bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization patterns for oral oncology medications in a specialty pharmacy cycle management program
Authors: Deutsch Sarah , Koerner Pamela , Miller Richard T , Craft Zoie , Fancher Karen 
Published: October 2014

Background The cycle management program (CMP) was implemented in 2008 at a national specialty pharmacy with a focus on providing specialized counseling and monitoring for patients on select oral oncology medications. The program now includes nine medications: bexarotene, dasatinib, erlotinib, everolimus, nilotinib, pazopanib, sorafenib, sunitinib, and vorinostat. Patients receive frequent assessments to encourage adherence, identify adverse events, and track discontinuations through a pharmacist outreach at the initiation of therapy, day 10 and 20 of the first month, then monthly thereafter. The use of oral agents is increasing in cancer patients, shifting away from regimens exclusively involving intravenous chemotherapy. This offers advantages for patients in terms of convenience, but introduces risk as patients become more responsible for the administration and monitoring of the medications. Purpose To evaluate utilization patterns of the oral oncology medications in the CMP including adverse event occurrence, medication discontinuations, and adherence markers. Methods This study is a retrospective review of patient-reported data from the CMP assessments completed in 2013. Data collected include adverse events and grades, adherence markers, and discontinuation rates. A total of 1163 assessments were reviewed from 557 patients. The assessments included in the analysis were the initial assessment, 10-day assessment, 20-day assessment, and the first monthly follow-up assessment, which encompasses the first two months of therapy. Results A total of 1453 adverse events were reported. Adverse events were cited as the reason for 39% of discontinuations and 28% of missed/held doses. A total of 101 discontinuations were reported across the nine CMP medications based on the first two months of data. Missed or held doses were reported in 130 assessments. Conclusions Patient engagement and pharmacist interventions, through programs such as the CMP, are important to help patients manage these complex, high-risk medications.
The impact of Indonesian generic medicine pricing policy on medicine prices
Authors: Anggriani Yusi , Ibrahim Mohamed Izham M , Suryawati Sri , Shafie Asrul A 
Published: October 2014

Introduction: The government of Indonesia has established a commitment to the provision of affordable medicines. The retail price of unbranded generic cannot exceed the maximum retail price set by the Ministry of Health. The generic medicine pricing policy that has been implemented by the Indonesian government must be evaluated. Objectives: To evaluate the impact of the generic medicine pricing policy on the price of selected medicines and to measure the differences between the prices paid by patients for unbranded generic medicines and the maximum retail price. Method: The study design was a cross-sectional survey and policy evaluation. Medicine prices were measured in 2010 at nine public hospitals, 64 private pharmacies, and nine non-governmental organisation hospitals in four provinces in Indonesia. The price of the lowest price generic (LPG) and innovator brand (IB) medicines in 2010 was compared to the price of the medicines before policy implementation. The results from a 2004 survey conducted by the Indonesian National Health Research Institute and Health Action International were used as the baseline data for the comparison. The price of unbranded generic medicine paid by patients was compared to the price in the generic medicine pricing policy 2010 edition. Results: The results indicated that the price of LPG and IB medicines was lower in 2010 than in 2004. The decline was approximately 40% to 2200%. Wide variations were observed in the excess of the unbranded generic medicine price paid by patients compared with the maximum retail price from the Ministry of Health, exceeding the maximum price by approximately 2% to 600%. Conclusion: Generic medicine pricing policies have succeeded in lowering the price of unbranded generic medicines. The price of IB medicines has declined but remains high compared to the international reference price. The prices paid by patients for unbranded generic medicines are more expensive than the maximum prices in the policy.
Impact of Poor Retention in HIV Medical Care on Hepatitis B Vaccination
Authors: Franco Ricardo A. , Tamhane Ashutosh , Overton Edgar Turner 
Published: October 2014

Background: We identified factors associated with complete hepatitis B vaccination of patients with HIV. Methods: Retrospective analysis of patients undergoing HIV clinic orientation from 2000 to 2010. Vaccine-eligible patients had negative hepatitis B serologies at baseline. Receipt of at least 3 doses was defined as complete vaccination. Results: Of 1242 patients, 519 (42%) were completely vaccinated. Complete vaccination was positively associated with missing ≤25% of the visits during the first year of care (adjusted odds ratio [aOR] = 2.35, 95% confidence interval [CI]: 1.79-3.09), being naive to care (aOR = 1.50, 95% CI: 1.13-1.99), and living at the clinic’s county (aOR = 1.33, 95% CI: 1.02-1.75). Complete vaccination was negatively associated with failure to remain in care >2 years (aOR = 0.18, 95% CI: 0.13-0.24), history of intravenous drug use (aOR = 0.48, 95% CI: 0.27-0.87), and baseline CD4 count <200 cells/mm3 (aOR = 0.69, 95% CI: 0.53-0.92). Conclusion: Poor retention in HIV care is strongly associated with suboptimal hepatitis B vaccination.
Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome
Authors: Ripoll Vera M. , Lambrianides Anastasia , Pierangeli Silvia S. , Poulton Katie , Ioannou Yiannis , Heywood Wendy E. , Mills Kevin , Latchman David S. , Isenberg David A. , Rahman Anisur , Giles Ian P. 
Published: October 2014

Key Points
Comprehensive proteomics analysis in human monocytes exposed to APS-IgG has identified and characterized several novel proteins. These proteins have functional relevance to the APS.
A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL
Authors: Woyach Jennifer A. , Awan Farrukh , Flinn Ian W. , Berdeja Jesus G. , Wiley Elizabeth , Mansoor Sharmeen , Huang Ying , Lozanski Gerard , Foster Paul A. , Byrd John C. 
Published: October 2014

Key PointsXmAb5574 is an Fc-engineered CD19 monoclonal antibody that is well tolerated as a single agent in patients with relapsed or refractory CLL. XmAb5574 has preliminary efficacy as a single agent in CLL and is of interest for further study in this disease.
Extraction and characterization of keratin from bovine hoof: A potential material for biomedical applications
Authors: Kakkar Prachi , Madhan Balaraman , Shanmugam Ganesh 
Published: October 2014

Abstract
Keratin from the hoof is a less explored source for making valuable products. In this paper we present the extraction of pure keratin from bovine hooves and characterized them to better address the possible exploitation of this bio-resource as an alternative material for tissue engineering applications. The keratin protein from the pulverized hooves was extracted by reduction, which was observed to be pure, and two polypeptide chains of molecular weight in the range of 45–50 and 55–60 KDa were determined using SDS-PAGE assay. FTIR analysis complementing circular dichroism (CD) data, established that hoof keratin predominantly adopted α-helical conformation with admixture of β-sheet. The keratin was shown to have appreciably high denaturation temperature (215°C) as indicated by differential scanning calorimetric (DSC) analysis. Thermogravimetric analysis (TGA) also showed the retention of 50% of the original weight of the sample even at a temperature of 346°C. The keratin from the hoof had been observed to be biocompatible when analyzed with MTT assay using fibroblast cells, showing more than 90% cell viability. Hence, hoof keratin would be useful for high value biomedical applications.
Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study
Authors: Mauri Tommaso , Coppadoro Andrea , Bombino Michela , Bellani Giacomo , Zambelli Vanessa , Fornari Carla , Berra Lorenzo , Bittner Edward A , Schmidt Ulrich , Sironi Marina , Bottazzi Barbara , Brambilla Paolo , Mantovani Alberto , Pesenti Antonio 
Published: October 2014

Abstract
Introduction
Timely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute-phase mediator produced by various cell types in the lungs. Animal studies have shown that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbial clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The aim of the present study was to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia.

Methods
We recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy, and Massachusetts General Hospital, Boston, MA, USA) undergoing bronchoalveolar lavage (BAL) as per clinical decision. We collected BAL fluid and plasma samples, together with relevant clinical and microbiological data. We assayed PTX3 and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in BAL fluid and PTX3, sTREM-1, C-reactive protein (CRP) and procalcitonin (PCT) in plasma. Two blinded independent physicians reviewed patient data to confirm pneumonia. We determined the PTX3 threshold in BAL fluid for pneumonia and compared it to other biomarkers.

Results
Microbiologically confirmed pneumonia of bacterial (n =12), viral (n =4) or fungal (n =8) etiology was diagnosed in 24 patients (29%). PTX3 levels in BAL fluid predicted pneumonia with an area under the receiving operator curve of 0.815 (95% CI =0.710 to 0.921, P <0.0001), whereas none of the other biomarkers were effective. In particular, PTX3 levels ≥1 ng/ml in BAL fluid predicted pneumonia in univariate analysis (β =2.784, SE =0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index PTX3 values ≥1 ng/ml in BAL fluid for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 patients who fulfilled the clinical criteria for the diagnosis of pneumonia at BAL fluid sampling, the diagnostic accuracy of PTX levels was confirmed in univariate and ROC curve analysis.

Conclusions
In this hypothesis-generating convenience sample, a PTX3 level ≥1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients.
Early activation of pro-fibrotic WNT5A in sepsis-induced acute lung injury
Authors: Villar Jesús , Cabrera-Benítez Nuria E , Ramos-Nuez Angela , Flores Carlos , García-Hernández Sonia , Valladares Francisco , López-Aguilar Josefina , Blanch Lluís , Slutsky Arthur S 
Published: October 2014

Abstract
Introduction
The mechanisms of lung repair and fibrosis in the acute respiratory distress syndrome (ARDS) are poorly known. Since the role of WNT/β-catenin signaling appears to be central to lung healing and fibrosis, we hypothesized that this pathway is activated very early in the lungs after sepsis.

Methods
We tested our hypothesis using a three-step experimental design: (1) in vitro lung cell injury model with human bronchial epithelial BEAS-2B and lung fibroblasts (MRC-5) cells exposed to endotoxin for 18 hours; (2) an animal model of sepsis-induced ARDS induced by cecal ligation and perforation, and (3) lung biopsies from patients who died within the first 24 hours of septic ARDS. We examined changes in protein levels of target genes involved in the Wnt pathway, including WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, matrix metalloproteinase-7 (MMP7), cyclin D1, and vascular endothelial growth factor (VEGF) by Western blotting and immunohistochemistry. Finally, we validated the main gene targets of this pathway in experimental animals and human lungs.

Results
Protein levels of WNT5A, non-phospho (Ser33/37/Thr41) β-catenin, total β-catenin, MMP7, cyclin D1, and VEGF increased after endotoxin stimulation in BEAS-2B and MRC-5 cells. Lungs from septic animals and from septic humans demonstrated acute lung inflammation, collagen deposition, and marked increase of WNT5A and MMP7 protein levels.

Conclusions
Our findings suggest that the WNT/β-catenin signaling pathway is activated very early in sepsis-induced ARDS and could play an important role in lung repair and fibrosis. Modulation of this pathway might represent a potential target for treatment for septic and ARDS patients.
Structural changes of hip osteoarthritis using magnetic resonance imaging
Authors: Teichtahl Andrew J , Wang Yuanyuan , Smith Sam , Wluka Anita E , Giles Graham G , Bennell Kim L , O’Sullivan Richard , Cicuttini Flavia M 
Published: October 2014

Abstract
Introduction
Few data are available concerning structural changes at the hip observed by magnetic resonance imaging (MRI) in people with or without hip osteoarthritis (OA). The aim of this study was to compare cartilage volume and the presence of cartilage defects and bone marrow lesions (BMLs) in participants with and without diagnosed hip OA.

Methods
Femoral head cartilage volume was measured by MRI for 141 community-based persons with no diagnosed hip OA, and 19 with diagnosed hip OA. Cartilage defects and BMLs were regionally scored at the femoral head and acetabulum.

Results
Compared with those without diagnosed hip OA, people with diagnosed hip OA had less femoral head cartilage volume (1763 mm3 versus 3343 mm3; p <0.001) and more prevalent cartilage defects and BMLs (all p ≤0.05) at all sites other than the central inferomedial region of the femoral head. In those with no diagnosed hip OA, cartilage defects in the anterior and central superolateral region of the femoral head were associated with reduced femoral head cartilage volume (all p ≤0.02). Central superolateral BMLs at all sites were associated with reduced femoral head cartilage volume (all p ≤0.003), with a similar trend occurring when BMLs were located in the anterior region of the hip (all p ≤0.08).

Conclusions
Compared with community-based adults with no diagnosed hip OA, people with diagnosed hip OA have less femoral head cartilage volume and a higher prevalence of cartilage defects and BMLs. For people with no diagnosed hip OA, femoral head cartilage volume was reduced where cartilage defects and/or BMLs were present in the anterior and central superolateral regions of the hip joint. Cartilage defects and BMLs present in the anterior and central superolateral regions may represent early structural damage in the pathogenesis of hip OA.
Canadian Organ Replacement Register (CORR): Reflecting the Past and Embracing the Future
Authors: Moist Louise M , Fenton Stanley , Kim Joseph S , Gill John S , Ivis Frank , de Sa Eric , Wu Juliana , Al-Jaishi Ahmed A , Sood Manish M , Klarenbach Scott , Hemmelgarn Brenda R , Kappel Joanne E 
Published: October 2014

Introduction: The Canadian Organ Replacement Register (CORR) is the only Canadian information system on kidney and extra-kidney organ failure and transplantation in Canada. CORR's mandate is to record and analyze the level of activity and outcomes of vital organ transplantation and treatment of end stage kidney disease using dialysis, either hemodialysis or peritoneal dialysis, activities across Canada. The Canadian Organ Replacement Register was officially launched in 1987, and it included transplantation of extra-renal vital organs (liver, heart, lung, pancreas, bowel), in addition to renal transplantation and replacement therapy, with new financial support from the provinces. Objective: This manuscript describes the process of data acquisition and reporting, focusing on the patients with end stage kidney disease on dialysis, with data reported from the 2014 CORR Annual Data Report and the Center-Specific Reports on Clinical Measures. Methods: CORR is currently housed in the Canadian Institute for Health Information and collects data from hospital dialysis programs, regional transplant programs, organ procurement organizations and kidney dialysis services offered at independent health facilities. Data on patients is collected by completion of survey forms for each patient at the start of dialysis or receiving a transplant, using the Initial Registration form, and yearly follow up forms, which collects data on the status of the patient as of October 31st. Results: The incident rate per million population (RPMP) has remained stable with the exception of the 65+ age group with has experience a modest decrease since 2001. However, there has been an increasing prevalence of ESKD diagnoses, with the highest rate per million population (RPMP) amongst the age group 65+ years. This is likely attributed to gradual improving patient survival. Between 2003 and 2012, nearly 90% of dialysis patients younger than < 18 and 26% of patients 75+ years survived for at least five years. Conclusion: As the number of people treated for end-stage organ failure grows, so does the importance of understanding their treatment and outcomes. In 2014, CORR continues to evolve and support the important information need to advance ESRD research and clinical practice.
Genetic Predisposition to Papillary Thyroid Carcinoma: Involvement of FOXE1, TSHR, and a Novel lincRNA Gene, PTCSC2
Authors: He Huiling , Li Wei , Liyanarachchi Sandya , Jendrzejewski Jaroslaw , Srinivas Mukund , Davuluri Ramana V. , Nagy Rebecca , de la Chapelle Albert 
Published: October 2014

Abstract

Context:
By genome-wide association studies, the risk allele [A] of SNP rs965513 predisposes strongly to papillary thyroid carcinoma (PTC). It is located in a gene-poor region of 9q22, some 60 kb from the FOXE1 gene. The underlying mechanisms remain to be discovered.

Objective:
Our objective was to identify novel transcripts in the 9q22 locus and correlate gene expression levels with the genotypes of rs965513.

Design:
We performed 3′ and 5′ rapid amplification of cDNA ends and RT-PCR to detect novel transcripts. One novel transcript was forcibly expressed in a cell line followed by gene expression array analysis. We genotyped rs965513 from PTC patients and measured gene expression levels by real-time RT-PCR in unaffected thyroid tissue and matched tumor.

Setting:
This was a laboratory-based study using cells from clinical tissue samples and a cancer cell line.

Main Outcome Measures:
We detected previously uncharacterized transcripts and evaluated the gene expression levels and the correlation with the risk allele of rs965513, age, gender, chronic lymphocyte thyroiditis (CLT), and TSH levels.

Results:
We found a novel long intergenic noncoding RNA gene and named it papillary thyroid cancer susceptibility candidate 2 (PTCSC2). Transcripts of PTCSC2 are down-regulated in PTC tumors. The risk allele [A] of rs965513 was significantly associated with low expression of unspliced PTCSC2, FOXE1, and TSHR in unaffected thyroid tissue. We also observed a significant association of age and CLT with PTCSC2 unspliced transcript levels. The correlation between the rs965513 genotype and the PTCSC2 unspliced transcript levels remained significant after adjusting for age, gender, and CLT. Forced expression of PTCSC2 in the BCPAP cell line affected the expression of a subset of noncoding and coding transcripts with enrichment of genes functionally involved in cell cycle and cancer.

Conclusions:
Our data suggest a role for PTCSC2, FOXE1, and TSHR in the predisposition to PTC.
MAP1S controls microtubule stability throughout the cell cycle in human cells
Authors: Tegha-Dunghu Justus , Bausch Elena , Neumann Beate , Wuensche Annelie , Walter Thomas , Ellenberg Jan , Gruss Oliver J. 
Published: October 2014

Understanding the molecular basis for proper cell division requires a detailed functional analysis of microtubule (MT) associated proteins. MT associated protein 1S (MAP1S), the most ubiquitously expressed MAP1 family member, is required for accurate cell division.
Using quantitative analysis of MT plus end tracking we show here that MAP1S knockdown alters MT dynamics throughout the cell cycle. Surprisingly, MAP1S downregulation results in faster growing, yet short-lived MT in all cell cycle stages and a global loss of MT acetylation. These aberrations correlate with severe defects in the final stages of cell division. In monopolar cytokinesis assays, we demonstrate that MAP1S guides MT dependent initiation of cytokinesis. Our data underline the key role of MAP1S as a global regulator of MT stability and demonstrate a novel primary function of MAP1S to regulate MT dynamics at cytokinesis onset.
eGEMs’ Early Adventures in Open Access Publishing
Authors: Holve Erin 
Published: October 2014

Introduction: In January 2013 AcademyHealth officially launched eGEMs (Generating
Evidence and Methods to improve patient outcomes) to rapidly disseminate peer-reviewed
approaches using electronic health data (EHD) to advance research and quality
improvement (QI), with the overall goal of improving patient and community outcomes.
Instigated by the publication of eGEMs 50th paper, Dr. Erin Holve, eGEMs editor-in-chief
reviews the EDM Forum’s early experiences with open access publishing.eGEMs to Date: As
of the end of September 2014 eGEMs has published 59 manuscripts and received nearly 150
submissions. These early findings demonstrate eGEMs is filling a need for dissemination
outlets that bridge the gap between the health research and practice communities.
Published papers are distributed across the EDM Forum’s four thematic domains:
governance (n=5), informatics (n=14), methods (n=13) and learning health systems (n=27).
While system design issues are a consistent theme, papers addressing priority health
topics such as diabetes, asthma, and obesity are frequently submitted. Authors include
more than two hundred experts in the field representing nearly all of the EDM Forum’s
core stakeholder groups: research/QI, nonprofit/policy, healthcare delivery, government,
industry, and patients/consumers.What’s Next: With the help of our diverse
community, eGEMs will continue to expand its depth and reach. Forthcoming special issues
on community-level transformation using Health IT, and ways to improve user-experience
and system design will add to the journal’s robust portfolio of work identifying and
addressing shared challenges using EHD. The EDM Forum, working closely with our partners
at the Agency for Healthcare Research and Quality, will work diligently to
ensure eGEMs is accelerating the pace at which the community translates and disseminates
key lessons, with the ultimate goal of helping transform knowledge into actions that can
improve health and health care.