bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2366 LOW DOSE CYCLOPHOSPHAMIDE CONDITIONING REGIMEN IN HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IS WORTH EXPLORING IN THE TREATMENT OF ACQUIRED APLASTIC ANEMIA
Authors: Cui S. , Kong F. , Fang Y. , Cui X. , Wang Y. , Wang J. , Liu K. , Ding S. , Shen M. , Xu R. 
Published: June 2019

Background:In recent years, haploid hematopoietic stem cell transplantation has made great progress in the treatment of acquired aplastic anemia, but the incidence of transplant related complications and transplant related mortality are still high, and the conditioning reginem needs to be further optimized.Aims:To investigate the safety and efficacy of haploidentical hematopoietic stem cell transplantation with different intensity conditioning regimen in the treatment of aplastic anemia (AA).Methods:27 AA patients who underwent haploidentical transplantation in Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2017 to July 2018 were enrolled. All patients received bone marrow plus peripheral blood stem cells.According to the dosage of cyclophosphamide in the conditioning regimen, 26 patients excluding one other conditioning regimens were divided into high‐dosage group (regimen 1, 16 cases) and low‐dosage group (regimen 2, 10 cases). The data of Engraftment, graft‐vs‐host disease (GVHD), hematopoietic reconstitution, relapse, infection, overall survival (OS) were analyzed. The comparison between the two groups was tested by χ(2) test.Results:ALL patients achieved primary engraftment. The activation rate of CMV and EBV was 63 % (17/27). Post‐transplant lymphocyte disease (PTLD) in 0 case. The cumulative incidences of acute GVHD grade I‐IV and chronic GVHD were 22.2% (6/27) and 18.5% (5/27) respectively and the incidence of extensive chronic GVHD was 0%. The median follow‐up time was 6.5 (0.5‐12.5) months, the OS was 96.3% (26/27). All survived patients were no longer dependent on blood transfusion and none of them had recurrence. Comparing the rates of overall survival(94%(15/16) vs.100%(10/10)) and rates of chronic GVHD(18.8%(3/16) vs. 20%(2/10)) in regimen 1 and regimen 2 group, there were no significant difference (P > 0.05). Significant difference was found at the incidence of I‐IV acute GVHD (12.5% (2/16) vs. 30% (3/10),P < 0.05).Summary/Conclusion:Haploidentical hematopoietic stem cell transplantation is effective and safe in the treatment of acquired aplastic anemia. It is suitable for patients who are not eligible for matched donor transplantation. Application of low dose cyclophosphamide preconditioning in haploid transplantation is worth exploring.
PB2418 CLINICAL PRESENTATION AND MOLECULAR IDENTIFICATION OF ALPHA GLOBIN VARIANTS
Authors: Salcioglu Z. , Aydoğan G. , Akıcı F. , Bayram C. , Özdemir G. N. 
Published: June 2019

Background:Alpha thalassemia is the most common genetic disease inthe world with the prevalence of carriers ranging from 5–50% in several populations. Alpha thalassemia, characterized by variable degrees of α‐globin chain deficit is highly prevalent throughout the world. Alpha thalassemia syndromes are caused by mutations on one or more of the four α‐globin genes.Aims:The aim of this study was to determine alpha thalassemia mutations in our patients and to evaluate types of mutations.Methods:In a retrospective review of 52 patients with alpha thalassemia. followed at our centre from 1990 to 2018. Information of patients were retrieved from patient files and from the records contained in the electronic information processing environment created after 2005. The samples were investigated for α‐thalassemia mutations.Results:Presending ages of our patients ranged between one year and 13 years of age (5 ± 4.3 year). Twenty four of them were girls and 28 were boys. Fourteen patients (27%) were asymptomatic at the time of diagnosis, 32 (61.5%) of whom were diagnosed in patients with unsolved hypochromic microcytic anemia and 6 (11.5%) by family history. Thirteen different mutations were determined in patients. The most common mutation was the 3.7 gene deletion and was found in 23 patients (44.2%). Others common mutations were the 20.5 kb gene deletion (18; 34.6%), MED gene deletion (2;3.8%), α2 polyA2 (2;3.8%). Double gen mutations were determined in 27 patients (51.9%). The most common double gen mutation was the 3.7 gene deletion and was found in 8 patients (29.6%).Summary/Conclusion:Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b‐thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey.
Opioid Toxidrome Following Grapefruit Juice Consumption in the Setting of Methadone Maintenance
Authors: Ershad Muhammed , Cruz Maricel Dela , Mostafa Ahmed , Mckeever Rita , Vearrier David , Greenberg Michael I. 
Published: June 2019

Background:
Methadone is a synthetic mu-opioid receptor agonist used in the treatment of chronic pain and opioid dependence. Methadone is metabolized by several cytochrome P450 isoenzymes; primarily CYP3A4, CYP2B6, and CYP2D6 before renal and fecal elimination. Exposure to substances like grapefruit juice, that inhibit these isoenzymes may result in increased blood levels of methadone, and thus may manifest clinically as unexpected opioid toxicity.

Case:
A 51-year-old male was found unresponsive. He was hypoxic and bradypneic with pinpoint pupils. Multiple boluses followed by infusion of naloxone were required before improvement of respiratory status. Upon awakening, the patient reported participating in an opioid treatment program where he is administered 90 mg of oral methadone daily and denied any other substance use. On further questioning, he admitted to drinking grapefruit juice (estimated to be approximately 500 mL/day) every day for 3 consecutive days before presentation. The patient was discharged home after being counseled to stop drinking grapefruit juice.

Discussion:
Grapefruit juice is known to be an inhibitor of the CYP3A4 isoenzyme. Various studies demonstrate that through CYP3A4 inhibition, grapefruit juice increases serum levels of opioids, such as methadone, though no clinically significant effects have been reported.

Conclusions:
Grapefruit juice inhibits the metabolism of methadone, raising its serum levels. To our knowledge, this is the first reported case in which the interaction between grapefruit juice and methadone was significant enough to cause an opioid toxidrome. It is, therefore, recommended that opioid treatment programs (OTPs) advise patients about this interaction before administering methadone.
Estimating the causal effect of annual PM2.5 exposure on mortality rates in the Northeastern and mid-Atlantic states
Authors: Yitshak-Sade Maayan , Kloog Itai , Zanobetti Antonella , Schwartz Joel D. 
Published: June 2019

Background:
Dozens of cohort studies have associated particulate matter smaller than 2.5 µm in diameter (PM2.5) exposure with early deaths, and the Global Burden of Disease identified PM2.5 as the fifth-ranking mortality risk factor in 2015. However, few studies have used causal modeling techniques. We assessed the effect of annual PM2.5 exposure on all-cause mortality rates among the Medicare population in the Northeastern and mid-Atlantic states, using the difference-in-differences approach for causal modeling.

Methods:
We obtained records of Medicare beneficiaries 65 years of age or more who reside in the Northeastern or mid-Atlantic states from 2000 to 2013 and followed each participant from the year of enrollment to the last year of follow-up. We estimated the causal effect of annual PM2.5 exposure on mortality rates using the difference-in-differences approach in the Poisson survival analysis. We controlled for individual confounders, for spatial differences using dummy variables for each ZIP code and for time trends using a penalized spline of year.

Results:
We included 112,376,805 person-years from 15,401,064 people, of whom 37.4% died during the study period. The interquartile range (IQR) of the annual PM2.5 concentration was 3 µg/m3, and the mean annual PM2.5 concentration ranged between 6.5 and 14.5 µg/m3 during the study period. An IQR incremental increase in PM2.5 was associated with a 4.04% increase (95% CI = 3.49%, 4.59%) in mortality rates.

Conclusions:
Assuming no omitted predictors changing differently across ZIP codes over time in correlation with PM2.5, we found a causal effect of PM2.5 on mortality incidence rate.
Ultraviolet radiation exposure and breast cancer risk in the Nurses’ Health Study II
Authors: VoPham Trang , Bertrand Kimberly A. , DuPré Natalie C. , James Peter , Vieira Verónica M. , Tamimi Rulla M. , Laden Francine , Hart Jaime E. 
Published: June 2019

Background:
Ultraviolet (UV) radiation exposure, the primary source of vitamin D for most people, may reduce breast cancer risk. To date, epidemiologic studies have shown inconsistent results.

Methods:
The Nurses’ Health Study II is a U.S. nationwide prospective cohort of female registered nurses. A UV exposure model was linked with geocoded residential address histories. Early-life UV exposure was estimated based on the state of residence at birth, age 15, and age 30. Self-reported breast cancer was confirmed from medical records. Time-varying Cox regression models adjusted for established breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:
From 1989 to 2013, 3,959 invasive breast cancer cases occurred among 112,447 participants. Higher UV exposure during adulthood was not associated with invasive breast cancer risk overall (adjusted HR comparing highest to lowest quintile = 1.00; 95% CI = 0.90, 1.11, P for trend = 0.64) or according to estrogen receptor (ER) status. There were suggestive inverse associations between ER− breast cancer and early-life UV exposure at birth (adjusted HR = 0.94; 95% CI = 0.88, 1.01 per interquartile range increase [15.7 mW/m2]), age 15 (adjusted HR = 0.96; 95% CI = 0.89, 1.04 per 18.0 mW/m2), and age 30 (adjusted HR = 0.90; 95% CI = 0.82, 1.00 per 27.7 mW/m2).

Conclusions:
Ambient UV exposure during adulthood was not associated with risk of invasive breast cancer overall or by ER status. However, we observed suggestive inverse associations between early-life UV exposure and ER− breast cancer risk.
Animal Models
Authors: Saloman Jami L. , Albers Kathryn M. , Cruz-Monserrate Zobeida , Davis Brian M. , Edderkaoui Mouad , Eibl Guido , Epouhe Ariel Y. , Gedeon Jeremy Y. , Gorelick Fred S. , Grippo Paul J. , Groblewski Guy E. , Husain Sohail Z. , Lai Keane K.Y. , Pandol Stephen J. , Uc Aliye , Wen Li , Whitcomb David C. 
Published: June 2019

Abstract
At the 2018 PancreasFest meeting, experts participating in basic research met to discuss the plethora of available animal models for studying exocrine pancreatic disease. In particular, the discussion focused on the challenges currently facing the field and potential solutions. That meeting culminated in this review, which describes the advantages and limitations of both common and infrequently used models of exocrine pancreatic disease, namely, pancreatitis and exocrine pancreatic cancer. The objective is to provide a comprehensive description of the available models but also to provide investigators with guidance in the application of these models to investigate both environmental and genetic contributions to exocrine pancreatic disease. The content covers both nongenic and genetically engineered models across multiple species (large and small). Recommendations for choosing the appropriate model as well as how to conduct and present results are provided.
Increasing Compliance with a New Interunit Handoff Process: A Quality Improvement Project
Authors: Pino Felicity A. , Sam Kenneth J. , Wood Stacey L. , Tafreshi Paresa A. , Parks Stacy L. , Bell Priscilla A. , Hoffman Elizabeth A. , Koebel Lindsey M. , St. Peter Shawn D. 
Published: June 2019

Introduction:
Current literature demonstrates that standardizing interunit patient handoff improves communication, information transfer, and patient safety. However, few studies have focused on increasing staff compliance with new handoff processes. The purpose of this quality improvement project was to incorporate both user input into process design and on-the-job coaching with a newly introduced nurse handoff process between the postanesthesia care unit and Medical/Surgical units. We hypothesized that staff compliance would be 100% within 90 days.

Methods:
The team’s intervention consisted of (1) involving representative frontline nursing staff in the standardization and modification of the handoff process and (2) providing on-the-job coaching as the new process was being trialed at the bedside. We designed the handoff process during a 2-day workshop and a 1.5-week pilot. Data included the number of observed noncompliant process elements and handoff duration. Three sequential 30-day plan-do-study-act cycles were followed, during which compliance observations and user feedback were used to refine the design and coaching iteratively.

Results:
A total of 1,800 process elements were observed and coached throughout a 90-day trial period. The number of observed noncompliant elements decreased from 15% (92) to 4% (22) from the first 30-day interval to the final 30-day interval. There was no undesirable increase in handoff duration (mean, 8.05 ± 4.72 minutes), and several potential errors—related to orders, charting, and patient placement—were prevented by using the new handoff.

Conclusions:
User input and on-the-job coaching resulted in iteratively increasing frontline compliance with a new standardized handoff process.
Prevent Safety Threats in New Construction through Integration of Simulation and FMEA
Authors: Colman Nora , Stone Kimberly , Arnold Jennifer , Doughty Cara , Reid Jennifer , Younker Sarah , Hebbar Kiran B. 
Published: June 2019

Introduction:
The built environment may impact safety and decisions made during the design phases can have unintended downstream effects that lead to patient harm. These flaws within the system are latent safety threats (LSTs). Simulation-based clinical systems testing (SbCST) provides a clinical context to examine the environment for safety threats postconstruction. Integration of Failure Mode Effect Analysis (FMEA) with SbCST provides a framework to identify, categorize, and prioritize LSTs before patient exposure.

Methods:
We implemented SbCST in a newly constructed pediatric subspecialty outpatient center before opening. We used in-situ simulations to evaluate both routine and high-risk clinical scenarios pertinent to each clinical area. FMEA was used as a methodology to assign risk, prioritize, and categorize LSTs identified during the simulation.

Results:
Over 3 months, we conducted 31 simulated scenarios for 15 distinct subspecialty clinics involving 150 participants and 151 observers. We identified a total of 334 LSTs from 15 distinct clinics. LSTs were further classified into process/workflow, facility, resource, or clinical performance issues.

Conclusions:
Integration of SbCST and FMEA risk assessment is effective in evaluating a new space for safety threats, workflow, and process inefficiencies in the postconstruction environment, providing a framework for prioritizing issues with the greatest risk for harm.
Comprehensive characterisation of molecular host-pathogen interactions in influenza A virus-infected human macrophages
Authors: Clohisey Sara , Parkinson Nicholas , Wang Bo , Bertin Nicolas , Wise Helen , Tomoiu Andru ,   FANTOM5 Consortium, Summers Kim M. , Carninci Piero , Forrest Alistair A. , Hayashizaki Yoshihide , Digard Paul , Hume David A. , Baillie J. Kenneth 
Published: June 2019

AbstractMacrophages in the lung detect and respond to influenza A virus (IAV), determining the nature of the immune response. Using terminal depth 5’-RNA sequencing (CAGE) we quantify transcriptional activity of both host and pathogen over a 24-hour timecourse of IAV infection in primary human monocyte-derived macrophages (MDM). We use a systems approach to describe the transcriptional landscape of the host response to IAV contrasted with bacterial lipopolysaccharide treated MDMs, observing a failure of IAV-treated MDMs to induce feedback inhibitors of inflammation. Systematic comparison of host RNA sequences incorporated into viral mRNA (“snatched”) against a complete survey of background RNA in the host cell enables an unbiased quantification of over-represented features of snatched host RNAs. We detect preferential snatching of RNAs associated with snRNA transcription and demonstrate that cap-snatching avoids transcripts encoding host ribosomal proteins, which are required by IAV for replication.
Graphical Abstract(A) Overview of bioinformatics pipeline. (B) Host gene expression reveals that human macrophages exposed to IAV exhibit sustained production of key inflammatory mediators and failure to induce expression of feedback inhibitors of inflammation. (C) Unbiased comparison with total background RNA expression demonstrates that IAV cap-snatching has a strong preference for, and aversion to, different groups of host transcripts.
Factors associated with the use of maternal health services by mothers in a post-conflict area of western Côte d’Ivoire in 2016
Authors: Mamadou Samba , Régine Attia-Konan Akissi , Dramane Sangaré Abou , Jules Youan Gotré , Philippe Kouadio Luc , Ramata Bakayoko-Ly 
Published: June 2019

AbstractIntroductionIn Côte d’Ivoire, maternal health service utilization indicators remain low despite improvements in health coverage and the availability of free health care for pregnant women. The objective of the study was to identify the determinants associated with the use of maternal health services in the department of Bloléquin, in western Côte d’Ivoire.MethodsWe conducted a cross-sectional study with an analytical focus. The study sample size was 400 women. Study participants were selected through a two-stage cluster survey. The data were collected using a standardized questionnaire whose items concerned socio-demographic data, the different uses of maternal health services, namely childbirth assisted by a health professional, use of family planning, prenatal consultation and post-natal consultation. Logistic regression was used to investigate factors associated with the use of maternal health services. The significance of the statistical tests was set at 5%. The odds ratios and 95% confidence intervals were calculated and interpreted.ResultsThe results showed that women made less use of family planning services (OR=0.4), prenatal consultation (OR=0.2) and assisted childbirth (OR=0.2) when they provided the funding for care themselves. Women with incomes above $26.8 used family planning services 4 times more than those with lower incomes. Married women used prenatal consultations 3 times more often than unmarried women (CI95% = 1.4 - 7.3). Desiring pregnancy increased the use of post-natal consultations by 3 times (CI95% = 1.5 - 6.1).ConclusionImproving the use of maternal health services in western Côte d’Ivoire requires taking into account women’s socio-cultural and economic challenges. In initiatives related to the financial empowerment of women, efforts must be made at the level of emotional factors related to pregnancy.
A survey of biosecurity measures applied on dairy cattle farms in Spain
Authors: Villaamil Francisco Javier , Arnaiz Ignacio , Allepuz Alberto , Molins Mikel , Lázaro Mercedes , Benavides Bibiana , Moya Sebastián Jesús , Casal Jordi , Yus Eduardo , Diéguez Francisco Javier 
Published: June 2019

AbstractAttention to biosecurity has been highlighted as the most important measure to reduce and prevent the introduction of diseases to farms. There is little published information about the biosecurity of dairy cattle in Spain. We therefore aimed to assess and characterize the current application of biosecurity measures on dairy cattle farms in Spain, and relate these to bovine viral diarrhea and infectious bovine rhinotracheitis. From July 2017 to April 2018, data on biosecurity measures for 124 dairy herds were collected using a questionnaire. We also assessed the sanitary status of these farms (efficacy of measures implemented against both diseases using antibody ELISA. Data were analyzed descriptively, and using multiple correspondence analysis and a two-step cluster analysis. Measures to prevent disease introduction were often poorly implemented. Three main clusters of farms were identified: Clusters 1 and 2 included herds of small and intermediate sizes, respectively. These, particularly cluster 1, showed the most deficiencies in the control of vehicles and visitors. However, individual purchases usually involved low numbers of animals, especially in cluster 2, and animals were tested for bovine viral diarrhea and infectious bovine rhinotracheitis at their places of origin or on arrival at farms. Farms in clusters 1 and 2 were frequently under voluntary control programs. Cluster 3 had the largest herd sizes, with somewhat better biosecurity control of vehicles and visitors. However, farms in this cluster also purchased the most animals, sometimes without testing, and hired external workers most often. Farms in cluster 1 showed the best sanitary level, followed by clusters 2 and 3. Collecting data such as these is an important first step to identification of biosecurity shortcomings, and to structuring of adequate follow-up to ensure that measures are implemented correctly on farms in Spain.
Facilitators and Barriers to Linkage to HIV Care and Treatment among Female Sex Workers in a Community-based HIV Prevention Intervention in Tanzania: a qualitative study
Authors: Nyato Daniel , Nnko Soori , Komba Albert , Kuringe Evodius , Plotkin Marya , Mbita Gaspar , Shao Amani , Changalucha John , Wambura Mwita 
Published: June 2019

AbstractBackgroundHIV-infected female sex workers (FSWs) have poor linkage to HIV care in sub-Sahara Africa.MethodsWe conducted 21 focus group discussions (FGDs) to explore factors influencing linkage to HIV care among FSWs tested for HIV through a comprehensive community-based HIV prevention project in Tanzania.ResultsInfluences on linkage to care were present at the system, societal and individual levels. System-level factors included unfriendly service delivery environment, including lengthy pre-enrolment sessions, concerns about confidentiality, stigmatising attitudes of health providers. Societal-level factors included myths and misconceptions about ART and stigma. On the individual level, most notable was fear of not being able to continue to have a livelihood if one’s status were to be known. Facilitators were noted, including the availability of transport to services, friendly health care providers and peer-support referral and networks.ConclusionFindings of this study underscore the importance of peer-supported linkages to HIV care and the need for respectful, high-quality care.