tbuckley/cabot-search huggingface dataset:
The NCI Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 is the new standard for oncology clinical trials
Authors: A. D. Colevas, A. Setser
Journal: Journal of Clinical Oncology (2004)

6098 Background: A need for reproducible, consistent and readily usable adverse event reports led the World Health Organization in 1979 to create a scale for adverse event (AE) description and grading. As the cancer clinical trials endeavor has become more complex, there has been a need for more complex yet easy to use AE criteria. The NCI published its 1st and 2nd versions of the CTC in 1982 and 1998 in response to this need. In 2001 The Cancer Therapy Evaluation Program of the NCI, in response to requersts from investigators, intiatated an effore to update the CTC. Methods: This updated version of naming and grading of adverse events in cancer clinical trials is the result of collaboration among academic, governmental, and pharmaceutical industry clinical investigators. The drafts of the CTCAE v3 were reviewed twice by more than 400 reviewers. Results: The CTCAE v. 3 was launched on the CTEP web site http://ctep.cancer.gov/reporting/ctc.html on June 10, 2003 and is used for all new NCI- sponsored clinical trials as of October 2003. The CTCAE v.3 contains 28 categories and 1056 specific adverse event terms, as compared to 24 and 395 respectively in the CTC v.2. Major changes include the elimination of duration and time- dependent grading of adverse events, integration of acute and late effects into one scoring system, and expansion of criteria relevant to surgical, radiation, and pediatric trials. The creation of supra-ordinate terms allows for greater site and organ specificity, especially in the categories of pain, infection, gastrointestinal and musculoskeletal adverse events. Conclusions: A direct mapping between CTCAE versions 2 and 3 is available to facilitate translation from one system to another . Additionally, both versions of the CTCAE have been mapped to the Medical Dictionary for Regulatory Activities (MedDRA™) for regulatory reporting purposes. It is anticipated that the CTCAE v.3 will replace v. 2 as the world standard for reporting of AEs in cancer clinical trials. The ASCO presentation will focus on changes to the CTCAE, comparisons with the older versions, and implications for AE recording and evaluation. No significant financial relationships to disclose.
Gastro-oesophageal reflux is a significant predictor of COPD exacerbations
Authors: Truls Sylvan Ingebrigtsen, Jacob Louis Marott, Jørgen Vestbo, Peter Lange
Journal: European Respiratory Journal (2013)

Background: Little is known on association between gastro-oesophageal reflux disease and medically treated exacerbations of COPD.  Methods: 1279 individuals with COPD and data on self-reported gastro-oesophageal reflux disease were identified among participants in the 3rd wave of the Copenhagen City Heart Study. The information, including severity of COPD, was linked with a nationwide prescription registry. Medically treated exacerbations of COPD were defined as at least one short course treatment with oral corticosteroids and/or the combination of oral corticosteroids with antibiotics. Univariate and multivariate logistic regression analyses were applied to explore the association between gastro-oesophageal reflux disease, and medically treated exacerbations of COPD during a five year follow-up period.  Findings: 162 (12.7%) of subjects with COPD had gastro-oesophageal reflux disease at baseline, and 192 (15.0%) had at least one medically treated exacerbation during follow-up. In univariate analysis, gastro-oesophageal reflux was significantly associated to having at least one medically treated exacerbation, OR=1.6 (95% CI, 1.03-2.4, p=0.03). In multivariate analyses, including age, gender, dysphagia, wheezing, gastric medication, breathlessness, GOLD stage (1-4), previous respiratory exacerbations, and chronic bronchitis as covariates, gastro-oesophageal reflux remained a significant predictor of COPD exacerbations, OR=1.7 (1.1-2.6, p=0.02).  Interpretation: Gastro-oesophageal reflux disease is a strong predictor of medically treated exacerbations in individuals with COPD selected from the general population.
Abstract 4423: Expected Outcomes of Superficial Femoral Artery Endovascular Interventions: A Meta-Analysis
Authors: Arun R Mahankali Sridhar, Vijay K Misra, Steven M Taylor, Todd A Dorfman, Alfred A Bartolucci, Brigitta C Brott, William B Hillegass
Journal: Circulation (2009)

A systematic review of English language literature from 1970 to 2009 identified 46 studies with 3189 patients reporting primary patency rates after consecutive SFA endovascular interventions. To mo...
Mortality from dementia in occupations at risk of exposure to bovine spongiform encephalopathy: analysis of death registrations Commentary: Uncertainty over length of incubation tempers optimism
Authors: P. Aylin, J. Bunting, B. De Stavola, M. P Coleman, A. Alperovitch
Journal: BMJ (1999)

# Mortality from dementia in occupations at risk of exposure to bovine spongiform encephalopathy: analysis of death registrations {#article-title-2}

Since the early 1980s close contact with animals or animal products infected with bovine spongiform encephalopathy has posed a putative risk of infection with Creutzfeldt-Jakob disease.Several groups with potentially high exposure have already been identified.1

To study whether transmissible spongiform encephalopathy has had any effect on people working in animal husbandry and slaughter, we used national mortality records to examine patterns of mortality from Creutzfeldt-Jakob disease and other dementias during 1979-80 and1982-96.

We studied people who died aged 20-74 years during 1979-1996 in England and Wales and for whom the occupational information recorded at death included butcher and abattoir worker,farmer and farm worker, or veterinarian. Women were selected on the basis of their own occupation, if recorded, or on the occupation of their spouse.

View this table:

Numbers of deaths, proportional mortality ratios (PMR), and 95% confidence intervals for Creutzfeldt-Jakob disease (CJD) and dementia among men and women aged 20-74 in selected occupational groups, England and Wales, 1979-96



The causes of death selected for study were Creutzfeldt-Jakob disease(ICD-9 046.1) and a wide range of dementias, including those most likely to be misdiagnosed as Creutzfeldt-Jakob disease.2 It was not possible to separate deaths from new variant disease. There were in any case too few deaths from new variant Creutzfeldt-Jakob disease within the study period (13 deaths during 1994-633) to include them as a separate category.

We calculated the age standardised proportional mortality ratio for …
A double-blind, placebo RCT evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer: The U.K. National Cancer Research Network (NCRN) Pomi-T study.
Authors: Robert J. Thomas, Madeleine M A Williams, Harbiner Sharma, Aasem Chaudry, Patricia Bellamy
Journal: Journal of Clinical Oncology (2013)

5008 Background: Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in cell lines and animal models. Although some have been investigated in small phase II studies, this combination had never been evaluated within an adequately powered nationally certified RCT. Methods: 203 men, average age 74 yrs, had localised prostate cancer, 59% managed with active surveillance and 41% with watchful waiting (progressive PSA relapse following previous radical interventions). They were randomised to receive a b.d. oral capsule containing a blend of pomegranate seed, green tea, broccoli and turmeric or an identical placebo for 6 months. The groups were statistically balanced in terms of gleason grade, body mass index (BMI), treatment category and fasting cholesterol although there was a difference in average age at baseline; 71.8 yrs in the food supplement group (FSG) versus 76.4 years in the placebo group (PG). Four men withdrew after randomisation. Results: The median rise in PSA in the FSG was 14.7% (95% CI 3.4-36.7%) versus 78.5% in the PG (95% CI 48.1-115.5%) (63.8% difference, ANCOVA analysis of covariance, p=0.0008). 46% of men had stable or lower PSA at trial completion in the FSG versus 14% in the PG (32% difference, chi 2 , p=0.00001). There were no significant differences in PSA% change within the predetermined subgroups (age, gleason grade, treatment category, BMI). There were no differences in cholesterol, blood pressure, blood sugar or c-reactive protein. 24% men recorded events in the FSG and 34% in the PG (non significant). Mild gastro-intestinal effects were (17%) in the FSG but 8% of these reported an improvement in stool quality. Conclusions: This study found a statistically significant short-term favourable effect on the percentage rise in PSA in these men managed with observation following intake of this specific food supplement. Although many men would see this as useful addition to their self help strategies, future trials should look at the longer-term clinical benefits particularly in terms of preventing medical intervention. Clinical trial information: 81263.
Middle East respiratory syndrome coronavirus not detected in children hospitalized with acute respiratory illness in Amman, Jordan, March 2010 to September 2012
Authors: N. Khuri-Bulos, D.C. Payne, X. Lu, D. Erdman, L. Wang, S. Faouri, A. Shehabi, M. Johnson, M.M. Becker, M.R. Denison, J.V. Williams, N.B. Halasa
Journal: Clinical Microbiology and Infection (2013)
A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII
Authors: Karam Kim, Gurpreet Lakhanpal, Hsiangmin E. Lu, Mustafa Khan, Akio Suzuki, Mariko Kato Hayashi, Radhakrishnan Narayanan, Thomas T. Luyben, Tomoki Matsuda, Takeharu Nagai, Thomas A. Blanpied, Yasunori Hayashi, Kenichi Okamoto
Journal: Neuron (2015)
Generalized cowpox infection in a patient with Darier disease
Authors: O. Haase, A. Moser, C. Rose, A. Kurth, D. Zillikens, E. Schmidt
Journal: British Journal of Dermatology (2011)

Funding sources: none. Conflicts of interest: none declared. Madam, Cowpox virus belongs to the family of Poxviridae, genus Orthopoxvirus, and is closely related to smallpox, vaccinia and monkeypox virus.1 Human cowpox is a zoonotic infection transmitted by mouse‐hunting cats or pet rats having their reservoir in wild rodents.2 The confusing names of cowpox and the closely related vaccinia virus originate from 1776 when Edward Jenner inoculated material from a dairymaid's hand to a boy who was subsequently protected against smallpox. Jenner described the difficulties of finding appropriate cowpox lesions in cows, suitable for vaccination.3 In fact, cows were later shown to be only accidental hosts of cowpox virus.4 In immunocompetent individuals, cowpox show a self‐healing disease with usually one painful lesion that passes the stages of a macule, papule or nodule, vesicle, pustule, ulcer and eschar with surrounding erythema and oedema.1 In contrast, in immunodeficient or eczematous patients, cowpox infection may become generalized, be accompanied with systemic symptoms or even be fatal.5, 6
CPAP titration in infants with severe airway obstruction
Authors: Sonia Khirani, Adriana Ramirez, Sabrina Aloui, Nicolas Leboulanger, Arnaud Picard, Brigitte Fauroux
Journal: European Respiratory Journal (2013)

Introduction   Noninvasive continuous positive airway pressure (CPAP) is recognised as an effective treatment for severe airway obstruction in young children.   Objectives   The aim of the study was to compare a clinical and a physiological setting of CPAP in infants with nocturnal alveolar hypoventilation due to severe upper airway obstruction (UAO) or bronchopulmonary dysplasia (BPD).   Methods   We retrospectively analysed the respiratory mechanics in infants who underwent a CPAP titration. CPAP set on clinical noninvasive parameters ( Clinical CPAP ) was compared to CPAP set on the normalisation or maximal reduction of the oesophageal (Poes) and transdiaphragmatic pressure (Pdi) swings  (Physiological CPAP ). Expiratory gastric pressure (Pgas) swing was measured.   Results   The data of twelve infants, mean age 10 ± 8 months, with UAO (n=7) or BPD (n=5) were analysed. The mean  Clinical CPAP  (8 ± 2 cmH 2 O) was associated with a significant decrease in Poes and Pdi swings (Poes swing decreased from 31 ± 15 cmH 2 O during spontaneous breathing to 21 ± 10 cmH 2 O during CPAP, p Physiological CPAP  level was 2 ± 2 cmH 2 O higher than the mean  Clinical CPAP  level and was associated with a significantly greater improvement in all indices of respiratory effort (Poes swing 11 ± 5 cm H 2 O, p Clinical CPAP ). An expiratory abdominal activity was present during the  Clinical CPAP  and decreased during the  Physiological CPAP.    Conclusion   A physiological setting of noninvasive CPAP, based on the recording of the Poes and Pgas, is superior to a clinical setting based on clinical noninvasive parameters. An expiratory abdominal activity was present during spontaneous breathing and decreased during the  Physiological CPAP  setting.
Abstract 1627: The novel camptothecin analog and antiapoptotic protein inhibitor FL118 appears to be a great backbone platform for development of personalized anticancer drugs
Authors: Fengzhi Li, Xiang Ling, David Westover, Xiaojun Liu, Chunyang Jin, Mansukh Wani
Journal: Cancer Research (2014)

Abstract We recently characterized a novel camptothecin analog FL118. Interestingly, different from the two clinically used camptothecin analogs irinotecan and topotecan, which are topoisomerase 1 (Top1) inhibitors, FL118 appears to be a poor Top1 inhibitor at its therapeutic dose range. Instead, FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins including survivin, Mcl-1, XIAP, and cIAP2. We have demonstrated that genetic knockdown or overexpression of survivin, Mcl-1, XIAP, or cIAP2 modulates FL118's ability to inhibit cancer cell growth and induce apoptosis. FL118 is able to eliminate both small and large human tumor xenografts in animal models. Importantly, FL118 effectively overcomes topotecan treatment-induced resistance of human colon tumor in animal models. Pharmacokinetics (PK) studies indicated that FL118 prefers to be accumulated in tumor and rapidly cleared in blood stream in animal models. Furthermore, our most recent studies demonstrated that maintenance of a free hydroxyl group in the lactone ring of FL118 is critical for its antitumor activity, and the superior antitumor efficacy of FL118 heavily depends on its steric configuration (Zhao et al., Molecular Pharmaceutics). Based on the current observation of FL118 properties, we hypothesize that FL118 is an ideal lead for development of novel analogs that may possess distinct antitumor selectivity to overcome different treatment resistance. In this regard, we tested 146 new camptothecin analogs, which were synthesized based on either the FL118 core structure or the camptothecin core structure, in four cancer cell lines and two normal cell lines. We identified 19 top candidates that showed inhibition of cancer cell growth and induction of apoptosis that are better than or comparable to FL118. Intriguingly, all of the 19 top compounds possess the FL118 core structure. Further investigation of the 19 compounds using cancer cells with distinct treatment resistant backgrounds indicated that these compounds showed distinct antitumor selectivity among different treatment resistant cancer cells. Therefore, while our finding would need further investigation using in vivo human tumor animal models, we propose to develop a series of FL118 analogs for personalized cancer treatment to overcome different treatment resistance. Citation Format: Fengzhi Li, Xiang Ling, David Westover, Xiaojun Liu, Chunyang Jin, Mansukh Wani. The novel camptothecin analog and antiapoptotic protein inhibitor FL118 appears to be a great backbone platform for development of personalized anticancer drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1627. doi:10.1158/1538-7445.AM2014-1627
Intranasal corticosteroids in allergic rhinitis
Authors: Damian Paddon
Journal: BMJ (1999)

Intranasal corticosteroids in allergic rhinitis Paper did not include all data on adverse effectsEditor-Weiner et al conclude that "results from [their] systematic review, together with data on safety and cost effectiveness, support the use of intranasal corticosteroids over oral antihistamines as first line treatment for allergic rhinitis." 1 They also state that "intranasal corticosteroids are considered safe [and] studies have failed to show significant effects on serum markers of bone metabolism and short term bone growth," referring to two studies, those by Martinati et al and Wolthers et al.They make no reference to two more recent studies, both of a larger number of subjects over longer periods, which established a significant reduction in paediatric bone growth. 2 3The issue of adverse effects was also addressed in a report by the Committee on Safety of Medicines and Medicines Control Agency, which concluded that intranasal corticosteroids can cause "clinically important systemic adverse effects at licensed doses." 4 The United Kingdom datasheet for Beconase aqueous nasal spray (beclomethasone dipropionate) recognises the potential for children to develop growth retardation at licensed doses and the need to refer patients to paediatric specialists while they are being prescribed intranasal corticosteroids (Allen and Hanburys, Sept 1998).I question the omission of such key data from Weiner et al's systematic review; it may well tip the risk:benefit ratio away from the use of intranasal corticosteroids in children and, hence, affect the validity of the review's conclusions.
Benzodiazepine dependence and withdrawal in elderly patients
Authors: E Schweizer, W G Case, K Rickels
Journal: American Journal of Psychiatry (1989)

Severity of withdrawal symptoms and clinical outcome were compared in 19 elderly and 22 younger benzodiazepine-dependent patients matched for benzodiazepine half-life, dosage, and duration of treatment. During gradual taper of benzodiazepine doses, the elderly patients showed significantly less severe withdrawal symptoms on several clinical measures and a comparably favorable outcome. Approximately half of each group remained benzodiazepine free for at least 4 weeks. Both groups of patients tolerated drug discontinuation without serious consequences such as seizures or psychosis. Tapered benzodiazepine withdrawal did not appear to be more risky for the elderly group than for the younger patients.
High-Dose Therapy and Autologous Stem-Cell Transplantation for Adult Patients With Hodgkin's Disease Who Do Not Enter Remission After Induction Chemotherapy: Results in 175 Patients Reported to the European Group for Blood and Marrow Transplantation
Authors: John W. Sweetenham, Angelo M. Carella, Golnaz Taghipour, David Cunningham, Robert Marcus, Aldo Della Volpe, David C. Linch, Norbert Schmitz, Anthony H. Goldstone
Journal: Journal of Clinical Oncology (1999)

To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors.A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses.Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value.High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy.
Relation of hepatitis C virus genotypes to risk factors and hepatic disease in Spanish patients
Authors: P. Alonso Alonso, A. Orduña, A. San Miguel, E. Dominguez, M.A. Bratos, M.P. Gutierrez, J.M. Eiros, L. Inglada, J. M. Gonzalez Hernandez, A. Rodriguez Torres
Journal: Clinical Microbiology and Infection (1997)
"Cross-talk" among a multiplicity of pro-inflammatory agents: main cause of tissue damage in pulmonary inflammation?
Authors: I Ginsburg
Journal: European Respiratory Journal (1999)

I was very interested by the letter of Z.T. Selc Ëuk and colleagues.Their papers on environmental exposure to erionite initiated by Y.I.Baris are universally known.I completely agree with their observations.With regard to tremolite exposure, we have found a very similar situation in Corsica [1].We all agree that thoracoscopy is better than fluid cytology and represents the gold standard for diagnosis and initial prognosis of mesothelioma.
Eyelashes hypertrichosis: A benign but frequent adverse effect with cetuximab
Authors: X. Tchiknavorian, L. Cals, I. Chabbert, H. Fezoui, N. Maille, P. Nouyrigat
Journal: Journal of Clinical Oncology (2005)

3747 Background: Cetuximab (ERBITUX) is a monoclonal antibody against R-EGF aproved in Europe since 2004 to use in combination with irinotecan in metastatics colorectal cancers resistant to a irinotecan based chemotherapy. It is still under unvestigation in head and neck cancers with platinium salt. Irinotecan and cisplatin both induce alopecia. Dueland and coll (2003) first report eyelashes hypertrichosis with cetuximab. Patients and Method: In this prospective study, we analysed all patients treated in a single institution who recieved cetuximab in combination with chemotherapy. Results: Among 15 patients (10 males, 5 females) we had 7 (46% ; 95% CI: 21–73) cases of hypertrichosis compelling to snip eyelashes. All patients but one had alopeciant systemic chemotherapy when occurs hypertrichosis. For one patient irinotecan was completed 2 weeks before. Conclusion: This benign adverse event is fairly frequent, to spare our patient the trouble of surprise. We should advise them. The confidence interval is to large in this small study and a new one should be done to specify the true frequency. References: Dueland S and coll. Acta Oncol. 2003;42(4):345–6 Clopper CJ, Pearson ES. Biometrika 1934;26:404 No significant financial relationships to disclose.