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.

Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial.

BACKGROUND: Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. METHODS: Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including microRNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. DISCUSSION: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia. TRIAL REGISTRATION: ISRCTN, ISRCTN90094835 . Registered on 18 February 2015.

Construction of a linked health and social care database resource--lessons on process, content and culture.

BACKGROUND: Combining routinely collected health and social care data on older people is essential to advance both service delivery and research for this client group. Little data is available on how to combine health and social care data; this article provides an overview of a successful data linkage process and discusses potential barriers to executing such projects. METHODS AND RESULTS: We successfully obtained and linked data on older people within Dundee from three sources: Dundee Social Work Department database (30,000 individuals aged 65 years and over), healthcare data held on NHS Tayside patients by the Health Informatics Centre (400,000 individuals), Dundee, and the Dundee of Medicine for the Elderly rehabilitation database (4300 individuals). Data were linked, anonymized and transferred to a Safe Haven environment to ensuring confidentiality and strict access control. Challenges were faced around workflows, culture and documentation. Exploiting the resultant data set raises further challenges centered on database documentation, understanding the way data were collected, dealing with missing data, data validity and collection at different time periods. CONCLUSION: Routinely collected health and social care data sets can be linked, but significant process barriers must be overcome to allow successful linkage and integration of data and its full exploitation.

Effect of vitamin D supplementation on orthostatic hypotension: data from the vitamin D in isolated systolic hypertension randomized controlled trial.

OBJECTIVE: Orthostatic hypotension commonly accompanies supine hypertension, and is associated with low 25-hydroxyvitamin D levels. We tested whether high-dose intermittent oral vitamin D therapy could ameliorate orthostatic hypotension in older patients with isolated systolic hypertension. METHODS: We conducted a subgroup analysis of data from a parallel-group, double-blind, randomized, placebo-controlled trial. Patients aged over 70 years with supine office SBP above 140 mmHg and DBP below 90 mmHg received 100 000 units oral vitamin D3 or matching placebo every 3 months for 1 year. Office supine and standing blood pressure were measured at baseline, and 3, 6, 9 and 12 months, along with arterial stiffness and flow-mediated dilatation of the brachial artery. RESULTS: Of 159 patients randomized to the main trial, 75 patients with orthostatic hypotension at baseline were included in this analysis. The mean age was 78 (SD 5) years, baseline blood pressure was 162/76 mmHg and the mean baseline orthostatic fall in blood pressure on standing was 32/5 mmHg. After adjustment for baseline age, 25-hydroxyvitamin D, SBP and orthostatic fall, the fall in SBP was less in the vitamin D group at 3 months [treatment effect 6 mmHg, 95% confidence interval (CI) 0 to 12], but repeated-measures analysis showed no significant treatment effect (3 mmHg for systolic fall, 95% CI -1 to 8; 1 mmHg for diastolic fall, 95% CI -1 to 3). CONCLUSION: Twelve months of intermittent, high-dose oral vitamin D3 did not significantly improve orthostatic hypotension in older patients with isolated systolic hypertension.

Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial.

IMPORTANCE: Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension. No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension, the most common pattern of hypertension in older people. OBJECTIVE: To test whether high-dose, intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension. DESIGN: Parallel group, double-blind, placebo-controlled randomized trial. SETTING: Primary care clinics and hospital clinics. PARTICIPANTS: Patients 70 years and older with isolated systolic hypertension (supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg) and baseline 25-hydroxyvitamin D levels less than 30 ng/mL were randomized into the trial from June 1, 2009, through May 31, 2011. INTERVENTIONS: A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year. MAIN OUTCOMES AND MEASURES: Difference in office blood pressure, 24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, insulin resistance, and b-type natriuretic peptide level during 12 months. RESULTS: A total of 159 participants were randomized (mean age, 77 years). Mean baseline office systolic blood pressure was 163/78 mm Hg. Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P < .001). No significant treatment effect was seen for mean (95% CI) office blood pressure (−1 [−6 to 4]/−2 [−4 to 1] mm Hg at 3 months and 1 [−2 to 4]/0 [−2 to 2] mm Hg overall treatment effect). No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance). There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P = .24). CONCLUSIONS AND RELEVANCE: Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN92186858.

Examining autonomy's boundaries: a follow-up review of perinatal mortality cases in UK independent midwifery.

BACKGROUND: An earlier matched cohort study in the United Kingdom found a significantly higher perinatal mortality rate for births booked under an independent midwife compared with births in National Health Service units (1.7% [25/1,508] vs 0.6% [45/7,366]). This study examined independent midwives' management and decision making in the 15 instances of perinatal death that occurred at term. METHODS: Thematic analysis of independent midwives' case notes was performed in instances of perinatal mortality. Semi-structured interviews were conducted with the midwives concerned. RESULTS: Home birth was attempted in 13 of the 15 cases. Significant (often multiple) antenatal risk factors were identified in 13 cases, including twin pregnancy, planned vaginal births after cesarean section, breech presentations, and maternal illness. Several women had declined some or all routine antenatal screening. Three deaths occurred before labor onset. Postmortem results were known in only four cases; many causes of death remained unexplained. Professional consensus was that seven deaths were unpreventable; elective cesarean section may have changed the outcome in eight cases. However, the pregnant women had declined this option; some were reported to be avoiding National Health Service care because of previous bad experiences. Transfer to hospital care, when it occurred, was often problematic. Care management was judged to be clinically acceptable within the parameters set by the mothers' choices. CONCLUSIONS: Information about clinical processes (and outcomes) is essential if informed decisions are to be made. The women in this review had reportedly accepted the potential consequences of their high-risk situations. If reality is to match rhetoric about "patient" autonomy, such decision making in high-risk situations must be accepted.

Outcomes for births booked under an independent midwife and births in NHS maternity units: matched comparison study.

OBJECTIVE: To compare clinical outcomes between women employing an independent midwife and comparable pregnant women using NHS services. DESIGN: Anonymised matched cohort analysis. Cases from the database of the Independent Midwives' Association (IMA) matched up to 1:5 with Scottish National Health Service (NHS) records for age, parity, year of birth, and socioeconomic status. Multivariable logistic regression models used to explore the relation between explanatory variables and outcomes; analyses controlled for potential confounding factors and adjusted for stratification. SETTING: UK databases 2002-5. PARTICIPANTS: Anonymised records for 8676 women (7214 NHS; 1462 IMA). MAIN OUTCOME MEASURES: Unassisted vertex delivery, live birth, perinatal death, onset of labour, gestation, use of analgesia, duration of labour, perineal trauma, Apgar scores, admission to neonatal intensive care, infant feeding. RESULTS: IMA cohort mothers were significantly more likely to achieve an unassisted vertex delivery than NHS cohort mothers (77.9% (1139) v 54.3% (3918); odds ratio 3.49, 95% confidence interval 2.99 to 4.07) but also significantly more likely to experience a stillbirth or a neonatal death (1.7% (25) v 0.6% (46); 5.91, 3.27 to 10.7). All odds ratios are adjusted for confounding factors. Exclusion of "high risk" cases from both cohorts showed a non-significant difference (0.5% (5) v 0.3% (18); 2.73, 0.87 to 8.55); the "low risk" IMA perinatal mortality rate is comparable with other studies of low risk births. Women in the IMA cohort had a higher incidence of pre-existing medical conditions (1.5% (22) v 1.0% (72) in the NHS cohort) and previous obstetric complications (21.0% (307) v 17.8% (1284)). The incidence of twin pregnancy was also higher (3.4% (50) v 3.1% (224)). In the IMA cohort, 66.0% of mothers (965/1462) had home births, compared with only 0.4% of NHS cohort mothers (27/7214). Spontaneous onset of labour was more common in the IMA group (96.6% (1405) v 74.5% (5365); 10.43, 7.74 to 14.0), and fewer mothers used pharmacological analgesia (40.2% (588) v 60.6% (4370); 0.42, 0.38 to 0.47). Mothers in the IMA cohort were much more likely to breast feed (88.0% (1286) v 64.0% (2759); 3.46, 2.84 to 4.20). Prematurity (4.3% (63) v 6.9% (498); 0.49, 0.35 to 0.69), low birth weight (4.0% (60) v 7.1%) (523); 0.93, 0.62 to 1.38), and rate of admission to neonatal intensive care (4.4% (65) v 9.3% (667); 0.43, 0.32 to 0.59) were all higher in the NHS dataset. CONCLUSIONS: Healthcare policy tries to direct patient choice towards clinically appropriate and practicable options; nevertheless, pregnant women are free to make decisions about birth preferences, including place of delivery and staff in attendance. While clinical outcomes across a range of variables were significantly better for women accessing an independent midwife, the significantly higher perinatal mortality rates for high risk cases in this group indicate an urgent need for a review of these cases. The significantly higher prematurity and admission rates to intensive care in the NHS cohort also indicate an urgent need for review.

A study to evaluate nurse-led on-treatment review for patients undergoing radiotherapy for head and neck cancer.

AIMS AND OBJECTIVES: To evaluate a nurse-led clinic for patients undergoing radiotherapy to the head and neck. BACKGROUND: The side effects of radiotherapy to the head and neck are superimposed on already significant physical and psychological morbidity. Medical review clinics tend to focus on treatment complications and there is evidence that specialist nurses can provide more holistic care for patients. However, doubts have been raised about the appropriateness of nurse-led review in this highly symptomatic and complex group. DESIGN: This evaluation compared medical on-treatment review (Phase 1) with a nurse-led clinic (Phase 2) for patients having radiotherapy to the head and neck, using an historical control group. METHODS: Twenty patients were reviewed by their consultant and 23 by a nurse specialist, using a clinic protocol. A mixed-method approach to data collection was taken. Patients completed weekly quality of life questionnaires and were asked about their experiences of support and care. General practitioners completed a questionnaire about the communication received from the clinic. Checklists assessed the content of clinic consultations. RESULTS: Patients valued the relationship developed with the nurse specialist, had longer, more frequent consultations and were more often referred to the multidisciplinary team. The nurse specialist managed 83% of consultations without referral to the consultant. Few significant differences in quality of life were found between the groups. There were indications that oral and nutritional problems were managed more effectively in the nurse-led clinic, although emotional functioning was higher in the medical group. GPs were positive about the timing and content of information received. CONCLUSIONS: On-treatment review for patients with head and neck cancer can be effectively managed by a nurse specialist. Relevance to Practice. Radiotherapy nurse specialists make an important contribution to the supportive care of patients with head and neck cancer. More investment is required to maximize their contribution.

An approximate Bayesian risk-analysis for the gastro-intestinal safety of ibuprofen.

PURPOSE: Although several studies on ibuprofen and its gastro-intestinal (GI) risk have been reported, the dose-response relationship was not clear due to the lack of information regarding high-dose exposure. Analysis using Bayesian methods is appropriate whenever data are sparse, although such methods are not easily implemented. METHODS: A retrospective cohort study to assess this dose-response relationship was carried out using a record linkage database. A Bayesian risk-analysis was conducted using the Bayesian bootstrap approximation. Risks of GI events at different dose levels were compared using the posterior distributions and the number of events predicted to occur in the future was estimated. Risk factors such as age, gender and co-morbidity were adjusted for in the analysis. This approximation was compared with the full Bayesian approach using the usual but more computer-intensive tool of Markov Chain Monte Carlo simulation. RESULTS: There were 1, 5 and 10 complicated GI events during exposure to high, medium and low dose ibuprofen with 0.2, 1.8 and 7.0 thousand person-years (PY) exposure, respectively. After adjusting for other risk factors the relative risks of high versus low and medium versus low doses were 6.3 (95% CI = 0.21, 24.17) and 2.5 (95% CI = 0.71, 5.85), respectively. Using the approximate Bayesian method prediction of the number of events in a population of females aged 50-59 with no previous medical problems with 1000 PY drug exposure showed that the estimated probability of having more than five events was 0.048 for the medium-dose group and 0.14 for the high-dose group. CONCLUSIONS: High dose ibuprofen appears to have a considerably greater risk of having a larger number of adverse GI events than a medium dose. The approximate Bayesian bootstrap method was demonstrated to be a robust and easily implemented alternative to the full Bayesian approach to risk analysis whenever data are sparse.