MRC ORACLE Children Study. Long term outcomes following prescription of antibiotics to pregnant women with either spontaneous preterm labour or preterm rupture of the membranes

BACKGROUND: The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate. METHODS: The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents. National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England. DISCUSSION: This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age. TRIAL REGISTRATION: The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660

Example of monitoring measurements in a virtual eye clinic using 'big data'

Aim: To assess the equivalence of measurement outcomes between patients attending a standard glaucoma care service, where patients see an ophthalmologist in a face-to-face setting, and a glaucoma monitoring service (GMS). Methods: The average mean deviation (MD) measurement on the visual field (VF) test for 250 patients attending a GMS were compared with a ‘big data’ repository of patients attending a standard glaucoma care service (reference database). In addition, the speed of VF progression between GMS patients and reference database patients was compared. Reference database patients were used to create expected outcomes that GMS patients could be compared with. For GMS patients falling outside of the expected limits, further analysis was carried out on the clinical management decisions for these patients. Results: The average MD of patients in the GMS ranged from +1.6dB to −18.9dB between two consecutive appointments at the clinic. In the first analysis, 12 (4.8%; 95% CI 2.5% to 8.2%) GMS patients scored outside the 90% expected values based on the reference database. In the second analysis, 1.9% (95% CI 0.4% to 5.4%) GMS patients had VF changes outside of the expected 90% limits. Conclusions: Using ‘big data’ collected in the standard glaucoma care service, we found that patients attending a GMS have equivalent outcomes on the VF test. Our findings provide support for the implementation of virtual healthcare delivery in the hospital eye service

Metformin versus placebo in obese pregnant women without diabetes mellitus

Background: Obesity is associated with increased risk of adverse pregnancy outcomes. Lifestyle intervention studies have not improved outcome. Metformin improves insulin sensitivity and leads to less weight gain. Methods: Our double-blind placebo-controlled trial randomized non-diabetic pregnant women with a body mass index >35 kg/m2 to metformin or placebo from 12-18 weeks’ gestation until delivery. Primary outcome was median neonatal birth weight z-score reduction by 0.3 standard deviations (equivalent to a 50% reduction in incidence of large-for-gestational-age neonates from 20% to 10%). Secondary outcomes included maternal gestational weight gain and incidence of gestational diabetes, and preeclampsia, as well as adverse neonatal outcomes. Women were randomized, by computer generated random numbers, to either daily metformin 3.0 grams (n=225) or to placebo (n=225). Analysis was by intention to treat. Results: Fifty women withdrew consent, leaving 202 in the metformin group and 198 in the placebo group. There was no significant difference in median neonatal birth weight z-score (metformin: 0.05, IQR -0.71 to 0.92; placebo: 0.17, IQR -0.62 to 0.89; p=0.655). In the metformin group, compared to placebo, median maternal gestational weight gain was lower (4.6 kg, IQR 1.3-7.2 vs. 6.3 kg, IQR 2.9-9.2, p<0.0001) and incidence of preeclampsia was lower (3.0% vs 11.3%; odds ratio 0.24, 95% CI 0.10-0.61; p=0.001), incidence of side effects was higher; there were no significant differences in gestational diabetes, large for gestational age neonates and adverse neonatal outcomes. Conclusions: In non-diabetic women with BMI >35 kg/m2, antenatal administration of metformin reduces maternal weight gain but not neonatal birth weight. (ClinicalTrials.gov number, NCT01273584

Dissimilarity of the gut-lung axis and dysbiosis of the lower airways in ventilated preterm infants.

BACKGROUND: Chronic lung disease of prematurity (CLD), also called bronchopulmonary dysplasia, is a major consequence of preterm birth but the role of the microbiome in its development remains unclear. We, therefore, assessed the progression of the bacterial community in ventilated preterm infants over time in the upper and lower airways, and assessed the gut-lung axis by comparing the upper and lower airways bacterial communities with the stool findings. Finally, we assessed if the bacterial communities were associated with lung inflammation to suggest dysbiosis. METHODS: We serially sampled multiple anatomical sites including the upper airway (nasopharyngeal aspirates, NPA), lower airways (tracheal aspirate fluid, TAF, and bronchoalveolar lavage fluid, BAL) and the gut (stool) of ventilated preterm-born infants. Bacterial DNA load was measured in all samples and sequenced using the V3-V4 region of the 16S rRNA gene RESULTS: From 1102 (539 NPA, 276 TAF, 89 BAL, 198 stool) samples from 55 preterm infants, 352 (32%) amplified suitably for 16 s RNA gene sequencing. Bacterial load was low at birth, quickly increased with time but was associated with predominant operational taxonomic units (OTUs) in all sample types. There was dissimilarity in bacterial communities between the upper and lower airways and the gut with a separate dysbiotic inflammatory process occurring in the lower airways of infants. Individual OTUs were associated with increased inflammatory markers. CONCLUSIONS: Taken together, these findings suggest that targeted treatment of the predominant organisms, including those not routinely treated such as Ureaplasma spp., may decrease the development of CLD in preterm-born infants

GP-SUM. Gaussian Processes Filtering of non-Gaussian Beliefs

This work studies the problem of stochastic dynamic filtering and state propagation with complex beliefs. The main contribution is GP-SUM, a filtering algorithm tailored to dynamic systems and observation models expressed as Gaussian Processes (GP), and to states represented as a weighted sum of Gaussians. The key attribute of GP-SUM is that it does not rely on linearizations of the dynamic or observation models, or on unimodal Gaussian approximations of the belief, hence enables tracking complex state distributions. The algorithm can be seen as a combination of a sampling-based filter with a probabilistic Bayes filter. On the one hand, GP-SUM operates by sampling the state distribution and propagating each sample through the dynamic system and observation models. On the other hand, it achieves effective sampling and accurate probabilistic propagation by relying on the GP form of the system, and the sum-of-Gaussian form of the belief. We show that GP-SUM outperforms several GP-Bayes and Particle Filters on a standard benchmark. We also demonstrate its use in a pushing task, predicting with experimental accuracy the naturally occurring non-Gaussian distributions.Comment: WAFR 2018, 16 pages, 7 figure

Identification and mapping real-world data sources for heart failure, acute coronary syndrome, and atrial fibrillation

BACKGROUND: Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF). METHODS: We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g. electronic health records, genomics, clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage. RESULTS: Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. Majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata. CONCLUSIONS: This review has created a comprehensive resource of cardiovascular data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes

Glaucoma detection: the content of optometric eye examinations for a presbyopic patient of African racial descent

Aims: Standardised patient (SP) methodology is the gold standard for evaluating clinical practice. We investigated the content of optometric eyecare for an early presbyopic SP of African racial descent, an “at-risk” patient group for primary open-angle glaucoma (POAG). Methods: A trained actor presented unannounced as a 44-year-old patient of African racial descent, complaining of recent near vision difficulties, to 100 community optometrists for an audio-recorded eye examination. The eye examinations were subsequently assessed via a checklist based on evidence-based POAG reviews, clinical guidelines and expert panel opinion. Results: Ninety-five per cent of optometrists carried out optic disc assessment and tonometry, which conforms to the UK College of Optometrists’ advice that those patients aged >40 years should receive at least two of the following tests: tonometry, optic disc assessment, visual field testing. Thirty-five per cent of optometrists carried out all of these tests and 6% advised the SP of increased POAG risk in those of African racial descent. Conclusion: SP encounters are an effective measure of optometric clinical practice. As in other healthcare disciplines, there are substantial differences between optometrists in the depth of their clinical investigations, challenging the concept of a “standard sight test”. There is a need for continuing professional development (CPD) in glaucoma screening, in which the increased risk of POAG in those of African racial descent should be emphasised

Kinks in dipole chains

It is shown that the topological discrete sine-Gordon system introduced by Speight and Ward models the dynamics of an infinite uniform chain of electric dipoles constrained to rotate in a plane containing the chain. Such a chain admits a novel type of static kink solution which may occupy any position relative to the spatial lattice and experiences no Peierls-Nabarro barrier. Consequently the dynamics of a single kink is highly continuum like, despite the strongly discrete nature of the model. Static multikinks and kink-antikink pairs are constructed, and it is shown that all such static solutions are unstable. Exact propagating kinks are sought numerically using the pseudo-spectral method, but it is found that none exist, except, perhaps, at very low speed.Comment: Published version. 21 pages, 5 figures. Section 3 completely re-written. Conclusions unchange

Cascaded complementary filter architecture for sensor fusion in attitude estimation

Copyright: © 2021 by the authors. Attitude estimation is the process of computing the orientation angles of an object with respect to a fixed frame of reference. Gyroscope, accelerometer, and magnetometer are some of the fundamental sensors used in attitude estimation. The orientation angles computed from these sensors are combined using the sensor fusion methodologies to obtain accurate estimates. The complementary filter is one of the widely adopted techniques whose performance is highly dependent on the appropriate selection of its gain parameters. This paper presents a novel cascaded architecture of the complementary filter that employs a nonlinear and linear version of the complementary filter within one framework. The nonlinear version is used to correct the gyroscope bias, while the linear version estimates the attitude angle. The significant advantage of the proposed architecture is its independence of the filter parameters, thereby avoiding tuning the filter’s gain parameters. The proposed architecture does not require any mathematical modeling of the system and is computationally inexpensive. The proposed methodology is applied to the real-world datasets, and the estimation results were found to be promising compared to the other state-of-the-art algorithms