First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.

Colorectal cancer (CRC) constitutes the second leading cause of cancer-related death worldwide and advanced CRCs are resistant to targeted therapies, chemotherapies and immunotherapies. p38α (Mapk14) has been suggested as a therapeutic target in CRC; however, available p38α inhibitors only allow for insufficient target inhibition. Here we describe a unique class of p38α inhibitors with ultralong target residence times (designated ULTR-p38i) that robustly inhibit p38α downstream signaling and induce distinct biological phenotypes.

Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies.

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

Provincial Intra-Action Review of the COVID-19 Vaccination Programme: Opportunities to Improve Vaccine Response in North Kivu, Democratic Republic of Congo.

Background: Low levels of COVID-19 vaccination coverage in many countries prompted the use of rapid assessments to characterize barriers to vaccination and identify corrective measures. The World Health Organization recommended the use of intra-action reviews (IARs) to identify best practices, gaps, and lessons learned to make real-time improvements to the COVID-19 vaccination response.

Objective: The Democratic Republic of the Congo (DRC) implemented a national IAR in July 2021 that was poorly attended by the provincial health level, where vaccination activities are planned and implemented.

COVID-19 Vaccination Coverage - World Health Organization African Region, 2021-2023.

With the availability of authorized COVID-19 vaccines in early 2021, vaccination became an effective tool to reduce COVID-19-associated morbidity and mortality. Initially, the World Health Organization (WHO) set an ambitious target to vaccinate 70% of the global population by mid-2022. However, in July 2022, WHO recommended that all countries, including those in the African Region, prioritize COVID-19 vaccination of high-risk groups, including older adults and health care workers, to have the greatest impact on morbidity and mortality.

Global VAX: A U.S. contribution to global COVID-19 vaccination efforts, 2021-2023.

In December 2021 the U.S. Government announced a new, whole-of-government $1.