bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia
Authors: Toth Peter P. , Worthy Gillian , Gandra Shravanthi R. , Sattar Naveed , Bray Sarah , Cheng Lung‐I. , Bridges Ian , Worth Gavin M. , Dent Ricardo , Forbes Carol A. , Deshpande Sohan , Ross Janine , Kleijnen Jos , Stroes Erik S. G. 
Published: October 2017

Background

The proprotein convertase subtilisin/kexin type 9 (
PCSK
9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (
LDL
‐C) when added to statin therapy in patients who need additional
LDL
‐C reduction.

Methods and Results

We conducted a systematic review and network meta‐analysis of randomized trials of lipid‐lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid‐lowering therapies that enrolled patients requiring further
LDL
‐C reduction while on maximally tolerated medium‐ or high‐intensity statin, of which 15 could be relevant for inclusion in
LDL
‐C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms.
PCSK
9 inhibitors significantly reduced
LDL
‐C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (−74.1%; 95% credible interval −79.81% to −68.58%), alirocumab 75 mg (−20.03%; 95% credible interval −27.32% to −12.96%), and alirocumab 150 mg (−13.63%; 95% credible interval −22.43% to −5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for
PCSK
9 inhibitor monthly dosing. Adverse events were similar between
PCSK
9 inhibitors and control. Rates of adverse events were similar between
PCSK
9 inhibitors versus placebo or ezetimibe.

Conclusions

PCSK
9 inhibitors added to medium‐ to high‐intensity statin therapy significantly reduce
LDL
‐C in patients requiring further
LDL
‐C reduction. The network meta‐analysis showed a significant treatment difference in
LDL
‐C reduction for evolocumab versus alirocumab.
DBZ (Danshensu Bingpian Zhi), a Novel Natural Compound Derivative, Attenuates Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Wang Jing , Xu Pengfei , Xie Xinni , Li Jiao , Zhang Jun , Wang Jialin , Hong Fan , Li Jian , Zhang Youyi , Song Yao , Zheng Xiaohui , Zhai Yonggong 
Published: October 2017

Background

DBZ (Danshensu Bingpian Zhi), a synthetic derivative of a natural compound found in traditional Chinese medicine, has been reported to suppress lipopolysaccharide‐induced macrophage activation and lipid accumulation in vitro. The aim of this study was to assess whether
DBZ
could attenuate atherosclerosis at early and advanced stages.

Methods and Results

The effects of
DBZ
on the development of atherosclerosis were studied using apolipoprotein E–deficient (apoE
−/−
) mice. For early treatment, 5‐week‐old apoE
−/−
mice were fed a Western diet and treated daily by oral gavage with or without
DBZ
or atorvastatin for 10 weeks. For advanced treatment, 5‐week‐old apoE
−/−
mice were fed a Western diet for 10 weeks to induce atherosclerosis, and then they were randomly divided into 4 groups and subjected to the treatment of vehicle, 20 mg/kg per day
DBZ
, 40 mg/kg per day
DBZ
, or 10 mg/kg per day atorvastatin for the subsequent 10 weeks. We showed that early treatment of apoE
−/−
mice with
DBZ
markedly reduced atherosclerotic lesion formation by inhibiting inflammation and decreasing macrophage infiltration into the vessel wall. Treatment with
DBZ
also attenuated the progression of preestablished diet‐induced atherosclerotic plaques in apoE
−/−
mice. In addition, we showed that
DBZ
may affect LXR (liver X receptor) function and that treatment of macrophages with
DBZ
suppressed lipopolysaccharide‐stimulated cell migration and oxidized low‐density lipoprotein–induced foam cell formation.

Conclusions

DBZ
potentially has antiatherosclerotic effects that involve the inhibition of inflammation, macrophage migration, leukocyte adhesion, and foam cell formation. These results suggest that
DBZ
may be used as a therapeutic agent for the prevention and treatment of atherosclerosis.
National Trends in Patients Hospitalized for Stroke and Stroke Mortality in France, 2008 to 2014
Authors: Lecoffre Camille , de Peretti Christine , Gabet Amélie , Grimaud Olivier , Woimant France , Giroud Maurice , Béjot Yannick , Olié Valérie 
Published: October 2017

Background and Purpose—
Stroke is the leading cause of death in women and the third leading cause in men in France. In young adults (ie, <65 years old), an increase in the incidence of ischemic stroke was observed at a local scale between 1985 and 2011. After the implementation of the 2010 to 2014 National Stroke Action Plan, this study investigates national trends in patients hospitalized by stroke subtypes, in-hospital mortality, and stroke mortality between 2008 and 2014.

Methods—
Hospitalization data were extracted from the French national hospital discharge databases and mortality data from the French national medical causes of death database. Time trends were tested using a Poisson regression model.

Results—
From 2008 to 2014, the age-standardized rates of patients hospitalized for ischemic stroke increased by 14.3% in patients <65 years old and decreased by 1.5% in those aged ≥65 years. The rate of patients hospitalized for hemorrhagic stroke was stable (+2.0%), irrespective of age and sex. The proportion of patients hospitalized in stroke units substantially increased. In-hospital mortality decreased by 17.1% in patients with ischemic stroke. From 2008 to 2013, stroke mortality decreased, except for women between 45 and 64 years old and for people aged ≥85 years.

Conclusions—
An increase in cardiovascular risk factors and improved stroke management may explain the increase in the rates of patients hospitalized for ischemic stroke. The decrease observed for in-hospital stroke mortality may be because of recent improvements in acute-phase management.
CMIP5 Diversity in Southern Westerly Jet Projections Related to Historical Sea Ice Area: Strong Link to Strengthening and Weak Link to Shift
Authors: Bracegirdle Thomas J. , Hyder Patrick , Holmes Caroline R. 
Published: October 2017

Abstract
A major feature of projected changes in Southern Hemisphere climate under future scenarios of increased greenhouse gas concentrations is the poleward shift and strengthening of the main eddy-driven belt of midlatitude, near-surface westerly winds (the westerly jet). However, there is large uncertainty in projected twenty-first-century westerly jet changes across different climate models. Here models from the World Climate Research Programme’s phase 5 of the Coupled Model Intercomparison Project (CMIP5) were evaluated to assess linkages between diversity in simulated sea ice area (SIA), Antarctic amplification, and diversity in projected twenty-first-century changes in the westerly jet following the representative concentration pathway 8.5 (RCP8.5) scenario. To help disentangle cause and effect in the coupled model analysis, uncoupled atmosphere-only fixed sea surface experiments from CMIP5 were also evaluated. It is shown that across all seasons, approximately half of the variance in projected RCP8.5 jet strengthening is explained statistically by intermodel differences in simulated historical SIA, whereby CMIP5 models with larger baseline SIA exhibit more ice retreat and less jet strengthening in the future. However, links to jet shift are much weaker and are only statistically significant in austral autumn and winter. It is suggested that a significant cross-model correlation between historical jet strength and projected strength change (r = −0.58) is, at least in part, a result of atmospherically driven historical SIA biases, which then feed back into the atmosphere in future projections. The results emphasize that SIA appears to act in concert with proximal changes in sea surface temperature gradients in relation to model diversity in westerly jet projections.
Cumulative Mass and NIOSH Variable Lifting Index Method for Risk Assessment: Possible Relations
Authors: Stucchi Giulia , Battevi Natale , Pandolfi Monica , Galinotti Luca , Iodice Simona , Favero Chiara 
Published: October 2017

Objective The aim of this study was to explore whether the Variable Lifting Index (VLI) can be corrected for cumulative mass and thus test its efficacy in predicting the risk of low-back pain (LBP). Background A validation study of the VLI method was published in this journal reporting promising results. Although several studies highlighted a positive correlation between cumulative load and LBP, cumulative mass has never been considered in any of the studies investigating the relationship between manual material handling and LBP. Method Both VLI and cumulative mass were calculated for 2,374 exposed subjects using a systematic approach. Due to high variability of cumulative mass values, a stratification within VLI categories was employed. Dummy variables (1–4) were assigned to each class and used as a multiplier factor for the VLI, resulting in a new index (VLI_CMM). Data on LBP were collected by occupational physicians at the study sites. Logistic regression was used to estimate the risk of acute LBP within levels of risk exposure when compared with a control group formed by 1,028 unexposed subjects. Results Data showed greatly variable values of cumulative mass across all VLI classes. The potential effect of cumulative mass on damage emerged as not significant ( p value = .6526). Conclusion When comparing VLI_CMM with raw VLI, the former failed to prove itself as a better predictor of LBP risk. Application To recognize cumulative mass as a modifier, especially for lumbar degenerative spine diseases, authors of future studies should investigate potential association between the VLI and other damage variables.
Using Temporal Sensitivity to Predict Performance Under Latency in Teleoperation
Authors: Scholcover Federico , Gillan Douglas J. 
Published: October 2017

Objective This article establishes a relationship between temporal sensitivity and task performance under one-way latency between input and response. Background As the latency between human input and telerobot response increases, performance (e.g., speed to complete task and accuracy) declines. Tools, such as predictive displays, have been developed to ameliorate performance costs. However, more work is needed to understand the relationship between individual differences and task performance. Temporal sensitivity in particular was the focus of this research. Method Participants completed two tasks. In the time estimation task, participants estimated the duration of a series of visual stimuli. In the second task, participants drove a remote-controlled (RC) car through a track. On each trial, there was a latency between the participant’s input into the controller and the response by the RC car, with latencies ranging from 400 to 1,000 milliseconds between trials. Completion time and the number of errors made were recorded. Results Temporal sensitivity predicted the total number of errors made during a trial but was not found to be a predictor of completion time. It was however predictive of error rate (i.e., errors per minute), suggesting a possible speed/accuracy trade-off. Conclusion This was an initial step in establishing a link between temporal sensitivity and performance with latency. Application The study has applications toward training teleoperators who may experience latency, such as astronauts and surgeons.
What Do Patients Want from Otolaryngologists? A Discrete Choice Experiment
Authors: Naunheim Matthew R. , Rathi Vinay K. , Naunheim Margaret L. , Alkire Blake C. , Lam Allen C. , Song Phillip C. , Shrime Mark G. 
Published: October 2017

ObjectivesPatient preferences are crucial for the delivery of patient‐centered care. Discrete choice experiments (DCEs) are an emerging quantitative methodology used for understanding these preferences. In this study, we employed DCE techniques to understand the preferences of patients presenting for an ear, nose, and throat clinic visit.Study DesignDCE.SettingDecision science laboratory.MethodsA DCE survey of 5 attributes—wait time, physician experience, physician personality, utilization of visit time, and cost/copayment—was constructed with structured qualitative interviews with patients. The DCE was administered to participants from the general population, who chose among hypothetical scenarios that varied across these attributes. A conditional logit model was used to determine relative attribute importance, with a separate logit model for determining subject effects.ResultsA total of 161 participants were included. Cost/copayment had the greatest impact on decision making (importance, 32.2%), followed by wait time and physician experience (26.5% and 24.7%, respectively). Physician personality mattered least (4.7%), although all attributes were significantly correlated to decision making. Participants preferred doctors who spent more time performing physical examination than listening or explaining. Participants were willing to pay $52 extra to avoid a 4‐week delay in appointment time; $87 extra for a physician with 10 years of experience (vs 0 years); and $9 extra for a caring, friendly, and compassionate doctor (vs formal, efficient, and business‐like).ConclusionDCEs allow for powerful economic analyses that may help physicians understand patient preferences. Our model showed that cost is an important factor to patients and that patients are willing to pay extra for timely appointments, experience, and thorough physical examination.
Computed tomography-guided preoperative localization of small lung nodules with indocyanine green
Authors: Nagai Keisuke , Kuriyama Keiko , Inoue Atsuo , Yoshida Yuriko , Takami Koji 
Published: October 2017

Background Small, deep-seated lung nodules and sub-solid nodules are often difficult to locate without marking. Purpose To evaluate the success and complication rates associated with the use of indocyanine green (ICG) to localize pulmonary nodules before resection. Material and Methods This retrospective study was approved by our institutional review board. Informed consent for performing preoperative localization using ICG marking was obtained from all patients. Thirty-seven patients (14 men, 23 women; mean age = 63.1 years; age range = 10–82 years) with small peripheral pulmonary nodules underwent computed tomography (CT)-guided ICG marking immediately before surgery between March 2007 and June 2016. The procedural details and complication rates associated with ICG marking are described. Results The average nodule size and depth were 9.1 mm (range = 2–22 mm) and 9.9 mm (range = 0–33 mm), respectively. Marking was detected at the pleural surface in 35 patients (95%). Three cases of mild pneumothorax (8%), five cases of cough (14%), and one case of mild bloody sputum (3%) with no clinical significance were noted. There were no severe complications. The average duration required to perform the marking was 19.4 min (range = 12–41 min). Conclusion Our results indicate that CT-guided ICG marking is safe and useful for detecting the location of small pulmonary nodules preoperatively.
CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior
Authors: Filiz Aslı , Tepe Nermin , Eftekhari Sajedeh , Boran H Evren , Dilekoz Ergin , Edvinsson Lars , Bolay Hayrunnisa 
Published: October 2017

Background and objective The present study aimed to investigate the effects of selective calcitonin gene related peptide (CGRP) receptor antagonist (MK-8825) on cortical spreading depression (CSD) induced pain behavior and anxiety in freely-moving rats, and neuronal activation in the correlated anatomical regions. Methods CSD was induced while keeping all meningeal layers and BBB intact and MK-8825 was administered in two different doses. Regional cerebral blood flow (rCBF), arterial pressure and DC shift were recorded. Behavioral studies were conducted in freely-moving rats. Spontaneous behavior, mechanical allodynia, ultrasonic vocalization, and anxiety were evaluated. Immunohistochemistry of c-fos, CGRP, calcitonin receptor like-receptor (CLR) and receptor activity modifying protein 1 (RAMP1) were studied. Results MK-8825 did not block DC shifts in the cerebral cortex and accompanied hemodynamic response. CSD significantly induced freezing and grooming behavior in freely-moving rats. MK-8825 reversed increased episodes of freezing, grooming, wet dog shake and head shake behavior. MK-8825 increased CSD-induced reductions in von Frey thresholds, but did not change elevated plus maze results. MK-8825 blocked c-fos induction by CSD in the brainstem trigeminal nucleus caudalis (TNC) and reticular nucleus of thalamus (TRN) but not in the amygdala. Immunofluorescence analysis showed no co-localization of CGRP, CLR or RAMP1 with c-fos positive cells. Conclusion CGRP receptor antagonist MK-8825 dose dependently attenuated CSD-induced trigeminal nerve mediated pain response without altering CSD waves and accompanied rCBF response. While blocking TNC activation, MK-8825 did not exert any effect on amygdala and anxiety behavior. CGRP receptor antagonists may also modulate thalamo-cortical gating.
A Prospective Evaluation of Femoral Tunnel Placement for Anatomic Anterior Cruciate Ligament Reconstruction Using 3-Dimensional Magnetic Resonance Imaging
Authors: Hart Adam , Sivakumaran Thiru , Burman Mark , Powell Tom , Martineau Paul A. 
Published: October 2017

Background: The recent emphasis on anatomic reconstruction of the anterior cruciate ligament (ACL) is well supported by clinical and biomechanical research. Unfortunately, the location of the native femoral footprint can be difficult to see at the time of surgery, and the accuracy of current techniques to perform anatomic reconstruction is unclear. Purpose: To use 3-dimensional magnetic resonance imaging (3D MRI) to prospectively evaluate patients with torn ACLs before and after reconstruction and thereby assess the accuracy of graft position on the femoral condyle. Study Design: Cohort study; Level of evidence, 3. Methods: Forty-one patients with unilateral ACL tears were recruited into the study. Each patient underwent 3D MRI of both the injured and uninjured knees before surgery. The contralateral (uninjured) knee was used to define the patient’s native footprint. Patients then underwent ACL reconstruction, and the injured knee underwent reimaging after surgery. The location and percentage overlap of the reconstructed femoral footprint were compared with the patient’s native footprint. Results: The center of the native ACL femoral footprint was a mean 12.0 ± 2.6 mm distal and 9.3 ± 2.2 mm anterior to the apex of the deep cartilage. The position of the reconstructed graft was significantly different, with a mean distance of 10.8 ± 2.2 mm distal ( P = .02) and 8.0 ± 2.3 mm anterior ( P = .01). The mean distance between the center of the graft and the center of the native ACL femoral footprint (error distance) was 3.6 ± 2.6 mm. Comparing error distances among the 4 surgeons demonstrated no significant difference ( P = .10). On average, 67% of the graft overlapped within the native ACL femoral footprint. Conclusion: Despite contemporary techniques and a concerted effort to perform anatomic ACL reconstruction by 4 experienced sports orthopaedic surgeons, the position of the femoral footprint was significantly different between the native and reconstructed ACLs. Furthermore, each surgeon used a different technique, but all had comparable errors in their tunnel placements.
Societal Costs of Micronutrient Deficiencies in 6- to 59-month-old Children in Pakistan
Authors: Wieser Simon , Brunner Beatrice , Tzogiou Christina , Plessow Rafael , Zimmermann Michael B. , Farebrother Jessica , Soofi Sajid , Bhatti Zaid , Ahmed Imran , Bhutta Zulfiqar A. 
Published: October 2017

Background: In Pakistan, nearly half of children younger than 5 years are stunted, and 1 in 3 is underweight. Micronutrient deficiencies, a less visible form of undernutrition, are also endemic. They may lead to increased morbidity and mortality as well as to impaired cognitive and physical development. Objective: To estimate the lifetime costs of micronutrient deficiencies in Pakistani children aged between 6 and 59 months. Methods: We develop a health economic model of the lifetime health and cost consequences of iodine, iron, vitamin A, and zinc deficiencies. We assess medical costs, production losses in terms of future incomes lost, and disability-adjusted life-years (DALYs). The estimation is based on large population surveys, information on the health consequences of micronutrient deficiencies extracted from randomized trials, and a variety of other sources. Results: Total societal costs amount to US$46 million in medical costs, US$3,222 million in production losses, and 3.4 million DALYs. Costs are dominated by the impaired cognitive development induced by iron-deficiency anemia in 6- to 23-month-old children and the mortality caused by vitamin A deficiency. Costs are substantially higher in poorer households. Conclusions: Societal costs amounted to 1.44% of gross domestic product and 4.45% of DALYs in Pakistan in 2013. These costs hinder the country's development. They could be eliminated by improved nutrition of 6- to 59-month-old children and public health measures. Our results may contribute to the design of cost-effective interventions aiming to reduce micronutrient deficiencies in early childhood and their lifetime consequences.
Household Consumption of Orange-Fleshed Sweet Potato and its Associated Factors in Chipata District, Eastern Province Zambia
Authors: Sakala Patricia , Kunneke Ernesta , Faber Mieke 
Published: October 2017

Background: The Integrating Orange Project promotes production and consumption of orange-fleshed sweet potato (OFSP) to address vitamin A deficiency among rural populations of Zambia since 2011. Objective: This study assessed household production and consumption of OFSP and identified factors associated with consumption thereof in Integrating Orange Project areas in Chipata district, Zambia. Methods: Respondents of 295 randomly selected households were interviewed using a structured questionnaire during the sweet potato harvest season. Associations between OFSP consumption and household factors were assessed using χ2 tests. Results: Frequency of OFSP consumption was categorized as ≥4 days during the last 7 days (30.2%), 1 to 3 days during the last 7 days (49.5%), eats OFSP but not during the last 7 days (7.1%), and never (13.2%). In total, 60.3% of households planted OFSP, and 40.0% bought OFSP, mostly from farmers within the community. Orange-fleshed sweet potato consumption was associated with the presence of children aged less than 5 years in the household ( P = .018), production of OFSP ( P < .001), purchasing of OFSP ( P < .001), and respondent having knowledge on health benefits of OFSP ( P = .014). Age and sex of the household head and household size had no association with OFSP consumption ( P > .05). Conclusion: A high percentage of households consumed OFSP during the harvesting season in Integrating Orange Project areas. Programs promoting OFSP consumption should thus focus on OFSP production and sensitizing households on nutritional benefits of OFSP and target households with children aged less than 5 years as entry point.