bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundFunding 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.MethodsEligible 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.DiscussionPublic-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

AbstractThe 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

SUMMARYStratified 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

Abstract

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

Abstract
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&lt;0.001). Time (p&lt;0.001), DM (p&lt;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

Abstract
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 &lt;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.
MON-618 A Framework for Understanding and Managing ‘The Diabetes Syndrome’: A Unified Pathophysiologic Approaching the Context of the Beta-Cell Classification of Diabetes
Authors: Schwartz Stanley S 
Published: May 2020

Abstract
We have previously presented a proposal for a new, beta-cell centric classification of diabetes based on a consilience of genetic, metabolic, and clinical research that have accrued since the current classification was instituted. It recognizes that the beta-cell is THE core defect in all patients with diabetes. Differences in the genetics (and epigenetics), insulin resistance, environment and inflammation/immune characteristics resulting in the damage to the beta-cell in each individual will determine the phenotypic presentation of hyperglycemia and allow for a patient-centric, precision-medicine therapeutic approach, part of which we labeled ‘the Egregious Eleven’.
We now recognize the same pathophysiologic mechanisms that account for damage to the beta-cells govern the susceptibility of the cells involved in the complications and other conditions ‘tied to’ diabetes to damage by the abnormal metabolic environment that typifies beta-cell dysfunction and ‘fuel excess’. This abnormal metabolic environment is typified by oxidative stress which alters metabolic pathways (a la Brownlee’s Hypothesis model), alterations in gene expression, epigenetics, and inflammation. This allows us to understand the varied risk of developing complications of diabetes, including malignancies, dementia, NASH, psoriasis with similar levels of glycemic control; how non-glycemic effects of some medications for diabetes result in marked complication risk modification; and the value treating co-morbidities of diabetes in modifying complication risk.
Principles we outlined in using ‘the Egregious Eleven’ model- use agents that preserve beta-cell function, treat with least number of agents that treat most number of mechanisms of hyperglycemia- can be extended to use those agents, in combination, that also engender weight loss, decrease CV outcomes and have real or potential benefits in cancers related to diabetes, dementia risk, NASH, psoriasis. This approach allows for a more accurate assessment of each patient’s disease and effecting true precision medicine
Schwartz, S, et al, Diabetes Care 2016, 39:179–186.
Schwartz SS, et al Trends Endocrinol Metab. 2017;28(9):645–655.
SAT-680 Diabetes Mellitus Induced by Programmed Cell Death-1 (PD-1) Inhibitors: A Case Report
Authors: Abuaisha Munder , Castillo Dan Ran , Imran Maha , Schultz Atara B 
Published: May 2020

Abstract
Introduction:
Immune checkpoint blockade has revealed a remarkable success in the treatment of a range of cancer types. Immune-related adverse events on the endocrine system may be permanent and carry high morbidity and mortality.
Case:
A 35-year-old black male presented to the ED with acute onset diffuse abdominal pain, along with nausea and vomiting. Review of systems was positive for polyuria and polydipsia. The examination was unremarkable apart from a sizeable fungating lesion of the left lower extremity by the ankle measuring 12 x 8 cm. Investigations indicated blood sugars around 600, serum bicarbonate of 19 mEq/L, an anion gap of 19 mEq/L, serum BHB was elevated, and lactate within normal. The patient was diagnosed with DKA, started on an insulin drip, and admitted to the ICU.
Our patient had no known personal or family history of diabetes. A few years ago, he had suffered from a non-healing chronic ulcer in his left ankle secondary to a motor vehicle accident. Three months ago, he had been diagnosed with a well-differentiated squamous cell carcinoma, arising from his chronic non-healing ulcer. One month ago, He had started Pembrolizumab 200mg Intravenously, and he had received a total of two cycles, the last cycle was one week ago. Shortly after he presented to the ED with the above chief complaint.
He made a complete recovery and further investigations revealed HbA1c of 7.2%, C-peptide levels of &lt;0.1 ng/mL, which supports the diagnosis of T1-DM. He was discharged home, and Pembrolizumab was continued.
Conclusion:
Autoimmune T1-DM has been reported after receiving anti-PD-1 therapy. In a recent study included 27 patients with a variety of solid-organ cancers, and all had received anti–PD-1 antibodies treatment, autoimmune, T1-DM diabetes occurred in close to 1% of patients (1). A systematic review and meta-analysis were conducted recently showed that people developed T1-DM within three months of the initial PD-1 inhibitor exposure. Since patients treated with anti–PD-1 antibodies can present with life-threatening DKA, a high index of suspicion is crucial as early detection is the key to successful treatment and prevention of morbidity and mortality. It remains unclear if it is safe to restart the checkpoint inhibitor after an immune-related adverse event, and further studies are necessary in order to resolve this dilemma. A recent retrospective study included patients with melanoma showed that anti–PD-1 therapy could be safely resumed after severe adverse event requiring immunosuppression (2).
References:
1. Stamatouli, A. M. et al. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 67, 1471–1480 (2018).
2. Menzies, A. M. et al. Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann. Oncol. 28, 368–376 (2017).