bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking antimicrobial resistance surveillance to antibiotic policy in healthcare settings: the COMBACTE-Magnet EPI-Net COACH project
Authors: Pezzani Maria Diletta , Mazzaferri Fulvia , Compri Monica , Galia Liliana , Mutters Nico T , Kahlmeter Gunnar , Zaoutis Theoklis E , Schwaber Mitchell J , Rodríguez-Baño Jesús , Harbarth Stephan , Tacconelli Evelina ,   the COACH working group, Anaya Blanca , Arieti Fabiana , Rajendran Nithya Babu , Palacios Baena Zaira R , Rodríguez-Baño Jesús , Brusaferro Silvio , Carrara Elena , Cattaneo Dario , Charani Esmita , Compri Monica , Eremin Sergey , Galia Liliana , Giacobbe Daniele Roberto , Gomila-Grange Aina , Harbarth Stephan , Laxminarayan Ramanan , Lo Cascio Giuliana , Mazzaferri Fulvia , Mazzolini Elena , McCarthy Michael , Canton Rafael , Mutters Nico T , Neth Olaf , Oualim Abdelhak , Pezzani Maria Diletta , Prioteasa Adelina , Saris Katia , Schwaber Mitchell J , Schrijver Remco , LP AstraZeneca , Tacconelli Evelina , Vuong Cuong , Wolkewitz Martin , Zaoutis Theoklis E
Published: October 2020

Objectives

To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings.

Methods

The research group identified 10 key questions about the link between AMR surveillance and AMS using a checklist of 9 elements for good practice in health research priority settings and a modified 3D combined approach matrix, and conducted a systematic review of published original studies and guidelines on the link between AMR surveillance and AMS.

Results

The questions identified focused on AMS team composition; minimum infrastructure requirements for AMR surveillance; organisms, samples and susceptibility patterns to report; data stratification strategies; reporting frequency; resistance thresholds to drive empirical therapy; surveillance in high-risk hospital units, long-term care, outpatient and veterinary settings; and surveillance data from other countries. Twenty guidelines and seven original studies on the implementation of AMR surveillance as part of an AMS programme were included in the literature review.

Conclusions

The evidence summarized in this review provides a useful basis for a more integrated process of developing procedures to report AMR surveillance data to drive AMS interventions. These procedures should be extended to settings outside the acute-care institutions, such as long-term care, outpatient and veterinary. Without proper AMR surveillance, implementation of AMS policies cannot contribute effectively to the fight against MDR pathogens and may even worsen the burden of adverse events from such interventions.
White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in long-term care facilities—practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks
Authors: Sibani Marcella , Mazzaferri Fulvia , Carrara Elena , Pezzani Maria Diletta , Arieti Fabiana , Göpel Siri , Paul Mical , Tacconelli Evelina , Mutters Nico T , Voss Andreas ,   the ARCH working group
Published: October 2020

Background

In long-term care facilities (LTCFs) residents often receive inappropriate antibiotic treatment and infection prevention and control practices are frequently inadequate, thus favouring acquisition of MDR organisms. There is increasing evidence in the literature describing antimicrobial stewardship (AMS) activities in LTCFs, but practical guidance on how surveillance data should be linked with AMS activities in this setting is lacking. To bridge this gap, the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks joined their efforts to provide practical guidance for linking surveillance data with AMS activities.

Materials and methods

Considering the three main topics [AMS leadership and accountability, antimicrobial usage (AMU) and AMS, and antimicrobial resistance (AMR) and AMS], a literature review was performed and a list of target actions was developed. Consensus on target actions was reached through a RAND-modified Delphi process involving 40 experts from 18 countries and different professional backgrounds adopting a One Health approach.

Results

From the 25 documents identified, 25 target actions were retrieved and proposed for expert evaluation. The consensus process produced a practical checklist including 23 target actions, differentiating between essential and desirable targets according to clinical relevance and feasibility. Flexible proposals for AMS team composition and leadership were provided, with a strong emphasis on the need for well-defined and adequately supported roles and responsibilities. Specific antimicrobial classes, AMU metrics, pathogens and resistance patterns to be monitored are addressed. Effective reporting strategies are described.

Conclusions

The proposed checklist represents a practical tool to support local AMS teams across a wide range of care delivery organization and availability of resources.
Treating COVID-19: are we missing out the window of opportunity?
Authors: Sundararaj Stanleyraj Jeremiah , Sethuraman Nandini , Gupta Rajesh , Thiruvoth Sohanlal , Gupta Manisha , Ryo Akihide
Published: October 2020

Severe COVID-19 is a biphasic illness, with an initial viral replication phase, followed by a cascade of inflammatory events. Progression to severe disease is predominantly a function of the inflammatory cascade, rather than viral replication per se. This understanding can be effectively translated to changing our approach in managing the disease. The natural course of disease offers us separate windows of specific time intervals to administer either antiviral or immunomodulatory therapy. Instituting the right attack at the right time would maximize the benefit of treatment. This concept must also be factored into studies that assess the efficacy of antivirals and immunomodulatory agents against COVID-19.
Detecting Ingested Host Plant DNA in Potato Leafhopper (Hemiptera: Cicadellidae): Potential Use of Molecular Markers for Gut Content Analysis
Authors: Avanesyan Alina , Illahi Nurani , Lamp William O
Published: October 2020

Detection of host plant DNA from sap-feeding insects can be challenging due to potential low concentration of ingested plant DNA. Although a few previous studies have demonstrated the possibility of detecting various fragments of plant DNA from some sap-feeders, there are no protocols available for potato leafhopper, Empoasca fabae (Harris) (Hemiptera: Cicadellidae), a significant agricultural pest. In this study we focused on optimizing a DNA-based method for host plant identification of E. fabae and investigating the longevity of the ingested plant DNA as one of the potential applications of the protocol. We largely utilized and modified our previously developed PCR-based method for detecting host plant DNA from grasshopper and the spotted lanternfly gut contents. We have demonstrated that the trnL (UAA) gene can be successfully utilized for detecting ingested host plant DNA from E. fabae and determining plant DNA longevity. The developed protocol is a relatively quick and low-cost method for detecting plant DNA from E. fabae. It has a number of important applications—from determining host plants and dispersal of E. fabae to developing effective pest management strategies.
EU General Court tackles notion of ‘average consumer’ when goods/services are aimed at both specialized and everyday consumers
Authors: Malovic Nedim
Published: October 2020

EU General Court, Teva Pharmaceutical Industries Ltd v European Union Intellectual Property Office (EUIPO), EU:T:2020:330, 8 July 2020
European Commission Merger Control Under Council Regulation No. 139/2004: Mapping The Most Expansive Acquirers In Merger And Acquisition Transactions In 2004–2015
Authors: Bartalevich Dzmitry
Published: October 2020

In EU merger control, the European Commission is empowered by Council Regulation (EC) No. 139/2004 to regulate changes in market structure by deciding whether two or more firms may merge, combine, or consolidate their businesses into one. These decisions affect various market players, including major EU and non-EU businesses, as well as vast product and geographic markets. Offering a network perspective on the cleared merger and acquisition transactions in Phase I decisions under Article 6(1)(b) of Council Regulation (EC) No. 139/2004 (20 January 2004–01 July 2015), this article aims to investigate the overall composition of mergers and acquisitions in terms of their industry sectors and domiciles and to identify the types of firms that acquire more targets than other firms (that is, more expansive firms). The analysis is conducted by using data from the European Commission (601 transactions) and Bureau van Dijk (992 transactions).
Effects of clonal integration, nutrients and cadmium on growth of the aquatic macrophytePistia stratiotes
Authors: Adomako Michael Opoku , Alpert Peter , Du Dao-Lin , Yu Fei-Hai
Published: October 2020

Aims

Many wetlands are polluted with both nutrients and toxic metals and vegetated largely by clonal plants. We hypothesized that eutrophication and clonal integration can increase phytoremediation of toxic metal pollution by increasing plant growth, even under the stress imposed by toxicity.

Methods

To test this hypothesis, single ramets of the common, widespread, floating, stoloniferous plant Pistia stratiotes L., were grown for 42 days at two levels of nutrient availability with and without 0.6 mg L−1 cadmium. Ramets were either severed from their vegetative offspring to prevent clonal integration or left connected, and severed offspring were either removed to eliminate intraclonal competition or left in place.

Important Findings

Plants subjected to cadmium addition accumulated almost twice as much dry mass if given the higher nutrient level, due mainly to a doubling of the number of clonal offspring. Severance had little effect on the final mass of the parent plus offspring ramets. Removing offspring following severance had no effect on the final mass of the parental ramet in the presence of added cadmium, but it did increase the final mass of the parent in the absence of cadmium. These results support the hypothesis that eutrophication can increase remediation of toxic metal pollution by aquatic macrophytes but provided no evidence that clonal integration can affect remediation. Species such as P. stratiotes may help remediate co-pollution of wetlands with toxic metals and nutrients, and fragmentation of clones may not affect their remediation capacity.
Lessons learned from a rubella outbreak: role of a travel medicine practitioner
Authors: Matsee Wasin , Piyaphanee Watcharapong
Published: October 2020

We highlight lessons learned from the 2018–19 rubella outbreak in Japan on the use of Measles-Mumps-Rubella vaccine among travellers. We underline that individual risk assessment during pre-travel counselling is still essential in all situations especially among immunocompromised and pregnant travellers.
Post-awakening Cortisol in Explosive Ordnance Disposal Technicians: A Replication Study in a Novel Population
Authors: Hernández Lisa M , Padilla Genieleah A , Koehn Blake W , Taylor Marcus K
Published: October 2020

Introduction

Amassing evidence suggests that post-awakening salivary cortisol rhythms (changes in cortisol throughout the day) may indicate health status. We previously established summary parameters for salivary cortisol in U.S. Navy Sea, Air, and Land and reported excellent parameter stability across 2 days of repeated sampling. To confirm the generalizability of our original findings to other military populations, we replicated the procedures of our prior report in another specialized military group. The purpose of this study was to (1) establish summary parameters of daily salivary cortisol rhythms, (2) evaluate summary parameter stability, and (3) assess the impact of sampling compliance in U.S. Navy Explosive Ordnance Disposal (EOD) technicians.

Materials and Methods

Seventy active duty, male Explosive Ordnance Disposal technicians (mean ± SD age; 34.9 ± 6.5 years) self-collected saliva samples in a nondeployed setting on two consecutive weekdays at WAKE, WAKE + 30 min, WAKE + 60 min, 4 p.m., and 9 p.m. For salivary cortisol, we computed summary parameters, i.e., measures of magnitude and measures of pattern, and then evaluated their stabilities via correlational analyses and Cronbach’s alpha (α). Compliance was objectively and subjectively evaluated using actigraphy and self-reported data, respectively. This research was conducted under a Naval Health Research Center Institutional Review Board approved study (NHRC.2015.0013).

Results

Average salivary cortisol concentrations increased at WAKE + 30 (mean ± SE reactivity; 48.9 + 6.8%) from WAKE, followed by a swift recovery at WAKE + 60. Approximately 10.9% of the group were classified as negative-responders (i.e., < 0% change from WAKE to WAKE + 30). The measures of magnitude demonstrated fair stability across two days (r value range: 0.37-0.45, ps < 0.01; α range: 0.54-0.62). Fifty-five percent of the sample was classified as compliant (defined as <15 min deviation from target sampling times) across both days. Compliance decreased to 31% when compliance criteria were refined to <5 min deviation; however, controlling for compliance did not overwhelmingly influence the more stable summary parameters of magnitude.

Conclusions

These findings demonstrate a thorough replication, with some additional refinement, of our prior study, implying generalizability across diverse military populations. Study limitations include unsupervised saliva collection in a free-living setting, which is counterbalanced by ecological validity. The noninvasive salivary sampling protocol used in this study yields stable estimations of daily cortisol rhythms in specialized military men and is recommended as an operational health surveillance tool by which to monitor chronically stressed military members.
Once in the Door, Grit May Matter More: An Evaluation of Grit in Medical Students
Authors: Ursua Francesca , Altholz Jacob , Durning Steven , Torre Dario , Dong Ting
Published: October 2020

Introduction

Health professions educators seek understanding of the process of learner performance and achievement. Grit, defined as passion and perseverance for long-term goals, has been implicated in this process. Research suggests that effort counts twice in achievement: skill times effort equals skill and, subsequently, skill times effort equals achievement. Research also suggests that an individual’s interest influences job performance and satisfaction. Grit, composed of Perseverance of Effort and Consistency of Interest, has been shown to positively correlate with performance and achievement in various disciplines. Limited research reveals Grit negatively correlates with resident attrition and physician burnout. This study evaluates relationships between Grit and medical student performance measures.

We gather validity evidence for Grit scale use among medical students and, subsequently, use this data to evaluate for differences in Grit score by gender and assess whether there is a relationship between Grit and standardized exam scores. We hypothesize that Grit will not vary with gender and that it will be positively associated with standardized examination scores.

Methods

Enrolled students receive the 12-item Grit survey. An exploratory factor analysis evaluates validity evidence of Grit. Descriptive statistical analysis, Pearson correlation, and moderation analysis evaluate if Grit score differs by gender and if there are relationships with standardized exams.

Results

The survey response rate is 59% (412/698) and exploratory factor analysis replicates the two-factor structure of Grit found in other fields—Perseverance of Effort and Consistency of Interest. Average Grit scores do not significantly differ by gender. Grit weakly correlates with United States Medical Licensing Exam Step 1 (r = 0.10,  = 0.36) and United States Medical Licensing Exam Step 2 Clinical Knowledge (r = 0.12, P=0.29). Grit weakly and negatively correlates with Medical College Admission Test score (r = − 0.18, P<0.05). Grit is not a significant moderator of the relationship between Medical College Admission score and Step exams scores.

Conclusion

Exploratory factor analysis results provide preliminary validity evidence for Grit scale use in medical students. Grit does not significantly moderate the Medical College Admission Test-Step score relationship. Grit correlates negatively with Medical College Admission Test scores. Though the correlations in this study were not significant, the results showed that Grit may tend to positively correlate with Step 1 and Step 2 Clinical Knowledge examinations. Given that these three exams are taken at different levels of training, the stepwise progression towards positive correlation may suggest that the theory “effort counts twice” applies to medical training.
Incidental Finding of Tuberculosis During Evaluation for Delayed Wound Healing
Authors: Kunciw Sabrina E , de la Cruz Eric C
Published: October 2020

Cutaneous tuberculosis (TB) is an uncommon form of extrapulmonary TB that can be difficult to diagnose. The following case is about a 14-year-old female who was experiencing delayed wound healing after an incision and drainage of a chest wall abscess. A computed tomography scan of her chest obtained 2 months after the procedure revealed pulmonary findings consistent with TB. An acid-fast bacilli culture was obtained from the wound after the computed tomography scan was performed and was positive for Mycobacterium tuberculosis 8 weeks later. Although TB is relatively uncommon in the United States, it is more prevalent in the Republic of Korea where the patient lives and was evaluated. This case serves to illustrate the long history of challenges the military medical community has faced with TB and to remind providers to be cognizant about local common diseases when serving overseas and include these diagnoses in their differentials.
Detailed studies of IPHAS sources - III. The highly extinguished bipolar planetary nebula IPHASX J191104.8+060845
Authors: Rodríguez-González J B , Sabin L , Toalá J A , Zavala S , Ramos-Larios G , Guerrero M A , Parker Q A , Guillén P F , Ritter A
Published: October 2020

We present the first detailed study of the bipolar planetary nebula (PN) IPHASX J191104.8+060845 (PN G 040.6−01.5) discovered as part of the Isaac Newton Telescope Photometric Hα Survey of the Northern Galactic plane (IPHAS). We present Nordic Optical Telescope (NOT) narrow-band images to unveil its true morphology. This PN consists of a main cavity with two newly uncovered extended low-surface brightness lobes located towards the NW and SE directions. Using near-IR WISE images we unveiled the presence of a barrel like structure, which surrounds the main cavity, which would explain the dark lane towards the equatorial regions. We also use Gran Telescopio de Canarias (GTC) spectra to study the physical properties of this PN. We emphasise the potential of old PNe detected in IPHAS to study the final stages of the evolution of the circumstellar medium around solar-like stars.
A combinatorial method to isolate short ribozymes from complex ribozyme libraries
Authors: Arriola Joshua T , Müller Ulrich F
Published: October 2020

In vitro selections are the only known methods to generate catalytic RNAs (ribozymes) that do not exist in nature. Such new ribozymes are used as biochemical tools, or to address questions on early stages of life. In both cases, it is helpful to identify the shortest possible ribozymes since they are easier to deploy as a tool, and because they are more likely to have emerged in a prebiotic environment. One of our previous selection experiments led to a library containing hundreds of different ribozyme clusters that catalyze the triphosphorylation of their 5′-terminus. This selection showed that RNA systems can use the prebiotically plausible molecule cyclic trimetaphosphate as an energy source. From this selected ribozyme library, the shortest ribozyme that was previously identified had a length of 67 nucleotides. Here we describe a combinatorial method to identify short ribozymes from libraries containing many ribozymes. Using this protocol on the library of triphosphorylation ribozymes, we identified a 17-nucleotide sequence motif embedded in a 44-nucleotide pseudoknot structure. The described combinatorial approach can be used to analyze libraries obtained by different in vitro selection experiments.
SC2disease: a manually curated database of single-cell transcriptome for human diseases
Authors: Zhao Tianyi , Lyu Shuxuan , Lu Guilin , Juan Liran , Zeng Xi , Wei Zhongyu , Hao Jianye , Peng Jiajie
Published: October 2020

SC2disease (http://easybioai.com/sc2disease/) is a manually curated database that aims to provide a comprehensive and accurate resource of gene expression profiles in various cell types for different diseases. With the development of single-cell RNA sequencing (scRNA-seq) technologies, uncovering cellular heterogeneity of different tissues for different diseases has become feasible by profiling transcriptomes across cell types at the cellular level. In particular, comparing gene expression profiles between different cell types and identifying cell-type-specific genes in various diseases offers new possibilities to address biological and medical questions. However, systematic, hierarchical and vast databases of gene expression profiles in human diseases at the cellular level are lacking. Thus, we reviewed the literature prior to March 2020 for studies which used scRNA-seq to study diseases with human samples, and developed the SC2disease database to summarize all the data by different diseases, tissues and cell types. SC2disease documents 946 481 entries, corresponding to 341 cell types, 29 tissues and 25 diseases. Each entry in the SC2disease database contains comparisons of differentially expressed genes between different cell types, tissues and disease-related health status. Furthermore, we reanalyzed gene expression matrix by unified pipeline to improve the comparability between different studies. For each disease, we also compare cell-type-specific genes with the corresponding genes of lead single nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) to implicate cell type specificity of the traits.
Is Foreign Policy Special?
Authors: Smith Ewan
Published: October 2020

People say foreign policy is a special sort of public policy. This article challenges that claim. It argues that judges should treat foreign policy in the same way they treat other sorts of policy. The article responds to four related lines of argument: that foreign policy is special on account of the constitutional separation of powers; that it demands a special sort of democratic legitimacy; that it is especially complex, secret and prophetic; and that it is simply more important than other aspects of public policy. These might be good reasons to defer to the government in general, but they are not good reasons to grant special deference to foreign policy.
LAZY1 Controls Tiller Angle and Shoot Gravitropism by Regulating the Expression of Auxin Transporters and Signaling Factors in Rice
Authors: Zhu Mo , Hu Yanjuan , Tong Aizi , Yan Bowen , Lv Yanpeng , Wang Shiyu , Ma Wenhong , Cui Zhibo , Wang Xiaoxue
Published: October 2020

Tiller angle is a key factor determining rice plant architecture, planting density, light interception, photosynthetic efficiency, disease resistance and grain yield. However, the mechanisms underlying tiller angle control are far from clear. In this study, we identified a mutant, termed bta1-1, with an enlarged tiller angle throughout its life cycle. A detailed analysis reveals that BTA1 has multiple functions because tiller angle, shoot gravitropism and tolerance to drought stress are changed in bta1-1 plants. Moreover, BTA1 is a positive regulator of shoot gravitropism in rice. Shoot responses to gravistimulation are disrupted in bta1-1 under both light and dark conditions. Gene cloning reveals that bta1-1 is a novel mutant allele of LA1 renamed la1-SN. LA1 is able to rescue the tiller angle and shoot gravitropism defects observed in la1-SN. The nuclear localization signal of LA1 is disrupted by la1-SN, causing changes in its subcellular localization. LA1 is required to regulate the expression of auxin transporters and signaling factors that control shoot gravitropism and tiller angle. High-throughput mRNA sequencing is performed to elucidate the molecular and cellular functions of LA1. The results show that LA1 may be involved in the nucleosome and chromatin assembly, and protein–DNA interactions to control gene expression, shoot gravitropism and tiller angle. Our results provide new insight into the mechanisms whereby LA1 controls shoot gravitropism and tiller angle in rice.
Effect of spontaneous breathing on atelectasis during induction of general anaesthesia in infants
Authors: Ji Sang-Hwan , Jang Hwan Suk , Jang Young-Eun , Kim Eun-Hee , Lee Ji-Hyun , Kim Jin-Tae , Kim Hee-Soo
Published: October 2020

BACKGROUND

Atelectasis occurs commonly during induction of general anaesthesia in children, particularly infants.

OBJECTIVES

We hypothesised that maintaining spontaneous ventilation can reduce atelectasis formation during anaesthetic induction in infants. We compared spontaneous ventilation and manual positive-pressure ventilation in terms of atelectasis formation in infants.

DESIGN

Randomised controlled study.

SETTING

Single tertiary hospital in Seoul, Republic of Korea, from November 2018 to December 2019.

PATIENTS

We enrolled 60 children younger than 1 year of age undergoing general anaesthesia, of whom 56 completed the study. Exclusion criteria were history of hypoxaemia during previous general anaesthesia, development of a respiratory tract infection within 1 month, current intubation or tracheostomy cannulation, need for rapid sequence intubation, preterm birth, age within 60 weeks of the postconceptional age and the presence of contraindications for rocuronium or sodium thiopental.

INTERVENTION

Patients were allocated randomly to either the ‘spontaneous’ group or ‘controlled’ group. During preoxygenation, spontaneous ventilation was maintained in the ‘spontaneous’ group while conventional bag-mask ventilation was provided in the ‘controlled’ group. After 5 min of preoxygenation, a lung ultrasound examination was performed to compare atelectasis formation in the two groups.

RESULTS

Atelectasis after preoxygenation was seen in seven (26.9%) of 26 patients in the ‘spontaneous’ group and 22 (73.3%) of 30 patients in the ‘controlled’ group (P = 0.001). The relative risk of atelectasis in the ‘spontaneous’ group was 0.39 (95% CI 0.211 to 0.723). Regarding ultrasound pictures of consolidation, the total score and sum of scores in the dependent regions were significantly lower in the ‘spontaneous’ group than in the ‘controlled’ group (P = 0.007 and 0.001, respectively).

CONCLUSION

Maintaining spontaneous ventilation during induction of general anaesthesia has a preventive effect against atelectasis in infants younger than 1 year of age, particularly in the dependent portions of the lungs.

TRIAL REGISTRATION

Clinicaltrials.gov (identifier: NCT03739697).
The synergistic effect of dexmedetomidine on propofol for paediatric deep sedation
Authors: Mason Keira P. , Park Raymond Seungjoon , Sullivan Cornelius A. , Lukovits Karina , Halpin Erin M. , Imbrescia Samantha T. , Cavanaugh David , Prescilla Randy , Fox Victor L.
Published: October 2020

BACKGROUND

Propofol and dexmedetomidine are used separately, and sometimes together, for paediatric deep sedation. Although their combination has been described in adults, the effect of dexmedetomidine as a potential synergist in children has not been studied before.

OBJECTIVES

The primary objective was to compare the propofol requirements of children who receive propofol alone with those who receive it in combination with dexmedetomidine for deep sedation for upper and lower endoscopic gastrointestinal procedures.

DESIGN

This was a prospective, open-label, randomised study comparing patients who received propofol alone (group P) with those who received dexmedetomidine and propofol (group DP). The depth of sedation was titrated to a target bispectral (BIS) index.

SETTING

A Gastroenterology Procedure Unit at a single, tertiary care academic medical centre from April 2018 until December 2019.

PATIENTS

Eligible patients were scheduled for upper endoscopy, lower endoscopy or both. A total of 39 patients were enrolled (20 DP) and (19 P).

INTERVENTIONS

Patients in Group DP received dexmedetomidine 0.5 μg kg−1 administered over 1 min followed by an infusion of 0.15 μg kg−1 h−1. In both groups, intravenous propofol was given in bolus increments titrated to a BIS index of 40 to 50 and then a continuous infusion of propofol to maintain BIS at 40 to 50.

MAIN OUTCOME MEASURES

The primary outcome measure was propofol requirement in each group. Secondary outcome measures were time to achieve the targeted sedation depth, time to achieve an Aldrete recovery score of 9, duration of sedation, mean BIS values, adverse events, ‘PAED’ scores and time to discharge from the postanaesthesia care unit (PACU).

RESULTS

The median (range) total dose of propofol was 0.23 (0.10 to 0.50) mg kg−1 min−1 in group DP and 0.40 (0.20 to 0.50) mg kg−1 min−1 in group P (P = 0.0004). Time of discharge from the PACU was 60 (20 to 121) min in group DP and 63 (46 to 91) min in group P (P = 0.0409).

CONCLUSION

The combination of dexmedetomidine and propofol for paediatric procedural sedation achieved a significant reduction in median propofol dose and a slightly shorter median time to discharge from PACU. Large-scale studies may determine whether this reduction decreases the risk of significant adverse events.

TRIAL REGISTRATION

ClinicalTrials.gov identifier NCT02952222
Unusual Fatigue and Failure to Utilize EMS Are Associated With Prolonged Prehospital Delay for Suspected Acute Coronary Syndrome
Authors: DeVon Holli A. , Daya Mohamud R. , Knight Elizabeth , Brecht Mary-Lynn , Su Erica , Zègre-Hemsey Jessica , Mirzaei Sahereh , Frisch Stephanie , Rosenfeld Anne G.
Published: October 2020

Background:

Rapid reperfusion reduces infarct size and mortality for acute coronary syndrome (ACS), but efficacy is time dependent. The aim of this study was to determine if transportation factors and clinical presentation predicted prehospital delay for suspected ACS, stratified by final diagnosis (ACS vs. no ACS).

Methods:

A heterogeneous sample of emergency department (ED) patients with symptoms suggestive of ACS was enrolled at 5 US sites. Accelerated failure time models were used to specify a direct relationship between delay time and variables to predict prehospital delay by final diagnosis.

Results:

Enrolled were 609 (62.5%) men and 366 (37.5%) women, predominantly white (69.1%), with a mean age of 60.32 (±14.07) years. Median delay time was 6.68 (confidence interval 1.91, 24.94) hours; only 26.2% had a prehospital delay of 2 hours or less. Patients presenting with unusual fatigue [time ratio (TR) = 1.71, P = 0.002; TR = 1.54, P = 0.003, respectively) or self-transporting to the ED experienced significantly longer prehospital delay (TR = 1.93, P < 0.001; TR = 1.71, P < 0.001, respectively). Predictors of shorter delay in patients with ACS were shoulder pain and lightheadedness (TR = 0.65, P = 0.013 and TR = 0.67, P = 0.022, respectively). Predictors of shorter delay for patients ruled out for ACS were chest pain and sweating (TR = 0.071, P = 0.025 and TR = 0.073, P = 0.032, respectively).

Conclusion:

Patients self-transporting to the ED had prolonged prehospital delays. Encouraging the use of EMS is important for patients with possible ACS symptoms. Calling 911 can be positively framed to at-risk patients and the community as having advanced care come to them because EMS capabilities include 12-lead ECG acquisition and possibly high-sensitivity troponin assays.
Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R/T790M mutant non-small cell lung carcinoma cell line
Authors: Verusingam Nalini Devi , Chen Yi-Chen , Lin Heng-Fu , Liu Chao-Yu , Lee Ming-Cheng , Lu Kai-Hsi , Cheong Soon-Keng , Han-Kiat Ong Alan , Chiou Shih-Hwa , Wang Mong-Lien
Published: October 2020

Background:

Lung cancer contributes to high cancer mortality worldwide with 80% of total cases diagnosed as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain serves as a druggable target in NSCLC patients with exon 19 deletion and L858R mutation. However, patients eventually succumbed to resistance to first- and second-generation EGFR-TK inhibitors through activation of T790M mutation. Third-generation EGFR-TKI, Osimertinib exhibits high efficacy in patients with exon 19 deletion/L858R/T790M mutation but they experienced acquired resistance thereafter. Available treatment options in NSCLC patients remains a challenge due to unknown molecular heterogeneity responsible for acquired resistance to EGFR-TKI. In this study, we aim to generate Osimertinib-resistant (OR) cells from H1975 carrying L858R/T790M double mutation which can be used as a model to elucidate mechanism of resistance.

Methods:

OR cells were established via stepwise-dose escalation and limiting single-cell dilution method. We then evaluated Osimertinib resistance potential via cell viability assay. Proteins expression related to EGFR-signalling, epithelial to mesenchymal transition (EMT), and autophagy were analyzed via western blot.

Results:

OR cell lines exhibited increased drug resistance potential compared to H1975. Distinguishable mesenchymal-like features were observed in OR cells. Protein expression analysis revealed EGFR-independent signaling involved in the derived OR cells as well as EMT and autophagy activity.

Conclusion:

We generated OR cell lines in-vitro as evidenced by increased drug resistance potential, increased mesenchymal features, and enhanced autophagy activity. Development of Osimertinib resistance cells may serve as in-vitro model facilitating discovery of molecular aberration present during acquired mechanism of resistance.
Reverse expression of α2,6-sialic acid ratios on IgG, IgM, and IgG/IgM autoantibodies correlates with mouse arthritis and rheumatoid arthritis disease activity
Authors: Liou Lieh-Bang , Huang Che-Ching
Published: October 2020

Background:

Sialic acids (SIAs), for example, α2,6-SIAs, can link to conserved N-glycans of immunoglobulin G (IgG). In this study, we investigated the correlation between α2,6-SIA on IgG and IgM and the disease activity of arthritis and rheumatoid arthritis (RA) in mice.

Methods:

We measured α2,6-SIA levels in IgGs and IgMs in collagen-induced arthritis (CIA). Additionally, α2,6-SIA levels in rheumatoid factors (RFs) and anti–cyclic citrullinated peptide (anti-CCP) antibodies in RA patients were measured. Correlations between α2,6-SIA on Igs and CIA were analyzed and also in RA patients by utilizing the disease activity score 28 (DAS28). The ability to differentiate RA progression by Ig and autoantibody α2,6-SIA levels was examined.

Results:

In CIA mice, plasma IgG-α2,6-SIA/IgG ratios decreased, whereas plasma IgM-α2,6-SIA/IgM ratios increased. Moreover, arthritis was not observed in collagen-injected mice with decreased IgG-α2,6-SIA/IgG ratios and without increased IgM-α2,6-SIA/IgM ratios. Isolated IgG-α2,6-SIA/IgG ratios displayed a significant inverse correlation with DAS28 scores (r = –0.383, p = 0.037). In contrast, isolated IgM-α2,6-SIA/IgM ratios correlated positively with DAS28 (r = 0.351, p = 0.009). Isolated IgG-anti-CCP-α2,6-SIA/plasma IgG-anti-CCP ratios were differentiated into either the remission (higher ratios) or the nonremission (lower ratios) category (p = 0.061), which is similar to the pattern for C-reactive protein (CRP) (p = 0.041) but different from that for the erythrocyte sedimentation rate (ESR) (p = 0.421). Using multiple linear regression analysis, plasma IgMRF-α2,6-SIA/IgMRF ratios displayed a correlation with DAS28 (p = 0.006), which was also observed in the ESR (p = 0.005), but was different from that for CRP (p = 0.222).

Conclusion:

Concurrent reverse expression of α2,6-SIA ratios on IgM and IgG correlated with the occurrence of CIA and RA disease activity. Thus, α2,6-SIA ratios on IgG-anti-CCP antibodies and IgMRF are potential markers for evaluating RA disease activities.
‘Doc, will I ever eat steak again?’: diagnosis and management of alpha-gal syndrome
Authors: Patel Chirag , Iweala Onyinye I.
Published: October 2020

Purpose of review

Alpha-gal syndrome encompasses a constellation of symptoms associated with immune-mediated hypersensitivity responses to galactose-alpha-1,3-galactose (alpha-gal). The purpose of this review is to discuss our current understanding of the etiology, clinical symptoms, natural history, epidemiology, and management of alpha-gal syndrome.

Recent findings

Sensitization to alpha-gal is associated with bites from ectoparasites like the lone star tick Amblyomma americanum. Allergic reactions in alpha-gal syndrome are often delayed and inconsistent. The magnitude of the allergic response depends on co-factors like exercise and alcohol consumption and the amount of alpha-gal and fat present in the food. Assaying alpha-gal-specific IgE in the serum is the primary diagnostic test used to confirm the allergy. Long-term management of the condition involves avoidance of both mammalian food products and tick bites.

Alpha-gal syndrome disrupts the current paradigm for understanding food allergy. Exposure to an ectoparasite is critical for the development of specific IgE antibodies underlying sensitization, and allergic reactions depend on the activation of mast cells and basophils sensitized with IgE against a carbohydrate rather than a protein. Research in this field may lead to the development of improved diagnostic and therapeutic tools that can revolutionize the management of patients with alpha-gal syndrome.
Implementing a Nurse Discharge Navigator
Authors: Weeks Karen , Kile Debbie , Garber Jeannie
Published: October 2020

Purpose/Objectives:

The purpose of this quality improvement project was to evaluate the impact of a nurse discharge navigator on reducing 30-day readmissions for the heart failure and sepsis populations.

Primary Practice Setting:

The 238-bed community hospital in central Virginia is part of a health care system that encompasses 13 acute care facilities.

Methodology and Sample:

The aim of this project was to identify, implement, and evaluate the transition of care of high-risk readmission patients from January 2019 to April 2019. Inclusion criteria included patients who were 55 years and older, English speaking, diagnosed with heart failure and/or sepsis, discharged to home with or without home health, and/or consults received from case management and social services. Forty-one potential participants were identified with 28 consented. Readmission data were collected pre- and postintervention. The pre-/postanalysis consisted of descriptive statistics, readmission rates, and cost avoidance.

Results:

Out of the 28 participants, 7 participants were readmitted within 30 days. The heart failure readmission rates during the project implementation were as follows: January 24.05%, February 20%, March 19.75%, and April 11.11%. After the project completion the readmission rates were 22.97% for May and 26.03% for June, respectively. The potential cost avoidance with sustained gain from the project is $405,316.00.

Implications for Case Management Practice:

This project demonstrated that a discharge navigator had an effect on 30-day readmissions for high-risk heart failure and sepsis populations, as evident by a steady decline in overall heart failure readmission rate during project implementation. The sepsis population needs further research. The discharge navigator project added to the body of knowledge for comprehensive discharge planning, coordination, and education that is needed for these types of patient populations that have a great deal of medical complexity.
Dissemination and Implementation Science in Plastic and Reconstructive Surgery: Perfecting, Protecting, and Promoting the Innovation That Defines Our Specialty
Authors: Dengler Jana , Padovano William M. , Davidge Kristen , McKay Virginia , Yee Andrew , Mackinnon Susan E.
Published: October 2020

Plastic and reconstructive surgery has an illustrious history of innovation. The advancement, if not the survival, of the specialty depends on the continual development and improvement of procedures, practices, and technologies. It follows that the safe adoption of innovation into clinical practice is also paramount. Traditionally, adoption has relied on the diffusion of new knowledge, which is a consistent but slow and passive process. The emerging field of dissemination and implementation science promises to expedite the spread and adoption of evidence-based interventions into clinical practice. The field is increasingly recognized as an important function of academia and is a growing priority for major health-related funding institutions. The authors discuss the contemporary challenges of the safe implementation and dissemination of new innovations in plastic and reconstructive surgery, and call on their colleagues to engage in this growing field of dissemination and implementation science.
Infections after anti-CD19 chimeric antigen receptor T-cell therapy for hematologic malignancies: timeline, prevention, and uncertainties
Authors: Haidar Ghady , Garner Will , Hill Joshua A.
Published: October 2020

Purpose of review

Data on the infectious complications of anti-CD19 chimeric antigen receptor-modified T-cell (CAR-T-cell) therapies are scant. The approaches to preventing and managing infections among CAR-T-cell recipients are extrapolated from those of patients with other hematological malignancies. Understanding the incidence and risk factors of infections in these patients will improve clinical outcomes.

Recent findings

Infections occur in 23–42% of CAR-T-cell recipients and are most frequent in the first month after infusion, declining sharply thereafter. Risk factors include preinfusion (e.g., prior hematopoietic cell transplant, underlying malignancy) and postinfusion variables (e.g., cytokine release syndrome [CRS], neutropenia). Neutropenic fever after CAR-T-cell therapy is nearly universal but is confounded by CRS. The timeline of infections can be divided into preinfusion (because of the preparative regimen); 0–30 days after infusion, when bacterial infections predominate; and 30 days onwards, when respiratory viral infections predominate. Fungal and herpesviridae infections are uncommon.

Recent studies have shed light on the epidemiology of infections after CAR-T-cell therapy. Future efforts should focus on identifying modifiable risk factors for infection, defining neutropenic fever in the setting of CRS, determining the benefit of antimold prophylaxis, and identifying the optimal approach to viral monitoring, vaccination, and immunoglobulin replacement.
The why and how of maintaining hydration during cancer therapy
Authors: Hwa Yi L. , Kull Michelle R.
Published: October 2020

Purpose of review

To provide an overview of the role hydration plays in the oncology population while providing a synopsis of recent scientifically relevant published practice advancements.

Recent findings

Dehydration causes substantial symptom burden in cancer patients, secondary to both disease process and treatment complications. Maintaining fluid and electrolytes balance is the key to hydration therapy. When oral intake is diminished, artificial hydration can be delivered via enteral, intravenous and subcutaneous routes. Use of artificial hydration in end-of-life care for cancer patients remains a highly debated topic with unclear benefits and lack of established standards. A holistic approach is required in the decision-making process.

Maintaining adequate hydration is important in patients receiving cancer therapy. Challenges exist, secondary to limited clinical guidelines of hydration in patients with advanced cancer. Artificial hydration may be indicated for selected patients at the end of life if used on an individualized basis as medical treatment.
Intraoperative Neuromonitoring of Blink Reflex During Posterior Fossa Surgeries and Its Correlation With Clinical Outcome
Authors: Aydinlar Elif Ilgaz , Kocak Muge , Soykam Huseyin O. , Mat Beril , Dikmen Pinar Y. , Sezerman Osman Ugur , Elmaci İlhan , Pamir Mustafa Necmettin
Published: October 2020

Purpose:

Blink reflex (BR) under general anesthesia as an intraoperative neuromonitoring method was used to monitor facial nerves in few studies. This study aimed to test the utility of intraoperative BR during cerebellopontine angle and skull base surgeries, assess its prognostic value for facial nerve functions, and compare it with facial corticobulbar motor evoked potentials (CoMEPs).

Methods:

Blink reflex and facial CoMEPs were recorded from 40 patients undergoing skull base surgeries. Subdermal needles were placed in the supraorbital notch for stimulation and in the orbicularis oculi muscle for recording the BR. A double train of 20 to 40 V intensity with an intertrain interval of 40 to 60 milliseconds, an interstimulus interval of 2.5 milliseconds, and a stimulus duration of 0.5 milliseconds were applied. Facial nerve functions were assessed with the House–Brackmann grading system in the postoperative day 1 and third-month period and correlated with intraoperative BR and CoMEPs measurements.

Results:

Of 40 patients, BR was recordable on the affected side in 32 (80%) and contralateral side in 35 (87.5%) patients. According to our statistical results, BR had a slightly better sensitivity than facial CoMEPs in predicting impairment of facial nerve functions for both postoperative and third-month time points. Blink reflex showed better accuracy for predicting postoperative nerve functions, whereas CoMEPs correlated better in predicting third-month outcome.

Conclusions:

We suggest that BR is a valuable intraoperative neuromonitoring method that can be used in addition to facial CoMEPs during skull base surgeries to assess real-time facial nerve integrity and predict prognosis.
Silencing NADPH-Cytochrome P450 reductase affects imidacloprid susceptibility, fecundity, and embryonic development inLeptinotarsa decemlineata
Authors: Moural Timothy W. , Ban Liping , Hernandez Jonathan A. , Wu Meixiang , Zhao Chaoyang , Palli Subba R. , Alyokhin Andrei , Zhu Fang
Published: October 2020

The Colorado potato beetle (CPB) is a prominent insect pest of potatoes, tomatoes and eggplants all over the world, however, the management of CPB remains a challenging task for more than one hundred years. We have successfully developed bacteria-expressed dsRNA-mediated feeding RNA interference (RNAi) approach in our previous study. A critical step towards field management of CPB via feeding RNAi is to identify effective and environmentally safe target genes. NADPH-Cytochrome P450 reductase (CPR) plays a central role in cytochrome P450 action. The full lengthLeptinotarsa decemlineataCPR (LdCPR) cDNA was isolated from an imidacloprid resistant population. TheLdCPRgene was ubiquitously expressed in all stages tested but showed an increase in expression during the early stage of embryonic development. The bacteria-expressed dsRNA-mediated feeding RNAi ofLdCPRin adults caused systemic knock down expression of the gene coding forLdCPRin both adults and their eggs. Suppression ofLdCPRexpression increased susceptibility of imidacloprid in resistant beetles, as well as a significant decrease of fecundity in female beetles (29% less eggs/day) and the hatching rate (47%) of their eggs. These data suggest thatLdCPRplays important roles in insecticide detoxification and biosynthetic pathways of endogenous compounds and may serve as an essential target to control CPB.

HIGHLIGHTS

High expression ofLdCPRwas observed in the egg stage.

Silencing ofLdCPRreduced the CPR enzymatic activities.

LdCPRknockdown increased imidacloprid susceptibility.

LdCPRknockdown decreased the fecundity and enhanced embryonic lethality.