tbuckley/cabot-search huggingface dataset:
A phase I, open-label, dose-escalation study to evaluate the safety, pharmacokinetics, and pharmacodynamics of oral azacitidine in subjects with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML)
Authors: B. S. Skikne, M. R. Ward, A. Nasser, L. Aukerman, G. Garcia-Manero
Journal: Journal of Clinical Oncology (2008)

7091 Background: Azacitidine, a cytidine analog, through its effects on DNA metabolism, gene expression, and cell differentiation, has proven beneficial in treatment of MDS and AML. Most notably, prolonged azacitidine therapy recently has been shown to approximately double 2-year survival in higher-risk MDS subjects compared to conventional care. Azacitidine is currently approved for intermittent subcutaneous (SC) and intravenous administration. Development of an oral formulation would provide more convenient dosing, eliminate injection-site reactions, and allow evaluation of novel, continuous low-dose regimens that may sustain demethylation and improve efficacy. A proprietary formulation of oral azacitidine was shown to be absorbed in a pilot, single-dose study (ASCO 2007). Methods: This is a multicenter, open-label, Phase 1, sequential design, dose-escalation study of oral azacitidine. The study is designed to evaluate the maximum tolerated dose (MTD), dose limiting toxicities (DLTs), safety, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of increasing doses of orally administered azacitidine in subjects with MDS or AML. Azacitidine was administered SC (75 mg/m2/day x 7 days) during cycle 1, then orally starting at 120 mg x 7 days/28 day cycle. Drug levels were measured in plasma and urine, and PD effects including global LINE methylation and gene-specific methylation were assayed. Results: Currently, no toxicities have been observed in subjects who have completed both the SC and oral phases of the study at 120 mg. The study continues at the 180 mg dose level. Preliminary PK analysis indicates detectable plasma levels at the 120 mg oral dose. A comparison of plasma PK profiles and PD effects of azacitidine administered at increasing oral doses compared to those of azacitidine administered SC at the approved dose of 75 mg/m2/day for all subjects evaluated to date will be presented. Conclusions: Initial results of oral 5-azacitidine indicate that this formulation is orally bioavailable and safe in subjects with MDS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pharmion Corporation Pharmion Corporation Pharmion Corporation Pharmion Corporation Pharmion Corporation
Abstract 15919: Impact of Bivalirudin Therapy on Mortality in Patients With High Risk Features Undergoing PCI: A Patient-Level Pooled Analysis From the REPLACE-2, ACUITY and HORIZONS-AMI Trials
Authors: George Dangas, Roxana Mehran, Usman Baber, Frederick Feit, David Cox, Bruce R Brodie, Bernhard Witzenbichler, Efthymios Deliargyris, Bernard J Gersh, Gregg W Stone
Journal: Circulation (2011)

Background. Compared to Heparin + GP IIb/IIIa inhibitors (GPI), bivalirudin has been shown to decrease bleeding complications in several clinical presentations including: percutaneous coronary inte...
Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography–defined subclinical cirrhosis
Authors: Mi Na Kim, Seung Up Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Ki Jun Song, Young Nyun Park, Kwang‐Hyub Han
Journal: Hepatology (2015)

Early detection of liver cirrhosis in its subclinical stage is of paramount importance to identify high‐risk individuals for developing hepatocellular carcinoma (HCC). This study investigated whether transient elastography (TE) can identify patients with subclinical cirrhosis (SCC) who are at increased risk of developing HCC among chronic hepatitis B (CHB) patients without clinical evidence of cirrhosis. A total of 2,876 CHB patients without clinical cirrhosis who received TE examinations between April 2006 and December 2012 were enrolled in this prospective study. SCC was defined as a nonclinical cirrhosis, but with a liver stiffness (LS) value ≥13 kilopascals (kPa). Mean age of the study population was 46.1 years, and male gender was predominant (n = 1,775; 61.7%). Mean LS value was 7.9 kPa, and SCC was identified in 285 (9.9%) patients. During the median follow‐up period of 48.9 months (range, 6.6‐96.2), HCC developed in 16 patients (13.3 per 1,000 person‐years) in the SCC group and 36 (3.4 per 1,000 person‐years) in the non‐SCC group. Cumulative incidence rate of HCC in the SCC group was significantly higher than that in the non‐SCC group ( P &lt; 0.001, log‐rank test). On multivariate analysis, SCC was independently associated with a risk of developing HCC, regardless of antiviral therapy (without antiviral therapy: hazard ratio [HR]: 4.680; 95% confidence interval [CI]: 1.187‐18.441; P = 0.027; with antiviral therapy: HR, 3.344; 95% CI: 1.526‐7.328; P = 0.003). Conclusion : TE can identify CHB patients with SCC who are at increased risk of developing HCC, even when cirrhosis is not clinically apparent. (H epatology 2015;61:1851‐1859)
Drug-Induced Brugada Syndrome in Children
Authors: Giulio Conte, Wendy Dewals, Juan Sieira, Carlo de Asmundis, Giuseppe Ciconte, Gian-Battista Chierchia, Giacomo Di Giovanni, Giannis Baltogiannis, Yukio Saitoh, Moises Levinstein, Mark La Meir, Francis Wellens, Gudrun Pappaert, Pedro Brugada
Journal: Journal of the American College of Cardiology (2014)
Cognitive decline after heart surgery is uncommon, review finds:
Authors: Jacqui Wise
Journal: BMJ (2015)

Cognitive impairment after cardiovascular surgery is uncommon in older people, a systematic evidence review published in the Annals of Internal Medicine has concluded.1 However, the researchers said that the evidence was limited and that the individual study quality was low.

Debate surrounds the possible relation between cardiovascular interventions and subsequent cognitive outcomes in older patients. Some early studies reported a high prevalence of …
Role of thrombin-activatable fibrinolysis inhibitor in lipopolysaccharide-induced acute lung injury
Authors: Masahiro Naito, Osamu Taguchi, Takehiro Takagi, Tetsu Kobayashi, Corina D'Alessandro-Gabazza, Esteban Gabazza
Journal: European Respiratory Journal (2011)

Background:  In acute lung injury, excessive coagulation induced by inflammatory responses may feedback to further increase the inflammatory response and promote fibrosis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is mainly synthesized in the liver and circulates in the bloodstream as an inactive proenzyme. It can be activated by the thrombin-thrombomodulin complex to a carboxypeptidase (TAFIa), which acts as an anti-fibrinolytic factor by inhibiting the activation of plasmin through the removal of carboxy-terminal lysines from fibrin. Recent studies have shown that TAFIa can also regulate inflammatory responses by its ability to inhibit complement C3a and C5a, and osteopontin.   Objective:  Our aim was to evaluate the effect of TAFI on acute lung injury in the mouse.   Methods:  Acute lung injury was induced in wild type and TAFI deficient (KO) C57/BL6 mice by intratracheal instillation of lipopolysaccharide (LPS:5mg/kg). Mice treated with saline served as controls. We compared the inflammatory response to LPS in both groups. Animals were sacrificed 24 hours after LPS injection and broncho-alveolar lavage fluid (BALF) was sampled.   Results:  TAFI KO mice had worse acute lung injury as their total protein, total cell count, and levels of IL-1β, IL-6 and TNF-α were increased in BALF in LPS-treated TAFI KO mice compared to wild type. The increase in cells in BALF was due to an increase in neutrophils. Complement C5a in both BALF and plasma was increased in LPS-treated TAFI KO mice compared to wild type.   Conclusions:  These results suggest that TAFI protects against acute lung injury at least partially through its ability to inactivate complement C5a.
R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by autologous stem cell transplantation: CORAL study
Authors: C. Gisselbrecht, B. Glass, N. Mounier, D. Gill, D. Linch, M. Trneny, A. Bosly, O. Shpilberg, N. Ketterer, C. Moskowitz, N. Schmitz
Journal: Journal of Clinical Oncology (2009)

8509 Background: Salvage chemotherapy followed by high dose therapy and autologous stem cell transplantation (ASCT) is the standard of treatment for chemosensitive relapses in diffuse large B cell lymphoma. This intergroup trial compared the association rituximab, ifosfamide, etoposide, carboplatinum, R-ICE and rituximab dexamethasone aracytine and cisplatinum R-DHAP. Methods: DLBCL CD 20+ in first relapse or pts refractory after first line therapy were randomized between R-DHAP and R-ICE. Responding patients received BEAM and ASCT and were randomized between observation or maintenance with rituximab for 1 yr. Results: Intent to treat analysis was made on the first 396 pts randomized in 11 countries (R ICE:202; R DHAP:194): median age 55 yrs.; 225 relapses &gt;12months, 166 refractory/early relapses; 244 pts with prior exposure to rituximab; Stage 3–4: 240 pts; elevated LDH: 198 pts; secondary IPI 0–1: 226 pts/ 2–3:149 pts. Patients with prior exposure to rituximab had more refractory disease and adverse prognostic factors. The overall response rate was 63%, with 38% complete remission. There was no difference in response rate between R-ICE 63.5% (CI 56–70%) and R-DHAP 62.8% (CI 55–69%), and in mobilization adjusted response rate. ASCT was performed in 206 pts. 90 SAE were reported in the R-ICE arm and 120 in the R-DHAP with 14 deaths. Factors significantly affecting response rate (p&lt;.0001) were: refractory/relapse &lt; 12 months:46 % vs 88 %, secondary IPI &gt;1:52% vs 71% and prior exposure to rituximab:51% vs 83%. There was not significant difference between R-ICE and R-DHAP for 3 yr EFS (26% vs 35% p=0.6) and OS (47% vs 51%, p=0.5). Three yrs EFS was affected by: prior treatment with rituximab, 21% vs none 47% (p&lt;.0001); early relapse&lt; 12 m 20% vs &gt;12m 45% (p &lt;.0001); secondary IPI 2–3: 18% vs 0–1: 40% (p=.0001). In Cox model, all these parameters were significant (p&lt;.0001) for EFS, PFS and OS but not the treatment arm. Longer follow up is necessary to evaluate the second randomization. Conclusions: There was no difference between R-ICE and R-DHAP. In pts without adverse prognostic factors a response rate &gt; 80% was observed. However, early relapses/ refractory pts to upfront rituximab-based chemotherapy have a poor response rate and prognosis. [Table: see text]
In brief
Authors: P Rigg
Journal: BMJ (2001)

All female sex workers employed by a chain of sex clubs in Spain will have to carry medical cards in future, after a drive to encourage the women to have regular checks for sexually transmitted diseases.

Clients will be able to access the details on the card by swiping it through an electronic reader. The scheme was condemned by a British AIDS specialist, who thought the scheme unbalanced and ineffective.

In four months Anela, the National Association of Sex Clubs, has brought together more than 100 …
A clinician's perspective on memory reconsolidation as the primary basis for psychotherapeutic change in posttraumatic stress disorder (PTSD)
Authors: Nathan A. Kimbrel, Eric C. Meyer, Jean C. Beckham
Journal: Behavioral and Brain Sciences (2015)

Abstract Lane et al.'s proposal that psychotherapeutic change comes about through memory reconsolidation is compelling; however, the model would be strengthened by the inclusion of predictions regarding additional factors that might influence treatment response, predictions for improving outcomes for non-responsive patients, and a discussion of how the proposed model might explain individual differences in vulnerability for mental health problems.
Caring for a family member with COPD: Exploring carers' needs
Authors: Raquel Gabriel, Cristina Jácome, Daniela Figueiredo, Alda Marques
Journal: European Respiratory Journal (2011)

Background:  Research of the impact of Chronic Obstructive Pulmonary Disease (COPD) on patients9 family carers is limited when compared to other chronic diseases such as cancer, heart disease or dementia. The disease places a particular burden on families but their support is crucial for the patient9s adjustment to the disease. However, current knowledge on the specific needs of family carers living with a patient with COPD is scarce.   Aims:  This exploratory study aimed to contribute to a better understanding of the family carers9 needs of patients with advanced COPD (stage III and IV).   Methods:  Qualitative semi-structured interviews were conducted with ten carers (female=8), with a mean age of 57.6 (SD=7.1) years old. The majority were spouses (n=9) and were caring for more than 4 years (n=6). All interviews were audio-recorded, transcribed and submitted to thematic analysis.   Results:  Main results suggest carers9 needs for: i) information about the disease to provide adequate care and to discern between kinds of attention needed to respond to symptoms (e.g., difficulties in recognising when a exacerbation is occurring) (n=8); ii) emotional support, like having someone trustworthy to talk about the caregiving experience (n=4); iii) respite care, in order to allow carers to take some time for their own (n=3); iv) instrumental support, as male carers reported difficulties in providing housework or meal preparation (n=2).   Conclusions:  The results strengthen the current state of knowledge regarding caregiving demands within the context of COPD. Understanding family needs providing carers with education about the disease and emotional support is essential to the management of COPD and to support carers in their caregiving role.
Abstract 1489: Vitamin D Receptor Activation Modulates the Effect of Uremia on Aortic Gene Expression and Endothelial Function
Authors: Jinshyun R Wu-Wong, Thomas J Campbell, Paul E Kroeger, William Noonan, Jason Segreti, Xiaoan Ruan, Masaki Nakane, Kristin A Brooks, James S Polakowski, Bryan F Cox
Journal: Circulation (2008)

Vitamin D receptor (VDR) activation therapy is associated with cardiovascular/survival benefit in chronic kidney disease (CKD), but the mechanism of action is not well understood. The aim of this study is to investigate how uremia affects gene expression in aorta and whether VDR activation modulates the uremic effect. DNA microarray technology was used to assess the gene expression profile in aorta prepared from SHAM and 5/6 nephrectomized (NX) rat, a model of Stage 4/5 CKD, treated with or without 0.17 μg/kg paricalcitol, a VDR activator. As expected, paricalcitol at 0.17 μg/kg after two weeks of treatment effectively suppressed serum parathyroid hormone (PTH); no significant difference was observed in ionized calcium or serum phosphorus. Uremia exhibited a significant effect on the gene expression pattern in the aorta, affecting 468 sequences ( ≥1.5-fold changes with p&lt;0.01 vs. SHAM). When the criteria were tightened to ≥ 2-fold changes with p&lt;0.01, uremia still affected 135 target sequences in the rat aorta with 63 up-regulated and 72 down-regulated. Target genes fell into various categories including metabolism and cellular metabolism. Paricalcitol treatment normalized 95 out of the 135 sequences affected by uremia; many of the genes were related to mitochondrial function and oxidative stress. As a follow-up to the microarray analysis, endothelial function was examined. Uremia significantly affected aortic relaxation (−50.0 ± 7.4% in NX rats vs. −96.2 ± 5.3% in SHAM at 30 μM acetylcholine). The endothelial-dependent relaxation response to acetylcholine (Ach) at 30 μM was improved to −58.2 ± 6.0%, −77.5 ± 7.3% and −90.5 ± 4.0% in NX rats treated with paricalcitol at 0.021, 0.042 and 0.083 μg/kg for two weeks, respectively, while blood pressure and heart rate were not changed. PTH suppression alone didn’t improve endothelial function since cinacalcet, a calcimimetic targeting calcium sensing receptor, suppressed PTH without affecting endothelial-dependent vasorelaxation. In conclusion, VDR activation by paricalcitol modulates the effect of uremia on aortic gene expression and endothelial function independent of PTH and blood pressure control, which may be one of the mechanisms responsible for paricalcitol’s cardiovascular benefit in CKD.
Profiles of ovarian cancer patients that benefit from taxane-platinum and platinum-based chemotherapy
Authors: J. Markowska, M. Bidziáski, J. Stelmachów, E. Kraszewska, I. Ziółkowska-Seta, R. Madry, A. Timorek, A. Rembiszewska, J. Kupryjaáczyk
Journal: Journal of Clinical Oncology (2007)

16005 Background: Taxane-platinum therapy (TP; regarded as more efficient than platinum-based therapy, PC) is a standard postoperative treatment of ovarian cancer patients; however, in 20 to 30% of patients the treatment is uneffective. Normal TP53 protein is a prerequisite of cancer cell response to PC, while TP53 inefficiency may enhance tumor sensitivity to taxanes. We compared the effectiveness of PC (n=253) and TP (n=199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease. Methods: Immunohistochemical analysis with PAb1801 antibody was performed on 452 archival tumors; multivariate analysis by the Cox and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)]. The therapeutic regimens were evaluated in comparison with each other and also with interactions with clinicopathological parameters. Results: TP enhanced probability of complete remission (CR, p=.05), platinum sensitivity (PS, p=.02) and longer survival (OS, p=.008) in the TP53(+) group. In the TP53(-) group TP did not show an advantage over PC in regard to CR and PS and it diminished a chance of platinum highly sensitive response (p=.04). However, in the TP53(-) group TP appeared to diminish risk of death of patients &gt;53 yrs (p=.063). Analysis of interactions revealed that TP therapy might be more efficient in patients with: endometrioid and clear cell carcinomas, stage III disease, G2 tumors or residual tumor &gt; 2cm. Nevertheless, in the TP53(-) group TP did not diminish risk of death of patients =53 yrs with these characteristics. Conclusions: Our results suggest that taxane-platinum therapy should be given to patients older than 53 years and to all with TP53 accumulation in their tumors. In the group of patients =53 yrs and with TP53(-) tumors (20% of patients in our study) treatment with PC may be equally or possibly more efficient than TP. No significant financial relationships to disclose.
M.Tuberculosis drug susceptibility testing results among previously treated patients in Georgia
Authors: Nino Kiria, Ucha Nanava, Nana Kiria, Nino Lomtadze
Journal: European Respiratory Journal (2013)

Aim: To study M.Tuberculosis Drug Susceptibility Testing (DST) Results among Previously Treated Patients in Georgia  Materials and methods: Retrospective analysis of DST results of TB patients previously treated with first line anti-TB drugs and registered during 2009-2011.  Results: In 2009-2011 total of 1836 previously treated TB patients were registered. TB case definitions were as follows: 34.6% relapse, 15% treatment after default, 3.6% treatment after failure and 46.8% other cases. Susceptibility to first-line anti-TB drugs was preserved among 34.3% of TB patients; 23.2% were mono-resistant, 11.1% poly-resistant and 31.4% multi-drug resistant (MDR). MDR-TB distribution among previously treated TB cases was as follows: 36.2% among relapsed cases, 20.7% treatment default, 48.5% among treatment failure and 30% among other cases.  Conclusions  The study has shown high prevalence of MDR-TB among previously treated patients. Patients who have failed previous anti TB treatment or relapsed have the highest prevalence of MDR.
Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.
Authors: K K Fu, T L Phillips, I J Silverberg, C Jacobs, D R Goffinet, C Chun, M A Friedman, M Kohler, K McWhirter, S K Carter
Journal: Journal of Clinical Oncology (1987)

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.
Amplification of chromosome 11q23 involving the MLL gene is recurrently observed in myeloid leukemias.
Authors: Lucienne Michaux, J. Dierlamm, M. Stul, Iwona Wlodarska, C. Herens, B Beverloo, C Duhem, M. Lecomte, G. Verhoef, Christine Dumoulin, Anne Hagemeijer
Journal: Blood (1998)
Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses
Authors: P. Rojas Sánchez, M. de Mulder, E. Fernandez-Cooke, L. Prieto, P. Rojo, S. Jiménez de Ory, M. José Mellado, M. Navarro, J. Tomas Ramos, Á. Holguín
Journal: Clinical Microbiology and Infection (2015)
Patient flow issues caused longer A&amp;E waits last winter, Monitor says
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The inability of most emergency departments in England to meet the four hour maximum waiting time standard last winter was largely attributable to problems in other parts of the health and social care system, a new analysis by the health sector regulator Monitor has found.

A&E Delays: Why Did Patients Wait Longer Last Winter? 1 2 3 examined why 91% of NHS trusts had failed to meet the target to see 95% of patients in emergency (A&E) departments within four hours last winter—the sector’s worst performance in 10 years.4

After conducting a detailed analysis of data from across the NHS including hospital episode statistics, situation reports on weekly A&E attendances and emergency admissions, and quarterly bed availability and occupancy returns, Monitor concluded …