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

Health on the Move (HOME) Study: Using a smartphone app to explore the health and wellbeing of migrants in the United Kingdom [version 1; peer review: 2 approved]

Background/Aim: We have a limited understanding of the broader determinants of health of international migrants and how these change over time since migration to the United Kingdom (UK). To address this knowledge gap, we aim to conduct a prospective cohort study with data acquisition via a smartphone application (app). In this pilot study, we aim to 1) determine the feasibility of the use of an app for data collection in international migrants, 2) optimise app engagement by quantifying the impact of specific design features on the completion rates of survey questionnaires and on study retention, 3) gather preliminary profile health status data, to begin to examine how risk factors for health are distributed among migrants. / Methods: We will recruit 275 participants through a social media campaign and through third sector organisations that work with or support migrants in the UK. Following consent and registration, data will be collected via surveys. To optimise app engagement and study retention, we will quantify the impact of specific design features (i.e. the frequency of survey requests, the time of day for app notifications, the frequency of notifications, and the wording of notifications) via micro-randomised process evaluations. The primary outcome for this study is survey completion rates with numerator as the number of surveys completed and denominator as the total number of available surveys. Secondary outcomes are study retention rates and ratings of interest after app usage. / Ethics and dissemination: We have obtained approval to use consented patient identifiable data from the University College London Ethics Committee. Improving engagement with the app and gathering preliminary health profile data will help us identify accessibility and usability issues and other barriers to app and study engagement prior to moving to a larger study

Virtual Support for Real-World Movement:Using Chatbots to Overcome Barriers to Physical Activity

Conversational agents (CAs, aka chatbots) for behavioral interventions have great potential to improve patient engagement and provide solutions that can benefit human health. In this study, we examined the potential efficacy of chatbots in assisting with the resolution of specific barriers that people frequently encounter when doing behavioral interventions for the purpose of increasing physical activity (PA). To do this, six common barriers (i.e., things that stand in the way of increasing PA) were targeted (e.g., stress and fatigue), we adopted domain knowledge (i.e., psychological theories and behavioral change techniques) to design six interventions aimed at tackling each of these six barriers. These interventions were then incorporated into consultative conversations, which were subsequently integrated into a chatbot. A user study was conducted on non-clinical samples (n=77) where all participants were presented with three randomly but equally distributed chatbot interventions and a control condition. Each intervention conversation addressed a specific barrier to PA, while the control conversation did not address any barrier. The outcome variables were beliefs in PA engagement, attitudes toward the effectiveness of each intervention to resolve the barrier, and the overall chatbot experience. The results showed a significant increase in beliefs of PA engagement in most intervention groups compared to the control group, and positive attitudes toward the effectiveness of the interventions in reducing their respective barriers to PA, and positive chatbot experience. The results demonstrate that theory-grounded interventions delivered by chatbots can effectively help people overcome specific barriers to PA, thereby increasing their beliefs in PA engagement. These promising findings indicate that chatbot interventions can be an accessible and widely applicable solution for a larger population to promote PA.</p

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

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.

The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2–2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells.

Cancer genome sequencing has implicated the cytosine deaminase activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) genes as an important source of mutations in diverse cancers, with APOBEC3B (A3B) expression especially correlated with such cancer mutations. To better understand the processes directing A3B over-expression in cancer, and possible therapeutic avenues for targeting A3B, we have investigated the regulation of A3B gene expression. Here, we show that A3B expression is inversely related to p53 status in different cancer types and demonstrate that this is due to a direct and pivotal role for p53 in repressing A3B expression. This occurs through the induction of p21 (CDKN1A) and the recruitment of the repressive DREAM complex to the A3B gene promoter, such that loss of p53 through mutation, or human papilloma virus-mediated inhibition, prevents recruitment of the complex, thereby causing elevated A3B expression and cytosine deaminase activity in cancer cells. As p53 is frequently mutated in cancer, our findings provide a mechanism by which p53 loss can promote cancer mutagenesis

Geometric least squares means ratios for the analysis of Plasmodium falciparum in vitro susceptibility to antimalarial drugs

<p>Abstract</p> <p>Background</p> <p>The susceptibility of microbes such as <it>Plasmodium falciparum </it>to drugs is measured in vitro as the concentration of the drug achieving 50% of maximum effect (IC₅₀); values from a population are summarized as geometric means. For antimalarial drugs, as well as for antibiotics, assessing changes in microbe susceptibility over time under drug pressure would help inform treatment policy decisions, but no standard statistical method exists as yet.</p> <p>Methods</p> <p>A mixed model was generated on log_e-transformed IC₅₀values and calculated geometric least squares means (GLSM) with 90% confidence intervals (CIs). In order to compare IC₅₀s between years, GLSM ratios (GLSMR) with 90%CIs were calculated and, when both limits of the 90%CIs were below or above 100%, the difference was considered statistically significant. Results were compared to those obtained from ANOVA and a generalized linear model (GLM).</p> <p>Results</p> <p>GLSMRs were more conservative than ANOVA and resulted in lower levels of statistical significance. The GLSMRs approach allowed for random effect and adjustment for multiple comparisons. GLM was limited in the number of year-to-year comparisons by the need for a single reference year. The three analyses yielded generally consistent results.</p> <p>Conclusion</p> <p>A robust analytical method can palliate inherent limitations of in vitro sensitivity testing. The random effects GLSMRs with adjustment for multiple comparisons and 90%CIs require only assumptions on the mixed model to be applied. Results are easy to display graphically and to interpret. The GLMSRs should be considered as an option for monitoring changes in drug susceptibility of <it>P. falciparum </it>malaria and other microbes.</p

The economic burden of bronchiectasis - known and unknown:a systematic review

Abstract Background The increasing prevalence and recognition of bronchiectasis in clinical practice necessitates a better understanding of the economic disease burden to improve the management and achieve better clinical and economic outcomes. This study aimed to assess the economic burden of bronchiectasis based on a review of published literature. Methods A systematic literature review was conducted using MEDLINE, Embase, EconLit and Cochrane databases to identify publications (1 January 2001 to 31 December 2016) on the economic burden of bronchiectasis in adults. Results A total of 26 publications were identified that reported resource use and costs associated with management of bronchiectasis. Two US studies reported annual incremental costs of bronchiectasis versus matched controls of US$5681 and US$2319 per patient. Twenty-four studies reported on hospitalization rates or duration of hospitalization for patients with bronchiectasis. Mean annual hospitalization rates per patient, reported in six studies, ranged from 0.3–1.3, while mean annual age-adjusted hospitalization rates, reported in four studies, ranged from 1.8–25.7 per 100,000 population. The average duration of hospitalization, reported in 12 studies, ranged from 2 to 17 days. Eight publications reported management costs of bronchiectasis. Total annual management costs of €3515 and €4672 per patient were reported in two Spanish studies. Two US studies reported total costs of approximately US$26,000 in patients without exacerbations, increasing to US$36,00–37,000 in patients with exacerbations. Similarly, a Spanish study reported higher total annual costs for patients with > 2 exacerbations per year (€7520) compared with those without exacerbations (€3892). P. aeruginosa infection increased management costs by US$31,551 to US$56,499, as reported in two US studies, with hospitalization being the main cost driver. Conclusions The current literature suggests that the economic burden of bronchiectasis in society is significant. Hospitalization costs are the major driver behind these costs, especially in patients with frequent exacerbations. However, the true economic burden of bronchiectasis is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost. We present a conceptual framework to facilitate a more comprehensive assessment of the true burden of bronchiectasis for individuals, healthcare systems and society