tbuckley/cabot-search huggingface dataset:
Adoption of Spironolactone Therapy for Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction in the United States, 1998–2001
Authors: Frederick A. Masoudi, Cary P. Gross, Yongfei Wang, Saif S. Rathore, Edward P. Havranek, JoAnne Micale Foody, Harlan M. Krumholz
Journal: Circulation (2005)

Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure. We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure.This is a study of serial cross-sectional samples of Medicare beneficiaries > or =65 years old discharged after hospitalization for the primary diagnosis of heart failure and with left ventricular systolic dysfunction. The first sample was discharged before (April 1998 to March 1999, n=9758) and the second sample after (July 2000 to June 2001, n=9468) publication of RALES in September 1999. We assessed spironolactone prescriptions at hospital discharge in patient groups defined by enrollment criteria for the trial. Using multivariable logistic regression, we identified factors independently associated with prescriptions not meeting these criteria. Spironolactone use increased >7-fold (3.0% to 21.3% P<0.0001) after RALES. Of patients meeting enrollment criteria, 24.1% received spironolactone, as compared with 17.4% of those not meeting the criteria. Of all prescriptions after RALES, 30.9% were provided to patients not meeting enrollment criteria. Spironolactone was prescribed to 22.8% of patients with a serum potassium value > or =5.0 mmol/L, to 14.1% with a serum creatinine value > or =2.5 mg/dL, and to 17.3% with severe renal dysfunction (estimated glomerular filtration rate <30 mL.min(-1).1.73 m(-2)). In multivariable analyses, factors associated with prescriptions not meeting enrollment criteria included advanced age, noncardiovascular comorbidities, discharge to skilled nursing facilities, and care provided by physicians without board certification.Spironolactone prescriptions increased markedly after the publication of RALES, and many treated patients were at risk for hyperkalemia. Simultaneously, many patients who might have benefited were not treated. These findings demonstrate the importance of balancing efforts to enhance use among appropriate patients and minimizing use in patients at risk for adverse events.
Serum Sex Hormone Levels After Menopause and Subsequent Breast Cancer
Authors: F. Berrino, P. Muti, A. Micheli, G. Bolelli, V. Krogh, R. Sciajno, P. Pisani, S. Panico, G. Secreto
Journal: JNCI Journal of the National Cancer Institute (1996)

BackgroundHigh levels of androgens and estrogens have been reported to be associated with breast cancer. However, the multiplicity of factors that influence hormone levels and methodologic issues complicate the study of the relationship between steroid sex hormones and breast cancer.
Immunogenicity of 2 Serogroup B Outer-Membrane Protein Meningococcal Vaccines
Authors: J W Tappero, R Lagos, A M Ballesteros, B Plikaytis, D Williams, J Dykes, L L Gheesling, G M Carlone, E A Høiby, J Holst, H Nøkleby, E Rosenqvist, G Sierra, C Campa, F Sotolongo, J Vega, J Garcia, P Herrera, J T Poolman, B A Perkins
Journal: JAMA (1999)

ContextMeningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group.ObjectiveTo evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy.DesignDouble-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994.SettingSantiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993.ParticipantsInfants younger than 1 year (n=187), children aged 2 to 4 years (n=183), and adults aged 17 to 30 years (n=173).InterventionParticipants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3.Main Outcome MeasureImmune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer.ResultsChildren and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen.ConclusionsThese data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain–specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.
Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide
Authors: P W Lowry
Journal: Gut (2001)

<h3>AIM</h3> We evaluated the effect of coadministration of sulphasalazine, mesalamine, and balsalazide on the pharmacokinetics and pharmacodynamics of azathioprine and 6-mercaptopurine. <h3>METHODS</h3> Thirty four patients with Crohn9s disease receiving azathioprine or 6-mercaptopurine were enrolled in an eight week non-randomised parallel group drug interaction study and treated with mesalamine 4 g/day, sulphasalazine 4 g/day, or balsalazide 6.75 g/day. The primary outcome measure was the occurrence of clinically important leucopenia during the study, defined separately as total leucocyte counts &lt;3.0 x 10<sup>9</sup>/l and ⩽3.5×10<sup>9</sup>/l. Whole blood 6-thioguanine nucleotide concentrations were determined. <h3>RESULTS</h3> Three patients could not be evaluated for the primary outcome measure. In the remaining 31 patients, the frequency of total leucocyte counts &lt;3.0 and ⩽3.5 were: 1/10 and 5/10 in the mesalamine group; 1/11 and 6/11 in the sulphasalazine group; and 0/10 and 2/10 in the balsalazide group. There were significant increases in mean whole blood 6-thioguanine nucleotide concentrations from baseline at most time points in the mesalamine and sulphasalazine groups but not in the balsalazide group. <h3>CONCLUSIONS</h3> In patients with Crohn9s disease receiving azathioprine or 6-mercaptopurine, coadministration of mesalamine, sulphasalazine, and possibly balsalazide results in an increase in whole blood 6-thioguanine nucleotide concentrations and a high frequency of leucopenia.
DNA polymerase activity in rheumatoid synovial membranes.
Authors: M Norval, M M Ogilvie, B P Marmion
Journal: Annals of the Rheumatic Diseases (1975)

RNAase-sensitive DNA polymerase activity was demonstrated in synovial membrane preparations from 23 out of 25 rheumatoid arthritis patients. Control groups consisted of twelve patients with osteoarthrosis, four with secondary osteoarthrosis, and twelve with other conditions. The last group showed no activity, while the results with the other two groups were varied. The properties of the polymerase enzyme, such as its stimulation by synthetic templates and inhibition by actinomycin D, were not consistent with it being associated with an oncogenic virus; it seems to be more like that found in stimulated normal human lymphocytes, described as an RNA-primed DNA-directed DNA polymerase.
Childhood Sibling Relationships as a Predictor of Major Depression in Adulthood: A 30-Year Prospective Study
Authors: Robert J Waldinger, George E Vaillant, E John Orav
Journal: American Journal of Psychiatry (2007)

Objective: The authors examined the quality of sibling relationships in childhood as a predictor of major depression in adulthood. Method: Study subjects were 229 men selected for mental and physical health and followed from ages 20 through 50 and beyond as part of a study of adult psychosocial development. Data were obtained from interviews with participants and their parents at intake and from follow-up interviews and self-report questionnaires completed by participants at regular intervals. These data were used to rate the quality of relationships with siblings, the quality of parenting received in childhood, and family history of depression as well as the occurrence, by age 50, of major depression, alcoholism, and use of mood-altering drugs (tranquilizers, sleeping pills, and stimulants). Results: Poorer relationships with siblings prior to age 20 and a family history of depression independently predicted both the occurrence of major depression and the frequency of use of mood-altering drugs by age 50, even after adjustment for the quality of childhood relationships with parents. Poor relationships with parents in childhood did not predict the occurrence of depression by age 50 when family history of depression and the quality of relationships with siblings were taken into account. Quality of sibling relationships and family history of depression did not predict later alcohol abuse or dependence. Conclusions: Poor sibling relationships in childhood may be an important and specific predictor of major depression in adulthood. Further study of links between childhood sibling relationships and adult depression is warranted.
You can't always get what you want, but if you try sometimes (with two tests—TST and IGRA—for tuberculosis) you get what you need: Figure 1
Authors: Kevin L Winthrop, Michael E Weinblatt, Charles L Daley
Journal: Annals of the Rheumatic Diseases (2012)

There is little disagreement that screening for latent tuberculosis (TB) infection (LTBI) prior to biologic therapy is necessary. Unfortunately, there is much less agreement with regard to how best to accomplish this task. A decade ago, we had just one screening tool, the tuberculin skin test (TST), and screening algorithms for such patients were presumably straightforward. With the recent introduction and fairly widespread adoption of interferon γ release assays (IGRAs), clinicians have a new tool that theoretically improves their ability to screen. However, since the introduction of IGRAs, the studies conducted within the biologic therapy setting that compare IGRAs and TST have been fraught with a lack of statistical power and heterogeneity (eg, differing underlying inflammatory disease states, variable immunosuppressive therapies or underlying BCG status),1 ,2 and firm conclusions regarding the relative sensitivity of these two screening tests (Quantiferon-Gold TB In-tube (QFT-IT) or the T-SPOT. TB assay) is only now becoming more clear. Kleinert et al and Mariette et al have published two studies to overcome some of these limitations,3 ,4 and along with other data, we believe the time has arrived to offer a screening algorithm that is practical in its approach. While we believe IGRAs have become the preferred screening tool in this setting, unfortunately these recent data argue that an IGRA alone is insufficient to identify all patients at risk.

TB is rumoured to infect nearly a third of the world's population. The risk of LTBI progression to active TB is clearly heightened by antitumour necrosis factor α (anti-TNF) therapy, and the absolute risk of this complication is driven by the background prevalence of LTBI in a particular region and the probability of infection in an individual. Within low prevalence countries, rates of anti-TNF-associated TB are typically 5–10-fold higher than background general populations, …
Psychometric properties of the Rheumatoid Arthritis Disease Activity Index (RADAI) in a cohort of consecutive Dutch patients with RA starting anti-tumour necrosis factor treatment
Authors: M M Veehof, P M ten Klooster, E Taal, P L C M van Riel, M A F J van de Laar
Journal: Annals of the Rheumatic Diseases (2007)

To examine the psychometric properties of the self-administered Dutch Rheumatoid Arthritis Disease Activity Index (RADAI) and its short form (RADAI-SF) in patients with rheumatoid arthritis starting anti-tumour necrosis factor treatment.Internal consistency was assessed with Cronbach's alpha. A confirmatory factor analysis (CFA) was carried out to test the single-factor structure. Construct validity was examined by correlating RADAI and RADAI-SF scores with Disease Activity Score in 28 joints (DAS28). Internal responsiveness was evaluated with the paired t test and the standardised response mean (SRM). External responsiveness was assessed with receiver operating characteristic analysis and the SRM, using the EULAR response criterion as external criterion. Change scores were correlated with changes in DAS28.At baseline and after 3 months' treatment, respectively, 191 and 171 patients completed the RADAI. The internal consistency of the RADAI and the RADAI-SF was satisfactory. CFAs confirmed the single-factor structure of both RADAI versions, but the short form provided the best model fit. Moderate correlations were found with the DAS28. SRMs of the RADAI and the RADAI-SF were, respectively, 0.76 and 0.80. Both versions had moderate accuracy to distinguish responders from non-responders. Changes scores were moderately correlated with DAS28 change scores.This study showed satisfactory psychometric properties of the Dutch version of the RADAI. Omission of the tender joint count (RADAI-SF) produced comparable results and is justified for research purposes. The tender joint count might be useful as additional clinical information in patient management.
A phase I trial of human corticotropin-releasing factor (hCRF) in patients with peritumoral brain edema
Authors: M A Villalona-Calero, J Eckardt, H Burris, M Kraynak, S Fields-Jones, C Bazan, J Lancaster, T Hander, R Goldblum, L Hammond, A Bari, R Drengler, M Rothenberg, G Hadovsky, D D Von Hoff
Journal: Annals of Oncology (1998)

Human corticotropin-releasing factor (hCRF) is an endogenous peptide responsible for the secretion and synthesis of corticosteroids. In animal models of peritumoral brain edema, hCRF has significant anti-edematous action. This effect, which appears to be independent of the release of adrenal steroids, appears mediated by a direct effect on endothelial cells. We conducted a feasibility and phase I study with hCRF given by continuous infusion to patients with brain metastasis.Peritumoral brain edema documented by MRI and the use of either no steroids or stable steroid doses for more than a week were required. MRIs were repeated at completion of infusion and estimations by dual echo-image sequence (Proton density and T2-weighted images) of the amount of peritumoral edema were performed. The study was performed in two stages. In the feasibility part, patients were randomized to receive either 0.66 or 1 microgram/kg/h of hCRF or placebo over 24 hours. The second part was a dose finding study of hCRF over 72 hours at escalating doses.Seventeen patients were enrolled; only one was receiving steroids (stable doses) at study entrance; dose-limiting toxicity (hypotension) was observed at 4 micrograms/kg/h x 72 hours in two out of four patients, while zero of five patients treated at 2 micrograms/kg/h developed dose-limiting toxicities. Flushing and hot flashes were also observed. Improvement of neurological symptoms and/or exam were seen in 10 patients. Only small changes were detected by MRI. Improvement in symptoms did not correlate with changes in cortisol levels, and changes in cortisol levels were not correlated with changes in peritumoral edema.hCRF is well tolerated in doses up to 2 micrograms/kg/h by continuous infusion x 72 hours. Hypotension limits administration of higher doses. The observation of clinical benefit in the absence of corticosteroids suggests hCRF may be an alternative to steroids for the treatment of patients with peritumoral brain edema. Further exploration of this agent in efficacy studies is warranted.
466 PREDICTORS OF SUSTAINED VIROLOGIC RESPONSE AMONG TREATMENT-NAIVE PATIENTS WITH HEPATITIS C VIRUS GENOTYPE 1 WHEN TREATED WITH BOCEPREVIR (BOC) PLUS PEGINTERFERON ALFA-2B/RIBAVIRIN (PR)
Authors: K.R. Reddy, S. Bruno, L. Rossaro, N. Ravendhran, M.P. Pauly, N. Boparai, V. Sniukiene, C.A. Brass, J.K. Albrecht, F. Poordad, I.M. Jacobson
Journal: Journal of Hepatology (2011)
Impaired Anaphylactic Responses with Intact Sensitivity to Endotoxin in Mice Lacking a Platelet-activating Factor Receptor
Authors: Satoshi Ishii, Tomoyuki Kuwaki, Takahide Nagase, Kazushige Maki, Fumi Tashiro, Shinji Sunaga, Wei-Hua Cao, Kazuhiko Kume, Yoshinosuke Fukuchi, Koichi Ikuta, Jun-ichi Miyazaki, Mamoru Kumada, Takao Shimizu
Journal: The Journal of Experimental Medicine (1998)

Platelet-activating factor (PAF) is a potent phospholipid mediator with diverse biological activities in addition to its well-known ability to stimulate platelet aggregation. Pharmacologic studies had suggested a role for PAF in pregnancy, neuronal cell migration, anaphylaxis, and endotoxic shock. Here we show that disruption of the PAF receptor gene in mice caused a marked reduction in systemic anaphylactic symptoms. Unexpectedly, however, the PAF receptor–deficient mice developed normally, were fertile, and remained sensitive to bacterial endotoxin. These mutant mice clearly show that PAF plays a dominant role in eliciting anaphylaxis, but that it is not essential for reproduction, brain development, or endotoxic shock.
MOTHER-TO-INFANT TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: ASSOCIATION WITH PREMATURITY OR LOW ANTI-gp120
Authors: JamesJ. Goedert, JamesE. Drummond, HowardL. Minkoff, Roy Stevens, WilliamA. Blattner, Hermann Mendez, Marjorie Robert-Guroff, Susan Holman, Arye Rubinstein, Anne Willoughby, SheldonH. Landesman
Journal: The Lancet (1989)
Response to: What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?
Authors: Trevor K Rogers, William Hamilton, Angela Tod, Richard Neal
Journal: Thorax (2014)

We appreciate the paper by O'Dowd et al 1 as an interesting contribution to the literature concerning the primary care diagnosis of lung cancer. By concentrating on those patients dying soon after diagnosis, this paper is addressing the issue of access to care of patients with lung cancer who are already gravely ill. The disappointingly low chest X-ray (CXR) referral rates (we calculate obtained in only 40.2% and 50.4% of the patients attending with medium/high frequency and dying before and after 90 days, respectively) may represent irregular recording of CXR requests in The Health Improvement Network (THIN). Electronic research databases store their data in …
Association Between Nonsteroidal Anti-Inflammatory Drug Use and the Incidence of Pancreatic Cancer
Authors: K. E. Anderson
Journal: JNCI Journal of the National Cancer Institute (2002)

Laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit pancreatic cancer, but epidemiologic data to support this finding are limited. We conducted a prospective study from 1992 through 1999 among 28 283 postmenopausal women who lived in Iowa to examine the association between the self-reported use of aspirin and other NSAIDs and the incidence of pancreatic cancer. Eighty incident cases of pancreatic cancer were identified during 7 years of follow-up. The multivariate-adjusted relative risk of pancreatic cancer associated with any current use of aspirin versus no use was 0.57 (95% confidence interval = 0.36 to 0.90). There was a trend of decreasing risk of pancreatic cancer incidence with increasing frequency of aspirin use per week (Ptrend = .005). Nonaspirin NSAID use was not associated with incident pancreatic cancer. These data indicate that aspirin might be chemopreventive for pancreatic cancer.
Rationale and design of Ferinject® Assessment in patients with IRon deficiency and chronic Heart Failure (FAIR‐HF) study: a randomized, placebo‐controlled study of intravenous iron supplementation in patients with and without anaemia
Authors: Stefan D. Anker, Josep Comin Colet, Gerasimos Filippatos, Ronnie Willenheimer, Kenneth Dickstein, Helmut Drexler, Thomas F. Lüscher, Claudio Mori, Barbara von Eisenhart Rothe, Stuart Pocock, Philip A. Poole‐Wilson, Piotr Ponikowski
Journal: European Journal of Heart Failure (2009)
MeV+R: using MeV as a graphical user interface for Bioconductor applications in microarray analysis
Authors: Vu T Chu, Raphael Gottardo, Adrian E Raftery, Roger E Bumgarner, Ka Yeung
Journal: Genome biology (2008)

We present MeV+R, an integration of the JAVA MultiExperiment Viewer program with Bioconductor packages. This integration of MultiExperiment Viewer and R is easily extensible to other R packages and provides users with point and click access to traditionally command line driven tools written in R. We demonstrate the ability to use MultiExperiment Viewer as a graphical user interface for Bioconductor applications in microarray data analysis by incorporating three Bioconductor packages, RAMA, BRIDGE and iterativeBMA.
The generation and function of soluble apoE receptors in the CNS
Authors: G William Rebeck, Mary Jo LaDu, Steven Estus, Guojun Bu, Edwin J Weeber
Journal: Molecular Neurodegeneration (2006)

Abstract More than a decade has passed since apolipoprotein E4 ( APOE-ε4 ) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein system integrates into the puzzle of AD etiology. The specific pathological actions of apoE4, methods of modulating apolipoprotein E4-associated risk, and possible roles of apoE in normal synaptic function are still being debated. These critical questions will never be fully answered without a complete understanding of the life cycle of the apolipoprotein receptors that mediate the uptake, signaling, and degradation of apoE. The present review will focus on apoE receptors as modulators of apoE actions and, in particular, explore the functions of soluble apoE receptors, a field almost entirely overlooked until now.
Drug points: Purpuric rash with donepezil treatment
Authors: C A Bryant, E Ouldred, S H D Jackson, M T Kinirons
Journal: BMJ (1998)

The most commonly reported adverse events with donepezil are gastrointestinal (nausea, diarrhoea, and constipation).1 Donepezil has been licensed in the United Kingdom since April 1997, and from April to December 1997 only seven adverse reactions affecting the skin were reported through the yellow card adverse drug reaction reporting scheme (Committee on Safety of Medicines, personal communication). To our knowledge, this is the first report of …
Adjuvant therapy in primary GIST: state-of-the-art
Authors: P. Reichardt, J-Y. Blay, I. Boukovinas, T. Brodowicz, J.M. Broto, P.G. Casali, M. Decatris, M. Eriksson, H. Gelderblom, P. Kosmidis, A. Le Cesne, A.L. Pousa, M. Schlemmer, J. Verweij, H. Joensuu
Journal: Annals of Oncology (2012)