tbuckley/cabot-search huggingface dataset:
Declining incidence of episodes of asthma
Authors: R BERNSEN
Journal: Thorax (2001)

With great interest we read the thought provoking contribution by Fleming et al on general practice consultation patterns for asthma.1 We would like to offer some alternative viewpoints to those posed by the authors.

First of all, we wonder whether the choice of statistical techniques obscures the view of what happened to respiratory morbidity. Given the sudden rise in asthma episodes at the end of 1991 and the subsequent fall after 1994, a step function would be more appropriate. Besides, the amplitude within the years studied appears to increase during the period 1991–4. This can be modelled by adding an interaction term season*time to the model. Furthermore, given the nature of the data, Poisson regression would be preferable to linear regression techniques.

Secondly, it is unclear whether the trend is specific for asthma and bronchitis or is relevant for all respiratory morbidity or, even broader, applies to all morbidity. In the discussion paragraph the authors point out that the broader category of respiratory infections shows the same trend, but they fail to explore the possible implications of this finding. How do their data compare with hospital data over the years? How about general practice consultation patterns?

Thirdly, the distinction between new episodes and repeat consultations may be a difficult one, especially for chronic diseases like asthma. Subtle changes in registration routines may have affected the outcomes of this study.

Apart from practice nurses, we wonder whether the introduction of asthma facilitators2 may be possible causes for the trends that are shown.

The authors suggest that the observed trends are due to fluctuations in prevalence. There is no evidence for this. The rise in consultations in the years 1991–4 could be due to a temporary increase in complaints in roughly the same number of prevalent asthma patients.

We invite …
Preprocessing of Tandem Mass Spectrometric Data Based on Decision Tree Classification
Authors: Jing-Fen Zhang, Si-Min He, Jin-Jin Cai, Xing-Jun Cao, Rui-Xiang Sun, Yan Fu, Rong Zeng, Wen Gao
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract In this study, we present a preprocessing method for quadrupole time-of-flight (Q-TOF) tandem mass spectra to increase the accuracy of database searching for peptide (protein) identification. Based on the natural isotopic information inherent in tandem mass spectra, we construct a decision tree after feature selection to classify the noise and ion peaks in tandem spectra. Furthermore, we recognize overlapping peaks to find the monoisotopic masses of ions for the following identification process. The experimental results show that this preprocessing method increases the search speed and the reliability of peptide identification.
Risk of mortality associated with formoterol: a systematic review and meta-analysis
Authors: M. Wijesinghe, M. Weatherall, K. Perrin, M. Harwood, R. Beasley
Journal: European Respiratory Journal (2009)

There is concern long-acting β-agonist (LABA) drugs may increase the risk of asthma mortality. We undertook a systematic review which included the AstraZeneca Formoterol Clinical Trial Safety Database and Novartis Food and Drug Aministration Formoterol Briefing Document. Randomised controlled clinical trials of duration ≥4 weeks that compared formoterol with a non-LABA comparator treatment in asthma were included in a meta-analysis of the risk of all-cause mortality and asthma death. Simple contingency tables, Peto's one-step method and a Bayesian analysis were used. There were 42 deaths (nine from asthma) recorded in 62 studies with 49,327 subjects. The simple contingency table odds ratio for risk of all-cause mortality with formoterol was 1.1 (95% CI 0.6–2.2) and for asthma death was 2.7 (95% CI 0.5–26.7). Analyses by the other methods using both “as randomised” and “as exposed” classifications of treatment gave similar risk estimates with wide confidence and credible intervals. We conclude that there was insufficient power to determine whether formoterol increases the risk of mortality. However, the point estimates of a 2.0- to 3.2-fold increased risk of asthma death are not reassuring and add weight to evidence that LABA use in certain circumstances may increase the risk of asthma mortality.
Potential Role of Platelets in Endothelial Damage Observed During Treatment With Cisplatin, Gemcitabine, and the Angiogenesis Inhibitor SU5416
Authors: B.C. Kuenen, M. Levi, J.C.M. Meijers, V.W.M. van Hinsbergh, J. Berkhof, A.K. Kakkar, K. Hoekman, H.M. Pinedo
Journal: Journal of Clinical Oncology (2003)

An increased incidence of thromboembolic events was observed during treatment with cisplatin-gemcitabine plus SU5416 (CG+SU5416), a tyrosine kinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor-1 and -2. Nine thromboembolic events occurred in eight of 19 patients. We performed an analysis of parameters of the coagulation cascade and vessel wall activation.Markers for thrombin generation and endothelial cell activation were measured in three patients treated with CG+SU5416, two of whom developed a thromboembolic event. The results were compared with measurements in six patients treated with CG alone, and in 17 patients treated with SU5416 alone.During cycles 1 and 2 of treatment with CG+SU5416, a significant cycle-dependent activation of both the coagulation cascade and endothelial cells occurred, whereas platelet counts decreased. Change in platelet number had a significant negative predictive effect on soluble (s)-E-selectin levels. Significant activation of the coagulation cascade only was observed in the patients treated with CG alone, whereas in patients treated with SU5416 alone, significant endothelial cell activation was observed.We hypothesize that endothelial cells deprived of VEGF after exposure to SU5416 became activated and more susceptible to damage during treatment with CG+SU5416, which was aggravated by a transient decrease in platelets, which are, among other things, carriers of VEGF. These results suggests that VEGF, in addition to being a permeability, proliferation, and migration factor, also is a maintenance and protection factor for endothelial cells, and that platelets may have a role in maintaining vascular integrity.
Severe Aortic Stenosis and Myocardial Function
Authors: Vitantonio Di Bello, Davide Giorgi, Paolo Viacava, Talini Enrica, Carmela Nardi, Caterina Palagi, Maria Grazia Delle Donne, Francesco Verunelli, Massimo A. Mariani, Jean Grandjean, Rita Dell’Anna, Andrea Di Cori, Giulio Zucchelli, Maria Francesca Romano, Mario Mariani
Journal: Circulation (2004)

The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology.Thirty-five subjects (AS: valve orifice < or =1 cm2; 12 female; mean age, 71.8+/-6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy).One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation.
Diet and Prevention of Dental Disease
Authors: A. W. Adams
Journal: BMJ (1965)

Treatment of Localized Myxoedema SIR,-We were surprised that your leading article (13 November, p. 1 138) did not mention the possible role of the long-acting thyroid stimulator (L.A.T.S.) in the pathogenesis of pretibial myxoedema.This thyroid stimulating agent, a 7S gamma-globulin,' present in
Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1)
Authors: Päivi Pajukanta, Heidi E Lilja, Janet S Sinsheimer, Rita M Cantor, Aldons J Lusis, Massimiliano Gentile, Xiaoqun Joyce Duan, Aino Soro-Paavonen, Jussi Naukkarinen, Janna Saarela, Markku Laakso, Christian Ehnholm, Marja-Riitta Taskinen, Leena Peltonen
Journal: Nature Genetics (2004)
Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism
Authors: Harry R Büller, Hervé Décousus, Michael A Grosso, Michele Mercuri, Saskia Middeldorp, Martin H Prins, Gary E Raskob, Sebastian M Schellong, Lee Schwocho, Annelise Segers, Minggao Shi, Peter Verhamme, Phil Wells, Dominique Mottier
Journal: New England Journal of Medicine (2013)

Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear.In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received heparin, to receive edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or to receive warfarin. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.A total of 4921 patients presented with deep-vein thrombosis, and 3319 with a pulmonary embolism. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P<0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with pulmonary embolism had right ventricular dysfunction, as assessed by measurement of N-terminal pro-brain natriuretic peptide levels; the rate of recurrent venous thromboembolism in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; 95% CI, 0.28 to 0.98).Edoxaban administered once daily after initial treatment with heparin was noninferior to high-quality standard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism. (Funded by Daiichi-Sankyo; Hokusai-VTE ClinicalTrials.gov number, NCT00986154.).
Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres
Authors: J Fransen, D Popa-Diaconu, R Hesselstrand, P Carreira, G Valentini, L Beretta, P Airo, M Inanc, S Ullman, A Balbir-Gurman, S Sierakowski, Y Allanore, L Czirjak, V Riccieri, R Giacomelli, A Gabrielli, G Riemekasten, M Matucci-Cerinic, D Farge, N Hunzelmann, F H J Van den Hoogen, M C Vonk
Journal: Annals of the Rheumatic Diseases (2011)

Objective Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. Methods A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). Results Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. Conclusion A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.
Individualised pelvic floor muscle training in women with pelvic organ prolapse (POPPY): a multicentre randomised controlled trial
Authors: Suzanne Hagen, Diane Stark, Cathryn Glazener, Sylvia Dickson, Sarah Barry, Andrew Elders, Helena Frawley, Mary P Galea, Janet Logan, Alison McDonald, Gladys McPherson, Kate H Moore, John Norrie, Andrew Walker, Don Wilson
Journal: The Lancet (2013)
Inflammatory biomarkers in urine of cystic fibrosis patients
Authors: Gita Parekh, Michael Tunney, Emilie Vallières, Stef McGrath, Leanne McIlreavey, Elinor Johnston, Damian Downey, Kevin Woolston, Paul Davis, Stuart Elborn
Journal: European Respiratory Journal (2014)

Introduction: 

Urinary biomarkers of pulmonary exacerbation in CF have not been as extensively studied as blood, sputum and bronchial fluid. However, urine collection is less invasive and would allow more frequent sampling at home or at point of care. This pilot study was intended to explore whether 24 rationally selected markers of inflammation were detectable in the urine of CF patients and healthy volunteers, and whether the levels of any of these were significantly different.

Methods: 

129 clinically stable CF patients (aged 6-68) attending the adult and paediatric CF centres in Belfast were recruited to the study. Some additional samples were collected at the start and/or end of antibiotic treatment of an infective exacerbation. 34 samples from healthy individuals (aged 24-60) were also included. Urinary biomarkers were measured with a combination of in-house assays (Mologic Ltd) and commercial assays (ELISA, lateral flow, substrate assays, zymography).

Results: 

All 24 analytes were detectable in the urine samples, 10 were found to be significantly different in CF patient samples compared to healthy individuals (T test; p<0.05). TIMP2 and A1AT both protease inhibitors were excreted in the urine at significantly higher levels in the CF patients (p=0.001 and p=0.004 respectively) and fMLP, a chemotactic for neutrophils was significantly lower (p=<0.0001).

Conclusion: 

Markers can be detected and quantified in urine. Further investigation is required to determine whether changes in levels of any of these can be used to predict exacerbation onset in order to instigate pre-emptive therapy.

This study was supported by the UK Translational Research Partnership (TRP) and a US Ireland Partnership Grant.
Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C
Authors: U Siebert
Journal: Gut (2003)

Peginterferon alpha-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive.To estimate the cost effectiveness of treatment with peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of patients with chronic hepatitis C.Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate.Compared with no antiviral therapy, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon alpha-2b plus ribavirin, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of 11,800 euros and 6600 euros per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments.Peginterferon alpha-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C.
Deficiency of invariant natural killer T cells in coeliac disease
Authors: R H Grose, A G Cummins, F M Thompson
Journal: Gut (2006)

Immunoregulatory invariant natural killer (iNK) T cells rapidly produce interleukin (IL)-4 and other cytokines that suppress a Th1 response and are deficient in some autoimmune diseases.The aim of this study was to investigate any deficiency of iNK T cells in coeliac disease.Blood was collected from 86 subjects with coeliac disease and from 152 healthy control subjects for investigation of Valpha24+ T cells by flow cytometry. iNK T cells were assessed by Valpha24 and alpha-galactosylceramide/CD1d tetramer markers in 23 normal controls and 13 subjects with coeliac disease. Intracellular IL-4 was measured after anti-CD3 antibody stimulation. Duodenal biopsies were obtained in a subgroup of subjects with coeliac disease and control subjects for Valpha24 mRNA expression using relative PCR and for Valpha24+ T cells by immunofluorescence.The mean numbers of circulating Valpha24+ T cells and iNK T cells in coeliac disease were 27% (p<0.001) and 16% (p<0.001), respectively, of levels in control subjects. After in vitro anti-CD3 stimulation, numbers of IL-4+ producing iNK T cells from subjects with coeliac disease were unchanged but increased by 21% in control subjects. In subjects with coeliac disease, Valpha24 mRNA intestinal expression was reduced to 17% (p<0.001) by relative PCR and numbers of intestinal Valpha24+ T cells were 16% (p<0.01) of levels in control subjects.We conclude that Valpha24+ T cells and iNK T cells are deficient in coeliac disease. We speculate that this deficiency could contribute to the failure of immunological oral tolerance that seems to underlie this disease.
THE MEDICAL ASPECT OF DENTISTRY AND THE NECESSITY OF DENTAL INSTRUCTION FOR MEDICAL STUDENTS
Authors: H. P. Pickerill
Journal: BMJ (1909)

FEB. I3, Ig909 all the children who have caught measles from the first case will sicken between the tenth and the fifteenth day- that is, during the time the school is closed.The advantage of the short closure of six days will be apparent to educationalists.It is evident that full co-operation between the public health and the medical inspector's departments is neces- sary in order that these methods be carried out thoroughly, and such co-operation will surely lead to the strengthening of the weak points in our defence against the infectious diseases of childhood.
Additional Hypotensive Effect of Endothelin-1 Receptor Antagonism in Hypertensive Dogs Under Angiotensin-Converting Enzyme Inhibition
Authors: Julian E. Donckier, Pierre-Emmanuel Massart, Dominique Hodeige, Henri Van Mechelen, Jean-Paul Clozel, Olivier Laloux, Jean-Marie Ketelslegers, André A. Charlier, Guy R. Heyndrickx
Journal: Circulation (1997)

Background Endothelin-1 (ET-1) may play a role in hypertension. ET-1 receptor antagonism by bosentan lowers blood pressure in hypertension. We evaluated whether the effect of bosentan is still observed under ACE inhibitors (ACEI). Methods and Results Thirty anesthetized and 18 conscious hypertensive dogs were studied randomly. Anesthetized dogs were divided into 4 groups: group 1 received cumulative doses of bosentan (bolus+30-minute infusion: 0.1 mg/kg+0.23 mg/kg per hour to 3 mg/kg+7 mg/kg per hour); group 2, the same dose-responses after 1 mg/kg enalaprilat; group 3, the vehicle after enalaprilat; and group 4, the dose responses to bosentan followed by enalaprilat. The conscious dogs were divided into 3 groups: group 5 received 2 cumulative doses of bosentan; group 6, the vehicle; and group 7, enalaprilat alone. In groups 1 and 2, bosentan produced dose-related decreases ( P =.0001) in left ventricular systolic pressure and mean aortic pressure (AOP). In group 1, bosentan decreased mean AOP by 22%. In group 2, enalaprilat decreased mean AOP by 25% (from 173±26 to 130±25 mm Hg; P &lt;.005); an additional 18% decrease was obtained with bosentan, the mean AOP reaching 98±21 mm Hg ( P &lt;.01). In group 3, the effect of enalaprilat alone was a 22% decrease in mean AOP ( P &lt;.005). The additive effect of the bosentan-ACEI association was also observed in group 4. In group 5, bosentan reduced mean AOP by 20% ( P &lt;.005), whereas mean AOP remained unchanged in group 6. The effect of ACEI alone (group 7) was similar to that of bosentan. Conclusions Bosentan produces an additional hypotensive effect to that of ACEI, which opens new therapeutic perspectives.
ON THE PRESENCE IN ANTIPNEUMOCOCCUS SERUM OF TYPE-SPECIFIC PROTECTIVE ANTIBODY NOT NEUTRALIZED BY HOMOLOGOUS SPECIFIC SOLUBLE SUBSTANCE
Authors: Albert B. Sabin
Journal: The Journal of Experimental Medicine (1931)

The mutual relationship of the anticarbohydrate precipitins and the protective action in antipneumococcus sera to the soluble specific substance was investigated. The assumption is made that there exists in antipneumococcus serum, type-specific protective antibody which is distinct from the anticarbohydrate precipitins and is not neutralized by the soluble specific substance. This assumption is based upon the following observations in experiments which were conducted primarily with Type I antipneumococcus horse serum. 1. Lack of proportionality between the quantity of SSS added and the amount of anticarbohydrate precipitin and protective action neutralized. 2. Protective capacity of specific precipitates (SSS-precipitin complex) is accounted for on the basis of a liberation of non-specifically adsorbed protective antibody. 3. SSS only partially neutralizes the protective action of antipneumococcus serum in vivo. 4. Type-specific protective antibody remains in antipneumococcus serum after complete precipitation of the anticarbohydrate precipitins. 5. This residual type-specific protective antibody is not neutralized by additional SSS nor by absorption with heterologous pneumococci; it is definitely absorbed by the homologous pneumococci.