2 research outputs found
Development of BloodâBrain Barrier Permeable Nitrocatechol-Based Catechol <i>O</i>âMethyltransferase Inhibitors with Reduced Potential for Hepatotoxicity
Recent efforts have been focused
on the development of centrally
active COMT inhibitors, which can be valuable assets for neurological
disorders such as Parkinsonâs disease, due to the severe hepatotoxicity
risk associated with tolcapone. New nitrocatechol COMT inhibitors
based on naturally occurring caffeic acid and caffeic acid phenethyl
ester were developed. All nitrocatechol derivatives displayed potent
inhibition of peripheral and cerebral COMT within the nanomolar range.
Druglike derivatives <b>13</b>, <b>15</b>, and <b>16</b> were predicted to cross the bloodâbrain barrier in vitro and were significantly less toxic than tolcapone and entacapone when
incubated at 50 ÎŒM with rat primary hepatocytes. Moreover, their
unique acidity and electrochemical properties decreased the chances
of formation of reactive quinone-imines and, as such, the potential
for hepatotoxicity. The binding mode of <b>16</b> confirmed
that the major interactions with COMT were established via the nitrocatechol
ring, allowing derivatization of the side chain for future lead optimization
efforts
Table_1_Increasing and sustaining blood-borne virus screening in Spain and Portugal throughout the COVID-19 pandemic: a multi-center quality improvement intervention.DOCX
BackgroundAround 57,000 people in Spain and Portugal currently living with HIV or chronic hepatitis C are unaware of their infection. The COVID-19 pandemic severely disrupted screening efforts for these infections. We designed an intervention to increase and sustain opportunistic blood-borne virus (BBV) screening and linkage to care (SLTC) by implementing the TEST model.MethodsThe Plan Do Study Act (PDSA) method of quality improvement (QI) was implemented in 8 healthcare organizations (HCOs), including four hospitals, two clusters of community health centers, and two community-based organizations (CBOs). Baseline assessment included a review of BBV SLTC practices, testing volume, and results 12 months before the intervention. Changes in BBV testing rates over time were measured before, during, and after the COVID-19 lockdowns in 2020. A mixed ANOVA model was used to analyze the possible effect on testing volumes among HCOs over the three study periods.InterventionBBV testing was integrated into normal clinical flow in all HCOs using existing clinical infrastructure and staff. Electronic health record (EHR) systems were modified whenever possible to streamline screening processes, implement systemic institutional policy changes, and promote QI.ResultsTwo years after the launch of the intervention in screening practices, testing volumes increased by 116%, with formal healthcare settings recording larger increases than CBOs. The start of the COVID-19 lockdowns was accompanied by a global 60% decrease in testing in all HCOs. Screening emergency department patients or using EHR systems to automate screening showed the highest resilience and lowest reduction in testing. HCOs recovered 77% of their testing volume once the lockdowns were lifted, with CBOs making the fullest recovery. Globally, enhanced screening techniques enabled HCOs to diagnose a total of 1,860 individuals over the research period.ConclusionsImplementation of the TEST model enabled HCOs to increase and sustain BBV screening, even during COVID-19 lockdowns. Although improvement in screening was noted in all HCOs, additional work is needed to develop strong patient linkage to care models in challenging times, such as global pandemics.</p