bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moderate-and-vigorous physical activity from adolescence to adulthood and subclinical atherosclerosis in adulthood: prospective observations from the European Youth Heart Study
Authors: Ried-Larsen Mathias , Grøntved Anders , Kristensen Peter Lund , Froberg Karsten , Andersen Lars Bo 
Published: April 2013

AimTo investigate the independent associations between mean exposure to or the change in moderate-and-vigorous physical activity (PA) from adolescence to adulthood and subclinical atherosclerosis in adulthood.MethodsThis was a prospective cohort study among Danish boys and girls (N=277) followed for up to 12 years (age 15.7 (0.4) at baseline) enrolled in the European Youth Heart Study. PA intensity was objectively measured at baseline and follow-up, and ultrasonography was performed on the Carotid arteries at follow-up. Data on carotid intima-media thickness (cIMT), Carotid Compliance and Young's Elastic Modules were used as outcome measures.ResultsIn the multivariable analyses (adjusted for personal—lifestyle and demographic factors) the mean exposure to moderate-and-vigorous PA from adolescence to adulthood was negatively associated with Young's Elastic Modules (β=−0.001×103 kPa (95% CI −0.0015 to −0.0002), p=0.02) and positively associated with Carotid Compliance (β=0.004 mm2 kPa−1(95% CI 0.002 to 0.008), p=0.003) and cIMT (β=0.0003 mm (95% CI 0.00001 to 0.0007), p=0.013). Increases in moderate-and-vigorous PA from adolescence to adulthood were negatively associated with Young's Elastic Modules in adulthood (β=−0.00007×103 kPa (95% CI −0.0012 to −0.0001), p=0.01). Furthermore, participants with the largest decline in moderate-and-vigorous PA from adolescence to adulthood displayed significantly less compliant arteries compared with the remaining sample (p<0.05).ConclusionsHigh mean exposure to moderate-and-vigorous PA levels and increases herein were independently associated with lower levels of carotid arterial stiffness in adulthood.
Assessment of statin-associated muscle toxicity in Japan: a cohort study conducted using claims database and laboratory information
Authors: Chang Chia-Hsien , Kusama Makiko , Ono Shunsuke , Sugiyama Yuichi , Orii Takao , Akazawa Manabu 
Published: April 2013

ObjectiveTo estimate the incidence of muscle toxicity in patients receiving statin therapy by examining study populations, drug exposure status and outcome definitions.DesignA retrospective cohort study.Setting16 medical facilities in Japan providing information on laboratory tests performed in and claims received by their facilities between 1 April 2004 and 31 December 2010.ParticipantsA database representing a cohort of 35 903 adult statin (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin) users was studied. Use of interacting drugs (fibrates, triazoles, macrolides, amiodarone and ciclosporin) by these patients was determined.Main outcome measureStatin-associated muscle toxicity (the ‘event’) was identified based on a diagnosis of muscle-related disorders (myopathy or rhabdomyolysis) and/or abnormal elevation of creatine kinase (CK) concentrations. Events were excluded if the patients had CK elevation-related conditions other than muscle toxicity. Incidence rates for muscle toxicity were determined per 1000 person-years, with 95% CI determined by Poisson regression.ResultsA total of 18 036 patients accounted for 42 193 person-years of statin therapy, and 43 events were identified. The incidence of muscle toxicity in the patients treated with statins was 1.02 (95% CI 0.76 to 1.37)/1000 person-years. The estimates varied when outcome definitions were modified from 0.09/1000 person-years, which met both diagnosis and CK 10× greater than the upper limit of normal range (ULN) criteria, to 2.06/1000 person-years, which met diagnosis or CK 5× ULN criterion. The incidence of muscle toxicity was also influenced by the statin therapies selected, but no significant differences were observed. Among 2430 patients (13.5%) received interacting drugs with statins, only three muscle toxicity cases were observed (incidence: 1.69/1000 person-years).ConclusionsThis database study suggested that statin use is generally well tolerated and safe; however, the risk of muscle toxicity related to the use of interacting drugs requires further exploration.
Ω-3 fatty acid supplement use in the 45 and Up Study Cohort
Authors: Adams Jon , Sibbritt David , Lui Chi-Wai , Broom Alex , Wardle Jonathan 
Published: April 2013

ObjectiveThere has been a dramatic increase in the use of dietary supplements in Western societies over the past decades. Our understanding of the prevalence of Ω-3 fatty acid supplement consumption is of significance for future nutrition planning, health promotion and care delivery. However, we know little about Ω-3 fatty acid supplement consumption or users. This paper, drawing upon the largest dataset with regard to Ω-3 fatty acid supplement use (n=266 848), examines the use and users of this supplement among a large sample of older Australians living in New South Wales.DesignA cross-sectional study. Data were analysed from the 45 and Up Study, the largest study of healthy ageing ever undertaken in the Southern Hemisphere.SettingNew South Wales, Australia.Participants266 848 participants of the 45 and Up Study.Primary and secondary outcome measuresParticipants’ use of Ω-3, demographics (geographical location, marital status, education level, income and level of healthcare insurance) and health status (quality of life, history of smoking and alcohol consumption, health conditions) were measured.ResultsOf the 266 848 participants, 32.6% reported having taken Ω-3 in the 4 weeks prior to the survey. Use of Ω-3 fatty acid supplements was higher among men, non-smokers, non-to-mild (alcoholic) drinkers, residing in a major city, having higher income and private health insurance. Osteoarthritis, osteoporosis, high cholesterol and anxiety and/or depression were positively associated with Ω-3 fatty acid supplement use, while cancer and high blood pressure were negatively associated with use of Ω-3 fatty acid supplements.ConclusionsThis study, analysing data from the 45 and Up Study cohort, suggests that a considerable proportion of older Australians consume Ω-3 fatty acid supplements. There is a need for primary healthcare practitioners to enquire with patients about this supplement use and for work to ensure provision of good-quality information for patients and providers with regard to Ω-3 fatty acid products.
Barriers to recruitment for surgical trials in head and neck oncology: a survey of trial investigators
Authors: Kaur Geetinder , Hutchison Iain , Mehanna Hisham , Williamson Paula , Shaw Richard , Tudur Smith Catrin 
Published: April 2013

ObjectivesMany randomised trials in surgery suffer from recruitment rates that lag behind projected targets. We aim to identify perceived barriers to recruitment among these pioneering trials in the field of head and neck cancer surgery.DesignRecruiting centres to all three trials (Selective Elective Neck Dissection (SEND), Positron Emission Tomography (PET)-Neck and Hyperbaric Oxygen in the Prevention of Osteoradionecrosis (HOPON)) were contacted by email by the chief investigators. Responders were asked to complete a web-based survey in order to identify the barriers to recruitment in their centre and grade each by severity.SettingSecondary care: 44 head and neck oncology regional referral centres.ParticipantsAnalysis was based on 85 responses evenly distributed between the three trials.ResultsThe most commonly identified perceived barriers to recruitment (more than 50% of responders identified the item as a barrier in all the three trials) in the order of frequency were: patients consent refusal because of expressed treatment preference, patients consent refusal owing to aversion to randomisation, excess complexity/amount of information provided to patients and lack of time in clinic to accommodate research. The most severely rated of these problems was consent refusal because of the expressed treatment preference and lack of time in the clinic.ConclusionsOur findings confirm others’ work in surgery that the most significant barrier to trial recruitment in head and neck cancer surgery is the patient's preference for one arm of the trial. It may be that additional training for those taking consent may be helpful in this regard. It is also important to adequately resource busy surgical clinics to support clinical trial recruitment.
The influence of time pressure on adherence to guidelines in primary care: an experimental study
Authors: Tsiga Evangelia , Panagopoulou Efharis , Sevdalis Nick , Montgomery Anthony , Benos Alexios 
Published: April 2013

ObjectivesEvidence from cognitive sciences has systematically shown that time pressure influences decision-making processes. However, very few studies have examined the role of time pressure on adherence to guidelines in clinical practice. The aim of this study was to examine the influence of time pressure on adherence to guidelines in primary care concerning: history taking, clinical examination and advice giving.DesignA within-subjects experimental design was used.SettingAcademic.Participants34 general practitioners (GPs) were assigned to two experimental conditions (time pressure vs no time pressure) consecutively, and presented with two scenarios involving virus respiratory tract infections.Primary and secondary outcome measuresOutcome measures included adherence to guidelines on history taking, clinical examination and advice giving.ResultsUnder time pressure, GPs asked significantly less questions concerning presenting symptoms, than the ones indicated by the guidelines, (p=0.019), conducted a less-thorough clinical examination (p=0.028), while they gave less advice on lifestyle (p=0.05).ConclusionsAs time pressure increases as a result of high workload, there is a need to examine how adherence to guidelines is affected to safeguard patient's safety.
Too tall for the tape: the weight of schoolchildren who do not fit the Broselow tape
Authors: Cattermole G N , Leung P Y M , Graham C A , Rainer T H 
Published: April 2013

BackgroundIn paediatric resuscitation, for a rapid and accurate estimate of children's weight, the Broselow tape can be used in children who are 46–144 cm tall. The Broselow tape has previously been found to provide the most accurate estimate of children's weight internationally, but it is not known how many fall outside the range of the tape, or whether such children can be assumed to be of adult weight, or how otherwise to estimate the weight of these children.ObjectivesTo determine what proportion of children in different age groups falls outside the limits of the Broselow tape, how their weight compares with that of the adults and what correlates most strongly with weight in these children.MethodsThis was a population-based prospective observational study of Chinese children up to 12 years old, from schools in Hong Kong. Weight was measured to the nearest 0.2 kg, and the height, foot-length and mid-arm circumference (MAC) were measured to the nearest 0.1 cm.Results40% of 10-year olds and 70% of 11-year olds were too tall for the tape. Their median weight was 41.9 kg. This was significantly less than the median weight of 18-year olds (55 kg, p<0.0001) in Hong Kong. The strongest correlate with weight in these children was MAC.ConclusionsThe Broselow tape is inappropriate for use in most children over 10 years old. Children too tall for the tape cannot be assumed to be of adult weight; to do so would imply an average overestimate of 30%. Weight estimates in older children could be based on MAC.
Pilot study of a protocol to administer inhaled nitric oxide to treat severe acute submassive pulmonary embolism
Authors: Kline Jeffrey A , Hernandez Jackeline , Garrett John S , Jones Alan E 
Published: April 2013

ObjectiveInhaled nitric oxide has been reported to benefit patients with acute pulmonary embolism (PE). To date, all published literature has derived from case reports or case series conducted without a structured protocol. Here we report the results of a phase I trial with a predefined clinical protocol to treat patients with CT-demonstrated, submassive PE and moderate to severe dyspnoea.MethodsPatients were recruited from the emergency department of an academic teaching hospital. Informed consent and the entire treatment protocol was administered by a study physician. Nitric oxide was administered using a commercial device (Inovent) and a custom-made non-rebreathing face mask. The NO concentration was increased at 1 ppm/min (parts per million) until a maximum of 25 ppm and continued for 120 min and then weaned at 1 ppm/min. Dyspnoea was assessed with the Borg score, oxygenation by pulse oximetry, and haemodynamic status by shock index (HR/SBP).ResultsEight patients were enrolled. All patients tolerated the entire protocol without adverse events, and all had decreased numerical Borg score by >50%. The changes from baseline to 155 min were as follows: Borg score 7.5±2.5 to 2.3±1.9 (p=0.06, Signed rank test), SaO2% 93±5 to 97±3 and shock index 1.0±0.11 to 0.86±0.09. No patient experienced worsening during weaning.ConclusionsInhaled NO reduced dyspnoea without adverse events in eight patients with severe submassive PE. This protocol can serve as the basis for a phase II trial or for a compassionate use protocol.
Physicochemical Study of Photocatalytic Activity of TiO2Supported Palygorskite Clay Mineral
Authors: Bouna Lahcen , Rhouta Benaissa , Maury Francis 
Published: April 2013

This study deals with the influence of physicochemical parameters, namely, the photocatalyst loading, dye concentration, and pH of polluted solutions, on the degradation efficiency of Orange G (OG) solutions containing TiO2nanoparticles supported on palygorskite clay mineral (TiO2-Pal). The TiO2photocatalyst attached to natural palygorskite fibers was elaborated by colloidal sol-gel route. It exhibits the anatase structure that is the most photoactive crystallographic form. The highest performances of supported photocatalyst on OG degradation were found using an optimum amount of TiO2-Pal around 0.8 g·L−1, which corresponds properly toca. 0.4 g·L−1of TiO2. This amount is interestingly lower than the 2.5 g·L−1generally reported when using pure unsupported TiO2powder. The photodegradation rate increases by decreasing OG initial concentration, and it was found significantly higher when the OG solution is either acidic (pH<4) or basic (pH≈11). For OG concentrations in the range5×10-6– 5×10-4 M, the kinetic law of the OG degradation in presence of TiO2-Pal is similar to that reported for unsupported TiO2nanopowder. It follows a Langmuir-Hinshelwood model with a first-order reaction and an apparent rate constant of about2.9×10-2 min−1.
In Vitro and In Vivo Antitumor Activity of a Novel Alkylating Agent, Melphalan-Flufenamide, against Multiple Myeloma Cells
Authors: Chauhan Dharminder , Ray Arghya , Viktorsson Kristina , Spira Jack , Paba-Prada Claudia , Munshi Nikhil , Richardson Paul , Lewensohn Rolf , Anderson Kenneth C. 
Published: April 2013

Abstract
Purpose: The alkylating agent melphalan prolongs survival in patients with multiple myeloma; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (mel-flufen), a novel dipeptide prodrug of melphalan in multiple myeloma.
Experimental Design: Multiple myeloma cell lines, primary patient cells, and the human multiple myeloma xenograft animal model were used to study the antitumor activity of mel-flufen.
Results: Low doses of mel-flufen trigger more rapid and higher intracellular concentrations of melphalan in multiple myeloma cells than are achievable by free melphalan. Cytotoxicity analysis showed significantly lower IC50 of mel-flufen than melphalan in multiple myeloma cells. Importantly, mel-flufen induces apoptosis even in melphalan- and bortezomib-resistant multiple myeloma cells. Mechanistic studies show that siRNA knockdown of aminopeptidase N, a key enzyme mediating intracellular conversion of mel-flufen to melphalan, attenuates anti–multiple myeloma activity of mel-flufen. Furthermore, mel-flufen–induced apoptosis was associated with: (i) activation of caspases and PARP cleavage; (ii) reactive oxygen species generation; (iii) mitochondrial dysfunction and release of cytochrome c; and (iv) induction of DNA damage. Moreover, mel-flufen inhibits multiple myeloma cell migration and tumor-associated angiogenesis. Human multiple myeloma xenograft studies showed a more potent inhibition of tumor growth in mice treated with mel-flufen than mice receiving equimolar doses of melphalan. Finally, combining mel-flufen with lenalidomide, bortezomib, or dexamethasone triggers synergistic anti–multiple myeloma activity.
Conclusion: Our preclinical study supports clinical evaluation of mel-flufen to enhance therapeutic potential of melphalan, overcome drug-resistance, and improve multiple myeloma patient outcome. Clin Cancer Res; 19(11); 3019–31. ©2013 AACR.
Metabolomics Identifies Pyrimidine Starvation as the Mechanism of 5-Aminoimidazole-4-Carboxamide-1-β-Riboside-Induced Apoptosis in Multiple Myeloma Cells
Authors: Bardeleben Carolyne , Sharma Sanjai , Reeve Joseph R. , Bassilian Sara , Frost Patrick , Hoang Bao , Shi Yijiang , Lichtenstein Alan 
Published: April 2013

Abstract
To investigate the mechanism by which 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAr) induces apoptosis in multiple myeloma cells, we conducted an unbiased metabolomics screen. AICAr had selective effects on nucleotide metabolism, resulting in an increase in purine metabolites and a decrease in pyrimidine metabolites. The most striking abnormality was a 26-fold increase in orotate associated with a decrease in uridine monophosphate (UMP) levels, indicating an inhibition of UMP synthetase (UMPS), the last enzyme in the de novo pyrimidine biosynthetic pathway, which produces UMP from orotate and 5-phosphoribosyl-α-pyrophosphate (PRPP). As all pyrimidine nucleotides can be synthesized from UMP, this suggested that the decrease in UMP would lead to pyrimidine starvation as a possible cause of AICAr-induced apoptosis. Exogenous pyrimidines uridine, cytidine, and thymidine, but not purines adenosine or guanosine, rescued multiple myeloma cells from AICAr-induced apoptosis, supporting this notion. In contrast, exogenous uridine had no protective effect on apoptosis resulting from bortezomib, melphalan, or metformin. Rescue resulting from thymidine add-back indicated apoptosis was induced by limiting DNA synthesis rather than RNA synthesis. DNA replicative stress was identified by associated H2A.X phosphorylation in AICAr-treated cells, which was also prevented by uridine add-back. Although phosphorylation of AICAr by adenosine kinase was required to induce multiple myeloma cell death, apoptosis was not associated with AMP-activated kinase activation or mTORC1 inhibition. A possible explanation for inhibition of UMP synthase activity by AICAr was a depression in cellular levels of PRPP, a substrate of UMP synthase. These data identify pyrimidine biosynthesis as a potential molecular target for future therapeutics in multiple myeloma cells. Mol Cancer Ther; 12(7); 1310–21. ©2013 AACR.
Prognostic Significance of Biomarkers in Predicting Outcome in Patients With Coronary Artery Disease and Left Ventricular Dysfunction
Authors: Feldman Arthur M. , Mann Douglas L. , She Lilin , Bristow Michael R. , Maisel Alan S. , McNamara Dennis M. , Walsh Ryan , Lee Dorellyn L. , Wos Stanislaw , Lang Irene , Wells Gretchen , Drazner Mark H. , Schmedtje John F. , Pauly Daniel F. , Sueta Carla A. , Di Maio Michael , Kron Irving L. , Velazquez Eric J. , Lee Kerry L. 
Published: April 2013

Background—
Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting, but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the biomarker substudies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or coronary artery bypass grafting, whereas those in STICH Hypothesis 2 were randomized to coronary artery bypass grafting or coronary artery bypass grafting with left ventricular reconstruction.

Methods and Results—

In substudy patients assigned to STICH Hypothesis 1 (n=606), plasma levels of soluble tumor necrosis factor-α receptor-1 (sTNFR-1) and brain natriuretic peptide (BNP) were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP: χ
2
=40.6;
P
<0.0001 and sTNFR-1: χ
2
=38.9;
P
<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ
2
=30.3) and sTNFR-1 (χ
2
=45.5) were highly predictive in univariate analysis (
P
<0.0001) and in multivariable analysis for the primary end point of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ
2
=6.0;
P
=0.049) and sTNFR-1 (χ
2
=8.8;
P
=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in
c
-index ≤0.1), net reclassification improvement for the primary end points was 0.29 for BNP and 0.21 for sTNFR-1 in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement.

Conclusions—
Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in 2 large and independent studies, thus providing important cross-validation for the prognostic importance of these 2 biomarkers.