bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study
Authors: Ponatshego Ponego Lloyd , Lawrence David Stephen , Youssouf Nabila , Molloy Sile F , Alufandika Melanie , Bango Funeka , Boulware David R , Chawinga Chimwemwe , Dziwani Eltas , Gondwe Ebbie , Hlupeni Admire , Hosseinipour Mina C , Kanyama Cecilia , Meya David B , Mosepele Mosepele , Muthoga Charles , Muzoora Conrad K , Mwandumba Henry , Ndhlovu Chiratidzo E , Rajasingham Radha , Sayed Sumaya , Shamu Shepherd , Tsholo Katlego , Tugume Lillian , Williams Darlisha , Maheswaran Hendramoorthy , Shiri Tinevimbo , Boyer-Chammard Timothée , Loyse Angela , Chen Tao , Wang Duolao , Lortholary Olivier , Lalloo David G , Meintjes Graeme , Jaffar Shabbar , Harrison Thomas S , Jarvis Joseph N , Niessen Louis Wilhelmus 
Published: May 2020

IntroductionCryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation.Methods and analysisCountry-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial.Ethics and disseminationThe AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings.Trial registrationISRCTN72509687; Pre-results.
‘Reducing Delays In Vaccination’ (REDIVAC) trial: a protocol for a randomised controlled trial of a web-based, individually tailored, educational intervention to improve timeliness of infant vaccination
Authors: Dempsey Amanda F , Wagner Nicole , Narwaney Komal , Pyrzanowski Jennifer , Kwan Bethany M , Kraus Courtney , Gleason Kathy , Resnicow Ken , Sevick Carter , Cataldi Jessica , Brewer Sarah E , Glanz Jason M 
Published: May 2020

IntroductionIncreasing numbers of children are failing to receive many recommended vaccines, which has led to significant outbreaks of vaccine-preventable diseases in the USA and worldwide. A major driver of undervaccination is parental vaccine hesitance. Prior research demonstrates that mothers are the primary decision maker for infant vaccination, and that their vaccination attitudes form primarily during pregnancy and early in their infant’s life.Methods and analysisThis manuscript describes the protocol for an ongoing three-armed randomised controlled trial done at Kaiser Permanente Colorado (KPCO). The trial aims to test the efficacy of provided tailored, individualised information via the Internet to pregnant and new mothers versus untailored information versus usual care on the timeliness of infant vaccination. The primary outcome to be assessed is vaccination status, which is a dichotomous outcome (up to date vs not) assessed at age 200 days, reflecting the time when infants should have completed the first set of vaccine provided (at age 2, 4 and 6 months). Infants with one or more age-appropriate recommended vaccines at least 30 days delayed are categorised as not up to date whereas all other infants are considered up to date. Secondary outcomes include vaccination status at age 489 days, reflecting receipt of recommended vaccines at age 12–15 months, as well as vaccination attitudes, hesitancy and intention. Vaccination data will be derived from the electronic medical record and the state immunisation registry. Other secondary outcomes will be assessed by online surveys.Ethics and disseminationThe study activities were approved by the Institutional Review Boards of the University of Colorado, KPCO and the University of Michigan. Results will be disseminated through peer-reviewed manuscripts and conference presentations.Trial registration numberNCT02665013; Pre-results.
Comparative fertility and pregnancy outcomes after local treatment for cervical intraepithelial neoplasia and stage 1a1 cervical cancer: protocol for a systematic review and network meta-analysis from the CIRCLE group
Authors: Athanasiou Antonios , Veroniki Areti Angeliki , Efthimiou Orestis , Kalliala Ilkka , Naci Huseyin , Bowden Sarah , Paraskevaidi Maria , Martin-Hirsch Pierre , Bennett Philip , Paraskevaidis Evangelos , Salanti Georgia , Kyrgiou Maria 
Published: May 2020

IntroductionThere are several local treatment methods for cervical intraepithelial neoplasia that remove or ablate a cone-shaped part of the uterine cervix. There is evidence to suggest that these increase the risk of preterm birth (PTB) and that this is higher for techniques that remove larger parts of the cervix, although the data are conflicting. We present a protocol for a systematic review and network meta-analysis (NMA) that will update the evidence and compare all treatments in terms of fertility and pregnancy complications.Methods and analysisWe will search electronic databases (CENTRAL, MEDLINE, EMBASE) from inception till October 2019, in order to identify randomised controlled trials (RCTs) and cohort studies comparing the fertility and pregnancy outcomes among different excisional and ablative treatment techniques and/or to untreated controls. The primary outcome will be PTB (<37 weeks). Secondary outcomes will include severe or extreme PTB, prelabour rupture of membranes, low birth weight (<2500 g), neonatal intensive care unit admission, perinatal mortality, total pregnancy rates, first and second trimester miscarriage. We will search for published and unpublished studies in electronic databases, trial registries and we will hand-search references of published papers. We will assess the risk of bias in RCTs and cohort studies using tools developed by the Cochrane collaboration. Two investigators will independently assess the eligibility, abstract the data and assess the risk of bias of the identified studies. For each outcome, we will perform a meta-analysis for each treatment comparison and an NMA once the transitivity assumption holds, using the OR for dichotomous data. We will use CINeMA (Confidence in Network meta-analysis) to assess the quality of the evidence for the primary outcome.Ethics and disseminationEthical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.PROSPERO registration numberCRD42018115495
Performance of OncoE6TMCervical Test in detecting cervical precancer lesions in HIV-positive women attending an HIV clinic in Bujumbura, Burundi: a cross-sectional study
Authors: Ndizeye Zacharie , Menon Sonia , Van Geertruyden Jean-Pierre , Sauvaget Catherine , Jacquemyn Y , Bogers John-Paul , Benoy Ina , Vanden Broeck Davy 
Published: May 2020

ObjectiveNew rapid and low-cost molecular tests for cervical cancer screening, such as the OncoE6 Cervical Test, are emerging and could be alternatives for low-income and middle-income countries. To this end, we evaluated the clinical performance of the OncoE6 Cervical Test in detecting cervical intraepithelial neoplasia (CIN) among HIV-infected women in Bujumbura, Burundi.MethodsFrom June to December 2017, a cross-sectional study was conducted in 680 HIV-positive women at the University Hospital. Women aged 25–65 years who declared having had vaginal intercourse were consecutively recruited, and cervical specimens for OncoE6, liquid-based cytology and human papillomavirus (HPV) genotyping were obtained and visual inspection with acetic acid performed. Thereafter, participants underwent a colposcopic examination. The sensitivity, specificity, and positive and negative predictive values of the different tests were calculated with reference to ‘colposcopic-histological’ diagnoses, and areas under the receiver operating curves of OncoE6 and cytology tests were compared.ResultsThe prevalence of CIN was 4.9%, and OncoE6 positivity was 3.1%. OncoE6 sensitivity varied from poor to low with increasing disease severity (42.1%, 95% CI 19.9% to 64.3% at CIN2+ threshold; and 58.3%, 95% CI 30.4% to 86.2% at CIN3+ threshold). OncoE6 had the highest specificity compared with all other tests used together. The performance of the OncoE6 test was significantly lower compared with cytology at atypical squamous cell of undetermined significance (ASCUS+) cut-off (AUC=0.68 vs 0.85, p=0.03) and low-grade squamous intraepithelial lesion (LSIL+) cut-off (AUC=0.68 vs 0.83, p=0.04) for CIN2+ diagnoses. However, the performance of the OncoE6 test was similar to that of cytology at high-grade squamous intraepithelial lesion (HSIL+) cut-off (AUC=0.68 vs 0.76; p=0.30) for CIN2+ diagnoses and was also similar to that of cytology at all cut-offs (ASCUS+, LSIL+ and HSIL+) for CIN3+ diagnoses (p1=0.76, p2=0.95 and p3=0.50, respectively).ConclusionThe current OncoE6 test proved to be a point-of-care test. However, given its poor performance for CIN2+ diagnoses, we do not recommend it for primary screening. We recommend to enrich it with more oncogenic HPV types, which may improve the performance of the test akin to that of cytology.
Associations between the SHARE frailty phenotype and common frailty characteristics: evidence from a large Danish population study
Authors: Jacobsen Katja Kemp , Jepsen Randi , Lembeck Maurice A , Nilsson Charlotte , Holm Ellen 
Published: May 2020

ObjectivesFrailty is a major clinical geriatric syndrome associated with serious adverse events including functional disability, falls, hospitalisation, increased morbidity and mortality. The aim of this study was to study associations between a frailty phenotype and frailty characteristics well known from the literature.DesignRegistry-based cross-sectional study.SettingThe target population consists of inhabitants above the age of 50 living in the Danish municipalities of Lolland and Guldborgsund. Excluded are incapacitated people, inhabitants unable to understand Danish or English and inhabitants without a permanent residence.Participants7327 individuals aged 50+ years were included.Outcome measuresWe examined associations between the frailty measurement and factors known to be associated with frailty: sex, age, income insufficiency, education, comorbidity, self-assessed health, morbidity and mortality.Results7327 individuals aged 50+ years were included. Of these, 6.5% had ≥3 frailty components (frail), 46.7% had 1–2 components (prefrail) and 46.9% had none (non-frail). Those who were frail were older and more likely female than those who were non-frail or prefrail. There was a stepwise decrease in educational level, and in self-assessed health with increasing frailty status, and a stepwise increase in difficulty in making ends meet, number of hospital contacts and mortality with increasing frailty status, p<0.0001 for each comparison. Compared with individuals who were non-frail, mortality was higher among those who were prefrail (HR: 2.90; 95% CI: 1.30 to 6.43) or frail (HR: 8.21; 95% CI: 3.37 to 20.0).ConclusionsBased on these findings, we consider the Lolland-Falster Health Study frailty assessment a valid instrument demonstrating the same characteristics as other validated frailty measures concerning associations with sex, age, income insufficiency, education, comorbidity, self-assessed health, morbidity and mortality.Trial registration numberNCT02482896.
Evaluation of the role of sex as a prognostic factor in critically ill adults with sepsis: systematic review protocol
Authors: Lopez-Alcalde Jesus , Antequera Martín Alba , Stallings Elena , Muriel Alfonso , Fernández-Félix Borja , Solà Ivan , del Campo Rosa , Ponce-Alonso Manuel , Gordo Federico , Fidalgo Pilar , Halperin Ana Verónica , Álvarez-Díaz Noelia , Madrid-Pascual Olaya , Urrutia Gerard , Zamora Javier 
Published: May 2020

IntroductionSepsis is a leading cause of mortality in critically ill patients. Recently, it has been recognised that sex may contribute to a differential risk for developing sepsis and it remains uncertain if the prognosis of sepsis varies between the sexes. The aim of this systematic review is to summarise the available evidence to assess the role of sex as a prognostic factor in patients with sepsis managed in the intensive care unit (ICU).Methods and analysisThis is a systematic review protocol of prognostic studies of sex in patients with sepsis managed in the ICU. The primary outcomes include all-cause hospital mortality and all-cause hospital mortality during the first 28 days. The secondary outcomes include all-cause hospital mortality during the first 7 days and all-cause mortality at 1 year. We will conduct a search strategy based on the population (sepsis), the prognostic factor (sex), the outcome of interest (mortality) and prognostic study methods. We will search in the following databases up to December 2019: MEDLINE Ovid (from 1976), Embase Elsevier (from 1974), Web of Science and two trial registries. We will impose no language restrictions. Two authors will independently screen titles, abstracts and full-text articles for eligibility of studies, and subsequently extract data. Two authors will independently assess the risk of bias of each study using the Quality in Prognostic Studies (QUIPS) tool. If possible, we will carry out a meta-analysis to provide a pooled prognostic effect estimate for each outcome. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence.Ethics and disseminationEthical approval will not be required. Findings from this review will be reported in a peer-reviewed scientific journal. Additionally, the results will be disseminated at conferences and in the mass media.PROSPERO registration numberCRD42019145054.
A Bayesian comparison between $$\Lambda $$CDM and phenomenologically emergent dark energy models
Authors: Rezaei M. , Naderi T. , Malekjani M. , Mehrabi A. 
Published: May 2020

AbstractIn this work we examine the recently proposed phenomenological emergent dark energy (PEDE) model by [1], using the latest observational data in both expansion and perturbation levels. Applying the statistical Bayesian evidence as well as the AIC and BIC information criteria, we compare the PEDE model with the concordance $$\Lambda $$ΛCDM model in both flat and non-flat universes. We combine the observational datasets as (i) expansion data (except CMB), (ii) expansion data (including CMB) and (iii) expansion data jointed to the growth rate dataset. Our statistical results show that the flat- $$\Lambda $$ΛCDM model is still the best model. In the case of expansion data (including CMB), we observe that the flat- PEDE model is well consistent with observations as well as the concordance $$\Lambda $$ΛCDM universe. While in the cases of (i) and (iii), the PEDE models in both of the flat and non-flat geometries are not favored. In particular, we see that in the perturbation level the PEDE model can not fit the observations as equally as standard $$\Lambda $$ΛCDM cosmology. As the ability of the model, we show that the PEDE models can alleviate the tension of Hubble constant value appearing between the local observations and Planck inferred estimation in standard cosmology.
On the hydrodynamics of nonlinear gauge-coupled quantum fluids
Authors: Buggy Yvan , Phillips Lawrence G. , Öhberg Patrik 
Published: May 2020

Abstract

By constructing a hydrodynamic canonical formalism, we show that the occurrence of an arbitrary density-dependent gauge potential in the meanfield Hamiltonian of a Bose-condensed fluid invariably leads to nonlinear flow-dependent terms in the wave equation for the phase, where such terms arise due to the explicit dependence of the mechanical flow on the fluid density. In addition, we derive a canonical momentum transport equation for this class of nonlinear fluid and obtain an expression for the stress tensor. Further, we study the hydrodynamic equations in a particular nonlinear fluid, where the effective gauge potential results from the introduction of weak contact interactions in an ultracold dilute Bose gas of optically-addressed two-level atoms. In the Cauchy equation of mechanical momentum transport of the superfluid, two non-trivial terms emerge due to the density-dependent vector potential. A body-force of dilation appears as a product of the gauge potential and the dilation rate of the fluid, while the stress tensor features a canonical flow pressure term given by the inner-product of the gauge potential and the canonical current density. By numerical simulation, we illustrate an interesting effect of the nonlinear gauge potential on the groundstate wavefunction of a superfluid in the presence of a foreign impurity. We find that the groundstate adopts a non-trivial local phase, which is antisymmetric under reversal of the gauge potential. The phase profile leads to a canonical-flow or phase-flow dipole about the impurity, resulting in a skirting mechanical flow. As a result, the pressure becomes asymmetric about the object and the condensate undergoes a deformation.

Graphical abstract
Synaptic Communication in Brain Cancer
Authors: Monje Michelle 
Published: May 2020

Abstract
Increasing evidence indicates that the nervous system plays a critical role in cancer progression. This is particularly true in cancers that occur within the central nervous system. Communication between neurons and cancer cells is a fundamental component of brain cancer pathophysiology, both for primary gliomas and for brain metastases. Neuronal activity drives growth of glial malignancies through secreted growth factors and through direct electrochemical synaptic communication. Reciprocally, brain cancers influence neuronal function, increasing neuronal activity and modulating the function of the circuits into which the cancer cells structurally and electrically integrate. Advancing understanding of neuron–cancer interactions will elucidate new therapeutic strategies for these presently lethal brain cancers.
Effect of a Digital Health Intervention on Decreasing Barriers and Increasing Facilitators for Colorectal Cancer Screening in Vulnerable Patients
Authors: Denizard-Thompson Nancy M. , Miller David P. , Snavely Anna C. , Spangler John G. , Case L. Doug , Weaver Kathryn E. 
Published: May 2020

Abstract

Background:
Colorectal cancer is the second leading cause of cancer-related death in the United States, in part, because one third of Americans fail to get screened. In a prior randomized controlled trial, we found that an iPad patient decision aid called Mobile Patient Technology for Health-CRC (mPATH-CRC) doubled the proportion of patients who completed colorectal cancer screening.

Methods:
All data for the current analysis were collected as part of a randomized controlled trial to determine the impact of mPATH-CRC on receipt of colorectal cancer screening within 24 weeks. Participants were enrolled from six community-based primary care practices between June 2014 and May 2016 and randomized to either usual care or mPATH-CRC. Six potential mediators of the intervention effect on screening were considered. The Iacobucci method was used to assess the significance of the mediation.

Results:
A total of 408 patients had complete data for all potential mediators. Overall, the potential mediators accounted for approximately three fourths (76.3%) of the effect of the program on screening completion. Perceived benefits, self-efficacy, ability to state a screening decision, and patient–provider discussion were statistically significant mediators. Patient–provider discussion accounted for the largest proportion of the effect of mPATH-CRC (70.7%).

Conclusions:
mPATH-CRC increased completion of colorectal cancer screening by affecting patient-level and system-level mediators. However, the most powerful mediator was the occurrence of a patient–provider discussion about screening. Digital interventions like mPATH-CRC are an important adjunct to the patient–provider encounter.

Impact:
Understanding the factors that mediated mPATH-CRC's success is paramount to developing other effective interventions.
A Phase 1b Dose Escalation Trial of NC-6300 (Nanoparticle Epirubicin) in Patients with Advanced Solid Tumors or Advanced, Metastatic, or Unresectable Soft-tissue Sarcoma
Authors: Chawla Sant P. , Goel Sanjay , Chow Warren , Braiteh Fadi , Singh Arun S. , Olson Juneko E. Grilley , Osada Atsushi , Bobe Iulian , Riedel Richard F. 
Published: May 2020

Abstract

Purpose:
NC-6300 is a novel nanoparticle formulation of epirubicin that has a pH-sensitive linker conjugated to epirubicin. It exhibits selective tumor accumulation owing to enhanced permeability and retention effect. We conducted a phase 1b trial to determine MTD and recommended phase II dose (RP2D) of NC-6300 monotherapy in advanced, metastatic, or unresectable solid tumors, including soft-tissue sarcomas.

Patients and Methods:
This phase 1b dose-escalation trial of NC-6300 monotherapy employed a Bayesian continuous reassessment method design. NC-6300 was administered on day 1 of every 21-day cycle, with epirubicin-equivalent dose increments from 125 to 215 mg/m2. Safety, efficacy, quality of life, and pharmacokinetic profile of NC-6300 monotherapy were evaluated.

Results:
Twenty-nine subjects (16 male) were enrolled: 17 with soft-tissue sarcoma, one with osteosarcoma, and 11 with other solid tumors. Observed dose-limiting toxicities included thrombocytopenia, stomatitis, lung infection, and febrile neutropenia. The most common grade 3/4 adverse events were neutropenia (59%), anemia (24%), thrombocytopenia (24%), and febrile neutropenia (21%). MTD and RP2D were determined to be 185 mg/m2 and 150 mg/m2, respectively. The objective response rate in the evaluable population was 11%. Partial response was observed in angiosarcoma and endometrial stromal sarcoma. A dose-dependent increase was observed in both total and released epirubicin concentrations.

Conclusions:
NC-6300 was well tolerated with a manageable side effect profile, despite the MTD and RP2D being higher than conventional epirubicin doses. A signal of preliminary activity was observed in angiosarcoma. NC-6300 warrants further investigation in patients with advanced solid tumors, including sarcoma.