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Article ; Online: Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion.

Esposito, Anthony J / Imani, Jewel / Shrestha, Shikshya / Bagwe, Shefali / Lamattina, Anthony M / Vivero, Marina / Goldberg, Hilary J / Rosas, Ivan O / Henske, Elizabeth P / El-Chemaly, Souheil Y

Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia

2023 Volume 49, Issue 2, Page(s) e20220356

Abstract: Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary ... ...

Abstract	Objective: Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. Methods: This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. Results: The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Conclusions: Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.
MeSH term(s)	Humans ; Lymphangioleiomyomatosis/complications ; Lymphangioleiomyomatosis/diagnosis ; Lymphangioleiomyomatosis/pathology ; Retrospective Studies ; Lung Diseases/complications ; Biomarkers ; Lung ; Lung Neoplasms/complications
Chemical Substances	Biomarkers
Language	Portuguese
Publishing date	2023-05-01
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2223157-2
ISSN	1806-3756 ; 1806-3713
ISSN (online)	1806-3756
ISSN	1806-3713
DOI	10.36416/1806-3756/e20220356
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Article ; Online: Increased Odds of Death for Patients with Interstitial Lung Disease and COVID-19: A Case-Control Study.

Esposito, Anthony J / Menon, Aravind A / Ghosh, Auyon J / Putman, Rachel K / Fredenburgh, Laura E / El-Chemaly, Souheil Y / Goldberg, Hilary J / Baron, Rebecca M / Hunninghake, Gary M / Doyle, Tracy J

American journal of respiratory and critical care medicine

2020 Volume 202, Issue 12, Page(s) 1710–1713

MeSH term(s)	Aged ; Aged, 80 and over ; COVID-19/epidemiology ; Case-Control Studies ; Cause of Death/trends ; Comorbidity ; Female ; Humans ; Lung Diseases, Interstitial/mortality ; Male ; Middle Aged ; Pandemics ; Retrospective Studies ; SARS-CoV-2 ; Survival Rate/trends ; United States/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-09-07
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202006-2441LE
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Article ; Online: Syndecan-2 regulates PAD2 to exert antifibrotic effects on RA-ILD fibroblasts.

Tsoyi, Konstantin / Esposito, Anthony J / Sun, Bo / Bowen, Ryan G / Xiong, Kevin / Poli, Fernando / Cardenas, Rafael / Chu, Sarah G / Liang, Xiaoliang / Ryter, Stefan W / Beeton, Christine / Doyle, Tracy J / Robertson, Matthew J / Celada, Lindsay J / Romero, Freddy / El-Chemaly, Souheil Y / Perrella, Mark A / Ho, I-Cheng / Rosas, Ivan O

Scientific reports

2022 Volume 12, Issue 1, Page(s) 2847

Abstract: Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression ... ...

Abstract	Rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD) is the most common pulmonary complication of RA, increasing morbidity and mortality. Anti-citrullinated protein antibodies have been associated with the development and progression of both RA and fibrotic lung disease; however, the role of protein citrullination in RA-ILD remains unclear. Here, we demonstrate that the expression of peptidylarginine deiminase 2 (PAD2), an enzyme that catalyzes protein citrullination, is increased in lung homogenates from subjects with RA-ILD and their lung fibroblasts. Chemical inhibition or genetic knockdown of PAD2 in RA-ILD fibroblasts attenuated their activation, marked by decreased myofibroblast differentiation, gel contraction, and extracellular matrix gene expression. Treatment of RA-ILD fibroblasts with the proteoglycan syndecan-2 (SDC2) yielded similar antifibrotic effects through regulation of PAD2 expression, phosphoinositide 3-kinase/Akt signaling, and Sp1 activation in a CD148-dependent manner. Furthermore, SDC2-transgenic mice exposed to bleomycin-induced lung injury in an inflammatory arthritis model expressed lower levels of PAD2 and were protected from the development of pulmonary fibrosis. Together, our results support a SDC2-sensitive profibrotic role for PAD2 in RA-ILD fibroblasts and identify PAD2 as a promising therapeutic target of RA-ILD.
MeSH term(s)	Animals ; Anti-Citrullinated Protein Antibodies/genetics ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/pathology ; Bleomycin/toxicity ; Citrullination/genetics ; Fibroblasts/metabolism ; Gene Expression Regulation/genetics ; Humans ; Lung/metabolism ; Lung/pathology ; Lung Injury/chemically induced ; Lung Injury/complications ; Lung Injury/genetics ; Lung Injury/pathology ; Mice ; Mice, Transgenic ; Phosphatidylinositol 3-Kinases/genetics ; Protein-Arginine Deiminase Type 2/genetics ; Proto-Oncogene Proteins c-akt/genetics ; Pulmonary Fibrosis/complications ; Pulmonary Fibrosis/drug therapy ; Pulmonary Fibrosis/genetics ; Pulmonary Fibrosis/pathology ; Receptor-Like Protein Tyrosine Phosphatases, Class 3 ; Sp1 Transcription Factor/genetics ; Syndecan-2/genetics
Chemical Substances	Anti-Citrullinated Protein Antibodies ; Sdc2 protein, mouse ; Sp1 Transcription Factor ; SP1 protein, human ; Bleomycin (11056-06-7) ; Syndecan-2 (149769-25-5) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTPRJ protein, human (EC 3.1.3.48) ; Receptor-Like Protein Tyrosine Phosphatases, Class 3 (EC 3.1.3.48) ; PADI2 protein, human (EC 3.5.3.15) ; Protein-Arginine Deiminase Type 2 (EC 3.5.3.15)
Language	English
Publishing date	2022-02-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-06678-7
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Article ; Online: Psychological impact of genetic and clinical screening for pulmonary fibrosis on asymptomatic first-degree relatives of affected individuals.

Carmichael, Nikkola / Martinez Manzano, Jose M / Quesada-Arias, Luisa D / Poli, Sergio de Frías / Baumgartner, Maura Alvarez / Planchart Ferretto, Maria A / DiGianni, Lisa / Gampala-Sagar, Shannon / Leone, Dominick A / Gulati, Swati / El-Chemaly, Souheil Y / Goldberg, Hilary J / Putman, Rachel / Hatabu, Hiroto / Rosas, Ivan O / Hunninghake, Gary M / Raby, Benjamin A

Thorax

2021 Volume 76, Issue 6, Page(s) 621–623

Abstract: Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after ... ...

Abstract	Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.
MeSH term(s)	Aged ; Female ; Follow-Up Studies ; Genetic Testing/methods ; Humans ; Male ; Mass Screening/methods ; Middle Aged ; Pedigree ; Pulmonary Fibrosis/diagnosis ; Pulmonary Fibrosis/genetics ; Pulmonary Fibrosis/psychology ; Retrospective Studies ; Surveys and Questionnaires ; Time Factors
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2020-216244
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Article: Increased Odds of Death for Patients with Interstitial Lung Disease and COVID-19: A Case-Control Study

Am. j. respir. crit. care med

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #748840
Database	COVID19

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Article ; Online: Biobanking and cryopreservation of human lung explants for omic analysis.

The European respiratory journal

2020 Volume 55, Issue 1

MeSH term(s)	Biological Specimen Banks ; Cell Survival ; Cryopreservation ; Humans ; Lung
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.01635-2018
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Pulmonary Vasculopathy Associated with FIGF Gene Mutation.

Bailey, Evan / Cui, Ye / Casey, Alicia / Stoler, Joan M / Ai, Xingbin / Ma, Dongdong / Handin, Robert / Sliz, Piotr / Vargas, Sara O / El-Chemaly, Souheil Y

The American journal of pathology

2017 Volume 187, Issue 1, Page(s) 25–32

Abstract: Vascular endothelial growth factor (VEGF)-D is capable of inducing angiogenesis and lymphangiogenesis through signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively. Mutations in the FIGF (c-fos-induced growth factor) gene encoding VEGF-D have ... ...

Abstract	Vascular endothelial growth factor (VEGF)-D is capable of inducing angiogenesis and lymphangiogenesis through signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively. Mutations in the FIGF (c-fos-induced growth factor) gene encoding VEGF-D have not been reported previously. We describe a young male with a hemizygous mutation in the X-chromosome gene FIGF (c.352 G>A) associated with early childhood respiratory deficiency. Histologically, lungs showed ectatic pulmonary arteries and pulmonary veins. The mutation resulted in a substitution of valine to methionine at residue 118 of the VEGF-D protein. The resultant mutant protein had increased dimerization, induced elevated VEGFR-2 signaling, and caused aberrant angiogenesis in vivo. Our observations characterize a new subtype of congenital diffuse lung disease, provide a histological correlate, and support a critical role for VEGF-D in lung vascular development and homeostasis.
MeSH term(s)	Animals ; Cell Line ; Chickens ; Child ; Child, Preschool ; Family ; Genetic Predisposition to Disease ; Humans ; Infant ; Infant, Newborn ; Lung/blood supply ; Lung/metabolism ; Lung/pathology ; Lung Diseases/blood ; Lung Diseases/genetics ; Male ; Mutation/genetics ; Neovascularization, Pathologic/genetics ; Vascular Diseases/blood ; Vascular Diseases/genetics ; Vascular Endothelial Growth Factor D/blood ; Vascular Endothelial Growth Factor D/genetics ; Vascular Endothelial Growth Factor D/metabolism
Chemical Substances	VEGFD protein, human ; Vascular Endothelial Growth Factor D
Language	English
Publishing date	2017-01
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2016.09.008
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Article ; Online: Quantitative computed tomography assessment of bronchiolitis obliterans syndrome after lung transplantation.

Gazourian, Lee / Ash, Samuel / Meserve, Emily E K / Diaz, Alejandro / Estepar, Raul San Jose / El-Chemaly, Souheil Y / Rosas, Ivan O / Divo, Miguel / Fuhlbrigge, Anne L / Camp, Phillip C / Ho, Vincent T / Bhatt, Ami S / Goldberg, Hilary J / Sholl, Lynette M / Washko, George R

Clinical transplantation

2017 Volume 31, Issue 5

Abstract: Background: Bronchiolitis obliterans syndrome (BOS) is a clinical manifestation of chronic allograft rejection following lung transplantation. We examined the quantitative measurements of the proximal airway and vessels and pathologic correlations in ... ...

Abstract	Background: Bronchiolitis obliterans syndrome (BOS) is a clinical manifestation of chronic allograft rejection following lung transplantation. We examined the quantitative measurements of the proximal airway and vessels and pathologic correlations in subjects with BOS. Methods: Patients who received a lung transplant at the Brigham and Women's Hospital between December 1, 2002 and December 31, 2010 were included in this study. We characterized the quantitative CT measures of proximal airways and vessels and pathological changes. Results: Ninety-four (46.1%) of the 204 subjects were included in the study. There was a significant increase in the airway vessel ratio in subjects who developed progressive BOS compared to controls and non-progressors. There was a significant increase in airway lumen area and decrease in vessel cross-sectional area in patients with BOS compared to controls. Patients with BOS had a significant increase in proximal airway fibrosis compared to controls. Conclusions: BOS is characterized by central airway dilation and vascular remodeling, the degree of which is correlated to decrements in lung function. Our data suggest that progressive BOS is a pathologic process that affects both the central and distal airways.
MeSH term(s)	Bronchiolitis Obliterans/diagnostic imaging ; Bronchiolitis Obliterans/etiology ; Bronchiolitis Obliterans/pathology ; Female ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Lung Transplantation/adverse effects ; Male ; Middle Aged ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2017-04-12
Publishing country	Denmark
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.12943
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Article ; Online: Densitometric and local histogram based analysis of computed tomography images in patients with idiopathic pulmonary fibrosis.

Ash, Samuel Y / Harmouche, Rola / Vallejo, Diego Lassala Lopez / Villalba, Julian A / Ostridge, Kris / Gunville, River / Come, Carolyn E / Onieva Onieva, Jorge / Ross, James C / Hunninghake, Gary M / El-Chemaly, Souheil Y / Doyle, Tracy J / Nardelli, Pietro / Sanchez-Ferrero, Gonzalo V / Goldberg, Hilary J / Rosas, Ivan O / San Jose Estepar, Raul / Washko, George R

Respiratory research

2017 Volume 18, Issue 1, Page(s) 45

Abstract: Background: Prior studies of clinical prognostication in idiopathic pulmonary fibrosis (IPF) using computed tomography (CT) have often used subjective analyses or have evaluated quantitative measures in isolation. This study examined associations ... ...

Abstract	Background: Prior studies of clinical prognostication in idiopathic pulmonary fibrosis (IPF) using computed tomography (CT) have often used subjective analyses or have evaluated quantitative measures in isolation. This study examined associations between both densitometric and local histogram based quantitative CT measurements with pulmonary function test (PFT) parameters and mortality. In addition, this study sought to compare risk prediction scores that incorporate quantitative CT measures with previously described systems. Methods: Forty six patients with biopsy proven IPF were identified from a registry of patients with interstitial lung disease at Brigham and Women's Hospital in Boston, MA. CT scans for each subject were visually scored using a previously published method. After a semi-automated method was used to segment the lungs from the surrounding tissue, densitometric measurements including the percent high attenuating area, mean lung density, skewness and kurtosis were made for the entirety of each patient's lungs. A separate, automated tool was used to detect and quantify the percent of lung occupied by interstitial lung features. These analyses were used to create clinical and quantitative CT based risk prediction scores, and the performance of these was compared to the performance of clinical and visual analysis based methods. Results: All of the densitometric measures were correlated with forced vital capacity and diffusing capacity, as were the total amount of interstitial change and the percentage of interstitial change that was honeycombing measured using the local histogram method. Higher percent high attenuating area, higher mean lung density, lower skewness, lower kurtosis and a higher percentage of honeycombing were associated with worse transplant free survival. The quantitative CT based risk prediction scores performed similarly to the clinical and visual analysis based methods. Conclusions: Both densitometric and feature based quantitative CT measures correlate with pulmonary function test measures and are associated with transplant free survival. These objective measures may be useful for identifying high risk patients and monitoring disease progression. Further work will be needed to validate these measures and the quantitative imaging based risk prediction scores in other cohorts.
MeSH term(s)	Absorptiometry, Photon/methods ; Absorptiometry, Photon/statistics & numerical data ; Adult ; Aged ; Aged, 80 and over ; Boston/epidemiology ; Female ; Humans ; Idiopathic Pulmonary Fibrosis/diagnostic imaging ; Idiopathic Pulmonary Fibrosis/mortality ; Idiopathic Pulmonary Fibrosis/pathology ; Male ; Middle Aged ; Observer Variation ; Prevalence ; Prognosis ; Radiographic Image Interpretation, Computer-Assisted/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Survival Rate ; Tomography, X-Ray Computed/methods ; Tomography, X-Ray Computed/statistics & numerical data ; Young Adult
Language	English
Publishing date	2017-03-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-9921
ISSN (online)	1465-993X
ISSN	1465-9921
DOI	10.1186/s12931-017-0527-8
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Article: Cesarean delivery among nulliparous women in Beirut: assessing predictors in nine hospitals.

Tamim, Hala / El-Chemaly, Souheil Y / Nassar, Anwar H / Aaraj, Alia M / Campbell, Oona M R / Kaddour, Afamia A / Yunis, Khalid A

Birth (Berkeley, Calif.)

2007 Volume 34, Issue 1, Page(s) 14–20

Abstract: Background: Obstetric practice has witnessed a worldwide trend of increasing cesarean section rates in recent years. Similar trends have been observed in Lebanon, according to 2 studies conducted in 1996 and 1999. The objective of the present study was ... ...

Abstract	Background: Obstetric practice has witnessed a worldwide trend of increasing cesarean section rates in recent years. Similar trends have been observed in Lebanon, according to 2 studies conducted in 1996 and 1999. The objective of the present study was to assess the differences in predictors of cesarean delivery among nulliparous women in a "control hospital" with a low cesarean delivery rate (12.5%) and the rest of the National Collaborative Perinatal Neonatal Network (NCPNN) "study hospitals" with a higher cesarean delivery rate (31.4%). Methods: Data were collected by the NCPNN database, which covers deliveries at 9 major hospitals located in the Greater Beirut area. Data analysis was performed on the 6,668 consecutive deliveries occurring between January 1, 2001, and December 31, 2002, at the NCPNN participating centers. The questionnaires included items that cover parental sociodemographic characteristics and maternal and newborn health characteristics. Sources of data included direct interviews with mothers after delivery and before hospital discharge and reviews of obstetric and nursery medical charts. Chi-square tests and t tests were performed for categorical and continuous clinical predictors of cesarean section. Logistic regression was performed to determine the odds of having a cesarean section for the study hospitals when compared with the control hospital. Odds ratios and 95% confidence intervals are reported. Results: Variables in the study hospitals that correlated with a higher cesarean delivery rate were male obstetricians, day of the week, and mode of payment compared with the control hospital. Conclusions: In a country with a high cesarean section rate, 1 hospital met World Health Organization criteria for acceptable cesarean section rates, with no compromise in neonatal outcome. Further studies are needed to investigate potential policies to decrease the high cesarean section rate.
MeSH term(s)	Adult ; Cesarean Section/statistics & numerical data ; Chi-Square Distribution ; Confidence Intervals ; Female ; Hospitals, Urban ; Humans ; Infant, Newborn ; Labor, Induced/statistics & numerical data ; Lebanon/epidemiology ; Logistic Models ; Medical Records/statistics & numerical data ; Odds Ratio ; Parity ; Pregnancy ; Pregnancy Outcome/epidemiology ; Socioeconomic Factors ; Surveys and Questionnaires
Language	English
Publishing date	2007-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	604869-9
ISSN	0730-7659
ISSN	0730-7659
DOI	10.1111/j.1523-536X.2006.00141.x
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