慢性阻塞性肺疾病:超级化~3He-MR成像定量分析支气管扩张剂的疗效

目的 3He-MR成像和肺功能检查评价短效支气管扩张药对慢性阻塞性肺疾病(COPD)的疗效。材料与方法本研究经学术审查委员会批准并取得所有病人的书面知情同意。COPD病人14例(现已戒烟),在给予400mg舒喘灵(羟甲叔丁肾上腺素)后平均(25±2)min前和后分别接受超     

Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W,Niger, 2015

In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013–2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa.Key words: Meningococcal meningitis, Neisseria meningitidis serogroup C, whole-genome sequencing, Niger, meningitis belt, bacteriaNeisseria meningitidis commonly causes meningitis in the African meningitis belt, where periodic meningococcal epidemics have contributed to the highest reported incidence of meningococcal meningitis in the world (1). Most meningococcal disease historically has been caused by N. meningitidis serogroup A (NmA); however, NmA disease dramatically decreased after the preventative MenAfriVac vaccination campaign was initiated in 2010 (2). Serogroup W (NmW) has been the major cause of meningococcal disease in the region since then (2).N. meningitidis serogroup C (NmC) disease has rarely been reported in the meningitis belt; it has not been detected in many molecular studies of invasive isolates (3,4) and is rarely found in carriage studies (5,6). The last large NmC epidemic in Africa occurred in Burkina Faso (then Upper Volta) in 1979 (7). During 2013 and 2014, NmC outbreaks were reported in Nigeria (8). The Nigerian outbreaks were caused by a novel NmC strain with a previously undescribed sequence type, 10217 (ST-10217), which does not belong to a defined clonal complex. In 2015, an epidemic of 9,367 meningococcal meningitis cases occurred in Niger, with NmC disease comprising most laboratory-confirmed cases (9).NmW disease has been reported in the meningitis belt since the 1980s (10,11), and NmW from clonal complex 11 (CC11) has been a major concern in the region since 2001 (12). The first large epidemic of disease caused by CC11 NmW occurred during 2002 in Burkina Faso (13). Subsequently, NmW disease outbreaks were reported in Niger during 2010 and 2011, both involving CC11 (14). These outbreaks were followed by another large epidemic caused by CC11 NmW in Burkina Faso during 2012 (15). Whole-genome sequencing (WGS) analysis of diverse NmW isolates from around the world has demonstrated that a clone within CC11, commonly associated with NmC, became globally dispersed after it switched to serogroup W (16,17). WGS analyses also provided sufficient resolution to assign isolates from the meningitis belt to a long-standing regional population and to a clone that became globally dispersed after an outbreak during the 2000 Hajj pilgrimage (16,17; A. Retchless, unpub. data).In addition to distinguishing among closely related strains, WGS provides information about allelic variation in genes that may affect antibiotic susceptibility and the coverage of protein-based vaccines. Two vaccines designed for serogroup B meningococcus have been approved for use in the United States and Europe: Trumenba and Bexsero. Trumenba targets the factor H–binding protein (FHbp), and includes components belonging to FHbp subfamilies A and B (18). Bexsero includes 4 different components: an FHbp of variant 1 (subfamily B); a Neisseria adhesion A protein (NadA); a neisserial heparin-binding antigen (NhbA); and outer membrane vesicles from a serogroup B strain containing PorA P1.4 (19). Recognizing the diversity of these genes among strains can aid in evaluating whether these vaccines may provide protection. Likewise, whole-genome sequences can be rapidly screened for indications of antibiotic resistance when the genetic determinants are well characterized, as with genes penA, gyrA, and rpoB, which are involved in reduced susceptibility to penicillin, ciprofloxacin, and rifampin, respectively. To clarify the meningococcal population in Niger during the 2015 epidemic season, we completed genomic analysis on the 102 NmC and NmW invasive isolates collected during this period.     

The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (Cutivate^TM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly ( P  < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy ( P  = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse ( P  = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.     

Value assignment of the WHO 2nd International Standard von Willebrand factor,concentrate (09/182)

To cite this article: Hubbard AR, Hamill M, Beeharry M, Bevan SA, Heath AB, on behalf of the SSC sub‐committee on von Willebrand factor of ISTH. Value assignment of the WHO 2nd International Standard von Willebrand factor, concentrate (09/182). J Thromb Haemost 2011; 9 : 1638–40.DOI: 10.1111/j.1538‐7836.2011.04365.x .     

The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

Summary. Background: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). Methods: The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. Results: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. Conclusions: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies.     

Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study

Summary. Background: Traditionally, patients with pulmonary embolism (PE) are initially treated in the hospital with low molecular weight heparin (LMWH). The results of a few small non‐randomized studies suggest that, in selected patients with proven PE, outpatient treatment is potentially feasible and safe. Objective: To evaluate the efficacy and safety of outpatient treatment according to predefined criteria in patients with acute PE. Patients and Methods: A prospective cohort study of patients with objectively proven acute PE was conducted in 12 hospitals in The Netherlands between 2008 and 2010. Patients with acute PE were triaged with the predefined criteria for eligibility for outpatient treatment, with LMWH (nadroparin) followed by vitamin K antagonists. All patients eligible for outpatient treatment were sent home either immediately or within 24 h after PE was objectively diagnosed. Outpatient treatment was evaluated with respect to recurrent venous thromboembolism (VTE), including PE or deep vein thrombosis (DVT), major hemorrhage and total mortality during 3 months of follow‐up. Results: Of 297 included patients, who all completed the follow‐up, six (2.0%; 95% confidence interval [CI] 0.8–4.3) had recurrent VTE (five PE [1.7%] and one DVT [0.3%]). Three patients (1.0%, 95% CI 0.2–2.9) died during the 3 months of follow‐up, none of fatal PE. Two patients had a major bleeding event, one of which was fatal intracranial bleeding (0.7%, 95% CI 0.08–2.4). Conclusion: Patients with PE selected for outpatient treatment with predefined criteria can be treated with anticoagulants on an outpatient basis. (Dutch Trial Register No 1319; http://www.trialregister.nl/trialreg/index.asp ).     

Prophylaxis therapy in haemophilia A: current situation in Spain

Summary. The Spanish Epidemiological Study in Haemophilia carried out in 2006 enrolled 2400 patients [2081–86.7% with haemophilia A (HA) and 319–13.3% with haemophilia B]; 465 of them (19.4%) were on prophylaxis. These rates were higher in patients with severe haemophilia (45.4%) and severe paediatric cases (72.5%). On the basis of information recorded in this study, we analysed the current situation of prophylaxis therapy administered to patients with HA in Spain, as well as their orthopaedic status. Prophylaxis was used in 399 (19.2%) patients with HA; such prophylaxis was primary (PP) in 20.3% and secondary (SP) in 75.9% of cases. Among severe HA patients, 313 (45.9%) were on prophylaxis (22.3% on PP and 74.7% on SP). Taking into account the patients’ age, 34.7% of severe HA adults were on prophylaxis (6% PP and 92.1% SP), whereas 71.5% of severe HA paediatric patients (40.5% PP and 55.4% SP) received this kind of treatment. Established haemophilic arthropathy (EHA) was detected in 142 from 313 severe HA patients (45.3%) on prophylaxis, but only in 2.9% of patients under PP vs. 59% of patients receiving SP. There was no EHA in adult severe HA patient on PP, whereas 70.4% on SP had joint damage (P < 0.00001). Among paediatric severe HA patients, EHA was detected in 3.3% under PP and 37.8% under SP (P < 0.00001). In conclusion, our data suggest that an early initiation of prophylaxis avoids EHA in the long‐term in patients with severe HA. We should emphasize the early onset of prophylaxis regimens.