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      Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients: A Systematic Overview. The SENATOR project ONTOP Series

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          Abstract

          Background

          Non-pharmacological intervention (e.g. multidisciplinary interventions, music therapy, bright light therapy, educational interventions etc.) are alternative interventions that can be used in older subjects. There are plenty reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients and clinicians need a synthesized, methodologically sound document for their decision making.

          Methods and Findings

          We performed a systematic overview of systematic reviews (SRs) of comparative studies concerning non-pharmacological intervention to treat or prevent delirium in older patients. The PubMed, Cochrane Database of Systematic Reviews, EMBASE, CINHAL, and PsychINFO (April 28th, 2014) were searched for relevant articles. AMSTAR was used to assess the quality of the SRs. The GRADE approach was used to assess the quality of primary studies. The elements of the multicomponent interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis. Risk ratios were estimated using a random-effects model. Twenty-four SRs with 31 primary studies satisfied the inclusion criteria. Based on the AMSTAR criteria twelve reviews resulted of moderate quality and three resulted of high quality. Overall, multicomponent non-pharmacological interventions significantly reduced the incidence of delirium in surgical wards [2 randomized trials (RCTs): relative risk (RR) 0.71, 95% Confidence Interval (CI) 0.59 to 0.86, I 2=0%; (GRADE evidence: moderate)] and in medical wards [2 CCTs: RR 0.65, 95%CI 0.49 to 0.86, I 2=0%; (GRADE evidence: moderate)]. There is no evidence supporting the efficacy of non-pharmacological interventions to prevent delirium in low risk populations (i.e. low rate of delirium in the control group)[1 RCT: RR 1.75, 95%CI 0.50 to 6.10 (GRADE evidence: very low)]. For patients who have developed delirium, the available evidence does not support the efficacy of multicomponent non-pharmacological interventions to treat delirium. Among single component interventions only staff education, reorientation protocol (GRADE evidence: very low)] and Geriatric Risk Assessment MedGuide software [hazard ratio 0.42, 95%CI 0.35 to 0.52, (GRADE evidence: moderate)] resulted effective in preventing delirium.

          Conclusions

          In older patients multi-component non-pharmacological interventions as well as some single-components intervention were effective in preventing delirium but not to treat delirium.

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          Most cited references72

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          Orthogeriatric care models and outcomes in hip fracture patients: a systematic review and meta-analysis.

          Hip fractures are common, morbid, and costly health events that threaten independence and function of older patients. The purpose of this systematic review and meta-analysis was to determine if orthogeriatric collaboration models improve outcomes. Articles in English and Spanish languages were searched in the electronic databases including MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, and the Cochrane Registry from 1992 to 2012. Studies were included if they described an inpatient multidisciplinary approach to hip fracture management involving an orthopaedic surgeon and a geriatrician. Studies were grouped into 3 following categories: routine geriatric consultation, geriatric ward with orthopaedic consultation, and shared care. After independent review of 1480 citations by 2 authors, 18 studies (9094 patients) were identified as meeting the inclusion criteria. In-hospital mortality, length of stay, and long-term mortality outcomes were collected. A random effects model meta-analysis determined whether orthogeriatric collaboration was associated with improved outcomes. The overall meta-analysis found that orthogeriatric collaboration was associated with a significant reduction of in-hospital mortality [relative risk 0.60; 95% confidence interval (95% CI), 0.43-0.84) and long-term mortality (relative risk 0.83; 95% CI, 0.74-0.94). Length of stay (standardized mean difference -0.25; 95% CI, -0.44 to -0.05) was significantly reduced, particularly in the shared care model (standardized mean difference -0.61; 95% CI, -0.95 to -0.28), but heterogeneity limited this interpretation. Other variables such as time to surgery, delirium, and functional status were measured infrequently. This meta-analysis supports orthogeriatric collaboration to improve mortality after hip repair. Further study is needed to determine the best model of orthogeriatric collaboration and if these partnerships improve functional outcomes.
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            Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability.

            To prospectively develop and validate a predictive model for delirium based on precipitating factors during hospitalization, and to examine the interrelationship of precipitating factors and baseline vulnerability. Two prospective cohort studies, in tandem. General medical wards, university teaching hospital. For the development cohort, 196 patients aged 70 years and older with no delirium at baseline, and for the validation cohort, 312 comparable patients. New-onset delirium by hospital day 9, defined by the Confusion Assessment Method diagnostic criteria. Delirium developed in 35 patients (18%) in the development cohort. Five independent precipitating factors for delirium were identified; use of physical restraints (adjusted relative risk [RR], 4.4; 95% confidence interval [CI], 2.5 to 7.9), malnutrition (RR, 4.0; 95% CI, 2.2 to 7.4), more than three medications added (RR, 2.9; 95% CI, 1.6 to 5.4), use of bladder catheter (RR, 2.4; 95% CI, 1.2 to 4.7), and any iatrogenic event (RR, 1.9; 95% CI, 1.1 to 3.2). Each precipitating factor preceded the onset of delirium by more than 24 hours. A risk stratification system was developed by adding 1 point for each factor present. Rates of delirium for low-risk (0 points), intermediate-risk (1 to 2 points), and high-risk groups (> or equal to 3 points) were 3%, 20%, and 59%, respectively (P < .001). The corresponding rates in the validation cohort, in which 47 patients (15%) developed delirium, were 4%, 20%, and 35%, respectively (P < .001). When precipitating and baseline factors were analyzed in cross-stratified format, delirium rates increased progressively from low-risk to high-risk groups in all directions (double-gradient phenomenon). The contributions of baseline and precipitating factors were documented to be independent and statistically significant. A simple predictive model based on the presence of five precipitating factors can be used to identify elderly medical patients at high risk for delirium. Precipitating and baseline vulnerability factors are highly interrelated and contribute to delirium in independent substantive, and cumulative ways.
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              Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.

              To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium. Randomized, double-blind, placebo-controlled trial. Large medical school-affiliated general hospital in Alkmaar, The Netherlands. A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium. Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients. The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay. The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted. Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                10 June 2015
                2015
                : 10
                : 6
                : e0123090
                Affiliations
                [1 ]Geriatrics and Geriatric Emergency Care, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy
                [2 ]Scientific Direction, Italian National Research Center on Aging (IRCCS-INRCA), Ancona, Italy
                [3 ]Servicio de Geriatría, Hospital Universitario Ramón y Cajal, Madrid, Spain
                [4 ]Department of Medicine for the Elderly, Woodend Hospital, Aberdeen, United Kingdom
                [5 ]Clinica di Medicina Interna e Geriatria, Politecnica University of the Marche Region, Ancona, Italy
                [6 ]Department of Medicine, University College Cork, Cork, Ireland
                D'or Institute of Research and Education, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: IA AC ACJ RLS DO. Performed the experiments: IA JMR FT ILM VP. Analyzed the data: IA JMR FT AC ACJ PDF VP ILM. Contributed reagents/materials/analysis tools: IA AC JMR AC PDF FT RLS DO FL. Wrote the paper: IA FT JMR AC ACJ ILM RLS VP PDF FL DO.

                Article
                PONE-D-14-47866
                10.1371/journal.pone.0123090
                4465742
                26062023
                4262405a-affe-4a22-9e01-74ed912b7567
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 4 November 2014
                : 27 February 2015
                Page count
                Figures: 5, Tables: 8, Pages: 31
                Funding
                The research leading to these results has received funding from the European Union Seventh Framework program (FP7/2007-2013) under grant agreement n° 305930 (SENATOR). The funders had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.
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