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).

Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker-Induced Angioedema.

Angioedema occurring in the head and neck region is a rare and sometimes life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI-induced angioedema (ACEI-AE) or ARB-induced angioedema (ARB-AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI-AE, ARB-AE, and 658 controls) was performed using exome-enriched sequence data. A common variant of the F5 gene that causes an increase in blood clotting (rs6025, p.Arg506Gln, also called factor V Leiden), was significantly associated with both ACEI-AE and ARB-AE (odds ratio: 2.85, 95% confidence interval (CI), 1.89-4.25). A burden test analysis of five rare missense variants in F5 was also found to be associated with ACEI-AE or ARB-AE, P = 2.09 × 10-3 . A combined gene risk score of these variants, and the common variants rs6025 and rs6020, showed that individuals carrying at least one variant had 2.21 (95% CI, 1.49-3.27, P = 6.30 × 10-9 ) times the odds of having ACEI-AE or ARB-AE. The increased risk due to the common Leiden allele was confirmed in a genome-wide association study from the United States. A high risk of angioedema was also observed for the rs6020 variant that is the main coagulation defect-causing variant in black African and Asian populations. We found that deleterious missense variants in F5 are associated with an increased risk of ACEI-AE or ARB-AE.

Intention, beliefs and mood assessed using electronic diaries predicts attendance at cardiac rehabilitation: An observational study.

BACKGROUND: Cardiac rehabilitationis effective in promoting physical/psychological recovery following acute coronary syndrome. Yet, rates of attendance at outpatient cardiac rehabilitation by eligible patients are low. OBJECTIVES: This study examined the determinants of attendance at outpatient cardiac rehabilitation in acute coronary syndrome patients following discharge until cardiac rehabilitation commencement. DESIGN: A weekly electronic diary measured cardiac-related cognitions and mood and examined their relation to attendance at outpatient cardiac rehabilitation. SETTINGS: Three United Kingdom National Health Service secondary care settings in two Health Board areas in Scotland. PARTICIPANTS: Acute coronary syndrome patients were recruited from March 2012 to June 2013 prior to hospital discharge. Of 488 eligible patients referred for cardiac rehabilitation, 214 consented. METHODS: Consecutive patients completed a pre-hospital discharge questionnaire targeting age, diagnosis, social class and smoking history. Acute coronary syndrome patients then completed a weekly electronic diary from the first week of discharge until the start of cardiac rehabilitation. Multilevel structural equation models estimated the effects of initial, i.e. baseline and rate of change in cardiac-related cognition and mood on attendance. Intention to attend cardiac rehabilitation was reflected, log transformed, reported thereafter as "do not intend". The role of "do not intend" was explored as a mediator of the relationship between cardiac-related cognition and mood on attendance. RESULTS: 166 participants provided, on average, 5 weeks of diary entries before cardiac rehabilitation commenced. High intention (i.e. low "do not intend") to attend CR and its rate of increase over time predicted attendance. Low negative emotional representation, high perceived necessity, high confidence in maintaining function, low negative affect, and high positive affect following discharge predicted attendance at cardiac rehabilitation. The rate of change in cardiac-related mood and these cognitions was not predictive. Baseline and rate of change in "do not intend" entirely mediated relationships between a) perceived necessity, b) negative affect and attendance at cardiac rehabilitation. CONCLUSIONS: Negative affect in the first weeks following discharge represents the key challenge to a patient maintaining their intention to attend cardiac rehabilitation. Intervention to improve attendance should focus on improving intention to attend following discharge and during recovery by improving patient understanding of cardiac rehabilitation and reducing negative affect.

'Just not for me' - contributing factors to nonattendance/noncompletion at phase III cardiac rehabilitation in acute coronary syndrome patients: a qualitative enquiry.

AIMS AND OBJECTIVES: To explore what reasons do nonattenders and noncompleters give for their patterns of participation or nonparticipation in cardiac rehabilitation programmes and how future uptake could be enhanced. BACKGROUND: Cardiac rehabilitation is a cost-effective clinical intervention designed for adults with acute coronary syndrome. Despite evidence from meta-analyses demonstrating that cardiac rehabilitation programmes facilitate physical and psychological recovery from acute coronary syndrome, only 20-50% of eligible patients attend Phase III outpatient programmes. DESIGN: A qualitative study using thematic analysis. METHOD: Within the context of a larger mixed-method study, acute coronary syndrome patients were recruited between 2012-2014 from three hospitals in Scotland. Of 214 patients who consented to enrol in the main study, a purposive subsample of 25 participants was recruited. Semi-structured interviews were conducted and analysed using thematic analysis. RESULTS: Three major influences of participation were identified: (1) personal factors, (2) programme factors and (3) practical factors. In addition, valuable suggestions for future programme modifications were provided. A significant barrier to attending cardiac rehabilitation programmes is that participants perceived themselves to be unsuitable for the programme alongside a lack of knowledge and/or misconceptions regarding cardiac rehabilitation. CONCLUSION: The responses of nonattenders and noncompleters revealed misconceptions related to programme suitability, the intensity of exercise required and the purpose of a cardiac rehabilitation programme. As long as these misconceptions continue to persist in coronary syndrome patients, this will impact upon attendance. The lack of perceived need for cardiac rehabilitation stems from a poor understanding of the programme, especially among nonattenders and noncompleters and subsequently an inability to comprehend possible benefits. RELEVANCE TO CLINICAL PRACTICE: The knowledge of common misconceptions puts clinical nurses in a better position to identify and pro-actively address these erroneous assumptions in their patients in order to improve participation in cardiac rehabilitation.

Promoting participation in cardiac rehabilitation: patient choices and experiences.

BACKGROUND: Cardiac rehabilitation can be an effective means for the secondary prevention of coronary heart disease, but a majority of eligible individuals fail to attend or drop out prematurely. Little research has examined patients' decisions about attendance. AIMS: This paper reports a study examining patients' beliefs and decision-making about cardiac rehabilitation attendance. METHODS: A purposive sample of patients from a mixed urban-rural region of Scotland was studied in 2001 using focus groups. Those who were eligible for a standardized 12-week cardiac rehabilitation programme were compared, with separate focus groups held for individuals with high attendance (>60% attendance; n = 27), high rates of attrition (<60% attendance; n = 9) and non-attendance (0% attendance; n = 8). A total of 44 patients (33 men; 11 women) took part in eight focus groups. RESULTS: Participants from all groups held sophisticated and cohesive frameworks of beliefs that influenced their attendance decisions. These beliefs related to the self, coronary heart disease, cardiac rehabilitation, other attending patients, and health professionals' knowledge base. An enduring embarrassment about group or public exercise also influenced attendance. Those who attended reported increased faith in their bodies, a heightened sense of fitness and a willingness to support new patients who attended. CONCLUSIONS: Reassurance to ease exercise embarrassment should be given before and during the early stages of programmes, and this could be provided by existing patients. Strategies to promote inclusion should address the inhibiting factors identified in the study, and should present cardiac rehabilitation as a comprehensive programme of activities likely to be of benefit to the individual irrespective of personal characteristics, such as age, sex or exercise capacity.

"The whole truth" versus "the admissible truth": an ethics dilemma for expert witnesses.

The expert witness testifies under oath to tell "the whole truth," yet certain aspects of the legal system itself make this ideal difficult or impossible. The authors present both a philosophical and a practical discussion of the challenges for the expert in attaining this goal. After review of oaths in general and truth-telling in particular, real-life examples are provided to examine the vicissitudes of the whole truth in court. Recommendations are provided for experts, to preserve the truth in the adversary system.