4 research outputs found
Key Topics on End-of-Life Care for African Americans
Racial classifications of human populations are politically and socially determined. There is no biological or genetic basis for these racial classifications. Health behaviors may be influenced by culture and poverty. Disparities in health outcomes, sometimes resulting in higher mortality rates for African-Americans appear to influence end of life decision-making attitudes and behaviors. To improve the quality of end of life care in African-American communities, health care professionals must better understand and work to eliminate disparities in health care, increase their own skills, knowledge and confidence in palliative and hospice care, and improve awareness of the benefits and values of hospice and palliative care in their patients and families
Synthesis of Akt Inhibitor Ipatasertib. Part 2. Total Synthesis and First Kilogram Scale-up
Herein,
the first-generation process to manufacture Akt inhibitor
Ipatasertib through a late-stage convergent coupling of two challenging
chiral components on multikilogram scale is described. The first of
the two key components is a <i>trans</i>-substituted cyclopentylpyrimidine
compound that contains both a methyl stereocenter, which is ultimately
derived from the enzymatic resolution of a simple triester starting
material, and an adjacent hydroxyl group, which is installed through
an asymmetric reduction of the corresponding cyclopentylpyrimidine
ketone substrate. A carbonylative esterification and subsequent Dieckmann
cyclization sequence was developed to forge the cyclopentane ring
in the target. The second key chiral component, a β<sup>2</sup>-amino acid, is produced using an asymmetric aminomethylation (Mannich)
reaction. The two chiral intermediates are then coupled in a three-stage
endgame process to complete the assembly of Ipatasertib, which is
isolated as a stable mono-HCl salt
Synthesis of Akt Inhibitor Ipatasertib. Part 2. Total Synthesis and First Kilogram Scale-up
Herein,
the first-generation process to manufacture Akt inhibitor
Ipatasertib through a late-stage convergent coupling of two challenging
chiral components on multikilogram scale is described. The first of
the two key components is a <i>trans</i>-substituted cyclopentylpyrimidine
compound that contains both a methyl stereocenter, which is ultimately
derived from the enzymatic resolution of a simple triester starting
material, and an adjacent hydroxyl group, which is installed through
an asymmetric reduction of the corresponding cyclopentylpyrimidine
ketone substrate. A carbonylative esterification and subsequent Dieckmann
cyclization sequence was developed to forge the cyclopentane ring
in the target. The second key chiral component, a β<sup>2</sup>-amino acid, is produced using an asymmetric aminomethylation (Mannich)
reaction. The two chiral intermediates are then coupled in a three-stage
endgame process to complete the assembly of Ipatasertib, which is
isolated as a stable mono-HCl salt
Risk of COVID-19 after natural infection or vaccinationResearch in context
Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health