The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Feasibility and acceptability of facilitated advance care planning in outpatient clinics: A qualitative study of health-care professionals experience.

OBJECTIVE: This study sought to determine the feasibility and acceptability of a facilitated advance care planning (ACP) intervention implemented in outpatient clinics, as perceived by health-care professionals (HCPs). METHODS: Data from seven focus groups (n = 27) and nine semi-structured interviews with HCPs recruited as part of a pragmatic, randomised controlled trial (RCT) were analysed using qualitative descriptive methodology. Components of the intervention included HCP education and training, tools to assist HCPs with patient selection, hardcopy information, and ACP documentation, and specialised nurse-facilitators to support HCPs to complete ACP conversations and documentation with patients and caregivers. RESULTS: Health-care professionals working in tertiary outpatient clinics perceived the facilitated ACP intervention as feasible and acceptable. Health-care professionals reported a high level of satisfaction with key elements of the intervention, including the specialised education and training, screening and assessment procedures and ongoing support from the nurse-facilitators. Health-care professionals reported this training and support increased their confidence and ACP knowledge, leading to more frequent ACP discussions with patients and their families. Health-care professionals noted their ability to conduct ACP screening and assessment in clinic was impeded by large clinical caseloads and patient-related factors (e.g., dementia diagnoses, and emotional distress). Additional barriers to ACP implementation identified by HCPs included poor collaboration, constrained time and clinical space, undefined roles and standardised recording procedures for HCPs. CONCLUSIONS: Facilitated ACP intervention in outpatient clinics is perceived by HCPs as feasible and acceptable. Addressing barriers and tailoring implementation strategies may improve the delivery of ACP as part of tertiary outpatient care.

Feasibility and Acceptability of Facilitated Advance Care Planning in Outpatient Clinics: A Qualitative Study of Patient and Caregivers Experiences.

Guidelines recommend advance care planning (ACP) for people with advanced illness; however, evidence supporting ACP as a component of outpatient care is lacking. We sought to establish the feasibility and acceptability of a facilitated ACP intervention for people attending tertiary outpatient clinics. Data from 20 semi-structured interviews with patient (M = 79.3 ± 7.7, 60% male) and caregiver (M = 68.1 ± 11.0, 60% female) participants recruited as part of a pragmatic, randomized controlled trial (RCT) were analyzed using qualitative descriptive methodology. Patients were randomized to intervention (e.g., facilitated support) or control (e.g., standard care). Intervention patients expressed high satisfaction, reporting the facilitated ACP session was clear, straightforward, and suited to their needs. Intervention caregivers did not report any significant concerns with the facilitated ACP process. Control participants reported greater difficulty completing ACP compared to intervention participants. Embedding facilitated ACP into tertiary outpatient care appears feasible and acceptable for people with advanced illnesses.

Advancing specificity in delirium: The delirium subtyping initiative.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study.

BACKGROUND: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy. OBJECTIVES: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population. METHODS: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds1) test. RESULTS: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman rs = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs = 0.61, 95%CI = [0.29, 0.81]). CONCLUSIONS: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Impaired glucose utilization in the brain of patients with delirium following hip fracture.

Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and ß-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, ß-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.

Regional cerebral hypometabolism on 18F-FDG PET/CT scan in delirium is independent of acute illness and dementia.

INTRODUCTION: Delirium is associated with new onset dementia and accelerated cognitive decline; however, its pathophysiology remains unknown. Cerebral glucose metabolism previously seen in delirium may have been attributable to acute illness and/or dementia. We aimed to statistically map cerebral glucose metabolism attributable to delirium. METHODS: We assessed cerebral glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in sick, older patients with and without delirium, all without clinical dementia (N = 20). Strict exclusion criteria were adopted to minimize the effect of established confounders on FDG-PET. RESULTS: Patients with delirium demonstrated hypometabolism in the bilateral thalami and right superior frontal, right posterior cingulate, right infero-lateral anterior temporal, and left superior parietal cortices. Regional hypometabolism correlated with delirium severity and performance on neuropsychological testing. DISCUSSION: In patients with acute illness but without clinical dementia, delirium is accompanied by regional cerebral hypometabolism. While some hypometabolic regions may represent preclinical Alzheimer's disease (AD), thalamic hypometabolism is atypical of AD and consistent with the clinical features that are unique to delirium.

Evaluation of IMproving Palliative care Education and Training Using Simulation in Dementia (IMPETUS-D) a staff simulation training intervention to improve palliative care of people with advanced dementia living in nursing homes: a cluster randomised controlled trial.

BACKGROUND: People with dementia have unique palliative and end-of-life needs. However, access to quality palliative and end-of-life care for people with dementia living in nursing homes is often suboptimal. There is a recognised need for nursing home staff training in dementia-specific palliative care to equip them with knowledge and skills to deliver high quality care. OBJECTIVE: The primary aim was to evaluate the effectiveness of a simulation training intervention (IMPETUS-D) aimed at nursing home staff on reducing unplanned transfers to hospital and/or deaths in hospital among residents living with dementia. DESIGN: Cluster randomised controlled trial of nursing homes with process evaluation conducted alongside. SUBJECTS & SETTING: One thousand three hundred four people with dementia living in 24 nursing homes (12 intervention/12 control) in three Australian cities, their families and direct care staff. METHODS: Randomisation was conducted at the level of the nursing home (cluster). The allocation sequence was generated by an independent statistician using a computer-generated allocation sequence. Staff from intervention nursing homes had access to the IMPETUS-D training intervention, and staff from control nursing homes had access to usual training opportunities. The predicted primary outcome measure was a 20% reduction in the proportion of people with dementia who had an unplanned transfer to hospital and/or death in hospital at 6-months follow-up in the intervention nursing homes compared to the control nursing homes. RESULTS: At 6-months follow-up, 128 (21.1%) people with dementia from the intervention group had an unplanned transfer or death in hospital compared to 132 (19.0%) residents from the control group; odds ratio 1.14 (95% CI, 0.82-1.59). There were suboptimal levels of staff participation in the training intervention and several barriers to participation identified. CONCLUSION: This study of a dementia-specific palliative care staff training intervention found no difference in the proportion of residents with dementia who had an unplanned hospital transfer. Implementation of the intervention was challenging and likely did not achieve adequate staff coverage to improve staff practice or resident outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618002012257 . Registered 14 December 2018.

Persistent delirium in older hospital patients: an updated systematic review and meta-analysis.

Introduction: Delirium is associated with future dementia progression. Yet whether this occurs subclinically over months and years, or persistent delirium merges into worsened dementia is not understood. Our objective was to estimate the prevalence of persistent delirium and understand variation in its duration. Methods: We adopted an identical search strategy to a previous systematic review, only including studies using a recognised diagnostic framework for ascertaining delirium at follow-up (persistent delirium). Studies included hospitalised older patients outside critical and palliative care settings. We searched MEDLINE, EMBASE, PsycINFO and the Cochrane Database of Systematic Reviews on 11th January 2022. We applied risk of bias assessments based on Standards of Reporting of Neurological Disorders criteria and assessed strength of recommendations using the grading of recommendation, assessment, development and evaluation (GRADE) approach. Estimates were pooled across studies using random-effects meta-analysis, and we estimated associations with follow-up duration using robust error meta-regression. Results: We identified 13 new cohorts, which we added to 10 from the previous systematic review (23 relevant studies, with 39 reports of persistent delirium at 7 time-points in 3186 individuals admitted to hospital care (mean age 82 years and 41% dementia prevalence). Studies were mainly at moderate risk of bias. Pooled delirium prevalence estimates at discharge were 36% (95% CI 22% to 51%, 13 studies). Robust error meta-regression did not show variation in prevalence of persistent delirium over time (-1.6% per month, 95% CI -4.8 to 1.6, p=0.08). Margins estimates for this model indicate a prevalence of persistent delirium of 16% (95% CI 6% to 25%) at 12 months. Conclusions: This systematic review emphasises the importance of delirium as a persistent and extensive problem (GRADE certainty = moderate), raising questions on chronic delirium as a clinical entity and how it might evolve into dementia. Addressing persistent delirium will require a whole-system, integrated approach to detect, follow-up and implement opportunities for recovery across all healthcare settings.

Older Persons' and Their Caregivers' Perspectives and Experiences of Research Participation With Impaired Decision-Making Capacity: A Scoping Review.

BACKGROUND AND OBJECTIVES: Human research ethics statements support the equitable inclusion of diverse groups. Yet older people are underrepresented in clinical research, especially those with impaired decision-making capacity. The aim of this study was to identify the perspectives and experiences of older persons and their caregivers of research participation with impaired decision-making capacity. RESEARCH DESIGN AND METHODS: Scoping review of the literature and online sources in January-February 2019 (updated June 2020) according to Joanna Briggs Institute methodology and PRISMA Extension for Scoping Reviews. English-language peer-reviewed research articles and Australian online narratives were included. Data were tabulated and narratively synthesized. RESULTS: From 4,171 database records and 93 online resources, 22 articles (2000-2019, 82% United States, 16 first authors) and one YouTube webinar (2018) were initially included; updated searches yielded an additional article (2020) and YouTube webinar (2020). Studies were heterogeneous in terminology, methods, and foci, with hypothetical scenarios, quantitative analyses, and examination of proxy consent predominating. Participants (N = 7,331) were older persons (71%), caregivers of older persons with dementia/cognitive impairment (23%), and older persons with dementia/cognitive impairment (6%). Synthesis identified 2 themes: willingness to participate and decision-making approaches. DISCUSSION AND IMPLICATIONS: Research participation by older persons with dementia may be optimized through reducing risks and burdens and increasing benefits for participants, greater consumer input into study development, and shared and supported decision-making. Older persons' and caregivers' perspectives and experiences of research participation with impaired decision-making capacity require investigation in a greater range of countries and conditions other than dementia, and dissemination through more varied media.

Intranasal insulin for treatment of delirium in older hospitalised patients: study protocol for a randomised controlled trial.

INTRODUCTION: Delirium is one of the most common conditions diagnosed in hospitalised older people and is associated with numerous adverse outcomes, yet there are no proven pharmacological treatments. Recent research has identified cerebral glucose hypometabolism as a pathophysiological mechanism offering a therapeutic target in delirium. Insulin, delivered via the intranasal route, acts directly on the central nervous system and has been shown to enhance cerebral metabolism and improve cognition in patients with mild cognitive impairment and dementia. This trial will determine whether intranasal insulin can reduce the duration of delirium in older hospitalised patients. METHODS AND ANALYSIS: This is a prospective randomised, placebo-controlled, double-blind study with 6 months follow-up. One hundred patients aged 65 years or older presenting to hospital with delirium admitted under geriatric medicine will be recruited. Participants will be randomised to intranasal insulin detemir or placebo administered twice daily until delirium resolves, defined as Confusion Assessment Method (CAM) negative for 2 days, or discharge from hospital. The primary outcome measure will be duration of delirium using the CAM. Secondary outcome measures will include length of hospital stay, severity of delirium, adherence to treatment, hospital complications, new admission to nursing home, mortality, use of antipsychotic medications during hospital stay and cognitive and physical function at 6 months postdischarge. ETHICS AND DISSEMINATION: This trial has been approved by the South Eastern Sydney Human Research and Ethics Committee. Dissemination plans include submission to a peer-reviewed journal for publication and presentation at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12618000318280.

Virtual models of care for people with palliative care needs living in their own home: A systematic meta-review and narrative synthesis.

BACKGROUND: Access to palliative care in the community enables people to live in their preferred place of care, which is often home. Community palliative care services struggle to provide timely 24-h services to patients and family. This has resulted in calls for 'accessible and flexible' models of care that are 'responsive' to peoples' changing palliative care needs. Digital health technologies provide opportunities to meet these requirements 24-h a day. AIM: To identify digital health technologies that have been evaluated for supporting timely assessment and management of people living at home with palliative care needs and/or their carer(s), and the evidence-base for each. DESIGN: A systematic review of systematic reviews ('meta-review'). Systematic reviews evaluating evidence for virtual models of palliative or end-of-life care using one or more digital health technologies were included. Systematic reviews were evaluated using the Risk of Bias Tool for Systematic Reviews. A narrative approach was used to synthesise results. DATA SOURCES: Medline, Embase, Web of Science, CINAHL and Cochrane Database of systematic reviews were searched for English-language reviews published between 2015 and 2020. RESULTS: The search yielded 2266 articles, of which 12 systematic reviews met criteria. Sixteen reviews were included in total, after four reviews were found via handsearching. Other than scheduled telehealth, video-conferencing, or after-hours telephone support, little evidence was found for digital health technologies used to deliver virtual models of palliative care. CONCLUSIONS: There are opportunities to test new models of virtual care, beyond telehealth and/or video conferencing, such as 24-h command centres, and rapid response teams. SYSTEMATIC REVIEW REGISTRATION NUMBER: Prospero CRD42020200266.

Clinicians' delirium treatment practice, practice change, and influences: A national online survey.

BACKGROUND: Recent studies cast doubt on the net effect of antipsychotics for delirium. AIM: To investigate the influence of these studies and other factors on clinicians' delirium treatment practice and practice change in palliative care and other specialties using the Theoretical Domains Framework. DESIGN: Australia-wide online survey of relevant clinicians. SETTING/PARTICIPANTS: Registered nurses (72%), doctors (16%), nurse practitioners (6%) and pharmacists (5%) who cared for patients with delirium in diverse settings, recruited through health professionals' organisations. RESULTS: Most of the sample (n = 475): worked in geriatrics/aged (31%) or palliative care (30%); in hospitals (64%); and saw a new patient with delirium at least weekly (61%). More (59%) reported delirium practice change since 2016, mostly by increased non-pharmacological interventions (53%). Fifty-five percent reported current antipsychotic use for delirium, primarily for patient distress (79%) and unsafe behaviour (67%). Common Theoretical Domains Framework categories of influences on respondents' delirium practice were: emotion (54%); knowledge (53%) and physical (43%) and social (21%) opportunities. Palliative care respondents more often reported: awareness of any named key study of antipsychotics for delirium (73% vs 39%, p < 0.001); changed delirium treatment (73% vs 53%, p = 0.017); decreased pharmacological interventions (60% vs 15%, p < 0.001); off-label medication use (86% vs 51%, p < 0.001: antipsychotics 79% vs 44%, p < 0.001; benzodiazepines 61% vs 26%, p < 0.001) and emotion as an influence (82% vs 39%, p < 0.001). CONCLUSION: Clinicians' use of antipsychotic during delirium remains common and is primarily motivated by distress and safety concerns for the patient and others nearby. Supporting clinicians to achieve evidence-based delirium practice requires further work.

Current Challenges in the Recognition and Management of Delirium Superimposed on Dementia.

Delirium occurring in a patient with preexisting dementia is referred to as delirium superimposed on dementia (DSD). DSD commonly occurs in older hospitalized patients and is associated with worse outcomes, including higher rates of mortality and institutionalization, compared to inpatients with delirium or dementia alone. This narrative review summarizes the screening, diagnosis, management, and pathophysiology of DSD and concludes by highlighting opportunities for future research. Studies were identified via Medline and PsycINFO keyword search, and handsearching reference lists. Conceptually, DSD could be considered an "acute exacerbation" of dementia precipitated by a noxious insult akin to an acute exacerbation of heart failure or acute on chronic renal failure. However, unlike other organ systems, there are no established biomarkers for delirium, so DSD is diagnosed and monitored clinically. Because cognitive dysfunction is common to both delirium and dementia, the diagnosis of DSD can be challenging. Inattention, altered levels of arousal, and motor dysfunction may help distinguish DSD from dementia alone. An informant history suggestive of an acute change in cognition or alertness should be investigated and managed as delirium until proven otherwise. The key management principles include prevention, identifying and treating the underlying precipitant(s), implementing multicomponent interventions to create an ideal environment for brain recovery, preventing complications, managing distress, and monitoring for resolution. Informing and involving family members or caregivers throughout the patient journey are essential because there is significant prognostic uncertainty, including the risk of persistent cognitive and functional decline following DSD and relapse. Furthermore, informal carers can provide significant assistance in management. Emerging evidence demonstrates that increased exposure to delirium is associated with neuronal injury and worse cognitive outcomes although the mechanisms through which this occurs remain unclear. Given the clinical overlap between delirium and dementia, studying shared pathophysiological pathways may uncover diagnostic tests and is an essential step in therapeutic innovation.

Delirium researchers' perspectives of the challenges in delirium biomarker research: A qualitative study.

BACKGROUND: Despite the prevalence and impact of delirium, its pathophysiology remains unclear. In order to advance this field of research, robust scientific methodology is required, yet quality of reporting in this field of research has been highly inconsistent. Delirium biomarker research poses several challenges, none of which have been documented in the literature before. The aim of this study was to explore the perspectives of delirium researchers about key methodological issues in delirium biomarker research. METHODS: Following a Delphi study with delirium experts resulting in 60 recommendations for reporting delirium biomarker studies, semi-structured interviews with international delirium researchers were conducted. Interviews were audio-taped and transcribed verbatim, followed by thematic analysis of the qualitative data. RESULTS: Fifteen participants were interviewed between August and November 2019. Most were male (n = 12; 75%), clinician researchers (n = 13; 86%), and had more than ten years' experience in conducting delirium research (n = 9; 60%). Analysis revealed two major themes and ten sub-themes, outlining key considerations to advance the field of delirium biomarker research. The major themes were: 1) Practical and scientific challenges of delirium biomarker research: stagnation versus driving improved methods and reporting; and 2) Valuing delirium research through investment and collaboration. CONCLUSION: Findings identified a range of factors that contribute to the practical and ethical challenges of conducting delirium biomarker research, which have not previously been explicitly acknowledged or reported. A clear vision for collaborative efforts to enhance research quality for improved impact was also presented by the delirium researchers. This work complements the preceding Delphi and together these studies provide an in-depth understanding of what is needed in the field to inform and improve methods and reporting of delirium biomarker research.

Delirium in older adults is associated with development of new dementia: a systematic review and meta-analysis.

OBJECTIVES: Observational studies have examined the association between delirium and development of new dementia. However, no recent review has collectively assessed the available evidence quantitatively and qualitatively. We systematically reviewed and critically evaluated the literature regarding the association between delirium and dementia, and calculated the odds of developing new dementia after having delirium. METHODS: This systematic review and meta-analysis was conducted according to Preferred reporting items for systematic reviews and meta-analyses guidelines. MEDLINE, EMBASE and PsycINFO, were searched for English-language articles that compared the incidence of new dementia in older adult (≥65) inpatients with delirium, to inpatients without delirium. A random effects model was used for meta-analysis, and overall effect size was calculated using reported raw data of event counts. The Newcastle-Ottawa Quality Assessment scale assessed risk of bias. RESULTS: Six observational studies met eligibility criteria, with follow-up times ranging from six months to five years. Four looked at hip fracture surgical patients; one was on cardiac surgery patients and one examined geriatric medical patients. All studies excluded patients with pre-existing dementia. Pooled meta-analysis revealed that older adult inpatients who developed delirium had almost twelve times the odds of subsequently developing new dementia compared to non-delirious patients (OR = 11.9 [95% CI: 7.29-19.6]; p < 0.001). CONCLUSIONS: Older adult inpatients who develop delirium are at significant risk of subsequently developing dementia. This emphasises the importance of delirium prevention and cognitive monitoring post-delirium. The included studies mainly examined post-surgical patients-further research on medical and intensive care unit cohorts is warranted. Future studies should assess whether delirium duration, severity and subtype influence the risk of developing dementia.

A call to action for delirium research: Meta-analysis and regression of delirium associated mortality.

BACKGROUND: Delirium is an extremely common hospital complication. No study to date has assessed whether a priori defined covariates; type of hospital setting and year of study publication, influence the relationship between delirium and mortality. This is also the first study to examine the longitudinal trend of delirium-associated mortality over recent decades, to analyse the trajectory of our efforts in combating this disease. METHODS: MEDLINE, EMBASE and PsycINFO, were searched from January 1981 to May 2018 for English-language primary articles. Rigorous title and abstract screen and full-text screen were conducted independently by two reviewers. This paper adhered to MOOSE guidelines. Data was extracted independently by one reviewer using standardised data-collection sheets, with a separate reviewer verifying for accuracy. The quality of included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Unadjusted effect sizes and event counts were analysed with a random effects model in primary meta-analysis and meta-regression, whereas a mixed effect model was used in secondary sub-group analysis. Mortality data at longest follow-up and cumulative mortality (hospital mortality combined with mortality at longest follow-up) data were analysed. RESULTS: As part of a larger project, 446 of 6790 articles were retrieved, including 71 studies that measured mortality. Our results demonstrate that elderly inpatients with delirium had significantly greater odds of mortality (OR 3.18 [95%CI: 2.73, 3.70]) compared to non-delirious controls. Patients with delirium in the ICU had the highest odds for mortality (OR: 7.09 [95%CI: 3.60, 14.0]); double the risk compared to the average. Curiously, despite advancements in delirium research, delirium associated in-hospital odds of mortality has not changed in 30 years. CONCLUSION: This is the largest meta-analysis to confirm the association between delirium and mortality, in older (age ≥ 65) hospital inpatients. The current meta-analysis highlights the significant odds of mortality after an episode of delirium, and these odds are much higher for ICU patients. However, in contrast to other medical conditions that have seen a decrease in associated mortality over the past few decades, delirium associated mortality remains unchanged. These findings underscore the urgent need for better delirium treatments. PROSPERO Registration Number: CRD42018098627, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=98627.

Prevention of Delirium in Older Adults With Dementia: A Systematic Literature Review.

Although dementia is the largest independent risk factor for delirium and leads to poor health outcomes, we know little about how to prevent delirium in persons with dementia (PWD). The purpose of the current systematic literature review was to identify interventions designed to prevent delirium in older PWD. Seven studies meeting inclusion criteria were extracted. Five studies were in the acute care setting and two were community settings. One study used a randomized controlled trial design. Five of the seven interventions comprised multiple components addressing delirium risk factors, including education. Two studies addressed delirium by administration of medication or vitamin supplementation. Using the GRADE framework for the evaluation of study quality, we scored three studies as moderate and four studies as low. Thus, high-quality research studies to guide how best to prevent delirium in PWD are lacking. Although more research is required, the current review suggests that multicomponent approaches addressing delirium risk factors should be considered by health care professionals when supporting older PWD. [Journal of Gerontological Nursing, 46(10), 43-54.].

The financial and social costs of delirium.

PURPOSE: Delirium is common with serious short- and long-term sequelae. However, there are no licensed treatments internationally and relatively little biomedical discovery with the target of finding a cure, with the invisibility or underestimation of the economic implications as a potential driver for this inertia. METHODS: We conducted a narrative review of published literature in English quantitatively evaluating the financial and social costs of delirium to the health and care systems, patients and their carers. RESULTS: Delirium increases the cost of the index hospitalisation as well as increasing the need for post-acute care and the demands on unpaid, often older, carers. Delirium may cause as much as 10% of all cases of dementia and the ongoing need for care of these people with dementia doubles the cost of delirium. Prevention of delirium not only reduces the cost of delirium but also may decrease subsequent rate of dementia. CONCLUSION: The high cost of delirium itself as well as the resultant dementia warrants greater efforts to prevent delirium and discover effective treatment.

A systematic review of the overlap of fluid biomarkers in delirium and advanced cancer-related syndromes.

BACKGROUND: Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis. METHODS: A systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others. RESULTS: The 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting. CONCLUSION: There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness.