bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional respiratory imaging assessment of glycopyrrolate and formoterol fumarate metered dose inhalers formulated using co-suspension delivery technology in patients with COPD
Authors: De Backer Wilfried , De Backer Jan , Verlinden Ilse , Leemans Glenn , Van Holsbeke Cedric , Mignot Benjamin , Jenkins Martin , Griffis Dianne , Ivanov Stefan , Fitzpatrick Jane , St Rose Earl , Martin Ubaldo J. , Reisner Colin
Published: May 2020

Background:

Functional respiratory imaging (FRI) is a quantitative postprocessing imaging technique used to assess changes in the respiratory system. Using FRI, we characterized the effects of the long-acting muscarinic antagonist (LAMA), glycopyrrolate metered dose inhaler (GP MDI), and the long-acting β2-agonist (LABA), formoterol fumarate metered dose inhaler (FF MDI), on airway volume and resistance in patients with moderate-to-severe chronic obstructive pulmonary disease.

Methods:

Patients in this phase IIIb, randomized, double-blind crossover study received twice-daily GP MDI (18 μg) and FF MDI (9.6 μg). Primary endpoints were specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and specific image-based airway resistance (siRaw), measured using FRI. Secondary and other endpoints included additional FRI, spirometry, and body plethysmography parameters. Postdose efficacy assessments were performed within 60–150 min of dosing on day 15.

Results:

A total of 23 patients were randomized and 19 completed both treatment periods. GP MDI and FF MDI both achieved significant improvements from baseline to day 15 in siVaw [11% ( p = 0.0187) and 23% ( p < 0.0001) increases, respectively] and siRaw [25% ( p = 0.0219) and 44% ( p < 0.0001) reductions, respectively]. Although, on average, improvements were larger for FF MDI than GP MDI, some individuals displayed greater responses with each of the two treatments. These within-patient differences increased with airway generation number. Spirometry and body plethysmography endpoints showed significant improvements from baseline in inspiratory capacity for both treatments, and numeric improvements for other endpoints.

Conclusion:

Both GP MDI and FF MDI significantly improved siRaw and siVaw at day 15 versus baseline. FRI endpoints demonstrated increased sensitivity relative to spirometry and body plethysmography in detecting differences between treatments in a small number of patients. Intra-patient differences in treatment response between the LAMA and the LABA provide further support for the benefit of dual bronchodilator therapies.

ClinicalTrials.gov registration number:

NCT02937584 The reviews of this paper are available via the supplemental material section.
Development and validation of a diverticular clinical score for symptomatic uncomplicated diverticular disease after acute diverticulitis in a prospective patient cohort
Authors: Lahat Adi , Fidder Herma H , Ben-Horin Shomron
Published: May 2020

Background:

Following an attack of acute diverticulitis (AD), many patients continue to suffer from a complex of symptoms, titled ‘symptomatic uncomplicated diverticular disease (SUDD)’. To date, there is no validated clinical score for standardized assessment of patients with SUDD, thereby hampering the interpretation of observational studies and the conductance of clinical trials. We aimed to develop a validated SUDD clinical score.

Methods:

Data from previous prospective study of patients after AD was used to devise the score’s first version. Validation was first performed using a focus group of patients after AD SUDD who underwent a structured cognitive personal interview. Thereafter, the diverticular clinical score (DICS) was applied for a second validation cohort. DICS scores of validation cohort were compared with physicians’ global assessment for disease severity and inflammatory markers.

Results:

In DICS second validation using 48 patients prospectively recruited after AD SUDD, a correlation matrix demonstrated strong correlation between total questionnaire’s score and the presence of elevated inflammatory markers ( ρ = 0.84). Mean score in patients with elevated inflammatory markers compared with those without inflammation was 17.8 versus 6.2, respectively, p < 0.001. Cronbach’s α for measuring internal consistency was 0.91. DICS discriminated accurately between patients with/without active disease, as gauged by the physicians global assessment (area under the curve receiver operating characteristic = 0.989).

Conclusions:

Patients suffering from post-AD SUDD exhibit a wide range of symptoms. The newly developed DICS accurately and reproducibly quantitates SUDD-related symptom severity. The DICS may prove useful for monitoring SUDD in clinical practice and in research settings, as well as facilitating patient stratification and therapeutic decisions.
Extracellular vesicle species differentially affect endothelial cell functions and differentially respond to exercise training in patients with chronic coronary syndromes
Authors: Kränkel Nicolle , Strässler Elisabeth , Uhlemann Madlen , Müller Maja , Briand-Schumacher Sylvie , Klingenberg Roland , Schulze P Christian , Adams Volker , Schuler Gerhard , Lüscher Thomas F , Möbius-Winkler Sven , Landmesser Ulf
Published: May 2020

Background

Extracellular vesicles are released upon cellular activation and mediate inter-cellular communication. Individual species of extracellular vesicles might have divergent roles in vascular homeostasis and may show different responses to therapies such as exercise training.

Aims

We examine endothelial effects of medium-size and small extracellular vesicles from the same individual with or without chronic coronary syndrome, and in chronic coronary syndrome patients participating in a four-week high-intensity interval training intervention.

Methods

Human aortic endothelial cells were exposed to medium-size extracellular vesicles and small extracellular vesicles isolated from plasma samples of study participants. Endothelial cell survival, activation and re-endothelialisation capacity were assessed by respective staining protocols. Extracellular vesicles were quantified by nanoparticle tracking analysis and flow cytometry. Extracellular vesicle microRNA expression was quantified by realtime-quantitative polymerase chain reaction.

Results

In patients with chronic coronary syndrome (n = 25), plasma counts of leukocyte-derived medium-size extracellular vesicles were higher than in age-matched healthy controls (n = 25; p = 0.04) and were reduced by high-intensity interval training (n = 15; p = 0.01 vs baseline). Re-endothelialisation capacity was promoted by medium-size extracellular vesicles from controls, but not by medium-size extracellular vesicles from chronic coronary syndrome patients. High-intensity interval training for 4 weeks enhanced medium-size extracellular vesicle-mediated support of in vitro re-endothelialisation. Small extracellular vesicles from controls or chronic coronary syndrome patients increased endothelial cell death and reduced repair functions and were not affected by high-intensity interval training.

Conclusion

The present study demonstrates that medium-size extracellular vesicles and small extracellular vesicles differentially affect endothelial cell survival and repair responses. This equilibrium is unbalanced in patients with chronic coronary syndrome where leukocyte-derived medium-size extracellular vesicles are increased leading to a loss of medium-size extracellular vesicle-mediated endothelial repair. High-intensity interval training partially restored medium-size extracellular vesicle-mediated endothelial repair, underlining its use in cardiovascular prevention and therapy to improve endothelial function.
A novel approach to resolve severe mediastinal and subcutaneous emphysema occurring in Pneumocystis jirovecii pneumonia using vacuum-assisted closure therapy
Authors: Bouwmeester Noor H , Kieft Hans , Shahin Ghada MM , Nierich Arno P
Published: May 2020

A 50-year-old human immunodeficiency virus positive patient who was diagnosed with Pneumocystis jirovecii pneumonia developed severe subcutaneous and mediastinal emphysema, which was progressive despite low pressure mechanical ventilation. Infraclavicular skin incisions and vacuum-assisted closure therapy were used to resolve the emphysema. The subcutaneous emphysema decreased significantly, and after 1 week the vacuum-assisted closure therapy was ended successfully. This technique has previously been described in several case reports, where it is a promising treatment in severe subcutaneous emphysema, but it is not yet widely used. This case report supports the further use of vacuum-assisted closure therapy in subcutaneous emphysema. Successful treatment of severe mediastinal and subcutaneous emphysema in Pneumocystis jirovecii pneumonia can be achieved by vacuum-assisted closure therapy on infraclavicular skin incisions.
Difference Among Similarity: A Study on Macao Students’ Adjustment Experiences in Taiwan’s Higher Education Systems
Authors: Chan (陈志峰) Chi Fong , Jheng (郑英杰) Ying-Jie
Published: May 2020

Purpose:

This study focused on cross-region student mobility to explore whether Macao students have adjustment issues while studying and living in Taiwan.

Design/Approach/Methods:

A total of 663 Macao students were surveyed in Taiwan, and the statistical methods, including correlation, t-test, analysis of variance, and hierarchical regression analysis were addressed to analyze the data.

Findings:

Macao students, even while studying in a Chinese context, did have social and psychological adjustment issues (i.e., social support and self-efficacy).

Originality/Value:

This study could shed some light on understanding cross-region students as well as providing practical guides for relevant governmental departments in their policy regarding outbound students.
Pilot Study: Outcomes of the Full Abdominopelvic Ultrasound Protocol for Diagnosis of Acute Appendicitis in Children: A Retrospective Chart Review
Authors: Dima Robert , Wang Yongdong , Zuccolo Sarah , Palmer Michelle , Cheong Kerry
Published: May 2020

Objective:

Sonographic evaluation for acute appendicitis in children often involves an exhaustive protocol, for which the therapeutic yield has not been formally evaluated. The purpose of the study was to pilot a retrospective chart review of children receiving an abdominopelvic sonogram upon presenting with suspected acute appendicitis.

Methods:

An annual retrospective chart review was designed to review abdominopelvic sonograms to rule out appendicitis and specifically performed at a Canadian children’s teaching hospital. Studies were excluded if the requisition stated multiple clinical concerns or if the patient was >18 years at the time of the sonogram.

Results:

Based on 230 patient cases reviewed, alternative diagnostic sonographic findings were found in 141 (61%) charts. Only 18 patient cases (8%) demonstrated both alternative sonographic findings as well as a change in management by the emergency room physician.

Conclusion:

Alternative diagnostic findings, based on a complete abdominopelvic sonogram, were common (61%) in this chart review but rarely changed patient management.
Survival following allogeneic transplant in patients with myelofibrosis
Authors: Gowin Krisstina , Ballen Karen , Ahn Kwang Woo , Hu Zhen-Huan , Ali Haris , Arcasoy Murat O. , Devlin Rebecca , Coakley Maria , Gerds Aaron T. , Green Michael , Gupta Vikas , Hobbs Gabriela , Jain Tania , Kandarpa Malathi , Komrokji Rami , Kuykendall Andrew T. , Luber Kierstin , Masarova Lucia , Michaelis Laura C. , Patches Sarah , Pariser Ashley C. , Rampal Raajit , Stein Brady , Talpaz Moshe , Verstovsek Srdan , Wadleigh Martha , Agrawal Vaibhav , Aljurf Mahmoud , Angel Diaz Miguel , Avalos Belinda R. , Bacher Ulrike , Bashey Asad , Beitinjaneh Amer M. , Cerny Jan , Chhabra Saurabh , Copelan Edward , Cutler Corey S. , DeFilipp Zachariah , Gadalla Shahinaz M. , Ganguly Siddhartha , Grunwald Michael R. , Hashmi Shahrukh K. , Kharfan-Dabaja Mohamed A. , Kindwall-Keller Tamila , Kröger Nicolaus , Lazarus Hillard M. , Liesveld Jane L. , Litzow Mark R. , Marks David I. , Nathan Sunita , Nishihori Taiga , Olsson Richard F. , Pawarode Attaphol , Rowe Jacob M. , Savani Bipin N. , Savoie Mary Lynn , Seo Sachiko , Solh Melhem , Tamari Roni , Verdonck Leo F. , Yared Jean A. , Alyea Edwin , Popat Uday , Sobecks Ronald , Scott Bart L. , Nakamura Ryotaro , Mesa Ruben , Saber Wael
Published: May 2020

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.
Mesenchymal stromal cell therapeutic potency is dependent upon viability, route of delivery, and immune match
Authors: Giri Jayeeta , Galipeau Jacques
Published: May 2020

Culture-adapted bone marrow mesenchymal stromal cells (MSCs) deploy paracrine anti-inflammatory and tissue regenerative functionalities that can be harnessed as a living cell pharmaceutical product. Independent of clinical indication, a near majority of human clinical trials administer MSC IV, often with an allogeneic MSC cell product immediately after thawing from cryostorage. Despite hundreds of studies in a wide assortment of inflammatory, degenerative, and acute tissue injury syndromes, human clinical outcomes often fail to mirror promising rigorously conducted preclinical animal studies. Using a mouse model of toxic colitis, we demonstrate that replication fit MSCs harvested in log phase of growth have substantial impact on colitis clinical and pathologic endpoints when delivered subcutaneously or intraperitoneally, whereas the maximum tolerated IV bolus dosing failed to do so. We also demonstrate that heat-inactivated MSCs lose all therapeutic utility and the observation is mirrored by use of viable MSC administered immediately postthaw from cryostorage. Using luciferase transgenic MSC as donor cells, we demonstrate that transient in vivo engraftment is severely compromised when MSCs are dead or thawed and further demonstrate that MSC redosing is feasible in relapsing colitis, but only syngeneic MSCs lead to sustained improvement of clinical endpoints. These data support the notion that pharmaceutical potency of MSC requires viability and functional fitness. Reciprocally, IV administration of thawed MSC products may be biased against positive clinical outcomes for treatment of colitis and that extravascular administration of syngeneic, fit MSCs allows for effect in a recurrent therapy model.
Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA)
Authors:   The PROLISA Study Group, Chevallier Marie , Durrmeyer Xavier , Ego Anne , Debillon Thierry
Published: May 2020

Background

One major limitation for less invasive surfactant administration (LISA) is the difficulty in providing sedation before this procedure and the competitive risk of respiratory depression versus avoidance of intubation for most sedative or analgesic drugs used in this context.

The objective of this study is to compare the need for mechanical ventilation within 72 h of life following premedication with propofol, versus placebo (rescue with ketamine), for the LISA procedure in preterm neonates born before 32 weeks gestational age (wGA).

Methods

ProLISA is a phase III, non-inferiority, multicenter, double blind, randomized, placebo controlled trial designed according to the SPIRIT Statement. Neonates born before 32 wGA in 12 geographically dispersed Neonatal Intensive Care Units in France needing surfactant will be included from September 2019 to September 2022. A sample of 542 patients is needed. The neonate is randomized to the intervention (propofol) or control placebo group. Open label rescue treatment with ketamine is possible in both groups if FANS (Faceless Acute Neonatal pain Scale) is ≥6. To guide drug administration, FANS is scored before attempting laryngoscopy. Once an adequate score has been obtained, LISA is performed according to a standardized protocol. The primary outcome is the need for mechanical ventilation within 72 h of life. Secondary outcomes are tolerance of the procedure, pain evaluation, hemodynamic and neurologic parameters after the intervention, morbidities before discharge and neurodevelopmental assessment at 2 years of age.

Discussion

This paper describes the first multicenter, double-blind, randomized, placebo-controlled trial on this topic and will provide crucial information to support implementation of the LISA procedure.

Trial registration

ClinicalTrials.gov: NCT04016246. Registered 06 June 2019, N°EUDRACT: 2018–002876-41.
Association of physical activity, sedentary behaviours and sleep duration with cardiovascular diseases and lipid profiles: a Mendelian randomization analysis
Authors: Zhuang Zhenhuang , Gao Meng , Yang Ruotong , Li Nan , Liu Zhonghua , Cao Weihua , Huang Tao
Published: May 2020

Background

Observational studies have shown that moderate-to-vigorous physical activity (MVPA), vigorous physical activity (VPA), sedentary behaviours, and sleep duration were associated with cardiovascular diseases (CVDs) and lipid levels. However, whether such observations reflect causality remain largely unknown. We aimed to investigate the causal associations of physical activity, sedentary behaviours, and sleep duration with coronary artery disease (CAD), myocardial infarction (MI), stroke and lipid levels.

Methods

We conducted a Mendelian randomization (MR) study using genetic variants as instruments which are associated with physical activity, sedentary behaviours, and sleep duration to examine the causal effects on CVDs and lipid levels. This study included analyses of 4 potentially modifiable factors and 7 outcomes. Thus, the threshold of statistical significance isP = 1.8 × 10− 3(0.05/4 × 7) after Bonferroni correction.

Results

In the present study, there was suggestive evidence for associations of genetically predicted VPA with CAD (odds ratio, 0.65; 95% confidence intervals, 0.47–0.90;P = 0.009) and MI (0.74; 0.59–0.93;P = 0.010). However, genetically predicted VPA, MVPA, sleep duration and sedentary behaviours did not show significant associations with stroke and any lipid levels.

Conclusions

Our findings from the MR approach provided suggestive evidence that vigorous exercise decreased risk of CAD and MI, but not stroke. However, there was no evidence to support causal associations of MVPA,sleep duration or sedentary behaviours with cardiovascular risk and lipid levels.

Translational perspective

The findings of this study did not point out specific recommendations on increasing physical activity required to deliver significant health benefits. Nevertheless, the findings allowed clinicians and public health practitioners to provide advice about increasing the total amount of excising time by demonstrating that such advice can be effective. Reliable assessment of the association of physical activity levels with different subtypes of CVDs is needed to provide the basis for a comprehensive clinical approach on CVDs prevention, which can be achieved through lifestyle interventions in addition to drug therapy.
The effect of weight loss and exercise on Health-Related Quality of Life (HRQOL) following Endoscopic Bariatric Therapies (EBT) for obesity
Authors: Lopez-Nava Gontrand , Asokkumar Ravishankar , Lacruz T. , Rull A. , Beltran L. , Bautista-Castaño Inmaculada
Published: May 2020

Introduction

Endoscopic bariatric therapies (EBT) have demonstrated to induce weight loss and improve comorbidities in obese patients. However, little is known about its impact on health-related quality of life (HRQOL) outcomes and physical activity status. This study aimed to evaluate the change in HRQOL and physical activity following EBT induced weight loss in obese patients.

Methods

We approached 181 patients who underwent EBT in a standardized multidisciplinary follow-up program to participate in the study. We provided them two questionnaires-a) Short Form-36 health survey with the physical (PSC) and mental (MSC) summary component scores to capture generic HRQOL, and b) international physical activity questionnaire (IPAQ) for physical activity (PA). We administered the survey at baseline and at 9 months post-procedure. We expressed the procedure outcome as percentage total body weight loss (%TBWL). We expressed continuous variables as mean (SD) or median and categorical variables as percentages. We used non-parametric tests for comparison and performed multivariable linear regression analysis to identify factors associated with improvement in HRQOL.

Results

The mean age was 42.2 (11.3) years, and the mean BMI was 38 (5.9)kg/m2. A majority of them were female (n-132, 73%). The EBT included intragastric balloons (n-136, 75%) and endoscopic sleeve gastroplasty (n-24, 25%). The mean %TBWL achieved after the intervention was 16.9 (9.7)%. We noticed a significant improvement in the median PSC (77.8 vs. 90.4, p < 0.001) and MSC (67 vs. 80.2, p < 0.001) scores after EBT. Similarly, we observed a significant positive change in physical activity compared to baseline (1606.2 vs. 2749 MET-minutes/week, p = < 0.001). Linear regression analysis showed an increase in %TBWL was associated with significant improvement in PSC (β = 0.193, p = 0.003) and MSC (β = 0.166, p = 0.02) scores of HRQOL, and likewise, increase in PA was independently associated with improvement in MSC (β = 0.192, p = 0.01). We did not find any difference in outcome based on gender or the type of intervention.

Conclusion

EBT improves HRQOL in obese patients regardless of the type of intervention. The weight loss induced by EBT and the improvement in PA positively influence the health outcomes and quality of life.
A rapid and sensitive method to assess seed longevity through accelerated aging in an invasive plant species
Authors: Fenollosa Erola , Jené Laia , Munné-Bosch Sergi
Published: May 2020

Background

Seed longevity and vigor assessment is crucial for efficient ex situ biodiversity conservation in genebanks but may also have potential applications for the understanding of ecological processes and in situ biodiversity conservation. In fact, one of the factors determining the persistence of invasive species, a main threat to global biodiversity, is the generation of soil seed banks where seeds may remain viable for several years. Artificial seed aging tests using high temperatures and high relative humidity have been described for seed longevity estimation but have been mainly optimized for species with commercial interest. Thus, the aim of the study is to define a rapid and sensitive method to assess seed longevity and vigor through accelerated aging in the worldwide distributed invasive speciesCarpobrotus edulisto provide tools to biodiversity managers to evaluate invasive potential and develop effective post-eradication plans.

Results

Slow seed deterioration rate was obtained whenC. edulisseeds were subjected to common accelerated aging temperatures (43–45 °C). This contrasts with the rapid viability decay between 24–72 h when seeds were subjected to temperatures superior to 55 °C, a strong inflection point for this species’ thermosensitivity. Relative humidity also played a role in defining seed survival curves, but only at high temperatures, speeding up the deterioration process. The selected aging conditions, 55 °C at 87% relative humidity were tested over twoC. edulispopulations and three measures were proposed to parametrize the differential sigmoidal seed survival curves, defining the seed resistance to deterioration (L5, aging time where 95% of seeds maintain their viability), medium longevity (L50, 50% of seeds lose their viability) and lethal aging time (L95, 95% of viability loss).

Conclusions

An accelerated aging test at 55 °C and 87% relative humidity constitutes a rapid and sensitive method that can be performed within a working week, allowing managers to easily test seed vigor and longevity. This test may contribute to assess invasive potential, design effective monitoring programs and soil seed bank eradication treatments.
The effect of probe geometry on rind puncture resistance testing of maize stalks
Authors: Cook Douglas D. , Meehan Kyler , Asatiani Levan , Robertson Daniel J.
Published: May 2020

Background

Stalk lodging (breaking of plant stems prior to harvest) is a major impediment to increasing agricultural yields of grain crops. Rind puncture resistance is commonly used to predict the lodging resistance of several crop species. However, there exist no standard operating procedures or suggested protocols for conducting rind penetration experiments. In addition, experimental details of rind penetration tests such as the shape and size of the penetrating probe are rarely reported in the literature. This has prevented meta-analysis of results and has likewise prevented key findings of past studies from being replicated. As a first step towards establishing an agreed upon measurement standard for rind puncture resistance this study investigates the effect of the puncturing probe’s geometry on test results.

Results

Results demonstrate that probe geometry has a significant impact on test results. In particular, results showed that a 2 mm diameter chamfered probe produced stronger correlations with stalk bending strength than a 1.5 mm diameter pointed probe. The chamfered probe was also more strongly correlated with geometric features of the stalk that are known to influence stalk lodging resistance (e.g., rind thickness, diameter and section modulus). In addition, several alternative rind penetration metrics were investigated, and some were found to be superior to the most common rind penetration metric of maximum load.

Conclusions

There is a need in the agricultural and plant science community to create agreed-upon operating procedures and testing standards related to mechanical traits of plant stems. In particular, a standardized probe geometry and insertion rate for rind penetration studies are needed to enable greater interoperability and meta-analysis of results. Probe shape and size should be reported in any study conducting rind penetration tests as these factors significantly impact test results.
“Emerging Technologies and Medical Countermeasures to Chemical, Biological, Radiological, and Nuclear (CBRN) Agents in East Ukraine”
Authors: Patel Sonny S. , Grace Robert M. , Chellew Patrick , Prodanchuk Mykola , Romaniuk Olha , Skrebets Yuriy , Ryzhenko Sergii A. , Erickson Timothy B.
Published: May 2020

Since 2014, Ukraine has been beset by an armed conflict with international and internal dimensions. The nature of this conflict is multidimensional, and disaster preparedness and response in this context must be as well. Health experts from Ukraine, the United States of America, United Kingdom, Czech Republic, and Norway convened for an educational event in Dnipro, East Ukraine on November 11-15, 2019. At the event, “Emerging Technologies and Countermeasures to CBRN Agents: Advanced Training Response to Conflict and Security Challenges in East Ukraine,” over 1,000 participants participated in panel discussions, didactic lectures, and an advanced training on various dimensions of disaster response. This report provides an overview of the key discussions and outcomes of the event.
The potential negative impact of antibiotic pack on antibiotic stewardship in primary care in Switzerland: a modelling study
Authors: Füri Julia , Widmer Andreas , Bornand Delia , Berger Christoph , Huttner Benedikt , Bielicki Julia Anna
Published: May 2020

Background

In Switzerland, oral antibiotics are dispensed in packs rather than by exact pill-count. We investigated whether available packs support compliance with recommended primary care treatment regimens for common infections in children and adults.

Methods

Hospital-based guidelines for oral community -based treatment of acute otitis media, sinusitis, tonsillopharyngitis, community-acquired pneumonia and afebrile urinary tract infection were identified in 2017 in an iterative process by contacting hospital pharmacists and infectious diseases specialists. Furthermore, newly available national guidelines published in 2019 were reviewed. Available pack sizes for recommended solid, dispersible and liquid antibiotic formulations were retrieved from the Swiss pharmaceutical register and compared with recommended regimens to determine optimal (no leftovers) and adequate (optimal +/− one dose) matches.

Results

A large variety of recommended regimens were identified. For adults, optimal and adequate packs were available for 25/70 (36%) and 8/70 (11%) regimens, respectively. Pack-regimen matching was better for WHO Watch (optimal: 15/24, 63%) than Access antibiotics (optimal: 7/39, 18%). For the four paediatric weight-examples and 42 regimens involving child-appropriate formulations, optimal and adequate packs were available for only 14/168 (8%) and 27/168 (16%), respectively. Matching was better for older children with higher body and for longer treatment courses > 7 days.

Conclusions

Fixed antibiotic packs often do not match recommended treatment regimens, especially for children, potentially resulting in longer than necessary treatments and leftover doses in the community. As part of national stewardship, a move to an exact pill-count system, including for child-appropriate solid formulations, should be considered.
Identification of C9-C11 unsaturated aldehydes as prediction markers of growth and feed intake for non-ruminant animals fed oxidized soybean oil
Authors: Yuan Jieyao , Kerr Brian J. , Curry Shelby M. , Chen Chi
Published: May 2020

Background

The benefits of using the oxidized oils from rendering and recycling as an economic source of lipids and energy in animal feed always coexist with the concerns that diverse degradation products in these oxidized oils can negatively affect animal health and performance. Therefore, the quality markers that predict growth performance could be useful when feeding oxidized oils to non-ruminants. However, the correlations between growth performance and chemical profiles of oxidized oils have not been well examined. In this study, six thermally oxidized soybean oils (OSOs) with a wide range of quality measures were prepared under different processing temperatures and processing durations, including 45 °C-336 h; 67.5 °C-168 h; 90 °C-84 h; 135 °C-42 h; 180 °C-21 h; and 225 °C-10.5 h. Broilers and nursery pigs were randomly assigned to diets containing either unheated control soybean oil or one of six OSOs. Animal performance was determined by measuring body weight gain, feed intake, and gain to feed ratio. The chemical profiles of OSOs were first evaluated by common indicative tests, including peroxide value, thiobarbituric acid reactive substances, p-anisidine value, free fatty acids, oxidized fatty acids, unsaponifiable matter, insoluble impurities, and moisture, and then analyzed by the liquid chromatography-mass spectrometry-based chemometric analysis.

Results

Among common quality indicators, p-anisidine value (AnV), which reflects the level of carbonyl compounds, had the greatest inverse correlation with the growth performance of both broilers and pigs, followed by free fatty acids and oxidized fatty acids. Among the 17 aldehydes identified in OSOs, C9-C11 alkenals, especially 2-decenal and 2-undecenal, had stronger inverse correlations (r < − 0.8) with animal performance compared to C5-C8 saturated alkanals, suggesting that chain length and unsaturation level affect the toxicity of aldehydes.

Conclusions

As the major lipid oxidation products contributing to the AnV, individual C9-C11 unsaturated aldehydes in heavily-oxidized oils could function as effective prediction markers of growth and feed intake in feeding non-ruminants.
CARGEL Bioscaffold improves cartilage repair tissue after bone marrow stimulation in a minipig model
Authors: Hede K. , Christensen B. B. , Olesen M. L. , Thomsen J. S. , Foldager C. B. , Lind M. C.
Published: May 2020

Purpose

To gain knowledge of the repair tissue in critically sized cartilage defects using bone marrow stimulation combined with CARGEL Bioscaffold (CB) compared with bone marrow stimulation (BMS) alone in a validated animal model.

Methods

Six adult Göttingen minipigs received two chondral defects in each knee. The knees were randomized to either BMS combined with CB or BMS alone. The animals were euthanized after 6 months. Follow-up consisted of histomorphometry, immunohistochemistry, semiquantitative scoring of the repair tissue (ICRS II), and μCT of the trabecular bone beneath the defect.

Results

There was significantly more fibrocartilage (80% vs 64%, p = 0.04) and a trend towards less fibrous tissue (15% vs 30%, p = 0.05) in the defects treated with CB. Hyaline cartilage was only seen in one defect treated with CB and none treated with BMS alone.

For histological semiquantitative score (ICRS II), defects treated with CB scored lower on subchondral bone (69 vs. 44, p = 0.04). No significant differences were seen on the other parameters of the ICRS II. Immunohistochemistry revealed a trend towards more positive staining for collagen type II in the CB group (p = 0.08). μCT demonstrated thicker trabeculae (p = 0.029) and a higher bone material density (p = 0.028) in defects treated with CB.

Conclusion

Treatment of cartilage injuries with CARGEL Bioscaffold seems to lead to an improved repair tissue and a more pronounced subchondral bone response compared with bone marrow stimulation alone. However, the CARGEL Bioscaffold treatment did not lead to formation of hyaline cartilage.
A protocol for co-creating research project lay summaries with stakeholders: guideline development for Canada’s AGE-WELL network
Authors: Wada Mineko , Sixsmith Judith , Harwood Gail , Cosco Theodore D. , Fang Mei Lan , Sixsmith Andrew
Published: May 2020

Background

Funding bodies increasingly require researchers to write lay summaries to communicate projects’ real-world relevance to the public in an accessible way. However, research proposals and findings are generally not easily readable or understandable by non-specialist readers. Many researchers find writing lay summaries difficult because they typically write for fellow subject specialists or academics rather than the general public or a non-specialist audience. The primary objective of our project is to develop guidelines for researchers in Canada’s AGE-WELL Network of Centres of Excellence, and ultimately various other disciplines, sectors, and institutions, to co-create lay summaries of research projects with stakeholders. To begin, we produced a protocol for co-creating a lay summary based on workshops we organized and facilitated for an AGE-WELL researcher. This paper presents the lay summary co-creation protocol that AGE-WELL researchers will be invited to use.

Methods

Eligible participants in this project will be 24 AgeTech project researchers who are funded by the AGE-WELL network in its Core Research Program 2020. If they agree to participate in this project, we will invite them to use our protocol to co-produce a lay summary of their respective projects with stakeholders. The protocol comprises six steps: Investigate principles of writing a good lay summary, identify the target readership, identify stakeholders to collaborate with, recruit the identified stakeholders to work on a lay summary, prepare for workshop sessions, and execute the sessions. To help participants through the process, we will provide them with a guide to developing an accessible, readable research lay summary, help them make decisions, and host, and facilitate if needed, their lay summary co-creation workshops.

Discussion

Public-facing research outputs, including lay summaries, are increasingly important knowledge translation strategies to promote the impact of research on real-world issues. To produce lay summaries that include information that will interest a non-specialist readership and that are written in accessible language, stakeholder engagement is key. Furthermore, both researchers and stakeholders benefit by participating in the co-creation process. We hope the protocol helps researchers collaborate with stakeholders effectively to co-produce lay summaries that meet the needs of both the public and project funders.
ILES of an array of three subsonic counter-flow jets issuing from a wing leading edge exposed to hypersonic aerodynamic heating
Authors: Shimada Tomonori , Ohwada Taku
Published: May 2020

The flow of an active thermal protection system exploiting subsonic counter-flow jets for wing leading edges of hypersonic vehicles is numerically studied on the basis of the three dimensional Navier-Stokes equations. The coolant air issuing from around the stagnation point as an array of three jets spreads over both the upper and the lower sides of the cylinder surface and about 40 ~ 60% cooling effectiveness is achieved in the range up to 5 degrees angle of attack despite the occurrence of various three-dimensional fluid-dynamic instabilities. The numerical scheme is second order accurate but simple inclusion of high order polynomial approximation in the reconstruction enables the capturing of finer structure of the flow field.
The application of stratified medicine to dementia care
Authors: Sidhom Emad , O'Brien John , Underwood Benjamin R.
Published: May 2020

Stratified medicine has been successfully used in many areas of medicine, perhaps most notably oncology. There is now both a growing evidence base and mounting enthusiasm, supported at a governmental level and across industry, academia and clinical medicine, to apply this approach to neurodegenerative illnesses, including dementia, as these provide the greatest clinical and social challenge of our times. In this article we consider definitions of stratified medicine, look at its application in other medical specialties, review the national context in the UK and consider the current state, future potential and specific considerations of applying stratified medicine to dementia.
Diagnose, indicate, and treat severe mental illness (DITSMI) as appropriate care: A three-year follow-up study in long-term residential psychiatric patients on the effects of re-diagnosis on medication prescription, patient functioning, and hospital bed utilization
Authors: Veereschild H. M. , Noorthoorn E. O. , Nijman H. L. I. , Mulder C. L. , Dankers M. , Van der Veen J. A. , Loonen A. J. M. , Hutschemaekers G. J. M.
Published: May 2020

Background.

While polypharmacy is common in long-term residential psychiatric patients, prescription combinations may, from an evidence-based perspective, be irrational. Potentially, many psychiatric patients are treated on the basis of a poor diagnosis. We therefore evaluated the DITSMI model (i.e., Diagnose, Indicate, and Treat Severe Mental Illness), an intervention that involves diagnosis (or re-diagnosis) and appropriate treatment for severely mentally ill long-term residential psychiatric patients. Our main objective was to determine whether DITSMI affected changes over time regarding diagnoses, pharmacological treatment, psychosocial functioning, and bed utilization.

Methods.

DITSMI was implemented in a consecutive patient sample of 94 long-term residential psychiatric patients during a longitudinal cohort study without a control group. The cohort was followed for three calendar years. Data were extracted from electronic medical charts. As well as diagnoses, medication use and current mental status, we assessed psychosocial functioning using the Health of the Nations Outcome Scale (HoNOS). Bed utilization was assessed according to length of stay (LOS). Change was analyzed by comparing proportions of these data and testing them with chi-square calculations. We compared the numbers of diagnoses and medication changes, the proportions of HoNOS scores below cut-off, and the proportions of LOS before and after provision of the protocol.

Results.

Implementation of the DITSMI model was followed by different diagnoses in 49% of patients, different medication in 67%, some improvement in psychosocial functioning, and a 40% decrease in bed utilization.

Conclusions.

Our results suggest that DITSMI can be recommended as an appropriate care for all long-term residential psychiatric patients.
MON-116 Metabolic Parameters in Cancer Patients with and Without Diabetes Mellitus
Authors: Karlin Nina , Kosiorek Heidi , Buras Matthew , Verona Patricia , Coppola Kyle , Cook Curtiss Bela
Published: May 2020

Background: We have previously examined the link between diabetes mellitus (DM) and malignancy with respect to mortality, but little is known about how the cancer affects glycemic control. Therefore, the aim of this study was to evaluate metabolic parameters in patients with cancer with and without DM. Methods: We selected 1404 patients with newly diagnosed prostate, breast, lung, colorectal, and pancreatic cancer from the institutional cancer registry from 2010–2015. Records were selected and matched 2:1 cancer without DM (n=936) and cancer and concurrent DM patients (n=468). Patients were matched by year of diagnosis, age, gender, and cancer type. Metabolic parameters during the year after cancer diagnosis were examined using linear mixed models with fixed effects for time, cancer type, DM status and individual-specific random effect allowing each patient to have a different intercept. Results: Prostate cancer accounted for the majority of cases (n=199), followed by lung cancer (n=91), breast cancer (n=71), colorectal cancer (n=54), and pancreas cancer (n=53). Mean overall hemoglobin A1c (HbA1c) was 6.9 (1.2)%. Pancreas cancer patients had higher HbA1c overall (p=0.02). There was no change in HbA1c one year post cancer diagnosis (p=0.28). Mean glucose in non-DM was 108(18) mg/dL and 146 (45) mg/dL in DM pts. Lung and pancreas cancer patients had higher glucose values overall (p<0.001). Time (p<0.001), DM (p<0.001) and time * DM (p=0.02) were significant in a mixed model. A decrease in glucose over the year was observed in DM patients across all cancer types. Conclusions: A diagnosis of malignancy does not worsen glycemic control within the first year of cancer diagnosis. This should be reassuring to endocrinologists and oncologists who treat patients with DM and cancer. Longer term studies, and analysis in larger and more diverse patients groups are needed.
SUN-288 Atypical Teratoid Rhabdoid Tumor of the Sellar Region: An Unusual Cause of Hypopituitarism
Authors: Laichuthai Nitchakarn , Snabboon Thiti
Published: May 2020

Background: Atypical teratoid/rhabdoid (AT/RT) tumor of the sellar region is an extremely rare malignant tumor in adults. To date, there are no definitive guidelines for optimal treatment and the prognosis of this tumor is poor. The pituitary insufficiency was rarely mentioned in previous literature and might be overlooked.

Clinical case: A 43 years old female presented to our clinic with severe periorbital pain. The magnetic resonance imaging of the brain revealed a 1.5x1.5x 3 cm sellar mass which showed inhomogeneous enhancement after gadolinium administration. Hormonal work up showed 8AM cortisol of 1.86 mcg/dL, free T4 1.0 (0.8–1.8 ng/dL), TSH 0.05 (0.3 - 4.1 uIU/ml), FSH 6.0 (1.6–9.3 IU/L), LH 1.8 (2.4–9.3 IU/L), estradiol <18.35 (80–790 pmole/L), IGF-1 96.6 (50.6–263.7 ng/ml), prolactin 56.6 ng/ml.

She underwent transsphenoidal surgery with tumor removal. The pathological result showed a mixture of pleomorphic spindle cell, oval shape tumor and poorly differentiated cell. The tumor was negative for INI1 (SMARCB1) compatible with AT/RT WHO grade IV. She developed pan hypopituitarism after surgery. She received 6 courses of 5950 cGy/25 fractions cranial irradiation and 6 courses of ifosfamide, cisplatin and etoposide. She completed the treatment regimen without significant toxicity. She continued hormonal replacement for panhypopituitarism and is still being followed at our clinic for 4 years without tumor progression or other complications.

In previously reported cases, all of the sellar AT/RT were female with a median age of 45 years old (range 20–61). The clinical presentations are rapidly enlarged sellar mass with compressive symptoms to the adjacent structures. The radiological findings of sellar AT/RT are non-specific. The diagnosis is based on histopathological findings. Presence of rhabdoid cells on histopathology and polyphenotypic immunopositivity for epithelial, mesenchymal, and neuroectodermal markers along with loss of expression of SMARCB1/INI1 help in establishing a diagnosis of AT/RT.

Currently, there are no definitive guidelines for optimal treatment. Multimodality treatment consisted of surgery, radiation and chemotherapy are the mainstays of treatment of the AT/RT. Of the 16 adults reported in the literature, 9 patients survived more than 12 months resulted in 47% of one-year survival rate. To our knowledge, this case is the sellar AT/RT with the longest survival to date.

Conclusion: AT/RT is one of the most aggressive tumors in the sellar area. Due to its aggressiveness, hypopituitarism is anticipated. Our patient had postoperative secondary adrenal insufficiency, secondary hypothyroid and hypogonadotropic hypogonadism. Apart from multimodality treatment required for tumor control, pituitary hormones should be evaluated preoperatively to prevent perioperative mortality and long-term improvement in the quality of life.