Piper crocatum Ruiz & Pav (P. crocatum) has been reported to accelerate the diabetic wound healing process empirically. Some studies showed the benefits of P. crocatum in treating various diseases but its mechanisms in diabetic wound healing have never been reported. In the present study we investigated the diabetic wound healing activity of the active fraction of P. crocatum on wounded hyperglycemia fibroblasts (wHFs). Bioassay-guided fractionation was performed to get the most active fraction. The selected active fraction was applied to wHFs within 72 h incubation. Mimicking a diabetic condition was done using basal glucose media containing an additional 17 mMol/L D-glucose. A wound was simulated via the scratch assay. The collagen deposition was measured using Picro-Sirius Red and wound closure was measured using scratch wound assay. Underlying mechanisms through p53, αSMA, SOD1 and E-cadherin were measured using western blotting. We reported that F_IV is the most active fraction of P. crocatum. We confirmed that F_IV\(7.81 µg/ml, 15.62 µg/ml, 31.25 µg/ml, 62.5 µg/ml, and 125 µg/ml) induced the collagen deposition and wound closure of wHFs. Furthermore, F_IV treatment (7.81 µg/ml, 15.62 µg/ml, 31.25 µg/ml) down-regulated the protein expression level of p53 and up-regulated the protein expression levels of αSMA, E-cadherin, and SOD1. Our findings suggest that ameliorating collagen deposition and wound closure through protein regulation of p53, αSMA, E-cadherin, and SOD1 are some of the mechanisms by which F_IV of P. crocatum is involved in diabetic wound healing therapy.

Introductions Therapy switches in patients with multiple sclerosis (MS) receiving treatment with fingolimod occur frequently in clinical practice but are not well represented in real-world data. The aim of this study was to identify and characterize treatment switches and reveal sociodemographic/clinical changes over time in fingolimod-treated people with MS (PwMS). Methods Data on 2536 fingolimod-treated PwMS extracted from the German MS Registry during different time periods were analyzed (2010–2019). Results Overall, 28.3% of PwMS were treatment-naïve before fingolimod initiation. Interferon beta (30.7%) was the most common pre-fingolimod treatment. Ocrelizumab (19.8%) was the most frequent subsequent treatment in the 944 patients on fingolimod who switched. Between 2010 and 2019, median disease duration at fingolimod initiation decreased from 8.5 to 7.1 years (p < 0.001), and patients taking fingolimod for ≥ 1 year after treatment initiation decreased from 89.6 to 80.5% (p < 0.001). Females (p < 0.001) and young patients (p = 0.003) showed a shorter time on fingolimod. The most frequent reason for switching was disease activity (relapse/MRI) despite treatment. The annualized relapse rate increased from 0.37 in patients on fingolimod to 0.47 after treatment cessation, decreasing to 0.19 after treatment with a subsequent disease-modifying drug (DMD) was initiated. Conclusion Treatment switches from fingolimod to subsequent DMDs currently occur after shorter treatment durations than 10 years ago, possibly due to the growing treatment spectrum. Planning adequate washout periods is essential and should be done on an individualized basis.

The tailored immunomodulatory treatment strategy for secondary progressive multiple sclerosis (SPMS) depends on disease activity. To assess the real-world situation in monitoring disease activity in SPMS patients and to identify associations of resulting subgroups with demographics, symptomatology, and therapy METHODS: This study included 4,263 SPMS patients from the German MS register (GMSR). For the classification into 'active' and 'inactive' according to relapse activity and MRI findings during the year prior to the latest clinical visit, we used the following definitions: active - gadolinium enhancing (Gd+)/new T2 lesions or ≥1 relapse, inactive - neither Gd+/new T2 lesions nor relapses. The active, inactive, and unclassifiable patients were compared in terms of clinical data, socio-demographics, symptomatology, healthcare, and DMT. Classification was possible for 1,513 (35.5%) SPMS patients, with 467 classified as active and 1,046 as inactive. For the classification, MRI data was available for 33.2% of the 4,263 patients. Higher MRI frequencies were observed for younger patients (OR 1.22 [1.12,1.33] per 10 years) with short disease duration (OR 1.19 [1.09, 1.30] per 10 years) (p < 0.001). MRI coverage was low, especially in elderly SPMS patients. Roughly one third of the SPMS patients presented markers of disease activity in the last year. Overall, the clinical differences (concerning symptomatology and care) between patients with active and inactive SPMS were small.

Regulatory authorities have encouraged the usage of a monitoring (RBM) system in clinical trials before trial initiation for detection of potential risks and inclusion of a mitigation plan in the monitoring strategy. Several RBM tools were developed after the International Council for Harmonization gave sponsors the flexibility to initiate an approach to enhance quality management in a clinical trial. However, various studies have demonstrated the need for improvement of the available RBM tools as each does not provide a comprehensive overview of the characteristics, focus, and application.

Despite protection from severe COVID-19 courses through vaccinations, some people with multiple sclerosis (PwMS) are vaccination-hesitant due to fear of post-vaccination side effects/increased disease activity. The aim was to reveal the frequency and predictors of post-SARS-CoV-2-vaccination relapses in PwMS. This prospective, observational study was conducted as a longitudinal Germany-wide online survey (baseline survey and two follow-ups). Inclusion criteria were age ≥18 years, MS diagnosis, and ≥1 SARS-CoV-2 vaccination. Patient-reported data included socio-demographics, MS-related data, and post-vaccination phenomena. Annualized relapse rates (ARRs) of the study cohort and reference cohorts from the German MS Registry were compared pre- and post-vaccination. Post-vaccination relapses were reported by 9.3% PwMS (247/2661). The study cohort’s post-vaccination ARR was 0.189 (95% CI: 0.167–0.213). The ARR of a matched unvaccinated reference group from 2020 was 0.147 (0.129–0.167). Another reference cohort of vaccinated PwMS showed no indication of increased post-vaccination relapse activity (0.116; 0.088–0.151) compared to pre-vaccination (0.109; 0.084–0.138). Predictors of post-vaccination relapses (study cohort) were missing immunotherapy (OR = 2.09; 1.55–2.79; p < 0.001) and shorter time from the last pre-vaccination relapse to the first vaccination (OR = 0.87; 0.83–0.91; p < 0.001). Data on disease activity of the study cohort in the temporal context are expected for the third follow-up.

Background: The globalization of clinical research should also benefit the population in developing markets. In this context, the approval of tested medicines and the associated expansion of medical care beyond clinical studies would be desirable as a possible long-term benefit. Objectives: This study was designed to compare the development of the number of clinical trials with the number of marketing authorizations of medicines on the African continent. To contrast these 2 parameters, the data were analyzed using the model of an ecological study. Methods: To reflect the broad spectrum of African developing countries with diverse levels of development, the data collection was based on 2 geographically selected sample countries each from Central, North, East, West, and Southern Africa. Based on the ClinicalTrials.gov registry, the first step was to collect trends data on the development of the clinical trials in the 10 selected countries of the country list of the African Region published by the World Health Organization for the period 2015 to 2018. Subsequently, data on the current number of marketing authorizations of medicines in the selected sample countries were identified using the online registries of the national authorities. The data were utilized in comparative analyses. Results: Eight out of 10 model countries showed an increase in the number of clinical trials, with the exceptions of Cameroon and Libya, which showed an overall decline in research activity over the entire time. In direct comparison with drug registrations, the numbers indicate a similar development. The only exception here is Nigeria, a country with a solid performance in clinical research and yet a decrease in medicine registrations since 2015. Conclusions: The expected increase in the development of clinical research as result of the globalization trend can basically be observed in most of the model countries. However, this increase does not guarantee an improvement in the number of medicine registrations. Although this is evident in some of the selected model countries, it cannot be projected to the entire African region. This may be linked to the diverse development of the individual countries due to the different political situations and the varying degrees of clinical research infrastructure. ( Curr Ther Res Clin Exp . 2022; 82:XXX-XXX) (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )