2023 Brazilian Society of Rheumatology guidelines for the treatment of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

Dental age estimation: development and testing of a reference data set for Qatari children, adolescents, and young adults aged between 5 and 25 years.

The purpose of this study is to establish and test a reference data set of dental development of Qatari subjects aged between 5 and 25 years. Radiographs of individuals aged between 5 and 25 years were re-used to establish a reference data set (RDS). A scheme comprising 8 tooth development stages (TDS) was used to assess all the teeth on the left side of the maxilla and mandible. The accuracy of dental age estimation (DAE) was tested with a separate sample of radiographs - the validation sample (VS) comprised 50 females and 50 males of known chronological age (CA). Dental panoramic tomographs (DPT) of 1,597 Qataris were assessed. The summary data for the individual TDS comprising the number (n-tds), mean ( x ¯ -tds), standard deviation (sd-tds), 0th%-ile (the minimum), 25th%-ile, 50th%-ile (the median), 75th%-ile, and 100th%-ile (the maximum) were used to estimate the age of the VS subjects using the simple average method (SAM). There is a significant difference in dental age of 4.8 months in the female group when compared to the CA. The difference in the male group is 4.5 months. This shows similar differences to assessments of other ancestral or ethnic groups.

Questions of logic in Atlas methods of dental age estimation.

PURPOSE: To review aspects of the underlying methodological procedures in Atlas Methods of Dental Age Estimation (DAE) research publications. Attention is paid to issues of Reference Data supporting the Atlases, details of analytic procedures in the development of the Atlases, the statistical reporting of results of Age Estimation (AE), the problems of expressing uncertainty, and the viability of conclusions in the reporting of DAE studies. METHODS: Research reports utilizing Dental Panoramic Tomographs for creating Reference Data Sets (RDS) were studied to unravel the processes of creating Atlases with a view to determining the appropriate procedures for developing numerical RDS and compiling them into an Atlas format to enable DAE of child subjects without birth records. RESULTS: The five different Atlases reviewed gave several different results in terms of AE. The possible causes of this were discussed - namely inadequate representation of Reference Data (RD) and lack of clarity in expressing uncertainty. It is suggested that the method of compiling Atlases needs to be more clearly defined. The yearly intervals described by some of the Atlases fails to take account of the Uncertainty of Estimates which is usually slightly greater than ±2½ years. CONCLUSION: The review of published Atlas design papers in the field of DAE shows a number of different study designs, statistical procedures, and presentational styles, particularly with regard to the statistical procedures and findings. These show that Atlas methods can only be accurate to what amounts to at best a year. RECOMMENDATIONS: Atlas methods lack the accuracy and precision of other methods of AE an example of which is the Simple Average Method (SAM).1 This inherent lack of accuracy must be taken into account when using Atlas methods for AE.

Stress biomarkers in individuals with fibromyalgia syndrome: a systematic review with meta-analysis.

ABSTRACT: Evidence suggests an involvement of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in the development and maintenance of fibromyalgia syndrome (FMS). However, studies on the stress response via the HPA-axis in individuals with FMS show conflicting results. To better understand the relationship between FMS and HPA-axis dysregulation, we (1) systematically summarized the current level of evidence on HPA biomarkers in individuals with FMS compared with individuals without and (2) evaluated whether FMS is associated with a specific pattern of HPA dysregulation. The main outcome measures were cortisol, adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), epinephrine, and norepinephrine. A systematic search of MEDLINE, EMBASE, and PsychMed yielded 47 studies eligible for meta-analysis, including 1465 individuals with FMS and 1192 FMS-free controls. No main effect of FMS was found on altered levels of blood cortisol, ACTH, CRH, and epinephrine. Compared with controls, salivary and urinary cortisol levels were decreased in individuals with FMS, whereas blood levels of norepinephrine were increased. However, heterogeneity of data was high with significant evidence for publication bias. Overall, the data are compatible with association of FMS with adrenocortical hypofunction in the presence of increased sympathetic tone. However, the data are partially contradictory, so it must be assumed that the data are highly dependent on the respective study designs, patient samples, and analytical methods and do not necessarily demonstrate an abnormal HPA-axis function in FMS.

Root canal width as a mandibular maturity marker at the 18-year threshold in the Maltese population.

INTRODUCTION: The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the ratio of the root canal widths (RCW) of the mandibular first, second and third molars is a useful indicator of age. METHODS: Nine hundred eighteen dental panoramic radiographs (DPT) were examined and the ratio of the mid-points of the distal roots of the left mandibular first, second and third molars assessed according to the RCW stages as described by Roberts (J Forensic Sci 62:351-354, 2017). RESULTS: Individuals who had reached stages RCW-A and RCW-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached Stage RCW-C were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons. DISCUSSION: Individuals categorised as stage RCW-C may be deemed to have reached the 18-year-old threshold. These results are consistent with other published studies. Variation in root morphology and in the rate of development of the third molar limits the applicability of this method. CONCLUSIONS: RCW staging is an accurate method of determining the 18-year-old threshold. Its limited applicability requires the use of substitute markers in a large number of cases.

[Psychosomatics in Pain Therapy - Challenges of Chronic Pain]. / Psychosomatik in der Schmerztherapie ­ Herausforderungen chronischer Schmerzen.

Although there is growing awareness among physicians regarding chronic pain, the patient with chronic pain is often considered a complex, if not "difficult" patient in practice. Patients with chronic pain are thus at increased risk of being hastily dismissed and sent on their way. At the same time, therapeutic options are often limited and therapeutic successes not satisfying.

Severity and mortality of COVID-19 in patients with systemic sclerosis: a Brazilian multicenter study.

INTRODUCTION: COVID-19 may be associated with greater severity and mortality in patients with systemic sclerosis (SSc). The present study aimed to evaluate the prevalence, severity and mortality of COVID-19 in a Brazilian cohort of SSc patients. METHODS: This multicenter, retrospective, observational study included 1,042 SSc patients followed in four centers of São Paulo between March 2020 and June 2021. Diagnosis of COVID-19 was established by proper positive RT-PCR testing or by highly suspicious infection. Patients were grouped into mild (outpatient setting treatment and no need for oxygen support) and moderate-to-severe (hospitalization and/or need for oxygen support) COVID-19. RESULTS: Of the 1,042 SSc patients, 118 patients were diagnosed with COVID-19. Interstitial lung disease (SSc-ILD) was present in 65.6% of the total cohort and in 46.3% of SSc patients with COVID-19. There were 78 (66.1%) cases of mild COVID-19, and 40 (33.9%) cases of moderate-to-severe disease, with 6 (5.1%) deaths. By univariate analysis, pulmonary arterial hypertension (OR 9.50, p=0.006), SSc-ILD (OR 3.90, p=0.007), FVC <80% (OR 2.90, p=0.01), cardiac involvement (OR 5.53, p=0.003), and use of rituximab (OR 3.92, p=0.039), but not age, gender, comorbidities or use of corticosteroids, were predictors of worse outcome for COVID-19. Using multivariate analysis, only SSc-ILD was significantly associated to a higher risk of moderate-to-severe COVID-19 (OR 2.73, 95% CI 1.12-6.69, p=0.02). Forty percent of the patients remained with symptoms after presenting COVID-19, predominantly dyspnea and/or cough (17%). CONCLUSION: In this cohort of patients with SSc, those with SSc-ILD were highly impacted by COVID-19, with a higher risk of moderate-to-severe COVID-19 infection and death.

Mortality in Systemic Sclerosis-Associated Interstitial Lung Disease in Brazil: A Real-Life, Long-Term Follow-up Observational Study.

OBJECTIVES: The aim of this study was to identify risk factors associated with mortality in patients with systemic sclerosis (SSc), particularly those with interstitial lung disease (ILD), over a long-term follow-up in a large Brazilian SSc cohort. METHODS: We conducted a medical records review study of 380 scleroderma patients from 1982 to 2019. Systemic sclerosis ILD was considered in those with evidence of ILD on chest high-resolution computed tomography (HRCT). Causes of death were determined. RESULTS: Among the 380 SSc patients, SSc-ILD on chest HRCT was observed in 227 patients (59.7%). Seventy-two patients (18.9%) died during a mean follow-up of 7.2 years since the SSc diagnosis; among them, 57 (79.2%) had SSc-ILD, compared with 15 (20.8%) without SSc-ILD (p < 0.001). Of the 72 deaths, 51.4% were considered related to SSc, and ILD was the leading cause of death. The overall survival rates at 5, 10, and 15 years were 87.9%, 81.5%, and 74.9%, respectively. Kaplan-Meier analysis showed a significantly worse prognosis among patients with SSc-ILD than among those without ILD (p < 0.001). Among patients with SSc-ILD, disease duration of less than 4 years (p < 0.001), forced vital capacity <80% at baseline (p = 0.017), and pulmonary systolic arterial pressure ≥40 mm Hg on echocardiography (p < 0.001) were significantly associated with mortality by multivariate analysis. CONCLUSIONS: In Brazilian SSc patients, the presence of ILD was associated with a worse prognosis. The higher mortality among SSc-ILD patients, especially those with a shorter disease duration and forced vital capacity <80%, highlights the need for early screening and closer monitoring before irreversible lung function deterioration occurs.

Dental age estimation: Development and validation of a reference data set for Kuwaiti children, adolescents, and young adults.

OBJECTIVES: This study was designed to establish a Reference Data Set for Dental Age Estimation of young Kuwaiti subjects. DESIGN: Dental Panoramic Tomographs of 1393 Kuwaiti children, adolescents, and young adults aged between 3 and 26 years were re-used to establish a Reference Data Set. The Tooth Development Stages described by Demirjian et al. in 1973 was used to assess all the teeth on the left side of the Maxilla and the Mandible. The Accuracy and Precision of Dental Age Estimation for Kuwaiti children and adolescents was investigated by calculating the age of children using 50 females and 50 males of known age separate from the main study sample. This was the Validation Sample. Summary data for the individual Tooth Development Stages, comprising the number, mean, and standard deviation were used to estimate the age of the subjects in the Validation Sample using the Simple Average Method to calculate the Dental Age. RESULTS: There was no statistically significant difference between the Chronological Age and the Dental Age in males with a mean difference of 0.14 years (1.75 months). The difference in females was significant at -0.33 years (-4.1 months). CONCLUSIONS: These data demonstrate that estimated Dental Age in Kuwaiti females is close, just over 4 months, and is very close, in males within 1.75 months of the Chronologic Age.

Deaths associated with GA for dentistry 1948 - 2016: the evolution of a policy for general anaesthesia (GA) for dental treatment.

BACKGROUND: Following the inception of the National Health Service in 1948 dental treatment under General Anesthesia (GA) became easily available. An unexpected consequence of this was a disconcerting number of deaths associated with GA. Over the decades since 1948 there have been a number of specialist medical society, royal college, and government working parties deliberating on the appropriateness of GA being conducted in general dental practice and community dental practice. METHODS: The figures for the number of general anaesthetics per annum in England and Wales were obtained from the general dental services board, the community dental service, and records from hospital inpatient episodes. The number of deaths per annum were obtained from coroners' enquiries and dental protection societies. FINDINGS: Prior to 2001 there is a strong correlation between the number of GA's per annum and deaths. Since 2001, when the UK government directed that all GAs for dentistry must be administered in a hospital with Intensive Care facilities the number of deaths per annum has reduced to nil. INTERPRETATION: The change in the arrangements under which GA for dentistry are administered was coincident with improved training and knowledge of GA for dentistry. This has led to a cessation of deaths associated with GA for dentistry. The incidence rate is now estimated at less than 1 death per 3.5 million GAs.

Root Pulp Visibility as a mandibular maturity marker at the 18-year threshold in the Maltese population.

INTRODUCTION: The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the Root Pulp Visibility (RPV) of the mandibular third molar is a useful indicator of age. METHODS: One thousand six dental panoramic radiographs (DPTs) were examined and the left mandibular third molar assessed according to the RPV stages using the method of Olze et al. (Int J Legal Med 124:183-186, 2010) as modified by Lucas et al. (Forensic Sci Int 270:98-102, 2017). Six hundred sixty-two DPTs, 288 males and 374 females, satisfied the inclusion criteria. RESULTS: Individuals who had reached stages RPV-A and RPV-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached stages RPV-C and RPV-D were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons. DISCUSSION: Individuals whose mandibular third molar exhibited stages RPV-C and RPV-D may be deemed to have reached the age of majority. These results are consistent with other published studies. Variation in the rate of development of the third molar limits the applicability of this method. CONCLUSIONS: RPV staging is an accurate method of determining the 18-year-old threshold. Substitute methods are required in a large number of cases.

Expressing Uncertainty in Dental Age Estimation: A Comparison between Two Methods of Calculating the "Average" Standard Deviation.

The expression of uncertainty is defined by the standard deviation and is usually expressed in multiples of the standard deviation (±1sd, ±2sd, and ±3sd). The objective was to use weighting of the sd calculation by the number or count of subjects for each tooth development stage. A comparison shows the difference between the range of uncertainty using the unweighted sd and the weighted sd. The range of uncertainty related to Dental Age Estimation is statistically significantly greater (p < 0.001) for the weighted sd compared to the unweighted sd. It is concluded that the number of subjects for each Tooth Development Stage in the Reference Data set should be included in the calculation for a single Dental Age Estimation using the Simple Average Method when presenting the uncertainty associated with the point estimate of the "mean" for Dental Age Estimation of a single subject of unknown age.

Dental Age Estimation-Root Pulp Visibility (RPV) patterns: A reliable Mandibular Maturity Marker at the 18 year threshold.

The purpose of this paper was to explore the potential application of Root Pulp Visibility (RPV) to determine whether or not a subject of unknown date of birth is under or over the 18year threshold. PATIENTS, MATERIALS AND METHODS: Two thousand Dental Panoramic Radiographs comprising equal numbers of females and males evenly distributed between the ages of 16 and 26 years were examined. All third molars were scored using the Anglo-Canadian 8 Stage Tooth Development system [1]. The Lower Left Third Molar was censored to avoid redundant data being included in the data array for the Age at Attainment of Stage H, the final stage of tooth development (Roberts et al., 2015 [2]). A filter cascade was applied to the data to select the data array for 1. Teeth in the final stage of development, 2. Female or male gender, 3. The definitive stage of RPV: RPV-A, RPV-B, RPV-C, or RPV-D. RESULTS: The summary data for each of these stages was derived and the minimum value for each was used to determine the relationship of the minimum value of A, B, C or D to the 18 Year threshold. It was found that for both females and males the minimum value for RPV-A and RPV-B indicated that subjects displaying this could be under 18 years old. For RPV-C and RPV-D, the minimum values show unequivocally that for both females and males the subject was over 18 years old. CONCLUSION: RPV has an important role in unambiguously determining whether a subject is below or above the 18year threshold.

Dental Age Estimation: Pattern Recognition of Root Canal Widths of Mandibular Molars. A Novel Mandibular Maturity Marker at the 18-Year Threshold.

The final stage of third molar development is used to assign a subject to above the 18-year threshold. Some subjects exhibiting this final stage are less than 18 years. Radiographs from 1000 females and 1000 males age 16.00-25.99 years were examined. Each half-year age band comprised 50 females and 50 males. Three categories of root canal widths (RCW) of the LL6, LL7, and LL8 [FDI 36, 37, and 38] were defined. Reproducibility was achieved by re-assessing the same subjects 12 months apart. For females, the minimum value for RCW-A was 16.33 years, RCW-B 17.23 years, and RCW-C 18.45 years. For males, the minimum values were RCW-A 17.16 years, RCW-B 18.29 years, and RCW-C 18.16 years. The presence of RCW-C in a female, and the presence of RCW-B or RCW-C in a male is compelling evidence that the subject is above the 18-year threshold.

Dental age estimation of children and adolescents: Validation of the Maltese Reference Data Set.

The purpose of this study was to validate a Reference Data Set, developed from the radiographic archives of the Dental Department, Mater Dei Hospital, Malta, for Dental Age Estimation of the Maltese population and to assess the accuracy of the method. Dental Panoramic Tomograms of 100 male and 100 females were selected. Tooth Development Stages were recorded for all 16 permanent teeth on the left and both third molars on the right. Summary and percentile data were calculated for each Tooth Development Stage and the Dental Age of each subject estimated using the unweighted average method. The distribution of the differences between the Dental and Chronological age was analysed. There was no statistically significant difference between the means of the Dental and Chronological ages and the mean differences were within acceptable limits. The conclusion was that the Dataset is valid for the Maltese population and the method used gives adequate accuracy.

Dental age estimation: periodontal ligament visibility (PLV)-pattern recognition of a conclusive mandibular maturity marker related to the lower left third molar at the 18-year threshold.

The purpose of this study was to explore the applicability of periodontal ligament visibility (PLV) at the 18-year threshold. This mandibular maturity marker is graded into four separate age related stages, PLV-A, PLV-B, PLV-C, and PLV-D. These are discernible on a dental panoramic tomograph (DPT). The sample comprised a total of 2000 DPTs evenly divided into half yearly age bands from 16.00 to 25.99 years with 50 females and 50 males in each age band. It was found that PLV-A and PLV-B had minimum values below the 18-year threshold. PLV-C and PLV-D in females had minimum values of 18.08 and 18.58 years, respectively. In males, the minimum values for PLV-C was 18.10 years and PLV-D was 18.67 years. It was concluded that the presence of PLV-C or PLV-D indicates that a subject is over 18 years with a very high level of probability.

Dental Age Estimation: A Test of the Reliability of Correctly Identifying a Subject Over 18 Years of Age Using the Gold Standard of Chronological Age as the Comparator.

This study was designed to test the reliability of using the third molars to demarcate between child and adult status. A total of 2000 dental panoramic tomographs were used for assessment of the calculated age using the 8-stage system of tooth development and applied to all four third molars. The LL8 was also assessed using this 8-stage system. For each tooth development stage, the Normal distribution and percentile summary data were estimated. The calculated dental age compared with the chronological age was statistically significantly different (p < 0.001) for both females and males giving underestimates of the true age. Comparison of single tooth dental age and chronological age was only slightly different. The most important finding is that the assignment to above or below the 18-year threshold, in the age range 17 years to 19 years, could be wrong on up to 50% of occasions.

Dental age assessment of Maltese children and adolescents. Development of a reference dataset and comparison with a United Kingdom Caucasian reference dataset.

The purpose of this study was to develop and validate a Reference Data Set for Dental Age Assessment of the Maltese population and compare the mean Age of Attainment to a UK Caucasian Reference Data Set. The Maltese Reference Data Set was developed from 1593 Dental Panoramic Tomograms of patients aged between 4 and 26 years, taken from the radiographic archives of the Dental Department, Mater Dei Hospital, Malta. Tooth Development Stages were recorded for all 16 maxillary and mandibular permanent teeth on the left side and both permanent third molars on the right, according to Demirjian's staging method. Summary and percentile data were calculated for each Tooth Development Stage, including the mean Age of Attainment. These means were used to estimate the Dental Age of each subject in the study sample using the simple unweighted average method. The estimated Dental Age was compared to the gold standard of the Chronological Age. Comparison of the Maltese and UK Caucasian Reference Data Set was by a series of t-tests, carried out for each paired Tooth Development Stage by gender. The mean Age of Attainment was slightly higher for the Maltese than the UK Caucasians in both males and females. However there was no statistically significant difference between the Chronological Age and Dental Age for either sex.

Dental Age Estimation (DAE): Data management for tooth development stages including the third molar. Appropriate censoring of Stage H, the final stage of tooth development.

INTRODUCTION: The final stage of dental development of third molars is usually helpful to indicate whether or not a subject is aged over 18 years. A complexity is that the final stage of development is unlimited in its upper border. Investigators usually select an inappropriate upper age limit or censor point for this tooth development stage. MATERIALS AND METHODS: The literature was searched for appropriate data sets for dental age estimation and those that provided the count (n), the mean (x¯), and the standard deviation (sd) for each of the tooth development stages. The Demirjian G and Demirjian H were used for this study. Upper and lower limits of the Stage G and Stage H data were calculated limiting the data to plus or minus three standard deviations from the mean. The upper border of Stage H was limited by appropriate censoring at the maximum value for Stage G. RESULTS: The maximum age at attainment from published data, for Stage H, ranged from 22.60 years to 34.50 years. These data were explored to demonstrate how censoring provides an estimate for the correct maximum age for the final stage of Stage H as 21.64 years for UK Caucasians. CONCLUSION: This study shows that confining the data array of individual tooth developments stages to ± 3sd provides a reliable and logical way of censoring the data for tooth development stages with a Normal distribution of data. For Stage H this is inappropriate as it is unbounded in its upper limit. The use of a censored data array for Stage H using Percentile values is appropriate. This increases the reliability of using third molar Stage H alone to determine whether or not an individual is over 18 years old. For Stage H, individual ancestral groups should be censored using the same technique.