tbuckley/cabot-search huggingface dataset:
Estimates of chronic obstructive pulmonary disease in terms of prevalence, mortality and costs for England and Scotland for 2011 and 2030
Authors: Susannah McLean, Martine Hoogendoorn, Rudolf Hoogenveen, Talitha Feenstra, Sarah Wild, Colin Simpson, Aziz Sheikh, Maureen Rutten Van Molken
Journal: European Respiratory Journal (2014)

Introduction: Governments require accurate projections of the numbers of patients with COPD in order to plan healthcare services for the future. These can be estimated using validated models. The aim of this work was to generate estimates of prevalence, mortality and costs for diagnosed COPD in England and Scotland in 2011 and 2030.  Methods: A published dynamic COPD population model developed in the Netherlands was adapted by including age and sex specific estimates of diagnosed COPD incidence and prevalence from primary and secondary care records for England and Scotland for 2011, population mortality data, relative risks of mortality among those with COPD from the Clinical Practice Research Datalink and cost data from recent studies, not accounting for inflation.  Results: The number of people diagnosed with COPD is estimated to rise between 2011 and 2030 from 952000 to 1349000 persons in England and from 108000 to 128000 persons in Scotland. This represents a rise in overall prevalence from 1.8% to 3.1% in England and from 2.1% to 3.1% in Scotland between 2011 and 2030. It is anticipated that there will be 134000 deaths among people with COPD in 2030, and 14000 deaths in Scotland in 2030. Assuming constant costs per patient, in England the health service costs of COPD are estimated to be £2275 million in 2030, increasing from an estimated £1489 million in 2011 In Scotland the cost will increase to £117 million by 2030 from £92 million in 2011.  Conclusion: This model suggests that prevalence and costs of COPD in England and Scotland will increase over the next 20 years due to delayed effects of smoking in the past and ageing of the population.
Abstract 1195: A Genomic Signature of Atherosclerosis among Individuals with Low Framingham Risk Score: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Chiang-Ching Huang, kiang Liu, Nalini Rajamannan, Pan Du, Simon Lin, Gregory Burke, Steven Shea, Moyses Szklo, Karol Watson, Craig Johnson, Donald Lloyd-Jones
Journal: Circulation (2008)

Background : The Framingham risk score (FRS) predicts low 10-year risks for the majority of women, even in the face of substantial burden of subclinical atherosclerosis (SA). However, many individuals predicted to be at low risk will still experience cardiovascular disease (CVD) events in the short term. We hypothesized that gene expression signatures in peripheral blood leukocytes (PBLs) could improve risk stratification among low-risk individuals, by identifying those with significant SA burden. Methods : We performed a case-control study of gene expression profiles among healthy women with low FRS (&lt;10%) and no diabetes; we selected 49 cases with subclinical atherosclerosis (SA; defined as coronary artery calcification (CAC) &gt;100 and carotid intima-media thickness (IMT) &gt;1.0) and 72 age and race matched controls with CAC=0 and carotid IMT &lt;0.65 from the MESA cohort. Microarray data were generated from Illumina BeadArray chips. Multiple cross-validation and gene ontology/pathway analysis were used to construct a classification model and identify genetic pathways involved in atherosclerosis. Results : A total of 2,462 genes with coefficient of variation &gt;0.03 were used for data analysis. A gene signature composed of 40 to 60 genes in a support vector machine classification model was associated with an odds ratio of 3.5 for SA (p=0.002), resulting in a 71% specificity and 59% sensitivity for SA. For the 251 most differentially expressed genes (p = 10 −8 ~ 0.0004, false discovery rate (FDR) &lt;0.2%) between those with and without SA, Ingenuity Pathway Analysis and Panther gene ontology analysis revealed this set of genes is enriched in innate immune function (p&lt;10 −7 ). Notably, the majority of the top 30 genes (p&lt;10 −6 , FDR&lt;10 −6 ) were involved in toll-like receptor (TLR) signaling and hypoxia signaling. Conclusion : The results of functional genomic analysis suggest the activation of innate immune system through TLR signaling is associated with high burden of SA that can be detected in PBLs of healthy women predicted to be at low risk for CVD events. Our findings merit validation in a larger cohort.
Cholesterol: how low is low enough?
Authors: A R P Walker, A S Wierzbicki, T M Reynolds
Journal: BMJ (1999)

Editor—In his editorial Rosengren considers that reaching target cholesterol concentrations may be better than relative reductions.1 He stated that “in observational studies a prolonged difference in usual serum cholesterol value of 0.06 mmol/l is associated with an almost 30% reduction in risk of coronary disease.”

No one would question the need for reducing serum cholesterol concentration in large proportions of adults in Western populations. However, the subject of cholesterol concentration and its pathological importance is complex.

Known risk factors for coronary heart disease, of which serum cholesterol concentration is one, explain only half of the variance in the occurrence of the disease.2 There are also numerous contextual problems. For example, in the Sheffield risk table, cholesterol reduction may be called for at 5.5 mmol/l in those at high risk, whereas intervention may not be needed until 9.0 mmol/l in those at low risk.3 The experience of coronary heart disease also differs between Belfast and Toulouse. Although mean cholesterol concentrations in the two cities are similar, 6.19 and 5.94 mmol/l, mortality from the disease is 3-4 times higher in Belfast than in Toulouse.4

Perplexities are also common in populations in developing countries, as in South Africa.5 In early studies mean cholesterol concentration in middle aged African men was about 4.0 mmol/l, with observations at necropsy showing a low rate of atherosclerotic lesions of the aorta and a negligible number of deaths from the disease. Currently, in Soweto (3-4 million inhabitants) the mean cholesterol concentration is about 5 mmol/l. Yet coronary heart disease remains uncommon, being responsible for less than 0.5% of total deaths. Similar reports of the disease’s comparative rarity have emanated from big cities in other countries in Africa. In comparison, in the seven countries study the same mean serum concentration of cholesterol (about 5.15 mmol/l) prevails in Mediterranean countries, but coronary heart disease is responsible for 4.7% of total deaths.

An additional complicating factor is the wide range of cholesterol concentrations in a community. In African village schoolchildren, almost all of the same poor socioeconomic state and accustomed to the same low atherogenic diet, cholesterol concentration varied from 2.5 to 4.2 mmol/l.

To reiterate, although cholesterol concentration has a role in coronary heart disease, a given concentration has widely different connotations for ill, being affected by familiality, ethnic group, sex, and environmental factors.
Social consequences of psychiatric disorders, II: Teenage parenthood
Authors: R C Kessler, P A Berglund, C L Foster, W B Saunders, P E Stang, E E Walters
Journal: American Journal of Psychiatry (1997)

The subject of this study was the relation between retrospectively reported early-onset psychiatric disorders and subsequent teenage parenthood in the general population.The data were from 5,877 respondents aged 15-54 years in the National Comorbidity Survey, a nationally representative household survey. Information on respondents' DSM-III-R anxiety disorders, mood disorders, substance abuse disorders, and conduct disorder, age at the birth of the first child, and teenage sexual activity was collected in face-to-face interviews.Early-onset psychiatric disorders were associated with subsequent teenage parenthood among both females and males, with significant odds ratios of 2.0-12.0 and population attributable risk proportions of 6.2%-33.7%. Disaggregation analyses showed that disorders were associated with increased probability of sexual activity but not with decreased probability of using contraception.These results add to a growing body of evidence that psychiatric disorders are associated with a variety of adverse life consequences. The current policy debate concerning universal insurance coverage needs to take this into consideration. Planners of interventions aimed at preventing teenage pregnancy should consider including a mental health treatment component in their intervention packages. Mental health professionals treating adolescents need to be sensitized to their higher risk of pregnancy, while family doctors and specialists treating teenage mothers or their children need to be sensitized to the mothers' higher risk of psychiatric disorder.Data from the US National Comorbidity Survey on 5877 respondents 15-54 years of age were used to assess the relationship between retrospectively identified early-onset psychiatric disorders and subsequent adolescent parenthood. Between 21-24% of the sample's male and female age cohorts reported having their first child at ages 15-19 years. The cumulative and conditional probability curves for adolescent parenthood were consistently higher among men and women with prior psychiatric diagnoses of anxiety, affective, addictive, and conduct disorders than among those without psychiatric diagnoses. The diagnosis most predictive of adolescent parenthood was addictive disorders. The population attributable risk proportions of births of first children to teenagers associated with the psychiatric disorders were 11.1% in the teenage female subsample with premarital childbearing, 6.2% in the teenage female subsample with marital childbearing, and 33.7% in the teenage male subsample with premarital parenthood. Physicians and mental health professionals who work with adolescents with psychiatric conditions should be aware of the increased risk of adolescent pregnancy and a mental health component should be added to adolescent pregnancy prevention programs.
Pharmacologic treatment of noncognitive behavioral disturbances in elderly demented patients
Authors: E F Coccaro, E Kramer, Z Zemishlany, A Thorne, C M Rice, B Giordani, K Duvvi, B M Patel, J Torres, R Nora
Journal: American Journal of Psychiatry (1990)

Fifty-nine elderly residents of long-term care facilities who had DSM-III diagnoses of dementia were studied in an 8-week randomized, double-blind comparison trial of haloperidol, oxazepam, and diphenhydramine to test the efficacy of these agents in the treatment of clinically significant behavioral disturbances in patients with dementia. All three agents demonstrated modest but significant efficacy as measured by clinician ratings of agitated behavior and activities of daily living. The absolute magnitude of improvement was greater for haloperidol and diphenhydramine than for oxazepam, but differences among groups did not approach statistical significance. Frequencies of acute adverse events during the trial were similar across the drug treatment groups. Although these drugs may differ in terms of long-term safety and efficacy, they appear to be equivalent for short-term management of agitated behavior in severely demented patients.
Abstract 5416: Exaggerated Mortality Risk in Patients With Severe Left Ventricular Hypertrophy
Authors: Michael Doumas, Vasilios Papademetriou, Nina Kukar, Charles Faselis, Costas Tsioufis, Peter Kokkinos
Journal: Circulation (2009)

Introduction: Mild to moderate left ventricular hypertrophy (LVH) has been identified as an independent predictor of increased mortality, but information in patients with severe or very severe LVH is scarce. Thus, we assessed the mortality risk associated with the severity of LVH in a large cohort of male veterans. Methods: From January of 1993 to March 2009, we identified 11,578 patients (mean age: 68±14) with a technically interpretable baseline echocardiogram at the Veterans Affairs Medical Center, Washington, DC. We calculated left ventricular mass index (LVMI) and classified patients as follows: No-LVH (LVMI &lt;125 g/m 2 ; n=6,835); Mild-Moderate-LVH (LVMI 125–160 g/m 2 ; n=2,673); Severe-LVH (LVMI 161–200 g/m 2 ; n=1,359); and Very-Severe-LVH (LVMI &gt;200 g/m 2 ; n=711). We then assessed mortality rate for a mean follow-up period of 5.8±4.5 years. Results : Echocardiographic parameters are presented in table . During the follow-up period we observed a total of 3,950 deaths for an annual mortality rate of 5.85% in the entire cohort. The annual mortality rate was 4.87%; 6.53%; 8%; and 11% for the No-LVH; Mild-Moderate-LVH; Severe-LVH; and Very-Severe-LVH groups respectively. Cox proportional hazard analysis, adjusted for age, heart failure, and diabetes mellitus, revealed a 10% increase in mortality risk for every 20 g/m 2 increase in LVMI. When compared to the No-LVH group, the mortality risk was 29% higher for the Mild-Moderate-LVH (CI: 1.2–1.4); 57% higher for the Severe-LVH (CI: 1.4–1.7) and 115% higher for the Very-Severe-LVH (CI: 1.9–2.4). Conclusions: LVMI is directly associated with increased mortality; Severe and very severe LVH are associated with exaggerated mortality risk and Approaches to prevent or reverse LVH are urgently needed.
Kinetic analysis of breast tumor decay and growth following ixabepilone plus capecitabine (IXA + CAP) versus capecitabine alone (CAP) to discern whether the superiority of the combination is a result of slower growth, enhanced tumor cell kill, or both.
Authors: A. T. Fojo, W. D. Stein, J. Wilkerson, S. E. Bates
Journal: Journal of Clinical Oncology (2010)

1096 Background: Utilizing a new method that analyzes tumor measurements obtained while a patient receives chemotherapy, we have previously shown for prostate and renal tumors that the growth rate constant of a tumor correlates with survival (Stein et al, Oncologist, 13:1046 and 1055; 2008). We have now applied this same approach to data collected in a clinical trial of IXA + CAP versus CAP alone in patients with metastatic breast cancer (MBC). Methods: Using CT tumor measurements obtained while patients were treated we determined the rate of tumor decay (d) and growth (g) reliably even before the nadir is reached. Results: (i) In patients treated with CAP, overall survival (OS) was strongly correlated (R > 0.59, p < 0.001) with the rate of tumor growth (log g) but less strongly (R > 0.21, p > 0.028) with the rate of decay (log d). The median growth rate constant for these tumors was 0.00288 days-1. For IXA + CAP, correlations of OS with both log g (R > 0.57, p < 0.001) and log d (R > 0.27, p > 0.0003) were similar to those for CAP. The median g value for IXA + CAP at 0.00191 days-1 was significantly lower than for CAP (p < 0.001), while median d values were similar (0.00840 days-1 for CAP; 0.00863 days-1 for CAP + IXA, p > 0.400 NS). (ii) For neither arm did g or d correlate with initial tumor burden. (iii) The median OS for the patients in this analysis treated with IXA + CAP (475 d) was significantly longer (p > 0.02) than that for the group treated with CAP (392 d) - in strict proportion to the reduction in the tumor growth rate constant. (iv) These median OS values were, however, shorter than those predicted from the on-study g and d parameters, suggesting continuation of drug treatment might have resulted in an increase in OS. Conclusions: We present a quantitative kinetic analysis of the response of breast tumors to chemotherapy as a robust and rapid method to assess results of clinical trials. Reduction of the on- study tumor growth rate with the addition of IXA was responsible for the enhanced OS seen with the combination. Continuation of treatment with IXA might conceivably have extended patient survival even further. No significant financial relationships to disclose.
The ICD-10 clinical field trial for mental and behavioral disorders: results in Canada and the United States
Authors: D A Regier, C T Kaelber, M T Roper, D S Rae, N Sartorius
Journal: American Journal of Psychiatry (1994)

To help evaluate the impact of proposed revisions to the chapter on mental and behavioral disorders for ICD-10, the World Health Organization (WHO) Division of Mental Health organized an international clinical field trial to evaluate draft clinical descriptions and diagnostic guidelines. The authors compare interrater diagnostic reliability results from this field trial for clinicians in Canada and the United States of American with those from all other clinicians worldwide, as well as with those from field trials conducted to evaluate drafts of DSM-III.Two or more clinicians at each clinical center independently evaluated each patient, following a study protocol that allowed clinicians to list up to six diagnoses. In Canada and the United States, 96 clinicians completed 1,781 assessments among 491 patients, and elsewhere in the world 472 clinicians completed 7,495 assessments among 1,969 patients.Summary kappa coefficients at two-, three-, and four-character ICD-10 code levels were 0.76, 0.65, and 0.52, respectively, for Canadian and U.S. clinicians and 0.83, 0.75, and 0.62 for clinicians elsewhere. The mean number of diagnoses per assessment for Canadian and U.S. clinicians was 2.1; for clinicians elsewhere it was 1.7. More multiple coding of diagnoses for substance use disorders, mood (affective) disorders, and personality disorders by Canadian and U.S. clinicians accounted for much of the difference in diagnostic coding and in interrater reliability between them and clinicians elsewhere.Interrater diagnostic reliability in Canada and the United States was similar to that of clinicians worldwide and also to results from the DSM-III field tests. Use of more multiple coding of selected disorders by Canadian and U.S. clinicians may reflect the influence of DSM-III and DSM-III-R, which encourage multiple diagnostic entries and the use of separate multiaxial coding for personality disorders, and may have reduced interrater concurrence for some categories. Further, collaborative development of ICD-10 with DSM-IV has aligned these two systems more closely.
Anal Canal Cancer Clinical Practice Guidelines in Oncology
Authors: Paul F. Engstrom, Al B. Benson, Yi Jen Chen, Michael A. Choti, Raza A. Dilawari, Charles A. Enke, Marwan G. Fakih, Charles Fuchs, Krystyna Kiel, James A. Knol, Lucille A. Leong, Kirk A. Ludwig, Edward W. Martin, Sujata Rao, M. Wasif Saif, Leonard Saltz, John M. Skibber, Alan P. Venook, Timothy J. Yeatman
Journal: Journal of the National Comprehensive Cancer Network (2005)

An estimated 3,990 new cases of anal cancer will occur in 2005, accounting for approximately 1.6% of digestive system cancers in the United States. Prognosis directly depends on the size of the primary tumor and the likelihood of lymphatic spread, with tumors 2 cm or smaller cured in 80% of cases. The NCCN guidelines recommend a thorough evaluation for any patient with a suspicious lesion in the anal canal and include additional recommendations for diagnosis, treatment, and follow up for anal canal cancer. For the most recent version of the guidelines, please visit NCCN.org
Abstract 674: Direct Comparison of Rest and Adenosine Stress Myocardial Perfusion CT With Rest and Stress SPECT
Authors: David R Okada, Ron Blankstein, Brian B Ghoshhajra, Jose A Rocha-Filho, Leonid D Shturman, Ian S Rogers, Hiram G Bezerra, Ammar Sarwar, Henry Gewirtz, Udo Hoffmann, Wilfred S Mamuya, Thomas J Brady, Ricardo C Cury
Journal: Circulation (2009)

INTRODUCTION: We have recently described a technique for assessing myocardial perfusion using adenosine-mediated stress imaging (CTP) with Dual Source Computed Tomography (DSCT) that offers sub-mil...
Hypoxia Inducible Factor (HIF)-2α Enhances Proliferation Of Malignant Hematopoietic Cells In The Hypoxic Malignant Bone Marrow
Authors: Catherine E Forristal, Falak Helwani, Sally Martin, Bianca Nowlan, Ingrid G Winkler, Andrew Zannettino, Jean-Pierre Levesque
Journal: Blood (2013)
SPECT findings on psychosis in Alzheimer's disease
Authors: K J Kotrla, R C Chacko, R G Harper, S Jhingran, R Doody
Journal: American Journal of Psychiatry (1995)

This study examined whether psychosis in Alzheimer's disease is associated with cerebral perfusion patterns appreciable by single photon emission computed tomography (SPECT) scans.All cooperative outpatients enrolled in an Alzheimer's disease research center with the diagnosis of probable Alzheimer's disease and a Clinical Dementia Rating of mild or moderate were interviewed with their primary caregivers. Current and past psychiatric functioning was assessed by using the Hamilton Depression Rating Scale, the Structured Clinical Interview for DSM-III-R, and the Behavioral Pathology in Alzheimer's Disease Rating Scale. Patients without premorbid psychosis received SPECT scans, and the scans of the patients with delusions or hallucinations (N = 30) were compared to the scans of patients without these symptoms (N = 16).The patients with delusions (N = 29) had hypoperfusion of the left frontal lobe in relation to the right frontal lobe. The patients with hallucinations (N = 10) had hypoperfusion in the parietal lobe.Psychotic patients with Alzheimer's disease had a pattern of cerebral blood flow deficits significantly different from that of nonpsychotic patients. This suggests that patterns of cerebral dysfunction may be expressed symptomatically as psychosis.
Surveillance for Cancers Associated with Tobacco Use — United States, 2010–2014
Authors: M. Shayne Gallaway, S. Jane Henley, C. Brooke Steele, Behnoosh Momin, Cheryll C. Thomas, Ahmed Jamal, Katrina F. Trivers, Simple D. Singh, Sherri L. Stewart
Journal: MMWR Surveillance Summaries (2018)

Tobacco use is the leading preventable cause of cancer, contributing to at least 12 types of cancer, including acute myeloid leukemia (AML) and cancers of the oral cavity and pharynx; esophagus; stomach; colon and rectum; liver; pancreas; larynx; lung, bronchus, and trachea; kidney and renal pelvis; urinary bladder; and cervix. This report provides a comprehensive assessment of recent tobacco-associated cancer incidence for each cancer type by sex, age, race/ethnicity, metropolitan county classification, tumor characteristics, U.S. census region, and state. These data are important for initiation, monitoring, and evaluation of tobacco prevention and control measures.
Targeted Proapoptotic Peptides Depleting Adipose Stromal Cells Inhibit Tumor Growth
Authors: Alexes C Daquinag, Chieh Tseng, Yan Zhang, Felipe Amaya-Manzanares, Fernando Florez, Ali Dadbin, Tao Zhang, Mikhail G Kolonin
Journal: Molecular Therapy (2015)

Progression of many cancers is associated with tumor infiltration by mesenchymal stromal cells (MSC). Adipose stromal cells (ASC) are MSC that serve as adipocyte progenitors and endothelium-supporting cells in white adipose tissue (WAT). Clinical and animal model studies indicate that ASC mobilized from WAT are recruited by tumors. Direct evidence for ASC function in tumor microenvironment has been lacking due to unavailability of approaches to specifically inactivate these cells. Here, we investigate the effects of a proteolysis-resistant targeted hunter-killer peptide D-WAT composed of a cyclic domain CSWKYWFGEC homing to ASC and of a proapoptotic domain KLAKLAK2. Using mouse bone marrow transplantation models, we show that D-WAT treatment specifically depletes tumor stromal and perivascular cells without directly killing malignant cells or tumor-infiltrating leukocytes. In several mouse carcinoma models, targeted ASC cytoablation reduced tumor vascularity and cell proliferation resulting in hemorrhaging, necrosis, and suppressed tumor growth. We also validated a D-WAT derivative with a proapoptotic domain KFAKFAK2 that was found to have an improved cytoablative activity. Our results for the first time demonstrate that ASC, recruited as a component of tumor microenvironment, support cancer progression. We propose that drugs targeting ASC can be developed as a combination therapy complementing conventional cancer treatments.