Effect of vitamin D supplementation on blood pressure:a systematic review and meta-analysis incorporating individual patient data

D-PRESSURE Collaboration: et al.[Importance]: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.[Objective]: To systematically review whether supplementation with vitamin D or its analogues reduce BP.[Data Sources]: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.[Study Selection]: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.[Data Extraction and Synthesis]: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.[Main Outcomes and Measures]: Difference in SBP and DBP measured in an office setting.[Results]: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.[Conclusions and Relevance]: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.Peer reviewe

Discovering the Relationship Between Investor Attention and Trade Volume in the Philippine Stock Exchange Using Google Search Analysis

This study investigates the relationship between daily Google search volume and trade volume in the Philippine Stock Exchange. This is completed by employing a sample consisting of listed stocks in the Philippine Stock Exchange from 2015 to 2019 and testing the veracity of three different keyword categories in proxying investor attention. The empirical results indicate that when using company names and stock tickers as Google search keywords, there is a strong positive relationship between Google search volume and trade volume. This implies that the more investors search for a stock’s company name or ticker, the more likely that there will be an increase in that stock’s trade volume the following day. Additionally, this study finds evidence that when using stock tickers as Google search keywords, aggregate investor sentiment can influence this relationship, such that it is more significant during periods of high consumer confidence. The findings support the notion that daily Google search volume can measure investor attention and potentially serve as a supplementary stock indicator for retail investors in the Philippine Stock Exchange

Discovering the Link between Investor Attention and Trade Volume in the Philippine Stock Exchange

Investors regard trade volume as a crucial technical indicator that can confirm trends, predict trend reversals, and determine liquidity (Westerhoff, 2006; Mahender et al., 2014). Trade volume is reported throughout the current trading day as often as once an hour; however, the reported hourly and end-of-the-day trade volumes are merely estimates. Actual and final trade volumes are reported the following day. Given the relative inconsistency of reported trade volumes and uncertainty of future trade volumes, investors miss the opportunity to reinforce their trading decisions through the trade volume indicator

Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo.

BACKGROUND: The low-density lipoprotein (LDL) receptor gene family is a highly conserved group of membrane receptors with diverse functions in developmental processes, lipoprotein trafficking, and cell signaling. The low-density lipoprotein (LDL) receptor-related protein 1b (LRP1B) was reported to be deleted in several types of human malignancies, including non-small cell lung cancer. Our group has previously reported that a distal extracellular truncation of murine Lrp1b that is predicted to secrete the entire intact extracellular domain (ECD) is fully viable with no apparent phenotype. METHODS AND PRINCIPAL FINDINGS: Here, we have used a gene targeting approach to create two mouse lines carrying internally rearranged exons of Lrp1b that are predicted to truncate the protein closer to the N-terminus and to prevent normal trafficking through the secretary pathway. Both mutations result in early embryonic lethality, but, as expected from the restricted expression pattern of LRP1b in vivo, loss of Lrp1b does not cause cellular lethality as homozygous Lrp1b-deficient blastocysts can be propagated normally in culture. This is similar to findings for another LDL receptor family member, Lrp4. We provide in vitro evidence that Lrp4 undergoes regulated intramembraneous processing through metalloproteases and gamma-secretase cleavage. We further demonstrate negative regulation of the Wnt signaling pathway by the soluble extracellular domain. CONCLUSIONS AND SIGNIFICANCE: Our results underline a crucial role for Lrp1b in development. The expression in mice of truncated alleles of Lrp1b and Lrp4 with deletions of the transmembrane and intracellular domains leads to release of the extracellular domain into the extracellular space, which is sufficient to confer viability. In contrast, null mutations are embryonically (Lrp1b) or perinatally (Lrp4) lethal. These findings suggest that the extracellular domains of both proteins may function as a scavenger for signaling ligands or signal modulators in the extracellular space, thereby preserving signaling thresholds that are critical for embryonic development, as well as for the clear, but poorly understood role of LRP1b in cancer

Recurrent delirium over 12 months predicts dementia: results of the Delirium and Cognitive Impact in Dementia (DECIDE) study.

BACKGROUND: Delirium is common, distressing and associated with poor outcomes. Previous studies investigating the impact of delirium on cognitive outcomes have been limited by incomplete ascertainment of baseline cognition or lack of prospective delirium assessments. This study quantified the association between delirium and cognitive function over time by prospectively ascertaining delirium in a cohort aged ≥ 65 years in whom baseline cognition had previously been established. METHODS: For 12 months, we assessed participants from the Cognitive Function and Ageing Study II-Newcastle for delirium daily during hospital admissions. At 1-year, we assessed cognitive decline and dementia in those with and without delirium. We evaluated the effect of delirium (including its duration and number of episodes) on cognitive function over time, independently of baseline cognition and illness severity. RESULTS: Eighty two of 205 participants recruited developed delirium in hospital (40%). One-year outcome data were available for 173 participants: 18 had a new dementia diagnosis, 38 had died. Delirium was associated with cognitive decline (-1.8 Mini-Mental State Examination points [95% CI -3.5 to -0.2]) and an increased risk of new dementia diagnosis at follow up (OR 8.8 [95% CI 1.9-41.4]). More than one episode and more days with delirium (>5 days) were associated with worse cognitive outcomes. CONCLUSIONS: Delirium increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition, with more episodes associated with worse cognitive outcomes. Given that delirium has been shown to be preventable in some cases, we propose that delirium is a potentially modifiable risk factor for dementia

Developing an Intervention for Fall-Related Injuries in Dementia (DIFRID): an integrated, mixed-methods approach

Background Falls in people with dementia can result in a number of physical and psychosocial consequences. However, there is limited evidence to inform how best to deliver services to people with dementia following a fall. The aim of the DIFRID study was to determine the feasibility of developing and implementing a new intervention to improve outcomes for people with dementia with fall-related injuries; this encompasses both short-term recovery and reducing the likelihood of future falls. This paper details the development of the DIFRID intervention. Methods The intervention was designed using an integrated, mixed-methods approach. This involved a realist synthesis of the literature and qualitative data gathered through interviews and focus groups with health and social care professionals (n=81). An effectiveness review and further interviews and observation were also conducted and are reported elsewhere. A modified Delphi panel approach with 24 experts was then used to establish a consensus on how the findings should translate into a new intervention. After feedback from key stakeholders (n=15) on the proposed model, the intervention was manualised and training developed. Results We identified key components of a new intervention covering three broad areas: • Ensuring that the circumstances of rehabilitation are optimised for people with dementia • Compensating for the reduced ability of people with dementia to self-manage • Equipping the workforce with the necessary skills and information to care for this patient group Consensus was achieved on 54 of 69 statements over two rounds of the Delphi surveys. The statements were used to model the intervention and finalise the accompanying manual and protocol for a feasibility study. Stakeholder feedback was generally positive and the majority of suggested intervention components were approved. The proposed outcome was a 12-week complex multidisciplinary intervention primarily based at the patient’s home. Conclusions A new intervention has been developed to improve outcomes for people with dementia following a fall requiring healthcare attention. The feasibility of this intervention is currently being tested. Trial registration ISRCTN41760734 (16/11/2015

Setting an International Research Agenda for Fear of Cancer Recurrence: an online delphi consensus study

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permissionBackground: Fear of cancer recurrence (FCR) is common amongst cancer survivors. There is rapidly growing research interest in FCR but a need to prioritise research to address the most pressing clinical issues and reduce duplication and fragmentation of effort. This study aimed to establish international consensus among clinical and academic FCR experts regarding priorities for FCR research. Methods: Members of the International Psycho-oncology Society (IPOS) Fear of Cancer Recurrence Special Interest Group (FORwards) were invited to participate in an online Delphi study. Research domains identified in Round 1 were presented and discussed at a focus group (Round 2) to consolidate the domains and items prior to presentation in further survey rounds (Round 3) aimed at gaining consensus on research priorities of international significance. Results: Thirty four research items were identified in Round 1 and 33 of the items were consolidated into 6 overarching themes through a focus group discussion with FCR experts. The 33 research items were presented in subsequent rounds of the delphi technique. Twenty one participants contributed to delphi round 1, 16 in round 2 and 25 and 29 participants for subsequent delphi rounds. Consensus was reached for 27 items in round 3.1. A further 4 research items were identified by panellists and included in round 3.2. After round 3.2, 35 individual research items were ratified by the panellists. Given the high levels of consensus and stability between rounds no further rounds were conducted. Overall intervention research was considered the most important focus for FCR research. Panellists identified models of care that facilitate greater access to FCR treatment and evaluation of the effectiveness of FCR interventions in real world settings as the two research items of highest priority. Defining the mechanisms of action and active components across FCR/P interventions, was the third highest priority identified. Conclusions: The findings of this study outline a research agenda for international FCR research. Intervention research to identify models of care that increase access to treatment, are based on a flexible approach based on symptom severity and can be delivered within routine clinical care, were identified as research areas to prioritise. Greater understanding of the active components and mechanisms of action of existing FCR interventions will facilitate increased tailoring of interventions to meet patient need

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β =-2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention

Social prescribing programmes to prevent or delay frailty in community-dwelling older adults

The increasing incidence of frailty is a health and social care challenge. Social prescription is advocated as an important approach to allow health professionals to link patients with sources of support in the community. This study aimed to determine the current evidence on the effectiveness of social prescribing programmes to delay or reduce frailty in frail older adults living in the community. A systematic literature review of published (DARE, Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL, NICE and SCIE, NHS Economic Evaluation Database) and unpublished databases (OpenGrey; WHO Clinical Trial Registry; ClinicalTrials.gov) were searched to July 2019. Studies were eligible if they reported health, social or economic outcomes on social prescribing, community referral, referral schemes, wellbeing programmes or interventions when a non-health link worker was the intervention provider to people who are frail living in the community. 1079 unique studies were screened for eligibility. No papers were eligible. There is therefore a paucity of evidence reporting the effectiveness of social prescribing programmes for frail older adults living in the community. Given that frailty is a clinical priority and social prescribing is considered a key future direction in the provision of community care, this is a major limitation