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.

Effect of medication timing on anticoagulation stability in users of warfarin (the INRange RCT): study protocol for a randomized controlled trial.

BACKGROUND: Warfarin is an oral anticoagulant medication that disrupts the liver's production of clotting factors. While this medication is highly effective for the prevention of thromboembolic events, it also has a narrow therapeutic range and a vulnerability to interactions with other drugs and vitamin K-containing foods. Warfarin is commonly ingested at dinnertime, the same time of day that dietary vitamin K consumption (found largely in green leafy vegetables) is most variable. While the long half-life of warfarin might make this irrelevant, the ultra short half-life of vitamin K and the possibility of a hepatic first-pass effect for warfarin make it worth evaluating whether morning ingestion of warfarin, when vitamin K levels are consistently low, leads to greater stability of its anticoagulant effect. An examination of the timing of administration on the effectiveness of warfarin has never before been conducted. METHODS/DESIGN: This is a 7-month Prospective Randomized Open Blinded End-point (PROBE) study in which established evening warfarin users (primary care managed Canadian outpatients in the provinces of British Columbia and Alberta) will be randomized to either switch to morning ingestion of warfarin (the intervention) or to continue with evening use (the control). The primary outcome is the percent change in the proportion of time spent outside the therapeutic range of the international normalized ratio (INR) blood test. Secondary outcomes include change in proportion of time spent within the therapeutic INR range (TTR), percentage of patients with TTR >75 %, percentage of patients with TTR <60 %, and major warfarin-related cardiovascular events (including all-cause mortality, hospitalization for stroke, hospitalization for GI bleeding, and deep venous thrombosis/pulmonary embolism). We will also compare whether day-to-day variability in the consumption of high vitamin K-containing foods at baseline affects the baseline TTR in this cohort of evening warfarin users. DISCUSSION: This study addresses whether the timing of warfarin ingestion influences the stability of its anticoagulant effect. Should morning ingestion prove superior, the safety and effectiveness of this medication, and hence the prevention of stroke, pulmonary embolus, and major hemorrhage, could potentially be improved with no added cost or inconvenience to the patient. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02376803 . Registered on 25 February 2015.

Access to dietitians in primary health care.

Primary health care aims to provide timely treatment of serious illness, teach health promotion, and maintain health for patients with chronic diseases. In partnership with the primary care network at Vancouver Coastal Health (VCH), family physicians (FPs), and dietitians, this practice needs assessment was undertaken to explore how VCH could support access to primary care nutrition services. Both qualitative and quantitative approaches were used. Data from two focus groups, one for dietitians and the other for physicians, were compiled and formed the questions for the survey. The data were analyzed using the inductive approach, to consider the messages or themes that appeared from the focus groups and the survey. A review of information from the focus groups, surveys, and literature revealed four common themes of findings: accessibility, collaboration in chronic disease management, health promotion, and information sharing. Sixty-six percent of FPs perceived that primary health nutrition services were fair to poor. Both dietitian and physician groups recognized that collaboration in the areas of chronic diseases and health promotion was essential, and that sharing of information among providers could improve this service.

Self-management and biomedical outcomes of a cooking, and exercise program for patients with chronic kidney disease.

BACKGROUND: Limited research has been done on integrating cooking and exercise classes into the routine care of chronic kidney disease (CKD) patients. The main purpose of the research was to determine whether the addition of these services would slow the progression of certain CKD parameters. METHODS: The study evaluated 5 endpoints, at baseline, 6 months, and 12 months: urinary protein, blood pressure, urinary sodium, glomerular filtration rate, and total cholesterol between 2 groups (control group receiving CKD standard care and experimental group receiving standard care plus cooking and exercise classes). Eighty percent of the experimental group was hypothesized to improve in 4 out of the 5 endpoints versus ≤50% in the control group with a P-value of 0.05. An overall difference of 30% was anticipated between the 2 groups. The research also compared self-efficacy and health status outcomes using a self-management questionnaire. RESULTS: Forty randomly assigned patients participated in the study (17 controls and 23 experimental). In the control group, 2 of 17 people improved in at least 4 of the 5 endpoints. In the experimental group, 14 of 23 people improved in at least 4 of the 5 endpoints. CONCLUSIONS: Sixty-one percent of experimental subjects showed improvements in 4 of 5 endpoints, showing a significant difference overall when compared with the control group (12% improved in 4 out of 5 endpoints). In looking at the trend in qualitative measures from the comparison of the self-management questionnaire, the overall trend showed more improved answers with the experimental group versus the control group.

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.