tbuckley/cabot-search huggingface dataset:
Is INTERdisciplinary COMmunity-based COPD management (INTERCOM) cost-effective?
Authors: M. Hoogendoorn, C. R. van Wetering, A. M. Schols, M. P. M. H. Rutten-van Mölken
Journal: European Respiratory Journal (2009)

The study aimed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease (COPD) management in patients with COPD. We conducted a cost-effectiveness analysis alongside a 2-yr randomised controlled trial, in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care. The INTERCOM programme consisted of exercise training, education, nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses. All-cause resource use during 2 yrs was obtained by self-report and from hospital and pharmacy records. Health outcomes were the St George's Respiratory Questionnaire (SGRQ), exacerbations and quality-adjusted life years (QALYs). The INTERCOM group had 30% (95% CI 3–56%) more patients with a clinically relevant improvement in SGRQ total score, 0.08 (95% CI -0.01–0.18) more QALYs per patient, but a higher mean number of exacerbations, 0.84 (95% CI -0.07–1.78). Mean total 2-yr costs were €2,751 (95% CI -€632–€6,372) higher for INTERCOM than for usual care, which resulted in an incremental cost-effectiveness ratio of €9,078 per additional patient with a relevant improvement in SGRQ or €32,425 per QALY. INTERCOM significantly improved disease-specific quality of life, but did not affect exacerbation rate. The cost per QALY ratio was moderate, but within the range of that generally considered to be acceptable.
Anorectal Cancer and Homosexuality-Reply
Authors: Preetham Kondlapoodi
Journal: JAMA (1983)

<h3>In Reply.—</h3> Dr Voeller's hypothesis on the carcinogenic role of oil lubricants in anorectal carcinoma is interesting. From the literature cited, I would tend to share Dr Voeller's concern that these substances may be possible causes of this cancer in homosexual men. He suggests a way to solve the etiologic puzzle by comparing populations with different sexual preferences and habits, eg, choice of lubricant. While such studies may provide valuable clues, the incidence of anal cancer in male homosexuals is so low (1982;247:1988-1990) that patient populations sufficient in numbers for adequate statistical analyses may be difficult to obtain. Indeed, I was able to gather only six cases of cloacogenic carcinoma of the anorectum in male homosexuals from the world literature for a recent publication.<sup>1</sup>The cloacogenic variety of anorectal cancer is the kind that has been described in this population. Recently, Li and associates<sup>2</sup>from the National Cancer
Presence of hypochlorite-modified proteins in human atherosclerotic lesions.
Authors: L J Hazell, L Arnold, D Flowers, G Waeg, E Malle, R Stocker
Journal: Journal of Clinical Investigation (1996)

Oxidation of LDL may contribute to atherogenesis, though the nature of the in vivo oxidant(s) remains obscure. Myeloperoxidase, the enzyme responsible for hypochlorous acid/hypochlorite (HOCl) production in vivo, is present in active form in human atherosclerotic lesions, and HOCl aggregates and transforms LDL into a high-uptake form for macrophages in vitro. Here we demonstrate HOCl-modified proteins in human lesions using an mAb raised against HOCl-modified LDL that recognizes HOCl-oxidized proteins but does not cross-react with Cu2+-, malondialdehyde-, or 4-hydroxynonenal-modified LDL. This antibody detected significantly more material in advanced atherosclerotic lesions than normal arteries, even though azide and methionine were included during sample work-up to inhibit myeloperoxidase and to scavenge HOCl. The epitope(s) recognized was predominantly cell associated and present in monocyte/macrophages, smooth muscle, and endothelial cells. The intima and cholesterol clefts stained more heavily than the center of the thickened vessels; adventitial staining was apparent in some cases. Immunostaining was also detected in a very early lesion from an accident victim, beside healthy areas that were unreactive. LDL oxidized by HOCl in vitro, but not native LDL, effectively competed with the epitopes in lesions for antibody binding. Density centrifugation of plaque homogenates and Western blot analysis showed that, in the apo B-containing lipoprotein fraction, the mAb recognized protein(s) of molecular mass greater than apo B, similar to those produced during oxidation of LDL with HOCl in vitro. Three major proteins were recognized by the anti-HOCl-modified protein antibody but not by an anti-apo B antibody in the apo B-free fraction. Together, these results demonstrate HOCl-oxidized proteins in human atherosclerotic lesions, implicating this oxidant in LDL modification in vivo.
Coffee Consumption and Risk of Cardiovascular Diseases and All-Cause Mortality Among Men With Type 2 Diabetes
Authors: Weili Zhang, Esther Lopez-Garcia, Tricia Y. Li, Frank B. Hu, Rob M. van Dam
Journal: Diabetes Care (2009)

OBJECTIVE Coffee consumption has been linked to detrimental acute metabolic and hemodynamic effects. We investigated coffee consumption in relation to risk of CVDs and mortality in diabetic men. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study including 3,497 diabetic men without CVD at baseline. RESULTS After adjustment for age, smoking, and other cardiovascular risk factors, relative risks (RRs) were 0.88 (95% CI 0.50–1.57) for CVDs (P for trend = 0.29) and 0.80 (0.41–1.54) for all-cause mortality (P for trend = 0.45) for the consumption of ≥4 cups/day of caffeinated coffee compared with those for non–coffee drinkers. Stratification by smoking and duration of diabetes yielded similar results. RRs for caffeine intake for the highest compared with the lowest quintile were 1.02 (0.70–1.47; P for trend = 0.96) for CVDs and 0.96 (0.64–1.44; P for trend = 0.69) for mortality. CONCLUSIONS These data indicate that regular coffee consumption is not associated with increased risk for CVDs or mortality in diabetic men.
Diastolic 'locking' of the mitral valve: possible importance of diastolic myocardial properties.
Authors: D David, E L Michelson, M Naito, C C Chen, M Schaffenburg, L S Dreifus
Journal: Circulation (1986)

The effects of pharmacologically induced changes in myocardial properties on diastolic mitral valve mechanics were studied in five open-chest dogs. After the induction of complete atrioventricular block, the dogs were subjected to a protocol of programmed pacing. During prolonged diastolic pauses, programmed atrial contractions were induced at progressively increasing coupling intervals. Echocardiographically determined mitral valve reopening time was established for each coupling interval in the control state as well as under the influence of calcium or verapamil. Compared with control, calcium caused an increase in myocardial tension from 23.8 +/- 3.0 to 30.0 +/- 4.6 g/cm2 (mean +/- SD, p less than .005) as well as an increase in mean septal contraction and relaxation velocities from 142 +/- 25.9 and 144 +/- 15.2 mm/sec to 188 +/- 21.7 and 174 +/- 19.5 mm/sec, respectively (each p less than .001). Conversely, verapamil caused a decrease in mean myocardial tension from 23.8 +/- 3.0 to 19.4 +/- 5.3 g/cm2 (p less than .001) and in mean septal contraction and relaxation velocities from 142 +/- 25.9 and 144 +/- 15.2 mm/sec to 112 +/- 32.7 and 112 +/- 21.6 mm/sec, respectively (each p less than .001). At every coupling interval, calcium significantly (p less than .01 to .001) prolonged, whereas verapamil significantly shortened (p less than .01 to .001), mitral reopening time compared with the control state. These pharmacologically induced changes in mitral valve mechanics occurred despite variations in left ventricular volume, as well as left ventricular and left atrial pressures that under normal conditions exert opposite effects on mitral valve mechanics.(ABSTRACT TRUNCATED AT 250 WORDS)
Patients With an Unclassified Genetic Variant in the <i>BRCA1</i> or <i>BRCA2</i> Genes Show Different Clinical Features From Those With a Mutation
Authors: Encarna B. Gómez-García, Ton Ambergen, Marinus J. Blok, Arthur van den Wijngaard
Journal: Journal of Clinical Oncology (2005)

To obtain and compare the probabilities of finding a mutation in the BRCA1 or BRCA2 genes, the clinical features, and the family history among patients with an unclassified variant (UV) and those with a pathogenic mutation.The study included 70 patients: 24 with a UV (BRCA1, n = 4; BRCA2, n = 19; both, n = 1), and 46 with a mutation (BRCA1, n = 32; BRCA2, n = 14). Two of the UVs were novel variants; the rest had been reported previously as UVs. Probabilities of finding a mutation were retrospectively obtained using BRCAPRO and Myriad II programs.The probability to detect a mutation was significantly lower in the group of patients with a UV than in those with a mutation (BRCAPRO [mean +/- standard deviation], 0.297 +/- 0.312 v 0.627 +/- 0.315, P = .001; and Myriad II, 0.124 +/- 0.090 v 0.283 +/- 0.176, P = .001, respectively). Independent predictive factors of finding either a UV or a mutation were number of affected relatives (2.9 +/- 1.4 v 4.0 +/- 1.9; P = .039) and number of tumors among relatives (3.3 +/- 1.4 v 4.4 +/- 1.8; P = .031), respectively.The combined data about the predictive models show significant differences between both groups. Individual probabilities can be regarded as a help to guide the clinical management of patients with a UV in those genes. However, a definitive conclusion about the pathogenicity of a UV can not be obtained from the clinical features alone, but only in combination with biochemical and epidemiologic data.
Genetic and environmental influences on objective intermediate asthma phenotypes in Dutch twins
Authors: T. Wu, H.M. Boezen, D.S. Postma, H. Los, P.E. Postmus, H. Snieder, D.I. Boomsma
Journal: European Respiratory Journal (2010)

It is unclear to what extent the same set of environmental or genetic factors regulate objective intermediate asthma phenotypes. We examined heritabilities of these phenotypes and estimated their environmental and genetic overlap. We studied baseline lung function (forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC), bronchial hyperresponsiveness, number of positive skin prick tests (SPT) to 11 allergens, serum total immunoglobulin (Ig)E, number of positive specific IgE tests to four allergens and eosinophil counts. 103 twin pairs were studied (46 monozygotic and 57 dizygotic; mean age: 22.5 yrs, range: 17.0–27.0 yrs). Univariate and bivariate genetic analyses were performed after adjustment for significant covariates. All intermediate asthma phenotypes showed significant heritabilities (47–83%). Most phenotypes were substantially correlated, which was mainly due to shared genetic factors. Pairs of phenotypes with the largest genetic correlations were specific IgE and SPT (0.98), and total IgE with specific IgE (0.87), with SPT (0.72), and with eosinophils (0.62). SPT showed significant environmental correlations with total IgE (0.65), specific IgE (0.70) and bronchial hyperresponsiveness (0.44). Genetic effects explain the majority of the variation in objective intermediate asthma phenotypes. Additionally, correlations between pairs of these traits are also mainly explained by genetic rather than environmental factors.
Levels of depression, anxiety and behavioural problems and frequency of psychiatric disorders in children with chronic idiopathic urticaria
Authors: S. Hergüner, G. Kılıç, S. Karakoç, Z. Tamay, Ü. Tüzün, N. Güler
Journal: British Journal of Dermatology (2010)

Several studies reported that adults with chronic idiopathic urticaria (CIU) frequently exhibit psychiatric comorbidity, most commonly depression and anxiety disorders. However the literature about children is limited.To investigate the frequency of psychiatric disorders and to determine the levels of depression, anxiety and behavioural problems in a group of children with CIU.The study included 27 children with CIU and 27 age- and sex-matched healthy subjects. Psychiatric assessment was done by using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL). The State-Trait Anxiety Inventory for Children (STAI-C), Children's Depression Inventory (CDI) and Child Behavior Checklist (CBCL) were used to examine the levels of depression, anxiety and behavioural behaviours, respectively.The study group had more frequent psychiatric diagnoses than the control group (70% vs. 30%) and the most common psychiatric disorders were social anxiety disorder, separation anxiety disorder and specific phobia. Depression, trait anxiety, internalizing problems, somatic complaints and anxiety/depressed scores were significantly higher in children with CIU. No correlation was found between the severity and duration of illness and psychological functioning.This study showed that children with CIU had high psychiatric morbidity. The results suggest that the psychological status of children with CIU should be screened by clinicians and that an interdisciplinary approach combining dermatological and psychiatric evaluations is necessary for the management of CIU.
278 AUGMENTED HEPATITIS B SPECIFIC T CELL RESPONSE AFTER CLEARANCE OF CHRONIC HEPATITIS B
Authors: A. de Niet, M.J. Tempelmans Plat-Sinnige, R.B. Takkenberg, H.W. Reesink, R.A.W. van Lier, E.M.M. van Leeuwen
Journal: Journal of Hepatology (2011)
Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors
Authors: Pedro Casado, Maria P Alcolea, Francesco Iorio, Juan-Carlos Rodríguez-Prados, Bart Vanhaesebroeck, Julio Saez-Rodriguez, Simon Joel, Pedro R Cutillas
Journal: Genome biology (2013)

Tumor classification based on their predicted responses to kinase inhibitors is a major goal for advancing targeted personalized therapies. Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid leukemia, lymphoma, and multiple myeloma. Mass spectrometry was used to quantify 2,000 phosphorylation sites across three acute myeloid leukemia, three lymphoma, and three multiple myeloma cell lines in six biological replicates. The intensities of the phosphorylation sites grouped these cancer cell lines according to their tumor type. In addition, a phosphoproteomic analysis of seven acute myeloid leukemia cell lines revealed a battery of phosphorylation sites whose combined intensities correlated with the growth-inhibitory responses to three kinase inhibitors with remarkable correlation coefficients and fold changes (> 100 between the most resistant and sensitive cells). Modeling based on regression analysis indicated that a subset of phosphorylation sites could be used to predict response to the tested drugs. Quantitative analysis of phosphorylation motifs indicated that resistant and sensitive cells differed in their patterns of kinase activities, but, interestingly, phosphorylations correlating with responses were not on members of the pathway being targeted; instead, these mainly were on parallel kinase pathways. This study reveals that the information on kinase activation encoded in phosphoproteomics data correlates remarkably well with the phenotypic responses of cancer cells to compounds that target kinase signaling and could be useful for the identification of novel markers of resistance or sensitivity to drugs that target the signaling network.
Clinical Trial Conundrums: More Art Than Science?
Authors: V. Brower
Journal: JNCI Journal of the National Cancer Institute (2009)

a rapidly changing regulatory landscape, new targeted therapies, trials that test endpoints ranging from effi cacy to superiority to noninferiority, and an increasing number of phase II trials being conducted in their stead for U.S. Food and Drug Administration review mean that, in practice, many treatments are now approved on the basis of trials that are not randomized or controlled. Also, sometimes RCTs may not be performed for rare medical conditions for which suffi cient patient accrual is unlikely. “The question of when RCTs should be conducted, and under what conditions they are not needed, has no easy answer and depends on so many different factors,” said Steve Pearson, M.D. , president of the Institute for Clini
The response of atrial natriuretic factor and sodium excretion to dietary sodium challenges in patients with chronic liver disease
Authors: Leonard C. Warner, Peter J. Campbell, Gilles A. Morali, Alexander G. Logan, Karl L. Skorecki, Laurence M. Blendis
Journal: Hepatology (1990)

Despite intensive investigation, the pathogenesis of sodium retention in patients with chronic liver disease is not fully known. We have studied 19 chronic liver disease patients, 13 without (group 1) and six with (group 2) histories of clinical sodium retention (ascites or edema) by varying dietary sodium intake. The patients were placed on a 20 mmol/day constant diet for 1 wk, followed by a constant 100 mmol/day sodium diet for 1 wk under strict metabolic conditions. After 5 days of equilibration on each diet, blood and urine samples were collected for plasma atrial natriuretic factor levels and urinary sodium excretion. Group 1 patients (n = 6) achieved near sodium balance in 5 days on both a 20-mmol (urinary sodium output = 17 ± 3 mmol/day) and a 100-mmol sodium diet (urinary sodium output = 80 ± 5 mmol/day). Atrial natriuretic factor levels in these patients tended to be elevated, but the increase was not significantly greater than that in normal control subjects (10 ± 4 pg/ml to 19 ± 4 pg/ml) on the same diets. In contrast, group 2 patients (n = 5) were in significant positive sodium balance on both the 20 mmol/day sodium diet (mean urinary sodium output = 9.5 ± 3.3 mol/day) and the 100 mmol/day sodium diet (urinary sodium output = 37 ± 13 mmol/day). This occurred despite significantly elevated baseline atrial natriuretic factor levels and a significant increase in plasma atrial natriuretic factor levels after sodium challenge (62 ± 9 pg/ml, p &lt; 0.05) on a 100 mmol/day sodium diet. These results indicate that renal resistance to the natriuretic actions of atrial natriuretic factor occurs in this group of patients with a history of sodium retention. In preascitic, uncomplicated chronic liver disease patients corrected sinusoidal pressure was positively correlated with atrial natriuretic factor levels (n = 13, r = 0.75; p &lt; 0.01). These results suggest that, in these patients, intrasinusoidal portal hypertension may have a role in the development of sodium retention and that sodium homeostasis is maintained on various sodium diets at the expense of a gradual elevation in atrial natriuretic factor levels. (Hepatology 1990;12:460-466).
Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus
Authors: M. Lech, C. Kantner, O. P. Kulkarni, M. Ryu, E. Vlasova, J. Heesemann, D. Anz, S. Endres, K. S. Kobayashi, R. A. Flavell, J. Martin, H.-J. Anders
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Interleukin-1 receptor-associated kinase (IRAK)-M suppresses Toll-like receptor (TLR)-mediated activation of innate immunity during infection. A similar role was hypothesised for IRAK-M in autoimmunity. <h3>Methods</h3> Irak-m-deficient mice were crossed with autoimmune C57BL/6-lpr/lpr mice and detailed phenotype analysis was performed. <h3>Results</h3> Irak-m deficiency converted the mild autoimmune phenotype of C57BL/6-lpr/lpr mice into a massive lymphoproliferative syndrome with lethal autoimmune lung disease and lupus nephritis. Irak-m deficiency induced a number of interferon-related genes, cytokines and plasma cell survival factors in spleen cells of these mice. Irak-m-deficient C57BL/6-lpr/lpr mice showed expansion of autoreactive T cells, dysfunctional regulatory T cells and plasma cells which was associated with increased lupus autoantibody production. TLR7 antagonism almost completely abrogated this phenotype consistent with IRAK-M-mediated suppression of TLR7 signalling in vitro. <h3>Conclusions</h3> These data identify a previously unknown function of IRAK-M—namely, suppression of TLR7-mediated autoimmunity—and mutant IRAK-M as a previously unknown genetic risk for murine SLE.
Maternal Body Mass Index and the Risk of Fetal Death, Stillbirth, and Infant Death
Authors: Dagfinn Aune, Ola Didrik Saugstad, Tore Henriksen, Serena Tonstad
Journal: JAMA (2014)

Evidence suggests that maternal obesity increases the risk of fetal death, stillbirth, and infant death; however, the optimal body mass index (BMI) for prevention is not known.To conduct a systematic review and meta-analysis of cohort studies of maternal BMI and risk of fetal death, stillbirth, and infant death.The PubMed and Embase databases were searched from inception to January 23, 2014.Cohort studies reporting adjusted relative risk (RR) estimates for fetal death, stillbirth, or infant death by at least 3 categories of maternal BMI were included.Data were extracted by 1 reviewer and checked by the remaining reviewers for accuracy. Summary RRs were estimated using a random-effects model.Fetal death, stillbirth, and neonatal, perinatal, and infant death.Thirty eight studies (44 publications) with more than 10,147 fetal deaths, more than 16,274 stillbirths, more than 4311 perinatal deaths, 11,294 neonatal deaths, and 4983 infant deaths were included. The summary RR per 5-unit increase in maternal BMI for fetal death was 1.21 (95% CI, 1.09-1.35; I2 = 77.6%; n = 7 studies); for stillbirth, 1.24 (95% CI, 1.18-1.30; I2 = 80%; n = 18 studies); for perinatal death, 1.16 (95% CI, 1.00-1.35; I2 = 93.7%; n = 11 studies); for neonatal death, 1.15 (95% CI, 1.07-1.23; I2 = 78.5%; n = 12 studies); and for infant death, 1.18 (95% CI, 1.09-1.28; I2 = 79%; n = 4 studies). The test for nonlinearity was significant in all analyses but was most pronounced for fetal death. For women with a BMI of 20 (reference standard for all outcomes), 25, and 30, absolute risks per 10,000 pregnancies for fetal death were 76, 82 (95% CI, 76-88), and 102 (95% CI, 93-112); for stillbirth, 40, 48 (95% CI, 46-51), and 59 (95% CI, 55-63); for perinatal death, 66, 73 (95% CI, 67-81), and 86 (95% CI, 76-98); for neonatal death, 20, 21 (95% CI, 19-23), and 24 (95% CI, 22-27); and for infant death, 33, 37 (95% CI, 34-39), and 43 (95% CI, 40-47), respectively.Even modest increases in maternal BMI were associated with increased risk of fetal death, stillbirth, and neonatal, perinatal, and infant death. Weight management guidelines for women who plan pregnancies should take these findings into consideration to reduce the burden of fetal death, stillbirth, and infant death.