PCN36 Cost Analysis Model Between The Cobas Braf Test And Sanger Sequencing When Treating Malignant Melanoma Based On The Presence Of V600 Mutations

L'informe de gestió de l'exercici 201

Freqüência de infecção por Toxocara em crianças atendidas em serviço público de Maringá, sul do Brasil

The lack of specific laboratorial diagnosis methods and precise symptoms makes the toxocariasis a neglected disease in Public Health Services. This study aims to determine the frequency of Toxocara spp. infection in children attended by the Health Public Service of Hospital Municipal de Maringá, South Brazil. To evaluate the association of epidemiological and clinical data, an observational and cross-section study was carried out. From 14,690 attended children/year aged from seven month to 12 years old, 450 serum samples were randomly collected from September/2004 to September/2005. A questionnaire was used to evaluate epidemiological, clinical and hematological data. An ELISA using Toxocara canis larval excretory-secretory products as antigen detected 130 (28.8%) positive sera, mainly between children from seven month to five years old (p = 0.0016). Significant correlation was observed between positive serology for Toxocara, and frequent playing in sandbox at school or daycare center (p = 0.011) and the presence of a cat at home (p = 0.056). From the families, 50% were dog owners which exposed soil backyards. Eosinophilia (p = 0.776), and signs and symptoms analyzed (fever p = 0.992, pneumonia p = 0.289, cold-like symptoms p = 0.277, cough p = 0.783, gastrointestinal problems p = 0.877, migraine p = 0.979, abdominal pain p = 0.965, joint pain p = 0.686 and skin rash p = 0.105) could not be related to the presence of anti-Toxocara antibodies. Therefore, two asthmatics children showed titles of 1:10,240 and accentuated eosinophilia (p = 0.0001). The authors emphasize the needs of prevention activities.A falta de métodos de diagnóstico laboratorial específico e sintomas específicos fazem da toxocaríase uma doença negligenciada nos serviços públicos de saúde. Este estudo teve por objetivo determinar a freqüência de infecção por Toxocara spp. em crianças atendidas no serviço público do Hospital Municipal de Maringá, sul do Brasil, e avaliar a associação com dados epidemiológicos e clínicos, em estudo observacional e transversal. De 14.690 crianças/ano atendidas, com idade entre sete meses a 12 anos, foram coletados 450 soros de setembro/2004 a setembro/2005. Um questionário foi utilizado para avaliar dados epidemiológicos, clínicos e hematológicos. Pelo teste ELISA, com antígeno de excreção/secreção de larvas de Toxocara canis, detectou-se 130 (28,8%) soros positivos, principalmente em crianças entre sete meses e cinco anos (p = 0,0016). Houve significante correlação entre sorologia positiva para Toxocara e freqüente recreação das crianças em caixas de areia da escola ou pré escola (p = 0,011) e presença do gato no domicilio (p = 0,056). Das famílias dessas crianças, 50% possuíam cachorros e o quintal com solo exposto. Eosinofilia (p = 0,776), sinais e sintomas (febre p = 0,992, pneumonia p = 0,289, resfriado p = 0,277, tosse p = 0,783, problema gastrointestinal p = 0877, dor de cabeça p = 0,979, dor abdominal p = 0,965, dores articulares p = 0,686, urticária p = 0,105) não se correlacionaram com a soropositividade. Todavia, duas crianças asmáticas apresentaram títulos de 1:10.240 (>; 1:320) e acentuada eosinofilia (p = 0.0001). Os autores enfatizam a necessidade de atividades preventivas

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Investigating patient exclusion bias in meta-analysis

BACKGROUND Trial investigators frequently exclude patients from trial analyses which may bias estimates of the effect of treatment. Combining these estimates in a meta-analysis could aggregate any such biases. METHODS To investigate how excluding patients from trials can affect the results of both trials and meta-analyses, we used 14 meta-analyses of individual patient data (IPD) that addressed therapeutic questions in cancer. These included 133 randomized controlled trials (RCT) and 21 905 patients. We explored whether exclusions were related to trial characteristics and categorized the reasons for exclusions. For each RCT and meta-analysis, we compared results of an intention-to-treat analysis of all randomized patients with an analysis based on those patients included in the investigators' analysis. RESULTS In all, 92 trials (69%) excluded between 0.3 and 38% of patients randomized. Trials excluding patients tended to be older and larger than those that did not. Most patients were excluded because of ineligibility or protocol violations. Exclusions varied substantially by meta-analysis, more patients tending to be excluded from the treatment arm. Comparing trial analyses there was no clear indication that exclusion of patients altered the results more in favour of either treatment or control. However, comparing meta-analysis results, there was a tendency for those based on ‘included’ patients to favour the research treatment (P = 0.03). Inconsistency of trial results was often increased as a result of the investigators' exclusions. CONCLUSIONS Trials, systematic reviews, and meta-analyses may be prone to bias associated with post-randomization exclusion of patients. Wherever possible, the level of such exclusions should be taken into account when assessing the potential for bias in trials, systematic reviews, and meta-analyses. Ideally, trials, systematic reviews, and meta-analyses should be based on all randomized patients

One-stage parametric meta-analysis of time-to-event outcomes

Methodology for the meta-analysis of individual patient data with survival end-points is proposed. Motivated by questions about the reliance on hazard ratios as summary measures of treatment effects, a parametric approach is considered and percentile ratios are introduced as an alternative to hazard ratios. The generalized log-gamma model, which includes many common time-to-event distributions as special cases, is discussed in detail. Likelihood inference for percentile ratios is outlined. The proposed methodology is used for a meta-analysis of glioma data that was one of the studies which motivated this work. A simulation study exploring the validity of the proposed methodology is available electronically. © 2010 John Wiley & Sons, Ltd

How individual participant data meta-analyses have influenced trial design, conduct, and analysis

To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer.Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials

Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis

CD-1 mice infected with the protozoan parasite Trypanosoma brucei brucei developed few signs of central nervous system pathology associated with the invasion of the central nervous system by these parasites and did not survive beyond 5–6 weeks with deaths common before this time point. However, use of the trypanocidal drug diminazene aceturate (40 mg/kg), which fails to cross the blood-brain barrier, on day 21 post-infection led to the development of central nervous system pathology similar to that seen in the fatal post-treatment reactive encephalopathies that can occur in human African trypanosomiasis. Enzyme-linked immunosorbent assays were used to measure autoantibody titres to double-stranded DNA, myelin basic protein and to the myelin-specific galactocerebrosides and gangliosides in groups of infected mice, with or without the post-treatment reaction, on day 30 post-infection and compared with uninfected controls. Infection with T. brucei brucei raised the titres of all of these autoantibodies. Treatment of infected mice with diminazene aceturate resulted in elevated levels of all of these autoantibodies compared to the untreated animals. There was a strong positive correlation between the central nervous system pathology and the levels of autoantibodies to myelin basic protein, galactocerebrosides and gangliosides, but not to double-stranded DNA. The elevated titres observed may be a consequence of the polyclonal B cell activation that is believed to occur in African trypanosomiasis, parasite epitopes that are cross-reactive with these central nervous system (CNS)-specific antigens or result from the CNS-damage associated with sub-curative chemotherapy

Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement

Item does not contain fulltextIMPORTANCE: Systematic reviews and meta-analyses of individual participant data (IPD) aim to collect, check, and reanalyze individual-level data from all studies addressing a particular research question and are therefore considered a gold standard approach to evidence synthesis. They are likely to be used with increasing frequency as current initiatives to share clinical trial data gain momentum and may be particularly important in reviewing controversial therapeutic areas. OBJECTIVE: To develop PRISMA-IPD as a stand-alone extension to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, tailored to the specific requirements of reporting systematic reviews and meta-analyses of IPD. Although developed primarily for reviews of randomized trials, many items will apply in other contexts, including reviews of diagnosis and prognosis. DESIGN: Development of PRISMA-IPD followed the EQUATOR Network framework guidance and used the existing standard PRISMA Statement as a starting point to draft additional relevant material. A web-based survey informed discussion at an international workshop that included researchers, clinicians, methodologists experienced in conducting systematic reviews and meta-analyses of IPD, and journal editors. The statement was drafted and iterative refinements were made by the project, advisory, and development groups. The PRISMA-IPD Development Group reached agreement on the PRISMA-IPD checklist and flow diagram by consensus. FINDINGS: Compared with standard PRISMA, the PRISMA-IPD checklist includes 3 new items that address (1) methods of checking the integrity of the IPD (such as pattern of randomization, data consistency, baseline imbalance, and missing data), (2) reporting any important issues that emerge, and (3) exploring variation (such as whether certain types of individual benefit more from the intervention than others). A further additional item was created by reorganization of standard PRISMA items relating to interpreting results. Wording was modified in 23 items to reflect the IPD approach. CONCLUSIONS AND RELEVANCE: PRISMA-IPD provides guidelines for reporting systematic reviews and meta-analyses of IPD