bluuebunny/crossref_metadata_2025_split huggingface dataset:
LDL-cholesterol decrease by anti-PCSK9 monoclonal antibodies: systematic review, meta-analysis and meta-regression of randomized controlled trials
Authors: Ma I , Angoulvant D , Azzopardi N , Ternant D , Ivanes F , Paintaud G , Bejan-Angoulvant T 
Published: November 2020

Abstract

Background
PCSK9 antibodies are novel potent and expansive lipid lowering agents that demonstrated clinical benefit in high risk patients. We hypothesized that optimization of dose and administration schedule, ideally adapted to the target population, could reduce costs while maintaining the clinical benefit.

Objective
To explore the relationship between LDL-Cholesterol (LDL-C) decrease by anti-PCSK9 monoclonal antibodies and several covariates such as drug dose, administration schedule, baseline LDL-C, population and statins.

Methods
We performed systematic review, meta-analysis and meta-regression of randomized controlled trials that compared alirocumab or evolocumab to placebo or no treatment and reported LDL-C decrease, with a minimum follow-up of 12 weeks and with a sample size of 30 patients or more. Electronic searches of MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov from inception to March 2019. We evaluated the quality of included studies and extracted aggregate data. We used random effect models and multivariate multilevel meta-regression to explore factors influencing LDL-C decrease. All analyses were performed with R.

Results
From 1479 references identified and screened on title/abstract, the full texts of 72 articles were screened. We included 32 studies (31 references.) Anti-PCSK9 mAbs decreased LDL-C by 53%, 95% CI (−56% to −50%), with no significant difference between the two drugs (p=0.07). In univariate meta-regressions, higher baseline LDL-C level, monthly administration, higher percentage of patients with high-dose statins were associated with a lower LDL-C decrease (p&lt;0.0001, p=0.02 and p=0.006 respectively). Drug dose and population did not influence LDL-C decrease in univariate analysis, but with a significant statistical interaction between drug dose and administration schedule (p=0.03). In multivariate meta-regression, LDL-C decrease remained significantly and negatively influenced by baseline LDL-C level
(p&lt;0.0001) and the percentage of patients with high-dose statins (p=0.0009), and was significantly and positively influenced by drug dose (p&lt;0.0001).

Conclusion
Alirocumab and evolocumab showed substantial LDL-C reductions in clinical trials, without significant differences in their biological efficacies. A higher baseline LDL-C, higher intensity of statin co-treatment and a lower dose seemed to negatively influence LDL-C decrease.

Funding Acknowledgement
Type of funding source: None
Selatogrel, the reversible and specific P2Y12 receptor antagonist, does not interfere with haemostasis
Authors: Riederer M.A , Crescence L , Caroff E , Hubler F , Panicot-Dubois L , Dubois C 
Published: November 2020

Abstract

Background
Combination of a P2Y12 receptor (P2Y12R) antagonist (clopidogrel, prasugrel, ticagrelor) with aspirin is the recommended standard of care for patients with acute coronary syndrome. Selatogrel is a reversible and potent antagonist of P2Y12R. Interestingly, in an experimental thrombosis model in rat, at equivalent antithrombotic effect, blood loss was lower in the presence of selatogrel, compared with clopidogrel or ticagrelor.

Purpose
To characterise the lower risk of bleeding previously observed with selatogrel

Methods
Mechanistic studies were performed to profile laser-induced thrombosis in wild-type and P2Y12 deficient mice with real-time intravital microscopy. Ticagrelor and clopidogrel were used as selatogrel comparators.

Results
Selatogrel, ticagrelor and clopidogrel dose-dependently inhibited laser-induced platelet thrombus formation. At maximal antithrombotic effect, only small mural platelets aggregates, corresponding to the haemostatic seals, were present. The phenotype of these haemostatic seals depended on the P2Y12R antagonist used. In the presence of clopidogrel or ticagrelor, the stability of haemostatic seals was reduced. In contrast, in the presence of selatogrel, the apparent stability was not disturbed. Moreover, equivalent antithrombotic dosing regimens of ticagrelor and clopidogrel interfered with laser-induced calcium mobilisation in the endothelium, restricted subsequent neutrophil adhesion and thus reduced fibrin-mediated stabilisation of the haemostatic seals in wild type mice. The effects of ticagrelor were also observed in P2Y12R-deficient mice, indicating that the effects are P2Y12R independent and off-target. In contrast, an equivalent antithrombotic dosing regimen of selatogrel did not interfere with the process of haemostasis in wild-type or P2Y12R-deficient mice. The degree of interference with the stability of the haemostatic seals correlated with the blood loss profile. The dosing regimens of clopidogrel and ticagrelor, corresponding to the equivalent antithrombotic effects, induced a more pronounced increase in blood loss than that observed with selatogrel.

Conclusion
Our data offer a novel mechanistic explanation for the differences in bleeding risk of clopidogrel, ticagrelor and selatogrel. Clopidogrel and ticagrelor were found to interfere with haemostasis due to off-target activities. In contrast, selatogrel did not interfere with haemostasis in wild-type and P2Y12-deficient mice, inferring that the process of haemostasis, as defined by formation of haemostatic seals, is independent of P2Y12R. In addition, our data emphasize that the absence of interference with haemostasis is paramount to preserve the advantage of P2Y12R antagonism.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Idorsia Pharmaceuticals Ltd. Allschwil, Switzerland
Successful case of direct puncture of a prosthetic bypass graft in endovascular treatment for long superficial artery chronic total occlusion: a case report
Authors: Sugihara Makoto , Ueda Yoko , Yano Yuiko , Miura Shin-Ichiro 
Published: November 2020

Abstract

Background
The access site for endovascular therapy (EVT) is often limited because of multi-vascular diseases. Prior lower limb bypass can potentially limit the availability of common femoral artery access when EVT is required.

Case summary
An 88-year-old woman who presented with non-healing ulceration in the dorsalis pedis of the left foot despite treatment for several months was admitted to our hospital. She had undergone axillo-bilateral femoral bypass surgery for right critical limb ischaemia 3 years previously. Ultrasound and contrast computed tomography demonstrated bypass graft occlusion, left superficial femoral artery (SFA)-popliteal artery long chronic total occlusion from the origin with severe calcification and severe stenosis in the bilateral common femoral artery close to the anastomotic site. EVT for the left SFA occlusion was necessary to save the left foot, but access sites for EVT were limited. We decided to puncture an occluded axillo-femoral prosthetic bypass graft. It is difficult to cross the wire with only an antegrade approach. Therefore, it was necessary to use a bi-directional approach with dorsalis pedis artery puncture and the Rendez-vous technique. Finally, angiogram demonstrated improved blood flow to the wound site, and haemostasis at the puncture site could be achieved by manual compression. The ulceration healed within a month.

Discussion
Direct puncture of a prosthetic bypass graft and additional techniques resulted in complete revascularization. Thus, direct puncture of a bypass graft could be a useful EVT strategy for patients with complex and extremely long chronic total occlusion.
A challenging case report of acute sinus of Valsalva aneurysm rupture in cardiogenic shock and multi-organ failure with an emphasis on rapid recognition and ‘never giving up’ in face of futility
Authors: Jin Quah Wy , Jeswant Dillon Jeffrey , Tjen Jhung Lee , Isman Rusani Beni 
Published: November 2020

Abstract

Background
Sinus of Valsalva aneurysm (SoVA) is a rare anomaly and can be divided into acquired and congenital forms, the latter being commonly associated with ventricular septal defects (VSDs). Rupture is a catastrophic complication with high mortality without urgent surgical intervention. We would like to highlight the use of echocardiography in an emergency setting for diagnosis and surgical intervention in a critically ill patient.

Case summary
We report a 27-year-old female with history of conservatively managed VSD known since childhood. She presented with acute decompensated cardiac failure requiring intubation and inotropic support. Bedside echocardiography performed in the emergency department suggested a ruptured SoVA at the right coronary cusp with underlying supracristal VSD. Despite the patient being critically ill with multi-organ failure, surgery was performed as it was the patient’s best chance for survival. Intraoperative findings tallied with the early echocardiographic results. She recovered gradually and was eventually discharged despite a stormy post-operative period.

Discussion
This case report highlights the importance of prompt recognition of SoVA rupture by using bedside echocardiography. Surgical intervention needs to be early despite ongoing sepsis in view of acute mechanical failure. This case was unique as it illustrates a successful management of an acutely ill patient with multi-organ failure through early diagnosis, intensive perioperative stabilization, and surgical intervention.
Projecting the timescale of initial increase in fishery yield after implementation of marine protected areas
Authors: Barceló Caren , White J Wilson , Botsford Louis W , Hastings Alan 
Published: November 2020

Abstract
Adaptive management of marine protected areas (MPAs) to determine whether they are meeting their intended goals requires predicting how soon those goals will be realized. Such predictions have been made for increases in fish abundance and biomass inside MPAs. However, projecting increases in fishery yield (“fishery spillover”) is more complex because it involves both how the fishery is managed and uncertainty in larval connectivity. We developed a two-patch, age-structured population model, based on a renewal equation approach, to project the initial timing of increase in fishery yield from larvae exported from a no-take MPA. Our results link our understanding of the predicted timing of increases in biomass (and thus reproduction) in MPAs with the time-lags associated with new recruits entering the fishery. We show that the time-lag between biomass peaking within the MPA and the increased fishery yield outside the MPA reaching its maximum depends, in a predictable way, on the age-dependent patterns of growth, natural mortality, and fishing mortality. We apply this analysis to 16 fishery species from the US Pacific coast; this difference ranged from 7 to 18 years. This model provides broadly applicable guidance for this important emerging aspect of fisheries management.
Measuring success: perspectives from three optimization programs on assessing impact in the age of burnout
Authors: Lourie Eli M , Stevens Lindsay A , Webber Emily C 
Published: November 2020

AbstractElectronic health record (EHR) optimization has been identified as a best practice to reduce burnout and improve user satisfaction; however, measuring success can be challenging. The goal of this manuscript is to describe the limitations of measuring optimizations and opportunities to combine assessments for a more comprehensive evaluation of optimization outcomes. The authors review lessons from 3 U.S. healthcare institutions that presented their experiences and recommendations at the American Medical Informatics Association 2020 Clinical Informatics conference, describing uses and limitations of vendor time-based reports and surveys utilized in optimization programs. Compiling optimization outcomes supports a multi-faceted approach that can produce assessments even as time-based reports and technology change. The authors recommend that objective measures of optimization must be combined with provider and clinician-defined value to provide long term improvements in user satisfaction and reduce EHR-related burnout.
Forest Resources Research in Canada
Authors: Smith J. Harry G. 
Published: November 2020

Abstract
Developments in Canadian science policy have given impetus to forest research, though funding and staffing are still inadequate. The Canadian Forestry Service (CFS) is responsible for most federal research on forest resources, and the National Research Council has stimulated university and industrial activity. While most provinces rely on CFS for research, Quebec, Ontario, and British Columbia have substantial programs of their own. At the six Canadian forestry schools the need for expansion is appreciated, but there are shortages of scientists and teachers. The Canadian Institute of Forestry is a strong advocate of research.
Managers' Views of Dispersed Recreation along Forest Roads
Authors: Downing Kent B. , Moutsinas Cynthia M. 
Published: November 2020

Abstract
A survey of public and private natural-resource managers in the Pacific Northwest revealed considerable generalized support for dispersed recreation along forest roads. Most managers indicated they would favor some activities, such as hiking, hunting, and fishing. But they would strongly discourage other activities such as extended living and most forms of off-road vehicle use.
Massive inguinoscrotal herniation of the bladder: challenges in non-operative management
Authors: Adasonla Kelvin , Gabriel Joseph , Quraishi Mohammed Kamil , Watson Graham 
Published: November 2020

Abstract
Massive inguinoscrotal hernias containing the bladder are rare but can present with significant complications such as obstructive uropathy and urinary sepsis. A comorbid 71-year-old gentleman presented with an enlarging inguinoscrotal mass and an acute kidney injury (AKI). Imaging revealed a large inguinoscrotal hernia containing the bladder, and bilateral hydronephrosis. Renal function improved on urethral catheterization. Admitted under general surgery originally, the patient declined any surgical intervention and had his catheter removed as an outpatient, without urological follow up. He represented 6 months later with urinary sepsis and a new AKI. Repeat imaging revealed a progression of the bilateral hydronephrosis. Subsequently admitted under urology, bilateral nephrostomies as well as a catheter were inserted. Once stable, he was discharged with both as part of his long-term management. Non-operative management of this condition may occasionally be necessary, and so requires effective multidisciplinary decision making. Real-world organizational and geographical factors contributed to the challenges in this case.
REM sleep behavior disorder and other sleep abnormalities in p. A53T SNCA mutation carriers
Authors: Simitsi Athina Maria , Koros Christos , Stamelou Maria , Papadimitriou Dimitra , Leonardos Athanasios , Bougea Anastasia , Papagiannakis Nikolaos , Pachi Ioanna , Angelopoulou Efthalia , Lourentzos Konstantinos , Bonakis Anastasios , Stefanis Leonidas 
Published: November 2020

Abstract

Study Objectives
Τo assess whether REM Sleep Behavior Disorder (RBD) and other sleep abnormalities occur in carriers of the p.A53T alpha-synuclein gene (SNCA) mutation, using both subjective and objective measures.

Methods
We have assessed 15 p.A53T carriers (10 manifesting Parkinson’s Disease [PD-A53T] and 5 asymptomatic carriers) with simultaneous Video-PSG (polysomnography) recording, the Epworth Sleepiness Scale (ESS) for daytime sleepiness, the Athens Insomnia Scale (AIS), the RBD Screening Questionnaire (RBDSQ) for clinical features of RBD, the Montreal Cognitive Assessment (MOCA) for cognition and the University of Pennsylvania Smell Identification Test (UPSIT) for olfaction.

Results
In our cohort, 90% of PD carriers had at least one sleep disorder and 40% had two: 4 RBD, 1 Periodic Limb Movements (PLM), 1 RBD plus PLM, 2 RBD plus moderate Obstructive Sleep Apnea (OSA), and 1 moderate OSA plus Restless Leg Syndrome. No asymptomatic carrier manifested a confirmed sleep disorder. 6/7 PD carriers with RBD had abnormal olfactory testing and 4/7 MOCA below cut off. There was a correlation of both impaired olfaction and cognition with RBD.

Conclusions
RBD occurs in the majority of PD-A53T, in contrast to most other genetic forms of PD, in which RBD is uncommon. The paucity of a sleep disorder in the asymptomatic carriers suggests that such carriers have not yet reached the prodromal phase when such sleep disorders manifest. Hyposmia in almost all subjects with RBD and cognitive decline in most of them are indicative of the general pattern of disease progression, which however is not uniform.
A Mixed-Methods Study to Investigate Barriers and Enablers to Nurses' Implementation of Nonpharmacological Interventions for Infants With Neonatal Abstinence Syndrome
Authors: Adrian Allison , Newman Susan , Mueller Martina , Phillips Shannon 
Published: November 2020

Background:
The incidence of neonatal abstinence syndrome has increased significantly as a result of the opioid epidemic. A lengthy hospitalization is often required to treat the infant's withdrawal symptoms. A comprehensive understanding of factors that influence nurses' implementation of nonpharmacological interventions for infants with neonatal abstinence syndrome is needed.

Purpose:
To investigate barriers and enablers to nurses' implementation of nonpharmacological interventions for infants with neonatal abstinence syndrome through the lens of the Theoretical Domains Framework, which provides a structure to examine factors that influence healthcare providers' behavior related to the implementation of evidence-based practice and interventions in clinical practice.

Methods:
A convergent parallel mixed-methods study was conducted. Qualitative data were collected using semistructured interviews and quantitative data were collected using a tailored Determinants of Implementation Behavior Questionnaire with neonatal nurses. Findings from the interviews and surveys were merged through joint review to compare and contrast themes.

Results:
Enablers and barriers to nurses' implementation of nonpharmacological interventions included education, experience, ability to implement nonpharmacological interventions, parental participation, stigmatization, lack of managerial/organizational support, staffing ratios, internal and external resources, and stress. Knowledge, Skills, Beliefs About Capabilities, Social/Professional Role and Identity, Organization, and Emotion of the Theoretical Domains Framework aligned with these themes.

Implications for Practice and Research:
Findings from this study will inform the development of programs to improve nurses' implementation of nonpharmacological interventions and health and utilization outcomes in infants with neonatal abstinence syndrome. Furthermore, future work should focus on the development of programs to improve nurses' implementation of nonpharmacological interventions, with specific strategies aimed to mitigate marginalization of vulnerable patient populations.
Treatment Modalities for Cherry Angiomas: A Systematic Review
Authors: Buslach Natalie , Foulad Delila P. , Saedi Nazanin , Mesinkovska Natasha Atanaskova 
Published: November 2020

BACKGROUND
Cherry angiomas are benign vascular proliferations of endothelial cells associated with aging. Currently, no mainstay of treatment for these vascular anomalies exists.

OBJECTIVE
To review existing evidence-based therapies for the treatment of cherry angiomas.

METHODS
A literature search in May 2019 was performed with PubMed Database and Cochrane Library using the following terms: “cherry angioma,” “senile hemangioma,” “senile angioma,” “cherry hemangioma,” and “Campbell de Morgan spots.”

RESULTS
Ten studies included in this systematic review reported laser therapy and nonlaser therapy as efficacious treatments for cherry angiomas. Among the laser therapies, pulsed dye laser (PDL) was preferred over potassium-titanyl-phosphate (KTP) and electrodessication (ED), based on decreased procedure-related pain. The neodymium-doped yttrium aluminum garnet (Nd:YAG) laser 1064 nm produced less pigmentary complications, whereas KTP and PDL risked pigmentary changes in darker-skinned individuals. Nonlaser therapies included cryotherapy, sclerotherapy, electrosurgery (i.e., ED, electrocoagulation), and radiofrequency ablation. No therapy proved to be superior.

CONCLUSION
A variety of therapeutic modalities exist for the treatment of cherry angiomas. However, a limited number of high-quality studies explored the efficacy of treatments and compared treatment modalities. Light-based methods such as argon, KTP, Nd:YAG, intense pulsed light, and PDL, along with non–light-based interventions such as cryotherapy, electrosurgery, and sclerotherapy effectively treated cherry angiomas.
Dry spinal tap during real-time ultrasound-guided paramedian spinal injection with patient in the lateral decubitus position
Authors: Somani Sunena , Areeruk Pornpatra , Mok Louis Yue Hong , Samy Winnie , Sivakumar Ranjith K. , Karmakar Manoj K. 
Published: November 2020

BACKGROUND
Real-time ultrasound-guided (USG) spinal injection is generally performed via the paramedian sagittal oblique (PMSO) ultrasound window.

OBJECTIVE
The aim of this retrospective study was to draw attention to the occurrence of ‘dry tap’ during real-time USG spinal injection.

DESIGN
Single-centre retrospective study.

SETTING
University teaching hospital, Hong Kong, China

PATIENTS
Data from 113 patients (aged 69.2 ± 18.0 years and BMI 22.3 ± 3.6 kg m−2) of American Society of Anesthesiologists physical status 1 to 3 scheduled for surgery under neuraxial blockade between 2007 to 2017 were reviewed.

INTERVENTIONS
Real-time USG spinal injections or combined spinal-epidural (CSE) using the PMSO ultrasound window with the patient in the lateral decubitus position and the spinal needle inserted from the nondependent side were studied.

MAIN OUTCOME MEASURES
‘Dry tap’ was defined as a failure of cerebrospinal fluid (CSF) to efflux from the hub of the needle, within 3 min, with the spinal needle visualised sonographically within the thecal sac. ‘Slow CSF efflux’ was defined as efflux of CSF within 1 to 3 min. Irrespective of whether it was a ‘dry tap’ or ‘slow CSF efflux’, the planned dose of local anaesthetic was injected through the spinal needle.

RESULTS
The combined incidence of ‘dry tap’ and ‘slow CSF efflux’ was 23.8% (27/113) with an individual incidence for each event of 9.7% (11/113) and 14.2% (16/113), respectively. Under the conditions of this study, successful spinal anaesthesia developed in all patients.

CONCLUSION
‘Dry tap’ occurs in 9.7% of cases during real-time USG spinal injection using the PMSO ultrasound window, with the patient in the lateral decubitus position and the spinal needle inserted from the nondependent side.

TRIAL REGISTRATION
ChiCTR-IOR-1800019011, Chinese Clinical Trials Registry (www.chictr.org.cn).