Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children.

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria. RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease. CONCLUSIONS: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Post-COVID-19 syndrome in patients with primary Sjögren's syndrome after acute SARS-CoV-2 infection.

OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome.

OBJECTIVE: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. METHODS: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents. RESULTS: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). CONCLUSION: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Tramadol for management of fibromyalgia pain and symptoms: Systematic review.

BACKGROUND: Fibromyalgia is a heterogeneous condition that appears to be associated with physiological and biochemical disturbances of pain modulation, and that consequently affects numerous other facets of life. Tramadol is currently being explored as an option to manage fibromyalgia pain and other symptoms because of its inhibitory activity of reuptake of neurotransmitters, but its safety and efficacy have not yet been established in these patients. OBJECTIVE: To evaluate the effectiveness and safety of tramadol on the management of symptoms of the syndrome. METHODS: We searched CENTRAL, MEDLINE, EMBASE, LILACS, Opengrey, ClinicalTrials.gov and WHO-ICTRP for randomised controlled trials analysing the association between tramadol used for fibromyalgia either single-agent or in combination with other drugs. Two reviewers independently extracted data and assessed risk of bias using the Cochrane risk-of-bias tool for all included studies. Quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Four RCTs comprising 459 patients were included. Tramadol-either as a single-agent or in combination with an antidepressant or analgesic-had a positive effect on pain. Tramadol combined with analgesic showed improved quality of life over placebo as measured by the Fibromyalgia Impact Questionnaire at 91 days. However, this difference did not hold for tramadol as a single agent against placebo. The evidence in these articles was rated "low" using the GRADE approach. No serious adverse events were reported. No improvement in depression and quality of sleep were observed. CONCLUSIONS: This systematic review found a dearth of clinical trials on tramadol in patients with fibromyalgia. Although the combination of monoamine and opioid mechanism of tramadol has shown positive effects for fibromyalgia, the available evidence is not sufficient to support or refute the use of tramadol in clinical practice for pain or symptom management. Protocol registration number in the PROSPERO database: CRD42017062139.

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium.

OBJECTIVES: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. RESULTS: We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). CONCLUSIONS: This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

Asymptomatic Atherosclerosis in Primary Sjögren Syndrome: Correlation Between Low Ankle Brachial Index and Autoantibodies Positivity.

BACKGROUND: Primary Sjögren syndrome is a chronic inflammatory autoimmune disease. The delay in diagnosis allows the establishment of a chronic inflammatory state, which makes primary Sjögren syndrome an interesting model for the study of atherosclerosis. OBJECTIVES: The aim of this study was to evaluate subclinical atherosclerosis in 49 patients with Sjögren syndrome using noninvasive methods. METHODS: We assessed traditional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and family history of atherosclerosis. Patients with prior cardiovascular events and a history of atherosclerosis were excluded. Clinical and laboratory features were recorded, as well as the European League Against Rheumatism Sjögren's Syndrome Activity Index calculation. The atherosclerosis evaluation was done by carotid intima-media thickness, measured by ultrasonography, and ankle-brachial index (ABI). RESULTS: Fifteen patients (31%) had at least 1 traditional risk factor, and 65.3% had a European League Against Rheumatism Sjögren's Syndrome Activity Index score from mild to moderate. Only 2 patients had increased carotid intima-media thickness. However, 59% presented ABI alterations. Multiple correspondence analysis showed a clear correlation between low ABI and the positivity of autoantibodies (antinuclear antibodies, anti-SSA, rheumatoid factor). CONCLUSIONS: The subgroup of patients with positive autoantibodies showed low ABI, which may represent a higher risk of early atherosclerosis and indicate the need for more careful monitoring in this group.

Biologic therapy for refractory scleritis: a new treatment perspective.

Scleritis is an umbrella term for a heterogeneous group of ocular diseases that can be associated with autoimmune or systemic disorders. The purpose of this article was to review the literature regarding the use of biologic drugs to treat refractory scleritis. A search of the MEDLINE, Embase, and LILACS electronic databases was conducted, and the reference lists of published articles were hand-searched. No language filters were used. This search strategy yielded no randomized trials of the use of biologic therapies to treat scleritis; only case reports and retrospective studies were retrieved. These studies suggest that monoclonal antibodies (infliximab and adalimumab) are superior to the soluble TNF receptor fusion protein etanercept for the treatment of scleritis in patients that do not respond to corticosteroids and/or to immunosuppressive treatment. Rituximab seems to be the best option for scleritis associated with vasculitis.

Risk factors for osteoporotic hip fracture among community-dwelling older adults: a real-world evidence study.

BACKGROUND: Hip fractures in the older adults lead to increased morbidity and mortality. Although a low bone mineral density is considered the leading risk factor, it is essential to recognize other factors that could affect the risk of hip fractures. This study aims to evaluate the contribution of clinical characteristics, patient-reported outcomes, and muscle and aerobic capacity for hip fractures in community-dwelling older adults. METHODS: This is a retrospective cohort study with real world-data from subjects ≥ 60 years old attending an outpatient clinic in Minas Gerais, Brazil, from May 1, 2019, to August 22, 2022. Data about clinical characteristics (multimorbidity, medications of long-term use, sedative and or tricyclic medications, number of falls), patient-reported outcomes (self-perception of health, self-report of difficulty walking, self-report of vision problems, and self-report of falls) and muscle and aerobic capacity (calf circumference, body mass index, and gait speed) were retrieved from an electronic health record. The association of each potential risk factor and hip fracture was investigated by a multivariable logistic regression analysis adjusted for age and sex. RESULTS: A total of 7,836 older adults were included with a median age of 80 years (IQR 72-86) and 5,702 (72.7%) were female. Hip fractures occurred in 121 (1.54%) patients. Multimorbidity was associated with an increased risk of hip fracture (OR = 1.12, 95%CI 1.06-1.18) and each episode of fall increased the chance of hip fracture by 1.7-fold (OR = 1.69, 95%CI 1.52-1.80). Patient-reported outcomes associated with increased fracture risk were regular or poor self-perception of health (OR = 1.59, 95%CI 1.06-2.37), self-report of walking difficulty (OR = 3.06, 95%CI 1.93-4.84), and self-report of falls (OR = 2.23, 95%CI 1.47-3.40). Body mass index and calf circumference were inversely associated with hip fractures (OR = 0.91, 95%CI 0.87-0.96 and OR = 0.93, 95%CI 0.88-0.97, respectively), while slow gait speed increased the chance of hip fractures by almost two-fold (OR = 1.80, 95%CI 1.22-2.66). CONCLUSION: Our study reinforces the importance of identified risk factors for hip fracture in community-dwelling older adults beyond bone mineral density and available fracture risk assessment tools. Data obtained in primary care can help physicians, other health professionals, and public health policies to identify patients at increased risk of hip fractures.

Effectiveness of sensorimotor training in patients with rheumatoid arthritis: a randomized controlled trial.

The objective of this study was to evaluate the effectiveness of a sensorimotor training in patients with rheumatoid arthritis on the improvement of functional skills and quality of life, a double-blinded, prospective, randomized controlled trial. One hundred two participants with rheumatoid arthritis were selected. After the baseline evaluation, the participants were randomized to two different groups: sensorimotor group (2 sessions per week, 30-50 min each session, besides continuing taking the same drugs as the control group) and control group (control group was only submitted to the clinical drug treatment with Methotrexate, Leflunomide and/or Prednisone (5 mg), being then evaluated 4 months later). Functional capacity [Health Assessment Questionnaire (HAQ) and Timed Up & Go Test (TU>)], Balance and Gait (Berg Balance Scale (BBS) and Tinetti Test) and Quality of Life (Short Form Health Survey-SF-36). The study had been concluded with ninety-one participants, and a statistically significant improvement was found in all variables assessed: HAQ (P < .01), TU> (P < .01), BBS (P < .01), Tinetti Test (P < .01) and improvement in the subscales of SF-36 (P < .01) in the sensorimotor group in comparison with the baseline evaluation and control group. No significant difference was found related to the pre- and post-evaluation in the control group. Therefore, the sensorimotor training is effective in the improvement of the functional capacity and quality of life of patients with rheumatoid arthritis.

Intravenous zoledronate for postmenopausal women with osteopenia and osteoporosis: a systematic review and metanalysis.

BACKGROUND: Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures. OBJECTIVES: To determine the efficacy and safety of zoledronate in postmenopausal women with osteopenia and osteoporosis. DESIGN AND SETTINGS: A systematic review and meta-analysis was conducted within the evidence-based health program at the Universidade Federal de São Paulo. METHODS: An electronic search of the CENTRAL, MEDLINE, Embase, and LILACS databases was performed until February 2022. Randomized controlled trials comparing zoledronate with placebo or other bisphosphonates were included. Standard methodological procedures were performed according to the Cochrane Handbook and the certainty of evidence for the Grading of Recommendations Assessment, Development, and Evaluation Working Group. Two authors assessed the risk of bias and extracted data on fractures, adverse events, bone turnover markers (BTM), and bone mineral density (BMD). RESULTS: Twelve trials from 6,652 records were included: nine compared zoledronate with placebo, two trials compared zoledronate with alendronate, and one trial compared zoledronate with ibandronate. Zoledronate reduced the incidence of fractures in osteoporotic [three years: morphometric vertebral fractures (relative risk, RR = 0.30 (95% confidence interval, CI: 0.24-0.38))] and osteopenic women [six years: morphometric vertebral fractures (RR = 0.39 (95%CI: 0.25-0.61))], increased incidence of post-dose symptoms [RR = 2.56 (95%CI: 1.80-3.65)], but not serious adverse events [RR = 0.97 (95%CI: 0.91-1.04)]. Zoledronate reduced BTM and increased BMD in osteoporotic and osteopenic women. CONCLUSION: This review supports the efficacy and safety of zoledronate in postmenopausal women with osteopenia for six years and osteoporosis for three years. PROSPERO REGISTRATION NUMBER: CRD42022309708, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309708.

Economic burden of respiratory syncytial and parainfluenza viruses in children of upper-middle-income countries: a systematic review.

OBJECTIVE: To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries. METHODS: The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757. RESULTS: No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed. CONCLUSION: The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.

Brazilian society of rheumatology methodological guide for the development of evidence-based clinical guidelines in rheumatology.

Clinical practice guidelines (CPG) are developed to align standards of health care around the world, aiming to reduce the incidence of misconducts and enabling more effective use of health resources. Considering the complexity, cost, and time involved in formulating CPG, strategies should be used to facilitate and guide authors through each step of this process. The main objective of this document is to present a methodological guide prepared by the Epidemiology Committee of the Brazilian Society of Rheumatology for the elaboration of CPG in rheumatology. Through an extensive review of the literature, this study compiles the main practical recommendations regarding the following steps of CPG drafting: distribution of working groups, development of the research question, search, identification and selection of relevant studies, evidence synthesis and quality assessment of the body of evidence, the Delphi methodology for consensus achievement, presentation and dissemination of the recommendations, CPG quality assessment and updating. This methodological guide serves as an important tool for rheumatologists to develop reliable and high-quality CPG, standardizing clinical practices worldwide.

Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort study.

Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27-2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22-2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01-1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22-1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16-2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.

Effectiveness of physical activity in reducing pain in patients with fibromyalgia: a blinded randomized clinical trial.

The purpose of this study was to evaluate and compare the effectiveness of muscle-strengthening exercises (MS) and a walking program (WA) in reducing pain in patients with fibromyalgia. Ninety women, 30-55 years of age, diagnosed with fibromyalgia according to the American College of Rheumatology 1990 criteria, were randomized into 3 groups: WA Group, MS Group, and control group. Pain (visual analog scale) was evaluated as the primary outcome. Physical functioning (Fibromyalgia Impact Questionnaire, FIQ), health-related quality of life (Short-Form 36 Health Survey, SF-36), and use of medication were evaluated as secondary outcomes. Assessments were performed at baseline, 8, 16, and 28 weeks. Intention-to-treat and efficacy analyses were conducted. Sixty-eight patients completed the treatment protocol. All 3 groups showed improvement after the 16-week treatment compared to baseline. At the 28-week follow-up, pain reduction was similar for the WA and MS groups (P = 0.39), but different from the control group (P = 0.01). At the end of the treatment, 80% of subjects in the control group took pain medication, but only 46.7% in the WA and 41.4% in the MS groups. Mean FIQ total scores were lower for the WA and MS groups (P = 0.96) compared with the control group (P < 0.01). Patients in the WA and MS groups reported higher scores (better health status) than controls in almost all SF-36 subscales. MS was as effective as WA in reducing pain regarding all study variables; however, symptoms management during the follow-up period was more efficient in the WA group.

Ventilatory weaning strategies for predicting extubation success in children following cardiac surgery for congenital heart disease: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Congenital heart disease (CHD) comprises the anatomic malformations that jeopardise the structure and function of the heart. It can be extremely complex and serious, corresponding to 30% of all deaths in the first month of life. The surgical approach for adequate treatment requires postoperative mechanical ventilation. The most critical decision related to the postoperative management of patients submitted to cardiac surgery is the right time for extubation, especially because not only abrupt or inadequate discontinuation of ventilatory support can lead to clinical decline and necessity of reintubation but also extended time of mechanical ventilation, which can lead to complications, such as pneumonia, atelectasis, diaphragm hypertrophy, and increasing morbidity and mortality. METHODS AND ANALYSIS: This systematic review plans to include individual parallel, cross-over and cluster randomised controlled trials regarding any breathing trial test to predict extubation success in children submitted to cardiac surgery due to CHD. Studies with paediatric patients submitted to cardiac surgery for congenital cardiopathy repair, attended at a critical care unit, and under mechanical ventilatory support will be included. The main outcomes analysed will be success of extubation, reduction of pulmonary complications and time reduction of mechanical ventilation. ETHICS AND DISSEMINATION: We will not treat patients directly; therefore, ethics committee approval was not necessary because it is not a primary study. We expect that this study may improve healthcare and medical assistance, helping healthcare professionals with routine daily decisions regarding the correct time for extubation. PROSPERO REGISTRATION NUMBER: CRD42021223999.

Hospitalization costs of coronaviruses diseases in upper-middle-income countries: A systematic review.

BACKGROUND: COVID-19, SARS and MERS are diseases that present an important health burden worldwide. This situation demands resource allocation to the healthcare system, affecting especially middle- and low-income countries. Thus, identifying the main cost drivers is relevant to optimize patient care and resource allocation. OBJECTIVE: To systematically identify and summarize the current status of knowledge on direct medical hospitalization costs of SARS, MERS, or COVID-19 in Upper-Middle-Income Countries. METHODS: We conducted a systematic review across seven key databases (PubMed, EMBASE, BVS Portal, CINAHL, CRD library, MedRxiv and Research Square) from database inception to February 2021. Costs extracted were converted into 2021 International Dollars using the Purchasing Power Parity-adjusted. The assessment of quality was based on the protocol by the BMJ and CHEERS. PROSPERO 2020: CRD42020225757. RESULTS: No eligible study about SARS or MERS was recovered. For COVID-19, five studies presented cost analysis performed in Brazil, China, Iran, and Turkey. Regarding total direct medical costs, the lowest cost per patient at ward was observed in Turkey ($900.08), while the highest in Brazil ($5,093.38). At ICU, the lowest was in Turkey ($2,984.78), while the highest was in China ($52,432.87). Service care was the most expressive (58% to 88%) cost driver of COVID-19 patients at ward. At ICU, there was no consensus between service care (54% to 87%) and treatment (72% to 81%) as key burdens of total cost. CONCLUSION: Our findings elucidate the importance of COVID-19 on health-economic outcomes. The marked heterogeneity among studies leaded to substantially different results and made challenging the comparison of data to estimate pooled results for single countries or regions. Further studies concerning cost estimates from standardized analysis may provide clearer data for a more substantial analysis. This may help care providers and policy makers to organize care for patients in the most efficient way.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary sjogren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian Society of Rheumatology (articular, pulmonary and renal).

Sjogren's Syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, these systemic manifestations are not routinely evaluated and there is no homogenous approach to their diagnosis or evaluation. To close this gap, a panel of experts from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis on the identification of epidemiologic and clinical features of these manifestations and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. The first part of this guideline summarizes the most important topics, and 11 recommendations are provided for the articular, pulmonary, and renal care of SS patients.

Recommendations for evaluation and diagnosis of extra-glandular manifestations of primary Sjögren syndrome: results of an epidemiologic systematic review/meta-analysis and a consensus guideline from the Brazilian society of rheumatology (hepatic, gastrointestinal and pancreatic).

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and other organs, associated with sicca syndrome but also with systemic involvement with varying degrees of severity. Despite their importance, some systemic manifestations, mainly liver, gastrointestinal, and pancreatic are not routinely evaluated. To address these manifestations, the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology conducted a broad systematic review of the literature on studies investigating prevalence and diagnosis of these symptoms in Sjogren´s patients and made recommendations based on the findings. Agreement between the experts was achieved using the Delphi method. This is the second part of this guideline, providing 6 recommendations for liver, gastrointestinal, and pancreatic care of SS patients.

Cardiovascular Effect of Physical Exercise on Primary Sjogren's Syndrome (pSS): Randomized Trial.

Objective: To evaluate the effects of an exercise program on aerobic capacity, echocardiographic parameters, metabolic profile, quality of life and safety in patients with primary Sjogren's syndrome in a randomized trial. Methods: 60 women with pSS were evaluated from the SF-36 Short-Form Health Survey (SF-36) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) questionnaires. The participants performed ergospirometry and echocardiography; blood samples were collected to evaluate the metabolic profile. Patients were randomly divided into 2 groups: a training group that participated in the supervised training program and a control group. All variables were analyzed at baseline and after 28 weeks for both groups and we performed an intention-to-treat analysis. The training program consisted of 16 weeks of resistance exercises and, after, the exercise became aerobic. Patients and coaches were not blinded, contrary to the evaluators of all examinations/procedures and data analysts. Statistical analysis included Wilcoxon's rank sum test, chi-square test, and ANOVA test. P values < 0.05 were considered to be statistically significant. Results: The 2 groups were homogeneous at baseline. The training group showed a significant improvement in oxygen maximum volume (VO2max) and anaerobic threshold (AT). Comparison of the training group and control group after 28 weeks showed a significant difference relating to VO2max and in AT. We did not find statistically significant diference in echocardiographic parameters, metabolic profile and in questionnaires SF-36 and ESSDAI. Conclusions: This study showed significant improvement in aerobic capacity and glycated hemoglobin after a supervised training program in patients with pSS with safety.

Transcranial direct current stimulation for fatigue in patients with Sjogren's syndrome: A randomized, double-blind pilot study.

BACKGROUND: Transcranial direct-current stimulation (tDCS) has shown promise to decrease fatigue. However, it has never been examined in primary Sjogren Syndrome (pSS). OBJECTIVE: To assess the effect of a tDCS protocol on fatigue in patients with pSS. METHODS: This is a parallel, double-blind pilot study (NCT04119128). Women aged 18-65 years, with pSS, on stable pharmacological therapy, with complaints of fatigue for at least three months, and with scores >5 on Fatigue Severity Scale (FSS) were included. We randomized 36 participants to receive five consecutive or sham tDCS sessions, with an intensity of 2 mA, for 20 min/day. RESULTS: After five tDCS sessions, fatigue severity assessed by the FSS (primary outcome) demonstrated a mean group difference of -0.85 [95% confidence interval (CI) -1.57, -0.13; effect size 0.80] favouring the active group. The active group presented significantly greater reductions in fatigue as measured by the EULAR Sjögren's Syndrome Patient Reported Index after five tDCS sessions [mean group difference: 1.40; 95%CI -2.33, -0.48; effect size 1.04]. Although there were no between-group differences in the secondary outcomes of sleep, mood and anxiety, within-group comparisons evidenced a small but significant difference in the active group for pain and sleep. There were no significant cortisol changes. All reported adverse events were mild and transitory. CONCLUSION: tDCS seems to be safe and reduce fatigue in pSS. A differential effect on pain and sleep may underlie its effects. Further studies are needed to optimise tDCS treatment strategies in pSS.