Automated Optimization of a Multistep, Multiphase Continuous Flow Process for Pharmaceutical Synthesis.

Flow synthesis is becoming increasingly relevant as a sustainable and safe alternative to traditional batch processes, as reaction conditions that are not usually achievable in batch chemistry can be exploited (for example, higher temperatures and pressures). Telescoped continuous reactions have the potential to reduce waste by decreasing the number of separate unit operations (e.g.

Evaluation of gadolinium-based contrast agents in juvenile CD-1 mice including behavioral evaluations.

Introduction: Seven gadolinium-based contrast agents (GBCAs), four linear and three macrocyclic, were evaluated for potential effects on development, including behavior of juvenile CD-1 mice.

Methods: The GBCAs were administered via intravenous injection once daily on postnatal day (PND) 9, 12, 15, 18, and 21 (PND 1 was the day of delivery) at doses up to twice the human equivalent clinical dose (i.e.

Evaluation of gadolinium-based contrast agents in pregnant CD-1 mice and subsequent in utero exposure of the developing offspring, including behavioral evaluations.

Introduction: The offspring of CD-1 mice exposed during pregnancy to one of seven gadolinium-based contrast agents (GBCAs) were evaluated for potential effects on postnatal development and behavior. The GBCAs, comprising four linear (gadopentetate dimeglumine, gadodiamide, gadobenate dimeglumine, and gadoxetate disodium) and three macrocyclic (gadoterate meglumine, gadoteridol, and gadobutrol), were administered via intravenous injection once daily from Gestation Day 6 through 17 following confirmed mating (Day 0) at doses of at least twice the human equivalent recommended clinical dose (i.e.

Burden of serious harms from diagnostic error in the USA.

Background: Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts.

Objective: We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence.

COVID-19 clinical outcomes by patient disability status: A retrospective cohort study.

Background: People with disabilities might experience worse clinical outcomes of SARS-CoV-2 infection, but evidence is limited.

Objective: To investigate if people with disabilities requiring assistance are more likely to experience severe COVID-19 or death.

Methods: Data from the Johns Hopkins COVID-19 Precision Medicine Analytics Platform Registry (JH-CROWN) included 6494 adult patients diagnosed with COVID-19 and admitted between March 4, 2020-October 29, 2021.