Human mass balance study of TAS-102 using (14)C analyzed by accelerator mass spectrometry.

BACKGROUND: TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite. TPI inhibits degradation of FTD by TP, increasing systemic exposure to FTD. METHODS: Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0-1) were enrolled on this study. Patients in group A (N = 4) received 60 mg TAS-102 with 200 nCi [(14)C]-FTD, while patients in group B (N = 4) received 60 mg TAS-102 with 1000 nCi [(14)C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h and were analyzed for (14)C by accelerator mass spectrometry and analytes by LC-MS/MS. RESULTS: FTD: 59.8% of the (14)C dose was recovered: 54.8% in urine mostly as FTY and FTD glucuronide isomers. The extractable radioactivity in the pooled plasma consisted of 52.7% FTD and 33.2% FTY. TPI: 76.8% of the (14)C dose was recovered: 27.0% in urine mostly as TPI and 49.7% in feces. The extractable radioactivity in the pooled plasma consisted of 53.1% TPI and 30.9% 6-HMU, the major metabolite of TPI. CONCLUSION: Absorbed (14)C-FTD was metabolized and mostly excreted in urine. The majority of (14)C-TPI was recovered in feces, and the majority of absorbed TPI was excreted in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide an enhanced understanding of the TAS-102 elimination profile.

A multicenter study of key stakeholders' perspectives on communicating with surrogates about prognosis in intensive care units.

RATIONALE: Surrogates of critically ill patients often have inaccurate expectations about prognosis. Yet there is little research on how intensive care unit (ICU) clinicians should discuss prognosis, and existing expert opinion-based recommendations give only general guidance that has not been validated with surrogate decision makers. OBJECTIVE: To determine the perspectives of key stakeholders regarding how prognostic information should be conveyed in critical illness. METHODS: This was a multicenter study at three academic medical centers in California, Pennsylvania, and Washington. One hundred eighteen key stakeholders completed in-depth semistructured interviews. Participants included 47 surrogates of adult patients with acute respiratory distress syndrome; 45 clinicians working in study ICUs, including physicians, nurses, social workers, and spiritual care providers; and 26 experts in health communication, decision science, ethics, family-centered care, geriatrics, healthcare disparities, palliative care, psychology, psychiatry, and critical care. MEASUREMENTS AND MAIN RESULTS: There was broad support among surrogates for existing expert recommendations, including truthful prognostic disclosure, emotional support, tailoring the disclosure strategy to each family's needs, and checking for understanding. In addition, stakeholders offered suggestions that add specificity to existing recommendations, including: (1) In addition to conveying prognostic estimates, clinicians should help families "see the prognosis for themselves" by showing families radiographic images and explaining the clinical significance of physical manifestations of severe disease at the bedside. (2) Many physicians did not support using numeric estimates to convey prognosis to families, whereas many surrogates, clinicians from other disciplines, and experts believed numbers could be helpful. (3) Clinicians should conceptualize prognostic communication as an iterative process that begins with a preliminary mention of the possibility of death early in the ICU stay and becomes more detailed as the clinical situation develops. (4) Although prognostic information should be initially disclosed by physicians, other members of the multidisciplinary team-nurses, social workers, and spiritual care providers-should be given explicit role responsibilities to reinforce physicians' prognostications and help families process a poor prognosis emotionally. CONCLUSIONS: Family members, clinicians, and experts identified specific communication behaviors that clinicians should use to discuss prognosis in the critical care setting. These findings extend existing opinion-based recommendations and should guide interventions to improve communication about prognosis in ICUs.

Nurse-led intervention to improve surrogate decision making for patients with advanced critical illness.

BACKGROUND: Problems persist with surrogate decision making in intensive care units, leading to distress for surrogates and treatment that may not reflect patients' values. OBJECTIVES: To assess the feasibility, acceptability, and perceived effectiveness of a multifaceted, nurse-led intervention to improve surrogate decision making in intensive care units. STUDY DESIGN: A single-center, single-arm, interventional study in which 35 surrogates and 15 physicians received the Four Supports Intervention, which involved incorporating a family support specialist into the intensive care team. That specialist maintained a longitudinal relationship with surrogates and provided emotional support, communication support, decision support, and anticipatory grief support. A mixed-methods approach was used to evaluate the intervention. RESULTS: The intervention was implemented successfully in all 15 patients, with a high level of completion of each component of the intervention. The family support specialist devoted a mean of 48 (SD 36) minutes per day to each clinician-patient-family triad. All participants reported that they would recommend the intervention to others. At least 90% of physicians and surrogates reported that the intervention (1) improved the quality and timeliness of communication, (2) facilitated discussion of the patient's values and treatment preferences, and (3) improved the patient-centeredness of care. CONCLUSIONS: The Four Supports Intervention is feasible, acceptable, and was perceived by physicians and surrogates to improve the quality of decision making and the patient-centeredness of care. A randomized trial is warranted to determine whether the intervention improves patient, family, and health system outcomes.