bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost‐Effectiveness of Cilostazol Added to Aspirin or Clopidogrel for Secondary Prevention After Noncardioembolic Stroke
Authors: Zhou Lily W. , Kraler Lironn , de Havenon Adam , Lansberg Maarten G. 
Published: June 2022

Background
The objective of the study was to assess the cost‐effectiveness of cilostazol (a selective phosphodiesterase 3 inhibitor) added to aspirin or clopidogrel for secondary stroke prevention in patients with noncardioembolic stroke.

Methods and Results
A Markov model decision tree was used to examine lifetime costs and quality‐adjusted life years (QALYs) of patients with noncardioembolic stroke treated with either aspirin or clopidogrel or with additional cilostazol 100 mg twice daily. Cohorts were followed until all patients died from competing risks or ischemic or hemorrhagic stroke. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model 10 000 cohorts of 10 000 patients. The addition of cilostazol to aspirin or clopidogrel is strongly cost saving. In all 10 000 simulations, the cilostazol strategy resulted in lower health care costs compared with aspirin or clopidogrel alone (mean $13 488 cost savings per patient; SD, $8087) and resulted in higher QALYs (mean, 0.585 more QALYs per patient lifetime; SD, 0.290). This result remained robust across a variety of sensitivity analyses, varying cost inputs, and treatment effects. At a willingness‐to‐pay threshold of $50 000/QALY, average net monetary benefit from the addition of cilostazol was $42 743 per patient over their lifetime.

Conclusions
Based on the best available data, the addition of cilostazol to aspirin or clopidogrel for secondary prevention following noncardioembolic stroke results in significantly reduced health care costs and a gain in lifetime QALYs.
Circulating S‐Glutathionylated cMyBP‐C as a Biomarker for Cardiac Diastolic Dysfunction
Authors: Zhou Xiaoxu , Jeong Euy‐Myoung , Liu Hong , Kaseer Bahaa , Liu Man , Shrestha Suvash , Imran Hafiz , Kavanagh Kylie , Jiang Ning , Desimone Lori‐Ann , Feng Feng , Shi Guangbin , Jeong Go Eun , Zhou Anyu , Stockwell Philip , Dudley Samuel C. 
Published: June 2022

Background
cMyBP‐C (Cardiac myosin binding protein‐C) regulates cardiac contraction and relaxation. Previously, we demonstrated that elevated myocardial S‐glutathionylation of cMyBP‐C correlates with diastolic dysfunction (DD) in animal models. In this study, we tested whether circulating S‐glutathionylated cMyBP‐C would be a biomarker for DD.

Methods and Results

Humans, African Green monkeys, and mice had DD determined by echocardiography. Blood samples were acquired and analyzed for S‐glutathionylated cMyBP‐C by immunoprecipitation. Circulating S‐glutathionylated cMyBP‐C in human participants with DD (n=24) was elevated (1.46±0.13‐fold,
P
=0.014) when compared with the non‐DD controls (n=13). Similarly, circulating S‐glutathionylated cMyBP‐C was upregulated by 2.13±0.47‐fold (
P
=0.047) in DD monkeys (n=6), and by 1.49 (1.22–2.06)‐fold (
P
=0.031) in DD mice (n=5) compared with the respective non‐DD controls. Circulating S‐glutathionylated cMyBP‐C was positively correlated with DD in humans.

Conclusions
Circulating S‐glutathionylated cMyBP‐C was elevated in humans, monkeys, and mice with DD. S‐glutathionylated cMyBP‐C may represent a novel biomarker for the presence of DD.
Association Between Systolic Blood Pressure Variability and Major Adverse Cardiovascular Events in Korean Patients With Chronic Kidney Disease: Findings From KNOW‐CKD
Authors: Park Cheol Ho , Kim Hyung Woo , Joo Young Su , Park Jung Tak , Chang Tae Ik , Yoo Tae‐Hyun , Park Sue Kyung , Chae Dong‐Wan , Chung Wookyung , Kim Yong‐Soo , Oh Kook‐Hwan , Kang Shin‐Wook , Han Seung Hyeok ,   on the behalf of the KNOW‐CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease) Investigators
Published: June 2022

Background
Whether visit‐to‐visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear.

Methods and Results
We investigated the relationship between SDs of visit‐to‐visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit‐to‐visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient‐years of follow‐up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit‐to‐visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80–3.36) and 2.23 (95% CI, 1.12–4.44), respectively, in a multivariable cause‐specific hazard model. In addition, the HR associated with each 5‐mm Hg increase in visit‐to‐visit SBP variability (SD) was 1.21 (95% CI, 1.01–1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03–4.35) and 2.28 (95% CI, 1.12–4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87–3.57) and 2.04 (95% CI, 1.03–4.03), respectively, with the variation independent of the mean.

Conclusions
Higher visit‐to‐visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01630486.
Genetic Determinants of Body Mass Index and Fasting Glucose Are Mediators of Grade 1 Diastolic Dysfunction
Authors: Vaitinadin Nataraja Sarma , Shi Mingjian , Shaffer Christian M. , Farber‐Eger Eric , Lowery Brandon D. , Agrawal Vineet , Gupta Deepak K. , Roden Dan M. , Wells Quinn S. , Mosley Jonathan D. 
Published: June 2022

Background
Early (grade 1) cardiac left ventricular diastolic dysfunction (G1DD) increases the risk for heart failure with preserved ejection fraction and may improve with aggressive risk factor modification. Type 2 diabetes, obesity, hypertension, and coronary heart disease are associated with increased incidence of diastolic dysfunction. The genetic drivers of G1DD are not defined.

Methods and Results

We curated genotyped European ancestry G1DD cases (n=668) and controls with normal diastolic function (n=1772) from Vanderbilt’s biobank. G1DD status was explored through (1) an additive model genome‐wide association study, (2) shared polygenic risk through logistic regression, and (3) instrumental variable analysis using 2‐sample Mendelian randomization (the inverse‐variance weighted method, Mendelian randomization‐Egger, and median) to determine potential modifiable risk factors. There were no common single nucleotide polymorphisms significantly associated with G1DD status. A polygenic risk score for BMI was significantly associated with increased G1DD risk (odds ratio [OR], 1.20 for 1‐SD increase in BMI [95% CI, 1.08–1.32];
P
=0.0003). The association was confirmed by the inverse‐variance weighted method (OR, 1.89 [95% CI, 1.37–2.61]). Among the candidate mediators for BMI, only fasting glucose was significantly associated with G1DD status by the inverse‐variance weighted method (OR, 4.14 for 1‐SD increase in fasting glucose [95% CI, 1.55–11.02];
P
=0.005). Multivariable Mendelian randomization showed a modest attenuation of the BMI association (OR, 1.84 [95% CI, 1.35–2.52]) when adjusting for fasting glucose.

Conclusions
These data suggest that a genetic predisposition to elevated BMI increases the risk for G1DD. Part of this effect may be mediated through altered glucose homeostasis.
Faculty Development Approaches for Life Support Courses: A Scoping Review
Authors: Ko Ying‐Chih , Hsieh Ming‐Ju , Cheng Adam , Lauridsen Kasper G. , Sawyer Taylor L. , Bhanji Farhan , Greif Robert , Bray Janet , Breckwoldt Jan , Duff Jonathan P , Eastwood Kathryn , Gilfoyle Elaine , Lin Yiqun , Lockey Andrew , Matsuyama Tasuku , Nation Kevin , Patocka Catherine , Pellegrino Jeffrey L , Schnaubelt Sebastian , Yang Chih‐Wei , Yeung Joyce , Finn Judith 
Published: June 2022

The aim of this scoping review initiated by the Education, Implementation and Teams Task Force of the International Liaison Committee on Resuscitation was to identify faculty development approaches to improve instructional competence in accredited life support courses. We searched PubMed, Ovid Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials to identify studies published from January 1, 1966 to December 31, 2021 on approaches to improve faculty development for life support courses. Data on participant characteristics, interventions, design, and outcomes of included studies were extracted. Of the initially identified 10 310 studies, we included 20 studies (5 conference abstracts, 1 short communication, 14 full‐length articles). Among them, 12 studies aimed to improve instructors/candidates’ teaching ability in basic life support courses. A wide variety of interventions were identified. The interventions were categorized into 4 themes: instructor qualification/training (n=9), assessment tools (n=3), teaching skills enhancement (n=3), and additional courses for instructors (n=5). Most studies showed that these interventions improved specific teaching ability or confidence of the instructors and learning outcomes in different kinds of life support courses. However, no studies addressed clinical outcomes of patients. In conclusion, the faculty development approaches for instructors are generally associated with improved learning outcomes for participants, and also improved teaching ability and self‐confidence of the instructors. It is encouraged that local organizations implement faculty development programs for their teaching staff of their accredited resuscitation courses. Further studies should explore the best ways to strengthen and maintain instructor competency, and define the cost‐effectiveness of various different faculty development strategies.
Ottoman Raiders (Akıncıs) as a Driving Force of Early Ottoman Conquest of the Balkans and the Slavery-Based Economy
Authors: Schmitt Oliver Jens , Kiprovska Mariya 
Published: June 2022

Abstract
The paper examines the akıncıs’ actions and hence the motivation for their raids as essential constituents within the process of Ottoman conquest of the Balkans in the late Middle Ages. Focusing on the raiders and their plundering activities, it asserts that the akıncıs played a crucial key role in the early Ottoman slave economy, as slave hunting was arguably the main economic driving force behind the Ottoman conquest. It hence argues that an analysis of the akıncıs allows for new insights into the nature of the early Ottoman Empire, but also advances the idea that their actions fall within a particular phase of the conquest period. To that end, the authors re-periodize the Ottoman conquest of the Balkans into the akıncı phase, which spanned eight to thirteen decades, depending on the region, and was characterized by continuous slave hunting and destruction of economic infrastructure, and the phase of administrative integration into the Ottoman Empire, which latter process was pursued by other actors, namely imperial elites from the center, and is usually characterized by at least partial repopulation of demographically weakened areas.
Ocean Reference Stations: Long-Term, Open-Ocean Observations of Surface Meteorology and Air–Sea Fluxes Are Essential Benchmarks
Authors: Weller Robert A. , Lukas Roger , Potemra James , Plueddemann Albert J. , Fairall Chris , Bigorre Sebastien 
Published: June 2022

Abstract
There is great interest in improving our understanding of the respective roles of the ocean and atmosphere in variability and change in weather and climate. Due to the sparsity of sustained observing sites in the open ocean, information about the air–sea exchanges of heat, freshwater, and momentum is often drawn from models. In this paper observations from three long-term surface moorings deployed in the trade wind regions of the Pacific and Atlantic Oceans are used to compare observed means and low-passed air–sea fluxes from the moorings with coincident records from three atmospheric reanalyses (ERA5, NCEP-2, and MERRA-2) and from CMIP6 coupled models. To set the stage for the comparison, the methodologies of maintaining the long-term surface moorings, known as ocean reference stations (ORS), and assessing the accuracies of their air–sea fluxes are described first. Biases in the reanalyses’ means and low-passed wind stresses and net air–sea heat fluxes are significantly larger than the observational uncertainties and in some case show variability in time. These reanalyses and most CMIP6 models fail to provide as much heat into the ocean as observed. In the discussion and conclusions section, long-term observing sites in the open ocean are seen as essential, independent benchmarks not only to document the coupling between the atmosphere and ocean but also to promote collaborative efforts to assess and improve the ability of models to simulate air–sea fluxes.
Extreme Heat Impacts on the Viability of Alternative Transportation for Reducing Ozone Pollution: A Case Study from Maricopa County, Arizona
Authors: Braun Rachel A. , Fraser Matthew P. 
Published: June 2022

Abstract
One commonly proposed strategy for reducing urban air pollution is transitioning from single-occupancy vehicle (SOV) travel to alternative transportation (AT) modes, such as walking, biking, and using public transportation. While many studies have addressed the benefits of switching from SOV to AT, fewer studies have examined the potential for negative outcomes due to increased exposure to heat when using AT modes. This work uses Maricopa County, Arizona, home to the metropolitan Phoenix area, as a test case to examine the potential impacts of heat on commuters who utilize AT. First, regions of the county with the most candidates for switching from SOV to AT were identified and used to develop an AT candidate index. This index was based on both the current rates of AT use and the number of SOV commuters with the shortest commuting times in the dataset (<10 min). Next, typical weather conditions during warnings for high ozone (O3) pollution were examined. From 2017 to 2020, over one-quarter of all days with an O3 warning also were subject to an excessive heat warning. Last, land surface temperature data were used to determine the potential for increased heat exposure during AT commuting at both the ZIP code and AT infrastructure (public transit stops and bikeways) scales. Although this work focuses on Maricopa County, the issues presented here are increasingly relevant for cities across the world that are subject to poor air quality, hotter temperatures, and heat waves.
Prospective case series of neuropathic cancer pain in patients treated with an EGFR-inhibitor
Authors: Cameron Marte Grønlie , Kersten Christian 
Published: June 2022

Background: Novel treatments of neuropathic pain are urgently needed. Rapid relief of neuropathic cancer pain in patients treated with epidermal growth factor receptor (EGFR) inhibitors have been reported. Experiments in rodent models confirm the pain relief and reveal novel mechanisms critically involving the EGFR. Clinical pain research is complicated and patients with advanced cancer are heterogeneous, often with complex, deteriorating clinical pictures, hampering feasibility of drug-trial procedures. Actual case: Prospective case series exploring the EGFR inhibition/neuropathic cancer pain association in order to inform planning clinical trials. Possible courses of action: Symptom assessment method was tailored to what was ethical, feasible, and clinically relevant for each patient. Formulation of a plan: Patients with neuropathic cancer pain treated off-label with the monoclonal antibody panitumumab were studied to assess feasibility of different measurement tools. Outcome: Fourteen of 20 patients (70%) experienced clinically significant pain relief. There was good concordance in patient and physician-reported outcomes. Lessons: Results support panitumumab’s potential to be of significant benefit to patients with refractory neuropathic cancer pain. Findings also reinforce the difficulty of using conventional drug trial endpoints and designs in this population. View: Innovative research methods must be considered for much needed pivotal trials.
Reducing False Alarms and Alarm Fatigue from Pulse Oximeters in a Neonatal Care Unit: A Quality Improvement Study
Authors: Patel Nawaz Z. , Patel Dipen Vasudev , Phatak Ajay Gajanan , Patel Vinit G. , Nimbalkar Somashekhar Marutirao 
Published: June 2022

Background: Pulse oximeters play a vital role in monitoring sick newborns, but majority of the times, their alarms are of little clinical significance. False alarms from pulse oximeters were frequent in our neonatal intensive care unit, causing desensitization of staff and inattention to clinically important alarms. Objectives: The objective of the study was to reduce the burden of false alarms and alarm fatigue. Methods: This was a quality improvement (QI) study. During the baseline phase, alarms for heart rate and SPO2 (percentage of oxygenated blood) were evaluated. Response to them within 30 s was checked. Major causes of false alarms were the movement of the newborns, inappropriate alarm limits, and loose probe. Fishbone chart was prepared, and Plan-Do-Study-Act (PDSA) model was designed using point of care quality improvement (POCQI) principles. During the first PDSA (implementation phase), the staff was trained to adjust alarm limits using the reference chart. A lecture on noise hazards, emphasis on muting the alarms, and advice to change probe site at beginning of their duty was given. In the second PDSA (sustenance phase), components of the first PDSA were strengthened by supportive supervision and guidance and the training of new staff. Results: Total 494, 329, and 162 alarms were observed during baseline, implementation, and sustenance phases, respectively. In the baseline phase majority, 364 (73.7%) were false alarms, which occurred at a frequency of 0.39 alarms/patient/h. More than one-third of the alarms were not responded timely. After QI, false alarms reduced to 214 (65%; 0.22 alarms/patient/h) and 100 (61.7%; 0.16 alarms/patient/h) in implementation and sustenance phases, respectively. Response to true alarms improved from 101 (77.7%) to 104 (90.4%) to 62 (100%) during the 3 phases consecutively. Conclusion: Frequent false alarms lead to desensitization of health care workers. POCQI principles can be a practical approach for reducing false alarms and improving alarm safety.
A Novel Prescription Method Reduces Postoperative Opioid Distribution and Consumption: A Randomized Clinical Trial
Authors: Yanik John M. , Glass Natalie A. , Caldwell Lindsey S. , Buckwalter V Joseph A. , Fowler Timothy P. , Lawler Ericka A. 
Published: June 2022

Background: Prescription opioid abuse in the United States has risen substantially over the past 2 decades. Narcotic prescription refill restrictions may paradoxically be contributing to this epidemic. We investigated a novel, refill-based opioid prescription method to determine whether it would alter postoperative narcotic distribution or consumption. Methods: In this randomized controlled trial, patients undergoing internal fixation of distal radius fractures or thumb carpometacarpal joint arthroplasty received either a single prescription for all postoperative narcotics (control arm) or the same amount of pain medication divided into 3 equal prescriptions to be filled as needed (experimental arm). Outcomes included total narcotics dispensed, measured in morphine milligram equivalents (MME) through a prescription monitoring program, patient-reported opioid consumption versus opioid not consumed, and a satisfaction survey. Results: Forty-eight participants were enrolled; 25 were randomized to the control arm and 23 to the experimental arm. At 8 weeks post-op, fewer opioids had been dispensed to the experimental arm (177 ± 94 vs 287 ± 123 MME, P = .0025). At 6-week follow-up, the experimental arm reported lower narcotic consumption (124 ± 105 vs 214 ± 110 MME, P = .0131). Subanalysis of the independent surgeries yielded similar results. Some patients reported insurance issues when filling subsequent prescriptions. Consequently, although 100% of control arm patients reported good pain control, only 82.6% of experimental arm patients said likewise ( P = .0455). Conclusions: This randomized clinical trial demonstrated that patients obtained and consumed fewer narcotics when postoperative opioids were given in a refill-based prescription method. More research is needed to determine whether this opioid distribution method is reproducible, translatable, and feasible.
Selective endovascular treatment of cervical arterial dissection using quantitative magnetic resonance angiography
Authors: McGuire Laura Stone , Kumar Prateek , Ryoo James S. , Alaraj Ali 
Published: June 2022

Introduction The role of endovascular treatment in cervical artery dissection (CAD) is equivocal. This study compared cerebral blood flow in CAD between medically and endovascularly treated patients using quantitative magnetic resonance angiography (QMRA). Methods Retrospective chart review was completed for patients with CAD. Inclusion criteria were adults (>18 years) with diagnosis of dissection of the internal carotid artery or vertebral artery who received QMRA. The cases were reviewed for clinical presentation, diagnosis, management, and imaging, and in particular, patients who underwent endovascular treatment were evaluated. Results Forty-one patients were included, 46.3% female and mean age 46.0+/− 11.9 years. 21 patients (51.2%) had contralateral (ICA) dissections while 19 (46.3%) had vertebral artery (VA) dissections, and 1 had both involved. Five patients underwent stenting, angioplasty, or both. Baseline characteristics between patients who underwent medical versus endovascular treatment were similar, although patients undergoing stenting/angioplasty were more likely to have diabetes (p = 0.015) and prior anticoagulation use (p = 0.007). All endovascular patients demonstrated ischemia on MRI versus 53.1% of those undergoing medical management (p = 0.047). Comparing ipsilateral vessel flow over time in these two patient groups showed those who underwent stenting or angioplasty had lower baseline flows, albeit non-significant (p = 0.629). Patients who underwent endovascular treatment had lower distal flow compared to the medical management group. Conclusion This study represents the first to assess vessel flow using QMRA in patients who underwent endovascular treatment of CAD. In combination with progressive symptoms, QMRA may serve as a useful adjunct in the selection of patients for endovascular intervention in arterial dissections.