bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a prioritisation tool for the updating of clinical guideline questions: the UpPriority Tool protocol
Authors: Martínez García Laura , Pardo-Hernandez Hector , Niño de Guzman Ena , Superchi Cecilia , Ballesteros Monica , McFarlane Emma , Penman Katrina , Posso Margarita , Roqué i Figuls Marta , Sanabria Andrea Juliana , Selva Anna , Vernooij Robin WM , Alonso-Coello Pablo 
Published: August 2017

IntroductionDue to a continuous emergence of new evidence, clinical guidelines (CGs) require regular surveillance of evidence to maintain their trustworthiness. The updating of CGs is resource intensive and time consuming; therefore, updating may include a prioritisation process to efficiently ensure recommendations remain up to date. The objective of our project is to develop a pragmatic tool to prioritise clinical questions for updating within a CG.Methods and analysisTo develop the tool, we will use the results and conclusions of a systematic review of methodological research on prioritisation processes for updating and will adopt a methodological approach we have successfully implemented in a previous experience.We will perform a multistep process including (1) generation of an initial version of the tool, (2) optimisation of the tool (feasibility test of the tool, semistructured interviews, Delphi consensus survey, external review by CG methodologists and users and pilot test of the tool) and (3) approval of the final version of the tool.At each step of the process, we will (1) calculate absolute frequencies and proportions (quantitative data), (2) use content analysis to summarise and draw conclusions (qualitative data) and (3) draft a final report, discuss results and refine the previous versions of the tool. Finally, we will calculate intraclass coefficients with 95% CIs for each item and overall as indicators of agreement among reviewers.Ethics and disseminationWe have obtained a waiver of approval from the Clinical Research Ethics Committee at the Hospital de la Santa Creu i Sant Pau (Barcelona). The results of the study will be published in peer-reviewed journal and communicated to interested stakeholders.The tool could support the standardisation of prioritisation processes for updating CGs and therefore have important implications for a more efficient use of resources in the CG field.
Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study
Authors: Sheehan Rory , Horsfall Laura , Strydom André , Osborn David , Walters Kate , Hassiotis Angela 
Published: August 2017

ObjectivesTo measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability.DesignCohort study using data from The Health Improvement Network.SettingUK primary care.ParticipantsAdults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs.Outcome measuresNew records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome.Results9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, p<0.001, after adjustment for potential confounders), with parkinsonism and akathisia showing the greatest difference between the groups. Neuroleptic malignant syndrome, although occurring infrequently, was three times more common in people with intellectual disability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013). Differences in rates of movement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs.ConclusionsThis study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group.
Cardiovascular risk after hospitalisation for unexplained syncope and orthostatic hypotension
Authors: Yasa Ekrem , Ricci Fabrizio , Magnusson Martin , Sutton Richard , Gallina Sabina , Caterina Raffaele De , Melander Olle , Fedorowski Artur 
Published: August 2017

ObjectiveTo investigate the relationship of hospital admissions due to unexplained syncope and orthostatic hypotension (OH) with subsequent cardiovascular events and mortality.MethodsWe analysed a population-based prospective cohort of 30 528 middle-aged individuals (age 58±8 years; males, 40%). Adjusted Cox regression models were applied to assess the impact of unexplained syncope/OH hospitalisations on cardiovascular events and mortality, excluding subjects with prevalent cardiovascular disease.ResultsAfter a median follow-up of 15±4 years, 524 (1.7%) and 504 (1.7%) participants were hospitalised for syncope or OH, respectively, yielding 1.2 hospital admissions per 1000 person-years for each diagnosis. Syncope hospitalisations increased with age (HR, per 1 year: 1.07, 95% CI 1.05 to 1.09), higher systolic blood pressure (HR, per 10 mm Hg: 1.06, 95% CI 1.01 to 1.12), antihypertensive treatment (HR: 1.26, 95% CI 1.00 to 1.59), use of diuretics (HR: 1.77, 95% CI 1.31 to 2.38) and prevalent cardiovascular disease (HR: 1.59, 95% CI 1.14 to 2.23), whereas OH hospitalisations increased with age (HR: 1.11, 95% CI 1.08 to 1.12) and prevalent diabetes (HR: 1.82, 95% CI 1.23 to 2.70). After exclusion of 1399 patients with prevalent cardiovascular disease, a total of 473/464 patients were hospitalised for unexplained syncope/OH before any cardiovascular event. Hospitalisation for unexplained syncope predicted coronary events (HR: 1.85, 95% CI 1.49 to 2.30), heart failure (HR: 2.24, 95% CI 1.65 to 3.04), atrial fibrillation (HR: 1.84, 95% CI 1.50 to 2.26), aortic valve stenosis (HR: 2.06, 95% CI 1.28 to 3.32), all-cause mortality (HR: 1.22, 95% CI 1.09 to 1.37) and cardiovascular death (HR: 1.72, 95% CI 1.23 to 2.42). OH-hospitalisation predicted stroke (HR: 1.66, 95% CI 1.24 to 2.23), heart failure (HR: 1.78, 95% CI 1.21 to 2.62), atrial fibrillation (HR: 1.89, 95% CI 1.48 to 2.41) and all-cause mortality (HR: 1.14, 95% CI 1.01 to 1.30).ConclusionsPatients discharged with the diagnosis of unexplained syncope or OH show higher incidence of cardiovascular disease and mortality with only partial overlap between these two conditions.
Diagnostic value of targeted next-generation sequencing in patients with suspected pancreatic or periampullary cancer
Authors: Sibinga Mulder Babs G , Mieog J Sven D , Farina Sarasqueta Arantza , Handgraaf Henricus JM , Vasen Hans F A , Swijnenburg Rutger-Jan , Luelmo Saskia A C , Feshtali Shirin , Inderson Akin , Vahrmeijer Alexander L , Bonsing Bert A , Wezel Tom van , Morreau Hans 
Published: August 2017

AimsRadiological imaging and morphological assessment of cytology material have limitations for preoperative classification of pancreatic or periampullary lesions, often resulting in surgical resection without definitive diagnosis. Our prospective study aims to define the diagnostic value of targeted next-generation sequencing (NGS) of DNA from cytology material.MethodsPatients with a suspect pancreatic or periampullary lesion underwent standard diagnostic evaluation including preoperative morphological cytology assessment. Treatment options for suspect lesions were surgical exploration with possible resection, follow-up or palliation. The cytology samples were analysed with NGS, in which 50 genes were sequenced for the presence of pathogenic variants. The NGS results were integrated with the clinical information during multidisciplinary team meetings, and changes in the treatment plan were scored. Diagnostic accuracy of NGS analysis (malignancy vs benign disease) was calculated.ResultsNGS results of the cytology samples were confirmed in the resection specimens of the first 10 included patients. The integration of the NGS results led to a change in treatment plan in 7 out of 70 patients (from exploration to follow-up, n=4; from follow-up to exploration and resection, n=2; from palliation to resection, n=1). In four patients, the NGS results were contradictory, but did not affect the treatment plan. In the remaining 59 patients, NGS analysis supported the initial treatment plan. The diagnostic accuracy of NGS analysis was 94% (sensitivity=93%; specificity=100%).ConclusionsNGS can change the treatment plan in a significant portion of patients with suspect pancreatic or periampullary lesions. Application of NGS can optimise treatment selection and diminish unnecessary surgeries.
Occupational pesticide exposure and subclinical hypothyroidism among male pesticide applicators
Authors: Lerro Catherine C , Beane Freeman Laura E , DellaValle Curt T , Kibriya Muhammad G , Aschebrook-Kilfoy Briseis , Jasmine Farzana , Koutros Stella , Parks Christine G , Sandler Dale P , Alavanja Michael C R , Hofmann Jonathan N , Ward Mary H 
Published: August 2017

ObjectivesAnimal studies suggest that exposure to pesticides may alter thyroid function; however, few epidemiologic studies have examined this association. We evaluated the relationship between individual pesticides and thyroid function in 679 men enrolled in a substudy of the Agricultural Health Study, a cohort of licensed pesticide applicators.MethodsSelf-reported lifetime pesticide use was obtained at cohort enrolment (1993-1997). Intensity-weighted lifetime days were computed for 33 pesticides, which adjusts cumulative days of pesticide use for factors that modify exposure (eg, use of personal protective equipment). Thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and antithyroid peroxidase (anti-TPO) autoantibodies were measured in serum collected in 2010-2013. We used multivariate logistic regression to estimate ORs and 95% CIs for subclinical hypothyroidism (TSH >4.5 mIU/L) compared with normal TSH (0.4-<4.5 mIU/L) and for anti-TPO positivity. We also examined pesticide associations with TSH, T4 and T3 in multivariate linear regression models.ResultsHigher exposure to the insecticide aldrin (third and fourth quartiles of intensity-weighted days vs no exposure) was positively associated with subclinical hypothyroidism (ORQ3=4.15, 95% CI 1.56 to 11.01, ORQ4=4.76, 95% CI 1.53 to 14.82, ptrend <0.01), higher TSH (ptrend=0.01) and lower T4 (ptrend=0.04). Higher exposure to the herbicide pendimethalin was associated with subclinical hypothyroidism (fourth quartile vs no exposure: ORQ4=2.78, 95% CI 1.30 to 5.95, ptrend=0.02), higher TSH (ptrend=0.04) and anti-TPO positivity (ptrend=0.01). The fumigant methyl bromide was inversely associated with TSH (ptrend=0.02) and positively associated with T4 (ptrend=0.01).ConclusionsOur results suggest that long-term exposure to aldrin, pendimethalin and methyl bromide may alter thyroid function among male pesticide applicators.
Performance of terahertz metamaterials as high-sensitivity sensor
Authors: He Yanan , Zhang Bo , Shen Jingling 
Published: August 2017

A high-sensitivity sensor based on the resonant transmission characteristics of terahertz (THz) metamaterials was investigated, with the proposal and fabrication of rectangular bar arrays of THz metamaterials exhibiting a period of 180 [Formula: see text] on a 25 [Formula: see text] thick flexible polyimide. Varying the size of the metamaterial structure revealed that the length of the rectangular unit modulated the resonant frequency, which was verified by both experiment and simulation. The sensing characteristics upon varying the surrounding media in the sample were tested by simulation and experiment. Changing the surrounding medium from that of air to that of alcohol or oil produced resonant frequency redshifts of 80 GHz or 150 GHz, respectively, which indicates that the sensor possessed a high sensitivity of 667 GHz per unit of refractive index. Finally, the influence of the sample substrate thickness on the sensor sensitivity was investigated by simulation. It may be a reference for future sensor design.
A new method to identify influential nodes based on combining of existing centrality measures
Authors: Fei Liguo , Mo Hongming , Deng Yong 
Published: August 2017

How to identify influential nodes in complex networks continues to be an open issue. A number of centrality measures have been presented to address this problem. However, these studies focus only on a centrality measure and each centrality measure has its own shortcomings and limitations. To solve the above problems, in this paper, a novel method is proposed to identify influential nodes based on combining of the existing centrality measures. Because information flow spreads in different ways in different networks, in the specific network, the appropriate centrality measures should be selected to calculate the ranking of nodes. Then, an interval can be generated for the ranking of each node, which includes the upper limit and lower limit obtained from different centrality measures. Next, the final ranking of each node can be determined based on the median of the interval. In order to illustrate the effectiveness of the proposed method, four experiments are conducted to identify vital nodes simulations on four real networks, and the superiority of the method can be demonstrated by the results of comparison experiments.
Factors Influencing Outcome in the Management of Scaphoid Non-union and Comparison of Matti Russe and Interpositional Grafting Techniques
Authors: Kiran Manish , Persaud Ian , Jariwala Arpit , Wigderowitz Carlos 
Published: August 2017

Background: Scaphoid non-union is often caused due to missed fractures, inadequate or inappropriate management. Matti-Russe and interpositional grafting techniques are used in the treatment of non-union. There are very few studies in literature that compare the outcomes of these techniques. The aim of our study was to analyse the factors influencing outcome in the management of scaphoid non-union and to compare the results of the Matti Russe procedure with interpositional grafting techniques. Methods: Fifty scaphoid non-unions with a mean follow-up of 39.9 ± 5.5 months were included in this retrospective study. Demographic parameters, treatment, functional and radiological outcomes were recorded. The influence of demographic and treatment factors on union in this cohort was statistically analysed. Results: Union was achieved in 76% of cases. Good to excellent results were achieved in 84% of patients. There was no significant difference in union rates, deformity correction achieved and period of immobilisation between the MR and IG techniques. The occurrence of arthritic changes correlated with the time interval between injury and surgery (p = 0.002). Conclusions: The most important factor that influences the outcome is the time period between the occurrence of the fracture and surgery for non-union. The Matti-Russe procedure can achieve comparable results to interpositional grafting techniques with a shorter period of immobilisation than previously thought to be required. We believe that the presence of a deformity is not a contraindication for the procedure.
Animal Models for Tendon Repair Experiments: A Comparison of Pig, Sheep and Human Deep Flexor Tendons in Zone II
Authors: Peltz Tim Sebastian , Hoffman Stuart William , Scougall Peter James , Gianoutsos Mark Peter , Savage Robert , Oliver Rema Antoinette , Walsh William Robert 
Published: August 2017

Background: This laboratory study compared pig, sheep and human deep flexor tendons in regards to their biomechanical comparability.Methods: To investigate the relevant biomechanical properties for tendon repair experiments, the tendons resistance to cheese-wiring (suture drag/splitting) was assessed. Cheese-wiring of a suture through a tendon is an essential factor for repair gapping and failure in a tendon repair.Results: Biomechanical testing showed that forces required to pulling a uniform suture loop through sheep or pig tendons in Zone II were higher than in human tendons. At time point zero of testing these differences did not reach statistical significance, but differences became more pronounced when forces were measured beyond initial cheese-wiring (2 mm, 5 mm and 10 mm). The stronger resistance to cheese-wiring was more pronounced in the pig tendons. Also regarding size and histology, sheep tendons were more comparable to human tendons than pig tendons.Conclusions: Differences in tendon bio-properties should be kept in mind when comparing and interpreting the results of laboratory tendon experiments.
The relationship between lymphangion chain length and maximum pressure generation established through in vivo imaging and computational modeling
Authors: Razavi Mohammad S. , Nelson Tyler S. , Nepiyushchikh Zhanna , Gleason Rudolph L. , Dixon J. Brandon 
Published: August 2017

The intrinsic contraction of collecting lymphatic vessels serves as a pumping system to propel lymph against hydrostatic pressure gradients as it returns interstitial fluid to the venous circulation. In the present study, we proposed and validated that the maximum opposing outflow pressure along a chain of lymphangions at which flow can be achieved increases with the length of chain. Using minimally invasive near-infrared imaging to measure the effective pumping pressure at various locations in the rat tail, we demonstrated increases in pumping pressure along the length of the tail. Computational simulations based on a microstructurally motivated model of a chain of lymphangions informed from biaxial testing of isolated vessels was used to provide insights into the pumping mechanisms responsible for the pressure increases observed in vivo. These models suggest that the number of lymphangions in the chain and smooth muscle cell force generation play a significant role in determining the maximum outflow pressure, whereas the frequency of contraction has no effect. In vivo administration of nitric oxide attenuated lymphatic contraction, subsequently lowering the effective pumping pressure. Computational simulations suggest that the reduction in contractile strength of smooth muscle cells in the presence of nitric oxide can account for the reductions in outflow pressure observed along the lymphangion chain in vivo. Thus, combining modeling with multiple measurements of lymphatic pumping pressure provides a method for approximating intrinsic lymphatic muscle activity noninvasively in vivo while also providing insights into factors that determine the extent that a lymphangion chain can transport fluid against an adverse pressure gradient. NEW & NOTEWORTHY Here, we report the first minimally invasive in vivo measurements of the relationship between lymphangion chain length and lymphatic pumping pressure. We also provide the first in vivo validation of lumped parameter models of lymphangion chains previously developed through data obtained from isolated vessel testing.
Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin
Authors: Young Jacob O. , Geurts Aron , Hodges Matthew R. , Cummings Kevin J. 
Published: August 2017

Sudden infant death syndrome (SIDS), occurring during sleep periods, is highly associated with abnormalities within serotonin (5-HT) neurons, including reduced 5-HT. There is evidence that future SIDS cases experience more apnea and have abnormal arousal from sleep. In rodents, a loss of 5-HT neurons is associated with apnea in early life and, in adulthood, delayed arousal. As the activity of 5-HT neurons changes with vigilance state, we hypothesized that the degree of apnea and delayed arousal displayed by rat pups specifically lacking central 5-HT varies with state. Two-week-old tryptophan hydroxylase 2-deficient ( TPH2−/−) and wild-type (WT) rat pups were placed in plethysmographic chambers supplied with room air. At the onset of active (AS) or quiet (QS) sleep, separate groups of rats were exposed to hypercapnia (5% CO2) or mild hypoxia (~17% O2) or maintained in room air. Upon arousal, rats received room air. Apnea indexes and latencies to spontaneous arousal from AS and QS were determined for pups exposed only to room air. Arousal latencies were also calculated for TPH2−/− and WT pups exposed to hypoxia or hypercapnia. Compared with WT, TPH2−/− pups hypoventilated in all states but were profoundly more apneic solely in AS. TPH2−/− pups had delayed arousal in response to increasing CO2, and AS selectively delayed the arousal of TPH2−/− pups, irrespective of the gas they breathed. Thus infants who are deficient in CNS 5-HT may be at increased risk for SIDS in AS because of increased apnea and delayed arousal compared with QS.NEW & NOTEWORTHY Sudden infant death syndrome (SIDS) occurs during sleep and is associated with central serotonin (5-HT) deficiency. We report that rat pups deficient in central 5-HT ( TPH2−/−) are profoundly more apneic in active sleep (AS) but not quiet sleep (QS). Unlike control pups, the arousal of TPH2−/− pups in air, CO2, and hypoxia was delayed in AS compared with QS. Thus for infants deficient in central 5-HT, the risk of SIDS may be higher in AS than in QS.
FDA Approval Summary: Trabectedin for Unresectable or Metastatic Liposarcoma or Leiomyosarcoma Following an Anthracycline-Containing Regimen
Authors: Barone Amy , Chi Dow-Chung , Theoret Marc R. , Chen Huanyu , He Kun , Kufrin Dubravka , Helms Whitney S. , Subramaniam Sriram , Zhao Hong , Patel Anuja , Goldberg Kirsten B. , Keegan Patricia , Pazdur Richard 
Published: August 2017

Abstract
On October 23, 2015, the FDA approved trabectedin, a new molecular entity for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who received a prior anthracycline-containing regimen. Approval was based on results of a single, randomized, active-controlled, 518-patient, multicenter study comparing the safety and efficacy of trabectedin 1.5 mg/m2 as a 24-hour continuous intravenous (i.v.) infusion once every 3 weeks with dacarbazine 1,000 mg/m2 i.v. once every 3 weeks. Treatment with trabectedin resulted in a statistically significant improvement in progression-free survival (PFS), with a PFS of 4.2 months and 1.5 months for trabectedin and dacarbazine, respectively (HR, 0.55; 95% confidence interval, 0.44–0.70; unstratified log-rank test, P &lt; 0.001). The most common adverse reactions (≥20%) were nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache. Serious adverse reactions included anaphylaxis, neutropenic sepsis, rhabdomyolysis, hepatotoxicity, cardiomyopathy, and extravasation resulting in tissue necrosis. A postmarketing trial was required to evaluate the serious risk of cardiomyopathy. This approval provides another treatment option in a setting where no drug has been shown to improve overall survival. A key regulatory consideration during review of this application was the use of PFS as an endpoint to support regular approval of trabectedin. Clin Cancer Res; 23(24); 7448–53. ©2017 AACR.