bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining Platelet-Rich Plasma Usage by Team Physicians in Elite Athletes
Authors: Kantrowitz David E. , Padaki Ajay S. , Ahmad Christopher S. , Lynch T. Sean 
Published: April 2018

Background: The indications for the use of platelet-rich plasma (PRP) are vaguely defined despite the frequency of its use as a treatment for athletes. While select studies have advocated for its efficacy, the majority of orthopaedic research conducted on the topic has been equivocal. Purpose: To define the use of PRP in elite athletes by team physicians from professional sports leagues. Study Design: Cross-sectional study. Methods: A survey assessing treatment timing, usage patterns, indications, and complications was generated by fellowship-trained sports medicine orthopaedic surgeons. The survey was distributed to team physicians from the National Football League, National Basketball Association, Major League Baseball, National Hockey League, Major League Soccer, and the “Power 5” Division I conferences of the National Collegiate Athletic Association. From a compilation of publicly available email addresses and those available from professional team physician associations, 149 team physicians were sent this PRP assessment tool. Results: Of the 149 professional and collegiate team physicians contacted, 59 started the survey and 46 completed it, resulting in a 39.6% participation rate and a 30.9% completion rate. Approximately 93% of physicians stated that they use PRP in their practices, and 72% use ultrasonography for injection guidance. On average, collegiate team physicians and National Football League physicians treated the most players per season with PRP (69.4 and 60.4 players, respectively), while National Hockey League physicians treated the fewest (18.0 players). The majority of respondents reported no complications from PRP injections (70%), with pain being the most common complication reported (26%). There was no consensus on the most important aspect of PRP formulation, with the top 2 responses being platelet concentration (48%) and white blood cell concentration (39%). When grading the importance of indications to use PRP, physicians found athlete desire on average (7.5 ± 2.2 [SD]; out of 10) to be more important than reimbursement (2.2 ± 2.2) ( P < .001). Importantly, physicians stated that they moderately (5.4 ± 2.3) believed in the evidence behind PRP. Physicians listed hamstring injuries as the most common injury treated with PRP. Hamstring injuries were treated with a mean 3.14 PRP injections, as opposed to 2.19 injections for nonhamstring injuries. Conclusion: Professional and collegiate team physicians frequently use PRP despite a lack of consensus regarding the importance of the formulation of the product, the timing of treatment, and the conditions that would most benefit from PRP treatment.
ERS/ECDC Statement: European Union standards for tuberculosis care, 2017 update
Authors: Migliori Giovanni Battista , Sotgiu Giovanni , Rosales-Klintz Senia , Centis Rosella , D'Ambrosio Lia , Abubakar Ibrahim , Bothamley Graham , Caminero Jose Antonio , Cirillo Daniela Maria , Dara Masoud , de Vries Gerard , Aliberti Stefano , Dinh-Xuan Anh Tuan , Duarte Raquel , Midulla Fabio , Solovic Ivan , Subotic Dragan R. , Amicosante Massimo , Correia Ana Maria , Cirule Andra , Gualano Gina , Kunst Heinke , Palmieri Fabrizio , Riekstina Vija , Tiberi Simon , Verduin Remi , van der Werf Marieke J. 
Published: April 2018

The International Standards for Tuberculosis Care define the essential level of care for managing patients who have or are presumed to have tuberculosis, or are at increased risk of developing the disease. The resources and capacity in the European Union (EU) and the European Economic Area permit higher standards of care to secure quality and timely TB diagnosis, prevention and treatment. On this basis, the European Union Standards for Tuberculosis Care (ESTC) were published in 2012 as standards specifically tailored to the EU setting. Since the publication of the ESTC, new scientific evidence has become available and, therefore, the standards were reviewed and updated.A panel of international experts, led by a writing group from the European Respiratory Society (ERS) and the European Centre for Disease Prevention and Control (ECDC), updated the ESTC on the basis of new published evidence. The underlying principles of these patient-centred standards remain unchanged. The second edition of the ESTC includes 21 standards in the areas of diagnosis, treatment, HIV and comorbidities, and public health and prevention.The ESTC target clinicians and public health workers, provide an easy-to-use resource and act as a guide through all the required activities to ensure optimal diagnosis, treatment and prevention of TB.
Early diagnosis from newborn screening maximises survival in severe cystic fibrosis
Authors: Tridello Gloria , Castellani Carlo , Meneghelli Ilaria , Tamanini Anna , Assael Baroukh M. 
Published: April 2018

Newborn screening (NBS) for cystic fibrosis (CF) has been gradually established in several countries, but scant data are available on its long-term effects on survival. Our objective was to evaluate the long-term effects of CF NBS on survival.586 patients, diagnosed and followed between 1971 and 2014 at the Verona CF Centre were analysed. Eligibility was confirmed in 342 cases diagnosed by NBS, 101 with meconium ileus and 143 through symptoms (44 out of 143 were NBS false negatives). The primary end-point was the 30-year overall survival in patients diagnosed by NBS. Patients were grouped according to the number of hospitalisations for respiratory or nutritional symptoms in the first 3 years of life: 0 (mild), 1–2 (moderate) and ≥3 (severe). Survival in NBS and symptoms groups was compared.The 30-year survival probability of the NBS group was 80.1% (95% CI 71.4–86.4%); in the symptoms group it was 71.0% (95% CI 62.2–78.2%). The 20-year survival was significantly higher in the NBSversussymptoms group in the severe (85%versus64%, p=0.007) and moderate (94%versus86%, p=0.016) groups. An adjusted Cox-model estimation confirmed differences in both the groups.Poor outcome associated with early severe presentation of CF is tempered by NBS.
CAFE MOCHA: An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer—An Example of Distant Metastasis– and Recurrence-Linked Classifiers in Head and Neck Squamous Cell Carcinoma
Authors: Krishnan Neeraja M. , I Mohanraj , Hariharan Janani , Panda Binay 
Published: April 2018

Purpose With large amounts of multidimensional molecular data on cancers generated and deposited into public repositories such as The Cancer Genome Atlas and International Cancer Genome Consortium, a cancer type agnostic and integrative platform will help to identify signatures with clinical relevance. We devised such a platform and showcase it by identifying a molecular signature for patients with metastatic and recurrent (MR) head and neck squamous cell carcinoma (HNSCC). Methods We devised a statistical framework accompanied by a graphical user interface–driven application, Clinical Association of Functionally Established MOlecular CHAnges ( CAFE MOCHA; https://github.com/binaypanda/CAFEMOCHA), to discover molecular signatures linked to a specific clinical attribute in a cancer type. The platform integrates mutations and indels, gene expression, DNA methylation, and copy number variations to discover a classifier first and then to predict an incoming tumor for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry–based algorithm called complete specificity margin-based clustering, which ensures maximum specificity. CAFE MOCHA classifies an incoming tumor sample using either its matched normal or a built-in database of normal tissues. The application is packed and deployed using the install4j multiplatform installer. We tested CAFE MOCHA in HNSCC tumors (n = 513) followed by validation in tumors from an independent cohort (n = 18) for discovering a signature linked to distant MR. Results CAFE MOCHA identified an integrated signature, MR44, associated with distant MR HNSCC, with 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage. Conclusion CAFE MOCHA is a cancer type and clinical attribute agnostic statistical framework to discover integrated molecular signatures.
Model for Predicting Breast Cancer Risk in Women With Atypical Hyperplasia
Authors: Degnim Amy C. , Winham Stacey J. , Frank Ryan D. , Pankratz V. Shane , Dupont William D. , Vierkant Robert A. , Frost Marlene H. , Hoskin Tanya L. , Vachon Celine M. , Ghosh Karthik , Hieken Tina J. , Carter Jodi M. , Denison Lori A. , Broderick Brendan , Hartmann Lynn C. , Visscher Daniel W. , Radisky Derek C. 
Published: April 2018

Purpose Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but existing risk prediction models do not provide accurate individualized estimates of risk in this subset of high-risk women. Here, we used the Mayo benign breast disease cohort to develop and validate a model of BC risk prediction that is specifically for women with AH, which we have designated as AH-BC. Patients and Methods Retrospective cohorts of women age 18 to 85 years with pathologically confirmed benign AH from Rochester, MN, and Nashville, TN, were used for model development and external validation, respectively. Clinical risk factors and histologic features of the tissue biopsy were selected using L1-penalized Cox proportional hazards regression. Identified features were included in a Fine and Gray regression model to estimate BC risk, with death as a competing risk. Model discrimination and calibration were assessed in the model-building set and an external validation set. Results The model-building set consisted of 699 women with AH, 142 of whom developed BC (median follow-up, 8.1 years), and the external validation set consisted of 461 women with 114 later BC events (median follow-up, 11.4 years). The final AH-BC model included three covariates: age at biopsy, age at biopsy squared, and number of foci of AH. At 10 years, the AH-BC model demonstrated good discrimination (0.63 [95% CI, 0.57 to 0.70]) and calibration (0.87 [95% CI, 0.66 to 1.24]). In the external validation set, the model showed acceptable discrimination (0.59 [95% CI, 0.51 to 0.67]) and calibration (0.91 [95% CI, 0.65 to 1.42]). Conclusion We have created a new model with which to refine BC risk prediction for women with AH. The AH-BC model demonstrates good discrimination and calibration, and it validates in an external data set.
Intravenous Chemotherapy Compounding Errors in a Follow-Up Pan-Canadian Observational Study
Authors: Gilbert Rachel E. , Kozak Melissa C. , Dobish Roxanne B. , Bourrier Venetia C. , Koke Paul M. , Kukreti Vishal , Logan Heather A. , Easty Anthony C. , Trbovich Patricia L. 
Published: April 2018

Purpose: Intravenous (IV) compounding safety has garnered recent attention as a result of high-profile incidents, awareness efforts from the safety community, and increasingly stringent practice standards. New research with more-sensitive error detection techniques continues to reinforce that error rates with manual IV compounding are unacceptably high. In 2014, our team published an observational study that described three types of previously unrecognized and potentially catastrophic latent chemotherapy preparation errors in Canadian oncology pharmacies that would otherwise be undetectable. We expand on this research and explore whether additional potential human failures are yet to be addressed by practice standards. Methods: Field observations were conducted in four cancer center pharmacies in four Canadian provinces from January 2013 to February 2015. Human factors specialists observed and interviewed pharmacy managers, oncology pharmacists, pharmacy technicians, and pharmacy assistants as they carried out their work. Emphasis was on latent errors (potential human failures) that could lead to outcomes such as wrong drug, dose, or diluent. Results: Given the relatively short observational period, no active failures or actual errors were observed. However, 11 latent errors in chemotherapy compounding were identified. In terms of severity, all 11 errors create the potential for a patient to receive the wrong drug or dose, which in the context of cancer care, could lead to death or permanent loss of function. Three of the 11 practices were observed in our previous study, but eight were new. Applicable Canadian and international standards and guidelines do not explicitly address many of the potentially error-prone practices observed. Conclusion: We observed a significant degree of risk for error in manual mixing practice. These latent errors may exist in other regions where manual compounding of IV chemotherapy takes place. Continued efforts to advance standards, guidelines, technological innovation, and chemical quality testing are needed.
Perceptions of Continued Smoking and Smoking Cessation Among Patients With Cancer
Authors: Alton Devon , Eng Lawson , Lu Lin , Song Yuyao , Su Jie , Farzanfar Delaram , Mohan Rahul , Krys Olivia , Mattina Katie , Harper Christopher , Liu Sophia , Yoannidis Tom , Milne Robin , Brown M. Catherine , Vennettilli Ashlee , Hope Andrew J. , Howell Doris , Jones Jennifer M. , Selby Peter , Xu Wei , Goldstein David P. , Liu Geoffrey , Giuliani Meredith E. 
Published: April 2018

Purpose: Continued smoking after a cancer diagnosis leads to poorer treatment outcomes, survival, and quality of life. We evaluated the perceptions of the effects of continued smoking on quality of life, survival, and fatigue among patients with cancer after a cancer diagnosis and the effects of these perceptions on smoking cessation. Patients and Methods: Patients with cancer from all disease subsites from Princess Margaret Cancer Centre (Toronto, Ontario) were surveyed between April 2014 and May 2016 for sociodemographic variables, smoking history, and perceptions of continued smoking on quality of life, survival, and fatigue. Multivariable regression models evaluated the association between patients’ perceptions and smoking cessation and the factors influencing patients’ perceptions of smoking. Results: Among 1,121 patients, 277 (23%) were smoking cigarettes up to 1 year before diagnosis, and 54% subsequently quit; 23% had lung cancer, and 27% had head and neck cancers. The majority felt that continued smoking after a cancer diagnosis negatively affected quality of life (83%), survival (86%), and fatigue (82%). Current smokers during the peridiagnosis period were less likely to perceive that continued smoking was harmful when compared with ex-smokers and never-smokers ( P < .01). Among current smokers, perceiving that smoking negatively affected quality of life (adjusted odds ratio [aOR], 2.68 [95% CI, 1.26 to 5.72]; P = .011), survival (aOR, 5.00 [95% CI, 2.19 to 11.43]; P < .001), and fatigue (aOR, 3.57 [95% CI, 1.69 to 7.54]; P < .001) were each strongly associated with smoking cessation. Among all patients, those with a greater smoking history were less likely to believe that smoking was harmful in terms of quality of life (aOR, 0.98 [95% CI, 0.98 to 0.99]; P < .001), survival (aOR, 0.98 [95% CI, 0.98 to 0.99]; P < .001), and fatigue (aOR, 0.99 [95% CI, 0.98 to 0.99]; P < .001). Conclusion: The perceptions of continued smoking after a cancer diagnosis among patients with cancer are strongly associated with smoking cessation. Counseling about the harms of continued smoking in patients with cancer, and in particular among those who have lower risk perceptions, should be considered when developing a smoking cessation program.
Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma
Authors: Chortis Vasileios , Taylor Angela E , Doig Craig L , Walsh Mark D , Meimaridou Eirini , Jenkinson Carl , Rodriguez-Blanco Giovanny , Ronchi Cristina L , Jafri Alisha , Metherell Louise A , Hebenstreit Daniel , Dunn Warwick B , Arlt Wiebke , Foster Paul A 
Published: April 2018

Abstract
Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry–based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.
Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity
Authors: Insenser María , Murri Mora , del Campo Rosa , Martínez-García M Ángeles , Fernández-Durán Elena , Escobar-Morreale Héctor F 
Published: April 2018

Abstract

Context
Gut microbiota play a major role in health and disease by influencing physiology, metabolism, nutrition, and immune function.

Objective
To evaluate the composition of gut microbiota in women with polycystic ovary syndrome (PCOS), focusing on the influence of sex, sex hormones and obesity on the associations found.

Design
Cross-sectional study.

Setting
Academic hospital.

Participants
We recruited 15 women with PCOS, 16 nonhyperandrogenic control women, and 15 control men. Participants were classified as nonobese (&lt;30 kg/m2) or obese (≥30 kg/m2) according to their body mass index.

Interventions
Standardization of diet for 3 consecutive days (at least 300 g of carbohydrates per day) followed by fecal sampling and a standard 75-g oral glucose tolerance test.

Main Outcome Measures
Analysis of bacterial abundance and composition of gut microbiota by massive sequencing of 16S ribosomal DNA amplicons in a MiSeq platform (Illumina).

Results
α Bacterial diversity was reduced in women compared with men, and β diversity was reduced particularly in obese patients with PCOS. Women with PCOS presented with specific abnormalities in gut microbiota consisting of an increased abundance of the Catenibacterium and Kandleria genera. When all participants as a whole were considered, indexes of bacterial diversity and the abundance of several bacterial genera correlated positively with serum androgen concentrations and negatively with estradiol levels.

Conclusions
The diversity and composition of the gut microbiota of young adults are influenced by the combined effects of sex, sex hormone concentrations, and obesity, presenting with specific abnormalities in women with PCOS.
Intralipid/Heparin Infusion Alters Brain Metabolites Assessed With 1H-MRS Spectroscopy in Young Healthy Men
Authors: Karczewska-Kupczewska Monika , Nikołajuk Agnieszka , Filarski Remigiusz , Majewski Radosław , Tarasów Eugeniusz 
Published: April 2018

Abstract

Context
We previously demonstrated that insulin infusion altered metabolite concentrations in cerebral tissues assessed with proton magnetic resonance spectroscopy (1H-MRS) in young subjects with high insulin sensitivity, but not in those with low insulin sensitivity. Fat overload is an important factor leading to insulin resistance.

Objective
The purpose of the current study was to examine the effect of elevated circulating free fatty acid (FFA) levels on metabolites in cerebral tissues assessed with 1H-MRS.

Design
The study group comprised 10 young, healthy male subjects. 1H-MRS was performed at baseline and after 4-hour Intralipid (Fresenius Kabi)/heparin or saline infusions administered in random order. Voxels were positioned in the left frontal lobe, left temporal lobe, and hippocampus. The ratios of N-acetylaspartate (NAA), choline (Cho)-containing compounds, myo-inositol (mI), and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined.

Results
Intralipid/heparin infusion resulted in a significant increase in circulating FFAs (P &lt; 0.0001). Significant changes in brain neurometabolite concentrations in response to Intralipid/heparin infusion were increases in frontal mI/Cr (P = 0.041) and mI/H2O (P = 0.037), decreases in frontal and hippocampal Glx/Cr (P = 0.018 and P = 0.015, respectively) and Glx/H2O (P = 0.03 and P = 0.067, respectively), and a decrease in hippocampal NAA/Cr (P = 0.007) and NAA/H2O (P = 0.019). No changes in neurometabolites were observed during the saline infusion.

Conclusions
Acute circulating FFA elevation influenced cerebral metabolites in healthy humans and lipid-induced insulin resistance could be partly responsible for these effects.
Opioid Oversupply After Joint and Spine Surgery: A Prospective Cohort Study
Authors: Bicket Mark C. , White Elizabeth , Pronovost Peter J. , Wu Christopher L. , Yaster Myron , Alexander G. Caleb 
Published: April 2018

BACKGROUND:
Many patients receive prescription opioids at hospital discharge after surgery, yet little is known regarding how often these opioids go unused. We estimated the prevalence of unused opioids, use of nonopioid analgesics, and storage and disposal practices after same-day and inpatient surgery.

METHODS:
In this prospective cohort study at a large, inner-city tertiary care hospital, we recruited individuals ≥18 years of age undergoing elective same-day or inpatient joint and spine surgery from August to November 2016. Using patient surveys via telephone calls, we assessed patient-reported outcomes at 2-day, 2-week, 1-month, and 6-month intervals, including: (1) stopping opioid treatment and in possession of unused opioid pills (primary outcome), (2) number of unused opioid tablets reported after stopping opioids, (3) use of nonopioid pain treatments, and (4) knowledge and practice regarding safe opioid storage and disposal.

RESULTS:
Of 141 eligible patients, 140 (99%) consented (35% taking preoperative opioids; mean age 56 years [standard deviation 16 years]; 47% women). One- and 6-month follow-up was achieved for 115 (82%) and 110 patients (80%), respectively. Among patients who stopped opioid therapy, possession of unused opioids was reported by 73% (95% confidence intervals, 62%–82%) at 1-month follow-up and 34% (confidence interval, 24%–45%) at 6-month follow-up. At 1 month, 46% had ≥20 unused pills, 37% had ≥200 morphine milligram equivalents, and only 6% reported using multiple nonopioid adjuncts. Many patients reported unsafe storage and failure to dispose of opioids at both 1-month (91% and 96%, respectively) and 6-month (92% and 47%, respectively) follow-up.

CONCLUSIONS:
After joint and spine surgery, many patients reported unused opioids, infrequent use of analgesic alternatives, and lack of knowledge regarding safe opioid storage and disposal. Interventions are needed to better tailor postoperative analgesia and improve the safe storage and disposal of prescription opioids.