Multimorbid Patients Research Articles

Examining the relationships between patients' multimorbidity trajectories and prognostic outcomes after the initial hip fracture.

Hip fractures significantly affect patients' health and quality of life. Despite therapeutic treatments, many patients continue to experience poor prognoses that include recurrent fractures and mortality, especially the older ones. Therefore, understanding important factors associated with post-fracture prognoses is critical. This study focuses on patients' multimorbidity trajectories and examines how the trajectory's time span, number of coexisting chronic diseases, and sequential disease patterns relate to distinct prognostic outcomes. From the National Health Insurance Research Database in Taiwan, we obtain a sample of 128,822 patients who suffered an initial hip fracture between 1996 and 2011. We use this sample to analyze the relationships between multimorbidity trajectories and prognostic outcomes after an initial hip fracture. The results reveal that a patient's multimorbidity trajectory's time span and number of chronic diseases significantly associate with his or her post-fracture prognosis. In addition, essential sequential patterns of chronic diseases relate to post-fracture prognoses too. We then leverage the discovered relationships to develop a cross-attention neural network method for estimating patients' post-fracture prognoses and demonstrate its predictive utilities relative to several prevalent machine leaning methods. This study underscores the importance of leveraging the time span, number of chronic diseases, and sequential disease patterns in patients' multimorbidity trajectory profile to estimate their prognoses within three years of an initial hip fracture, which can support physicians' clinical decisions and patient management.

Impact of musculoskeletal joint complaints on quality of life in patients with inflammatory bowel disease: a cross-sectional study

BackgroundMusculoskeletal joint complaints (MSCs) are the most common extraintestinal manifestation of inflammatory bowel disease (IBD). We aimed to investigate the effect of MSC on the health-related quality of life (QoL)...

Risks associated with cancer screening programmes among multimorbid patients: a systematic review

Abstract Background Cancer screening programmes have been implemented to facilitate early detection of cancer. However, there are risks associated with cancer screening, such as overdiagnosis. This means identifying problems that were never going to cause harm1. This includes identification of abnormalities that do not progress, or that progress too slowly to cause symptoms or harm during a person’s remaining lifetime in the context of multi-morbidity1,2. Aim We conducted a systematic review of the literature to explore the harms associated with overdiagnosis in multimorbid patients when they undergo three different types of cancer screening programmes. Methods The search was conducted on MEDLINE, EMBASE, PSYCHINFO and Scopus from 1960 (cancer screening programmes implementation) until November 2023. Inclusion criteria involved studies with multimorbid participants (having two or more chronic conditions), having one of three common types of cancers (i.e., breast, prostate and lung), and used a standardised method for screening (i.e., mammography, Prostate-specific antigen test, and Low Dose Computed tomography (LDCT) or Computed Tomography scans (CT)). Only peer-reviewed studies published in English were included. Four keyword sets were used, “Multimorbidity”, “Overdiagnosis “, “Patient harms” and “Cancer screening”. Two independent reviewers conducted the search and data extraction. Rayyan web application was used to help with title, and abstract screening, and to compare the independent reviews. The Newcastle-Ottawa scale was used for quality assessment. This systematic review was registered with PROSPERO database (CRD42024475175) and followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidance. Ethical approval was not required to undertake this review. Results A total of 200 studies resulted from all the databases search and duplicates (n=29) removed. Titles, abstracts and full-texts were screened, with seven studies meeting the inclusion criteria. Quality assessment of the included studies showed two studies of good quality and five studies of poor quality. All included studies were conducted in the United States. Breast cancer overdiagnosis increased with increasing the number of comorbidities. Rates of overdiagnosis with prostate cancer were higher compared to breast cancer, with multimorbid patients having a 15% higher risk of overdiagnosed malignancies, compared to non-multimorbid individuals. Harms of overdiagnosis were categorised into psychological (e.g. anxiety), physical (e.g. side effects of medications) and financial (e.g. costs to healthcare systems). Overdiagnosis with lung cancer was associated with increased anxiety, with more individuals dying from other causes than lung cancer in post-mortem studies, questioning the risk versus benefit of lung cancer screening result interpretation for non-progressive disease. Conclusion The emergence of sophisticated testing technologies and greater access to screening tests can contribute to overdiagnosis. We found many different types of harm related to overdiagnosis in common types of cancer. Further research is required to explore the risk of overdiagnosis with other types of cancer. Awareness of clinicians about the risks of overdiagnosis, particularly in high-risk population, such as multimorbid patients, could guide their decision-making regarding non-progressive cancer treatment.

Long-Term Follow-Up After Non-Curative Endoscopic Submucosal Dissection for Early Gastrointestinal Cancer-A Retrospective Multicenter Analysis.

Background: Endoscopic Submucosal Dissection (ESD) has become the standard therapy for early malignant lesions in the gastrointestinal tract and has shown as good oncological surgery results. Approximately 30% of ESDs do not meet the criteria for oncological curability, and upfront surgery is indicated. Hence, about 40% of patients with an indication for surgery are advised against surgery because of comorbidities and an advanced age. Methods: We performed a multicenter retrospective cohort study on the long-term outcomes of non-curative ESDs, performed between 2009 and May 2024, without additional tumor therapy. The primary outcome was the recurrence of malignancy, either local malignancy or lymph node metastasis during follow-up, or death. We compared the outcomes between two cohorts: after non-curative ESD (ncESD) and after curative ESD (cESD). Results: A total of 374 ESDs were analyzed in this study. Overall, the technical success rate was 91%, and the oncological curative resection criteria were met in 70.9% of patients. Severe complications occurred in 5% of cases without procedure-associated mortality. In the ncESD group, 20% (7/35) of patients had a recurrence of malignancy primarily due to positive horizontal margins in the resection specimens, and 3 out of 35 died due to a non-oncological reason during the follow-up (mean length 36.6 months). In the cESD group, 3% (1/33) of patients had tumor recurrence, and 1 patient died because of a non-oncological reason. The tumor recurrence rate between the cohorts was significant (p = 0.017), and overall mortality did not show significance (p = 0.33). Conclusions: Especially in the elderly and multimorbid patients, the recommendation to perform rescue surgery after non-curative ESD remains challenging. Residual malignancy rates in surgical resection specimens are low, recurrence rates of malignancy are low, and mortality rates for non-oncological reasons are high in this population. There is a need for more data for the individualization of patient management after non-curative ESD.

Effect of integrated medicines management on quality of discharge medication information - a secondary endpoint in a randomized controlled trial.

High-quality discharge information is important to promote patient safety when patients are transferred from hospital to primary care. Patients with multiple long-term conditions are especially vulnerable to insufficient transfer of medication information, as they use many medications and have complex interactions with the healthcare services. The aim of this study was to investigate the effect of integrated medicines management provided to hospitalized multimorbid patients on the quality of the discharge medication information. Multimorbid patients ≥18 years, using a minimum of four regular medications from a minimum of two therapeutic medication classes were recruited from the Internal Medicine ward, Oslo University Hospital, Norway, from August 2014 to March 2016 and randomly assigned, 1:1, to the intervention or control group. Intervention patients received integrated medicines management throughout the hospital stay. Control patients received standard care. This paper reports the results of a pre-specified secondary endpoint analysis of a randomized controlled trial; the difference between the intervention and control group in the quality of discharge medication information. The analysis population comprised 384 patients. Integrated medicines management improved the discharge summary quality score of the medication information from 5.8 ± 1.5 to 8.6 ± 2.6 (mean difference 2.7, 95% CI 2.3-3.2, p < 0.001). In total 171 intervention patients (89%) received a patient discharge information letter, compared to 66 control patients (35%), p < 0.001. The quality score of the medication information in the patient discharge information letter was improved from 6.0 ± 1.8 in the control group to 10.0 ± 1.3 in the intervention group (mean difference 4.0, 95% CI 3.6-4.4, p < 0.001). Integrated medicines management delivered to multimorbid patients during a hospital stay improved the quality of the medication information in discharge summaries as well as patient discharge information letters and ensured that a discharge information letter in lay language was prepared for almost all patients who were involved in the management of their medications after discharge.

The Impact of Poor Air Quality on Hospitalisation of Multi-morbid Patients: A Systematic Review

Abstract Background Exposure to poor air quality worsen existing health conditions, particularly amongst vulnerable patients, leading to increased healthcare utilization. We conducted a systematic review to explore the impact of exposure to poor quality on healthcare requirements in multi-morbid patients. Methods We searched six major databases (Medline via Ovid, Embase via Ovid, Web of Science, CINAHL, Global Health, and Scopus) using search terms grouped into sets relating to ‘air pollution,’ ‘multimorbidity,’ “association” and ‘hospitalisation.’ We were interested in the impact of common air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and articles were screened independently by two researchers. The review was registered with The International Prospective Register of Systematic Reviews (CRD42022369757) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results A total of nineteen studies were included. All six air pollutants increased hospitalisation amongst multi-morbid patients, especially those with diabetes and cardiovascular comorbidity. Females and the elderly (&amp;gt;65 years old) were the most vulnerable to the effects of air pollution, with an increase in hospitalisations of 9.23% and 6.35% when exposed to PM2.5 and PM10, respectively. Patients &amp;gt;65 years had a higher likelihood of hospitalisation for ischemic and haemorrhagic stroke when exposed to PM2.5 or PM10 at warm season. Patients (≥70 years) who had cardiovascular and pulmonary comorbidity were 3.9% more likely to be hospitalised for a cardiopulmonary event with a rise in NO2 levels. We found an intersectional effect (referred to as “the CADC effect” - Climatic changes, Air pollutant, Demographics, Chronic conditions) that influenced the likelihood of hospitalisation. Conclusions Future research is required to further understand this CADC effect in other high-risk population. Key messages • Females, elderly, those with cardiovascular, and pulmonary comorbidity are at the highest risk of hospitalisation with poor air quality. • The CADC effect explains the intersectional effect between hospitalisation in multimorbid patients, patients demographics and chronic conditions, and air pollution and temperature effects.

A systematic review of cancer overdiagnosis in multimorbid patients

Abstract Background Cancer screening looks for early signs of cancer in people who do not currently exhibit symptoms. However, screening can also identify abnormalities that do not progress to produce symptoms or death. This could include the identification of tumours, which stop growing or grow very slowly; patients usually die with them rather than from them. We systematically reviewed the literature to investigate the harmful consequences of cancer overdiagnosis in multi-morbid patients. Methods We followed the PRISMA reporting guidelines and registered the review with PROSPERO (CRD42024475175). A Population, Intervention, Comparator, Outcome and Study design (PICOS) framework was used as an organising framework. Peer-reviewed studies were included except case series, case report reviews and conference abstracts. Four large databases (Medline, Embase, APA Psych INFO and Scopus) were searched in Nov23 using appropriate keywords grouped into categories: multimorbidity, overdiagnosis, patient harms, cancer screening. Titles were screened according to the eligibility criteria and their quality assessed. Studies needed to have investigated the extent of harm caused by overdiagnosis (e.g., overtreatment). Results A total of 200 articles were retrieved, with seven meeting our inclusion criteria. All included studies were based in the US. Breast and prostate cancer overdiagnosis was reported to be 15% higher in multimorbid populations compared to the average-risk population. Multimorbid individuals were more vulnerable to the harms of cancer overdiagnosis, with psychological, physical and financial harms reported. Conclusions These findings contribute valuable insights into the intricate interplay between comorbidities, cancer overdiagnosis, and associated harms. Radical treatment interventions in multi-morbid patients can carry greater risk of complications. Current screening guidelines only address average-risk populations; future guidelines need to reflect these findings. Key messages • Cancer overdiagnosis was found to be higher in multimorbid populations compared to the average-risk population. • Multimorbid individuals are also more vulnerable to the harms of cancer overdiagnosis.

Predicting hospital readmission in multimorbid patients with the use of AI: A systematic review

Abstract Background Multimorbid patients are at higher risk of hospital readmission due to the complex nature of their conditions. Identifying those who may be at particularly high risk would allow us to intervene early and potentially delay or prevent such readmissions occurring, thus reducing healthcare costs. We conducted a systematic review investigating the use of machine learning models in predicting 30-days unplanned hospital readmission of multimorbid patients. Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, and was registered with PROSPERO (CRD42022373937). We searched MEDLINE, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Included studies developed an AI model for prediction of 30-days hospital readmission for adult patients with two or more health conditions. The CHARM and PROBAST checklists for data extraction and bias assessment were used. The quality of included studies was assessed with the CASP checklist. Results Eighteen papers were eligible for inclusion. A total of 669 predictors were reported with an average of 37 used per model. Predictors were classified as modifiable and non-modifiable with the most common modifiable predictors being hospital length of stay, hypertension, anaemia and obesity. Average sensitivity and specificity of the models was reported to be 72% in 13 studies and 79.2 in 11 studies, respectively. Area under the curve (AUC) was reported in 13 studies, five of which were considered to have good discrimination power (AUC&amp;gt;0.8). Conclusions Machine learning models are capable of accurately predicting 30-days hospital readmission of multimorbid patients. Identifying modifiable predictors with highest weight allows for better planning and resource allocation to potentially reduce the risk of 30-days readmissions. An important area for future work would be the implementation of these high performance models in practice. Key messages • Hospital readmissions are preventable and identifying those at higher risk allows us to intervene early. • Machine learning models are capable of predicting 30-days readmission of multimorbid patients.

Using HIS administrative data for initial assessment of comorbid patients’ status (Covid-19 case)

Abstract Background Despite numerous published articles, most of the studies on COVID-19 focused on influence of clinical characteristics and treatments on severity. Yet, the epidemiological viewpoint was rarely discussed. Based on our experience with comorbid hospitalized COVID-19 patients, we aim to show that HIS administrative data can be used to identify individuals that are more prone to worse outcome thus improving patient management not only during pandemics. Methods A retrospective single-center study was conducted using archived anonymized HIS administrative data for all 8319 COVID-19 patients in the university hospital ‘Saint Marina’-Varna, Bulgaria, in the period 14/06/2020-31/12/2021. Up to 7 comorbidities per patient were registered in HIS with ICD-10 codes, used for our analyses. Non-parametric tests and logistic regression were used at α=.05, 95%CI. Results Comorbid patients were 5741(69%), 50.3% ≥69y, 52% male; 1602(27.9%) died, 64% ≥69y, 54.4% male. Deceased were older (p&amp;lt; .01) and had more comorbidities (p&amp;lt; .01). Multimorbid patients (OR = 4.43; 3.80-5.17), male (OR = 4.72; 3.83-5.82) and older ones (OR = 1.91; 1.57-2.34) had higher odds of dying. The odds of dying increased with the number of comorbidities from OR=.635; .559-.721 for 1 to OR = 4.23; 3.28-5.46 for 7. From 4967 comorbid diseases (451 ICD-10 codes), only those from code groups A, J, N, E, I, Z were suitable for analysis. Patients with A41.9 (OR = 213.69; 52.88-863.43), J80 (OR = 52.88; 32.58-85.56), N17 (OR = 18.63; 10.24-33.87), E11.7 (OR = 4.72; 3.09-7.19), I13.2 (OR = 4.67; 3.151-6.93), Z95 (OR = 3.81; 2.74-5.31), I63 (OR = 3.56; 2.25-5.61), E66 (OR = 3.12; 2.10-4.64) died more often. Conclusions Our findings match the results based on EMR data: death with COVID-19 was associated with comorbidities (sepsis, acute RDS and kidney, heart and renal failure, diabetes, cerebral infarction, obesity, implants and grafts), age, gender, i.e. HIS administrative data can be used for quick assessment of comorbid patients’ status. Key messages • HIS administrative data can be used for quick assessment of multimorbidity and following personalized treatment is highly recommended to decrease hospital mortality not only in times of pandemic. • Older Bulgarians have many comorbidities from ICD code groups A, J, N, E, I, Z, and are more prone to death, especially in times of pandemic. Public health measures are needed to prevent comorbidity.

The implementation of modern guideline-directed medical therapy among hospitalized patients with heart failure with reduced ejection fraction: real-world experience from two tertiary cardiac centers

Abstract Background According to the 2021 ESC HF Guidelines (GLs), the conventional triple therapy (TT) (RASi+βB+MRA) of HFrEF has been supplemented with the SGLT2 inhibitor dapa- and empagliflozin as the fourth pillar of the foundational quadruple therapy (QT) recommended for all HFrEF patients. Aim To assess the changes in the implementation of GDMT and investigate its impact on the prognosis among hospitalized HFrEF patients in light of the 2021 HF GLs. Patients and methods A retrospective data analysis of a consecutive cohort of HFrEF patients hospitalized due to HF between 01/01/2019 and 31/12/2023 at two tertiary cardiac centers was performed. Patients were classified into two groups: those hospitalized before and those after the publication of the 2021 ESC HF GLs (27/08/2021). Differences in the implementation of the drug therapy were analysed using the Chi-square test. 1-year all-cause mortality (ACM) was compared using Kaplan-Meier method and log-rank test. The independent predictors of the 1-year ACM were investigated with uni-, and multivariate Cox-regression analysis. Results A total cohort of 560 patients (male: 76%, age: 63 [51-72] years, coronary artery disease: 46%, diabetes: 38%, atrial fibrillation: 44%, LVEF: 25 [20-30]%, eGFR: 57 [43-74]mL/min/1.73m²; NT-proBNP: 5574 [2529-10960]pg/mL) was treated with a high proportion of TT (80%) and with QT (TT + SGLT2i) in 34% at discharge. After the publication of the 2021 ESC HF GLs, the proportion of patients on these SGTL2is improved (10% vs 57%, p&amp;lt;0.001; in the group before vs. after the publication of the GLs), resulting in an increased proportion of patients on QT (10% vs. 52%, p&amp;lt;0.001). There was no significant difference between groups regarding the use of TT (6% vs. 3%) or QT (1% vs. 3%) at target doses. The 1-year ACM was more favourable for those receiving QT (non-QT and non-TT: 41% vs. TT: 16% vs. QT: 11%, p&amp;lt;0.001). According to the multivariate Cox-regression analysis, older age, and more advanced left ventricular systolic dysfunction proved to be negative independent predictors of 1-year ACM, while "de novo" diagnosis of HFrEF and the application of TT/QT (adjusted HR: 0.303, 95% CI: 0.207-0.445, p&amp;lt;0.001) resulted in better outcomes. Conclusions The 2021 ESC HF GLs have led to a breakthrough regarding the modern drug treatment recommended for all patients in HFrEF. Our results demonstrated that the introduction of SGLT2is and the use of QT was feasible even in the everyday practice among complex, multimorbid HFrEF patients requiring hospitalization and the implementation of TT/QT was accompanied by a better prognosis.

Management strategies in rheumatoid arthritis.

Management of rheumatoid arthritis (RA) has evolved from simply the direct translation of drug efficacy results from clinical trials to patient care, to a more complex longitudinal process that considers not only drug efficacy but also the safety gestaltof a treatment and patient profiles and preferences, as well as health-economic factors. With numerous DMARDs available to treat RA, knowledge about trial efficacy becomes less important than data that inform an appropriate clinical strategy for their optimal selection and use. Overly ambitious approaches targeting the 'maximum' level of success could, for example, be prone to failure and create frustration, and lead to a large number of patients then being considered as 'difficult to treat'. Safety profiles might be more informative than efficacy profiles for precision medicine approaches. Contemporary RA management strategies might therefore take a more holistic approach, beyond merely efficacy, to the setting of targets that lead to improved compliance rather than aspirational successes, with consideration of each patient's multimorbidity profile and preferences, as well as the safety profileof each treatment. Ultimately, the goal remains unchanged: maximizing health-related quality of life; however, with a focus on optimal balance rather than superlatives.

Missing Medical Data in Neurological Emergency Care Compromise Patient Safety and Healthcare Resources.

Background: Acute care of patients in the emergency department (ED) can be very challenging when patients attend EDs without their important medical information. This is especially problematic for multimorbid patients under polypharmacy. The aim of this study was to assess systematically the frequency and clinical relevance of incomplete medical data upon ED admission. Methods: The study was conducted in the neurological ED of a German tertiary hospital. The availability and accuracy of medical data of all neurological patients in the ED were assessed upon arrival. Treating ED physicians were asked about the acute care of the patients to clarify whether missing data resulted in delays or complications in the emergency treatment. Additionally, doctors responsible for the inpatient care of patients who were admitted to a ward via the ED were questioned about the course of the inpatient stay to monitor how initially missing data might have influenced the hospital stay. Results: Medical data of 27% of the 272 included patients were missing or incomplete upon admission in the ED. The ED physicians had to make additional phone calls to gather information in 57% of these cases (vs. 22% in patients with complete data, p < 0.0001). Delays between 5 and 240 min were documented due to initially missing data. Unnecessary diagnostic procedures (e.g., lumbar puncture) were performed in 5% of these patients, thus compromising patient safety. Even the inpatient stay was complicated by initially missing data, as doctors still had to spend time (between 10 and 180 min) to gain relevant information. Retrospectively, 5% of hospitalizations could have been avoided if all medical information had been available upon ED admission. Conclusions: Missing medical data caused complications and delays in acute as well as inpatient care of patients admitted to the neurological ED. This compromised patient safety and led to a waste of medical resources and valuable time of the responsible medical team. Therefore, a comprehensive, digital data management system is urgently needed to improve patient safety and facilitate efficient patient care in the ED and beyond.

Opportunities to rehabilitation of multimorbid patients with asthma and obesity

BACKGROUND: The challenges of rehabilitation and achieving asthma control in patients with multimorbid conditions remain relevant despite advances in asthma treatment. Improving therapeutic approaches requires not only the development of new drugs, but also the creation of comprehensive individualized rehabilitation programs. AIM: To develop complex rehabilitation programs for patients with asthma and multimorbid diseases (obesity, osteoarthritis) and assess their impact on asthma and comorbid conditions. MATERIALS AND METHODS: 70 patients with asthma and obesity were divided into two groups: a rehabilitation group and a control group. The study evaluated external respiration functions, quality of life using Asthma Quality of Life Questionnaire (standardized), asthma control with Asthma Control Questionnaire-5 (ACQ-5), multimorbid pathology with Cumulative Illness Rating Scale (CIRS), Lequesne index, exercise capacity via 6-minute walk test, physical activity using questionnaire ODA23+, and levels of interleukin-6, interleukin-4, tumor necrosis factor alpha, leptin. RESULTS: Both groups were comparable across all assessed parameters, with most participants presenting moderate to severe asthma. Physical activity levels were low to moderate. The CIRS index was 10.0 ± 1.1 in group 1 and 9.2 ± 1.1 in group 2 (p 0.05), while the Lequesne index was 9.70 ± 1.47 and 8.80 ± 1 (p = 0.3900), respectively. After rehabilitation program, the Lequesne index in the group 1 decreased by 2.37 ± 0.60 (р 0,05), which correlated with improved exercise tolerance (6-minute walk test) and increased physical activity by 6.57 ± 2.00 (р 0.05), and increased asthma control (with ACQ-5 decreasing by 0.74 ± 0.20 points; р 0.05) and quality of life with Asthma Quality of Life Questionnaire (standardized) 3.8 ± 0.4 to 4.5 ± 0.3 (р 0.05). In group 2, no significant changes were observed in the Lequesne index, physical activity, asthma control, or quality of life (p 0.05). Proinflammatory cytokines, including interleukin-6, tumor necrosis factor alpha, and leptin, decreased significantly in group 1, while the control group showed no significant changes. CONCLUSIONS: Multicomponent rehabilitation programs tailored to the individual characteristics of patients with multimorbid conditions contribute to better management of both asthma and comorbidities. Rehabilitation improves asthma control, quality of life, and exercise tolerance. It also helps to reduce pain syndrome, increase physical activity, and decrease proinflammatory cytokines and leptin levels.

Patients with Non-Specific Complaints in Emergency Departments: A Growing Patient Safety Concern in an Aging Population with Multimorbidity.

In this opinion, we offer a new perspective on the important and persistent problem of diagnostic errors for patients with non-specific complaints (NSCs). As an increasing number of complex patients present clinicians with challenging diagnostic work in the time-pressured and high-volume contexts of EDs, we need to improve how clinicians and healthcare organizations can understand and perform safe diagnostics for patients with NSCs. The combination of a growing number of patients with NSCs and the ways in which clinicians use the categories 'non-specific complaints' and 'non-specific diagnosis' in diagnostic work in emergency departments presents a growing patient safety concern especially for older patients with multimorbidity that require the integration of clinical and organizational research. We argue why the growing numbers of patients with NSCs and clinicians' use of these categories have implications for patient safety both within and beyond the acute care context. We end by pointing to the importance of an interdisciplinary patient safety research agenda, ideally followed by the development of targeted usable protocols for older multimorbid patients with non-specific complaints.

Fisetin as a senotherapeutic agent: Evidence and perspectives for age-related diseases

Fisetin, a flavonoid naturally occurring in plants, fruits, and vegetables, has recently gained attention for its potential role as a senotherapeutic agent for the treatment of age-related chronic diseases. Senotherapeutics target senescent cells, which accumulate with age and disease, in both circulating immune cell populations and solid organs and tissues. Senescent cells contribute to development of many chronic diseases, primarily by eliciting systemic chronic inflammation through their senescence-associated secretory phenotype. Here, we explore whether fisetin as a senotherapeutic can eliminate senescent cells, and thereby alleviate chronic diseases, by examining current evidence from in vitro studies and animal models that investigate fisetin’s impact on age-related diseases, as well as from phase I/II trials in various patient populations. We discuss the application of fisetin in humans, including challenges and future directions. Our review of available data suggests that targeting senescent cells with fisetin offers a promising strategy for managing multiple chronic diseases, potentially transforming future healthcare for older and multimorbid patients. However, further studies are needed to establish the safety, pharmacokinetics, and efficacy of fisetin as a senotherapeutic, identify relevant and reliable outcome measures in human trials, optimize dosing, and better understand the possible limitations of fisetin as a senotherapeutic agent.

8243 Euglycemic Diabetic Ketoacidosis Unveiled: Delayed Presentation and Complications of SGLT-2 Inhibitor Therapy in a Multimorbid Patient - A Case Report

Abstract Disclosure: T. Amin: None. A.K. Bala: None. M.A. Jones: None. M.S. Akula: None. K. Chalasani: None. M. Patel: None. J. Cheng: None. Introduction: Normal serum glucose levels (&amp;lt;200 mg/dL) in euglycemic diabetic ketoacidosis (EDKA) can complicate the typical clinical presentation of diabetic ketoacidosis (DKA), posing a diagnostic challenge. SGLT-2 inhibitors, a class of antihyperglycemic drugs, have been rarely but significantly associated with EDKA. These inhibitors enhance renal glucose clearance by preventing glucose reabsorption via sodium-glucose cotransport. The increased renal clearance may contribute to the euglycemic picture, potentially leading to an underestimation of required insulin dosage, thereby precipitating ketoacidosis in EDKA. Although the mechanisms of EDKA are not fully understood, the association with SGLT-2 inhibitors is becoming increasingly evident. Case A 53-year-old male with a medical history of type 2 Diabetes Mellitus, coronary artery disease, chronic kidney disease, hyperlipidemia, was admitted to the trauma bay after a fall. Medications included empagliflozin, metformin, aspirin, amlodipine, spironolactone, and carvedilol. Upon presentation, he had a brief loss of consciousness, complained of headache and chest pain, and was found to have an epidural hematoma with regional brain compression on the CT head. Admission labs showed a blood glucose level of 172, an unremarkable anion gap, and normal renal and liver function tests. Due to traumatic brain injury, he was admitted to the ICU for neurological monitoring. Despite remaining neurologically stable, he developed hypoxia, necessitating intubation. After successful extubation, he exhibited worsening metabolic acidosis on the fourth day, with an elevated anion gap of 22 and a blood glucose level of 174. Arterial blood gas analysis revealed a pH of 7.3 (and elevated beta-hydroxybutyrate (&amp;gt;4), while lactic acid levels remained normal. Urine analysis showed elevated blood glucose (&amp;gt;1000) and ketones (&amp;gt;40). Home medications, metformin, and empagliflozin were appropriately withheld, but euglycemic DKA attributed to empagliflozin was diagnosed. Treatment included intravenous fluid resuscitation and insulin infusion, leading to resolution of acidosis and improved mentation within 24 hours. Conclusion: EDKA is a diagnosis of exclusion often overlooked in ICU patients due to diverse causes of high-anion gap metabolic acidosis. Typical cases occur while the patient is using the drug, often associated with triggers like illness, alcohol use, surgery, or starvation. SGLT2 inhibitors, such as empagliflozin, with a half-life of 12.4 hours, are expected to clear the bloodstream in about 48 hours, yet this case suggests an association with EDKA both during use and after drug cessation. This delayed presentation highlights additional risk considerations associated with SGLT2 inhibitors, guiding future clinical diagnoses of EDKA even several days post discontinuation. Presentation: 6/3/2024

B-221 Combined RT-PCR and Whole Exome Sequencing Pharmacogenetic Testing in Polypharmacy Patient: A Case Report

Abstract Background Pharmacogenetics has become one of the main branches of Precision Medicine owing to its usefulness for patients’s optimal therapeutic management. Notwithstanding, pharmacogenetic testing results must be taken carefully, specially in multimorbidity patients with a variety of drugs prescribed. The aim of the present work is to introduce a combined RT-PCR and Whole Exome Sequencing Approach for pharmacogenetic testing in a patient with multiple drug-related adverse events. Case Background A 67 years old female was derived to our Clinical Chemistry Unit for pharmacogenetic testing due to multiple drug-related adverse events: nifedipine-voriconazole interaction, voriconazole-related neurological toxicity and moxifloxacin-related dizziness. Aditionally, she had been receiving morphine, corticoid for her reumatoid arthritis and antituberculous therapy (r isoniazid / pyrazinamide / rifampin and ethambutol). Methods Patient’s DNA was extracted from a blood sample and undergone by pharmacogenetic testing in two parallel ways: -A first genotyping assay was carried out using Taqman® OpenArray™ PGx Express 120 panel (ThermoFisher™), according to manufacturer’s instructions. -Simultaneusly, in order to cover possible copy number variants and SNPs not covered by our RT-PCR array, a whole exome sequencing run was performed on IlluminaTM NextSeq 1000. Sample library was prepared applying a custom GRCh38 pipeline. Results Relevant variants related to patient’s therapy found by RT-PCR are shown in table 1. SNPs genotyped by RT-PCR were confirmed by NGS. Moreover, whole exome sequencing revealed a deletion in exon 5 of SLCO1B1 gene, which corresponds to SLCO1B1*49 (loss of function); and some variants in NAT2 that may cause toxicity in antituberculous treatment (diplotype NAT2*6C/*7C). Conclusions In those challenging cases that involve multimorbidity and polypharmacy patients, pharmacogenetic testing must be approached taking into account variants that are not covered by the analytical method routinely used and the possibility of complement it with alternative proccedures.

Care manager role for older multimorbid heart failure patients' needs in relation to psychological distress and quality of life: a cross-sectional study.

There are few studies investigating patients' needs in healthcare focusing on disease severity and psychological characteristics of elderly heart failure (HF) patients with multimorbidity, specifically addressed by a care manager (CM). To explore the role of a CM dealing with elderly multimorbid HF patients' needs/preferences according to NYHA class, ejection fraction, psychological/psychosomatic distress and quality of life (QoL), utilizing a Blended Collaborative Care (BCC) approach (ESCAPE; Grant agreement No 945377). Cue cards, self-reported questionnaires, and a semi-structured interview were used to collect data. Twenty-five Italian patients (mean age ± SD = 77.5 ± 6.68) were enrolled between June 2021 and March 2022. The most relevant patients' needs to be addressed by a CM were: education (e.g., on medical comorbidities), individual treatment tailoring (e.g., higher number of appointments with cardiologists) and symptom monitoring. The study highlights the importance of targeting HF patients' needs according to psychological characteristics, whose healthcare requires person-centered care with CM assistance. In view of ESCAPE BCC intervention, a CM should consider specific patients' needs of elderly multimorbid HF patients with psychological, psychosomatic distress, particularly somatization, and lower QoL to achieve a more personalized health care pathway. The «Evaluation of a patient-centred biopsychosocial blended collaborative care pathway for the treatment of multi-morbid elderly patients» (ESCAPE) study has been registered at the University of Göttingen Medical Centre (UMG Reg. No 02853) and the German Clinical Trials Register (DRKS00025120).

Detection of Prescribing Cascades in Multimorbid Older Patients Hospitalized with Acute Unselected Illness

Abstract Background Prescribing cascades (PCs) occur when a new medication is prescribed to treat an unrecognized side-effect of another medication. PCs represent an important but often underrecognized aspect of inappropriate prescribing in older people with multimorbidity and associated polypharmacy and can result in avoidable morbidity and mortality. Numerous PCs are described in the literature, however, there are no prospective studies describing PC prevalence in older people. Therefore, we aimed to investigate the prevalence of PCs in acutely hospitalized older adults. Methods We undertook a prospective observational study, including adults ≥65years with polypharmacy (≥5 daily drugs) and multimorbidity (≥3 chronic disorders). Prescription medication lists were examined for the co-prescription of 31 drug pairs according to two pre-defined PC lists– ThinkCasades1 and of the explicit cascades published by Doherty et al2. PCs were defined as ‘definite’, ‘probable’, ‘possible’, ‘uncertain’ or ‘indeterminate’ according to specific criteria. Results We obtained prospective data on 300 patients (56% female, mean age 80.4yrs SD 7.2). 233 drug pairs were prescribed in the sequence of drug A → drug B, these occurred in 43% (n=130) of patients. Of the 233 pairs, 38% (n=88) were probable or possible PCs and 62% (n=145) were uncertain. 45 patients (15%) had ≥1 possible or probable PCs. The most commonly identified probable/possible PCs were diuretic → overactive bladder medication and calcium channel blocker → diuretic. Patients with an identified PC experienced higher mean levels of polypharmacy than patients with no PCs (11.7, SD 4.0 vs 9.6, SD 3.1, T= -4.97, p &amp;lt;0.001). Conclusion In this first-ever study to report prospective prevalence of PCs, possible or probable PCs were significantly prevalent among acutely hospitalized multimorbid older patients and were associated with higher levels of polypharmacy.McCarthy LM, et al. Drgs &amp; aging. 2022 Oct;39(10):829-40.Doherty AS, et al. Pharmacology research &amp; perspectives. 2022 Oct;10(5): e01008.

Managing End of Life Needs of Frail, Older Adults in the Community: The Role of a Hospital-Based Community Outreach Team

Abstract Background Our current healthcare systems are designed around periods of acute illness and are ill equipped to meet the needs of multimorbid and frail adults with worsening mobility, cognition and function. According to The Irish Longitudinal Study on Aging (TILDA), Ireland has a high proportion of hospital deaths, indicating inadequate community and home care supports. Recognizing patients who are likely to benefit from supportive and palliative approaches with a goal to die at home can be done using a combination of tools and based on advanced care planning discussions. Methods In 2021, our Department for Older Persons Services allocated a team consisting of a Registrar and Advanced Nurse Practitioner in Frailty to form an outreach service. Inpatients who appear nearing end of life who have expressed wishes to avoid further hospitalization and to die at home are identified during their admission. Home visits allow for a holistic assessment and family members are given the opportunity to ask questions. We provide education on end of life, trying to anticipate needs and often see patients and families through periods of deterioration until they stabilize again in a ‘new normal’ or begin the process of active dying. We communicate with Public Health Nurses, General Practitioners and the Community Palliative Care Team. Results Families and carers supporting loved ones who wish to avoid further hospitalization and die at home benefit from combined medical and nursing support &amp; specialist expertise the team brings. Conclusion Addressing end of life for multimorbid patients living with severe frailty is a global challenge. Hospital admission is an ideal time to begin conversations regarding goals of care and initiate advanced care planning. The outreach team work together with hospital and community colleagues to the common goal of following patients’ wishes at end of life.