Prognostic algorithms for post-discharge readmission and mortality among mother-infant dyads: an observational study protocol

IntroductionIn low-income country settings, the first six weeks after birth remain a critical period of vulnerability for both mother and newborn. Despite recommendations for routine follow-up after delivery and facility discharge, few mothers and newborns receive guideline recommended care during this period. Prediction modelling of post-delivery outcomes has the potential to improve outcomes for both mother and newborn by identifying high-risk dyads, improving risk communication, and informing a patient-centered approach to postnatal care interventions. This study aims to derive post-discharge risk prediction algorithms that identify mother-newborn dyads who are at risk of re-admission or death in the first six weeks after delivery at a health facility.MethodsThis prospective observational study will enroll 7,000 mother-newborn dyads from two regional referral hospitals in southwestern and eastern Uganda. Women and adolescent girls aged 12 and above delivering singletons and twins at the study hospitals will be eligible to participate. Candidate predictor variables will be collected prospectively by research nurses. Outcomes will be captured six weeks following delivery through a follow-up phone call, or an in-person visit if not reachable by phone. Two separate sets of prediction models will be built, one set of models for newborn outcomes and one set for maternal outcomes. Derivation of models will be based on optimization of the area under the receiver operator curve (AUROC) and specificity using an elastic net regression modelling approach. Internal validation will be conducted using 10-fold cross-validation. Our focus will be on the development of parsimonious models (5–10 predictor variables) with high sensitivity (>80%). AUROC, sensitivity, and specificity will be reported for each model, along with positive and negative predictive values.DiscussionThe current recommendations for routine postnatal care are largely absent of benefit to most mothers and newborns due to poor adherence. Data-driven improvements to postnatal care can facilitate a more patient-centered approach to such care. Increasing digitization of facility care across low-income settings can further facilitate the integration of prediction algorithms as decision support tools for routine care, leading to improved quality and efficiency. Such strategies are urgently required to improve newborn and maternal postnatal outcomes. Clinical trial registrationhttps://clinicaltrials.gov/, identifier (NCT05730387)

The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast

Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture

Monitoring the newly qualified nurses in Sweden: the Longitudinal Analysis of Nursing Education (LANE) study

BACKGROUND: The Longitudinal Analysis of Nursing Education (LANE) study was initiated in 2002, with the aim of longitudinally examining a wide variety of individual and work-related variables related to psychological and physical health, as well as rates of employee and occupational turnover, and professional development among nursing students in the process of becoming registered nurses and entering working life. The aim of this paper is to present the LANE study, to estimate representativeness and analyse response rates over time, and also to describe common career pathways and life transitions during the first years of working life. METHODS: Three Swedish national cohorts of nursing students on university degree programmes were recruited to constitute the cohorts. Of 6138 students who were eligible for participation, a total of 4316 consented to participate and responded at baseline (response rate 70%). The cohorts will be followed prospectively for at least three years of their working life. RESULTS: Sociodemographic data in the cohorts were found to be close to population data, as point estimates only differed by 0-3% from population values. Response rates were found to decline somewhat across time, and this decrease was present in all analysed subgroups. During the first year after graduation, nearly all participants had qualified as nurses and had later also held nursing positions. The most common reason for not working was due to maternity leave. About 10% of the cohorts who graduated in 2002 and 2004 intended to leave the profession one year after graduating, and among those who graduated in 2006 the figure was almost twice as high. Intention to leave the profession was more common among young nurses. In the cohort who graduated in 2002, nearly every fifth registered nurse continued to further higher educational training within the health professions. Moreover, in this cohort, about 2% of the participants had left the nursing profession five years after graduating. CONCLUSION: Both high response rates and professional retention imply a potential for a thorough analysis of professional practice and occupational health

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Synthesis, cytotoxicity, and haemolytic activity of chacotrioside lupane-type neosaponins and their germanicane-type rearrangement products

The concise synthesis, via a stepwise glycosylation approach, of lupeol, betulin and betulinic acid O-glycosides bearing a chacotriosyl moiety at the C-3 position is described. All neosaponins as well as their rearrangement products of the germanicane-type were evaluated in vitro for their anticancer and haemolytic activities. Although betulinic acid and betulin 3β-O-chacotriosides were neither cytotoxic nor haemolytic, their rearrangement products allobetulin and 28-oxoallobetulin 3β-O-chacotriosides (9 and 10) exhibited a cytotoxicity profile up to fourfold superior to betulinic acid against human breast (MCF7) and prostate (PC-3) adenocarcinomas cell lines (IC50 = 10–18 μM). One important result was that only chacotriosides featuring non-polar functions at the C-28 position (6, 9 and 10) exerted a haemolytic activity against red blood cells