bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxyurea Optimization through Precision Study (HOPS): study protocol for a randomized, multicenter trial in children with sickle cell anemia
Authors: Meier Emily R. , Creary Susan E. , Heeney Matthew M. , Dong Min , Appiah‐Kubi Abena O , Nelson Stephen C. , Niss Omar , Piccone Connie , Quarmyne Maa-Ohui , Quinn Charles T. , Saving Kay L. , Scott John P. , Talati Ravi , Latham Teresa S. , Pfeiffer Amanda , Shook Lisa M. , Vinks Alexander A. , Lane Adam , McGann Patrick 
Published: October 2020

Abstract
Background : Sickle cell disease (SCD) is a severe and devastating hematological disorder that affects over 100,000 persons in the United States and millions worldwide. Hydroxyurea is the primary disease-modifying therapy for the SCD, with proven benefits to reduce both short-term and long-term complications. Despite the well-described inter-patient variability in pharmacokinetics (PK), pharmacodynamics and optimal dose, hydroxyurea is traditionally initiated at a weight-based dose with a subsequent conservative dose escalation strategy to avoid myelosuppression. Because the dose escalation process is time consuming and requires frequent laboratory checks, many providers default to a fixed dose, resulting in inadequate hydroxyurea exposure and suboptimal benefits for many patients. Results from a single-center trial of individualized, PK-guided dosing of hydroxyurea for children with SCD suggest that individualized dosing achieves the optimal dose more rapidly and provides superior clinical and laboratory benefits than traditional dosing strategies. However, it is not clear whether these results were due to individualized dosing, the young age that hydroxyurea treatment was initiated in the study, or both. The Hydroxyurea Optimization through Precision Study (HOPS) aims to validate the feasibility and benefits of this PK-guided dosing approach in a multi-center trial. Methods : HOPS is a randomized, multicenter trial comparing standard vs. PK-guided dosing for children with SCD as they initiate hydroxyurea therapy. Participants (ages 6 months through 21 years), recruited from 11 pediatric sickle cell centers across the United States, are randomized to receive hydroxyurea either using a starting dose of 20 mg/kg/day (Standard Arm) or a PK-guided dose (Alternative Arm). PK data will be collected using a novel sparse microsampling approach requiring only 10μL of blood collected at 3 time-points over 3 hours. A protocol-guided strategy more aggressive protocols is then used to guide dose escalations and reductions in both arms following initiation of hydroxyurea. The primary endpoint is the mean %HbF after 6 months of hydroxyurea. Discussion: HOPS will answer important questions about the clinical feasibility, benefits, and safety of PK-guided dosing of hydroxyurea for children with SCD with potential to change the treatment paradigm from a standard weight-based approach to one that safely and effectively optimize the laboratory and clinical response. Trial registration: ClinicalTrials.gov, NCT03789591. Registered on December 28, 2018.
Influence of diabetes on short-term outcome after major hepatectomy – an underestimated risk?
Authors: Fischer Alexander , Fuchs Juri , Stravodimos Christos , Hinz Ulf , Billeter Adrian , Büchler Markus W. , Mehrabi Arianeb , Hoffmann Katrin 
Published: October 2020

Abstract
Background: Patient-related risk factors such as diabetes mellitus and obesity are increasing in western countries. At the same time the indications for liver resection in both benign and malignant diseases have been significantly extended in recent years. Major liver resection is performed more frequently in a patient population of old age, comorbidity and high rates of neoadjuvant chemotherapy. The aim of this study was to evaluate whether diabetes mellitus, obesity and overweight are risk factors for the short-term post-operative outcome after major liver resection. Methods: Four hundred seventeen major liver resections (≥3 segments) were selected from a prospective database. Exclusion criteria were prior liver resection in patient’s history and synchronous major intra-abdominal procedures. Overweight was defined as BMI ≥ 25 kg/m 2 and < 30 kg/m 2 and obesity as BMI ≥ 30 kg/m 2 . Primary end point was 90-day mortality and logistic regression was used for multivariate analysis. Secondary end points included morbidity, complications according to Clavien-Dindo classification, unplanned readmission, bile leakage, and liver failure. Morbidity was defined as occurrence of a post-operative complication during hospital stay or within 90 days postoperatively. Results: Fifty-nine patients had diabetes mellitus (14.1%), 48 were obese (11.6%) and 147 were overweight (35.5%). There were no statistically significant differences in mortality rates between the groups. In the multivariate analysis, diabetes was an independent predictor of morbidity (OR = 2.44, p = 0.02), Clavien-Dindo grade IV complications (OR = 3.6, p = 0.004), unplanned readmission (OR = 2.44, p = 0.04) and bile leakage (OR = 2.06, p = 0.046). Obese and overweight patients did not have an impaired post-operative outcome compared patients with normal weight. Conclusions: Diabetes has direct influence on the short-term postoperative outcome with an increased risk of morbidity but not mortality. Preoperative identification of high-risk patients will potentially decrease complication rates and allow for individual patient counseling as part of a shared decision-making process. For obese and overweight patients, major liver resection is a safe procedure.
Cell-specific Characterization of the Placental Methylome
Authors: Yuan Victor , Hui Desmond , Yin Yifan , Peñaherrera Maria , Beristain Alexander , Robinson Wendy 
Published: October 2020

Abstract
Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.
Developing a complex intervention to support pregnant women with mild to moderate anxiety: application of the Medical Research Council framework
Authors: Evans Kerry , Spiby Helen , Morrell Jane C 
Published: October 2020

Abstract
Aim: To design and develop an intervention to support women with symptoms of mild to moderate anxiety in pregnancy.Methods: The development followed the MRC framework for complex interventions, utilising psychological theory, review level evidence and professional and public involvement. Two systematic reviews were completed which helped identify potentially beneficial intervention components. The theory underpinning the components was explored to consider the potential benefit for women with mild to moderate anxiety symptoms in pregnancy. Methods of delivering the intervention within maternity services were explored. The intervention comprised: group discussions, one to one support and assisted self-help resources. Midwives were identified as ideally placed to facilitate the intervention supported by midwifery support workers. A bespoke training package was provided by subject experts to prepare the facilitators. Discussion: The absence of established interventions and a paucity of evidence based approaches for pregnant women with symptoms of mild to moderate anxiety indicated the need for a rigorous and systematic approach to the intervention design. This approach led to the development of an intervention feasible for implementation in maternity care systems tailored to the needs of pregnant women. The involvement of a multi-professional advisory team and active engagement of service users helped to consider the acceptability of the intervention for women and the feasibility of delivering the intervention in the context of maternity care. Conclusion: The MRC Framework provided useful overarching guidance to develop a midwife facilitated intervention for women with symptoms of anxiety in pregnancy. The framework assisted the development of a robust rationale for each intervention component and considered the processes of evaluation and implementation into maternity care systems.
Implementation and factors affecting the nursing process among nurses working in selected government hospital in southwest Ethiopia
Authors: Adasho Zerihun Adraro , Bekele Daniel Mengistu 
Published: October 2020

Abstract
Background: The nursing process was initially adopted from the general system theory, and was developed and implemented in the field of education in the early years.Objective: The purpose of this study was to assess implementation and factors affecting the nursing process among nurses working in selected government hospitals in Southwest Ethiopia.Methods: An institution-based cross-sectional descriptive study was conducted from March 10 to April 1, 2015 in three hospitals in southwest Ethiopia using self-administered questionnaires. This study included a total of 138 nurses using simple random sampling. Data were classified, coded and entered into epidemiological information version 3.5.3, and exported to the statistical package for social science version 20 for analysis, descriptive statistics were used to describe the variables, bivariable and multivariable logistic regression were used to see the effect of each variable on the dependent variable.Result: The nursing process was found to be 73.9 percent implemented. Compared to a Bachelor of Science nurses’, the likelihood of implementing the nursing process was less likely among diploma nurses. Nurses working in administratively supported hospitals implemented the nursing process more compared to those without administrative support. The nursing process had been implemented higher by trained nurses compared to untrained nurses.Conclusion: The implementation of nursing process was good where; nearly seven in every ten nurses implemented the nursing process. Low educational qualification, lack of training, and non-supportive hospital administration were predictors of the nursing process implementation.
Women’s appraisal, interpretation and help-seeking for possible symptoms of breast and cervical cancer in South Africa: a qualitative study&nbsp;
Authors: Harries Jane , Scott Suzanne E , Walter Fiona M , Mwaka Amos D , Moodley Jennifer 
Published: October 2020

Abstract
Background: In South Africa, breast cancer is the most commonly diagnosed cancer and cervical cancer the leading cause of cancer mortality. Most cancers are diagnosed at a late-stage and following symptomatic presentation. The overall purpose of the study was to inform interventions aimed at improving timely diagnosis of breast and cervical cancer.Methods: In-depth interviews were conducted with women with potential breast or cervical cancer symptoms from urban and rural South Africa. Participants were recruited from a community-based cross-sectional study on breast and cervical cancer awareness. Data were analysed using a thematic analysis approach. Results: Eighteen women were interviewed (10 urban, 8 rural): the median age was 34.5 years (range 22-58). Most were unemployed, and five were HIV positive. Themes included impact and attribution of bodily changes; influence of social networks and health messaging in help-seeking; management of symptoms and help-seeking barriers. Breast changes were often attributed to manual activities or possible cancer. Women were often unsure how to interpret vaginal symptoms, attributing them to HIV, hormonal contraceptives, or partner infidelity. Concerns about cancer were based on health information from the radio, social networks, or from primary care providers. Prompt care seeking was triggered by impact of symptoms on personal lives. Rural women, especially with possible symptoms of cervical cancer, experienced challenges during help-seeking including judgmental attitudes of clinic staff. Most participants were skeptical of traditional medicine. Conclusions: This is the first study exploring interpretation of possible breast and cervical cancer symptoms at a community level in South Africa. The process of interpreting bodily changes, symptom attribution and help-seeking is complex and influenced by women’s everyday life experiences. Timely diagnosis interventions should not only include cancer symptom awareness but also address individual, structural and health systems related barriers to care.
Association of gestational diabetes mellitus with offspring weight status across infancy: a prospective birth cohort study in China
Authors: Hu Jiajin , Liu Yilin , Wei Xiaotong , Li Lin , Gao Ming , Liu Yang , Ma Yanan , Wen Deliang 
Published: October 2020

Abstract
Background: The association between gestational diabetes mellitus (GDM) and childhood body weight remains controversial, and additional study is needed, especially in Asian populations.Methods: This prospective study investigated the association between maternal glucose concentration, and GDM status and infant body weight from birth to 12 months of age. Linear mixed effects (LME) models and multiple linear regression were used to assess the longitudinal association of GDM with infant growth measured by weight-for-length (WFLZ), weight-for-age (WFAZ), and length-for-age (LFAZ) z-scores at birth, 1, 3, 6, 8, and 12 months of age.Results: Offspring born to mothers with GDM had higher WFLZ [β: 0.26 SD units (95% CI: 0.13–0.40)] across infancy than those of mothers without GDM. The association was more pronounced in normal-weight and overweight/obese women (P for interaction< 0.05). Multiple linear regression found that the effect estimate of GDM on infant WFLZ was highest at birth [β: 0.32 SD units (95% CI: 0.07– 0.57)], remained significant at 1 [β: 0.24 SD units (95% CI: 0.05–0.43)] and 3 [β:0.20 SD units (95% CI: 0.01–0.39)] months of age and decreased across infancy. Maternal GDM status was not associated with infant WFAZ or LFAZ.Conclusions: Maternal GDM status was associated with infant WFLZ, but not WFAZ or LFAZ. The association of GDM status with offspring WFLZ was more pronounced in early infancy or in normal-weight and overweight/obese women. The results may help to identify the critical period and specific GDM-risk groups for childhood weight status.
Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes
Authors: Abdulaal Ahmed , Patel Aatish , Charani Esmita , Denny Sarah , Alqahtani Saleh A , Davies Gary W , Mughal Nabeela , Moore Luke SP 
Published: October 2020

Abstract
Background: Accurately predicting patient outcomes in SARS-CoV-2 could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2. Method: Between March 1 - April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: 1) a Cox regression model and 2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration. Results: Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI): 73.8 - 91.1 and 90.0%, 95% CI: 81.2 - 95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI: 91.1 - 94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI: 85.7 - 88.2), p=0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively. Conclusion: We demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.
Preparing Lifelong Learners for Delivering Pharmaceutical Care in an Ever-Changing World: A Study of Pharmacy Students
Authors: Khamis Sarah , Abdi Abdikarim Mohamed , Basgut Bilgen 
Published: October 2020

Abstract
Background Continuing professional development (CPD) continues to gain acceptance as a model for health care professionals to engage in lifelong learning (LLL). Many pharmacy schools have not adopted yet specific programs targeting the development of LLL skills , though LLL is widely accepted as an essential competence. This paper examines the effectiveness and utility of a longitudinal CPD training program.

Methods

A CPD simulation course was introduced to a cohort of fifth year students in Northern Cyprus in the 2018-2019 academic year. The program was delivered as an interactive orientation course in one semester; meanwhile, in the second semester, the students applied the CPD cycle and completed their portfolios during their final experiential practice. A mixed-methods approach was used to evaluate the outcomes of the intervention using students’ preparedness for lifelong learning (SPLLL) self-administered questionnaire delivered pre-post program, focus group sessions for students to reflect on the course experience, and instructors’ evaluations of portfolios.

Results

Following the implementation of the course, students’ assessment scores were significantly higher overall and for all scale domains, including “knowledge, skills, attitude and practice”, compared to the baseline assessment. Additionally, compared to fifth year students who responded to the second SPLLL questionnaire, the intervention group students’ assessment was significantly higher in knowledge, skills, and practice. The qualitative analysis reported high student satisfaction and achievement of the course objectives. Nineteen of the students scored high on their portfolios.

Conclusion

The CPD simulation course provided students with opportunities to practice and develop self-assessment and self-management skills that are all desirable for lifelong learning and prepared them for CPD.
Fluoroquinolone resistance of Staphylococcus epidermidis isolated from healthy conjunctiva and analysis of their mutations in quinolone-resistance determining region
Authors: Kang Jung Youb , Lee Woonhyoung , Noh Gwang Myeong , Jeong Bo Hyun , Park Indal , Lee Sang Joon 
Published: October 2020

Abstract
Background: S. epidermidis is the most common pathogen in postoperative endophthalmitis and causes various infectious eye diseases. However, there is very little information on fluoroquinolone antibiotic resistance to S. epidermidis identified in conjunctival microbe and analysis of related genes. Here, the authors investigated the rate of resistance to fluoroquinolones of Staphylococcus epidermidis isolated from normal conjunctival microbes and mutations in the quinolone-resistance determining region (QRDR).Methods: 377 eye samples from 187 patients who underwent intravitreal injection and cataract surgery were included. Specimens were taken from the bilateral lower conjunctival sacs using a cotton swab and cultured. The cultures were identified using MALDI-TOP MS and gyrA, gyrB, parC, and parE gene mutations of QRDR were confirmed by DNA extraction from resistant strains of S. epidermidis with a micro-dilution method using ciprofloxacin, levofloxacin, and moxifloxacin.Results: The culture positive rate was 61.8% (231) for 374 eye samples. Of the 303 total strains cultured, S. epidermidis was the most common with 33.7% (102). Ten types of gene mutations were observed in the resistant S. epidermidis of 21 strains. One-point mutation was observed mainly in gyrA and parC, and a small number of mutations were observed in parE in the form of a double point mutations. When there were multiple point mutations in both gyrA and parC, the highest minimum inhibitory concentration (MIC) was observed.Conclusions: The quinolone resistance rate of S. epidermidis increased in comparison with previous studies, and resistant S. epidermidis showed mostly QRDR mutations, which were mainly found in gyrA and parC, and showed strong resistance when mutated in both genes.
Increasing newly diagnosed inflammatory bowel disease and improving prognosis in China: a 30-year retrospective study from a single center
Authors: Lv Hong , Jin Meng , Zhang Huimin , Chen Xuanfu , Wu Meixu , Guo Mingyue , Zhou Runing , Wang Zheng , Yang Hong , Qian Jiaming 
Published: October 2020

Abstract
Background: We aimed to characterize the trends of prognosis in ulcerative colitis (UC) and Crohn’s disease (CD) in a Chinese tertiary hospital. Methods: A 30-year retrospective cohort analysis was conducted at Peking Union Medical College Hospital. Consecutive patients newly diagnosed with UC or CD from 1985 to 2014 were included. The primary outcome was in-hospital mortality. The secondary outcomes included surgery and length of stay in hospital. The Pearson correlation coefficient was applied to determine the relationship between time and prognosis. Multivariable logistic regression analysis was performed to determine the risk factors for in-hospital mortality and surgery. Results: In total, 1467 patients were included in this study (898 cases with UC and 569 cases with CD). Annual admissions for UC and CD have increased significantly over the last 30 years (UC, r=0.918, P<0.05; CD, r=0.898, P<0.05). Decreased in-hospital mortality was observed both in patients with UC and CD (UC, from 2.44% to 0.27%, r=-0.827, P<0.05; CD, from 12.50% to 0.00%, r=-0.978, P<0.05). A decreasing surgery rate was observed in patients with CD (r=-0.847, P<0.05), while an increasing surgery rate was observed in patients with UC (r=0.956, P<0.05). Shortened average lengths of hospital stay were observed in both UC and CD patients (UC, from 47.83±34.35 days to 23.58±20.05 days, r=-0.970, P<0.05; CD, from 65.50±50.57 days to 26.41±18.43 days, r=-0.913, P<0.05). Toxic megacolon and septic shock were independent risk factors for in-hospital mortality in patients with UC. Intestinal fistula and intestinal perforation were independent risk factors for in-hospital mortality in patients with CD. Conclusions: In this cohort, the admissions of patients with UC and CD were increased, with significantly improved prognoses during the past 30 years.