bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Dialytic Clearance of Apixaban During In Vitro Continuous Renal Replacement Therapy
Authors: Andrews Lauren , Benken Scott , Tan Xing , Wenzler Eric 
Published: August 2020

Abstract
Objective: To evaluate the transmembrane clearance (CLTM) of apixaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. Design: In vitro pharmacokinetic (PK) study.Setting: University research laboratory.Subjects: Not applicable. Interventions: Apixaban was added to the CRRT circuit and serial, undiluted pre-filter bovine blood samples were collected along with analogous post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types (M150 and HF1400), flow rates (2 and 4 L/h), and point of CVVH replacement fluid dilution (pre, post, and pre/post filter). Concentrations of apixaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma PK parameters for apixaban were estimated via noncompartmental analysis in WinNonlin. CLTM was calculated via the estimated area under the curve (AUC) and by the product of the sieving/saturation coefficient (SC/SA) and flow rate. Two and three-way ANOVA models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLTM by each method. Optimal doses were suggested by matching the AUC observed in vitro to the systemic exposure demonstrated in Phase 2/3 studies of apixaban. Linear regression was then utilized to provide dosing estimations for flow rates from 0.5-5 L/h. Measurements and Main Results: Mean adsorption to the HF1400 and M150 filters differed significantly at 38% and 13%, respectively, while mean (±SD) percent protein binding was 70.81±0.01%. Effect of CVVH point of replacement fluid dilution did not differ across filter types, although CLTM was consistently significantly higher during CRRT with the HF1400 filter compared to the M150. The three-way ANOVA demonstrated improved fit when CLTM values calculated by AUC were used (adjusted R2 0.87 vs. 0.52), and therefore, these values were used to generate optimal dosing recommendations. Linear regression revealed significant effects of filter type and flow rate on CLTM by AUC, suggesting doses of 5-10 mg BID may be needed for flow rates ranging from 0.5-5 L/h respectively. Conclusion: CLTM of apixaban during CRRT resulted in estimated dosing recommendations ranging from 5 mg BID for flow rates ≤3 L/h up to 7.5-10 mg BID for rates >3 L/h, depending on filter type, in order to match target systemic exposure thresholds. The safety and efficacy of these proposed dosing regimens warrants further investigation in clinical studies.
Intrathymic differentiation of natural antibody-producing plasma cells in human neonates
Authors: Cordero Hector , King Rodney , Dogra Pranay , Dufeu Chloe , See Sarah , Chong Alexander , Uhlemann Anne-Catrin , Ho Siu-Hong , Kalfa David , Bacha Emile , Kearney John , Zorn Emmanuel 
Published: August 2020

Abstract
The thymus is a central lymphoid organ responsible for the development of T cells. Here, we show that the thymus of human neonates also contains a consistent contingent of CD138+ plasma cells, producing all classes and subclasses of immunoglobulins with the exception of IgD. These antibody-secreting cells (ASC) are comprised within a larger subset of B cells lacking expression of the complement receptors CD21 and CD35 and sharing the expression of signature genes defining mouse B1 B cells. Single-cell transcriptomic analyses supported the intrathymic differentiation of CD138+ plasma cells alongside other B cell subsets with distinctive molecular phenotypes. Neonatal thymic plasma cells also included clones reactive to pathogenic bacteria that commonly infect children born with antibody deficiency. Thus, our findings point to the thymus as a source of innate humoral immunity in human neonates.
The Patient, Investigator, Nurse, Carer Questionnaire (PINC-Q): A Cross-Sectional, Retrospective, Non-Interventional Study Exploring the Impact of Less Frequent Medication Administration with Paliperidone Palmitate 3-Monthly as Maintenance Treatment for Schizophrenia
Authors: Wooller Annette , Pungor Katalin , Attal Jerome , Leopold Karolina , Pappa Sofia , Sanchez Pedro , Steegen Geertie , Vita Antonion , Marsella Carol , Verrijcken Caroline , Lahaye Marjolein 
Published: August 2020

Abstract
BackgroundTo understand the implications of switching from paliperidone palmitate 1-monthly (PP1M) to paliperidone palmitate 3-monthly (PP3M) treatment of schizophrenia from the perspective of four key stakeholders: patients, physicians, nurses and carers. Methods PINC-Q was a cross-sectional, retrospective, non-interventional study comprising a one-time questionnaire for adult patients (aged ≥18 years) with schizophrenia (International Classification of Diseases; ICD-10) and their physician, nurse and carer. Questionnaires were developed in association with patient and carer advocacy groups (GAMIAN and EUFAMI) and following an advisory board formed of psychiatrists and nurses. The degree of alignment between stakeholders was also examined.ResultsResponses were received from a total of 224 evaluable patients. For most patients (88.4%), responses were received from at least two other stakeholders. Patients were moderately ill with mild-to-moderate lack of insight and had received PP1M for a mean (standard deviation [SD]) of 23.9 (21.28) months before switching to PP3M (duration mean [SD] 12.8 [3.72] months). The most frequently reported reasons to switch from PP1M to PP3M were ‘to live life as normally as possible’ and ‘patient convenience’. Over 79% of responses within each stakeholder group stated that PP3M helped the patients, with increased patient activity and social involvement, improved frequency and quality of physician–patient and nurse–patient communication and decreased perceived stigma.ConclusionsThe results of the PINC-Q study add to the increasing body of evidence supporting the benefits of PP3M in a population of patients with schizophrenia representative of real-world clinical practice.
Urine CA-2 as a biomarker for diagnosis urinary stone and prediction of&nbsp;its complications
Authors: Leng Yuan-jing , Zhou Hai-bin , Fu Jiang-ling , Wang Wen-juan 
Published: August 2020

Abstract
PURPOSECarbonic anhydrase-2 (CA-2) plays a role in mineralization and calcification in organism. Strong evidence suggests that CA-2 is associated with urolithiasis. However, the relationship between CA-2 and urinary stone remains unclear. The study aimed to assess the association of urine CA-2 (uCA-2) level and the potential risk of urinary stone.METHODSFrom March 2017 to November 2019, a prospective cohort study was conducted on patients with urinary stones and healthy subjects to determine the pretreatment uCA-2 level detection by Enzyme linked immunosorbent assay (ELISA). The difference of uCA-2 level between patients with urinary stones and healthy subjects was compared. Then comparison between stone patients with complications and without complications was carried out as well as correlation analysis to detect factors associated with biomarker expression.RESULTS118 patients with urinary stones were into urinary stones group and 42 healthy subjects were into healthy control group. The mean pretreatment uCA-2 level was significantly higher in patients with urinary stones group than healthy controls group (P=0.028). Furthermore, The uCA-2 level was positive correlation with urinary stones complications (R=0.379, P=0.000), especially pain complications (R=0.524, P=0.000) and hematuria complications (R=0.374, P=0.000). Receiver operating characteristic curve (ROC) analysis that a uCA-2 level threshold of 10.94 ng/mL had 83.67% sensitivity and 68.12% specificity for predicting urinary stones complications. CONCLUSIONSExcessive uCA-2 excretion is a major risk factor for urinary stone. Our findings suggested that uCA-2 may be used as an unappreciated biomarker for the diagnosis urinary stone in patients and to predict its complications.
Recurrent wheezing after respiratory syncytial virus infection in children under 3 years of age: a 1-year follow-up study
Authors: Zhou Li , Li Jing , Hu Fang , Zhang Lin , Xiang Hua , Ren Juan 
Published: August 2020

Abstract
Background: Wheezing in infancy is very common. RSV infection can cause recurrent wheezing. The aim of this study was to explore the risk factors of recurrent wheezing in children under 3 years of age after RSV infection. Methods：We chose children with initial wheezing before 3 years of age who were hospitalized for medical treatment. Wheezing frequency was determined by follow-up at 1 week, 1 month, 3 months, 6 months, and 1 year. Information such as birth status, age, sex, preterm, mode of delivery, birth order, eczema history, personal allergy history, family allergy history, passive smoking, and place of residence (urban/rural) was collected. Total serum IgE level, serum allergen testing, routine blood tests, C-reactive protein level, procalcitonin level, respiratory pathogens tests, sputum culture, chest radiography or computed tomography were performed in all patients. The correlation between each factor and wheezing recurrence was evaluated. Results: A total of 259 children were included in the study. They were divided into single recurrence, multiple recurrences, and no recurrence groups. There were significant differences between the single recurrence and multiple recurrences groups in terms of personal allergy history, passive smoking, total serum IgE level, age, hospital stay duration, and wheezing duration (p<0.05). The percentage of children with a personal allergy history in the multiple recurrences group was significantly higher than that of children in the single recurrence and no recurrence groups (p=0.031 and 0.008, respectively). The age of children in the multiple recurrences group was significantly lower than that of children in the single recurrence group (p=0.000). The cost of re-hospitalization in the multiple recurrences group was significantly higher than that in the single recurrence and no recurrence groups (p=0.000 and 0.000, respectively). Conclusions: Children with a personal allergy history were more likely to have wheezing episodes. The frequency of wheezing in children under 3 years of age within 1 year of a respiratory syncytial virus infection was related to age. The younger the age at the time of the onset of wheezing, the more wheezing recurrences in the following year.
Elite Rugby and COVID-19: Protecting the Wellbeing of Rugby Players and Support Staff from an Occupational Safety and Health Perspective
Authors: Chen Yanbing , Buggy Conor , Kelly Seamus 
Published: August 2020

Abstract
Background: The contact nature of rugby with its’ intensive physical interaction often exposes players to a high risk of injury and illness. Compliance with prescribed safety guidelines when returning to play during the COVID-19 pandemic is important for both rugby players and their support staff’s health and wellbeing. However, elite rugby has an inherent level of risk acceptance that has been a cultural norm in the game for decades. This paper aims to identify risk factors that influence players’ awareness and actions in relation to the highly communicable disease COVID-19, and provide rugby clubs and associations with practical return to play solutions from a health and safety perspective. Methods: This study thematically analysed interviews with 15 senior rugby support staff employed in elite rugby union that explored key factors impacting health-and-safety in elite rugby. With the emphasis on rugby players’ health-and-safety awareness (e.g. illness/injury reporting awareness) and rugby environment micromanagement (e.g. player hygiene) and rugby physical contact nature, analysing the factors that may be normalised in elite sporting settings in the context of managing return to play during the COVID-19 pandemic.Results: Due to physical contact nature of rugby, players are exposed to the risk of trauma resulting in skin abrasions and lacerations etc. which may aggregate the risk of infectious diseases. A level of micromanagement practices such as player hygiene management and health condition surveillance that builds on the current situation are effective and essential, considering rugby players in a high level of fitness condition and at a relatively young age can be overly confident with their ability to deal with the risk of illness. Furthermore, player awareness such as symptom reporting and return-to-play (RTP) after unwellness is due to improve for ensuring their health and wellbeing and of their fellow players as well as support staff during the back to field process in the context of COVID-19.Conclusions: Returning to rugby practice and competition will require a level of micromanagement and player safety awareness education in order to achieve the goal of optimally protecting the players from potential illness and / or spreading it to fellow players and support staff. Rugby rituals such as the New Zealand haka could be considered for keeping social distance between players while affirming the rugby nature of aggression exhibition.
A Revealed Preference Analysis to Develop Composite Scores Approximating Lung Allocation Policy in the U.S.
Authors: Stewart Darren , Wood Dallas , Alcorn James , Hayes Michael , Hauber Brett , Goff Rebecca 
Published: August 2020

Abstract
Background: The patient ranking process for donor lung allocation in the United States is carried out by a classification-based, computerized algorithm, known as the match system. Experts have wondered whether a continuous, points-based allocation framework would better serve waiting list candidates by removing hard boundaries and increasing transparency into the relative importance of factors used to order candidates. We applied discrete choice modeling to match run data to determine the feasibility of approximating current lung allocation policy by one or more composite scores. Our study aimed to demystify the points-based approach to allocation; quantify the relative importance of factors used in allocation under current policy; and provide a viable policy option that adapts the current, classification-based system to the continuous allocation framework.Methods: Rank ordered logistic regression models were estimated using 6,466 match runs for 5,913 adult donors and 534 match runs for 488 pediatric donors from 2018. Four primary attributes are used to rank candidates and were included in the models: (1) medical priority, (2) candidate age, (3) candidate’s transplant center proximity to the donor hospital, and (4) blood type compatibility with the donor.Results: Two composite scores were developed, one for adult and one for pediatric donor allocation. Candidate rankings based on the composite scores were highly correlated with current policy rankings (Kendall’s Tau ~0.80, Spearman correlation >90%), indicating both scores strongly reflect current policy. In both models, candidates are ranked higher if they have higher medical priority, are registered at a transplant center closer to the donor hospital, or have an identical blood type to the donor. Proximity was the most important attribute. Under a points-based scoring system, candidates in further away zones are sometimes ranked higher than more proximal candidates compared to current policy. Conclusions: Revealed preference analysis of match runs produced composite scores that capture the essence of current policy while removing hard boundaries of the current classification-based system. A carefully crafted, continuous version of lung allocation policy has the potential to make better use of the limited supply of donor lungs in a manner consistent with the priorities of the transplant community.
A Multicenter Prospective Double Blinded Randomized Controlled Pilot Trial of Intravenous Iron (Ferric Derisomaltose (FDI)) in Iron Deficient but not Anemic Patients with Chronic Kidney Disease on Functional Status.
Authors: Bhandari Sunil , Allgar Victoria , Lamplugh Archie , Macdougall Iain , Kalra Philip 
Published: August 2020

Abstract
Background Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality of life measurements; however, data in patients with CKD are lacking.Methods The Iron and the Heart Study was a prospective double blinded randomized study in non-anemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI) ) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on hematinic profiles and hemoglobin, safety analysis and quality of life questionnaires (QoL).Results We randomly assigned 54 patients mean (SD) age for FDI (n=26) 61.6 (10.1) years vs placebo (n=28; 57.8 (12.9) years) and mean eGFR (32.1 (9.6) vs. 29.1 (9.6) ml/min/1.73m2) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month (p=0.736), or 3 months (p=0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Hemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months (p<0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron. Conclusion This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anemic non-dialysis CKD patients without heart failure to improve the 6MWT.Trial Registration: European Clinical Trials Database (EudraCT) No: 2014-004133-16https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-004133-16/GBREC no: 14/YH/1209Date First Registered: 2015-02-17 and date of end of trail 2015-05-23Sponsor ref R1766 and Protocol No: IHI 141
A Mixed-Methods Feasibility Study of an Arts-Based Intervention for Patients Receiving Maintenance Haemodialysis.
Authors: Carswell Claire , Reid Joanne , Walsh Ian , Johnston William , McAneney Helen , Mullan Robert , Lee Jenny Baxley , Nelson Hugh , Matthews Michael , Weatherup Elizabeth , Spencer Andrea , Michelo Jean , Quail Anne , Kielty Grainne , Elliott Jenny , Mackenzie Alistair , Arbuckle Nicola , Wilson Anna , Noble Helen 
Published: August 2020

Abstract
BackgroundHaemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysisMethodsA parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. ResultsOut of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n=3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n=11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. ConclusionAn arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial.Trial registrationThe trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496.
Diagnosis and management of Adenosine Deaminase 2 Deficiency children: the experience from China
Authors: Wang Wei , Zhang Tiannan , Zheng Wenjie , Zhong Linqing , Wang Lin , Li Ji , Liu Qian , Dong Yanqing , Song Hongmei 
Published: August 2020

Abstract
BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a rare autoinflammatory disease caused by mutations in the ADA2 gene. Few Chinese cases have been reported. We describe and compare the clinical features, genotypes, and treatments of Chinese DADA2 patients and non-Chinese patients.METHODS: Primary immunodeficiency disease panel or whole-exome sequencing was performed for suspected cases, and assays for adenosine deaminase 2 (ADA2) enzyme activity were also carried out for the patients and their parents. Case reports of Chinese and non-Chinese patients with DADA2 were searched in PubMed and Chinese national databases.RESULTS: Seven unrelated children from China with DADA2 were included in our study. Five were identified at Peking Union Medical College Hospital, and two had been reported previously (1 on PubMed and 1 in Chinese literature). Fourteen mutations in ADA2 were identified, 7 of which have not previously been reported in non-Chinese patients. Four children who underwent enzymatic analysis had lower ADA2 activity compared with their parents. Phenotypic manifestations included fever, skin symptoms, vasculitis, and neurologic involvement. Treatments varying from steroids, immunosuppressants, and tocilizumab, anti-TNF therapy and hematopoietic stem cell transplantation (HSCT) were effective depending on phenotype and severity.CONCLUSION: This study includes the largest number of Chinese DADA2 patients to date. We recommend the combination of enzymatic analysis with gene screening to confirm the diagnosis. Different genotypes were observed among Chinese DADA2 patients; most phenotypes were similar to those of non-Chinese DADA2 patients, except for growth retardation. Disease remission might not be achieved with anti-IL-6 therapy.