Efficacy, safety, and immunogenicity of rurioctocog alfa pegol for prophylactic treatment in previously treated patients with severe hemophilia A: a systematic review and meta-analysis of clinical trials

Background: Patients with severe hemophilia often present with painful joint and soft tissue bleeding which may restrict them from their daily activities. The current standard of care still relies on a regular prophylactic factor VIII (FVIII), which has a high daily treatment burden. Recently, rurioctocog alfa pegol, a third-generation recombinant FVIII with a modification in its polyethylene glycol (PEG) component, has been developed. Several trials have studied this synthetic drug as bleeding prophylaxis in severe hemophilia A. This study aims to evaluate the efficacy, safety, and immunogenicity of rurioctocog alfa pegol for previously treated patients with severe hemophilia A. Methods: This study was conducted in conformity with the PRISMA guidelines. Data were retrieved from PubMed, Scopus, Cochrane Library, Wiley Online Library, and CINAHL (via EBSCOhost). Study qualities were assessed using the Methodological Index for Non-Randomized Studies (MINORS) and Modified Jadad scales. Results: Four studies involving 517 previously treated severe hemophilia A patients were included in this study. The pooled mean of total annualized bleeding rate (ABR) and hemostatic efficacy was 2.59 (95% CI = 2.04–3.14) and 92% (95% CI = 85%–97%), respectively. Only 30 (2.3%) non-serious and one (1.4%) serious adverse events were considered related to rurioctocog alfa pegol treatment. At the end of the studies, no development of FVIII inhibitory antibodies was observed. None of the developed binding antibodies to FVIII, PEG-FVIII, or PEG was correlated to the treatment efficacy and safety. Conclusions: Despite the limited availability of direct comparison studies, our analyses indicate that rurioctocog alfa pegol could serve as a safe and effective alternative for bleeding prophylaxis in previously treated hemophilia A patients. Moreover, it appears to have low immunogenicity, which further increases the safety profile of the drug in such clinical conditions.

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA like Adjuvant Arthritis in Rats.

Objective: Nanomedicine has become one of the promising research areas, opening new horizons in disease diagnosis and treatment. Recent years have witnessed a surge in the development of nanomedicine for combating rheumatoid arthritis (RA), the most common autoimmune arthritis. RA is characterized by progressive inflammation and persistent synovitis, leading to joint destruction, functional incapability, and ultimately disability. Although there has been a tremendous evolution in disease assess­ment and treatment, many patients still fail to attain remission. Therefore, developing new drugs that specifically target inflamed joints and simultaneously attenuate other possible damages to healthy tissues is indispensable. This study was done to evaluate the potential of folic acid conjugated silver nanoparticles (FA-AgNPs) as RA therapy.Methods: In the CFA-arthritic rat model, FA-AgNPs & methotrexate were administered for 8 consecutive weeks. Therapeutic efficacy was evaluated by measuring paw volume, ESR, CRP, TNF-α, and IL-6 levels. For safety concerns, CBC, liver, and renal function tests were evaluated. Joints histological assessment was also carried out.Results: FA-AgNPs significantly reduced paw volume, paw weight, ESR, CRP, RF, TNF-α, and IL-6 levels compared with arthritic non-treated rats, demonstrating good anti-inflammatory activity. Likewise, histology of tarsal joints depicted comparatively lesser inflammatory cellular infiltration and diminished cartilage erosions. Methotrexate displayed comparable results. In contrast to methotrexate, FA-AgNPs showed normal CBC & significantly improved liver and renal function tests. Conclusion: FA-AgNPs exhibited substantial anti-arthritic activity. This notable anti-arthritic potential of FA-AgNPs was as good as the current standard treatment of MTX with higher biosafety.

Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.

Reverse dot blot hybridization assay— An expeditious diagnostic tool for drug resistant TB

Tuberculosis (TB) is one of the leading infectious diseases that is highly transmissible. It is reported to cause approximately 10 million infections and 1.4 million deaths globally in the year of 2019.¹ Prompt detection and treatment of TB are essential to intercept the proliferation of the disease. In the case of drug- resistant TB, failure to detect the resistance of anti TB drugs may give rise to extensively drug- resistant tuberculosis (XDR-TB). Thus, the rapid detection of drug resistance is vital;, however, the current standard drug susceptibility tests (DST) may take up to 12 weeks raising an alarming concern.² A study was done in China by Li Wan et al, on the accuracy of the reverse dot blot hybridization assay (RDBH) for rapidly detecting the resistance of four anti TB drugs (rifampicin (RIF), isoniazid (INH), streptomycin (SM) and ethambutol (EMB)) in mycobacterium tuberculosis (MTB) isolates.³ Continuous...

Pydiflumetofen Co-Formulated with Prothioconazole: A Novel Fungicide for Fusarium Head Blight and Deoxynivalenol Control

Fusarium head blight (FHB) is an important disease of small grain cereals worldwide, resulting in reduced yield and quality as well as the contamination of harvested grains with mycotoxins. The key mycotoxin of concern is deoxynivalenol (DON), which has legislative and advisory limits in numerous countries. Cereal growers have a number of control options for FHB including rotation, cultivation, and varietal resistance; however, growers are still reliant on fungicides applied at flowering as part of an IPM program. Fungicides currently available to control FHB are largely restricted to triazole chemistry. This study conducted three field experiments to compare a new co-formulation of pydiflumetofen (a succinate dehydrogenase inhibitor (SDHI) with the tradename ADEPIDYN™) and prothioconazole (a triazole) against current standard fungicides at various timings (flag leaf fully emerged, mid-head emergence, early flowering, and late flowering) for the control of FHB and DON. Overall, the co-formulation showed greater efficacy compared to either pydiflumetofen alone or current fungicide chemistry. This greater activity was demonstrated over a wide range of spray timings (flag leaf fully emerged to late flowering). The availability of an SDHI with good activity against FHB and the resulting DON contamination of harvested grain will give growers an additional tool within an IPM program that will provide a greater flexibility of spray application windows and reduce fungicide resistance selection pressure.

Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections

Antibiotics are the current standard of care treatment for uncomplicated urinary tract infections (uUTIs). However, increasing rates of bacterial antibiotic resistance necessitate novel therapeutic options. Gepotidacin is a first-in-class triazaacenaphthylene antibiotic that selectively inhibits bacterial DNA replication by interaction with the bacterial subunits of DNA gyrase (GyrA) and topoisomerase IV (ParC). Gepotidacin is currently in clinical development for the treatment of uUTIs and other infections. In this article, we review data for gepotidacin from nonclinical studies including: in-vitro activity, in-vivo animal efficacy, and pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) models that informed dose selection for phase III clinical evaluation of gepotidacin. Based on this translational package of data, a gepotidacin 1,500 mg oral dose twice-daily for 5 days was selected for two ongoing, randomized, multicenter, parallel-group, double-blind, double-dummy, active-comparator phase III clinical studies evaluating the safety and efficacy of gepotidacin in adolescent and adult female participants with uUTIs (NCT04020341 and NCT04187144).

Gaussian Process Classification for Galaxy Blend Identification in LSST

A significant fraction of observed galaxies in the Rubin Observatory Legacy Survey of Space and Time (LSST) will overlap at least one other galaxy along the same line of sight, in a so-called “blend.” The current standard method of assessing blend likelihood in LSST images relies on counting up the number of intensity peaks in the smoothed image of a blend candidate, but the reliability of this procedure has not yet been comprehensively studied. Here we construct a realistic distribution of blended and unblended galaxies through high-fidelity simulations of LSST-like images, and from this we examine the blend classification accuracy of the standard peak-finding method. Furthermore, we develop a novel Gaussian process blend classifier model, and show that this classifier is competitive with both the peak finding method as well as with a convolutional neural network model. Finally, whereas the peak-finding method does not naturally assign probabilities to its classification estimates, the Gaussian process model does, and we show that the Gaussian process classification probabilities are generally reliable.

Development of a New Shoe Fitting for Obese Adults

Background: Standard fit as well as wide-fit footwear not currently being pertinent and comfortable for the obese adults. The biometric measurements of obese foot (such as foot length, foot width, heel girth, instep girth, waist girth, and ball girth,) significantly differ from healthy adults. Aim: This study aims to develop a new shoe fitting for obese adults based on significant relationships among the relevant biometric parameters of the foot. Method: These measurements of obese foot were determined using a Brannock device and measuring tape. All kinds of foot girth measurements were analyzed against scaling based on foot width or current fitting, BMI, foot length, heel girth, instep girth, waist girth and ball girth and compared these data with ANOVA. Result: Results showed that responses of all kinds of girths against waist girth scaling provide best fitting prospects of obese adults than current standard fit as well as other parameters. Conclusion: From the study and results, it can be concluded that shoe fitting based on waist girth can give more precise comfort and improve the ergonomic fitness of the product for obese users. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 45-53

Dynamical systems implementation of intrinsic sentence meaning

This paper proposes a model for implementation of intrinsic natural language sentence meaning in a physical language understanding system, where 'intrinsic' is understood as 'independent of meaning ascription by system-external observers'. The proposal is that intrinsic meaning can be implemented as a point attractor in the state space of a nonlinear dynamical system with feedback which is generated by temporally sequenced inputs. It is motivated by John Searle's well known (1980) critique of the then-standard and currently still influential Computational Theory of Mind (CTM), the essence of which was that CTM representations lack intrinsic meaning because that meaning is dependent on ascription by an observer. The proposed dynamical model comprises a collection of interacting artificial neural networks, and constitutes a radical simplification of the principle of compositional phrase structure which is at the heart of the current standard view of sentence semantics because it is computationally interpretable as a finite state machine.