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Meta-Analysis
. 2021 Jul 19;7(7):CD013307.
doi: 10.1002/14651858.CD013307.pub2.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients

Jennifer K Burton  1 , Louise E Craig  2 , Shun Qi Yong  3 , Najma Siddiqi  4 , Elizabeth A Teale  5 , Rebecca Woodhouse  6 , Amanda J Barugh  7 , Alison M Shepherd  8 , Alan Brunton  9 , Suzanne C Freeman  10 , Alex J Sutton  10 , Terry J Quinn  2
Affiliations
Meta-Analysis

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients

Jennifer K Burton et al. Cochrane Database Syst Rev. .

Abstract

Background: Delirium is an acute neuropsychological disorder that is common in hospitalised patients. It can be distressing to patients and carers and it is associated with serious adverse outcomes. Treatment options for established delirium are limited and so prevention of delirium is desirable. Non-pharmacological interventions are thought to be important in delirium prevention. OBJECTIVES: To assess the effectiveness of non-pharmacological interventions designed to prevent delirium in hospitalised patients outside intensive care units (ICU).

Search methods: We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP to 16 September 2020. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search.

Selection criteria: We included randomised controlled trials (RCTs) of single and multicomponent non-pharmacological interventions for preventing delirium in hospitalised adults cared for outside intensive care or high dependency settings. We only included non-pharmacological interventions which were designed and implemented to prevent delirium. DATA COLLECTION AND ANALYSIS: Two review authors independently examined titles and abstracts identified by the search for eligibility and extracted data from full-text articles. Any disagreements on eligibility and inclusion were resolved by consensus. We used standard Cochrane methodological procedures. The primary outcomes were: incidence of delirium; inpatient and later mortality; and new diagnosis of dementia. We included secondary and adverse outcomes as pre-specified in the review protocol. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes and between-group mean differences for continuous outcomes. The certainty of the evidence was assessed using GRADE. A complementary exploratory analysis was undertaker using a Bayesian component network meta-analysis fixed-effect model to evaluate the comparative effectiveness of the individual components of multicomponent interventions and describe which components were most strongly associated with reducing the incidence of delirium.

Main results: We included 22 RCTs that recruited a total of 5718 adult participants. Fourteen trials compared a multicomponent delirium prevention intervention with usual care. Two trials compared liberal and restrictive blood transfusion thresholds. The remaining six trials each investigated a different non-pharmacological intervention. Incidence of delirium was reported in all studies. Using the Cochrane risk of bias tool, we identified risks of bias in all included trials. All were at high risk of performance bias as participants and personnel were not blinded to the interventions. Nine trials were at high risk of detection bias due to lack of blinding of outcome assessors and three more were at unclear risk in this domain. Pooled data showed that multi-component non-pharmacological interventions probably reduce the incidence of delirium compared to usual care (10.5% incidence in the intervention group, compared to 18.4% in the control group, risk ratio (RR) 0.57, 95% confidence interval (CI) 0.46 to 0.71, I2 = 39%; 14 studies; 3693 participants; moderate-certainty evidence, downgraded due to risk of bias). There may be little or no effect of multicomponent interventions on inpatient mortality compared to usual care (5.2% in the intervention group, compared to 4.5% in the control group, RR 1.17, 95% CI 0.79 to 1.74, I2 = 15%; 10 studies; 2640 participants; low-certainty evidence downgraded due to inconsistency and imprecision). No studies of multicomponent interventions reported data on new diagnoses of dementia. Multicomponent interventions may result in a small reduction of around a day in the duration of a delirium episode (mean difference (MD) -0.93, 95% CI -2.01 to 0.14 days, I2 = 65%; 351 participants; low-certainty evidence downgraded due to risk of bias and imprecision). The evidence is very uncertain about the effect of multicomponent interventions on delirium severity (standardised mean difference (SMD) -0.49, 95% CI -1.13 to 0.14, I2=64%; 147 participants; very low-certainty evidence downgraded due to risk of bias and serious imprecision). Multicomponent interventions may result in a reduction in hospital length of stay compared to usual care (MD -1.30 days, 95% CI -2.56 to -0.04 days, I2=91%; 3351 participants; low-certainty evidence downgraded due to risk of bias and inconsistency), but little to no difference in new care home admission at the time of hospital discharge (RR 0.77, 95% CI 0.55 to 1.07; 536 participants; low-certainty evidence downgraded due to risk of bias and imprecision). Reporting of other adverse outcomes was limited. Our exploratory component network meta-analysis found that re-orientation (including use of familiar objects), cognitive stimulation and sleep hygiene were associated with reduced risk of incident delirium. Attention to nutrition and hydration, oxygenation, medication review, assessment of mood and bowel and bladder care were probably associated with a reduction in incident delirium but estimates included the possibility of no benefit or harm. Reducing sensory deprivation, identification of infection, mobilisation and pain control all had summary estimates that suggested potential increases in delirium incidence, but the uncertainty in the estimates was substantial. Evidence from two trials suggests that use of a liberal transfusion threshold over a restrictive transfusion threshold probably results in little to no difference in incident delirium (RR 0.92, 95% CI 0.62 to 1.36; I2 = 9%; 294 participants; moderate-certainty evidence downgraded due to risk of bias). Six other interventions were examined, but evidence for each was limited to single studies and we identified no evidence of delirium prevention. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence regarding the benefit of multicomponent non-pharmacological interventions for the prevention of delirium in hospitalised adults, estimated to reduce incidence by 43% compared to usual care. We found no evidence of an effect on mortality. There is emerging evidence that these interventions may reduce hospital length of stay, with a trend towards reduced delirium duration, although the effect on delirium severity remains uncertain. Further research should focus on implementation and detailed analysis of the components of the interventions to support more effective, tailored practice recommendations.

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Conflict of interest statement

JKB has no known conflicts of interest

LC has no known conflicts of interest

SQY has no known conflicts of interest

NS is an author on a study included in the review (Young 2020), she played no part in the study selection, data extraction or quality assessment of the work

EAT is an author on a study included in the review (Young 2020), she played no part in the study selection, data extraction or quality assessment of the work

RW has no known conflicts of interest

AJB has no known conflicts of interest

AMS has no known conflicts of interest

AB has no known conflicts of interest

SCF has no known conflicts of interest

AJS has no known conflicts of interest

TJQ has no known conflicts of interest

Figures

1
1
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot:  Multi‐component delirium prevention intervention (MCI) versus usual care for incident delirium
4
4
Forest plot:  Multi‐component delirium prevention intervention (MCI) versus usual care for inpatient mortality
5
5
Forest plot:  Multi‐component delirium prevention intervention (MCI) versus usual care for length of hospital stay
6
6
Forest plot summarising component network meta‐analysis results
1.1
1.1. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 1: Incident Delirium
1.2
1.2. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 2: Inpatient mortality
1.3
1.3. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 3: Mortality at 1 to 3 months
1.4
1.4. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 4: Mortality at 12 months
1.5
1.5. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 5: Duration of delirium episode
1.6
1.6. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 6: Peak severity of delirium
1.7
1.7. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 7: Length of hospital stay
1.8
1.8. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 8: Withdrawal from protocol
1.9
1.9. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 9: Readmission to hospital
1.10
1.10. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 10: New care home admission on discharge
1.11
1.11. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 11: Falls
1.12
1.12. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 12: Pressure ulcers
1.13
1.13. Analysis
Comparison 1: Multi‐component delirium prevention intervention (MCI) versus usual care, Outcome 13: Incidence of delirium in patients with dementia
2.1
2.1. Analysis
Comparison 2: Liberal versus restrictive blood transfusion thresholds, Outcome 1: Incident delirium
2.2
2.2. Analysis
Comparison 2: Liberal versus restrictive blood transfusion thresholds, Outcome 2: Delirium severity
2.3
2.3. Analysis
Comparison 2: Liberal versus restrictive blood transfusion thresholds, Outcome 3: Length of hospital stay
2.4
2.4. Analysis
Comparison 2: Liberal versus restrictive blood transfusion thresholds, Outcome 4: Withdrawal
3.1
3.1. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 1: Incident delirium
3.2
3.2. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 2: Inpatient mortality
3.3
3.3. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 3: Incident dementia at 12 months
3.4
3.4. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 4: Duration of delirium
3.5
3.5. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 5: Severity of delirium
3.6
3.6. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 6: Length of hospital stay
3.7
3.7. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 7: Falls
3.8
3.8. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 8: Pressure ulcers
3.9
3.9. Analysis
Comparison 3: Geriatric unit care versus orthopaedic unit care, Outcome 9: New care home admission at 12 months
4.1
4.1. Analysis
Comparison 4: Exercise therapy versus usual care, Outcome 1: Incident Delirium
4.2
4.2. Analysis
Comparison 4: Exercise therapy versus usual care, Outcome 2: Mortality at 1 to 3 months
4.3
4.3. Analysis
Comparison 4: Exercise therapy versus usual care, Outcome 3: Length of hospital stay
4.4
4.4. Analysis
Comparison 4: Exercise therapy versus usual care, Outcome 4: New care home admission on discharge
4.5
4.5. Analysis
Comparison 4: Exercise therapy versus usual care, Outcome 5: Falls
5.1
5.1. Analysis
Comparison 5: Computerised clinical decision support system (CCDS) versus usual care, Outcome 1: Incident delirium
5.2
5.2. Analysis
Comparison 5: Computerised clinical decision support system (CCDS) versus usual care, Outcome 2: Mortality at 1 to 3 months
5.3
5.3. Analysis
Comparison 5: Computerised clinical decision support system (CCDS) versus usual care, Outcome 3: Length of hospital stay
5.4
5.4. Analysis
Comparison 5: Computerised clinical decision support system (CCDS) versus usual care, Outcome 4: Falls
5.5
5.5. Analysis
Comparison 5: Computerised clinical decision support system (CCDS) versus usual care, Outcome 5: Pressure sores
6.1
6.1. Analysis
Comparison 6: Listening to music verus usual care, Outcome 1: Incident delirium
7.1
7.1. Analysis
Comparison 7: Transcutaneous electrical acupoint stimulation versus placebo, Outcome 1: Incident delirium
8.1
8.1. Analysis
Comparison 8: Continuous positive airway pressure (CPAP) verus usual care, Outcome 1: Incident delirium
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Freter 2017 {published data only}
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Gorski 2017 {published data only}
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Greaves 2020 {published data only}
    1. Greaves D, Psaltis PJ, Lampit A, Davis DH, Smith AE, Bourke A, et al. Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial. BMJ Open 2020;10(2):e034551. - PMC - PubMed
Groshaus 2012 {published data only}
    1. Groshaus H, Boscan A, Khandwala F, Holroyd-Leduc J. Use of clinical decision support to improve the quality of care provided to older hospitalized patients. Applied Clinical Informatics 2012;3(1):94-102. - PMC - PubMed
Gustafson 1991 {published data only}
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Hammond 2017 {published data only}
    1. Hammond SP, Cross JL, Shepstone L, Backhouse T, Henderson C, Poland F, et al. PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial. Trials 2017;18(1):583. - PMC - PubMed
Hea‐Jeong 2014 {published data only}
    1. Hea-Jeong Hwang, Yeonghee Shin. Effects of nursing intervention program on reducing acute confusion in hospitalized older adults. Korean Journal of Adult Nursing 2014;26(1):89-97.
Heim 2017 {published data only}
    1. Heim N, Stel HF, Ettema RG, Mast RC, Inouye SK, Schuurmans MJ. HELP! Problems in executing a pragmatic, randomized, stepped wedge trial on the Hospital Elder Life Program to prevent delirium in older patients. Trials 2017;18(1):220. - PMC - PubMed
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    1. Strijbos MJ, Steunenberg B, Mast RC, Inouye SK, Schuurmans MJ. Design and methods of the Hospital Elder Life Program (HELP), a multicomponent targeted intervention to prevent delirium in hospitalized older patients: efficacy and cost-effectiveness in Dutch health care. BMC Geriatrics 2013;13:78. - PMC - PubMed
Holly 2019 {published data only}
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Holroyd‐Leduc 2010 {published data only}
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Hoolahan 2011 {published data only}
    1. Hoolahan A. OVoiD delirium and improved outcomes in acute care. Introducing a model of care. Australian Journal of Advanced Nursing 2011;29(2):30-5.
Hudetz 2015 {published data only}
    1. Hudetz JA, Patterson KM, Iqbal Z, Gandhi SD, Pagel PS. Remote ischemic preconditioning prevents deterioration of short-term postoperative cognitive function after cardiac surgery using cardiopulmonary bypass: results of a pilot investigation. Journal of Cardiothoracic and Vascular Anesthesia 2015;29(2):382-8. - PubMed
Illioska 2014 {published data only}
    1. Illioska P, Brendel L, Kruger N, Navratil D, Kiessling AH, Moritz A, et al. Neurologic outcome following axillary artery versus classic aortic cannulation in high risk patients: preliminary results from a prospective randomized study. Thoracic and Cardiovascular Surgeon 2014;62:S01.
Inouye 1999 {published data only}
    1. Inouye SK, Bogardus ST Jr, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. New England Journal of Medicine 1999;340(9):669-76. - PubMed
Inouye 2000b {published data only}
    1. Inouye SK. Prevention of delirium in hospitalized older patients: risk factors and targeted intervention strategies. Annals of Medicine 2000;32(4):257-63. - PubMed
Jia 2014 {published data only}
    1. Jia Y, Jin G, Guo S, Gu B, Jin Z, Gao X, et al. Fast-track surgery decreases the incidence of postoperative delirium and other complications in elderly patients with colorectal carcinoma. Langenbecks Archives of Surgery 2014;399:77-84. - PMC - PubMed
Ko 2019 {published data only}
    1. Ko F. Multi component exercise program can reverse hospitalization-associated functional decline in elderly patients. Journal of Clinical Outcomes Management 2019;26(2):57-9.
Lei 2017 {published data only}
    1. Lei L, Katznelson R, Fedorko L, Carroll J, Poonawala H, Machina M, et al. Cerebral oximetry and postoperative delirium after cardiac surgery: a randomised, controlled trial. Anaesthesia 2017;72(12):1456-66. - PubMed
Li 2017 {published data only}
    1. Li Q-P, Lin L, Yang L, Jiang P-F, Yang Y. Effect of nursing intervention based on Roy adaptation model on postoperative gastrointestinal function recovery and incidence of postoperative delirium in patients with colorectal cancer. Wolrd Chinese Journal of Digestology 2017;25(7):632-7.
Lisann 2016 {published data only}
    1. Lisann L, Pagnini F, Langer E, Deiner S. Remind: reducing delirium and improving patient satisfaction with a perioperative mindfulness intervention. In: Journal of Alternative and Complementary Medicine. Vol. 22. 2016:A94-5.
Llera 2005 {published data only}
    1. Llera FG. Delirium in hospitalized elderly patients. Medicina Clinica 2005;124(14):538-40. - PubMed
Lundstrom 2005 {published data only}
    1. Lundstrom M, Edlund A, Karlsson S, Brannstrom B, Bucht G, Gustafson Y. A multifactorial intervention program reduces the duration of delirium, length of hospitalization, and mortality in delirious patients. Journal of the American Geriatrics Society 2005;53(4):622-8. - PubMed
McCaffrey 2004 {published data only}
    1. McCaffrey R, Locsin R. The effect of music listening on acute confusion and delirium in elders undergoing elective hip and knee surgery. Journal of Clinical Nursing 2004;13(6B):91-6. - PubMed
Moppett 2017 {published data only}
    1. Moppett IK, White S, Griffiths R, Buggy D. Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial. Trials 2017;18(1):350. - PMC - PubMed
Mudge 2008 {published data only}
    1. Mudge AM, Giebel AJ, Cutler AJ. Exercising body and mind: an integrated approach to functional independence in hospitalized older people. Journal of the American Geriatrics Society 2008;56(4):630-5. - PubMed
Mudge 2017 {published data only}
    1. Mudge AM, Banks MD, Barnett AG, Blackberry I, Graves N, Green T, et al. CHERISH (collaboration for hospitalised elders reducing the impact of stays in hospital): protocol for a multi-site improvement program to reduce geriatric syndromes in older inpatients. BMC Geriatrics 2017;17(1):1-9. - PMC - PubMed
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Nikelski 2019 {published data only}
    1. Nikelski A, Keller A, Schumacher-Schonert F, Dehl T, Laufer J, Sauerbrey U, et al. Supporting elderly people with cognitive impairment during and after hospital stays with intersectoral care management: study protocol for a randomized controlled trial. Trials 2019;20:543. - PMC - PubMed
O'Gara 2020 {published data only}
    1. O'Gara B, Marcantonio ER, Pascual-Leone A, Shaefi S, Mueller A, Banner-Goodspeed V, et al. Prevention of early postoperative decline (peapod): protocol for a randomized, controlled feasibility trial. Trials 2018;19(1):676. - PMC - PubMed
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    1. Rice KL, Bennett MJ, Berger L, Jennings B, Eckhardt L, Fabre-LaCoste N, et al. A pilot randomized controlled trial of the feasibility of a multicomponent delirium prevention intervention versus usual care in acute stroke. Journal of Cardiovascular Nursing 2017;32(1):E1-E10. - PubMed
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References to studies awaiting assessment

NCT01998997 2013 {published data only}
    1. NCT01998997. A Family intervention for delirium prevention. Trial Registry 2013.
NCT03470662 2018 {published data only}
    1. NCT03470662. Prevention of delirium among elderly patients with hip fractures. https://clinicaltrials.gov/show/nct03470662 2018.
NCT04188795 2019 {published data only}
    1. NCT04188795 2019. Evaluation of the effectiveness of Delirium Preventive Care protocol. https://clinicaltrials.gov/ct2/show/NCT04188795 2019.
UMIN000027181 2017 {published data only}
    1. UMIN000027181. Impact of perioperative passive cycling exercise on postoperative delirium, cognitive function: randomized controlled trial. Trial Registry 2017.

References to ongoing studies

Boltz 2018 {published data only}
    1. Boltz M, Kuzmik A, Resnick B, Trotta R, Mogle J, Belue R, et al. Reducing disability via a family centered intervention for acutely ill persons with Alzheimer's disease and related dementias: protocol of a cluster-randomized controlled trial (Fam-FFC study) 11 Medical and Health Sciences 1117 Public Health and Health Services. Trials 2018;19:496. - PMC - PubMed
ChiCTR1900027115 2019 {published data only}
    1. Effects of acupuncture on postoperative delirium in elderly patients after laparoscopic surgery. Ongoing study. 1/11/2019. Contact author for more information.
DRKS00013158 2017 {published data only}
    1. DRKS00013158. Influence of perinterventional acupuncture on the incidence of postoperative delirium after elective, endoprosthetic replacement of the hip joint. http://www.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00013158 2017.
DRKS00016352 2019 {published data only}
    1. DRKS00016352. Evaluation of incidence of delirium in an acute care hospital by engaging an innovative and multidisciplinary approach. http://www.drks.de/DRKS00016352 2019.
Humeidan 2015 {published data only}
    1. Humeidan ML, Otey A, Zuleta-Alarcon A, Mavarez-Martinez A, Stoicea N, Bergese S. Perioperative cognitive protection-cognitive Exercise and cognitive reserve (The Neurobics Trial): a single-blind randomized trial. Clinical Therapeutics 2015;37(12):2641-50. - PubMed
    1. NCT02230605. Perioperative Cognitive Protection - Cognitive Exercise and Cognitive Reserve (The Neurobics Trial). https://clinicaltrials.gov/show/nct02230605 2014. - PubMed
IRCT20180910040995N1 2019 {published data only}
    1. IRCT20180910040995N1. Effect of HELP model on prevention of delirium. http://en.irct.ir/trial/33830.
JPRN 2017 {published data only}
    1. JPRN 2017. A multi-center, cluster randomized controlled study comparing usual care and a multidisciplinary intervention such as the DELirium Team Approach program to manage delirium among hospitalized cancer patients. http://www.whoint/trialsearch/Trial2aspx?TrialID=JPRN-UMIN000030062 2017.
NCT03060174 2017 {published data only}
    1. NCT03060174. Study of prevention of postoperative delirium to reduce incidence of postoperative cognitive dysfunction. https://clinicaltrials.gov/show/nct03060174 2017.
NCT03158909 2017 {published data only}
    1. NCT03158909. Trial of a non-pharmacological intervention to prevent delirium among elderly in-patients. https://clinicaltrials.gov/show/NCT03158909 2017.
NCT03541408 2018 {published data only}
    1. NCT03541408. Preventative delirium protocol in elderly patients. https://clinicaltrials.gov/ct2/show/nct03541408 2018.
NCT03573843 2018 {published data only}
    1. NCT03573843. Software-guided cognitive stimulation to prevent delirium. https://clinicaltrialsgov/show/NCT03573843 2018.
NCT03704090 2018 {published data only}
    1. NCT03704090. Non-pharmacological Prevention of Postoperative Delirium by Occupational Therapy Teams (PREPODOT). https://clinicaltrials.gov/ct2/show/NCT03704090 2018. - PMC - PubMed
NCT03832192 2019 {published data only}
    1. NCT03832192. Care.Coach Avatars for improvement of outcomes in hospitalized elders, including mitigation of falls and delirium: a multi-site clinical study (AvatarHELP). https://clinicaltrials.gov/ct2/show/NCT03832192 2019.
NCT03894709 2019 {published data only}
    1. NCT03894709. A care model for elderly hip-fractured persons with cognitive impairment and their family caregivers. https://clinicaltrials.gov/ct2/show/nct03894709 2019.
NCT03980782 2019 {published data only}
    1. NCT03980782 2019. The effect of music therapy on delirium. https://clinicaltrials.gov/ct2/show/NCT03980782 2019.
NTR7036 2018 {published data only}
    1. NTR7036. Effect van muziek op de klinische uitkomst na heupfractuur operaties (MCHOPIN): een multicenter gerandomiseerde studie. http://www.who.int/trialsearch/Trial2.aspx?TrialID=NTR7036 2018.
Piotrowicz 2018 {published data only}
    1. Piotrowicz K, Rewiuk K, Gorski S, Kalwak W, Wizner B, Pac A, et al. The "Wholesome Contact" non-pharmacological, volunteer-delivered multidisciplinary programme to prevent hospital delirium in elderly patients: study protocol for a randomised controlled trial. Trials 2018;19(1):439. - PMC - PubMed
Sanchez 2019 {published data only}
    1. DRKS00013311. Patient safety, cost-effectiveness and quality of life: reduction of delirium risk and post-operative cognitive dysfunction (POCD) after elective procedures in the elderly. German Clinical Trials Register 2017.
    1. Sanchez A, Thomas C, Deeken F, Wagner S, Kloppel S, Kentischer F, et al. Patient safety, cost-effectiveness, and quality of life: reduction of delirium risk and postoperative cognitive dysfunction after elective procedures in older adults-study protocol for a stepped-wedge cluster randomized trial (PAWEL Study). Trials 2019;20(1):71. - PMC - PubMed
Wong 2018 {published data only}
    1. NCT02954224. Prevention of delirium in elderly with obstructive sleep apnea (PODESA). https://clinicaltrials.gov/show/nct02954224.
    1. Wong J, Lam D, Choi S, Singh M, Siddiqui N, Sockalingam S, et al. The prevention of delirium in elderly with obstructive sleep apnea (PODESA) study: protocol for a multi-centre prospective randomized, controlled trial. BMC Anesthesiology 2018;18:1. - PMC - PubMed

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