FdCyd

We evaluated the definitions of five comorbidities (renal and hepatic impairments, anemia, neutropenia, and thrombocytopenia) in women with breast cancer using data from electronic health records.

In 11,097 women receiving adjuvant chemotherapy for stage I-IIIA breast cancer at Kaiser Permanente Northern California or Kaiser Permanente Washington, we assessed comorbidity definitions in two commonly used lookback windows (1 year before diagnosis, T1; and extending until chemotherapy initiation, T1-2). Within each, we assessed data availability and agreement between International Classification of Diseases (ICD)–defined and lab-defined comorbidities of varying severity. To assess how different pieces of information may affect providers in making treatment decisions, we used multivariable logistic regression to evaluate four-category (with comorbidity indicated by both ICD and lab, ICD-only, lab-only, or neither) and collapsed binary (comorbidity indicated by either ICD or lab v neither) definitions in relation to first cycle chemotherapy dose reduction (FCDR).

Extending the lookback period to chemotherapy initiation increased laboratory data availability (missingness ≤4.1% in T1-2 v >40% in T1). Assessment of agreement guided selection of laboratory cutpoints. In both time periods, the four-category and binary comorbidity variables were associated with use of FCDR, but binary variables had larger cell sizes and more stability of regression models. Ultimately, the comorbidity variables in T1 were defined by a combination of either ICD/qualifying laboratory values. Results were similar in T1-2, except laboratory data alone outperformed the combination variable for renal and hepatic comorbidity.

Leveraging both ICD and lab data and extending the lookback period to include postdiagnosis but prechemotherapy initiation may provide better capture of comorbidity. Future studies may consider validating our findings with a gold-standard comorbidity status and in other community health care settings.

Fluorinated nucleosides are well-established as anticancer and antiviral medications.As with many pharmaceuticals, the effects of fluorine modifications are often only partially understood.In this work, the effects of 5-fluorination of the cytosine nucleobase on the structures and glycosidic bond stabilities of the protonated canonical DNA and RNA cytidine nucleosides (dCyd and Cyd) are examinedIR multiple photon dissociation action spectroscopy experiments and electronic structure calculations are employed to probe the structural influences of 5-fluorination.Spectral signatures in the IR fingerprint and hydrogen-stretching regions indicate that 5-fluorination heavily directs for and solely produces O2 protonation para to the 5-fluoro substituent.This differs from the canonical cytidine nucleosides where roughly equal populations of O2 and N3 protonated structures were observedEnergy-resolved collision-induced dissociation experiments combined with survival yield analyses are performed to probe the influence of 5-fluorination on glycosidic bond stability.Trends in the energy-dependence of the survival yield curves indicate that 5-fluorination weakens the glycosidic bond, and that the influence of 5-fluorination on glycosidic bond stability is much greater for dCyd than Cyd.Theory also finds that 5-fluorination weakens the glycosidic bond but predicts that the influence of 5-fluorination on N-glycosidic bond stability is roughly the same for dCyd and Cyd.Oh, what a difference the 2′-hydroxy substituent makes