The Effect of Warfarin Administration Time on Anticoagulation Stability (INRange): A Pragmatic Randomized Controlled Trial.

PURPOSE: Without supporting evidence, clinicians commonly recommend that warfarin be taken in the evening. We conducted a randomized controlled trial to evaluate the effect of administration time (morning vs evening) on the stability of warfarin's anticoagulant effect. METHODS: A total of 236 primary care physicians serving 54 western Canadian communities mailed letters of invitation to all their warfarin-using patients. Eligible patients were community-dwelling warfarin users (any indication) with at least 3 months of evening warfarin use and no plans for discontinuation. Participants were randomized (by web-based allocation) to morning vs continued evening warfarin ingestion. We used the Rosendaal method to determine the proportion of time within therapeutic range (TTR) of the international normalized ratio (INR) blood test month 2 to 7 postrandomization vs the 6 months prerandomization. The primary outcome was the percent change in proportion of time outside target INR range (with an a priori minimum clinically important difference of ±20%). All analyses were intention to treat. RESULTS: Between March 8, 2015 and September 30, 2016, we randomized 109 participants to morning and 108 to evening warfarin use. TTR rose from 71.8% to 74.7% in the morning group, and from 72.6% to 75.6% in the evening group, for a change in TTR of 2.9% in the former vs 3.0% in the latter (difference, -0.1%; P = .97; 95% CI for the difference, -6.1% to 5.9%). The difference in percent change in proportion of time outside the therapeutic INR range (obtained via Hodges-Lehmann estimation of the difference in medians) was 4.4% (P = .62; 95% CI for the difference, -17.6% to 27.3%). CONCLUSIONS: Administration time has no statistically significant nor clinically important impact on the stability of warfarin's anticoagulant effect. Patients should take warfarin whenever regular compliance would be easiest.

Assessing the metabolic and clinical consequences of early enteral feeding in the malnourished patient.

BACKGROUND: It is often thought that enteral feeding should be initiated slowly in those who are severely malnourished. This descriptive study examined the effect of an enteral feeding protocol on the typical metabolic consequences seen in refeeding syndrome. METHODS: A retrospective chart review was conducted on 51 patients who had been placed on hospital-wide enteral feeding and electrolyte replacement protocols over a 9-month period to determine whether there were any negative clinical consequences to early feeding. RESULTS: Goal feeding rate was achieved within 17.6 +/- 8.7 hours. Forty patients (80%) developed depletions in phosphate, magnesium, or potassium after initiation of enteral feeding, including 93% of those deemed "at risk" and 74% of those "not at risk." All patients received electrolyte replacement according to protocols, and no patients showed any negative clinical effect. CONCLUSIONS: This study showed that malnourished patients at risk for refeeding syndrome can be fed early without observed negative clinical consequences. An electrolyte replacement protocol may be an effective means of minimizing the electrolyte imbalances associated with early feeding. It also demonstrated the significance of applying such protocols to all patients requiring enteral support, as current methods of assessing "risk"for refeeding syndrome may be inadequate.