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.</p

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 &amp; 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.</p

‘She would wash the patients as if she was scrubbing a dirty plate in the sink’: Exploring nursing students experiences of care delivery

Background While much is known about nursing students' clinical placement experiences in general, less has been reported about their specific encounters with poor care delivery. A few small-scale qualitative studies have been undertaken, which suggest that nursing students do witness poor care but often decide not to act on what they see. This study sought to explore a wider international perspective on this issue. Aims To explore nursing students' experiences of the care delivery practices witnessed during clinical placements and to provide descriptions of poor care. Setting and participants Nursing students from undergraduate pre-registration nursing programmes across three universities, two in the United Kingdom (UK) and one in Australia. Design and analysis A qualitative/quantitative survey design was utilised, and data were descriptively analysed. Results Two hundred and sixty-five students participated in the study. Overall the results were positive. Nevertheless, the participants did provide multiple and recurring examples of poor nursing care which related to a lack of compassion, poor communication, unkind and indifferent provision of personal care, and patient safety. Reporting of poor care was viewed as difficult and many participants highlighted potential repercussions should they take this course of action. Conclusion This research provides contemporary international insights into care delivery practices from the perspective of a large number of nursing students. The results, although mainly positive, outline multiple examples of poor and ineffective practice. While the precise prevalence of these remains unknown, educators, practitioners and students should consider how best to address them when they occur

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)

Endogenous Urotensin II Selectively Modulates Erectile Function through eNOS

Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway.Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 µM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II-induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 µM) in human corpus cavernosum strips. Finally, a co-immunoprecipitation study demonstrated that UT receptor and eNOS co-immunoprecipitate following U-II challenge of human corpus cavernosum tissue.U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts