Occurrence and Clinical Predictors of Osteoporosis in patients with Ankylosing Spondylitis in a Tertiary Care Center in South India

INTRODUCTION : Ankylosing spondylitis (AS) is an inflammatory disorder of unknown cause that primarily involves the axial skeleton, though peripheral joints and exta-articular structures are also involved. It usually manifests in the second to third decade and has a male to female ratio varying in literature from 4-10:1, however most recent studies show a ratio between 5:1 to 3:1(1-3). Enthesitis is a classical feature of this disease. Subchondral bone marrow edema, infiltration of lymphocytes and macrophages, and synovitis have been seen in early stages of this disease in the sacroiliac as well as peripheral joints. These processes lead to pannus formation similar to rheumatoid arthritis, joint erosion and ultimately new bone formation. Even though new bone formation is one of the cardinal features of the disease, osteoporosis has been found to occur in patients with AS(4). The prevalence of osteoporosis in AS among Caucasians has been found in various studies to range from 4.3 to 31%(5-10). These studies utilized various means of assessing bone mineral density (BMD). It has been found that the ideal measure for osteoporosis in AS is the Dual energy X ray absorptiometry (DEXA) of femoral neck and a lateral projection of L3 vertebra(11, 12). In recent times however Quantitative CT (QCT) has been proposed as an alternative and has been shown to correlate well with BMD(10). QCT may in fact be able to pick up osteoporosis at an earlier stage than DEXA, however it is more expensive and less well standardized than DEXA(13). OBJECTIVES : 1. To determine the occurrence of osteoporosis among a cohort of patients with Ankylosing Spondylitis(AS). 2. To assess whether the following disease indices - the BASDAI(Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), or BAS-G (Bath Ankylosing Spondylitis Global Index) have a correlation with osteoporosis in AS. 3. To assess if demographic factors, disease duration, treatment with steroids, DMARDS or laboratory parameters of inflammation have an association with occurrence of osteoporosis in AS. PATIENTS AND METHODS : Study Setting : The study was conducted in Christian Medical College Hospital, Vellore, a 1800 bedded tertiary care teaching hospital in South India. Patients for the study were drawn from the out patient clinics of the Department of Medicine II and Rheumatology of the Christian Medical College Hospital. The regular rheumatology clinics function twice a week and have an average attendance of 200 patients with rheumatological diseases each day. In addition to this patients were also drawn from the Spondyloarthritis and crystal arthritis clinic. The Department provides both out-patient and in-patient care for these patients. Patients are drawn from all parts of the country and represent a wide area stretching far beyond Tamil Nadu. Study Design : The study was a cross-sectional study. The study design and methods were approved by the Institutional Research Committee of the Christian Medical College, Vellore. Subjects : All patients with Ankylosing Spondylitis attending the out-patient clinic who fulfilled the inclusion criteria and consented to participate in the study were recruited. Inclusion Criteria : 1. Age > 18 years 2. Satisfying the Modified New York Criteria for Ankylosing Spondylitis Modified New York Criteria : 1. Low back pain of at least 3 months duration, improved by exercise and not relieved by Rest. 2. Limitation of lumbar spine in sagittal and frontal planes. 3. Chest expansion decreased relative to normal values for age and sex. 4. Bilateral sacroiliitis grade 2-4. 5. Unilateral sacroiliitis grade 3-4. Patients require one radiological criterion and one clinical criterion for diagnosis. Exclusion Criteria : 1. Patients on bisphosphonates or on other medications which influence bone metabolism, 2. Severe infections or co-morbidities, 3. Patients with other diseases, which may influence bone density. CONCLUSIONS : Osteoporosis at the spine was found in 38%, while at the hip, it was found in 8.3% of Indian patients with Ankylosing Spondylitis. Osteopenia at the spine was found in 33%, while at the hip, the corresponding figure was 57%. This data suggests that osteoporosis is a common complication of AS and almost two thirds of AS patients have abnormal BMD. • Bone loss occurs early at the spine and can be seen within the first 5 years of disease onset (42%). Thus, in early cases, BMD at the spine is required to pick up osteoporosis, but later in the disease, BMD hip will help to detect patients who have an artefactual increase in spinal BMD due to paraspinal ossification. • BMD at the spine (r=0.4,p<0.001) and hip (r=0.32,p=0.001) correlates positively with BMI. Thus AS patients with higher BMI are at less risk to develop osteoporosis. • BMD at the hip correlates inversely with functional status as measured by BASFI (r=-0.38,p<0.001) and also with FFD (r=-0.47,p<0.01). • Paradoxically, syndesmophytes are strongly associated with osteoporosis or osteopenia at the hip (p=0.012). Thus utilization of simple tools such as the BASFI as well as metrological measurements such as FFD may help identify AS patients requiring BMD measurement. • Based on this study, we recommend that all AS patients at diagnosis should have spinal BMD measurements, and in patients with disease duration more than 5 years or having syndesmophytes, this should be coupled with BMD measurement at the hip

Altered levels of toll-like receptors in circulating extracellular vesicles in multiple sclerosis

Extracellular vesicles (EVs) are involved in inter-cellular communication and their cargo may provide prognostic/diagnostic biomarkers. To discover EV-associated biomarkers for Multiple Sclerosis (MS), we used an immune marker array to identify surface proteins on circulating EVs that differ between MS patients and controls (n = 3 each). We identified toll-like receptor-3 (TLR3) as a potential target for further validation. We utilized prospectively collected serum from relapsing-remitting MS patients (n = 18) and controls (n = 16) and confirmed lower concentration of TLR3 and higher concentration of mechanistically related TLR4 in MS EVs compared to controls. Future studies may further evaluate the utility of EV-associated TLRs as MS biomarkers and uncover their mechanistic significance

Applying an Open-Source Segmentation Algorithm to Different OCT Devices in Multiple Sclerosis Patients and Healthy Controls: Implications for Clinical Trials

Background. The lack of segmentation algorithms operative across optical coherence tomography (OCT) platforms hinders utility of retinal layer measures in MS trials. Objective. To determine cross-sectional and longitudinal agreement of retinal layer thicknesses derived from an open-source, fully-automated, segmentation algorithm, applied to two spectral-domain OCT devices. Methods. Cirrus HD-OCT and Spectralis OCT macular scans from 68 MS patients and 22 healthy controls were segmented. A longitudinal cohort comprising 51 subjects (mean follow-up: 1.4 ± 0.9 years) was also examined. Bland-Altman analyses and interscanner agreement indices were utilized to assess agreement between scanners. Results. Low mean differences (−2.16 to 0.26 μm) and narrow limits of agreement (LOA) were noted for ganglion cell and inner and outer nuclear layer thicknesses cross-sectionally. Longitudinally we found low mean differences (−0.195 to 0.21 μm) for changes in all layers, with wider LOA. Comparisons of rate of change in layer thicknesses over time revealed consistent results between the platforms. Conclusions. Retinal thickness measures for the majority of the retinal layers agree well cross-sectionally and longitudinally between the two scanners at the cohort level, with greater variability at the individual level. This open-source segmentation algorithm enables combining data from different OCT platforms, broadening utilization of OCT as an outcome measure in MS trials

Optical Beamforming Techniques for Solid-State Automotive LIDAR

The advent of new products in advanced driver assistance systems, virtual reality headsets, robotics, and biometrics has led to increasing demand for high resolution 3D depth maps. LIDAR (Light Detection and Ranging) has emerged as a strong candidate sensor to supply these applications with depth maps of the environment. In fact, LIDAR is already used as a primary sensor in experimental self-driving vehicles, since it provides high-resolution 3D images that existing RADAR solutions do not. However, the reliability and cost of these automotive LIDAR sensors has precluded their use in high-volume mainstream applications.This thesis explores and demonstrates beamsteering architectures that significantly reduce the size, weight, power and cost of LIDAR sensors. In particular, we focus on designs which achieve the high-volume, reliability, and resolution that automotive applications demand. We begin with an overview of existing LIDAR sensor architectures, and show that the key to improving cost and scalability is switching from traditional mechanical beam-steering to solid-state beam-steering using silicon photonic platforms. We then model and analyze the performance of different solid-state beam steering choices in the context of automotive applications, and arrive at a design for a thermal optical phased array. This thesis then outlines silicon implementation results from from the first 3D integrated the LIDAR SoC based on the aforementioned thermal optical phased array design. Next, we analyze several key issues that prevent this prototype from scaling to more demanding specifications, and propose a new beamsteering architecture based on focal-plane arrays which circumvents these fundamental issues. Finally, the models and automated electronic-photonic design methodologies developed in this work culminate in the design of a scalable monolithically integrated focal-plane array transmitter in a zero-change 45nm SOI CMOS process

An update on the evidence base for peginterferon β1a in the treatment of relapsing–remitting multiple sclerosis

Peginterferon β1a is a modified form of interferon β1a with a polyethylene glycol (PEG) group attached to the α-amino group of the N terminus of the interferon molecule. This modification alters the pharmacokinetic and pharmacodynamic properties of interferon β1a, enabling reduced frequency of dosing and may also result in reduced immunogenicity of the interferon β1a molecule. The efficacy of peginterferon β1a 125 µg administered subcutaneously every 2 or 4 weeks was demonstrated at the end of the placebo-controlled period in the phase III ADVANCE study; both dosing regimens met their primary endpoint of reducing annualized relapse rate (ARR) compared with placebo. Peginterferon β1a administered every 2 weeks resulted in a more robust treatment effect on ARR, sustained disability progression and magnetic resonance imaging endpoints (new or enlarging T2 lesions and gadolinium-enhanced lesions) than peginterferon β1a every 4 weeks. Further reductions in the ARR with additional positive impact on magnetic resonance imaging outcomes were noted in year 2 of the ADVANCE study with the every 2-week dosing regimen. An adverse-effect profile similar to other interferon β formulations coupled with the advantage of a significant reduction in the number of injections, could lead to improved long-term adherence to peginterferon β1a. We review the evidence base for the role of peginterferon β1a in the treatment of relapsing–remitting multiple sclerosis

A Hybrid Marine Predator Sine Cosine Algorithm for Parameter Selection of Hybrid Active Power Filter

Power quality issues are handled very well by filter technologies. In recent years, the advancement of hybrid active power filters (HAPF) has been enhanced due to ease of control and flexibility as compared to other filter technologies. These filters are a beneficial asset for a power producer that requires a smooth filtered output of power. However, the design of these filters is a daunting task to perform. Often, metaheuristic algorithms are employed for dealing with this nonlinear optimization problem. In this work, a new hybrid metaheuristic algorithm (Marine Predator Algorithm and Sine Cosine Algorithm) has been proposed for selecting the best parameters for HAPF. The comparison of different algorithms for obtaining the HAPF parameters is also performed to show case efficacy of the proposed hybrid algorithm. It can be concluded that the proposed algorithm produces robust results and can be a potential tool for estimating the HAPF parameters. The confirmation of the performance of the proposed algorithm is conducted with the results of fitness statistical results, boxplots, and different numerical analyses