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

Regression of Intracranial Meningiomas Following Treatment with Cabozantinib

Recurrent meningiomas remain a substantial treatment challenge given the lack of effective therapeutic options aside from surgery and radiation therapy, which yield limited results in the retreatment situation. Systemic therapies have little effect, and responses are rare; the search for effective systemic therapeutics remains elusive. In this case report, we provide data regarding significant responses in two radiographically diagnosed intracranial meningiomas in a patient with concurrent thyroid carcinoma treated with cabozantinib, an oral multitarget tyrosine kinase inhibitor with potent activity against MET and VEGF receptor 2. Given the clinical experience supporting the role of VEGF agents as experimental therapeutics in meningioma and the current understanding of the biological pathways underlying meningioma growth, this may represent a new oral therapeutic alternative, warranting prospective evaluation. Keywords: VEGF; cabozantinib; meningioma; targeted therapy

Lightweight Object Detection Ensemble Framework for Autonomous Vehicles in Challenging Weather Conditions

The computer vision systems driving autonomous vehicles are judged by their ability to detect objects and obstacles in the vicinity of the vehicle in diverse environments. Enhancing this ability of a self-driving car to distinguish between the elements of its environment under adverse conditions is an important challenge in computer vision. For example, poor weather conditions like fog and rain lead to image corruption which can cause a drastic drop in object detection (OD) performance. The primary navigation of autonomous vehicles depends on the effectiveness of the image processing techniques applied to the data collected from various visual sensors. Therefore, it is essential to develop the capability to detect objects like vehicles and pedestrians under challenging conditions such as like unpleasant weather. Ensembling multiple baseline deep learning models under different voting strategies for object detection and utilizing data augmentation to boost the models' performance is proposed to solve this problem. The data augmentation technique is particularly useful and works with limited training data for OD applications. Furthermore, using the baseline models significantly speeds up the OD process as compared to the custom models due to transfer learning. Therefore, the ensembling approach can be highly effective in resource-constrained devices deployed for autonomous vehicles in uncertain weather conditions. The applied techniques demonstrated an increase in accuracy over the baseline models and were able to identify objects from the images captured in the adverse foggy and rainy weather conditions. The applied techniques demonstrated an increase in accuracy over the baseline models and reached 32.75% mean average precision (mAP) and 52.56% average precision (AP) in detecting cars in the adverse fog and rain weather conditions present in the dataset. The effectiveness of multiple voting strategies for bounding box predictions on the dataset is also demonstrated. These strategies help increase the explainability of object detection in autonomous systems and improve the performance of the ensemble techniques over the baseline models

Bush animal attacks: management of complex injuries in a resource-limited setting

Though animal-related injuries and fatalities have been documented throughout the world, the variety of attacks by wild animals native to rural East Africa are less commonly described. Given the proximity of our northwestern Tanzania hospital to Lake Victoria, Lake Tanganyika, and the Serengeti National Park, and presentation of several patients attacked by bush animals and suffering a variety of complex injuries, we sought to report the pattern of attacks and surgical management in a resource-limited setting. Four patients who were admitted to the northwestern Tanzania tertiary referral hospital, Bugando Medical Centre (BMC), in 2010-2011 suffered attacks by different bush animals: hyena, elephant, crocodile, and vervet monkey. These patients were triaged as trauma patients in the Casualty Ward, then admitted for inpatient monitoring and treatment. Their outcomes were followed to discharge. The age and gender of the patients attacked was variable, though all but the pediatric patient were participating in food gathering or guarding activities in rural locations at the time of the attacks. All patients required surgical management of their injuries, which included debridement and closure of wounds, chest tube insertion, amputation, and external fixation of an extremity fracture. All patients survived and were discharged home. Though human injuries secondary to encounters with undomesticated animals such as cows, moose, and camel are reported, they often are indirect traumas resulting from road traffic collisions. Snake attacks are well documented and common. However, this series of unique bush animal attacks describes the initial and surgical management of human injuries in the resource-limited setting of the developing world. Animal attacks are common throughout the world, but their pattern may vary in Africa throughout jungle and bush environmental settings. It is important to understand the management of these attacks in resource-limited health care environment. Further, the growing population and human encroachment on previously wild habitats such as the northwestern Tanzania bush argues for increased community awareness to assist in prevention of human injuries by animals

Virtual clinics in glaucoma care: face-to-face versus remote decision-making

BACKGROUND/AIMS: To examine the agreement in clinical decisions of glaucoma status made in a virtual glaucoma clinic with those made during a face-to-face consultation. METHODS: A trained nurse and technicians entered data prospectively for 204 patients into a proforma. A subsequent face-to-face clinical assessment was completed by either a glaucoma consultant or fellow. Proformas were reviewed remotely by one of two additional glaucoma consultants, and 12 months later, by the clinicians who had undertaken the original clinical examination. The interobserver and intraobserver decision-making agreements of virtual assessment versus standard care were calculated. RESULTS: We identified adverse disagreement between face-to-face and virtual review in 7/204 (3.4%, 95% CI 0.9% to 5.9%) patients, where virtual review failed to predict a need to accelerated follow-up identified in face-to-face review. Misclassification events were rare, occurring in 1.9% (95% CI 0.3% to 3.8%) of assessments. Interobserver κ (95% CI) showed only fair agreement (0.24 (0.04 to 0.43)); this improved to moderate agreement when only consultant decisions were compared against each other (κ=0.41 (0.16 to 0.65)). The intraobserver agreement κ (95% CI) for the consultant was 0.274 (0.073 to 0.476), and that for the fellow was 0.264 (0.031 to 0.497). CONCLUSIONS: The low rate of adverse misclassification, combined with the slowly progressive nature of most glaucoma, and the fact that patients will all be regularly reassessed, suggests that virtual clinics offer a safe, logistically viable option for selected patients with glaucoma

The Safety of Continued Oral Anticoagulation Therapy in Joint Injections and Aspirations: A Qualitative Review of the Current Evidence

Performing joint aspirations and injections on patients taking long-term oral anticoagulants poses a clinical conundrum. This review aimed to quantify the safety of performing joint procedures in these patients in terms of bleeding risk. In addition, it aimed to identify, in those receiving vitamin K antagonists, what level of international normalized ratio (INR) is the safest.A review of the medical literature was performed (electronic searches in Ovid [MEDLINE], EMBASE, and the Cochrane Library). English language original reports of patients undergoing joint injections or aspirations performed on anticoagulant therapy, published within the last 10 years, were included.Seven studies met the inclusion criteria. Patients were taking a variety of anticoagulants: warfarin, acenocoumarol, and direct oral anticoagulants. Four cases of hemorrhage were reported after 5427 procedures, over a pooled 32-year period, across 9 centers. The INR values were available for 3 cases with bleeding complications: values were 1.9, 2.3, and 3.4.Authors of all studies concluded that joint injection is safe in patients on anticoagulants. A variety of joints and approaches, reversal, or withholding of anticoagulation and bridging with low molecular weight heparin did not seem to alter bleeding risk. Bleeding complications remained low even in those with renal or hepatic impairment or those taking concomitant antiplatelets.In conclusion, joint aspiration and injection are safe in patients taking anticoagulants. Anticoagulation should not be routinely discontinued in these patients; decisions should be made on a case-by-case basis. Because of low event numbers, a recommended safe maximum INR value for joint procedures cannot be determined

Qualitative investigation of patients' experience of a glaucoma virtual clinic in a specialist ophthalmic hospital in London, UK

OBJECTIVES: To explore how patients felt about delivery of care in a novel technician-delivered virtual clinic compared with delivery of care in a doctor-delivered model. DESIGN: A qualitative investigation using one-to-one interviews before and after patients' appointments at either the standard outpatient glaucoma clinic or the new technician-delivered virtual glaucoma clinic (Glaucoma Screening and Stable Monitoring Service, GSMS). SETTING: A glaucoma clinic based in a tertiary ophthalmic specialist hospital in London. PARTICIPANTS: 43 patients (38 Caucasian, 5 African/Afro-Caribbean) were interviewed prior to their glaucoma appointment; 38 patients were interviewed between 4 and 6 weeks after their appointment. Consecutive patients were identified from patient reception lists and telephoned prior to their appointment inviting them to participate. RESULTS: Trust in the patient-provider relationship emerged as a key theme in patients' acceptance of not being seen in a traditional doctor-delivered service. Patients who were well informed regarding their glaucoma status and low risk of progression to sight loss were more accepting of the GSMS. Patients valued the reassurance received through effective communication with their healthcare practitioner at the time of their appointment. CONCLUSIONS: This study suggests that patients are accepting of moving to a model of service delivery whereby the doctor is removed from the consultation as long as they are informed about the status of their condition and reassured by the interaction with staff they meet. This study highlights the importance of patient engagement when introducing new models of service delivery

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

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