Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates

Clinical epidemiolog

Scrub typhus ecology: a systematic review of Orientia in vectors and hosts

Abstract Scrub typhus, caused by Orientia tsutsugamushi, is an important and neglected vector-borne zoonotic disease with an expanding known distribution. The ecology of the disease is complex and poorly understood, impairing discussion of public health interventions. To highlight what we know and the themes of our ignorance, we conducted a systematic review of all studies investigating the pathogen in vectors and non-human hosts. A total of 276 articles in 7 languages were included, with 793 study sites across 30 countries. There was no time restriction for article inclusion, with the oldest published in 1924. Seventy-six potential vector species and 234 vertebrate host species were tested, accounting for over one million trombiculid mites (‘chiggers’) and 83,000 vertebrates. The proportion of O. tsutsugamushi positivity was recorded for different categories of laboratory test and host species. Vector and host collection sites were geocoded and mapped. Ecological data associated with these sites were summarised. A further 145 articles encompassing general themes of scrub typhus ecology were reviewed. These topics range from the life-cycle to transmission, habitats, seasonality and human risks. Important gaps in our understanding are highlighted together with possible tools to begin to unravel these. Many of the data reported are highly variable and inconsistent and minimum data reporting standards are proposed. With more recent reports of human Orientia sp. infection in the Middle East and South America and enormous advances in research technology over recent decades, this comprehensive review provides a detailed summary of work investigating this pathogen in vectors and non-human hosts and updates current understanding of the complex ecology of scrub typhus. A better understanding of scrub typhus ecology has important relevance to ongoing research into improving diagnostics, developing vaccines and identifying useful public health interventions to reduce the burden of the disease.</jats:p

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Critical realist case studies of foreign subsidiary development

info:eu-repo/semantics/draf

Differences between infants with sepsis with and without thrombocytopenia.

<p>Differences between infants with sepsis with and without thrombocytopenia.</p

Baseline characteristics of Gram positive and Gram negative sepsis groups.

<p>Baseline characteristics of Gram positive and Gram negative sepsis groups.</p

Multivariate analysis of predictors of mortality in neonatal sepsis.

<p>Multivariate analysis of predictors of mortality in neonatal sepsis.</p

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates

\u3cp\u3eOver 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age &lt;34 weeks, admitted to a neonatal intensive care unit, who developed severe thrombocytopenia (platelet count &lt;50×10 \u3csup\u3e9\u3c/sup\u3e/L). The study endpoint was major bleeding. We obtained predictions of bleeding risk using a proportional baselines landmark supermodel. Of 640 included neonates, 71 (11%) had a major bleed. We included the variables gestational age, postnatal age, intrauterine growth retardation, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (interquartile range, 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential instrument for supporting clinical decisions. \u3c/p\u3

Dynamic prediction of bleeding risk in thrombocytopenic preterm neonates

Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age <34 weeks, admitted to a neonatal intensive care unit, who developed severe thrombocytopenia (platelet count <50×10 9/L). The study endpoint was major bleeding. We obtained predictions of bleeding risk using a proportional baselines landmark supermodel. Of 640 included neonates, 71 (11%) had a major bleed. We included the variables gestational age, postnatal age, intrauterine growth retardation, necrotizing enterocolitis, sepsis, platelet count and mechanical ventilation in the model. The median cross-validated c-index was 0.74 (interquartile range, 0.69-0.82). This is a promising dynamic prediction model for bleeding in this population that should be explored further in clinical studies as a potential instrument for supporting clinical decisions