bluuebunny/crossref_metadata_2025 huggingface dataset:
Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta‐analysis
Authors: Weibel S. , Schaefer M. S. , Raj D. , Rücker G. , Pace N. L. , Schlesinger T. , Meybohm P. , Kienbaum P. , Eberhart L. H. J. , Kranke P.
Published: November 2020

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti‐emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta‐analyses to compare, and rank in terms of efficacy and safety, single anti‐emetic drugs and their combinations, including 5‐hydroxytryptamine3, dopamine‐2 and neurokinin‐1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo‐controlled and head‐to‐head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta‐Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class‐specific side‐effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin‐1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18–0.38); ramosetron, 0.44 (0.32–0.59); granisetron, 0.45 (0.38–0.54); dexamethasone, 0.51 (0.44–0.57); and ondansetron, 0.55 (0.51–0.60). It was moderate for fosaprepitant, 0.06 (0.02–0.21) and droperidol, 0.61 (0.54–0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side‐effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.
Low false‐positive rate of perfusion index as a screening tool for neonatal aortic coarctation
Authors: Lannering Katarina , Elfvin Anders , Mellander Mats
Published: November 2020

Aim

Adding perfusion index (PI) to pulse oximetry screening (POS) may increase neonatal detection of CoA (aortic coarctation). A cut‐off <0.7% has been suggested but is associated with a high rate of false positives. We aimed to evaluate the specificity of PI when using repeated instead of single measurements.

Methods

A pilot study was conducted in 50 neonates. PI was recorded in right hand and a foot by pulse oximeter. If PI was <0.7%, the measurement was immediately repeated up to 3 times. If all three measurements were <0.7% in hand and/or foot the screen was positive and echocardiography was performed. There were 3/50 false‐positive screens. The protocol was therefore modified requiring 30 min intervals between measurements.

Results

An additional 463 neonates were included using the modified protocol at a median age of 18 h. There were no false positives. The only neonate with CoA had a negative screen (PI hand 1.2% and foot 0.8%). The measurement required on average an extra 3 min and 30 s compared with POS only.

Conclusion

The false‐positive rate of PI was reduced by using repeated PI measurements. The sensitivity for CoA using this protocol should be evaluated in large‐scale prospective studies.
Counterpoint: There is a best duration of deep molecular response for treatment‐free remission, but it is patient‐specific, and that is the challenge
Authors: Ross David M. , Hughes Timothy P.
Published: November 2020

There is considerable clinical and scientific interest in identifying reliable predictors of treatment‐free remission in chronic myeloid leukaemia. Most predictors have been identified from non‐randomized clinical trials or retrospective cohorts that could be subject to bias. The validity of predictive factors, such as duration of treatment or of deep molecular response, has been questioned. We briefly review the relevant data and the potential for bias, arguing that the risk of bias may be overstated, and that accumulating data strongly suggest that depth and duration of molecular response are critical factors to enable us to predict the probability of treatment‐free remission.
Smoking impairs molecular response, and reduces overall survival in patients with chronic myeloproliferative neoplasms: A retrospective cohort study
Authors: Sørensen Anders Lindholm , Knudsen Trine A. , Skov Vibe , Kjær Lasse , Holm Nanna , Ellervik Christina , Hasselbalch Hans Carl
Published: November 2020

The effects of smoking on the molecular response (MR) and overall survival (OS) in patients with chronic myeloproliferative neoplasms (MPNs) have not been investigated before. We analysed a historical cohort of 498 consecutive patients diagnosed with MPNs. Moreover, we analysed a subgroup of 270 consecutive patients with MPNs with > 1 measurement of the JAK2V617F variant allele frequency. The data were analysed using Kaplan–Meier plots and Cox regression analysis, along with linear regression models. In all patients, the rate of MR was significantly higher in never‐smokers compared with current smokers in the univariate model (HR, 1·9; 95% CI, 1·1–3·3; P = 0·033) and the multivariate model (HR, 1·9; 95% CI, 1·1–3·5; P = 0·029). Similar findings were observed with different cut‐off values for a partial MR. A subgroup analysis including only interferon‐α2‐treated patients showed similar results. In multivariate analyses, the OS was significantly better for never‐smokers (HR, 0·46; 95% CI, 0·29–0·75; P = 0·002) than current smokers. The differences were more pronounced in the pegylated interferon‐α2‐treated patients. However, no significant interaction of interferon‐α2 treatment was observed. In conclusion, we found that tobacco smoking reduced the rate of MR and OS in patients with MPNs. Cessation of smoking should be encouraged.
The DPP4 inhibitor linagliptin ameliorated renal injury and accelerated resolution in a rat model of crescentic nephritis
Authors: Mayer Anna‐Lena , Scheitacker Iris , Ebert Nadja , Klein Thomas , Amann Kerstin , Daniel Christoph
Published: November 2020

Background and Purpose

Dipeptidyl peptidase 4 (DPP‐4) inhibitors are a class of oral glucose‐lowering drugs used in the treatment of type 2 diabetes. In a pilot study using human kidney biopsies, we observed high DPP‐4 expression in early crescent formation. This glomerular lesion occurs in different kidney diseases and is a hallmark in the pathogenesis of renal dysfunction. Therefore, we investigated the potential involvement of DPP‐4 in the pathogenesis of nephritis induced by anti‐glomerular basement membrane (GBM) antibody in rats.

Experimental Approach

Linagliptin and vehicle were used to treat anti‐GBM nephritis in a 2‐ and 8‐week regimen, that is either preventive or therapeutic (treatment started 7 days or 4 weeks after disease induction). Kidney function, morphologic changes, inflammation and fibrosis were monitored.

Key Results

In the long‐term experiment, linagliptin preventive treatment in anti‐GBM nephritic rats significantly reduced the number of crescents, glomerulosclerosis, tubular injury and renal fibrosis, compared with those in untreated nephritic rats. Both linagliptin regimes significantly lowered the number of Pax8+ cells on the glomerular tuft in anti‐GBM nephritis, indicating accelerated resolution of the cellular crescents. The linagliptin treatment did not change the number but the podocyte stress in both therapeutic groups. Therapeutic intervention with linagliptin resulted in weaker amelioration of renal disease on Week 8 than did preventive intervention.

Conclusion and Implications

DPP‐4 inhibition with linagliptin ameliorates renal injury in a rat model of anti‐GBM, indicating that linagliptin not only is a secure therapy in diabetes but also can improve resolution of glomerular injury and healing in non‐diabetic renal disease.
Nutrient‐induced hyperosmosis evokes vasorelaxation via TRPV1 channel‐mediated, endothelium‐dependent, hyperpolarisation in healthy and colitis mice
Authors: Guo Yanjun , Lu Cheng , Zhang Luyun , Wan Hanxing , Jiang Enlai , Chen Yao , Dong Hui
Published: November 2020

Background and Purpose

In humans, blood flow in the mesenteric circulation is greatly increased after meals, but the mechanisms underlying postprandial mesenteric vasorelaxation induced by nutrients and whether this process is involved in the pathogenesis of colitis, are not well understood. Here we have studied the direct actions of nutrients on mesenteric arterial tone and the underlying molecular mechanisms in healthy and colitis mice.

Experimental Approach

Colitis in C57BL/6 mice was induced with dextran sodium sulphate. Nutrient‐induced vasorelaxation of mesenteric arterioles from humans and mice was studied with wire myograph assays. Ca2+ and Na+ imaging were performed in human vascular endothelial cells and vascular smooth muscle cells, using selective pharmacological agents and shRNA knockdown of TRPV1 channels.

Key Results

Glucose, sodium and mannitol concentration‐dependently induced endothelium‐dependent relaxation of human and mouse mesenteric arterioles via hyperosmotic action,. Hyperosmosis‐induced vasorelaxation was almost abolished by selective blockers for TRPV1, IKCa and SKCa channels. Glucose markedly stimulated Ca2+ influx through endothelial TRPV1 channels, an effect attenuated by selective blockers and shRNA knockdown of TRPV1 channels. Capsaicin synergised the glucose‐induced vasorelaxation. Nutrient‐induced hyperosmosis also activated Na+/K+‐ATPase and the Na/Ca exchanger (NCX) to decrease [Ca2+]i in VSMCs. Glucose‐induced vasorelaxation was impaired in mouse colitis.

Conclusion and Implications

Nutrient‐induced hyperosmosis evoked endothelium‐dependent mesenteric vasorelaxation via the TRPV1/Ca2+/ endothelium‐dependent hyperpolarisation pathway to increase normal mucosal perfusion, which is impaired in our model of colitis. The TRPV1/Ca2+/ endothelium‐dependent hyperpolarisation pathway could provide novel drug targets for gastrointestinal diseases with hypoperfusion, such as chronic colitis and mesenteric ischaemia.
Overcoming Cost Disadvantages in Procurement Auctions
Authors: Wooten Joel O. , Cho Sanghoon , Fry Timothy D. , Donohue Joan M.
Published: November 2020

An increasingly studied auction format is the asymmetric procurement auction, which features an advantaged bidder selling a good or service to a buyer. Such asymmetric setups, although generally believed to be more realistic, are also more complex. We investigate one such setting where one bidder has a cost advantage. Our central question is whether bidders who are cost disadvantaged can overcome their inferior cost position. In a design that mirrors real construction procurement auctions, our laboratory experiment tests whether two information asymmetries (more precise cost estimates and knowledge about the cost estimating abilities of a competitor) allow cost‐disadvantaged sellers to better compete. We begin by testing bidder performance in a procurement auction where the only asymmetry is due to a cost. In this setting, analytical benchmarks are known. We find—consistent with other studies—that all bidder types submit aggressive bids well below the Nash equilibrium predictions. Over time, subjects submit less aggressive bids, moving closer to what theory would predict. We then extend our experiments to include our novel, multiple asymmetry setup. We find that endowing cost‐disadvantaged bidders with higher cost estimate precision benefits the bidder, as one might expect. Notably, providing market knowledge about a rival's ability to estimate costs may not provide a benefit; in fact, it seems bidders are not able to use this information effectively and performance suffers. Finally, we show how bidders behave myopically when making these decisions. These implications raise important questions about how asymmetries interact in complex auction settings.
Initial fetal to initial postnatal echocardiogram in uncomplicated atrioventricular septal defects: Do significant changes occur?
Authors: Belfrage Katharine , Richards Bernadette , Corbitt Rebecca , Hersey Diane , Texter Karen , Stiver Corey , Cua Clifford L.
Published: November 2020

Background

Yield of serial echocardiography in fetuses with atrioventricular septal defects (fAVSD) has not been well defined. The goal of this study was to document if any major changes occurred from initial fetal to initial postnatal echocardiogram in uncomplicated fAVSD.

Methods

fAVSD were excluded if initial fetal scan documented complex CHD or any concerns. Changes in ventricular function, valvular regurgitation, or diagnosis between first fetal and first postnatal echocardiogram were recorded.

Results

Fifty‐seven fAVSD met criteria. Ninety‐six fetal echocardiograms were done in 57 patients. Initial fetal scan was performed at 24.3 ± 3.7 weeks of estimated gestational age. All fAVSD had normal function, 38 had no atrioventricular valve regurgitation (AVVR), and 19 had mild AVVR. First postnatal echocardiogram was performed at 6.3 ± 15.3 days. Fifty‐six patients had normal function, 1 patient had mild dysfunction, 16 patients had no AVVR, 36 had mild AVVR, and 5 had moderate AVVR. Three patients (5%) had an improvement in AVVR by one degree, 27 patients (47%) had no change in AVVR, 24 patients (42%) had an increase in AVVR by one degree, and 3 patients (5%) had an increase in AVVR by two degrees. There was no major missed anatomical diagnosis from first prenatal to first postnatal echocardiogram.

Conclusion

In fAVSD that had no concerns on their initial fetal echocardiogram, the majority of patients had no major changes noted between their initial fetal echocardiogram and their first postnatal echocardiogram. Repeat fetal echocardiograms may not necessarily be needed in this cohort of patients.
Combining multiple tactics over time for cost‐effective eradication of invading insect populations
Authors: Lampert Adam , Liebhold Andrew M.
Published: November 2020

Because of the profound ecological and economic impacts of many non‐native insect species, early detection and eradication of newly founded, isolated populations is a high priority for preventing damages. Though successful eradication is often challenging, the effectiveness of several treatment methods/tactics is enhanced by the existence of Allee dynamics in target populations. Historically, successful eradication has often relied on the application of two or more tactics. Here, we examine how to combine three treatment tactics in the most cost‐effective manner, either simultaneously or sequentially in a multiple‐annum process. We show that each tactic is most efficient across a specific range of population densities. Furthermore, we show that certain tactics inhibit the efficiency of other tactics and should therefore not be used simultaneously; but since each tactic is effective at specific densities, different combinations of tactics should be applied sequentially through time when a multiple‐annum eradication programme is needed.
Prognostic impact of non‐urothelial carcinoma of the upper urinary tract: Analysis of hospital‐based cancer registry data in Japan
Authors: Nagumo Yoshiyuki , Kawai Koji , Kojima Takahiro , Shiga Masanobu , Kojo Kosuke , Tanaka Ken , Kandori Shuya , Kimura Tomokazu , Kawahara Takashi , Okuyama Ayako , Higashi Takahiro , Nishiyama Hiroyuki
Published: November 2020

Objectives

To identify the prognosis of patients with non‐urothelial carcinoma of the upper urinary tract and compare it with that of patients with urothelial carcinoma.

Methods

We used hospital‐based cancer registry data in Japan to extract histologically confirmed non‐urothelial carcinoma and urothelial carcinoma cases of the upper urinary tract diagnosed in 2008–2009. We estimated the 5‐year overall survival by a Kaplan–Meier analysis. The Cox proportional hazards regression analysis was used to evaluate prognostic factors.

Results

A total of 2567 upper urinary tract cancer patients with confirmed histological subtypes were identified. The most common histology of non‐urothelial carcinoma was squamous cell carcinoma (n = 88, 3.4%) followed by adenocarcinoma (n = 33, 1.3%) and small cell carcinoma (n = 10, 0.4%). The proportion of advanced stage in the squamous cell carcinoma patients was significantly higher than that in the urothelial carcinoma patients (P = 0.003). In stage IV, the proportion of patients who received a combination of surgery + chemotherapy in the urothelial carcinoma group was higher than that in the non‐urothelial carcinoma group (34% vs 16%, respectively). The 5‐year overall survival rates of the non‐urothelial carcinoma patients at stages I–III and stage IV were significantly worse than those of the urothelial carcinoma patients (P = 0.003, P < 0.001, respectively). In multivariate analyses, age ≥73 years, advanced stage (stage IV), tumor location (ureter) and the presence of non‐urothelial carcinoma histology were independent poor prognosis factors.

Conclusion

The prognosis of non‐urothelial carcinoma patients is worse than that of urothelial carcinoma patients, especially for non‐urothelial carcinoma patients at stage IV. More effective systemic therapies are required to improve these patients’ oncological outcomes.
What is needed for Trauma Informed Mental Health Services in Australia? Perspectives of clinicians and managers
Authors: Isobel Sophie , Wilson Allyson , Gill Katherine , Schelling Kathleen , Howe Deborah
Published: November 2020

Trauma Informed Care is an approach to the delivery of mental health care that requires sensitivity to the prevalence and effects of trauma in the lives of people accessing services. While TIC is increasingly emphasized in mental health policy and frameworks in Australia, people working in mental health settings have reportedly struggled to translate the values and principles into their everyday practice. This qualitative study used an experience‐based co‐design methodology to explore the potential for implementation of Trauma Informed Care into mental health services in Australia. The experiences of consumers, carers, clinicians, and managers were gathered. This paper presents the perspectives of clinicians (n = 64) and senior managers (n = 9) from across three Local Health Districts in New South Wales in Australia. All data were analysed thematically to address the research question: What is needed for Trauma Informed Mental Health Services in Australia? To be trauma‐informed, managers required: leadership at all levels, access to resource, relevant and accessible training, support for staff, resolution of wider systems issues, and clarification of the concept and actions of TIC. Clinicians identified that to be trauma‐informed they required services to: be aware of staff well‐being, support different ways of working, address workplace cultures and provide increased resources. The findings have implications for any service, team or individual seeking to implement TIC within mental health settings.
Project leaders as boundary spanners in open source software development: A resource dependence perspective
Authors: Dong John Qi , Götz Sebastian Johannes
Published: November 2020

Digital social innovation is important for addressing various social needs, especially from those who are economically disadvantaged. For instance, open source software (OSS) is developed by mass collaboration on digital communities to provide software users free alternatives to commercial products. OSS is particularly valuable to meet the needs of numerous disadvantaged users for whom proprietary software is not affordable. While OSS projects are lack of formal organizational structure, project leaders play a significant role in initiating and managing these projects and eventually, influencing the degree to which the developed software is used and liked by users. Drawing on resource dependence theory, we investigate the impacts of two team‐level characteristics of OSS project leaders (ie, size and tenure) on how well the developed software can address users' needs, with regard to the quantity of software being used by users and the quality of software to users' satisfaction. Further, from a resource dependence perspective, we examine the moderating role of project leaders' network ties in shaping the contingency of these effects. By using a large‐scale dataset from 43 048 OSS development projects in SourceForge community, we find empirical evidence corroborating our theory. Taken together, our findings suggest the boundary‐spanning role of project leaders in developing digital social innovation.
The role of ecological specialization in shaping patterns of insular communities
Authors: Sfenthourakis Spyros , Triantis Kostas A. , Proios Konstantinos , Rigal Francois
Published: November 2020

Aim

Research on the response of species richness to area and environmental heterogeneity so far has not addressed possible effects of species’ differences in ecological specialization. Herein we provide a new metric, ‘ecorichness’, in an attempt to fill this gap.

Location

Aegean islands (Greece).

Taxon

Terrestrial isopods.

Methods

‘Ecorichness’ estimates an island's biodiversity by integrating species richness and the specialists‐generalists spectrum. We calculated ‘ecorichness’ for terrestrial isopods from 43 Aegean islands based on the habitats they exploit. ‘Ecorichness’ then was regressed on area, habitat diversity and the K‐parameter of the Choros model using linear and quadratic models, compared based on AICc. A reduced data set, without halophilous species and coastal habitats, as well as an alternative description of habitat diversity, also was explored. The small island effect (SIE) thresholds identified using both a path analysis approach and piecewise continuous linear models were compared to the area of maximum ‘ecorichness’.

Results

‘Ecorichness’ response to area and habitat heterogeneity was best fitted by quadratic models with peaks located at an area similar to the SIE threshold identified by path analysis. Different measures of habitat diversity produced similar patterns. Exclusion of coastal species and habitats shows that the response of ‘ecorichness’ to area is mostly shaped by the increasing contribution of specialists in the assemblages of larger islands.

Main conclusions

‘Ecorichness’ facilitates exploration of the role of ecological specialization in shaping community patterns. It can be applied to different community data sets, whenever habitat range exploitation can be quantified. Results from the case study accord with previous suggestions that the relative contribution of generalists and specialists differs between small and large island communities.
Embryology of the naso‐palatal complex in Gekkota based on detailed 3D analysis in Lepidodactylus lugubris and Eublepharis macularius
Authors: Kaczmarek Paweł , Metscher Brian , Rupik Weronika
Published: November 2020

The vomeronasal organ (VNO), nasal cavity, lacrimal duct, choanal groove, and associated parts of the superficial (soft tissue) palate are called the naso‐palatal complex. Despite the morphological diversity of the squamate noses, little is known about the embryological basis of this variation. Moreover, developmental data might be especially interesting in light of the morpho‐molecular discordance of squamate phylogeny, since a ‘molecular scenario’ implies an occurrence of unexpected scale of homoplasy also in olfactory systems. In this study, we used X‐ray microtomography and light microscopy to describe morphogenesis of the naso‐palatal complex in two gekkotans: Lepidodactylus lugubris (Gekkonidae) and Eublepharis macularius (Eublepharidae). Our embryological data confirmed recent findings about the nature of some developmental processes in squamates, for example, involvement of the lateral nasal prominence in the formation of the choanal groove. Moreover, our study revealed previously unknown differences between the studied gekkotans and allows us to propose redefinition of the anterior concha of Sphenodon. Interpretation of some described conditions might be problematic in the phylogenetic context, since they represent unknown: squamate, nonophidian squamate, or gekkotan features.
Bioactivity of abobotulinum toxin is preserved till 2 weeks upon storage at room temperature: Half body comparative study on rabbit model
Authors: Esme Pelin , Botsali Aysenur , Erbil Hakan , Aksoy Okan Ali , Caliskan Ercan
Published: November 2020

Background

Breakages of the cold chain of botulinum neurotoxin A (BONT‐A) preparations is not a rare event and occurs due to several unexpected and unintentional reasons during daily practice and intervention schedules could not be proposed due to the lack of data.

Objective

To investigate the heat stability of abobotulinum toxin A (AboBONT‐A) in terms of efficacy and duration of action upon storage at room temperature (25°C) for 2, 4, and 8 weeks.

Methods and Materials

Twenty rabbits were divided into four groups and received an injection of ideally stored AboBONT‐A (Group 1) and stored AboBONT‐A for 2 (Group 2), 4 (Group 3), and 8 weeks (Group 4) at room temperature into the anterior auricular muscle. All rabbits were followed up and photographed by weekly for 16 weeks. Grade of paralysis was evaluated by using a modified visual scoring system.

Results

No significant alteration was found in initial potency of stored AboBONT‐A at room temperature for up to 4 weeks. Storage at room temperature for 2 weeks did not affect the duration of action (group 2; P = .69), and faster recovery was observed in group 3 and group 4.

Conclusion

The bioactivity of AboBONT‐A is not altered till 2 weeks upon storage at room temperature.
How long and how much? Wait times and costs for initial private child mental health appointments
Authors: Mulraney Melissa , Lee Cindy , Freed Gary , Sawyer Michael , Coghill David , Sciberras Emma , Efron Daryl , Hiscock Harriet
Published: November 2020

Aim

To determine: (i) wait times and out‐of‐pocket costs for children attending private specialists for initial mental health appointments; and (ii) whether these differed between specialists working in metropolitan versus rural areas and in low, medium and high socio‐economic areas.

Methods

Prospective secret shopper study whereby a researcher posed as a parent seeking an appointment for her child with anxiety or attention‐deficit/hyperactivity disorder. We contacted 317 private paediatrician, psychiatrist and psychologist practices in Victoria and South Australia between 12 March and 5 May 2019.

Results

One third (29.8%) of private practices were closed to new referrals. The average wait times for paediatricians, psychiatrists, and psychologists were 44, 41 and 34 days, respectively. Average out‐of‐pocket costs quoted were AU$120 for paediatricians, AU$176 for psychiatrists and AU$85 for psychologists.

Conclusion

Parents face extensive wait times and substantial out‐of‐pocket costs when seeking private mental health services for their child.
Comparing prescribing patterns for topical corticosteroids based on their FDA indication by age
Authors: Freeze Megan E. , Balogh Esther A. , Cline Abigail , Feldman Steven R. , Fleischer Alan B.
Published: November 2020

Background/Objectives

Atopic dermatitis (AD) affects up to 20% of the pediatric population, with a growing prevalence over the past 30 years. Topical corticosteroids (TCS) are commonly used as a first‐line topical therapy for AD and are prescribed in 59% of all AD visits. However, some topical corticosteroids are prescribed outside of their age range indications. This paper aims to explore the frequency with which topical corticosteroids are prescribed for AD outside of their FDA‐approved age range.

Methods

Data on prescribing patterns for AD were obtained from the National Ambulatory Medical Care Survey (NAMCS). We assessed the frequency of off‐label use of topical corticosteroids with respect to age indications in four specific age‐groups, as delineated in the data (0‐1, 2‐7, 8‐18, and 19+ years).

Results

All prescribed topical corticosteroids found in the NAMCS database have an indication for AD or other inflammatory dermatoses or pruritic dermatoses. However, some medications were prescribed outside of their FDA‐approved age indications. These off‐label prescription rates ranged from 52% for desoximetasone to 0% for halobetasol and alclometasone, or rates lower than could be detected by our study.

Conclusions

Much like other medications for AD treatment, TCS are sometimes used off‐label. The off‐label use of topical corticosteroids to treat pediatric AD highlights a gap between clinical practice and regulating guidelines. Additional pediatric studies would offer a greater body of evidence to maintain or expand label indications for the use of TCS in younger patients.
Robust Tests for Treatment Effect in Survival Analysis under Covariate-Adaptive Randomization
Authors: Ye Ting , Shao Jun
Published: November 2020

Covariate-adaptive randomization is popular in clinical trials with sequentially arrived patients for balancing treatment assignments across prognostic factors that may have influence on the response. However, existing theory on tests for the treatment effect under covariate-adaptive randomization is limited to tests under linear or generalized linear models, although the covariate-adaptive randomization method has been used in survival analysis for a long time. Often, practitioners will simply adopt a conventional test to compare two treatments, which is controversial since tests derived under simple randomization may not be valid in terms of type I error under other randomization schemes. We derive the asymptotic distribution of the partial likelihood score function under covariate-adaptive randomization and a working model that is subject to possible model misspecification. Using this general result, we prove that the partial likelihood score test that is robust against model misspecification under simple randomization is no longer robust but conservative under covariate-adaptive randomization. We also show that the unstratified log-rank test is conservative and the stratified log-rank test remains valid under covariate-adaptive randomization. We propose a modification to variance estimation in the partial likelihood score test, which leads to a score test that is valid and robust against arbitrary model misspecification under a large family of covariate-adaptive randomization schemes including simple randomization. Furthermore, we show that the modified partial likelihood score test derived under a correctly specified model is more powerful than log-rank-type tests in terms of Pitman’s asymptotic relative efficiency. Simulation studies about the type I error and power of various tests are presented under several popular randomization schemes.
First report of cross resistance to silver and antibiotics in Klebsiella pneumoniae isolated from patients and polluted water in Tunisia
Authors: Ben Miloud Samar , Ali Md Muntasir , Boutiba Ilhem , Van Houdt Rob , Chouchani Chedly
Published: November 2020

Klebsiella pneumoniae, ubiquitously found in a variety of environmental sources, is an important pathogen in burn wounds and nosocomial infections. Burn wounds have been commonly treated with silver compounds, which are also used in a multitude of (non)medical products. As the latter increased silver discharge into different environments, we evaluated and compared silver resistance in K. pneumoniae isolates collected from patients hospitalized at the Charles‐Nicolle hospital (Tunis, Tunisia) with isolates collected from different metal polluted waters in the north and south of Tunisia. All K. pneumoniae isolates harboured blaTEM‐1 and blaSHV‐1. In addition, all clinical isolates showed a multidrug phenotype and harboured the blaCTX‐M‐15, blaOXA‐1 and blaNDM‐1. Furthermore, all isolates showed resistance to silver nitrate. The silver resistance determinant, screened via the silE gene, was located for all isolates on a large plasmid with a size similar to pMG101. This study showed cross‐resistance between silver and beta‐lactams in clinical as well as environmental K. pneumoniae isolates from Tunisia and showed for the first time that NDM‐1‐producing K. pneumoniae developed resistance to silver.
Calibration of an Electrical Analog Model of Liver Hemodynamics in Fontan Patients
Authors: Abbasi Bavil Elyar , Doyle Matthew G. , Debbaut Charlotte , Wald Rachel M. , Mertens Luc , Forbes Thomas L. , Amon Cristina H.
Published: November 2020

Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient (PPG)). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model (LPM) of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of PPGs in these patients. An existing LPM of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step toward models suitable to assess liver health in Fontan patients and improve its long-term management.
Heterotopic pancreas: the added value of endoscopic ultrasound with Computed Tomography for diagnosis
Authors: Park Jae Yong , Lee Eun Sun , Hwang Hye Won , Park Hyung Jeong , Kim Beom Jin , Choi Chang Hwan
Published: November 2020

Aims: To investigate the added value of endoscopic ultrasound (EUS) with computed tomography (CT) in distinguishing heterotopic pancreas (HP) from other pathologies, when gastroduodenal subepithelial tumors (SETs) are suspected on an upper endoscopic examination.Material and methods: We retrospectively included 54 consecutive patients with gastroduodenal SETs who had undergone both abdominal CT and EUS within a 3-month interval. All EUS, endoscopy, and CT images were reviewed and evaluated in a blinded manner by an endoscopist and a radiologist, respectively. Univariate and multivariate analyses were performed to identify EUS/CT findings related to HP. Diagnostic performance of CT only and CT combined with EUS was compared for distinguishing HP from other SETs.Results: We included patients with HP (n=17; pathologically confirmed, n=6), gastrointestinal stromal tumor (GIST, n=24), and other pathologies (n=13). Multivariate logistic regression analyses revealed that irregular margin, origin from submucosal layer, internal microcystic-tubular structure, and oval shape were independent factors in diagnosing HP by EUS, whereas a micro-lobulating contour was the only significantly independent factor in CT. In assessments of diagnostic performance, CT combined with EUS showed significantly superior diagnostic performance in comparison with CT only (area under the curve, 0.961 vs. 0.833, p=0.028) in the consensus interpretation of an endoscopist and a radiologist.Conclusions: CT combined with EUS with a comprehensive and complementary interpretation showed significant added value compared to CT only in diagnosing gastroduodenal HP
Understanding the role of echocardiography in patients with obstructive sleep apnea and right ventricular subclinical myocardial dysfunction – comparison with other conditions affecting RV deformation
Authors: Chetan Ioana Maria , Domokos Gergely Bianca , Albu Adriana , Tomoaia Raluca , Todea Doina Adina
Published: November 2020

Despite efforts to treat obstructive sleep apnea syndrome (OSA), the condition remains an important risk factor in the development of cardiovascular disease. Early detection of RV dysfunction with novel echocardiographic techniques (speckle tracking echocardiography) may be useful in preventing progression to pulmonary hypertension, with subsequent heart failure and cardiovascular death. Echocardiography is the method of choice for the evaluation of OSA consequences on the heart. Although standard echocardiographic parameters are routinely used in these patients, there are several limitations in the early detection of RV dysfunction. The main concerns are the complex geometry of RV and the impact of pre- and afterload on RV myocardium, which cannot be assessed through standard measurements. The aim of this review is to highlight the utility of advanced echocardiographic parameters in the identification of OSA patients with subclinical myocardial dysfunction, which are at risk of developing heart failure and later adverse events. Speckle tracking echocardiography might provide higher sensitivity in unmasking alterations in RV function when conventional echocardiographic methods cannot detect them. Therefore, this method has a major role in the detection of early stages of RV dysfunction, along with better risk stratification and better timing in the initiation of therapy.
Phylogenetic and Biogeographic Patterns of Vibrio parahaemolyticus Strains from North America Inferred from Whole-Genome Sequence Data
Authors: Miller John J. , Weimer Bart C. , Timme Ruth , Lüdeke Catharina H. M. , Pettengill James B. , Bandoy D. J. Darwin , Weis Allison M. , Kaufman James , Huang B. Carol , Payne Justin , Strain Errol , Jones Jessica L.
Published: November 2020

Vibrio parahaemolyticusis the most common cause of seafood-borne illness reported in the United States and is frequently associated with shellfish consumption. This study contributes to our knowledge of the biogeography and functional genomics of this species around North America.
Seroprevalence of SARS-CoV-2 antibodies in children: a prospective multicentre cohort study
Authors: Waterfield Thomas , Watson Chris , Moore Rebecca , Ferris Kathryn , Tonry Claire , Watt Alison , McGinn Claire , Foster Steven , Evans Jennifer , Lyttle Mark David , Ahmad Shazaad , Ladhani Shamez , Corr Michael , McFetridge Lisa , Mitchell Hannah , Brown Kevin , Amirthalingam Gayatri , Maney Julie-Ann , Christie Sharon
Published: November 2020

Background

Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection.

Design

This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2–15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms.

Results

1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4).

Discussion

Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity.

Trial registration number

NCT0434740.
Agreement and predictive value of the Rockwood Clinical Frailty Scale at emergency department triage
Authors: Shrier William , Dewar Colin , Parrella Piervirgilio , Hunt David , Hodgson Luke Eliot
Published: November 2020

Aim

To determine the agreement and predictive value of emergency department (ED) triage nurse scoring of frailty using the Rockwood Clinical Frailty Scale (CFS) when compared with inpatient medical assessment using the same scale.

Methods

Prospective, dual-centre UK-based study over a 1-year period (1 April 2017 to 31 March 2018) of CFS recorded digitally at nursing triage on ED arrival and on hospital admission by a medical doctor. Inclusion criteria were emergency medical admission in those aged ≥65 staying at least one night in hospital with a CFS completed in both ED and at hospital admission. Agreement between ED triage nurse and inpatient hospital physician was assessed using a weighted Kappa statistic and Spearman’s correlation coefficient. The ability of the ED to diagnose frailty (defined by a CFS ≥5) was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and receiver operating characteristic (ROC) curves. At both time points the ability of the CFS to predict inpatient mortality was also assessed.

Results

From 29 211 admissions aged ≥65 who stayed at least one night in hospital, 12 385 (42.3%) were referred from the ED. Of the ED referrals, 8568 cases (69.2%) were included with paired CFS performed. Median age was 84 (IQR 77 to 89) with an inpatient mortality of 6%. Median CFS in ED was 4 (3 to 5) and on hospital admission 5 (4 to 6). Agreement between the ED CFS and admission CFS was weak (Kappa 0.21, 95% CI 0.19 to 0.22, rs0.366). The area under the ROC curve (AUC) was 0.67 (95% CI 0.66 to 0.68) for the ED CFS ability to predict an admission CFS ≥5. To predict inpatient mortality the ED CFS AUC was 0.56 (0.53 to 0.59) and admission CFS AUC 0.70 (0.68 to 0.73).

Conclusion

Agreement between ED CFS and inpatient CFS was found to be weak. In addition the ability of ED CFS to predict clinically important outcomes was limited. NPV and PPV for ED CFS cut-off value of ≥5 were found to be low. Further work is required on the feasibility, clinical impact and appropriate tools for screening of frailty in EDs.
Secondary transfer of emergency stroke patients eligible for mechanical thrombectomy by air in rural England: economic evaluation and considerations
Authors: Coughlan Diarmuid , McMeekin Peter , Flynn Darren , Ford Gary A , Lumley Hannah , Burgess David , Balami Joyce , Mawson Andrew , Craig Dawn , Rice Stephen , White Phil
Published: November 2020

Background

Mechanical thrombectomy (MT) is a time-sensitive emergency procedure for patients who had ischaemic stroke leading to improved health outcomes. Health systems need to ensure that MT is delivered to as many patients as quickly as possible. Using decision modelling, we aimed to evaluate the cost-effectiveness of secondary transfer by helicopter emergency medical services (HEMS) compared with ground emergency medical services (GEMS) of rural patients eligible for MT in England.

Methods

The model consisted of (1) a short-run decision tree with two branches, representing secondary transfer transportation strategies and (2) a long-run Markov model for a theoretical population of rural patients with a confirmed ischaemic stroke. Strategies were compared by lifetime costs: quality-adjusted life years (QALYs), incremental cost per QALY gained and net monetary benefit. Sensitivity and scenario analyses explored uncertainty around parameter values.

Results

We used the base case of early-presenting (<6 hours to arterial puncture) patient aged 75 years who had stroke to compare HEMS and GEMS. This produced an incremental cost-effectiveness ratio (ICER) of £28 027 when a 60 min reduction in travel time was assumed. Scenario analyses showed the importance of the reduction in travel time and futile transfers in lowering ICERs. For late presenting (>6 hours to arterial puncture), ground transportation is the dominant strategy.

Conclusion

Our model indicates that using HEMS to transfer patients who had stroke eligible for MT from remote hospitals in England may be cost-effective when: travel time is reduced by at least 60 min compared with GEMS, and a £30 000/QALY threshold is used for decision-making. However, several other logistic considerations may impact on the use of air transportation.
Technical factors associated with first-pass success during endotracheal intubation in children: analysis of videolaryngoscopy recordings
Authors: Miller Kelsey A , Monuteaux Michael C , Nagler Joshua
Published: November 2020

Background

First-pass success (FPS) during intubation is associated with lower morbidity for paediatric patients. Using videolaryngoscopy (VL) recordings, we reviewed technical aspects of intubation, including factors associated with FPS in children.

Methods

We performed a retrospective study of intubation attempts performed using video-assisted laryngoscopy in a paediatric ED between January 2014 and December 2018. Data were abstracted from a quality assurance database, the electronic medical record and VL recordings. Our primary outcome was FPS. Intubation practices were analysed using descriptive statistics. Patient and procedural characteristics associated with FPS in univariate testing and clinical factors identified from the literature were included as covariates in a multivariable logistic regression. An exploratory analysis examined the relationship between position of the glottic opening on the video screen and FPS.

Results

Intubation was performed during 237 patient encounters, with 231 using video-assisted laryngoscopy. Data from complete video recordings were available for 129 attempts (59%); an additional 31 (13%) had partial recordings. Overall, 173 (73%) of first attempts were successful. Adjusting for patient age, placing the blade tip into the vallecula adjusted OR ((aOR) 7.2 (95% CI 1.7 to 30.1)) and obtaining a grade 1 or 2a-modified Cormack-Lehane glottic view on the videolaryngoscope screen (aOR 6.1 (95% CI 1.5 to 25.7) relative to grade 2b) were associated with increased FPS in the subset of patients with complete recordings. Exploratory analysis suggested that FPS is highest (81%) and duration is shortest when the glottic opening is located in the second quintile of the video screen.

Conclusions

Placement of the blade tip into the vallecula regardless of blade type, sufficient glottic visualisation and locating the glottic opening within the second quintile of the video screen were associated with FPS using video-assisted laryngoscopy in the paediatric ED.