Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

BACKGROUND: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 µg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).

Effect of two different participant information sheets on recruitment to a falls trial: An embedded randomised recruitment trial.

BACKGROUND/AIMS: Recruitment to trials of intervention for older people who fall is challenging. Evidence suggests that the word falls has negative connotations for older people, and this may present a barrier to engaging with trials in this area. We therefore tested whether a participant information sheet that minimised reference to falls could improve recruitment rates. METHODS: We conducted a study within a trial, embedded within a randomised controlled trial of vitamin K versus placebo to improve postural sway in patients aged 65 and over with a history of falls. Potential participants were identified from primary care lists in 14 practices and were randomised to receive either a standard participant information sheet or an information sheet minimising use of the word falls, instead focussing on maintenance of health, fitness and balance. The primary outcome for this embedded trial was the proportion of responses expressing interest in participating received in each arm. Secondary outcomes were the proportion of those contacted attending a screening visit, consenting at screening, and the proportion contacted who were randomised into the main trial. RESULTS: In all, 4145 invitations were sent, with an overall response rate of 444 (10.7%). In all, 2148 individuals received the new information sheet (minimising reference to falls); 1997 received the standard information sheet. There was no statistically significant difference in response rate between those individuals sent the new information sheet and those sent the standard information sheet (10.1% vs 11.4%; difference 1.3% (95% confidence interval -0.6% to 3.2%); p = 0.19). Similarly, we found no statistically significant difference between the percentage of those who attended and consented at screening in the two groups (2.1% vs 2.7%; difference 0.6% (95% confidence interval: -0.4% to 1.6%); p = 0.20), and no statistically significant difference between the percentage randomised in the two groups (2.0% vs 2.6%; difference 0.6% (95% confidence interval -0.4% to 1.6%); p = 0.20). CONCLUSIONS: Use of a participant information sheet minimising reference to falls did not lead to a greater response rate in this trial targeting older people with a history of falls.

Effect of Vitamin K2 on Postural Sway in Older People Who Fall: A Randomized Controlled Trial.

OBJECTIVES: Vitamin K is thought to be involved in both bone health and maintenance of neuromuscular function. We tested the effect of vitamin K2 supplementation on postural sway, falls, healthcare costs, and indices of physical function in older people at risk of falls. DESIGN: Parallel-group double-blind randomized placebo-controlled trial. SETTING: Fourteen primary care practices in Scotland, UK. PARTICIPANTS: A total of 95 community-dwelling participants aged 65 and older with at least two falls, or one injurious fall, in the previous year. INTERVENTION: Once/day placebo, 200 µg or 400 µg of oral vitamin K2 for 1 year. MEASUREMENTS: The primary outcome was anteroposterior sway measured using sway plates at 12 months, adjusted for baseline. Secondary outcomes included the Short Physical Performance Battery, Berg Balance Scale, Timed Up & Go Test, quality of life, health and social care costs, falls, and adverse events. RESULTS: Mean participant age was 75 (standard deviation [SD] = 7) years. Overall, 58 of 95 (61%) were female; 77 of 95 (81%) attended the 12-month visit. No significant effect of either vitamin K2 dose was seen on the primary outcome of anteroposterior sway (200 µg vs placebo: -.19 cm [95% confidence interval [CI] -.68 to .30; P = .44]; 400 µg vs placebo: .17 cm [95% CI -.33 to .66; P = .50]; or 400 µg vs 200 µg: .36 cm [95% CI -.11 to .83; P = .14]). Adjusted falls rates were similar in each group. No significant treatment effects were seen for other measures of sway or secondary outcomes. Costs were higher in both vitamin K2 arms than in the placebo arm. CONCLUSION: Oral vitamin K2 supplementation did not improve postural sway or physical function in older people at risk of falls. J Am Geriatr Soc 67:2102-2107, 2019.

Validation of an individualised quality of life measure in older day hospital patients.

BACKGROUND: To test the ease of use, reliability, responsiveness and construct validity of the Patient Generated Index, an individualised quality of life score, in older people attending a Medicine for Older People Day Hospital. METHODS: Prospective longitudinal study in patients attending a specialist Medicine for Older People Day Hospital in Scotland. The Patient Generated Index was administered at baseline, one week later, and at the end of Day Hospital attendance. Functional Limitations Profile, Hospital Anxiety and Depression Score, Barthel index and global subjective impressions of change were also collected and compared with baseline scores and change in Patient Generated Index scores. Reliability was assessed using intraclass correlation coefficients in subjects reporting no change in global quality of life; responsiveness was assessed using effect size and Guyatt coefficients in subjects reporting change in global quality of life. External validity was assessed via correlation with measures of physical function, comorbid disease and psychological state. RESULTS: 75 patients were enrolled, mean age 81 years. Mean completion time was 5.0 minutes at baseline. Reliability was moderate (intraclass correlation coefficient 0.72) but there were weak and inconsistent responses to change (effect sizes 0.02 to 0.15; Guyatt responsiveness coefficient 0.29). Patient Generated Index scores correlated with Functional Limitation Profile scores (r = 0.51, p < 0.001), baseline anxiety score (r = -0.25, P = 0.039) and baseline depression score (r = -0.37, P = 0.002) but displayed only weak, non-significant correlation with number of comorbid diseases (r = -0.22, P = 0.07), number of medications (r = -0.21, P = 0.08) and Barthel score (r = 0.09, p = 0.45). CONCLUSION: The Patient Generated Index appears moderately reliable and easy to complete, but is poorly responsive to change, limiting its usefulness in clinical practice or research.

Efficacy and cost of an exercise program for functionally impaired older patients with heart failure: a randomized controlled trial.

BACKGROUND: Little is known about the optimum way to deliver exercise to older, functionally impaired patients with heart failure. We tested whether an exercise program tailored to the needs of these patients could improve exercise capacity and quality of life or reduce costs to the National Health Service. METHODS AND RESULTS: The study design was a parallel-group, single-blind, randomized controlled trial. Patients aged ≥70 years with symptomatic heart failure and left ventricular systolic dysfunction were randomized to either 24 weeks of exercise training or usual care. Six-minute walk distance was the primary outcome; markers of physical function, quality of life, health status, and daily activity were measured at baseline and 8 and 24 weeks. Carer strain and healthcare costs were also recorded. A total of 107 participants were randomized (mean age, 80 years; men, 72 [67%]). Six-minute walk distance did not improve compared to that of the control group at 8 weeks (-16.9 m; 95% CI, -41.8 to 7.9 m; P=0.18) or at 24 weeks (-5.3 m; 95% CI, -32.6 to 22.0 m; P=0.70). For secondary outcomes, only the sit-to-stand test improved significantly at 24 weeks (-6.4 s; 95% CI, -12.2 to 0.6 s; P=0.03); there was no difference in change for the Minnesota Living With Heart Failure score (0.1 points; 95% CI, -0.9 to 1.1 points; P=0.83) at 24 weeks. Carer strain did not decrease at 24 weeks (difference, -0.5 points; 95% CI, -8.3 to 7.3 points; P=0.80), and there was no difference in overall healthcare costs. CONCLUSIONS: This exercise intervention did not improve exercise capacity or quality of life in older patients with heart failure and was not cost saving to the National Health Service. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN51615566.