bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Low‐dose Domperidone for Treating Nausea and Vomiting Due to Acute Gastroenteritis in Children
Authors: Leitz Gerhard , Hu Peter , Appiani Carlos , Li Qing , Mitha Essack , Garces‐Sanchez Maria , Gupta Rajeev 
Published: June 2019

ABSTRACTBackground:This study was conducted based on a request from the European Medicines Agency to generate robust data on domperidone efficacy in children in the relief of symptoms of nausea and vomiting by assessing the effect of a low‐dose and short treatment duration.Methods:In this randomized, double‐blind, phase 3 study, children ages 6 months to 12 years with acute gastroenteritis randomly (1:1) received oral domperidone 0.25 mg/kg with oral rehydration therapy (ORT) or matching placebo thrice daily for 2 to 7 days. The proportion of patients with no vomiting episodes (primary endpoint) and patients ages ≥4 years with no nausea episodes (key secondary endpoint) within 48 hours of first treatment administration were evaluated.Results:The study was terminated early following futility analysis. At early termination, 292 patients randomly received domperidone (n = 147) or placebo (n = 145). The proportion of patients with no vomiting episodes within 48‐hours of first treatment administration was similar between domperidone (32.0%) and placebo groups (33.8%). Similarly, there was no significant difference in proportion of patients ages ≥4 years with no nausea episodes within 48 hours of first treatment administration between domperidone (35.7%) and placebo (38.6%). Total 13 patients (domperidone, 3.4% [5/147] vs placebo, 5.5% [8/145]) reported ≥1 treatment‐emergent adverse events. No deaths or adverse events of special interest (extrapyramidal symptoms and QT prolongation) were reported.Conclusions:Low‐dose of domperidone with ORT did not significantly differ from placebo in reducing vomiting and nausea episodes in pediatric patients with acute gastroenteritis (AG), and the safety profile was similar between both groups.
New Algorithm for the Integration of Ultrasound Into Cystic Fibrosis Liver Disease Screening
Authors: Sellers Zachary M. , Lee Lori W. , Barth Richard A. , Milla Carlos 
Published: June 2019

ABSTRACTObjectives:Liver nodularity occurs across the spectrum of cystic fibrosis liver disease (CFLD), from regenerative nodules to cirrhosis, and can occur without liver enzyme abnormalities. Our aims were to determine if incorporating abdominal ultrasound (US) with annual laboratory testing improves the detection of CFLD and establish CF‐specific thresholds for liver screening labs.Methods:CF patients at least 6 years old who were exocrine pancreatic‐insufficient had an US with Doppler and shear wave elastography. Patients were divided into Normal, Echogenic, or Nodular groups, based on US findings. Results were compared with aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, AST to platelet ratio index (APRI), Fibrosis 4 (FIB‐4), and gamma‐glutamyl transferase (GGT) to platelet ratio (GPR). Receiver operator curve, sensitivity, specificity, positive predictive value, negative predictive value, and optimal cut‐off with Youden Index were calculated.Results:From 82 patients, incorporation of US identified more nodular livers than using labs alone. The Nodular group had significantly greater median AST (44), ALT (48), GGT (46), APRI (0.619), FIB‐4 (0.286), GPR (1.431). Optimal cut‐offs to detect liver nodularity in CF were AST >33, ALT >45, GGT >21, Platelets <230, APRI >0.367, FIB‐4 >0.222, GPR >0.682. Using GGT, APRI, and GPR, we generated an algorithm to direct the use of US in CFLD screening.Conclusions:Using modified serum lab thresholds, addition of liver fibrosis indices, and/or abdominal US can increase detection of liver nodularity in CF. A combination of GGT, GPR, and APRI can help direct which CF children should undergo US evaluation. These tools may improve earlier identification of fibrosis and/or cirrhosis in CF patients.
Abundant Expression of Lysyl Oxidase‐like 2 Protein in Intrahepatic Bile Ducts of Infants With Biliary Atresia
Authors: Honigbaum Stefany , Zhu Qingfeng , Layman Andrew , Anders Robert A. , Schwarz Kathleen B. 
Published: June 2019

ABSTRACTIntroduction: :Biliary atresia (BA) is characterized by rapidly progressive inflammation and fibrosis of the biliary tract, which usually progresses despite surgical intervention (Kasai hepatoportoenterostomy). Lysyl oxidase‐like (LOXL2) is an extracellular matrix enzyme that catalyzes the cross‐linking of fibrillar collagen and elastin and is thought to play a crucial role in tissue fibrosis; anti‐LOXL2 drugs have been shown to be antifibrotic in animals.Objective:The aim of the study was to investigate the presence of LOXL2 in BA livers and hepatic and extrahepatic control tissues.Methods:Liver wedge biopsies from infants with BA (n = 20) were obtained at Kasai, and were compared with non‐BA livers (n = 20). Liver fibrosis was scored using the Ishak scale, and immunohistochemistry was performed using a commercially available polyclonal anti‐LOXL2 antibody. The expression of LOXL2 was scored for intensity and for distribution of bile duct staining by a pathologist blinded to the diagnosis. Staining of LOXL2 in pediatric control tissue, muscle (n = 5), heart (n = 5), and bone (n = 10) was performed.Results:Tissue from patients with BA abundantly expressed LOXL2 (intensity score 2.0 vs 1.4 [P ⩽ 0.001]) for non‐BA and distribution of bile duct‐staining score of 3.0 versus 2.8 (P = 0.001) for non‐BA. Fibrosis score of all BA samples was 4.2 versus 3.1 for non‐BA. Nonhepatic pediatric tissue displayed minimal to no LOXL2 staining.Conclusions:There is significant overexpression of LOXL2 in BA hepatic tissue with minimal expression in extrahepatic tissue. The over expression noted in human hepatic tissue at Kasai suggests the rationale for further investigation of anti‐LOXL2 therapeutics in BA.
Using Patient-Reported Outcomes to Measure Symptoms in Children With Advanced Cancer
Authors: Montgomery Kathleen E. , Raybin Jennifer L. , Ward Jessica , Balian Chelsea , Gilger Elizabeth , Murray Paula , Li Zhanhai 
Published: June 2019

Background
Children with advanced cancer experience symptoms despite access to quality care. Symptom research has previously relied upon retrospective designs and parent proxy rather than prospective measurement with self-report.

Objective
This study evaluated the feasibility of electronic data collection in children with advanced cancer using self-report of symptom frequency, severity, and distress.

Methods
A multisite prospective cohort design was used for this study. Children who were 7 to 18 years of age and English-speaking and had a diagnosis of advanced cancer were included. Symptom frequency, severity, and level of distress were measured every 2 weeks.

Results
Forty-six children completed 563 of 622 (91%) administered electronic symptom assessments. Pain, fatigue, nausea, and sleeping difficulties were the most reported symptoms across all assessments and during the last 12 weeks of life. Symptoms with the highest composite scores included pain, fatigue, nausea, and sleeping difficulties. During the last 12 weeks of life, pain, fatigue, diarrhea, and sleeping difficulties had the highest composite scores. When the domains of frequency, severity, and distress were compared between groups, children reported significantly higher frequency of pain and eating difficulty during the last 12 weeks of life.

Conclusions
Electronic data collection is a feasible way to evaluate the constellation of symptoms. Children with advanced cancer continue to experience physical and psychological symptoms, especially during the last 12 weeks of life despite quality care.

Implications for Practice
Assessment of symptom domains, including frequency, severity, and distress when symptoms are present may allow clinicians to better understand and manage symptoms of most concern to the patient.
Development and Validation of the Just Culture Assessment Tool for Nursing Education
Authors: Walker Danielle , Altmiller Gerry , Barkell Nina , Hromadik Lora , Toothaker Rebecca 
Published: June 2019

Background
Patient safety efforts in practice have focused on creating a just culture where errors can be identified and reported, and system remedies created to prevent reoccurrence. The same is not true of nursing education where student experiences with error and the sequelae that follow focus on individual performance.

Purpose
The purpose of this study was to adapt the Just Culture Assessment Tool (JCAT) used in practice settings into a valid and reliable instrument to evaluate just culture in academic settings.

Methods
A 27-item instrument was adapted for academia. Content validity was established. Reliability was determined in a pilot study with 133 prelicensure nursing students.

Results
The scale content validity index (CVI) was calculated at 1. The reliability of the instrument is strong (α = .75).

Conclusions
The CVI and pilot study findings support the use of the JCAT for Nursing Education as a valid and reliable instrument to evaluate student perception of just culture in academia.
Experience of Perinatal Death From the Father’s Perspective
Authors: Lizcano Pabón Lucero del Mar , Moreno Fergusson María Elisa , Palacios Ana Maria 
Published: June 2019

Background
Although perinatal deaths are still a common pregnancy outcome in developing countries, little is known about the effect perinatal death has on fathers.

Objective
The aim of the study was to understand and describe the meaning of perinatal death in a sample of fathers from northeastern Colombia.

Methods
Using purposive and snowball sampling approaches, we identified 15 participants from northeastern Colombia who agreed to participate. We used a descriptive phenomenological design. Data were collected through in-depth, semistructured interviews.

Results
Men suffer in solitude and hide their emotions as they feel the need to be the main supporters of their partners. Three major themes emerged: experience of loss, coming to terms with an irreparable loss, and overcoming the loss.

Discussion
While women are receiving care, health staff may neglect or forget men. Men suffer alone while seeking ways of attunement with their partners’ emotions to support them during the grieving process. Fathers can overcome and adjust to the loss when they transcend it and find new meaning. Men felt neglected and marginalized at hospitals while their partners were receiving treatment. Health professionals should recognize and acknowledge the pain of fathers who face perinatal death and include them as much as possible in the standard of care. The results identify opportunities for healthcare providers in clinical and outpatient settings to acknowledge the importance of men within the context of pregnancy and to learn about their pain and suffering when they face a perinatal death.
Living Donor Nephrectomy: Is It as Safe as It Can Be? Analysis of Living Donor Deaths in the United States
Authors: Keith Douglas Scott , Brown Joe , Andreoni Kenneth 
Published: June 2019

Introduction
The reported 90-day rate of death from living donor nephrectomy is 3 in 10,000 donations. Although this risk is low, the important question is how many deaths are preventable?

Methods
To study this question, all living donor nephrectomy cases, 139,186 procedures, recorded in the Scientific Registry of Transplant Recipients database since its inception in 1987 were analyzed to determine the death rate and the number of deaths that were potentially preventable. Preventable deaths were defined as any death in the first 7 days except due to clearly unrelated events or death from hemorrhage, pulmonary embolism, infection, cardiovascular cause, or suicide in the first 90 days.

Results
The numbers of deaths at 7, 30, 90, and 365 days after donation were 16, 26, 38, and 86, which translated into 1.15, 1.87, 2.73, and 6.18 deaths per 10,000 donations, respectively. From 2000 onward, when coding was available for cause of death, 19 of the 30 deaths were deemed potentially preventable. The nonrisk-adjusted rate of death with laparoscopic donation was higher than open nephrectomy, but this difference did not reach statistical significance. Conversion from laparoscopic to open nephrectomy occurs in approximately 1 in 100 surgeries, and this rate has remained fairly steady since 2005.

Conclusions
This analysis suggests that up to two thirds of deaths are potentially preventable. The transplant community should consider additional safety strategies such as simulation training of rare complications to lower donor risk.
The Impact of the Built Environment on Patient Falls in Hospital Rooms: An Integrative Review
Authors: Pati Debajyoti , Valipoor Shabboo , Lorusso Lesa , Mihandoust Sahar , Jamshidi Saman , Rane Apoorva , Kazem-Zadeh Mahshad 
Published: June 2019

Objectives
The aims of this study were to identify and evaluate scientific evidence examining the impact of the built environment on patient falls in hospital rooms.

Methods
An integrative review (IR) with a systematic literature search was performed using the patient, intervention, comparison, outcome framework. We searched CINAHL, PsychINFO, PubMED, and Web of Science databases. The search included peer-reviewed studies from 1990 to 2017 written in English. An additional hand search was also conducted. Selected articles were reviewed and rated based on a hierarchical categorization, comprising six evidence levels, developed by the American Association of Critical-Care Nurses and adapted for evidence-based design systematic literature reviews.

Results
After a multitiered process, 30 articles met the selection criteria. Thematic areas were created based on the examined elements of the physical environment including patient room configuration and available space, bathroom configuration, bathtub and shower, door, bed height and bed rail, flooring, floor mats, patient chair, lighting, toilet, handrail, grab bars, intravenous pole, sink, ceiling lift, and wheelchair and walking aids. Findings of studies on each element are discussed in detail.

Conclusions
Some environmental elements have not been examined in past relational or causal studies, and the level of evidence for the examined attributes is not high enough to gain robust confidence in healthcare design decision-making. Because of the low level of evidence for several environmental elements, conclusions must be taken with caution. More studies using quantitative, relational, or causal designs are recommended to develop actionable interventions on patient falls in hospital rooms.
Role of Postoperative Anticoagulation in Predicting Digit Replantation and Revascularization Failure
Authors: Retrouvey Helene , Solaja Ogi , Baltzer Heather L. 
Published: June 2019

Purpose
The use of intravenous heparin after digit replantation or revascularization (DRR) varies greatly. The insufficient evidence presents a lack of clinical equipoise needed for a randomized trial; as such, a matched propensity score analysis was performed to evaluate the role of postoperative anticoagulation after DRR. The purpose of this study was to determine if the use of postoperative therapeutic anticoagulation reduced the risk of digit failure.

Methods
A retrospective cohort of patients who underwent DRR from 2005 to 2016 was identified. A propensity score was calculated based on age, smoking, injury mechanism, procedure type, vein graft, and number of digits injured. Patients were matched 1:2 by propensity score to create 2 groups with similar risks of receiving anticoagulation postoperatively. Generalized estimating equation logistic model was used to determine differences in digit failure between groups.

Results
Digit replantation or revascularization was performed on 282 patients (92% male; median age, 43 years). Postoperative anticoagulation was administered in 69 (24%) patients, with continuous IV heparin in 34 patients and intravenous heparin with dextran in 35 patients. Digit failure occurred in 88 patients overall, representing 38% of patients receiving anticoagulation and 29% of those not. Major complications were higher among the anticoagulated patients (13% vs 3.3%). After propensity score matching, use of anticoagulation was not associated with digit failure (odds ratio, 0.79; 95% confidence interval, 0.47–1.32).

Conclusions
Among DRR patients with similar predisposing characteristics for postoperative therapeutic heparin or dextran, the use of therapeutic anticoagulation does not have a protective effect against digit failure. Studies are needed to define the role of postoperative IV anticoagulation in DRR and to justify the risk of its administration.
Anatomical and Clinical Comparison of Small Free Flaps for Repairing Finger Skin Defects
Authors: He Bo , Liu Jianghui , Pang Vincent , Zhu Lei , Huang Yongjun , Wang Zengtao , Xu Yangbin , Zhu Zhaowei , Wang Kun 
Published: June 2019

Abstract
The reconstruction of finger defects requires improved functional outcomes and acceptable esthetic outcomes, and small free flaps present a good alternative technique for repairing finger skin defects. From January 2006 to December 2018, we investigated the number and diameter of proximal digital artery perforators, medial plantar artery perforators, and peroneal proper plantar digital arteries of the hallux by dissection and then transplanted free digital arterial perforator flaps, free medial plantar flaps, and free peroneal flaps from the hallux to repair small finger skin defects. The number (SD) of perforators from the medial plantar artery was approximately 2.2 (0.5), and these perforators measured 0.53 (0.20) mm in diameter. The diameter (SD) of the first metatarsal dorsal artery was approximately 1.16 (0.30) mm. A total of 25 patients were included in this study. The transplantation times (SD) for free digital arterial perforator flaps, free medial plantar flaps, and free peroneal flaps from the hallux were 3.5 (0.5) hours, 3.2 (0.7) hours, and 2.0 (0.4) hours, respectively. The follow-up period ranged from 8 to 15 months. All flaps survived and were appropriately shaped. The donor site was either covered with a free flap or directly sutured. Among these 3 types of small flaps, the free peroneal flap from the hallux can be recommended for clinical use because of the large diameter of the contributing vessels, the short operative time, the ease of access, and the improved appearance of the donor site.
TEO-Transanal Intersphincteric Intramesorectal and Laparoscopic Approach in Proctosigmoidectomy for Benign Disease
Authors: Serra-Aracil Xavier , Pascua-Solé Mireia , Serra-Pla Sheila , Mora-López Laura , Pallisera-Lloveras Anna , Calvet Xavier , Navarro-Soto Salvador 
Published: June 2019

Purpose:Completion proctectomy is the traditional approach in the rectal stump remaining after subtotal colectomy for benign disease. It is associated with high morbidity and urinary and sexual dysfunction. To reduce this risk, a minimally invasive approach is presented, intersphincteric intramesorectal proctosigmoidectomy by transanal endoscopic operation and laparoscopy.Patients and Methods:Patients who had undergone total or subtotal colectomy for benign disease, those with a rectosigmoid stump who had rejected intestinal reconstruction and with refractory symptoms or risk of degeneration were selected. The technique proposed and the morbidity outcomes are described.Results:Three patients underwent this minimally invasive approach, operative time was 130 to 150 minutes. The median postoperative hospital stay was 6.6 days. Genitourinary and sexual tests performed in the male patient showed no dysfunction.Conclusions:This minimally invasive technique, with intersphincteric resection and dissection close to the rectal wall, theoretically reduces morbidity and the damage to the autonomic pelvic nerves.
A novel mode of communication between blood and the germline for the inheritance of paternal experiences
Authors: van Steenwyk Gretchen , Gapp Katharina , Jawaid Ali , Germain Pierre-Luc , Manuella Francesca , Tanwar Deepak K. , Zamboni Nicola , Gaur Niharika , Efimova Anastasiia , Thumfart Kristina , Miska Eric A. , Mansuy Isabelle M. 
Published: June 2019

AbstractIn many species, environmental stimuli can affect the germline and contribute to phenotypic changes in the offspring, without altering the genetic code1–5. So far, little is known about which biological signals can link exposure to germ cells. Using a mouse model of postnatal trauma with transgenerational effects, we show that exposure alters lipid-based metabolites in blood of males and their non-exposed offspring. Comparable alterations are validated in serum and saliva of orphan children exposed to trauma. Peroxisome proliferator-activated receptor (PPAR) is identified as mediating the effects of metabolites alterations. Mimicking PPAR activation with a dual PPARα/γ agonist in vivo induces changes in the sperm transcriptome similarly to trauma, and reproduces metabolic phenotypes in the offspring. Injecting serum collected from adult males exposed to postnatal trauma into controls recapitulates metabolic phenotypes in the offspring. These results suggest conserved effects of early life adversity on blood metabolites, and causally involve paternal blood factors and PPAR nuclear receptor in phenotype heritability.
Staufen blocks autophagy in neurodegeneration
Authors: Paul Sharan , Dansithong Warunee , Gandelman Mandi , Figueroa Karla P. , Zu Tao , Ranum Laura P.W. , Scoles Daniel R. , Pulst Stefan M. 
Published: June 2019

AbstractObjectiveThe mechanistic target of rapamycin (mTOR) kinase is one of the master coordinators of cellular stress responses, regulating metabolism, autophagy, and apoptosis. We recently reported that Staufen1 (STAU1), a stress granule (SG) protein, was overabundant in fibroblast cell lines from patients with spinocerebellar ataxia type 2 (SCA2), amyotrophic lateral sclerosis, frontotemporal degeneration, Huntington’s, Alzheimer’s, and Parkinson’s diseases as well as animal models, and patient tissues. STAU1 overabundance is associated with mTOR hyperactivation and links SG formation with autophagy. Our objective was to determine the mechanism of mTOR regulation by STAU1.MethodsWe determined STAU1 abundance with disease- and chemical-induced cellular stressors in patient cells and animal models. We also used RNA binding assays to contextualize STAU1 interaction with MTOR mRNA.ResultsSTAU1 and mTOR were overabundant in BAC-C9orf72, ATXN2Q127, and Thy1-TDP-43 transgenic mouse models. Reducing STAU1 levels in these mice normalized mTOR levels and activity and autophagy-related marker proteins. We also saw increased STAU1 levels in HEK293 cells transfected to express C9orf72-relevant dipeptide repeats (DPRs). Conversely, DPR accumulations were not observed in cells treated by STAU1 RNAi. Overexpression of STAU1 in HEK293 cells increased mTOR levels through direct MTOR mRNA interaction, activating downstream targets and impairing autophagic flux. Targeting mTOR by rapamycin or RNAi normalized STAU1 abundance in a SCA2 cellular model.InterpretationSTAU1 interaction with mTOR drives its hyperactivation and inhibits autophagic flux in multiple models of neurodegeneration. Staufen, therefore, constitutes a novel target to modulate mTOR activity, autophagy, and for the treatment of neurodegenerative diseases.