Multisource and temporal variability in Portuguese hospital administrative datasets: Data quality implications

[EN] Background: Unexpected variability across healthcare datasets may indicate data quality issues and thereby affect the credibility of these data for reutilization. No gold-standard reference dataset or methods for variability assessment are usually available for these datasets. In this study, we aim to describe the process of discovering data quality implications by applying a set of methods for assessing variability between sources and over time in a large hospital database. Methods: We described and applied a set of multisource and temporal variability assessment methods in a large Portuguese hospitalization database, in which variation in condition-specific hospitalization ratios derived from clinically coded data were assessed between hospitals (sources) and over time. We identified condition-specific admissions using the Clinical Classification Software (CCS), developed by the Agency of Health Care Research and Quality. A Statistical Process Control (SPC) approach based on funnel plots of condition-specific standardized hospitalization ratios (SHR) was used to assess multisource variability, whereas temporal heat maps and Information-Geometric Temporal (IGT) plots were used to assess temporal variability by displaying temporal abrupt changes in data distributions. Results were presented for the 15 most common inpatient conditions (CCS) in Portugal. Main findings: Funnel plot assessment allowed the detection of several outlying hospitals whose SHRs were much lower or higher than expected. Adjusting SHR for hospital characteristics, beyond age and sex, considerably affected the degree of multisource variability for most diseases. Overall, probability distributions changed over time for most diseases, although heterogeneously. Abrupt temporal changes in data distributions for acute myocardial infarction and congestive heart failure coincided with the periods comprising the transition to the International Classification of Diseases, 10th revision, Clinical Modification, whereas changes in the DiagnosisRelated Groups software seem to have driven changes in data distributions for both acute myocardial infarction and liveborn admissions. The analysis of heat maps also allowed the detection of several discontinuities at hospital level over time, in some cases also coinciding with the aforementioned factors. Conclusions: This paper described the successful application of a set of reproducible, generalizable and systematic methods for variability assessment, including visualization tools that can be useful for detecting abnormal patterns in healthcare data, also addressing some limitations of common approaches. The presented method for multisource variability assessment is based on SPC, which is an advantage considering the lack of gold standard for such process. Properly controlling for hospital characteristics and differences in case-mix for estimating SHR is critical for isolating data quality-related variability among data sources. The use of IGT plots provides an advantage over common methods for temporal variability assessment due its suitability for multitype and multimodal data, which are common characteristics of healthcare data. The novelty of this work is the use of a set of methods to discover new data quality insights in healthcare data.The authors would like to thank the Central Authority for Health Services, I.P. (ACSS) for providing access to the data. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI) and by Portuguese funds through FCT- Fundacao para a Ciencia e a Tecnologia in the framework of the project POCI-01-0145-FEDER-030766 ("1st.IndiQare-Quality indicators in primary health care: validation and implementation of quality indicators as an assessment and comparison tool") . In addition, we would like to thank to projects GEMA (SBPLY/17/180501/000293) -Generation and Evaluation of Models for Data Quality, and ADAGIO (SBPLY/21/180501/000061) - Alarcos Data Governance framework and systems generation, both funded by the Department of Education, Culture and Sports of the JCCM and FEDER; and to AETHER-UCLM: A smart data holistic approach for context -aware data analytics focused on Quality and Security project (Ministerio de Ciencia e Innovacion, PID2020- 112540RB-C42) . CSS thanks the Universitat Politecnica de Valencia contract no. UPV-SUB.2-1302 and FONDO SUPERA COVID-19 by CRUE- Santander Bank grant "Severity Subgroup Discovery and Classification on COVID-19 Real World Data through Machine Learning and Data Quality assessment (SUBCOVERWD-19) ."Souza, J.; Caballero, I.; Vasco Santos, J.; Lobo, M.; Pinto, A.; Viana, J.; Sáez Silvestre, C.... (2022). Multisource and temporal variability in Portuguese hospital administrative datasets: Data quality implications. Journal of Biomedical Informatics. 136:1-11. https://doi.org/10.1016/j.jbi.2022.10424211113

Infecção sistêmica fatal por Mortierella wolfii em um bezerro neonato na região Sul do Brasil

This study described the pathological and microbiological aspects of a fatal systemic Mortierella wolfii infection in a neonatal calf in southern Brazil. The calf was born clinically normal, but on the third day of life it presented apathy, unilateral hypopyon, and neurological signs, and in the next day it was euthanized. At necropsy, multiple soft, and white-yellow nodules were observed in the liver, spleen, kidneys, mesenteric lymph nodes, heart, and lungs. In the brain, reddish, and friable areas were found. In the eye, there were anterior and posterior synechiae, diffuse thickening of choroid, and anterior chamber filled by whitish and friable material. Microscopically, areas of necrosis, pyogranulomatous inflammation, vasculitis, thrombosis, and intralesional fungal hyphae were observed, and the latter were better evidenced through Grocott Methenamine Silver technique. The fungus was identified as M. wolfii through mycological culture and molecular methods. To our knowledge, this is the first description of systemic disease caused by M. wolfii in a neonatal calf outside of Oceania.Descrevem-se os aspectos patológicos e microbiológicos de uma infecção sistêmica fatal por Mortierella wolfii em um bezerro neonato na região Sul do Brasil. O bezerro nasceu clinicamente normal, porém no terceiro dia de vida apresentou apatia, hipópion unilateral e sinais neurológicos, e no dia seguinte foi submetido à eutanásia. Na necropsia, foram observados múltiplos nódulos macios e branco-amarelados no fígado, baço, rins, linfonodos mesentéricos, coração e pulmões. No encéfalo, havia áreas avermelhadas e friáveis. No olho, notou-se sinéquia anterior e posterior, espessamento difuso da coroide, e câmara anterior preenchida por material brancacento e friável. Histologicamente, foram observadas áreas de necrose, inflamação piogranulomatosa, vasculite, trombose e hifas fúngicas intralesionais, que foram melhor visualizadas por meio da técnica de Prata Metenamina de Grocott. O fungo foi identificado como M. wolfii por meio da cultura micológica e técnicas moleculares. Com base no conhecimento dos autores, este é o primeiro relato de doença sistêmica causada por M. wolfii em um bezerro neonato fora da Oceania

Longitudinal strain is an independent predictor of survival and response to therapy in patients with systemic AL amyloidosis

AIMS: Cardiac involvement, a major determinant of prognosis in AL (light-chain immunoglobulin) amyloidosis, is characterized by an impairment of longitudinal strain (LS%). We sought to evaluate the utility of LS% in a prospectively observed series of patients. METHODS AND RESULTS: A total of 915 serial newly diagnosed AL patients with comprehensive baseline assessments, inclusive of echocardiography, were included. A total of 628/915 (68.6%) patients had cardiac involvement. The LS% worsened with advancing cardiac stage with mean −21.1%, −17.1%, −12.9%, and −12.1% for stages I, II, IIIa, and IIIb, respectively (P < 0.0001). There was a highly significant worsening of overall survival (OS) with worsening LS% quartile: LS% ≤−16.2%: 80 months, −16.1% to −12.2%: 36 [95% confidence interval (CI) 20.9–51.1] months, −12.1% to −9.1%: 22 (95% CI 9.1–34.9) months, and ≥−9.0%: 5 (95% CI 3.2–6.8) months (P < 0.0001). Improvement in LS% was seen at 12 months in patients achieving a haematological complete response (CR) (median improvement from −13.8% to −14.9% in those with CR and difference between involved and uninvolved light chain <10 mg/L). Strain improvement was associated with improved OS (median not reached at 53 months vs. 72 months in patients without strain improvement, P = 0.007). Patients achieving an LS% improvement and a standard N-terminal pro-brain natriuretic peptide-based cardiac response survived longer than those achieving a biomarker-based cardiac response alone (P < 0.0001). CONCLUSION: Baseline LS% is a functional marker that correlates with worsening cardiac involvement and is predictive of survival. Baseline LS% and an absolute improvement in LS% are useful additional measures of prognosis and response to therapy in cardiac AL amyloidosis, respectively

Lipossomas miméticos de exossomas: composição e uso

info:eu-repo/semantics/publishedVersio

Developmental neurotoxic effect of nanoparticles: towards real-time assessment using zebrafish embryos as vertebrate model

Exposure to neurotoxic agents during embryonic development can cause irreparable short- and long-term damage to vertebrates, including for humans, as it may affect the central nervous system (CNS) and the blood brain barrier (BBB)[1]. The reported CNS susceptibility during embryogenesis suggests that there may be a critical window of exposure during brain development. Nowadays, therapies using nanoparticles are an important alternative for most of the diseases, since they allow, for example, more effective and localized delivery of drugs and higher success in treatments [2]. However, the exposure to them at an embryonic stage can cause neurotoxic damages. In this study, the putative toxicity of two different nanoparticle formulations was evaluated, namely gold nanoparticles, which were produced by Green synthesis, and liposomal nanoparticles. Both have known and interesting bioactivities, such as anti-inflammatory, antioxidant, antifungal and antibacterial[3][4]. Thus the capacity of the neuroprotective effect of the nanoparticles in contact with toxins was tested, the evaluation was done through the ZET assay. with the endpoits shown in the figure and following parameters, mortality, epiboly, malformation, heart beat, spotaneus movements, hedd-trunk angle, hatching and free-swimming. 2D cell models are easy to reproduce, however they fail to mimic real conditions. Animal models are better than 2D models, however many ethical problems are involved. Zebrafish embryos compose a low-cost and highly informative non- animal alternative to evaluate early developmental responses associated with neurotoxicity[5][6]. As model has multiple advantages for its use in toxicity tests including ex-utero fertilization, transparency of the embryos which allow observations at real time, rapid development and high fecundity[5][6]. Zebrafish embryos possess neural development characteristics similar to the vertebrate ones, which makes them ideal to assess embryo neurotoxicity in vivo. Obtained results show that zebrafish is a profitable and reliable model organism for neurotoxicity tests. Nevertheless, there is a need to continue these neurotoxic tests in more complex models so that these nanoparticles can become an alternative therapy.This work was supported by the strategic programme UID/BIA/04050/2019, funded by national funds through the FCT IP, and project FUN2CYT: Harnessing the potential for biomedical applications of pleiotropic cytokines LIF and oncostatin M (PTDC/BTM-MAT/30568/2017, POCI-01-0145-FEDER-030568) supported by POCI through FEDER and FCT IP

Infecção sistêmica fatal por Mortierella wolfii em um bezerro neonato na região Sul do Brasil

This study described the pathological and microbiological aspects of a fatal systemic Mortierella wolfii infection in a neonatal calf in southern Brazil. The calf was born clinically normal, but on the third day of life it presented apathy, unilateral hypopyon, and neurological signs, and in the next day it was euthanized. At necropsy, multiple soft, and white-yellow nodules were observed in the liver, spleen, kidneys, mesenteric lymph nodes, heart, and lungs. In the brain, reddish, and friable areas were found. In the eye, there were anterior and posterior synechiae, diffuse thickening of choroid, and anterior chamber filled by whitish and friable material. Microscopically, areas of necrosis, pyogranulomatous inflammation, vasculitis, thrombosis, and intralesional fungal hyphae were observed, and the latter were better evidenced through Grocott Methenamine Silver technique. The fungus was identified as M. wolfii through mycological culture and molecular methods. To our knowledge, this is the first description of systemic disease caused by M. wolfii in a neonatal calf outside of Oceania.Descrevem-se os aspectos patológicos e microbiológicos de uma infecção sistêmica fatal por Mortierella wolfii em um bezerro neonato na região Sul do Brasil. O bezerro nasceu clinicamente normal, porém no terceiro dia de vida apresentou apatia, hipópion unilateral e sinais neurológicos, e no dia seguinte foi submetido à eutanásia. Na necropsia, foram observados múltiplos nódulos macios e branco-amarelados no fígado, baço, rins, linfonodos mesentéricos, coração e pulmões. No encéfalo, havia áreas avermelhadas e friáveis. No olho, notou-se sinéquia anterior e posterior, espessamento difuso da coroide, e câmara anterior preenchida por material brancacento e friável. Histologicamente, foram observadas áreas de necrose, inflamação piogranulomatosa, vasculite, trombose e hifas fúngicas intralesionais, que foram melhor visualizadas por meio da técnica de Prata Metenamina de Grocott. O fungo foi identificado como M. wolfii por meio da cultura micológica e técnicas moleculares. Com base no conhecimento dos autores, este é o primeiro relato de doença sistêmica causada por M. wolfii em um bezerro neonato fora da Oceania

Association between obesity and amino acids: a metabolomics approach

Conselho Nacional de Desenvolvimento Científico e Tecnologico (CNPq)Fundação de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Sao Paulo, Nutr, Sao Paulo, BrazilUniv Fed Sao Paulo, Ginecol, Sao Paulo, BrazilUniv Fed Sao Paulo, Ginecol, Sao Paulo, BrazilCNPq: 473778/2010-6FAPESP: 2011/19788-1Web of Scienc

Pneumonia by Cryptococcus neoformans in a goat in the Southern region of Brazil

ABSTRACT: This report describes the clinical, pathological, and molecular aspects of a pneumonia by Cryptococcus neoformans in a goat in the Southern region of Brazil. A goat with a history of prolonged transportation presented dyspnea, nasal discharge and cough, and was subjected to necropsy, histopathology, and mycological evaluation. Grossly, cranio-ventral pulmonary consolidation was observed, characterized by firm and grayish areas interspersed with dark red foci. Histopathology of the lungs showed areas of parenchymal necrosis, containing blastoconidia with a slightly basophilic central cell, surrounded by an unstained capsule. It was associated with moderate granulomatous inflammatory infiltrate and peripheral fibrosis. The capsule and fungus cell exhibited marked Alcian Blue and periodic acid-Schiff staining, respectively. Diagnosis of fungal pneumonia by C. neoformans was based on clinical, pathological, and molecular findings

Novel and efficient transformation of wild passion fruit (Passiflora cincinnata Mast.) using sonication-assisted Agrobacterium-mediated transformation

Passiflora cincinnata stands out among Passifloraceae because of its medicinal properties and its resistance to pathogens, which promotes its use as a rootstock for other Passiflora species. A valuable strategy for obtaining disease-resistant passion fruit plants is represented by genetic transformation; however, this requires efficient regeneration. Here, we aimed to establish an efficient protocol for generating transgenic passion fruit plants using sonication-assisted Agrobacterium-mediated transformation of somatic embryos. The latter were obtained from anthers, sonicated, and exposed to an Agrobacterium suspension for 15 or 30 s. As a comparison, non-sonicated embryos were also exposed to the same bacterial treatment, whereas non-infected embryos were used as controls. Plant identity was confirmed by PCR, qPCR, and histochemical assay. Transgenic plants were obtained at higher rates in the treatments applying sonication. Overall, 171 plantlets were regenerated, 38 of which showed stable uidA reporter gene expression. Of these 38 transgenic plants, 22 (57.89%) and 13 (34.21%) were obtained by sonication-assisted Agrobacterium-mediated transformation for 30 s and 15 s, respectively, whereas the remaining 3 (7.89%) were exposed for 30 s but without prior sonication. Our results indicate that sonication-assisted Agrobacterium-mediated transformation for 30 s enhanced transformation efficiency in P. cincinnata. We believe that this system will allow for more efficient production of transgenic passion fruit plants

In vitro regeneration of triploid plants from mature endosperm culture of commercial passionfruit (Passiflora edulis Sims)

Due to the triploid nature of endosperm, an embryonic reserve tissue, in vitro culture of endosperm tissues has been considered a direct method for production of polyploids. In the present study, we report the establishment of an in vitro regeneration system from endosperm culture for production of triploid Passiflora edulis plants, the main commercial species of passionfruit. Surface-sterilized endosperms were cultured in MS medium with different concentrations of benzyladenine (BA), thidiazuron (TDZ), and kinetin (KIN). The cultures were maintained in a growth chamber under controlled conditions, for 60 days. Thidiazuron was the only type of cytokinin that induced shoot production in the endosperm tissues; the highest number of shoots was produced in the presence of 4.5 and 9.0 μM TDZ. Flow cytometry and chromosomal analysis confirmed that endosperm-derived plants were triploid. The internal standard, Pisum sativum, and the diploid control, seed-derived Passiflora edulis plants (2n = 2× = 18), showed average DNA quantities of 9.09 and 3.35 pg respectively. Endosperm-derived P. edulis plants showed an average DNA content of 5.10 pg and a chromosome count of 27 (3n = 3× = 27), the same ploidy level as the endosperm (triploid). Our data open new prospects for breeding of passionfruit by means of a stable and reproducible regeneration system from endosperm culture leading to generation of triploid plants