Health state utilities associated with attributes of treatments for hepatitis C

BACKGROUND: Cost-utility analyses are frequently conducted to compare treatments for hepatitis C, which are often associated with complex regimens and serious adverse events. Thus, the purpose of this study was to estimate the utility associated with treatment administration and adverse events of hepatitis C treatments. DESIGN: Health states were drafted based on literature review and clinician interviews. General population participants in the UK valued the health states in time trade-off (TTO) interviews with 10- and 1-year time horizons. The 14 health states described hepatitis C with variations in treatment regimen and adverse events. RESULTS: A total of 182 participants completed interviews (50 % female; mean age = 39.3 years). Utilities for health states describing treatment regimens without injections ranged from 0.80 (1 tablet) to 0.79 (7 tablets). Utilities for health states describing oral plus injectable regimens were 0.77 (7 tablets), 0.75 (12 tablets), and 0.71 (18 tablets). Addition of a weekly injection had a disutility of −0.02. A requirement to take medication with fatty food had a disutility of −0.04. Adverse events were associated with substantial disutilities: mild anemia, −0.12; severe anemia, −0.32; flu-like symptoms, −0.21; mild rash, −0.13; severe rash, −0.48; depression, −0.47. One-year TTO scores were similar to these 10-year values. CONCLUSIONS: Adverse events and greater treatment regimen complexity were associated with lower utility scores, suggesting a perceived decrease in quality of life beyond the impact of hepatitis C. The resulting utilities may be used in models estimating and comparing the value of treatments for hepatitis C. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10198-014-0649-6) contains supplementary material, which is available to authorized users

Excessive Biologic Response to IFNβ Is Associated with Poor Treatment Response in Patients with Multiple Sclerosis

Interferon-beta (IFNβ) is used to inhibit disease activity in multiple sclerosis (MS), but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified.he relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70) or poor response (n = 15). Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs).The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual ‘IFN response fingerprint’. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections.MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients

Insights on the interaction of SARS-CoV-2 variant B.1.617.2 with antibody CR3022 and analysis of antibody resistance

Abstract Background The existence of mutated Delta (B.1.617.2) variants of SARS-CoV-2 causes rapid transmissibility, increase in virulence, and decrease in the effectiveness of public health. Majority of mutations are seen in the surface spike, and they are considered as antigenicity and immunogenicity of the virus. Hence, finding suitable cross antibody or natural antibody and understanding its biomolecular recognition for neutralizing surface spike are crucial for developing many clinically approved COVID-19 vaccines. Here, we aim to design SARS-CoV-2 variant and hence, to understand its mechanism, binding affinity and neutralization potential with several antibodies. Results In this study, we modelled six feasible spike protein (S1) configurations for Delta SARS-CoV-2 (B.1.617.2) and identified the best structure to interact with human antibodies. Initially, the impact of mutations at the receptor-binding domain (RBD) of B.1.617.2 was tested, and it is found that all mutations increase the stability of proteins (ΔΔG) and decrease the entropies. An exceptional case is noted for the mutation of G614D variant for which the vibration entropy change is found to be within the range of 0.133–0.004 kcal/mol/K. Temperature-dependent free energy change values (ΔG) for wild type is found to be − 0.1 kcal/mol, whereas all other cases exhibit values within the range of − 5.1 to − 5.5 kcal/mol. Mutation on spike increases the interaction with the glycoprotein antibody CR3022 and the binding affinity (CLUSpro energy =  − 99.7 kcal/mol). The docked Delta variant with the following antibodies, etesevimab, bebtelovimab, BD-368–2, imdevimab, bamlanivimab, and casirivimab, exhibit a substantially decreased docking score (− 61.7 to − 112.0 kcal/mol) and the disappearance of several hydrogen bond interactions. Conclusion Characterization of antibody resistance for Delta variant with respect to the wild type gives understanding regarding why Delta variant endures the resistance boosted through several trademark vaccines. Several interactions with CR3022 have appeared compared to Wild for Delta variant, and hence, it is suggested that modification on the CR3022 antibody could further improve for the prevention of viral spread. Antibody resistance decreased significantly due to numerous hydrogen bond interactions which clearly indicate that these marketed/launched vaccines (etesevimab) will be effective for Delta variants. Graphical Abstrac

Insights on the interaction of SARS-CoV-2 variant B.1.617.2 with antibody CR3022 and analysis of antibody resistance

Abstract Background The existence of mutated Delta (B.1.617.2) variants of SARS-CoV-2 causes rapid transmissibility, increase in virulence, and decrease in the effectiveness of public health. Majority of mutations are seen in the surface spike, and they are considered as antigenicity and immunogenicity of the virus. Hence, finding suitable cross antibody or natural antibody and understanding its biomolecular recognition for neutralizing surface spike are crucial for developing many clinically approved COVID-19 vaccines. Here, we aim to design SARS-CoV-2 variant and hence, to understand its mechanism, binding affinity and neutralization potential with several antibodies. Results In this study, we modelled six feasible spike protein (S1) configurations for Delta SARS-CoV-2 (B.1.617.2) and identified the best structure to interact with human antibodies. Initially, the impact of mutations at the receptor-binding domain (RBD) of B.1.617.2 was tested, and it is found that all mutations increase the stability of proteins (ΔΔG) and decrease the entropies. An exceptional case is noted for the mutation of G614D variant for which the vibration entropy change is found to be within the range of 0.133–0.004 kcal/mol/K. Temperature-dependent free energy change values (ΔG) for wild type is found to be − 0.1 kcal/mol, whereas all other cases exhibit values within the range of − 5.1 to − 5.5 kcal/mol. Mutation on spike increases the interaction with the glycoprotein antibody CR3022 and the binding affinity (CLUSpro energy =  − 99.7 kcal/mol). The docked Delta variant with the following antibodies, etesevimab, bebtelovimab, BD-368–2, imdevimab, bamlanivimab, and casirivimab, exhibit a substantially decreased docking score (− 61.7 to − 112.0 kcal/mol) and the disappearance of several hydrogen bond interactions. Conclusion Characterization of antibody resistance for Delta variant with respect to the wild type gives understanding regarding why Delta variant endures the resistance boosted through several trademark vaccines. Several interactions with CR3022 have appeared compared to Wild for Delta variant, and hence, it is suggested that modification on the CR3022 antibody could further improve for the prevention of viral spread. Antibody resistance decreased significantly due to numerous hydrogen bond interactions which clearly indicate that these marketed/launched vaccines (etesevimab) will be effective for Delta variants. Graphical Abstract </jats:sec

Molecular dynamics and docking studies on potentially active natural phytochemicals for targeting SARS-CoV-2 Main Protease

Abstract In this study, we screened eighty seven novel phytochemical compounds and identified the best for targeting the main protease (Mpro) receptor of SARS-CoV-2. Interestingly, the studied phytochemicals are present in four natural herbs namely, Aegle Marmelos, Coleus Amboinicus, Aerva Lanta and Biophytum Sensitivum. After categorizing all the phytochemicals based upon LibDock scores, we identified six compounds with scores over 120, namely, Ervoside, Epoxyaurapten, Epicatechin, Feruloyltyramine, Marmin and Aegelinosides B. Among them Aegelinosides B leads with a very high LibDock value of 142.50 (binding energy: -8.54 kcal/mol). We also made molecular dynamics simulations for the best six systems and explored their structural stability (RMSD), Cα fluctuations (RMSF), intermolecular hydrogen bond interactions, effect of solvent accessibility (SASA) and compactness (Rg) factors. Satisfactory ADMET and druglikeness features were found for all these compounds and we therefore strongly propose the initiation of trial studies on these compounds for fighting SARS-CoV-2.</jats:p

An Infrequent Adenosarcoma Mimicking other Uterine Rhabdoid Tumours

Uterine sarcomas are relatively rare and account for only 1-3% of all malignancies in the Female Genital Tract (FGT). Adenosarcomas of the uterus are uncommon accounting for only 5% of uterine sarcomas. They are considered less recurrent and less metastatic. However, those with sarcomatous overgrowth and heterologous differentiation are very rare, considered aggressive and need to be differentiated histologically from other sarcomas that mimic the same clinically and histologically. In the index case, a 50-year-old female presented with symptoms of pain in the abdomen and bleeding per vagina. Magnetic Resonance Imaging (MRI) showed a large polypoid solid mass in the endometrium, suggestive of a sarcoma. Positron Emission Tomography (PET) scan showed an Fluorodeoxyglucose (FDG) avid lesion in the endometrial cavity (SUV max-13.33). Total abdominal hysterectomy and salpingooophorectomy was performed. Histology showed a biphasic tumour (benign glands and malignant mesenchymal component) with rhabdomyoblastic differentiation and sarcomatous overgrowth. Presence of rhabdoid cells raises the possibility of other sarcomas with these features making the diagnosis challenging. Immunohistochemistry (IHC) confirmed it to be a high grade adenosarcoma with sarcomatous overgrowth. Desmin positivity was noted in the rhabdoid cells. Majority cases of adenosarcoma are low grade, the index case was however high grade with presence of heterologous elements and sarcomatous overgrowth. Neither radiology nor clinical features can reliably differentiate adenosarcomas from other uterine sarcomas. A definitive diagnosis can be made by understanding the overlapping morphological features and correlate it with IHC to reliably differentiate it with other similar looking uterine sarcomas.</jats:p

Comparative Pharmacognostic and Phytochemical Analysis of Three Market Samples of Rasna: Pluchea lanceolata, Alpinia officinarum, and Alpinia calcarata: Comparative analysis of Rasan types from Raw material market

Introduction: Ayurveda, an ancient system of medicine, utilizes a vast array of medicinal plants, each offering unique therapeutic properties that contribute to holistic health and well-being. However, misidentification of species is most common which comes in the way of authenticity. To cite an example - Pluchea lanceolata when mixed with varieties of Alpinia can lead to inconsistencies in their medicinal use. This underscores the need for accurate identification and standardization to ensure the efficacy of treatments and the safety of stakeholders. This research paper explores the botanical and medicinal profiles of Pluchea lanceolata, Alpinia calcarata, and Alpinia officinarum, emphasizing the importance of proper classification and the need for quality control in Ayurvedic herbal remedies. Materials and Methods: Raw materials were collected from Thrissur market and organoleptic, pharmacognostic and phytochemical analysis were done. Results and Discussion: Three varieties of Rasna (Pluchea lanceolata, Alpinia calcarata, and Alpinia officinarum) share common physical characteristics, such as scaly, rough rhizomes that are fibrous and tough, making them suitable for drying, grinding, or slicing (for medicinal use.) All three species exhibit starch grains, fibers, and stone cells in their rhizomes, contributing to energy storage, structural support, and resilience. Pluchea lanceolata has the highest total ash content, indicating a richer mineral composition, while A. calcarata and A. officinarum show lower mineral content. All three species contain phenols, sugars, carbohydrates, flavonoids, glycosides, steroids, and other bioactive compounds, contributing to their therapeutic properties. Conclusion: Standardization in preparation and use of Ayurvedic remedies is critical for preserving the integrity of Ayurveda, ensuring reliable therapeutic benefits, and positioning Ayurvedic medicine as a credible and effective global health solution