Interest In Clinical Research Research Articles

Cannabidiol (CBD) Use by Older Adults for Acute and Chronic Pain.

Legalization of cannabidiol (CBD) products has ignited interest in clinical practice and research. One desired indication includes possible pain-relieving effects of CBD. The purposes of the current article are to (1) clarify terminology relevant to cannabinoids; (2) explain and understand the pharmacotherapeutics of CBD; (3) examine research of the current use of CBD by older adults for treating pain; (4) discuss safety considerations with using CBD products; and (5) provide best practice recommendations for clinicians as they advise their older adult patients. A review of the literature demonstrated mixed results on the efficacy of CBD in relieving pain in older adults. There is inconsistency in the labeling of over-the-counter CBD products that can result in safety issues and will require more federal quality control. Likewise, gaps in knowledge regarding safety and efficacy of CBD use in older adults are vast and require further research. [Journal of Gerontological Nursing, 47(7), 6-15.].

Design and Impact of a Novel Otolaryngology Virtual Sub-Internship in the Time of COVID-19

Objective: To discuss the design and impact of a novel otolaryngology virtual sub-internship created as a substitute for the visiting electives that were suspended due to the COVID-19 pandemic.Methods: A two-week virtual elective was designed and registered with the Visiting Student Learning Opportunities (VSLO) program. The virtual elective consisted of two blocks held during the first two weeks of August and again during the first two weeks of September. A total of 12 medical students enrolled, 5 in August and 7 in September. Surveys were distributed at the beginning and end of the rotation to obtain feedback and assess impact.Results: Over the course of the rotation students participated in a total of approximately 60–70 hours of virtual interactive sessions including clinical and surgical lectures, resident Q&A panels, hospital and home virtual tours, alumni information sessions, faculty “Meet & Greets” and structural/organizational program overviews. Each visiting student delivered an end-of-rotation presentation to the department on a clinical topic or research interest of their choice. Post-rotation survey data suggests the virtual rotation was an important and meaningful opportunity for visiting students to better understand the program structure and culture. Students reported that the rotation was influential in the creation of their rank lists and should continue to be offered even after in-person sub-internships resume.Conclusion: Although there is no substitute for an in-person visiting sub-internship, a well-designed virtual elective can be an interactive, worthwhile and impactful alternative during these challenging times.

The Role of Cannabidiol in Neurological Disorders.

Cannabis has been used for both recreational and medicinal purposes for more than 4 millennia. Cannabis has been studied in various medical disorders including neurological disorders. There are well-known risks of long-term use of cannabis, including low motivation, lowered cognitive capabilities, and diminished IQ and brain mass. Cannabinoids are compounds in cannabis that are known to have therapeutic potential. The most abundant chemicals in cannabinoids are delta-9-tetrahydrocannabinol and cannabidiol. Delta-9-tetrahydrocannabinol has psychotropic effects that limits its use as a pharmacotherapeutic agent. Cannabidiol is a nonpsychotropic chemical and therefore has become a compound of interest for clinical researchers to study its therapeutic potential. This article reviews the efficacy and safety of cannabidiol in various neurological disorders in humans.

Separating the wheat from the chaff: Observations on the analysis of lysergamides LSD, MIPLA, and LAMPA.

Lysergic acid diethylamide (LSD) is a potent psychoactive substance that has attracted great interest in clinical research. As the pharmacological exploration of LSD analogs continues to grow, some of those analogs have appeared on the street market. Given that LSD analogs are uncontrolled in many jurisdictions, it is important that these analogs be differentiated from LSD. This report presents the analysis of blotters found to contain the N-methyl-N-isopropyl isomer of LSD (MIPLA), and techniques to differentiate it from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography (GC)-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion also provided sufficient information to distinguish the three isomers on mass spectral grounds alone, where chromatographic separation proved challenging. Derivatization with 2,2,2-trifluoro-N,N-bis (trimethylsilyl)acetamide (BSTFA) also led to improved GC separation. Liquid chromatography single quadrupole mass spectrometry (LC-Q-MS) and in-source collision-induced dissociation allowed for the differentiation between MIPLA and LAMPA based on distinct m/z 239 ion ratios when co-eluting. An alternative LC-MS/MS method improved the separation between all three lysergamides, but LSD was found to co-elute with iso-LSD. However, a comparison of ion ratios recorded for transitions at m/z 324.2> 223.2 and m/z 324.2> 208.2 facilitated their differentiation. The analysis of two blotters by LC-Q-MS revealed the presence of 180 and 186 μg MIPLA per blotter. These procedures may be used to avoid inadvertent misidentification of MIPLA or LAMPA as LSD.

Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b'a' Domain.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes. In our present study, the solubility of hGM-CSF was examined when combined with three N-terminal fusion tags in five E. coli strains at three different expression temperatures. In the five E. coli strains BL21 (DE3), ClearColi BL21 (DE3), LOBSTR, SHuffle T7 and Origami2 (DE3), the hexahistidine-tagged hGM-CSF showed the best expression but was insoluble in all cases at each examined temperature. Tagging with the maltose-binding protein (MBP) and the b′a′ domain of protein disulfide isomerase (PDIb′a′) greatly improved the soluble overexpression of hGM-CSF at 30 °C and 18 °C. The solubility was not improved using the Origami2 (DE3) and SHuffle T7 strains that have been engineered for disulfide bond formation. Two conventional chromatographic steps were used to purify hGM-CSF from the overexpressed PDIb′a′-hGM-CSF produced in ClearColi BL21 (DE3). In the experiment, 0.65 mg of hGM-CSF was isolated from a 0.5 L flask culture of these E. coli and showed a 98% purity by SDS-PAGE analysis and silver staining. The bioactivity of this purified hGM-CSF was measured at an EC50 of 16.4 ± 2 pM by a CCK8 assay in TF-1 human erythroleukemia cells.

ASGE Past President's Address.

John J. Vargo, MD, MPH, MASGE (Author photo 1, Author photo 2, Author photo 3, Author photo 4, Author photo 5, Author photo 6), is an associate professor of medicine at the Cleveland Clinic Lerner College of Medicine at Case Western University. He is a member of the Department of Gastroenterology, Hepatology and Nutrition in the Digestive Disease and Surgery Institute at the Cleveland Clinic.Author photo 2Department of Gastroenterology and Hepatology at the Cleveland Clinic. I am blessed to be surrounded by one of the finest faculties and groups of fellows in the world.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Author photo 3World Cup of Endoscopy at Digestive Disease Week. The alter ego comes out. Now, what to do with the costumes?View Large Image Figure ViewerDownload Hi-res image Download (PPT)Author photo 4With my dear friends Seiichiro Abe, Yutaka Saito, and Amit Bhatt.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Author photo 5With my friend of many years, the incomparable G.S. Raju.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Author photo 6My family: my wife Mary and our sons (left to right) Kevin, John, and Matthew.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Dr Vargo received his medical degree from the University of Rochester School of Medicine and Dentistry and completed his internal medicine residency training at the University of Pittsburgh Medical Center. He then completed gastroenterology and hepatology fellowships at the Cleveland Clinic and received training in advanced endoscopy at the same institution. After fulfilling a 3-year commitment in the United States Navy while stationed at Bethesda National Naval Medical Center as director of endoscopy and consultant in gastroenterology for the United States Capitol, he returned to the Cleveland Clinic in the section of advanced endoscopy. During his tenure, Dr Vargo developed a keen interest in clinical research. After securing a career development award from the American Society for Gastrointestinal Endoscopy (ASGE) and the American Digestive Health Foundation, Dr Vargo obtained a Master of Public Health degree from Case Western University. This turned out to be a transformational event, which led to the development of numerous endoscopic research projects focusing on clinical outcomes, quality, and cost-effectiveness. This resulted in the publication of over 250 articles in the peer-reviewed literature. Dr Vargo served as chair of the Department of Gastroenterology and Hepatology and vice chair for the Digestive Disease and Surgery Institute for 8 years. He also served as president of the Cleveland Clinic’s medical staff and sat on the institution’s Board of Governors. He is currently the director of Enterprise Endoscopy Operations, director of Endoscopic Research and Innovation, and head of the Section of Advanced Endoscopy. He has lectured and performed endoscopic demonstrations around the globe and has been honored with fellowships in 3 international gastroenterology societies. He has been invited faculty for numerous courses for ASGE and has been co-director of ASGE’s annual postgraduate course twice. He has held numerous positions in ASGE, including chair of the Training Committee. During his tenure, the committee was able to develop an advanced endoscopy training directory and began development of the forerunner of the advanced endoscopy match program. Dr Vargo served as president of ASGE from 2019 to 2020. During this entropic time of the COVID-19 pandemic, he led the society through a transition to a virtual education and communications platform, which ensured that information on the COVID-19 pandemic was expediently distributed via weekly webinars, fast-tracked articles in GIE, and expedient practice guidelines that were co-authored with ASGE’s sister societies. During his presidency, the entire framework of ASGE’s educational mission was reframed and crystallized to meet the needs of gastroenterologists in the United States and around the world. Dr Vargo has trained a multitude of general gastroenterology and advanced endoscopy fellows over the years, who are now scattered around the United States and throughout the world. He is a perennial Top Doctors and Best Doctors in America selection. Dr Vargo received teacher-of-the-year awards from his gastroenterology fellows a total of 5 times over his career. Areas of interest in his practice include ERCP, EUS, the treatment of Barrett’s esophagus, artificial intelligence, and the development of endoscopic devices. All authors disclosed no financial relationships. https://www.videogie.org/cms/asset/776b53df-e503-4e22-94df-3f45da5ce4ab/mmc1.mp4Loading ... Download .mp4 (179.53 MB) Help with .mp4 files Video 1

Feasibility and Acceptability of Self-Report and Biologically Measured Energy Intake in Adults With Multiple Sclerosis

Diet is a modifiable behavior of interest in epidemiological, disease modification, and clinical rehabilitation research involving persons with multiple sclerosis (MS). The current study is the first focal examination of the feasibility and acceptability of measuring energy intake in persons with MS that can guide future approaches for assessing compliance in diet interventions.

Quality of life among head and neck cancer treated patients in South India: A cross-sectional study

Background and aimThe impact of oral health related disease and treatment on the patient’s overall well-being and functioning is a topic of growing interest in clinical research and practice. Research shows that there is a significant reduction in the quality of life for the patients throughout the treatment of head and neck cancer. Therefore, the aim of the study is to assess the quality of life among treated head and neck cancer patients. Materials and methodThe cross sectional study was conducted among 225 head and neck cancer patients. The European Organization for Research and Treatment of Cancer (EORTC QLQ C-30), Quality Of Life Head and Neck35” (QLQ-HN35) instruments were used to assess their quality of life. The study population was divided into three groups based on the treatment done: Group I (Surgery), Group II (Surgery and Radiotherapy) and Group III (Surgery, Radiotherapy and Chemotherapy). Independent t-test and one way ANOVA test were done to analyze the data. ResultsTrouble with opening mouth (34.66 ​± ​30.58) was one of the highest rated symptoms among the study population. Salivary dysfunction leading to dry mouth (33.33 ​± ​34.06), sticky saliva (33.33 ​± ​26.72) were also found to be severe. Among the three groups, the Global Health Status, Symptom Scale mean scores were more high in Group I, Functional Scale and H&N35 symptoms mean scores was high in Group III however no statistical significance was observed (p ​> ​0.05). ConclusionHead and neck cancer has severe effects on the quality of life. As observed from the findings of the current study, Global Health Status indicated a healthy level of living among patients who have undergone surgery alone; head and neck symptoms were more severe and problematic among patients who had surgery and radiotherapy. Therefore, assessing health related quality of life can be a factor that is weighed against treatment burden, toxicity, survival benefit. It can be more integral to treatment planning, refining treatment protocols and a better post-operative care and support.

Characteristics and Biomarkers of Ferroptosis.

The induction and consequences of regulated cell death (RCD) are accompanied by changes in gene and protein expression, biochemical pathways, as well as cell morphology and size. Such RCDs have a significant impact on development, tissue homeostasis, and the occurrence and progression of disease. Among different forms of RCD, ferroptosis appears to be the main cause of tissue damage driven by iron overload and lipid peroxidation. In fact, the dysfunctional ferroptotic response is implicated in a variety of pathological conditions and diseases, such as neurodegenerative diseases, tissue ischemia-reperfusion injury, tumorigenesis, infections, and immune diseases. Ferroptotic response can be fine-tuned through various oxidative stress and antioxidant defense pathways, coupling with metabolism, gene transcription, and protein degradation machinery. Accordingly, a series of ferroptosis inducers or inhibitors targeting redox- or iron metabolism-related proteins or signal transduction have been developed. Although this kind of RCD has recently attracted great interest in basic and clinical research, detecting and monitoring a ferroptotic response still faces challenges. In this mini-review, we not only summarize the latest knowledge about the characteristics of ferroptosis in vitro and in vivo, but also discuss the specificity and limitations of current biomarkers of ferroptosis.

Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill

Transcranial direct current stimulation (tDCS)-based interventions for augmenting motor learning are gaining interest in systems neuroscience and clinical research. Current approaches focus largely on monofocal motorcortical stimulation. Innovative stimulation protocols, accounting for motor learning related brain network interactions also, may further enhance effect sizes. Here, we tested different stimulation approaches targeting the cerebro-cerebellar loop. Forty young, healthy participants trained a fine motor skill with concurrent tDCS in four sessions over two days, testing the following conditions: (1) monofocal motorcortical, (2) sham, (3) monofocal cerebellar, or (4) sequential multifocal motorcortico-cerebellar stimulation in a double-blind, parallel design. Skill retention was assessed after circa 10 and 20 days. Furthermore, potential underlying mechanisms were studied, applying paired-pulse transcranial magnetic stimulation and multimodal magnetic resonance imaging-based techniques. Multisession motorcortical stimulation facilitated skill acquisition, when compared with sham. The data failed to reveal beneficial effects of monofocal cerebellar or additive effects of sequential multifocal motorcortico-cerebellar stimulation. Multimodal multiple linear regression modelling identified baseline task performance and structural integrity of the bilateral superior cerebellar peduncle as the most influential predictors for training success. Multisession application of motorcortical tDCS in several daily sessions may further boost motor training efficiency. This has potential implications for future rehabilitation trials.

Vitamin D and atherosclerosis

<p>Cardiovascular diseases rank first on the mortality list globally or 31%. The basic measure of prevention in accordance with the recommendations of the World Health Organization is a change in risk lifestyle in terms of diet, physical activity, tobacco and alcohol consumption. Vitamin D was previously recognized as a regulator of calcium and phosphorus ratio, bone remodeling or the main controller of skeletal pathophysiology. However, vitamin D enjoys great interest in clinical and epidemiological research in terms of its possible impact on reducing the risk of cardiovascular diseases. Among other things, vitamin D deficiency is associated with an increased risk of endothelial dysfunction. Although the deficiency has been identified as a risk marker for cardiovascular diseases, the mechanism of action of vitamin D on the path from endothelial dysfunction to cardiovascular diseases has not been fully revealed. The findings in this segment of activity of vitamin D would be significant in terms of reducing morbidity and mortality from cardiovascular diseases.</p>

Research advances and new challenges in overcoming triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a pathological term used to identify invasive breast cancers that lack expression of estrogen and progesterone receptors and do not have pathologic overexpression of the HER2 receptor or harbor ERBB2 gene amplification. TNBC includes a collection of multiple distinct disease entities based upon genomic, transcriptomic and phenotypic characterization. Despite improved clinical outcomes with the development of novel therapeutics, TNBC still yields the worst prognosis among all clinical subtypes of breast cancer. We will systematically review evidence of the genomic evolution of TNBC, as well as potential mechanisms of disease progression and treatment resistance, defined in part by advances in next-generation DNA sequencing technology (including single cell sequencing), providing a new perspective on treatment strategies, and promise to reveal new potential therapeutic targets. Moreover, we review novel therapies aimed at homologous recombination deficiency, PI3 kinase/AKT/PTEN pathway activation, androgen receptor blockade, immune checkpoint inhibition, as well as antibody-drug conjugates engaging novel cell surface targets, including recent progress in pre-clinical and clinical studies which further validate the role of targeted therapies in TNBC. Despite major advances in treatment for TNBC, including FDA approval of 2 PARP inhibitors for metastatic TNBC, the crossing of the superiority boundary in a phase 3, placebo-controlled study of adjuvant olaparib in early-stage patients with germline BRCA-mutated high-risk HER2-negative early breast cancer, the FDA approval of 2 PD-(L)1 checkpoint antibodies for metastatic TNBC, and the FDA approval of the first antibody drug conjugate for TNBC, significant challenges remain. For example, despite the dawn of immunotherapy in metastatic TNBC, durable responses are limited to a small subset of patients, definitive biomarkers for patient selection are lacking, and the Oncology Drug Advisory Committee to the FDA has recently voted against approval of an anti-PD-1 checkpoint antibody high risk early-stage TNBC in the neoadjuvant setting. Also, despite early positive randomized phase 2 studies of AKT inhibition in metastatic TNBC, a recent phase 3 registration trial failed to validate earlier phase 2 data. Finally, we note that level one evidence for clinical efficacy of androgen receptor blockade in TNBC is still lacking. To meet these and other challenges, we will catalogue the ongoing exponential increase in interest in basic, translational, and clinical research to develop new treatment paradigms for TNBC.

Roles of Genetic Predisposition in the Sex Bias of Pulmonary Pathophysiology, as a Function of Estrogens : Sex Matters in the Prevalence of Lung Diseases.

In addition to studies focused on estrogen mediation of sex-different regulation of systemic circulations, there is now increasing clinical relevance and research interests in the pulmonary circulation, in terms of sex differences in the morbidity and mortality of lung diseases such as inherent-, allergic- and inflammatory-based events. Thus, female predisposition to pulmonary artery hypertension (PAH) is an inevitable topic. To better understand the nature of sexual differentiation in the pulmonary circulation, and how heritable factors, in vivo- and/or in vitro-altered estrogen circumstances and changes in the live environment work in concert to discern the sex bias, this chapter reviews pulmonary events characterized by sex-different features, concomitant with exploration of how alterations of genetic expression and estrogen metabolisms trigger the female-predominant pathological signaling. We address the following: PAH (Sect.7.2)is characterized as an estrogenic promotion of its incidence (Sect. 7.2.2), as a function of specific germline mutations, and as an estrogen-elicited protection of its prognosis (Sect.7.2.1). More detail is provided to introduce a less recognized gene of Ephx2 that encodes soluble epoxide hydrolase (sEH) to degrade epoxyeicosatrienic acids (EETs). As a susceptible target of estrogen, Ephx2/sEH expression is downregulated by an estrogen-dependent epigenetic mechanism. Increases in pulmonary EETs then evoke a potentiation of PAH generation, but mitigation of its progression, a phenomenon similar to the estrogen-paradox regulation of PAH. Additionally, the female susceptibility to chronic obstructive pulmonary diseases (Sect. 7.3) and asthma (Sect.7.4), but less preference to COVID-19 (Sect. 7.5), and roles of estrogen in their pathogeneses are briefly discussed.

Comparison of the central human and mouse platelet signaling cascade by systems biological analysis

BackgroundUnderstanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC).ResultsThe CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12.ConclusionsOur results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.

Glial activation is moderated by sex in response to amyloidosis but not to tau pathology in mouse models of neurodegenerative diseases

BackgroundIn vivo assessment of neuroinflammation by 18-kDa translocator protein positron-emission-tomography (TSPO-PET) ligands receives growing interest in preclinical and clinical research of neurodegenerative disorders. Higher TSPO-PET binding as a surrogate for microglial activation in females has been reported for cognitively normal humans, but such effects have not yet been evaluated in rodent models of neurodegeneration and their controls. Thus, we aimed to investigate the impact of sex on microglial activation in amyloid and tau mouse models and wild-type controls.MethodsTSPO-PET (18F-GE-180) data of C57Bl/6 (wild-type), AppNL-G-F (β-amyloid model), and P301S (tau model) mice was assessed longitudinally between 2 and 12 months of age. The AppNL-G-F group also underwent longitudinal β-amyloid-PET imaging (Aβ-PET; 18F-florbetaben). PET results were confirmed and validated by immunohistochemical investigation of microglial (Iba-1, CD68), astrocytic (GFAP), and tau (AT8) markers. Findings in cerebral cortex were compared by sex using linear mixed models for PET data and analysis of variance for immunohistochemistry.ResultsWild-type mice showed an increased TSPO-PET signal over time (female +23%, male +4%), with a significant sex × age interaction (T = − 4.171, p < 0.001). The Aβ model AppNL-G-F mice also showed a significant sex × age interaction (T = − 2.953, p = 0.0048), where cortical TSPO-PET values increased by 31% in female AppNL-G-F mice, versus only 6% in the male mice group from 2.5 to 10 months of age. Immunohistochemistry for the microglial markers Iba-1 and CD68 confirmed the TSPO-PET findings in male and female mice aged 10 months. Aβ-PET in the same AppNL-G-F mice indicated no significant sex × age interaction (T = 0.425, p = 0.673). The P301S tau model showed strong cortical increases of TSPO-PET from 2 to 8.5 months of age (female + 32%, male + 36%), without any significant sex × age interaction (T = − 0.671, p = 0.504), and no sex differences in Iba-1, CD68, or AT8 immunohistochemistry.ConclusionFemale mice indicate sex-dependent microglia activation in aging and in response to amyloidosis but not in response to tau pathology. This calls for consideration of sex difference in TSPO-PET studies of microglial activation in mouse models of neurodegeneration and by extension in human studies.

Computed tomography-derived body composition analysis in patients with advanced cancer: clinical utility and future research.

With weight loss increasingly occurring against a background of obesity across a variety of advanced cancers, there has been increasing interest in computed tomography (CT)-derived body composition analysis. Various imaging software packages and thresholds are commonly in use in CT-derived body composition analysis. This review discusses the current research in field of body composition with emphasis on the information required for such measurements to be taken into routine clinical practice. CT is widely used for tumour staging in patients with cancer. Over the last decade, this imaging modality has been exploited to make measurements of body composition. Using a common landmark (L3) several different thresholds have been developed to stratify adipose and muscle tissue areas according to age, sex and BMI and their relationship with survival. A significant relationship between CT-derived body composition and clinical outcomes has been shown in different tumour types and geographical locations. However, there is considerable variation with methods, thresholds and muscle groups used for analysis. Therefore, there would appear to be a need to develop reliable methodology and population-specific reference ranges to guide clinical interpretation and enable routine clinical use. There has been an explosion of clinical research interest in CT-derived body composition analysis. Such body composition analysis provides important host phenotype information which has prognostic value. For CT-derived body composition to be fit for use in routine clinical practice, there is need for universally accepted terminology, software, muscle group selection, prognostic thresholds to standardize such body composition analysis.

Family perceptions of clinical research and the informed consent process in the ICU.

We investigated experiences of families who provide consent for research on behalf of a loved-one hospitalized in intensive care (ICU). Multicentre, qualitative, descriptive study using semi-directive interviews in 3 ICUs. Eligible relatives were aged >18 years, and had provided informed consent for a clinical trial on behalf of a patient hospitalized in ICU. Interviews were conducted from 06/2018 to 06/2019 by a qualified sociologist, recorded and transcribed. Fifteen relatives were interviewed; average age 50.3 ± 15 years. All emphasized their interest in clinical research, seeing it as a duty. Involving their loved-one in research allowed them to find meaning in the events. Participants underlined that trust in caregivers and communication are determinant. The strict regulation of research was perceived as a guarantee of safety. Participants felt they lacked the intellectual capacity and knowledge to question explanations. The greatest fear was not that they might incur a risk for the patient, but rather, that they might deprive the patient of a chance at a cure. Acceptance of research opportunities by relatives on behalf of decisionally-incapacitated patients is underpinned by trust in the physicians and the legislative framework. Communication and the quality of information provided by the caregivers are key.

Preparing pharmacy trainees for a future in research and contributing to the medical literature

AbstractClinical research is a skill that can be honed and cultivated in the right educational environment. Creating experiences to maximize growth and interest in clinical research can occur both during pharmacy school and throughout postgraduate training. The purpose of this “how‐to” guide is to assist pharmacists, as well as their students and residents, with effectively structuring experiences and programs that instill and cultivate a lifelong desire to contribute to the medical literature. The overarching areas of focus are threefold: (1) identifying trainees and mentors, (2) crafting research training experiences, and (3) supporting continued interest and growth in research after completion of the initial experience. Early introduction of a positive research culture in the trainee experience through structured and thoughtful curricula and experiences can maximize learner potential. Several thoughtful steps and recommendations can maximize these experiences and opportunities for learners and new practitioners. Instilling and cultivating a lifelong desire to contribute to the medical literature in pharmacy trainees remains a challenge that is both worthy and necessary to pursue for the sakes of our profession, patients, and trainees.

1778P Clinical research at the time of COVID-19: A passion or a real job?

During Coronavirus pandemic, public opinion has returned to a great deal of interest in clinical research and the key role of researchers. Particularly in Italy, deeply affected by the emergency, people have returned to believe in the work of health professionals and have loudly asked for a profound research effort, a field hitherto suspiciously looked at. Yet, until then, few had worried about nation's big contradictions as the total nonexistence of the profession of the researcher in the National Health System. The only effort in the recent years has been a ministerial reform ”Researchers’ pyramid”, a 10 year working path characterized by a 5 year contract, renewable once and with annual reconfirmation exams, with the final hope of recognition within the national health system. An initiative that has been the subject of strong contradictions. In September 2019, the Italian Group of Clinical Research Coordinators shared an online survey, meant for the Italian biomedical research personnel, to investigate opinions about the reform. The questionnaire was completed by 147 respondents, the majority (53.1%) employed at public research institute or public Hospitals/University/Local Health Company (34.0%).Respondent’s job for the greater part corresponded to a profession included in the “Clinical Research Assistant” (55.1%) and “Clinical Researcher” categories (25.9%). Over half declared to be optimistic regarding the actual benefit of the reform for employment stability. Between “not optimistic respondents”, 50% considers Pyramid a false stabilization path. Concerns were also expressed in relation to the evaluation criteria, considered too exclusive and often not suitable by a third of the interviewed. Many individuals (41.5%) report the poor valorization of personnel and much apprehension was recorded relating to the possibility of extending the reform to other institutes. The reform overall seems an important opportunity for entry level personnel, a watered-down compromise for expert professionals. The fear conveyed from the great majority of the interviewed is that the pyramid is only a trick. When the emergency is over, will institutions finally begin to understand the importance of research? A job, not just a passion.

Frequency of genomic secondary findings among 21,915 eMERGE network participants

PurposeDiscovering an Incidental or Secondary Finding (IF) is a potential result of genomic testing, but little data exists describing types and frequencies of IFs likely to appear in broader clinical populations.MethodsThe Electronic Medical Records and Genomics network phase III (eMERGEIII) developed a CLIA-compliant sequencing panel of 109 genes and 1551 variants of clinical relevance or research interest and deployed this panel at 10 clinical sites. We evaluated medically actionable IFs across 67 genes and 14 SNVs in a diverse cohort of 21,915 participants drawn from a variety of settings (e.g. primary care, biobanks, specialty clinics).ResultsCorrecting for testing indication, we found a 3.02% overall frequency of IFs; 2.54% from 59 genes the American College of Medical Genetics and Genomics recommends for IF return, and 0.48% in other genes, primarily HFE and PALB2. IFs associated with cancer susceptibility were most frequent (1.38%), followed by cardiovascular diseases (0.87%), and lipid disorders (0.50%). After removing HFE, the frequency of IFs and proportion of pathogenic vs. likely pathogenic IFs did not differ in those self-identifying as white vs. others.ConclusionHere we present frequencies and types of medically actionable incidental findings to support informed decision-making by patients, participants, and practitioners engaged in genomic medicine.