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- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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- Johansson, Fredrik, 1988, et al.
(författare)
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Predicting response to tocilizumab monotherapy in rheumatoid arthritis: A real-world data analysis using machine learning
- 2021
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 1499-2752 .- 0315-162X. ; 48:9, s. 1364-1370
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Tocilizumab (TCZ) has shown similar efficacy when used as monotherapy as in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCTs). We derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data and performed an external validation of the prediction score using real-world data (RWD). Methods. We identified patients in the Corrona RA registry who used TCZm (n = 452), and matched the design and patients from 4 RCTs used in previous work (n = 853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic disease-modifying antirheumatic drug monotherapies (bDMARDm) to improve prediction. Results. The fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n = 53) in RWD vs 15% (n = 127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTs, with area under the receiver-operating characteristic curve (AUROC) of 0.69 (95% CI 0.62-0.75). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on held-out TCZm patients to 0.72 (95% CI 0.63-0.81). Extending the variable set and adding regularization further increased it to 0.76 (95% CI 0.67-0.84). Conclusion. The remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD.
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- Ohlin, Mats, et al.
(författare)
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Inferred Allelic Variants of Immunoglobulin Receptor Genes : A System for Their Evaluation, Documentation, and Naming
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.
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- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 8. |
- Solomon, Daniel H., et al.
(författare)
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The sequence of disease-modifying anti-rheumatic drugs: pathways to and predictors of tocilizumab monotherapy
- 2021
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are numerous non-biologic and biologic disease-modifying anti-rheumatic drugs (bDMARDs) for rheumatoid arthritis (RA). Typical sequences of bDMARDs are not clear. Future treatment policies and trials should be informed by quantitative estimates of current treatment practice. Methods: We used data from Corrona, a large real-world RA registry, to develop a method for quantifying sequential patterns in treatment with bDMARDs. As a proof of concept, we study patients who eventually use tocilizumab monotherapy (TCZm), an IL-6 antagonist with similar benefits used as monotherapy or in combination. Patients starting a bDMARD were included and were followed using a discrete-state Markov model, observing changes in treatments every 6 months and determining whether they used TCZm. A supervised machine learning algorithm was then employed to determine longitudinal patient factors associated with TCZm use. Results: 7300 patients starting a bDMARD were followed for up to 5 years. Their median age was 58 years, 78% were female, median disease duration was 5 years, and 57% were seropositive. During follow-up, 287 (3.9%) reported use of TCZm with median time until use of 25.6 (11.5, 56.0) months. Eighty-two percent of TCZm use began within 3 years of starting any bDMARD. Ninety-three percent of TCZm users switched from TCZ combination, a TNF inhibitor, or another bDMARD. Very few patients are given TCZm as their first DMARD (0.6%). Variables associated with the use of TCZm included prior use of TCZ combination therapy, older age, longer disease duration, seronegative, higher disease activity, and no prior use of a TNF inhibitor. Conclusions: Improved understanding of treatment sequences in RA may help personalize care. These methods may help optimize treatment decisions using large-scale real-world data.
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- Soranno, Patricia A., et al.
(författare)
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LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
- 2017
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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| 10. |
- Tran-Gia, Johannes, et al.
(författare)
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On the use of solid 133Ba sources as surrogate for liquid 131I in SPECT/CT calibration : a European multi-centre evaluation
- 2023
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Ingår i: EJNMMI Physics. - 2197-7364. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging. Materials and methods: Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68–107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I. Results: As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12–1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction. Conclusion: This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.
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