Robustness, flexibility, and sensitivity in a multifunctional motor control model

Abstract

Motor systems must adapt to perturbations and changing conditions both within and outside the body. We refer to the ability of a system to maintain performance despite perturbations as "robustness," and the ability of a system to deploy alternative strategies that improve fitness as "flexibility." Different classes of pattern-generating circuits yield dynamics with differential sensitivities to perturbations and parameter variation. Depending on the task and the type of perturbation, high sensitivity can either facilitate or hinder robustness and flexibility. Here we explore the role of multiple coexisting oscillatory modes and sensory feedback in allowing multiphasic motor pattern generation to be both robust and flexible. As a concrete example, we focus on a nominal neuromechanical model of triphasic motor patterns in the feeding apparatus of the marine mollusk Aplysia californica. We find that the model can operate within two distinct oscillatory modes and that the system exhibits bistability between the two. In the "heteroclinic mode," higher sensitivity makes the system more robust to changing mechanical loads, but less robust to internal parameter variations. In the "limit cycle mode," lower sensitivity makes the system more robust to changes in internal parameter values, but less robust to changes in mechanical load. Finally, we show that overall performance on a variable feeding task is improved when the system can flexibly transition between oscillatory modes in response to the changing demands of the task. Thus, our results suggest that the interplay of sensory feedback and multiple oscillatory modes can allow motor systems to be both robust and flexible in a variable environment.

http://ift.tt/2hWz4lI

Lung Adenocarcinoma with Miliary Metastases and Left Femur Pathologic Fracture: an Unusual Case Mimicking Disseminated Tuberculosis

http://ift.tt/2igAFzu

Highly improved permeation property of thin-film-composite polyamide membrane for water desalination

Abstract

Thin-film-composite (TFC) polyamide membranes with flux-enhancement were prepared by the interfacial polymerization of m-phenylenediamine with trimesoyl chloride on porous polysulfone support. The addition of 1,3-propanesultone (PS) in the organic phase is used to influence the interfacial polymerization process and the morphology of polyamide layer to improve water flux. FTIR, ¹H NMR and UV spectra were performed to investigate the effect of PS on interfacial polymerization process. In order to study the forming mechanism of TFC membrane, the resulting TFC membranes were characterized by SEM, AFM, ATR-FTIR, XPS, as well as static contact angle. In comparison with conventional polyamide membrane, the TFC membranes fabricated with PS as the additive exhibit much more improved water flux without NaCl rejection decreasing. Notably, the optimal TFC membrane with 0.04% (wt/v) PS as the additive in organic phase shows the best performance with a NaCl rejection of 99.39% and a water flux of 48.57 L m⁻² h⁻¹ at 1.55 MPa, which has increased 41% compared to the value of the conventional TFC membrane.

http://ift.tt/2i1YoUS

Identification of MSH2 inversion of exons 1–7 in clinical evaluation of families with suspected Lynch syndrome

Abstract

Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1–7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1–7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1–7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.

http://ift.tt/2hb10Bb

Tension fecopneumothorax secondary to unrecognized delayed traumatic diaphragmatic hernia

Abstract

Traumatic diaphragmatic hernia is an uncommon but severe problem that is usually seen in patients suffered from blunt or penetrating thoracoabdominal injuries. Despite advances in modern technology, 30–50% of traumatic diaphragmatic ruptures are missed on initial presentation. We report a case of tension fecopneumothorax secondary to an undiagnosed delayed traumatic diaphragmatic hernia in a patient, who sustained blunt trauma chest 15 years back. This case is being presented to emphasize readers that, the diagnosis of diaphragmatic injuries is challenging and requires a high index of clinical suspicion, late presentations are associated with increased morbidity and mortality.

http://ift.tt/2h2VEEK

Cutaneous Side Effects and Transepidermal Water Loss To Gefitinib: A Study of 11 Patients

Abstract

Introduction

Cutaneous side effects caused by epidermal growth factor receptor (EGFR) inhibitors occurred in 45–100% of patients which may lead to therapy modification or interruption. This study aimed to evaluate cutaneous side effects and transepidermal water loss (TEWL) values in non-small cell lung carcinoma (NSCLC) patients who received gefitinib EGFR inhibitor.

Methods

A descriptive observational study with cross-sectional design and a consecutive sampling method was conducted from 1 February to 4 March 2016. Eleven NSCLC patients with EGFR mutation who visited the Hemato-Oncology Clinic/Internal Medicine Department, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, were assessed through history taking, physical examination, and TEWL examination using Tewameter.

Results

Ten of the eleven patients experienced cutaneous side effects. The most frequently observed was xerosis cutis (8/10 patients), followed by acneiform eruptions (7/10 patients), and paronychia (3/10 patients). None of these patients experienced hair changes, mucositis, or drug hypersensitivity. Mean TEWL value of these patients was higher than normal (11.205 ± 1.881 g/m²/h).

Conclusions

Patients who received gefitinib EGFR inhibitor experienced cutaneous side effects including xerosis cutis, acneiform eruptions, and paronychia, and have mean TEWL values higher than normal. Therefore, it might affect the skin barrier function.

http://ift.tt/2hdEIAw

Collaborative Localization for Multi-Robot System with Fault Detection and Exclusion Based on the Kullback-Leibler Divergence

Abstract

Multi-robot system attracted attention in various applications in order to replace the human operators. To achieve the intended goal, one of the main challenges of this system is to ensure the integrity of localization by adding a sensor fault diagnosis step to the localization task. In this paper, we present a framework able, in addition of localizing a group of robots, to detect and exclude the faulty sensors from the group with an optimized thresholding method. The estimator has the informational form of the Kalman Filter (KF) namely Information Filter (IF). A residual test based on the Kullback-Leibler divergence (KLD) between the predicted and the corrected distributions of the IF is developed. It is generated from two tests: the first acts on the means and the second deals with the covariance matrices. Thresholding using entropy based criterion and Receiver Operating Characteristics (ROC) curve are discussed. Finally, the validation of this framework is studied on real experimental data from a group of robots.

http://ift.tt/2hdA5q2

Erratum to: Does the initiation of urate-lowering treatment during an acute gout attack prolong the current episode and precipitate recurrent attacks: a systematic literature review

http://ift.tt/2hUmXDq

Hepatocyte Nuclear Factor 4 Alpha Promotes Definitive Endoderm Differentiation from Human Induced Pluripotent Stem Cells

Abstract

Hepatocyte nuclear factor 4 alpha (HNF4α) is a key transcription factor for liver development. Although HNF4α is necessary for hepatoblast differentiation, the function of HNF4α before the hepatoblast differentiation, such as in definitive endoderm differentiation, is not well known. In addition, it is known that there are nine HNF4α isoforms, but the expression and function of each HNF4α isoform during the definitive endoderm differentiation is also not clear. In this study, we examined the expression pattern of HNF4α and its functions in the definitive endoderm differentiation from human induced pluripotent stem (iPS) cells. We found that the HNF4α-1D isoform expression levels were significantly increased during the definitive endoderm differentiation, while the HNF4α-1A isoform expression levels did not change. Therefore, we further examined the function of the HNF4α-1D isoform in definitive endoderm differentiation. HNF4α-1D overexpression or knockdown was found to promote or prevent the definitive endoderm differentiation, respectively. Interestingly, Lefty1 was directly regulated by HNF4α-1D, and Lefty1 knockdown also prevented the definitive endoderm differentiation. These results suggest that HNF4α-1D promotes definitive endoderm differentiation through the regulation of Lefty1. To our knowledge, this is the first report to clarify the expression pattern and function of HNF4α during the definitive endoderm differentiation.

http://ift.tt/2i1mted

Longitudinal transition trajectory of gouty arthritis and its comorbidities: a population-based study

Abstract

The aim of the study was to investigate the longitudinal transition trajectory of gout and its comorbidities in male patients with gout in different age groups. A total of 3973 male patients who received a new diagnosis of gouty arthritis were identified from the Taiwan Longitudinal Health Insurance Database and divided into two age cohorts (<50 and ≥50 years). Each patient was individually followed from 2000 to 2009 to identify associated comorbidities, namely hypertension, hypercholesterolemia, diabetes mellitus, cardiovascular diseases, and chronic kidney disease. Two outcome measurements of stroke and all-cause cancer were further identified until 2010. The transition trajectory was divided into the following five phenotype groups: persistent hypertension combined with a high prevalence of various gout-related comorbidities, persistent hypercholesterolemia combined with a moderate prevalence of various gout-related comorbidities, persistent low prevalence of various gout-related comorbidities, moderate to high prevalence of various gout-related comorbidities, and low to high prevalence of various gout-related comorbidities. Although the younger and older patients had a similar longitudinal transition trajectory of gout-related comorbidities, the older patients had a higher 10-year likelihood of transition from a low or moderate to a high prevalence of various gout-related comorbidities. In addition, the incidences of stroke and all-cause cancer were higher in the groups with high and moderate to high prevalences of various gout-related comorbidities than in the other groups. The occurrence of gouty arthritis in different life stages can cause cluster effects involving varying degrees of comorbidities over time. The findings of the current study can provide additional knowledge and increase clinical awareness regarding the early assessment and management of gout-related comorbidities in clinical practice.

http://ift.tt/2hIr8UI

Long-term use of biologic agents does not increase the risk of serious infections in elderly patients with rheumatoid arthritis

Abstract

This study aimed to determine whether the long-term use of biologic agents increases serious infections in elderly patients with rheumatoid arthritis (RA) and to determine the risk factors of serious infections in biologics-treated elderly RA patients. We retrospectively analyzed the incidence rate of serious infections that required hospitalization between biologics-treated and non-biologic disease-modifying antirheumatic drug (DMARD)-treated elderly RA patients (aged over 65 years). We examined the risk factors for serious infections in biologics-treated elderly RA patients. We found that, during a 3-year observation period, the incidence rate of serious infections was not significantly different between biologics-treated and non-biologic DMARD-treated elderly RA patients [8.0 (95% CI 4.7–13.5) and 6.3 (95% CI 4.1–9.5) events per 100 person-years of follow-up, respectively, P = 0.78]. The time to the first serious infection did not significantly differ between the two groups by the analysis of the Kaplan–Meier curves, either (P = 0.46). We then found that prednisolone doses alone were significantly associated with serious infections in biologics-treated elderly RA patients. Furthermore, we found that prednisolone at 1–4 mg/day was associated with serious infections in biologics-treated patients, but not non-biologic DMARD-treated patients. On the other hand, prednisolone at greater than 5 mg/day was associated with serious infections in both biologics-treated and non-biologics-treated patients. We show that there is not a significant difference between the incidence of serious infections between biologics group and non-biologics group in elderly RA patients (≧65 years) and that even very low-dose glucocorticoid use (prednisolone 1–4 mg/day) is a risk factor for serious infections in biologics-treated elderly RA patients.

http://ift.tt/2h84DrB

Optimization of conditions for cadmium selenide quantum dot biosynthesis in Saccharomyces cerevisiae

Abstract

The biosynthesis of quantum dots has been explored as an alternative to traditional physicochemical methods; however, relatively few studies have determined optimal synthesis parameters. Saccharomyces cerevisiae sequentially treated with sodium selenite and cadmium chloride synthesized CdSe quantum dots in the cytoplasm. These nanoparticles displayed a prominent yellow fluorescence, with an emission maximum of approximately 540 nm. The requirement for glutathione in the biosynthetic mechanism was explored by depleting its intracellular content through cellular treatments with 1-chloro-2,4-dinitrobenzene and buthionine sulfoximine. Synthesis was significantly inhibited by both of these reagents when they were applied after selenite treatment prior to the addition of cadmium, thereby indicating that glutathione contributes to the biosynthetic process. Determining the optimum conditions for biosynthesis revealed that quantum dots were produced most efficiently at entry into stationary phase followed by direct addition of 1 mM selenite for only 6 h and then immediately incubating these cells in fresh growth medium containing 3 mM Cd (II). Synthesis of quantum dots reached a maximum at 84 h of reaction time. Biosynthesis of 800-μg g⁻¹ fresh weight cells was achieved. For the first time, significant efforts have been undertaken to optimize each aspect of the CdSe biosynthetic procedure in S. cerevisiae, resulting in a 70% increased production.

http://ift.tt/2ibqznA

Tunable recombinant protein expression in E . coli : promoter systems and genetic constraints

Abstract

Tuning of transcription is a promising strategy to overcome challenges associated with a non-suitable expression rate like outgrowth of segregants, inclusion body formation, metabolic burden and inefficient translocation. By adjusting the expression rate—even on line—to purposeful levels higher product titres and more cost-efficient production processes can be achieved by enabling culture long-term stability and constant product quality. Some tunable systems are registered for patents or already commercially available. Within this contribution, we discuss the induction mechanisms of various Escherichia coli inherent promoter systems with respect to their tunability and review studies using these systems for expression tuning. According to the current level of knowledge, some promoter systems were successfully used for expression tuning, and in some cases, analytical evidence on single-cell level is still pending. However, only a few studies using tunable strains apply a suitable process control strategy. So far, expression tuning has only gathered little attention, but we anticipate that expression tuning harbours great potential for enabling and optimizing the production of a broad spectrum of products in E. coli.

http://ift.tt/2h2yCxO

Comparative transcriptomes reveal novel evolutionary strategies adopted by Saccharomyces cerevisiae with improved xylose utilization capability

Abstract

Production of ethanol from xylose by recombinant Saccharomyces cerevisiae is suboptimal with slow fermentation rate, compared with that from glucose. In this study, a strain-expressing Scheffersomyces stipitis xylose reductase–xylitol dehydrogenase (XR-XDH) pathway was subjected to adaptive evolution on xylose; this approach generated populations with the significantly improved cell growth and ethanol production rate. Mutants were isolated, and the best one was used for sporulation to generate eight stable mutant strains with improved xylose fermentation ability. They were used in a microarray assay to study the molecular basis of the enhanced phenotype. The enriched transcriptional differences among the eight mutant strains and the native strain revealed novel responses to xylose, which likely contributes to the improved xylose utilization. The upregulated vitamin B1 and B6 biosynthesis indicated that thiamine served as an important cofactor in xylose metabolism and may alleviate the redox stress. The increased expression of genes involved in sulfur amino acid biosynthesis and the decreased expression of genes related to Fe(II) transport may alleviate redox stress as well. Meanwhile, it was remarkable that several glucose-repressible genes, including genes of the galactose metabolism, gluconeogenesis, and ethanol catabolism, had a lower expression level after adaptive evolution. Concomitantly, the expression levels of two regulators of the glucose signaling pathway, Rgs2 and Sip4, decreased, indicating a reshaped signaling pathway to xylose after adaptive evolution. Our findings provide new targets for construction of a superior bioethanol producing strain through inverse metabolic engineering.

http://ift.tt/2ibxWv2

Studies on the removal of Cd ions by gastrointestinal lactobacilli

Abstract

Accumulation of toxic metal ions in food and water is nowadays a growing health-related problem. One detoxification method involves the use of microorganisms naturally inhabiting the gastrointestinal tract (GIT). The purpose of this study was to prove that lactic acid bacteria derived from the GIT are able to effectively remove Cd²⁺ from water solution. Seven strains of lactobacilli, out of 11 examined, showed tolerance to high concentrations of cadmium ions. The metal-removal efficiencies of these seven lactobacilli ranged from 6 to 138.4 μg/h mg. Among these bacteria, Lactobacillus gallinarum and Lactobacillus crispatus belonged to the highest (85%) Cd-removal efficiency class. An analysis of the zeta potential (ζ) indicated that the bacterial cell surface had a negative charge at the pH ranging from 3 to 10. The presence of carboxyl, amide, and phosphate groups was favorable for Cd²⁺ binding to the cell surface, which found confirmation in FTIR-ATR spectra. Elemental SEM/EDS analysis and TEM imaging not only confirmed the adsorption of Cd²⁺ on the cell envelope but also gave us a reason to suppose that Lb. crispatus accumulates metal ions inside the cell. Our findings open perspectives for further research on the new biological function of GIT lactobacilli as natural biosorbents.

http://ift.tt/2h2IQOV

A hybrid frequency–time domain symmetric adaptive decorrelator

Abstract

Symmetric adaptive decorrelation (SAD) is a semi-blind method of separating convolutely mixed signals. While it has restrictions on the physical layout of the demixing equipment, it is better suited for some applications (e.g., live sound mixing) as no post-processing is required to ascertain which output corresponds with which source. Since SAD is based on the least mean squares algorithm, it can be modified to perform the bulk of the processing in the frequency domain. This makes it more efficient for larger filter sizes and/or larger number of sources but renders it unsuitable for real-time applications as there is a lag between the output and the input. In this paper, we propose a hybrid approach that does not suffer from the lag of the frequency domain approach. While the proposed algorithm is slightly less computationally efferent than the pure frequency domain algorithm, it is significantly more efficient than the time domain approach. A comparison of the frequency domain and hybrid algorithms shows that both achieve separation equivalent to the time domain algorithm in a real-world environment.

http://ift.tt/2hU8WFH

Hydrophobic ionic liquids for quantitative bacterial cell lysis with subsequent DNA quantification

Abstract

DNA is one of the most frequently analyzed molecules in the life sciences. In this article we describe a simple and fast protocol for quantitative DNA isolation from bacteria based on hydrophobic ionic liquid supported cell lysis at elevated temperatures (120–150 °C) for subsequent PCR-based analysis. From a set of five hydrophobic ionic liquids, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide was identified as the most suitable for quantitative cell lysis and DNA extraction because of limited quantitative PCR inhibition by the aqueous eluate as well as no detectable DNA uptake. The newly developed method was able to efficiently lyse Gram-negative bacterial cells, whereas Gram-positive cells were protected by their thick cell wall. The performance of the final protocol resulted in quantitative DNA extraction efficiencies for Gram-negative bacteria similar to those obtained with a commercial kit, whereas the number of handling steps, and especially the time required, was dramatically reduced.

Graphical Abstract

After careful evaluation of five hydrophobic ionic liquids, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([BMPyr ⁺][Ntf ₂^-]) was identified as the most suitable ionic liquid for quantitative cell lysis and DNA extraction. When used for Gram-negative bacteria, the protocol presented is simple and very fast and achieves DNA extraction efficiencies similar to those obtained with a commercial kit. ddH ₂O double-distilled water, qPCR quantitative PCR

http://ift.tt/2haGVLy

Surface-enhanced Raman spectroscopy introduced into the International Standard Organization (ISO) regulations as an alternative method for detection and identification of pathogens in the food industry

Abstract

We show that surface-enhanced Raman spectroscopy (SERS) coupled with principal component analysis (PCA) can serve as a fast, reliable, and easy method for detection and identification of food-borne bacteria, namely Salmonella spp., Listeria monocytogenes, and Cronobacter spp., in different types of food matrices (salmon, eggs, powdered infant formula milk, mixed herbs, respectively). The main aim of this work was to introduce the SERS technique into three ISO (6579:2002; 11290–1:1996/A1:2004; 22964:2006) standard procedures required for detection of these bacteria in food. Our study demonstrates that the SERS technique is effective in distinguishing very closely related bacteria within a genus grown on solid and liquid media. The advantages of the proposed ISO-SERS method for bacteria identification include simplicity and reduced time of analysis, from almost 144 h required by standard methods to 48 h for the SERS-based approach. Additionally, PCA allows one to perform statistical classification of studied bacteria and to identify the spectrum of an unknown sample. Calculated first and second principal components (PC-1, PC-2) account for 96, 98, and 90% of total variance in the spectra and enable one to identify the Salmonella spp., L. monocytogenes, and Cronobacter spp., respectively. Moreover, the presented study demonstrates the excellent possibility for simultaneous detection of analyzed food-borne bacteria in one sample test (98% of PC-1 and PC-2) with a goal of splitting the data set into three separated clusters corresponding to the three studied bacteria species. The studies described in this paper suggest that SERS represents an alternative to standard microorganism diagnostic procedures.

Graphical Abstract

New approach of the SERS strategy for detection and identification of food-borne bacteria, namely S. enterica, L. monocytogenes, and C. sakazakii in selected food matrices

http://ift.tt/2haHs01

Gelatin Tannate for Acute Childhood Gastroenteritis: A Randomized, Single-Blind Controlled Trial

Abstract

Background

Oral rehydration therapy is the recommended treatment for acute childhood gastroenteritis. The aim of this study was to assess the efficacy and safety of gelatin tannate plus oral rehydration compared with oral rehydration alone.

Methods

We conducted a multicenter, parallel, randomized, controlled, single-blind, prospective, open-label trial. A central randomization center used computer generated tables to allocate treatments. The study was performed in two medical centers in Italy. Sixty patients 3–72 months of age with acute gastroenteritis were recruited (median age 18 months; age range 3–66 months): 29 received an oral rehydration solution (ORS) and 31 an ORS plus gelatin tannate (ORS + G). The primary outcome was the number of bowel movements 48 and 72 h after initiating treatment. Secondary outcomes were: duration of diarrhea, stool characteristics and adverse events.

Results

No patient was lost at follow-up. No significant difference in the number of bowel movements after 48 h was reported (2.7 ± 1.3 ORS + G; 3.2 ± 0.8 ORS; p = 0.06), although the ORS + G group showed a significant improvement in stool consistency (3.7 ± 1.0 vs. 4.3 ± 0.8; p = 0.005). At 72 h, a significant reduction in bowel movements was reported in the ORS + G group compared with the ORS group (1.0 ± 1.4 vs. 2.0 ± 1.7; p = 0.01). Mean duration of diarrhea was significantly lower in the ORS + G group than in the ORS only group (76.8 ± 19.2 vs. 108 ± 24.0 h; p < 0.0001). No adverse events were reported.

Conclusions

Gelatin tannate added to oral rehydration in children with acute diarrhea was associated with a significant decrease in bowel movements at 72 h, with an early improvement in the stool consistency and shorter disease duration.

Clinical Trial Registration

NCT02644200—Gelatin Tannate as Treatment for Acute Childhood Gastroenteritis (http://ift.tt/1xHjpsE).

http://ift.tt/2hVTfAx

Topiramate in the Treatment of Generalized Convulsive Status Epilepticus in Adults: A Systematic Review with Individual Patient Data Analysis

Abstract

Background

Generalized convulsive status epilepticus (GCSE) is a medical emergency associated with high morbidity and mortality that requires prompt medical intervention. Topiramate (TPM) is an antiepileptic drug effective against a broad spectrum of seizure types, and has been proposed as a possible therapeutic option for super-refractory status epilepticus (SRSE), the most severe form of GCSE.

Aim

This review aimed to evaluate the role of TPM in GCSE, including SRSE.

Methods

MEDLINE, CENTRAL, ClinicalTrials.gov, LILACS, Google Scholar, and Opengrey.eu were systematically searched. We compared: (1) patients who did and who did not receive TPM as their last drug; (2) patients receiving TPM as the last drug and achieving SE control and patients receiving TPM as the last drug but without termination of SE.

Results

The literature search yielded 1164 results, with individual data available for 35 patients (six with SRSE) from four studies. SE was controlled in 68.6% of patients receiving TPM either as the last drug (20) or not (15), and in 14 of the 20 patients receiving TPM as the last drug (70%). Only six patients received TPM for SRSE; in five of them, TPM was administered as the last drug with resolution of SE in four. When comparing patients who did and did not receive TPM as the last drug, no statistically significant difference was found for any of the variables considered; similarly, no difference was found comparing patients receiving TPM as the last drug and achieving SE control with those receiving TPM as the last drug but without termination of SE.

Conclusions

The lack of a statistically significant difference is likely to be due to the small sample size. In only a few patients was TPM used for SRSE. There is an unmet need for high-quality studies to evaluate the role of TPM in GCSE.

http://ift.tt/2hrP9fR

Erratum to: Thoracic and cardiovascular surgery in Japan during 2013

http://ift.tt/2hrQhjE

A new strategy for full-length Ebola virus glycoprotein expression in E.coli

Abstract

Ebola virus (EBOV) causes severe hemorrhagic fever in humans and non-human primates with high rates of fatality. Glycoprotein (GP) is the only envelope protein of EBOV, which may play a critical role in virus attachment and entry as well as stimulating host protective immune responses. However, the lack of expression of full-length GP in Escherichia coli hinders the further study of its function in viral pathogenesis. In this study, the vp40 gene was fused to the full-length gp gene and cloned into a prokaryotic expression vector. We showed that the VP40-GP and GP-VP40 fusion proteins could be expressed in E.coli at 16 °C. In addition, it was shown that the position of vp40 in the fusion proteins affected the yields of the fusion proteins, with a higher level of production of the fusion protein when vp40 was upstream of gp compared to when it was downstream. The results provide a strategy for the expression of a large quantity of EBOV full-length GP, which is of importance for further analyzing the relationship between the structure and function of GP and developing an antibody for the treatment of EBOV infection.

http://ift.tt/2hd84yN

The 2016 Tamio Yamakawa award

http://ift.tt/2ha7b8O

Rapid MRSA PCR on respiratory specimens from ventilated patients with suspected pneumonia: a tool to facilitate antimicrobial stewardship

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in ventilated patients. Our objective was to evaluate the GeneXpert MRSA/SA SSTI Assay (Xpert MRSA/SA) (Cepheid, Sunnyvale, CA) for use in lower respiratory tract (LRT) specimens for rapid MRSA detection and to determine the potentially saved antibiotic-days if a culture-based identification method was replaced by this assay. Remnant LRT samples from ventilated patients submitted to the microbiology laboratory for routine culture were tested using conventional culture and Xpert MRSA/SA. One hundred of 310 LRT specimens met the inclusion criteria. Ten samples were positive for MRSA by Xpert MRSA/SA, while six were positive by routine culture methods. Xpert MRSA/SA correctly identified 5/6 positive and 89/94 negative MRSA specimens, for a sensitivity of 83.3%, specificity of 94.7%, positive predictive value of 45.6%, and negative predictive value of 98.9%. The assay also correctly detected 3/3 positive and 90/97 negative methicillin-susceptible S. aureus (MSSA) specimens, for a sensitivity of 100%, specificity of 92.8%, positive predictive value of 30%, and negative predictive value of 100%. A total of 748 vancomycin and 305 linezolid antibiotic-days were associated with the enrolled specimens. Vancomycin and linezolid utilization could decrease by 68.4% and 83%, respectively, if discontinued 1 day after negative polymerase chain reaction (PCR) results. The Xpert MRSA/SA SSTI rapid MRSA PCR assay performed well in respiratory samples from ventilated patients with suspected pneumonia and has the potential to facilitate stewardship efforts such as reducing empiric vancomycin and linezolid therapy.

http://ift.tt/2hVA49F

Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients

Abstract

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group (p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group (p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344–13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse.

http://ift.tt/2i1429J

Sediment related impacts of climate change and reservoir development in the Lower Mekong River Basin: a case study of the Nam Ou Basin, Lao PDR

Abstract

This study applies the soil and water assessment tool (SWAT), with climate (precipitation and temperature) outputs from four general circulation models (GCMs) and a regional circulation model (PRECIS), to evaluate (1) the impacts of climate change on reservoir sedimentation and (2) the impacts of climate change and reservoir development on sediment outflow in the Nam Ou River Basin located in northern Laos. Three reservoir–density scenarios, namely one reservoir (1R), three reservoirs in series (3R), and five reservoirs in series (5R), were evaluated for both no climate change and climate change conditions. The results show that under no climate change conditions, by 2070, around 17, 14, and 15% of the existing reservoir storage volume in the basin will be lost for 1R, 3R, and 5R scenarios, respectively. Notably, under climate change scenario with highest changes in erosion and sediment outflux from the basin, the additional reduction in reservoir storage capacity due to sedimentation is estimated to be nearly 26% for 1R, 21% for 3R, and 23% for 5R. Climate change alone is projected to change annual sediment outflux from the basin by −20 to 151%. In contrast, the development of reservoirs in the basin will reduce the annual sediment outflux from the basin varying from 44 to 80% for 1R, 44–81% for 3R, and 66–89% for 5R, considering climate change. In conclusion, climate change is expected to increase the sediment yield of the Nam Ou Basin, resulting in faster reduction of the reservoir's storage capacity. Sediment yield from the Nam Ou River Basin is likely to decrease significantly due to the trapping of sediment by planned reservoirs. The impact of reservoirs is much more significant than the impact of climate change on the sediment outflow of the basin. Hence, it is necessary to investigate appropriate reservoir sediment management strategies.

http://ift.tt/2hc04Ov

Dank an die Gutachter 2016

http://ift.tt/2hV2VLs

A powered prosthetic ankle joint for walking and running

Current prosthetic ankle joints are designed either for walking or for running. In order to mimic the capabilities of an able-bodied, a powered prosthetic ankle for walking and running was designed. A powered ...

http://ift.tt/2gVnoeJ

Assessment of transfemoral amputees using a passive microprocessor-controlled knee versus an active powered microprocessor-controlled knee for level walking

In transfemoral (TF) amputees, the forward propulsion of the prosthetic leg in swing has to be mainly carried out by hip muscles. With hip strength being the strongest predictor to ambulation ability, an activ...

http://ift.tt/2i2WPsY

Towards active lower limb prosthetic systems: design issues and solutions

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Theoretical implementation of prior knowledge in the design of a multi-scale prosthesis satisfaction questionnaire

In product development for lower limb prosthetic devices, a set of special criteria needs to be met. Prosthetic devices have a direct impact on the rehabilitation process after an amputation with both perceive...

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Movement visualisation in virtual reality rehabilitation of the lower limb: a systematic review

Virtual reality (VR) based applications play an increasing role in motor rehabilitation. They provide an interactive and individualized environment in addition to increased motivation during motor tasks as wel...

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Patient-specific 3D hemodynamics modelling of left coronary artery under hyperemic conditions

Abstract

The purpose of this study is to investigate the effect of various degrees of percentage stenosis on hemodynamic parameters during the hyperemic flow condition. 3D patient-specific coronary artery models were generated based on the CT scan data using MIMICS-18. Numerical simulation was performed for normal and stenosed coronary artery models of 70, 80 and 90% AS (area stenosis). Pressure, velocity, wall shear stress and fractional flow reserve (FFR) were measured and compared with the normal coronary artery model during the cardiac cycle. The results show that, as the percentage AS increase, the pressure drop increases as compared with the normal coronary artery model. Considerable elevation of velocity was observed as the percentage AS increases. The results also demonstrate a recirculation zone immediate after the stenosis which could lead to further progression of stenosis in the flow-disturbed area. Highest wall shear stress was observed for 90% AS as compared to other models that could result in the rupture of coronary artery. The FFR of 90% AS is found to be considerably low.

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Out of sight, out of mind: Matching bias underlies confirmatory visual search

Abstract

Confirmation bias has recently been reported in visual search, where observers who were given a perceptual rule to test (e.g. "Is the p on a red circle?") search stimuli that could confirm the rule stimuli preferentially (Rajsic, Wilson, & Pratt, Journal of Experimental Psychology: Human Perception and Performance, 41(5), 1353–1364, 2015). In this study, we compared the ability of concrete and abstract visual templates to guide attention using the visual confirmation bias. Experiment 1 showed that confirmatory search tendencies do not result from simple low-level priming, as they occurred when color templates were verbally communicated. Experiment 2 showed that confirmation bias did not occur when targets needed to be reported as possessing or not possessing the absence of a feature (i.e., reporting whether a target was on a nonred circle). Experiment 3 showed that confirmatory search also did not occur when search prompts referred to a set of visually heterogenous features (i.e., reporting whether a target on a colorful circle, regardless of the color). Together, these results show that the confirmation bias likely results from a matching heuristic, such that visual codes involved in representing the search goal prioritize stimuli possessing these features.

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Osteitis: a retrospective feasibility study comparing single-source dual-energy CT to MRI in selected patients with suspected acute gout

Abstract

Objective

Dual-energy computed tomography detects tophi in patients with chronic gout. However, other information that can be obtained from the same scan is not the focus of the current research, e.g., the detection of bone marrow edema (BME) using virtual bone marrow imaging (VBMI). The aim of this study was to evaluate if BME in patients with acute arthritis can be detected with VBMI using magnetic resonance imaging (MRI) as the standard of reference.

Materials and methods

This retrospective study included 11 patients who underwent both MRI and dual-energy computed tomography (mean interval of 40 days). BME in MRI (standard of reference) and VBMI was judged independently by two different blinded readers. φ-correlation coefficient and Cohen's κ were performed for statistical analysis. Approval was waived by the IRB.

Results

Two patients with a final diagnosis of RA and one with septic arthritis showed osteitis on MRI and VBMI. However, in each case, there were individual bones identified with osteitis on MRI but not VBMI. Three additional patients with the final diagnosis of RA were identified correctly as negative for BME. There was a good correlation between both modalities (φ = 0.8; κ = 0.8). Inter-rater reliability was excellent for both modalities (κ = 0.9).

Conclusions

We have shown that detecting osteitis using VBMI is feasible in patients with inflammatory arthritis. Further studies are needed on larger, more-targeted populations to better define the indications, accuracy, and added value of this technique.

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Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome: MRI features of intraosseous fat necrosis involving the feet and knees

Abstract

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is extremely rare and presents as a triad of the three diseases. The patient usually presents with mild or absent abdominal symptoms. Here, we report on a case of a 66-year-old male who presented with pain and swelling in both legs and mild abdominal pain. He was diagnosed with acute pancreatitis by pancreatic enzyme analysis and abdominal computed tomography (CT) and with skin lesions of panniculitis through a biopsy. Magnetic resonance imaging (MRI) revealed multifocal intraosseous fat necrosis and arthritis involving both the feet and the knees. Therefore, we report a case of PPP syndrome with intraosseous fat necrosis involving both the feet and the knees.

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Evaluation of the clinical relevance of anti-annexin-A5 antibodies in Chinese patients with antiphospholipid syndrome

Abstract

A hallmark feature of antiphospholipid syndrome (APS) is the presence of antiphospholipid antibodies (aPLs). Few studies have addressed the clinical relevance of anti-annexin A5 antibodies (aANXA5) in Chinese patients with APS. In this study, we evaluated the clinical performance of aANXA5 in the diagnosis of APS. Sera from 313 subjects were tested, including 170 samples from patients with APS, 104 samples from patients with non-APS diseases as disease controls (DC), and 39 healthy controls (HC). Serum IgG and IgM aANXA5 were determined by ELISA. Overall, the levels of both IgG and IgM aANXA5 were significantly increased in patients with primary APS (PAPS) and APS associated to other diseases (APSAOD) compared with DC and HC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for IgG and IgM aANXA5 in the diagnosis of APS were 33.5 and 15.3, 99.0 and 99.0, 98.3 and 96.3, and 47.7 and 41.7%, respectively. Significant associations between IgG aANXA5 and arterial thrombotic events (OR, 2.60; 95% CI, 1.44–4.71) and between IgG aANXA5 and venous thrombotic events (OR, 2.80; 95% CI, 1.55–5.06) were identified. No correlations were identified between IgG or IgM aANXA5 and obstetric complications. Our data suggest that aANXA5 could serve as a diagnosis biomarker for patients with APS. More importantly, our data highlighted a potential role of IgG aANXA5 in identifying APS patients with high risk of thrombosis.

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Two cases demonstrating thalidomide’s efficacy in refractory lupus nephritis

Abstract

Renal involvement in systemic lupus erythematosus (SLE) is common and has been associated with an increased risk of mortality [1]. Early diagnosis is imperative to control proteinuria and prevent the progression to end-stage renal disease. Standard induction therapies include cyclophosphamide (CYC) and mycophenolate mofetil (MMF); however, it has been estimated that approximately 30% of patients are refractory to these standard treatments after 1 year [2]. We present two cases of patients diagnosed with lupus nephritis (LN) who demonstrated persistent proteinuria while on standard treatments that markedly improved after addition of thalidomide (THD). A literature review was performed indicating that THD use with prednisolone (PL) was more efficacious than MMF with PL in resolving lupus nephritis in a mouse model. Thalidomide, which was well tolerated, was associated with a reduction in the protein-to-creatinine ratio with sustained results in both of our patient cases. These cases suggest more clinical data is needed to explore the potential utility of thalidomide in the treatment of LN.

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Public health awareness of autoimmune diseases after the death of a celebrity

Abstract

Autoimmune disorders impose a high burden, in terms of morbidity and mortality worldwide. Vasculitis is an autoimmune disorder that causes inflammation and destruction of blood vessels. Harold Allen Ramis, a famous American actor, director, writer, and comedian, died on the February 24, 2014, of complications of an autoimmune inflammatory vasculitis. To investigate the relation between interests and awareness of an autoimmune disease after a relevant event such as the death of a celebrity, we systematically mined Google Trends, Wikitrends, Google News, YouTube, and Twitter, in any language, from their inception until October 31, 2016. Twenty-eight thousand eight hundred fifty-two tweets; 4,133,615 accesses to Wikipedia; 6780 news; and 11,400 YouTube videos were retrieved, processed, and analyzed. The Harold Ramis death of vasculitis resulted into an increase in vasculitis-related Google searches, Wikipedia page accesses, and tweet production, documenting a peak in February 2014. No trend could be detected concerning uploading YouTube videos. The usage of Big Data is promising in the fields of immunology and rheumatology. Clinical practitioners should be aware of this emerging phenomenon.

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Adsorption of Toxic Metals on Modified Polyacrylonitrile Nanofibres: A Review

Abstract

Removal of toxic metals from aqueous solutions is of high priority in environmental chemistry. Most of the available techniques for this task are considered expensive; however, the adsorption process has been considered the easiest and the cheapest way of removing toxic metals from aqueous solution. The performance of adsorption setup largely depends on the characteristic of adsorbents. One of these characteristic is availability of large surface area. The more the available sites for chelation, the more the amount of metals removed. Therefore, the production of materials of nanoscale is expedient for adsorption purposes. Electrospinning process is one of the technologies that have been employed to produce polyacrylonitrile nanofibres (PAN-nfs). Moreover, PAN-nfs surfaces have also been chemically modified so as to introduce chelating groups such as amine, carboxyl, imines, etc. Here we review PAN-nfs as metal ion adsorbent. With characteristics such as high surface area as well as good mechanical strength, modified PAN-nfs are considered good adsorbents and have been used to remove toxic metals such as cadmium, lead, chromium, mercury, uranium, silver and copper in different ion states from their aqueous solutions. The ease of immobilization of metal-specific ligands on PAN-nfs has been of great interest in selective extraction of metal ions from their aqueous solutions. Also, toxic metals adsorbed on modified PAN-nfs can be recovered through desorption process using acids or bases of various concentrations.

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Removal of Phenolic Compounds from Aqueous Solutions Using Sludge-Based Activated Carbons Prepared by Conventional Heating and Microwave-Assisted Pyrolysis

Abstract

Sludge-derived activated carbons (ACs) were prepared by conventional heating and microwave pyrolysis. The ACs were characterized using several analytical and functional techniques and used for removal of six phenolic compounds from aqueous solutions. The adsorbents exhibited similar features and possessed hydrophobic surfaces. The ACs were assigned mesoporous materials, with specific surface areas of up to 641 and 540 m² g⁻¹ for CAC-500 and MAC-980, respectively. The preliminary results indicated that phenol removal onto the ACs increased in the order: m-cresol < phenol < o-cresol < 2-chrorophenol < 2-nitrophenol < hydroquinone. Hydroquinone exhibited the highest adsorption capacity and was chosen to continue the remaining part of the experimental work—kinetic and isothermal studies. The adsorption kinetic and isotherm data were well described by the Avrami fractionary order and Redlich–Peterson models, respectively. The maximum amounts (Q _max) of hydroquinone adsorbed at 25 °C were too high, reaching 1218.3 and 1202.1 mg g⁻¹ for CAC-500 and MAC-980, respectively. The mechanism of adsorption was proposed in this work, and it was suggested that donor–acceptor complex and π–π interactions play major roles in the adsorption process. The adsorbents were also tested on simulated effluents. The two ACs displayed good efficiency for the treatment of industrial simulated effluents.

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Determination of Arsenic in Water Samples by Using a Green Hydrophobic-Hydrophilic Switchable Liquid-Solid Dispersive Microextraction Method

Abstract

A simple and green preconcentration method of hydrophobic to hydrophilic switchable liquid-solid dispersive microextraction (HSL-SDM) has been first time introduced as separation method for arsenic ion in real water samples. Multiwall carbon nanotube (MWCNT) was immobilized with diethylenetriamine (DETA) and then used as solid phase adsorbent for the determination of trace level of arsenic ion by HSL-SDM method prior to analysis by hydride generation atomic absorption spectrometry. Reversibly hydrophobic-hydrophilic switchable of functionalized MWCNT can occur due to the exposing of carbon dioxide (CO₂) as anti-solvent trigger. The reversibly hydrophobic-hydrophilic switchable phenomena of immobilized MWCNT in the liquid-solid dispersive microextraction were checked by using FT-IR and SEM. The optimized analytical condition for arsenic ion analysis such as enrichment factor and limits of detection were obtained 83 and 3.05 ng L⁻¹, respectively. Accuracy of the developed HSL-SDM method was confirmed by the analysis of certified reference materials. Our developed HSL-SDM method was successfully applicable for measurements of arsenic ions in real water samples.

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The Impact of Provider Networks on the Co-Prescriptions of Interacting Drugs: A Claims-Based Analysis

Abstract

Introduction

Multiple provider prescribing of interacting drugs is a preventable cause of morbidity and mortality, and fragmented care is a major contributing factor. We applied social network analysis to examine the impact of provider patient-sharing networks on the risk of multiple provider prescribing of interacting drugs.

Methods

We performed a retrospective analysis of commercial healthcare claims (years 2008–2011), including all non-elderly adult beneficiaries (n = 88,494) and their constellation of care providers. Patient-sharing networks were derived based on shared patients, and care constellation cohesion was quantified using care density, defined as the ratio between the total number of patients shared by provider pairs and the total number of provider pairs within the care constellation around each patient.

Results

In our study, 2% (n = 1796) of patients were co-prescribed interacting drugs by multiple providers. Multiple provider prescribing of interacting drugs was associated with care density (odds ratio per unit increase in the natural logarithm of the value for care density 0.78; 95% confidence interval 0.74–0.83; p < 0.0001). The effect of care density was more pronounced with increasing constellation size: when constellation size exceeded ten providers, the risk of multiple provider prescribing of interacting drugs decreased by nearly 37% with each unit increase in the natural logarithm of care density (p < 0.0001). Other predictors included increasing age of patients, increasing number of providers, and greater morbidity.

Conclusion

Improved care cohesion may mitigate unsafe prescribing practices, especially in larger care constellations. There is further potential to leverage network analytics to implement large-scale surveillance applications for monitoring prescribing safety.

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Caregiver Preference and Treatment Compliance in Patients with Mild-to-Moderate Alzheimer’s Disease in South Korea: RECAP Study Results

Abstract

Introduction

The aim of this study was to assess caregiver preference and treatment compliance with oral and transdermal medications in a "real-world" setting in patients with mild-to-moderate Alzheimer's disease (AD) in South Korea.

Methods

Real-world evaluation of compliance and preference in Alzheimer's disease treatment (RECAP) was a 24-week, multicenter, prospective, non-interventional study in patients with AD treated with oral or transdermal therapy. Here, we report data from patients living in South Korea. Eligible patients were grouped into one of two treatment cohorts: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). Caregiver preference, patient compliance, and physician preference were assessed at week 24 (end of the study). Safety was assessed by reported adverse events (AEs).

Results

A total of 398 patients were enrolled (oral 51.8%; transdermal 48.2%) and 79.4% completed the study. Caregivers of patients that were exposed to either the oral or transdermal monotherapy showed a preference for the treatment to which the patients were exposed (both p < 0.0001). However, caregivers of patients that were exposed to both forms of treatments reported a higher preference for transdermal monotherapy (65.9%; p < 0.0041). Patients in both treatment cohorts showed good compliance, with an overall mean (SD) score of 8.84 (1.514) (a median of 9). Of the 15 participating physicians, eight indicated their preference for transdermal therapy and seven preferred oral therapy at week 24. A total of 133 (33.4%) patients reported at least one AE during the study period (oral: 60 patients; transdermal: 73 patients).

Conclusion

The study showed higher caregiver preference for transdermal monotherapy over oral monotherapy when patients with AD were exposed to both forms of treatment and good patient compliance for both oral and transdermal treatments.

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Patient Satisfaction with Collection of Patient-Reported Outcome Measures in Routine Care

Abstract

Introduction

Systematic collection of patient-reported outcome measures (PROMs) during ambulatory clinic visits can enhance communication between patient and provider, and provide the ability to evaluate outcomes of care. Little is known about patient satisfaction of PROM data collection in routine clinical care. To evaluate patient reaction to the routine collection of PROMs in the ambulatory setting.

Methods

Before all ambulatory clinic visits at our neurological institute, patients electronically complete health status questionnaires. We administered an 8-question patient satisfaction survey to a sample of patients seen across the institute after their clinical visit.

Results

Of 343 patients approached, 323 agreed to participate. The majority responded that the questionnaire system was easy to use, was an appropriate length, and benefited their care overall (strongly agree or agree = 92.3%, 87.6%, and 77.3%, respectively). Provider review of the PROMs with the patient during the clinic visit was associated with significantly higher positive responses to all questions, even those regarding logistical aspects of the collection process. There were significant age and race differences in response to perceived benefit: those in the Black/other race category had a markedly lower probability of viewing the process favorably with increasing age.

Conclusions

Systematic collection of PROMs via an electronic questionnaire appears to be well accepted by patients. A minority of patients did not feel the questionnaire content applied to their appointment or that the system was a beneficial feature of the clinical practice. The provider can significantly improve the patient's perception of PROM collection and the patient–physician encounter by reviewing the questionnaire results with the patient.

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Relative Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor, Dacarbazine, and Glycoprotein 100 in Metastatic Melanoma: An Indirect Treatment Comparison

Abstract

Introduction

Advances in the treatment of metastatic melanoma have been achieved in recent years: immunotherapies and targeted therapies have demonstrated survival benefits over older agents such as granulocyte-macrophage colony-stimulating factor (GM-CSF), dacarbazine, and glycoprotein peptide vaccine (gp100) in pivotal phase 3 trials. It is important to compare therapies to guide the treatment decision-making process, and establishing the relationship between older agents can strengthen the networks of evidence for newer therapies. We report the outcome of an indirect comparison of GM-CSF, dacarbazine, and gp100 in metastatic melanoma through meta-analysis of absolute treatment effect.

Methods

A systematic literature review identified trials for inclusion in the meta-analysis. A valid network meta-analysis was not feasible: treatment-specific meta-analysis was conducted. A published algorithm was used to adjust overall survival estimates from trials of GM-CSF, dacarbazine, and gp100 for heterogeneity in baseline prognostic factors. Survival estimates were compared in three patient groups: stage IIIB–IV M1c, stage IIIB–IV M1a, and stage IV M1b/c.

Results

One trial of GM-CSF, four of dacarbazine, and one of gp100 were included in the analysis. After adjusting for differences in baseline prognostic factors, median overall survival (OS) in all patient groups was longer for those receiving GM-CSF than for those receiving dacarbazine or gp100. The observed survival over time for GM-CSF was similar to the adjusted survival for dacarbazine and greater than for gp100 in all patient groups.

Conclusion

The relative treatment effect of GM-CSF, dacarbazine, and gp100 has been reliably estimated by adjusting for differences in baseline prognostic factors. Results suggest that OS with GM-CSF is at least as good as with dacarbazine and greater than with gp100. Given the role of these agents as controls in phase 3 trials of new immunotherapies and targeted agents, these results can be used to contextualize the efficacy of newer therapies.

Funding

Amgen Inc.

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Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma

Abstract

The approval of one of the first anti-vascular endothelial growth factor (VEGF) agents for the treatment of neovascular age-related macular degeneration one decade ago marked the beginning of a new era in the management of several sight-threatening retinal diseases. Since then, emerging evidence has demonstrated the utility of these therapies for the treatment of other ocular conditions characterized by elevated VEGF levels. In this article we review current perspectives on the use of anti-VEGF drugs as adjuvant therapy in the management of neovascular glaucoma (NVG). The use of anti-VEGFs for modifying wound healing in glaucoma filtration surgery (GFS) is also reviewed. Selected studies investigating the use of anti-VEGF agents or antimetabolites in GFS or the management of NVG have demonstrated that these agents can improve surgical outcomes. However, anti-VEGF agents have yet to demonstrate specific advantages over the more established agents commonly used today. Further studies are needed to evaluate the duration of action, dosing intervals, and toxicity profile of these treatments.

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Cost-Effectiveness of Different Strategies for the Prevention of Venous Thromboembolism After Total Hip Replacement in China

Abstract

Introduction

The aim of this study was to evaluate the cost-effectiveness of rivaroxaban and apixaban versus enoxaparin for the universal prophylaxis of venous thromboembolism (VTE) and associated long-term complications in Chinese patients after total hip replacement (THR).

Methods

A decision model, which included both acute VTE (represented as a decision tree) and the long-term complications of VTE (represented as a Markov model), was developed to assess the economic outcomes of the three prophylactic strategies for Chinese patients after THR. Transition probabilities for acute VTE were derived from two randomized controlled studies, RECORD1 and ADVANCE3, of patients after THR. The transition probabilities of long-term complications after acute VTE, utilities, and costs were derived from the published literature and local healthcare settings. One-way and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty concerning the model parameters. The quality-adjusted life years (QALYs) and direct medical costs were reported over a 5-year horizon, and incremental cost-effectiveness ratios (ICERs) were also calculated.

Results

Thromboprophylaxis with apixaban was estimated to have a higher cost (US $178.70) and more health benefits (0.0025 QALY) than thromboprophylaxis with enoxaparin over a 5-year time horizon, which resulted in an ICER of US $71,244 per QALY gained and was more than three times the GDP per capita of China in 2014 (US $22,140). Owing to the higher cost and lower generated QALYs, rivaroxaban was inferior to enoxaparin among post-THR patients. The sensitivity analyses confirmed these results.

Conclusions

The analysis found that apixaban was not cost-effective and that rivaroxaban was inferior to enoxaparin. This finding indicates that compared with enoxaparin, the use of apixaban for VTE prophylaxis after THR does not represent a good value for the cost at the acceptable threshold in China; in addition, the cost of rivaroxaban was higher with lower QALYs.

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