tbuckley/cabot-search huggingface dataset:
Topical Chemotherapy in Cutaneous T-cell Lymphoma
Authors: Stuart R. Lessin, Madeleine Duvic, Joan Guitart, Amit G. Pandya, Bruce E. Strober, Elise A. Olsen, Christopher M. Hull, Elizabeth H. Knobler, Alain H. Rook, Ellen J. Kim, Mark F. Naylor, David M. Adelson, Alexa B. Kimball, Gary S. Wood, Uma Sundram, Hong Wu, Youn H. Kim
Journal: JAMA Dermatology (2012)

To evaluate the efficacy and safety of a novel mechlorethamine hydrochloride, 0.02%, gel in mycosis fungoides. DESIGN Randomized, controlled, observer-blinded, multicenter trial comparing mechlorethamine, 0.02%, gel with mechlorethamine, 0.02%, compounded ointment. Mechlorethamine was applied once daily for up to 12 months. Tumor response and adverse events were assessed every month between months 1 and 6 and every 2 months between months 7 and 12. Serum drug levels were evaluated in a subset of patients.Academic medical or cancer centers.In total, 260 patients with stage IA to IIA mycosis fungoides who had not used topical mechlorethamine within 2 years and were naive to prior use of topical carmustine therapy.Response rates of all the patients based on a primary clinical end point (Composite Assessment of Index Lesion Severity) and secondary clinical end points (Modified Severity-Weighted Assessment Tool and time-to-response analyses).Response rates for mechlorethamine gel vs ointment were 58.5% vs 47.7% by the Composite Assessment of Index Lesion Severity and 46.9% vs 46.2% by the Modified Severity-Weighted Assessment Tool. By the Composite Assessment of Index Lesion Severity, the ratio of gel response rate to ointment response rate was 1.23 (95% CI, 0.97-1.55), which met the prespecified criterion for noninferiority. Time-to-response analyses demonstrated superiority of mechlorethamine gel to ointment (P< .01). No drug-related serious adverse events were seen. Approximately 20.3% of enrolled patients in the gel treatment arm and 17.3% of enrolled patients in the ointment treatment arm withdrew because of drug-related skin irritation. No systemic absorption of the study medication was detected.The use of a novel mechlorethamine, 0.02%, gel in the treatment of patients with mycosis fungoides is effective and safe.clinicaltrials.gov Identifier:NCT00168064.
Ask-Advise-Connect
Authors: Jennifer Irvin Vidrine, Sanjay Shete, Yumei Cao, Anthony Greisinger, Penny Harmonson, Barry Sharp, Lyndsay Miles, Susan M. Zbikowski, David W. Wetter
Journal: JAMA Internal Medicine (2013)

Several national health care-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence-based treatments, such as quitline (telephone-based tobacco cessation services) assistance. The most notable examples are the 5 As (Ask, Advise, Assess, Assist, Arrange) and Ask. Advise. Refer. (AAR) programs. Unfortunately, rates of primary care referrals to quitlines are low, and most referred smokers fail to call for assistance.To evaluate a new approach--Ask-Advise-Connect (AAC)--designed to address barriers to linking smokers with treatment.A pair-matched, 2-treatment-arm, group-randomized design in 10 family practice clinics in a single metropolitan area. Five clinics were randomized to the AAC (intervention) and 5 to the AAR (control) conditions. In both conditions, clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record, and smokers were given brief advice to quit. In the AAC clinics, the names and telephone numbers of smokers who agreed to be connected were sent electronically to the quitline daily, and patients were called proactively by the quitline within 48 hours. In the AAR clinics, smokers were offered a quitline referral card and encouraged to call on their own. All data were collected from February 8 through December 27, 2011.Ten clinics in Houston, Texas.Smoking status assessments were completed for 42,277 patients; 2052 unique smokers were identified at AAC clinics, and 1611 smokers were identified at AAR clinics.Linking smokers with quitline-delivered treatment.Impact was based on the RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) conceptual framework and defined as the proportion of all identified smokers who enrolled in treatment.In the AAC clinics, 7.8% of all identified smokers enrolled in treatment vs 0.6% in the AAR clinics (t4 = 9.19 [P < .001]; odds ratio, 11.60 [95% CI, 5.53-24.32]), a 13-fold increase in the proportion of smokers enrolling in treatment.The system changes implemented in the AAC approach could be adopted broadly by other health care systems and have tremendous potential to reduce tobacco-related morbidity and mortality.
Pharmacogenomic Predictor Discovery in Phase II Clinical Trials for Breast Cancer
Authors: Lajos Pusztai, Keith Anderson, Kenneth R. Hess
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We examined if supervised analysis of gene expression data from phase II studies could identify HER-2 overexpression as a predictor of response to trastuzumab. Experimental Design: Gene expression data from 132 newly diagnosed breast cancers were used to simulate 50,000 single-agent phase II trastuzumab studies. True HER-2 amplification was assessed by fluorescence in situ hybridization. Results: Only 3.67% of the simulated studies yielded HER-2 as the top predictor, &amp;gt;96% of the individual “studies” picked a different gene as the most predictive of trastuzumab response. HER-2 was included in the top 10 gene list 9.73% of the time. When HER-2 was a priori defined as a potential predictor, 99.6% of the simulated studies confirmed overexpression among responders. Candidate marker testing may be more efficient than de novo predictor discovery in phase II trials. We describe a tandem, two-step phase II trial design for rapid marker assessment that combines two optimal two-stage phase II trials into a single study. In the first stage, unselected patients are treated, and if insufficient responses are seen, the trial remains open for marker-positive patients only and a second two-stage trial commences. Conclusions: The probability of successful discovery of drug-specific pharmacogenomic response markers in a typical phase II study is small. The evaluation of predefined predictors using tandem two-step phase II design has the advantages of estimating response rates in both unselected and marker-selected patient populations and allows for simultaneous screening of multiple different predictors for the same drug and several distinct predictor-drug pairs in a single, parallel multiarm trial.
Posterior Rotation of the Atrial Vector
Authors: ALTON I. SUTNICK, LOUIS A. SOLOFF
Journal: Circulation (1962)

ACUTE left ventricular failure frequently, if not always, produces acute left atrial distention.Such distention, if clinically recognizable, would be a useful sign of left ventricular failure, a disorder that notoriously may lack discriminatory findings.Angiocardiography that may specifically diagnose left atrial distention, and cardiac catheterization that may specifically diagnose acute left ventricular failure are not practical procedures simply to establish such diagnoses.The purpose of this study is to show that acute changes in the electrocardiographic P waves are useful and perhaps sensitive signs of acute left ventricular failure.
Transesophageal Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) and Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) Biopsy: a Combined Approach in the Evaluation of Mediastinal Lesions
Authors: P. Vilmann, M. Krasnik, S. S. Larsen, G. K. Jacobsen, P. Clementsen
Journal: Endoscopy (2005)

It would be desirable to develop minimally invasive methods of tissue diagnosis from lymph nodes as well as solid lesions in the mediastinum. The aim of the present study was to test the combined method of transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the evaluation of mediastinal lesions.EUS-FNA and EBUS-TBNA were compared in 33 patients, for the staging of lung cancer in patients with an established diagnosis of non-small-cell lung cancer (n = 20) or for diagnosis of a suspicious mediastinal lesion in patients with suspected lung cancer (n = 13). EBUS-TBNA and EUS-FNA were unsuccessful in one patient each. The diagnoses were verified in 28 of the remaining 31 patients either at thoracotomy (n = 9) or during the clinical follow-up (n = 19).A total of 119 lesions were sampled by EUS-FNA (n = 59) and EBUS-TBNA (n = 60). EUS-FNA and EBUS-TBNA demonstrated cancer in 26 and 28 lesions, respectively, and benign cytology in 30 and 28 lesions, respectively. Suspicious cells were found in three and four lesions by EUS-FNA and EBUS-TBNA, respectively. When the 60 EBUS-TBNA samples were compared with the 59 EUS-FNA samples, 11 additional cancer diagnoses and three samples with suspicious cells were obtained by EBUS-TBNA that had not been obtained by EUS-FNA. Conversely, EUS-FNA diagnosed 12 additional cancer diagnoses, one suspicious and one specific benign diagnosis (sarcoidosis) in addition to EBUS-TBNA. With a combined approach (EUS-FNA + EBUS-TBNA) in 28 of the 31 patients in whom a final diagnosis was obtained in the evaluation of mediastinal cancer, 20 patients were found to have mediastinal involvement, whereas no mediastinal metastases were found in eight patients. The accuracy of EUS-FNA and EBUS-TBNA, in combination, for the diagnosis of mediastinal cancer was 100 % (95 % CI, 83 - 100 %).EUS-FNA and EBUS-TBNA appear to be complementary methods. A combined approach with both EUS-FNA and EBUS-TBNA may be able to replace more invasive methods for evaluating lung cancer patients with suspected hilar or mediastinal metastases, as well as for evaluating unclear mediastinal or hilar lesions.
Ian Colin Stuart Normand
Authors: C. Rolles, T. Rolles
Journal: BMJ (2011)

Colin Normand was appointed to the foundation chair of child health at the new medical school of Southampton in 1971. His early years in Southampton were an exciting time as the new medical school took shape and there was the chance to innovate. Colin was very involved in the new curriculum, particularly as part of the team developing the then ground breaking fourth year study in depth, which was a unique feature of the Southampton course. He was also instrumental in promoting the use of regional centres for clinical teaching in paediatrics, making peripheral consultants honorary staff members of what was unofficially known as the Wessex Medical School. This involved him in the politics of increasing consultant numbers in the peripheral units where consultants often worked singlehanded. Over the years he became active in almost every aspect of university administration, and his skills as a chairman were sought after. He served on many august committees and boards in Southampton, in the region, and nationally, and he was an examiner and adviser to numerous bodies. He was deputy dean to the faculty of medicine from 1977 to 1980 and then dean from 1990 to 1993, during which time he oversaw the incorporation of the schools of physiotherapy, occupational therapy, and nursing into the faculty of medicine and worked hard to increase the collaboration between the university and the NHS—in particular NHS funding of certain university posts.

Under his guidance the paediatric department was a harmonious and stimulating place to work. He built it into a well-balanced and respected unit and somehow avoided the factions and tensions that can so easily develop. Sometimes he …
Electron-Beam Computed Tomography in the Assessment of Coronary Artery Disease After Heart Transplantation
Authors: Friedrich D. Knollmann, Wolfgang Bocksch, Susanne Spiegelsberger, Roland Hetzer, Roland Felix, Manfred Hummel
Journal: Circulation (2000)

Background —Our aim was to compare the electron-beam CT (EBCT) features of coronary arteries in heart transplant recipients with those of biplane coronary angiography and intracoronary ultrasound (ICUS). Methods and Results —We examined 112 heart transplant recipients (25 female; age, 17 to 69 years; median, 52 years) 1 to 153 months (median, 46 months) after surgery by EBCT to detect coronary artery calcifications. Calcifications were quantified by the Agatston scoring system. EBCT scores were compared with coronary angiography in all patients and ICUS of the left anterior descending coronary artery (LAD) in 100 patients. Coronary artery calcifications were found in 84 patients (75%). Angiographically, 16 patients displayed &gt;50% coronary artery stenoses, all of whom had some degree of coronary artery calcification and only 1 of whom had a score of &lt;55 ( P &lt;0.0001). With this threshold, EBCT had a sensitivity of 94%, a specificity of 79%, a positive predictive value of 43%, and a negative predictive value of 99% for detecting stenosis. ICUS confirmed the presence of calcified plaques in all patients with an LAD score &gt;9. EBCT total calcium score was associated with the degree of intimal proliferation in that patients without ICUS features of allograft vasculopathy had a median score of 0 (25th percentile, 0; 75th percentile, 0), whereas patients with Stanford class IV vasculopathy had a median score of 41 (9 to 98, P &lt;0.0001). Conclusions —EBCT is a promising noninvasive test for the detection of coronary heart disease in cardiac transplant recipients.
Prediction of Infant Birth Weight by GDM Screening Tests: Importance of plasma triglyceride
Authors: Robert H Knopp, M Scott Magee, Carolyn E Walden, Bartolome Bonet, Thomas J Benedetti
Journal: Diabetes Care (1992)

OBJECTIVE We measured plasma glucose, GHb, GPro, IRI and TG at 24–28-wk gestation to determine the extent of elevations in GDM and relationships to glucose intolerance and infant macrosomia. RESEARCH DESIGN AND METHODS Plasma samples were obtained 1 h after ingestion of 50 g glucose after an overnight fast in 521 randomly selected negative screenees, 264 positive screenees with GTT−, and 96 positive screenees with GTT+ (GDM). RESULTS Screening test values in GDM subjects exceeded the GTT− group, whose values exceeded those of negative screenees: glucose, 9.6*, 8.7*, 6.3 mM; GHb, 5.2*, 4.9*, 4.7%; GPro, 3.1*, 3.0*, 2.8%; IRI, 791*, 662*, 410 pM; and TG, 2.3*, 1.9, 1.9 mM, (*P &amp;lt; 0.005 vs. negative screenees). TG was the only test elevated in the GDM but not in the GTT− groups. Screening test values correlated with GTT values in the following order (strongest to weakest): glucose* &amp;gt; TG* &amp;gt; GHb* &amp;gt; IRI &amp;gt; GPro (*statistical significance). Plasma TG was the only screening test significantly associated with birth weight corrected for gestational age (birth-weight ratio) (r = 0.09–0.16) (P &amp;lt; 0.05 to &amp;lt; 0.01) and was of the same order as 1- and 2-h GTT associations with birth weight (r = 0.13 and 0.14, respectively) (P &amp;lt; 0.05 to &amp;lt; 0.01). Plots of TG/birth-weight ratio increased linearly to the 80–90th TG percentile in negative screenees and GTT− subjects. GDM subjects followed this trend but with more variation. Above the 90th percentile for TGs, birth-weight ratio trended lower, significantly so when the groups were combined (P &amp;lt; 0.05). In multivariate analysis, TG was associated with birth-weight ratio even when maternal prepregnancy weight and pregnancy weight gain associations with TG and birth-weight ratio were controlled (P &amp;lt; 0.019). CONCLUSIONS Of the five screening tests evaluated, all were elevated in GDM, but TG is the best discriminator of GDM from the GTT− group, and it is the only test significantly related to birth-weight ratio—and to glucose intolerance besides glucose itself. The TG association with birth weight is not explained fully by maternal weight. The results suggest that plasma TG may be a physiological contributor to infant birth weight. Further evaluation of plasma TG in GDM screening is justified, but GHb, GPro, and IRI appear to hold less promise.
Incidence of Second Primary Malignancies During a Long-term Surveillance of Patients With Differentiated Thyroid Carcinoma in Relation to Radioiodine Treatment
Authors: Babak Fallahi, Khadijeh Adabi, Mahnaz Majidi, Armaghan Fard-Esfahani, Ramin Heshmat, Bagher Larijani, Vahid Haghpanah
Journal: Clinical Nuclear Medicine (2011)

Controversies remain over the actual risk of developing a second primary malignancy (SPM) as a consequence of I-131 treatment in patients with differentiated thyroid carcinoma (DTC). The objective of this study was to evaluate the adjusted rate and risk estimate of SPM in radioiodine-treated patients after controlling for confounding factors.A retrospective cohort study was conducted on 973 cases randomly selected from a population of 9550 radioiodine-treated DTC patients. The cases with prior or coincident nonthyroid malignancies and those with SPM during the first 3 years of the initial I-131 treatment were not included. Age-standardized rate of SPM and its 95% confidence interval (CI) during a median of 6 (3-26) years follow-up in DTC patients was compared with that of the general population. A logistic multivariable analysis was also conducted to identify the potential covariate factors that might influence the risk of SPM.Eleven patients from 7370 person-years at risk developed an SPM. The standardized rate ratio of nonthyroid malignancy was 0.81 (95% CI, 0.57-1.04) for the studied patients relative to the general population. The cumulative dose of I-131 more than 40 GBq (1.08 Ci) was the sole factor associated with increased odds of SPM, after adjusting for age, follow-up duration, histology of DTC, presence of metastasis, and history of external radiotherapy (odds ratio, 113; 95% CI, 8.6-1495.6; P < 0.0001).The overall rate of SPMs was not significantly increased after a minimum interval of 3 years from the first I-131 treatment; however, the chance of this event may be radically increased in patients who had received a cumulative activity of I-131 exceeding 40 GBq (1.08 Ci).
Discordant Findings in Technetium-99m Pertechnetate and lodine-123 Thyroid Imaging Caused by Vascular Retention in the Superior Vena Cava
Authors: TIMOTHY S. BURKE, JAMES L. TATUM, MELVIN J. FRATKIN
Journal: Clinical Nuclear Medicine (1985)

This report demonstrates superior vena cava (SVC) retention of Tc-99m pertechnetate as a cause of discordant findings in thyroid imaging performed with Tc-99m pertechnetate and l-123.
Is dermatitis herpetiformis a proxy of prosperity?
Authors: F.R. Ali, J.T. Lear
Journal: British Journal of Dermatology (2013)

Funding sources: none. Conflicts of interest: J.T.L. has accepted honoraria for speaking at meetings by Leo, Galderma, Almirall, Astellas and GlaxoSmithKline. Madam, We read with interest the recent paper in this journal that sheds further light upon the reduced mortality observed among individuals with dermatitis herpetiformis.1 While Hervonen et al. corroborate previous findings of reduced smoking and lower rates of hyperlipidaemia among patients with dermatitis herpetiformis, they do not account for socioeconomic class in their analysis. A retrospective review of case records previously reported the association of development of dermatitis herpetiformis with both reduced prevalence of cardiovascular disease and higher social class.2 The recent Marmot Review of social determinants of health presented evidence that higher socioeconomic status is associated with better health outcomes and increased longevity, owing to the interaction of a myriad of factors including reduced prevalence of both smoking and poor diet.3 If dermatitis herpetiformis is a disease more likely to affect the affluent, reduced mortality may reflect the many facets of better living. The immunomodulatory properties of cigarette smoke may protect from dermatitis herpetiformis, possibly by suppressing natural killer lymphocytes4 or reducing intestinal IgA secretion.5 A similar phenomenon may be observed in other diseases for which smoking appears to confer protection, such as coeliac disease and ulcerative colitis. If recent public health campaigns to banish smoking and encourage healthier diets are successful, prolonged life may be enjoyed by greater swaths of society.
A 'Highly Significant' Comment
Authors: Charles N. Ellis
Journal: JAMA (1983)

To the Editor.—  A recent lead article (1983;249:3047) uses the termhighly significantseveral times in reference to the statistical difference between groups. This term, which is frequently misused in medical literature, is misleading because it implies that the difference was either important or more  than it might otherwise have been.  In fact, the termhighly significantonly means that the results were very unlikely to have been caused by chance alone. Usually, we accept a one-in-20 risk. For example, if the mean hematocrit value in a control group is different from the value for an experimental group and by appropriate statistical testing is shown to be different with aPvalue less than.05, we say that the two groups' hematocrit values are significantly different. If thePvalue had been highly significant at less than.001, we can only state that our conclusion is less likely to be in
Leukotriene receptor antagonists as first line or add-on treatment for asthma
Authors: F. M. Ducharme
Journal: BMJ (2011)

as adjuncts in the adjunctive treatment trial. The drugs were prescribed in an open label fashion, with doctors being able to add,switch,orstoptreatmentasindicatedandpatientsclaiming them at pharmacies as needed. More patients in the LTRA groups were prescribed a change in drug class or step-up treatment over the two years of the trials than their counterparts (31% v 21% in the monotherapy group and 25% v 0% in the adjunctive treatment group), suggesting that the response to LTRAs was suboptimal. Patients were clearly more adherent to LTRAs than to long acting β2 agonists as adjunctive treatment. The high retention rate (>90%) of both trials surpassedthoseoftraditionalefficacystudies.Ofnote,contrary to efficacy trials, no significant difference between the groups was found in quality of life, symptom scores, or exacerbations that required oral corticosteroids.