[Temporomandibular dysfunction and bruxism in patients with early rheumatoid arthritis and at-risk patients: a cross-sectional study]. / Temporomandibulaire disfunctie en bruxisme bij patiënten met vroege reumatoïde artritis en risicopatiënten: een cross-sectioneel onderzoek.

What is the prevalence of temporomandibular dysfunction in patients with early rheumatoid arthritis and individuals at risk of rheumatoid arthritis? 3 groups (of 50 participants each) were examined for a possible TMD diagnosis: 1. patients with early rheumatoid arthritis, 2. at-risk individuals, and 3. healthy controls. A possible association with bruxism, determined on the basis of self-reporting and clinical features, was also examined. At-risk patients had a higher prevalence of TMD pain diagnoses compared to healthy controls (p = 0.046). Within the early rheumatoid arthritis group, seronegative patients had a higher prevalence of TMD pain diagnoses than seropositive patients (p = 0.048). No further differences in the prevalence of TMD diagnoses were found between the groups. Participants with a TMD pain diagnosis were more often diagnosed with probable sleep bruxism than those without a TMD pain diagnosis. The prevalence of TMD pain is increased in individuals at risk of rheumatoid arthritis and seronegative early rheumatoid arthritis patients, and is associated with signs of bruxism.

Swallowing performance in older adults: Associated cognitive, neuroanatomical and demographic factors.

BACKGROUND: Swallowing problems are frequently seen in older adults, especially in individuals with cognitive impairment (CI). The brain plays a crucial role in both cognition and swallowing. Using magnetic resonance imaging (MRI) data, researchers identified regions associated with swallowing. However, it is not yet fully elucidated which factors influence the swallowing performance in older adults. OBJECTIVES: The current study investigated which factors, such as cognitive function, neuroanatomical factors (e.g., the cortical thickness and volume of specific brain regions) and demographical factors are associated with swallowing performance in older adults. Secondly, it was investigated whether there is a difference in neuroanatomical factors between individuals with and without CI. RESEARCH DESIGN AND METHODS: In total, 15 CI individuals (73.1 ± 9.1 years; 46.7% male) and 48 non-CI controls (69.0 ± 5.1 years; 29.2% male) were included. The repetitive saliva swallowing test (RSST) was performed, and an MRI scan was acquired from the participants. RESULTS: Multivariate linear regression analysis showed that the cortical thickness of the right supramarginal gyrus and female gender were positively associated, and a higher age was negatively associated with the RSST in older adults (p < .05). CI was not significantly associated with swallowing performance. Furthermore, it was found that the cortical volume differs more frequently between CI and non-CI than the cortical thickness. CONCLUSION: A thinner cortex of the right supramarginal gyrus and being an older female are associated with poorer swallowing performance. Secondly, cortical volume was more often found to differ between CI and non-CI individuals than cortical thickness.

Predictors of patients' satisfaction after temporomandibular disorder treatment in a referral clinic.

BACKGROUND: Evaluating patients' satisfaction after received care for temporomandibular disorders (TMD) pain provides oral health care professionals with knowledge and tools to improve their clinical procedures. However, knowledge on patient characteristics that determine satisfaction with the received care for TMD pain is lacking. OBJECTIVE: To identify potential baseline predictors for patients' satisfaction regarding the management of TMD pain upon treatment completion in a referral clinic. METHODS: Eligible patients, viz., individuals of ≥16 years of age, with a TMD-pain diagnosis according the diagnostic criteria for TMD (DC/TMD), and who were treated in a referral clinic, were included. As part of their standard care, a set of diagnostic questionnaires was filled in (e.g. TMD-pain screener, graded chronic pain scale (GCPS), etc.). After completion of the received care, patients filled in a custom-made questionnaire based on patient reported experience measures (PREMs) to quantify their satisfaction with their treatment results and received care. To identify potential predictors associated with patients' satisfaction, univariate and multivariate linear regression analyses were used. RESULTS: Twenty-seven patients (mean 39.6, SD 15.0) were included in this study. Overall, the patients were satisfied with the treatment results and the received care. Depressive feelings were negatively associated with satisfaction of treatment results (p = .01) and positively associated with satisfaction of received care (p = .01), while pain intensity was negatively associated with satisfaction of the received care. CONCLUSION: Depressive feelings are a significant negative predictor of patients' satisfaction with the treatment result for TMD pain, while average pain intensity is a significant negative predictor of patients' satisfaction with the received care.

ASSOCIATIONS BETWEEN SCREENING FOR FUNCTIONAL JAW DISTURBANCES AND PATIENT REPORTED OUTCOMES ON JAW LIMITATIONS AND ORAL BEHAVIORS.

OBJECTIVES: Temporomandibular disorders (TMDs) is a collective term for pain and functional disturbances related to the jaw muscles and the temporomandibular joint. In contrast to screening for orofacial pain, knowledge is limited on the association between patient-reported outcomes and screening for joint-related functional jaw disturbances. Therefore, our aim was to evaluate the association between a screening question for functional jaw disturbances, and disease-specific outcome measures for functional jaw limitations and oral behaviors. METHODS: This study included 299 individuals (201 women; 20-69 years, median 37.0) in a general population sample from Västerbotten, Northern Sweden in 2014. A single screening question for functional jaw disturbances "Does your jaw lock or become stuck once a week or more?" was used to categorize individuals as cases or controls. Patient-reported outcomes on functional jaw disturbances were assessed with the 20-item jaw functional limitation scale (JFLS-20) and oral behaviors with the 21-item Oral Behaviors Checklist (OBC-21). RESULTS: The strongest predictive probability to have a positive screening outcome was functional jaw limitations related to mobility (AUCboot=0.78, 95 CI:0.71-0.86, P < .001), followed by limitations related to communication (AUCboot = 0.74, 95 CI:0.63-0.80, P < .001) and mastication (AUCboot = 0.73, 95 CI:0.66-0.81, P < .001). The frequency of oral behaviors was not significantly associated with a positive screening outcome (AUCboot = 0.65, 95 CI:0.55-0.72, P = .223). CONCLUSIONS: Self-reported functional limitations, but not oral behaviors, are strongly associated with a single screening question for frequent functional jaw disturbances. This finding provides support for incorporating a question on jaw catching/locking once a week or more in screening instruments for TMDs.

The Longitudinal Relationship between Jaw Catching/Locking and Pain.

Orofacial pain and joint-related dysfunction can negatively affect daily jaw function. A common cause for limitations in jaw movements is joint-related dysfunction such as various forms of catching and locking. However, knowledge is limited regarding the development and natural course of joint-related jaw dysfunction and its relationship to the onset and course of orofacial pain. Therefore, the aim was to evaluate the incidence, prevalence, and gender differences in jaw catching/locking over time and in relation to orofacial pain in the general population. Data from 3 validated screening questions on orofacial pain and jaw catching/locking were collected from all routine dental checkups in the Public Dental Health Services in Västerbotten, Sweden, from 2010 to 2017. Logistic generalized estimating equation was used to account for repeated observations and Poisson regression for incidence analysis. In total, 180,308 individuals (aged 5-104 y) were screened in 525,707 dental checkups. In 2010, based on 37,647 individuals, the prevalence of self-reported catching/locking was higher in women than in men (3.2% vs. 1.5%; odds ratio, 2.11; 95% confidence interval [CI], 1.83-2.43), and this relationship and magnitude remained similar throughout the study period. The annual incidence rate was 1.1% in women and 0.5% in men. Women were at a higher risk than men for reporting both first onset (incidence rate ratio [IRR], 2.29; 95% CI, 2.11-2.49) and persistent (IRR, 2.31; 95% CI, 2.04-2.63) catching/locking. For the onset subcohort (n = 135,801), an independent onset of orofacial pain or jaw catching/locking exclusively was reported by 84.1%, whereas a concurrent onset was reported by 13.4%. Our findings of higher incidence, prevalence, and persistence in women than in men indicate that the gender differences seen for orofacial pain are evident also for jaw catching/locking. The findings also suggest independent onset of self-reported catching/locking and orofacial pain, which reinforces the pathophysiological differences between these conditions.

Effects of maxillomandibular advancement on respiratory function and facial aesthetics in obstructive sleep apnoea patients with versus without maxillomandibular deficiency.

The aim of this study was to compare the effects of maxillomandibular advancement (MMA) on respiratory function between obstructive sleep apnoea (OSA) patients with and without maxillomandibular deficiency, and to compare the changes in facial aesthetics after MMA between the two groups. MMA-treated patients who had both baseline and follow-up polysomnography (PSG) data and lateral cephalograms were enrolled in this retrospective study. In addition to PSG and cephalometric data, patient satisfaction with postoperative breathing and facial aesthetics, and overall satisfaction with the treatment were assessed. Twenty-one patients were classified as not having maxillomandibular deficiency (without-deficiency group) and 40 patients as having maxillomandibular deficiency (with-deficiency group). The improvements in respiratory parameters (e.g., apnoea-hypopnoea index) and patient satisfaction with postoperative breathing were comparable in the two groups (P = 0.094-0.713). The changes in facial profile measurements (e.g., nasal prominence, nasolabial angel, and lip positions relative to the true vertical line) and patient satisfaction with postoperative facial aesthetics were also comparable in the two groups (P = 0.148-0.983). In conclusion, no significant difference in the effects of MMA on respiratory function and facial aesthetics between OSA patients with and without maxillomandibular deficiency was observed.

An interim oral appliance as a screening tool during drug-induced sleep endoscopy to predict treatment success with a mandibular advancement device for obstructive sleep apnea.

PURPOSE: Previous studies have shown a wide range of efficacy (29 to 71%) of a mandibular advancement device (MAD) in the treatment of obstructive sleep apnea (OSA). Currently, the ability to preselect suitable patients for MAD therapy based on individual characteristics related to upper airway collapsibility is limited. We investigated if the use of non-custom interim MAD during drug-induced sleep endoscopy (DISE) could be a valuable screening tool to predict MAD treatment outcome. METHODS: In a single-center prospective study including a consecutive series of patients with OSA, we compared DISE outcomes with a MAD in situ with polysomnography results after 3 months of using the same MAD that was used during DISE. RESULTS: Of 41 patients who completed the study, the median apnea-hypopnea index (AHI) was 16.0 events/h [IQR 7.4-23.4]. Respiratory outcomes on polysomnography, including apnea index (AI), total AHI, AHI in supine position, and oxygen desaturation index, all significantly improved after 3 months of MAD treatment. With complete improvement of the upper airway obstruction with the MAD in situ during DISE in supine position, patients were 6.3 times more likely to be a responder to MAD treatment compared to patients with a persisting complete obstruction, although not statistically significant (OR 6.3; 95%CI 0.9-42.7; p = 0.060). CONCLUSION: The potential predictive value with regard to MAD therapy outcomes of the use of an interim MAD during DISE would be an important finding, since the prediction of MAD therapy outcome is of great clinical and scientific interest. A study with a larger cohort should be performed to further investigate our findings.

[A lifetime of proper chewing: oral health and quality of life]. / Een leven lang goed kauwen: mondgezondheid en levenskwaliteit.

Being able to chew properly is crucial to a good quality of life. This, in turn, is based on good oral health. This not only applies to healthy people, but also to those who are vulnerable. To achieve this good oral health, the authors of this opinion paper argue for more integration of medical and dental education, in order to promote shared expertise and, thus, interprofessional collaboration. It is expected this will ultimately benefit both general health and oral health for everyone.

The Global Need for Easy and Valid Assessment Tools for Orofacial Pain.

The World Health Organization recently adopted a historic resolution (WHA74.5) on the urgent need for global oral health improvement. This resolution is particularly relevant in the perspective of the high prevalence of untreated oral diseases. However, one important aspect has been mentioned only in passing, namely that poor oral health often leads to orofacial pain, which is the most common reason for emergency dental visits worldwide. Therefore, an evidence-based decision-making process on oral health should include data related to orofacial pain complaints. To that end, the availability of reliable and valid assessment tools of orofacial pain and related treatment outcomes is essential. INfORM (International Network for Orofacial Pain and Related Disorders Methodology) of the International Association for Dental Research has been one of the driving forces behind the development and implementation of comprehensive sets of tools for such assessments. However, as a prerequisite for the desired global implementation, reliable and valid tools that are also brief, easy to translate, and culturally adaptable need to be further developed and tested. Some of the groundwork to facilitate this process has already been carried out. In addition, a working group within INfORM has developed a short clinical assessment tool for orofacial pain diagnostics that is near completion and will soon be ready for dissemination. Ultimately, reliable and valid orofacial pain assessment is a necessary step toward the development and implementation of appropriate "best buy" interventions that address this major driver of need for oral health care worldwide.

Parkinson's disease, temporomandibular disorder pain and bruxism and its clinical consequences: a protocol of a single-centre observational outpatient study.

INTRODUCTION: A recent questionnaire-based study suggested that bruxism and painful temporomandibular disorders (TMD pain) may be more prevalent in patients with Parkinson's disease (PD) compared with controls. The presence of both bruxism and TMD pain may negatively influence patients' quality of life. The present study is designed to clinically and more objectively investigate the presence of bruxism and TMD pain in patients with PD. The secondary aim of the study is to identify factors associated with bruxism and TMD pain in patients with PD, such as disease severity and dopaminergic medication usage. Furthermore, the presence of tooth wear in patients with PD will be studied as this can be a major consequence of bruxism. Finally, deviations in saliva composition that may contribute to tooth wear will be studied. METHODS AND ANALYSIS: This is a single-centre observational outpatient study at the Amsterdam University Medical Centres, location VUmc. All patients with a clinical diagnosis of PD will be eligible for inclusion. Participants will fill in a set of questionnaires. Subsequently, patients will be examined clinically for, among others, TMD pain, presence and severity of tooth wear, and deviations in saliva composition. Sleep-time registrations will take place for 5 nights with the GrindCare GC4 (ie, a portable, single-channel electromyographic recorder) to assess sleep bruxism and simultaneously by the use of the BruxApp for 5 days to assess awake bruxism. We will partly use data collected during standard clinical care to minimise patient burden. ETHICS AND DISSEMINATION: The scientific and ethical aspects of this study protocol have been approved by the Medical Ethics Review Committee of the Amsterdam UMC, location VUmc; NL. 2019.143. Informed consent will be obtained from all participants. The results will be published in a peer-reviewed journal, if relevant presented at conferences, and published as part of a PhD thesis. TRIAL REGISTRATION NUMBER: NL8307.

[Orofacial pain: a discipline on the brink of a new era]. / Orofaciale pijn: een vakgebied aan de vooravond van een nieuw tijdperk.

The orofacial pain discipline is on the brink of a new era. The introduction of a new definition of pain that, unlike the previous definition, also applies to individuals who cannot verbally express their pain, as well as the publication of the new international classification for orofacial pain, will contribute significantly to the improvement of the quality of the diagnostic process, thus increasing the chance of a successful treatment. Ultimately, the orofacial pain patient will emerge as the winner. The purpose of this article is to introduce the reader to these important recent developments and to provide him/her with an understanding of the implications of these developments for orofacial pain diagnosis and treatment in general and specialized dental practice.

Is dopaminergic medication dose associated with self-reported bruxism in Parkinson's disease? A cross-sectional, questionnaire-based study.

OBJECTIVES: It is not clear whether dopaminergic medication influences bruxism behaviour in patients with Parkinson's disease (PD). Therefore, the aims are to investigate (i) the prevalence of possible (i.e., self-reported) bruxism (sleep and awake) in PD patients, and (ii) whether the use of dopaminergic medication and other factors (viz., demographic characteristics, PD-related factors, and possible consequences of bruxism) are associated with possible bruxism (sleep or awake). MATERIALS AND METHODS: This study concerns a secondary analysis of an earlier published study. Three hundred ninety-five PD patients (67.9 ± 8.6 years of age; 58.7% males) were included. The levodopa equivalent daily dosage (LEDD) was used as a measure of the dopaminergic medication level. Subsequently, a logistic regression analysis was performed for the dependent variables 'awake bruxism' and 'sleep bruxism', with the following predictors: gender, age, LEDD, time since PD diagnosis, temporomandibular disorder (TMD) pain, jaw locks, and tooth wear. RESULTS: The prevalence of possible awake and sleep bruxism was 46.0% and 24.3%, respectively. Awake bruxism was associated with sleep bruxism (OR = 8.52; 95% CI 3.56-20.40), TMD pain (OR = 4.51; 95% CI 2.31-8.79), and tooth wear (OR = 1.87; 95% CI 1.02-3.43). Sleep bruxism was associated with tooth wear (OR = 12.49; 95% CI 4.97-31.38) and awake bruxism (OR = 9.48; 95% CI 4.24-21.19). Dopaminergic medication dose was not associated with awake bruxism (OR = 1.0; 95% CI 0.99-1.00) or sleep bruxism (OR = 1.0; 95% CI 0.99-1.00). CONCLUSION: Bruxism is a common condition in PD patients, but is not associated with the dopaminergic medication dose. CLINICAL RELEVANCE: (Oral) health care providers should be alerted about the possibility of sleep and awake bruxism activity in PD patients, along with this activity's possible negative health outcomes (viz., TMD pain, tooth wear).

[Stress and the orofacial area: stress, painful TMD and oral habits]. / Stress en het orofaciale gebied: stress, TMD-pijn en mondgewoonten.

In the context of the growing knowledge about the influence of psychosocial factors on health, this article focuses on the role of stress in painful temporomandibular disorder and oral habits. Knowledge about the influence of stress on health, oral habits, and painful temporomandibular disorders is summarized, making clear that although knowledge is increasing, there is a lot still unclear. With regards to oral habits, it turns out that awake oral habits are, but oral habits during sleep are not influenced by stress, but better diagnostic procedures and more research distinguishing the different types of oral habits are needed in order to further our understanding. Increasing knowledge about the aetiology of painful temporomandibular disorders is showing a complex interplay of aetiological factors. Stress and oral habits are part of this, but much remains to be discovered about the way in which the aetiological factors interact and influence outcomes. When it comes to stress, especially childhood adversity appears to be a promising focus for further research.

[The objective oral health of Parkinson's disease patients]. / De objectieve mondgezondheid van personen met de ziekte van Parkinson.

In this article, the results of a research project on the objective oral health of Parkinson's disease patients, related to the duration and the progression of the disease, are reported. Participants were 74 patients with Parkinson's disease and 74 control persons. All participants were orally examined. Dentate Parkinson's disease patients had statistically significantly more teeth with carious lesions, more tooth root remnants, and more biofilm and food particles when compared to dentate control persons. Within the group of dentate Parkinson's disease patients, the number of teeth with restorations as well as the number of mobile teeth were positively related to the duration of the disease. Additionally, in this group the number of teeth with carious lesions, the number of teeth with restorations, and the number of tooth root remnants were positively related to the progression of the disease. Parkinson's disease patients need daily oral hygiene care support, particularly in advanced stages of the disease.

Does playing a wind instrument influence tooth position and facial morphology? : Systematic review and meta-analysis.

PURPOSE: To systematically search the scientific literature concerning the influence of playing a wind instrument on tooth position and/or facial morphology. METHODS: The PubMed, EMBASE and Cochrane databases were searched up to September 2019. Orthodontic journals were hand searched and grey literature was sought via Google Scholar. Observational studies and (randomized) controlled clinical trials that assessed tooth position and/or facial morphology by profile cephalograms, dental casts or clinical examination were included. The potential risk of bias was assessed. Data from wind instrument players and controls were extracted. Descriptive analysis and meta-analysis were performed. RESULTS: In total, 10 eligible studies with a cross-sectional (n = 7) or longitudinal design (n = 3) and an estimated low to serious risk of bias were included. Sample sizes ranged from 36 to 170 participants, varying from children to professional musicians. Descriptive analysis indicated that adults playing a single-reed instrument may have a larger overjet than controls. Playing a brass instrument might be associated with an increase in maxillary and mandibular intermolar width among children. Longitudinal data showed less increase in anterior facial height among brass and single-reed players between the age of 6 and 15. Children playing a wind instrument showed thicker lips than controls. Meta-analysis revealed that after a follow-up of 6 months to 3 years, children playing brass instruments had a significant reduction in overjet as compared to controls. The magnitude of the effect was of questionable clinical relevance and the generalizability was limited. CONCLUSIONS: Playing a wind instrument can influence tooth position and facial morphology in both children and adults. Aspects that stand out are overjet, arch width, facial divergence/convergence and lip thickness. However, evidence was sparse and the strength of the premise emerging from this review was graded to be "very low".

Temporomandibular joint function, periodontal health, and oral microbiome in early rheumatoid arthritis and at-risk individuals: a prospective cohort study protocol.

OBJECTIVES/AIMS: Rheumatoid arthritis (RA) is an autoimmune disease affecting the joints, including the temporomandibular joint (TMJ). Early diagnosis and treatment can alleviate symptoms and prevent progression. Predictors for disease outcome in individuals at risk for RA are therefore valuable. While limited information is available on the prevalence of TMJ involvement in early RA, previous studies suggest that RA, periodontitis and the oral microbiome are interrelated. Predictive factors for RA development may thus be present in the oral cavity. Our two aims are: (1) to assess the prevalence of TMJ involvement in early RA, and (2) to investigate the predictive value of oral factors in RA development. MATERIALS AND METHODS: We will include 150 individuals in this multi-center, prospective cohort study: 50 patients with early RA, 50 at-risk individuals, and 50 healthy controls. At baseline, the TMJ, periodontal health, and the oral microbiome will be examined. The general health will be followed over time, on four occasions up to 3 years. DISCUSSION: Our results will provide insight into the prevalence and clinical characterization of TMJ involvement in early RA. For at-risk individuals, oral factors can be studied as possible predictors for the development of RA.

[Dental sleep medicine: A further introduction to an emerging dental discipline]. / Tandheelkundige slaapgeneeskunde: nadere kennismaking met een jong vakgebied.

Dental sleep medicine is a discipline traditionally focusing on sleep-breathing disorders like snoring and obstructive sleep apnea. In everyday clinical practice, however, such disorders rarely occur in isolation. Rather, they frequently co-occur with other sleep disorders linked to dentistry, such as orofacial pain, dry mouth, hypersalivation, gastroesophageal reflux, and sleep bruxism. Therefore, a new definition has been formulated in which dental sleep medicine has been described to include the diagnostic and treatment aspects of all dental sleep disorders. In this article, the reasons why this development was initiated and the current status of dental sleep medicine as a broader discipline are described, along with a brief description of the various dental sleep disorders.

[The subjective oral health of Parkinson's disease patients]. / De subjectieve mondgezondheid van mensen met de ziekte van Parkinson.

This article comprises a report on a research project on the subjective oral health of Parkinson's disease patients, related to the duration and the progression of the disease. Participants were 74 patients with Parkinson's disease and a 74-person control group. All participants were interviewed about educational level, smoking habits, length of time since the last oral health consultation, number of oral health consultations during the previous 5 years, daily oral care, type of toothbrush used, chewing problems, biting problems, loss of taste, burning mouth, xerostomia, halitosis, remaining food particles, painful and bleeding gums, tooth mobility, toothache and tooth sensitivity. More patients with Parkinson's disease than people in the control group reported daily oral care support and had chewing problems, biting problems, loss of taste, tooth mobility and xerostomia. Among the patients with Parkinson's disease, the prevalence of chewing problems was related to the duration as well as the progression of the disease. Furthermore, a relation was demonstrated between the progression of the disease on the one hand and biting problems and daily oral care support on the other.

A stepwise titration protocol for oral appliance therapy in positional obstructive sleep apnea patients: proof of concept.

PURPOSE: In patients with positional obstructive sleep apnea (POSA), oral appliance therapy (OAT) is among the first-line treatments. The aim of this study was to evaluate the effects of a new standardized stepwise titration protocol for OAT in a group of patients with POSA. METHODS: This was an observational intervention trial. Patients who were previously randomized to the OAT intervention arm of a comparison study comprised the subjects for this study. These patients, who had mild to moderate POSA, were assessed after 3 and 12 months for treatment efficacy, objective adherence by temperature microsensor, and side effects. The titration of OAT was performed using a standardized stepwise titration protocol including advancement levels of 60%, 75%, and 90% of the maximum mandibular protrusion. The optimal advancement level per individual was based on a weighted compromise between efficacy and side effects. RESULTS: In total, 36 patients were included and all completed the titration protocol after 3 months. At baseline, the OAT was set at 60% of the maximal mandibular protrusion position. At a 3-month evaluation, the advancement remained at 60% in 16 patients (44%) and reached 75% advancement in 20 patients (56%). Mean apnea-hypopnea index decreased from 12.9 events per hour (9.1-16.7) to 6.9 (3.7-10.3) (P < 0.001), and median objective adherence was 97.4 (61.4-100.00) after 3 months. The 12-month analysis showed consistent results and good OAT tolerance. Six patients (16.7%) terminated OAT and one patient (2.8%) was lost to follow-up. CONCLUSIONS: This standardized stepwise titration protocol for OAT showed good efficacy, good OAT tolerance, and good objective adherence in patients with mild to moderate POSA. Therefore, the protocol is recommended in research projects to improve standardization of methods between studies and in clinical practice for its practical feasibility.