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BackgroundOur knowledge of how to better manage elevated blood pressure (BP) in the presence of comorbidities is limited, in part due to exclusion or underrepresentation of patients with multiple chronic conditions from major clinical trials. We aimed to investigate the burden and types of comorbidities in patients with hypertension and to assess how such comorbidities and other variables affect BP levels over time.Methods and findingsIn this multiple landmark cohort study, we used linked electronic health records from the United Kingdom Clinical Practice Research Datalink (CPRD) to compare systolic blood pressure (SBP) levels in 295,487 patients (51% women) aged 61.5 (SD = 13.1) years with first recorded diagnosis of hypertension between 2000 and 2014, by type and numbers of major comorbidities, from at least 5 years before and up to 10 years after hypertension diagnosis. Time-updated multivariable linear regression analyses showed that the presence of more comorbidities was associated with lower SBP during follow-up. In hypertensive patients without comorbidities, mean SBP at diagnosis and at 10 years were 162.3 mm Hg (95% confidence interval [CI] 162.0 to 162.6) and 140.5 mm Hg (95% CI 140.4 to 140.6), respectively; in hypertensive patients with \u22655 comorbidities, these were 157.3 mm Hg (95% CI 156.9 to 157.6) and 136.8 mm Hg (95% 136.4 to 137.3), respectively. This inverse association between numbers of comorbidities and SBP was not specific to particular types of comorbidities, although associations were stronger in those with preexisting cardiovascular disease. Retrospective analysis of recorded SBP showed that the difference in mean SBP 5 years before diagnosis between those without and with \u22655 comorbidities was \u22129 mm Hg (95% CI \u22129.7 to \u22128.3), suggesting that mean recorded SBP already differed according to the presence of comorbidity before baseline. Within 1 year after the diagnosis, SBP substantially declined, but subsequent SBP changes across comorbidity status were modest, with no evidence of a more rapid decline in those with more or specific types of comorbidities. We identified factors, such as prescriptions of antihypertensive drugs and frequency of healthcare visits, that can explain SBP differences according to numbers or types of comorbidities, but these factors only partly explained the recorded SBP differences. Nevertheless, some limitations have to be considered including the possibility that diagnosis of some conditions may not have been recorded, varying degrees of missing data inherent in analytical datasets extracted from routine health records, and greater measurement errors in clinical measurements taken in routine practices than those taken in well-controlled clinical study settings.ConclusionsBP levels at which patients were diagnosed with hypertension varied substantially according to the presence of comorbidities and were lowest in patients with multi-morbidity. Our findings suggest that this early selection bias of hypertension diagnosis at different BP levels was a key determinant of long-term differences in BP by comorbidity status. The lack of a more rapid decline in SBP in those with multi-morbidity provides some reassurance for BP treatment in these high-risk individuals.
\n \n\n \n \nBACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk of severe COVID-19 related complications, and maternal morbidity and mortality. OBJECTIVES: To analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes, when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 is a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes, as well as vaccine effectiveness (VE). Women diagnosed with laboratory-confirmed COVID-19 in pregnancy were compared with two 'non-diagnosed', unmatched women recruited concomitantly and consecutively in pregnancy or at delivery. Mother/newborn dyads were followed until hospital discharge. Primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index (SNMI), severe perinatal morbidity and mortality index (SPMMI), preterm birth, neonatal death, referral to neonatal intensive care unit (NICU), and diseases during the neonatal period. VE was estimated adjusted by maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) non-diagnosed mothers. Amongst diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (RR=0.46; 95%CI=0.23, 0.91) the risk of being diagnosed with COVID-19 compared to those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically-indicated preterm birth, respiratory distress syndrome and number of days in NICU. Newborns of unvaccinated mothers had double the risk of neonatal death (RR=2.06; 95% CI=1.06, 4.00) compared to those of non-diagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the significantly highest VE (64%; 95% CI=10-86%); VE was not as high for mRNA vaccines only. VE against moderate/severe neonatal outcomes was much lower: 13% in the booster-vaccinated group (all vaccines), and 25% and 28% in the completely and booster-vaccinated groups, respectively (mRNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women 100 days (14 weeks) or less before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks).. Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk of infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk of neonatal death. Neonates of vaccinated mothers had a decreased risk of preterm birth and adverse neonatal outcomes. As the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19 mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.
\n \n\n \n \nThroughout pregnancy, some degree of insulin resistance is necessary to divert glucose towards the developing foetus. In gestational diabetes mellitus (GDM), insulin resistance is exacerbated in combination with insulin deficiency, causing new-onset maternal hyperglycaemia. The rapid reversal of insulin resistance following delivery strongly implicates the placenta in GDM pathogenesis. In this case\u2013control study, we investigated the proteomic cargo of human syncytiotrophoblast-derived extracellular vesicles (STBEVs), which facilitate maternal\u2013fetal signalling during pregnancy, in a UK-based cohort comprising patients with a gestational age of 38\u201340 weeks. Medium/large (m/l) and small (s) STBEVs were isolated from GDM (n = 4) and normal (n = 5) placentae using ex vivo dual-lobe perfusion and subjected to mass spectrometry. Bioinformatics were used to identify differentially carried proteins and mechanistic pathways. In m/lSTBEVs, 56 proteins were differently expressed while in sSTBEVs, no proteins reached statistical difference. Differences were also observed in the proteomic cargo between m/lSTBEVs and sSTBEVs, indicating that the two subtypes of STBEVs may have divergent modes of action and downstream effects. In silico functional enrichment analysis of differentially expressed proteins in m/lSTBEVs from GDM and normal pregnancy found positive regulation of cytoskeleton organisation as the most significantly enriched biological process. This work presents the first comparison of two populations of STBEVs\u2019 protein cargos (m/l and sSTBEVs) from GDM and normal pregnancy isolated using placenta perfusion. Further investigation of differentially expressed proteins may contribute to an understanding of GDM pathogenesis and the development of novel diagnostic and therapeutic tools.
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