tbuckley/cabot-search huggingface dataset:
Network analyses to define chemotherapy toxicity clusters in patients with colorectal cancer (CRC)
Authors: G. Aprile, M. Ramoni PhD, D. Keefe, S. Sonis
Journal: Journal of Clinical Oncology (2007)

9045 Background: CRC patients undergoing CT are likely to experience multiple concurrent toxicities. Rather than appearing singularly, the hypothesis that certain toxicities occur in clusters may suggest a common pathobiology. We used Markov networks (MN), a probabilistic graphical born at the confluence of statistics and artificial intelligence describing the dependency among set of variables, to identify clusters of CT-induced toxicities, to examine how clusters are connected to each other, and how single toxicities are related to a specific cluster. Methods: Using a standardized data collection tool, we retrospectively reviewed electronic medical charts of 300 consecutive CRC pts receiving FOLFOX, FOLFIRI or 5-FU to record baseline demographic and clinical information. Toxicities were recorded using NCI-CTC criteria during the first cycle of CT. Following the standard Bayesian approach, the MN clustering the CT-induced toxicities was learned from the data as the network with the highest posterior probability given the data. Results: The network, in which associations between toxicities are represented as links, identified five strongly-related symptom clusters: a constitutional cluster involving fatigue, anorexia, and weight loss; a gastrointestinal cluster where dehydration was the connector between diarrhea, constipation and bloating on a side and taste nausea and vomiting, taste alteration, fever and chills on the flipside; a dermatological cluster composed by dry skin, HFS, rash and itching and connected with hemorrhage/bleeding and wound complication toxicity. Furthermore, we noticed strong connections between cough, dyspnea and infection, with palpitation and pain and we detected another cluster where depression and anxiety where connected with cystitis. Conclusions: The application of network analyses to define CT-induced toxicity clusters is new. The technique was effective in defining the relationships between individual toxicities associated with cycle 1 therapy. The lack of randomness between the relationships defined by the network provides a strong suggestion that each cluster shares a common pathobiological basis, which may provide an opportunity for intervention. [Table: see text]
Abstract P387: Risk Factors for Neonatal Intensive Care Unit Admission; Project Watch, 2012-2017
Authors: Ksheeraja Sriram, Amna Umer, Candice Hamilton, Collin C John, Christa LILLY
Journal: Circulation (2020)

Background: Neonatal intensive care unit (NICU) admission is often due to specific cardiovascular conditions. Low birthweight, another common reason for NICU admission, is also linked to later cardiovascular risk. Within the past decade, the rate of NICU admissions in the United States has significantly increased. Identification of emerging risk factors for NICU admission will help inform efforts to reduce the number of newborns requiring intensive care. Methods: The objective of this study was to identify risk factors for NICU admission in all infants born in West Virginia (WV), 2012-2017, via Project WATCH. Fifteen exposure variables including demographics, maternal and infant characteristics, were included in multivariable logistic regression analyses, stratified by preterm and term births. Results: Of 120,894 neonates, 6,393 (5.3%) were admitted to NICU. Among preterm infants (Table 1), predictors included male sex (OR: 1.11), insurance status (OR: 1.29), APGAR scores less than or equal to 3 (OR: 2.57), maternal diabetes (OR: 1.68 and 2.01), residence outside WV (OR: 1.27), intrauterine substance exposure (OR: 1.94), congenital abnormalities (OR: 2.58), and low birthweight (OR: 1.73 and 6.64). Risk factors in term infants included all factors identified for preterm infants, as well as maternal smoking, maternal age, and number of previous pregnancies. Conclusions: In addition to infant characteristics predictive of NICU admission (e.g., birthweight and APGAR score), socioeconomic factors (e.g., insurance status and rurality) and preventable risk factors (e.g., maternal smoking and substance use) provide an opportunity for intervention during pregnancy, with the goal to decrease the number of newborns requiring intensive care.
Abstract P524: Protein Biomarkers Mediate the Association Between Diet Quality and Incident Cardiovascular Disease and All-cause Mortality
Authors: Jiantao Ma, Sophia Lu, Jennifer E Ho, Chen Yao, Tianxiao Huan, Daniel Levy
Journal: Circulation (2020)

Objectives: Molecular mechanism underlying diet and cardiovascular disease (CVD) remains unclear. We aimed to examine the association between habitual diet and protein biomarkers and test whether these proteins mediate the association between diet and incident CVD and mortality. Methods: We included 6,596 participants (mean age 50 years; 54% women) of the Framingham Heart Study. A panel of 71 CVD-related circulating protein biomarkers were measured using a modified Sandwich ELISA method, multiplexed on a Luminex xMAP platform. We used three diet scores to represent overall diet quality: Alternate Health Eating Index (AHEI), a Mediterranean-style Diet Score (MDS), and the Dietary Approaches to Stop Hypertension (DASH). Primary outcomes were incident CVD (coronary heart disease, myocardial infarction, stroke, and others), CVD death, and all-cause mortality with median follow-up 14 years. Results: After adjusting for sex, age, and energy intake, 40 proteins were associated with at least one diet score at P &lt;0.0007 (Bonferroni correction for 71 proteins) and with P &lt;0.05 for the other diet scores. Additional adjustments for smoking status, physical activity level, and alcohol intake did not materially change these associations. Further adjustment for BMI attenuated association; however, the association remained significant for 36 of 40 proteins (P &lt;0.001 with at least one diet score). Pathway analysis using coding genes of the 36 diet-associated proteins showed, after Bonferroni correction, enrichment of 157 Gene Ontology (GO) biological processes such as regulation of immune response (GO:0050776; P=0.003) and regulation of vasoconstriction (GO:0019229; P=0.03). All three diet scores were significantly associated with incident CVD and all-cause mortality. Among the 36 diet-associated proteins, four proteins (GDF15, UCMGP, ADM, and sICAM1) significantly mediated the association between at least one diet score and all-cause mortality at P &lt;0.001 and with P &lt;0.05 for other diet scores, after adjustment for covariates including BMI and cardiometabolic risk factors at baseline. GDF15 significantly mediated the association of diet scores and incident CVD (fatal and nonfatal). The proportion of mediation by GDF15 ranged from 11% to 21% for diet scores and incident CVD and from 30% to 34% for diet scores and all-cause mortality. In addition, we observed that nine proteins were nominally significant in mediation analyses for incident CVD or all-cause mortality (0.001&lt; P &lt;0.05). Conclusions: The present study demonstrates that diet quality is associated with 36 of 71 selected CVD-related circulating protein markers. Our study sheds light into potential pathways underlying the association of diet and CVD and mortality.
Management of dependent use of illicit opioids
Authors: Caroline Mitchell, Neil Dolan, Kenneth M Dürsteler
Journal: BMJ (2020)

### What you need to know

Use of illicit opioids, most commonly heroin, has a wide ranging impact on individuals and society.1 It may lead to dependence, which is best conceptualised using a “chronic disease” model: effective treatments are available, but illness is often characterised by relapses, remissions, and risk of premature death.23

Across Europe, four trends are noteworthy: a decline in the use of intravenous heroin, a rise in the use of high potency synthetic opioids (for example, fentanyl), a rise in opioid related deaths, and an increase in the number of long term opioid users aged over 40.4 The widely reported “epidemic” of opioid associated deaths in the US and Canada is also of global concern and has been attributed to under-regulated medical prescribing of high potency synthetic opioids and a growth in internet supply chains.567 Concurrent use of other substances, for example, alcohol, cocaine, benzodiazepines, neuropathic agents, and novel drugs such as “spice,” increases the risk of adverse outcomes of opioid use in all settings.8910

In this review we describe an evidence based collaborative approach to caring for people who are dependent on illicit opioids (heroin or synthetic opioids that have been obtained illegally, against custom, and used harmfully) and …
The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China
Authors: Lei Wang, Yong-hua Gao, Li-Li Lou, Guo-Jun Zhang
Journal: European Respiratory Journal (2020)

<b>SARS-CoV-2 can be transmitted from person to person, with infection ranging from mild disease to severe pneumonia and radiological abnormalities on chest CT for most patients, improving after RT-PCR conversion</b>http://bit.ly/2TiMSck
THE NATURAL HISTORY OF SERUM IRON INDICES FOR HFE-ASSOCIATED C282Y HOMOZYGOTES OVER 55 YEARS OF AGE
Authors: Lyle C Gurrin, Nicholas Csborne, Clare C Constantine, Christine E McLaren, Dallas English, Doroto M Gertig, Martin Delatycki, Melissa Southey, John L Hopper, Graham Giles, Gregory J Anderson, John K Olynyk, Lawrie W Powell, Katrina J Allen
Journal: Hepatology (2008)
Abstract P560: Serum Non-esterified Fatty Acids and Risk of Incident Stroke in Older Adults: The Cardiovascular Health Study
Authors: Neil K Huang, Nirupa R Matthan, Mary L Biggs, W T Longstreth, David S Siscovick, Luc Djousse, Kenneth J Mukamal, Alice H Lichtenstein
Journal: Circulation (2020)

Introduction: Serum non-esterified fatty acids (NEFAs) have been linked to both local and systemic inflammation and are higher in individuals with obesity, diabetes, cardiovascular disease, and ischemic stroke risk. Significant associations between total plasma NEFA concentrations and incident ischemic stroke have been reported in some but not all prospective studies. Given the functional and structural diversity among circulating NEFA, the associations of individual or clusters of circulating NEFAs may provide additional insight into their relationship with incident stroke. Hypothesis: Fasting serum n-3 NEFAs are inversely associated, and saturated and trans NEFAs are positively associated with incident stroke. Methods: We analyzed the incidence of stroke among Cardiovascular Health Study (CHS) participants who were free of stroke in 1996-1997 and underwent fasting NEFA profile measurement. At baseline, mean age was 77.8±4.5, body mass index was 26.7±4.4 and 61% were female. A total of 38 individual NEFAs in 5 classes (saturated, monounsaturated, polyunsaturated n-6, polyunsaturated n-3 and trans NEFAs) were measured using gas chromatography. Cox regression was used to evaluate the association of individual NEFA species with incident stroke, adjusting for: age, sex, race, and field center (model 1); model 1 covariates plus smoking, education, physical activity, alcohol consumption, eGFR, BMI, aspirin use, waist circumference, hypertension, prevalent diabetes, and cholesterol (model 2). Results: A total of 338 cases of incident stroke occurred during median follow-up of 10.5 years. In the fully adjusted model, trans -palmitoleic acid was inversely associated with incident stroke (HR per 1 mol% of NEFA composition: 0.03 [95% CI: 0.00 to 0.77], P &lt;0.03). Serum docosahexaenoic acid levels were associated with lower risk of incident stroke (HR: 0.63 [95% CI: 0.40 to 1.00], P &lt;0.05). Total n-3 fatty acids (HR: 0.78 [95% CI: 0.63 to 0.97]) and docosapentaenoic acid (HR: 0.12 [95% CI: 0.02 to 0.88]) were each associated with lower risk of incident stroke only in model 1. No significant association of saturated NEFAs with incidence of stroke was observed. Conclusion: Among fasting serum NEFA, docosahexaenoic acid and trans -palmitoleic acid were inversely associated with incident stroke, suggesting that these fatty acids may protect older adults from stroke.
Abstract P539: The Association Between Social Isolation and Metabolic Syndrome in Japanese Adults: The Tohoku Medical Megabank Project
Authors: Yuka Kotozaki, Kozo Tanno, Kotaro Otsuka, Ryouhei Sasaki, Nobuyuki Takanashi, Takahiro Mikami, Tomohiro Nakamura, Atsushi Hozawa, Koichi Asahi, Mamoru Satoh, Atsushi Shimizu, Yasushi Ishigaki, Kiyomi Sakata, Makoto Sasaki
Journal: Circulation (2020)

Metabolic syndrome (MetS) and its components are well established as risk factors for cardiovascular disease (CVD). On the other hand, it has also been reported that social isolation is associated with an increased risk of CVD. However, the relationship between social isolation and MetS and its components is not clear. Thus, the purpose of this study is to investigate the association between social isolation and the number of MetS components in Japanese adults. Participants were 28,917 individuals (male/female = 10,226/18,691, age = 59.9±11.6 years) from the Iwate area of the Tohoku Medical Megabank Organization Community-based cohort study (TMM CommCohort study). They had no history of coronary heart disease or stroke. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6). The participants were classified into two groups, the social isolation group and the non-isolation group, based on a cutoff point of 11/12 on the LSNS-6. An assessment of MetS used the criteria defined by the Japanese societies’ committee. The multivariate-adjusted odds ratios (95% confidence intervals) [AORs (95% CIs)] of the social isolation group versus the non-isolation group were calculated using ordered logistic analyses and compared to the number of MetS components. We used gender, age, education, current smoker, current alcohol drinker, total physical activity, current job status, and depression as covariates. AORs (95% CIs) of social isolation against non-isolation were 1.02 (0.95-1.09) for one component of MetS, 1.09 (1.01-1.19) for two components of MetS, and 1.16 (1.06-1.28) for three or more components of MetS, when compared to 0 component of MetS. In conclusion, Japanese adults who experience social isolation might have a greater number of MetS components.
Effectiveness of the Extension for Community Health Outcomes Model as Applied to Primary Care for Autism
Authors: Micah O. Mazurek, Robert A. Parker, James Chan, Karen Kuhlthau, Kristin Sohl
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> The Extension for Community Health Outcomes (ECHO) model is a widely adopted technology-based model for training primary care physicians and practitioners (PCPs) to care for patients with complex conditions. Despite its popularity, to our knowledge, direct effects of ECHO on clinical practice have not been tested in a large-scale study. <h3>Objective</h3> To test the effectiveness of the ECHO model as applied to primary care for autism and whether it resulted in improved clinical practice, knowledge, and self-efficacy regarding autism screening and comorbidity management. <h3>Design, Setting, and Participants</h3> Primary care physicians and practitioners were recruited to participate in a 6-month ECHO Autism program delivered by 1 of 10 academic medical center sites. A sequential, staggered rollout of ECHO Autism was delivered to 5 cohorts of participants (15 per site; 2 sites per cohort). Sites were randomized after recruitment to cohort/start time. Cohorts launched every 3 months. The ECHO Autism program used videoconferencing technology to connect community-based PCPs with interdisciplinary expert teams at academic medical centers. There were 148 participants (PCPs [family practice physicians, pediatricians, nurse practitioners, and physician assistants] providing outpatient services to underserved children) studied between December 2016 and November 2018. <h3>Interventions</h3> The 6-month ECHO Autism program included twelve 2-hour sessions connecting PCP participants with an interdisciplinary expert team. Sessions included didactics, case-based learning, guided practice, and discussion. <h3>Main Outcomes and Measures</h3> Coprimary outcomes were autism screening practices and comorbidity management (assessed by medical record review). Secondary outcomes were knowledge (assessed by direct testing) and self-efficacy (assessed by self-report survey). Assessments were conducted at baseline, mid-ECHO, post-ECHO, and follow-up (3 months after ECHO). <h3>Results</h3> Ten sites were randomized to 1 of 5 cohorts. Participants were 82% female (n = 108), 76% white (n = 100), and 6% Hispanic or Latino (n = 8); the median age was 46 years (interquartile range, 37-55 years). Significant changes in autism screening and treatment of comorbidities in children with autism were not observed. Participants demonstrated significant improvements in knowledge (9%; 95% CI, 4-13;<i>P</i> &lt; .001) and self-efficacy (29%; 95% CI, 25-32;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The ECHO model was developed to increase access to high-quality health care for underserved patients with complex conditions. Study results provide support for the model in improving clinician knowledge and confidence but little support for achieving practice change. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03677089
Burnout and Emotional Well-Being among Nephrology Fellows: A National Online Survey
Authors: Varun Agrawal, Laura Plantinga, Khaled Abdel-Kader, Kurtis Pivert, Anthony Provenzano, Sandeep Soman, Michael J. Choi, Bernard G. Jaar
Journal: Journal of the American Society of Nephrology (2020)

Physician burnout and emotional distress are associated with work dissatisfaction and provision of suboptimal patient care. Little is known about burnout among nephrology fellows.Validated items on burnout, depressive symptoms, and well being were included in the American Society of Nephrology annual survey emailed to US nephrology fellows in May to June 2018. Burnout was defined as an affirmative response to two single-item questions of experiencing emotional exhaustion or depersonalization.Responses from 347 of 808 eligible first- and second-year adult nephrology fellows were examined (response rate=42.9%). Most fellows were aged 30-34 years (56.8%), male (62.0%), married or partnered (72.6%), international medical graduates (62.5%), and pursuing a clinical nephrology fellowship (87.0%). Emotional exhaustion and depersonalization were reported by 28.0% and 14.4% of the fellows, respectively, with an overall burnout prevalence of 30.0%. Most fellows indicated having strong program leadership (75.2%), positive work-life balance (69.2%), presence of social support (89.3%), and career satisfaction (73.2%); 44.7% reported a disruptive work environment and 35.4% reported depressive symptoms. Multivariable logistic regression revealed a statistically significant association between female gender (odds ratio [OR], 1.90; 95% confidence interval [95% CI], 1.09 to 3.32), poor work-life balance (OR, 3.97; 95% CI, 2.22 to 7.07), or a disruptive work environment (OR, 2.63; 95% CI, 1.48 to 4.66) and burnout.About one third of US nephrology fellows surveyed reported experiencing burnout and depressive symptoms. Further exploration of burnout-especially that reported by female physicians, as well as burnout associated with poor work-life balance or a disruptive work environment-is warranted to develop targeted efforts that may enhance the educational experience and emotional well being of nephrology fellows.
Abstract 52: Plasma Metabolomic Signatures of the American Heart Association Diet Score: Findings From the Boston Puerto Rican Health Study
Authors: Danielle E Haslam, Jun Li, Liming Liang, Clary Clish, Alice H Lichtenstein, Chao-Qiang Lai, Jose M ORDOVAS, Joann E Manson, Clemens Wittenbecher, Frank B Hu, Qibin Qi, Katherine L Tucker, Shilpa N Bhupathiraju
Journal: Circulation (2020)

Introduction: Puerto Rican adults living on the US mainland tend to have poor quality diets and adverse cardiometabolic risk. Plasma metabolomic signatures reflect dietary intakes and variability in metabolic response to diet. Hypothesis: A plasma metabolomic signature reflecting adherence to the American Heart Association (AHA) dietary guidelines will be associated with cardiometabolic risk. Methods: We used LC/MS to measure plasma metabolites (&gt;700) among Boston Puerto Rican Health Study participants, aged 45-75 years, without (n=252) and with (n=254) type 2 diabetes (T2D). We calculated a modified version of a previously validated AHA diet score (AHA-DS), which included variety and amounts of fruits/vegetables, whole grains, fish, saturated fat, trans fat, sodium, and added sugars. We used elastic net regression to identify a metabolomic signature that associated with higher adherence to the AHA-DS among those without T2D (training set) and replicated the associations among those with T2D (testing set). A metabolomic score was calculated as the weighted sum of the diet associated metabolites. We used general linear models to determine the cross-sectional associations between the AHA-DS, metabolomic score, and cardiometabolic risk factors. Results: A diet-associated metabolomic signature with 58 metabolites, primarily lipids and amino acids, was identified. This metabolomic score correlated moderately with the AHA-DS among those with and without T2D (r=0.42-0.46, P &lt;5.7x10 -12 ). In all participants (n=506), the metabolomic score, but not the AHA-DS, was significantly associated with higher HDL-C and LDL-C concentrations, and lower waist circumference ( P &lt;0.004; Table 1). No associations were observed for triglyceride concentrations, glycemia measures, or blood pressure. Conclusions: In individuals of Puerto Rican descent, we identified a metabolomic signature that reflected adherence and metabolic response to the AHA dietary guidelines and that associated with cardiometabolic risk factors.
Substantial and sustained improvement of serrated polyp detection after a simple educational intervention: results from a prospective controlled trial
Authors: Arne G C Bleijenberg, Monique E van Leerdam, Marloes Bargeman, Jan Jacob Koornstra, Yasmijn J van Herwaarden, Manon CW Spaander, Silvia Sanduleanu, Barbara A J Bastiaansen, Erik J Schoon, Niels van Lelyveld, Evelien Dekker, Joep E G IJspeert
Journal: Gut (2020)

Serrated polyps (SPs) are an important cause of postcolonoscopy colorectal cancers (PCCRCs), which is likely the result of suboptimal SP detection during colonoscopy. We assessed the long-term effect of a simple educational intervention focusing on optimising SP detection.An educational intervention, consisting of two 45 min training sessions (held 3 years apart) on serrated polyp detection, was given to endoscopists from 9 Dutch hospitals. Hundred randomly selected and untrained endoscopists from other hospitals were selected as control group. Our primary outcome measure was the proximal SP detection rate (PSPDR) in trained versus untrained endoscopists who participated in our faecal immunochemical test (FIT)-based population screening programme.Seventeen trained and 100 untrained endoscopists were included, who performed 11 305 and 51 039 colonoscopies, respectively. At baseline, PSPDR was equal between the groups (9.3% vs 9.3%). After training, the PSPDR of trained endoscopists gradually increased to 15.6% in 2018. This was significantly higher than the PSPDR of untrained endoscopists, which remained stable around 10% (p=0.018). All below-average (ie, PSPDR ≤6%) endoscopists at baseline improved their PSPDR after training session 1, as did 57% of endoscopists with average PSPDR (6%-12%) at baseline. The second training session further improved the PSPDR in 44% of endoscopists with average PSPDR after the first training.A simple educational intervention was associated with substantial long-term improvement of PSPDR in a prospective controlled trial within FIT-based population screening. Widespread implementation of such interventions might be an easy way to improve SP detection, which may ultimately result in fewer PCCRCs.NCT03902899.