1,720,969 research outputs found
Development of a prognostic model for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis
No full textIntroduction:
Macrophage activation syndrome (MAS) is a potentially life-threatening complication of systemic juvenile idiopathic arthritis (SJIA) characterized by heterogeneous organ involvement and severity. Early identification of patients at high risk of complicated clinical course may improve outcome by helping initiate prompt, appropriate immunosuppressive and supportive treatments. Yet, despite recent progress in clarifying the underlying immunological mechanisms, factors driving organ damage and severe outcome are not entirely understood, nor has the prognostic value of routinely gathered clinical and laboratory factors been fully explored.
Objectives:
To develop a prognostic model for SJIA-MAS based on routinely available parameters at disease onset, accounting for patient heterogeneity, possible latent factors, non-linear relationships and confounders.
Methods:
We examined a retrospective multinational cohort of 362 patients diagnosed with SJIA-MAS. The relationships between demographic, laboratory features at MAS onset (such as hemoglobin, whole blood cells, platelets, ERS, CRP, AST, ALT, bilirubin, fibrinogen, d-dimer, ferritin and creatinine), therapeutic interventions and outcomes were analyzed. Outcomes of interest included a “severe course” (defined as ICU admission or death), occurring of organs failure and CSN dysfunction. To identify potential phenotypes related to clinical features and outcome, we explored laboratory parameter patterns at MAS onset through Latent class modeling, which detects multiple unobserved clusters in heterogeneous populations. A structural causal approach was then used for investigating causal pathways leading to severe outcomes. Directed acyclic graphs (DAGs) were employed to depict possible causal relationships between the candidate biomarkers, potential confounding variables, and the outcomes, and inform the choice of adjustment sets in multivariate regression models. We assessed the possible relationships between variables and outcomes by penalized likelihood logistic regression and identified optimal cut off points for prognostic factors using Multiple Adaptive Regression Splines (MARS) and Classification and Regression Trees (CART). To account for possible treatment confounders, the effect of cyclosporine and etoposide use on outcomes was estimated using augmented inverse probability weighting (IPW) with double robust methods. Finally, results from previous analyses were incorporated in a probabilistic framework through a Bayesian network (BN) model, which provides risk estimates for specific clinical scenarios and quantifies the amount of information contributed from the identified prognostic variables.
Results:
The latent class model revealed six clusters based on biomarkers at MAS onset, characterized by the following features: mild alterations of white blood cells, platelets, fibrinogen, d-dimer and ferritin values, considered the baseline type (cluster 1, n =115); hyperferritinemia with low organs involvement (cluster 2, n = 101); elevation of inflammatory markers (cluster 3, n =51); hepatobiliary involvement (cluster 4, n = 41); severe pancytopenia, liver and kidney failure with higher elevation of LDH, d-dimer, ferritin (cluster 5, n = 30); biliary and renal dysfunction (cluster 6, n = 24). Cluster 2 and 3 presented lower age and SJIA duration at MAS onset compared to other subgroups. Cluster membership was predictive of severe course (p<0.001), CSN involvement (p<0.001), Hemorrhagic complications (p <0.001) and Heart failure (p<0.001), with patients in cluster 5 showing the highest risk of severe course and heart failure, and increased occurrence of CNS and Hemorrhagic manifestations in both cluster 5 and 6. In multivariate regression models, parameters at onset associated with risk of severe course were creatinine (OR 1,6 [95% CI 1.13–2.3]; p = 0.008) and albumin levels (OR 0,65 [95% CI 0.44–0.98]; p = 0.044) Higher risk of CNS involvement was found for patients younger at MAS onset (OR 0,62 [95% CI 0.42–0.92]; p = 0.018). Na (OR 0.0,89 [95% CI 0.82–0.96]; p = 0.006) and creatinine values (OR 1.69 [95% CI 1.14–2.5]; p = 0.009) were identified as independent predictors of mortality. There was no evidence for an effect of etoposide (OR 1.03 [95% CI 0.91–1.12]) and cyclosporine (OR 1.04 [95% CI 0.92–1.19]) on severe course. BNs defined distinct groups with different probability of severe outcomes, achieving a c-index of 0.76 for mortality, 0.81 for severe course and 0.81 for CNS involvement. Adding the obtained latent clusters to the BN model increased the prediction accuracy for severe course up to a c-index of 0.83. Based on information theory metrics (mutual information) from the BN model, decision algorithms for each outcome and a web-based decision support tool for external users were implemented.
Conclusions:
We developed a probabilistic prognostic model of SJIA-MAS based on routinely available data. This stratification tool may facilitate informed decision-making about the clinical management of these patients. The probabilistic and information-theoretic approach offers a framework for further validation, expansion and integration of the model with emerging molecular biomarkers
Update on the pathogenesis and treatment of juvenile idiopathic arthritis
No full textPURPOSE OF REVIEW: To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA). RECENT FINDINGS: In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process. There is a growing interest for the role of the gut microbiome in disease pathogenesis, which may open the way to future therapeutic manipulations of fecal microbial population. Recent therapeutic studies have provided important information in large patient samples on the effectiveness and toxicity profile of biologic medications used in JIA. Concomitant administration of methotrexate was found to increase the effectiveness of intra-articular corticosteroid therapy in children with oligoarticular JIA. SUMMARY: A great deal of work is being conducted to better define the molecular phenotype of the individual subsets of JIA and to identify potential new targets for therapeutic interventions. The results of the ongoing large-scale international data collections will help establish the long-term safety profiles of biologic medications, in particular the risk of malignancy
Impact of the First Year of the COVID-19 Pandemic on Pediatric Emergency Department Attendance in a Tertiary Center in South Italy: An Interrupted Time-Series Analysis
Full text linkBackground: The evidence shows a reduction in pediatric emergency department (PED) flows during the early stages of the COVID-19 pandemic. Using interrupted time-series analysis, we evaluated the impact of different stages of the pandemic response on overall and cause-specific PED attendance at a tertiary hospital in south Italy. Our methods included evaluations of total visits, hospitalizations, accesses for critical illnesses and four etiological categories (transmissible and non-transmissible infectious diseases, trauma and mental-health) during March-December 2020, which were compared with analogous intervals from 2016 to 2019; the pandemic period was divided into three segments: the "first lockdown" (FL, 9 March-3 May), the "post-lockdown" (PL, 4 May-6 November) and the "second lockdown" (SL, 7 November-31 December). Our results showed that attendance dropped by a mean of 50.09% during the pandemic stages, while hospitalizations increased. Critical illnesses decreased during FL (incidence rate ratio -IRR- 0.37, 95% CI 0.13, 0.88) e SL (IRR 0.09, 95% CI 0.01, 0.74) and transmissible disease related visits reduced more markedly and persistently (FL: IRR 0.18, 95% CI 0.14, 0.24; PL: IRR 0.20, 95% CI 0.13, 0.31, SL: IRR 0.17, 95% CI 0.10, 0.29). Non-infectious diseases returned to pre-COVID-19 pandemic levels by PL. We concluded that that the results highlight the specific effect of the late 2020 containment measures on transmissible infectious diseases and their burden on pediatric emergency resources. This evidence can inform resource allocation and interventions to mitigate the impact of infectious diseases on pediatric populations and the health-care system
The Effect of Morning Stiffness Duration on the Definition of Clinically Inactive Disease in Juvenile Idiopathic Arthritis
No full textObjective To investigate the impact of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinical inactive disease (CID).
Methods 652 visits in which patients fulfilled 2004 or 2011 Wallace criteria for CID were examined. Parent-reported outcomes were compared among patients with no MS or with MS < or ≥ 15 minutes.
Results Among 652 visits with CID by 2004 criteria, no MS was reported in 554 visits (85%), MS < 15 minutes in 53 (8%), and MS ≥ 15 minutes in 45 (7%). The frequency of altered physical function, health-related quality of life, and well-being, pain and disease activity visual analog scales was proportionally greater from patients without MS to those with longer MS. The frequency of parent subjective rating of disease state as remission was 87.7%, 58% and 27.7% among patients with no MS, MS < 15 minutes and MS ≥ 15 minutes, respectively.
Conclusion Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered
Open issues in the assessment and management of pain in juvenile idiopathic arthritis
No full textPain is the major symptom of children with juvenile idiopathic arthritis (JIA) and its reduction is a key goal of treatment. It is widely agreed that assessment of pain is a fundamental component of the rheumatology evaluation and should be carried out at each clinic visit. However, so far there has been insufficient attention to the impact and causes of pain in children with chronic arthritis in both clinical practice and research. Quantitative measures of pain are seldom used regularly in daily care and pain assessment has not been incorporated in the most popular composite outcome measures for JIA, including the criteria employed to measure improvement in therapeutic trials. A recent advance in the development of pain tools involves mobile devices, particularly smartphones, and the internet to collect real-time self-reported data via electronic diaries. Concern has been raised by the recent observations of persistence of pain in some children with JIA despite adequate treatment with the modern biologic medications and good disease controls. These findings underscore the need of large-scale studies of the prevalence and determinants of pain in patients treated with contemporary care. In addition, the reasons that explain the persistence of pain after the resolution of the inflammatory process should be investigated through research on neurobiological mechanisms of pain and by addressing the role of factors external to the disease, such as mood, anxiety, and pain sensitisation and coping
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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