BackgroundEvidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed.MethodsThis was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables.ResultsFirst, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity.ConclusionThese results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1345-y) contains supplementary material, which is available to authorized users.

Objectives: Pen devices offer advantages compared with vial and syringe (VaS). The purpose of this article was to evaluate efficacy of pen devices compared to VaS. Methods: A systematic review of literature was performed in 8 different databases. References were independently screened and selected. Primary observational or experimental studies comparing pen devices with VaS for insulin administrations were included. Studies on specific populations were excluded. Risk of bias was evaluated using appropriate tools. Data on glycosylated hemoglobin (HbA1c), hypoglycemia, adherence, persistence, patient preference, and quality of life (QOL) were collected. Meta-analysis was performed when appropriate. Heterogeneity and risk of publication bias were evaluated. Otherwise, descriptive analyses of the available data was done. Results: In all, 10 348 articles were screened. A total of 17 studies were finally selected: 7 experimental and 10 analytical. The populations of the included articles were mainly composed of adults with type 2 diabetes mellitus. Important risk of bias was found in all of the articles, particularly experimental studies. Meta-analyses were performed for HbA1c, hypoglycemia, adherence and persistence. Pen device showed better results in mean HbA1c change, patients with hypoglycemia, adherence and persistence compared to VaS. No difference was observed in number of patients achieving <7% HbA1c. Preference studies showed a tendency favoring pen devices, however nonvalidated tools were used. One QoL study showed improvements in some subscales of SF-36. Conclusions: There is evidence that pen devices offer benefits in clinical and, less clearly, patient-reported outcomes compared to VaS for insulin administration. However, these results should be taken with caution.

Objectives To assess the economic impact of dengue in Latin America and the Caribbean using a systematic review that includes studies not previously considered by other reviews. Methods Cochrane methodology was used to conduct a systematic review of the cost of dengue in Latin America. PubMed Central, EMBASE, and the Biblioteca Virtual en Salud—which includes scientific, peer-reviewed journals not indexed by other databases—were searched from inception through August 2016. All articles that reported cost of illness data for countries in Latin America were included. Included studies underwent a methodological appraisal using a seven-question instrument designed for cost of illness studies. Extracted data were direct and indirect costs for outpatient and hospitalized cases and total cost of the disease. Values were adjusted to 2015 US dollars using the consumer price index. Results From a total of 848 initial references, 17 studies were included, mainly from Brazil, Colombia, Cuba, Mexico, and Puerto Rico; costs were available for 39 countries. The methodological appraisal showed that 70% of the studies met more than 70% of the evaluated items. The main economic impact of dengue was due to productivity costs. Average annual cost was more than US$ 3 billion. Direct costs represented over 70% of the total share for hospitalized cases. For outpatients, direct medical costs were low, but social costs were significant since indirect costs may account for up to 80% of the total cost. Conclusions Dengue fever has a significant economic impact in Latin America. It is essential to develop new public health interventions, such as dengue vaccination, to decrease the propagation of the disease and its total cost.

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Objective:Poor sleep patterns are common in undergraduates and may turn them prone to mood disorders, substance abuse and impaired academic performance. The aim of this study was to assess sleep disturbances among medical students, and whether associations with academic performance, depressive symptoms or substance use were present.Methods:Cross-sectional study in which 544 medical students of the Pontificia Universidad Javeriana in Bogota, Colombia were included. Using a computer-based survey, self-reported variables were assessed, including demographics, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Berlin Questionnaire, Diagnostic and Statistical Manual of Mental Disorders (DSM) - IV depression criteria, Grade Point Average (GPA), and substance use. Associations between these variables were obtained.Results:Fifty-four percent of students were women. Poor sleep quality (PSQI>5) and daytime sleepiness (ESS>10) were found in 65% of the population. A higher GPA was more frequent in students with good sleep quality (OR= 2.6 [1.5-4.5]), lack of daytime sleepiness (OR= 2 [1.3-3.1]) and low risk of Obstructive Sleep Apnea Syndrome (OSAS) (OR= 3.1 [1.6-5.9]). DSM-IV depression criteria were fulfilled by 26% of the students and were associated with poor sleep patterns. Energy drinks use was associated with poor sleep quality.Discussion:Poor sleep quality, daytime sleepiness and depressive symptoms are frequent among medical students and are associated with lower academic performance. The identification of students at risk and the implementation of targeted interventions are warranted. Fostering adequate sleep habits and training on sleep medicine may partly counteract these issues.

Objective To describe the impact of COVID-19 pandemic on Latin American rheumatologists from a professional, economic, and occupational point of view. Methods We conducted an observational cross-sectional study using an online survey sent to rheumatologists of each non-English-speaking country member of the Pan American League of Rheumatology Associations (PANLAR). A specific questionnaire was developed. Results Our survey included 1097 rheumatologists from 19 Latin American countries. Median (IQR) age of respondents was 48 (40-59) years and 618 (56.3%) were female. Duration of practice since graduation as rheumatologist was 17 years, and 585 (53.3%) were under 50 years of age. Most rheumatologists worked in private practice (81.8%) and almost half worked in institutional outpatient centers (55%) and in-patient care (49.9%). The median number of weekly hours (IQR) of face-to-face practice before the pandemic was 27 (15-40) but it was reduced to 10 (5- 20) during the pandemic. Telehealth was used by 866 (78.9%) respondents during the pandemic. Most common methods of communication were video calls (555; 50.6%), telephone calls (499; 45.5%) and WhatsApp voice calls (423; 38.6%). A reduction in monthly wages was reported by 946 (86.2%) respondents. Consultation fees also were reduced and 88 (8%) rheumatologists stated they had lost their jobs. A reduction in patient adherence to medication was reported by nearly 50% of respondents. Eighty-one (7.4%) rheumatologists received a COVID-19 diagnosis and 7 (8.6%) of them were hospitalized. Conclusion COVID-19 pandemic has reshaped rheumatology practice in Latin America and has had a profound impact on rheumatologists' behaviors and clinical practice.

Background Although there are thousands of published recommendations in anesthesiology clinical practice guidelines, the extent to which these are supported by high levels of evidence is not known. This study hypothesized that most recommendations in clinical practice guidelines are supported by a low level of evidence. Methods A registered (Prospero CRD42020202932) systematic review was conducted of anesthesia evidence-based recommendations from the major North American and European anesthesiology societies between January 2010 and September 2020 in PubMed and EMBASE. The level of evidence A, B, or C and the strength of recommendation (strong or weak) for each recommendation was mapped using the American College of Cardiology/American Heart Association classification system or the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The outcome of interest was the proportion of recommendations supported by levels of evidence A, B, and C. Changes in the level of evidence over time were examined. Risk of bias was assessed using Appraisal of Guidelines for Research and Evaluation (AGREE) II. Results In total, 60 guidelines comprising 2,280 recommendations were reviewed. Level of evidence A supported 16% (363 of 2,280) of total recommendations and 19% (288 of 1,506) of strong recommendations. Level of evidence C supported 51% (1,160 of 2,280) of all recommendations and 50% (756 of 1,506) of strong recommendations. Of all the guidelines, 73% (44 of 60) had a low risk of bias. The proportion of recommendations supported by level of evidence A versus level of evidence C (relative risk ratio, 0.93; 95% CI, 0.18 to 4.74; P = 0.933) or level of evidence B versus level of evidence C (relative risk ratio, 1.63; 95% CI, 0.72 to 3.72; P = 0.243) did not increase in guidelines that were revised. Year of publication was also not associated with increases in the proportion of recommendations supported by level of evidence A (relative risk ratio, 1.07; 95% CI, 0.93 to 1.23; P = 0.340) or level of evidence B (relative risk ratio, 1.05; 95% CI, 0.96 to 1.15; P = 0.283) compared to level of evidence C. Conclusions Half of the recommendations in anesthesiology clinical practice guidelines are based on a low level of evidence, and this did not change over time. These findings highlight the need for additional efforts to increase the quality of evidence used to guide decision-making in anesthesiology. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background: Secondary amyloidosis, a rare complication of Crohn disease (CD), is triggered by persistent systemic inflammation. Kidney involvement is the most frequent manifestation and is often characterized by nephrotic syndrome and kidney failure. This complication usually appears in patients with long-standing disease and is associated with increased morbidity and mortality risk. Diagnosis is by microscopic amyloid observation of tissue biopsy, and when the diagnosis is confirmed, the therapeutic objective is disease activity control. Response assessment is challenging because of a lack of reliable biomarkers. Case Report: A 56-year-old male with a long-standing history of CD treated with a tumor necrosis factor-α inhibitor presented with an acute elevation of creatinine in association with clinical and laboratory markers of nephrotic syndrome. Kidney biopsy revealed renal amyloidosis. After treatment adjustment, although a stable creatinine was achieved, the patient had persistent impaired glomerular filtration rate. Conclusion: As a systemic chronic inflammatory disorder, CD may present multisystemic morbidity, for which increased awareness among gastroenterologists is warranted. Renal amyloidosis is an infrequent extraintestinal complication of CD that may lead to chronic kidney impairment. Although evidence-based treatment is lacking, disease activity control is pivotal for management.