tbuckley/cabot-search huggingface dataset:
Steroid-Based Therapy and Risk of Infectious Complications
Authors: Lionel Rostaing, Paolo Malvezzi
Journal: PLoS Medicine (2016)

Steroid-based therapy is widely used in the treatment of different diseases, across many health care settings.In a study based on the National Health and Nutrition Examination Survey (NHANES), conducted between 1999 and 2005, the prevalence of long-duration glucocorticoid use in the United States general population was 1.2% (95% CI 1.1-1.4)[1].In a study of the United Kingdom general population, over 20 years, the long-term use of glucocorticoids (>3 months) was 0.75% (95% CI 0.74-0.75)[2].Over this time period, long-term corticosteroid prescriptions for rheumatoid arthritis, polymyalgia rheumatica/giant cell arteritis, ulcerative colitis, asthma, chronic obstructive pulmonary disease (COPD), and Crohn's disease were evident.In addition, among patients with a solid-organ transplant, who number more than 1 million worldwide, at least 50% take 5-10 mg of glucocorticoids per day over the long term.With this in mind, it is of utmost importance that patients are managed in the best way with regards to side effects, particularly infectious complications.What evidence is available about adverse events associated with steroid treatment?In 1958, Kass and Finland first reported on corticosteroid use and infections [3].More recently, in a meta-analysis that included 28 studies (2,382 patients), the overall risk of adverse events was 150 per 100 patient-years (95% CI 132-169).Psychological and behavioral adverse events (e.g., minor mood disturbances) were reported most frequently, followed by gastrointestinal events (e.g., dyspepsia and dysphagia).Infectious complications included bacterial infections; reactivation of tuberculosis or toxoplasmosis; and viral infections, including herpes virus, varicella zoster virus, and reactivation of viral hepatitis [4].In an analysis of pooled data from 71 randomized controlled trials that compared treatment with steroids versus no steroids, the overall rate of infectious complications was greater for those receiving steroids, i.e., the relative risk was increased by 60% (95% CI 30%-90%).However, infectious complications were not increased in those receiving a daily dose of <10 mg or a cumulative dose of <700 mg of prednisone [5].More recently, a study examined the risk of nonserious infection in older patients with rheumatoid arthritis (n = 16,207) receiving chronic systemic glucocorticoids: the overall incidence of a nonserious infectious complication was 47.5 per 100 person-years, with an adjusted risk ratio increased by 20% (95% CI 15%-25%) in patients given glucocorticoids; in addition, a dose-response effect was evident [6].In this issue of PLOS Medicine, Fardet and colleagues report on a study that examined common infections in UK patients prescribed systemic glucocorticoids in primary care [7].Anonymized electronic medical data from patients were retrieved from THIN (The Health Improvement Network).In the UK, ~98% of the population is registered with a general practitioner.Participating general practitioners systematically and prospectively enter and retrieve
Antinuclear antibodies in chronic psychotic patients treated with chlorpromazine
Authors: F P Quismorio, D F Bjarnason, W F Kiely, E L Dubois, G J Friou
Journal: American Journal of Psychiatry (1975)

The authors found a significantly higher incidence of antinuclear antibodies (ANA) and positive lupus erythematosus cell tests in chronic psychotic patients who received 400 mg a day or more of chlorpromazine (CPZ) for at least 7 weeks than in those who had taken 50 to 300 mg a day for varying periods or those who had received no CPZ for at least 3 months. Despite the high incidence of ANA, there was no observed development of lupuslike syndrome. The authors suggest that CPZ in high doses may induce ANA in humans.
How to report toxicity associated with targeted therapies?
Authors: B. Cabarrou, J.M. Boher, E. Bogart, E. Tresch-Bruneel, N. Penel, A. Ravaud, B. Escudier, C. Mahier Ait-Oukhatar, J.P. Delord, H. Roché, T. Filleron
Journal: Annals of Oncology (2016)
Abstract P3-05-15: Spatial and temporal genomic heterogeneity of estrogen receptor and clinical impact in a patient with advanced breast cancer
Authors: S Rizel, A Dvir, L Soussan-Gutman
Journal: Cancer Research (2016)

Abstract Endocrine therapy targeting Estrogen receptor alpha (ERα) is a key therapeutic strategy for hormone-driven breast cancer. Resistance to endocrine therapy may be intrinsic, arising from different clones or acquired by evolution influenced by selective pressure conditioned by therapy. Emerging evidence points to the role of acquired ERα mutations in driving resistance, when detected in the metastases but were absent from primary tumor. Here we studied tumor genomic evolution in a patient who developed two distinct recurrent consequences. The first recurrence was located at the lung and developed 14 years from diagnosis. In the adjuvant setting, the patient was treated with chemotherapy and had no endocrine therapy incorporated. On initial recurrence, the patient was treated with aromatase-inhibitor which resulted in complete response and the site is free of tumor now for 5.7 years. However, 2 years into endocrine therapy with aromatase-inhibitor the patient developed a single hepatic metastasis and treatment was changed to fulvestrant for 8 months with slow ongoing progression. The patient had partial hepatectomy, cholecystectomy and metastatectomy 3 months after fulvestrant was stopped. Histology and immunohistochemical stains confirmed breast origin, ER +2, 100%, PR +3, 100%. The endocrine therapy resistant hepatic lesion was sequenced by hybrid capture Next Generation Sequencing (NGS) and ERα (D538G) mutation was detected along with PIK3CA and GATA3 typical for hormone+ breast cancer. We have studied the primary tumor by same NGS method and detected only the PIK3CA and GATA3 mutations. In the lung lesions, responsive for endocrine therapy when sequenced by NGS the ERα (D538G) resistant mutation was absent. Clinical data for treatment of ERα (D538G) mutation driving endocrine resistance is lacking. The patient could not tolerate tamoxifen and failed treatments with aromatase-inhibitor and chemotherapy, losing 14 kg in weight. Treatment with megestrol acetate 160 mg was initiated and patient achieved partial response confirmed by hepatic MRI and an improved performance status which is now ongoing for 8 months. This case represents the first evidence of heterogeneous response to endocrine therapy explained by presence/absence of ERα (D538G) resistant mutation along with evidence for an active treatment in not an uncommon scenario. Citation Format: Rizel S, Dvir A, Soussan-Gutman L. Spatial and temporal genomic heterogeneity of estrogen receptor and clinical impact in a patient with advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-05-15.
Determining Optimal Therapy — Randomized Trials in Individual Patients
Authors: Gordon Guyatt, David Sackett, D. Wayne Taylor, John Ghong, Robin Roberts, Stewart Pugsley
Journal: New England Journal of Medicine (1986)

Abstract Although the treatment of an individual patient in routine clinical practice has been likened to an experiment, the method is so susceptible to bias that we have come to demand multi-patient, double-blind, randomized controlled trials on matters of efficacy. Unfortunately, such trials have not or cannot be carried out for many clinical disorders; even when they have been executed their results may be difficult to extrapolate to individual patients. To resolve this problem, we have begun to use double-blind randomized trials in which a single patient under-goes a series of pairs of treatments, consisting of one active and one placebo or alternative treatment per pair, with the order determined by random allocation. Appropriate treatment targets (signs, symptoms, or laboratory tests) are used as the measure of efficacy, and the trial is continued until efficacy is established or disproved. We describe such a trial, which resulted in a dramatically beneficial modification of treatment in a patient with partially reversible airflow limitation. We have established a clinical service that facilitates the widespread use of the method in our community. (N Engl J Med 1986; 314:889–92.)
Is the 315/P Tumor an IgA Lymphoma?
Authors: T. F. Warner, R. G. Krueger
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Is the 315/P Tumor an IgA Lymphoma? Get access JNCI: Journal of the National Cancer Institute, Volume 63, Issue 3, September 1979, Page 538, https://doi.org/10.1093/jnci/63.3.538 Published: 01 September 1979
Arterial Coronary Bypass Grafting
Authors: Kyriakos Anastasiadis, Georgios Tagarakis, Polychronis Antonitsis
Journal: Journal of the American College of Cardiology (2016)

We read with great interest the article by Gaudino et al. [(1)][1] on the choice of conduits in coronary artery surgery. They propose an algorithm for graft selection for the second target vessel considering technical, anatomic, and conduit patency characteristics. They focus on the lateral wall, as
Definitions of depression: concordance and prediction of outcome
Authors: I F Brockington, J E Helzer, V F Hillier, A F Francis
Journal: American Journal of Psychiatry (1982)

Using patient samples in London hospitals, the authors compared three methods of diagnosing and subdividing depressive illness in terms of their ability to predict outcome. The Catego class D+ selected patients who continued to suffer from episodes of psychotic depression. The Research Diagnostic Criteria selected patients with schizoaffective depressions whose outcome a completely different from that of major depressive disorder. DSM-III had advantages over the other systems, since it divides depression into three subtypes that differ from each other and from schizophrenia. Patients with a DSM-III diagnosis of mood-incongruent psychotic depression had persistent schizophrenic psychopathology, but their outcome differed from that of both schizophrenic and manic-depressive patients.
Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF)
Authors: Karen Sliwa, Albertino Damasceno, Beth A. Davison, Bongani M. Mayosi, Mahmoud U. Sani, Okekuchwu Ogah, Charles Mondo, Dike Ojji, Anastase Dzudie, Charles Kouam Kouam, Gerald Yonga, Serigne Abdou Ba, Elijah Ogola, Christopher Edwards, Olga Milo, Gad Cotter
Journal: European Journal of Heart Failure (2016)
<i>nab</i>-paclitaxel (<i>nab</i>-P) plus gemcitabine (Gem) vs Gem alone as adjuvant treatment for resected pancreatic cancer (PC) in a phase III trial (APACT).
Authors: Margaret A. Tempero, Dana Backlund Cardin, Andrew Biankin, David Goldstein, Malcolm Moore, Eileen Mary O'Reilly, Philip Agop Philip, Hanno Riess, Teresa Macarulla, Lotus Yung, Mingyu Li, Brian Lu
Journal: Journal of Clinical Oncology (2015)

TPS4153 Background: Adjuvant chemotherapy for resected PC has been shown to decrease recurrence and increase survival. Gem alone is a standard adjuvant therapy option. nab-P + Gem was superior to Gem alone as first-line treatment in a phase III trial in patients (pts) with metastatic PC, including the primary endpoint of overall survival (median, 8.5 vs 6.7 months; HR 0.72; P < 0.001). Toxicities were manageable. Based on these findings in the metastatic setting, the APACT trial will compare nab-P + Gem vs Gem alone in the adjuvant setting. Methods: Pts with histologically confirmed PC who underwent macroscopic complete resection (R0 or R1) within 12 weeks of randomization, with no evidence of metastasis at screening, are eligible for enrollment. Other eligibility criteria include staging of T1-3, N0-1, M0; Eastern Cooperative Oncology Group performance status of 0 or 1; acceptable hematologic function; CA19-9 < 100 U/mL prior to randomization; and no prior neoadjuvant therapy or radiation for PC. Pts with neuroendocrine tumors, any other malignancy within 5 years of randomization, infection with HIV or hepatitis B or C, or prior neoadjuvant treatment or radiation therapy for PC are ineligible. The planned enrollment of ≈ 800 pts will allow 90% power to detect an HR for disease-free survival (DFS) of 0.74 at a 2-sided significance level of 0.05. One interim safety analysis and 2 interim efficacy analyses (the first for futility and the second for futility and efficacy) will be performed. Pt enrollment is ongoing. Clinical trial NCT01964430. Clinical trial information: NCT01964430. Planned N ≈ 800 Investigational arm nab-P 125 mg/m2 plus Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle × 6 cycles Control arm Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle × 6 cycles Randomization 1:1 Stratification factors Resection status (R0 vs R1) Nodal status (lymph node + vs lymph node −) Geographic region (North America vs Europe vs Australia vs Asia Pacific) Primary endpoint DFS (independently assessed) Secondary endpoints OS, safety Exploratory endpoints Molecular profiling of tumor tissue to correlate tumor heterogeneity with clinical outcome Quality of life as assessed by the EORTC questionnaires QLQ-C30 and QLQ-PAN26
The relationship between personality and DSM-III axis I disorders in the population: results from an epidemiological survey
Authors: G Nestadt, A J Romanoski, J F Samuels, M F Folstein, P R McHugh
Journal: American Journal of Psychiatry (1992)

The aim of this study was to assess the relationships between specific personality disorders and DSM-III axis I conditions in a community sample.A total of 810 subjects were examined by psychiatrists in the second stage of the Eastern Baltimore Mental Health Survey, part of the Epidemiological Catchment Area Program of the National Institute of Mental Health. A semistructured examination, the Standardized Psychiatric Examination, was employed to assess axis I and axis II conditions. Scales for compulsive and antisocial personality disorders were derived from DSM-III criteria. The relationships between scores on these personality disorder scales and the presence of generalized anxiety disorder, alcohol use disorders (alcohol abuse and alcohol dependence), and simple phobia were evaluated by using logistic regression.Higher compulsive personality scores were associated with a greater odds of generalized anxiety disorder and simple phobia but a smaller odds of alcohol use disorders. In contrast, higher antisocial personality scores were associated with a greater odds of alcohol use disorders but a smaller odds of generalized anxiety disorder. There was no relationship between antisocial personality scores and simple phobia.Personality disorders have specific relationships to axis I conditions, which suggests different vulnerabilities but also different protective influences.
Computing tumor trees from single cells
Authors: Alexander Davis, Nicholas E. Navin
Journal: Genome biology (2016)

Computational methods have been developed to reconstruct evolutionary lineages from tumors using single-cell genomic data. The resulting tumor trees have important applications in cancer research and clinical oncology. Please see related Research articles: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0929-9 and http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0936-x .
Prognostic importance of subdividing clinically staged IIIa and IIIb patients with non-small-cell lung cancer.
Authors: P D Bonomi, M Gale, L P Faber, S Reddy
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.2.357 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1846408 Prognostic importance of subdividing clinically staged IIIa and IIIb patients with non-small-cell lung cancer. P D BonomixP D BonomiSearch for articles by this author , M GalexM GaleSearch for articles by this author , L P FaberxL P FaberSearch for articles by this author , S ReddyxS ReddySearch for articles by this author https://doi.org/10.1200/JCO.1991.9.2.357 First Page PDF © 1991 by American Society of Clinical Oncology
Tuberculosis in a shopping centre, Portugal, 2004-5
Authors: R Duarte, A Miranda, R Braga, A Carvalho, J Rola, A Marques, H Barros
Journal: Eurosurveillance (2008)

Genotyping enables to confirm or exclude a tuberculosis (TB) cluster. Excluding the link between cases is particularly important in countries with intermediate/high incidence of TB where the emergence of several TB cases in a particular location in space or time (higher than the expected) could be explained by chance alone. During 2004 and 2005, five TB cases occurred in five shops of a Portuguese shopping centre which employed a total of about 1000 workers. After an epidemiological survey, 52 close contacts were identified and screened. Latent tuberculosis infection was diagnosed in 10 contacts (eight family members and two work colleagues of cases). Genotyping of the Mycobacterium tuberculosis isolates revealed no link between the cases. For this reason no screening of all staff of the shopping centre was carried out. However, close contacts (52) and all fellow workers (1000) were kept under surveillance for two years, and no additional cases were diagnosed. The present analysis demonstrates that the exclusion of a chain of ongoing transmission by genotyping for the investigation of a cluster is cost-effective from the perspective of the public health service, because it allows to avoid unnecessary large scale screening operation and instead to direct resources to more effective measures of TB control.
Abstract P6-03-04: Amplification of the WHSC1L1 oncogene regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over expression in breast cancer
Authors: SP Ethier, J Irish, J Mills, B Ivey, G Hardiam, R Wilson, A Domkowski, S Guest
Journal: Cancer Research (2016)

Abstract The 8p11-p12 amplicon occurs in approximately 15% of breast cancers and occurs almost exclusively in aggressive luminal B type tumors. Our lab and other labs have identified the WHSC1L1 oncogene as a driving oncogene from this region with potent transforming activity. In the present studies, we found that over expression of WHSC1L1 is linked to over expression of the ESR1 and ERα protein in the SUM-44 breast cancer cell line, and also in primary human breast cancer specimens. Knockdown of WHSC1L1, and particularly the short isoform of WHSC1L1, had a dramatic effect on ESR1 mRNA and ERα protein levels. SUM-44 cells do not require exogenous estrogen for continuous growth in vitro; however these cells are dependent on ERα expression as determined from ESR1 knockdown experiments, and potent growth inhibition and ERα degradation following exposure to the selective estrogen receptor degrader (SERD) fulvestrant. ChIP-Seq experiments utilizing ERα antibodies demonstrated potent ERα binding to chromatin in SUM-44 cells under estrogen-free conditions. ERα bound to ERE and FOXA1 binding motifs under estrogen-free conditions and regulated expression of number of well-known estrogen responsive genes. Short term treatment with estradiol enhanced binding of ERα to chromatin and influenced expression of many of the same genes expressed and to which ERα was bound under estrogen-free conditions. Finally, knockdown of WHSC1L1 in SUM-44 cells resulted in loss of ERα binding to chromatin under estrogen-free conditions; however treatment estradiol restored ERα binding to chromatin at key estrogen-response elements and genes. These results indicate the SUM-44 cells are a good model for a subset of luminal B breast cancers that have the 8p11-p12 amplicon, over express the WHSC1L1 oncogene, and over express ERα that is independent of estrogen for binding to chromatin and regulation of gene expression. Dependence on ERα activity for growth and survival of breast cancer cells but independence of estradiol is a major cause of breast cancer mortality as such cells become non-responsive to current hormonally based therapies. Citation Format: Ethier SP, Irish J, Mills J, Ivey B, Hardiam G, Wilson R, Domkowski A, Guest S. Amplification of the WHSC1L1 oncogene regulates expression and estrogen-independent activation of ERα in SUM-44 breast cancer cells and is associated with ERα over expression in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-04.
A Difference-in-Differences Approach to Assess the Effect of a Heat Action Plan on Heat-Related Mortality, and Differences in Effectiveness According to Sex, Age, and Socioeconomic Status (Montreal, Quebec)
Authors: Tarik Benmarhnia, Zinzi Bailey, David Kaiser, Nathalie Auger, Nicholas King, Jay S. Kaufman
Journal: Environmental Health Perspectives (2016)

The impact of heat waves on mortality and health inequalities is well documented. Very few studies have assessed the effectiveness of heat action plans (HAPs) on health, and none has used quasi-experimental methods to estimate causal effects of such programs.We developed a quasi-experimental method to estimate the causal effects associated with HAPs that allows the identification of heterogeneity across subpopulations, and to apply this method specifically to the case of the Montreal (Quebec, Canada) HAP.A difference-in-differences approach was undertaken using Montreal death registry data for the summers of 2000-2007 to assess the effectiveness of the Montreal HAP, implemented in 2004, on mortality. To study equity in the effect of HAP implementation, we assessed whether the program effects were heterogeneous across sex (male vs. female), age (≥ 65 years vs. < 65 years), and neighborhood education levels (first vs. third tertile). We conducted sensitivity analyses to assess the validity of the estimated causal effect of the HAP program.We found evidence that the HAP contributed to reducing mortality on hot days, and that the mortality reduction attributable to the program was greater for elderly people and people living in low-education neighborhoods.These findings show promise for programs aimed at reducing the impact of extreme temperatures and health inequities. We propose a new quasi-experimental approach that can be easily applied to evaluate the impact of any program or intervention triggered when daily thresholds are reached. Citation: Benmarhnia T, Bailey Z, Kaiser D, Auger N, King N, Kaufman J. 2016. A difference-in-differences approach to assess the effect of a heat action plan on heat-related mortality, and differences in effectiveness according to sex, age, and socioeconomic status (Montreal, Quebec). Environ Health Perspect 124:1694-1699; http://dx.doi.org/10.1289/EHP203.