bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trainee doctors’ experiences of common problems in the antibiotic prescribing process: an activity theory analysis of narrative data from UK hospitals
Authors: Kajamaa Anu , Mattick Karen , Parker Hazel , Hilli Angelique , Rees Charlotte 
Published: June 2019

IntroductionPrescribing antibiotics is an error-prone activity and one of the more challenging responsibilities for doctors in training. The nature and extent of challenges experienced by them at different stages of the antibiotic prescribing process are not well described, meaning that interventions may not target the most problematic areas.ObjectivesOur aim was to explore doctors in training experiences of common problems in the antibiotic prescribing process using cultural–historical activity theory (CHAT). Our research questions were as follows: What are the intended stages in the antibiotic prescribing process? What are the challenges and where in the prescribing process do these occur?MethodsWe developed a process model based on how antibiotic prescribing is intended to occur in a ‘typical’ National Health Service hospital in the UK. The model was first informed by literature and refined through consultation with practising healthcare professionals and medical educators. Then, drawing on CHAT, we analysed 33 doctors in training narratives of their antibiotic prescribing experiences to identify and interpret common problems in the process.ResultsOur analysis revealed five main disturbances commonly occurring during the antibiotic prescribing process: consultation challenges, lack of continuity, process variation, challenges in patient handover and partial loss of object. Our process model, with 31 stages and multiple practitioners, captures the complexity, inconsistency and unpredictability of the process. The model also highlights ‘hot spots’ in the process, which are the stages that doctors in training are most likely to have difficulty navigating.ConclusionsOur study widens the understanding of doctors in training prescribing experiences and development needs regarding the prescribing process. Our process model, identifying the common disturbances and hot spots in the process, can facilitate the development of antibiotic prescribing activities and the optimal design of interventions to support doctors in training.
Protocol for a feasibility study of a cohort embedded randomised controlled trial comparingNEphronSparingTreatment (NEST) for small renal masses
Authors: Neves Joana B , Cullen David , Grant Lee , Walkden Miles , Bandula Steve , Patki Prasad , Barod Ravi , Mumtaz Faiz , Aitchison Michael , Pizzo Elena , Ranieri Veronica , Williams Norman , Wildgoose William , Gurusamy Kurinchi , Emberton Mark , Bex Axel , Tran Maxine G B 
Published: June 2019

IntroductionSmall renal masses (SRMs; ≤4 cm) account for two-thirds of new diagnoses of kidney cancer, the majority of which are incidental findings. The natural history of the SRM seems largely indolent. There is an increasing concern regarding surgical overtreatment and the associated health burden in terms of morbidity and economy. Observational data support the safety and efficacy of percutaneous cryoablation but there is an unmet need for high-quality evidence on non-surgical management options and a head-to-head comparison with standard of care is lacking. Historical interventional trial recruitment difficulties demand novel study conduct approaches. We aim to assess if a novel trial design, the cohort embedded randomised controlled trial (RCT), will enable carrying out such a comparison.Methods and analysisSingle-centre prospective cohort study of adults diagnosed with SRM (n=200) with an open label embedded interventional RCT comparing nephron sparing interventions. Cohort participants will be managed at patient and clinicians’ discretion and agree with longitudinal clinical data and biological sample collection, with invitation for trial interventions and participation in comparator control groups. Cohort participants with biopsy-proven renal cell carcinoma eligible for both percutaneous cryoablation and partial nephrectomy will be randomly selected (1:1) and invited to consider percutaneous cryoablation (n=25). The comparator group will be robotic partial nephrectomy (n=25). The primary outcome of this feasibility study is participant recruitment. Qualitative research techniques will assess barriers and recruitment improvement opportunities. Secondary outcomes are participant trial retention, health-related quality of life, treatment complications, blood transfusion rate, intensive care unit admission and renal replacement requirement rates, length of hospital stay, time to return to pre-treatment activities, number of work days lost, and health technologies costs.Ethics and disseminationEthical approval has been granted (UK HRA REC 19/EM/0004). Study outputs will be presented and published.Trial registrationISRCTN18156881; Pre-results.
Short-Run Bond Risk Premia
Authors: Mueller Philippe , Vedolin Andrea , Zhou Hao 
Published: June 2019

In the short-run, bond risk premia exhibit pronounced spikes around major economic and financial crises. In contrast, long-term bond risk premia feature cyclical swings. We empirically examine the predictability of the market variance risk premium — a proxy of economic uncertainty — for bond risk premia and we show the strong predictive power for the one-month horizon that quickly recedes for longer horizons. The variance risk premium is largely orthogonal to well-established bond return predictors — forward rates, jumps, and macro variables. We rationalize our empirical findings in an equilibrium model of uncertainty about consumption and inflation which is coupled with recursive preferences. We show that the model can quantitatively explain the levels of bond and variance risk premia as well as the predictive power of the variance risk premium, while jointly matching salient features of other asset prices.
Vorinostat Potentiates 5-Fluorouracil/Cisplatin Combination by Inhibiting Chemotherapy-Induced EGFR Nuclear Translocation and Increasing Cisplatin Uptake
Authors: Piro Geny , Roca Maria Serena , Bruzzese Francesca , Carbone Carmine , Iannelli Federica , Leone Alessandra , Volpe Maria Grazia , Budillon Alfredo , Di Gennaro Elena 
Published: June 2019

Abstract
The 5-fluorouracil/cisplatin (5FU/CDDP) combination is one of the most widely used treatment options for several solid tumors. However, despite good anticancer responses, this regimen is often associated with high toxicity and treatment resistance. In our study, we evaluated whether the histone deacetylase inhibitor (HDACi), vorinostat, may induce synergistic antitumor and proapoptotic effects in combination with 5FU/CDDP in squamous cancer cell models. We demonstrated in cancer cell lines, including the intrinsic CDDP-resistant Cal27 cells, that simultaneous exposure to equitoxic doses of vorinostat plus 5FU/CDDP results in strong synergistic antiproliferative and proapoptotic effects related to cell-cycle perturbation and DNA damage induction. These effects were confirmed in vivo in both orthotopic and heterotopic xenograft mouse models of Cal27 cells. Mechanistically, vorinostat reverted 5FU/CDDP-induced EGFR phosphorylation and nuclear translocation, leading to the impairment of nuclear EGFR noncanonical induction of genes such as thymidylate synthase and cyclin D1. These effects were exerted by vorinostat, at least in part, by increasing lysosomal-mediated EGFR protein degradation. Moreover, vorinostat increased platinum uptake and platinated DNA levels by transcriptionally upregulating the CDDP influx channel copper transporter 1 (CTR1). Overall, to our knowledge, this study is the first to demonstrate the ability of vorinostat to inhibit two well-known mechanisms of CDDP resistance, EGFR nuclear translocation and CTR1 overexpression, adding new insight into the mechanism of the synergistic interaction between HDACi- and CDDP-based chemotherapy and providing the rationale to clinically explore this combination to overcome dose-limiting toxicity and chemotherapy resistance.
Patient Characteristics Associated With Antianginal Medication Escalation and De-Escalation Following Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Hirai Taishi , Qintar Mohammed , Grantham J. Aaron , Sapontis James , Cohen David J. , Lombardi William , Karmpaliotis Dimitri , Moses Jeffrey , Nicholson William J. , Nugent Karen , Gosch Kensey L. , Spertus John A. , Salisbury Adam C. ,   on behalf of the OPEN CTO Study Group
Published: June 2019

Background:
Prior research has shown that providers may infrequently adjust antianginal medications (AAMs) following chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Patient characteristics associated with AAM titration and the variation in postprocedure AAM management after CTO PCI across hospitals have not been reported. We sought to determine the frequency and potential correlates of AAM escalation and de-escalation after CTO PCI.

Methods and Results:

Using the 12-center OPEN CTO registry (Outcomes, Patient Health Status, and Efficiency iN Chronic Total Occlusion Hybrid Procedures), we assessed AAM use at baseline and 6 months after CTO PCI. Escalation was defined as any addition of a new class of AAM or dose increase, whereas de-escalation was defined as a reduction in the number of AAMs or dose reduction. Angina was assessed 6 months after the index CTO PCI attempt using the Seattle Angina Questionnaire Angina Frequency domain. Potential correlates of AAM escalation (vs no change) or de-escalation (vs no change) were evaluated using multivariable modified Poisson regression models. Adjusted variation across sites was evaluated using median rate ratios. AAMs were escalated in 158 (17.5%), de-escalated in 351 (39.0%), and were unchanged at 6-month follow-up in 392 (43.5%). Patient characteristics associated with escalation included lung disease, ongoing angina, and periprocedural major adverse cardiac and cerebral events (periprocedural myocardial infarction, stroke, death, emergent cardiac surgery, or clinically significant perforation), whereas de-escalation was more frequent among patients taking more AAMs, those treated with complete revascularization, and after treatment of non-CTO lesions at the time of the index procedure. There was minimal variation in either escalation (median rate ratio, 1.11;
P
=0.36) or de-escalation (median rate ratio, 1.10;
P
=0.20) compared to no change of AAMs across sites.

Conclusions:
Escalation or de-escalation of AAMs was less common than continuation following CTO PCI, with little variation across sites. Further research is needed to identify patients who may benefit from AAM titration after CTO PCI and develop strategies to adjust these medications in follow-up.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02026466.
The Priestly Referent of 4QMMT B 64–72 and Its Implications for the Organization and Origin of the Text
Authors: Wearne Gareth 
Published: June 2019

AbstractAmong the enduring enigmas of 4QMMT are the organizational principles which govern its halakhic section. Focusing primarily on the halakhah concerning skin disease in B 64–72, this article argues that the arrangement of MMT’s halakhot was influenced, at least in part, by similar collocations of topics in Leviticus 21–22 and possibly Ezek 44:15–31. It seems that the selection of sources is attributable to a specific focus on priestly conduct in the halakhah. By recognizing the nature and extent of this dependence it is possible to better understand MMT’s origin and the writers’ exegetical and halakhic methods.
Questioning the Criminal Justice Imperative
Authors: Cullen Miriam 
Published: June 2019

Abstract
The Security Council’s structure as a small but powerful executive, combined with its primary responsibility for international peace and security, leads to a presumption against the application of ordinary standards of procedural fairness. At the same time, explicit provisions of the UN Charter and its own rules of procedure indicate that some balance was to be struck. This article questions whether the attainment of international criminal jurisdiction through Security Council decision-making really outweighs the need to ensure procedural integrity in every step of the process. It posits that a lack of procedural fairness in the Council’s methods of work at least undermines the justice imperative that the Council so espouses and at most violates an ancillary legal obligation.
A Comparative Verification of Raw and Bias-Corrected ECMWF Seasonal Ensemble Precipitation Reforecasts in Java (Indonesia)
Authors: Ratri Dian Nur , Whan Kirien , Schmeits Maurice 
Published: June 2019

AbstractDynamical seasonal forecasts are afflicted with biases, including seasonal ensemble precipitation forecasts from the new ECMWF seasonal forecast system 5 (SEAS5). In this study, biases have been corrected using empirical quantile mapping (EQM) bias correction (BC). We bias correct SEAS5 24-h rainfall accumulations at seven monthly lead times over the period 1981–2010 in Java, Indonesia. For the observations, we have used a new high-resolution (0.25°) land-only gridded rainfall dataset [Southeast Asia observations (SA-OBS)]. A comparative verification of both raw and bias-corrected reforecasts is performed using several verification metrics. In this verification, the daily rainfall data were aggregated to monthly accumulated rainfall. We focus on July, August, and September because these are agriculturally important months; if the rainfall accumulation exceeds 100 mm, farmers may decide to grow a third rice crop. For these months, the first 2-month lead times show improved and mostly positive continuous ranked probability skill scores after BC. According to the Brier skill score (BSS), the BC reforecasts improve upon the raw reforecasts for the lower precipitation thresholds at the 1-month lead time. Reliability diagrams show that the BC reforecasts have good reliability for events exceeding the agriculturally relevant 100-mm threshold. A cost/loss analysis, comparing the potential economic value of the raw and BC reforecasts for this same threshold, shows that the value of the BC reforecasts is larger than that of the raw ones, and that the BC reforecasts have value for a wider range of users at 1- to 7-month lead times.
Acceptability and feasibility of a self-management intervention for women prescribed tamoxifen
Authors: Moon Zoe , Moss-Morris Rona , Hunter Myra S , Goodliffe Samantha , Hughes Lyndsay D 
Published: June 2019

Objective: Up to 50% of breast cancer survivors prescribed tamoxifen do not take it as prescribed for the full duration, which is linked to increased risk of recurrence and mortality. This paper tests the feasibility and acceptability of a self-directed psychoeducational intervention to support medication taking. Design: A single arm pre–post design was used with 33 women with suboptimal adherence to tamoxifen (scores ⩽ 24 on the Medication Adherence Rating Scale, range 5–25) taking part in the intervention over 2–12 weeks. Method: Feasibility was assessed via eligibility, uptake and retention. Questionnaires were completed pre- and post-intervention, and qualitative interviews were conducted to assess acceptability of the materials. Results: Recruitment and uptake were good, with 87% of eligible participants agreeing to participate. Two thirds of participants recruited to the study completed the follow-up questionnaires (66%). The qualitative interviews showed that the participants found the materials acceptable and helpful. Paired samples t-tests showed small improvements in adherence over time, as well as improvements in psychosocial targets of the intervention, namely; necessity and concern beliefs, personal control, coherence, distress, symptom experience and self-efficacy for managing side-effects. Conclusion: The intervention appears to be acceptable and feasible in this population and has the potential to improve both adherence and quality of life in breast cancer survivors prescribed tamoxifen. Larger scale trials are needed however to establish the efficacy of the materials.
People with intellectual disabilities, relationship and sex education programmes: A systematic review
Authors: McCann Edward , Marsh Lynne , Brown Michael 
Published: June 2019

Objective: The aim of this systematic review was to examine the research evidence concerning the views and experiences of people with intellectual disabilities regarding their participation in and the effectiveness of relationship and sex education programmes. Methods: A systematic search of relevant electronic databases was conducted using defined inclusion criteria. All papers reviewed were from October 1998 to October 2018. PRISMA guidelines were followed in the design and reporting of the systematic review. Results: A total of eight studies published in English were included in the review. Data were analysed and the key themes identified were (1) designing and developing relationship and sex education programmes, (2) participating in relationship and sex education programmes and (3) perceived benefits of relationship and sex education programme participation. Conclusion: This review identified that people with intellectual disabilities are accessing relationship and sex education programmes and appear to find them helpful. Further research is required to investigate the extent to which programmes impact on long-term behaviours that enable the development of sustainable relationships and reduce the unintended consequences of sexual activities. Implications for policy, practice and future research developments are discussed.
Comparison of Predictions Between an EMG-Assisted Approach and Two Optimization-Driven Approaches for Lumbar Spine Loading During Walking With Backpack Loads
Authors: Li Simon S. W. , Chow Daniel H. K. 
Published: June 2019

Objective The efficacy of two optimization-driven biomechanical modeling approaches has been compared with an electromyography-assisted optimization (EMGAO) approach to predict lumbar spine loading while walking with backpack loads. Background The EMGAO approach adopts more variables in the optimization process and is complex in data collection and processing, whereas optimization-driven approaches are simple and include the fewest possible variables. However, few studies have been conducted on the efficacy of using the optimization-driven approach to predict lumbar spine loading while walking with backpack loads. Method Anthropometric information of 10 healthy male adults as well as their kinematic, kinetic, and electromyographic data acquired while they walked with various backpack loads (no-load, 5%, 10%, 15%, and 20% of body weight) served as inputs into the model for predicting lumbosacral joint compression forces. The efficacy of two optimization-driven models, namely double linear optimization with constraints on muscle intensity and single linear optimization without any constraints, was investigated by comparing the resulting force profile with that provided by a current EMGAO approach. Results The double and single linear optimization approaches predicted mean deviations in peak force of −5.1%, and −19.2% as well as root-mean-square differences in force profile of 16.2%, and 25.4%, respectively. Conclusion The double linear optimization approach was a relatively comparable estimator to the EMGAO approach in terms of its consistency, slight bias, and efficiency for predicting peak lumbosacral joint compression forces. Application The double linear optimization approach is a useful biomechanical model for estimating peak lumbar compression forces while walking with backpack loads.
Risk Factors for Mortality and Pre-ICU Fluid Balance Among Critically Ill Hematopoietic Stem Cell Transplant Patients
Authors: Mueller Dana M. , Markovitz Barry P. , Zinter Matt S. , Takimoto Sarah W. , Khemani Robinder G. 
Published: June 2019

Objective: To examine if fluid balance surrounding pediatric intensive care unit (PICU) admission in hematopoietic stem cell transplant (HSCT) patients was associated with mortality, ventilator-free days, and intensive care unit (ICU)-free days. To explore other population-specific factors associated with poor outcome. Materials and Methods: Retrospective review of HSCT patients admitted to 2 quaternary PICUs, Children’s Hospital Los Angeles and University of California San Francisco Benioff Children’s Hospital from January 2009 to December 2014. Results: Of 144 patients, 92 were identified with complete fluid balance data available. No difference in fluid balance between survivors and nonsurvivors in the 24 hours preceding PICU admission ( P = .81) or when the first 24 hours of PICU stay were taken into account ( P = .48) was identified. There was no difference in ventilator-free or ICU-free days. Comparing Pediatric Index of Mortality (PIM)-2, Pediatric Risk of Mortality (PRISM)-3, and a multivariable model using independent risk factors identified through multivariable analysis, the receiver operating characteristic plot for the multivariable model (area under the curve = 0.844 [95% confidence interval: 0.77-0.92]) was superior to both PIM-2 and PRISM-3 in discriminating mortality. Conclusions: Fluid balance immediately preceding and early in the course of admission was not associated with mortality in PICU HSCT patients. A subset of variables was identified which better discriminated mortality in this cohort than accepted PICU severity of illness scores.
Increased Length of Stay Associated With Antibiotic Use in Older Adults With Advanced Cancer Transitioned to Comfort Measures
Authors: Datta Rupak , Zhu Mojun , Han Ling , Allore Heather , Quagliarello Vincent , Juthani-Mehta Manisha 
Published: June 2019

Background: Antibiotic use may increase hospital length of stay (LOS) among older patients with advanced cancer who are transitioned to comfort measures. Methods: We studied a cohort of patients with advanced cancer aged ≥65 years who were transitioned to comfort measures during admission from July 1, 2014, through November 30, 2016. We evaluated the association between antibiotic exposure and LOS using a Poisson regression model adjusted for age, gender, cancer type, comorbidities, infection, and intensive care unit admission. Results: Among 461 patients with advanced cancer, median age was 74 years (range: 65-99), 49.0% (n = 226) were female, and 20.6% (n = 95) had liquid tumors. Overall, 82.9% (n = 382) received ≥1 antibiotic and 64.6% (n = 298) had ≥1 infection diagnosis during hospitalization. Infection diagnoses commonly included sepsis (35%, n = 161/461), pneumonia (25%, n = 117/461), and urinary tract infection (14%, n = 66/461). Among those receiving antibiotics, the most common choices included vancomycin (79%, n = 300/382), cephalosporins (63%, n = 241/382), and penicillins (45%, n = 172/382). In a multivariable Poisson regression model, LOS was 34% longer (count ratio = 1.34, [95% confidence interval: 1.20-1.51]) among those exposed versus unexposed to antibiotics. Conclusions: Antibiotic use among patients with advanced cancer who are transitioned to comfort measures is associated with longer LOS. These data illustrate the importance of tradeoffs associated with antibiotic use, such as unintended increased LOS, when striving for goal-concordant care near the end of life.