tbuckley/cabot-search huggingface dataset:
Variation in Diabetes Care Among States
Authors: David R. Arday, Barbara B. Fleming, Dana K. Keller, Peter W. Pendergrass, Robert J. Vaughn, James M. Turpin, David A. Nicewander
Journal: Diabetes Care (2002)

OBJECTIVE—To examine state variability in diabetes care for Medicare beneficiaries and the impact of certain beneficiary characteristics on those variations. RESEARCH DESIGN AND METHODS—Medicare beneficiaries with diabetes, aged 18–75 years, were identified from 1997 to 1999 claims data. Claims data were used to construct rates for three quality of care measures (HbA1c tests, eye examinations, and lipid profiles). Person-level variables (e.g., age, sex, race, and socioeconomic status) were used to adjust state rates using logistic regression. RESULTS—A third of 2 million beneficiaries with diabetes aged 18–75 years did not have annual HbA1c tests, biennial eye examinations, or biennial lipid profiles. There was wide variability in the measures among states (e.g., receipt of HbA1c tests ranged from 52 to 83%). Adjustment using person-level variables reduced the variance in HbA1c tests, eye examinations, and lipid profiles by 30, 23, and 27%, respectively, but considerable variability remained. The impact of the adjustment variables was also inconsistent across measures. CONCLUSIONS—Opportunities remain for improvement in diabetes care. Large variations in care among states were reduced significantly by adjustment for characteristics of state residents. However, much variability remained unexplained. Variability of measures within states and variable impact of the adjustment variables argues against systems effects operating with uniformity on the three measures. These findings suggest that a single approach to quality improvement is unlikely to be effective. Further understanding variability will be important to improving quality.
Granuloma annulare and diabetes tnellitus—an association
Authors: M.F. Muhlemann, D.R.R. Williams
Journal: British Journal of Dermatology (1984)

Journal Article Granuloma annulare and diabetes tnellitus—an association Get access M.F. Muhlemann, M.F. Muhlemann Addenbrooke's Hospital, Cambridge Search for other works by this author on: Oxford Academic Google Scholar D.R.R. Williams D.R.R. Williams Addenbrooke's Hospital, Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 12–13, https://doi.org/10.1111/j.1365-2133.1984.tb05226.x Published: 01 July 1984
Risk Factors for Development of Toxic Shock Syndrome
Authors: Walter F. Schlech
Journal: JAMA (1982)

In September 1980, we interviewed by telephone 50 patients with menstrually associated toxic shock syndrome (TSS) who had onset of illness in July or August 1980. These women were asked to provide information about the type of menstrual sanitary products used during the menstrual period associated with their illness. We also interviewed 150 age-matched control subjects, who were asked the same questions for the menstrual period that occurred in the same month as the illness of the matched case. All 50 cases, but only 125 of 150 controls, used tampons. Among women using tampons, cases were more likely to have used Rely<sup>®</sup>brand tampons when compared with controls. No differences were found between cases and controls in the absorbency of tampon products used. No other factors studied through analysis of a follow-up questionnaire mailed five months after the first study were found to be significantly associated with the development of menstrually associated TSS. (<i>JAMA</i>1982;248:835-839)
Chronic coronary artery constriction leads to moderate myocyte loss and left ventricular dysfunction and failure in rats.
Authors: P Anversa, X Zhang, P Li, J M Capasso
Journal: Journal of Clinical Investigation (1992)

Coronary artery narrowing, ranging from 19% to 61%, was induced in rats and ventricular performance, myocardial damage, and myocyte hypertrophy were examined 1 mo later. Animals were separated into two groups, exhibiting ventricular dysfunction and failure, respectively. Dysfunction consisted of a 2.4-fold increase in left ventricular end diastolic pressure (LVEDP), 15% decrease in left ventricular peak systolic pressure (LVPSP), 24% reduction in developed pressure (DP), and a 16% depression in-dP/dt. Failure was defined on the basis of a 4.7-fold elevation in LVEDP, and a 26%, 47%, 45%, and 41% decrease in LVPSP, DP, +dP/dt, and -dP/dt. Moreover, in this group, right ventricular end diastolic and systolic pressures increased 5.5- and 1.2-fold. Left and right ventricular weights expanded 23% and 51% with dysfunction and 30% and 56% with failure. Left ventricular hypertrophy was characterized by ventricular dilation and wall thinning which were more severe in the failing animals. Foci of damage were found in both groups but tissue injury was more prominent in the endomyocardium and in failing rats. Finally, myocyte loss in the ventricle was 10% and 20% with dysfunction and failure whereas the corresponding enlargements of the unaffected myocytes were 34% and 53%. Thus, coronary narrowing led to abnormalities in cardiac dynamics with an increase in diastolic wall stress and extensive ventricular remodeling in spite of a moderate loss of myocytes and compensatory reactive hypertrophy of the viable cells.
Preferential adherence of T lymphocytes and neutrophils to psoriatic epidermis
Authors: J.N.W.N. BARKER, R.W. GROVES, M.H. ALLEN, D.M. MACDONALD
Journal: British Journal of Dermatology (1992)

Journal Article Preferential adherence of T lymphocytes and neutrophils to psoriatic epidermis Get access J.N.W.N. BARKER, J.N.W.N. BARKER Laboratory of Applied Dermatopathology, United Medical and Dental Schools, Guy's Hospital, London, U.K. Dr J.N.W.N. Barker, Department of Dermatology, Guy's Hospital, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.W. GROVES, R.W. GROVES Laboratory of Applied Dermatopathology, United Medical and Dental Schools, Guy's Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.H. ALLEN, M.H. ALLEN Laboratory of Applied Dermatopathology, United Medical and Dental Schools, Guy's Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.M. MACDONALD D.M. MACDONALD Laboratory of Applied Dermatopathology, United Medical and Dental Schools, Guy's Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 3, 1 September 1992, Pages 205–211, https://doi.org/10.1111/j.1365-2133.1992.tb00115.x Published: 01 September 1992
Comprehensive functional analysis of chymotrypsin C (<i>CTRC</i>) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk
Authors: Sebastian Beer, Jiayi Zhou, András Szabó, Steven Keiles, Giriraj Ratan Chandak, Heiko Witt, Miklós Sahin-Tóth
Journal: Gut (2012)

<h3>Objective</h3> The digestive enzyme chymotrypsin C (CTRC) protects against pancreatitis by promoting degradation of trypsinogen, thereby curtailing potentially harmful trypsinogen activation. Loss-of-function variants in <i>CTRC</i> increase the risk for chronic pancreatitis. The aim of the present study was to perform comprehensive functional analysis of all missense <i>CTRC</i> variants identified to date. <h3>Design</h3> We investigated secretion, activity and degradation of 27 published and five novel CTRC mutants. We also assessed the effect of five mutants on endoplasmic reticulum (ER) stress. <h3>Results</h3> None of the mutants exhibited a gain of function, such as increased secretion or activity. By contrast, 11 mutants showed marked loss of function, three mutants had moderate functional defects, whereas 18 mutants were functionally similar to wild-type CTRC. The functional deficiencies observed were diminished secretion, impaired catalytic activity and degradation by trypsin. Mutants with a secretion defect caused ER stress that was proportional to the loss in secretion. ER stress was not associated with loss-of-function phenotypes related to catalytic defect or proteolytic instability. <h3>Conclusions</h3> Pathogenic <i>CTRC</i> variants cause loss of function by three distinct but mutually non-exclusive mechanisms that affect secretion, activity and proteolytic stability. ER stress may be induced by a subset of CTRC mutants, but does not represent a common pathological mechanism of <i>CTRC</i> variants. This phenotypic dataset should aid in the classification of the clinical relevance of <i>CTRC</i> variants identified in patients with chronic pancreatitis.
Further thoughts about the ILLUMINATE studies of tabalumab in SLE
Authors: David Isenberg
Journal: Annals of the Rheumatic Diseases (2015)

Further thoughts about the ILLUMINATE studies of tabalumab in SLEChiche and colleagues make some very pertinent comments about the apparent failure of Tabalimumab (in the ILLUMINATE trials) set against the 'deemed' success of Benlysta (in the BLISS trials) when in fact an analysis of the results indicates that there is little to choose between them.I would point out that the least successful of these four trials, ILLUMINATE 1, was not helped by the decision made by the company to consider patients who changed their concomitant dose of steroids to have failed the trial even if that change was a reduction in the steroids.The authors also suggest that the failure to 'label', that is, approve, Benlysta in the UK was because its effects were too modest.This was indeed part of the issue but the other aspect was the very high price (around $30 000 per patient per annum).They further propose that B-lymphocyte stimulator (Blys)/ B-cell activating factor (BAFF) levels at baseline are insufficient to define likely responders to B cell targeted therapy.My colleagues and I have pointed out elsewhere 1 that a group of patients with SLE responds to rituximab with a rapidly rising BLyS level which has led us to prose a trial in which rituximab followed by Benlysta will be evacuated (BEAT-lupus).In my opinion it is often clinical trial design which mitigates against success in SLE clinical trials.I think, in particular, that unreasonable targets-setting the bar too high, coupled with an excess of steroids and immunosuppressives used have made it very hard indeed for primary end points to be achieved.
The Relative Importance of Unmeasured Covariates in Racial/Ethnic Disparities Research
Authors: Colin R. Cooke, Danielle Frank, Reanne Frank
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

To the Editor:Dr. Barnato and colleagues (1) present results from a populationbased analysis of race-specific incidence and case fatality in severe sepsis.Using hospital discharge data from six states, the authors determined that the rate of severe sepsis for blacks was almost double that of whites.We commend the authors for documenting this racial/ethnic disparity.Identifying disparities in health outcomes and treatment effects is an important first step in eventually curtailing their occurrence.An important subsequent step involves appropriately identifying the fundamental causes of such disparities.It is here that we take issue with the article.Confronted with a residual association between race/ethnicity and sepsis incidence after adjusting for measured confounders, the authors acknowledge that unmeasured confounders may be the cause.This is the most obvious conclusion given the crude indicators of social status used in their analysis.However, they are more enthusiastic about a second possibility: unexplained racial disparities in sepsis incidence could be due to ''different genetic susceptibility to sepsis between blacks and whites.''The common argument that, after accounting for social/environmental factors, genetic differences are responsible for residual racial disparities in complex diseases is flawed for several reasons (2-4).From a purely probabilistic standpoint, even in situations where social factors can be measured without error, and are appropriately accounted for in the analysis, social/ environmental explanations for the higher rates of sepsis among black patients are far more likely than genetic ones (2, 5).This is because the variability in social/environmental factors that influence health across racial/ethnic groups (e.g., education, health insurance, poverty) is orders of magnitude greater than any genetic variability between groups (4).In other words, race is likely to be much more highly correlated with social/environmental factors than with genetic factors.The authors' enthusiasm for future research efforts that would determine the genetic basis of racial differences in the pathophysiology of sepsis ignores the fact that race serves as a risk factor for both genetic and environmental effects.Issues of confounding, coupled with the weak correlation between human genetic diversity and racial/ethnic categories, will ultimately limit the promise of such research efforts (6).While we appreciate the assertion that ''hypotheses regarding potential race-associated differences in innate susceptibility do not belie the [importance of] differences in healthy lifestyles,'' we feel that the purported genetic and biologic differences between blacks and whites with sepsis are mainly conjecture and detract from the known social and environmental causes that likely explain the vast majority of the difference.
Molecular Phylogeny of the Plant Pathogenic Genus Botrytis and the Evolution of Host Specificity
Authors: M. Staats
Journal: Molecular Biology and Evolution (2004)

The cosmopolitan genus Botrytis contains 22 recognized species and one hybrid. The current classification is largely based on morphological characters and, to a minor extent, on physiology and host range. In this study, a classification of the genus was constructed based on DNA sequence data of three nuclear protein-coding genes (RPB2, G3PDH, and HSP60) and compared with the traditional classification. Sexual reproduction and the host range, important fitness traits, were traced in the tree and used for the identification of major evolutionary events during speciation. The phylogenetic analysis corroborated the classical species delineation. In addition, the hybrid status of B. allii (B. byssoidea x B. aclada) was confirmed. Both individual gene trees and combined trees show that the genus Botrytis can be divided into two clades, radiating after the separation of Botrytis from other Sclerotiniaceae genera. Clade 1 contains four species that all colonize exclusively eudicot hosts, whereas clade 2 contains 18 species that are pathogenic on either eudicot (3) or monocot (15) hosts. A comparison of Botrytis and angiosperm phylogenies shows that cospeciation of pathogens and their hosts have not occurred during their respective evolution. Rather, we propose that host shifts have occurred during Botrytis speciation, possibly by the acquisition of novel pathogenicity factors. Loss of sexual reproduction has occurred at least three times and is supposed to be a consequence of negative selection.
CaSm-Mediated Cellular Transformation Is Associated with Altered Gene Expression and Messenger RNA Stability
Authors: Melissa M. Fraser, Patricia M. Watson, Mostafa M. Fraig, Joseph R. Kelley, Peter S. Nelson, Alice M. Boylan, David J. Cole, Dennis K. Watson
Journal: Cancer Research (2005)

Abstract CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm encodes a 133 amino acid protein that contains two Sm motifs found in the common small nuclear RNA proteins and the LSm (like-Sm) family of proteins. Compared with normal human prostate tissue and primary prostate epithelial cells, some primary prostate tumors and prostate cancer–derived cell lines have elevated CaSm expression. Expression of antisense CaSm RNA in DU145 cells results in reduced CaSm protein levels and less transformed phenotype, measured by anchorage-independent growth in vitro and tumor formation in severe combined immunodeficient mice in vivo. Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins. Consistent with failure of antisense-treated cells to enter mitosis, microarray analysis identified altered expression of NEK2 and nucleophosmin/B23. Although the mechanisms by which CaSm contributes to neoplastic transformation and cellular proliferation are unknown, it has been shown that the yeast homologue (spb8/LSm1) of CaSm is required for 5′ to 3′ degradation of specific mRNAs. We provide data consistent with a similar role for CaSm in human cells, supporting the hypothesis that elevated CaSm expression observed in cancer leads to destabilization of multiple gene transcripts, contributing to the mutator phenotype of cancer cells.
Postchemotherapy Adjuvant Tamoxifen Therapy Beyond Five Years in Patients With Lymph Node-Positive Breast Cancer
Authors: D. C. Tormey, R. Gray, H. C. Falkson
Journal: JNCI Journal of the National Cancer Institute (1996)

Data from a pilot study published in 1984 suggested that tamoxifen administration (as adjuvant hormonal therapy) for more than 5 years after initial breast cancer surgery might have therapeutic benefit. A randomized trial was performed to assess the efficacy of maintaining tamoxifen therapy beyond 5 years in women with axillary lymph node-positive breast cancer who had been treated with surgery followed by 1 year of chemotherapy and 5 years of tamoxifen. One hundred ninety-four women (87 postmenopausal and 107 premenopausal) enrolled in two concurrent Eastern Cooperative Oncology Group adjuvant trials (E4181 for postmenopausal patients and E5181 for premenopausal patients) were randomly assigned to continued tamoxifen therapy or observation. Data for 193 women (87 postmenopausal and 106 premenopausal) were available for analysis. Median follow-up is 5.6 years since the randomization at 5 years, with the longest follow-up being 8.0 years. The major analyses measured events from the time of randomization until relapse or death; these included time-to-relapse analyses, with new opposite-breast cancers counted as treatment failures, and survival analyses. Time-to-relapse comparisons and survival comparisons for women in the two treatment groups were made by use of the Kaplan-Meier method and the logrank test. Reported P values are two-sided. Five years after the randomization, no statistically significant differences were noted in either time to relapse or survival between women continuting to receive tamoxifen and those on observation. Eighty-five percent of the women receiving tamoxifen were disease free at this time compared with 73% of those on observation ( P = .10); survival was 86% for those continuing to receive tamoxifen and 89% for those on observation ( P = .52). Differences in the time to relapse and survival between premenopausal and postmenopausal women assigned to the two treatment groups were also not statistically significant (time to relapse: P = .38 and P = .16 for premenopausal and postmenopausal patients, respectively; survival: P = .18 and P = .72 for premenopausal and postmenopausal patients, respectively). There was an indication that women with estrogen receptor-positive tumors may experience a longer time to relapse with continued tamoxifen therapy ( P = .014); however, the survival difference for this subgroup was not statistically significant ( P = .81). The toxicity paterns in the two treatment groups were similar. Our results suggest that further evaluation of adjuvant tamoxifen therapy beyond 5 years in women with axillary lympth node-positive, estrogen receptor-positive breast cancer who have also been treated with adjuvant chemotherapy would be appropriate. [J Natl Cancer Inst 1996;88:1828–33]
Biomarker-Adaptive Threshold Design: A Procedure for Evaluating Treatment With Possible Biomarker-Defined Subset Effect
Authors: W. Jiang, B. Freidlin, R. Simon
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundMany molecularly targeted anticancer agents entering the definitive stage of clinical development benefit only a subset of treated patients. This may lead to missing effective agents by the traditional broad-eligibility randomized trials due to the dilution of the overall treatment effect. We propose a statistically rigorous biomarker-adaptive threshold phase III design for settings in which a putative biomarker to identify patients who are sensitive to the new agent is measured on a continuous or graded scale.
Negative Regulation of Immunoreceptor Signaling
Authors: André Veillette, Sylvain Latour, Dominique Davidson
Journal: Annual Review of Immunology (2002)

Immune cells are activated as a result of productive interactions between ligands and various receptors known as immunoreceptors. These receptors function by recruiting cytoplasmic protein tyrosine kinases, which trigger a unique phosphorylation signal leading to cell activation. In the recent past, there has been increasing interest in elucidating the processes involved in the negative regulation of immunoreceptor-mediated signal transduction. Evidence is accumulating that immunoreceptor signaling is inhibited by complex and highly regulated mechanisms that involve receptors, protein tyrosine kinases, protein tyrosine phosphatases, lipid phosphatases, ubiquitin ligases, and inhibitory adaptor molecules. Genetic evidence indicates that this inhibitory machinery is crucial for normal immune cell homeostasis.
Impact of Primary Care–Based Disease Management on the Health-Related Quality of Life in Patients With Type 2 Diabetes and Comorbidity
Authors: Dominik Ose, Michel Wensing, Joachim Szecsenyi, Stefanie Joos, Katja Hermann, Antje Miksch
Journal: Diabetes Care (2009)

OBJECTIVE This study examined the effectiveness of the German diabetes disease management program (DMP) for patients with varying numbers of other medical conditions with respect to their health-related quality of life (HRQoL). RESEARCH DESIGN AND METHODS A questionnaire, including the HRQoL-measured EQ-5D, was mailed to a random sample of 3,546 patients with type 2 diabetes (59.3% female). The EQ-5D score was analyzed by grouping patients according to those on a DMP and those receiving routine care. RESULTS The analysis showed that participation in the DMP (P &amp;lt; 0.001), the number of other medical conditions (P &amp;lt; 0.001), and the interaction between the DMP and the number of other conditions (P &amp;lt; 0.05) had a significant impact on the EQ-5D score. CONCLUSIONS Our findings suggest that the number of other medical conditions may have a negative impact on the HRQoL of patients with type 2 diabetes. The results demonstrate that the German DMP for type 2 diabetes may help counterbalance this effect.