When Science is Not Enough: A Framework Towards More Customer-Focused Drug Development

Abstract

Introduction

The purpose of this study was to identify the key barriers to a customer-focused drug development process and develop a comprehensive framework to overcome them.

Methods

The paper draws on existing literature, both academic and practitioner, across a range of disciplines (innovation management, marketing, organizational behavior, behavioral economics, health economics, industry reports). On the basis of this extensive review, a conceptual framework is developed that offers concrete suggestions on how organizations can overcome the barriers and enable a more customer-focused development process.

Results

The barriers to collaboration are organized into three distinct categories (economic, behavioral, organizational), and within each category, a one-to-one mapping between barriers and solutions is developed.

Conclusion

The framework is specifically designed with the objective of offering actionable and practical advice to executives who face these challenges in their organizations. The paper provides a unique theoretical contribution by synthesizing findings from several academic disciplines with concrete examples from the pharmaceutical industry.

Funding

Mundipharma International Limited.

http://ift.tt/2ty7ptv

Systematic identification and characterization of miRNAs and piRNAs from porcine testes

Abstract

microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) execute important regulatory roles in testis development and spermatogenesis, while previous studies mainly focus on the expression profiles in immature and mature porcine testes, which may cause a bottleneck for further understanding their complex physiological processes in porcine testes development and spermatogenesis. Thus, we presented the expression and characterization of miRNAs and piRNAs in DS (60-day-old), DN (90-day-old), DT (120-day-old) and DF (150-day-old) pig testes. In total, 12,834,628, 13,359,726, 12,851,249 and 12,938,601 clean reads were generated from these libraries, respectively. 293 mature and 36 novel miRNAs as well as 4923 piRNA clusters were identified from pig testes, and they showed an age-dependent manner. GO enrichment analysis of miRNA target genes and piRNA generated genes showed that they participated widely in regulating the pig spermatogenesis process. In addition, 12 differentially expressed miRNAs were randomly selected to validate using qRT-PCR. Our results provided novel comprehensive expression profiles of miRNAs and piRNAs in pig testes at different stages of sexual maturity, which will promote our knowledge of them in regulating the pig testes development and spermatogenesis process.

http://ift.tt/2sbF7qM

Identification and comparative analysis of the pearl oyster Pinctada fucata hemocytes microRNAs in response to Vibrio alginolyticus infection

Abstract

MicroRNAs (miRNAs) are a class of noncoding RNA molecules that function as negative regulators of gene expression and play important roles in a wide spectrum of biological processes, including in immune response. However, the physiological regulation function of Pinctada fucata miRNAs, specially their immunomodulation has not been explored yet. Here, two small RNA libraries from hemocytes of P. fucata with or without Vibrio alginolyticus infection were constructed and sequenced using the high-throughput Illumina deep sequencing technology. In total, 11,939,992 and 11,083,327 raw reads, corresponding to 10,993,546 and 9,988,179 clean reads, were respectively obtained in the control and infected libraries. A total of 276 miRNAs, including 225 known miRNAs and 51 putative novel miRNAs, were identified by bioinformatic analysis. By using pairwise comparison between two libraries, 93 miRNAs were found to be significantly differentially expressed, with 42 and 51 miRNAs exhibiting up-regulation and down-regulation, respectively. Thereinto, some known miRNAs were considered to be immune-related. Real-time PCR were implemented for 6 miRNAs co-expressed in the control and infected samples, and agreement was confirmed between the high-throughput sequencing and real-time PCR data. After miRNA targets were predicted, GO and KEGG pathway enrichment analysis were performed, and the results indicated that ten of the differentially expressed miRNAs were involved in immune-related pathways, and might participate in the host immune response to V. alginolyticus. These results of identification and comparative analysis of miRNAs might deepen our understanding of host-pathogen interactions and immune defense mechanisms in P. fucata.

http://ift.tt/2rG9Kl0

Genome-wide analysis of the PHB gene family in Glycine max (L.) Merr.

Abstract

Prohibitins (PHBs) have one SPFH domain in common and present in species ranging from prokaryotes to eukaryotes. Although a number of researches on PHBs were performed in different plant species, a systematic analysis of the PHB family in soybean is still remains uncharacterized. In the present study, 24 putative PHB genes have been first systemically identified in soybean. According to phylogenetic analysis, these GmPHBs could be classified into four groups. Gene structures and motif patterns showed high levels of conservation within the phylogenetic subgroups. Several members of this family have undergone purifying selection based on Ka/Ks analysis on duplicated PHB genes in soybean. We performed microsynteny analysis across four legume species based on the comparisons among the specific regions contained in PHB genes. As a result, numerous microsyntenic gene pairs among soybean, Medicago, Lotus and Phaseolus were identified. Most soybean PHB genes exhibited different expression levels in various tissues and developmental stages through expression analysis using publicly available RNA-seq datasets. The 11 GmPHB genes from III_B subgroup were examined by qPCR for their expression in two soybean cultivar after infection by Phytophthora sojae. Besides three GmPHB genes previous reported by us, here other four genes also were rapidly induced by P. sojae infection in the resistant genotype, while induction was very weak in the susceptible genotype. The comprehensive overview of the PHB gene family in soybean genome will provide useful information for further functional analysis of the PHB gene family in soybean.

http://ift.tt/2sbwqNn

MDCT-based lung volumetry as a prognostic tool—miles to go before we sleep

http://ift.tt/2tcl8H7

Local rainfall trends and their perceptions by Amazonian communities

Abstract

Climate change in the Amazon region is the subject of many studies not only due to its stance as an emblematic ecosystem but also as a region where changes have been dramatic for over 30 years, mainly due to deforestation. We investigate how people settled in the Amazon perceive environmental changes by comparing these perceptions with satellite rainfall data for 12 sites representing the community diversity in the region. Perceptions are varied and agreement with physical, measured data is not always good. However, the arc of deforestation, where the downward trend of rainfall is more strongly observed, also appears as the region where the populations have the highest perception of rainfall change.

http://ift.tt/2sJ6IRz

Preparation of Activated Carbon from Sugarcane Bagasse Soot and Methylene Blue Adsorption

Abstract

Sugarcane bagasse soot is an agro-industrial residue rich in carbon that can be transformed into value-added materials, such as activated carbons. Therefore, this work aimed at producing activated carbon from sugarcane bagasse soot, using CO₂ at 800, 850, and 900 °C, and investigating its efficiency to adsorb methylene blue as model contaminant. The results showed that the surface area and pore volume increased in the obtained carbons, with high specific areas (up to 829 m²/g), and the isotherms of the N₂ adsorption describe mesoporous materials. The morphology of the prepared activated carbons showed that sugarcane bagasse soot and the activated carbons kept the fibrous structure of sugarcane bagasse, but after activation, they have cavities that resemble a honeycomb. Adsorption studies with methylene blue dye showed that the activation process resulted in adsorption capacities up to 11 times higher than sugarcane bagasse soot, which is comparable with commercial activated carbon. Dye adsorption kinetics could be described by a pseudo-second-order dependency in the studied materials, and the adsorption isotherms were better fitted by the Langmuir model. It is emphasized that cost-effective materials that are similar to commercial activated carbon were obtained.

http://ift.tt/2sCMzNi

Switching Between Reference Biologics and Biosimilars for the Treatment of Rheumatology, Gastroenterology, and Dermatology Inflammatory Conditions: Considerations for the Clinician

Abstract

Purpose of Review

Biosimilars of the reference biologic therapeutics infliximab, etanercept, adalimumab, and rituximab are entering the market. Clinical and real-world data on the effects of reference → biosimilar switching are limited. This review was carried out to assess the current body of switching data.

Recent Findings

Fifty-three switching studies were identified. Infliximab publications covered CT-P13 (25 studies), SB2 (1), infliximab NK (1), and unspecified infliximab biosimilars (2). Etanercept publications covered SB4 (2) and GP2015 (2). Adalimumab publications covered ABP 501 (2) and SB5 (1). Rituximab publications covered CT-P10 (1). Efficacy and safety data generally showed no differences between patients who switched treatments versus those who did not. No differences were seen pre- and post-switch. Immunogenicity data were presented in 19/37 (51%) studies.

Summary

Additional data from switching studies of these therapies are still required, as is continuing pharma-covigilance. Switching should remain a case-by-case clinical decision made by the physician and patient on an individual basis supported by scientific evidence.

http://ift.tt/2sCtavN

Post infarction left ventricular aneurysm—our experience

Abstract

Background

Left ventricular aneurysms (LVAs) stand as one of the serious complications of myocardial infarction and are associated with increased mortality. Considerable differences exist regarding the optimal surgical management of LVAs. In this study, we report our single center/single surgeon experience with post infarction LVAs.

Methods

This is a retrospective analysis of 25 patients, who underwent endoventricular circular patch plasty (Dor procedure) for LVAs of ischemic origin from 2009 to 2013. The demographic data was collected in addition to patients mode of presentation, New York Heart Association (NYHA) class, past medical history particularly ischemic heart disease, preoperative electrocardiography, chest X-ray, echocardiography, and coronary angiography. The postoperative functional class and the echocardiography data were also collected and analysed. All patients underwent follow-up cardiac computerized tomogram (CT) scan to calculate the sphericity index (SI).

Results

The mean age of presentation was 60.76 ± 9.57 years. Seventeen were males and eight were females. The associated comorbidities were, diabetes and hypertension. The most common presentations were, the angina and the left ventricular failure. Among the study group, two (8%) patients presented within 72 h of myocardial infarction (MI) owing to the hemodynamic instability due to ventricular septal rupture (VSR) and severe mitral regurgitation (MR), and required moderate doses of inotropes and intra-aortic balloon pump. The time of presentation in the remaining 23 (92%) patients ranged from 14 to 38 days following the MI (mean −21.36 ± 0.38 days). The preoperative mean NYHA functional class was 2.44 ± 0.71. Posterior aneurysms were predominated in our study. The mean left ventricular internal diameter in diastole (LVIDd), the left ventricular internal diameter in systole (LVIDs) and the ejection fraction (EF) were; 6.52 ± 0.40 cm, 5.24 ± 0.37 cm, and 37.44 ± 3.92% respectively. The mean end-diastolic volume (EDV) was 167 ± 28.38 ml and the mean end-systolic volume (ESV) was 87.84 ± 12.90 ml. The mean pulmonary artery systolic pressure (PASP) was 51.48 ± 5.72 mmHg. The mean tricuspid annular plane systolic excursion (TAPSE) was 11.52 ± 0.71 mm. Six cases showed mural thrombus, four had MR, and one had an associated ventricular septal defect (VSD). The coronary angiogram showed multivessel coronary artery disease in majority of patients. The hospital mortality was 8% (two cases). The mean follow-up period was 2.4 ± 0.91 years. The postoperative mean NYHA class was 1.76 ± 0.43. There was a significant improvement in the left ventricular function. There was a significant improvement in MR following concomitant Dor procedure and mitral valve interventions. Patients with mitral interventions had trivial to mild MR and were asymptomatic. The mean SI was 0.5 ± 0.11.

Conclusion

Dor procedure is reproducible and simple to perform, restores the natural left ventricular geometry and is associated with significant improvement in the left ventricular performance and hemodynamics, which translates into improved functional class of the patient.

http://ift.tt/2tce7WS

Multi detector computed tomography based volumetric assessment of lung parenchymal injury in isolated blunt thoracic trauma patients acts as predictor of clinical outcome: a prospective observational study

Abstract

Introduction

The role of multi detector computed tomography (MDCT) in thoracic trauma is continuously evolving with identification of occult injuries and better characterization of potentially life threatening injuries. Keeping this in mind, we have done a prospective study for volumetric analysis of lung parenchymal injury in isolated blunt thoracic trauma patients, explored its prognostic implications, and evaluated its correlation with clinical outcome of patient.

Methods

Prospective evaluation of patients with isolated blunt thoracic trauma coming from the trauma center was done with MDCT. Patients with poly trauma, pregnancy, penetrating thoracic trauma, pre-existing pulmonary or renal disease, and any other significant co-morbid medical or surgical illness and requirement of urgent thoracotomy (surgery) were excluded from the study. Data was collected regarding patient demographics, mechanism of injury, involvement of thoracic viscera and thoracic wall, uninvolved mean lung volume and overall prognosis in relation to eventless recovery, need for mechanical ventilation, and mortality which were taken as primary outcome parameters. Mean lung volumes of both lungs were compared in between groups of eventless recovery, need of mechanical ventilation and mortality with p value <0.05 considered to be significant.

Results

Sixty-two patients age range from 18 to 60 years, of blunt chest trauma were evaluated with MDCT after initial radiographs and the results were tabulated. The commonest mode of injury was motor vehicle accidents (74%). Overall mortality of thorax trauma-related death was 8% (five cases). Incidence of lung contusion was 90%, hemopneumothorax was 45%, rib fracture was 93%, cardiac injury was 1.6%, and diaphragmatic injury was 1.6%. Significant association (p < 0.05) of mortality and requirement for ventilation was found with remaining uninvolved mean volume of both lungs 1401.60±744.71 and 1676.00±360.31 cc respectively on volumetric analysis by MDCT 64-slice scan. Remaining uninvolved mean volume of both lungs 2645.00±609.57 cc on volumetric analysis by MDCT 64-slice scan was significantly associated (p < 0.05) with eventless recovery of patients.

Conclusion

Multi detector computed tomogram based calculation of uninvolved mean lung volumes following blunt thoracic trauma can help in determination of clinical outcome and requirement for mechanical ventilation. This study re-emphasizes the role of MDCT in thoracic trauma with providing help in better injury characterization and early assessment of prognostic implications. This information can act as guide to identify patients at high risk of complications, initiate early and aggressive kinetic chest therapy and explaining prognosis to patients or attendants. This study may also help in opening up other avenues for further research in thoracic trauma.

http://ift.tt/2sCBX0W

Switching Between Reference Biologics and Biosimilars for the Treatment of Rheumatology, Gastroenterology, and Dermatology Inflammatory Conditions: Considerations for the Clinician

Abstract

Purpose of Review

Biosimilars of the reference biologic therapeutics infliximab, etanercept, adalimumab, and rituximab are entering the market. Clinical and real-world data on the effects of reference → biosimilar switching are limited. This review was carried out to assess the current body of switching data.

Recent Findings

Fifty-three switching studies were identified. Infliximab publications covered CT-P13 (25 studies), SB2 (1), infliximab NK (1), and unspecified infliximab biosimilars (2). Etanercept publications covered SB4 (2) and GP2015 (2). Adalimumab publications covered ABP 501 (2) and SB5 (1). Rituximab publications covered CT-P10 (1). Efficacy and safety data generally showed no differences between patients who switched treatments versus those who did not. No differences were seen pre- and post-switch. Immunogenicity data were presented in 19/37 (51%) studies.

Summary

Additional data from switching studies of these therapies are still required, as is continuing pharma-covigilance. Switching should remain a case-by-case clinical decision made by the physician and patient on an individual basis supported by scientific evidence.

http://ift.tt/2sCtavN

Antibiotic susceptibility profiles among Campylobacter isolates obtained from international travelers between 2007 and 2014

Abstract

Campylobacter infection is a common cause of diarrhea among international travelers. We studied antibiotic resistance patterns among Campylobacter isolates obtained from international travelers according to travel destination. Three collections of isolates obtained from international travelers between 2007 and 2014 (Institute of Tropical Medicine, the "Laboratoire Hospitalier Universitaire de Bruxelles "and the Belgian National Reference Centre for Campylobacter) were used. Isolates were tested for minimal inhibitory concentration (MIC) values (E-test macromethod) for fluoroquinolones, macrolides, tetracyclines, amoxicillin–clavulanic acid, and meropenem. Single isolates from 261 travelers were available; median (IQR) age was 25.4 (4–42) years, 85.8% were symptomatic (information for 224 patients available). Overall resistance to ciprofloxacin was 60.9%, ranging from 50.8% in Africa to 75.0% in Asia. Resistance to erythromycin was 4.6%, with the highest rate observed for Southern Asia (15.2%, seven isolates, six of them recovered from patients returning from India). A total of 126 isolates (48.3%) were resistant to tetracycline. No resistance to amoxicillin–clavulanic acid or meropenem was detected. Ciprofloxacin resistance tended to increase over time (53.9% in 2007 versus 72.2% in 2014), erythromycin resistance remained stable (median annual resistance 4.2%). Most (86.2%) ciprofloxacin-resistant isolates had MIC values ≥32 mg/l, and all erythromycin-resistant isolates had MIC values ≥256 mg/l. Co-resistance to ciprofloxacin and erythromycin was observed in 11 (4.2%) isolates, seven of which came from Southern Asia. Among all regions of travel, more than half of Campylobacter isolates were resistant to ciprofloxacin. Overall resistance to erythromycin was below 5% but reached 15.2% in Southern Asia.

http://ift.tt/2skt6xV

Enhanced visualization of the retinal vasculature using depth information in OCT

Abstract

Retinal vessel tree extraction is a crucial step for analyzing the microcirculation, a frequently needed process in the study of relevant diseases. To date, this has normally been done by using 2D image capture paradigms, offering a restricted visualization of the real layout of the retinal vasculature. In this work, we propose a new approach that automatically segments and reconstructs the 3D retinal vessel tree by combining near-infrared reflectance retinography information with Optical Coherence Tomography (OCT) sections. Our proposal identifies the vessels, estimates their calibers, and obtains the depth at all the positions of the entire vessel tree, thereby enabling the reconstruction of the 3D layout of the complete arteriovenous tree for subsequent analysis. The method was tested using 991 OCT images combined with their corresponding near-infrared reflectance retinography. The different stages of the methodology were validated using the opinion of an expert as a reference. The tests offered accurate results, showing coherent reconstructions of the 3D vasculature that can be analyzed in the diagnosis of relevant diseases affecting the retinal microcirculation, such as hypertension or diabetes, among others.

http://ift.tt/2sb0FnP

Tooth brushing motion patterns with manual and powered toothbrushes—a randomised video observation study

Abstract

Introduction

Systematic reviews have shown that powered toothbrushes (PTs) are more effective than manual toothbrushes (MTs), but with only minor effect sizes. Whether PTs are used adequately, however, has not been investigated so far. The aim of the present study was therefore to analyse motion habits with PT in comparison to MT toothbrushes by video observation.

Materials and methods

One hundred subjects were enrolled in this observational trial and brushed their teeth in randomised order with a MT and PT while being video-filmed, resulting in 95 analysable sets of recordings. Parameters of interest were brushing duration (s; median (min;max)), type of brushing strokes, area of brushing, changes between areas (n; median (min;max)) and brushing sequence.

Results

Brushing duration was 145 s (60;354) and 135 s (48;271) for PT and MT, respectively (p ≤ 0.001). Subjects brushed vestibular surfaces completely, but reached oral surfaces to a much lesser extent, regardless of the toothbrush type. With both toothbrushes, subjects moved frequently between areas (MT 35 (14;79); PT 33 (14;85); n.s.) and brushed predominantly with circling and horizontal strokes; with the PT, 50.5% of the subjects spent only <10% of the brushing duration with passive brushing (positioning the brush head on the teeth with ≤2 movements/s).

Conclusions

Intra-individual motion patterns were similar with both MT and PT, and most subjects persisted in their habitual motion patterns regardless of the toothbrush type.

Clinical relevance

The use of PT and MT may need intensive training and supervision from oral hygiene educators in order to help subjects taking full advantage from these devices.

http://ift.tt/2roO0e0

A Singular Role of I K1 Promoting the Development of Cardiac Automaticity during Cardiomyocyte Differentiation by I K1 – Induced Activation of Pacemaker Current

Abstract

The inward rectifier potassium current (I_K1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that I_K1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (I_f) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of I_K1 to activate I_f and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only I_K1 and I_f, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i.e. HEK293T cells and undifferentiated mouse embryonic stem cells [ESCs]). We termed this effect I_K1-induced I_f activation. Consistent with previous findings, our electrophysiological recordings observed that around 50% of mouse (m) and human (h) ESC-differentiated CMs could spontaneously fire action potentials (APs). We found that spontaneously-firing ESC-CMs displayed more hyperpolarized maximum diastolic potential and more outward I_K1 current than quiescent-yet-excitable m/hESC-CMs. Rather than classical depolarization pacing, quiescent mESC-CMs were able to fire APs spontaneously with an electrode-injected small outward-current that hyperpolarizes MP. The automaticity to spontaneously fire APs was also promoted in quiescent hESC-CMs by an I_K1-specific agonist zacopride. In addition, we found that the number of spontaneously-firing m/hESC-CMs was significantly decreased when I_f was acutely upregulated by Ad-CGI-HCN infection. Our study reveals a novel role of I_K1 promoting the development of cardiac automaticity in m/hESC-CMs through a mechanism of I_K1-induced I_f activation and demonstrates a synergistic interaction between I_K1 and I_f that regulates cardiac automaticity.

http://ift.tt/2rA42Ww

Goldenhar syndrome: current perspectives

Abstract

Background

Progress in medical branches that has taken place since the first child with Goldenhare syndrome (GS) had been described in 1952 by Maurice Goldenhar, facilitated better understanding of this congenital defect. It also gave new perspectives and the opportunity to achieve satisfactory treatment results, mainly due to development of surgical techniques.

Data sources

Based on the literature and own experience, we discussed the phenotype of presentation of GS, ethiopathogenesis, genetic counselling and treatment with particular emphasis on surgery correction of hemifacial microsomia.

Results

The spectrum of GS abnormalities ranges from mild to severe ones and include patients with barely noticeable facial asymmetry to very pronounced facial defect with more or less severe abnormalities of internal organs and/ or skeleton. It is characterized most commonly by impaired development of eyes, ears, lips, tongue, palate, mandible, maxilla, zygomatic and orbital structures and deformations of the teeth structures. Ethiopathogenesis is multifactorial and dependent on genetic and environmental factors but there are still many unknowns about the syndrome which should be revealed.

Conclusions

Patients with GS due to a large variety of abnormalities and different severity of symptoms pose a challenge for clinicians. All of this necessitate an individual approach to each single patient and involvement a team of specialists in treatment planning. It is a complex, long-lasting, multidisciplinary process and should be divided into stages, according to patient's age, as well as the extent and severity of observed abnormalities. Neonatologists and pediatricians are involved in care of these patients from the onset.

http://ift.tt/2sBLpS0

Characteristics and clinical role of bronchoscopy in diagnosis of childhood endobronchial tuberculosis

Abstract

Background

Endobronchial tuberculosis (EBTB) is the most frequent complication of primary pulmonary tuberculosis (PTB) in children. The aim of the study was to analyze characteristics and clinical role of bronchoscopy in diagnosis of childhood EBTB.

Methods

A retrospective, descriptive study was undertaken in 157 children with EBTB undergone fl exible bronchoscopy (FB) between January 2006 and June 2014.

Results

The median age of the enrolled patients was 3.4 years, with 73.2% of patients under five years old. The most common subtype was tumorous type (145/157, 92.4%). If only involved bronchus were considered, the common affected sites were right middle lobe bronchus (49/228, 21.5%), left upper lobe bronchus (41/228, 18.0%), right upper lobe bronchus (41/228, 18.0%), right main bronchus (35/228, 15.4%), respectively. Children younger than five years old were at higher risk to have multiple endobronchial lesions (P=0.044), with an odds ratio of 2.313 (95% confidence interval: 1.009-5.299). Before the bronchoscopy, only 16 (10.2%) patients were highly suspected of EBTB, while the others were diagnosed as PTB without EBTB (69.4%), or misdiagnosed as pneumonia or foreign body aspiration (20.4%) on admission.

Conclusions

The patients under five years old are at high risk to progress to EBTB and have multiple endobronchial lesions. The most frequent subtype of EBTB in children is tumorous type. The lesions are seen in the right bronchial system more frequently. FB should be performed to detect the endobronchial lesions in suspected patients as soon as possible.

http://ift.tt/2tbqpPn

Novel Attempt Using Bioabsorbable Reinforcement Material on the Crotch of a Side-to-Side Anastomosis

Abstract

Side-to-side anastomoses are more frequently performed. This method is relatively simple, timesaving, and can be applied in a variety of settings where anastomoses are necessary. Despite some advances, stapled anastomoses have inherent weak points. With any type of side-to-side anastomosis, the crotch is formed at the tip portion of the stapler; this crotch area is the weak point. We describe a novel surgical technique for side-to-side anastomosis using a reinforced crotch. After distal gastrectomy, a small incision was made on the greater curvature of the remnant stomach and the posterior side of the duodenum. We use a 60-mm linear stapler, namely, the Endo GIA^TM Reinforce Reload (Covidien Japan). Therefore, the stapler length inserted into the stomach and duodenum is 45 mm. The reinforce reloads have a preloaded reinforcement material on the both anvil and cartridge. One or two supporting sutures were added to the center of the common enterotomy. Pulling up on the two pieces of Neoveil^® and the sutures, the common enterotomy was closed with a linear stapler. Delta-shaped anastomosis is then accomplished. We also use a reinforced reload in a side-to-side anastomosis between two segments of jejunum. Neoveil^® is thin and soft; we found no problem using either a hand thrown suture or stapler to close the entry hole. In fact, we found that the excess Neoveil^® is very useful. Neoveil^® can be a substitute for the sutures. Only one or two hand thrown sutures were then necessary to close the common enterotomy. And we do not add the reinforce suture of the crotch at all. This novel method is a simple and useful method and can be used in side-to-side anastomoses in a variety of settings.

http://ift.tt/2rospSL

Fast calibration of electromagnetically tracked oblique-viewing rigid endoscopes

Abstract

Purpose

The oblique-viewing (i.e., angled) rigid endoscope is a commonly used tool in conventional endoscopic surgeries. The relative rotation between its two moveable parts, the telescope and the camera head, creates a rotation offset between the actual and the projection of an object in the camera image. A calibration method tailored to compensate such offset is needed.

Methods

We developed a fast calibration method for oblique-viewing rigid endoscopes suitable for clinical use. In contrast to prior approaches based on optical tracking, we used electromagnetic (EM) tracking as the external tracking hardware to improve compactness and practicality. Two EM sensors were mounted on the telescope and the camera head, respectively, with considerations to minimize EM tracking errors. Single-image calibration was incorporated into the method, and a sterilizable plate, laser-marked with the calibration pattern, was also developed. Furthermore, we proposed a general algorithm to estimate the rotation center in the camera image. Formulas for updating the camera matrix in terms of clockwise and counterclockwise rotations were also developed.

Results

The proposed calibration method was validated using a conventional \(30{^{\circ }}\) , 5-mm laparoscope. Freehand calibrations were performed using the proposed method, and the calibration time averaged 2 min and 8 s. The calibration accuracy was evaluated in a simulated clinical setting with several surgical tools present in the magnetic field of EM tracking. The root-mean-square re-projection error averaged 4.9 pixel (range 2.4–8.5 pixel, with image resolution of \(1280 \times 720)\) for rotation angles ranged from \(-40.3{^{\circ }}\) to \(174.7{^{\circ }}\) .

Conclusions

We developed a method for fast and accurate calibration of oblique-viewing rigid endoscopes. The method was also designed to be performed in the operating room and will therefore support clinical translation of many emerging endoscopic computer-assisted surgical systems.

http://ift.tt/2twl8kM

Diffusion tensor imaging can predict surgical outcomes of patients with cervical compression myelopathy

Abstract

Purpose

The aim of this study was to assess the potential role of diffusion tensor imaging (DTI) as a predictor of surgical outcomes in patients with cervical compressive myelopathy (CCM). Surgical decompression is often recommended for symptomatic CCM. It is important to know the prognosis of surgical outcomes and to recommend appropriate timing for surgery.

Methods

We enrolled 26 patients with CCM who underwent surgery. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was evaluated before and 6 months after surgery. Surgical outcomes were regarded as good if there was a change in JOA score of three points or more, or the recovery rate of JOA score was 50% or more. The patients were examined using a 3.0 T magnetic resonance system before surgery. Measured diffusion parameters were fractional anisotropy (FA) and mean diffusivity (MD). The correlations between DTI parameters and surgical outcomes were analyzed.

Results

Both change and recovery rate of JOA score moderately correlated with FA. Furthermore, the area under the receiver–operator characteristic curve based on FA for prognostic precision of surgical outcomes indicates that FA is a good predictive factor. The cut-off values of FA for predicting good surgical outcomes evaluated by change and recovery rate of JOA score were 0.65 and 0.57, respectively. Neither change nor recovery rate of JOA score correlated with MD.

Conclusions

FA in spinal cord DTI can moderately predict surgical outcomes. DTI can serve as a supplementary tool for decision-making to guide surgical intervention in patients with CCM.

http://ift.tt/2tw70Ia

New Approaches to Gastroesophageal Reflux Disease

Abstract

Background

Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disorder of the esophagus. It is a chronic, progressive disorder that presents most typically with heartburn and regurgitation and atypically with chest pain, dysphagia, chronic cough, globus, or sore throat. The mainstay for diagnosis and characterization of the disorder is esophagoduodenoscopy (EGD), high-resolution esophageal manometry, and symptom-associated ambulatory esophageal pH impedance monitoring. Additional studies that can be useful in certain clinical presentations include gastric scintigraphy and oral contrast upper gastrointestinal radiographic series.

Discussion

Refractory GERD can be surgically managed with various techniques. In obese individuals, laparoscopic Roux-en-Y gastric bypass should be considered due to significant symptom improvement and lower incidence of recurrent symptoms with weight loss. Otherwise, laparoscopic Nissen fundoplication is the preferred surgical technique for treatment of this disease with concomitant hiatal hernia repair when present for either procedure. The short-term risks associated with these procedures include esophageal or gastric injury, pneumothorax, wound infection, and dysphagia. Emerging techniques for treatment of this disease include the Linx Reflux Management System, EndoStim LES Stimulation System, Esophyx® and MUSE™ endoscopic fundoplication devices, and the Stretta endoscopic ablation system. Outcomes after surgical management of refractory GERD are highly dependent on adherence to strict surgical indications and appropriate patient-specific procedure selection.

http://ift.tt/2roCn6X

Molecular and morphological evidence for nine species in North American Australapatemon (Sudarikov, 1959): a phylogeny expansion with description of the zygocercous Australapatemon mclaughlini n. sp.

Abstract

Zygocercous (aggregating) cercarial larvae were recently discovered emerging from a physid snail during a molecular survey of cercariae from molluscs in lakes in central Alberta, Canada. This manuscript delves into the characterization of these cercariae through morphological and molecular techniques and provides the first genetic information for a zygocercous larval trematode. Analyses of cytochrome c oxidase I of mitochondrial DNA and two partial regions of nuclear ribosomal DNA sequences revealed the zygocercous cercariae to belong to the genus Australapatemon Sudarikov, 1959. Further analyses of sequences of Australapatemon burti (Miller, 1923), from cercariae and adults collected from across North America, indicate a complex of nine genetically-distinct lineages within this species, a surprising level of diversity. The zygocercous cercariae, along with adult worms collected from ducks in Manitoba, Canada, and from Mexico, represent one of these lineages, and are herein described as Australapatemon mclaughlini n. sp. Seven lineages cannot yet be identified, but one is tentatively identified as Australapatemon burti.

http://ift.tt/2sH8OBg

Predicting EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) Utilities from Older People’s Quality of Life Brief Questionnaire (OPQoL-Brief) Scores

Abstract

Background and Objective

Economic evaluation of healthcare treatment and services targeted at older people requires measurement of utility-based quality-of-life outcomes but it is not always possible to collect such outcome data. It may, however, be possible to estimate these outcomes using non-utility measures of quality of life where the latter have been collected. The objective of this study was to develop a regression-based algorithm to map a non-utility-based outcome, the Older People's Quality of Life brief questionnaire (OPQoL-brief), onto a utility-based outcome, the EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L).

Methods

The estimation sample comprised 330 community-based Australian older people (>65 years), while the validation sample consisted of 293 older people from a separate study. Six regression techniques were employed to estimate utilities from OPQoL-brief. The predictive accuracy of 54 regression models (six regression techniques × nine model specifications) was assessed using six criteria: mean absolute error (MAE), root mean squared error (RMSE), correlation, distribution of predicted utilities, distribution of residuals, and proportion of predictions with absolute errors <0.05.

Results

The 54 regression models predicted EQ-5D-5L utilities that performed differently when assessed by the six criteria. However, best results were obtained from an ordinary least squares (OLS) model where all 13 OPQoL-brief items were included as continuous variables (OLS 4). RMSE and MAE estimates for this model (0.2201 and 0.1638, respectively) were within the range of published estimates.

Conclusions

It is possible to predict valid utilities from OPQoL-brief using regression methods. We recommend OLS model (4) for this exercise.

http://ift.tt/2sjEqKG

Immobilization of Saccharomyces cerevisiae Cells on Luffa cylindrica : a Study of a Novel Material for the Adsorption of Textile Dye

Abstract

The textile industry is responsible for the disposal of a large volume of effluents containing synthetic dyes, which are considered to be highly toxic compounds for both human health and the environment. The aim of the present study was to test potential use of a renewable, low-cost product—Luffa cylindrica in disk and powder form—as adsorbent material for the treatment of textile effluents containing dyes. Saccharomyces cerevisiae cells were also immobilized on L. cylindrica to increase the adsorbent capacity. Batch experiments were conducted for the evaluation of the removal of the azo dye Direct Red 23. The Langmuir, Freundlich, and Temkin isotherms were used for a better interpretation of the data. The results showed that adsorption is more efficient at acidic pH and all adsorbent materials best fit the Langmuir model, indicating the formation of a monolayer. The isotherm results also demonstrated that the materials immobilized with the yeast had a greater sorption rate, but the cell-free L. cylindrica powder had a higher adsorbate/adsorbent interaction. The comparison with a spectrophotometrically defined standard revealed that the powder without and with yeast cells was able to achieve an acceptable removal rate of the dye from the solution. Moreover, the difference in adsorption between the powder without and with yeast cells was very small. Thus, the application of the cell-free L. cylindrica powder is economically more feasible. The findings demonstrate the potential use of L. cylindrica powder as an adsorbent for the treatment of effluents containing textile dyes.

http://ift.tt/2sxTGFY

Multimodal Medical Imaging Fusion for Patient Specific Musculoskeletal Modeling of the Lumbar Spine System in Functional Posture

Abstract

Current musculoskeletal modeling does not take the functionally initial standing posture of the lumbar spine system into consideration. This may lead to inaccurate simulation outcomes for clinical decision support. This present study aimed to develop a fusion process from multimodal medical images for developing, simulating, and assessing patient specific musculoskeletal model of the lumbar spine system in functional posture. Computed tomography (CT) and X-rays were acquired on a patient. A 3D/2D matching procedure was developed using feature-based approach to transform CT-based 3D geometries into standing posture. Then, a musculoskeletal model was developed including 7 segments, 18-DOF (degrees of freedom) and 126 muscle fascicles. Model evaluation was performed using X-ray data and curvature metric. Muscle force deviations were quantified for the comparison between image-based model and generic-scaled model as well as for the sensitivity of psoas major attachment point definition. Curvatures of the simulation outcomes fall within the range of X-ray data for extension posture. Difference was noted for flexed posture. The use of generic model leads to a deviation of 66% of the muscle forces according to the image-based model. A maximal relative deviation of 4% of the estimated psoas major fascicle force was found for the analysis of the sensitivity of muscle attachment point. This study proposed a useful data fusion process from multimodal medical images to create patient specific lumbar spine model in correct initial posture leading to perform accurate dynamic simulations. Moreover, this study suggested that image-based model needs to be developed for clinical decision making related to spinal disorders.

http://ift.tt/2rElwfL

Investigating the Suitability of Carbon Nanotube Reinforced Polymer in Transcatheter Valve Applications

Abstract

The current delivery size of transcatheter aortic valves, limited by the thickness of their pericardial leaflets, correlates with a high prevalence of major vascular complications. Polyurethane valves can be developed to a fraction of the thickness of pericardial valves through the addition of carbon nanotubes to reinforce their leaflets. This study investigates the suitability of a novel carbon nanotube reinforced leaflet to reduce the delivery profile of transcatheter aortic valves. Carbon nanotube polyurethane composites were developed with thicknesses of 50 μm and their mechanical properties were determined in relation to various environmental effects. The composites demonstrated improvements to the material stiffness, particularly at increasing strain rates compared to the neat polymer. However, increasing nanotube concentrations significantly decreased the fatigue life of the composites. Key findings highlighted a potential for carbon nanotube reinforcement in valve replacement which experience very high strain rates during the cardiac cycle. Further testing is needed to achieve a strong nanotube–matrix interface which will prolong the cyclic fatigue life and further strengthen tensile properties. Testing on the durability and haemocompatibility of these composite heart valves are ongoing.

http://ift.tt/2s9nU1v

Assessment of typical SpA lesions on MRI of the spine: do local readers and central readers agree in the DESIR-cohort at baseline?

Abstract

Comparing local reading (LocR) with central reading (CentR) of typical spondyloarhritis lesions including bone marrow edema (BME) and structural lesions on magnetic resonance imaging of the spine (MRI-spine), in patients with inflammatory back pain (IBP; ≥3 months, <3 years). Baseline data of 667 patients, age 18–50 years, from the Devenir des Spondylarthopathies Indifferenciees Recentes (DESIR)-cohort were used. Two trained central readers scored anterior and posterior corner BME, fatty lesions, erosions and syndesmophytes on MRI-spine. Presences of lesions, based on average scores, were used for CentR. A local radiologist and/or rheumatologist scored MRI-spine on presence/doubt/absence of 'inflammation' and 'structural lesions'. Agreement between central readers and readings was calculated (Cohen's kappa: κ). Agreement between central readers was moderate (BME κ = 0.55, fatty lesions κ = 0.50) to slight (erosions κ = 0.12, syndesmophytes κ = 0.19). Agreement between LocR and CentR was κ = 0.32 (BME) and κ = 0.13 (structural lesions). In 78/160 patients (48.8%) LocR were in doubt while CentR scored BME lesions, for structural lesions this was 17.8% (28/157 patients). Agreement between 2 central readers for scoring spondyloarhritis-like lesions on MRI-spine was moderate but better compared to LocR and CentR agreement. LocR often doubt about the presence of MRI-spine lesions while central trained readers score lesions.

http://ift.tt/2qSLgrJ

Improving skills in pediatric rheumatology in Colombia: a combined educational strategy supported by ILAR

Abstract

Colombia is a densely populated country with a small number of pediatric rheumatology specialists, including 14 specialists for a population of 1,927,000 children in 2014. The objective of the study was to improve the skills required for early identification, timely referral, and management of musculoskeletal diseases, especially juvenile idiopathic arthritis (JIA), in a group of pediatricians and pediatric residents in a remote region of Colombia. Supported by grant programs developed by the International League of Associations for Rheumatology (ILAR), a combined educational strategy (blended learning) was implemented based on two classroom educational activities and four online modules. The students' acquired knowledge and perception of the strategy were evaluated. Scores were reported as median values and interquartile ranges (IQR), and the differences between scores were estimated using the Wilcoxon test for equal medians. Forty-one students were enrolled, 37 completed the online modules, and 33 attended the final in-person session. The results of the written tests demonstrated an improved ability to solve clinical problems compared with the results of the tests before the course (the median initial vs. final test scores 3 (IQR = 1) vs. 5 (IQR = 0), p = 0.000). The students reported high levels of satisfaction related to compliance with the proposed objectives, the relevance of the contents and activities performed, and the impact on everyday practice. These types of strategies are useful as tools for continuing medical education. However, the results pertain only to short-term learning. It is necessary to evaluate their impact on "lifelong learning."

http://ift.tt/2sji9MQ

Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia

Abstract

The prevalence of HLA-B27 in the general population and in axial spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this study was to evaluate the prevalence of HLA-B27 in these two populations and describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in the general population was evaluated using cord blood and healthy organ transplant donor databases. Data from patients with axSpA were collected retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed based on a positive X-ray, as evaluated by two independent readers. Patients with inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males. HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non-radiographic axSpA (nr-axSpA), respectively. The median and interquartile range (IQR) ages at symptom onset and disease diagnosis were 26 (20–33) and 30 (25–38) years, respectively. The median delay to diagnosis was 3 (1–6) years. There was a negative correlation between the time of onset of symptoms and the delay in diagnosis (r = −0.587). Male gender and HLA-B27 positivity were associated with a younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in 82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ transplant donor databases, respectively. The prevalence of HLA-B27 is lower in the general Saudi population and in axSpA patients compared to Caucasians, thus, limiting its utility as a diagnostic criterion.

http://ift.tt/2sAsKpR

Minimal disease activity in patients with psoriatic arthritis treated with ustekinumab: results from a 24-week real-world study

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease affecting around 40% of psoriasis patients. Minimal disease activity (MDA) criteria have been proposed to identify a state of low disease activity, one of the principal goals of treatment for psoriatic disease. This study investigated treatment with ustekinumab (UST) in the context of a real-world setting. Thirty-four PsA patients who had failure or inadequate response to conventional synthetic disease-modifying antirheumatic drugs or to anti-tumour necrosis factor alpha were enrolled. Demographic and clinical features, MDA criteria, and the impact of psoriatic skin manifestations on patients' quality of life (QoL) using the dermatology life quality index (DLQI) questionnaire were evaluated at baseline and after 24-week treatment. Adverse events were recorded. At week 24, 70.5% of patients (n = 24) achieved MDA. A sub-analysis of dermatological indices of the MDA criteria showed that the psoriasis area severity index score was significantly improved and body surface area was significantly decreased at 24 weeks compared with that at baseline (both p < 0.001). For the rheumatologic indexes, tender joint count, swollen joint count, and tender entheseal points were all significantly improved at 24 weeks of therapy (all p < 0.01 vs. baseline). Mean DLQI value decreased approximately fourfold, and there were no safety concerns. The achievement of MDA as well as the significant improvement in DLQI and lack of adverse events in the context of a real-life setting shown here confirms the efficacy and safety of UST in PsA.

http://ift.tt/2rVxzcI

Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey

Abstract

Leflunomide is indicated for the treatment of adults with rheumatoid arthritis, yet is underutilized. Given the cost of biologic therapy, understanding real-life effectiveness, safety, and sustainability of leflunomide, particularly in patients who have failed methotrexate, would be of value. The primary objective was to assess the proportion of patients achieving clinically meaningful benefit following an adequate trial of leflunomide. A retrospective analysis of a cohort supplemented with patient self-reported data using a standardized questionnaire. Data were analyzed using descriptive statistics, with a database multivariate logistic regression analysis to determine predictors of leflunomide response. Of the cohort available (N = 2591), 1671 patients with confirmed leflunomide use were included in the retrospective analysis, of whom 249 were incident users. Low disease activity (DAS-28 < 3.2) was achieved or maintained by 20% of incident users, with 19% achieving a clinical response (DAS-28 decrease ≥1.2) at 3 months. Adverse effects (AE) were reported by 29% of incident users and after 1 year, 45% remained on leflunomide. Achievement of "minimal or no joint symptoms" was reported by 34% in the 661 analyzable survey responses (39% response rate). AE were reported by 55%, with nuisance (hair loss, nausea, stomach pain) AE and diarrhea being most common. Leflunomide was discontinued by 67% of responders within 1 year. An important proportion of patients, the majority of whom had previously failed methotrexate, achieved disease response with leflunomide with a low risk of serious adverse effects, suggesting that a trial of leflunomide may be a reasonable and cost-effective strategy prior to biologic therapy.

http://ift.tt/2qoEI0Z

Clinical patterns and characteristics of ankylosing spondylitis in China

Abstract

The study aimed to determine whether unique clinical patterns of AS may exist in China, specifically to explore the different clinical manifestations caused by gender, HLA-B27 status, and age at disease onset. The multicenter cross-sectional survey was conducted and 1251 patients were enrolled across China, representing a broad spectrum of Chinese AS patients. The mean age at onset and diagnosis were 29.2 (11.4) and 33.5 (12.6) years, respectively. The male/female ratio was 2.7:1. Acute anterior uveitis (AAU) was experienced in 10.3% of AS patients and 9.1% patients had juvenile-onset AS (JoAS). Men were significantly younger at onset and diagnosis and showed a higher frequency of HLA-B27 positivity, JoAS, and AAU than women. HLA-B27-positive patients had a younger age of onset than HLA-B27-negative patients. HLA-B27-positive patients were nearly three times as likely to develop AAU than negative patients (P = 0.04). JoAS patients had a family history of AS more often than adult-onset AS (AoAS) patients, and 4.9% of JoAS patients underwent surgical treatments, a rate more than six times that of AoAS patients (P = 0.01). Men had higher levels of C-reactive protein than women, as did HLA-B27 positives compared to negative patients, and JoAS compared to AoAS (all P < 0.05). The clinical patterns of our AS patients were similar to those in other studies in non-Chinese cohort: (1) the age at onset was 29.2 (11.4) years, which was older than found in other studies; (2) men were more likely be HLA-B27 carriers than women; and (3) AAU was less common in Chinese patients.

http://ift.tt/2qtqNWR

Presidents’ Day reflections. Why Donald Trump could not be a rheumatologist

http://ift.tt/2puGjBu

Response to “Vaccine-related serious adverse events might have been under-recognized in the pivotal HPV vaccine randomized trial”

http://ift.tt/2tarK8Y

Erratum to: Predictors of poor sleep quality in patients with systemic lupus erythematosus

http://ift.tt/2pWW9ZV

Fibromyalgia in patients with thyroid autoimmunity: prevalence and relationship with disease activity

Abstract

Fibromyalgia (FM) is a syndrome characterised by chronic musculoskeletal pain, tenderness and other somatic symptoms. The prevalence of FM is approximately 2–7% in the general global population and is 30–40% in the population of Hashimoto thyroiditis (HT) with a structural pathology. In 2010, new classification criteria for FM were proposed, as an alternative to the American College of Rheumatology (ACR) 1990 criteria. The objectives of the present study were to identify the prevalence of FM in the HT population and evaluate the associated features by using the new diagnostic criteria. The study group included 79 consecutive patients with HT with or without FM. Recorded data included age, gender, laboratory parameters, sociodemographic features and clinical findings, presence of somatic symptoms, and disease activity indices. The prevalence of FM in patients with HT was 62%. Antithyroid peroxidase antibody (TPOAb) positivity, duration of disease, and waist circumference were significantly associated with concomitant FM (p = 0.000, p = 0.000, and p = 0.015, respectively). A strong positive correlation was noted between fibromyalgia impact questionnaire (FIQ) scores and disease duration, age, values of thyroid-stimulating hormone (TSH) and TPOAb, waist circumference and marital status. TPOAb was found to be independent of body mass index, age and TSH. Concomitant FM is a common clinical problem in HT and its recognition is important for the optimal management of the disease. The new set of diagnostic criteria for FM reinforces this situation. Consideration of the FM component in the management of HT increases the likelihood of treatment success.

http://ift.tt/2kkmtqr

Voriconazole-induced periostitis vs. hypertrophic osteoarthropathy

http://ift.tt/2nrbbX1

Prevalence and features of metabolic syndrome in childhood-onset systemic lupus erythematosus

Abstract

To estimate the prevalence and features of metabolic syndrome (MetS) in childhood-onset systemic lupus erythematosus (cSLE), we performed a cross-sectional study of 76 consecutive cSLE patients and 54 healthy controls, age and sex matched. All individuals were assessed for anthropometric and MetS features according to World Health Organization (WHO), NCEP Adult Treatment Panel III (NCEP-ATP III), and International Diabetes Federation (IDF) criteria. The cSLE patients were further assessed for clinical and laboratory manifestations, disease activity (Systemic Lupus Erythematosus Disease Activity Index), cumulative damage (Systemic Lupus International Collaborating Clinics (SLICC)), and current and cumulative drug exposures. Sixty-nine (90.8%) patients were female with mean age of 16.8 years [standard deviation (SD) ±4.0 years]. Mean disease duration was 4.8 years (SD ± 4.1). Based on the WHO MetS criteria, MetS was observed in two (2.6%) cSLE patients. We observed high prevalence of the MetS in cSLE patients according to NCEP-ATP III MetS criteria (18.4%) (p = 0.002) and according to IDF MetS criteria (17.1%) (p = 0.003). We did not observe MetS in the control group. No difference in cSLE patients <18 and ≥18 years was observed. We observed an association between the presence of MetS and SLICC scores in cSLE <18 years and cumulative corticosteroid dose adjusted by weight in cSLE ≥18 years. This study showed that MetS is frequently observed in cSLE using NCEP-ATP III MetS criteria and IDF MetS criteria. The identification of MetS is important to indicate cardiovascular morbidity and mortality in cSLE.

http://ift.tt/2oosftp

Indirect comparisons of the efficacy of biological agents in patients with active ankylosing spondylitis: a systematic review and meta-analysis

Abstract

Patients with ankylosing (AS) often do not have a satisfactory response to, or could not tolerate, non-steroidal anti-inflammatory drugs (NSAIDs). Several biologic agents are available for such patients. However, the comparative efficacy of these treatments remains unknown as head-to-head randomized controlled trials (RCTs) are not available. RCTs examining the efficacy of biologic agents in patients with AS who had inadequate response to, or could not tolerate, NSAIDs were identified. If at least two RCTs were available for a given biologic agent, the pooled odds ratio (OR) and 95% confidence interval (CI) of achieving 20% improvement according to the Ankylosing Spondylitis Assessment Study group response criteria 20 (ASAS20) across trials were calculated. The pooled OR for each biologic agent was then compared to each other using the indirect comparison technique. A total of 14 RCTs of older TNF inhibitors, two RCTs of secukinumab, one RCT of certolizumab, and one RCT of tofacitinib were identified. No significant difference in any indirect comparisons was observed with the p values ranging from 0.12 to 0.74. The likelihood of achieving the ASAS20 response in patients AS who failed or could not tolerate NSAIDs was not significantly different between older TNF inhibitors, secukinumab, certolizumab, and tofacitinib. However, the analysis is limited by the small sample size with only one RCT for certolizumab and tofacitinib.

http://ift.tt/2s8IxYw

Association of anti-triosephosphate isomerase antibodies with aseptic meningitis in patients with neuropsychiatric systemic lupus erythematosus

Abstract

Autoantibodies to triosephosphate isomerase (TPI), which is an important glycolytic enzyme in red blood cells and neuronal cells, have been reported to be associated with neuropsychiatric systemic lupus erythematosus (NPSLE) pathogenesis. However, the clinical features regarding anti-TPI antibody (anti-TPI)-positive NPSLE are not yet known. The aim of this study is to investigate the clinical features of anti-TPI-positive NPSLE patients using anti-TPI index values determined by enzyme-linked immunosorbent assay (ELISA). Thirty-one NPSLE patients treated in our department were included in this study. Serum samples were collected, and serum anti-TPI titers were measured by ELISA. The anti-TPI index values were defined as follows: (OD₄₀₅ of samples − OD₄₀₅ of negative control)/(OD₄₀₅ of positive control − OD₄₀₅ of negative control) × 100. Anti-TPI index values greater than 2 standard deviations above the mean of healthy controls were regarded as positive. The clinical features of anti-TPI-positive and anti-TPI-negative NPSLE were compared. Ten of the 31 NPSLE patients had anti-TPI positivity (32.3%). The clinical features of anti-TPI-positive NPSLE were comparable with those of anti-TPI-negative NPSLE, except for a higher frequency of aseptic meningitis (p = 0.027) and a lower frequency of acute confusional state (P = 0.026). Laboratory data in patients with anti-TPI-positive NPSLE showed significantly higher serum IgG levels. Furthermore, anti-TPI index values positively correlated with serum IgG levels. Our study indicates that serum anti-TPI increases in the presence of elevated IgG levels and can be associated with the pathogenesis of aseptic meningitis in NPSLE.

http://ift.tt/2rywNDb

Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia

Abstract

The prevalence of HLA-B27 in the general population and in axial spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this study was to evaluate the prevalence of HLA-B27 in these two populations and describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in the general population was evaluated using cord blood and healthy organ transplant donor databases. Data from patients with axSpA were collected retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed based on a positive X-ray, as evaluated by two independent readers. Patients with inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males. HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non-radiographic axSpA (nr-axSpA), respectively. The median and interquartile range (IQR) ages at symptom onset and disease diagnosis were 26 (20–33) and 30 (25–38) years, respectively. The median delay to diagnosis was 3 (1–6) years. There was a negative correlation between the time of onset of symptoms and the delay in diagnosis (r = −0.587). Male gender and HLA-B27 positivity were associated with a younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in 82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ transplant donor databases, respectively. The prevalence of HLA-B27 is lower in the general Saudi population and in axSpA patients compared to Caucasians, thus, limiting its utility as a diagnostic criterion.

http://ift.tt/2sAsKpR

Response to “Vaccine-related serious adverse events might have been under-recognized in the pivotal HPV vaccine randomized trial”

http://ift.tt/2tarK8Y

Magnetic resonance imaging in diffuse idiopathic skeletal hyperostosis: similarities to axial spondyloarthritis

Abstract

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory condition that involves calcification and ossification of the spinal ligaments and entheses. While, characteristic magnetic resonance imaging (MRI) lesions of the spine in patients with axial spondyloarthritis, another enthesitis-related disease, have been described and defined, there is a paucity of information regarding the MRI findings in DISH. The aim of this study was to describe the MRI findings of patients with DISH. We collected computed tomography studies with findings characteristic of DISH and that also had corresponding and concurrent MRI studies of the spine. For each patient, sagittal T1-weighted and STIR MRI sequences were evaluated for anterior/posterior vertebral corners of bone marrow edema (BME) and fat deposition. In total, we assessed 156 vertebral units in 10 patients that had both radiographic evidence of DISH and available MRI studies of the spine. Lesions consistent with BME corners were detected in five patients, and in three of them, three separate sites were involved, a finding that is suggestive of axial spondyloarthritis (SpA) according to the ASAS/OMERACT consensus statement. Fat deposition corners were detected in eight patients and in seven of them, several sites were involved. Spinal MRI lesions that are characteristic of axial SpA were commonly observed in a cohort of patients with DISH. This bears relevance to cases with diagnostic uncertainty and may imply overlapping pathogenetic mechanisms for new bone formation in both SpA and DISH. Further study is indicated to better characterize the similarities and differences between the MRI lesions of DISH and SpA.

http://ift.tt/2sAmOND

Failure to replace a CO 2 -absorber due to shifted metal pins: a potential source of hazard to patients

http://ift.tt/2rDQjJq

Notfälle aufgrund psychischer Störungen

Zusammenfassung

Notfälle aufgrund psychischer Störungen stellen eine häufige und interdisziplinäre Herausforderung dar. Die Diagnostik ist durch die akuten psychopathologischen Auffälligkeiten oft erschwert und die Compliance des Patienten krankheitsbedingt nicht selten eingeschränkt. Zu den psychiatrischen Notfallsyndromen gehören v. a. akute Erregungszustände, Suizidalität, delirante Syndrome, stuporöse Zustände und spezifische substanzinduzierte Syndrome. Manchmal reichen bereits ein Zuwendungs- und Gesprächsangebot aus, um den Zustand des Patienten zu bessern. Wird eine medikamentöse Intervention notwendig, gehören Benzodiazepine und Antipsychotika zu den wichtigsten psychiatrischen Notfallmedikamenten.

http://ift.tt/2rDRQPJ

Minimal barcode distance between two water mite species from Madeira Island: a cautionary tale

Abstract

In this work, we compare morphological and molecular data in their ability to distinguish between species of water mites (Acari, Prostigmata, Hydrachnidia). We have focused on the two species of the genus Lebertia inhabiting the island of Madeira. While traditional morphological traits were initially sufficient to distinguish between these two species, the molecular data were more dependable on the kind of analysis carried out. Single arbitrary genetic distance (e.g. a K2P distance below 2%) may lead to the conclusion that the specimens under study belong to the same species. Analysing the same specimens with the coalescent model has proved the evolutionary independence of both Lebertia clades in Madeira. Furthermore, multi-rate Poisson Tree Process analysis confirmed both lineages as independent species. Our results agree with previous studies warning of the dangers of rigid species delimitation based on arbitrary molecular distances. In addition, the importance of different molecular data approaches for correct species delimitation in water mites is highlighted.

http://ift.tt/2sxlxpz

Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals

Abstract

Background

Increased muscle mitochondrial mass is characteristic of elite professional endurance athletes (PAs), whereas increased blood lactate levels (lactatemia) at the same absolute submaximal exercise intensities and decreased mitochondrial oxidative capacity are characteristics of individuals with low aerobic power. In contrast to PAs, patients with metabolic syndrome (MtS) are characterized by a decreased capacity to oxidize lipids and by early transition from fat to carbohydrate oxidation (FATox/CHOox), as well as elevated blood lactate concentration [La⁻] as exercise power output (PO) increases, a condition termed 'metabolic inflexibility'.

Objective

The aim of this study was to assess metabolic flexibility across populations with different metabolic characteristics.

Methods

We used indirect calorimetry and [La⁻] measurements to study the metabolic responses to exercise in PAs, moderately active individuals (MAs), and MtS individuals.

Results

FATox was significantly higher in PAs than MAs and patients with MtS (p < 0.01), while [La⁻] was significantly lower in PAs compared with MAs and patients with MtS. FATox and [La⁻] were inversely correlated in all three groups (PA: r = −0.97, p < 0.01; MA: r = −0.98, p < 0.01; MtS: r = −0.92, p < 0.01). The correlation between FATox and [La⁻] for all data points corresponding to all populations studied was r = −0.76 (p < 0.01).

Conclusions

Blood lactate accumulation is negatively correlated with FATox and positively correlated with CHOox during exercise across populations with widely ranging metabolic capabilities. Because both lactate and fatty acids are mitochondrial substrates, we believe that measurements of [La⁻] and FATox rate during exercise provide an indirect method to assess metabolic flexibility and oxidative capacity across individuals of widely different metabolic capabilities.

http://ift.tt/2swWxyX

Ethnopharmacological uses, phytochemistry, biological activities, and biotechnological applications of Eclipta prostrata

Abstract

Eclipta prostrata belongs to a family of medicinal plants (Asteraceae) and plays a role in the treatment of several diseases, including infectious hepatitis, snake venom poisoning, gastritis, and respiratory diseases such as a cough and asthma. A number of compounds, including thiophene derivatives, steroids, triterpenes, flavonoids, polyacetylenes, polypeptides, and coumestans, have been isolated from E. prostrata. The plant functional compounds can act as reducing agent in the field of nanoparticle synthesis. The extracts of E. prostrata are widely used for green biosynthesis of various metal and metal oxide nanoparticles, nanoparticles, which showed a potential for pharmaceutical, biotechnological, and biomedical applications. Establishment of a efficient in vitro regeneration and genetic transformation method of E. prostrata is a vital prerequisite for application of biotechnology in order to improve secondary metabolite yields. The present mini-review discusses its pharmacological profile, chemical constituents, biotechnological, and ethnomedical uses, mainly focusing on antimyotoxic, antihemorrhagic, antiproliferative, antioxidant, antitumor, antihyperglycemic, antidementia, antimicrobial, antihyperlipidemic, antivenom, anti-HIV, and larvicidal activities, so that the pharmaceutical potential of the plant can be better evaluated. The mini review, providing up-to-date phytochemical and other information on E. prostrata, will serve a reference for further studies.

http://ift.tt/2sidbzX

Carbon and hydrogen isotope fractionation during aerobic biodegradation of quinoline and 3-methylquinoline

Abstract

Compound-specific isotope analysis has been used extensively to investigate the biodegradation of various organic pollutants. To date, little isotope fractionation information is available for the biodegradation of quinolinic compounds. In this study, we report on the carbon and hydrogen isotope fractionation during quinoline and 3-methylquinoline aerobic microbial degradation by a Comamonas sp. strain Q10. Degradation of quinoline and 3-methylquinoline was accompanied by isotope fractionation. Large hydrogen and small carbon isotope fractionation was observed for quinoline while minor carbon and hydrogen isotope fractionation effects occurred for 3-methylquinoline. Bulk carbon and hydrogen enrichment factors (ε _bulk) for quinoline biodegradation were −1.2 ± 0.1 and −38 ± 1‰, respectively, while −0.7 ± 0.1 and −5 ± 1‰ for 3-methylquinoline, respectively. This reveals a potential advantage for employing quinoline as the model compound and hydrogen isotope analysis for assessing aerobic biodegradation of quinolinic compounds. The apparent kinetic isotope effects (AKIE_C) values of carbon were 1.008 ± 0.0005 for quinoline and 1.0048 ± 0.0005 for 3-methylquinoline while AKIE_H values of hydrogen of 1.264 ± 0.011 for quinoline and 1.0356 ± 0.0103 for 3-methylquinoline were obtained. The combined evaluation of carbon and hydrogen isotope fractionation yields Λ values (Λ = Δδ²H/Δδ¹³C ≈ εH_bulk/εC_bulk) of 29 ± 2 for quinoline and 8 ± 2 for 3-methylquinoline. The results indicate that the substrate specificity may have a significant influence on the isotope fractionation for the biodegradation of quinolinic compounds. The substrate-specific isotope enrichment factors would be important for assessing the behavior and fate of quinolinic compounds in the environment.

http://ift.tt/2rymmz8

Resistance Mechanisms to Colorectal Cancer Therapeutics and the Clinical Implications

Abstract

Purpose of Review

Colorectal cancer (CRC) is a leading cause of cancer-related death and additional treatment options are urgently needed. Cytotoxic chemotherapy has been the mainstay of treatment options for patients for many years, including FOLFOX (leucovorin, 5-fluorouracil (5-FU), and oxaliplatin) or FOLFIRI (5-FU, leucovorin, and irinotecan) Here we review the current clinical use of systemic therapies for metastatic CRC and mechanisms of resistance to these agents.

Recent Findings

Biologic therapies, including anti-angiogenic and anti-epidermal growth factor monoclonal antibodies, have shown increased efficacy for patients with metastatic CRC. Most recently, immunotherapies have also been an option for some patients.

Summary

Identification of molecular markers predictive of response or resistance has led to enhanced ability to treat patients with metastatic CRC in a more personalized fashion.

http://ift.tt/2rDxFRU

The brain behaves as a muscle?

Abstract

It is known that lactate accumulates in the skeletal muscle during intense anaerobic exercise but is rapidly cleared from the muscles when they resume aerobic metabolism; however, at least some lactate reaches the blood stream. It has been observed that during maximal exercise, blood lactate increases with transport of the blood to the brain. This could be interpreted as a mechanism to protect against possible "central fatigue" in times of maximal activity during the course of which the lactate would preserve the functionality of the primary cortical motor and sensory areas, even at the expense of the efficiency of the other structures. In this way, the role of lactate, both at the muscular level and in the CNS, appears to shift from being responsible for fatigue to protector from fatigue, which represents a real transition similar to that of how the image of Mr. Hyde changes to that of Dr. Jekyll.

http://ift.tt/2t9woUD

Normal appearing white matter permeability: a marker of inflammation and information processing speed deficit among relapsing remitting multiple sclerosis patients

Abstract

Purpose

Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS).

Methods

Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression.

Results

rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impaired patients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068–2.956; p = 0.026), NAGM (OR 2.138; 1.100–4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120–4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups.

Conclusion

rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.

http://ift.tt/2ryPiqN

The implication of neuronimmunoendocrine (NIE) modulatory network in the pathophysiologic process of Parkinson’s disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder implicitly marked by the substantia nigra dopaminergic neuron degeneration and explicitly characterized by the motor and non-motor symptom complexes. Apart from the nigrostriatal dopamine depletion, the immune and endocrine study findings are also frequently reported, which, in fact, have helped to broaden the symptom spectrum and better explain the pathogenesis and progression of PD. Nevertheless, based on the neural, immune, and endocrine findings presented above, it is still difficult to fully recapitulate the pathophysiologic process of PD. Therefore, here, in this review, we have proposed the neuroimmunoendocrine (NIE) modulatory network in PD, aiming to achieve a more comprehensive interpretation of the pathogenesis and progression of this disease. As a matter of fact, in addition to the classical motor symptoms, NIE modulatory network can also underlie the non-motor symptoms such as gastrointestinal, neuropsychiatric, circadian rhythm, and sleep disorders in PD. Moreover, the dopamine (DA)–melatonin imbalance in the retino-diencephalic/mesencephalic-pineal axis also provides an alternative explanation for the motor complications in the process of DA replacement therapy. In conclusion, the NIE network can be expected to deepen our understanding and facilitate the multi-dimensional management and therapy of PD in future clinical practice.

http://ift.tt/2rDm31u

Preface

http://ift.tt/2rDIiEa

Patient-specific simulation: a new avenue to be explored

http://ift.tt/2rxSLGp

Erratum to: Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

http://ift.tt/2rDop07

Benefit-risk trade-offs for treatment decisions in moderate-to-severe rheumatoid arthritis: focus on the patient perspective

Abstract

Given the increasing number of available treatments for rheumatoid arthritis (RA) with varying efficacy and safety profiles, it is critical to understand the level of trade-offs that patients are willing to make between benefits and risks. Adult patients with moderate to severe RA were invited to participate in a discrete choice experiment that solicited their preferences for hypothetical RA treatments. Each participant was presented with 14 choice cards asking about their preference between two hypothetical RA treatments with varying levels of efficacy, adverse events, and process-related attributes. A multivariable logistic regression model assessed the association between the attributes and the patient's decision and risk-increases were calculated. 510 eligible patients with moderate to severe RA completed the study. The average age of the participants was 56.4 years, 64.7% were female, and 45.1% received biologic agents. To achieve a 50% improvement in physical function, patients were willing to accept risk-increases of 91.1, 4.7, and 18.4% for abnormal laboratory results, cancer, and serious infection, respectively. Similarly, to achieve a 50% reduction in RA-related pain, patients were willing to accept risk-increases of 70.6, 3.7, and 14.2% for each AE. Moreover, patients were willing to trade risk-increases of 42.0, 2.2, and 8.5% for each AE to obtain a 50% reduction in the number of swollen joints. Patients with moderate to severe RA are willing to accept increased treatment risks to achieve improved physical function and disease control. These attributes are helpful to clinicians to make informed treatment choices.

http://ift.tt/2rDd2W5

Increases in circulating amino acids with in-feed antibiotics correlated with gene expression of intestinal amino acid transporters in piglets

Abstract

In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic. Piglets were weaned at day 23 after birth, and fed the same diets until day 42. In-feed antibiotics did not affect the BW of 23-day-old (P = 0.248), or 42-day-old piglets (P = 0.089), but increased the weight gain to feed ratio from day 23 to 42 (P = 0.020). At day 42 after birth, antibiotic treatment increased the concentrations of most AAs in serum (P < 0.05), and decreased the concentrations of most AAs in jejunal and ileal digesta. Antibiotics upregulated (P < 0.05) the mRNA expression levels for jejunal AAs transporters (CAT1, EAAC1, ASCT2, y⁺LAT1), peptide transporters (PepT1), and Na⁺–K⁺–ATPase (ATP1A1), and ileal AA transporters (ASCT2, y⁺LAT1, b^0,+AT, and B⁰AT1), and ATP1A1. The antibiotics also upregulated the mRNA expression of jejunal AAs receptors T1R3 and CaSR, and ileal T1R3. Protein expression levels for jejunal AA transporters (EAAC1, b^0,+AT, and ASCT2) and PepT1 were also upregulated. Correlation analysis revealed that the alterations of AA profiles in serum after the in-feed antibiotics were correlated with the upregulations of mRNA expression levels for key AA transporters and receptors in the small intestine. In conclusion, the in-feed antibiotics increased serum level of most AAs and decreased most AAs in the small intestine. These changes correlated with the upregulations of mRNA expression levels for key AA transporters and receptors in the small intestine. The findings provide further insights into the mechanism of in-feed antibiotics, which may provide new framework for designing alternatives to antibiotics in animal feed in the future.

http://ift.tt/2szhM3T

36th Meeting of the Pediatric Section of the German Society of Trauma Surgery (DGU)

http://ift.tt/2turEIH

Feature fusion for lung nodule classification

Abstract

Purpose

This article examines feature-based nodule description for the purpose of nodule classification in chest computed tomography scanning.

Methods

Three features based on (i) Gabor filter, (ii) multi-resolution local binary pattern (LBP) texture features and (iii) signed distance fused with LBP which generates a combinational shape and texture feature are utilized to provide feature descriptors of malignant and benign nodules and non-nodule regions of interest. Support vector machines (SVMs) and k-nearest neighbor (kNN) classifiers in serial and two-tier cascade frameworks are optimized and analyzed for optimal classification results of nodules.

Results

A total of 1191 nodule and non-nodule samples from the Lung Image Data Consortium database is used for analysis. Classification using SVM and kNN classifiers is examined. The classification results from the two-tier cascade SVM using Gabor features showed overall better results for identifying non-nodules, malignant and benign nodules with average area under the receiver operating characteristics (AUC-ROC) curves of 0.99 and average f1-score of 0.975 over the two tiers.

Conclusion

In the results, higher overall AUCs and f1-scores were obtained for the non-nodules cases using any of the three features, showing the greatest distinguishability over nodules (benign/malignant). SVM and kNN classifiers were used for benign, malignant and non-nodule classification, where Gabor proved to be the most effective of the features for classification. The cascaded framework showed the greatest distinguishability between benign and malignant nodules.

http://ift.tt/2swIv00

Effect of Artemisia annua extract on treating active rheumatoid arthritis: A randomized controlled trial

Abstract

Objective

To investigate the effect and safety of the complementary use of the extract of Artemisia annua L. (EAA) on treating active rheumatoid arthritis (RA).

Methods

A randomized controlled clinical trial was performed. All the 159 participates with active RA were randomly assigned to the control group (80 cases) and EAA group (79 cases) using concealed random allocation method. In the control group, patients were medicated with leflflunomide and methotrexate for 48 weeks; and patients in the EAA group were administrated with leflflunomide, methotrexate plus EAA (30 g/d). At the time points of 0, 12, 24 and 48 weeks, the clinical outcome measures, including objective pain score, tenderness score, number of painful joints, number of swollen joints, health assessment questionnaire (HAQ) score for quality of life, levels of serum rheumatoid factor (RF), anti-cyclic citrullinated protein antibodies (CCP-Ab), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), visual analogue score for pain (VAS), and the overall effificacy were detected and recorded.

Results

The objective pain score, number of painful joints and ESR at 12 weeks, tenderness score and HAQ at 24 weeks, and the tenderness score, number of painfull joints, number of swollen joints, HAQ, CRP, RF and CCP-Ab at 48 weeks were signifificantly improved in the EAA group compared with the control group (P<0.01 or P<0.05). At 24 and 48 weeks, the overall effificacy of the EAA group was signifificantly higher than the control group (P<0.01). There were signifificantly higher withdrawal rate of corticosteroids within 12 weeks post-treatment and lower incidence rate of adverse effects in the EAA group compared with the control group (P<0.01 or P<0.05).

Conclusion

EAA plus methotrexate and leflflunomide were more effective and safer than the routine use of methotrexate and leflflunomide in the treatment of active RA.

http://ift.tt/2sisbOz

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility on uric acid metabolism and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in rats with hyperuricemia

Abstract

Objective

To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility (PR) on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in rats with hyperuricemia.

Methods

Seventy male Sprague Dawley (SD) rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses (3.5, 7, 14 g/kg). Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid (SUA), blood urea nitrogen (BUN) and creatinine (Cr) were determined. In addition, the contents of NGAL and KIM-1 in urine and the mRNA and protein expressions of xanthine oxidase (XOD) in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin (HE) stain method.

Results

Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD mRNA and protein in the hyperuricemia rats were increased signifificantly (P<0.01). PR signifificantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the mRNA and protein expressions of hepatic XOD (P<0.05 or P<0.01). In addition, the pathological changes of kidney were signifificantly suppressed by oral administration of PR.

Conclusions

PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

http://ift.tt/2kmPod9

Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel First-in-Class Analgesic

Abstract

Background and Objectives

Cebranopadol is a novel first-in-class analgesic acting as a nociceptin/orphanin FQ peptide and opioid peptide receptor agonist with central analgesic activity. It is currently in clinical development for the treatment of chronic pain conditions. This trial focuses on the clinical pharmacokinetic (PK) properties of cebranopadol after oral single- and multiple-dose administration.

Methods

The basic PK properties of cebranopadol were assessed by means of noncompartmental methods in six phase I clinical trials in healthy subjects and patients. A population PK analysis included two further phase I and six phase II clinical trials.

Results

After oral administration of the immediate-release (IR) formulation, cebranopadol is characterized by a late time to reach maximum plasma concentration [C _max] (4–6 h), a long half-value duration [HVD] (14–15 h), and a terminal phase half-life in the range of 62–96 h. After multiple once-daily dosing in patients, an operational half-life (the dosing interval resulting in an accumulation factor [AF] of 2) of 24 h was found to be the relevant factor to describe the multiple-dose PKs of cebranopadol. The time to reach steady state was approximately 2 weeks, the AF was approximately 2, and peak-trough fluctuation (PTF) was low (70–80%). Dose proportionality at steady state was shown for a broad dose range of cebranopadol 200–1600 µg. A two-compartment disposition model with two lagged transition compartments and a first-order elimination process best describes cebranopadol data in healthy subjects and patients after single- and multiple-dose administration.

Conclusions

Cebranopadol formulated as an IR product can be used as a once-daily formulation; it reaches C _max after only 4–6 h, and has a long HVD and a low PTF. Therefore, from a PK perspective, cebranopadol is an attractive treatment option for patients with chronic pain.

http://ift.tt/2rDmQQ1

AbobotulinumtoxinA: A Review in Pediatric Lower Limb Spasticity

Abstract

AbobotulinumtoxinA (Dysport^®) is currently the only botulinum toxin A formulation approved by the US FDA for the treatment of lower limb spasticity in pediatric patients aged ≥2 years. Intramuscular abobotulinumtoxinA was approved based on the results of a pivotal phase 3 trial in children with lower limb spasticity due to cerebral palsy. In this trial, a single treatment cycle with abobotulinumtoxinA 10–15 U/kg/leg injected into the gastrocnemius and soleus muscles significantly improved ankle plantar flexor muscle tone (primary endpoint), with abobotulinumtoxinA recipients showing a significant response to treatment relative to placebo. AbobotulinumtoxinA treatment also improved spasticity grade. The improvements in muscle tone and spasticity were associated with an improved ability to attain functional goals. Clinical benefits of abobotulinumtoxinA treatment lasted for 16–22 weeks in most patients, and were maintained with multiple treatment cycles during 1 year in an open-label extension study. AbobotulinumtoxinA was generally well tolerated, with a relatively low incidence of treatment-related adverse events. In summary, abobotulinumtoxinA is an effective and generally well tolerated treatment option for children with lower limb spasticity.

http://ift.tt/2rD4xdF

Cost-effectiveness analysis of a non-contrast screening MRI protocol for vestibular schwannoma in patients with asymmetric sensorineural hearing loss

Abstract

Purpose

We aimed to determine if a non-contrast screening MRI is cost-effective compared to a full MRI protocol with contrast for the evaluation of vestibular schwannomas.

Methods

A decision tree was constructed to evaluate full MRI and screening MRI strategies for patients with asymmetric sensorineural hearing loss. If a patient were to have a positive screening MRI, s/he received a full MRI. Vestibular schwannoma prevalence, MRI specificity and sensitivity, and gadolinium anaphylaxis incidence were obtained through literature review. Institutional charge data were obtained using representative patient cohorts. One-way and probabilistic sensitivity analyses were completed to determine CE model threshold points for MRI performance characteristics and charges.

Results

The mean charge for a full MRI with contrast was significantly higher than a screening MRI ($4089 ± 1086 versus $2872 ± 741; p < 0.05). The screening MRI protocol was more cost-effective than a full MRI protocol with a willingness-to-pay from $0 to 20,000 USD. Sensitivity analyses determined that the screening protocol dominated when the screening MRI charge was less than $4678, and the imaging specificity exceeded 78.2%. The screening MRI protocol also dominated when vestibular schwannoma prevalence was varied between 0 and 1000 in 10,000 people.

Conclusion

A screening MRI protocol is more cost-effective than a full MRI with contrast in the diagnostic evaluation of a vestibular schwannoma. A screening MRI likely also confers benefits of shorter exam time and no contrast use. Further investigation is needed to confirm the relative performance of screening protocols for vestibular schwannomas.

http://ift.tt/2t9whsi

Hypotonicity-induced cell swelling activates TRPA1

Abstract

Hypotonic solutions can cause painful sensations in nasal and ocular mucosa through molecular mechanisms that are not entirely understood. We clarified the ability of human TRPA1 (hTRPA1) to respond to physical stimulus, and evaluated the response of hTRPA1 to cell swelling under hypotonic conditions. Using a Ca²⁺-imaging method, we found that modulation of AITC-induced hTRPA1 activity occurred under hypotonic conditions. Moreover, cell swelling in hypotonic conditions evoked single-channel activation of hTRPA1 in a cell-attached mode when the patch pipette was attached after cell swelling under hypotonic conditions, but not before swelling. Single-channel currents activated by cell swelling were also inhibited by a known hTRPA1 blocker. Since pre-application of thapsigargin or pretreatment with the calcium chelator BAPTA did not affect the single-channel activation induced by cell swelling, changes in intracellular calcium concentrations are likely not related to hTRPA1 activation induced by physical stimuli.

http://ift.tt/2szGC3B

Benefit-risk trade-offs for treatment decisions in moderate-to-severe rheumatoid arthritis: focus on the patient perspective

Abstract

Given the increasing number of available treatments for rheumatoid arthritis (RA) with varying efficacy and safety profiles, it is critical to understand the level of trade-offs that patients are willing to make between benefits and risks. Adult patients with moderate to severe RA were invited to participate in a discrete choice experiment that solicited their preferences for hypothetical RA treatments. Each participant was presented with 14 choice cards asking about their preference between two hypothetical RA treatments with varying levels of efficacy, adverse events, and process-related attributes. A multivariable logistic regression model assessed the association between the attributes and the patient's decision and risk-increases were calculated. 510 eligible patients with moderate to severe RA completed the study. The average age of the participants was 56.4 years, 64.7% were female, and 45.1% received biologic agents. To achieve a 50% improvement in physical function, patients were willing to accept risk-increases of 91.1, 4.7, and 18.4% for abnormal laboratory results, cancer, and serious infection, respectively. Similarly, to achieve a 50% reduction in RA-related pain, patients were willing to accept risk-increases of 70.6, 3.7, and 14.2% for each AE. Moreover, patients were willing to trade risk-increases of 42.0, 2.2, and 8.5% for each AE to obtain a 50% reduction in the number of swollen joints. Patients with moderate to severe RA are willing to accept increased treatment risks to achieve improved physical function and disease control. These attributes are helpful to clinicians to make informed treatment choices.

http://ift.tt/2rDd2W5

Dual-dissimilarity measure-based statistical video cut detection

Abstract

Video cut detection is an essential process of temporal continuity-based video applications such as video segmentation, video retargeting, and frame rate up-conversion. The performance of these applications highly depends on the performance of cut detection. This paper proposes an effective and low-complexity approach for detecting video cuts. The proposed method uses two simple dissimilarity measures for video cut detection: inter-frame luminance variation and temporal variation of inter-frame variations over several frames. The first is used to detect abrupt changes, and the second is used to reduce the influence of disturbances, e.g., object or camera motion. The proposed method is comprised of the following three steps. First, it computes the two dissimilarity measures. Then, it combines them using Bayesian estimation and linear regression. Finally, it decides on the possibility of cuts using the combined dissimilarity measure. Experimental results show that the average F₁ score of the proposed method was up to 0.252 (37.0%) higher than those of the benchmark methods. Moreover, the algorithmic simplicity of the proposed method reduced the average computation time per pixel by up to 99.8%, when compared with state-of-the-art methods. Thus, the proposed method is superior to existing methods in terms of computational complexity and detection accuracy.

http://ift.tt/2sAen4K

Use of Lysimeters to Assess Water Balance Components in Grassland and Atlantic Forest in Southern Brazil

Abstract

This study aimed to quantify the water balance components at a grassland and a forest site representative of the Atlantic Forest biome in southern Brazil using drainage lysimeters. Since it was not possible to place mature trees on the forest lysimeter, it was planted with young trees and understory vegetation. Data from this lysimeter and computations with the water balance and the Penman-Monteith equation were then used to assess the values of the water balance components for the mature forest.

Total precipitation during the study period was 2308 mm. In the forest environment, 46% thereof was intercepted by the canopy from where it later evaporated. Hence, much less rain reached the ground than under grassland. Runoff from both sites was <1% of precipitation and therefore not a significant factor in the water balance. Cumulative drainage amounted to 1136 mm from grassland: from the mature forest, it was estimated to be 389 mm. There were two reasons for this low value under forest: Interception prevented a lot of water from reaching the ground, and the actual evapotranspiration from the mature forest was much higher than from grassland (1231 mm compared to 1964 mm).

http://ift.tt/2sG0VvU

Microcirculatory Characteristics in Neck/Shoulder of the Adults with Sedentary and Exercise Lifestyles

Abstract

High risk of musculoskeletal diseases had been demonstrated in many people with a sedentary lifestyle. As microcirculation provides primary information on tissue health, this paper aims to compare the perfusion characteristics in neck/shoulder of individuals at different physical activity levels. High power laser Doppler flowmetry (LDF) system and averaging algorithm were used to obtain the microcirculatory characteristics. Thirty-two participants with different exercise habit were recruited, which were divided into sedentary group (n = 16) and exercise group (n = 16). The participants in both groups were matched in age, gender, and body mass index. Peripheral blood perfusion signals on the neck-shoulder region pre- and post- upper trapezius stretching were acquired using LDF with a noninvasive wide separation probe. A modified beat-to-beat algorithm was then applied for the analysis of the microcirculatory signals, including pulsatile and nonpulsatile components. The Mann–Whitney U test was used to compare the differences of perfusion characteristics between these two groups. The pulsatile component of LDF signals in the exercise group was greater than that of the sedentary counterparts after the upper trapezius stretching (P < 0.05). Furthermore, the index of perfusion pulsatility (ratio of pulsatile component to mean LDF signal) of the exercise group was significantly higher than that of the sedentary group (P < 0.01). This index could differentiate these two groups both at the baseline and post- stretching. Even with low exercise volume, exercise group with regular physical activity appear noticeably different in microcirculatory characteristics in this study. The subjects who exercised had higher values of microcirculatory pulsatility. These findings may encourage people to exercise more often based on the benefit in microcirculation even with small increases in physical activity volume.

http://ift.tt/2s8pa53