Validation of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Geriatric Outpatients.

OBJECTIVES: Before being used in clinical practice, a prediction model should be tested in patients whose data were not used in model development. Previously, we developed the ADFICE_IT models for predicting any fall and recurrent falls, referred as Any_fall and Recur_fall. In this study, we externally validated the models and compared their clinical value to a practical screening strategy where patients are screened for falls history alone. DESIGN: Retrospective, combined analysis of 2 prospective cohorts. SETTING AND PARTICIPANTS: Data were included of 1125 patients (aged ≥65 years) who visited the geriatrics department or the emergency department. METHODS: We evaluated the models' discrimination using the C-statistic. Models were updated using logistic regression if calibration intercept or slope values deviated significantly from their ideal values. Decision curve analysis was applied to compare the models' clinical value (ie, net benefit) against that of falls history for different decision thresholds. RESULTS: During the 1-year follow-up, 428 participants (42.7%) endured 1 or more falls, and 224 participants (23.1%) endured a recurrent fall (≥2 falls). C-statistic values were 0.66 (95% CI 0.63-0.69) and 0.69 (95% CI 0.65-0.72) for the Any_fall and Recur_fall models, respectively. Any_fall overestimated the fall risk and we therefore updated only its intercept whereas Recur_fall showed good calibration and required no update. Compared with falls history, Any_fall and Recur_fall showed greater net benefit for decision thresholds of 35% to 60% and 15% to 45%, respectively. CONCLUSIONS AND IMPLICATIONS: The models performed similarly in this data set of geriatric outpatients as in the development sample. This suggests that fall-risk assessment tools that were developed in community-dwelling older adults may perform well in geriatric outpatients. We found that in geriatric outpatients the models have greater clinical value across a wide range of decision thresholds compared with screening for falls history alone.

Monitoring the Well-being of Older People by Energy Usage Patterns: Systematic Review of the Literature and Evidence Synthesis.

BACKGROUND: Due to the aging population, there is a need for monitoring well-being and safety while living independently. A low-intrusive monitoring system is based on a person's use of energy or water. OBJECTIVE: The study's objective was to provide a systematic overview of studies that monitor the health and well-being of older people using energy (eg, electricity and gas) and water usage data and study the outcomes on health and well-being. METHODS: CENTRAL, Embase, MEDLINE (Ovid), Scopus, Web of Science, and Google Scholar were searched systematically from inception until November 8, 2021. The inclusion criteria were that the study had to be published in English, have full-text availability, target independent-living people aged 60 years and older from the general population, have an observational design, and assess the outcomes of a monitoring system based on energy (ie, electricity, gas, or water) usage on well-being and safety. The quality of the studies was assessed by the QualSyst systematic review tool. RESULTS: The search strategy identified 2920 articles. The majority of studies focused on the technical algorithms underlying energy usage data and related sensors. One study was included in this review. This study reported that the smart energy meter data monitoring system was considered unobtrusive and was well accepted by the older people and professionals involved. Energy usage in a household acted as a unique signature and therefore provided useful insight into well-being and safety. This study lacked statistical power due to the small number of participants and the low number of observed events. In addition, the quality of the study was rated as low. CONCLUSIONS: This review identified only 1 study that evaluated the impact of an energy usage monitoring system on the well-being and safety of older people. The absence of reliable evidence impedes any definitive guidance or recommendations for practice. Because this emerging field has not yet been studied thoroughly, many questions remain open for further research. Future studies should focus on the further development of a monitoring system and the evaluation of the implementation and outcomes of these systems. TRIAL REGISTRATION: PROSPERO CRD42022245713; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=245713.

Implementation of a medicine management plan (MMP) to reduce medication-related harm (MRH) in older people post-hospital discharge: a randomised controlled trial.

BACKGROUND: Medication-related harm (MRH) is an escalating global challenge especially among older adults. The period following hospital discharge carries high-risk for MRH due to medication discrepancies, limited patient/carer education and support, and poor communication between hospital and community professionals. Discharge Medical Service (DMS), a newly introduced NHS scheme, aims to reduce post-discharge MRH through an electronic communication between hospital and community pharmacists. Our study team has previously developed a risk-prediction tool (RPT) for MRH in the 8-weeks period post discharge from a UK hospital cohort of 1280 patients. In this study, we aim to find out if a Medicines Management Plan (MMP) linked to the DMS is more effective than the DMS alone in reducing rates of MRH. METHOD: Using a randomized control trial design, 682 older adults ≥ 65 years due to be discharged from hospital will be recruited from 4 sites. Participants will be randomized to an intervention arm (individualised medicine management plan (MMP) plus DMS) or a control arm (DMS only) using a 1:1 ratio stratification. Baseline data will include patients' clinical and social demographics, and admission and discharge medications. At 8-weeks post-discharge, a telephone interview and review of GP records by the study pharmacist will verify MRH in both arms. An economic and process evaluation will assess the cost and acceptability of the study methods. DATA ANALYSIS: Univariate analysis will be done for baseline variables comparing the intervention and control arms. A multivariate logistic regression will be done incorporating these variables. Economic evaluation will compare the cost-of-service use among the study arms and modelled to provide national estimates. Qualitative data from focus-group interviews will explore practitioners' understanding, and acceptance of the MMP, DMS and the RPT. CONCLUSION: This study will inform the use of an objective, validated RPT for MRH among older adults after hospital discharge, and provide a clinical, economic, and service evaluation of a specific medicines management plan alongside the DMS in the National Health Service (UK).

A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.

BACKGROUND: Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. METHODS: A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. RESULTS: Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). CONCLUSION: This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.

The Association Between the Kyphosis Angle and Physical Performance in Community-Dwelling Older Adults.

BACKGROUND: We investigated prospectively among community-dwelling older adults aged 65 years and older whether a larger kyphosis angle is associated with poorer physical performance (balance, muscle strength, or both), and whether this association is unidirectional. METHODS: Male and female participants performed a multicomponent physical performance test with subscores for gait, muscle strength, and balance at baseline and after 2 years. Hand grip strength was also measured at baseline and at follow-up. The Cobb angle was measured on DXA-based Vertebral Fracture Assessments, made at the baseline and follow-up visit. Through linear and logistic regression analysis, we investigated the association between the kyphosis angle and physical performance and vice versa. We stratified for sex, and tested for effect modification by age and study center. RESULTS: The mean kyphosis angle was 37° and 15% of the participants (n = 1 220, mean age 72.9 ± 5.7 years) had hyperkyphosis (Cobb angle ≥50°). A larger kyphosis angle at baseline was independently associated with a poorer total physical performance score in women of the oldest quartile (≥77 years) in both the cross-sectional and longitudinal analyses (baseline B -0.32, 95% confidence interval [CI] -0.56-0.08; follow-up B 0.32, 95% CI -0.55-0.10). There was no association between physical performance at baseline and kyphosis progression. CONCLUSION: A larger kyphosis angle is independently associated with a poorer physical performance at baseline and over time, and the direction of this association is unidirectional. These results emphasize the importance of early detection and treatment of hyperkyphosis to prevent further worsening of the kyphosis angle, thereby potentially preserving physical performance.

The association between hyperkyphosis and fall incidence among community-dwelling older adults.

Hyperkyphosis, an increased kyphosis angle of the thoracic spine, was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Hyperkyphosis could serve as an indicator of an increased fall risk as well as a treatable condition. INTRODUCTION: Hyperkyphosis is frequently found in adults aged 65 years and older and may be associated with falls. We aimed to investigate prospectively in community-dwelling older adults whether hyperkyphosis or change in the kyphosis angle is associated with fall incidence. METHODS: Community-dwelling older adults (n = 1220, mean age 72.9 ± 5.7 years) reported falls weekly over 2 years. We measured thoracic kyphosis through the Cobb angle between the fourth and 12th thoracic vertebra on DXA-based vertebral fracture assessments and defined hyperkyphosis as a Cobb angle ≥ 50°. The change in the Cobb angle during follow-up was dichotomized (< 5 or ≥ 5°). Through multifactorial regression analysis, we investigated the association between the kyphosis angle and falls. RESULTS: Hyperkyphosis was present in 15% of the participants. During follow-up, 48% of the participants fell at least once. In the total study population, hyperkyphosis was not associated with the number of falls (adjusted IRR 1.12, 95% CI 0.91-1.39). We observed effect modification by age (p = 0.002). In the oldest quartile, aged 77 years and older, hyperkyphosis was prospectively associated with a higher number of falls (adjusted IRR 1.67, 95% CI 1.14-2.45). Change in the kyphosis angle was not associated with fall incidence. CONCLUSIONS: Hyperkyphosis was associated with a higher fall incidence in the oldest quartile of a large prospective cohort of community-dwelling older adults. Because hyperkyphosis is a partially reversible condition, we recommend investigating whether hyperkyphosis is one of the causes of falls and whether a decrease in the kyphosis angle may contribute to fall prevention.

Know-Me: A Toolkit for Designing Personalised Dementia Care.

Personalisation is a crucial element in providing person-centred care for people with dementia. This paper presents the development and evaluation of a design toolkit to facilitate the work of designers and healthcare professionals in personalising dementia care. This toolkit, named "Know-me", was grounded in the findings of Ergonomics in Aging, Co-design, and Data-enabled Design, derived from literature review and from the field during a four-year doctorate project. "Know-me" was designed to be easily accessible, flexible, and engaging, providing concrete and hands-on guidance for designers and healthcare professionals to use in designing for personalised dementia care. A proof-of-concept evaluation of the "Know-me" toolkit was conducted via student projects on design for dementia care. During this process, we found that "Know-me" could be adapted flexibly so that the care team could use some of the tools by themselves. A feature-by-feature comparison of the "Know-me" toolkit with similar state-of-the-art toolkits was conducted, and based upon this, the strengths and weaknesses of the "Know-me" toolkit are discussed. This preliminary study indicates that the "Know-me" toolkit is a helpful addition to the current pool of toolkits on designing for dementia care.

A Digital Platform for Facilitating Personalized Dementia Care in Nursing Homes: Formative Evaluation Study.

BACKGROUND: Care personalization is key to the well-being of people with dementia according to person-centered care. With the development of the internet of things, a large quantity of personal data can be collected securely and reliably, which has the potential to facilitate care personalization for people with dementia. Yet, there are limited assistive technologies developed for this purpose, and the user acceptance of assistive technologies is low in nursing homes. Therefore, through a data-enabled design approach, a digital platform was developed for helping the care team in a nursing home to personalize dementia care, specifically in the management of behavioral and psychological dementia symptoms. OBJECTIVE: This study aimed to evaluate the digital platform in a real-life context with potential users from the following two aspects: (1) to explore if the digital platform could help with generating insights on the current state of each person with dementia and (2) to gather feedback on the digital platform from the care team. METHODS: The digital platform was deployed in the nursing home for 7 weeks and the data collected were visualized and presented to the care team via the digital platform. The visualizations were analyzed by the researchers for pattern detection. Meanwhile, the care team was asked to examine the visualizations and were interviewed for the following: (1) if any insights and actions were generated from the examination, (2) the usefulness of the digital platform, and (3) the improvements they would like to see. RESULTS: The data collected on the digital platform demonstrated its potential for pattern detection. Insights were generated by the care team and categorized into "client level," "ward level," and "team level." The corresponding actions taken by the care team were classified into "investigation" and "implementation." User acceptance varied across the care team, and three aspects of improvement for the digital platform were identified. CONCLUSIONS: By evaluating the digital platform, this study gained insights on applying data-enabled design for personalizing dementia care; besides, it offers future researchers some recommendations on how to integrate assistive technologies in the nursing home context.

New horizons in falls prevention and management for older adults: a global initiative.

BACKGROUND: falls and fall-related injuries are common in older adults, have negative effects both on quality of life and functional independence and are associated with increased morbidity, mortality and health care costs. Current clinical approaches and advice from falls guidelines vary substantially between countries and settings, warranting a standardised approach. At the first World Congress on Falls and Postural Instability in Kuala Lumpur, Malaysia, in December 2019, a worldwide task force of experts in falls in older adults, committed to achieving a global consensus on updating clinical practice guidelines for falls prevention and management by incorporating current and emerging evidence in falls research. Moreover, the importance of taking a person-centred approach and including perspectives from patients, caregivers and other stakeholders was recognised as important components of this endeavour. Finally, the need to specifically include recent developments in e-health was acknowledged, as well as the importance of addressing differences between settings and including developing countries. METHODS: a steering committee was assembled and 10 working Groups were created to provide preliminary evidence-based recommendations. A cross-cutting theme on patient's perspective was also created. In addition, a worldwide multidisciplinary group of experts and stakeholders, to review the proposed recommendations and to participate in a Delphi process to achieve consensus for the final recommendations, was brought together. CONCLUSION: in this New Horizons article, the global challenges in falls prevention are depicted, the goals of the worldwide task force are summarised and the conceptual framework for development of a global falls prevention and management guideline is presented.

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

BACKGROUND: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. METHODS: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. RESULTS: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. CONCLUSION: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

Personalising Management of Behavioural and Psychological Symptoms of Dementia in Nursing Homes: Exploring the Synergy of Quantitative and Qualitative Data.

Researchers have been exploring how to manage Behavioural and Psychological Symptoms of Dementia (BPSD) in a personalised way, meanwhile, assistive technologies have been developed to collect a variety of personal data. This urges more research in investigating the combination of: data collected by the care team, which are mainly qualitative; and data collected by assistive technologies, the majority of which are quantitative. Previous studies, however, have yet to explore if and how a combination of quantitative and qualitative data could facilitate the care team to better understand each resident with dementia in the nursing home context for personalised BPSD management. Guided by a Research through Design approach, a prototype for collecting and visualising the quantitative and qualitative data towards personalised BPSD management was developed together with the care team. Via developing this prototype, knowledge was gained in what types of data could be combined for personalised BPSD management in nursing homes, what are their values, how to collect and present them, and how to introduce them in the working routine of the care team for analysis. The main findings suggest that the types of data to be collected could be unique for each resident with dementia; the quantitative and qualitative data are of value to each other during data collection and analysis; data collection should be quick and standardised yet flexible for the care team; the overview page is vital for data presentation; and user scenarios could be created to nudge the care team to analyse the data at certain points of their working routine. In general, a combination of qualitative data and quantitative data could help the care team to discover more insights about each resident with dementia and thus improve the current practice of personalised BPSD management.

Serum vitamin D levels are associated with structural and functional properties of the carotid artery in older men and women.

BACKGROUND AND AIMS: This cross-sectional study aimed to assess the relationship between serum vitamin D levels and carotid and brachial artery distensibility in patients older than 55 years, referred to the outpatient clinic of the department of internal medicine and geriatric medicine of the Erasmus Medical Center, in Rotterdam. METHODS AND RESULTS: From April to July 2006 we consecutively enrolled 49 elder patients (21 men and 28 women, mean age 78 ± 8 years) without a cardiovascular event within 6 weeks before the visit. Carotid and brachial artery distensibility coefficients and serum 25(OH)D levels (mean 50 ± 28.8 nmol/L) were assessed. Multivariate analysis (with linear regression model) was performed to investigate the relation between these parameters: carotid artery distensibility coefficient was associated with serum 25(OH)D levels (ß = 0.112; 95% CI 0.053 0.172; p = 0.001). Moreover, a negative association was also observed between carotid artery distensibility coefficient and mean arterial pressure (ß = -0.279; 95% CI, -0.339 -0.159; p = 0.0001). On the contrary, brachial artery distensibility has shown no association with 25(OH)D levels, being negatively linked to LDL-cholesterol levels and heart rate. An association was also observed between serum 25(OH)D level and carotid artery intima-media thickness. CONCLUSION: Our results revealed that serum 25(OH)D levels of older men and women were associated with both structural and functional properties of the carotid artery. No association was found with the brachial artery distensibility.

Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool.

OBJECTIVES: To develop and validate a tool to predict the risk of an older adult experiencing medication-related harm (MRH) requiring healthcare use following hospital discharge. DESIGN, SETTING, PARTICIPANTS: Multicentre, prospective cohort study recruiting older adults (≥65 years) discharged from five UK teaching hospitals between 2013 and 2015. PRIMARY OUTCOME MEASURE: Participants were followed up for 8 weeks in the community by senior pharmacists to identify MRH (adverse drug reactions, harm from non-adherence, harm from medication error). Three data sources provided MRH and healthcare use information: hospital readmissions, primary care use, participant telephone interview. Candidate variables for prognostic modelling were selected using two systematic reviews, the views of patients with MRH and an expert panel of clinicians. Multivariable logistic regression with backward elimination, based on the Akaike Information Criterion, was used to develop the PRIME tool. The tool was internally validated. RESULTS: 1116 out of 1280 recruited participants completed follow-up (87%). Uncertain MRH cases ('possible' and 'probable') were excluded, leaving a tool derivation cohort of 818. 119 (15%) participants experienced 'definite' MRH requiring healthcare use and 699 participants did not. Modelling resulted in a prediction tool with eight variables measured at hospital discharge: age, gender, antiplatelet drug, sodium level, antidiabetic drug, past adverse drug reaction, number of medicines, living alone. The tool's discrimination C-statistic was 0.69 (0.66 after validation) and showed good calibration. Decision curve analysis demonstrated the potential value of the tool to guide clinical decision making compared with alternative approaches. CONCLUSIONS: The PRIME tool could be used to identify older patients at high risk of MRH requiring healthcare use following hospital discharge. Prior to clinical use we recommend the tool's evaluation in other settings.

Co-designing with people with dementia: A scoping review of involving people with dementia in design research.

Co-designing with people with dementia (PwD) can uncover their needs and preferences, which have been often overlooked. It is difficult for PwD to understand designers and express themselves in a conventional co-design session. This study aims to evaluate the effects of involving PwD in design research on both PwD and the design process; to identify the trends of involving PwD in design research; to extract tools, recommendations, and limitations of involving PwD from reviewed studies to update the recommendations on how to co-design with PwD. A scoping review was carried out within the electronic databases PubMed and Scopus, and eight research questions were proposed, in order to gain specific knowledge on the involvement of PwD in design research. Twenty-six studies met the inclusion criteria, and 32 sessions were evaluated. Beneficial effects on both PwD and the design process were reported. The number of studies involving PwD in the moderate and severe stages of dementia has increased. Based on the review, an update of the existing tools and recommendations for co-designing with PwD is provided and a list of limitations of involving PwD is presented. The review shows that involving PwD in design research is beneficial for both the PwD and the design process, and there is a shift towards involving people who are in the moderate and severe stages of dementia. The authors propose that multidisciplinary meetings and case studies should be carried out to evaluate and refine the list of tools and recommendations as well as the list of limitations generated in this review.

Shoe design for older adults: Evidence from a systematic review on the elements of optimal footwear.

Due to changes in foot morphology and the occurrence of foot deformities and foot pain with ageing, older people frequently wear ill-fitting shoes. This can lead to discomfort and reduced mobility. A review of the literature was performed in Medline, Scopus and Embase with three aims: (a) to evaluate the effects of shoes or shoe elements on the comfort and mobility of older adults, (b) to summarise the evidence-based elements of a safe and comfortable shoe for older adults, and (c) from that, to compile those elements into design recommendations for a safe and comfortable shoe for older adults. Safe elements of footwear include proper anatomical fit, a well-fitting toe box, limited heel height, a broad enough heel, a firm insole and midsole, an outsole with sufficient tread, bevelled heel, firm heel counter with snug fit, and an easy and effective closing mechanism. We conclude that there is a need for shoe design specifically aimed at the foot morphology and demands of older people. The shoe market should increase the availability of well-fitting shoes designed for the older foot and person.

Electronic assistive technology for community-dwelling solo-living older adults: A systematic review.

The proportion of older adults who live alone in single households is growing continuously. In the care of these solo-living older adults, electronic assistive technology (EAT) can play an important role. The objective of this review is to investigate the effects of EAT on the wellbeing of community-dwelling older adults living alone in single households. A systematic review of English articles was conducted based on PMC, Scopus, Web of Science and the Cochrane database. Additional studies were identified from the references. In total, 16 studies were identified, six of them with follow-up. There is evidence that EAT can improve the physical and mental wellbeing of older adults. There was little evidence that EAT can improve social wellbeing. We conclude that more personalized designs and interventions, and more user engagement could be embedded in the design of EAT for solo-living community-dwelling older adults and that more evidence is needed regarding the effects of those interventions.

Differences in potential biomarkers of delirium between acutely ill medical and elective cardiac surgery patients.

BACKGROUND/AIMS: The pathophysiology of delirium is poorly understood. Increasing evidence suggests that different pathways might be involved in the pathophysiology depending on the population studied. The aim of the present study was to investigate potential differences in mean plasma levels of neopterin, amino acids, amino acid ratios and homovanillic acid between two groups of patients with delirium. METHODS: Data from acutely ill medical patients aged 65 years and older, and patients aged 70 years and older undergoing elective cardiac surgery, were used. Differences in biomarker levels between the groups were investigated using univariate ANOVA with adjustments for age, sex, comorbidities, C-reactive protein (CRP) and the estimated glomerular filtration rate (eGFR), where appropriate. Linear regression analysis was used to identify potential determinants of the investigated biochemical markers. RESULTS: Eighty patients with delirium were included (23 acutely ill medical patients and 57 elective cardiac surgery patients). After adjustment, higher mean neopterin levels (93.1 vs 47.3 nmol/L, P=0.001) and higher phenylalanine/tyrosine ratios (1.39 vs 1.15, P=0.032) were found in acutely ill medical patients when compared to elective cardiac surgery patients. CRP levels were positively correlated with neopterin levels in acutely ill medical patients, explaining 28.4% of the variance in neopterin levels. eGFR was negatively correlated with neopterin in elective cardiac surgery patients, explaining 53.7% of the variance in neopterin levels. CONCLUSION: In this study, we found differences in mean neopterin levels and phenylalanine/tyrosine ratios between acutely ill medical and elective cardiac surgery patients with delirium. Moreover, our findings may suggest that in acutely ill medical patients, neopterin levels are mainly determined by inflammation/oxidative stress whereas in elective cardiac surgery patients, neopterin levels are mainly driven by renal function/fluid status. These findings suggest that the markers and pathways that might be involved in the pathophysiology of delirium may differ between specific groups of patients.