tbuckley/cabot-search huggingface dataset:
Comparative Efficacy and Acceptability of Pharmacological, Psychotherapeutic, and Combination Treatments in Adults With Posttraumatic Stress Disorder
Authors: Jasmin Merz, Guido Schwarzer, Heike Gerger
Journal: JAMA Psychiatry (2019)

Posttraumatic stress disorder (PTSD) is a prevalent mental disorder, with a high risk of chronicity, comorbidity, and functional impairment; PTSD is complicated to treat, and the debate on the best treatment approach is ongoing.To examine comparative outcomes and acceptability of psychotherapeutic and pharmacological treatments and their combinations in adults with PTSD.Embase, MEDLINE, PsycINFO, Cochrane Controlled Trials Register, and PSYNDEX were searched for studies published from January 1, 1980, to February 28, 2018. Reference lists of included studies and of previously published guidelines and systematic reviews were also searched.Of 11 417 records identified, 12 published randomized clinical trials (RCTs) comprising 922 participants, contributing 23 direct comparisons between psychotherapeutic and pharmacological treatments or their combinations were included.Standardized mean differences (SMDs) and odds ratios were aggregated using random-effects network and pairwise meta-analyses. Risk of bias and indirectness was rated for each study, and network confidence was rated using the Confidence in Network Meta-Analysis framework.The primary outcome was the comparative benefit between 2 treatment approaches to PTSD symptom improvement, and secondary outcome was the comparative acceptability of the treatment approaches, as indicated by patient dropout rates before treatment termination.No treatment approach was found to be superior at the end of treatment (for all, 95% CI included 0). At the last follow-up, psychotherapeutic treatments showed greater benefit than pharmacological treatments in both network (SMD, -0.83; 95% CI, -1.59 to -0.07) and pairwise (SMD, -0.63; 95% CI, -1.18 to -0.09, 3 RCTs) meta-analyses. No difference was found between combined treatments and psychotherapeutic treatments at long-term follow-up, and combined treatments were associated with better outcomes than pharmacological treatments in the network meta-analysis (SMD, -0.96; 95% CI, -1.87 to -0.04), but not in the pairwise meta-analysis, which included 2 RCTs (SMD, -1.02; 95% CI, -2.77 to 0.72). No evidence was found for differential acceptability of the 3 treatment approaches.These results suggest superiority of psychotherapeutic treatments over pharmacological treatments; network, but not pairwise, meta-analyses suggest superiority of combined treatments over pharmacological treatments in improving PTSD symptom severity in the long term. The scarcity of reported long-term findings hampers definite conclusions and demonstrates the need for robust evidence from large-scaled comparative trials providing long-term follow-up data.
Tumor Angiogenesis Is Differentially Regulated by Phosphorylation of Endothelial Cell Focal Adhesion Kinase Tyrosines-397 and -861
Authors: Ana-Rita Pedrosa, Natalia Bodrug, Jesus Gomez-Escudero, Edward P. Carter, Louise E. Reynolds, Paraskivi Natalia Georgiou, Isabelle Fernandez, Delphine M. Lees, Vassiliki Kostourou, Annika N. Alexopoulou, Silvia Batista, Bernardo Tavora, Bryan Serrels, Maddy Parsons, Thomas Iskratsch, Kairbaan M. Hodivala-Dilke
Journal: Cancer Research (2019)

Abstract Expression of focal adhesion kinase (FAK) in endothelial cells (EC) is essential for angiogenesis, but how FAK phosphorylation at tyrosine-(Y)397 and Y861 regulate tumor angiogenesis in vivo is unknown. Here, we show that tumor growth and angiogenesis are constitutively reduced in inducible, ECCre+;FAKY397F/Y397F–mutant mice. Conversely, ECCre+;FAKY861F/Y861F mice exhibit normal tumor growth with an initial reduction in angiogenesis that recovered in end-stage tumors. Mechanistically, FAK-Y397F ECs exhibit increased Tie2 expression, reduced Vegfr2 expression, decreased β1 integrin activation, and disrupted downstream FAK/Src/PI3K(p55)/Akt signaling. In contrast, FAK-Y861F ECs showed decreased Vegfr2 and Tie2 expression with an enhancement in β1 integrin activation. This corresponds with a decrease in Vegfa–stimulated response, but an increase in Vegfa+Ang2- or conditioned medium from tumor cell–stimulated cellular/angiogenic responses, mimicking responses in end-stage tumors with elevated Ang2 levels. Mechanistically, FAK-Y861F, but not FAK-Y397F ECs showed enhanced p190RhoGEF/P130Cas-dependent signaling that is required for the elevated responses to Vegfa+Ang2. This study establishes the differential requirements of EC-FAK-Y397 and EC-FAK-Y861 phosphorylation in the regulation of EC signaling and tumor angiogenesis in vivo. Significance: Distinct motifs of the focal adhesion kinase differentially regulate tumor blood vessel formation and remodeling.
Infographic. The effect of protein supplementation on resistance training-induced gains in muscle mass and strength
Authors: Robert W Morton, Kevin T Murphy, Sean R McKellar, Brad J Schoenfeld, Menno Henselmans, Eric Helms, Alan A Aragon, Michaela C Devries, Laura Banfield, James W Krieger, Stuart M Phillips
Journal: British Journal of Sports Medicine (2019)

When you lift weights you get stronger and your muscles can get bigger, a process we call hypertrophy, and these changes can mean a big advantage in certain sports. We all ‘know’ that we need to consume supplemental protein when we lift weights to get bigger muscles, right? But what’s the real (science-based) answer? A meta-analysis is a way of looking at all of the studies that have been done in a particular area of science. In our study,1 we performed …
Abstract 16852: The Role of Repeat Stress Radionuclide Myocardial Perfusion Imaging for New or Progressive Cardiovascular Symptoms
Authors: Marcelo Fernandes, Manuel Rivera-Maza, Salih Grevious, Louis Vincent, George Marzouka, Simon Chakko
Journal: Circulation (2018)

Background: The appropriateness use criteria (AUC) offers guidance to assist with the appropriate use of cardiac imaging. The recent AUC consensus is that follow-up radionuclide myocardial perfusion imaging (MPI) within 2-years of a normal MPI is rarely appropriate in asymptomatic patients or in those with stable symptoms. The utility of repeat testing in a patient with new or progressive symptoms has not been studied. Methods: After IRB approval, records from veterans who underwent multiple MPI stress testing within 2-years of a negative MPI, between 2013 and 2016, at our VA Medical Center were accessed and variables of interest collected. Descriptive analysis as well as direct comparison by means of χ2 for dichotomous variables was conducted. Results: A total of 318 male veterans underwent repeat MPI within 2-years of a normal MPI. The median age was 65 [IQR, 59-70]. Among this group, repeat testing for new or progressive symptoms was done in 206 veterans (65%), compared to 112 (35%) veterans without symptoms. 50 cases had reversible ischemia on repeat MPI. Of these, 37 (18%) were symptomatic. Among asymptomatic veterans with a positive repeat MPI, 3 out of the 11 (27%) were noted to have obstructive coronary artery disease (CAD) on coronary angiogram. In contrast, 24 out of 37 veterans with symptoms underwent coronary angiogram, with 15 (40.6%) found to have obstructive CAD. Overall, 2.6% of asymptomatic veterans who underwent repeat MPI had obstructive CAD on coronary angiogram, compared to 7.2% of veterans who had repeat testing for new or progressive symptoms. Comparison of angiogram findings for abnormal MPIs based on the presence of symptoms on presentation did not reach statistical significance (p=0.053). Conclusion: Among asymptomatic veterans who underwent repeat MPI, &lt; 3% of veterans had obstructive CAD. These findings support the AUC’s position that for asymptomatic patients, repeat MPI within 2-years of a normal study is rarely appropriate. However, among veterans with symptoms, 7 % were found to have obstructive CAD, but the difference between asymptomatic and symptomatic patients did not reach statistical significance. In the setting of symptoms, a negative MPI within 2-years is possibly a marker of low risk for obstructive CAD.
Abstract 19432: Burden of Coronary Artery Disease in Patients With Out-of-Hospital Refractory Ventricular Fibrillation Cardiac Arrest
Authors: Demetris Yannopoulos, Jason A Bartos, Ganesh Raveendran, Marc Conterato, RJ Frascone, Alexander Trembley, Ranjit John, John Connett, David Benditt, Keith G Lurie, Robert F Wilson, Tom P Aufderheide
Journal: Circulation (2017)

Background: The incidence of coronary artery disease (CAD) among patients with refractory out-of-hospital (OOH) ventricular fibrillation/ventricular tachycardia (VF/VT) cardiac arrest is unknown. O...
Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine
Authors: Xiyan Xu, Lenee Blanton, Anwar Isa Abd Elal, Noreen Alabi, John Barnes, Matthew Biggerstaff, Lynnette Brammer, Alicia P. Budd, Erin Burns, Charisse N. Cummings, Shikha Garg, Rebecca Kondor, Larisa Gubareva, Krista Kniss, Sankan Nyanseor, Alissa O’Halloran, Melissa Rolfes, Wendy Sessions, Vivien G. Dugan, Alicia M. Fry, David E. Wentworth, James Stevens, Daniel Jernigan
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Influenza activity* in the United States during the 2018-19 season (September 30, 2018-May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)
PF285 ZELLA‐101: PHASE 1 STUDY OF ALVOCIDIB FOLLOWED BY 7+3 INDUCTION IN NEWLY DIAGNOSED AML PATIENTS
Authors: D. Lee, B. Smith, M. Frattini, S. Anthony, D. Bearss, J. Zeidner
Journal: HemaSphere (2019)

Background: Alvocidib, a potent cyclin‐dependent kinase‐9 (CDK‐9) inhibitor, has been studied extensively in newly diagnosed and relapsed/refractory AML in a timed sequential combination with cytarabine and mitoxantrone (ACM) with promising activity. Inhibition of CDK‐9 leads to downregulation of BCL‐2 family member, MCL‐1, which in turn inhibits tumor growth. We hypothesized that alvocidib followed by 7+3 induction therapy would be safe and effective in newly diagnosed non‐favorable risk AML. Aims: To evaluate the safety and clinical activity of alvocidib, in combination with cytarabine and daunorubicin (7+3), in previously untreated AML Methods: We are conducting a multicenter, open‐label, dose‐escalation, safety and biomarker prediction study (Zella 101) of alvocidib given as timed sequential therapy prior to cytarabine and daunorubicin for adults with previously untreated AML. The key eligibility criteria are: ages 18–65 years; previously untreated AML; ECOG PS 0–2; and no major organ dysfunction. Treatment consisted of increasing dose levels of alvocidib starting at 20 mg/m 2 as a 30‐minute IV bolus followed by 30 mg/m 2 over 4 hours on days 1–3, cytarabine 100 mg/m 2 /day by continuous IV infusion on days 5–11, and daunorubicin 60 mg/m 2 IV on days 5–7. Dose escalation was assessed by standard 3+3 design. Reinduction therapy with alvocidib (same dose as induction) days 1–3, followed by cytarabine 100 mg/m 2 /day continuous IV days 5–9 and daunorubicin 45 mg/m 2 IV days 5–6 was recommended in patients with &gt;10% and &gt;5% cellularity and blasts, respectively. Results: A total of 13 patients have been enrolled to date with the median age of 59 years (Range: 31–65 years) (See Table 1). The maximum dose of alvocidib administered was 30 mg/m 2 as a 30‐minute IV bolus followed by 60 mg/m 2 over 4 hours on days 1–3 as previously given in prior studies. Overall, alvocidib was well tolerated. The most common NCI CTCAE ≥Grade 3 treatment emergent nonhematologic AEs noted in ≥3 patients in the safety population were device related infection (30.8%), diarrhea (30.8%) and lung infection (23.1%). Cytogenetics were reported on 7 patients, 5 were intermediate to high risk. Ten patients were evaluable with post baseline response assessments, two patients were too early for disease assessment, and one patient died prior to disease assessment due to septic shock. Nine of the 10 evaluable patients achieved CR (9/10, 90%). Summary/Conclusion: Alvocidib given as timed sequential therapy prior to cytarabine and daunorubicin (7+3) induction in newly diagnosed AML demonstrated an acceptable safety profile with an MTD (30 mg/m 2 IV bolus followed by 60 mg/m 2 infusion over 4 hours) similar to previously investigated timed sequential regimens of alvocidib. Future directions include a randomized phase 2 expansion comparing cytarabine and daunorubicin with or without preceding timed sequential alvocidib, and prospective BH3 profiling of AML patients. image
Doctors alleging sexism at BMA welcome appointment of QC to lead review
Authors: Elisabeth Mahase
Journal: BMJ (2019)

A leading employment lawyer who specialises in discrimination has been appointed to lead an independent review of sexism in the BMA, which will begin this month and publish recommendations later this year.

Daphne Romney QC will head the review, which follows allegations of sexist remarks made to senior BMA General Practitioners Committee representatives Zoe Norris and Katie Bramall-Stainer at the conference of UK local medical committees earlier this year.1 The allegations led to other doctors speaking out about their own experiences of sexism, harassment, and inappropriate behaviour during BMA activities.

The appointment was announced ahead of the BMA’s annual representative meeting in Belfast next week (23 to 27 June),2 where a motion on the investigation will be …
Abstract P375: Secular Trends in Validity of Troponin I Assays for Myocardial Infarction Classification Among Four US Communities: Findings From the ARIC Study
Authors: Matthew S Loop, Jason P Fine, Aaron R Folsom, Wayne Rosamond
Journal: Circulation (2018)

Introduction: The Atherosclerosis Risk In Communities (ARIC) study conducted community surveillance of hospitalized myocardial infarction (MI) from 1987 to 2014 among four US communities (Jackson MS, Forsyth County NC, Washington County MD, and Minneapolis MN). Surveillance of MI during the troponin era (1996 - ) has been complicated by increasing sensitivity of troponin I assays. It is unclear to what extent increased assay sensitivity has affected the validity of event classification. We hypothesized that among events that would have been classified as a definite/probable MI or a suspect/no MI regardless of cardiac biomarkers, the sensitivity and specificity of troponin I assays to identify abnormal enzyme levels (ARIC community surveillance criterion: 2x upper limit of normal) has changed over time in hospitals participating in ARIC community surveillance. Methods and results: From 33,995 community hospitalizations with suspicion of MI or coronary heart disease with a troponin I measurement that occurred between 1996 and 2014, 2,143 met ARIC criteria as MI cases (ARIC computer algorithm classification of definite or probable MI regardless of cardiac biomarker levels) and 9,909 we considered noncases (ARIC computer algorithm classification of no or suspect MI regardless of cardiac biomarker levels). In order to be an MI case, the event had to include an evolving diagnostic ECG. To be an noncase, the event had to include no chest pain and an equivocal or absent/uncodable ECG. We used survey-weighted logistic regression models to predict sensitivity and specificity from 1996 - 2014. The sensitivity of troponin I assay being abnormal was approximately 50% for most of the time period, with a potential increase to 70% after 2010. The specificity was approximately 90% in the late 1990s and early 2000s, but fell to 68% (95% confidence interval: 63% - 73%) by 2014. The median upper limit normal (ULN) for troponin I among all 33,995 hospitalizations dropped from 1.4 ng/mL in 1996 to 0.045 ng/mL in 2014. Conclusions: For most of the troponin era among the four ARIC communities, hospitalizations that were classified as an MI regardless of cardiac biomarker levels were equally likely to have or not have abnormal troponin I. In recent years, the likelihood that hospitalizations that were classified as no MI regardless of cardiac biomarker levels had normal troponin I decreased, potentially affecting the usefulness of troponin I measurements to separate hospitalized MIs from non-MIs in the context of community surveillance, particularly among hospitalizations with few other signs of MI. These shifts in assay validity were likely due in part to a decrease in ULN for troponin I in the four ARIC communities.
PB2159 CHOLESTEROL LEVELS PROVIDE PROGNOSTIC INFORMATION IN PATIENTS WITH MULTIPLE MYELOMA
Authors: X. Peipei
Journal: HemaSphere (2019)

Background: Hypocholesterolaemia has been reported to be associated with cancer risk and progression. Aims: he aim of this retrospective study was to investigate the prognostic value of cholesterol levels in patients with multiple myeloma (MM). Methods A total of 153 patients newly diagnosed with MM were retrospectively enrolled. The relationship between cholesterol levels and clinical characteristics was evaluated. The prognostic value of cholesterol levels was explored. Results: The levels of low‐density lipoprotein cholesterol (LDL‐c), high‐density lipoprotein cholesterol (HDL‐c) and triglycerides (TC) were significantly lower in MM patients (P &lt; 0.001). What is more, multivariate analyses showed that low TC and LDL‐c levels were independent predictors of a better OS (overall survival; HR = 6.893 and 0.204; CI = 1.135‐41.868 and 0.045‐0.930, P = 0.036 and 0.040) and PFS (progression‐free survival; HR = 7.416 and 0.216; CI = 1.365‐40.290 and 0.047‐0.999, P = 0.020 and 0.049). Summary/Conclusion: Serum cholesterol levels in MM patients were low, and TC and LDL‐c levels could be used as prognostic markers for MM patients.
The Carcinogenome Project: <i>In Vitro</i> Gene Expression Profiling of Chemical Perturbations to Predict Long-Term Carcinogenicity
Authors: Amy Li, Xiaodong Lu, Ted Natoli, Joshua Bittker, Nisha S. Sipes, Aravind Subramanian, Scott Auerbach, David H. Sherr, Stefano Monti
Journal: Environmental Health Perspectives (2019)

Most chemicals in commerce have not been evaluated for their carcinogenic potential. The de facto gold-standard approach to carcinogen testing adopts the 2-y rodent bioassay, a time-consuming and costly procedure. High-throughput in vitro assays are a promising alternative for addressing the limitations in carcinogen screening.We developed a screening process for predicting chemical carcinogenicity and genotoxicity and characterizing modes of actions (MoAs) using in vitro gene expression assays.We generated a large toxicogenomics resource comprising [Formula: see text] expression profiles corresponding to 330 chemicals profiled in HepG2 (human hepatocellular carcinoma cell line) at multiple doses and replicates. Predictive models of carcinogenicity and genotoxicity were built using a random forest classifier. Differential pathway enrichment analysis was performed to identify pathways associated with carcinogen exposure. Signatures of carcinogenicity and genotoxicity were compared with external sources, including Drugmatrix and the Connectivity Map.Among profiles with sufficient bioactivity, our classifiers achieved 72.2% Area Under the ROC Curve (AUC) for predicting carcinogenicity and 82.3% AUC for predicting genotoxicity. Chemical bioactivity, as measured by the strength and reproducibility of the transcriptional response, was not significantly associated with long-term carcinogenicity in doses up to [Formula: see text]. However, sufficient bioactivity was necessary for a chemical to be used for prediction of carcinogenicity. Pathway enrichment analysis revealed pathways consistent with known pathways that drive cancer, including DNA damage and repair. The data is available at https://clue.io/CRCGN_ABC , and a portal for query and visualization of the results is accessible at https://carcinogenome.org .We demonstrated an in vitro screening approach using gene expression profiling to predict carcinogenicity and infer MoAs of chemical perturbations. https://doi.org/10.1289/EHP3986.
Abstract 1834: Temporal Stability of Complex Fractionated Atrial Electrograms in Human Left Atrium during Atrial Fibrillation
Authors: Daniel Scherr, Darshan Dalal, Aamir Cheema, Saman Nazarian, Ibrahim Almasry, Kenneth Bilchick, Alan Cheng, Charles A Henrikson, David Spragg, Joseph E Marine, Ronald D Berger, Hugh Calkins, Jun Dong
Journal: Circulation (2007)

Introduction: Complex fractionated atrial electrograms (CFAEs) have been reported as ablative targets for the treatment of atrial fibrillation (AF). However, the temporal stability of CFAEs has not...
AB1100 PREVALENCE OF SARCOPENIA IN ECUADORIAN POPULATION BASED ON SCREENING AND DIAGNOSTIC TOOLS
Authors: Genessis Maldonado, Carlos Rios
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Sarcopenia is defined as an abnormal loss of muscle mass associated with aging. It has been validated that sarcopenia can predict functional deterioration. <h3>Objectives</h3> The purpose of this study is to determine the diagnosis of sarcopenia by conventional methods and gold standard. <h3>Methods</h3> Prospective observational study of patients attending a rheumatology center, to whom anthropometric and densitometric measurements were taken in order to determine sarcopenia. <h3>Results</h3> A total of 110 patients were studied, from which 91% were women and 9% men. 66% presented sarcopenia by means of the gold standard test (DXA). The mean age was 65.80±9.84 [44-89]. The mean age for women was 66.2±9.9 [44-86] and the average age of menopause was 46.08±8.53 and 63% were found to have sarcopenia. In men, the mean age was 73.3±13.8 [63-89] and 30% had sarcopenia. Anthropometric measures were determined. The mean body mass index was 26.58±4.67, which corresponds to overweight. Three tests were performed in addition to the gold standard. The average gait speed test was 1.12±0.74 seconds and 45% were positive for sarcopenia. The mean of the muscle strength test (dynamometer) was 19.33± 9.52 and 63% had sarcopenia. The mean of the SARC-F screening questionnaire was 3.02±2.24 and 22% were positive for sarcopenia. According to the measurement of muscle mass by DXA, the mean appendicular skeletal muscle mass (ASMM) was 16.08±3.52, ASMM index 6.77±1.12 and the total skeletal muscle was 21.39±4.68. Men presented a higher muscle mass index compared to women [7.82±1.93 vs. 6.66±0.95]. When grouping patients by BMI, sarcopenia was present in all of the patients with low weight, 88% in the ideal weight group, 67% in the overweight group and 25% in the obesity group. A statistically significant relationship was found between sarcopenia and sex [0.01], weight and height [&lt;0.001], gait test [0.04], muscle strength test [&lt;0.001] and DXA [&lt;0.001]. In addition, the sensitivity and specificity of the tests were determined. SARC-F had a 15% sensitivity and a 9% specificity, with a positive predictive value of 74% and a negative predictive value of 37%. The gait speed test 24% sensitivity and 38% specificity, with a positive predictive value of 57% and negative predictive value of 27%. The muscle strength test had a 78% sensitivity and 65% specificity, with a positive predictive value of 84% and negative predictive value of 96% (Figure 1). <h3>Conclusion</h3> This is the first study of determination of Sarcopenia in a Rheumatology Center in the city of Guayaquil. 66% of the studied population presented sarcopenia. It is evident that conventional methods may determine a diagnosis, however, a definitive diagnosis can be established by DEXA. Because Sarcopenia is a multidisciplinary entity, more studies are needed to determine the usefulness of the conventional methods. <h3>Disclosure of Interests</h3> None declared