bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Renin‐Angiotensin System Antagonist Medication Adherence and Economic Outcomes Among Commercially Insured US Adults: A Retrospective Cohort Study
Authors: Campbell Patrick J. , Axon David R. , Taylor Ann M. , Pickering Matthew , Black Heather , Warholak Terri , Chinthammit Chanadda 
Published: August 2020

Background
Medication non‐adherence can result in considerable morbidity, mortality, and costs. The Pharmacy Quality Alliance hypertension medication adherence measure is used by US healthcare payers and providers to assess renin‐angiotensin system antagonist medication adherence. However, associations between renin‐angiotensin system antagonist adherence as calculated in quality measures, and healthcare service use and expenditure in commercial populations over a 1‐year timeframe has not been assessed.

Methods and Results
This retrospective cohort study used eligible commercially insured individuals from the Truven Health MarketScan Commercial Claims and Encounters Research Databases (2009–2015). Generalized linear models with log link and gamma distribution (expenditure) or negative binomial distribution (usage) assessed relationships between hypertension adherence (≥80% proportion of days covered) and healthcare use and expenditures (in 2015 US dollars) while adjusting for covariates (age, sex, geographic region; health plan; Deyo‐Charlson Comorbidity Index, number of chronic medications, and treatment naivety). Beta coefficients were used to compute cost ratios and rate ratios. A total of 4 842 058 subjects were eligible; of those, 3 310 360 (68%) were adherent (adherent mean age 53.3±8.0 years, 55.9% men; non‐adherent mean age 50.3±9.1 years, 53.1% men). Adherence was associated with fewer inpatient (rate ratios, 0.612; 95% CI, 0.607–0.617) and outpatient visits (rate ratios, 0.995; 95% CI, 0.994–0.997); and lower total costs (cost ratios, 0.876; 95% CI, 0.874–0.878) compared with non‐adherence. Adherence was associated with lower average per member per month total costs ($97.98) compared with non‐adherence.

Conclusions
Adherence to renin‐angiotensin system antagonists was associated with fewer outpatient and inpatient visits, and lower total costs compared with non‐adherence in a 1‐year time frame.
First Human Use of RUC‐4: A Nonactivating Second‐Generation Small‐Molecule Platelet Glycoprotein IIb/IIIa (Integrin αIIbβ3) Inhibitor Designed for Subcutaneous Point‐of‐Care Treatment of ST‐Segment–Elevation Myocardial Infarction
Authors: Kereiakes Dean J. , Henry Tim D. , DeMaria Anthony N. , Bentur Ohad , Carlson Marilyn , Seng Yue Corinne , Martin Linda H. , Midkiff Jeff , Mueller Michele , Meek Terah , Garza Deborah , Gibson C. Michael , Coller Barry S. 
Published: August 2020

Background
Despite reductions in door‐to‐balloon times for primary coronary intervention, mortality from ST‐segment–elevation myocardial infarction has plateaued. Early pre–primary coronary intervention treatment of ST‐segment–elevation myocardial infarction with glycoprotein IIb/IIIa inhibitors improves pre–primary coronary intervention coronary flow, limits infarct size, and improves survival. We report the first human use of a novel glycoprotein IIb/IIIa inhibitor designed for subcutaneous first point‐of‐care ST‐segment–elevation myocardial infarction treatment.

Methods and Results
Healthy volunteers and patients with stable coronary artery disease receiving aspirin received escalating doses of RUC‐4 or placebo in a sentinel‐dose, randomized, blinded fashion. Inhibition of platelet aggregation (IPA) to ADP (20 μmol/L), RUC‐4 blood levels, laboratory evaluations, and clinical assessments were made through 24 hours and at 7 days. Doses were increased until reaching the biologically effective dose (the dose producing ≥80% IPA within 15 minutes, with return toward baseline within 4 hours). In healthy volunteers, 15 minutes after subcutaneous injection, mean±SD IPA was 6.9%+7.1% after placebo and 71.8%±15.0% at 0.05 mg/kg (n=6) and 84.7%±16.7% at 0.075 mg/kg (n=6) after RUC‐4. IPA diminished over 90 to 120 minutes. In patients with coronary artery disease, 15 minutes after subcutaneous injection of placebo or 0.04 mg/kg (n=2), 0.05 mg/kg (n=6), and 0.075 mg/kg (n=18) of RUC‐4, IPA was 14.6%±11.7%, 53.6%±17.0%, 76.9%±10.6%, and 88.9%±12.7%, respectively. RUC‐4 blood levels correlated with IPA. Aspirin did not affect IPA or RUC‐4 blood levels. Platelet counts were stable and no serious adverse events, bleeding, or injection site reactions were observed.

Conclusions
RUC‐4 provides rapid, high‐grade, limited‐duration platelet inhibition following subcutaneous administration that appears to be safe and well tolerated.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NTC03844191.
Deep Learning Based Software to Identify Large Vessel Occlusion on Noncontrast Computed Tomography
Authors: Olive-Gadea Marta , Crespo Carlos , Granes Cristina , Hernandez-Perez Maria , Pérez de la Ossa Natalia , Laredo Carlos , Urra Xabier , Carlos Soler Juan , Soler Alexander , Puyalto Paloma , Cuadras Patricia , Marti Cristian , Ribo Marc 
Published: August 2020

Background and Purpose:
Reliable recognition of large vessel occlusion (LVO) on noncontrast computed tomography (NCCT) may accelerate identification of endovascular treatment candidates. We aim to validate a machine learning algorithm (MethinksLVO) to identify LVO on NCCT.

Methods:
Patients with suspected acute stroke who underwent NCCT and computed tomography angiography (CTA) were included. Software detection of LVO (MethinksLVO) on NCCT was tested against the CTA readings of 2 experienced radiologists (NR-CTA). We used a deep learning algorithm to identify clot signs on NCCT. The software image output trained a binary classifier to determine LVO on NCCT. We studied software accuracy when adding National Institutes of Health Stroke Scale and time from onset to the model (MethinksLVO+).

Results:
From 1453 patients, 823 (57%) had LVO by NR-CTA. The area under the curve for the identification of LVO with MethinksLVO was 0.87 (sensitivity: 83%, specificity: 71%, positive predictive value: 79%, negative predictive value: 76%) and improved to 0.91 with MethinksLVO+ (sensitivity: 83%, specificity: 85%, positive predictive value: 88%, negative predictive value: 79%).

Conclusions:
In patients with suspected acute stroke, MethinksLVO software can rapidly and reliably predict LVO. MethinksLVO could reduce the need to perform CTA, generate alarms, and increase the efficiency of patient transfers in stroke networks.
Impact of a Dense Surface Network on High-Resolution Dynamical Downscaling via Observation Nudging
Authors: Yi Xue , Li Deqin , Zhao Chunyu , Shen Lidu , Zhou Xiaoyu 
Published: August 2020

AbstractHigh-density surface networks have become available in recent years in a number of regions throughout the world, but their utility in high-resolution dynamic downscaling has not been examined. As an attempt to fill such a gap, a suite of high-resolution (4 km) dynamical downscaling simulations is developed in this study with the Weather Research and Forecasting (WRF) Model and observation nudging over Liaoning in northeastern China. Three experiments, including no nudging (CTL), analysis nudging (AN), and combined analysis nudging and observation nudging with surface observations (AON), are conducted to downscale the CFSv2 reanalysis with the WRF Model for the year 2015. The three 1-yr regional climate simulations were compared with the independent surface observations. The results show that observational nudging can improve the simulation of surface variables, including temperature, wind speed, humidity, and pressure, more than nudging large-scale driving data with AN alone. The two nudging simulations can improve the cold bias for the temperature of the WRF Model. For precipitation, both the simulations with AN and observation nudging can capture the pattern of precipitation; however, with the introduction of small-scale information at the surface, AON cannot further improve the simulation of precipitation.
A Mass and Energy Conservation Analysis of Drift in the CMIP6 Ensemble
Authors: Irving Damien , Hobbs Will , Church John , Zika Jan 
Published: August 2020

AbstractCoupled climate models are prone to “drift” (long-term unforced trends in state variables) due to incomplete spinup and nonclosure of the global mass and energy budgets. Here we assess model drift and the associated conservation of energy, mass, and salt in CMIP6 and CMIP5 models. For most models, drift in globally integrated ocean mass and heat content represents a small but nonnegligible fraction of recent historical trends, while drift in atmospheric water vapor is negligible. Model drift tends to be much larger in time-integrated ocean heat and freshwater flux, net top-of-the-atmosphere radiation (netTOA) and moisture flux into the atmosphere (evaporation minus precipitation), indicating a substantial leakage of mass and energy in the simulated climate system. Most models are able to achieve approximate energy budget closure after drift is removed, but ocean mass budget closure eludes a number of models even after dedrifting and none achieve closure of the atmospheric moisture budget. The magnitude of the drift in the CMIP6 ensemble represents an improvement over CMIP5 in some cases (salinity and time-integrated netTOA) but is worse (time-integrated ocean freshwater and atmospheric moisture fluxes) or little changed (ocean heat content, ocean mass, and time-integrated ocean heat flux) for others, while closure of the ocean mass and energy budgets after drift removal has improved.
Rossby and Yanai Modes of Tropical Instability Waves in the Equatorial Pacific Ocean and a Diagnostic Model for Surface Currents
Authors: Wang Minyang , Xie Shang-Ping , Shen Samuel S. P. , Du Yan 
Published: August 2020

AbstractMesoscale activities over the equatorial Pacific Ocean are dominated by the Rossby and Yanai modes of tropical instability waves (TIWs). The TIW-induced surface velocity has not been accurately estimated in previous diagnostic models, especially for the meridional component across the equator. This study develops a diagnostic model that retains the acceleration terms to estimate the TIW surface velocity from the satellite-observed sea surface height. Validated against moored observations, the velocity across the equator is accurately estimated for the first time, much improved from existing products. The results identify the Rossby- and Yanai-mode TIWs as the northwest–southeastward (NW–SE) velocity oscillations north of the equator and the northeast–southwestward (NE–SW) velocity oscillations on the equator, respectively. Barotropic instability is the dominant energy source of the two TIW modes. The NE–SW velocity oscillation of the Yanai mode is associated with the counterclockwise shear of the South Equatorial Current on the equator. The two TIW modes induce different sea surface temperature patterns and vertical motions. Accurate estimates of TIW velocity are important for studying equatorial ocean dynamics and climate variability in the tropical Pacific Ocean.
An Automated Common Algorithm for Planetary Boundary Layer Retrievals Using Aerosol Lidars in Support of the U.S. EPA Photochemical Assessment Monitoring Stations Program
Authors: Caicedo Vanessa , Delgado Ruben , Sakai Ricardo , Knepp Travis , Williams David , Cavender Kevin , Lefer Barry , Szykman James 
Published: August 2020

AbstractA unique automated planetary boundary layer (PBL) retrieval algorithm is proposed as a common cross-platform method for use with commercially available ceilometers for implementation under the redesigned U.S. Environmental Protection Agency Photochemical Assessment Monitoring Stations program. This algorithm addresses instrument signal quality and screens for precipitation and cloud layers before the implementation of the retrieval method using the Haar wavelet covariance transform. Layer attribution for the PBL height is supported with the use of continuation and time-tracking parameters, and uncertainties are calculated for individual PBL height retrievals. Commercial ceilometer retrievals are tested against radiosonde PBL height and cloud-base height during morning and late-afternoon transition times, critical to air quality model prediction and when retrieval algorithms struggle to identify PBL heights. A total of 58 radiosonde profiles were used, and retrievals for nocturnal stable layers, residual layers, and mixing layers were assessed. Overall good agreement was found for all comparisons, with one system showing limitations for the cases of nighttime surface stable layers and daytime mixing layer. It is recommended that nighttime shallow stable-layer retrievals be performed with a recommended minimum height or with additional verification. Retrievals of residual-layer heights and mixing-layer comparisons revealed overall good correlations with radiosonde heights (square of correlation coefficientsr2ranging from 0.89 to 0.96, and bias ranging from approximately −131 to +63 m for the residual layer andr2from 0.88 to 0.97 and bias from −119 to +101 m for the mixing layer).
Effect of Enhanced Recovery After Surgery Protocol Implementation on Cost and Outcomes by Type of Colectomy Performed
Authors: Landry Miles , Lewis Rachel , Antill Andrew , Eric Heidel R. , Taylor Jessica , Casillas Mark A. , Russ Andrew J. , Daley Brian , McLoughlin James 
Published: August 2020

Background Enhanced recovery after surgery (ERAS) protocols are widely utilized for elective colorectal surgery to improve outcomes and decrease costs, but few studies have evaluated the impact of ERAS protocols on cost with respect to anatomic site of resection. This study evaluated the impact of ERAS protocol on elective colon resections by site and longitudinal impact over time. Methods A single-center retrospective cohort study of 598 consecutive patients undergoing elective colorectal resection before and after implementation of ERAS protocol from 2013 to 2017 was performed. The primary outcomes were length of stay (LOS) and cost. Comparative and multivariate inferential statistics were used to assess additional outcomes. Results A total of 598 patients (100 pre-ERAS vs 498 post-ERAS) were evaluated with an overall median LOS of 4 days for right and left colectomies and 3 days for transverse colectomies. When comparing type of resection before and after ERAS protocol introduction, an increased LOS for left hemicolectomies from 3.09 to 4.03 days ( P = .047) was noted, with all other comparisons failing to reach statistical significance. Over time, an initial decrease in LOS for MIS approach after protocol introduction was observed; however, this effect diminished in the ensuing years and had no significant effect overall. Total cost of care was significantly increased post-ERAS for all cohorts except transverse colectomies. No further statistically significant differences were found. Conclusion After an initial improvement in outcomes, continued utilization of ERAS protocols demonstrated no improvement in LOS compared to pre-ERAS data and increased cost overall for patients regardless of site of resection.
Preclinical assessment of tramadol abuse potential: Effects of acute and repeated tramadol on intracranial self-stimulation in rats
Authors: Altarifi Ahmad A , Moerke Megan J , Alsalem Mohammad I , Negus S Stevens 
Published: August 2020

Background: Tramadol is a widely used analgesic that activates mu-opioid receptors (MOR) and inhibits serotonin and norepinephrine transporters. This mixed pharmacology may limit both its own abuse potential and its modulation of abuse potential of other MOR agonists. Aims: This study used an intracranial self-stimulation (ICSS) procedure to compare abuse-related effects produced by acute or repeated treatment with tramadol or morphine in rats. Abuse potential in ICSS procedures is indicated by a drug-induced increase (or ‘facilitation’) of ICSS responding. Methods: Adult male Sprague–Dawley rats were implanted with electrodes targeting the medial forebrain bundle and trained to respond on a lever for pulses of electrical brain stimulation. Tramadol effects were evaluated after acute administration (3.2–32 mg/kg) in the absence or presence of the opioid antagonist naltrexone, the CYP2D6 hepatic-enzyme inhibitor quinine or a combination of both. Additionally, both tramadol and morphine were also tested before and after repeated tramadol (32 mg/kg/day for six days) or repeated morphine (3.2 mg/kg/day for six days). Results: Acute tramadol produced primarily ICSS rate-decreasing effects that were antagonised by naltrexone but not by quinine or naltrexone + quinine. Tramadol also produced little or no ICSS facilitation after repeated tramadol or repeated morphine, and repeated tramadol did not enhance ICSS facilitation by morphine. By contrast, morphine-induced ICSS facilitation was enhanced by repeated morphine treatment. Conclusions: These results suggest that tramadol has lower abuse potential than other abused MOR agonists and that repeated tramadol exposure produces relatively little enhancement of abuse potential of other MOR agonists.
Hypertension and orthostatic hypotension with venlafaxine treatment in depressed older adults
Authors: Wathra Rafae , Mulsant Benoit H , Thomson Lauren , Goldberger Kyle W , Lenze Eric J , Karp Jordan F , Sanches Marcos , Reynolds Charles F , Blumberger Daniel M 
Published: August 2020

Background: Venlafaxine, a serotonin–norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects. Methods: Adults ⩾60 years of age in a current major depressive episode were treated in a protocolized manner with venlafaxine XR; 429 participants were treated for 8–16 weeks with a daily dose up to 300 mg to achieve remission from depression. Cardiac measures included sitting and standing BP and heart rate. Results: Of participants who were normotensive at baseline, 6.5% were found to have elevated BP during the study (1.9% <225 mg/day; 9.8% ⩾225 mg/day). There was no significant change in mean BP in the overall sample, or in the subgroup treated with doses ⩾225 mg/day. Additionally, 20.1% of the participants who did not have orthostatic hypotension at baseline were found to have orthostatic hypotension (16.8% <225 mg/day; 22.4% ⩾225 mg/day). Participants with new-onset orthostatic hypotension were significantly more likely to fall than the other participants. Conclusion: A large proportion of older adults treated with venlafaxine experience orthostatic hypotension, putting them at risk for falls. A smaller proportion experience elevated BP. Older patients prescribed venlafaxine, particularly at high doses, should be advised and counseled about these adverse effects.
Asymmetric dimethylarginine predicts perioperative cardiovascular complications in patients undergoing medium-to-high risk non-cardiac surgery
Authors: Appel Daniel , Böger Rainer , Windolph Julia , Heinze Gina , Goetz Alwin E. , Hannemann Juliane 
Published: August 2020

Objectives Perioperative cardiovascular events remain an important factor that affects surgery outcome. We assessed if asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, predicts perioperative risk, and if pre-operative supplementation with L-arginine/L-citrulline improves the plasma L-arginine/ADMA ratio. Methods In this prospective study, planned thoracic and/or abdominal surgery patients were randomized to receive L-arginine/L-citrulline (5 g/day) or placebo 1 to 5 days before surgery. We measured perioperative plasma ADMA and L-arginine levels. The primary outcome was a 30-day combined cardiovascular endpoint. Results Among 269 patients, 23 (8.6%) experienced a major adverse cardiovascular event. ADMA and C-reactive protein were significantly associated with the incidence of cardiovascular complications in the multivariable-adjusted analysis. The L-arginine plasma concentration was significantly higher on the day of surgery with L-arginine/L-citrulline supplementation compared with placebo. In patients with high pre-operative ADMA, there was a non-significant trend towards reduced incidence of the primary endpoint with L-arginine/L-citrulline supplementation (six vs. nine events). Conclusions ADMA is a predictor of major adverse cardiovascular complications in the perioperative period for patients who are undergoing major abdominal and/or thoracic surgery. Supplementation with L-arginine/L-citrulline increased the L-arginine plasma concentration, enhanced the L-arginine/ADMA ratio, and induced a trend towards fewer perioperative events.
Innovative alignment of sprinting prostheses for persons with transfemoral amputation: Exploratory study on a gold medal Paralympic athlete
Authors: Migliore Gian Luca , Petrone Nicola , Hobara Hiroaki , Nagahara Ryu , Miyashiro Kenji , Costa Gian Fabio , Gri Antonio , Cutti Andrea G 
Published: August 2020

Background:
Recommendations for the alignment of the socket and foot in the sprinting prosthesis of athletes with transfemoral amputation are either based on walking biomechanics or lack public scientific evidence.

Objectives:
To explore the biomechanical changes and the sensations of a gold medal Paralympic sprinter, while running with three bench alignments: a conventional reference (A0), an innovative alignment based on the biomechanics of elite able-bodied sprinters (A2), and an intermediate alignment (A1).

Study design:
Single subject with repeated measures.

Methods:
A1 and A2 feature a progressively greater socket tilt and a plantar-flexed foot compared to A0. The 30-year-old female athlete trained with three prostheses, one per alignment, for at least 2 months. We administered a questionnaire to collect her impressions. Then, she ran on a treadmill at full speed (5.5 m/s). We measured the kinematics and moments of the prosthetic side, and the ground reaction forces of both sides.

Results:
A2 reduced the prosthetic side hip extension at foot-off while preserving hip range of motion, decreased the impulse of the hip moment, and increased the horizontal propulsion, leaving sufficient margin to prevent knee buckling without increasing sound side braking forces. Biomechanical outcomes matched well with subjective impressions.

Conclusions:
A2 appears promising to improve the performance and comfort of sprinters with transfemoral amputation, without compromising safety.

Clinical relevance:
Observation of elite able-bodied sprinters led to the definition of a new specific alignment for the sprinting prosthesis of athletes with transfemoral amputation, which appears promising to improve performance and comfort, without compromising safety. This may constitute a major improvement compared to alignments based on walking biomechanics.