Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

Objective To determine the effectiveness of management strategies for uninvestigated dyspepsia. Design Systematic review and network meta-analysis. Data sources Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019. Eligibility criteria for selecting studies Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive (“test and treat”); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months). Results The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. “Test and treat” ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than “test and treat.” Participants assigned to “test and treat” were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with “test and treat” (relative risk v “test and treat” 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design. Conclusions “Test and treat” was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. “Test and treat” led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms. Systematic review registration PROSPERO registration number CRD42019132528

Inpatient prescribing systems used in NHS Acute 65 66 Trusts across England: a managerial perspective

Objective The individualised patient prescription chart, either paper or electronic, is an integral part of communication between healthcare professionals. The aim of this study is to ascertain the extent to which different prescribing systems are used for inpatient care in acute hospitals in England and explore chief pharmacists’ opinions and experiences with respect to electronic prescribing and medicines administration (EPMA) systems. Method Audio-recorded semistructured telephone interviews with chief pharmacists or their nominated representatives of general acute hospital trusts across England. Results Forty-five per cent (65/146) of the chief pharmacists agreed to participate. Eighteen per cent (12/65) of the participants interviewed stated that their trust had EPMA systems fully or partially implemented on inpatient wards. The most common EPMA system in place was JAC (n=5) followed by MEDITECH (n=3), iSOFT (n=2), PICS (n=1) and one in-house created system. Of the 12 trusts that had EPMA in place, 4 used EPMA on all of their inpatient wards and the remaining 8 had a mixture of paper and EPMA systems in use. Fifty six (86% 56/65) of all participants had consulted the standards for the design of inpatient prescription charts. From the 12 EPMA interviews qualitatively analysed, the regulation required to provide quality patient care is perceived by some to be enforceable with an EPMA system, but that this may affect accuracy and clinical workflow, leading to undocumented, unofficial workarounds that may be harmful. Conclusions The majority of inpatient prescribing in hospital continues to use paper-based systems; there was significant diversity in prescribing systems in use. EPMA systems have been implemented but many trusts have retained supplementary paper drug charts, for a variety of medications. Mandatory fields may be appropriate for core prescribing information, but the expansion of their use needs careful consideration

Accuracy of Intravenous and Enteral Preparations Involving Small Volumes for Paediatric Use: A Review

Background: Children often need to be administered very small volumes of medicines that are authorised for use in adults. Neonatal drug delivery is particularly challenging and doses are often immeasurable with the equipment currently available. Aim: To summarise research to date on the accuracy of intravenous and enteral medicine preparation requiring small volumes (<0.1mL), with a focus on paediatric use and to identify areas for further work. Method: Twenty-three publications were identified for the narrative review via: Web of Science (1950-2016), Cumulative Index to Nursing and Allied Health Literature (1976-2016), Excerpta Medica Database (1974-2016) and International Pharmaceutical Abstracts (1970-2016) searches. Nine additional papers were identified through backward citation tracking and a further 17 were included from the personal knowledge of the review team. Results: Measurement of volumes (<0.1mL), for enteral and intravenous dosing, account for 25% of medicine manipulations within paediatric hospitals. Inaccuracies are described throughout the literature with dose administration errors attributed to technique, calculation, dilution and problems associated with equipment. Whilst standardised concentrations for intravenous infusion and drug concentrations which avoid measurement of small volumes would ameliorate problems, further work is needed to establish accurate methods for handling small volumes during the administration of medicines to children and risk minimisation strategies to support staff involved are also necessary. Conclusion: This review has revealed a paucity of information on the clinical outcomes from problems in measuring small volumes for children and highlighted the need for further work to eliminate this source of inaccurate dosing and potential for medication error

An impulse-based approach to estimating forces in unsteady flow

The ready availability of full-field velocity measurements in present-day experiments has kindled interest in using such data for force estimation, especially in situations where direct measurements are difficult. Among the methods proposed, a formulation based on impulse is attractive, for both practical and physical reasons. However, evaluation of the impulse requires a complete description of the vorticity field, and this is particularly hard to achieve in the important region close to a body surface. This paper presents a solution to the problem. The incomplete experimental-vorticity field is augmented by a vortex sheet on the body, with strength determined by the no-slip boundary condition. The impulse is then found from the sum of vortex-sheet and experimental contributions. Components of physical interest can straightforwardly be recognised; for example, the classical 'added mass' associated with fluid inertia is represented by an explicit term in the formulation for the vortex sheet. The method is implemented in the context of two-dimensional flat-plate flow, and tested on velocity-field data from a translating wing experiment. The results show that the vortex-sheet contribution is significant for the test data set. Furthermore, when it is included, good agreement with force-balance measurements is found. It is thus recommended that any impulse-based force calculation should correct for (likely) data incompleteness in this way.The second author thanks the Engineering and Physical Sciences Research Council (EPSRC) for financial support via its 'Doctoral Training' scheme

Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug

Hot melt extrusion has been used to produce a solid dispersion of the thermolabile drug artemisinin. Formulation and process conditions were optimized prior to evaluation of dissolution and biopharmaceutical performance. Soluplus®, a low Tg amphiphilic polymer especially designed for solid dispersions enabled melt extrusion at 110 °C although some drug-polymer incompatibility was observed. Addition of 5% citric acid as a pH modifier was found to suppress the degradation. The area under plasma concentration time curve (AUC0–24h) and peak plasma concentration (Cmax) were four times higher for the modified solid dispersion compared to that of pure artemisinin

Advancing Marine Biogeochemical and Ecosystem Reanalyses and Forecasts as Tools for Monitoring and Managing Ecosystem Health

Ocean ecosystems are subject to a multitude of stressors, including changes in ocean physics and biogeochemistry, and direct anthropogenic influences. Implementation of protective and adaptive measures for ocean ecosystems requires a combination of ocean observations with analysis and prediction tools. These can guide assessments of the current state of ocean ecosystems, elucidate ongoing trends and shifts, and anticipate impacts of climate change and management policies. Analysis and prediction tools are defined here as ocean circulation models that are coupled to biogeochemical or ecological models. The range of potential applications for these systems is broad, ranging from reanalyses for the assessment of past and current states, and short-term and seasonal forecasts, to scenario simulations including climate change projections. The objectives of this article are to illustrate current capabilities with regard to the three types of applications, and to discuss the challenges and opportunities. Representative examples of global and regional systems are described with particular emphasis on those in operational or pre-operational use. With regard to the benefits and challenges, similar considerations apply to biogeochemical and ecological prediction systems as do to physical systems. However, at present there are at least two major differences: (1) biogeochemical observation streams are much sparser than physical streams presenting a significant hinderance, and (2) biogeochemical and ecological models are largely unconstrained because of insufficient observations. Expansion of biogeochemical and ecological observation systems will allow for significant advances in the development and application of analysis and prediction tools for ocean biogeochemistry and ecosystems, with multiple societal benefits

Adolescents’ responses to the promotion and flavouring of e-cigarettes

Objectives The purpose of the study is to examine adolescents’ awareness of e-cigarette marketing and investigate the impact of e-cigarette flavour descriptors on perceptions of product harm and user image. Methods Data come from the 2014 Youth Tobacco Policy Survey, a cross-sectional in-home survey conducted with 11–16 year olds across the UK (n = 1205). Adolescents’ awareness of e-cigarette promotion, brands, and flavours was assessed. Perceptions of product harm, and likely user of four examples of e-cigarette flavours was also examined. Results Some participants had tried e-cigarettes (12 %) but regular use was low (2 %) and confined to adolescents who had also smoked tobacco. Most were aware of at least one promotional channel (82 %) and that e-cigarettes came in different flavours (69 %). Brand awareness was low. E-cigarettes were perceived as harmful (M = 3.54, SD = 1.19) but this was moderated by product flavours. Fruit and sweet flavours were perceived as more likely to be tried by young never smokers than adult smokers trying to quit (p < 0.001). Conclusions There is a need to monitor the impact of future market and regulatory change on youth uptake and perceptions of e-cigarettes

Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

Testing for hepatitis C virus (HCV) infection may reduce the risk of liver-related morbidity, by facilitating earlier access to treatment and care. This review investigated the effectiveness of targeted testing interventions on HCV case detection, treatment uptake, and prevention of liver-related morbidity. A literature search identified studies published up to 2013 that compared a targeted HCV testing intervention (targeting individuals or groups at increased risk of HCV) with no targeted intervention, and results were synthesised using meta-analysis. Exposure to a targeted testing intervention, compared to no targeted intervention, was associated with increased cases detected [number of studies (n) = 14; pooled relative risk (RR) 1.7, 95 % CI 1.3, 2.2] and patients commencing therapy (n = 4; RR 3.3, 95 % CI 1.1, 10.0). Practitioner-based interventions increased test uptake and cases detected (n = 12; RR 3.5, 95 % CI 2.5, 4.8; and n = 10; RR 2.2, 95 % CI 1.4, 3.5, respectively), whereas media/information-based interventions were less effective (n = 4; RR 1.5, 95 % CI 0.7, 3.0; and n = 4; RR 1.3, 95 % CI 1.0, 1.6, respectively). This meta-analysis provides for the first time a quantitative assessment of targeted HCV testing interventions, demonstrating that these strategies were effective in diagnosing cases and increasing treatment uptake. Strategies involving practitioner-based interventions yielded the most favourable outcomes. It is recommended that testing should be targeted at and offered to individuals who are part of a population with high HCV prevalence, or who have a history of HCV risk behaviour

Justification of the symmetric damping model of the dynamical Casimir effect in a cavity with a semiconductor mirror

A "microscopic" justification of the "symmetric damping" model of a quantum oscillator with time-dependent frequency and time-dependent damping is given. This model is used to predict results of experiments on simulating the dynamical Casimir effect in a cavity with a photo-excited semiconductor mirror. It is shown that the most general bilinear time-dependent coupling of a selected oscillator (field mode) to a bath of harmonic oscillators results in two equal friction coefficients for the both quadratures, provided all the coupling coefficients are proportional to a single arbitrary function of time whose duration is much shorter than the periods of all oscillators. The choice of coupling in the rotating wave approximation form leads to the "mimimum noise" model of the quantum damped oscillator, introduced earlier in a pure phenomenological way.Comment: 9 pages, typos corrected, corresponds to the published version, except for the reference styl