Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.
Hemorrhage and infection are the leading causes of mifepristone-related morbidity and mortality. AERs relied upon by the FDA to monitor mifepristone's postmarketing safety are grossly deficient due to extremely poor quality.
Introduction: The number and outcomes of pregnancies experienced by a woman are consequential determinants of her health status. However, there is no published research comparing the patterns of subsequent pregnancy outcomes following a live birth, natural fetal loss, or induced abortion. Objectives: The objective of this study was to describe the characteristic patterns of subsequent pregnancy outcomes evolving from each of three initiating outcome events (birth, induced abortion, natural fetal loss) occurring in a Medicaid population fully insured for all reproductive health services. Methods: We identified 7,388,842 pregnancy outcomes occurring to Medicaid-eligible women in the 17 states which paid for abortion services between 1999-2014. The first known pregnancy outcome for each woman was marked as the index outcome which assigned each woman to one of three cohorts. All subsequent outcomes occurring up to the fifth known pregnancy were identified. Analyses of the three index outcome cohorts were conducted separately for all pregnancy outcomes, three age bands (<17, 17-35, 36+), and three race/ethnicity groups (Hispanic, Black, White). Results: Women with index abortions experienced more lifetime pregnancies than women with index births or natural fetal losses and were increasingly more likely to experience another pregnancy with each subsequent pregnancy. Women whose index pregnancy ended in abortion were also increasingly more likely to experience another abortion at each subsequent pregnancy. Both births and natural fetal losses were likely to result in a subsequent birth, rather than abortion. Women with natural losses were increasingly more likely to have a subsequent birth than women with an index birth. All age and racial/ethnic groups exhibited the characteristic pattern we have described for all pregnancy outcomes: abortion is associated with more subsequent pregnancies and abortions; births and fetal losses are associated with subsequent births. Other differences between groups are, however, apparent. Age is positively associated with the likelihood of a birth following an index birth, but negatively associated with the likelihood of a birth following an index abortion. Hispanic women are always more likely to have a birth and less likely to have an abortion than Black or White women, for all combinations of index outcome and the number of subsequent pregnancies. Similarly, Black women are always more likely to have an abortion and less likely to experience a birth than Hispanic or White women. Conclusion: Women experiencing repeated pregnancies and subsequent abortions following an index abortion are subjected to an increased exposure to hemorrhage and infection, the major causes of maternal mortality, and other adverse consequences resulting from multiple separation events.
Objectives: To evaluate English, Afrikaans, and Xhosa mother-retained ‘Road-to- Health Book’ (RTH book) for children, and an electronic calculator.
Design: Researchers D Harrison (DH) and H Harker (HH) informed clinic staff about the contents and significance of the RTH book. They requested nurses to use this book in conjunction with the Road-to-Health Card and to issue and explain its use to every visiting client. The use of an electronic calculator that plotted horizontal centile and Z-score charts was demonstrated and explained. To determine the relevance of the book and the electronic calculator, nurses involved in the study for 6 months were given three standardised descriptive questionnaires with ‘yes’, ‘no’ and ‘don’t know’ responses. Clients were traced and interviewed by the researchers after 6 -1 2 months to obtain their views on the book.
Setting: Clinics that provided children with healthcare in 24 locations in the Western Cape Province participated in the study. The children lived in informal settlements, in low-, middle- and high-income residential areas, and on farms in the Cape Town. Stellenbosch, and Paarl regions.
Subjects: One hundred and fourteen nurses were enrolled in the study as well as 581 clients to whom the RTH book was issued.
Outcome measures: The use of and comments on the RTH book by nurses and clients were based on analysis of the questionnaires.
Results: The majority of nurses (81.6%) and clients (96%) found the RTH book useful. The horizontal and Z-score growth charts and electronic calculator were less acceptable because their use was time-consuming and less well understood.
Conclusion: The RTH book with appropriate modifications should be issued to clients in place of the current Road-to-Health card and educational material
Introduction Multiple abortions are consistently associated with adverse health consequences. Prior abortion is a known risk factor for another abortion. Objective To determine the persistence of the association of a first-pregnancy abortion with the likelihood of subsequent pregnancy outcomes. Methods Data was extracted for a study population of 5453 continuously eligible Medicaid beneficiaries in states which funded and reported elective abortions 1999–2015. Women age 16 in 1999 were organized into three cohorts based upon the first pregnancy outcome: abortion, birth, natural loss. Results Women in the abortion cohort are more likely than those in the birth cohort to experience another abortion rather than a birth or natural loss, and less likely to experience a live birth rather than an abortion or natural loss, for every subsequent pregnancy. The tendency toward abortion (OR 2.99, CL 2.02-4.43) and away from birth (OR 0.49, CL 0.39-0.63) peaks at the sixth pregnancy, but persists throughout the reproductive period ages 16–32. The pattern is reversed, but similarly consistent, for women in the birth cohort. They remain likelier to have another birth rather than an abortion or natural loss in subsequent pregnancies. Compared to the birth cohort, the abortion cohort had 1.35 times as many pregnancies: 4.31 times the abortions, 1.53 times the natural losses, but only 0.52 times the births. They were 4.3 and 5.0 times as likely to have 2-plus and 3-plus abortions, but only 0.47 times and 0.31 times as likely to have 2-plus and 3-plus births. Of the abortion cohort, 37.1% had no births. By contrast, 73.6% of the birth cohort had no abortions. Conclusion The first-pregnancy abortion maintains a strong and persistent association with the likelihood of another abortion in subsequent pregnancies, enabling a cascade of adverse events associated with multiple abortions.
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