalgia.

Analysis of the reliability of the Italian version of the Oral Behaviours Checklist and the relationship between oral behaviours and trait anxiety in healthy individuals.

BACKGROUND: The Oral Behaviours Checklist (OBC) is a valid 21-item instrument quantifying the self-reported frequency of oral behaviours. An Italian version (OBC-It) has been released recently. Anxiety and oral behaviours are known to be associated in individuals with oro-facial pain due to temporomandibular disorders (TMD). However, information about this relationship in pain-free individuals is still limited. OBJECTIVES: The aim of this study was to test the reliability of the OBC-It and its reduced version (OBC-It 6), focusing on tooth clenching-related wake-time oral behaviours, and the effect of patient instructions on reliability. A second aim was to test the association between trait anxiety and oral behaviours in pain-free individuals. METHODS: Two hundred and eighty-two TMD-free students, divided into 2 groups (Group A, n = 139, mean age ± SD = 22.6 ± 5.4 years; Group B, n = 143, 23.7 ± 4.2 years), filled in the State-Trait Anxiety Inventory and the OBC-It. Group B received instructions about the OBC-It, while Group A did not. After 2 weeks, both groups filled in the OBC-It again. However, Group B was further divided into 2 subgroups, B1 and B2 . The first received the same instructions again, while B2 did not. RESULTS: The test-retest reliability of the OBC-It (A: ICC = .87; B1 : ICC = .94; B2 : ICC = .95) and OBC-It 6 (A: ICC = .85; B1 : ICC = .89; B2 : ICC = .93) was excellent in all groups. Trait anxiety was weakly associated with OBC-It only in women (R2  = .043, P = .021). CONCLUSIONS: The OBC-It is a reliable tool but further subjects' instructions might be needed. Trait anxiety has a limited effect on oral behaviours in TMD-free subjects.

Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2-) advanced breast cancer patients: New insights beyond clinical trials. The EVA study.

BACKGROUND: The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. PATIENTS AND METHODS: This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. RESULTS: From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33-83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1-7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4-58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). CONCLUSIONS: The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

Translation and validation of the italian version of the Psychosocial Impact of Dental Aesthetics Questionnaire (pidaq) among adolescents.

AIM: The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) is a valid tool aiming to evaluate the self-reported influence of dental aesthetics on quality of life. This questionnaire was developed in English for young adults, and later translated and validated with an Italian population. A new version of the questionnaire was recently introduced to be used in adolescents (11-17 years- old), but it had not been translated in Italian yet. Hence, the purpose of this study was to translate, cross-culturally adapt and validate the PIDAQ for adolescents, for its use among Italian subjects. METHODS: To develop the Italian PIDAQ, the original version was translated, back-translated, cross-culturally adapted and pre-tested. Afterwards, the Italian PIDAQ was administered to a convenience sample of 677 subjects, aged 11-17 years, together with two other written questionnaires: the Aesthetic Component of the Index of Orthodontic Treatment Need (IOTN-AC) and the Perception of Occlusion Scale (POS), which are instruments dedicated to assess the self-reported degree of malocclusion. A one-way ANOVA was performed to assess the difference between groups, within each PIDAQ factor, according to POS and IOTN-AC scores. The correlation between PIDAQ factors and POS/IOTN-AC scores was measured as Spearman's rank correlation. The internal consistency was assessed as Cronbach's alpha coef?cient (α), and the test-retest reproducibility as Intra-Class Correlation Coef?cient (ICC). RESULTS: The one-way ANOVA showed that all the factors of the self- reported impact of dental aesthetics on quality of life significantly increased as the degree of malocclusion worsened (P<0.001). Furthermore, all the factors showed statistically significant correlations with both IOTN-AC and POS scores. The α ranged between 0.79 and 0.90, and the ICC ranged between 0.93-0.97. CONCLUSION: The Italian adolescent PIDAQ showed good reliability and validity. The psychometric properties of this version of the questionnaire support its use for the assessment of the psychosocial impact of dental aesthetics among Italian adolescents.

Delayed-onset muscle soreness does not influence occlusal sensitivity and position sense of the mandible.

Masticatory muscle-pain patients often complain about sensorimotor changes, but the effects of pain on the psychophysical properties remain unclear. This study aimed to investigate the effects of delayed-onset muscle soreness (DOMS) on the jaw's position sense (PS) and occlusal sensitivity (OS). In all, 12 participants underwent intense concentric-eccentric jaw exercises. Self-reported muscle fatigue and pain, pain-free maximum mouth opening (MMO), pain pressure thresholds (PPTs) at right and left masseter and right and left anterior temporalis, maximum voluntary bite force (MVBF), PS and OS were recorded before, immediately after, 24 h, 48 h and 1 week after the exercises. Data were analysed with repeated measures anova. Pain and fatigue increased significantly after the exercises, while fatigue also increased 24 h afterwards. Time and site had a significant effect for PPTs, not for MVBF. MMO decreased significantly 24 h after the exercises. OS and PS did not change significantly. Experimentally induced DOMS does not influence the psychophysical properties of the masticatory system.

Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2- breast cancer: results from two prospective trials.

PURPOSE: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response. METHODS: Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed. RESULTS: StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy. CONCLUSIONS: This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.

Influence of culture on pain comorbidity in women with and without temporomandibular disorder-pain.

Evidence on cultural differences in prevalence and impact of common chronic pain conditions, comparing individuals with temporomandibular disorders (TMD) versus individuals without TMD, is limited. The aim was to assess cross-cultural comorbid pain conditions in women with chronic TMD pain. Consecutive women patients (n = 122) with the index condition of chronic TMD pain diagnosed per the research diagnostic criteria for TMD and TMD-free controls (n = 121) matched for age were recruited in Saudi Arabia, Italy and Sweden. Self-report questionnaires assessed back, chest, stomach and head pain for prevalence, pain intensity and interference with daily activities. Logistic regression was used for binary variables, and ancova was used for parametric data analysis, adjusting for age and education. Back pain was the only comorbid condition with a different prevalence across cultures; Swedes reported a lower prevalence compared to Saudis (P < 0·01). Saudis reported higher prevalence of work reduced >50% due to back pain compared to Italians or Swedes (P < 0·01). Headache was the most common comorbid condition in all three cultures. The total number of comorbid conditions did not differ cross-culturally but were reported more by TMD-pain cases than TMD-free controls (P < 0·01). For both back and head pain, higher average pain intensities (P < 0·01) and interference with daily activities (P < 0·01) were reported by TMD-pain cases, compared to TMD-free controls. Among TMD-pain cases, Italians reported the highest pain-related disability (P < 0·01). Culture influences the associated comorbidity of common pain conditions. The cultural influence on pain expression is reflected in different patterns of physical representation.

Effect of weather on temporal pain patterns in patients with temporomandibular disorders and migraine.

Patients with masticatory muscle pain and migraine typically report that the intensity of pain fluctuates over time and is affected by weather changes. Weather variables, such as ambient temperature and humidity, may vary significantly depending on whether the individual is outdoor or indoor. It is, therefore, important to assess these variables at the individual level using portable monitors, during everyday life. This study aimed to determine and compare the temporal patterns of pain in individuals affected with facial and head pain and to investigate its relation with weather changes. Eleven patients (27·3 ± 7·4 years) with chronic masticatory muscle pain (MP) and twenty (33·1 ± 8·7 years) with migraine headache (MH) were asked to report their current pain level on a visual analogue scale (VAS) every hour over fourteen consecutive days. The VAS scores were collected using portable data-loggers, which were also used to record temperature, atmospheric pressure and relative humidity. VAS scores varied markedly over time in both groups. Pain VAS scores fluctuate less in the MP group than in the MH group, but their mean, minimum and maximum values were higher than those of migraine patients (all P < 0·05). Pain scores <2 cm were more common in the MH than in the MP group (P < 0·001). Perceived intensity of pain was negatively associated with atmospheric pressure in the MP group and positively associated with temperature and atmospheric in the MH group. Our results reveal that patients with masticatory muscle pain and patients with migraine present typical temporal pain patterns that are influenced in a different way by weather changes.

Skeletal and dental effects of Class III orthopaedic treatment: a systematic review and meta-analysis.

To summarise the skeletal, dental and soft tissue effects of orthopaedic treatment on growing skeletal class III patients compared with a concurrent untreated similar control group and to evaluate whether the design of the primary studies may affect the results. A literature search was performed up to the end of February 2016. No restrictions were applied concerning language and appliances. Once the quality score was assessed, a meta-analysis was performed for the appliances used in more than three studies. A moderator analysis for study design was performed. The level of evidence was evaluated by means of the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool. The search resulted in 21 papers. The quality of most of the studies was medium. Each study reported skeletal sagittal improvement and overjet correction. Fourteen studies reported a significant increase in lower facial height. Follow-up data showed slight relapses in about 15% of patients. Meta-analyses were performed for the facemask and chin cup. The two appliances were efficient for correcting the sagittal discrepancy, increasing the divergence. In the analysis for study design, the retrospective studies showed a more efficient appliance than RCTs for 6 of 13 variables. The level of evidence was between very low and moderate. There is very low to low evidence that orthopaedic treatment is effective in the correction of Class III skeletal discrepancies and moderate evidence for the correction of the overjet. A common side effect is mandibular clockwise rotation in older subjects.

Self-management programmes in temporomandibular disorders: results from an international Delphi process.

Self-management (SM) programmes are commonly used for initial treatment of patients with temporomandibular disorders (TMD). The programmes described in the literature, however, vary widely with no consistency in terminology used, components of care or their definitions. The aims of this study were therefore to construct an operationalised definition of self-management appropriate for the treatment of patients with TMD, identify the components of that self-management currently being used and create sufficiently clear and non-overlapping standardised definitions for each of those components. A four-round Delphi process with eleven international experts in the field of TMD was conducted to achieve these aims. In the first round, the participants agreed upon six principal concepts of self-management. In the remaining three rounds, consensus was achieved upon the definition and the six components of self-management. The main components identified and agreed upon by the participants to constitute the core of a SM programme for TMD were as follows: education; jaw exercises; massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. This Delphi process has established the principal concepts of self-management, and a standardised definition has been agreed with the following components for use in clinical practice: education; self-exercise; self-massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. The consensus-derived concepts, definitions and components of SM offer a starting point for further research to advance the evidence base for, and clinical utility of, TMD SM.

Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET).

BACKGROUND: This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2. PATIENTS AND METHODS: Post-menopausal women aged ≥18 years with hormone receptor-positive, human epidermal growth factor-receptor-2-negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity. RESULTS: The median treatment duration was 5.1 months [95% confidence interval (CI) 4.8-5.6] for EVE and 5.3 months (95% CI 4.8-5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related. CONCLUSIONS: This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2012-000073-23.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Dental and skeletal effects of palatal expansion techniques: a systematic review of the current evidence from systematic reviews and meta-analyses.

The aim was to assess the quality and to summarise the findings of the Systematic Reviews (SRs) and Meta-Analyses (MAs) on the dental and skeletal effects of maxillary expansion. Electronic and manual searches have been independently conducted by two investigators, up to February 2015. SRs and MAs on the dentoalveolar and skeletal effects of fixed expanders were included. The methodological quality was assessed using the AMSTAR (A Measurement Tool to Assess Systematic Reviews). The design of the primary studies included in each SR/MA was assessed with the LRD (Level of Research Design scoring). The evidence for each outcome was rated applying a pre-determined scale. Twelve SRs/MAs were included. The AMSTAR scores ranged from 4 to 10. Two SRs/MAs included only RCTs. The current findings from SRs/MAs support with high evidence a significant increase in the short-term of maxillary dentoalveolar transversal dimensions after Rapid Maxillary Expansion (RME). The same effect is reported with moderate evidence after Slow Maxillary Expansion (SME). However, there is moderate evidence of a non-significant difference between the two expansion modalities concerning the short-term dentoalveolar effects. With both RME and SME, significant increase of skeletal transversal dimension in the short-term is reported, and the skeletal expansion is always smaller than the dentoalveolar. Even though dental relapse to some extent is present, long-term results of the dentoalveolar effects show an increase of the transversal dimension, supported by moderate evidence for RME and low evidence for SME. Skeletal long-term effects are reported only with RME, supported by very low evidence.

Incidence of temporomandibular joint clicking in adolescents with and without unilateral posterior cross-bite: a 10-year follow-up study.

Among different malocclusions, posterior cross-bite is thought to have a strong impact on the correct functioning of the masticatory system. The association between unilateral posterior cross-bite (UPCB) and temporomandibular joint (TMJ) clicking, however, remains still controversial. The aim of this study was to investigate whether the presence of UCPB during early adolescence increases the risk of reporting TMJ clicking after a long-term follow-up. A longitudinal survey design was carried out in a group of 12-year-old young adolescents, who were examined at baseline for TMJ clicking sounds and unilateral posterior cross-bite. After 10 years, 519 subjects could be reached by a telephone survey. Standardised questions were used to collect self-reported TMJ sounds and to determine whether participants had received an orthodontic treatment. Logistic regression analysis revealed a significant association between unilateral posterior cross-bite and subjectively reported TMJ clicking (odds ratio = 6·0; 95% confidence limits = 3·4-10·8; P < 0·0001). The incidence of TMJ clicking was 12%. At a ten-year follow-up, self-reports of TMJ clicking were significantly associated with the presence of UPCB at baseline, but not with the report of having received an orthodontic treatment. Within the limitation of this study, the presence of unilateral posterior cross-bite in young adolescents may increase the risk of reporting TMJ sounds at a 10-year follow-up. The provision of an orthodontic treatment, however, does not appear to reduce the risk of reporting TMJ sounds.

The effect of culture on pain sensitivity.

Cross-cultural differences in pain sensitivity have been identified in pain-free subjects as well as in chronic pain patients. The aim was to assess the impact of culture on psychophysical measures using mechanical and electrical stimuli in patients with temporomandibular disorder (TMD) pain and pain-free matched controls in three cultures. This case-control study compared 122 female cases of chronic TMD pain (39 Saudis, 41 Swedes and 42 Italians) with equal numbers of age- and gender-matched TMD-free controls. Pressure pain threshold (PPT) and tolerance (PPTo) were measured over one hand and two masticatory muscles. Electrical perception threshold and electrical pain threshold (EPT) and tolerance (EPTo) were recorded between the thumb and index fingers. Italian females reported significantly lower PPT in the masseter muscle than other cultures (P < 0.001) and in the temporalis muscle than Saudis (P = 0.003). Swedes reported significantly higher PPT in the thenar muscle than other cultures (P = 0.017). Italians reported significantly lower PPTo in all muscles than Swedes (P ≤ 0.006) and in the masseter muscle than Saudis (P < 0.001). Italians reported significantly lower EPTo than other cultures (P = 0.01). Temporomandibular disorder cases, compared to TMD-free controls, reported lower PPT and PPTo in all the three muscles (P < 0.001). This study found cultural differences between groups in the PPT, PPTo and EPTo. Overall, Italian females reported the highest sensitivity to both mechanical and electrical stimulation, while Swedes reported the lowest sensitivity. Mechanical pain thresholds differed more across cultures than did electrical pain thresholds. Cultural factors may influence response to type of pain test.