bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local anaesthetics combined with vasoconstrictors in patients with cardiovascular disease undergoing dental procedures: systematic review and meta-analysis
Authors: Guimaraes Caio Chaves , Lopes Luciane Cruz , Bergamaschi Cristiane de Cássia , Ramacciato Juliana Cama , Silva Marcus Tolentino , Araújo Jimmy de Oliveira , de Andrade Natalia Karol , Motta Rogério Heládio Lopes 
Published: July 2021

ObjectivesThere is a lack of evidence about the use of local anaesthetics (LAs) in patients with cardiovascular diseases (CVD) in dental procedures. Thus, this study evaluated the safety of using LA with vasoconstrictor to determine the risk of cardiovascular events in patients with CVD.DesignSystematic review and meta-analysis.MethodsWe have searched in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid), EMBASE (via Ovid), Healthstar (via Ovid), CINAHL, Web of Science and ClinicalTrials.gov for randomised controlled trials (RCTs) up to January 2020. We have included RCTs involving adults with CVD within two groups: intervention group with LA with vasoconstrictor and control group with LA without vasoconstrictor. The primary outcomes assessed were death, mortality by a specific cause, stroke, acute myocardial infarction, hospitalisation, pain, bleeding and arrhythmias. The secondary outcomes were ST segment depression, anxiety, adverse effects and changes in haemodynamic parameters. The data were pooled using random effects meta-analyses and the confidence in the estimates was verified using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsTen RCTs (n=478 participants) were included. Most of them had a high risk of bias. There were more cases of pain and bleeding in groups without vasoconstrictor. Meta-analysis demonstrated a decrease in the systolic blood pressure with the use of LA with vasoconstrictor (standard mean difference −0.95, 95% CI −1.35 to −0.55) after procedure. Overall, for the other outcomes assessed there was no statistical difference. The quality of evidence was considered low according to the GRADE profile.ConclusionsThe results suggest that the use of LA with vasoconstrictors (epinephrine in low doses) is safe in patients with some types of CVD. However, the low quality of evidence demonstrated that literature needs further studies in order to confirm these results.Protocol registrationPROSPERO (CRD42016045421).
Determinants of drug prices: a systematic review of comparison studies
Authors: Janssen Daalen Jules M , den Ambtman Anouk , Van Houdenhoven Mark , van den Bemt Bart J F 
Published: July 2021

ObjectiveIn this systematic review on drug price comparison studies, we report on recent determinants of drug prices in a national and international context to facilitate regulation of drug prices by purchasers and policymakers worldwide. Determinants of drug prices were divided into non-modifiable and modifiable and were categorised as pertaining to a country’s income level, pharmaceutical market system and its policies and government.Primary outcomeDeterminants of drug prices or price variance.DesignWe systematically searched PubMed, EMBASE, Web of Science and Cochrane Library for peer-reviewed articles published between 2004 and 22 July 2020 that reported an association of the primary outcome with one or more determinants. We performed a best-evidence synthesis of these associations for determinants covered in at least three studies.Results31 publications were included. Only one publication described net drug prices and 30 described retail drug prices. Five modifiable determinants were associated with lower retail prices: generic market portion, discounts, tendering policies, central (governmental) purchasing and pricing regulation schemes. The originators market portion and a system in which mark-ups are common were associated with higher retail prices. Retail prices were highest in the USA, even compared with other high-income countries. A positive association between national income level and drug retail prices could not be established among middle-income and high-income countries. Retail prices were highest in low-income countries when adjusted for purchasing power parity.ConclusionsLiterature on determinants of net drug prices is extremely sparse. Various healthcare system interventions, market-specific and governmental regulations are consistently associated with lower retail prices. Some interventions are easily implementable in developing or middle-income countries, such as tendering, central purchasing and fixed pricing regulation schemes. Net drug price comparison studies are needed to overcome the lack of price transparency and to quantify the effectiveness of policy measures on net drug prices.
Cohort profile of Acutelines: a large data/biobank of acute and emergency medicine
Authors: ter Avest Ewoud , van Munster Barbara C , van Wijk Raymond J , Tent Sanne , Ter Horst Sanne , Hu Ting Ting , van Heijst Lisanne E , van der Veer Felien S , van Beuningen Fleur E , ter Maaten Jan Cornelis , Bouma Hjalmar R 
Published: July 2021

PurposeResearch in acute care faces many challenges, including enrolment challenges, legal limitations in data sharing, limited funding and lack of singular ownership of the domain of acute care. To overcome these challenges, the Center of Acute Care of the University Medical Center Groningen in the Netherlands, has established a de novo data, image and biobank named ‘Acutelines’.ParticipantsClinical data, imaging data and biomaterials (ie, blood, urine, faeces, hair) are collected from patients presenting to the emergency department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy) is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure used ensures automated capturing of all bed-side monitoring data (ie, vital parameters, electrophysiological waveforms) and securely importing data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration and pharmacy. Data are collected from all included participants during the first 72 hours of their hospitalisation, while follow-up data are collected at 3 months, 1 year, 2 years and 5 years after their ED visit.Findings to dateEnrolment of the first participant occurred on 1 September 2020. During the first month, 653 participants were screened for eligibility, of which 180 were approached as potential participants. In total, 151 (84%) provided consent for participation of which 89 participants fulfilled criteria for collection of biomaterials.Future plansThe main aim of Acutelines is to facilitate research in acute medicine by providing the framework for novel studies and issuing data, images and biomaterials for future research. The protocol will be extended by connecting with central registries to obtain long-term follow-up data, for which we already request permission from the participant.Trial registration numberNCT04615065.
Cancer related fatigue—light therapy: updated meta-analysis of randomised controlled trials
Authors: Hung Chao-Ming , Zeng Bing-Yan , Zeng Bing-Syuan , Sun Cheuk-Kwan , Cheng Yu-Shian , Su Kuan-Pin , Wu Yi-Cheng , Chen Tien-Yu , Lin Pao-Yen , Liang Chih-Sung , Hsu Chih-Wei , Chu Che-Sheng , Chen Yen-Wen , Yeh Pin-Yang , Wu Ming-Kung , Tseng Ping-Tao , Matsuoka Yutaka J 
Published: July 2021

BackgroundModerate-to-severe cancer related fatigue occurs in 45% of patients with cancer and interferes with many aspects of quality of life. Although physical exercise has level 1 evidence for improvement of cancer related fatigue, it has a relatively high behavioural demand compared with other non-pharmacological interventions. The aim of this updated meta-analysis was to address the efficacy of light therapy in improving cancer related fatigue in patients with cancer.MethodsWe included randomised controlled trials investigating the efficacy of bright white light (BWL) therapy in ameliorating cancer related fatigue in patients with cancer. This meta-analysis was conducted using a random-effects model. The target outcomes were changes in cancer related fatigue associated with BWL or dim red light (DRL).ResultsThere were 9 articles with 231 participants included. The main results revealed that daily morning BWL for 30 min was associated with significantly better improvement in fatigue severity compared with DRL (k=5, Hedges’g=−0.414, 95% CI −0.740 to −0.087, p=0.013). The subgroup without psychiatric comorbidities (k=4, Hedges’g=−0.479, 95% CI −0.801 to −0.156, p=0.004) was associated with significantly better improvement in fatigue severity with BWL than with DRL. In contrary, BWL was not associated with significantly different changes in depression severity or quality of life compared with DRL. Finally, BWL was associated with similar acceptability (ie, dropout rate) and safety profile (ie, any discomfort) as those of DRL.ConclusionsThis meta-analysis provides an updated evidence on the rationale for application of BWL in ameliorating cancer related fatigue in patients with different types of cancer.Trial registration numberINPLASY202140090.
Endovascular thrombectomy without versus with intravenous thrombolysis in acute ischemic stroke: a non-inferiority meta-analysis of randomized clinical trials
Authors: Lin Chun-Hsien , Saver Jeffrey L , Ovbiagele Bruce , Huang Wen-Yi , Lee Meng 
Published: July 2021

ObjectiveTo conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0–2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO).MethodsWe searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: −15%, −10%, −6.5%, −5%, and −1.3% for the risk difference for functional independence at 90 days.ResultsFour trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI −4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of −4% fell within the non-inferiority margins of −15%, −10%, −6.5%, and −5%, but not −1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI −3% to 5%) for mRS 0–1, and 1% (95% CI −1% to 3%) for symptomatic intracranial hemorrhage.ConclusionsThis meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.
Making your geriatric and palliative programs a strength: TQIP guideline implementation and the VRC perspective
Authors: Ho Vanessa P , Adams Sasha D , O'Connell Kathleen M , Cocanour Christine S , Arbabi Saman , Powelson Elisabeth B , Cooper Zara , Stein Deborah M 
Published: July 2021

BackgroundOlder patients compose approximately 30% of trauma patients treated in the USA but make up nearly 50% of deaths from trauma. To help standardize and elevate care of these patients, the American College of Surgeons (ACS) Trauma Quality Improvement Program’s best practice guidelines for geriatric trauma management was published in 2013 and that for palliative care was published in 2017. Here, we discuss how palliative care and geriatrics quality metrics can be tracked and used for performance improvement and leveraged as a strength for trauma verification.MethodsWe discuss the viewpoint of the ACS Verification, Review, and Consultation and three case studies, with practical tips and takeaways, of how these measures have been implemented at different institutions.ResultsWe describe the use of (1) targeted educational initiatives, (2) development of a consultation tool based on institutional resources, and (3) application of a nurse-led frailty screen.DiscussionSpecialized care and attention to these vulnerable populations is recommended, but the implementation of these programs can take many shapes.Level of evidenceV
Temporal dynamics of dissolved organic matter (DOM) in mountain lakes: the role of catchment characteristics
Authors: Olson Mark H. , Fischer Janet M. , Hayashi Masaki 
Published: July 2021

Climate change is affecting mountain ecosystems by increasing vegetation coverage and altering meteorological conditions. These changes are likely to impact the timing and magnitude of dissolved organic matter (DOM) inputs to lakes from the surrounding catchment. We examined temporal dynamics of DOM using in situ optical sensors that measured DOM fluorescence (fDOM) through the ice-free season in five lakes with differing catchment characteristics. We also measured changes in lake level and compiled daily meteorological data from nearby weather stations. At a seasonal time scale, fDOM dynamics occurred in two phases. fDOM declined in the first phase, which lasted until late July – mid-August, and corresponded to a decline in lake level following spring snowmelt. This decline was more pronounced in lakes with more vegetated catchments. At a shorter time scale, fDOM increased following precipitation events with a 0- to 1-day lag. Rates of fDOM increase per centmetre change in lake level were greater in lakes with vegetated catchments. As climate change increases vegetation coverage, DOM will likely become more dynamic at daily and seasonal time scales and impact water transparency and productivity of mountain lakes.
Physical and chemical depositional processes when volcanoes meet lacustrine environments: the Cretaceous Imjado Volcanics, Jeungdo, southwestern Korea
Authors: Gihm Yong Sik 
Published: July 2021

Abstract
A Cretaceous volcano-sedimentary succession (Imjado Volcanics, Jeungdo, SW Korea) was analysed to understand volcanic influences on physical and chemical depositional processes of a shallow alkaline lake during and after explosive eruptions. The succession is composed of primary and resedimented volcaniclastic deposits interbedded with fine-grained sediments and a bedded chert. The primary volcaniclastic deposits are characterized by two end-members: thick (20 m), welded lapilli tuff and thin (0.9 m), planar stratified tuff deposits. The first member deposits were accumulated by steady pyroclastic density currents that displaced the lake water from the shoreline. The second end-member deposits were accumulated by unsteady pyroclastic density currents that rapidly disintegrated at the shoreline and transformed into turbidity currents. The reverse to normally graded volcaniclastic sandstone is one of the resedimented volcaniclastic deposits accumulated by hyperpycnal flows originating from subaerial discharge. On top of this deposit, a bedded chert is exposed and composed of microcrystalline texture without biogenic remains. The microscopic analysis and stratigraphic relationship suggest that the chert bed was formed by chemical precipitation as a result of changes in the hydrochemistry of lake water by interaction between fresh water (hyperpycnal flows) and the alkaline bottom water of the lake.
Wound Healing Activities of Hydromethanolic Crude Extract and Solvent Fractions of Bersama abyssinica Leaves in Mice
Authors: Taddese Solome Melkamu , Gurji Tiruzer Bekele , Abdulwuhab Mohammedbrhan , Aragaw Tezera Jemere 
Published: July 2021

Background. Bersama abyssinica leaves are traditionally used for management of wounds in several communities of Ethiopia, despite no scientifically approved studies done on wound healing. Our study planned to work out the wound healing effects of B. abyssinica leaves extract in mice. Methods. B. abyssinica leaves were extracted with 80% hydromethanol and fractioned with chloroform, hexane, and water. The acute dermal toxicity of the crude extract was evaluated in mice. The crude extract formulated at 5% and 10% w/w ointment was investigated in excision, incision, and burn wound models and solvent fractions in the excision model using simple ointment (negative control) and nitrofurazone 0.2% w/v (positive control). We evaluated histopathological analysis, wound contraction rate, complete epithelialization period, and skin durability. One-way ANOVA followed by the post hoc Tukey HSD test with IBM SPSS software version 23.0 was used for data analysis, and

p

< 0.05 was considered statistically significant. Results. Hydromethanolic crude extract produced 5% (99.5%) and 10% (100%) wound contraction on the 16th day of the treatment and 5% (18.8) and 10% (28.2) percent reduction in the epithelization period on the excision wound healing model. Hydromethanolic crude extract produced 5% (47.5) and 10% (61.17) percent durability on the incision wound healing model. Hydromethanolic crude extract produced 5% (99.82%) and 10% (100%) wound contraction on the 20th day of treatment and 5% (13%) and 10% (21.7%) reduction in the epithelization period on the burn wound healing model. The chloroform fraction produced 5% (90.17%) and 10% (91.01%), hexane fraction produced 5% (85.81%) and 10% (86.78%), and aqueous fraction produced 5% (99.17%) and 10% (99.38%) wound contraction on the 14th day of the treatment and 5% (18.8) and 10% (28.2) percent reduction in the epithelization period on the excision wound healing model. Both hydromethanolic crude extract and solvent fractions at 5% and 10% (w/w) were significant (

p

< 0.001) compared with negative control. Conclusion. The results of this study showed that both 5% w/w and 10% w/w of 80% hydromethanolic crude extract and solvent fractions of B. abyssinica leaves have wound healing effects.
Mevalonate Blockade in Cancer Cells Triggers CLEC9A+ Dendritic Cell-Mediated Antitumor Immunity
Authors: Xu Feifei , Wang Zining , Zhang Hongxia , Chen Jiemin , Wang Xiaojuan , Cui Lei , Xie Chunyuan , Li Mengyun , Wang Fang , Zhou Penghui , Liu Jinyun , Huang Peng , Xia Xiaodong , Xia Xiaojun 
Published: July 2021

Abstract

Hyperactive mevalonate (MVA) metabolic activity is often observed in cancer cells, and blockade of this pathway inhibits tumor cell lipid synthesis and cell growth and enhances tumor immunogenicity. How tumor cell MVA metabolic blockade promotes antitumor immune responses, however, remains unclear. Here we show that inhibition of the MVA metabolic pathway in tumor cells elicits type 1 classical dendritic cells (cDC1)–mediated tumor recognition and antigen cross-presentation for antitumor immunity. Mechanistically, MVA blockade disrupted prenylation of the small GTPase Rac1 and induced cancer cell actin filament exposure, which was recognized by CLEC9A, a C-lectin receptor specifically expressed on cDC1s, in turn activating antitumor T cells. MVA pathway blockade or Rac1 knockdown in tumor cells induced CD8+ T-cell-mediated antitumor immunity in immunocompetent mice but not in Batf3−/− mice lacking CLEC9A+ dendritic cells. These findings demonstrate tumor MVA metabolic blockade stimulates a cDC1 response through CLEC9A-mediated immune recognition of tumor cell cytoskeleton, illustrating a new immune surveillance mechanism by which dendritic cells monitor tumor metabolic dysregulation and providing insight into how MVA pathway inhibition may potentiate anticancer immunity.

Significance:
These findings suggest that mevalonate blockade in cancer cells disrupts Rac1 prenylation to increase recognition and cross-presentation by conventional dendritic cells, suggesting this axis as a potential target for cancer immunotherapy.
Hypothermia Is a Potential New Therapy for a Subset of Tumors with Mutant p53
Authors: Hu Wenwei , Feng Zhaohui 
Published: July 2021

Abstract
The tumor suppressor p53 gene is mutated in approximately 50% of all human tumors. Many tumor-associated mutant p53 proteins misfold into a common, denatured conformation and accumulate to high levels in human tumors. In such tumors, these mutant forms of p53 provide a “gain of function” to promote tumor progression. Therefore, targeting mutant p53 has become an attractive approach for cancer therapy. In this issue, the study by Lu and colleagues supports the premise that certain forms of mutant p53 are temperature sensitive in conformation; these forms of p53 are mutant in conformation at physiologic temperature, but can refold into a normal, or “wild-type” conformation at lower temperature (32°C to 34°C). Notably, these temperature-sensitive mutants account for up to 7.5% of all human tumors that carry mutant p53, so this fraction of patients is estimated to be quite significant. Results from this study show that employing therapeutic hypothermia to reduce the core temperature of mice bearing tumors with these temperature-sensitive mutant forms of p53 (ts mutant p53) causes ts mutant p53 to switch to a wild-type conformation in tumors, inhibiting tumor growth. Moreover, combining hypothermia with chemotherapy leads to durable remission of such tumors, with no obvious toxicity to normal tissues.
See related article by Lu et al., p. 3905
Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors
Authors: Colombo Ilaria , Genta Sofia , Martorana Federica , Guidi Monia , Frattini Milo , Samartzis Eleftherios Pierre , Brandt Simone , Gaggetta Sheila , Moser Laura , Pascale Mariarosa , Terrot Tatiana , Sessa Cristiana , Stathis Anastasios 
Published: July 2021

Abstract

Purpose:
This phase I study evaluated safety, tolerability, pharmacokinetics, and preliminary activity of the PI3K/mTORC1/2 dual inhibitor gedatolisib combined with carboplatin and paclitaxel.

Patients and Methods:
Patients with advanced solid tumors treated with ≤ 2 prior chemotherapies received intravenous gedatolisib on days 1, 8, 15, and 22 (95, 110, or 130 mg according to dose level); carboplatin (AUC5) on day 8 (day 1 following protocol amendment); and paclitaxel at 80 mg/m2 on days 8, 15, and 22 (1, 8, and 15 after amendment), every 28 days. Patients without progressive disease after cycle 6 received maintenance gedatolisib until progression.

Results:
Seventeen patients were enrolled [11 ovarian (10 clear cell ovarian cancer, CCOC), 4 endometrial, 2 lung cancers]. Median number of prior chemotherapies was 1 (range, 0–2). Median number of administered cycles was 6 (range, 2–16). Dose-limiting toxicities occurred in 4 patients: 2 (cycle 2 delay due to G2–G3 neutropenia) at 110 mg leading to a change in the treatment schedule, 2 at 130 mg (G2 mucositis causing failure to deliver ≥ 75% of gedatolisib at cycle 1). The recommended phase II dose is gedatolisib 110 mg on days 1, 8, 15, and 22 with carboplatin AUC5 on day 1 and paclitaxel 80 mg/m2 on days 1, 8, and 15. The most frequent ≥G3 treatment-related adverse events were neutropenia (35%), anemia (18%), and mucositis (12%). The overall response rate was 65% (80% in CCOC). Pharmacokinetic parameters of gedatolisib were consistent with single-agent results.

Conclusions:
Gedatolisib combined with carboplatin and paclitaxel is tolerable, and preliminary efficacy was observed especially in CCOC.