Formalization and computation of quality measures based on electronic medical records

Ambiguous definitions of quality measures in natural language impede their automated computability and also the reproducibility, validity, timeliness, traceability, comparability, and interpretability of computed results. Therefore, quality measures should be formalized before their release. We have previously developed and successfully applied a method for clinical indicator formalization (CLIF). The objective of our present study is to test whether CLIF is generalizable--that is, applicable to a large set of heterogeneous measures of different types and from various domains. We formalized the entire set of 159 Dutch quality measures for general practice, which contains structure, process, and outcome measures and covers seven domains. We relied on a web-based tool to facilitate the application of our method. Subsequently, we computed the measures on the basis of a large database of real patient data. Our CLIF method enabled us to fully formalize 100% of the measures. Owing to missing functionality, the accompanying tool could support full formalization of only 86% of the quality measures into Structured Query Language (SQL) queries. The remaining 14% of the measures required manual application of our CLIF method by directly translating the respective criteria into SQL. The results obtained by computing the measures show a strong correlation with results computed independently by two other parties. The CLIF method covers all quality measures after having been extended by an additional step. Our web tool requires further refinement for CLIF to be applied completely automatically. We therefore conclude that CLIF is sufficiently generalizable to be able to formalize the entire set of Dutch quality measures for general practic

Focus on autonomy: Using 'Skills for Growing Up' in pediatric rehabilitation care

PURPOSE: Youth with disabilities face challenges regarding achieving autonomy. The 'Skills for Growing Up' tool was adapted for use in Dutch pediatric rehabilitation (SGU-D) to support development of autonomy. This study presents the experiences with the SGU-D tool. METHODS: The SGU-D was implemented in 18 settings, of which 4 participated in the evaluation. Rehabilitation professionals were trained in the use of the SGU-D. In a qualitative study, participants were interviewed for their opinions regarding the tool. RESULTS: Experience with the SGU-D was evaluated in 11 youth with disabilities, 11 parents and 8 rehabilitation professionals. They perceived the SGU-D as a helpful tool: i) to support development of autonomy, ii) to focus on future perspectives, and iii) to facilitate communication with family and rehabilitation professionals. Additional support from rehabilitation professionals on using the SGU-D was appreciated. CONCLUSION: Youth with disabilities, their parents and rehabilitation professionals value the SGU-D as a practical tool for working on autonomy, and to identify important areas of development

Experimental Probes of Localized Gravity: On and Off the Wall

The phenomenology of the Randall-Sundrum model of localized gravity is analyzed in detail for the two scenarios where the Standard Model (SM) gauge and matter fields are either confined to a TeV scale 3-brane or may propagate in a slice of five dimensional anti-deSitter space. In the latter instance, we derive the interactions of the graviton, gauge, and fermion Kaluza-Klein (KK) states. The resulting phenomenological signatures are shown to be highly dependent on the value of the 5-dimensional fermion mass and differ substantially from the case where the SM fields lie on the TeV-brane. In both scenarios, we examine the collider signatures for direct production of the graviton and gauge KK towers as well as their induced contributions to precision electroweak observables. These direct and indirect signatures are found to play a complementary role in the exploration of the model parameter space. In the case where the SM field content resides on the TeV-brane, we show that the LHC can probe the full parameter space and hence will either discover or exclude this model if the scale of electroweak physics on the 3-brane is less than 10 TeV. We also show that spontaneous electroweak symmetry breaking of the SM must take place on the TeV-brane.Comment: 62 pages, Latex, 22 figure

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Nasal polyposis: Advances in diagnosis and management

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic disease which has a significant negative impact on the quality of life (QoL). Despite decades of research, still a group of patients remain symptomatic under current state-of-the-art medical and surgical treatment. This thesis focused on analyzing and thereby optimizing different treatments and obtaining further insight in the pathophysiologic mechanisms of CRSwNP. We describe a trial with mepolizumab, which demonstrates a statistically significant reduction of patients eligible for surgery 4 weeks after the last dose in the mepolizumab group compared with placebo. This suggests that mepolizumab might offer a viable alternative to surgery in a selected group of patients with severe CRSwNP. Furthermore we demonstrate that operating patients with CRSwNP with the microdebrider on top of traditional instruments is safe and very time efficient. We performed a systematic review and meta-analysis of randomised controlled trials for operative outcomes on the perioperative role of corticosteroids. Next we showed that FESS is a very effective and safe treatment in children with CRSwNP even in children with CF. We performed micro-array expression profiling on epithelial cells from CRSwNP patients and healthy controls, where we showed that many of the 27 significantly different genes could be linked to pathogenic mechanisms in neoplasm formation and cell cycle control. Furthermore we showed that the active disease duration of CRSwNP is relatively constant at about eleven years, regardless of the age of onset. This could be a first indication that CRSwNP is a self-limiting disease

Convolutional neural network allows amylose content prediction in yam (Dioscorea alata L.) flour using near infrared spectroscopy

Background: Yam (Dioscorea alata L.) is the staple food of many populations in the intertropical zone where it is grown. The lack of phenotyping methods for tuber quality hinders the adoption of new genotypes from the breeding programs. Recently, near infrared spectroscopy (NIRS) has been used as a reliable tool to characterize the chemical composition of the yam tuber. However, it failed to predict the amylose content, although this trait is strongly involved in the quality of the product. Results: This study used NIRS to predict the amylose content from 186 yam flour samples. Two calibration methods were developed and validated on an independent dataset: Partial Least Square (PLS) and Convolutional Neural Network (CNN). To evaluate final model performances, the coefficient of determination (R2 ), the root mean square error (RMSE), and the Ratio of Performance to Deviation (RPD) were calculated using predictions on an independent validation dataset. Tested models showed contrasting performances (i.e. R2 of 0.72 and 0.89, RMSE of 1.33 and 0.81, RPD of 2.13 and 3.49 respectively, for the PLS and the CNN model). Conclusion: According to the quality standard for NIRS model prediction used in food science, the PLS method proved unsuccessful (RPD<3 and R2 <0.8) for predicting amylose content from yam flour, while the CNN proved reliable and efficient method. With the application of deep learning method, this study established the proof of concept that amylose content, a key driver of yam textural quality and acceptance, could be predicted accurately using NIRS as a high throughput phenotyping method. This article is protected by copyright. All rights reserved

Therapeutic effect of a peptide inhibitor of TGF-β on pulmonary fibrosis

Pulmonary fibrosis encompasses several respiratory diseases characterized by epithelial cell injury, inflammation and fibrosis. Transforming growth factor (TGF)-β1 is one of the main profibrogenic cytokines involved in the pathogenesis of lung fibrosis. It induces fibroblast differentiation into myofibroblasts, which produce high levels of collagen and concomitantly loss of lung elasticity and reduction of the respiratory function. In the present study, we have investigated the effects of P17 (a TGF-β inhibitor peptide) on IMR-90 lung fibroblast differentiation in vitro, as well as on the inhibition of the development of bleomycin-induced pulmonary fibrosis in mice. It was found that in IMR-90 cells, P17 inhibited TGF-β1-induced expression of connective tissue growth factor and α-smooth muscle actin. In vivo, treatment of mice with P17 2days after bleomycin administration decreased lung fibrosis, areas of myofibroblast-like cells and lymphocyte infiltrate. P17 also reduced mRNA expression of collagen type I, fibronectin and the fibronectin splice isoform EDA in the lung, and increased the expression of IFN-γ mRNA. Finally, therapeutic treatment with P17 in mice with already established fibrosis was able to significantly attenuate the progression of lung fibrosis. These results suggest that P17 may be useful in the treatment of pulmonary fibrosis

The international sinonasal microbiome study (ISMS): a multi-centre, multi-national characterization of sinonasal bacterial ecology

First published: 13 March 2020The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterise the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus, and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; p = 0.02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardised methodology described within our study will enable further characterisation and translational application of the sinus microbiota.Sathish Paramasivan, Ahmed Bassiouni ... Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis ... Sarah Vreugde ... et al