tbuckley/cabot-search huggingface dataset:
Alignment of Do-Not-Resuscitate Status With Patients’ Likelihood of Favorable Neurological Survival After In-Hospital Cardiac Arrest
Authors: Timothy J. Fendler, John A. Spertus, Kevin F. Kennedy, Lena M. Chen, Sarah M. Perman, Paul S. Chan
Journal: JAMA (2015)

<h3>Importance</h3> After patients survive an in-hospital cardiac arrest, discussions should occur about prognosis and preferences for future resuscitative efforts. <h3>Objective</h3> To assess whether patients’ decisions for do-not-resuscitate (DNR) orders after a successful resuscitation from in-hospital cardiac arrest are aligned with their expected prognosis. <h3>Design, Setting, and Participants</h3> Within Get With The Guidelines–Resuscitation, we identified 26 327 patients with return of spontaneous circulation (ROSC) after in-hospital cardiac arrest between April 2006 and September 2012 at 406 US hospitals. Using a previously validated prognostic tool, each patient’s likelihood of favorable neurological survival (ie, without severe neurological disability) was calculated. The proportion of patients with DNR orders within each prognosis score decile and the association between DNR status and actual favorable neurological survival were examined. <h3>Exposures</h3> Do-not-resuscitate orders within 12 hours of ROSC. <h3>Main Outcomes and Measures</h3> Likelihood of favorable neurological survival. <h3>Results</h3> Overall, 5944 (22.6% [95% CI, 22.1%-23.1%]) patients had DNR orders within 12 hours of ROSC. This group was older and had higher rates of comorbidities (all<i>P</i> &lt; .05) than patients without DNR orders. Among patients with the best prognosis (decile 1), 7.1% (95% CI, 6.1%-8.1%) had DNR orders even though their predicted rate of favorable neurological survival was 64.7% (95% CI, 62.8%-66.6%). Among patients with the worst expected prognosis (decile 10), 36.0% (95% CI, 34.2%-37.8%) had DNR orders even though their predicted rate for favorable neurological survival was 4.0% (95% CI, 3.3%-4.7%) (<i>P</i>for both trends &lt;.001). This pattern was similar when DNR orders were redefined as within 24 hours, 72 hours, and 5 days of ROSC. The actual rate of favorable neurological survival was higher for patients without DNR orders (30.5% [95% CI, 29.9%-31.1%]) than it was for those with DNR orders (1.8% [95% CI, 1.6%-2.0%]). This pattern of lower survival among patients with DNR orders was seen in every decile of expected prognosis. <h3>Conclusions and Relevance</h3> Although DNR orders after in-hospital cardiac arrest were generally aligned with patients’ likelihood of favorable neurological survival, only one-third of patients with the worst prognosis had DNR orders. Patients with DNR orders had lower survival than those without DNR orders, including those with the best prognosis.
Relative frequency of BRCA2 versus BRCA1 mutations in Spanish families with hereditary breast/ovarian cancer
Authors: E. Polo, R. Andres, J. Mayordomo, J. Godino, R. Lara, J. Lambea, T. Caldes, M. De La Hoya, P. Perez-Segura, A. Tres
Journal: Journal of Clinical Oncology (2004)

9687 Background: BRCA 1 and BRCA 2 have been identified as the genes responsible of hereditary breast/ovarian cancer in many families. Initial publications reported BRCA 1 germline mutations to be more frequent than those involving BRCA 2. We want to assess the relative frequency of BRCA 1 versus BRCA 2 mutations in families with hereditary breast/ovarian cancer from the region of Aragón, Spain. Methods: All patients attending the family cancer clinic of the University Hospital of Zaragoza, Spain, who fullfilled the following criteria: (1) At least 3 cases of breast/ovarian cancer in more than 2 generations and at least one case < 45 years old or/and (2) male breast cancer associated with female breast cancer in first-degree relatives, were offered BRCA 1 & BRCA 2 testing. BRCA 1 was performed first. Results: In 40 families tested for BRCA 1, 3 germline mutations were identified (7.5%). BRCA 2 testing is complete in 27 of these families. 6 BRCA 2 mutations (22.2%) were identified. Clinical features of families harbouring BRCA 1 vs BRCA 2 mutation will be presented. Conclusions: BRCA 2 mutations are significantly more frequent than those involving BRCA 1 in families with breast/ovarian cancer from the region of Aragon, Spain. No significant financial relationships to disclose.
Letter by Loboda et al Regarding Article, “Bach1 Represses Wnt/β-Catenin Signaling and Angiogenesis”: IL-8 Is Not Present in Murine Genome Hence it Cannot Be Responsible for the Bach1 Effect on Angiogenesis in Mice
Authors: Agnieszka Loboda, Urszula Florczyk, Agnieszka Jazwa, Anna Grochot-Przeczek, Witold Nowak, Alicja Jozkowicz, Jozef Dulak
Journal: Circulation Research (2015)

Recently, we read the article by Jiang et al 1 describing the effect exerted by Bach1 on revascularization in murine hindlimb ischemia and on angiogenic properties of murine and human endothelial cells.The authors have demonstrated, using Bach1-deficient mice that lack of this gene, encoding for an inhibitor of Nrf2 transcription factor, resulted in the enhanced perfusion and vascular density during 14 days after induction of ischemia (Figure 1A).Reversely, overexpression of Bach1 impaired blood flow restoration and angiogenesis in wild-type C57BL/6J animals.Investigating for the mechanisms of the observed changes in murine model, the authors demonstrated that lack of Bach1 is associated with increased vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression in ischemic muscles, as shown in Figure 1D and 1E, respectively.Similarly, in mouse lung endothelial cells isolated from Bach1 -/-mice, significant increase in IL-8 and VEGF mRNA expression was detected in comparison with cells isolated from wild-type littermates (Figure 2D).In addition, the authors showed that overexpression of Bach1 in wild-type animals decreased the expression of those growth factors respectively).Later on in the study, it was demonstrated that Bach1 regulates also the expression of VEGF and IL-8 in human endothelial cells.Accordingly, the authors concluded that diminished IL-8 and VEGF were responsible for antiangiogenic effect of Bach1.Indeed, ours 2 and others 3 studies indicated the significance of Nrf2-heme oxygenase-1 pathway in regulation of angiogenesis.As Nrf2 and heme oxygenase-1 have been demonstrated to play a proangiogenic role, 4 the antiangiogenic effect of Bach1, an inhibitor of Nrf2 activity, could be reasonably considered.In line with that was also our previous observation, cited by the authors as Reference 36 that Nrf2 regulates IL-8 expression in human endothelial cells. 5 We are, however, confused by the results from animal models showing that IL-8 is regulated (inhibited) by Bach1 and that IL-8, together with VEGF, could be a mediator of the observed effects in mouse ischemic legs.Our concern is because IL-8 is not expressed by rodent cells and it is a well-known example of so-called gene death in murine genome. 6Moreover, there is no murine ortholog of the human IL-8 gene, however, the chemokines CXCL1/KC, CXCL2/MIP-2, and CXCL5-6/LIX are regarded as functional homologs of IL-8 in rodents. 7In the commented article, the authors claim to detect murine IL-8 expression by reverse transcription polymerase chain reaction.
Postmarketing surveillance does not catch all adverse events
Authors: P. O'Brien
Journal: BMJ (1996)

EDITOR,—H B M Reijnen and W J Atsma, of Organon Pharmaceuticals, use data from the company's product surveillance database to show that the risk of venous thromboembolism with the pills Marvelon and Mercilon, both of which contain desogestrel, is highest in the first few months of use and falls dramatically thereafter.1 The World Health Organisation's …
How are we using systemic drugs to treat psoriasis in children? An insight into current clinical U.K. practice
Authors: E. Burden‐Teh, M.L. Lam, S.M. Taibjee, A. Taylor, S. Webster, S. Dolman, C. Jury, D. Caruana, S. Darne, A. Carmichael, S. Natarajan, T. McPherson, A. Moore, R. Katugampola, M. Kalavala, D. Al‐Ismail, L. Richards, V. Jones, S. Batul Syed, M. Glover, J. Hughes, E. Anderson, B. Hughes, I. Helbling, R. Murphy
Journal: British Journal of Dermatology (2015)
Alteration of the pharmacokinetics of high-dose ara-C by its metabolite, high ara-U in patients with acute leukemia.
Authors: R L Capizzi, J L Yang, E Cheng, T Bjornsson, D Sahasrabudhe, R S Tan, Y C Cheng
Journal: Journal of Clinical Oncology (1983)

The pharmacokinetics of high-dose cytosine arabinoside (HiDAC) given as a three-hour intravenous infusion at 3 g/m2 were studied in five patients with acute leukemia during relapse and/or remission of their disease. Apparent steady state plasma levels of ara-C during 13 infusions averaged 115 +/- 32 microM. Upon cessation of the infusion, cytosine arabinoside (ara-C) was rapidly cleared from the plasma. The apparent postinfusion kinetics of ara-C were triexponential with a distribution half-life of 16 minutes and elimination half-lives of 1.8 hours and six hours. Total clearance averaged 86 L per hour and mean residence time averaged 0.47 hours. Disease status (relapse or remission) had no apparent effect on the pharmacokinetic characteristics of ara-C. Peak levels of ara-U averaged 310 microM and the metabolite had an average apparent elimination half-life of 3.75 hours. Despite the persistence of ara-U at about 100 microM at the time of administration of subsequent infusions of ara-C, there was no further accumulation of ara-U in the plasma with repetitive infusions of HiDAC. In vitro studies indicate that ara-U can exert an inhibitory effect on deoxycytidine (dCyd) deaminase activity. The ratio of the Ki of ara-U to the Km of ara-C for cytidine (Cyd)-dCyd deaminase is 40:1; however, during the gamma phase of ara-C elimination, the ratio of ara-U:ara-C in plasma is at least 100:1. Thus, a retardation of systemic catabolism of ara-C by ara-U is possible. Two to three hours after the termination of the HiDAC infusion, the ara-C cerebrospinal fluid: plasma ratio is 1-3:1, a feature of potential therapeutic significance. The slower elimination of ara-C from the CSF may also contribute to the plasma gamma half-life.
Genomic landscapes of breast fibroepithelial tumors
Authors: Jing Tan, Choon Kiat Ong, Weng Khong Lim, Cedric Chuan Young Ng, Aye Aye Thike, Ley Moy Ng, Vikneswari Rajasegaran, Swe Swe Myint, Sanjanaa Nagarajan, Saranya Thangaraju, Sucharita Dey, Nur Diyana Md Nasir, Giovani Claresta Wijaya, Jing Quan Lim, Dachuan Huang, Zhimei Li, Bernice Huimin Wong, Jason Yong Sheng Chan, John R McPherson, Ioana Cutcutache, Gregory Poore, Su Ting Tay, Wai Jin Tan, Thomas Choudary Putti, Buhari Shaik Ahmad, Philip Iau, Ching Wan Chan, Anthony P H Tang, Wei Sean Yong, Preetha Madhukumar, Gay Hui Ho, Veronique Kiak Mien Tan, Chow Yin Wong, Mikael Hartman, Kong Wee Ong, Benita K T Tan, Steven G Rozen, Patrick Tan, Puay Hoon Tan, Bin Tean Teh
Journal: Nature Genetics (2015)
Multivariate Analysis of Glycosylated Haemoglobin in Insulin-Treated Diabetics
Authors: D F Child, Jane Wood, P R Hudson, C P Williams, D R Roberts, C Smith
Journal: Journal of the Royal Society of Medicine (1985)

Glycosylated haemoglobin (HbAl), as an assessment of overall control, was estimated in 858 insulin-treated diabetics attending for changeover to U100 insulin in North East Wales. Details of age, sex, duration of diabetes, insulin regimen and monitoring method were recorded. Multivariate analysis revealed lower HbAl in patients receiving twice-daily (mean 11.01) as compared with once-daily insulin (11.42, P=0.011), but no difference was found between urine and blood glucose testers when other variables were taken into consideration. HbAl was lower in men (mean 10.94) compared with women (mean 11.39, P=0.004) and there was a positive correlation of HbAl in men with age (P= 0.046) and in women with duration of disease (P=0.005).
Abstract 18043: Time Divergence Between Osteoblast Transformation and Aortic Valve Calcification; an Important Insight Into the Possible Treatment for Valve Calcification
Authors: Mony Shuvy, Suzan Abedat, Ronen Beeri, Nitsan Duvdevan, Mahmoud Mustafa, Chaim Lotan
Journal: Circulation (2010)

Introduction: Aortic valve calcification (AVC) is a highly regulated process involving osteoblast transformation in valve tissue. Medical therapy has thus far failed to stop or revert this process....
Perception of lung function in asthmatics by visual analogue scale
Authors: Nicholas Tayler, Judith Holloway, Kerry Gove, Chris Grainge
Journal: European Respiratory Journal (2014)

Introduction: The majority of asthmatics self-manage their condition in relation to their symptoms, so it is important that the patient can recognise when their lung function is deteriorating. This can be quantified by a visual analogue scale (VAS). VAS has been shown to correlate to lung function, but the repeatability has not been examined.  Aim: To discover whether asthmatic patients can use VAS as an accurate and repeatable indicator of their lung function.  Methods: 17 patients were recruited and underwent two methacholine challenges and an allergen challenge. At each challenge stage the patient was asked to indicate their lung function by marking a 200mm horizontal line labelled “No asthma symptoms” at one end and “Worst possible asthma symptoms” at the other.  Results: In all three challenges decreasing FEV1 correlated with increased VAS measurements showing that patients can perceive changes in lung function (R=0.572 p  The variability between VAS scores for the whole study population was high (R2= 0.33), which was dramatically reduced by examining each patient individually (mean R2=0.87 95%CI=0.82 to 0.91).  Changes in gradient of FEV1:VAS were examined in each patient between challenges to test repeatability, and no significant difference was found between gradients (p=0.43, p=0.20, p=0.26 ) indicating this may be a repeatable measure.  Conclusions: We can conclude that asthmatics can accurately perceive their lung function, and that this may be repeatable if calibrated to the individual patient. Further study is warranted to determine if this would make a suitable monitoring tool, which could be a simpler tool than the current BTS recommended questionnaires.
Weekend hospital death rates are not just an English problem:
Authors: Jacqui Wise
Journal: BMJ (2015)

The raised risk of death after admission to hospital at a weekend is not just a problem in England but is common in other developed countries, new research published in BMJ Quality and Safety shows.1

Researchers examined data from the Global Comparators project covering almost three million admissions to 28 city hospitals in England, Australia, the Netherlands, and the United States during 2009-12.

The risk of dying within 30 days was higher …
Graphene Oxides Show Angiogenic Properties
Authors: Sudip Mukherjee, Pavithra Sriram, Ayan Kumar Barui, Susheel Kumar Nethi, Vimal Veeriah, Suvro Chatterjee, Kattimuttathu Ittara Suresh, Chitta Ranjan Patra
Journal: Advanced Healthcare Materials (2015)

Angiogenesis, a process resulting in the formation of new capillaries from the pre‐existing vasculature plays vital role for the development of therapeutic approaches for cancer, atherosclerosis, wound healing, and cardiovascular diseases. In this report, the synthesis, characterization, and angiogenic properties of graphene oxide (GO) and reduced graphene oxide (rGO) have been demonstrated, observed through several in vitro and in vivo angiogenesis assays. The results here demonstrate that the intracellular formation of reactive oxygen species and reactive nitrogen species as well as activation of phospho‐eNOS and phospho‐Akt might be the plausible mechanisms for GO and rGO induced angiogenesis. The results altogether suggest the possibilities for the development of alternative angiogenic therapeutic approach for the treatment of cardiovascular related diseases where angiogenesis plays a significant role.
Long-term outcomes of autologous stem cell transplantation for follicular non-Hodgkin’s lymphoma: Effect of histologic grade
Authors: J. Vose, P. Bierman, J. Lynch, G. Bociek, J. Armitage
Journal: Journal of Clinical Oncology (2005)

6567 Background: The potential for long term disease-free survival for patients with recurrent follicular lymphoma receiving high-dose chemotherapy and an autologous hematopoietic stem cell transplant is unknown. Few large studies with extensive follow-up are available for analysis. Methods: Between 7/87 and 6/03, 248 patients (pts) with recurrent follicular non-Hodgkin’s lymphoma (NHL) were treated with high-dose chemotherapy and an autologous stem cell transplant. The median age of the patients was 47 (range 20–67). Sixty-four pts had follicular grade I NHL (FL1), 98 (40%) had follicular grade II (FL2) and 86 (35%) had follicular grade III (FL3). The majority of the patients, 189 (76%) were undergoing transplant > 12 months from the time of their original diagnosis. Pts had received a median of 2 prior chemotherapies and 82% of the patients were chemosensitive to their last chemotherapy regimen. Sixty-seven (27%) of the patients had an elevated lactic dehydrogenase (LDH) at the time of transplant and 81 (35%) of the pts had bone marrow involvement with NHL at the time of transplant. One hundred and ten patients received a chemotherapy only high-dose regimen, 99 received a chemotherapy/total body irradiation regimen, and 39 received a chemotherapy/monoclonal antibody based transplant regimen. Results: The median follow-up of surviving pts is 6.0 years (range 1.0 to 16.0 years). One hundred seventeen patients (47%) have progressed; 80 of whom have subsequently died and 37 remain alive after progression. Thirty-three (13%) have died without NHL progression due to other causes. The overall 5 year event-free survival (EFS) is 44% and the 5 year overall survival (OS) is 63%. The 5 year EFS by histologic grade is FL1 (47%), FL2 (48%), FL3 (36%) (p=0.21). The 5 year OS by histologic type is FL1 (61%), FL2 (70%), FL3 (57%) (p=0.35). Conclusions: Long-term EFS is possible following high-dose chemotherapy and autologous stem cell transplantation for follicular lymphoma. Histologic grade of the follicular lymphoma does not effect the results of the transplant. However, the timing of the transplant does effect outcome with the best results seen in patients in first or second relapse. No significant financial relationships to disclose.
Unique hemodynamic profile of HIV patients with portal hypertension: Comparison with HIV-associated PAH and porto-pulmonary hypertension
Authors: Masayuki Nigo, Gianfranco Tulliano, Roxana Sulica
Journal: European Respiratory Journal (2012)

Introduction and Objectives   HIV-associated PAH (HIV-PAH) and porto-pulmonary hypertension (PoPHTN) have well described cardiopulmonary profiles. However, little is known about the hemodynamic characteristics when both conditions coexist (HIV-PoPHTN). We hypothesise that in these cases right heart catheterisation (RHC) findings differ from those with HIV-PAH and PoPHTN alone.   Methods   We performed a retrospective analysis of consecutive patients with HIV-PAH, PoPHTN and HIV-PoPHTN and compared their baseline RHC results: right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary artery occlusion pressure (PAOP), cardiac index (CI), pulmonary vascular resistance index (PVRI) and pulmonary artery saturation (PAsat). One-way ANOVA and Student t-test between groups were used for analysis.   Results   We identified 93 patients; 37 HIV-PAH, 40 PoPHTN and 16 HIV-PoPHTN. Table 1 presents their hemodynamic characteristics.  Table 2 shows comparisons between two groups.   Conclusion   HIV-PoPHTN has a similar hemodynamic profile to HIV-PAH. Both groups have worse RV function compared to PoPHTN.
Where do UK health services researchers publish their findings?
Authors: Nick Black, Sally C Davies
Journal: Journal of the Royal Society of Medicine (1999)

Health services research has emerged as the third vital requirement for understanding and improving health care, alongside basic science and clinical research. This has coincided with more stringent management of research, in particular by funding bodies. The latter are seeking to use bibliographic databases to aid the monitoring of the output of their investments. The principal source of data in the UK is the Research Outputs Database (ROD) set up by the Wellcome Trust primarily to monitor basic and clinical research. Health services researchers' output is difficult to monitor in view of the large number and wide variety of journals in which they publish. In addition, nearly half the journals (representing 35% of the articles) are not currently covered by the ROD. Funding bodies will underestimate the quantity of health services researchers' output unless they take these findings into account.
Graves' Disease
Authors: Gregory A Brent
Journal: New England Journal of Medicine (2008)

A 23-year-old woman has palpitations. Over the past 6 months, she has had a 10-lb (4.5-kg) weight loss. Her pulse is 119 beats per minute, and blood pressure is 137/80 mm Hg. Her thyroid gland is diffusely enlarged. She has eyelid lag but no proptosis. The level of thyrotropin is 0.02 μU per ml (normal range, 0.35 to 4.50), and free thyroxine is 4.10 ng per deciliter (normal range, 0.89 to 1.76). How should she be further evaluated and treated?
The Dilemma of Antenatal HIV Testing: What Goes on in the European Community?
Authors: C N Hudson, A Bergenström, E Bell, E McCann, L Sherr
Journal: Journal of the Royal Society of Medicine (1999)

The aura of therapeutic nihilism that embraced the diagnosis of HIV seropositivity in symptom-free individuals at the beginning of the 1990s has largely been dispersed, so that official advice is that on balance it is better to know than not to knowl2. Nowhere is this more true than in the sphere of maternity care. In addition to the basic benefits to the woman herself, there is the important issue of mother-tochild transmission3. Not only has a serious and usually lethal infection of infants and children been recognized, but also we have now learned that transmission of this disorder from mother to child can largely be prevented by measures taken during late pregnancy, during labour and in the early neonatal period. These include prophylactic anti-retroviral therapy given to the mother4, avoidance of breastfeeding5 and caesarean section6. If we wish to achieve a substantial reduction in HIV transmission from mother to child, a fundamental requirement is to know the sero-status of the mother in time for appropriate interventions. This requirement has provoked a maelstrom of ethical, legal, special-interest, professional and economic arguments in an area already made tempestuous by issues of confidentiality, insurance loading, discrimination and minority rights, together with the move towards 'demedicalization'7.