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Background

Expert opinion recommends performing exercise testing with initiation of Class Ic antiarrhythmic medication.

Objective

To evaluate the rate and reason for discontinuation of Ic agent within the first year of follow up, with particular attention to rate of proarrhythmia and the value of routine treadmill testing.

Methods

This is a single center retrospective cohort study including consecutive patients with atrial arrhythmias who were initiated on a Class Ic agent from 2011 to 2016. Data was collated from chart review and pharmacy database.

Results

The study population included 300 patients (55% male, mean age 61; mean ejection fraction, 56%) started on flecainide (n = 153; 51%) and propafenone (n = 147; 49%). Drug initiation was completed while hospitalized on telemetry and the staff electrophysiologists directed dosing. There was one proarrhythmic event during initiation (0.3%). The primary reason for not being discharged on Ic agent was due to detection of proarrhythmia (n = 15) or ischemia (n = 1) with treadmill testing (5.3%). Exercise testing was the single significant variable to affect the decision to discontinue Ic drug, p < 0.0001 (95% CI: 1.89–6.08%). During follow up, the primary reason for discontinuation of Ic agent was lack of efficacy, 32%.

Conclusions

With proper screening, initiation of Class Ic agent is associated with very low rate of proarrhythmia. Treadmill testing is of incremental value and should be completed in all patients after loading Class Ic antiarrhythmic.  相似文献   
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An experiment was conducted to study the effect of plant extracts on soluble sugar, soluble phenol and defence-related enzymes response against Alternaria blight in mustard crop. The efficacy of six selected plant extracts (5 and 10%) used as foliar sprays at 60 and 70 days after sowing and mustard leaves was used for investigation. The results indicate that soluble phenol and sugar content in mustard leaves significantly increases in response to spraying of Azadirachta indica seed kernel, Calotropis procera and A. indica leaf extracts. The soluble protein, viz. peroxidase, polyphenol oxidase and phenylalanine ammonia lyase content, was higher in mustard leaves sprayed with C. procera leaves extract, A. indica seed kernel and Allium sativum bulb extract.  相似文献   
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Two genotypes of mungbean differing in the leaf shape, K-851 (trifoliate) and a mutant (pentafoliate), were exposed to salinity (0, 2.5, 5, 10 dS m–1) for 3, 6 and 9 d at flowering stage (40 – 45 d after sowing) to see the effect of salinity on nodule functioning. In both the genotypes, osmotic potential (s) and relative water content (RWC) of nodules decreased significantly, and proline content increased with increasing the salinity. The s of nodules was more decreased in the mutant than in genotype K-851, while reverse was true for RWC and proline accumulation. A remarkable increase in ethylene evolution was noticed from nodulated roots with the increasing level and duration of salinity and was much higher in K-851. A sharp decline in leghemoglobin content and acetylene reduction assay (ARA) of the nodules was observed with the salinity and this decrease was more marked in K-851 than the mutant. N content declined while Na+/K+ ratio and Cl content increased significantly. The mutant maintained better N status but lower Na+/K+ ratio and Cl content in nodules than K-851. Nodule dry matter also declined with salinity and the decrease was more expressed in K-851. Thus the functioning of nodules in the mutant was better than in the genotype K-851 under stress conditions.  相似文献   
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Biotherapeutics have become the focus of the pharmaceutical industry due to their proven effectiveness in managing complex diseases. Downstream processes of these molecules consist of several orthogonal, high resolution unit operations designed so as to be able to separate variants having very similar physicochemical properties. Typical process development involves optimization of the individual unit operations based on Quality by Design principles in order to define the design space within which the process can deliver product that meets the predefined specifications. However, limited efforts are dedicated to understanding the interactions between the unit operations. This paper aims to showcase the importance of understanding these interactions and thereby arrive at operating conditions that are optimal for the overall process. It is demonstrated that these are not necessarily same as those obtained from optimization of the individual unit operations. Purification of Granulocyte Colony Stimulating Factor (G‐CSF), a biotherapeutic expressed in E. coli., has been used as a case study. It is evident that the suggested approach results in not only higher yield (91.5 vs. 86.4) but also improved product quality (% RP‐HPLC purity of 98.3 vs. 97.5) and process robustness. We think that this paper is very relevant to the present times when the biotech industry is in the midst of implementing Quality by Design towards process development. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:355–362, 2016  相似文献   
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Cotton leaf curl disease (CLCuD), caused by monopartite begomoviruses and its satellite molecules, is one of the serious constrains in cultivation of cotton in India. In the present study, five CLCuD-begomovirus and its associated satellite molecules were characterized based on rolling circle amplification and sequencing of complete genome. Sequence analysis showed 82–99 % nucleotide identity among them. The phylogenetic analysis and nt identity matrix determined that of the five CLCuD-begomovirus isolates, three IARI-34, IARI-42 and IARI-50 were members of Cotton leaf curl Multan virus (CLCuMuV)-Rajasthan isolates, designated as CLCuMuV-Rajasthan-34 and two, IARI-30 and IARI-45 of Cotton leaf curl Kokhran virus (CLCuKoV)-Burewala isolates, designated as CLCuKoV-Burewala-45. The present CLCuMuV-Rajasthan-34 is recombinant isolate showing recombination events in IR, C1 and C4 regions of its genome with high probality (P = 9.9 × 10?10–3.2 × 10?6). Same species of betasatellite (1371 nt) molecules obtained from both the present isolates was related with cotton leaf curl Multan betasatellite by 89–97 % nt identity. Three alphasatellites (1366–1396 nt) related to Cotton leaf curl Burewala alphasatellite and Gossypium darwinii symptomless alphasatellite by 86 % nt identity were also obtained. This is the first report of appearance of CLCuKoV-Burewala isolate and CLCuD associated alphasatellites in New Delhi. The present study demonstrated that CLCuD in New Delhi is caused by three kinds of variants, two are strains of CLCuMuV and one of CLCuKoV, either by single or mixed infection along with beta- and alpha-satellite molecues.  相似文献   
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Development of a chromatographic step in a time and resource efficient manner remains a serious bottleneck in protein purification. Chromatographic performance typically depends on raw material attributes, feed material attributes, process factors, and their interactions. Design of experiments (DOE) based process development is often chosen for this purpose. A challenge is, however, in performing a DOE with such a large number of process factors. A split DOE approach based on process knowledge in order to reduce the number of experiments is proposed. The first DOE targets optimizing factors that are likely to significantly impact the process and their effect on process performance is unknown. The second DOE aims to fine-tune another set of interacting process factors, impact of whom on process performance is known from process understanding. Furthermore, modeling of a large set of output response variables has been achieved by fitting the output responses to an empirical equation and then using the parametric constants of the equation as output response variables for regression modeling. Two case studies involving hydrophobic interaction chromatography for removal of aggregates and cation exchange chromatography for separation of charge variants and aggregates have been utilized to illustrate the proposed approach. Proposed methodology reduced total number of experiments by 25% and 72% compared to a single DOE based on central composite design and full factorial design, respectively. The proposed approach is likely to result in a significant reduction in resources required as well as time taken during process development. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2730, 2019  相似文献   
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Journal of Industrial Microbiology & Biotechnology - Adaptive laboratory evolution (ALE) is a powerful tool used to increase strain fitness in the presence of environmental stressors. If...  相似文献   
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