tbuckley/cabot-search huggingface dataset:
Impact of All‐Oral Direct‐Acting Antivirals on Clinical and Economic Outcomes in Patients With Chronic Hepatitis C in the United States
Authors: Haesuk Park, Wei Wang, Linda Henry, David R. Nelson
Journal: Hepatology (2018)

Approved treatment for hepatitis C virus (HCV) with all-oral direct-acting antivirals (DAA) therapy is now entering into its fourth year; however, little has been reported on the real-world clinical (decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]) and economic outcomes. A retrospective cohort analysis of the Truven Health MarketScan Database (2012-2016) was conducted. In a cohort of 26,105 patients with newly diagnosed HCV, 30% received all-oral DAA therapy (DAA group) and 70% were not treated (untreated group). Multivariate Cox proportional hazards models were used to compare the risk of developing HCC and DCC, stratified by cirrhosis status. Among patients with cirrhosis (n = 2157), DAA therapy was associated with a 72% and a 62% lower incidence of HCC (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.15-0.52) and DCC (HR, 0.38; 95% CI, 0.26-0.56). Similarly, DAA therapy was associated with a 57% and a 58% lower incidence of HCC (HR, 0.43; 95% CI, 0.26-0.71) and DCC (HR, 0.42; 95% CI, 0.30-0.58) in patients with noncirrhotic HCV (n = 23,948). A propensity score-matched cohort of 8064 HCV-infected patients who had at least a 12-month follow-up after HCV treatment was included for economic analysis. For patients with cirrhosis in the DAA group, the mean adjusted liver-related costs ($1749 vs. $4575; P < 0.001) and all-cause medical costs ($19,300 vs. $33,039; P < 0.001) were significantly lower compared with those in the untreated group. The mean adjusted costs were not statistically different between the two groups among patients without cirrhosis. Conclusion: In the short term, all-oral DAA treatment for HCV infection was associated with a decreased risk of developing HCC and DCC, resulting in decreased health care costs, especially in patients with cirrhosis. A longitudinal study is necessary to confirm our findings.
Transcriptome Profiling of the Myeloma-Bone Niche Identifies BMP Signaling Role in Bone Destruction and Niche Maintenance, and Potential As a Therapeutic Target
Authors: Sarah Gooding, Siobhan Webb, Sam Olechnowicz, Seint Lwin, Andrew Armitage, Karthik Ramasamy, Claire M. Edwards, Alexander Drakesmith
Journal: Blood (2016)
Somatic mutations as markers of outcome after azacitidine and allogeneic stem cell transplantation in higher-risk myelodysplastic syndromes
Authors: Giulia Falconi, Emiliano Fabiani, Alfonso Piciocchi, Marianna Criscuolo, Luana Fianchi, Elisa L. Lindfors Rossi, Carlo Finelli, Elisa Cerqui, Tiziana Ottone, Alfredo Molteni, Matteo Parma, Stella Santarone, Anna Candoni, Simona Sica, Giuseppe Leone, Francesco Lo-Coco, Maria Teresa Voso
Journal: Leukemia (2018)
External Beam Radiotherapy Increases the Risk of Bladder Cancer When Compared with Radical Prostatectomy in Patients Affected by Prostate Cancer: A Population-based Analysis
Authors: Marco Moschini, Emanuele Zaffuto, Pierre I. Karakiewicz, David D. Andrea, Beat Foerster, Mohammad Abufaraj, Francesco Soria, Agostino Mattei, Francesco Montorsi, Alberto Briganti, Shahrokh F. Shariat
Journal: European Urology (2018)
Abstract P323: Pulse Pressure and Incident Acute Coronary Heart Disease Events in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Stephen P Glasser, Daniel L Halberg, Charles Sands, Paul Muntner, Monika Safford
Journal: Circulation (2013)

Background: Increased attention has been given to pulse pressure (PP) as a potential independent risk factor of cardiovascular disease. We examined the relationship between PP and incident acute coronary heart disease (CHD). Methods: We used data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study of 30,239 black and white participants aged 45 years or older and enrolled between 2003 and 2007. Baseline data included a 45-minute interview and in-home visit during which blood pressure was assessed and recorded as the average of two measurements obtained after a 5 minute seated rest. PP (SBP-DBP) was classified into 4 groups (&lt;45, 45-54, 54.1-64, &gt;64.1 mmHg). Telephone follow-up occurred every six months for self or proxy-reported suspected events, triggering medical record retrieval and adjudication by experts. Cox-proportional hazards models examined the association of incident CHD with PP groups, adjusting for socio-demographic and clinical risk factors. Results: This analysis included 22,909 participants free of CHD at baseline, with mean age 64.7±9.4 years; 40.4%were black, 44.6% were male and they experienced a total of 515 incident CHD events over a mean 3.4 yrs of follow-up (maximum 6 years). In unadjusted analyses, compared with PP&lt;45 mmHg, each higher PP group had incrementally higher hazard ratios (HR) for incident CHD (HR 1.28 {95% CI 1.02-1.60}, 2.05 {1.63-2.56}, 3.82 {3.08-4.74}, p&lt;0.001 for linear trend). This relationship persisted after fully adjusting including SBP for the highest PP group (HR 0.96 {0.75-1.21}, 1.12 {0.86-1.46}, 1.51 {1.09-2.10}, p trend &lt;0.0001). Conclusions: High PP was associated with incident CHD, even when accounting for SBP and numerous other CVD risk factors.
Raised intracranial pressure in those presenting with headache
Authors: Susan P Mollan, David Spitzer, David J Nicholl
Journal: BMJ (2018)

### What you need to know Untreated raised intracranial pressure (ICP) can lead to permanent sight loss, permanent neurological deficits, and ultimately death. Typical characteristics of new onset constant or near constant severe headache are non-specific, and only one third of patients with raised pressure report that the headache is worse on waking. A 24 year old woman attended the emergency department after experiencing a blackout. She was diagnosed with a panic attack and discharged. She returned two days later with increasing headaches and visual disturbances, and was admitted to hospital for investigation. Computed tomography scans of the head and a computed tomography venogram taken on day 3 were normal. On day 7, she underwent lumbar puncture and her cerebrospinal fluid opening pressure was 70 cm CSF. On day 8, she was examined with an ophthalmoscope and found to have papilloedema. Her best corrected visual acuity was reduced at 6/24 bilaterally and she had bilateral peripheral visual field loss to confrontation. She received a diagnosis of fulminant idiopathic intracranial hypertension and was transferred to the neuroscience centre, where on day 9 she underwent an emergency lumbar peritoneal shunt. Within two weeks, her vision improved to 6/9 bilaterally. Speaking to the BBC about her experience, she says, "I can't imagine what it would have been like to have been blind"( video 1 ). Video 1 Patient experience Raised intracranial pressure (ICP) is an abnormal elevation of brain pressure and is a medical emergency. Data on the frequency of raised ICP are lacking (box 1). It has many causes, including some serious ones (box 2), and can be sight and life threatening. The headache history is important, as is examination for signs of papilloedema and documentation of visual function. Box 2 ### Causes of raised intracranial pressureRETURN TO TEXT
Impact of antimicrobial treatment duration on outcome of Staphylococcus aureus bacteraemia: a cohort study
Authors: C.-J. Kim, K.-H. Song, K.-H. Park, M. Kim, P.G. Choe, M.-d. Oh, S.H. Lee, H.-C. Jang, S.-J. Kang, H.Y. Kim, S. Cheon, Y.G. Kwak, H.J. Choi, K.T. Kwon, J.H. Jeon, E.S. Kim, H.B. Kim, J.E. Cho, Y.J. Choi, J.I. Park, S.-I. Jung, N.J. Kim, W.B. Park, P.G. Choe, N.-H. Kim, M.J. Lee, K.H. Kim, Y.K. Kim, H.K. Choi, M.S. Han, Y.-S. Kim, C.R. Cho, H.S. Song, Y.S. Lee, H.-I. Kim, S.M. Kiem, D.-K. Kim, S.-A. Song, M.J. Kang, J.G. Shin
Journal: Clinical Microbiology and Infection (2018)
Abstract 330: MicroRNA Dysregulation in Patients with Hereditary Hemorrhagic Telangiectasia
Authors: Anthony Cannavicci
Journal: Circulation Research (2017)

Hereditary hemorrhagic telangiectasia (HHT) is a rare, understudied, autosomal dominant disorder that is characterized by angiogenic abnormalities. Gene mutations in HHT involve key angiogenic factors. Clinical manifestations of HHT include benign telangiectasias and potentially life threatening arteriovenous malformations (AVMs) that can occur in the pulmonary and cerebral circulation. Currently, there is no effective treatment for HHT. PBMCs have been implicated in the pathogenesis of HHT and the goal of this study was to profile and characterize PBMC microRNAs, to determine whether they had a role in the observed angiogenic abnormalities. A total of 28 HHT patients with confirmed mutations in either ENG , ACVRL1 or SMAD4 , and 25 controls were recruited. PBMCs were isolated from 16 ml of peripheral blood and total RNA was obtained. PBMC expression profiling was conducted with a human miR array analysis. Dysregulated miRs identified from the analysis were then validated with RT-qPCR. Significant differences were determined using a two-tailed t- test. Of the 800 miRs screened, 167 dysregulated miRs were identified in PBMCs. Selected PBMC miRs (MiRs-28-5p, -30b-5p, -361-3p and -374a-5p) were validated with RT-qPCR. PBMC miR-361-3p ( p =0.025) known to target IGF1, was found to be significantly decreased compared to controls. IGF1 messenger RNA (mRNA) levels in PBMCS of HHT patients was significantly elevated (p=0.005) compared to controls. Our results show dysregulation of select miRs in PBMCs from HHT patients. We also show an increase in IGF1 mRNA, an important angiogenic factor, in PBMCs that may be related to the downregulation of miR-361-3p in HHT patients. This may represent an important pathogenic mechanism that is involved in the angiogenic dysfunction observed in HHT and may provide for a unique miR therapeutic target.
Long-term trends in incidence and risk factors for ischaemic stroke subtypes: Prospective population study of the South London Stroke Register
Authors: Hatem A. Wafa, Charles D. A. Wolfe, Anthony Rudd, Yanzhong Wang
Journal: PLoS Medicine (2018)

As the average life expectancy increases, more people are predicted to have strokes. Recent studies have shown an increasing incidence in certain types of cerebral infarction. We aimed to estimate time trends in incidence, prior risk factors, and use of preventive treatments for ischaemic stroke (IS) aetiological subtypes and to ascertain any demographic disparities.Population-based data from the South London Stroke Register (SLSR) between 2000 and 2015 were studied. IS was classified, based on the underlying mechanism, into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). After calculation of age-, sex-, and ethnicity-specific incidence rates by subtype for the 16-year period, we analysed trends using Cochran-Armitage tests, Poisson regression models, and locally estimated scatterplot smoothers (loess). A total of 3,088 patients with first IS were registered. Between 2000-2003 and 2012-2015, the age-adjusted incidence of IS decreased by 43% from 137.3 to 78.4/100,000/year (incidence rate ratio [IRR] 0.57, 95% CI 0.5-0.64). Significant declines were observed in all subtypes, particularly in SVO (37.4-18; p < 0.0001) and less in CE (39.3-25; p < 0.0001). Reductions were recorded in males and females, younger (<55 years old) and older (≥55 years old) individuals, and white and black ethnic groups, though not significantly in the latter (144.6-116.2; p = 0.31 for IS). A 4-fold increase in prior-to-stroke use of statins was found (adjusted odds ratio [OR] 4.39, 95% CI 3.29-5.86), and despite the increasing prevalence of hypertension (OR 1.54, 95% CI 1.21-1.96) and atrial fibrillation (OR 1.7, 95% CI 1.22-2.36), preventive use of antihypertensive and antiplatelet drugs was declining. A smaller number of participants in certain subgroup-specific analyses (e.g., black ethnicity and LAA subtype) could have limited the power to identify significant trends.The incidence of ISs has been declining since 2000 in all age groups but to a lesser extent in the black population. The reported changes in medication use are unlikely to fully explain the reduction in stroke incidence; however, innovative prevention strategies and better management of risk factors may contribute further reduction.
Abstract 21224: Coronary Microvascular Dysfunction in Patients With Normal and Abnormal Diastolic Function in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Kathryn Dryer, Nikhil Narang, Mark Gajjar, Jeanette Y Cheng, Margaret Lee, Jonathan Paul, Sandeep Nathan, Atman P Shah, Mihai Gheorghiade, Charles J Davidson, William F Fearon, Sanjiv J Shah, John E A Blair
Journal: Circulation (2017)

Introduction: A potential mechanism for impaired diastolic relaxation and stiffness in patients with heart failure with preserved ejection fraction (HFpEF) is the presence of coronary microvascular dysfunction (CMD). Invasive studies have demonstrated that HFpEF can be present in patients regardless of the presence or absence of echocardiographic diastolic dysfunction. Hypothesis: We hypothesize that CMD is common in HFpEF with normal and abnormal echocardiographic diastolic function. Methods: In a prospective study of HFpEF patients (n=30), clinical, echocardiographic, hemodynamic, and coronary physiology (CP) data were evaluated. CP parameters measured included coronary flow reserve (CFR) and index of microvascular resistance (IMR). Echocardiographic diastolic dysfunction (DD) was graded according to current ASE guidelines. Baseline clinical, echocardiographic, hemodynamic, and CP data were compared between grade 0 DD (n=10) and grade 1-3 DD (n=11), excluding patients with indeterminate DD grade (n=10). Results: Age, gender, and comorbidities were similar in the grade 0 compared to grade 1-3 DD groups. Median BNP was higher in the grade 1-3 compared to the grade 0 DD group (462 vs. 98, p=0.012). All DD and strain measurements were significantly abnormal in the grade 1-3 compared to grade 0 DD groups, as were mean pulmonary artery, and left-sided filling pressures. Mean IMR was elevated and similar in patients with and without DD (30.5 vs. 27.9, p=0.58), however mean CFR was abnormal and lower in the grade 1-3 compared to grade 0 DD groups (2.05 vs. 3.30, p=0.053). Conclusions: Although BNP, LV and left atrial strain, and LV filling pressures were higher in HFpEF patients with abnormal diastolic function compared to "normal" diastolic function, we found that elevated microvascular resistance is present in patients with HFpEF and "normal" diastolic function, but these patients have relatively preserved CFR.
Serious adverse events and fatal adverse events associated with nivolumab treatment in cancer patients
Authors: Bin Zhao, Hong Zhao, Jiaxin Zhao
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Nivolumab, an immune checkpoint inhibitor, has revolutionized the treatment of many cancers. Due to its novel mechanisms of action, nivolumab induces a distinct profile of adverse events. Currently, the incidence and risk of developing serious adverse events (SAEs) or fatal adverse events (FAEs) following nivolumab administration are unclear. <h3>Methods</h3> We conducted a systematic search for phase 2 and phase 3 nivolumab trials in PubMed and Embase from inception to June 2018. Data on SAEs/FAEs were extracted from each study and pooled to calculate the overall incidence and odds ratios (ORs). <h3>Results</h3> A total of 21 trials with 6173 cancer patients were included in this study. The overall incidence of SAEs and FAEs with nivolumab were 11.2% (95% CI, 8.7–13.8%) and 0.3% (95% CI, 0.1–0.5%), respectively. The incidence of SAEs varied significantly with cancer type and clinical phase, but no evidence of heterogeneity was found for FAEs. Compared with conventional treatment, the administration of nivolumab did not increase the risk of SAEs (OR, 0.69; 95% CI, 0.34–1.40; <i>p</i> = 0.29) or FAEs (OR, 0.61; 95% CI, 0.27–1.39; <i>p</i> = 0.24). SAEs occurred in the major organ systems in a dispersed manner, with the most common toxicities appearing in the respiratory (21.4%), gastrointestinal (7.7%), and hepatic systems (6.6%). The most common cause of SAEs/FAEs was pneumonitis. <h3>Conclusions</h3> Although nivolumab is a relatively safe antitumor agent, nononcologists should be advised of the potential adverse events. Additionally, future studies are needed to identify patients at high risk of SAEs/FAEs to aid in the development of optimal monitoring strategies and the exploration of treatments to decrease the risks.
Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism
Authors: Martin Feller, Marieke Snel, Elisavet Moutzouri, Douglas C. Bauer, Maria de Montmollin, Drahomir Aujesky, Ian Ford, Jacobijn Gussekloo, Patricia M. Kearney, Simon Mooijaart, Terry Quinn, David Stott, Rudi Westendorp, Nicolas Rodondi, Olaf M. Dekkers
Journal: JAMA (2018)

The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of previous meta-analyses.To conduct a meta-analysis of the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism.PubMed, EMBASE, ClinicalTrials.gov, Web of Science, Cochrane Library, CENTRAL, Emcare, and Academic Search Premier from inception until July 4, 2018.Randomized clinical trials that compared thyroid hormone therapy with placebo or no therapy in nonpregnant adults with subclinical hypothyroidism were eligible. Two reviewers independently evaluated eligibility based on titles and abstracts of all retrieved studies. Studies not excluded in this first step were independently assessed for inclusion after full-text evaluation by 2 reviewers.Two independent reviewers extracted data, assessed risk of bias (Cochrane risk-of-bias tool), and evaluated the quality of evidence (GRADE tool). For synthesis, differences in clinical scores were transformed (eg, quality of life) into standardized mean differences (SMDs; positive values indicate benefit of thyroid hormone therapy; 0.2, 0.5, and 0.8 correspond to small, moderate, and large effects, respectively). Random-effects models for meta-analyses were applied.General quality of life and thyroid-related symptoms after a minimum follow-up of 3 months.Overall, 21 of 3088 initially identified publications met the inclusion criteria, with 2192 adults randomized. After treatment (range, 3-18 months), thyroid hormone therapy was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo (range, 0.5-3.7 mIU/L vs 4.6 to 14.7 mIU/L) but was not associated with benefit regarding general quality of life (n = 796; SMD, -0.11; 95% CI, -0.25 to 0.03; I2=66.7%) or thyroid-related symptoms (n = 858; SMD, 0.01; 95% CI, -0.12 to 0.14; I2=0.0%). Overall, risk of bias was low and the quality of evidence assessed with the GRADE tool was judged moderate to high.Among nonpregnant adults with subclinical hypothyroidism, the use of thyroid hormone therapy was not associated with improvements in general quality of life or thyroid-related symptoms. These findings do not support the routine use of thyroid hormone therapy in adults with subclinical hypothyroidism.
Abstract P208: Anger During Young Adulthood Increases the Risk of Developing Coronary Heart Disease
Authors: Benjamin D Pollock, Wei Chen, Emily Harville, Qi Zhao, Lydia Bazzano
Journal: Circulation (2016)

Background: Some cohort studies have found that anger in adults aged 45+ is associated with incident coronary heart disease (CHD). However, this relationship has not been tested rigorously in young adults. We took advantage of longitudinal measures collected by the Bogalusa Heart Study to examine this association prospectively in young adults. Methods: From 1985-1986, 768 young adults from the Bogalusa Heart Study completed the State Trait Anger Expression Inventory (STAXI) and were followed for cardiovascular risk factors. STAXI score is summed from a ten-point test with four response options (1=”never angry”; 2=”sometimes angry”; 3=”often angry”; 4=”almost always angry”). Multivariable linear regression, adjusted for race, BMI, pulse, blood glucose, and alcohol use, was used to test the association between anger and Framingham risk score as a global indicator of CHD risk. Participants were followed through 2010 and a general estimating equations model was used to assess the association between young adult anger (modeled using a restricted cubic spline function) and longitudinal development of CHD risk. Results: Our study population was (63.3%) female and (23.2%) black. At baseline, age ranged from 17-27 with a mean (SD) of 22.7 (2.4), and mean STAXI score was 18.6 (5.2). In cross-sectional analyses, STAXI score was not associated with CHD risk at baseline (p=0.20). However, after a median follow-up of 18 years, young adult anger was strongly associated (p=.006) with risk of CHD, with “always angry” subjects having a greater Framingham risk score at follow-up compared to “never angry” subjects (RR=1.71; 95%CI, 1.08 to 2.71), corresponding to a four-fold increase in 10-year risk of incident CHD (4% vs 1%, respectively). Conclusions: While it is currently established that anger in middle or late adulthood increases CHD risk, our analysis shows that, in fact, this relationship may be etiologically present much earlier in adulthood and among populations with a low overall CHD risk.