bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial
Authors: Donnino Michael W. , Mortensen Sharri J. , Andersen Lars W. , Chase Maureen , Berg Katherine M. , Balkema Julia , Radhakrishnan Jeejabai , Gazmuri Raúl J. , Liu Xiaowen , Cocchi Michael N. 
Published: June 2015

Abstract
Introduction
We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function.

Methods
We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age ≥18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models.

Results
We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 ± 16 years and 47 % were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes.

Conclusions
In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population.

Trial registration
Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013.
Breaking Bad News in Oncology: A Metasynthesis
Authors: Bousquet Guilhem , Orri Massimiliano , Winterman Sabine , Brugière Charlotte , Verneuil Laurence , Revah-Levy Anne 
Published: June 2015

Purpose The delivery of bad news by oncologists to their patients is a key moment in the physician-patient relationship. We performed a systematic review of qualitative studies (a metasynthesis) that focused on the experiences and points of view of oncologists about breaking bad news to patients. Methods We searched international publications to identify relevant qualitative research exploring oncologists' perspectives about this topic. Thematic analysis, which compensates for the potential lack of generalizability of the primary studies by their conjoint interpretation, was used to identify key themes and synthesize them. NVivo qualitative analysis software was used. Results We identified 40 articles (> 600 oncologists) from 12 countries and assessed their quality as good according to the Critical Appraisal Skills Programme (CASP). Two main themes emerged: the patient-oncologist encounter during the breaking of bad news, comprising essential aspects of the communication, including the process of dealing with emotions; and external factors shaping the patient-oncologist encounter, composed of factors that influence the announcement beyond the physician-patient relationship: the family, systemic and institutional factors, and cultural factors. Conclusion Breaking bad news is a balancing act that requires oncologists to adapt continually to different factors: their individual relationships with the patient, the patient's family, the institutional and systemic environment, and the cultural milieu. Extending the development of the ability to personalize and adapt therapeutic treatment to this realm of communications would be a major step forward from the stereotyped way that oncologists are currently trained in communication skills.
Pemetrexed Plus Cisplatin Versus Gemcitabine Plus Cisplatin According to Thymidylate Synthase Expression in Nonsquamous Non–Small-Cell Lung Cancer: A Biomarker-Stratified Randomized Phase II Trial
Authors: Sun Jong-Mu , Ahn Jin Seok , Jung Sin-Ho , Sun Jiyu , Ha Sang Yun , Han Joungho , Park Keunchil , Ahn Myung-Ju 
Published: June 2015

Purpose We investigated whether thymidylate synthase (TS) expression is a predictive marker for the clinical outcome of pemetrexed/cisplatin in patients with nonsquamous non–small-cell lung cancer. Patients and Methods Eligible patients were tested for TS expression by immunohistochemistry and stratified into either a TS-negative or a TS-positive group. After stratification, patients in each group were randomly assigned (1:1 ratio) to receive either pemetrexed/cisplatin or gemcitabine/cisplatin for a maximum of six cycles until disease progression. The primary end point was evaluation of the interaction between TS groups and treatment allocation for objective response rate. Results Of 321 enrolled patients with nonsquamous non–small-cell lung cancer, 315 received at least one dose of study chemotherapy and were analyzed. By investigator assessment, response rates were 47% for the pemetrexed/cisplatin arm and 21% for the gemcitabine/cisplatin arm in the TS-negative group and 40% and 39%, respectively, for the TS-positive group (interaction P = .0084). By independent reviewers, response rates of pemetrexed/cisplatin and gemcitabine/cisplatin were 39% and 21%, respectively, in the TS-negative group and 40% and 48% in the TS-positive group (interaction P = .0077). The median progression-free survival times for the pemetrexed/cisplatin and the gemcitabine/cisplatin arms were 6.4 and 5.5 months, respectively, in the TS-negative group and 5.9 and 5.3 months in the TS-positive group (interaction P = .07). Conclusion With regard to response rate and progression-free survival, pemetrexed/cisplatin was superior to gemcitabine/cisplatin in the TS-negative group but not in the TS-positive group, indicative of TS expression as a potential predictive marker. Additional prospective studies involving larger cohorts are warranted to confirm the predictive role of TS expression.
Clinical Utility of Patient-Derived Xenografts to Determine Biomarkers of Prognosis and Map Resistance Pathways in EGFR-Mutant Lung Adenocarcinoma
Authors: Stewart Erin L. , Mascaux Celine , Pham Nhu-An , Sakashita Shingo , Sykes Jenna , Kim Lucia , Yanagawa Naoki , Allo Ghassan , Ishizawa Kota , Wang Dennis , Zhu Chang-Qi , Li Ming , Ng Christine , Liu Ni , Pintilie Melania , Martin Petra , John Tom , Jurisica Igor , Leighl Natasha B. , Neel Benjamin G. , Waddell Thomas K. , Shepherd Frances A. , Liu Geoffrey , Tsao Ming-Sound 
Published: June 2015

Purpose Although epidermal growth factor receptor (EGFR) –mutated adenocarcinomas initially have high response rates to EGFR tyrosine kinase inhibitors (TKIs), most patients eventually develop resistance. Patient-derived xenografts (PDXs) are considered preferred preclinical models to study the biology of patient tumors. EGFR-mutant PDX models may be valuable tools to study the biology of these tumors and to elucidate mechanisms of resistance to EGFR-targeted therapies. Methods Surgically resected early-stage non–small-cell lung carcinoma (NSCLC) tumors were implanted into nonobese diabetic severe combined immune deficient (NOD-SCID) mice. EGFR TKI treatment was initiated at tumor volumes of 150 μL. Gene expression analysis was performed using a microarray platform. Results Of 33 lung adenocarcinomas with EGFR activating mutations, only 6 (18%) engrafted and could be propagated beyond passage one. Engraftment was associated with upregulation of genes involved in mitotic checkpoint and cell proliferation. A differentially expressed gene set between engrafting and nonengrafting patients could identify patients harboring EGFR-mutant tumor with significantly different prognoses in The Cancer Genome Atlas Lung Adenocarcinoma datasets. The PDXs included models with variable sensitivity to first- and second-generation EGFR TKIs and the monoclonal antibody cetuximab. All EGFR-mutant NSCLC PDXs studied closely recapitulated their corresponding patient tumor phenotype and clinical course, including response pattern to EGFR TKIs. Conclusion PDX models closely recapitulate primary tumor biology and clinical outcome. They may serve as important laboratory models to investigate mechanisms of resistance to targeted therapies, and for preclinical testing of novel treatment strategies.
Accountable Care Organizations: The National Landscape
Authors: Shortell Stephen M. , Colla Carrie H. , Lewis Valerie A. , Fisher Elliott , Kessell Eric , Ramsay Patricia 
Published: June 2015

Abstract
There are now more than seven hundred accountable care organizations (ACOs) in the United States. This article describes some of their most salient characteristics including the number and types of contracts involved, organizational structures, the scope of services offered, care management capabilities, and the development of a three-category taxonomy that can be used to target technical assistance efforts and to examine performance. The current evidence on the performance of ACOs is reviewed. Since California has the largest number of ACOs (N=67) and a history of providing care under risk-bearing contracts, some additional assessments of quality and patient experience are made between California ACOs and non-ACO provider organizations. Six key issues likely to affect future ACO growth and development are discussed, and some potential “diagnostic” indicators for assessing the likelihood of potential antitrust violations are presented.
Integration of Substance Abuse Treatment Organizations into Accountable Care Organizations: Results from a National Survey
Authors: D'Aunno Thomas , Friedmann Peter D. , Chen Qixuan , Wilson Donna M. 
Published: June 2015

Abstract
To meet their aims of managing population health to improve the quality and cost of health care in the United States, accountable care organizations (ACOs) will need to focus on coordinating care for individuals with substance abuse disorders. The prevalence of these disorders is high, and these individuals often suffer from comorbid chronic medical and social conditions. This article examines the extent to which the nation's fourteen thousand specialty substance abuse treatment (SAT) organizations, which have a daily census of more than 1 million patients, are contracting with ACOs across the country; we also examine factors associated with SAT organization involvement with ACOs. We draw on data from a recent (2014) nationally representative survey of executive directors and clinical supervisors from 635 SAT organizations. Results show that only 15 percent of these organizations had signed contracts with ACOs. Results from multivariate analyses show that directors' perceptions of market competition, organizational ownership, and geographic location are significantly related to SAT involvement with ACOs. We discuss implications for integrating the SAT specialty system with the mainstream health care system.
Accountable Care Organizations and Antitrust Enforcement: Promoting Competition and Innovation
Authors: Feinstein Deborah L. , Kuhlmann Patrick , Mucchetti Peter J. 
Published: June 2015

Abstract
The antitrust laws stand to protect consumers of health care services from conduct that would raise prices, lower quality, and decrease innovation by lessening competition. Importantly, though, vigorous antitrust enforcement does not impede accountable care organizations (ACOs) and similar collaborations that advance these same goals of better and more efficient care; in fact, by fostering competitive markets, the antitrust laws encourage such initiatives. This article summarizes the legal framework that the federal antitrust agencies — the Federal Trade Commission and the Antitrust Division of the US Department of Justice — use to analyze ACOs and other collaborations among health care providers. It outlines the guidance provided by the federal antitrust agencies concerning when ACOs and other provider collaborations likely would harm competition and consumers. In addition, it reviews common antitrust issues that can arise with ACOs and provides examples of enforcement actions that have prevented health care providers from taking or continuing anticompetitive actions.
The Affordable Care Act versus Medicare for All
Authors: Seidman Laurence 
Published: June 2015

Abstract
Many problems facing the Affordable Care Act would disappear if the nation were instead implementing Medicare for All — the extension of Medicare to every age group. Every American would be automatically covered for life. Premiums would be replaced with a set of Medicare taxes. There would be no patient cost sharing. Individuals would have free choice of doctors. Medicare's single-payer bargaining power would slow price increases and reduce medical cost as a percentage of gross domestic product (GDP). Taxes as a percentage of GDP would rise from below average to average for economically advanced nations. Medicare for All would be phased in by age.
Medicare for All — if It Were Politically Possible — would Necessarily Replicate the Defects of Our Current System
Authors: Pollack Harold 
Published: June 2015

Abstract
Medicare for All, ideally implemented, could offer powerful advantages over our current health care financial system. Unfortunately, the political obstacles to such a system are formidable and are likely to remain so for decades. More to the point, a politically viable single-payer system would not replace our currently dysfunctional health care politics. It would be a product of that same legislative process and political economy and thus be disfigured by the same interest group politics, path dependence, and fragmentation that Laurence Seidman rightly laments.
The viability of chondrocytes after an in vivo injection of local anaesthetic and/or corticosteroid
Authors: Sola M. , Dahners L. , Weinhold P. , Svetkey van der Horst A. , Kallianos S. , Flood D. 
Published: June 2015

This in vivo controlled laboratory study was performed to evaluate various intra-articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH-balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague–Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live–dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone. Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity. Cite this article: Bone Joint J 2015; 97-B:933–8.
Seronegative infections in hip and knee arthroplasty
Authors: McArthur B. A. , Abdel M. P. , Taunton M. J. , Osmon D. R. , Hanssen A. D. 
Published: June 2015

The aim of our study was to describe the characteristics, treatment, and outcomes of patients with periprosthetic joint infection (PJI) and normal inflammatory markers after total knee arthroplasty (TKA) and total hip arthroplasty (THA).In total 538 TKAs and 414 THAs underwent surgical treatment for PJI and met the inclusion criteria. Pre-operative erythrocyte sedimentation rate (ESR) and C-reactive protein level (CRP) were reviewed to identify the seronegative cohort. An age- and gender-matched cohort was identified from the remaining patients for comparison. Overall, 4% of confirmed infections were seronegative (21 TKA and 17 THA). Of those who underwent pre-operative aspiration, cultures were positive in 76% of TKAs (n = 13) and 64% of THAs (n = 7). Cell count and differential were suggestive of infection in 85% of TKA (n = 11) and all THA aspirates (n = 5). The most common organism was coagulase-negative Staphylococcus. Seronegative infections were associated with a lower aspirate cell count and a lower incidence of Staphylococcus aureus infection. Two-stage revision was performed in 35 cases (95%). At a mean of five years (14 to 162 months) following revision, re-operation for infection occurred in two TKAs, and one THA. From our study we estimate around 4% of patients with PJI may present with normal ESR and CRP. When performed, pre-operative aspirate is useful in delivering a definitive diagnosis. When treated, similar outcomes can be obtained compared with patients with positive serology.Cite this article: Bone Joint J 2015;97-B:939–44.
Hemiarthroplasty versus internal fixation for displaced intracapsular fractures of the hip in elderly men
Authors: Parker M. J. 
Published: June 2015

A total of 56 male patients with a displaced intracapsular fracture of the hip and a mean age of 81 years (62 to 94), were randomised to be treated with either a cemented hemiarthroplasty (the Exeter Trauma Stem) or reduction and internal fixation using the Targon Femoral Plate. All surviving patients were reviewed one year after the injury, at which time restoration of function and pain in the hip was assessed. There was no statistically significant difference in mortality between the two groups (7/26; 26.9% for hemiarthroplasty vs 10/30; 33.3% for internal fixation). No patient treated with a hemiarthroplasty required further surgery, but eight patients treated by internal fixation did (p = 0.005), five requiring hemiarthroplasty and three requiring total hip arthroplasty. Those treated by internal fixation had significantly more pain (p = 0.02). The restoration of mobility and independence were similar in the two groups. These results indicate that cemented hemiarthroplasty gives better results than internal fixation in elderly men with a displaced intracapsular fracture of the hip. Cite this article: Bone Joint J 2015;97-B:992–6.
Infantile developmental thoracolumbar kyphosis with segmental subluxation of the spine
Authors: Ganesan S. , Karampalis C. , Garrido E. , Tsirikos A. I. 
Published: June 2015

Acute angulation at the thoracolumbar junction with segmental subluxation of the spine occurring at the level above an anteriorly hypoplastic vertebra in otherwise normal children is a rare condition described as infantile developmental thoracolumbar kyphosis. Three patient series with total of 18 children have been reported in the literature. We report five children who presented with thoracolumbar kyphosis and discuss the treatment algorithm. We reviewed the medical records and spinal imaging at initial clinical presentation and at minimum two-year follow-up. The mean age at presentation was eight months (two to 12). All five children had L2 anterior vertebral body hypoplasia. The kyphosis improved spontaneously in three children kept under monitoring. In contrast, the deformity was progressive in two patients who were treated with bracing. The kyphosis and segmental subluxation corrected at latest follow-up (mean age 52 months; 48 to 60) in all patients with near complete reconstitution of the anomalous vertebra. The deformity and radiological imaging on a young child can cause anxiety to both parents and treating physicians. Diagnostic workup and treatment algorithm in the management of infantile developmental thoracolumbar kyphosis is proposed. Observation is indicated for non-progressive kyphosis and bracing if there is evidence of kyphosis and segmental subluxation deterioration beyond walking age. Surgical stabilisation of the spine can be reserved for severe progressive deformities unresponsive to conservative treatment.Cite this article: Bone Joint J 2015;97-B:982–7.
A placebo-controlled randomised trial to assess the effect of TGF-ß1-expressing chondrocytes in patients with arthritis of the knee
Authors: Lee M C , Ha C-W , Elmallah R. K. , Cherian J. J. , Cho J J , Kim T W , Bin S-I , Mont M. A. 
Published: June 2015

The aim of this study was to assess the effect of injecting genetically engineered chondrocytes expressing transforming growth factor beta 1 (TGF-β1) into the knees of patients with osteoarthritis. We assessed the resultant function, pain and quality of life.A total of 54 patients (20 men, 34 women) who had a mean age of 58 years (50 to 66) were blinded and randomised (1:1) to receive a single injection of the active treatment or a placebo. We assessed post-treatment function, pain severity, physical function, quality of life and the incidence of treatment-associated adverse events. Patients were followed at four, 12 and 24 weeks after injection.At final follow-up the treatment group had a significantly greater improvement in the mean International Knee Documentation Committee score than the placebo group (16 points; -18 to 49, vs 8 points; -4 to 37, respectively; p = 0.03). The treatment group also had a significantly improved mean visual analogue score at final follow-up (-25; -85 to 34, vs -11 points; -51 to 25, respectively; p = 0.032). Both cohorts showed an improvement in Western Ontario and McMaster Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome Scores, but these differences were not statistically significant. One patient had an anaphylactic reaction to the preservation medium, but recovered within 24 hours. All other adverse events were localised and resolved without further action.This technique may result in improved clinical outcomes, with the aim of slowing the degenerative process, leading to improvements in pain and function. However, imaging and direct observational studies are needed to verify cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing.Cite this article: Bone Joint J 2015;97-B:924–32.
Everybody is a musician, everybody is an orchestra: Musical and bodily dialogues with physically disabled children in Turkey
Authors: Boon Ebru Tuncer 
Published: June 2015

Abstract
This study documents a reflective journey of a series of music workshops initiated by a university Performing Arts faculty member in Istanbul, Turkey. The purpose of this narrative enquiry is to explore and examine the musical and bodily dialogues, engagements and critical thoughts between a music educator and children with developmental disabilities. Focusing particularly on the theories and practices of community music, this study illustrates the vision of community music, which says that everybody deserves the chance to interact musically through their body and psyche and to play alongside others in a community with the help of a facilitator.