Comparative safety and benefit-risk profile of biologics and oral treatment for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data

Background The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. Objective To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. Methods A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). Results Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. Limitations The results may not be generalizable to real-world populations. Conclusions Anti–interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term

Citizen-centric E-Governance Project in Uttaranchal, India

Abstract: The paper deals with a UNDP-funded, e-governance pilot project which was implemented by Indian Institute of Technology Roorkee in Uttaranchal, India. A Participatory Rural Appraisal exercise was carried out to assess peoples needs and aspirations, which was followed by a Business Process Reengineering exercise to make government departmental working more efficient, transparent and adaptable to computerization. A n-tier architecture citizen centric Uttara portal with information and data on 115 departments/ organizations of the state, was developed. The delivery of the services of some select government departments has been tried in Nainital district of Uttaranchal, India, through Information Kiosks (Soochna Kutirs) which are run by local people

The Kinnaur earthquake, Himachal Pradesh, India, of 19 January, 1975

Determination of the fault-plane solution of the Kinnaur earthquake by first motion and amplitude data of P waves, along with other geological and geophysical data, indicates a N-S-trending and westward-dipping fault plane with purely dip-slip displacement. This plane coincides with the N-S extending zone of aftershocks, ground fissures and faults observed in the epicentral tract following the earthquake. The cumulative strain release pattern displays a characteristic release of logarithmic recovery followed by exponential recovery. The aftershocks display a notable migration in space. They also show two distinct phases of seismic activity. The main earthquake is estimated to have a fault length of 25 km, fault area of 575 km2, volume of strain of ~2900 km3, displacement of 59 cm, stress drop of 36 bars, and strain release of 5.9 . 10-5

Microearthquake seismicity and active tectonics of northwestern Greece

We carried out a microearthquake survey lasting for six weeks in northwest Greece using 18 portable seismograph stations to examine a region in which normal and thrust faulting have been reported in close proximity to one another. With this array we located 148 events and determined fault plane solutions for eight events using only rays radiated upwards. The seismicity of the region is diffuse with events extending to depths of nearly 30 km, and there is a minimum in activity near a depth of 15 km. The fault plane solutions exhibit a wide spectrum of fault types and orientations and are not consistent with simple zones of shortening or extension. Neither tractions applied to the edges or bottom of the region nor deviatoric stresses that compensate for lateral variations in crustal thickness can account for the variety of fault plane solutions. We think that the complicated behavior is a manifestation of inhomogeneous deformation due, at least in part, to a pre-existing complicated juxtaposition of structures and formations

Long-term efficacy and safety of risankizumab for the treatment of moderate-to-severe plaque psoriasis : interim analysis of the LIMMitless open-label extension trial beyond 3 years of follow-up

AbbVie Inc.Background: Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long-term evaluation to assess the durability of their efficacy and safety profiles over time. Objectives: To evaluate the long-term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. Methods: LIMMitless is an ongoing, phase III, open-label extension study evaluating the long-term efficacy and safety of RZB in adults with moderate-to-severe plaque psoriasis following multiple phase II/III studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥ 90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90 and PASI 100), static Physician's Global Assessment of clear or almost clear (sPGA 0/1) and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. The study is registered at ClinicalTrials.gov (identifier: NCT03047395). Results: Of 955 patients randomized to RZB 150 mg in the base studies, 897 patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI 90, 54·4% achieved PASI 100, 85·2% achieved sPGA 0/1, and 78·4% achieved DLQI 0/1 using modified nonresponder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long-term treatment and comparable with those identified in the base studies. Conclusions: Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks