Work absenteeism, disability, and lost wages among patients with acute myeloid leukemia and their caregivers: a cohort study using US administrative claims and productivity data.

OBJECTIVE: We describe the impact of acute myeloid leukemia (AML) diagnosis on workplace absenteeism and disability days among patients and their caregivers. METHODS: This retrospective study included adults with newly diagnosed AML (2009-2019) and adult caregivers of patients with newly diagnosed AML, identified from the US Merative™ MarketScan® Commercial Database. The Merative MarketScan Health and Productivity Management Database provided linked patient-level records of workplace absence and short-term (STD) and long-term disability (LTD) data. Endpoints included workplace absence, STD and LTD for patients and caregivers during 12 months pre-AML (baseline) and ≤3 years' follow-up, and corresponding cost of work loss. RESULTS: Patient workplace absence decreased in the months post-AML diagnosis, but the number of STD and LTD leave days claimed increased significantly by sixfold and fourfold, respectively. The proportion of patients making STD leave claims increased within 4-5 months of diagnosis, while the proportion making LTD leave claims increased significantly starting from month 5. Caregiver workplace absence peaked in the first 2 months post-diagnosis and remained elevated versus baseline throughout the study. CONCLUSION: AML diagnosis leads to workplace absenteeism and increased economic burden for patients with AML and their caregivers.

Impact of COVID-19 on patient and healthcare professional attitudes, beliefs, and behaviors toward the healthcare system and on the dynamics of the healthcare pathway.

BACKGROUND: COVID-19 has dramatically changed how healthcare is delivered and experienced. METHODS: One-on-one interviews and a virtual ethnographic roundtable were conducted among 45 patients, caregivers, and healthcare professionals (HCPs) in 4 therapeutic areas from the United States and Japan: overactive bladder, vasomotor symptoms, prostate cancer, and metastatic urothelial carcinoma. The goal was to identify the impact of COVID-19 on patient/caregiver and HCP attitudes, interactions, beliefs, and behaviors toward the healthcare system and care pathway. RESULTS: Four foundational themes were identified: 1) COVID-19 risk is relative; 2) isolation is collateral damage; 3) telehealth is a parallel universe; and 4) COVID-19 is destabilizing the foundations of healthcare. Numerous insights, influenced by diverse cultural, social, and psychological factors, were identified within each theme. CONCLUSIONS: The impacts of COVID-19 were noticeable at multiple points of care during the "universal" care pathway, including at initial screening, referral to specialists, diagnosis, treatment initiation/surgery, and during ongoing care. Greater appreciation of the short- and long-term impacts of COVID-19 and resulting gaps in care may act as a catalyst for positive change in future patient care.

Competition between intramolecular hydrogen bonds and solvation in phosphorylated peptides: simulations with explicit and implicit solvent.

The atomic-level mechanisms of protein regulation by post-translational phosphorylation remain poorly understood, except in a few well-studied systems. Molecular mechanics simulations can in principle be used to help understand and predict the effects of protein phosphorylation, but the accuracy of the results will of course depend on the quality of the force field parameters for the phosphorylated residues as well as the quality of the solvent model. The phosphorylated residues typically carry a -2 charge at physiological pH; however, the effects of phosphorylation can sometimes be mimicked by substituting Asp or Glu for the phosphorylated residue. Here we examine the suitability of explicit and implicit solvent models for simulating phospho-serine in both the -1 and -2 charge states. Specifically, we simulate a capped phosphorylated peptide, Ace-Gly-Ser-pSer-Ser-Nme, and compare the results to each other and to experimental observables from an NMR experiment. The first major conclusion is that explicit water models (TIP3P, TIP4P and SPC/E) and a Generalized Born implicit solvent model provide reasonable agreement with the experimental observables, given appropriate partial charges for the phosphate group. The Generalized Born results, however, show greater hydrogen bonding propensity than the explicit solvent results. Distance dependent dielectric treatments perform poorly. The second major conclusion is that many ensemble-averaged properties obtained for the phosphopeptide in the -1 and -2 charge states are strikingly similar; the -1 species has a slightly higher propensity to form internal hydrogen bonds. All of the results can be rationalized by quantifying the strength of the P-O/H-N hydrogen bond, which depends on a sensitive balance between strongly favorable charge/dipole and dipole/dipole interactions and strongly unfavorable desolvation.