The high prevalence and chronicity of chronic obstructive pulmonary disease (COPD) imply that many of these patients are treated and controlled in primary-care centres, often without contact with ...specialized pneumologist care. We conducted the present study to evaluate the treatment administered in stable and exacerbated COPD in GP-setting clinics and to investigate which factors could be associated with the different prescriptions.
This is a cross-sectional observational study of ambulatory COPD patients. General practitioners (
n=201) were selected throughout Spain by regionally stratified sampling. We recorded the physician-reported prescription drug use in ambulatory treatment of stable COPD and acute exacerbations of COPD through a standard questionnaire. Factors independently associated with the prescription of drugs were ascertained by multiple logistic regression analysis.
Of 1078 questionnaires reviewed, 1001 fulfilled quality criteria. There were 878 men (88%) and 123 women (12%); 777 (78%) were smokers or ex-smokers with a mean age of 68 years. Mean FEV
1 was 47% predicted (% pred.) (
sd=13%). The median number of exacerbations was two per year (range=0–16). Regular treatment for COPD was received by 878 (88%): the most commonly used drugs were inhaled
β
2-agonists (71%), theophyllines (53%) and inhaled corticosteroids (ICs) (50%), followed by mucolytics (25%), ipratropium bromide (23%), and oral corticosteroids (OCs) (4%). Treatment for exacerbations included inhaled bronchodilators (90%), antibiotics (89%), ICs (71%) and OCs (43%).
Impairment of FEV
1 was the factor most strongly associated in multiple regression analysis with increasing drug prescription in stable COPD, except for mucolytics, while the number of previous acute exacerbations was the main factor associated with exacerbation treatment except for OCs, the use of which was associated with more impaired pulmonary function.
A significant number of the treatments prescribed in primary care for stable and exacerbated COPD do not follow current recommendations. Impairment in FEV
1 is the factor most strongly associated with increasing prescription in stable COPD and the number of previous exacerbations is the main factor associated with exacerbation treatment.
We describe a fully GPU-based implementation of the first level trigger for the upgrade of the LHCb detector, due to start data taking in 2021. We demonstrate that our implementation, named Allen, ...can process the 40 Tbit/s data rate of the upgraded LHCb detector and perform a wide variety of pattern recognition tasks. These include finding the trajectories of charged particles, finding proton–proton collision points, identifying particles as hadrons or muons, and finding the displaced decay vertices of long-lived particles. We further demonstrate that Allen can be implemented in around 500 scientific or consumer GPU cards, that it is not I/O bound, and can be operated at the full LHC collision rate of 30 MHz. Allen is the first complete high-throughput GPU trigger proposed for a HEP experiment.
We describe a fully GPU-based implementation of the first level trigger for the upgrade of the LHCb detector, due to start data taking in 2021. We demonstrate that our implementation, named Allen, ...can process the 40 Tbit/s data rate of the upgraded LHCb detector and perform a wide variety of pattern recognition tasks. These include finding the trajectories of charged particles, finding proton-proton collision points, identifying particles as hadrons or muons, and finding the displaced decay vertices of long-lived particles. We further demonstrate that Allen can be implemented in around 500 scientific or consumer GPU cards, that it is not I/O bound, and can be operated at the full LHC collision rate of 30 MHz. Allen is the first complete high-throughput GPU trigger proposed for a HEP experiment.
The calibration and performance of the LHCb Calorimeter system in Run 1 and 2 at the LHC are described. After a brief description of the sub-detectors and of their role in the trigger, the ...calibration methods used for each part of the system are reviewed. The changes which occurred with the increase of beam energy in Run 2 are explained. The performances of the calorimetry for \(\gamma\) and \(\pi^0\) are detailed. A few results from collisions recorded at \(\sqrt {s}\) = 7, 8 and 13 TeV are shown.
The high prevalence and chronicity of chronic obstructive pulmonary disease (COPD) imply that many of these patients are treated and controlled in primary-care centres, often without contact with ...specialized pneumologist care. We conducted the present study to evaluate the treatment administered in stable and exacerbated COPD in GP-setting clinics and to investigate which factors could be associated with the different prescriptions. This is a cross-sectional observational study of ambulatory COPD patients. General practitioners (n = 201) were selected throughout Spain by regionally stratified sampling. We recorded the physician-reported prescription drug use in ambulatory treatment of stable COPD and acute exacerbations of COPD through a standard questionnaire. Factors independently associated with the prescription of drugs were ascertained by multiple logistic regression analysis. Of 1078 questionnaires reviewed, 1001 fulfilled quality criteria. There were 878 men (88%) and 123 women (12%); 777 (78%) were smokers or ex-smokers with a mean age of 68 years. Mean FEV1 was 47% predicted (% pred.) (SD = 13%). The median number of exacerbations was two per year (range = 0-16). Regular treatment for COPD was received by 878 (88%): the most commonly used drugs were inhaled beta 2-agonists (71%), theophyllines (53%) and inhaled corticosteroids (ICs) (50%), followed by mucolytics (25%), ipratropium bromide (23%), and oral corticosteroids (OCs) (4%). Treatment for exacerbations included inhaled bronchodilators (90%), antibiotics (89%), ICs (71%) and OCs (43%). Impairment of FEV1 was the factor most strongly associated in multiple regression analysis with increasing drug prescription in stable COPD, except for mucolytics, while the number of previous acute exacerbations was the main factor associated with exacerbation treatment except for OCs, the use of which was associated with more impaired pulmonary function. A significant number of the treatments prescribed in primary care for stable and exacerbated COPD do not follow current recommendations. Impairment in FEV1 is the factor most strongly associated with increasing prescription in stable COPD and the number of previous exacerbations is the main factor associated with exacerbation treatment.
The aim of this study was to develop and validate two models to estimate the probabilities of frequent exacerbations (more than 1 per year) and admissions for chronic obstructive pulmonary disease ...(COPD) that can be used in a primary care setting.
Information was obtained in a cross-sectional observational study on ambulatory COPD patients performed in 201 general practices located throughout Spain. The model for admissions included 713 cases, 499 for the developmental sample and 214 in the validation sample; the model for frequent exacerbations included 896 patients, 627 in the developmental sample and 269 in the validation model. Candidate variables to be included in both models were: age, sex, body mass index (BMI), FEV(1) as percent predicted FEV(1 )(% pred.), active smoking, chronic mucus hypersecretion (CMH) and significant comorbidity.
The admission model contained 2 readily obtainable variables: comorbidity (OR = 1.97; CI 95% = 1. 24-3.14) and FEV(1)(% pred.) (OR = 0.72; 0.58-0.88, for every 10 units), and well calibrated in developmental and validation samples (goodness-of-fit tests: p = 0.989 and p = 0.720, respectively). The model for frequent exacerbations included 3 variables: age (OR = 1. 21; 1.01-1.44; for every 10 years of increasing age), FEV(1 )(% pred. ) (OR = 0.82; 0.70-0.96, for every 10 units) and CMH (OR = 1.54; 1. 11-2.14) and also well calibrated (p = 0.411 and p = 0.340 in the developmental and validation samples, respectively).
Our results suggest that FEV(1) impairment explains part of the risk of frequent exacerbations and hospital admissions. Furthermore, CMH and increasing age are significantly associated with the risk of frequent exacerbations, but severity of exacerbations provoking hospital admissions is associated with the presence of significant comorbidity. These important and easily measurable variables contain valuable information for optimal management of ambulatory patients with COPD.
Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS ...Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children.
Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document.
Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C).
Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.
Background Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. Methods After breast ...cancer surgery, women with lymph node–positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study—5-year disease-free survival (DFS)—was assessed by Kaplan–Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. Results Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval CI = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio HR = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. Conclusions Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.
Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations ...of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10−11. SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 ...markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766T shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766T is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.