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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce daniel martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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Predicting intensive care unit-acquired weakness:A multilayer perceptron neural network approach

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World Journal of Clinical Cases 2024年第12期12卷 2023-2030页

作者： Carlos martin Ardila daniel González-Arroyave Mateo Zuluaga-Gómez Department of Basic Sciences University of AntioquiaMedellín 52-59Colombia Department of Surgery Pontificia Universidad BolivarianaMedellín 0057Colombia Department of Emergency Universidad Pontificia BolivarianaMedellín 0057Colombia

In this editorial,we comment on the article by Wang and Long,published in a recent issue of the World Journal of Clinical Cases.The article addresses the challenge of predicting intensive care unit-acquired weakness(ICUAW),a neuromuscular disorder affecting critically ill patients,by employing a novel processing strategy based on repeated machine learning.The editorial presents a dataset comprising clinical,demographic,and laboratory variables from intensive care unit(ICU)patients and employs a multilayer perceptron neural network model to predict ICUAW.The authors also performed a feature importance analysis to identify the most relevant risk factors for ICUAW.This editorial contributes to the growing body of literature on predictive modeling in critical care,offering insights into the potential of machine learning approaches to improve patient outcomes and guide clinical decision-making in the ICU setting.

关键词： Intensive care units Intensive care unit-acquired weakness Risk factors Machine learning Computer neural network

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Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

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World Journal of Gastroenterology 2024年第10期30卷 1280-1286页

作者： Valerie Josephine Dirjayanto Jessica Audrey daniel martin Simadibrata Faculty of Medicine Universitas IndonesiaJakarta Pusat 10430DKI JakartaIndonesia Division of Gastroenterology and Hepatology Mayo ClinicRochesterMinnesota 55905United States Nuffield Department of Population Health University of OxfordOxford OX37LFUnited Kingdom

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

关键词： Vonoprazan Saccharomyces boulardii Helicobacter pylori Rescue therapy Eradication rate

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Alcohol and illicit drugs:prevalence of alcohol and illicit drug use and their predictors in young people from Argentina,Bulgaria,Chile and Romania

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Global Health Journal 2024年第1期8卷 16-23页

作者： daniel Vankov David Jankovszky Borislav Vankov martin Galanternik Claudia Rodriguez Michiel de Ruyter Scientific Organization from Partium Oradea 410204Romania Queensland University of Technology BrisbaneQueensland 4001Australia Association for Youth and Students in Partium Oradea 410102Romania Community Centre Bright Day-2009 Vidin 3700Bulgaria MiNU Civil.Association Buenos Aires 4918Argentina ONG No Chat Santiago 832000Chile

Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,with AID being a major direct risk factor for disability-adjusted youth life-years lost and death.It further contributes to assaults,road crashes,accidental poisoning,and suicide,leading to long-term issues and public health concerns.Objective:This study aimed at disclosing current AID prevalence data for Argentinian,Bulgarian,Chilean and Romanian youth.It shed light on the predictors of AID in young people from those countries.Method:The study used an online survey to gather data from people aged 18 to 25(n=1,297).The survey was underpinned by the theory of planned behaviour(TPB).Predictors were investigated separately for drinking alcohol and using illicit drugs.Results:Our data revealed that across the four target countries,49%to 90%of the participants drank alcohol,and 8%to 35%used illicit drugs in the past three months.Between 20%and 91%of them intended to drink,and between 8%and 31%intended to use illicit drugs in the following three months.Our TPB model predicted statistically significant(P<0.001)amounts of variance in drinking alcohol(between 61%and 72%)and using illicit drugs(between 20.3%and 74.4%).Intention was consistent in significantly predicting both behaviours.Evidence around the predictive validity of self-efficacy,age and gender was mixed across the investigated countries.Conclusion:This research provided an update on the scarce AID epidemiological data.It also supplied evidence about what theoretically-informed measures might be useful targets of interventions in the case of Argentina,Bulgaria,Chile and Romania.This new knowledge of understanding substance abuse determinants and prevalence may help researchers and practitioners better meet young people's health prevention needs.

关键词： Young people Alcohol Ilicit drugs Intention Self-efficacy

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新天鹅护理休闲区,本特利,澳大利亚

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世界建筑 2024年第6期 66-71页

作者：无 Adrian Iredale Finn Pedersen Martyn Hook Tom See Hoo Rebecca Angus Mary McAree Rebecca Hawkett Catherine Dupuy Gian Tonossi Jordan Blagaich Jake Gethin daniel martin Peter Bennetts(摄影) 伊代尔-佩德森-霍克建筑事务所不详

新天鹅护理休闲区旨在通过减少隔离、鼓励安全的活动和社交互动来改善居民的健康和福祉,并欢迎朋友、家人和周边居民的到来。Iph建筑事务所挑战了之前的总体规划,将车辆和道路从中心空间移除,取而代之的是一条宽阔、笔直且清静的人行林... 详细信息

新天鹅护理休闲区旨在通过减少隔离、鼓励安全的活动和社交互动来改善居民的健康和福祉,并欢迎朋友、家人和周边居民的到来。Iph建筑事务所挑战了之前的总体规划,将车辆和道路从中心空间移除,取而代之的是一条宽阔、笔直且清静的人行林荫道。林荫大道从天鹅护理中心的主要入口街道(阿迪苑)延伸至新的休闲区,并继续通向到远处的老年人关怀设施。一条蜿蜒曲折的小路与林荫大道相接,方便人们慢步闲逛。随着总体规划逐渐深化,这些小路将继续延伸,为老年痴呆症患者提供安全的活动空间。

关键词：护理中心建筑事务所主要入口林荫大道本特利休闲区蜿蜒曲折林荫道

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A novel saliva-based miRNA profile to diagnose and predict oral cancer

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International Journal of Oral Science 2024年第1期16卷 97-109页

作者： Jaikrishna Balakittnen Chameera Ekanayake Weeramange daniel F.Wallace Pascal H.G.Duijf Alexandre S.Cristino Gunter Hartel Roberto A.Barrero Touraj Taheri Liz Kenny Sarju Vasani martin Batstone Omar Breik Chamindie Punyadeera Saliva&Liquid Biopsy Translational Laboratory Griffith Institute for Drug DiscoveryGriffith UniversityNathanQLDAustralia Department of Medical Laboratory Sciences Faculty of Allied Health SciencesUniversity of JaffnaJaffnaSri Lanka Menzies Health Institute Griffith UniversityGold CoastQLDAustralia School of Biomedical Sciences Faculty of HealthQueensland University of TechnologyBrisbaneQLDAustralia Centre for Cancer Biology Clinical and Health SciencesUniversity of South Australia&SA PathologyAdelaideSAAustralia Institute of Clinical Medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Genetics Oslo University HospitalOsloNorway Griffith Institute for Drug Discovery Griffith UniversityNathanQLDAustralia QIMR Berghofer Medical Research Institute Statistics UnitBrisbaneQLDAustralia School of Public Health The University of QueenslandBrisbaneQLDAustralia School of Nursing Queensland University of TechnologyBrisbaneQLDAustralia eResearch Research InfrastructureAcademic DivisionQueensland University of TechnologyBrisbaneQLDAustralia Department of Anatomical Pathology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Faculty of Medicine The University of QueenslandBrisbaneQLDAustralia Royal Brisbane and Women’s Hospital Cancer Care ServicesHerstonQLDAustralia Department of Otolaryngology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Department of Oral and Maxillofacial Surgery Royal Brisbane and Women’s HospitalHerstonQLDAustralia

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

关键词： specificity salivary diagnosis

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住院患者认知障碍识别和信息管理的整合性综述

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International Journal of Nursing Sciences 2024年第1期11卷 120-132页

作者：熊蓓蓓 daniel X.Bailey Paul Prudon Elaine M.Pascoe Leonard C.Gray Frederick Graham Amanda Henderson Melinda martin-Khan Centre for Health Services Research Faculty of MedicineThe University of QueenslandBrisbaneAustralia Centre for Clinical Research Faculty of MedicineThe University of QueenslandRoyal Brisbane&Women’s HospitalBrisbaneAustralia Dementia and Delirium Division of MedicinePrincess Alexandra HospitalBrisbaneAustralia School of Nursing Faculty of HealthQueensland University of TechnologyBrisbaneAustralia Nursing Practice Development Unit Princess Alexandra HospitalBrisbaneAustralia School of Nursing Midwifery and Social SciencesCentral Queensland UniversityBrisbaneAustralia Griffith Health Griffith UniversityBrisbaneAustralia School of Nursing Midwifery and ParamedicineThe University of the Sunshine CoastBrisbaneAustralia Department of Health and Life Sciences University of ExeterExeterUnited Kingdom School of Nursing University of Northern British ColumbiaPrince GeorgeCanada

目的旨在对目前提供急性照护的医院识别认知障碍患者以及在病历中记录和管理认知相关信息的实际情况及政策要求和推荐方法进行综述。方法采用Whittemore和Knaf1的五步法,系统检索Medline,CINAHL和Scopus数据库,并检索了灰色文献来源。... 详细信息

目的旨在对目前提供急性照护的医院识别认知障碍患者以及在病历中记录和管理认知相关信息的实际情况及政策要求和推荐方法进行综述。方法采用Whittemore和Knaf1的五步法,系统检索Medline,CINAHL和Scopus数据库,并检索了灰色文献来源。纳人了提供急性照护的医院已实施的患者认知障碍识别和认知信息管理相关的文献。采用混合方法评价工具和灰色文献质量评估清单对文章质量进行评价。采用主题分析法呈现和整合结果。该综述已在PROSPERO预注册(CRD42022343577)。结果共22篇原始研究文献和10篇政府/行业文件被纳人分析。结果显示,实践和政策之间存在差距。尽管在政策层面上高度重视认知障碍的识别、认知相关信息的透明度,以及与患者、家属和照顾者(如适用)之间的互动,但有时在临床实践中,认知评估是非正式的,患者的认知相关信息未作记录,与患者、家属和照顾者的互动也存在不足。结论.通过整合认知评估,利用信息技术开发信息管理综合系统,建立相关法律法规,提供教育与和培训,并采用国家层面的策略,有可能显著改善对认知障碍患者的识别和护理。

关键词：急性照护认知功能障碍数据透明度谵妄痴呆健康信息管理与患者互动.

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Application of near-infrared spectroscopy for fast germplasm analysis and classification in multi-environment using intact-seed peanut(Arachis hypogaea L.)

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Oil Crop Science 2024年第2期9卷 132-141页

作者： Fentanesh Chekole Kassie Gilles Chaix Hermine Bille Ngalle Maguette Seye Coura Fall Hodo-Abalo Tossim Aissatou Sambou Olivier Gibert Fabrice Davrieux Joseph martin Bell Jean-Francois Rami daniel Fonceka Joel Romaric Nguepjop Department of Plant Biology and Physiology Faculty of SciencesUniversity of Yaounde IYaoundeP.O.Box 337Cameroon Department of Plant Science College of AgricultureWolaita Sodo UniversitySodoP.O.Box 138Ethiopia CIRAD UMR AGAP InstitutMontpellierFrance AGAP Institut Univ MontpellierCIRADINRAEInstitut AgroMontpellierFrance ChemHouse Research Group MontpellierFrance Centre D’Etudes Regional Pour L’Amelioration de L’Adaptation a La Secheresse(CERAAS/ISRA) Route de KhomboleThiesBP 3320Senegal Dispositif de Recherche et de Formation en Partenariat Innovation et Amelioration Varietale en Afrique de L’Ouest(IAVAO)CERAASRoute de KhomboleThiesBP 3320Senegal CIRAD UMR QUALISUDSaint PierreFrance

Peanut is a worldwide oilseed crop and the need to assess germplasm in a non-destructive manner is important for seed nutritional breeding.In this study,Near Infrared Spectroscopy(NIRS)was applied to rapidly assess germplasm variability from whole seed of 699 samples,field-collected and assembled in four genetic and environmentbased sets:one set of 300 varieties of a core-collection and three sets of 133 genotypes of an interspecific population,evaluated in three environments in a large spatial scale of two countries,Mbalmayo and Bafia in Cameroon and Nioro in Senegal,under rainfed conditions.NIR elemental spectra were gathered on six subsets of seeds of each sample,after three rotation scans,with a spectral resolution of 16 cm-1over the spectral range of867 nm to 2530 nm.Spectra were then processed by principal component analysis(PCA)coupled with Partial least squares-discriminant analysis(PLS-DA).As results,a huge variability was found between varieties and genotypes for all NIR wavelength within and between environments.The magnitude of genetic variation was particularly observed at 11 relevant wavelengths such as 1723 nm,usually related to oil content and fatty acid composition.PCA yielded the most chemical attributes in three significant PCs(i.e.,eigenvalues>10),which together captured 93%of the total variation,revealing genetic and environment structure of varieties and genotypes into four clusters,corresponding to the four samples sets.The pattern of genetic variability of the interspecific population covers,remarkably half of spectrum of the core-collection,turning out to be the largest.Interestingly,a PLS-DA model was developed and a strong accuracy of 99.6%was achieved for the four sets,aiming to classify each seed sample according to environment origin.The confusion matrix achieved for the two sets of Bafia and Nioro showed 100%of instances classified correctly with 100%at both sensitivity and specificity,confirming that their seed quality was different from each other and all other samples.Overall,NIR

关键词： Groundnut Oilseed Near infrared spectroscopy Germplasm analysis Environment Nutritional Breeding

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Impact of postoperative intravenous fluid administration on complications following elective hepato-pancreato-biliary surgery

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 402-407页

作者： daniel martin Panagis M.Lykoudis Gabriel Jones David Highton Alan Shaw Sarah James Qiang Wei Giuseppe Fusai Division of Surgery&Interventional Science University College LondonGower StBloomsburyLondonWC1E 6BTUK Free Perioperative Research Group Royal Free HospitalPond stLondonNW3 2QGUK Department of Hepato-Pancreato-Biliary Surgery&Liver Transplantation Royal Free HospitalPond stLondonNW3 2QGUK King’s College Hospital Denmark HillLondon SE5 9RSUK Neurocritical Care Unit the National Hospital for Neurology and NeurosurgeryQueen SquareLondonWC1N 3BGUK London School of Hygiene&Tropical Medicine Keppel StreetLondonWC1E 7HTUK Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalZhejiang University School of Medicine79 Qingchun RoadHangzhou 310003China

Background: The impact of perioperative intravenous fluid administration on surgical outcomes has been documented in literature, but not specifically studied in the context of hepato-pancreato-biliary(HPB) surgery. This study aimed to investigate the impact of postoperative intravenous fluid administration on intensive care unit(ICU), in this subgroup of patients. Methods: A single-center retrospective cohort of 241 HPB patients was assessed, focusing on intravenous fluid administration in ICU, during the first 24 h. Intravenous fluid variables were compared to hospital stay and postoperative complications. Data were assessed using Spearman's correlation test for bivariate correlations and logistic regression for multivariate analysis. Results: The median volume of intravenous fluid administered in the first 24 h postoperatively was 4380 mL, of which 2200 mL was crystalloid, 1500 mL colloid and 680 mL "other" fluid. Patients with one or more complications had a higher median total intravenous fluid input(4790 vs. 4300 mL), higher colloid volume(20 0 0 vs. 150 0 mL), lower urine output(1595 vs. 1900 mL) and greater overall fluid balance( + 3040 vs. + 2553 mL) than those without complications. There were correlations between total intravenous fluid volume administered( r = 0.278, P < 0.001), intravenous colloid input( r = 0.278, P < 0.001), urine output( r =-0.295, P < 0.001), positive fluid balance( r = 0.344, P < 0.001) and length of hospital stay. Logistic regression model was constructed to predict the occurrence of one or more complications; total intravenous fluid volume and overall fluid balance were both independent significant predictors(OR = 2.463, P = 0.007; OR = 1.001, P = 0.011; respectively). Conclusions: Administration of high volumes of intravenous fluids in the first 24 hours post-HPB surgery, along with higher positive fluid balance is associated with a higher rate of complications and longer hospital stay. Moreover, lower urine output is associated with longer hospital stay. Whether these are the

关键词： Intravenous fluids Hepato-pancreato-biliary surgery Postoperative outcome

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Exclusive breastfeeding greater than 50%, success of education in a university hospital in Bogotá: Case-control study

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World Journal of Clinical Pediatrics 2024年第1期13卷 23-30页

作者： Marcela Murillo Galvis Sofia Ortegon Ochoa Clara Eugenia Plata García Maria Paula Valderrama Junca Dayanna Alejandra Inga Ceballos daniel Mauricio Mora Gómez Claudia M Granados martin Rondón Department of Pediatrics Hospital Universitario San IgnacioBogotá110111Colombia Department of Clinical Epidemiology and Biostatistics Pontifica Universidad JaverianaBogotá110111Colombia

BACKGROUND Maintenance rates of exclusive breastfeeding(EBF)worldwide are low,thus,one of the objectives of the summary of policies on breastfeeding(BF)in world nutrition goals for 2025 are that at least 50%of infants under six months of age receive EBF that year.The Objective of this study is to document the rates of EBF in children born in San Ignacio University Hospital(HUSI)and identify factors associated with maintenance.AIM To document the percentages of EBF in those that were born at HUSI and identify factors associated to their maintenance.METHODS This is a study of cases and controls in an analytic,retrospective cohort that took children born alive between January 2016 and January 2019 at HUSI located in the city of Bogotá,Colombia.RESULTS Receiving information about BF at HUSI was able to maintain EBF up until 4 mo(OR=1.65;95%CI:1.02-2.66).The presence of gynecologic and obstetric comorbidities(OR=0.32;95%CI:0.12-0.83),having mastitis(OR=0.56;95%CI:0.33-0.94),and receiving information from mass media(OR=0.52;95%CI:0.31-0.84)are factors associated with not maintaining EBF.CONCLUSION Receiving education at a Women-and Child-Friendly Institution was the only significant factor to achieve EBF until 4 mo,with a frequency greater than the one reported in the country,which matches multiple studies where counseling and individualized support on BF achieve this purpose.Knowledge about BF and early detection of obstetric/gynecologic complications must be strengthened among the healthcare staff in charge of mothers during post-partum.Additionally,strategies must be promoted to continue BF such as creating milk banks with the objective of increasing BF rates even when mothers return to work.

关键词： Breastfeeding Women-and Child-Friendly Institutional Strategy Strategies Adherence Education

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