tbuckley/cabot-search huggingface dataset:
The Y Chromosome Takes the Field to Modify BMPR2 Expression
Authors: Andrea L. Frump, Tim Lahm
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

injury, the severity of the brain injury, levels of consciousness, and the time after injury (12, 13).Traumatic brain injury is a heterogeneous condition and has been reported to contribute to Alzheimer's disease and frontotemporal dementia independently of bacterial infection (14, 15).These could be confounding factors, and future studies will ideally be undertaken in critically ill patients not affected by brain injury.Careful serial assessment of cognitive function and neurological status before and also repeatedly during and after intensive care treatment and pneumonia will be critical to correlate bacterial infection with Ab and tau oligomer neurotoxicity.Although it may seem that this study raises more questions than answers, it also shows how much is yet unknown.A more detailed assessment of the nature and aggregation status of Ab and tau proteins beyond A11 and T22 reactivity is crucial and should reveal additional insights about these biomarker dynamics in critically ill patients.Longitudinal biomarker assessment in large cohorts and additional in vitro toxicity studies would address whether nosocomial pneumonia is indeed a risk factor for cognitive symptoms related to post-intensive care syndrome.Although Lin and colleagues raise a provocative hypothesis, if bacterial infection is indeed related to Alzheimer's disease-like biomarker changes and symptoms in post-intensive care syndrome, interventions to block or reverse these processes could be of great benefit to these patients (5).
SKI controls MDS-associated chronic TGF-β signaling, aberrant splicing, and stem cell fitness
Authors: David E. Muench, Kyle Ferchen, Chinavenmeni S. Velu, Kith Pradhan, Kashish Chetal, Xiaoting Chen, Matthew T. Weirauch, Clemencia Colmenares, Amit Verma, Nathan Salomonis, H. Leighton Grimes
Journal: Blood (2018)
A Three-Arm Randomized Trial of Different Renal Denervation Devices and Techniques in Patients With Resistant Hypertension (RADIOSOUND-HTN)
Authors: Karl Fengler, Karl-Philipp Rommel, Stephan Blazek, Christian Besler, Philipp Hartung, Maximilian von Roeder, Martin Petzold, Sindy Winkler, Robert Höllriegel, Steffen Desch, Holger Thiele, Philipp Lurz
Journal: Circulation (2019)

Both radiofrequency and ultrasound endovascular renal sympathetic denervation (RDN) have proven clinical efficacy for the treatment of hypertension. We performed a head-to-head comparison of these technologies.Patients with resistant hypertension were randomly assigned in a 1:1:1 manner to receive either treatment with (1) radiofrequency RDN of the main renal arteries; (2) radiofrequency RDN of the main renal arteries, side branches, and accessories; or (3) an endovascular ultrasound-based RDN of the main renal artery. The primary end point was change in systolic daytime ambulatory blood pressure at 3 months.Between June 2015 and June 2018, 120 patients were enrolled (mean age, 64±9 years±SD; mean daytime blood pressure, 153/86±12/13 mm Hg). Of these, 39 were randomly assigned to radiofrequency main renal artery ablation, 39 to combined radiofrequency ablation of the main artery and branches, and 42 to ultrasound-based treatment. Baseline daytime blood pressure, clinical characteristics, and treatment were well balanced between the groups. At 3 months, systolic daytime ambulatory blood pressure decreased by 9.5±12.3 mm Hg ( P<0.001) in the whole cohort. Although blood pressure was significantly more reduced in the ultrasound ablation group than in the radiofrequency ablation group of the main renal artery (-13.2±13.7 versus -6.5±10.3 mm Hg; mean difference, -6.7 mm Hg; global P=0.038 by ANOVA, adjusted P=0.043), no significant difference was found between the radiofrequency ablation groups (-8.3±11.7 mm Hg for additional side branch ablation; mean difference, -1.8 mm Hg; adjusted P>0.99). Similarly, the blood pressure reduction was not found to be significantly different between the ultrasound and the side branch ablation groups. Frequencies of blood pressure response ≥5 mm Hg were not significantly different (global P=0.77).In patients with resistant hypertension, endovascular ultrasound-based RDN was found to be superior to radiofrequency ablation of the main renal arteries only, whereas a combined approach of radiofrequency ablation of the main arteries, accessories, and side branches was not.URL: https://www.clinicaltrials.gov . Unique identifier: NCT02920034.
Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990–2016
Authors: Ibrahim A Khalil, Christopher Troeger, Brigette F Blacker, Puja C Rao, Alexandria Brown, Deborah E Atherly, Thomas G Brewer, Cyril M Engmann, Eric R Houpt, Gagandeep Kang, Karen L Kotloff, Myron M Levine, Stephen P Luby, Calman A MacLennan, William K Pan, Patricia B Pavlinac, James A Platts-Mills, Firdausi Qadri, Mark S Riddle, Edward T Ryan, David A Shoultz, A Duncan Steele, Judd L Walson, John W Sanders, Ali H Mokdad, Christopher J L Murray, Simon I Hay, Robert C Reiner
Journal: The Lancet Infectious Diseases (2018)

BackgroundShigella and enterotoxigenic Escherichia coli (ETEC) are bacterial pathogens that are frequently associated with diarrhoeal disease, and are a significant cause of mortality and morbidity worldwide. The Global Burden of Diseases, Injuries, and Risk Factors study 2016 (GBD 2016) is a systematic, scientific effort to quantify the morbidity and mortality due to over 300 causes of death and disability. We aimed to analyse the global burden of shigella and ETEC diarrhoea according to age, sex, geography, and year from 1990 to 2016.MethodsWe modelled shigella and ETEC-related mortality using a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We used a compartmental meta-regression tool to model the incidence of shigella and ETEC, which enforces an association between incidence, prevalence, and remission on the basis of scientific literature, population representative surveys, and health-care data. We calculated 95% uncertainty intervals (UIs) for the point estimates.FindingsShigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212 438 deaths (95% UI 136 979–326 913) and about 13·2% (9·2–17·4) of all diarrhoea deaths. Shigella was responsible for 63 713 deaths (41 191–93 611) among children younger than 5 years and was frequently associated with diarrhoea across all adult age groups, increasing in elderly people, with broad geographical distribution. ETEC was the eighth leading cause of diarrhoea mortality in 2016 among all age groups, accounting for 51 186 deaths (26 757–83 064) and about 3·2% (1·8–4·7) of diarrhoea deaths. ETEC was responsible for about 4·2% (2·2–6·8) of diarrhoea deaths in children younger than 5 years.InterpretationThe health burden of bacterial diarrhoeal pathogens is difficult to estimate. Despite existing prevention and treatment options, they remain a major cause of morbidity and mortality globally. Additional emphasis by public health officials is needed on a reduction in disease due to shigella and ETEC to reduce disease burden.FundingBill & Melinda Gates Foundation.
Symptom Burden in Extensive Disease Small Cell Lung Cancer (ED-SCLC): A prospective, observational study in U.S. community practices.
Authors: Donald A. Richards, Maen A. Hussein, Steven L. McCune, Brian Kent Ulrich, Mark D. Danese, Michelle L. Gleeson, Deborah P. Lubeck, Pranav Abraham, Jenine Sanzari, Beata Korytowsky, Lee Steven Schwartzberg
Journal: Journal of Clinical Oncology (2018)

196 Background: There is a paucity of data describing the effect of treatment on symptom burden and health status for patients with ED-SCLC receiving care in US community oncology centers. This study explores ED-SCLC patient-reported outcomes independently for either first-line (1L), second-line (2L) or third-line (3L) therapy. Methods: CA209-118 is a prospective observational study of adult patients with lung cancer, including patients with ED-SCLC, in 70 US community practices enrolled between 2014-2017. Participants completed the Lung Cancer Symptom Scale (LCSS) and Euro-QoL 5-D (EQ-5D) utility index and visual analog scale (VAS) at the start of 1L, 2L, or 3L treatment and at follow-up visits. The LCSS is summarized in 3 scales: LCSS total scale which ranges from 0 – 100, average symptom burden scale (ASBI) ranging from 0 – 100, and a three-item global scale (3-IGI) ranging from 0 – 300 (lower scores reflect reduced burden). The EQ-5D scale is a preference based measure of health status with higher scores reflecting better quality and ranges from 0 to 1.0 (index) or 0 – 100 (VAS). LCSS and EQ-5D values at 60 days were predicted in a repeated measures model for patients having a score at baseline and at least 1 follow-up. Results: The mean LCSS and EQ-5D scores at the start of each line of therapy and predicted 60 day change are presented in the table . 60-day improvement was observed only for appetite and cough in 1L. A slight declining trend was seen in 2L and 3L. Conclusions: Patients with ED-SCLC treated in the community reported a high symptom burden at the start of each line of therapy which did not diminish throughout 60 days of treatment. [Table: see text]
Impact of novel chronic lymphocytic leukemia drugs on public spending.
Authors: Elena Mow, James Keech, Rohini Naipaul, Jaclyn Marie Beca, Scott Gavura, C. Tom Kouroukis
Journal: Journal of Clinical Oncology (2018)

103 Title: Impact Of Novel Chronic Lymphocytic Leukemia Drugs On Public Spending Background: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy that mainly affects the elderly. Over the past five years, the treatment pathway for CLL has dramatically changed with the emergence of multiple novel agents. In Ontario, Canada, the Ontario Drug Benefit (ODB) program and the New Drug Funding Program (NDFP) primarily provide public coverage for CLL drugs. Given advances in treatment, we evaluated utilization trends for publicly-funded CLL drugs over a five year period (fiscal years 2012/13 to 2016/17). Methods: Drugs with primary CLL indications funded under the two public funding programs (i.e., ODB and NDFP) by 16/17 were included (n = 6). Claims and costs data were obtained from the Institute for Clinical Evaluative Sciences and Cancer Care Ontario‘s datasets. Results: Over five years, expenditures on CLL drugs have increased approximately ten-fold (1000 percent), reaching nearly CAD 43 million (i.e., USD 32.8 million) in 16/17. In the front-line setting, spending on rituximab remained consistent over the five years. Spending on single agent bendamustine decreased with the introduction of obinutuzumab which became the main cost driver by 16/17. In the previously-treated CLL population, ibrutinib has dominated expenditures since it was funded in July 2015. By 16/17, ibrutinib accounted for approximately ninety eight percent of spending in the previously-treated population. Conclusions: In the past five years, public spending on CLL drugs increased rapidly and substantially with the introduction of four novel agents, and may continue to evolve as Canadian provinces consider funding additional indications or newer agents. These findings warrant exploring whether the incremental spending is providing survival benefit or improvement in patients’ quality of life in a real-world setting. Declaration of funding: None
Lessons from Reporting National Performance Measures in a Regional Setting: Washington State Community Cancer Care Report.
Authors: Laura Elizabeth Panattoni, Catherine R. Fedorenko, Karma L. Kreizenbeck, Qin Sun, Li Li, Gary H. Lyman, Scott David Ramsey
Journal: Journal of Clinical Oncology (2018)

105 Background: While many quality metrics are generated and reported at a national level, regionally reported metrics may be more meaningful to stakeholders and more amenable to locally-generated interventions aimed at improving quality. We present the lessons learned from adapting national performance reporting standards to our regional setting. Methods: We linked 2014-2016 Washington State cancer registry records with Medicare and commercial insurance claims, capturing about 70% of the state’s cancer patients. A consortium of payers, oncology providers, and patients selected metrics from national initiatives (QOPI, MACRA, OCM, and the Choosing Wisely Campaign). We then searched the National Quality Forum and the National Quality Measures Clearinghouse for published specifications on those metrics. If none were available or there was a lack of consensus, we constructed algorithms with clinical and technical expert review. We calculated clinic-level risk standardized rates (RSRs) using hierarchical regression modeling to adjust for variation in clinic size and constructed quality composites. Results: We generated 13 quality metrics for 36,900 cancer patients cared for at 27 clinics. Our adaptation of national performance measures and implications include: 1) Many treatment process measures had too few numbers to individually report annually requiring us to group quality metrics and cancer types, and report over a three year period. 2) Although we were able to include tumor characteristics (e.g. AJCC stage) from registry records, risk adjustment was challenged by limitations in the number of risk adjustors due to the smaller number of patients. 3) After applying the hierarchical models, risk adjustment had minimal effect on clinic rankings. 4) The small number of clinics and limited range of clinic RSRs were more accurately captured by a quality composite that reflected clinic level differences to the regional average rather than national quintile groupings. Conclusions: Refinement of national metrics is necessary for public reporting in a regional setting. Further methodological development is critical for robust reporting and applications to value based purchasing.
Clinical work intensity among medical oncologists.
Authors: Matthew F. Hudson, Mark Allen O'Rourke, Dawn W. Blackhurst, Jennifer Caldwell, Regina A. Franco, Rebecca Russ-Sellers, Ronnie Horner
Journal: Journal of Clinical Oncology (2018)

118 Background: Oncology faces workforce shortages and increasing stress. Oncology provider well-being and resilience are mediated by organizational factors through clinical work intensity. Clinical work intensity (CWI) is the level of requisite technical skill, physical and mental effort and clinical judgement necessary, plus care provision-associated stress. Suboptimal clinical work intensity may result from unfavorable practice organizational factors preceding burnout. This pilot study assess CWI experienced by medical oncologists and oncologic advanced practice registered nurses (APRNs)/nurse practitioners as a prelude to a study of provider resilience. Methods: Investigators solicited seventeen medical oncologists-12 physicians and 5 nurse practitioners-from five oncology clinics in the Northwest, Midwest, and Southern regions of the United States Providers reported on level of work intensity associated with 339 patient visits occurring over an 8 week period where for each provider 5 visits were randomly selected from each of 4 randomly selected clinic days. Intensity was measured by the NASA-Task Load Index that assesses 6 dimensions (subscales) with additional questions measuring stress and visit satisfaction. Results: Compared to medical oncologists, APRNs reported a higher work intensity score on average (38.6 vs. 32.9; p &lt; 0.0064), and higher scores on the frustration subscale (36.5 vs. 21.5; p &lt; 0.0001). APRNs also scored higher on stress (27.8 vs. 22.2; p &lt; 0.048), and scored lower on provider-perceived satisfaction with the visit (73.0 vs. 81.1; p &lt; 0.0001). There was no difference between oncologists and nurse practitioners on the other dimensions, including mental, time, and physical demand, and effort. Conclusions: Oncologic APRNs may experience greater work intensity than medical oncologists. Future research will consider whether APRN work intensity scores reflect different or disproportionate challenges owing to scope of practice, workload, or administrative responsibilities, and determine those dimensions of higher work intensity that portend provider burnout. The goal is to identify strategies optimizing work intensity among oncology providers, mitigating provider burnout and enhancing the practice environment.
Tracking the clinical experience of women with metastatic breast cancer at an academic cancer center.
Authors: Stacey A. Ingram, Courtney Williams, Aidan Gilbert, Stevie Nappoe, Kelly Kenzik, Andres Azuero, Stephen T. Mennemeyer, Ryan David Nipp, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2018)

93 Background: Time-driven activity-based costing (TDABC) can be used by health systems to identify inefficiencies and improve the patient experience in clinical encounters. This quality improvement project utilized a Plan, Do, Study, Act (PDSA) cycle to evaluate routine clinic-based care for women with metastatic breast cancer (MBC). Methods: A project plan was developed to directly observe the time spent by MBC patients in clinic (Plan). Patient clinical encounters could include a physician visit along with scans, infusion, and/or labs. We then created process maps of typical patient clinical experiences (Do). Next, we tabulated times (mean, standard deviation [SD]) that patients spent in waiting areas and with each clinical team member (physician, fellow, nurse practitioner, registered nurse, medical assistant, chaplain, social worker, pharmacist, navigator) to identify care inefficiencies (Study). Lastly, we discussed results with providers and identified and implemented strategies for improving efficiency (Act). Results: We directly observed clinic visits (n = 33) for MBC patients from November 2016 to June 2017. On average, patients spent 219 minutes (SD 108) at clinic visits including 71 minutes (SD 45) spent with clinical team members and 85 minutes (SD 43) spent in waiting areas. We identified several opportunities for efficiency improvement, including the delay prior to rooming by medical assistants (n = 31; mean 22, SD 20 minutes), delays with port lab draws in infusion (n = 5; mean 22, SD 13 minutes), and delays awaiting drug from pharmacy (n = 22; mean 15, SD 29 minutes). To improve efficiency, we implemented strategies including having a dedicated infusion nurse assigned to draw labs from patient ports and modifications to medical assistants’ workflow. Conclusions: In this PDSA cycle, we found that patients spend a substantial amount of time at clinic visits, and the majority of this time is spent in waiting areas. Our use of process mapping and evaluation of time spent receiving care identified important opportunities for improving care delivery and efficiency for patients with MBC.
Abstract P081: Psychosocial Resources Are Protective of Diabetes Among African Americans in the Jackson Heart Study
Authors: LáShauntá Glover, Alain Bertoni, Sherita Hill-Golden, Peter Baltrus, Yuan-I Min, Mercedes Carnethon, Herman Taylor, Mario Sims
Journal: Circulation (2018)

Introduction: African Americans (AAs) have among the highest prevalence of type 2 diabetes in the U.S. Research has shown that positive affect and supportive networks are associated with better health outcomes and may improve regulation of physiological processes. We examined the extent to which psychosocial resources were protective of diabetes outcomes among a sample of 5,306 AAs. Hypothesis: Psychosocial resource measures are inversely associated with prediabetes and diabetes [defined by hemoglobin (Hb)A1c categories] and prevalent diabetes (defined by self-report diabetes status and medication use). Methods: Using data from the Jackson Heart Study (JHS), we evaluated the cross-sectional associations of four psychosocial-resource indicators (social support, optimism, religiosity, social networks) with two diabetes outcomes [1) HbA1c categories: normal (HbA1c ≤ 5.7%), at risk/pre-diabetic (5.7% &lt; HbA1c &lt; 6.5%), diabetic (HbA1c ≥ 6.5%) and 2) prevalent diabetes (vs. no diabetes)]. For each psychosocial-resource measure, we created high vs. low categories (median split) and continuous standard deviation (SD) units. Associations with HbA1c categories were examined using multinomial logistic regression to estimate odds ratios (OR 95% confidence interval-CI) of pre-diabetes (vs. normal) and diabetes (vs. normal). Associations with prevalent diabetes were examined using Poisson regression to estimate prevalence ratios (PR 95% CI) of diabetes (vs. no diabetes). Models adjusted for demographics, SES, waist circumference, health behaviors, and depression. Results: Participants with diabetes reported fewer psychosocial resources than those with pre-diabetes and normal HbA1c ( p &lt;0.01). After full adjustment, 1-SD unit increase in social support was associated with an 11% lower odds of pre-diabetes (vs. normal HbA1c) (OR 0.89, 95% CI 0.81-0.99). High (vs. low) religiosity was associated with an increased odds of diabetes (vs. normal Hba1c) (OR 1.29, 95% CI 1.01-1.64) after full adjustment. Optimism and social networks were only associated with lower diabetes prevalence after adjustment for demographics and education, respectively. Conclusion: With the exception of religiosity, psychosocial-resource measures were inversely associated with diabetes. Social support and social networks, especially, should be considered when addressing the reduction of diabetes burden among AAs.