tbuckley/cabot-search huggingface dataset:
P184 Identifying learning strategies used by respiratory trainees in bronchoscopy
Authors: S. Wiscombe
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Medical bronchoscopy is a key skill for respiratory physicians taking years to achieve competency. The majority of trainees learn traditionally by one-to-one mentorship. However, introduction of the European Working Time Directive and increase in numbers of trainees has led to a breakdown in the mentorship model and reduced opportunity to attend procedural lists. In 2009, Du Rand and Lewis presented results of a national survey of training in Bronchoscopy. “Learning curves” of average number of procedures required to become competent in different aspects of sampling in bronchoscopy were presented, but no information was gathered on different approaches to learning or factors affecting these curves. Indeed, there have been no studies examining “how” trainees learn in bronchoscopy. This study aimed to identify learning strategies currently being used by respiratory trainees in bronchoscopy and any helpful or unhelpful factors in this learning strategy. <h3>Methods</h3> A qualitative study in two parts was conducted between April and June 2011. Firstly, a questionnaire to all respiratory trainees in the Northern Deanery. Thematic analysis was used to identify core themes and design the format for a subsequent focus group. The focus group was transcribed in full and two independent evaluators identified themes from the raw data. Triangulation was sought through a separate questionnaire to trainers. Validation of results was provided through local presentation of results. <h3>Results</h3> 19 trainees and seven consultants completed questionnaires and five trainees took part in the focus group. Abstract P184 table 1 summarises themes identified. Few trainees had an explicit learning plan, however, trainees and trainers readily identified key steps involved in the primary approach of “learning from experience”. Furthermore, many participants identified similar helpful and unhelpful factors within their own learning, their trainers9 behaviour and the training environment. Many of these findings are supported by established learning theory and procedural-based learning (Kolb, 1984, Thuraisingam <i>et al</i>, 2006). <h3>Conclusions</h3> Experience of the procedure is the key learning approach used by trainees in bronchoscopy. There are core steps within this that trainees and trainers can utilise to maximise learning. This is particularly important at the current time as training opportunities in bronchoscopy are reduced.
Death, Hospitalization, and Economic Associations among Incident Hemodialysis Patients with Hematocrit Values of 36 to 39%
Authors: ALLAN J. COLLINS, SUYING LI, WENDY ST. PETER, JIM EBBEN, TRICIA ROBERTS, JENNIE Z. MA, WILLARD MANNING
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Anemia treatment with epoetin has led to dramatic increases in hematocrit levels since 1989. Studies have demonstrated that morbidity and mortality rates are lower when hematocrit values are within the Disease Outcomes Quality Initiative (DOQI) target range (33 to 36%). Recently, clinical studies demonstrated that patients without cardiovascular disease exhibited lower morbidity rates and improved cognitive function with hematocrit values of >36%. One prospective trial, in contrast, demonstrated that normal hematocrit values among patients with cardiac disease were associated with higher mortality rates. These conflicting results have led to concerns regarding the risks and benefits associated with hematocrit values between 36 and 42%. To address these concerns, a recent cohort of 1996 to 1998 incident hemodialysis patients was studied, with assessments of the risks of death and hospitalization and the medical costs associated with hematocrit values of >36%. Patients survived at least 9 mo after dialysis initiation, and comorbidity, disease severity, and hematocrit levels were determined for months 4 to 9. Patients were grouped on the basis of hematocrit values, i.e., <30, 30 to <33, 33 to <36, 36 to <39, or ≥39%, with 1 yr of follow-up monitoring. A Cox regression model was used to evaluate all-cause and cause-specific mortality and hospitalization rates. The economic evaluations included analyses with Medicare Parts A and B allowable expenditures as the dependent variable and the same clinical characteristics as independent variables. For patients with hematocrit values of ≥36%, mortality rates were not different, hospitalization rates were 16 to 22% lower, and expenditures were 8.3 to 8.5% less, compared with patients with hematocrit values of 33 to <36%. These observations do not demonstrate causality. Additional long-term studies are needed to assess the risks of higher hematocrit values among all patients and patients with cardiovascular disease.
FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin
Authors: Aruna Kode, Ioanna Mosialou, Barbara C. Silva, Marie-Therese Rached, Bin Zhou, Ji Wang, Tim M. Townes, Rene Hen, Ronald A. DePinho, X. Edward Guo, Stavroula Kousteni
Journal: Journal of Clinical Investigation (2012)

Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element-binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation.
Encapsulated hepatocellular carcinoma in the absence of cirrhosis: A favorable prognosis
Authors: Fenton Schaffner
Journal: Hepatology (1987)

Clinicopathological features were studied in 41 patients with histology-proven hepatocellular carcinoma without cirrhosis. Of these, 13 (31.7%) were positive for hepatitis B virus surface antigen (HBsAg) and 28 were negative. Twenty-six of 28 (92.9%) HBsAg negative cases had anticore antibody (anti-HBc) of low titres. The age of patients at the time of diagnosis of hepatocellular carcinoma was significantly younger in the HBsAg positive cases compared with the negative. The initial diagnostic clue was either abdominal mass or abdominal pain in 18 (43.9%) patients. However, the number of patients in whom hepatocellular carcinoma was detected by imaging in the absence of such clinical signs has increased recently. The tumour was encapsulated in 31 cases (75.6%) and most solitary encapsulated tumours were growing expansively. Tumours were resectable in 29 (70.7%) cases, and the prognosis of resected cases was much better than that of 12 non-operated cases. Twenty-one out of 29 (72.4%) resected tumours were solitary and encapsulated. However, recurrence of tumour occurred in 12 out of 28 (42.9%) cases, and it was within 2 years of resection in 11 cases. These observations and data seem to indicate that early detection and resection of tumour is very important in management, but tumour recurrence is inevitable in a considerable proportion of the patients with non-cirrhotic hepatocellular carcinoma.
Improvements in health-related quality of life with belimumab, a B-lymphocyte stimulator-specific inhibitor, in patients with autoantibody-positive systemic lupus erythematosus from the randomised controlled BLISS trials
Authors: Vibeke Strand, Roger A Levy, Ricard Cervera, Michelle A Petri, Helen Birch, William W Freimuth, Z John Zhong, Ann E Clarke
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> Assess the effects of belimumab treatment plus standard systemic lupus erythematosus (SLE) therapy on health-related quality of life (HRQOL) in patients with active, autoantibody-positive SLE. <h3>Methods</h3> Patients received standard therapy plus placebo or belimumab 1 or 10 mg/kg in two multicentre, randomised controlled trials of 52 (BLISS-52; N=865) and 76 (BLISS-76; N=819) weeks' duration. Responders were evaluated by SLE Responder Index at week 52. Patient-reported outcome assessments included SF-36, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, and EQ-5D. <h3>Results</h3> Mean SF-36 Physical Component Summary (PCS) scores at week 24 was a major secondary endpoint. Baseline SF-36 scores were 1.5 SDs below age-/sex-matched US norms with similar improvement at week 24 across treatment groups. Mean changes from baseline in PCS scores were significantly (p&lt;0.05) greater with belimumab 1 mg/kg (4.20) and 10 mg/kg (4.18) versus placebo (2.96) in BLISS-52, week 52. In BLISS-76, significantly (p&lt;0.05) greater improvements were seen with belimumab 1 mg/kg in PCS (belimumab 1 mg/kg=4.37, 10 mg/kg=3.41 vs placebo=2.85) and Mental Component Summary (MCS) scores (belimumab 1 mg/kg=3.14, 10 mg/kg=2.70 vs placebo=1.40) at week 52, and in MCS score at week 76 (belimumab 1 mg/kg=3.05, 10 mg/kg=2.28 vs placebo=1.36). In pooled analysis, significantly greater improvements in PCS, SF-36 vitality domain, and FACIT-Fatigue scores at week 52 were evident with both belimumab doses. <h3>Conclusions</h3> The clinically meaningful improvements in HRQOL in autoantibody-positive patients with active SLE treated with belimumab and standard therapy are consistent with the reductions in disease activity observed in these trials. <h3>ClinicalTrials.gov number</h3> NCT00424476, NCT00410384.
Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin
Authors: John S. Strauss, James J. Leyden, Anne W. Lucky, Donald P. Lookingbill, Lynn A. Drake, Jon M. Hanifin, Nicholas J. Lowe, Terry M. Jones, Daniel M. Stewart, Michael T. Jarratt, Irving Katz, David M. Pariser, Robert J. Pariser, Eduardo Tschen, Dan K. Chalker, Elyse S. Rafal, Ronald P. Savin, Harry L. Roth, Lawrence K. Chang, David J. Baginski, Steven Kempers, John McLane, Douglas Eberhardt, Eileen E. Leach, Graeme Bryce, Joseph Hong
Journal: Journal of the American Academy of Dermatology (2001)
Factors determining outcome in patients with heart failure and normal ejection fraction
Authors: Caroline Tufaro, Julia Mascherbauer, Beatrice Marzluf, Thomas Binder, Irene Lang, Diana Bonderman
Journal: European Respiratory Journal (2012)

Background: Patients with heart failure and normal left ventricular ejection fraction (HFNEF) face an adverse outcome. Our aim was to identify factors that determine prognosis.

Methods: Patients diagnosed according to current ESC guidelines were recruited. Death and/or hospitalization for HF were defined as primary outcome variables. Outcome groups were compared with respect to potential prognostic predictors using the t-test. Multivariable logistic regression analysis determined whether parameters of interest were associated with adverse outcome. P<0.05 indicated statistical significance.

Results: Between December 2010 and January 2012, 49 patients (34 f/ 15 m, mean age 70±8 years) were registered. After a mean follow-up of 5±9 months, 14 (29%) patients were hospitalized or died. The adverse outcome group was characterized by higher body mass index (BMI, 35±7 versus 29±5, p=0.004), higher systolic pulmonary pressure on echo (sPAP in mmHg, 69±15 versus 55±14, p=0.004), shorter 6-minute walk distance (6-MWD in m, 271±131 versus 364±100, p=0.019), higher transpulmonary gradient (TPG in mmHg, 15±4 versus 12±4, p=0.013) and a higher pulmonary vascular resistance (PVR in dynes.s/cm5, 257±97 versus 198±71, p=0.030). Diabetes mellitus II (DM II, 75% versus 24%, p=0.002) and atrial fibrillation (92% versus 51%, p=0.013) were more prevalent among patients with adverse outcome. In the multivariable regression model, only DM II (OR 25.34[95% CI, 2.06 to 311.45]; p=0.012), BMI (OR 1.25[95% CI, 1.00 to 1.56]; p=0.048), and PVR (OR 1.02[95% CI, 1.00 to 1.05]; p=0.032) remained independent predictors of outcome.

Conclusions: Presence of DM II, higher BMI and higher PVR worsen prognosis in HFNEF patients.
OUTCOMES OF THE IMPLEMENTATION OF A MYOCARDIAL INFARCTION SYSTEM OF CARE IN A LARGE BRAZILIAN URBAN AREA
Authors: Bruno Ramos Nascimento, Milena Marcolino, Luisa Brant, Lucas Junqueira, Janaina Araujo, Luiz Ricardo A. Castro, Paula Martins, Antonio Ribeiro
Journal: Journal of the American College of Cardiology (2013)
Survival Advantage with Imatinib Mesylate Therapy in Chronic-Phase Chronic Myelogenous Leukemia (CML-CP) after IFN-α Failure and in Late CML-CP, Comparison with Historical Controls
Authors: Hagop Kantarjian, Susan O’Brien, Jorge Cortes, Francis Giles, Jianqin Shan, Mary Beth Rios, Stefan Faderl, Srdan Verstovsek, Guillermo Garcia-Manero, William Wierda, Steven Kornblau, Alessandra Ferrajoli, Michael Keating, Moshe Talpaz
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to compare the survival of patients with Philadelphia chromosome (Ph) -positive chronic myelogenous leukemia (CML) post-IFN-α failure treated with imatinib to historical experiences with standards of care or other therapies. Experimental Design: The outcome of 261 patients with Ph-positive chronic phase CML post-IFN failure treated with imatinib was compared with 204 historical control patients treated for a similar disease status with existing therapies. A subset of 147 patients in late chronic phase CML and 100% Ph-positive status treated with imatinib was compared with 95 patients in a similar disease status treated with IFN. Multivariate analyses were conducted to assess the independent prognostic effect of therapy (imatinib versus other) on survival. Results: In the first analysis involving 261 patients on imatinib plus 204 historical patients, the complete cytogenetic response rates were 62% and 19%, respectively (P &amp;lt; 0.001). A multivariate analysis identified pretreatment peripheral blasts and thrombocytosis to be independent poor prognostic factors for survival. Imatinib therapy (versus others) was a significant independent favorable prognostic factor for survival (hazard ratio, 0.17; P &amp;lt; 0.0001). In the second analysis involving the subset of 147 patients receiving imatinib plus 95 historical patients treated with IFN regimens, the complete cytogenetic response rates were 41% and 7%, respectively (P &amp;lt; 0.001). A multivariate analysis selected pretreatment anemia and peripheral blasts to be significant independent poor prognostic factors for survival. Imatinib therapy (versus IFN) was an independent favorable prognostic factor for survival (hazard ratio, 0.20; P &amp;lt; 0.0001). Three-month and 6-month landmark analyses showed that patients in all cytogenetic response categories (major, minor, and none) after imatinib therapy had survival outcomes better than the historical control population. Within each cytogenetic response category, survival was also better with imatinib than with other therapies. Conclusions: This analysis provides evidence for a survival advantage with imatinib versus other therapies in chronic-phase CML post-IFN failure, and for a survival advantage with imatinib versus IFN in late chronic-phase CML.
Comparative study of nasopharyngeal aspirate and nasal swab specimens for detection of influenza
Authors: T. Heikkinen
Journal: BMJ (2001)

The neuraminidase inhibitors zanamivir and oseltamivir have been shown to be effective in the treatment of influenza A and B viral infections. Both of these drugs are ineffective against respiratory infections caused by other microbes. Although the onset of influenza is often abrupt with prominent systemic features, the clinical spectrum of this disease is extremely broad and it cannot be reliably distinguished from other respiratory infections on clinical grounds alone.1 To help them decide which patients will benefit from the new treatments for influenza doctors therefore need rapid and sensitive point of care tests to verify the cause of the infection.

A nasopharyngeal aspirate is generally considered the best specimen for detection of …
Heterogeneity of type-specific and cross-reactive antigenic determinants within a single M protein of group A streptococci.
Authors: J B Dale, I Ofek, E H Beachey
Journal: The Journal of Experimental Medicine (1980)

The heterogeneity of a pepsin extract of type-24 M protein (pep M24) was demonstrated by absorption of type-specific and cross-reactive human antisera with M protein fragments and heterologous serotypes of M proteins, pepsin extract of type-5 M protein (pep M5) and pepsin extract of type-6 M protein (pep M6). 2 of 12 individuals immunized with pep M24 developed significant rises in antibody titers against pep M5 and pep M6, as measured by the enzyme-linked immunosorbent assay. The sam individuals also developed opsonic antibodies against type-6, but not type-5, streptococci, which suggested the development of cross-protective immunity. Inhibition studies of one of these sera with the heterologous pep M proteins showed that the cross-reactive antibodies against pep M6 could not be blocked by high concentrations of pep M24, the immunizing antigen; these antibodies could be blocked, however, by cyanogen bromide-derived peptide fragments of pep M24, which suggested that the cross-reactive antibody was raised against an inaccessible site(s) in the pep M24 molecule. Inhibition studies of type-specific immune sera with pep M24 and peptides derived therefrom indicated that the M protein molecule contained multiple distinct as well as identical type-specific antigenic determinants that are unequally distributed among the seven derived peptide fragments.
Measuring Adherence to Asthma Medication Regimens
Authors: Cynthia S. Rand, Robert A. Wise
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The failure of patients to adhere to physician-prescribed regimens, either pharmacologic or behavioral, has been well documented in medical literature. Poor adherence to asthma medication regimens has been repeatedly demonstrated in both children and adults, with rates of nonadherence commonly reported from 30 to 70%. Medication regimens for asthma care are particularly vulnerable to adherence problems because of their duration, the use of multiple medications, and the periods of symptom remission. The clinical effects of this nonadherence by asthmatic patients can include treatment failure, unnecessary and dangerous intensification of therapy, and costly diagnostic procedures, complications, and hospitalizations. Although the measurement of adherence is an important component of both medical and behavioral interventions to control asthma, relatively little research has directly addressed the reliability and validity of the measures most widely used to assess asthma medication compliance. This review will discuss methods and issues in the measurement of adherence in general, and where available, measures that have been specifically used in evaluating adherence to asthma medication. Common measures used to assess compliance with asthma medications include direct measures, which confirm the use of medication by assaying it in blood, urine, or saliva, or which confirm the to use a medication, such as observed skill in using a metered dose inhaler. Indirect measures infer use with varying degrees of reliability, by use of clinical judgment, self-report/asthma diaries, medication measurement, and electronic medication monitors. The uses and limitations of these measures will be discussed.
A 22 year old man with acute genital oedema and a swollen ankle
Authors: D. J. C. Komen, M. B. A. V. Doorn, J. E. Zeegelaar
Journal: BMJ (2011)

A 22 year old man was referred to our outpatient department with a painless non-pruritic swelling of the genitals that had spontaneously developed in the course of a few hours. He had taken no medication in the past few months and denied having allergies. His medical history included intermittent “joint swellings,” which started at the age of 12. These swellings were sometimes preceded by a tingling sensation and usually resolved spontaneously within two days. Furthermore, at the age of 22 he was admitted to hospital with an episode of acute and severe abdominal pain for which no apparent cause was found.

Physical examination showed scrotal and penile oedema (fig 1⇓), with no mucosal defects or skin abnormalities. He also had subtle swelling around the right ankle (fig 2⇓). His vital signs were within the normal range and his temperature was 36.8°C. Ultrasonography of the scrotum and penis showed extensive subcutaneous oedema but no other abnormalities. Screening laboratory analyses (blood and urine) were unremarkable.







### 1 What are the likely diagnosis and the differential diagnoses?

#### Short answer

The signs and symptoms and his medical history suggest a diagnosis of hereditary angio-oedema. The main differential diagnosis is Quincke’s oedema. Other differential diagnoses are idiopathic scrotal oedema, allergic reactions, drug reactions, and penile friction oedema.

#### Long answer

The main diagnosis to consider in this case is hereditary angio-oedema. This is a rare autosomal dominant disease caused by mutations in the gene encoding the broad spectrum protease inhibitor C1 esterase inhibitor (C1INH), which leads to reduced plasma concentrations of functional C1INH.1 This enzyme is the primary inhibitor of the complement proteases C1r and C1s as well as the contact system proteases, activated Hageman factor (coagulation factors XIIa and XIIf), …
GPER Mediates Activation of HIF1α/VEGF Signaling by Estrogens
Authors: Ernestina Marianna De Francesco, Michele Pellegrino, Maria Francesca Santolla, Rosamaria Lappano, Emilia Ricchio, Sergio Abonante, Marcello Maggiolini
Journal: Cancer Research (2014)

Abstract Biological responses to estrogens in normal and malignant tissues are mainly mediated by the estrogen receptors ERα and ERβ, which function as ligand-activated transcription factors. In addition, the G protein–coupled receptor GPR30 (GPER) mediates estrogenic signaling in breast cancer cells and cancer-associated fibroblasts (CAF) that contribute to cancer progression. In this study, we evaluated the role elicited by GPER in the estrogen-regulated expression and function of vascular endothelial growth factor (VEGF) in ER-negative breast cancer cells and CAF. We demonstrated that 17β-estradiol (E2) and the GPER-selective ligand G-1 triggered a GPER/EGFR/ERK/c-fos signaling pathway that leads to increased VEGF via upregulation of HIF1α. In further extending the mechanisms involved in E2-supported angiogenesis, we also showed that conditioned medium from CAF treated with E2 and G-1 promoted human endothelial tube formation in a GPER-dependent manner. In vivo, ligand-activated GPER was sufficient to enhance tumor growth and the expression of HIF1α, VEGF, and the endothelial marker CD34 in a mouse xenograft model of breast cancer. Our findings offer important new insights into the ability of estrogenic GPER signaling to trigger HIF1α-dependent VEGF expression that supports angiogenesis and progression in breast cancer. Cancer Res; 74(15); 4053–64. ©2014 AACR.