Climatic sensitivity of migraine: a 14-year time series analysis of primary care consultations in Spain Juan Nicolás Cuenca-Zaldívar Journal of Oral and Facial Pain and Headache, 2026 Background: Climatic variability has been proposed as a trigger for migraine; however, evidence from long-term primary care datasets remains scarce. Understanding how atmospheric conditions influence healthcare utilization may improve migraine prediction and management. This study aimed to analyze the association between climatic variables and weekly migraine consultations over a 14-year period in Spanish primary care and to identify the most accurate predictive time-series model. Methods: Weekly migraine consultations from 2010 to 2023 were extracted from electronic medical records using the International Classification of Primary Care, Second Edition (ICPC-2) code N89.01. Meteorological variables—temperature, diurnal variability, day-to-day change, wind direction and speed, barometric pressure, and sunshine hours—were obtained from the Spanish State Meteorological Agency (AEMET). Time-series analyses used exponential smoothing state-space models with external regressors (ETSX) and AutoRegressive Integrated Moving Average models with eXogenous regressors (ARIMAX). Model performance was assessed using Root Mean Squared Error (RMSE), Symmetric Mean Absolute Percentage Error (SMAPE), and Mean Absolute Scaled Error (MASE). Results: A total of 3176 migraine consultations were identified (mean age 47.6 ± 15.3 years; 81.7% female). The ARIMAX model showed the best predictive performance (RMSE = 3.485, SMAPE = 73.840, MASE = 0.875). Stationarity was confirmed using the Augmented Dickey–Fuller test (p = 0.01), and residuals showed no autocorrelation (Ljung–Box test, p = 0.833). After multivariable adjustment, female sex was the only variable independently associated with weekly migraine consultations; temperature, barometric pressure, diurnal variability, and wind speed showed no independent effects. Forecasting indicated a stable trend over the subsequent four years. Conclusions: This long-term time-series analysis showed that female sex was the only variable independently associated with weekly migraine consultations in primary care. Although most atmospheric indicators did not retain significance, climate-informed ARIMAX modeling improved prediction accuracy and may support personalized, weather-adapted preventive strategies.
Botulinum toxin effects on biochemical biomarkers related to inflammation-associated head and neck chronic conditions: a systematic review of clinical research Ines Novo Pereira, Sara Durão, Haidar Hassan, Ana Cristina Braga, André Mariz Almeida, et al. Journal of Neural Transmission, 2025 Botulinum toxin type A (BoNT) has emerged as a potential alternative to conventional therapies to many debilitating chronic diseases characterised by inflammatory states. However, the biological rationale remains ambiguous. Our review aimed to systematically assessed which biochemical biomarkers have been reported in clinical research to evaluate BoNT analgesic and mood-lifting effects in head and neck chronic conditions related to inflammation. We searched databases and registries between inception and September 29, 2023. Of the nine included studies, there were concerns about risk of bias for six studies. The leading biomarker with five studies was the calcitonin gene-related peptide (CGRP), followed by serotonin with two studies. Oxidative stress biomarkers were only reported in one study. Several important players in inflammatory processes and different immune cell classes have been evaluated in four studies. There was only one trial measuring changes in beta Tubulin and SNAP-25, and another study evaluating cutaneous neuropeptide substance-P. After BoNT, a significant effect was reported in six studies, including decrease in plasma levels of CGRP in chronic migraine and trigeminal neuralgia; serotonin decrease when collected from human tears in refractory intractable dry eye disease and increase in peripheral blood platelets in painful cervical dystonia associated to depression and anxiety; decrease in plasma concentration of markers of oxidative damage to proteins and increase in biomarkers for antioxidant power; decrease in expression of gene sets involved in inflammatory pathways and immune cells classes in the periosteum and metalloproteinase-9 molecule in the tears. BoNT seems to affect some biomarkers present in chronic inflammatory conditions. However, the certainty evidence found was very low to moderate. This study is registered on PROSPERO (CRD42023432131).
Evaluating online information on temporomandibular disorders: readability, reliability, content and quality: a scoping review protocol Carolina Venda Nova, Jessica Silva, Natacha Faustino, Juan Nicolás Cuenca-Zaldívar, Nina Cadeau Comte, et al. BMJ Open, 2025 Introduction Temporomandibular disorders (TMDs) are a prevalent group of musculoskeletal conditions affecting the temporomandibular joint, associated structures and masticatory muscles. The internet has become a primary source of health information for many patients; however, the readability, reliability, content and quality of online information on TMDs vary widely. A comprehensive synthesis of the characteristics and evaluation methods of such content is currently lacking. Methods and analysis This scoping review will follow the Joanna Briggs Institute methodology and be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Peer-reviewed primary and secondary studies assessing online information on TMDs will be included if they report on readability, reliability, content or quality. Eligible information sources include publicly available websites, videos and social media; discussion forums and printed materials will be excluded. No language, date or geographical restrictions will be applied. A three-step search strategy will be implemented across PubMed, Web of Science, Embase, PsycINFO and CINAHL, followed by citation tracking. Screening will be conducted independently by two reviewers using Rayyan. Data will be extracted with a pilot-tested charting tool and synthesised narratively and descriptively in tabular and graphical formats. Ethics and dissemination As this study will only use data from publicly available sources, ethical approval is not required. Findings will be disseminated through publication in a peer-reviewed journal, conference presentations and professional networks, with the aim of guiding the development of accessible and reliable digital resources for individuals seeking information on TMDs. Registration This protocol has been prospectively registered on the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/TAH7K .
Botulinum Toxin Effects on Biochemical Biomarkers Related to Inflammation-Associated Head and Neck Chronic Conditions: A Systematic Review of Preclinical Research Ines Novo Pereira, Giancarlo De la Torre Canales, Sara Durão, Rawand Shado, Ana Cristina Braga, et al. Toxins, 2025 Current research reported that the number of clinical studies found for botulinum toxin (BoNT) key effects on biochemical biomarkers in head and neck chronic conditions linked to inflammation was very low. There are no systematic reviews of animal studies on this topic, and hence our review aimed to evaluate the quality of the preclinical evidence. We searched PubMed, Scopus, and Web of Science databases, and registries up to 29 January 2024. There were 22 eligible records, and data were available for 11 randomised controlled trials. There were concerns about the risk of bias and great variations of data obtained regarding chronic conditions, which included mostly trigeminal neuralgia. The leading biomarkers were proinflammatory cytokines (IL-1β, TNF-α) and synaptosomal-associated protein-25 (SNAP25), followed by neuron activation marker c-Fos and calcitonin gene-related peptide (CGRP). Overall, data found that BoNT significantly altered the under/over-expression of biomarkers evoked by the investigated disease models and had no effect when the levels of these biomarkers were not changed by the induced chronic conditions in animals. However, there were some mixed results and exceptions, and the certainty evidence found was very low to low. Although the sample sizes detected significant effect size (p < 0.05), most studies are based on male inferior animals, which may limit the recommendations for clinical trials. This study is registered on PROSPERO (CRD42023432411).
Efficacy of botulinum toxin type A in myogenic temporomandibulardisorders: a single arm, prospective, pilot study Bruno Macedo de Sousa, Nansi López-Valverde, Carolina Ferreira, André Mariz de Almeida, Antonio López-Valverde, et al. Frontiers in Rehabilitation Sciences, 2025 Background Myogenous temporomandibular disorders (TMDs) is commonly associated with myofascial pain and functional limitations. Botulinum toxin type A (BoNT-A) has shown potential in relieving chronic muscular pain. Methods In this single arm, prospective, pilot study, 25 patients diagnosed with myofascial TMDs received a single bilateral intramuscular injection of 50 units of BoNT-A. Assessments using the Visual Analog Scale (VAS), Chronic Pain Index (CPI), Jaw Functional Limitation Scale (JFLS-8), and Oral Health Impact Profile (OHIP-14) were performed at baseline, 6 weeks, and 12 weeks post-treatment. Results Significant reductions in pain (VAS: 6.84 ± 1.03 to 0.84 ± 0.94) and CPI (61.87 ± 8.12 to 9.86 ± 4.46) were observed. Functional improvement (JFLS-8: 5.82 ± 0.56 to 1.08 ± 0.51) and enhanced quality of life (OHIP-14: 24.56 ± 8.39 to 5.96 ± 2.79) were also significant. No adverse effects were reported. Conclusions BoNT-A showed promising results in reducing pain and improving function in patients with myofascial pain in Temporomandibular Disorders (M-TMDs). However, the single-arm design, small sample size, and short follow-up limit causal inference and external validity. These findings should be interpreted as preliminary. Clinical Trial Registration : Clinicaltrials.gov , identifier NCT05651256.
Temporalis Muscle Changes Following Botulinum Toxin A Injections in Masseter Hypertrophy Patients: A Randomized Triple-Blinded Trial Bryanne B. de Souza Nobre, Luciana de Oliveira Resende Machado, Rodrigo Lorenzi Poluha, Mariana Barbosa Câmara-Souza, Ana Claudia Carbone, et al. Aesthetic Plastic Surgery, 2024 Background This study aimed to elucidate the effects of botulinum toxin A (BoNT-A) treatment for patients diagnosed with masseter hypertrophy on the temporalis muscle, with a particular focus on assessing alterations in muscle thickness, electromyographic (EMG) activity, and the development of muscle pain. Methods The present randomized triple-blinded clinical trial enrolled 26 female participants aged between 25 and 50 years complaining about masseter hypertrophy. Participants received 75U of BoNT-A (abobotulinumtoxinA) in both masseter muscles and after three months were randomized to receive a second treatment session of saline solution (S-BoNT-A) or BoNT-A (M-BoNT-A). Longitudinal assessments included temporalis muscle thickness through ultrasound, EMG activity, subjective pain, and masseter prominence severity after one, three, and six months of the first injection session. Muscle thickness, EMG, and subjective pain were analysed using two-way ANOVA with repeated measures and post hoc Sidak test, and for masseter prominence severity, Friedman and Mann–Whitney tests were used. Results Regarding inter-group comparisons, a higher muscle thickness (p < 0.02) and a higher EMG activity (p < 0.01) were found in the M-BoNT-A group at the 6-month follow-up. For subjective pain assessments, inter-group comparisons showed a higher prevalence of painful regions in M-BoNT-A group at the 6-month follow-up (p < 0.02). No significant differences were found in masseter prominence severity at the 6 months assessment between groups. Conclusion BoNT-A treatment for masseter hypertrophy lead to structural and functional changes in the temporalis muscle, presenting higher changes after multiple injections of this treatment. Level of Evidence I This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Do sociodemographic factors influence the levels of health and oral literacy? A cross-sectional study Francisco Manuel Veigas Veladas, Giancarlo De la Torre Canales, Bryanne Brissian de Souza Nobre, Ana Escoval, Ana Rita Pedro, et al. BMC Public Health, 2023 Background Oral health literacy has gained importance in dental literature, and its relationship with oral health status and association with health status (HL) has been reported. Then, an association between the levels of HL and OHL could be expected. This study aimed to assess the levels of HL and OHL according to sociodemographic factors and to explore a possible association between HL and OHL. Methods The European Health Literacy Survey and Oral Health Literacy Adults Questionnaire were applied to a convenience sample from Portuguese individuals. Also, sociodemographic factors such as sex, age, schooling level of the participants and their parents, and if the participants were professionals or students of the health field were assessed. To analyze the data, the Kruskal–Wallis and Mann–Whitney U tests were used to compared sociodemographic variables and the levels of literacy in general and oral health. The Spearman correlation test assessed the correlation between the levels of HL and OHL. Results HL results showed that 45.1% of the volunteers were considered in a “problematic level” and 10.3% in “excellent level”. However, 75% presented an adequate level of OHL. Regarding the levels of HL in each sociodemographic variable, significant higher levels of “excellent level” were found in health professionals and students when compared with participants not related to health area (p < 0.001). Comparisons between the levels of OHL in each sociodemographic variable showed, significant differences regarding sex (p < 0.05), age (p < 0.001), levels of schooling of the participants and their parents (p < 0.009 and p < 0.001) and relationship with health field. (p < 0.001). A significant positive – weak correlation was found between HL and OHL (p < 0.001). Conclusions HL and OHL levels are associated and could be influenced by sociodemographic factors.
