Platelet function and response to low-dose aspirin in pregnancy

Pre-eclampsia is a serious multisystem disorder unique to pregnant women and associated with significant maternal and perinatal morbidity and mortality worldwide. Despite the investment of decades of basic science and clinical research, the pathophysiology of pre-eclampsia has been incompletely illustrated. In low doses, the cyclooxygenase inhibitor and antiplatelet, aspirin, can redress the thromboxane/prostacyclin imbalance observed in pregnancies affected by pre-eclampsia. Low-dose aspirin is currently recommended for high risk pregnancies in many countries, despite affording only modest overall risk reduction. It has been demonstrated that aspirin-treated individuals experience variable antiplatelet and clinical effects, with ‘non-responders’ having a preponderance for adverse clinical outcomes. The aim of this research was to investigate whether aspirin non-responsiveness exists in pregnant women at high risk of pre-eclampsia and assess whether platelet response to aspirin relates to markers of placental function and/or adverse clinical outcomes. An additional aim was to conduct an unbiased genome-wide assessment of genetic factors which may influence an individual’s response to aspirin. This was made possible by first establishing reference ranges for cyclooxygenase-selective platelet function in pregnancy and developing nuclear magnetic resonance and liquid chromatography mass spectrometry protocols to detect aspirin metabolites and determine adherence. Women at high risk of pre-eclampsia, according to National Institute of Health and Care Excellence criteria, were assessed longitudinally for adherence and platelet function. With exact adherence assessments and cyclooxygenase-selective platelet function testing, aspirin non-responsiveness could not be identified. Additionally, there were no significant associations between platelet response to aspirin, markers of placental function, genetic factors and adverse clinical outcomes. However, a significant proportion of women exhibited variable response to low-dose aspirin, changing their response status throughout their pregnancies. This variable response strongly suggests suboptimal aspirin adherence and/or suboptimal dosing in this population. With the recent findings of increased reduction in the risk of pre-eclampsia with higher doses of aspirin, there is now a valuable opportunity to deepen our understanding of the pharmacokinetics and pharmacodynamics of aspirin in pregnancy. Advances in technology available for genomics and access to biobanked maternal DNA from high-quality, well-phenotyped cohorts provide a strong foundation from which to examine pre-eclampsia disease genomics

Posterior Uterine Rupture Causing Fetal Expulsion into the Abdominal Cavity: A Rare Case of Neonatal Survival

Introduction. Uterine rupture is a potentially catastrophic complication of vaginal birth after caesarean section. We describe the sixth case of posterior uterine rupture, with intact lower segment scar, and the first neonatal survival after expulsion into the abdominal cavity with posterior rupture. Case Presentation. A multiparous woman underwent prostaglandin induction of labour for postmaturity, after one previous caesarean section. Emergency caesarean section for bradycardia revealed a complete posterior uterine rupture, with fetal and placental expulsion. Upon delivery, the baby required inflation breaths only. The patient required a subtotal hysterectomy but returned home on day 5 postnatally with her healthy baby. Discussion. Vaginal birth after caesarean section constitutes a trial of labour, and the obstetrician must be reactive to labour events. Posterior uterine rupture is extremely rare and may occur without conventional signs. Good maternal and fetal outcome is possible with a prompt, coordinated team response

Cardiovascular outcomes following a respiratory tract infection among adults with non-CF bronchiectasis: a general population based study

Rationale: Studies suggest that people with bronchiectasis are at increased risk of cardiovascular co-morbidities. Objectives: We aimed to quantify the relative risk of incident cardiovascular events following a respiratory tract infection amongst people with bronchiectasis. Methods: Using UK electronic primary care records, we conducted a within-person comparison using the self-controlled case series method. We calculated the relative risk of first time cardiovascular events (either first myocardial infarction [MI] or stroke) following a respiratory tract infection compared with the individual’s baseline risk. Results: Our cohort consisted of 895 individuals with non-CF bronchiectasis with a first MI or stroke and at least one respiratory tract infection. There was an increased rate of first time cardiovascular events in the 91 day period after a respiratory tract infection (Incidence Rate Ratio [IRR] 1.56; 95% CI 1.20 to 2.02). The rate of a first cardiovascular event was highest in the first three days following a respiratory tract infection (IRR 2.73, 95% CI 1.41 to 5.27). Conclusions: These data suggest that respiratory tract infections are strongly associated with a transient increased risk of first time MI or stroke amongst people with bronchiectasis. As respiratory tract infections are six times more common in people with bronchiectasis than the general population, the increased risk has a disproportionately greater impact in these individuals. These findings may have implications for including cardiovascular risk modifications in airway infection treatment pathways in this population

A Ten Year Retrospective Follow-Up Of Drug Dependence Career.

This research report presents findings on addiction careers over a ten year period. One of the objectives of this study is to describe the patterns of drug use, criminality, arrest, incarceration and legitimate employment which characterised the addicts, and to relate these configurations to characteristics prior to addiction, during the periods of abstinence and at the point of interview

Women Involved In Drug Dependence In Malaysia An In-Depth Study.

This study is a follow-up of an epidemiological study published in a report entitled Women Involved 1n Drug Dependence in Malaysia - A Preliminary Study (Foong, Navaratnam and Wong,1987). It was felt that the socio-demographic and drug use patterns data in the preliminary study would not be sufficient to provide a more in-depth understanding of drug dependence among women. This present study 1S conducted to co~t1n~e where the first left off

A multi-centre phase IIa clinical study of predictive testing for preeclampsia: Improved pregnancy outcomes via early detection (IMPROvED)

Background: 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia.Methods/Design: We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks' gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit.Discussion: The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If 'at risk' patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome.Trial registration: Trial registration number NCT01891240. The IMPROvED project is funded by the seventh framework programme for Research and Technological development of the EU. http://www.fp7-improved.eu/

Diagnosis and assessment of dilated cardiomyopathy: a guideline protocol from the British Society of Echocardiography.

Heart failure (HF) is a debilitating and life-threatening condition, with 5-year survival rate lower than breast or prostate cancer. It is the leading cause of hospital admission in over 65s, and these admissions are projected to rise by more than 50% over the next 25 years. Transthoracic echocardiography (TTE) is the first-line step in diagnosis in acute and chronic HF and provides immediate information on chamber volumes, ventricular systolic and diastolic function, wall thickness, valve function and the presence of pericardial effusion, while contributing to information on aetiology. Dilated cardiomyopathy (DCM) is the third most common cause of HF and is the most common cardiomyopathy. It is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease) or coronary artery disease sufficient to cause global systolic impairment. This document provides a practical approach to diagnosis and assessment of dilated cardiomyopathy that is aimed at the practising sonographer

Estimating Nosocomial Infection and its Outcomes in Hospital Patients in England with a Diagnosis of COVID-19 Using Machine Learning

BACKGROUND: COVID-19 nosocomial infections (NIs) may have played a significant role in the dynamics of the pandemic in England, but analysis of their impact at the national scale has been lacking. Our aim was to provide a comprehensive account of NIs, identify their characteristics and outcomes in patients with a diagnosis of COVID-19 and use machine learning modelling to refine these estimates. METHODS: From the Hospital Episodes Statistics database all adult hospital patients in England with a diagnosis of COVID-19 and discharged between March 1st 2020 and March 31st 2021 were identified. A cohort of suspected COVID-19 NIs was identified using four empirical methods linked to hospital coding. A random forest classifier was designed to model the relationship between acquiring NIs and the covariates: patient characteristics, comorbidities, frailty, trust capacity strain and severity of COVID-19 infections. FINDINGS: In total, 374,244 adult patients with COVID-19 were discharged during the study period. The four empirical methods identified 29,896 (8.0%) patients with NIs. The random forest classifier estimated a mean NI rate of 10.5%, with a peak close to 18% during the first wave, but much lower rates thereafter and around 7% in early spring 2021. NIs were highly correlated with longer lengths of stay, high trust capacity strain, greater age and a higher degree of patient frailty. NIs were also found to be associated with higher mortality rates and more severe COVID-19 sequelae, including pneumonia, kidney disease and sepsis. INTERPRETATION: Identification of the characteristics of patients who acquire NIs should help trusts to identify those most at risk. The evolution of the NI rate over time may reflect the impact of changes in hospital management practices and vaccination efforts. Variations in NI rates across trusts may partly reflect different data recording and coding practice

Changing causes of death for patients with chronic respiratory disease in England, 2005-2015

Background: Chronic respiratory diseases (CRD) are common, increasing in prevalence, and cause significant morbidity and mortality worldwide. However, we have limited knowledge on causes of death of patients with CRD in the general population. Objective: We evaluated mortality rates and causes of death over time in CRD patients.Methods: We used linked primary care and mortality data to determine mortality rates and the most common causes of death in people with CRD (including asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILD)) during 2005-2015 in England. Results: We identified 558,888 CRD patients (451,830 asthma, 137,709 COPD, 19,374 bronchiectasis, 10,745 ILD). The age-standardised mortality rate of patients with CRD was 1,607 per 100,000 persons (asthma=856, COPD=1,503, ILD=2,609, bronchiectasis=1,463). CRD mortality was overall 54% higher than the general population. One third of CRD patients died from respiratory-related causes. Respiratory-related mortality was constant, while cardiovascular-related mortality decreased significantly over time. COPD accounted for the majority of respiratory-related deaths (66% overall) in all patient groups except ILD. Conclusions: CRD patients continue to experience substantial morbidity and mortality due to respiratory diseases. Disease-modifying intervention strategies are needed to improve outcomes for patients with CRD