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Surgeons perceive that some surgical transfers are futile, but the incidence and risk factors of futile transfer are not quantified. Identifying futile interfacility transfers could save cost and undue burdens to patients and families. We sought to describe the incidence and factors associated with futile transfers. We conducted a retrospective cohort study from 2009 to 2013 including patients transferred to a tertiary referral center for general or vascular surgical care. Futile transfers were defined as resulting in death or hospice discharge within 72 hours of transfer without operative, endoscopic, or radiologic intervention. One per cent of patient transfers were futile (27/1696). Characteristics of futile transfers included older age, higher comorbidity burden and illness severity, vascular surgery admission, Medicare insurance, and surgeon documentation of end-stage disease as a factor in initial decision-making. Among futile transfers, 82 per cent were designated as do not resuscitate (vs 9% of nonfutile, P < 0.01), and 59 per cent received a palliative care consult (vs 7%, P < 0.01). A small but salient proportion of transferred patients undergo deliberate care de-escalation and early death or hospice discharge without intervention. Efforts to identify such patients before transfer through improved communication between referring and accepting surgeons may mitigate burdens of transfer and facilitate more comfortable deaths in patients' local communities.
Valacyclovir, the L-valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], approximately 15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h dosing interval (AUC(tau)) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF.