| 1. |
- Garnier, Nicolas, et al.
(författare)
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Genetic newborn screening and digital technologies : A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe
- 2023
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.
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| 2. |
- Rudolf, Frauke, et al.
(författare)
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Increasing smear positive tuberculosis detection using a clinical score - A stepped wedge multicenter trial from Africa
- 2021
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Ingår i: International Journal of Infectious Diseases. - : Elsevier Science Ltd. - 1201-9712 .- 1878-3511. ; 113, s. S55-S62
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Bandim TBscore is a clinical score that predicts treatment outcome in Tuberculosis (TB) patients and proved useful as an indicator of which healthcare-seeking adults to refer for sputum smear microcopy. We aimed to test in a randomized trial if the TBscore could be used to enhance the detection of smear positive (SP) TB. Methods: We carried out a stepped wedge cluster-randomized trial at six health centers in Bissau, GuineaBissau, and Gondar, Ethiopia. The primary outcome was diagnostic yield for SP TB. Secondary outcomes were successful treatment and effect on overall 12 months mortality. The study was registered at the Pan African Clinical Trials Registry (PACTR201611001838365). Results: We included 3571 adults. Overall, there was no effect of the intervention on SP PTB detected (OR 1.39 (95%CI 0.75 - 2.56). Analysis stratified by country, showed that the TBscore increased case detection in Gondar (OR 4.05 (95%CI 1.67 - 9.85)) but no effect was found in Bissau (OR 0.47 (95%CI 0.22 - 1.05)) where take-up was much lower. Overall mortality decreased during the intervention (HR 0.31 (95%CI 0.13-0.72)). Conclusion: Using the TBscore for triage before smear microscopy may improve case detection and decrease mortality if there is sufficient laboratory capacity to increase sputum smears. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
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| 3. |
- Rudolf, Frauke, et al.
(författare)
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TBscore II: Refining and validating a simple clinical score for treatment monitoring of patients with pulmonary tuberculosis
- 2013
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 45:11, s. 825-836
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Tidskriftsartikel (refereegranskat)abstract
- Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start score and failure (i.e. death or treatment failure), responsiveness using Cohens effect size, and the relationship between severity class at treatment start and a decrease andlt; 25% in score from the start until the end of the second treatment month and subsequent mortality. Results: We analyzed data from 1070 Guinean (2003-2012) and 432 Ethiopian (2007-2012) pulmonary tuberculosis patients. For the refined score, items with less than substantial agreement (kappa andlt;= 0.6) and/or not associated with the underlying constructs were excluded. Items kept were: cough, dyspnea, chest pain, anemia, body mass index (BMI) andlt; 18 kg/m(2), BMI andlt; 16 kg/m(2), mid upper arm circumference (MUAC) andlt; 220 mm, and MUAC andlt; 200 mm. The effect sizes for the change between the start of treatment and the 2-month follow-up were 0.51 in Guinea-Bissau and 0.68 in Ethiopia, and for the change between the start of treatment and the end of treatment were 0.68 in Guinea-Bissau and 0.74 in Ethiopia. Severity class placement at treatment start predicted failure (p andlt; 0.001 Guinea-Bissau, p = 0.208 Ethiopia). Inability to decrease at least 25% in score was associated with a higher failure rate during the remaining 4 months of treatment (p = 0.063 Guinea-Bissau, p = 0.008 Ethiopia). Conclusion: The TBscore II could be a useful monitoring tool, aiding triage at the beginning of treatment and during treatment.
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| 4. |
- Thysen, Sanne M., et al.
(författare)
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Neonatal BCG vaccination and child survival in TB-exposed and TB-unexposed children : A prospective cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess the association between neonatal BCG vaccination and mortality between 28 days and 3 years of age among tuberculosis (TB)-exposed and TB-unexposed children. Design Prospective cohort study. Setting Bandim Health Project runs an urban Health and Demographic Surveillance site in Guinea-Bissau with registration of mortality, vaccination status and TB cases. Participants Children entered the analysis when their vaccination card was inspected after 28 days of age and remained under surveillance to 3 years of age. Children residing in the same house as a TB case were classified as TB-exposed from 3 months prior to case registration to the end of follow-up. Methods Using Cox-proportional hazards models with age as underlying time scale, we compared mortality of children with and without neonatal BCG between October 2003 and September 2017. Main outcome measure HR for neonatal BCG compared with no neonatal BCG by TB-exposure status. Results Among the 39 421 children who entered the analyses, 3022 (8%) had observation time as TB-exposed. In total, 84% of children received neonatal BCG. Children with neonatal BCG had lower mortality both in TB-exposed (adjusted HR: 0.57 (0.26 to 1.27)) and in TB-unexposed children (HR: 0.57 (95% CI 0.47 to 0.69)) than children without neonatal BCG. Children exposed to TB had higher mortality than TB-unexposed children if they had not received neonatal BCG. Conclusion Neonatal BCG vaccination was associated with lower mortality among both TB-exposed and TB-unexposed children, consistent with neonatal BCG vaccination having beneficial non-specific effects. Interventions to increase timely BCG vaccination are urgently warranted.
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