bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study
Authors: Vervloet Marc G , Boletis Ioannis N , de Francisco Angel L M , Kalra Philip A , Ketteler Markus , Messa Piergiorgio , Stauss-Grabo Manuela , Derlet Anja , Walpen Sebastian , Perrin Amandine , Ficociello Linda H , Rottembourg Jacques , Wanner Christoph , Cannata-Andía Jorge B , Fouque Denis
Published: October 2020

Background

The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis.

Methods

This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels.

Results

The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: −1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%.

Conclusions

SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.
Factors affecting pre-end-stage kidney disease haemoglobin control and outcomes following dialysis initiation: a nationwide study
Authors: Xu Yang , Evans Marie , Barany Peter , James Glen , Sjölander Arvid , Carrero Juan Jesus
Published: October 2020

Background

Attaining the narrow haemoglobin (Hb) range recommended by European Renal Best Practice Guidelines renal anaemia guidelines may be difficult, and whether this leads to better outcomes following dialysis initiation is not known.

Methods

This was an observational study from the Swedish Renal Registry 2012–16, including all patients with non-dialysis-dependent chronic kidney disease (CKD) initiating renal anaemia treatment. We evaluated factors associated with off-target Hb attainment (<10 and >12 g/dL). For those who initiated dialysis, we explored associations between the pre-end-stage kidney disease (pre-ESKD) time in which Hb was within or above range, and pre-ESKD Erythropoietin Resistance Index (ERI) with the 1-year risk of death or major adverse cardiovascular events + (MACE+).

Results

About 5000 patients initiated anaemia treatment, contributing to 25 431 consecutive visits over time. Patients with polycystic kidney disease, diabetic nephropathy and nephrosclerosis, with recent bleeding/transfusion, with higher C-reactive protein or abnormal phosphate had higher odds of maintaining Hb below range. Conversely, patients with older age, CKD Stages 3b–4, pyelonephritis, kidney transplant, iron medication, higher ESA doses or abnormal serum calcium and albumin had higher odds of maintaining Hb above range. A total of 1361 patients initiated dialysis, among whom 220 deaths and 453 MACE+ occurred. A greater time spent with a pre-ESKD Hb >12 g/dL was associated with a lower risk of MACE+ (hazard ratio = 0.76; 95% confidence interval 0.61–0.94) after dialysis initiation, and a lower pre-ESKD Erythropoietin Resistance Index (ERI) was associated with improved survival (1.39; 1.02–1.90).

Conclusions

Our study identified populations that require additional efforts to control their Hb. Our outcome analysis supports the value of pre-ESKD anaemia care while illustrating the problems of ESA hyporesponsiveness in clinical practice.
FLAKE: Fuzzy Graph Centrality-based Automatic Keyword Extraction
Authors: Jain Amita , Mittal Kanika , Vaisla Kunwar Singh
Published: October 2020

Keyword extraction is one of the most important aspects of text mining. Keywords help in identifying the document context. Many researchers have contributed their work to keyword extraction. They proposed approaches based on the frequency of occurrence, the position of words or the similarity between two terms. However, these approaches have shown shortcomings. In this paper, we propose a method that tries to overcome some of these shortcomings and present a new algorithm whose efficiency has been evaluated against widely used benchmarks. It is found from the analysis of standard datasets that the position of word in the document plays an important role in the identification of keywords. In this paper, a fuzzy logic-based automatic keyword extraction (FLAKE) method is proposed. FLAKE assigns weights to the keywords by considering the relative position of each word in the entire document as well as in the sentence coupled with the total occurrences of that word in the document. Based on the above data, candidate keywords are selected. Using WordNet, a fuzzy graph is constructed whose nodes represent candidate keywords. At this point, the most important nodes (based on fuzzy graph centrality measures) are identified. Those important nodes are selected as final keywords. The experiments conducted on various datasets show that proposed approach outperforms other keyword extraction methodologies by enhancing precision and recall.
Effects of simulated drought on biological soil quality, microbial diversity and yields under long-term conventional and organic agriculture
Authors: Kundel Dominika , Bodenhausen Natacha , Jørgensen Helene Bracht , Truu Jaak , Birkhofer Klaus , Hedlund Katarina , Mäder Paul , Fliessbach Andreas
Published: October 2020

Drought and agricultural management influence soil microorganisms with unknown consequences for the functioning of agroecosystems. We simulated drought periods in organic (biodynamic) and conventional wheat fields and monitored effects on soil water content, microorganisms and crops. Above the wilting point, water content and microbial respiration were higher under biodynamic than conventional farming. Highest bacterial and fungal abundances were found in biodynamically managed soils, and distinct microbial communities characterised the farming systems. Most biological soil quality parameters and crop yields were only marginally affected by the experimental drought, except for arbuscular mycorrhizal fungi (AMF), which increased in abundance under the experimental drought in both farming systems. AMF were further strongly promoted by biodynamic farming resulting in almost three times higher AMF abundance under experimental drought in the biodynamic compared with the conventional farming system. Our data suggest an improved water storage capacity under biodynamic farming and confirms positive effects of biodynamic farming on biological soil quality. The interactive effects of the farming system and drought may further be investigated under more substantial droughts. Given the importance of AMF for the plant's water supply, more in-depth studies on AMF may help to clarify their role for yields under conditions predicted by future climate scenarios.
Evaluation of hand hygiene behaviour in basic schools in Ghana: a case study of the Ablekuma Central Municipality in the greater region of Ghana
Authors: Fianko Joseph Richmond , Akosua Gawu Josephine
Published: October 2020

Hand washing is effective for the prevention and transmission of pathogens but washing with water only is not effective at reducing contamination. The study focussed on the evaluation of hand washing behaviour in Basic schools (Primary and Junior High Schools) in Ghana. Results of the study revealed that 75% of responding schools have hand washing stands to promote hand washing with soap. Sixty percent of the hand washing facilities were functional at the time of the study in the schools. Hand washing facilities were found to be inadequate as most of the schools lacked running water and soap for hand washing. The school children (72%) were found to have knowledge on hand hygiene. The school children were aware that they can get cholera, typhoid fever, dysentery, diarrhoea, stomach cramps and pains when they do not wash their hands with soap. Majority (68.2%) of school children reported that washing hands after defecation is important but only 17.5% reported actually follow this practice. The school children (51%) reported washing their hands before eating. Many of the schools did not have toilet facilities for the school children. The school children (35%) learnt hand washing from their parents and 60% from the teachers.
Portfolio optimization of power plants by using renewable energy in Iran
Authors: Ahmadi Seyedeh Asra , Mirlohi Seyed Mojtaba , Ahmadi Mohammad Hossein , Ameri Majid
Published: October 2020

Lack of investment in the electricity sector has created a huge bottleneck in the continuous flow of energy in the market, and this will create many problems for the sustainable growth and development of modern society. The main reason for this lack of investment is the investment risk in the electricity sector. One way to reduce portfolio risk is to diversify it. This study applies the concept of portfolio optimization to demonstrate the potential for greater use of renewable energy, which reduces the risk of investing in the electricity sector. Besides, it shows that investing in renewable energies can offset the risk associated with the total input costs. These costs stem from the volatility of associated prices, including fossil fuel, capital costs, maintenance, operation and environmental costs. This case study shows that Iran can theoretically supply ~33% of its electricity demand from renewable energy sources compared to its current 15% share. This case study confirms this finding and predicts that Iran, while reducing the risk of investing in electricity supply, can achieve a renewable energy supply of ~9% with an average increase in supply costs. Sensitivity analysis further shows that with a 10% change in input cost factors, the percentage of renewable energy supply is only partially affected, but basket costs change according to the scenario of 5–32%. Finally, suggestions are made that minimize risk rather than cost, which will bring about an increase in renewable energy supply.
Governing Complexity: Design Principles for the Governance of Complex Global Catastrophic Risks
Authors: Kreienkamp Julia , Pegram Tom
Published: October 2020

Why are existing global governance structures “not fit for purpose” when it comes to addressing complex global catastrophic risks (CGCRs) such as climate breakdown, ecosystem collapse, or parasitic artificial general intelligence? This article argues that a deeper appreciation of these risks as complex—as opposed to complicated—is vital to an effective global governance response. It joins other IR scholarship seeking to invigorate a rigorous research agenda on complex system dynamics within world politics, highlighting the value of complexity theory, not simply as a contextual descriptor, but as a conceptual toolkit to inform CGCR governance research and action. Taking seriously the implications of “restricted complexity,” it interrogates why the legacy governing toolkit—the assumptions, heuristics, models, and practices conventionally employed to solve international collective action problems—are unlikely to suffice. It further draws laterally upon design science to offer a novel design model for governing complex systems, with broad application across global policy domains. A case study of the COVID-19 pandemic response illustrates the importance of supplementing inherited “complicated” governance system design and practices with design principles explicitly oriented to working with complexity, rather than against it. We contend that IR scholars and practitioners must update old ways of thinking in light of a complexification of the discipline. Such a shift involves both revisiting the design logics underlying how we build global governance structures, as well as pursuing a generative research agenda more capable of responding adequately to instability, surprise, and extraordinary change.
White Paper: Bridging the gap between surveillance data and antimicrobial stewardship in the animal sector—practical guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks
Authors: Compri Monica , Mader Rodolphe , Mazzolini Elena , de Angelis Giulia , Mutters Nico T , Babu Rajendran Nithya , Galia Liliana , Tacconelli Evelina , Schrijver Remco ,   the ARCH working group, Adegnika Ayola Akim , Arieti Fabiana , Rajendran Nithya Babu , Bielicki Julia , Borrmann Steffen , Carrara Elena , Cauda Roberto , Compri Monica , De Angelis Giulia , Filippitzi Maria-Eleni , Frost Isabel , Galia Liliana , Giske Christian , Göpel Siri , Guardabassi Luca , Heuvelink Annet , Kahlmeter Gunnar , Kanj Souha S , Kostyanev Tomislav , Leibovici Leonard , Lucet Jean-Christophe , López-Cerero Lorena , Mader Rodolphe , Mazzaferri Fulvia , Mazzolini Elena , Mendelson Marc , Murri Rita , Mutters Nico T , Paul Mical , Pezzani Maria Diletta , Presterl Elisabeth , Renk Hanna , Song Le Huu , Sanguinetti Maurizio , Schrijver Remco , Scudeller Luigia , Sharland Mike , Sibani Marcella , Tacconelli Evelina , Torumkuney Didem , Velavan Thirumalaisamy P , Voss Andreas
Published: October 2020

Background

The JPIAMR ARCH and COMBACTE-MAGNET EPI-Net networks have joined efforts to formulate a set of target actions to link the surveillance of antimicrobial usage (AMU) and antimicrobial resistance (AMR) with antimicrobial stewardship (AMS) activities in four different settings. This White Paper focuses on the veterinary setting and embraces the One Health approach.

Methods

A review of the literature was carried out addressing research questions in three areas: AMS leadership and accountability; AMU surveillance and AMS; and AMR surveillance and AMS. Consensus on target actions was reached through a RAND-modified Delphi process involving over 40 experts in infectious diseases, clinical microbiology, AMS, veterinary medicine and public health, from 18 countries.

Results/discussion

Forty-six target actions were developed and qualified as essential or desirable. Essential actions included the setup of AMS teams in all veterinary settings, building government-supported AMS programmes and following specific requirements on the production, collection and communication of AMU and AMR data. Activities of AMS teams should be tailored to the local situation and capacities, and be linked to local or national surveillance systems and infection control programmes. Several research priorities were also identified, such as the need to develop more clinical breakpoints in veterinary medicine.

Conclusions

This White Paper offers a practical tool to veterinary practitioners and policy makers to improve AMS in the One Health approach, thanks to surveillance data generated in the veterinary setting. This work may also be useful to medical doctors wishing to better understand the specificities of the veterinary setting and facilitate cross-sectoral collaborations.
Efficacy and safety of tolvaptan in patients with malignant ascites: a phase 2, multicenter, open-label, dose-escalation study
Authors: Kudo Toshihiro , Murai Yoshiyuki , Kojima Yoshitsugu , Uehara Kenji , Satoh Taroh
Published: October 2020

Objective

This phase 2 study examined the efficacy and safety of tolvaptan, an aquaretic drug, in the treatment of ascites associated with cancer.

Methods

In the dose-escalation phase, oral tolvaptan was initiated at a dose of 3.75 mg/day, and the dose was increased daily to 7.5, 15 and 30 mg/day. Dose escalation was terminated once the increase from baseline in the daily urine volume reached 500 ml, at which point the patient proceeded to the maintenance phase of 5–7 days. Improvement of ascites was determined primarily by reduction in body weight and ascitic fluid volume.

Results

The mean change from baseline in body weight was maintained below 0 kg throughout the study. The mean change (±standard deviation) from baseline in ascitic fluid volume at the end of treatment (EOT) was 237.45 ± 868.14 ml in 33 evaluable patients. Although an increase from baseline in ascitic fluid volume at the EOT was observed in 23 of 33 patients (maximum: 1589.3 ml, minimum: 3.83 ml), a reduction in ascitic fluid volume was observed in the remaining 10 patients (maximum: −2304.3 ml, minimum: −27.5 ml). The common treatment-emergent adverse events included vomiting (5 of 43 patients, 11.6%), abdominal distension, constipation, thirst, blood osmolarity increased and renal impairment (3 of 43 patients, 7.0% each).

Conclusions

Tolvaptan seemed to have no definitive effect on reducing ascites; however, it might be effective in at least some cancer patients. No new safety concerns were identified at doses of 3.75–30 mg/day.
A Frequency-Specific Factorization to Identify Commonalities with an Application to the European Bond Markets
Authors: Boffelli Simona , Novotny Jan , Urga Giovanni
Published: October 2020

We propose a frequency-specific framework to link the common features in the multivariate high-frequency price jumps with the low-frequency exogenous factors. We introduce the measure of commonality and the measure of multiplicity based on high-frequency data and define the notions of coarrivals and cojumps to explore the contribution of individual assets. We employ the framework to study the 10-year high-frequency European government bond yields over June 2009–April 2019 as a function of macrofactors, macroannouncements, bond auctions, and unconventional monetary policy announcements. Both idiosyncratic and common jump arrivals are significant, with the idiosyncratic arrivals being more sensitive to financial distress as characterized by a low level of commonality in jump arrivals.
Health Behaviors Among Service Members Injured on Deployment: A Study From the Wounded Warrior Recovery Project
Authors: McCabe Cameron T , Watrous Jessica R , Galarneau Michael R
Published: October 2020

Introduction

Service members (SMs) who are injured on deployment are at risk for myriad long-term health problems that may be ancillary to their physical injury, including high rates of depression and posttraumatic stress disorder, and poor health behaviors (e.g., problem drinking, cigarette and tobacco use, poor sleep quality, and sedentary lifestyle). As the specific health behaviors injured SMs engage in have been largely ignored, the primary aim of this study was to compare health behavior patterns among those with and without mental health problems in a large, representative sample of SMs injured on combat deployment.

Materials and Methods

Participants (N = 3,303) completed behavioral health assessments between September 2018 and April 2019 as part of the Wounded Warrior Recovery Project. Multivariate linear regressions and binary logistic regressions were used to evaluate differences between mental health screening status and health behavior outcomes, adjusting for injury severity, age, and years since injury.

Results

Overall, about half of participants screened positive for posttraumatic stress disorder and/or depression (49%). Participants reported high rates of alcohol use and problems, cigarette and tobacco use, inadequate sleep and poor sleep quality, and low levels of physical activity. With the exception of number of drinking days and likelihood of current tobacco use, participants who screened positive for a mental health disorder evidenced significantly worse health behavior outcomes.

Conclusions

The results provide a preliminary glance into the mental health and health behaviors of SMs roughly a decade after injury, and underscore the importance of examining the interplay between mental, physical, and behavioral health outcomes among wounded warriors to promote health and wellness.
Penetrating Neck Injuries Treated at a U.S. Role 3 Medical Treatment Facility in Afghanistan During Operation Resolute Support
Authors: Breeze John , Gensheimer William G , DuBose Joseph J
Published: October 2020

Introduction

Military trauma registries can identify broad epidemiological trends from neck wounds but cannot reliably demonstrate temporal casualty from clinical interventions or differentiate penetrating neck injuries (PNI) from those that do not breach platysma.

Materials and Methods

All casualties presenting with a neck wound to a Role 3 Medical Treatment Facility in Afghanistan between January 1, 2016 and September 15, 2019 were retrospectively identified using the Emergency Room database. These were matched to records from the Operating Room database, and computed tomography (CT) scans reviewed to determine damage to the neck region.

Results

During this period, 78 casualties presented to the Emergency Room with a neck wound. Forty-one casualties underwent surgery for a neck wound, all of whom had a CT scan. Of these, 35/41 (85%) were deep to platysma (PNI). Casualties with PNI underwent neck exploration in 71% of casualties (25/35), with 8/25 (32%) having surgical exploration at Role 2 where CT is not present. Exploration was more likely in Zones 1 and 2 (8/10, 80% and 18/22, 82%, respectively) compared to Zone 3 (2/8, 25%).

Conclusion

Hemodynamically unstable patients in Zones 1 and 2 generally underwent surgery before CT, confirming that the low threshold for exploration in such patients remains. Only 25% (2/8) of Zone 3 PNI were explored, with the high negative predictive value of CT angiography providing confidence that it was capable of excluding major injury in the majority of cases. No deaths from PNI that survived to treatment at Role 3 were identified, lending evidence to the current management protocols being utilized in Afghanistan.
Toward a “Dashboard” Indicator of Retention in U.S. Navy Personnel
Authors: Taylor Marcus K , Hernández Lisa M , Clinton-Sherrod A Monique
Published: October 2020

Introduction

Retention is a top priority for the U.S. Navy. However, our understanding of factors influencing retention of Navy personnel is limited. Current research implies that poor mental health, low appraisals of unit cohesion, low leadership satisfaction, and low social support may adversely affect retention. There is a need to understand how these and other factors influence retention in U.S. Navy personnel. We evaluated a broad range of factors influencing job satisfaction and career intentions (proxies of retention) in a large sample of Navy service members.

Materials and Methods

Seven hundred and ninety-eight U.S. Navy men and women participated in this study as part of the Naval Unit Behavioral Health Needs Survey (NHRC.2014.0006). Independent variables included personal and unit morale, unit cohesion, affective organizational commitment, social support, behavioral health, sleep, leadership satisfaction, and perceived stress. Dependent variables include job satisfaction and career intentions. Separate multivariate regression models examined the unique and combined associations of independent and demographic variables with each dependent variable, respectively.

Results

Regression models accounted for 48% of variance in job satisfaction and 55% of variance in career intentions, respectively. The most robust predictors of job satisfaction were affective organizational commitment (i.e., one’s emotional attachment to, identification with, and involvement in an organization), depressive symptoms, unit cohesion, and perceived stress; primary predictors of career intentions included affective organizational commitment, years of military service, marital status, and race/ethnicity.

Conclusion

In this study, we identified diverse predictors of job satisfaction and career intentions of Navy men and women, with overall models accounting for substantial variance in both outcomes. This study informs evidence-based policies, programs, practices, and processes designed to influence job satisfaction, career intentions, and retention in U.S. Navy service members. These study findings also inform the development of a dashboard indicator of retention of U.S. Navy men and women.
Prolonged Field Care Research Approach and Its Relevance to Civilian Medicine
Authors: Cohen Adam B , Davis Michael , Herman Sarah E M
Published: October 2020

In early March 2020, Johns Hopkins University Applied Physics Lab hosted an Association of Military Surgeons of the United States regional conference to address medical demands of the future battlefield for which prolonged field care is expected. Arising from this conference, we propose here an approach to prolonged field care research—and also summarize the major concepts discussed at the conference. We draw parallels to prolonged field care investments and advancements that apply beyond the combat environment. The exceedingly daunting medical challenges of the future battlefield, on land and at sea, must be addressed to maintain an effective force able to compete with modern highly capable adversaries. Since the human element, and its health, will allow future mission success, we propose here an approach to making soldier health-related research most impactful.
Fluorescence Guidance and Intraoperative Adjuvants to Maximize Extent of Resection
Authors: Orillac Cordelia , Stummer Walter , Orringer Daniel A
Published: October 2020

Safely maximizing extent of resection has become the central goal in glioma surgery. Especially in eloquent cortex, the goal of maximal resection is balanced with neurological risk. As new technologies emerge in the field of neurosurgery, the standards for maximal safe resection have been elevated. Fluorescence-guided surgery, intraoperative magnetic resonance imaging, and microscopic imaging methods are among the most well-validated tools available to enhance the level of accuracy and safety in glioma surgery. Each technology uses a different characteristic of glioma tissue to identify and differentiate tumor tissue from normal brain and is most effective in the context of anatomic, connectomic, and neurophysiologic context. While each tool is able to enhance resection, multiple modalities are often used in conjunction to achieve maximal safe resection. This paper reviews the mechanism and utility of the major adjuncts available for use in glioma surgery, especially in tumors within eloquent areas, and puts forth the foundation for a unified approach to how leverage currently available technology to ensure maximal safe resection.
Experience Does Not Eliminate Bubbles: Experimental Evidence
Authors: Kopányi-Peuker Anita , Weber Matthias
Published: October 2020

We study the role of investor experience in the formation of asset price bubbles. We conduct a call market experiment in which participants trade assets with each other and a learning-to-forecast experiment in which participants only forecast future prices (while trade based on these forecasts is computerized). Each experiment comprises three treatments varying the information that participants receive about the fundamental value. Each experimental market is repeated three times. Throughout, we observe sizable bubbles that persist despite participant experience. Our findings in the call market experiment contrast with those in the literature. Our findings in the learning-to-forecast experiment are novel.
Efficacy of a step-down regimen of oral prednisolone in axial spondyloarthritis: result of a double-blind randomized controlled trial (COBRA-AS Study)
Authors: Mishra Debashish , Dhir Varun , Naidu G S R S N K , Khullar Aastha , Kumar Vishal , Sharma Shefali , Sharma Aman , Jain Sanjay
Published: October 2020

Objectives

To evaluate the efficacy and safety of a step-down regimen of oral prednisolone over 24 weeks in patients of axial SpA (axSpA).

Methods

This proof-of-concept double-blind randomized controlled trial enrolled patients with active axSpA (BASDAI ≥4) having predominantly axial disease (≤1 active joint currently) and inadequate response to NSAIDs. They were randomized to receive either oral prednisolone (n = 32) or placebo (n = 33) at a dose of 60, 40, 30, 20, 15 and 10 mg daily for 1 week each, following which they received 5 mg prednisolone (or placebo) daily for 18 weeks. The primary endpoint was a 50% improvement in the BASDAI (BASDAI50) at week 24. Analysis was intention to treat.

Results

A BASDAI50 was achieved by 12 of 32 patients (37.5%) in the prednisolone arm and 3 of 33 patients (9.1%) in the placebo arm at 24 weeks [difference 28.4% (95% CI 7.9, 46.7)]. However, there was no difference in achieving a 20 or 40% improvement in the Assessment of SpondyloArthritis international Society response between the groups. Although there was a significant intergroup difference in adjusted ΔBASDAI and ΔAnkylosing Spondylitis Disease Activity Score with CRP at 24 weeks, there was no difference at 12 weeks. There was also no significant difference in ΔBASFI, ΔBAS-G or ΔBASMI at 12 or 24 weeks. No serious adverse events were noted. There was significant weight gain in the first 12 weeks in the prednisolone group vs placebo [0.9 (s.d. 0.4) kg], but not at 24 weeks.

Conclusions

In this small study, oral prednisolone was efficacious in axSpA in achieving the primary outcome, but many crucial secondary outcomes such as functional improvement were not met. Its impact on bone loss was not studied.

Trial registration: CTRI/2018/01/011342.
Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery
Authors: Susano Maria J. , Grasfield Rachel H. , Friese Matthew , Rosner Bernard , Crosby Gregory , Bader Angela M. , Kang James D. , Smith Timothy R. , Lu Yi , Groff Michael W. , Chi John H. , Grodstein Francine , Culley Deborah J.
Published: October 2020

Background

Frailty and cognitive impairment are associated with postoperative delirium, but are rarely assessed preoperatively. The study was designed to test the hypothesis that preoperative screening for frailty or cognitive impairment identifies patients at risk for postoperative delirium (primary outcome).

Methods

In this prospective cohort study, the authors administered frailty and cognitive screening instruments to 229 patients greater than or equal to 70 yr old presenting for elective spine surgery. Screening for frailty (five-item FRAIL scale [measuring fatigue, resistance, ambulation, illness, and weight loss]) and cognition (Mini-Cog, Animal Verbal Fluency) were performed at the time of the preoperative evaluation. Demographic data, perioperative variables, and postoperative outcomes were gathered. Delirium was the primary outcome detected by either the Confusion Assessment Method, assessed daily from postoperative day 1 to 3 or until discharge, if patient was discharged sooner, or comprehensive chart review. Secondary outcomes were all other-cause complications, discharge not to home, and hospital length of stay.

Results

The cohort was 75 [73 to 79 yr] years of age, 124 of 219 (57%) were male. Many scored positive for prefrailty (117 of 218; 54%), frailty (53 of 218; 24%), and cognitive impairment (50 to 82 of 219; 23 to 37%). Fifty-five patients (25%) developed delirium postoperatively. On multivariable analysis, frailty (scores 3 to 5 [odds ratio, 6.6; 95% CI, 1.96 to 21.9; P = 0.002]) versus robust (score 0) on the FRAIL scale, lower animal fluency scores (odds ratio, 1.08; 95% CI, 1.01 to 1.51; P = 0.036) for each point decrease in the number of animals named, and more invasive surgical procedures (odds ratio, 2.69; 95% CI, 1.31 to 5.50; P = 0.007) versus less invasive procedures were associated with postoperative delirium.

Conclusions

Screening for frailty and cognitive impairment preoperatively using the FRAIL scale and the Animal Verbal Fluency test in older elective spine surgery patients identifies those at high risk for the development of postoperative delirium.

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What This Article Tells Us That Is New
Cryoneurolysis and Percutaneous Peripheral Nerve Stimulation to Treat Acute Pain
Authors: Ilfeld Brian M. , Finneran John J.
Published: October 2020

Two regional analgesic modalities currently cleared by the U.S. Food and Drug Administration hold promise to provide postoperative analgesia free of many of the limitations of both opioids and local anesthetic-based techniques. Cryoneurolysis uses exceptionally low temperature to reversibly ablate a peripheral nerve, resulting in temporary analgesia. Where applicable, it offers a unique option given its extended duration of action measured in weeks to months after a single application. Percutaneous peripheral nerve stimulation involves inserting an insulated lead through a needle to lie adjacent to a peripheral nerve. Analgesia is produced by introducing electrical current with an external pulse generator. It is a unique regional analgesic in that it does not induce sensory, motor, or proprioception deficits and is cleared for up to 60 days of use. However, both modalities have limited validation when applied to acute pain, and randomized, controlled trials are required to define both benefits and risks.
Perioperative Open-lung Approach, Regional Ventilation, and Lung Injury in Cardiac Surgery
Authors: Lagier David , Velly Lionel J. , Guinard Benoit , Bruder Nicolas , Guidon Catherine , Vidal Melo Marcos F. , Alessi Marie-Christine
Published: October 2020

Background

In the Protective Ventilation in Cardiac Surgery (PROVECS) randomized, controlled trial, an open-lung ventilation strategy did not improve postoperative respiratory outcomes after on-pump cardiac surgery. In this prespecified subanalysis, the authors aimed to assess the regional distribution of ventilation and plasma biomarkers of lung epithelial and endothelial injury produced by that strategy.

Methods

Perioperative open-lung ventilation consisted of recruitment maneuvers, positive end-expiratory pressure (PEEP) = 8 cm H2O, and low-tidal volume ventilation including during cardiopulmonary bypass. Control ventilation strategy was a low-PEEP (2 cm H2O) low-tidal volume approach. Electrical impedance tomography was used serially throughout the perioperative period (n = 56) to compute the dorsal fraction of ventilation (defined as the ratio of dorsal tidal impedance variation to global tidal impedance variation). Lung injury was assessed serially using biomarkers of epithelial (soluble form of the receptor for advanced glycation end-products, sRAGE) and endothelial (angiopoietin-2) lung injury (n = 30).

Results

Eighty-six patients (age = 64 ± 12 yr; EuroSCORE II = 1.65 ± 1.57%) undergoing elective on-pump cardiac surgery were studied. Induction of general anesthesia was associated with ventral redistribution of tidal volumes and higher dorsal fraction of ventilation in the open-lung than the control strategy (0.38 ± 0.07 vs. 0.30 ± 0.10; P = 0.004). No effect of the open-lung strategy on the dorsal fraction of ventilation was noted at the end of surgery after median sternotomy closure (open-lung = 0.37 ± 0.09 vs. control = 0.34 ± 0.11; P = 0.743) or in extubated patients at postoperative day 2 (open-lung = 0.63 ± 0.18 vs. control = 0.59 ± 0.11; P > 0.999). Open-lung ventilation was associated with increased intraoperative plasma sRAGE (7,677 ± 3,097 pg/ml vs. 6,125 ± 1,400 pg/ml; P = 0.037) and had no effect on angiopoietin-2 (P > 0.999).

Conclusions

In cardiac surgery patients, open-lung ventilation provided larger dorsal lung ventilation early during surgery without a maintained benefit as compared with controls at the end of surgery and postoperative day 2 and was associated with higher intraoperative plasma concentration of sRAGE suggesting lung overdistension.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Genomic Screening for Malignant Hyperthermia Susceptibility
Authors: Biesecker Leslie G. , Dirksen Robert T. , Girard Thierry , Hopkins Philip M. , Riazi Sheila , Rosenberg Henry , Stowell Kathryn , Weber James
Published: October 2020

It is timely to consider the utility and practicability of screening for malignant hyperthermia susceptibility using genomic testing. Here the authors pose a simple, but bold question: what would it take to end deaths from malignant hyperthermia? The authors review recent advances and propose a scientific and clinical pathway toward this audacious goal to provoke discussion in the field.
Clinical Outcomes Following Tocilizumab Administration in Mechanically Ventilated Coronavirus Disease 2019 Patients
Authors: Sirimaturos Michael , Gotur Deepa B. , Patel Samir J. , Dreucean Diane , Jakowenko Nicholas , Cooper Megan H. , Brahmbhatt Nishal , Graviss Edward A. , Nguyen Duc T. , Pingali Sai Ravi , Lin Jiejian , Musick William L.
Published: October 2020

Objectives:

Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement.

Design:

A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020.

Setting:

Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States.

Patients:

The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease.

Interventions:

Tocilizumab was administered either at a weight-based dose of 4–8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician’s discretion.

Measurements and Main Results:

The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%).

Conclusions:

Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.
Prophylactic fibrinogen concentrate administration in surgical correction of paediatric craniosynostosis
Authors: Machotta Andreas , Huisman Elise J. , Appel Inge M. , Luijnenburg Saskia E. , Lopez-Yurda Marta , Cnossen Marjon H. , van Ommen Cornelia H.
Published: October 2020

BACKGROUND

Surgical craniosynostosis repair in children is associated with massive blood loss and significant transfusion of blood products. Fibrinogen concentrate is claimed to be useful in reducing blood loss and transfusion requirements.

OBJECTIVE

We investigated whether prophylactic administration of fibrinogen concentrate will reduce blood loss and transfusion requirements during paediatric craniofacial surgery.

DESIGN

Randomised, placebo-controlled, double-blind clinical trial.

SETTING

University medical centre.

PATIENTS

A total of 114 infants and children up to 25 months of age (median age 10 months).

INTERVENTION

Surgical craniosynostosis repair by calvarial remodelling was performed in each patient. Patients were randomised to receive prophylactic fibrinogen concentrate (Haemocomplettan P) at a mean dose of 79 mg kg−1 body weight or placebo.

MAIN OUTCOME MEASURES

Primary outcome was the volume of transfused blood products. Secondary outcomes were peri-operative blood loss, duration of surgery, length of stay in the paediatric ICU, length of hospital stay, postoperative complications and adverse effects of fibrinogen concentrate infusion.

RESULTS

No significant differences (P < 0.05) were found in the volume of transfused blood products (median 29 ml kg−1 body weight vs. 29 ml kg−1 body weight), intra-operative estimated blood loss (45 vs. 46 ml kg−1), calculated blood loss (57 vs. 53 ml kg−1), or postoperative blood loss (24 vs. 24 ml kg−1) between the intervention and placebo groups. In addition, duration of surgery, length of stay in the paediatric ICU, hospital stay and complications were not significantly different between the two groups.

CONCLUSION

During surgical craniosynostosis repair in young children, prophylactic administration of high-dose fibrinogen concentrate did not reduce the amount of transfused blood products or decrease peri-operative blood loss.

TRIAL REGISTRATION

National Trial Register (NTR2975) and EudraCT (2011-002287-24).
Peri-operative swelling of fingers
Authors: Bucx Martin J.L. , Sedik Ibrahim Oulad , Jenniskens Marc , Kox Matthijs , Heijne Amon
Published: October 2020

BACKGROUND

In most Dutch hospitals, because of putative peri-operative swelling of the fingers, patients must remove rings before entering the operating theatre. If this proves impossible, destructive methods for removal may be required. For some patients, this might be too radical, as the risk of wearing rings may not be in proportion to the economic and emotional damage to the patient.

OBJECTIVE

The objective of this study was to determine whether peri-operative swelling of fingers occurs in elective surgery patients.

DESIGN

A prospective observational study.

SETTING

University Medical Centre.

PATIENTS

Five groups of patients: major cardiothoracic surgery, major noncardiothoracic surgery, nonmajor surgery with a minimum of one overnight stay, nonmajor surgery without overnight stay and surgery under intrathecal anaesthesia.

MAIN OUTCOME MEASURE

Finger swelling, as measured by the circumference of the first phalanx of the middle and ring fingers of both hands, pre-operatively and at 3, 24 and 48 h postsurgery, using a roller tape with one winding and 20-g weights in a custom-made frame.

RESULTS

One hundred and forty-eight patients were enrolled. Peri-operative swelling reached statistical significance in all groups and was most prominent in major cardiothoracic and noncardiothoracic surgery (maximum increases in circumference were 10.6 and 7.3%, respectively). In all groups, maximal swelling was observed 24 h postsurgery.

CONCLUSION

Peri-operative swelling of fingers is a common phenomenon, which is related to the extent of the surgical procedure.

TRIAL REGISTRATION

Netherlands Trial Register NL8066.
Effect of rectus sheath block vs. spinal anaesthesia on time-to-readiness for hospital discharge after trans-peritoneal hand-assisted laparoscopic live donor nephrectomy
Authors: Bhatia Kailash , Columb Malachy , Wadsworth Richard , Macnab William , Jepegnanam Chandran , Campbell Tunde , Van Dellen David
Published: October 2020

BACKGROUND

The role of spinal anaesthesia in patients having a transperitoneal hand-assisted laparoscopic donor nephrectomy in an enhanced recovery setting has never been investigated.

OBJECTIVE

We explored whether substituting a rectus sheath block (RSB) with spinal anaesthesia, as an adjunct to a general anaesthetic technique, influenced time-to-readiness for discharge in patients undergoing hand-assisted laparoscopic donor nephrectomy.

DESIGN

Prospective randomised open blinded end-point (PROBE) study with two parallel groups.

SETTING

Tertiary University Hospital.

PATIENTS

Ninety-seven patients undergoing a trans-peritoneal hand-assisted laparoscopic donor nephrectomy.

INTERVENTION

Patients (n=52) were randomly assigned to receive a general anaesthetic and a surgical RSB with 2 mg kg−1 of levobupivacaine at the time of surgical closure or a spinal anaesthetic with hyperbaric bupivacaine 12.5 mg and diamorphine 0.5 mg (n=45) before general anaesthesia.

PRIMARY OUTCOME

The primary outcome was the time-to-readiness for discharge following surgery.

RESULTS

Median [IQR] times-to-readiness for discharge were 75 [56 to 83] and 79 [67 to 101] h for RSB and spinal anaesthesia and there was no significant difference in times-to-readiness for discharge (median difference 4 (95% CI, 0 to 20h; P 
= 0.07)). There were no significant differences in pain scores at rest (P 
= 0.91) or on movement (P = 0.66). Median 24-h oxycodone consumptions were similar (P 
= 0.80). Nausea and vomiting scores were similar (P = 0.57) and urinary retention occurred in one vs. four patients with RSB and spinal anaesthesia, respectively (P 
= 0.077).

CONCLUSION

Substitution of RSB with spinal anaesthesia using 12.5 mg hyperbaric bupivacaine and 0.5 mg diamorphine, together with a general anaesthetic failed to confer any benefit on time-to-discharge readiness following transperitoneal hand-assisted laparoscopic donor nephrectomy. RSB provided similar analgesia in the immediate postoperative period with a low frequency of side-effects in this cohort.

TRIAL REGISTRATION

ClinicalTrial.gov identifier: NCT02700217.
Development of a High-Throughput Quantification Method for Pazopanib Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Clinical Application in Patients With Soft Tissue Tumors
Authors: Shiraiwa Ken , Suzuki Yosuke , Tanaka Kazuhiro , Kawano Masanori , Iwasaki Tatsuya , Matsumoto Asami , Tanaka Ryota , Tatsuta Ryosuke , Tsumura Hiroshi , Itoh Hiroki
Published: October 2020

Background:

Pazopanib is widely used to treat renal cell carcinomas and soft tissue tumors in Japan. Pazopanib has significant therapeutic efficacy but it is associated with frequent severe adverse effects. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A more convenient and rapid pazopanib assay is desirable for the application of TDM in clinical settings. In this study, the authors developed a high-throughput method for quantifying pazopanib in human plasma using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

Methods:

After a simple solid-phase extraction step using a 96-well plate, pazopanib was analyzed by UHPLC-MS/MS in the positive electrospray ionization mode.

Results:

The novel method fulfilled the requirements of the US Food and Drug Administration and the European Medicines Agency guidelines for assay validation, and the lower limit of quantification was 0.5 mcg/mL. The calibration curves were linear over the concentration range of 0.5–100 mcg/mL. The average recovery rate was 102.0% ± 3.9% (mean ± SD). The precision was below 5.0%, and the accuracy was within 12.0% for all quality control levels. Matrix effect varied between 90.9% and 97.1%. This assay was successfully applied to TDM of pazopanib trough concentrations in 3 patients treated with the drug for soft tissue tumors.

Conclusions:

The authors succeeded in developing a novel high-throughput UHPLC-MS/MS method for quantifying pazopanib in human plasma. This method can be applied to TDM of patients receiving pazopanib in clinical settings.