tbuckley/cabot-search huggingface dataset:
Systematic review and meta-analysis of the magnitude of the effect on AQLQ and ACQ in asthma clinical trials
Authors: Eric Bateman, Dirk Esser, Costel Chirila, Maria Fernandez, Andy Fowler, Petra Moroni-Zentgraf, Mark FitzGerald
Journal: European Respiratory Journal (2013)

Background:  The Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) are commonly used in clinical trials to assess patient disease-specific health status and asthma control.  Objectives:  We investigated the magnitude of effect observed in trials of different treatments with the AQLQ and ACQ instruments. A systematic literature review identified randomised controlled trials (RCTs) reporting changes from baseline in AQLQ and/or ACQ overall scores in adult patients with uncontrolled/symptomatic asthma at baseline.  Results:  Fifty-five RCTs (35,863 patients) met the inclusion criteria. The mixed treatment comparison (MTC) model for the AQLQ (48 RCTs) included statistically significant (P ≤0.05) covariates for study treatment, whether inhaled corticosteroid (ICS) was administered during a run-in phase, whether study treatment was administered on top of an ICS, AQLQ instrument type, and interaction between study and background treatment (Figure).  Findings for ACQ (6 RCTs) were broadly similar, but less robust because of small trial numbers.  Conclusions:  For both AQLQ and ACQ, the minimal important difference (MID) of 0.5 was achieved with most established asthma therapies vs. study baseline, but not for most between-groups comparisons against placebo. The magnitude of AQLQ score changes was also sensitive to trial design.  Funding: This study was funded by Boehringer Ingelheim.
Specificity and sensitivity of the methacholine challenge test for the diagnosis of asthma in athletes
Authors: Alexander Cherniak, Tatyana Pashkova, Malika Mustaphina, Svetlana Chikina, Tatyana Molostova, Zaurbek Aisanov
Journal: European Respiratory Journal (2012)

The report of recurrent symptoms of bronchial obstruction as chest tightness, wheeze and cough provoked by exercise is a prerequisite for the diagnosis of asthma or exercise-induced bronchospasm (EIB) in athletes. The report of symptoms should be verified by the demonstration of reversibility of airflow obstruction, EIB or other methods of diagnosing either indirect or direct bronchial hyperresponsiveness (BHR). The purpose of this study was to examine specificity and sensitivity of the methacholine challenge test (MCT) for the diagnosis of asthma in athletes.  Twenty seven athletes (16 M/11 F, mean age 22.0±4.3 yrs) with respiratory symptoms were studied. Lung function with assessment of reversibility to salbutamol (n=27) and challenge tests with methacholine (n=25) were performed. The specificity and sensitivity of the MCT were evaluated.  Significant reversibility to salbutamol was found in 7 athletes. The fall in forced expiratory volume in one second (FEV1) following the methacholine inhalation (≤8 mg/ml) was more than 20 % in 16 athletes (30.0±9.6 % vs 12.3±7.1 % in nonresponders (n=9), p  Assessment of bronchial responsiveness by a direct method (bronchial provocation with methacholine) is a good procedure of diagnosing asthma in athletes. The MCT-BHR test in athletes with respiratory symptoms had a high specificity and sensitivity and cutoff value for high BHR may be more useful.
Improved prediction of disease-free survival in tamoxifen-treated patients using an expression signature of estrogen-regulated genes as compared to progesterone receptor
Authors: C. Creighton, J. Rae, A. Chinnaiyan, M. Lippman
Journal: Journal of Clinical Oncology (2006)

535 Background: Progesterone receptor (PR) is a direct downstream target of activated estrogen receptor (ER) and its expression is a marker of estrogen signaling within breast tumors. Studies suggest the absence of PR predicts the likelihood of distant recurrence in patients treated with hormonal therapies such as tamoxifen, but better clinical measures are needed. Methods: Through analysis of public mRNA expression profiling datasets, we identified 36 genes with the following expression patterns similar to PR: (1) induced by 17β-estradiol (E2) in estrogen receptor (ER)-positive breast cancer cell lines in vitro, (2) under-expressed in ER-negative compared to ER-positive breast tumors, and (3) correlated with PR expression in ER-positive tumors. The average expression of these 36 genes was used as a “risk index” for assessing disease-specific survival in two independent tumor profile datasets of 60 and 67 patients treated with tamoxifen (these data not having been used to initially select the 36 genes), with a high risk group in each dataset defined as those with the bottom 25% of risk index values. Results: The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk and high-risk groups were 24% and 64% in the one dataset and 32% and 72% in the other dataset. In both validation datasets, the rate in the low-risk group was significantly lower than that in the high-risk group (P=0.008 and P=0.006 by log-rank, respectively), whereas patient groups defined by histologically-assigned PR status did not show significant risk differences (P=0.70 and P=0.94, respectively). In a univariate Cox model, the risk index combined across both validation datasets provided significant predictive power (P=0.03). Conclusions: Through RT-PCR assay of a larger independent cohort of breast tumor samples, we are currently validating the prognostic value of individual genes within the 36-gene signature. No significant financial relationships to disclose.
The "SAPHO" syndrome: a case report of a patient with unusual bone scan findings.
Authors: PRIYADARSHANI BHOSALE, BRUCE BARRON, LAMK LAMKI
Journal: Clinical Nuclear Medicine (2001)

Purpose The authors describe the clinical and bone scintigraphic findings of the SAPHO syndrome, which is characterized by synovitis, acne, palmoplantar pustulosis, hyperostosis, and osteitis. The case report illustrates the significance of bone scintigraphy in the diagnosis. It shows that Tc-99m MDP scanning can detect signs of arthritis not seen with other imaging methods, because the arthritis is inflammatory in nature and does not always cause bone erosion. Thus it is not visualized on plain radiographs. Knowledge of this disorder may help in the differential diagnosis of arthritis. Materials and Methods Tc-99m MDP bone scintigraphy was used to diagnose arthritic changes. Whole-body and multiple delayed spot images were obtained in a 39-year-old diabetic, hypertensive woman who had tenderness in the plantar aspect of her heels. Swelling of the small and large joints of the feet, ankles, knees, hips, right sacroiliac joints, and shoulders was noted. She also had hydradenitis suppurativa and a history of a previous episode in which the arthritis improved after surgical treatment for the hydradenitis. Results All active joint lesions were visualized on the bone scan, including the arthritis, which was not detected with other imaging methods. They were all well demonstrated in the bone scintiscan. The scan findings, along with the presence of hydradenitis, led to the correct diagnosis of SAPHO syndrome. Conclusion Tc-99m MDP bone scanning may be helpful in diagnosing arthritis as associated with the SAPHO syndrome.
Health Policy Basics: Implementation of the International Classification of Disease, 10th Revision
Authors: Brian Outland, Mary M. Newman, Margo J. William
Journal: Annals of Internal Medicine (2015)

The International Classification of Diseases (ICD) standardizes diagnostic codes into meaningful criteria to enable the storage and retrieval of information regarding patient care. Whereas other countries have been using ICD, 10th Revision (ICD-10), for years, the United States will transition from ICD, Ninth Revision, Clinical Modification (ICD-9-CM), to ICD-10, on 1 October 2015. This transition is one of the largest and most technically challenging changes that the medical community has experienced in the past several decades. This article outlines the implications of moving to ICD-10 and recommends resources to facilitate the transition.
Abstract 9174: Global Variation in the Etiology and Management of Atrial Fibrillation: Results from a Global Atrial Fibrillation Registry
Authors: Jeff S Healey, Jonas Oldgren, Amit Parekh, Patrick J Commerford, Alvaro Avezum, Prem Pais, Jun Zhu, Petr Jansky, Alben Sigami, Carlos A Morillo, Lisheng Liu, Albertino Damasceno, Alex Grinvalds, Paul Reilly, Michael Ezekowitz, Lars Wallentin, Stuart J Connolly, Salim Yusuf
Journal: Circulation (2011)

Background: Atrial fibrillation (AF) is the most common arrhythmia worldwide. A truly global registry is needed. Methods: The AF registry enrolled unselected patients who presented to an emergency department with AF. Results: A total of 14,434 patients were enrolled: 45% with AF as their primary diagnosis and 36% with their first documented episode of AF. The number of sites and patients were: North America (18; 1787), Latin America (23; 1116), Western Europe (19; 1903), Eastern Europe (22; 2445), Middle East (8; 813), Africa (20; 891), India (24; 2450), China (20; 1905) and Asia (12; 1124). The average age of patients in North America was 70.2 years and 57.7 % of patients were male. Patients in Africa and India were 12 years younger and were more likely to be female. Hypertension was the most common risk factor, present in 62% of patients worldwide. Its prevalence ranged from 41.5% in India to 80.0% in Eastern Europe. Heart failure was the second most common risk factor, present in 35% of patients worldwide. Its prevalence ranged from 17.4% in India to 70.5% in Africa. Rheumatic heart disease was present in only 2.1% of North American patients with AF, compared to 15.3% in both the Middle East and China, 22.0% in Africa and 30.9% in India. In Africa, more than 5% of AF cases were associated with pericarditis or endomyocardial fibrosis, while these conditions were present in &lt; 1% of patients elsewhere. In North America, the use of oral anticoagulation (OAC) among patients with AF and a CHADS 2 score of ≥ 2 was 72.6%. Elsewhere, the rate was from 19% in China to 63% in Eastern and Western Europe. For patients treated with OAC, the proportion of INR values between 2.0 and 3.0 ranged from 32.6% in India to 66.5% in Western Europe. Conclusions: Although advanced age, hypertension and heart failure are the most common predisposing conditions for AF in all regions, rheumatic heart disease remains an important cause in low-income countries. Appropriate use of OAC is low, particularly in low-income countries.
Epidemiology and comorbidity of anxiety disorders in the elderly
Authors: A J Flint
Journal: American Journal of Psychiatry (1994)

The author reviewed the epidemiology and comorbidity of anxiety disorders in the elderly.Data from 1970 onward were obtained through a computerized literature search, a review of Index Medicus, and the bibliographies of retrieved articles. Eight random-sample community surveys of anxiety disorders in persons 60 years of age or older were identified. Studies relating to the comorbidity of late-life anxiety and depression, dementia, alcoholism, and medical illness were also reviewed.The majority of studies showed that anxiety disorders are less common in the elderly than in younger adults. Generalized anxiety disorder and phobias account for most anxiety in late life; panic disorder is rare. Agoraphobia, and possibly obsessive-compulsive disorder in females, may occur as a primary disorder for the first time in old age, whereas simple phobia, obsessive-compulsive disorder in males, and panic disorder either persist from younger years or arise in the context of another psychiatric or medical disorder. There is considerable comorbidity of geriatric depression and generalized anxiety disorder and phobias, although the depression usually goes untreated or is inappropriately treated with benzodiazepines. The rate of comorbidity of anxiety and medical illness and alcoholism is lower in the elderly than in younger persons.Epidemiologic data on the prevalence of posttraumatic stress disorder (PTSD) and the first occurrence of generalized anxiety disorder and PTSD in late life are still needed. Further comorbidity studies are needed to determine the extent to which anxiety arises secondary to depression, as well as the optimal treatment and prognosis for this mixed state.
Overexpression of peroxiredoxin 6 protect mice from ovalbumin-induced airway inflammation and hypersecretion of MUC5AC by reducing ROS levels
Authors: Chunling Dong, Bo Li, Dong Yang, Guifang Wang, Xiangdong Wang, Chunxue Bai
Journal: European Respiratory Journal (2011)

Background: Oxidative stress plays an important role in the pathogenesis of asthma. Peroxiredoxin 6 (Prdx 6), as a newly identified peroxidase, protect cell or organ from reactive oxygen species (ROS)-induced oxidative stress.  Objective: The present study aimed at investigating the involvement of prdx 6 in asthma.  Methods: The ovalbumin (OVA) - induced allergic airway inflammation and MUC5AC production were examined in wild-type (WT), overexpressing (Prdx 6+/+) or Prdx6 null (Prdx 6–/–) mice. Prdx 69s expression in lung and intracellular ROS levels in bronchoalveolar lavage fluid (BALF) were evaluated.  Results: The expression of Prdx 6 was reduced significantly and up-regulated by dexamethasone and ambroxol in lung from WT mice. Prdx 6+/+ mice had significantly low airway inflammation, low levels of IL-13 in BALF as compared with those in WT mice. In addition, lower expression of MUC5AC in airway epithelial cells, less secretion of MUC5AC in BALF were found in Prdx6+/+ model mice, especially with fewer intracellular ROS levels in BALF. However, Prdx6–/– mice showed no significant difference compared to WT mice.  Conclusions: Our data indicate that overexpression of Prdx 6 prevent allergic airway inflammation and hypersecretion by reducing ROS levels. While due to several compensatory mechanisms, targeted disruption of Prdx 6 fails to increase OVA-induced asthma.
Acute-on Chronic Liver Failure (ACLF): A distinct clinical syndrome
Authors: R Jalan, R Moreau, P Gines, M Pavesi, P Angeli, P Caraceni, C Hopf, C Alessandria, P Solis-Munoz, W Laleman, J Trebicka, F Saliba, S Zeuzem, A Albillos, T Gustot, MY Baenas, L Elkrief, D Benten, J Luis Montero, M Vega Catalina, M Concepcion, J Cordoba, A McCormick, RE Stauber, W Vogel, A De Gottardi, M Peck-Radosavljevic, H van Vlierberghe, S Frankova, S Karlsen, CO Mortensen, M Coenraad, F Morando, AL Gerbes, A Risso, E Garcia, C Deulofeu, M Bernardi, Arroyo
Journal: Hepatology (2012)
Abstract 1536: Histone Demethylase LSD1 Modulates Angiotensin II Induced Interleukin-6 Expression in Human Aortic Smooth Muscle Cells
Authors: Bill Lian, Christine Guo, Rui Fang, Pei Wu, Thiago Leonor, Fumigo Shimizu, Gail K Adler, Gordon H Williams, Yujiang Shi
Journal: Circulation (2006)

The dynamics of chromatin structure and the modifications of histones, which are coordinated by protein complexes containing multiple enzymatic activities, are key underlying mechanisms for eukaryo...
Treatment of Systemic Necrotizing Vasculitides in Patients Aged Sixty‐Five Years or Older: Results of a Multicenter, Open‐Label, Randomized Controlled Trial of Corticosteroid and Cyclophosphamide–Based Induction Therapy
Authors: Christian Pagnoux, Thomas Quémeneur, Jacques Ninet, Elisabeth Diot, Xavier Kyndt, Benoît de Wazières, Jean-Luc Reny, Xavier Puechal, Pierre-Yves Le Berruyer, Olivier Lidove, Philippe Vanhille, Pascal Godmer, Olivier Fain, Daniel Blockmans, Boris Bienvenu, Florence Rollot, Séverine Aït El Ghaz-Poignant, Alfred Mahr, Pascal Cohen, Luc Mouthon, Elodie Perrodeau, Philippe Ravaud, Loïc Guillevin, French Vasculitis Study Group
Journal: Arthritis & Rheumatology (2015)

To investigate a new therapeutic strategy, with rapid corticosteroid dose tapering and limited cyclophosphamide (CYC) exposure, for older patients with systemic necrotizing vasculitides (SNVs; polyarteritis nodosa [PAN], granulomatosis with polyangiitis [Wegnener's] [GPA], microscopic polyangiitis [MPA], or eosinophilic GPA [Churg-Strauss] [EGPA]).A multicenter, open-label, randomized controlled trial comprising patients ≥65 years old and newly diagnosed as having SNV was conducted. The experimental treatment consisted of corticosteroids for ∼9 months and a maximum of six 500-mg fixed-dose intravenous (IV) CYC pulses, every 2-3 weeks, then maintenance azathioprine or methotrexate. The control treatment included ∼26 months of corticosteroids for all patients, combined with 500 mg/m(2) IV CYC pulses, every 2-3 weeks until remission, then maintenance for all patients with GPA or MPA and for those with EGPA or PAN with a Five-Factors Score (FFS) of ≥1. Randomization used a 1:1 ratio computer-generated list and was performed centrally with sealed opaque envelopes. The primary outcome measure was ≥1 serious adverse event (SAE) occurring within 3 years of followup. Secondary outcome measures included remission and relapse rates.Among the 108 patients randomized, 4 were excluded (early consent withdrawal or protocol violation). Mean ± SD age at diagnosis was 75.2 ± 6.3 years. Analysis at 3 years included 53 patients (21 GPA, 21 MPA, 8 EGPA, and 3 PAN) in the experimental arm and 51 patients (15 GPA, 23 MPA, 6 EGPA, and 7 PAN) in the conventional arm. In total, 32 (60%) versus 40 (78%) had ≥1 SAE (P = 0.04), most frequently infections; 6 (11%) versus 7 (14%) failed to achieve remission (P = 0.71); 9 (17%) versus 12 (24%) died (P = 0.41); and 20 (44%) of 45 versus 12 (29%) of 41 survivors in remission experienced a relapse (P = 0.15).For older SNV patients, an induction regimen limiting corticosteroid exposure and with fixed low-dose IV CYC pulses reduces SAEs in comparison to conventional therapy, and does not affect the remission rate. Three-year relapse rates remain high for both arms.
Şiddetli Siyaladenit: Eozinofili ve sistemik semptomlarla seyreden ilaç alerjisinin yeni bir komplikasyonu
Authors: Sophia Abecassis, Jean-Claude Roujeau, Hélène Bocquet, Christiane Copie-Bergman, Catherine Radier, Jean Revuz veAnne CosnesCréteil
Journal: Journal of the American Academy of Dermatology (2004)
Lung diffusion at high altitude after endurance exercise in high- and lowlanders
Authors: Maria Overbeek, Jean-Benoit Martinot, Claire De Bisschop, Cristina Scoditti, Sofia Beloka, Herman Groepenhoff, Mart Van der Plas, Francisco Villafuerte, Jose Luis Macarlupu, Robert Naeije, Herve Guenard
Journal: European Respiratory Journal (2011)

Introduction:  Both the membrane (Dm) and the capillary (Vc) component of lung diffusing capacity (DL) have been shown to be increased in high altitude residents and to remain essentially unchanged in high altitude sojourners. Maximal exercise has been reported to decrease Dm at sea level (Manier 1993). The effects of high altitude exercise on Dm and Vc as evaluated from the DL for carbon monoxide (DLCO) and nitric oxide (DLNO) respectively, are incompletely understood.   Methods:  Lowlanders (n=10) and highlanders (n=14) were tested at 4380m above sea level (Cerro de Pasco, Peru); lowlanders also underwent tests at sea level. Spirometry, alveolar volume (VA), DLCO, DLNO, Dm and Vc were assessed (Hypercompact Medisoft, Belgium) using the NO/CO transfer technique. Values were corrected for PcapO 2 , Hb and are presented as mean predicted value (Aguilaniu 2008) ±SEM. Measurements took place at rest and after an endurance test at 80% of VO 2 max at heart rate returned to rest values.   Results:  Spirometry was normal in all subjects. Hb nor SaO 2  at rest were significantly different between the groups.  At sea level, lowlanders did not demonstrate alterations in diffusion parameters pre-  vs.  post-endurance test.   Conclusion:  Strenuous exercise in lowlanders resulted in a decrease of DLCO which was probably caused by interstitial lung edema thickening the alveolocapillary membrane, whereas highlanders were capable of maintaining DLCO-levels by an increase in Dm.
Raising the Roof: The Preferential Pharmacological Stimulation of Th1 and Th2 Responses Mediated by NKT Cells
Authors: James E. East, Andrew J. Kennedy, Tonya J. Webb
Journal: Medicinal Research Reviews (2012)

Abstract Natural killer T (NKT) cells serve as a bridge between the innate and adaptive immune systems, and manipulating their effector functions can have therapeutic significances in the treatment of autoimmunity, transplant biology, infectious disease, and cancer. NKT cells are a subset of T cells that express cell‐surface markers characteristic of both natural killer cells and T cells. These unique immunologic cells have been demonstrated to serve as a link between the innate and adaptive immune systems through their potent cytokine production following the recognition of a range of lipid antigens, mediated through presentation of the major histocompatibility complex (MHC) class I like CD1d molecule, in addition to the NKT cell's cytotoxic capabilities upon activation. Although a number of glycolipid antigens have been shown to complex with CD1d molecules, most notably the marine sponge derived glycolipid alpha‐galactosylceramide (α‐GalCer), there has been debate as to the identity of the endogenous activating lipid presented to the T‐cell receptor (TCR) via the CD1d molecule on antigen‐presenting cells (APCs). This review aims to survey the use of pharmacological agents and subsequent structure–activity relationships (SAR) that have given insight into the binding interaction of glycolipids with both the CD1d molecules as well as the TCR and the subsequent immunologic response of NKT cells. These studies not only elucidate basic binding interactions but also pave the way for future pharmacological modulation of NKT cell responses.
Long-Term Treatment of Tardive Dyskinesia with Haloperidol and Tetrabenazine
Authors: HAJIME KAZAMATSURI, CHING-PIAO CHIEN, JONATHAN O. COLE
Journal: American Journal of Psychiatry (1973)

Thirteen patients with tardive dyskinesia were treated with either haloperidol or tetrabenazine for 18 weeks. Haloperidol produced a statistically significant reduction in the frequency of oral dyskinesia, though the effect was most striking during the first two weeks; reversible extrapyramidal symptoms appeared to be negatively correlated with oral dyskinesia. Tetrabenazine also produced a significant reduction in the frequency of oral dyskinesia, with almost complete suppression in two patients throughout the study; the correlation between oral dyskinesia and reversible extrapyramidal symptoms was less clear than with haloperidol. No exacerbation of the dyskinesia was observed after administration of the study drugs was discontinued.