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.

A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

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.

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.

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.

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.

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.

Toward best practice methods for delirium biomarker studies: An international modified Delphi study.

BACKGROUND: Delirium is a serious and distressing neurocognitive condition common in people with advanced illness. The understanding of delirium pathophysiology is limited and largely hypothetical. To accelerate empirical understanding of delirium pathophysiology, robust scientific methods for conducting and reporting delirium biomarker studies are urgently needed. The aim of this study was to develop international consensus on the core elements of high-quality delirium biomarker studies. METHODS: A three-round modified Delphi survey was conducted from February to August 2019. Participants were international researchers experienced in conducting delirium studies from a range of settings (hospital, university, research centres). Round one commenced with open-ended questions developed from results from a prior systematic review and the REMARK (REporting recommendations for tumour MARKer prognostic studies) checklist. Responses were qualitatively analysed, and closed statements were developed. Participants then ranked the importance of these statements using a 5-point Likert scale in rounds 2 and 3. A priori consensus was defined as ≥70% participant agreement. Descriptive statistics for each item were computed including the mean Likert scores, SD and median participant scores. RESULTS: Twenty-eight participants completed survey round one, 16 completed round two and 19 completed the final round. Consensus was achieved for a total of 60 items. CONCLUSION: The Delphi survey identified items that expert researchers agreed were important in the conduct of delirium biomarker studies. These reporting items provide a strong platform for improved methodological quality and opportunities to synthesise future delirium biomarker studies.

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.

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.].

A systematic review of neuroimaging in delirium: predictors, correlates and consequences.

OBJECTIVE: Neuroimaging advances our understanding of delirium pathophysiology and its consequences. A previous systematic review identified 12 studies (total participants N = 764, delirium cases N = 194; years 1989-2007) and found associations with white matter hyperintensities (WMH) and cerebral atrophy. Our objectives were to perform an updated systematic review of neuroimaging studies in delirium published since January 2006 and summarise the available literature on predictors, correlates or outcomes. METHODS: Studies were identified by keyword and MeSH-based electronic searches of EMBASE, MEDLINE and PsycINFO combining terms for neuroimaging, brain structure and delirium. We included neuroimaging studies of delirium in adults using validated delirium assessment methods. RESULTS: Thirty-two studies (total N = 3187, delirium N = 1086) met the inclusion criteria. Imaging included magnetic resonance imaging (MRI; N = 9), computed tomography (N = 4), diffusion tensor imaging (N = 3), transcranial Doppler (N = 5), near infrared spectroscopy (N = 5), functional-MRI (N = 2), single photon emission computed tomography (N = 1), proton MRI spectroscopy (N = 1), arterial spin-labelling MRI (N = 1) and 2-13 fluoro-2-deoxyglucose positron emission tomography (N = 1). Despite heterogeneity in study design, delirium was associated with WMH, lower brain volume, atrophy, dysconnectivity, impaired cerebral autoregulation, reduced blood flow and cerebral oxygenation and glucose hypometabolism. There was evidence of long-term brain changes following intensive care unit delirium. CONCLUSIONS: Neuroimaging is now used more widely in delirium research due to advances in technology. However, imaging delirious patients presents challenges leading to methodological limitations and restricted generalisability. The findings that atrophy and WMH burden predict delirium replicates findings from the original review, while advanced techniques have identified other substrates and mechanisms that warrant further investigation.

Medicine information exchange networks among healthcare professionals and prescribing in geriatric medicine wards.

AIMS: Effective transfer of information is vital for rational drug therapy. This is particularly important for older patients, who have a high prevalence of polypharmacy and are managed by multidisciplinary teams. We aimed to assess medicine information exchange (MIE) networks in geriatric medicine wards and whether they are associated with prescribing patterns. METHODS: We conducted network analysis in acute geriatric medicine wards from four hospitals to characterize MIE networks among multidisciplinary team members. Corresponding patient data were collected to analyze high-risk prescribing in conjunction with network characteristics. RESULTS: We found that junior doctors, senior nurses and pharmacists were central to MIE across all four hospitals. Doctors were more likely than other professions to receive medicines information in three hospitals. Reciprocity and the tendency to communicate within one's own profession also influenced network formation. No difference was observed in prescribing practice between hospitals. CONCLUSIONS: Understanding MIE networks can identify gaps in multidisciplinary communication that can be addressed. Networks may identify targets for dissemination of interventions to improve prescribing.

A multidisciplinary intervention to prevent subsequent falls and health service use following fall-related paramedic care: a randomised controlled trial.

Background: approximately 25% of older people who fall and receive paramedic care are not subsequently transported to an emergency department (ED). These people are at high risk of future falls, unplanned healthcare use and poor health outcomes. Objective: to evaluate the impact of a fall-risk assessment and tailored fall prevention interventions among older community-dwellers not transported to ED following a fall on subsequent falls and health service use. Design, setting, participants: Randomised controlled trial involving 221 non-transported older fallers from Sydney, Australia. Intervention: the intervention targeted identified risk factors and used existing services to implement physiotherapy, occupational therapy, geriatric assessment, optometry and medication management interventions as appropriate. The control group received individualised written fall prevention advice. Measurements: primary outcome measures were rates of falls and injurious falls. Secondary outcome measures were ambulance re-attendance, ED presentation, hospitalisation and quality of life over 12 months. Analysis was by intention-to-treat and per-protocol according to self-reported adherence using negative binominal regression and multivariate analysis. Results: ITT analysis showed no significant difference between groups in subsequent falls, injurious falls and health service use. The per-protocol analyses revealed that the intervention participants who adhered to the recommended interventions had significantly lower rates of falls compared to non-adherers (IRR: 0.53 (95% CI : 0.32-0.87)). Conclusion: a multidisciplinary intervention did not prevent falls in older people who received paramedic care but were not transported to ED. However the intervention was effective in those who adhered to the recommendations. Trial registration: the trial is registered at the Australian New Zealand Clinical Trials Registry: ACTRN 12611000503921, 13/05/2011.

Appropriate care for older people with cognitive impairment in hospital.

More than half of the patients in adult hospitals are over 65 years of age. Although not a normal part of ageing, many older people will present to hospital with cognitive impairment (dementia or delirium) along with other complex comorbidities. Older people, and particularly those with dementia, are also at increased risk of developing delirium during their hospital stay. Delirium has serious short and long term consequences, such as increased mortality, falls, accelerated functional and cognitive decline, and earlier entry to residential care. Appropriate delirium care consists of introducing evidence-based prevention strategies for all patients at risk. For patients with delirium, it is crucial that delirium is not missed and that the underlying causes are identified and treated. Screening, assessment and a systematic workup is vital. As well as treating the underlying medical and surgical causes, the involvement of family members and a calm, safe environment are important. Patients with cognitive impairment should receive person-centred, goal-directed care so that their particular risks of harm are identified and minimised, and their care is aligned with their preferences and is medically appropriate for their circumstances. Three de-identified, composite case scenarios illustrate, respectively, the role of medicines in causing delirium, how family members can assist in evaluation, and the importance of the appropriate management of post-operative delirium.

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.

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.

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.

Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium.

BACKGROUND: The aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration. METHODS: Using a 13-plex Discovery Assay®, we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer's disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium. RESULTS: Here we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status. CONCLUSIONS: Several CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored.

Delirium is a syndrome in which there are substantial changes in a person's ability to focus, understand, or pay attention to events. Delirium often occurs in response to sudden trauma and is more common in persons with pre-existing cognitive impairment. What happens in the brain during delirium is not well understood. To learn more, we have studied whether markers in the cerebrospinal fluid were altered in people with delirium compared to people without delirium. To understand differences specifically caused by delirium, we included two control groups without acute trauma, one with cognitively healthy participants and one with dementia patients. We found several markers altered in people with delirium, with most of the markers similarly altered in people with cognitive impairment due to dementia. One marker was directly linked to delirium and could potentially shed light on the brain processes that cause the syndrome.