Outcomes from hematopoietic stem cell transplantation following treosulfan-based conditioning: A clinical and pharmacokinetic analysis.

BACKGROUND: The aims of this study are to report our experience with treosulfan-based conditioning regimens for patients with non-malignant hematologic conditions, correlating clinical outcomes at different time points post-transplant with treosulfan exposure (AUC). METHODS: This study was a single-center observational study investigating overall survival (OS), disease-free survival (DFS), and event-free survival (EFS) end-points post-transplant. The consequences of treosulfan AUC with respect to toxicity, correction of underlying disease, and long-term chimerism were also explored using pharmacokinetic analysis. RESULTS: Forty-six patients received 49 transplants with treosulfan and fludarabine-based conditioning between 2005 and 2023. Twenty-four patients also received thiotepa. Donor chimerism was assessed on either whole blood or sorted cell lines at different time points post-transplant. Thirty-nine patients received treosulfan pharmacokinetic assessment to evaluate cumulative AUC, with five infants receiving real-time assessment to facilitate daily dose adjustment. OS, DFS, and EFS were 87%, 81%, and 69%, respectively. Median follow-up was 32.1 months (range 0.82-160 months) following transplant. Lower EFS was associated with patient age (<1 year; p = .057) and lower cumulative treosulfan dose (<42 g/m2; p = .003). Stable donor chimerism in B-cell, NK-cell, and granulocyte lineages at 1-year post-transplant were more prevalent in patients receiving thiotepa conditioning. Two infants required daily dose adjustment to treosulfan to avoid high AUC. CONCLUSIONS: Excellent clinical outcomes and stable chimerism were observed in this patient series. The addition of thiotepa conferred no significant toxicity and trended toward sustained ongoing donor engraftment. Correlating treosulfan AUC with long-term patient outcomes is required.

Impact of Repeated Reimbursement Penalties on Hospital Total Quality Scores.

OBJECTIVES: The incidence of hospital-acquired conditions (HACs) is a serious public health issue with implications ranging from patient morbidity and mortality to negative financial impacts on patients and health care systems. Despite substantial efforts to address and reduce HACs, research into the effect of quality improvement programs is inconclusive. This study seeks to better understand the relationship between repeated reimbursement penalties and improvement in HAC quality scores. METHODS: A quantitative comparative analysis of U.S. health care data was conducted. Data on quality outcomes and hospital characteristics were sourced from the Hospital-Acquired Condition Reduction Program from fiscal years 2018 and 2019 and the Centers for Medicare & Medicaid Services Inpatient Prospective Payment System impact files, respectively. RESULTS: In total, 3123 U.S. hospitals were analyzed to compare differences between total HAC scores of hospitals with and without penalties in consecutive years. Hospitals with repeated penalties had significantly greater improvement in scores ( t497.262 = -13.00, P < 0.001), and the impact was greatest in small hospitals (<100 beds). Repeated penalties had a smaller impact on disproportionate share hospitals (Cohen d = 0.73). Among all hospitals, the effect of repeated penalties was large (Cohen d = 0.75). CONCLUSIONS: This study suggests that repeated penalties can improve quality scores in U.S. hospitals. However, the effect may be exaggerated for smaller hospitals and those that serve patient populations with a relatively higher socioeconomic status. The reason disproportionate share hospitals did not show as much improvement as nondisproportionate hospitals may be because hospitals serving vulnerable populations often have fewer resources.

Interplay between core and peripheral chirality in polyethers.

A chiral-base mediated reaction has been used to synthesise the polyethers illustrated and their enantiomers; CD spectroscopy revealed that the homochiral isomers A may be viewed as a C3-symmetric arrangement of fixed paddles while the heterochiral isomers B form a C3-symmetric arrangement of rotating paddles.