Effects of a clinical decision support system and patient portal for preventing medication-related falls in older fallers:Protocol of a cluster randomized controlled trial with embedded process and economic evaluations (ADFICE_IT)

BackgroundFalls are the leading cause of injury-related mortality and hospitalization among adults aged ≥ 65 years. An important modifiable fall-risk factor is use of fall-risk increasing drugs (FRIDs). However, deprescribing is not always attempted or performed successfully. The ADFICE_IT trial evaluates the combined use of a clinical decision support system (CDSS) and a patient portal for optimizing the deprescribing of FRIDs in older fallers. The intervention aims to optimize and enhance shared decision making (SDM) and consequently prevent injurious falls and reduce healthcare-related costs.MethodsA multicenter, cluster-randomized controlled trial with process evaluation will be conducted among hospitals in the Netherlands. We aim to include 856 individuals aged ≥ 65 years that visit the falls clinic due to a fall. The intervention comprises the combined use of a CDSS and a patient portal. The CDSS provides guideline-based advice with regard to deprescribing and an individual fall-risk estimation, as calculated by an embedded prediction model. The patient portal provides educational information and a summary of the patient’s consultation. Hospitals in the control arm will provide care-as-usual. Fall-calendars will be used for measuring the time to first injurious fall (primary outcome) and secondary fall outcomes during one year. Other measurements will be conducted at baseline, 3, 6, and 12 months and include quality of life, cost-effectiveness, feasibility, and shared decision-making measures. Data will be analyzed according to the intention-to-treat principle. Difference in time to injurious fall between the intervention and control group will be analyzed using multilevel Cox regression.DiscussionThe findings of this study will add valuable insights about how digital health informatics tools that target physicians and older adults can optimize deprescribing and support SDM. We expect the CDSS and patient portal to aid in deprescribing of FRIDs, resulting in a reduction in falls and related injuries

Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: extended follow-up of the B-PROOF trial

Background & aims: In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk.Methods: Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 mg) and vitamin-B12 (500 mg) versus placebo (n = 2,919). Primary outcome was verified self reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease.Results: A total of 1,298 individuals (4 4.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic-and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 mmol/l). No age-dependent effects were present.Conclusions: This study supports and extends previous null -findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated. (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Barriers and facilitators in using a clinical decision support system in falls clinics for older people: a European survey

Purpose Fall-Risk Increasing Drugs (FRIDs) are an important and modifiable fall-risk factor. A Clinical Decision Support System (CDSS) could support doctors in optimal FRIDs deprescribing. Understanding barriers and facilitators is important for a successful implementation of any CDSS. We conducted a European survey to assess barriers and facilitators to CDSS use and explored differences in their perceptions. Methods We examined and compared the relative importance and the occurrence of regional differences of a literature-based list of barriers and facilitators for CDSS usage among physicians treating older fallers from 11 European countries. Results We surveyed 581 physicians (mean age 44.9 years, 64.5% female, 71.3% geriatricians). The main barriers were technical issues (66%) and indicating a reason before overriding an alert (58%). The main facilitators were a CDSS that is beneficial for patient care (68%) and easy-to-use (64%). We identified regional differences, e.g., expense and legal issues were barriers for significantly more Eastern-European physicians compared to other regions, while training was selected less often as a facilitator by West-European physicians. Some physicians believed that due to the medical complexity of their patients, their own clinical judgement is better than advice from the CDSS. Conclusion When designing a CDSS for Geriatric Medicine, the patient’s medical complexity must be addressed whilst maintaining the doctor’s decision-making autonomy. For a successful CDSS implementation in Europe, regional differences in barrier perception should be overcome. Equipping a CDSS with prediction models has the potential to provide individualized recommendations for deprescribing FRIDs in older falls patients

CD133+ and Nestin+ Glioma Stem-Like Cells Reside Around CD31+ Arterioles in Niches that Express SDF-1α, CXCR4, Osteopontin and Cathepsin K

Poor survival of high-grade glioma is at least partly caused by glioma stem-like cells (GSLCs) that are resistant to therapy. GSLCs reside in niches in close vicinity of endothelium. The aim of the present study was to characterize proteins that may be functional in the GSLC niche by performing immunohistochemistry on serial cryostat sections of human high-grade glioma samples. We have found nine niches in five out of five high-grade glioma samples that were all surrounding arterioles with CD31+ endothelial cells and containing cellular structures that were CD133+ and nestin+. All nine niches expressed stromal-derived factor-1alpha (SDF-1alpha), its receptor C-X-C chemokine receptor type 4 (CXCR4), osteopontin and cathepsin K. SDF-1alpha plays a role in homing of CXCR4+ stem cells and leukocytes, whereas osteopontin and cathepsin K promote migration of cancer cells and leukocytes. Leukocyte-related markers, such as CD68, macrophage matrix metalloprotease-9, CD177 and neutrophil elastase were often but not always detected in the niches. We suggest that SDF-1alpha is involved in homing of CXCR4+ GSLCs and leukocytes and that cathepsin K and osteopontin are involved in the migration of GSLCs out of the niches

Barriers and facilitators influencing medication-related CDSS acceptance according to clinicians: A systematic review

Background A medication-related Clinical Decision Support System (CDSS) is an application that analyzes patient data to provide assistance in medication-related care processes. Despite its potential to improve the clinical decision-making process, evidence shows that clinicians do not always use CDSSs in such a way that their potential can be fully realized. This systematic literature review provides an overview of frequently-reported barriers and facilitators for acceptance of medication-related CDSS. Materials and methods Search terms and MeSH headings were developed in collaboration with a librarian, and database searches were conducted in Medline, Scopus, Embase and Web of Science Conference Proceedings. After screening 5404 records and 140 full papers, 63 articles were included in this review. Quality assessment was performed for all 63 included articles. The identified barriers and facilitators are categorized within the Human, Organization, Technology fit (HOT-fit) model. Results A total of 327 barriers and 291 facilitators were identified. Results show that factors most often reported were related to (a lack of) usefulness and relevance of information, and ease of use and efficiency of the system. Discussion This review provides a valuable insight into a broad range of barriers and facilitators for using a medication-related CDSS as perceived by clinicians. The results can be used as a stepping stone in future studies developing medication-related CDSSs

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. Methods: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC–MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. Results: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07–5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. Conclusion: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed