bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physicians working in oncology identified challenges and factors that facilitated communication with families when children could not be cured
Authors: Udo Camilla , Kreicbergs Ulrika , Axelsson Bertil , Björk Olle , Lövgren Malin 
Published: June 2019

AbstractAimWe explored physicians’ experiences of communicating with families when their child had cancer and a cure was no longer an option, by focusing on barriers and facilitating factors.MethodsPhysicians from the six cancer centres in Sweden took part in focus group discussions between December 2017 and May 2018, and the data were analysed using qualitative content analysis. Focus groups enabled us to gather individual and shared perspectives.ResultsThe 35 physicians (20 male) had a mean age of 47 (range 31‐74) and a mean of 11 years’ experience in oncology, ranging from under one year to 43 years. They reported communication challenges when a cure was not possible, namely: emotional and mental drain, lack of mutual understanding and uncertainty about communication skills. They also reported facilitating factors: flexibility in complex conversations, the child’s position in the conversations, continuity and trusting relationships, support from colleagues and having discussed the potentially life‐threatening nature of cancer from the very start of treatment.ConclusionTraining to overcome communication issues could support the early integration of palliative care.
Prospective randomized trial comparing two doses of rabbit anti‐thymocyte globulin in patients with severe aplastic anaemia
Authors: Narita Atsushi , Zhu Xiaofan , Muramatsu Hideki , Chen Xiaojuan , Guo Ye , Yang Wenyu , Zhang Jingliao , Liu Fang , Jang Jun H. , Kook Hoon , Kim Hawk , Usuki Kensuke , Yamazaki Hirohito , Takahashi Yoshiyuki , Nakao Shinji , Wook Lee Jong , Kojima Seiji ,   the Aplastic Anaemia Working Party of the Asia‐Pacific Blood, Marrow Transplantation Group
Published: June 2019

SummaryThe treatment of choice for patients with severe aplastic anaemia (SAA) includes immunosuppressive therapy (IST) with anti‐thymocyte globulin (ATG) and ciclosporin A. However, the optimal dose for rabbit ATG has yet to be established. We herein report the first prospective, randomized, multicentre study comparing two doses of rabbit ATG in patients with SAA. Patients with SAA who required initial IST in Japan (n = 89), China (n = 85) and Korea (n = 48) were enrolled between May 2012 and October 2017. A 1:1 block randomization was employed for two doses of rabbit ATG. In total, 222 patients were randomized, with 112 patients receiving 2·5 mg/kg and 110 receiving 3·5 mg/kg of rabbit ATG for 5 days. The primary endpoint was the haematological response at day 180. After 6 months, no significant difference in response rates was observed between the 2·5 and 3·5 mg/kg groups (49% vs. 48%, P = 0·894). Overall survival at 3 years was similar between the two groups [85% (95% confidence interval [CI], 76%−91%) vs. 91% (95% CI, 82%−96%); P = 0·107]. The current study revealed no significant differences in the efficacy and safety between the 2·5 and 3·5 mg/kg doses of rabbit ATG in patients with SAA.Trial registration: UMIN000011134.
Clinical, fiscal and environmental benefits of a specialist‐led virtual ureteric colic clinic: a prospective study
Authors: Connor Martin J. , Miah Saiful , Edison Marie Alexandra , Brittain James , Smith Mitra Kondjin , Hanna Milad , El‐Husseiny Tamer , Dasgupta Ranan 
Published: June 2019

ObjectivesTo evaluate the clinical, fiscal and environmental impact of a specialist‐led acute ureteric colic virtual clinic (VC) pathway.Patients and MethodsAll patients with uncomplicated acute ureteric colic, referred to a single tertiary centre, were prospectively entered into the study over a 4‐year period (January 2015–December 2018). Inclusion criteria were: low‐dose non‐contrast computed tomography of kidneys, ureters and bladder; white blood cell count <16 × 109/L; pain controlled; normal renal function; and no clinical concern. Primary outcomes were: time (days) from referral to VC outcome; VC outcome (discharge, further VC, face‐to‐face [FTF] clinic, extracorporeal shockwave lithotripsy [ESWL], ureterorenoscopy [URS], percutaneous nephrolithotomy [PCNL]); and adverse events (sepsis or obstruction). Secondary outcomes were patient and stone demographics, cost and environmental analysis. The minimum follow‐up was 3 months.ResultsA total of 1008 patients entered the study, of whom 91.5% (n = 922) were of working age. The median (interquartile range) time from presentation to VC outcome was 2 (4) days. VC outcomes were as follows: 16.3% of patients (n = 164) were discharged; 18.2% (n = 183) were discharged after further VC; 17.2% (n = 173) underwent an intervention; and 48.4% (n = 488) were referred to an FTF clinic. Interventions comprised: PCNL 0.5% (n = 5); ESWL 7.7% (n = 78); and URS 8.9% (n = 90). Stone demographics were as follows: 570 patients (56.5%) had lower, 157 (15.6%) had upper, 96 (9.5%) had mid‐ureteric and 163 (16.2%) had renal calculi, and in 22 patients (2.2%) the stones had recently passed. The mean (sd) stone size was 3.5 (2.3) mm. Two adverse events (0.2%) were reported. Introducing a VC saved £145,152 for Clinical Commissioning Groups, the equivalent NHS tariff payment of performing 106 URS procedures or 211 ureteric stent insertions. Overall, 15,085 patient journey kilometres were avoided, equal to 0.70–2.93 metric tonnes of carbon dioxide equivalent production and the need to plant 14.7 trees to achieve carbon balance.ConclusionA specialist‐led acute ureteric colic VC reduced time to treatment decision to a median of 2 days. This creates additional clinic capacity and reduces the fiscal burden of traditional clinics and their associated carbon footprint.
Impact of hospital nephrectomy volume on intermediate‐ to long‐term survival in renal cell carcinoma
Authors: Hsu Ray C. J. , Barclay Matthew , Loughran Molly A. , Lyratzopoulos Georgios , Gnanapragasam Vincent J. , Armitage James N. 
Published: June 2019

ObjectiveTo evaluate the relationship between hospital volume and intermediate‐ and long‐term patient survival for patients undergoing nephrectomy for renal cell carcinoma (RCC).Patients and MethodsAdult patients with RCC treated with nephrectomy between 2000 and 2010 were identified from the English Hospital Episode Statistics database and National Cancer Data Repository. Patients with nodal or metastatic disease were excluded. Hospitals were categorised into low‐ (LV; <20 cases/year), medium‐ (20–39 cases/year) and high‐volume (HV; ≥40 cases/year), based on annual cases of RCC nephrectomy. Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) for all‐cause mortality by hospital volume, adjusting for patient, tumour and surgical characteristics. We assessed conditional survival over three follow‐up periods: short (30 days to 1 year), intermediate (1–3 years) and long (3–5 years). We additionally explored whether associations between volume and outcomes varied by tumour stage.ResultsA total of 12 912 patients were included. Patients in HV hospitals had a 34% reduction in mortality risks up to 1 year compared to those in LV hospitals (HR 0.66, 95% confidence interval 0.53–0.83; P < 0.01). Assuming causality, treatment in HV hospitals was associated with one fewer death in every 71 patients treated. Benefit of nephrectomy centralisation did not change with higher T stage (P = 0.17). No significant association between hospital volume and survival was observed beyond the first year.ConclusionsNephrectomy for RCC in HV hospitals was associated with improved survival for up to 1 year after treatment. Our results contribute new insights regarding the value of nephrectomy centralisation.
Effect of tadalafil 5 mg on post‐micturition dribble in men with lower urinary tract symptoms: a multicentre, double‐blind, randomized, placebo‐controlled trial
Authors: Yang Dae Yul , Jeong Hyun Cheol , Ko Kyungtae , Lee Seong Ho , Lee Sang Kon , Shin Tae Young , Cho Jin Seon , Lee Won Ki 
Published: June 2019

ObjectivesTo compare the effects of taking tadalafil 5 mg and placebo once daily on post‐micturition dribble (PMD) in men with lower urinary tract symptoms (LUTS).Patients and MethodsOur prospective, randomized, double‐blind, placebo‐controlled, multicentre trial enrolled 102 men with PMD and other LUTS. PMD was assessed using the Hallym Post‐Micturition Dribble Questionnaire (HPMDQ) and according to PMD volume. Over a 12‐week period, patients took either tadalafil 5 mg (n = 51) or placebo (n = 51) once daily and their HPMDQ and PMD volume results were evaluated. Adverse events (AEs) were also reported.ResultsOver the course of 12 weeks, total HPMDQscores and PMD volumes improved significantly more in the tadalafil group than in the placebo group (reduction of total HPMDQ score of ≥2 points in the tadalafil and placebo group in 68.8% and 31.9% of patients (P < 0.001) and decreased mean PMD volume in the tadalafil and placebo group at 0.48 mL and 0.22 mL, respectively (P = 0.046). Specifically, PMD frequency decreased and quality of life increased significantly more in the tadalafil group than in the placebo group (P = 0.029 and P < 0.001, respectively). Furthermore, 66.7% of the tadalafil group reported moderate and significant PMD improvement, whereas only 4.2% reported that tadalafil was ineffective. Treatment‐emergent AEs did not significantly differ between the groups (all P > 0.05), and no serious AEs were observed.ConclusionTaking tadalafil 5 mg once daily reduced PMD symptom severity and PMD volume in men with PMD, without inducing serious AEs, more effectively than placebo, suggesting that taking tadalafil 5 mg once daily may be an effective and well‐tolerated PMD treatment.
Buried Late Weichselian thermokarst landscape discovered in the Czech Republic, central Europe
Authors: Hošek Jan , Prach Jindřich , Křížek Marek , Šída Petr , Moska Piotr , Pokorný Petr 
Published: June 2019

Pronounced climatic warming associated with the Late Weichselian Pleniglacial‐to‐Lateglacial transition caused considerable environmental changes throughout the former periglacial zones (in Europe ~53°–46°N). During permafrost degradation and subsequent ground subsidence (i.e. thermokarst processes), the landscape changed rapidly. In this study we investigated a flat mid‐altitude area in south Bohemia, Czech Republic, lying close to the southern limit of the Weichselian permafrost. We discovered palaeo‐lake basins with sedimentary infillings up to 11 m in depth. According to radiocarbon and palynostratigraphical dating, these basins were formed at the onset of the Late Pleniglacial‐to‐Lateglacial transition, whereas the smaller depressions were formed later. We suggest that the basins resulted from thermal and fluvio‐thermal erosion of the former permafrost and represent remnants of discontinuous gullies and possibly collapsed frost mounds (pingo/lithalsa scars). The formation of this a fossil thermokarst landscape was climatically driven and multiple phased, with the major phase during the climatic warming and wetting at the onset of GI‐1e (Bølling) and the minor phase during GI‐1c (Allerød). This study enhances knowledge of the palaeogeography of the former European periglacial zone by showing that Late Pleistocene thermokarst activity could have had a significant impact on the evolution of the landscape of at least some regions of central Europe along the southern limit of the continuous permafrost zone. The research also points to a similar history for the physical transformation of the landscape of the former European periglacial zone and current thermokarst landscapes and could be a valuable source of information with respect to the future transformation of the Arctic under conditions of ongoing global warming.
Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy
Authors: Kuot Abraham , Ronci Maurizio , Mills Richard , Klebe Sonja , Snibson Grant , Wiffen Steven , Loh Raymond , Corbett Mark , Zhou Tiger , Chataway Tim , Burdon Kathryn P. , Craig Jamie E. , Urbani Andrea , Sharma Shiwani 
Published: June 2019

AbstractBackgroundFuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD‐affected and unaffected Descemet's membrane.MethodsLabel‐free quantitative proteomics using nanoscale ultra‐performance liquid chromatography‐mass spectrometry (nUPLC‐MSE) was employed on affected and unaffected Descemet's membrane extracts, and interesting findings were further investigated using quantitative reverse transcription‐polymerase chain reaction and immunohistochemical techniques.ResultsQuantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down‐regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD‐affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis.ConclusionsThis is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.
Development and preliminary evaluation of ilearnKAS: An animated video about kidney allocation to support transplant decision‐making
Authors: Kayler Liise K. , Keller Maria M. , Crenesse‐Cozien Natalia , Dolph Beth , Cadzow Renee , Feeley Thomas H. 
Published: June 2019

AbstractBackgroundWe aimed to develop and feasibility test an educational video culturally targeted to African American (AA) patients regarding kidney allocation.MethodsWe iteratively refined an animated video for AAs with multiple stakeholder input and conducted a one‐group, pre–post study with 50 kidney transplant candidates to assess video feasibility and acceptability. A mixed population was chosen to obtain race‐specific acceptability data and efficacy estimates for a larger study.ResultsMedian participant age was 56 years, and 50% were AA. Comparing pre–post video scores, large knowledge effect sizes were found for the cohort (r = 0.7) and in the context of AA race (r = 0.8), low health literacy (r = 0.6), low educational achievement (r = 0.7), age >55 years (r = 0.6), dialysis vintage ≥1 year (r = 0.8), low income (r = 0.7) and low technology access (r = 0.8). Over 87% of participants provided positive ratings on each of the seven acceptability items. The frequency of positive responses increased pre–post video for kidney allocation understanding (78% vs 94%, P = 0.008), decisional self‐efficacy (64% vs 88%, P < 0.001) and belief in fairness (76% vs 90%, P = 0.02).ConclusionsIn collaboration with key stakeholders, a culturally targeted educational video was developed that was well received. Results are promising to impact kidney allocation knowledge among AA and non‐AA kidney transplant candidates.
A randomized, open‐label pharmacokinetic trial of tacrolimus extended‐release dosing in obese de novo kidney transplant recipients
Authors: Jasiak‐Panek Natalia M. , Wenzler Eric , Patel Shree , Thielke James J. , Progar Kristin , Patel Shitalben , Brandt Shane , Huang Yi‐jen , Benedetti Enrico , West‐Thielke Patricia M. 
Published: June 2019

AbstractPurposeTacrolimus extended‐release (TAC‐ER; Astagraf XL®) is utilized in many immunosuppressive regimens post‐renal transplantation. Current dosing recommendation for the TAC‐ER in renal transplant is 0.15‐0.2 mg/kg/day administered once daily. The purpose of this study was to determine the best method of dosing TAC‐ER in obese renal transplant recipients.MethodsDe novo obese kidney transplant recipients were randomized to receive TAC‐ER 0.15 mg/kg/day based on either adjusted body weight (aBW) or ideal body weight (IBW). Post‐transplant patients underwent three pharmacokinetic assessments over 14 days. The primary endpoint was the difference in TAC‐ER exposure (AUC0‐24) in obese patients dosed using aBW compared with IBW.ResultsA total of 20 obese renal transplant recipients were randomized to participate in the study (10 aBW and 10 IBW). Results of the primary outcome (AUC0‐24) on Study Day 1, 7, and 14 were not statistically different between the two groups. There was no difference in the number of days to therapeutic trough concentration between the two dosing weights (aBW = 5.1, IBW = 4.9, days; P = 0.90).ConclusionIn a population of obese renal transplant recipients, comparable trough concentrations and overall exposure in both groups indicate that IBW may be preferred, as less initial drug was needed to attain adequate exposure.
Impact of intentional weight loss on diabetic kidney disease
Authors: Holland John A. , Martin William P. , Docherty Neil G. , le Roux Carel W. 
Published: June 2019

AbstractType 2 diabetes mellitus (T2DM) and obesity constitute interwoven pandemics challenging healthcare systems in developed countries, where diabetic kidney disease (DKD) is the most common cause of end‐stage renal disease. Obesity accelerates renal functional decline in people with T2DM. Intentional weight loss (IWL) strategies in this population hold promise as a means of arresting DKD progression. In the present paper, we summarize the impact of IWL strategies (stratified by lifestyle intervention, medications, and metabolic surgery) on renal outcomes in obese people with DKD. We reviewed the Medline, EMBASE and Cochrane databases for relevant randomized control trials and observational studies published between August 1, 2018 and April 15, 2019. We found that IWL improves renal outcomes in the setting of DKD and obesity. Rate of progression of DKD slows with IWL, but varying outcome measures among studies makes direct comparison difficult. Furthermore, established means of estimating renal function are imperfect owing to loss of lean muscle mass with IWL strategies. The choice of optimal IWL strategy needs to be individualized; future work should establish the comparative efficacy of IWL strategies in obese people with DKD to better inform such decisions.
Do health system reforms stand a chance?
Authors: Zweifel Peter 
Published: June 2019

AbstractWhile most major reforms of health systems fail, those that succeed are motivated by politicians' quest for reducing the health burden on their budget in response to a shift in voters' preferences away from public health. An Edgeworth box is used to depict their preferences, in addition to those of (potential) patients and health‐care providers. Politicians are found to severely constrain the area of mutual advantage, suggesting that only minor reforms are possible unless they promise to lower health‐care expenditure. An efficiency‐enhancing change that would enlarge the box and hence the area of mutual advantage would be to suppress the requirement imposed on health insurers to purchase domestically, rather than being free to directly import health‐care services and drugs.
Is entrepreneurship a virtue?
Authors: Miller Robert C B 
Published: June 2019

AbstractEntrepreneurship is rarely (if ever) discussed by virtue ethicists. And economists analysing entrepreneurship have rarely described it as a virtue. Entrepreneurship is indeed a virtue and the entrepreneur can be seen as the creative counterpart of Aristotle's ‘Magnificent Man’, the virtuous possessor of wealth. But entrepreneurship is also a virtue for anyone who is economically active. By reviewing analyses of entrepreneurship by economists such as Cantillon, Schumpeter, Knight, Baumol, Kirzner and Casson, particular features of entrepreneurial practice are identified from which characteristic virtues (and vices) are isolated and analysed. The characteristic features of the vicious Entrepreneur (or crooked businessman) are also described.
Epilepsy in nonhuman primates
Authors: Croll Leah , Szabo Charles A. , Abou‐Madi Noha , Devinsky Orrin 
Published: June 2019

AbstractObjectivesNonhuman primates (NHPs) are model organisms for understanding the pathophysiology and treatment of epilepsy in humans, while data from human patients informs the diagnosis and treatment ofNHPwith seizures and epilepsy. We reviewed the literature and surveyed veterinarians at zoos andNHPresearch centers to (a) better define the range of seizures and epilepsy inNHP, (b) understand howNHPs can inform our knowledge of the pathophysiology and treatment of epilepsy in humans, and (c) identify gaps of knowledge and develop more effective guidelines to treat seizures and epilepsy inNHP.MethodsWe searched PrimateLit, PubMed, and Google Scholar for studies on experimental models of epilepsy inNHPsand on naturally occurring seizures and epilepsy inNHPsin captivity. In addition, we created a survey to assess methods to diagnose and treat epilepsy inNHPs. This survey was sent to 41 veterinarians at major international zoos and research facilities withNHPpopulations to study seizure phenomenology, diagnostic criteria for seizures and epilepsy, etiology, and antiseizure therapies inNHPs.ResultsWe summarize the data from experimental and natural models of epilepsy inNHPsand case reports of epilepsy of unknown origin in captive primates. In addition, we present survey data collected from veterinarians at eight zoos and one research facility. Experimental data fromNHPepilepsy models is abundant, whereas data from primates who develop epilepsy in the wild or in zoos is very limited, constraining our ability to advance evidence‐based medicine.SignificanceCharacterization of seizure or epilepsy models inNHPswill provide insights into mechanisms and new therapies that cannot be addressed by other animal models.NHPresearch will better inform species‐specific diagnoses and outcomes.
ARC 118925XX stimulates cation influx in bEND.3 endothelial cells
Authors: Wu King‐Chuen , Cheng Ka‐Shun , Wong Kar‐Lok , Shiao Lian‐Ru , Leung Yuk‐Man , Chang Li‐Yun 
Published: June 2019

AbstractIn a previous publication when we studied the purinergic receptor with which ATP interacted in mouse brain bEND.3 endothelial cells, we observed addition of 3 μm ARC 118925XX (ARC; selective P2Y2 antagonist) strongly suppressed ATP‐triggered Ca2+ release, suggesting the response was mediated via P2Y2 receptors. We here report ARC unexpectedly promoted substantial Ca2+ influx even when ATP‐triggered Ca2+ release was largely inhibited. Since this large Ca2+ influx may have important pharmacological significance, we proceeded to investigate its mechanism. ARC did not trigger intracellular Ca2+ release thus suggesting Ca2+ influx triggered by ARC was not store‐operated. ARC‐triggered Ca2+ influx could be blocked by 1 mm Ni2+, a general Ca2+ channel blocker, but not by SK&F 96365, a nonselective TRP channel blocker. Unexpectedly, ARC promoted influx of Na+ and La3+, but not Mn2+. This is a surprising finding, since Mn2+ is conventionally used as a Ca2+ surrogate ion (as it permeates Ca2+ channel), and La3+ is classically used as a potent Ca2+ channel antagonist. Electrophysiological examination showed ARC did not stimulate any cation currents. Therefore, ARC opened, rather than a cation channel pore, an unidentified Ca2+ influx pathway which was Na+‐ and La3+‐permeable but Mn2+‐impermeable.