bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estriol: emerging clinical benefits
Authors: Ali Emad S. , Mangold Cheyenne , Peiris Alan N. 
Published: April 2017

AbstractObjective:Estriol is the main estrogen in pregnancy, but has received less attention outside gestation. It is well known that pregnancy has an immunosuppressive effect on many autoimmune diseases such as multiple sclerosis, psoriasis, thyroiditis, uveitis, and rheumatoid arthritis. Emerging evidence indicates that estriol has potential immunomodulatory benefits for many disease states including autoimmune, inflammatory, and neurodegenerative conditions. In this review, we discuss emerging roles for estriol in the treatment of menopausal symptoms, osteoporosis, cancer, hyperlipidemia, vascular disease, and multiple sclerosis. Estriol appears to offer a potentially cost-effective approach to a variety of conditions and may offer a wide range of health benefits.Methods:We reviewed the English language MEDLINE literature with estriol in the title with emphasis on publications including nonpregnant females between January 1974 and August 2016. Approximately 393 such articles were considered and 72 articles have been referenced in this review.Results:Estriol offers considerable benefits for postmenopausal women with reduced risks that are normally associated with traditional hormone therapies. These benefits include improved control of menopausal symptoms and better urogenital health. Moreover, the immunomodulatory role of estriol in reducing proinflammatory cytokines may be an important new therapeutic option for chronic autoimmune and neurodegenerative illnesses. Since it is a relatively weak estrogen, there is potential for use in men for conditions such as multiple sclerosis.Conclusions:We conclude transvaginal estriol potentially offers a suitable physiologic delivery and cost-effective alternative to currently available estrogen regimens in selected patients. Additional studies on mode of delivery, safety, and efficacy merit further investigation.
Quantitative analysis of placebo response and factors associated with menopausal hot flashes
Authors: Li Lujin , Xu Ling , Wu Junyi , Dong Lidan , Lv Yinghua , Zheng Qingshan 
Published: April 2017

Abstract

Objective:
The aim of the study was to quantitatively analyze the placebo response and the factors associated with menopausal hot flashes.

Methods:
The PubMed and Cochrane Library databases were searched for placebo-controlled trials that reported the treatment of menopausal hot flashes, with a retrieval deadline of December 31, 2015. The clinical and demographic characteristics of participants and placebo responses, defined as the percentage of reduction in hot flashes at each observation time point compared with that of baseline values, were extracted from the studies. Model-based meta-analysis was used to describe the time course of placebo response and identify the related factors.

Results:
Eighty-five trials in 78 articles, involving 8,302 women, were included in the analysis. Of these, 47 trials were about hormonal drugs, 37 were about nonhormonal drugs, and 1 included both hormonal and nonhormonal drugs. Our results indicated that the placebo responses for hot flashes increased in a time-dependent manner and reached a plateau after week 12. Additionally, the placebo responses were significantly higher in the trials of hormonal drugs than in the trials of nonhormonal drugs at week 24 (−51.2% vs -40.4%; P < 0.05), and the difference between them was comparable with the effect of paroxetine.

Conclusions:
The placebo response for menopausal hot flashes was related to the active comparator; a higher response rate was observed in trials of hormonal drugs than in trials of nonhormonal drugs. These findings suggest that subjective expectations affect the treatment efficacy of menopausal hot flashes.
Intraoperative Optical Coherence Tomography-Assisted Descemet Stripping Automated Endothelial Keratoplasty for Anterior Chamber Fibrous Ingrowth
Authors: Shazly Tarek A. , To Lillian K. , Conner Ian P. , Espandar Ladan 
Published: April 2017

Purpose:
Here, we present the first reported case of intraoperative optical coherence tomography (OCT)-assisted Descemet membrane stripping automated endothelial keratoplasty (DSAEK) in a patient with anterior segment fibrous ingrowth.

Methods:
A 61-year-old woman with corneal edema and chronic angle-closure glaucoma secondary to fibrous ingrowth after 2 glaucoma shunt device implantations underwent dissection and removal of anterior chamber fibrous ingrowth and DSAEK. The surgical techniques using intraoperative OCT and outcome are described.

Results:
Intraoperative OCT provided a clear dissection plane of the fibrous membranes in the anterior chamber and view of their relation to the iris and corneal endothelium, despite an opacified cornea. The placement of the donor lenticule and absence of interface fluid were also verified intraoperatively. The postoperative course was uncomplicated with satisfactory outcome.

Conclusions:
We conclude that intraoperative OCT is a useful tool during DSAEK surgery, particularly in complicated cases such as anterior segment fibrous ingrowth and significant corneal edema.
Implications for Ophthalmic Formulations: Ocular Buffers Show Varied Cytotoxic Impact on Human Corneal–Limbal and Human Conjunctival Epithelial Cells
Authors: Schuerer Nadine , Stein Elisabeth , Inic-Kanada Aleksandra , Pucher Marion , Hohenadl Christine , Bintner Nora , Ghasemian Ehsan , Montanaro Jacqueline , Barisani-Asenbauer Talin 
Published: April 2017

Purpose:
To investigate toxicity associated with buffers commonly used in topical ocular drug formulations using a human corneal–limbal epithelial (HCLE) and a human conjunctival epithelial (HCjE) cell model.

Methods:
HCLE and HCjE cells were incubated for 10, 30, or 60 minutes with 4 different buffers based on borate, citrate, phosphate, and Tris-HCl at 10, 50, and 100 mM concentrations. To detect possible delayed effects on cell viability, after 60 minutes of buffer incubation, cells were further incubated for 24 hours with a cell medium. Cell viability was determined using a colorimetric XTT–based assay. The morphology of cells was also investigated.

Results:
HCjE cells showed more sensitivity to buffer incubation than HCLE cells. The 100 mM phosphate buffer displayed significant delayed effects on cell viability of HCLE 16.8 ± 4.8% and HCjE 39.2 ± 6.1% cells after 60 minutes of exposure (P < 0.05). HCjE cell viability was reduced after 60 minutes incubations with 50 and 100 mM citrate buffer to 42.8 ± 6.5% and 39.3 ± 7.9%, respectively, and even lower percentages at the delayed time point (both P < 0.05). HCLE cell morphology was distinctly altered by 100 mM phosphate and Tris buffers after 30 minutes, whereas HCjE cells already showed marked changes after 10 minutes of exposure to 100 mM citrate and phosphate buffers.

Conclusions:
We observed a time-dependent decrease of viability in both HCLE and HCjE cells exposed to higher buffer concentrations. Therefore, we propose further in vivo studies to translate these finding to humans to discern the real effects of the buffer concentration in eye drops on the ocular surface.
Characterization of Corneal Involvement in Eyes With Mucous Membrane Pemphigoid by In Vivo Confocal Microscopy
Authors: Tepelus Tudor C. , Huang Jianyan , Sadda SriniVas R. , Lee Olivia L. 
Published: April 2017

Purpose:
To describe the morphological features of the corneal epithelial layers, subbasal nerve plexus, stroma, and endothelium in patients with mucous membrane pemphigoid (MMP) as shown by in vivo confocal microscopy (IVCM).

Methods:
Central corneal images were captured from 10 healthy age-matched control eyes and 30 eyes with clinically diagnosed MMP by in vivo laser scanning confocal microscopy (HRT III RCM). Morphological changes of the corneal epithelial layers, stroma, and endothelium, characteristics of corneal nerves, and presence of inflammatory dendritic cells (DCs) were evaluated.

Results:
Images obtained by IVCM from 40 eyes were analyzed. The eyes with MMP were divided into 2 groups based on clinical staging: 16 eyes with end-stage MMP and 14 eyes with non–end-stage MMP. Compared with controls, IVCM in eyes with end-stage MMP displayed severe conjunctivalization and neovascularization of the cornea, with otherwise limited identifiable cellular or structural elements. Those with non–end-stage MMP showed metaplasia of the corneal epithelial layers, presence of hyperreflective cells similar to conjunctival cells, intraepithelial defects, fibrosis of anterior stroma, and hyperreflective endothelial deposits. Images of the subbasal nerve plexus demonstrate significant reduction in density (1251.3 ± 806.9 μm/frame vs. 2688.8 ± 607.33 μm/frame, P < 0.001), increased tortuosity (2.76 ± 0.6 vs. 2.3 ± 0.42, not significant), decreased reflectivity (2.73 ± 0.4 vs. 3.46 ± 0.52, P < 0.01), and increased density of DCs (115 ± 88 cells/mm2 vs. 43.9 ± 28.14 cells/mm2, P < 0.05) in MMP-affected eyes compared with controls.

Conclusions:
IVCM reveals profound and variable microstructural changes in the corneas of patients with MMP compared with normal controls. Our study demonstrated decreased corneal nerve density and elevated DC density in eyes with non–end-stage MMP compared with normal controls. Frequent scarring, conjunctivalization, and neovascularization observed in eyes with end-stage MMP preclude recognition by IVCM of the morphologic architecture of the corneal layers. Our findings suggest implications for using IVCM to evaluate and monitor patients with MMP.
Long-term Visual and Ocular Sequelae in Patients With Congenital Cytomegalovirus Infection
Authors: Jin Haoxing Douglas , Demmler-Harrison Gail J. , Coats David K. , Paysse Evelyn A. , Bhatt Amit , Edmond Jane C. , Yen Kimberly G. , Steinkuller Paul , Miller Jerry 
Published: April 2017

Background:
Cytomegalovirus (CMV) is the most common congenital viral infection in the United States. Visual and ocular sequelae in adolescents and adults who are congenitally infected with CMV have not been well studied. Better understanding of the long-term visual and ocular sequelae can help with early detection, intervention and appropriate educational accommodations.

Methods:
This study evaluated 237 patients (77 symptomatic, 109 asymptomatic and 51 control) who underwent a series of age-appropriate ophthalmologic, audiologic and neurodevelopmental examinations from 1982 to 2013. The frequency and etiology of visual impairment and other nonophthalmologic findings were recorded for each patient. Ophthalmologic findings were tabulated, and risk factors for abnormalities were analyzed.

Results:
Fourteen of the 77 (18.2%) symptomatic and none of the asymptomatic and control subjects had severe visual impairments (P ≤ 0.006). Moderate visual impairment did not differ between symptomatic and asymptomatic subjects. Three asymptomatic subjects had retinal scars. The most common visual or ocular sequelae in the symptomatic group were strabismus (23.4%), chorioretinal scars (19.5%), cortical visual impairment (14.3%), nystagmus (14.3%) and optic nerve atrophy (11.7%). Three symptomatic patients had delayed visual deterioration because of later occurring retinal disorders: peripheral retinal scar, rhegmatogenous retinal detachment and Coats’ disease.

Conclusion:
Symptomatic CMV patients experienced more ophthalmologic sequelae and significantly worse visual outcomes than asymptomatic CMV and control patients. Later occurring retinal disorders were found in symptomatic patients, and there is no clear evidence that CMV can reactivate in the retinas of children who were congenitally infected. Major risk factors for severe visual impairment included symptomatic status, optic nerve atrophy, chorioretinitis, cortical visual impairment and sensorineural hearing loss.
Staphylococcus aureus Central Nervous System Infections in Children
Authors: Vallejo Jesus G. , Cain Alexandra N. , Mason Edward O. , Kaplan Sheldon L. , Hultén Kristina G. 
Published: April 2017

Background:
Central nervous system (CNS) infections caused by Staphylococcus aureus are uncommon in pediatric patients. We review the epidemiology, clinical features and treatment in 68 patients with a S. aureus CNS infection evaluated at Texas Children’s Hospital.

Methods:
Cases of CNS infection in children with positive cerebrospinal fluid cultures or spinal epidural abscess (SEA) for S. aureus at Texas Children’s Hospital from 2001 to 2013 were reviewed.

Results:
Seventy cases of S. aureus CNS infection occurred in 68 patients. Forty-nine cases (70%) were secondary to a CNS device, 5 (7.1%) were postoperative meningitis, 9 (12.8%) were hematogenous meningitis and 7 (10%) were SEAs. Forty-seven (67.2%) were caused by methicillin-sensitive S. aureus (MSSA) and 23 (32.8%) by methicillin-resistant S. aureus (MRSA). Community-acquired infections were more often caused by MRSA that was clone USA300/pvl
+. Most patients were treated with nafcillin (MSSA) or vancomycin (MRSA) with or without rifampin. Among patients with MRSA infection, 50% had a serum vancomycin trough obtained with the median level being 10.6 μg/mL (range: 5.4–15.7 μg/mL). Only 1 death was associated with S. aureus infection.

Conclusions:
The epidemiology of invasive of S. aureus infections continues to evolve with MSSA accounting for most of the infections in this series. The majority of cases were associated with neurosurgical procedures; however, hematogenous S. aureus meningitis and SEA occurred as community-acquired infections in patients without predisposing factors. Patients with MRSA CNS infections had a favorable response to vancomycin, but the beneficial effect of combination therapy or targeting vancomycin trough concentrations of 15–20 μg/mL remains unclear.
Effect of Disease Definition on Perceived Burden of Acute Respiratory Infections in Children
Authors: Zoch Beate , Günther Annette , Karch André , Mikolajczyk Rafael 
Published: April 2017

Background:
Acute respiratory infections (ARIs) are among the most frequent childhood diseases in Western countries. Assessment of ARI episodes for research purposes is usually based on parent-administered retrospective questionnaires or prospective symptom diaries. The aim of our analysis was to compare the effect of ARI definitions on the corresponding disease burden in a prospective cohort study using symptom diaries.

Methods:
A literature search was performed to identify definitions of ARI used in research studies. The definitions were applied to a symptom diary dataset from a cohort study of 1–3-year-old children conducted in the winter season 2013/2014. We compared the total number of ARI episodes, the total number of days with ARI and the median and mean duration of ARI episodes resulting from the use of the different definitions.

Results:
Six ARI definitions were identified in the literature. Depending on ARI definition, the total number of ARI episodes and the total number of days with ARI in our dataset varied by a factor of 1.69 and 1.53, respectively, between the lowest and the highest. The median duration of the episodes ranged from 7 to 10 days.

Discussion:
Different definitions led to considerable differences in the number and duration of ARI episodes, making direct comparisons of studies with different methods questionable. We propose the use of a standardized ARI definition in upcoming cohort studies working with diary data. This process could be conducted using a Delphi survey with experts in this study field.
No small matter: pediatric resuscitation
Authors: McCormick Taylor , McVaney Kevin , Pepe Paul E. 
Published: April 2017

Purpose of review
To present advancements in pediatric cardiac arrest research, highlighting articles most relevant to clinical practice published since the latest international guidelines for cardiopulmonary resuscitation (CPR).

Recent findings
Clinical trials examining targeted temperature management in children support avoidance of hyperthermia for both pediatric in-hospital cardiac arrest (PIHCA) and out-of-hospital cardiac arrest (POHCA), but no statistically significant outcome differences were confirmed comparing 33 and 36 °C in the limited populations studied. Retrospective analyses of population-based POHCA registries revealed several associations: both bystander CPR and public-access defibrillation were associated with improved POHCA outcomes; conflicting results overshadow the benefits of conventional versus compression-only CPR; extracorporeal CPR was associated with improved PIHCA outcomes regardless of cause; intubation in PIHCA was associated with decreased survival, whereas there were no significant differences in outcomes between advanced airway management and bag-valve-mask ventilation in POHCA; and early epinephrine delivery in nonshockable rhythms during PIHCA was associated with improved outcomes. Length, age, and weight-based dosing systems can reduce time to medication delivery, quantitative errors, and anxiety among care providers.

Summary
Mounting evidence continues to align management priorities for resuscitation of children and adults.
The past, present, and future of ventilation during cardiopulmonary resuscitation
Authors: Chang Mary P. , Idris Ahamed H. 
Published: April 2017

Purpose of review
To evaluate the past and present literature on ventilation during out of hospital cardiac arrest, highlighting research that has informed current guidelines.

Recent findings
Previous studies have studied what are optimal compression-to-ventilation ratios, ventilation rates, and methods of ventilation. Continuous chest compression cardiopulmonary resuscitation (CPR) has not shown to provide a significant survival benefit over the traditional 30 : 2 CPR. The optimal ventilation rate is recommended at 8 to 10 breaths per minute. Methods such as capnography and thoracic impedance are being used to evaluate ventilation in research studies.

Summary
Future out of hospital cardiac arrest studies are still exploring how to optimize the delivery of ventilation during the initial stages of resuscitation. More prospective studies focusing on ventilation are needed to inform guidelines.
Can Vertical Integration Reduce Hospital Readmissions? A Difference-in-Differences Approach
Authors: Lopes Sílvia , Fernandes Óscar B. , Marques Ana Patrícia , Moita Bruno , Sarmento João , Santana Rui 
Published: April 2017

Background:
Vertical integration is expected to improve communication and coordination between inpatient care and care after discharge. Despite being used across health systems worldwide, evidence about its impact on readmissions is sparse and contradictory.

Objective:
To assess the impact of vertical integration on hospital readmissions.

Research Design, Subjects, and Measures:
Using difference-in-differences we compared readmissions before and after vertical integration in 6 Portuguese hospitals for years 2004–2013. A control group with 6 similar hospitals not integrated was utilized. Considered outcome was 30-day unplanned readmission. We used logistic regression at the admission level and accounted for patients’ risk factors using claims data. Analyses for each hospital and selected conditions were also run.

Results:
Our results suggest that readmissions decreased overall after vertical integration [odds ratio (OR)=0.900; 95% confidence interval (CI), 0.812–0.997]. Hospital analysis indicated that there was no impact for 2 hospitals (OR=0.960; 95% CI, 0.848–1.087 and OR=0.944; 95% CI, 0.857–1.038), and a positive effect in 4 hospitals (greatest effect: OR=0.811; 95% CI, 0.736–0.894). A positive evolution was observed for a limited number of conditions, with better results for diabetes with complications (OR=0.689; 95% CI, 0.525–0.904), but no impact regarding congestive heart failure (OR=1.067; 95% CI, 0.827–1.377).

Conclusions:
Merging acute and primary care providers was associated with reduced readmissions, even though improvements were not found for all institutions or condition-specific groups. There are still challenges to be addressed regarding the success of vertical integration in reducing 30-day hospital readmissions.
New insights into redox homeostasis as a therapeutic target in B-cell malignancies
Authors: Graczyk-Jarzynka Agnieszka , Zagozdzon Radoslaw , Muchowicz Angelika , Siernicka Marta , Juszczynski Przemyslaw , Firczuk Malgorzata 
Published: April 2017

Purpose of review
The goal of this review is to summarize recent advances in our understanding of the regulation of redox homeostasis and the subtype-specific role of antioxidant enzymes in B-cell-derived malignancies. Furthermore, it presents selected prooxidative therapeutic strategies against B-cell neoplasms.

Recent findings
Recent reports have shown that the disturbed redox homeostasis in B-cell malignancies is regulated by cancer-specific signaling pathways and therefore varies between the individual subtypes. For instance, in a subtype of diffuse large B-cell lymphoma with increased oxidative phosphorylation, elevated reactive oxygen species are accompanied by higher levels of thioredoxin and glutathione and inhibition of either of these systems is selectively toxic to this subtype. In addition, growing number of small molecule inhibitors targeting antioxidant enzymes, such as auranofin, SK053, adenanthin, or decreasing glutathione level, such as imexon, buthionine sulfoximine, and L-cysteinase, trigger specific cytotoxic effects against B-cell malignancies. Lastly, attention is drawn to recent reports of effective treatment modalities involving prooxidative agents and interfering with redox homeostasis provided by stromal cells.

Summary
Recent findings reveal important differences in redox homeostasis within the distinct subsets of B-cell-derived malignancies that can be therapeutically exploited to improve existing treatment and to overcome drug resistance.
National Study of Off‐label Proton Pump Inhibitor Use Among New Zealand Infants in the First Year of Life (2005–2012)
Authors: Blank Mei‐Ling , Parkin Lianne 
Published: April 2017

AbstractObjectives:Off‐label prescribing of proton pump inhibitors (PPIs) to infants to treat symptoms attributed to gastroesophageal reflux disease (GERD) is widely reported, despite evidence that PPIs are no more effective than placebo in relieving those symptoms. To initiate discussion about appropriate prescribing of these drugs for infants, we describe the characteristics of PPI use among infants in New Zealand.Methods:In this population‐based study we used routinely collected dispensing data to identify all children born between 2005 and 2012 who were dispensed a government‐subsidized PPI (omeprazole, lansoprazole, pantoprazole) before their first birthday. Unique patient identifiers were used to link administrative datasets containing patient‐level demographic, dispensing, and health information.Results:In total, 22,643 children were dispensed a study PPI before their first birthday. The prevalence of infant PPI use as a proportion of all live births increased from 2.4% for children born in 2005 to 5.2% for children born in 2012. Overall, 71.6% of infants were dispensed a PPI by 3 months of age, and 8.7% received a PPI within the first month of life. Before PPI initiation, only 7.0% of infants had a hospital‐based diagnosis of GERD (with or without esophagitis), and 4.7% of infants had a hospital‐based diagnosis of one or more known or suspected GERD risk factors.Conclusions:Off‐label prescribing of PPIs to New Zealand infants was relatively common and increased over the study period. The appropriateness of PPI treatment should be questioned, as the majority of infants who received these drugs were not diagnosed with severe GERD.