Do we need another trial on exercise in patients with knee osteoarthritis?: No new trials on exercise in knee OA

© 2019 Osteoarthritis Research Society International Objective: We aim to investigate if we need additional trials on exercise in knee osteoarthritis (OA) to accept a certain effect size to be a ‘true’ effect size, and new studies are not needed anymore. Design: We performed a secondary analyses of a meta-analysis of studies on patients with knee osteoarthritis, on pain immediately post treatment. We performed five different analysis: a) we evaluated publication bias, b) we performed subgroup analysis, c) a sensitivity analysis based on the overall risk of bias (RoB) score, d) a cumulative meta-analysis and e) we developed an extended funnel plot to explore the potential impact of a new study on the summary effect estimate. Results: We included 42 studies with in total 6863 patients. The analyses showed that a) there is no clear publication bias, b) subgrouping did not affect the overall effect estimate, c) the effect estimate of exercise is more consistent (no heterogeneity) in the studies of low RoB, d) the benefit of exercise was clear since 2010 and e) the extended funnel plot suggests that an additional study has a none or very limited impact to change the current effect estimate. Conclusion: Exercise is effective and clinically worthwhile in reducing pain immediately post treatment compared to no or minimal interventions in patients with knee OA and adding new data will unlikely change this conclusion

Responders to Exercise Therapy in Patients with Osteoarthritis of the Hip: A Systematic Review and Meta-Analysis.

The Outcome Measures in Rheumatology workgroup (OMERACT), together with the Osteoarthritis Research Society International (OARSI) developed the OMERACT-OARSI responder criteria. These criteria are used to determine if a patient with osteoarthritis (OA) 'responds' to therapy, meaning experiences a clinically relevant effect of therapy. Recently, more clinical OA trials report on this outcome and most OA trials have data to calculate the number of responders according to these criteria. A systematic review and meta-analysis were performed on the response to exercise therapy, compared to no or minimal intervention in patients with hip OA using the OMERACT-OARSI responder criteria. The literature was searched for relevant randomized trials. If a trial fit the inclusion criteria, but number of responders was not reported, the first author was contacted. This way the numbers of responders of 14 trials were collected and a meta-analysis on short term (directly after treatment, 12 trials n = 1178) and long term (6-8 months after treatment, six trials n = 519) outcomes was performed. At short term, the risk difference (RD) was 0.14 (95% confidence interval (CI) 0.06-0.22) and number needed to treat (NNT) 7.1 (95% CI 4.5-17); at long term RD was 0.14 (95% CI 0.07-0.20) and NNT 7.1 (95% CI 5.0-14.3). Quality of evidence was moderate for the short term and high for the long term. In conclusion, 14% more hip OA patients responded to exercise therapy than to no therapy

Weierstrass meets Enriques

We study in detail the degeneration of K3 to T^4/Z_2. We obtain an explicit embedding of the lattice of collapsed cycles of T^4/Z_2 into the lattice of integral cycles of K3 in two different ways. Our first method exploits the duality to the heterotic string on T^3. This allows us to describe the degeneration in terms of Wilson lines. Our second method is based on the blow-up of T^4/Z_2. From this blow-up, we directly construct the full lattice of integral cycles of K3. Finally, we use our results to describe the action of the Enriques involution on elliptic K3 surfaces, finding that a Weierstrass model description is consistent with the Enriques involution only in the F-theory limit.Comment: 35 pages, 9 figure

Giant aneurysm of the atrial septum associated with premature closure of foramen ovale

Premature closure or restriction of foramen ovale (PCFO) is a rare congenital anomaly that can lead to a wide spectrum of cardiac malformations. This spectrum of secondary malformations appears to depend on the gestational timing of closure of the foramen ovale and to the degree of restriction. Earlier in the gestation, closure of the foramen has been associated with severe hypoplasia of the left ventricle whereas later closure has been associated with right heart failure and rarely with the formation of an aneurysm of the atrial septum. We describe the case of a 1 day old infant in whom PCFO resulted in severe right heart failure in addition to the formation of a giant atrial septal aneurysm

Confiabilidad de un instrumento para clasificar al recién nacido de acuerdo con la complejidad de la atención

Na maioria das maternidades, a classificação, a avaliação e a definição da unidade a encaminhar o recém-nascido (RN) após o nascimento são realizadas pelo médico. A\ud avaliação ocorre na sala de parto considerando: peso ao nascer; idade gestacional;\ud condutas que definem quadro clínico e doença. Este estudo observacional teve\ud como objetivo avaliar a confiabilidade de um instrumento de classificação de RN. A pesquisa foi realizada no berçário de um hospital público, São Paulo. Nove enfermeiras\ud aplicaram o instrumento a 63 RN, sendo duas simultaneamente em cada um dos\ud cinco setores do berçário. Verificou-se que o nível de concordância Kappa entre as enfermeiras foi excelente para a maioria das áreas de cuidado (69,0%). Concluiu-se que houve consenso e concordância das enfermeiras quanto ao instrumento ser completo, de fácil entendimento e aplicável, porém despende muito tempo. As enfermeiras reconhecem a importância do instrumento para o dimensionamento dos profissionais, organização e planejamento do cuidado.In most maternity units, the physician classifies, evaluates, and determines which unit will receive the newborn (NB) after birth. Evaluation occurs in the delivery room, taking into consideration the following factors: birth weight, gestational age, and behaviors that define the clinical picture and disease. This observational study evaluates the reliability of an NB classification instrument. The study was conducted at the nursery of a public hospital in São Paulo. Nine nurses applied the instrument to 63 NB, with two of the nurses working simultaneously in each of the nursery’s fi ve sectors. The Kappa level of agreement among the nurses was found to be excellent for most care areas\ud (69.0%). It was concluded that there was a consensus and agreement among the\ud nurses that the instrument was complete, easy to understand and applicable, but was\ud very time consuming. The nurses recognize the instrument’s importance for the allocation of professionals, organization, and care planning.En la mayoría de las maternidades la clasificación, la evaluación y la definición de la unidad para referir el recién nacido (RN), son realizadas por el médico. La evaluación se realiza en la sala de parto, considerando: peso al nacer, edad gestacional y conductas que definen el cuadro clínico y la enfermedad. Este estudio observacional tuvo como objetivo evaluar la confiabilidad de un instrumento de clasificación del RN. Fue realizada en el servicio de neonatología de un hospital público en Sao Paulo. Nueve enfermeras\ud aplicaron el instrumento a 63 RN, siendo aplicados dos de forma simultánea en los cinco sectores de la unidad neonatal. El nivel de concordancia Kappa fue excelente para la mayoría de las áreas de atención (69,0%). Se concluyó que hubo consenso y\ud concordancia entre las enfermeras, quienes expresaron que el instrumento es completo, fácil de entender y de aplicar, pero se necesita mucho tempo. Las enfermeras reconocen la importancia de este instrumento para dimensionar el número de profesionales, la organización y la planificación de la atención

Three-Dimensional Imaging of the Mouse Neurovasculature with Magnetic Resonance Microscopy

Knowledge of the three-dimensional (3D) architecture of blood vessels in the brain is crucial because the progression of various neuropathologies ranging from Alzheimer's disease to brain tumors involves anomalous blood vessels. The challenges in obtaining such data from patients, in conjunction with development of mouse models of neuropathology, have made the murine brain indispensable for investigating disease induced neurovascular changes. Here we describe a novel method for “whole brain” 3D mapping of murine neurovasculature using magnetic resonance microscopy (μMRI). This approach preserves the vascular and white matter tract architecture, and can be combined with complementary MRI contrast mechanisms such as diffusion tensor imaging (DTI) to examine the interplay between the vasculature and white matter reorganization that often characterizes neuropathologies. Following validation with micro computed tomography (μCT) and optical microscopy, we demonstrate the utility of this method by: (i) combined 3D imaging of angiogenesis and white matter reorganization in both, invasive and non-invasive brain tumor models; (ii) characterizing the morphological heterogeneity of the vascular phenotype in the murine brain; and (iii) conducting “multi-scale” imaging of brain tumor angiogenesis, wherein we directly compared in vivo MRI blood volume measurements with ex vivo vasculature data

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome

<p>Abstract</p> <p>Background</p> <p>Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies.</p> <p>Objectives</p> <p>Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis.</p> <p>Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication.</p> <p>Design</p> <p>The <b>a</b>pproach to a <b>qua</b>ntitative <b>f</b>ollow-up <b>o</b>f <b>n</b>on-<b>t</b>hyroidal <b>i</b>llness <b>s</b>yndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes.</p> <p>The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00591032</p

Adaptation and validation of the Charlson Index for Read/OXMIS coded databases

BACKGROUND: The Charlson comorbidity index is widely used in ICD-9 administrative data, however, there is no translation for Read/OXMIS coded data despite increasing use of the General Practice Research Database (GPRD). Our main objective was to translate the Charlson index for use with Read/OXMIS coded data such as the GPRD and test its association with mortality. We also aimed to provide a version of the comorbidity index for other researchers using similar datasets. METHODS: Two clinicians translated the Charlson index into Read/OXMIS codes. We tested the association between comorbidity score and increased mortality in 146 441 patients from the GPRD using proportional hazards models. RESULTS: This Read/OXMIS translation of the Charlson index contains 3156 codes. Our validation showed a strong positive association between Charlson score and age. Cox proportional models show a positive increasing association with mortality and Charlson score. The discrimination of the logistic regression model for mortality was good (AUC = 0.853). CONCLUSION: We have translated a commonly used comorbidity index into Read/OXMIS for use in UK primary care databases. The translated index showed a good discrimination in our study population. This is the first study to develop a co-morbidity index for use with the Read/OXMIS coding system and the GPRD. A copy of the co-morbidity index is provided for other researchers using similar database