bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Outcomes of Direct-Acting Antiviral Treatment and Retreatment in United Kingdom–Based Patients Infected With Hepatitis C Virus Genotypes/Subtypes Endemic in Africa
Authors: Aranday-Cortes Elihu , McClure C Patrick , Davis Christopher , Irving William L , Adeboyejo Kazeem , Tong Lily , da Silva Filipe Ana , Sreenu Vattipally , Agarwal Kosh , Mutimer David , Stone Benjamin , Cramp Matthew E , Thomson Emma C , Ball Jonathan K , McLauchlan John 
Published: February 2021

Abstract

Background
Chronic hepatitis C virus (HCV) infection affects 71 million individuals, mostly residing in low- and middle-income countries (LMICs). Direct-acting antivirals (DAAs) give high rates of sustained virological response (SVR) in high-income countries where a restricted range of HCV genotypes/subtypes circulate.

Methods
We studied United Kingdom–resident patients born in Africa to examine DAA effectiveness in LMICs where there is far greater breadth of HCV genotypes/subtypes. Viral genome sequences were determined from 233 patients.

Results
Full-length viral genomic sequences for 26 known subtypes and 5 previously unidentified isolates covering 5 HCV genotypes were determined. From 149 patients who received DAA treatment/retreatment, the overall SVR was 93%. Treatment failure was associated primarily with 2 subtypes, gt1l and gt4r, using sofosbuvir/ledipasvir. These subtypes contain natural resistance-associated variants that likely contribute to poor efficacy with this drug combination. Treatment failure was also significantly associated with hepatocellular carcinoma.

Conclusions
DAA combinations give high SVR rates despite the high HCV diversity across the African continent except for subtypes gt1l and gt4r, which respond poorly to sofosbuvir/ledipasvir. These subtypes are widely distributed across Western, Central, and Eastern Africa. Thus, in circumstances where accurate genotyping is absent, ledipasvir and its generic compounds should not be considered as a recommended treatment option.
Hospital nurses’ intention to report near misses, patient safety culture and professional seniority
Authors: Toren Orly , Dokhi Mohanad , Dekeyser Ganz Freda 
Published: February 2021

Abstract

Objectives
To determine the extent nurses reported near miss events; to describe the relationship between patient safety culture, professional seniority and intention to report near misses; and to determine predictors of intention to report near miss events.

Design
This was a descriptive cross-sectional correlational study.The sampling method was cluster convenience sampling. Surveys were based on the Hospital Survey on Patient Safety (HSOPS).

Setting
Three general Hospitals (a small, large and a tertiary center) located in the north and center of Israel.

Participants
ICU and inpatient ward nurses working in general hospitals.

Main outcome measures
Patient safety culture, reporting medical errors and near miss events, intention to report near miss events, professional seniority.

Results
The sample included 227 nurses. Most nurses rated the patient safety culture components as moderately positive. Approximately 80% stated their intention to report a near miss, however 52.4% indicated that they did not report a near miss event in the past year. A positive correlation was found between all components of the patient safety culture and the intention to report a near miss event. Professional seniority was not related to any safety culture components or intention to report a near-miss event. Three variables predicted intention to report: team work, feedback and communication about errors, and the amount of near misses reported in the last year.

Conclusions
There is a discrepancy between what nurses describe as their intent to report a near miss event and their actual reporting of an event. Components of safety culture, especially communication openness, teamwork and reported near misses in the last year are significant predictors of the intent to report. Therefore, reinforcement of these components should be encouraged at the policy level to enable nurses to report near misses and thus improve patient safety.
Impact of pre-existing drug resistance on risk of virological failure in South Africa
Authors: Li Jonathan Z , Stella Natalia , Choudhary Manish C , Javed Aneela , Rodriguez Katherine , Ribaudo Heather , Moosa Mahomed-Yunus , Brijkumar Jay , Pillay Selvan , Sunpath Henry , Noguera-Julian Marc , Paredes Roger , Johnson Brent , Edwards Alex , Marconi Vincent C , Kuritzkes Daniel R 
Published: February 2021

Abstract

Objectives
There is conflicting evidence on the impact of pre-existing HIV drug resistance mutations (DRMs) in patients infected with non-B subtype virus.

Methods
We performed a case–cohort substudy of the AIDS Drug Resistance Surveillance Study, which enrolled South African patients initiating first-line efavirenz/emtricitabine/tenofovir. Pre-ART DRMs were detected by Illumina sequencing of HIV pol and DRMs present at &lt;20% of the viral population were labelled as minority variants (MVs). Weighted Cox proportional hazards models estimated the association between pre-ART DRMs and risk of virological failure (VF), defined as confirmed HIV-1 RNA ≥1000 copies/mL after ≥5 months of ART.

Results
The evaluable population included 178 participants from a randomly selected subcohort (16 with VF, 162 without VF) and 83 additional participants with VF. In the subcohort, 16% of participants harboured ≥1 majority DRM. The presence of any majority DRM was associated with a 3-fold greater risk of VF (P = 0.002), which increased to 9.2-fold (P &lt; 0.001) in those with &lt;2 active drugs. Thirteen percent of participants harboured MV DRMs in the absence of majority DRMs. Presence of MVs alone had no significant impact on the risk of VF. Inclusion of pre-ART MVs with majority DRMs improved the sensitivity but reduced the specificity of predicting VF.

Conclusions
In a South African cohort, the presence of majority DRMs increased the risk of VF, especially for participants receiving &lt;2 active drugs. The detection of drug-resistant MVs alone did not predict an increased risk of VF, but their inclusion with majority DRMs affected the sensitivity/specificity of predicting VF.
Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases
Authors: Álvarez-Marín Rocío , López-Cerero Lorena , Guerrero-Sánchez Francisca , Palop-Borras Begoña , Rojo-Martín María Dolores , Ruiz-Sancho Andrés , Herrero-Rodríguez Carmen , García María Victoria , Lazo-Torres Ana María , López Inmaculada , Martín-Hita Lina , Nuño-Álvarez Enrique , Sánchez-Yebra Waldo , Galán-Sánchez Fátima , Reguera-Iglesias José María , Lepe José Antonio , Peñalva Germán , Pascual Álvaro , Cisneros José Miguel ,   the CarbaPIRASOA team, Rodríguez-Mateos María Eugenia , Gallego-Fernández Carmen , Rueda Félix Gómez-de , Soria Raquel Saldaña , Pérez-Moreno María Antonia , Fernández-Cuenca Felipe , Guindo Pablo Nieto , Peña Alejandro , Márquez-Gómez Ignacio , Valiente Lucía , Ferra-Murcia Sergio , Rodríguez Miguel Ángel , Gea-Lázaro Isabel , Bermejo José Molina-Gil 
Published: February 2021

AbstractBackgroundCarbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB.MethodsWe conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends.ResultsA decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) −1.5%, P &lt; 0.001] and a −8.170 (−16.064 to −0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC −3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC −0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae.ConclusionsIn conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.
Optimal initial antibiotic regimen for the treatment of acute appendicitis: a systematic review and network meta-analysis with surgical intervention as the common comparator
Authors: Wang Chih-Hung , Yang Chi-Chun , Hsu Wan-Ting , Qian Frank , Ding Julia , Wu Han-Ping , Tsai Jih-Jin , Yang Chia-Jui , Su Ming Yang , Chen Shyr-Chyr , Lee Chien-Chang 
Published: February 2021

Abstract

Background
The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens.

Methods
We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a β-lactam/β-lactamase inhibitor combination.

Results
A total of 9 RCTs (adults, n = 8; paediatrics, n = 1) and 12 observational studies (adults, n = 3; paediatrics, n = 9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a β-lactam/β-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8–127.64] or β-lactam/β-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87–187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55–38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01–0.85).

Conclusions
Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.
Changing the way we think: competition, platforms and ecosystems
Authors: Jenny Frederic 
Published: February 2021

ABSTRACT
Many of the traditional tools used by competition authorities to assess relevant markets or the intensity of competition between firms are difficult to use or inadequate to assess competition issues between ecosystems in the digital world. Further economic thinking and an understanding of the business models of ecosystems are required to allow competition authorities to make informed and relevant decisions about competition on digital markets. This article reviews some of the challenges they face.
Dronedarone HCl–Quercetin Co-Amorphous System: Characterization and RP-HPLC Method Development for Simultaneous Estimation
Authors: Navya Sree K S , Dengale Swapnil J , Mutalik Srinivas , Bhat Krishnamurthy 
Published: February 2021

Abstract

Background
Dronedarone HCl (DRN) is an anti-arrhythmic drug indicated for atrial fibrillation. DRN has a low solubility of 2 µg/mL and 4% bioavailability, thus it is formulated as a co-amorphous system to enhance its solubility by using quercetin (QCT) as a co-former. A sensitive, accurate, and economic method for the simultaneous quantification of DRN and QCT in formulation is not found in the literature.

Objective
To develop a Reverse Phase -HPLC method for the simultaneous estimation of DRN and QCT in a DRN–QCT co-amorphous system.

Method
The co-amorphous system was prepared using a solvent evaporation technique with DRN and QCT in a 1:1 molar ratio. The separation was achieved on a Purospher® STAR C18 (250 mm × 4.6 mm × 5 μm id (internal diameter)) column with the mobile phase comprising of acetonitrile and a 25 mM phosphate buffer pH 3.6 (60:40%, v/v).

Results
DRN and QCT were retained on the column for 6.7 and 3.5 min, respectively. For both molecules, the method was developed with a wide linearity range of 0.2–500 µg/mL. The LOD for DRN was found to be 0.0013 µg/mL and for QCT it was found to be 0.0026 µg/mL. The LOQ for DRN was found to be 0.0041 µg/mL, and for QCT it was 0.0078 µg/mL.

Conclusions
The method was validated as per International Conference on Harmonization (ICH) guidelines for linearity, precision, accuracy, and robustness. The method was used in simultaneous quantification of DRN and QCT in co-amorphous samples.

Highlights
The method developed was used for the analysis of content uniformity and solubility samples of co-amorphous system, where the method was able to successfully quantify DRN and QCT. Low detection and quantification limits contribute to the sensitivity of the method and wide linearity range assures the robust and precise quantification of molecules.
Pertuzumab and trastuzumab as adjuvant treatment for HER2-positive early breast cancer: outcomes in Chinese patients in the APHINITY study
Authors: Shao Zhimin , Tseng Ling-Ming , Huang Chiun-Sheng , Pang Da , Yang Youngsen , Li Wei , Liao Ning , Geng Cuizhi , Zhang Qingyuan , Xu Binghe , Liu Donggeng , Kwong Ava ,   et al (continued in the appendix)
Published: February 2021

Abstract

Background
The addition of pertuzumab to trastuzumab plus standard chemotherapy as adjuvant therapy following surgery significantly improved invasive disease-free survival (IDFS) in patients with HER2-positive early breast cancer in the multinational randomized APHINITY trial (NCT01358877, BIG 4–11/BO25126/TOC4939G). We analyzed clinical outcomes in the subgroup of patients recruited at Chinese sites.

Methods
Patients were randomized to standard adjuvant chemotherapy plus 1 year of trastuzumab with pertuzumab or placebo. Patients recruited in mainland China, Hong Kong and Taiwan are included in this descriptive analysis.

Results
Chinese patients had similar demographic characteristics to the global population, but a higher proportion had nodal involvement. Although this subgroup analysis was not powered to detect statistical significance, a numerical improvement in IDFS was observed with the addition of pertuzumab to trastuzumab in Chinese patients (hazard ratio, 0.69; 95% confidence interval: 0.39–1.19; 3-year IDFS event-free estimates 92.5% [pertuzumab] and 91.7% [placebo]), which was consistent with the primary analysis of the global population. Further subgroup analyses showed numerical improvements in the Chinese node-positive, hormone receptor-negative and -positive subgroups, although confidence intervals were wide due to the low number of events. The incidence of diarrhea was higher in the pertuzumab arm, and no primary cardiac events occurred in Chinese patients in either arm.

Conclusions
Pertuzumab, used in combination with trastuzumab and chemotherapy in APHINITY, is effective as an adjuvant treatment regimen for Chinese patients with HER2-positive early breast cancer in a setting with curative intent. The safety profile in Chinese patients was consistent with that of the global population.
Patient-Reported Outcomes and Long-Term Nonadherence to Aromatase Inhibitors
Authors: Hershman Dawn L , Neugut Alfred I , Moseley Anna , Arnold Kathryn B , Gralow Julie R , Henry N Lynn , Hillyer Grace Clarke , Ramsey Scott D , Unger Joseph M 
Published: February 2021

Abstract

Background
Nonadherence to aromatase inhibitors (AIs) is common and increases risk of breast cancer (BC) recurrence. We analyzed factors associated with nonadherence among patients enrolled in S1105, a randomized trial of text messaging.

Methods
At enrollment, patients were required to have been on an adjuvant AI for at least 30 days and were asked about financial, medication, and demographic factors. They completed patient-reported outcomes (PROs) representing pain (Brief Pain Inventory), endocrine symptoms (Functional Assessment of Cancer Therapy–Endocrine Symptoms), and beliefs about medications (Treatment Satisfaction Questionnaire for Medicine; Brief Medication Questionnaire). Our primary endpoint was AI nonadherence at 36 months, defined as urine AI metabolite assay of less than 10 ng/mL or no submitted specimen. We evaluated the association between individual baseline characteristics and nonadherence with logistic regression. A composite risk score reflecting the number of statistically significant baseline characteristics was examined.

Results
We analyzed data from 702 patients; median age was 60.9 years. Overall, 35.9% patients were nonadherent at 36 months. Younger patients (younger than age 65 years) were more nonadherent (38.8% vs 28.6%, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.05 to 2.16; P = .02). Fourteen baseline PRO scales were each statistically significantly associated with nonadherence. In a composite risk model categorized into quartile levels, each increase in risk level was associated with a 46.5% increase in the odds of nonadherence (OR = 1.47, 95% CI =1.26 to 1.70; P &lt; .001). The highest-risk patients were more than 3 times more likely to be nonadherent than the lowest-risk patients (OR = 3.14, 95% CI = 1.97 to 5.02; P &lt; .001).

Conclusions
The presence of multiple baseline PRO-specified risk factors was statistically significantly associated with AI nonadherence. The use of these assessments can help identify patients for targeted interventions to improve adherence.
Repurposing of sildenafil as antitumour; induction of cyclic guanosine monophosphate/protein kinase G pathway, caspase-dependent apoptosis and pivotal reduction of Nuclear factor kappa light chain enhancer of activated B cells in lung cancer
Authors: AboYoussef Amira M , Khalaf Marwa M , Malak Marina N , Hamzawy Mohamed A 
Published: February 2021

Abstract

Objectives
Lung cancer is one of the most frequent types of cancers that lead to death. Sildenafil is a potent inhibitor of phosphodiesterase-5 and showed potential anticancer effects, which has not yet been fully evaluated. Thus, this study aims to investigate the potential anticancer effect of sildenafil in urethane-induced lung cancer in BALB/c mice.

Methods
Five-week-old male BALB/c mice were treated with either (i) normal saline only, (ii) sildenafil only 50 mg kg-1/ P.O every other day for the last four successive weeks, (iii) urethane 1.5 gm kg-1 i.p (at day 1 and day 60), (iv) carboplatin after urethane induction, or (v) sildenafil after urethane induction.

Key findings
It was shown that sildenafil significantly increased the levels of cGMP and Caspase-3 with a reduction of NF-κB, Bcl-2, Cyclin D1, intercellular adhesion molecule 1, matrix metalloproteinase-2 levels and normalisation of Nrf2 along with pronounced improvement in the histological patterns.

Conclusions
These results indicated that sildenafil markedly induces cell cycle arrest, apoptosis and inhibits the metastatic activity through activation of cyclic guanosine monophosphate/protein kinase G pathway and down-regulation of cyclin D1 and nuclear factor kappa light chain enhancer of activated B cells with downstream anti-apoptotic gene Bcl-2, which underscores the critical importance of future using sildenafil in the treatment of lung cancer.
Mechanisms exploration of Xiaojin Pills on lung cancer based on metabolomics and network pharmacology
Authors: Cao Bo , Lin Junzhi , Wu Zhenfeng , Liu Huimin , Zhang Dingkun , Xu Hong , Xu Runchun , Han Li 
Published: February 2021

Abstract

Objectives
This study was designed to evaluate the pharmacological activity and therapeutic mechanism of Xiaojin Pills (XJW) on lung cancer.

Methods
Mice were orally administered with Xiaojin Pills for 21 days. Tumour samples were collected to evaluate the antilung cancer effect, and blood samples were collected to identify differential metabolites with metabolomics. Through the analysis of network pharmacology, the active ingredients and targets related to XJW therapy for lung cancer were filtered.

Key findings
Different expression of seven metabolites related to seven pathways, including Arachidonic acid metabolism, Citrate cycle, tryptophan metabolism, glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, primary bile acid biosynthesis and nicotinate and nicotinamide metabolism, were demonstrated to explain the efficacy of XJW in the treatment of lung cancer. Furthermore, a total of 19 active ingredients (ursolic acid, α-thujone, pelargonidin, succinic acid, boswellic acid, muscone, daidzein, xanthorrhizol, isoeugenol, oleic acid, β-caryophyllene, vanillin, β-sitosterol, lupeol, palmitic acid, eugenol, methylbutenol, β-elemene and quercetin) acted directly on 9 targets (CAT, PTGS2, PTGS1, CTH, ABTA, ALT1, ME2, AGXT and AGXT 2) and regulated 3 out of 7 metabolites (3-Hydroxyanthranilic acid, Pyruvate and Prostaglandin G2).

Conclusions
Through metabolomics and network pharmacology analyses, this study demonstrated that the major metabolites of XJW in treating lung cancer were regulated by multitarget and multicomponent interaction network.
Splenic artery aneurysm, case series of seven patients
Authors: Salimi Javad , Omrani Zahra , Cheraghali Roozbeh 
Published: February 2021

Abstract
Splenic artery aneurysms (SAA) account for 46–60% of all visceral artery aneurysms. Small SAAs are usually asymptomatic, but giant aneurysms are more likely to cause symptoms and can result in life-threatening complications. Treatment of a splenic artery aneurysms includes laparotomy, laparoscopy or endovascular techniques. Case presentation: In this article, seven interesting cases of splenic artery aneurysms in different size and parts of artery and various interventions (open, endovascular and hybrid surgery) are discussed. Six of the patients were male. Five of them had giant SAAs (≥5 cm). Two patients underwent hybrid surgery. Coil embolization was carried out for one patient. All seven patients discharged with no procedure-related complications. Endovascular procedures considered as a first choice of treatment for splenic artery aneurysm. Open surgery is reserved mostly for the treatment of complications or if the endovascular techniques fail, lack of availability of endovascular procedures or allergy to contrast medium.