Multimorbid Patients Research Articles

Association between multimorbidity and postoperative mortality in patients undergoing major surgery: a prospective study in 29 countries across Europe.

Multimorbidity poses a global challenge to healthcare delivery. This study aimed to describe the prevalence of multimorbidity, common disease combinations and outcomes in a contemporary cohort of patients undergoing major abdominal surgery. This was a pre-planned analysis of a prospective, multicentre, international study investigating cardiovascular complications after major abdominal surgery conducted in 446 hospitals in 29 countries across Europe. The primary outcome was 30-day postoperative mortality. The secondary outcome measure was the incidence of complications within 30 days of surgery. Of 24,227 patients, 7006 (28.9%) had one long-term condition and 10,486 (43.9%) had multimorbidity (two or more long-term health conditions). The most common conditions were primary cancer (39.6%); hypertension (37.9%); chronic kidney disease (17.4%); and diabetes (15.4%). Patients with multimorbidity had a higher incidence of frailty compared with patients ≤ 1 long-term health condition. Mortality was higher in patients with one long-term health condition (adjusted odds ratio 1.93 (95%CI 1.16-3.23)) and multimorbidity (adjusted odds ratio 2.22 (95%CI 1.35-3.64)). Frailty and ASA physical status 3-5 mediated an estimated 31.7% of the 30-day mortality in patients with one long-term health condition (adjusted odds ratio 1.30 (95%CI 1.12-1.51)) and an estimated 36.9% of the 30-day mortality in patients with multimorbidity (adjusted odds ratio 1.61 (95%CI 1.36-1.91)). There was no improvement in 30-day mortality in patients with multimorbidity who received pre-operative medical assessment. Multimorbidity is common and outcomes are poor among surgical patients across Europe. Addressing multimorbidity in elective and emergency patients requires innovative strategies to account for frailty and disease control. The development of such strategies, that integrate care targeting whole surgical pathways to strengthen current systems, is urgently needed for multimorbid patients. Interventional trials are warranted to determine the effectiveness of targeted management for surgical patients with multimorbidity.

Prognostic Features of Sarcopenia in Older Hospitalized Patients: A 6-Month Follow-Up Study.

Background: Sarcopenia is associated with adverse health outcomes. Understanding the association between sarcopenia, multidimensional frailty, and prognosis is essential for improving patient care. The aim of this study was to assess the prevalence and prognostic signature of sarcopenia in an acute hospital setting co-led by internists and geriatricians. Methods: Sarcopenia was assessed by applying the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm, including the SARC-F score, handgrip strength, bioelectrical impedance analysis (BIA), and Timed Up and Go (TUG) test, to 97 older multimorbid inpatients (76.5 ± 6.8 years, 55% women). The patients underwent a Comprehensive Geriatric Assessment (CGA) including an evaluation of Geriatric Syndromes (GSs) and Resources (GR) and prognosis calculation using the CGA-based Multidimensional Prognostic Index (MPI), European Quality of life-5 Dimensions (EQ-5D-5L) scale, Rosenberg Self-Esteem Scale (RSES), and Geriatric Depression Scale (GDS). Information on survival and rehospitalizations was collected 1, 3, and 6 months after discharge. Results: Sarcopenia was present in 63% (95% CI: 54-72%) of patients and categorized as probable (31%), confirmed (13%), and severe sarcopenia (18%). Sarcopenic patients showed significantly higher median MPI-values (p < 0.001), more GSs (p = 0.033), fewer GR (p = 0.003), lower EQ-5D-5L scores (p < 0.001), and lower RSES scores (p = 0.025) than non-sarcopenic patients. Six months after discharge, being sarcopenic at baseline was predictive of falls (p = 0.027) and quality of life (p = 0.043), independent of age, gender, and MPI. Conclusions: Sarcopenia is highly prevalent in older hospitalized multimorbid patients and is associated with poorer prognosis, mood, and quality of life up to 6 months after discharge, independent of age, sex, and MPI as surrogate markers of biological age.

#1838 SGLT2 computational structural studies investigating polypharmacy

Abstract Background and Aims Sodium Glucose Cotransporter 2 (SGLT2) is the main active transport protein involved in sodium and glucose reabsorption in the kidney. SGLT2 inhibitors (SGLT2i) are widely recommended for patients with diabetes, heart failure and chronic kidney disease (CKD). Many multimorbid patients will be prescribed these compounds resulting in polypharmacy. We have performed a computational drug repurposing screen to identify other licensed drugs capable of binding at or near the SGLT2i active site aiming to identify compounds that could either compete with SGLT2i or inhibit sodium and glucose transport. Method The library of BNF listed compounds was obtained from NCBI PubChem. D-I-TASSER was used to generate monomeric structural models and MODELLER was used to incorporate MAP-17 and empaglifozin from a reference structure (PDB 7VSI). CHARM-GUI was used to insert the protein into a membrane. The centroid of a 5 nanosecond GROMACS molecular dynamics (MD) equilibration was used for docking studies using PLANTS. A bespoke tool was used to identify compounds interacting with key protein residues. CHARM-GUI and bespoke software were used to prepare membrane-bound systems to run in GROMACS using GPU's in Google Colab. 10 nanosecond simulations were undertaken (300 Kelvin and 1 bar) to discriminate between binding and non-binding events. Results The SGLT2-MAP17 structure in the inward-open conformation obtained showed good agreement with published structures. Existing SGLT2i (empaglifozin, dapaglifozin, canaglifozin, ertuglifozin) all feature in the top 1% of docked compounds in the repurposing screen. 17 compounds were investigated by MD, with all remaining bound to the protein in simulation. Ceftriaxone, tobramycin, clindamycin, fluvastatin, atorvastatin and ticagrelor were among the compounds with potentially significant interactions. It is not clear whether the stable ligand interactions identified here would result in inhibition of sodium and glucose transport, or if the interactions might provide competitive inhibition for SGLT2i compounds currently used. The compounds identified have no hitherto recognised interactions with SGLT2i; nor do they result in adverse effects suggesting inhibition of the protein. This study is limited by considering only the protein-ligand interaction and not wider pharmacokinetic or pharmacodynamic factors. Conclusion The indication of interactions with several compounds likely to be prescribed alongside SGLT2 inhibitors, such as antibiotics, statins and antiplatelet agents, warrants further investigation of the potential for polypharmacological complications.

Distinct Clinical Endpoints of Staphylococcus aureus Bacteraemia Complicate Assessment of Outcome.

We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to Staphylococcus aureus bacteremia (SAB). We conducted a retrospective observational study of adults with SAB between 20 December 2019 and 23 August st2022 (n = 464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical, and microbiologic features. Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14.4% of cohort), metastatic SAB (without attributable mortality, 22.2%), neither complication (56.7%), and overlapping fatal/metastatic SAB (6.7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteremia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset. Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality versus improve clinical response in patients with metastatic SAB.

Managing malnutrition and multimorbidity in primary care: dietary approaches to reduce treatment burden.

There are many health and nutrition implications of suffering from multimorbidity, which is a huge challenge facing health and social services. This review focuses on malnutrition, one of the nutritional consequences of multimorbidity. Malnutrition can result from the impact of chronic conditions and their management (polypharmacy) on appetite and nutritional intake, leading to an inability to meet nutritional requirements from food. Malnutrition (undernutrition) is prevalent in primary care and costly, the main cause being disease, accentuated by multiple morbidities. Most of the costs arise from the deleterious effects of malnutrition on individual's function, clinical outcome and recovery leading to a substantially greater burden on treatment and health care resources, costing at least £19·6 billion in England. Routine identification of malnutrition with screening should be part of the management of multimorbidity together with practical, effective ways of treating malnutrition that overcome anorexia where relevant. Nutritional interventions that improve nutritional intake have been shown to significantly reduce mortality in individuals with multimorbidities. In addition to food-based interventions, a more 'medicalised' dietary approach using liquid oral nutritional supplements (ONS) can be effective. ONS typically have little impact on appetite, effectively improve energy, protein and micronutrient intakes and may significantly improve functional measures. Reduced treatment burden can result from effective nutritional intervention with improved clinical outcomes (fewer infections, wounds), reducing health care use and costs. With the right investment in nutrition and dietetic resources, appropriate nutritional management plans can be put in place to optimally support the multimorbid patient benefitting the individual and the wider society.

Anticholinergic burden and the cognitive functions in elderly and senile patients with arterial hypertension

The aim of the study was to evaluate the effect of anticholinergic load (AHN) on cognitive functions (CF) in elderly and senile multimorbid patients with arterial hypertension (AH).Materials and methods. 330 patients aged 60 years and older with essential AH were included in the study (median age 79 [72; 84] years, 158 (51 %) of women). All the patients were underwent the assesment of CF using the Montreal Cognitive Assessment Scale (MoCA), Mini-Mental Status Scale (MMS), Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog), Trial Making Test (TMT), Digit Symbol Substitution Test (DSST), Verbal Association Test (literal (letter) and categorical (animal) associations), Boston Naming Test (BNT), Word-Color Interference Test, Stroop colorword conflict test. The anticholinergic load was determined using the anticholinergic load scale (Anticholinergic Cognitive Burden Scale, ACB).Results. Compared with patients who do not take anticholinergic drugs, multimorbid elderly and senile hypertensive patients with 2 or more points on the ACB scale had significantly lower final scores on the MoCA test (23 [21; 24.3] versus 24 [22; 25] points, respectively, p=0.042) and on MMSE (26 [24; 29] vs. 27.5 [25; 29] points, respectively, p=0.015), they spent statistically more time completing part B of the TMT test (217.5 [187.3; 246.3] vs. 204 [166.8; 247.3] seconds, respectively, p=0.038). The difference between the execution time of part B and part A of the TMT test in patients with 2 or more points on the ACB scale was statistically significantly greater than in patients with 0 points on this scale (141 [103.8; 168.5] versus 124 [83.8; 162] sec, respectively, p=0.034). Age, gender, education, and the structure of concomitant diseases did not differ between the groups.Conclusion. The results obtained indicate the adverse effect of аnticholinergic вurden on CF of multimorbid elderly and senile hypertensive patients and dictate the need to optimize pharmacotherapy in this category of patients.

A multimorbid patient with heart failure and long-term treatment with enhanced external counterpulsation: a case report

A multimorbid patient with heart failure and long-term treatment with enhanced external counterpulsation: a case report

Renal replacement therapy in critical ill patients

Acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression of chronic kidney disease (CKD), financial burden on the health care system, and increases mortality in various entities. Extended renal replacement therapy (CRRT) is the predominant form of renal replacement therapy (RRT) in intensive care units (ICU) by providing hemodynamic stability in critically ill patients, more precise control of fluid balance, correction of acid-base imbalances, electrolyte disorders and achieving a stable level of osmolarity correction, including in multimorbid patients. This article examines the various aspects of CRRT in critically ill patients with severe AKI with high comorbidity, as well as in patients with sepsis and multiple organ failure. An analytical evaluation of the choice of CRRT over intermittent/intermittent hemodialysis (IHD) in selected clinical settings is being conducted. Filter/dialyzer life is assessed, including assessment of filtration fraction, use of anticoagulation options including regional citrate anticoagulation (RCA), dose of CRRT prescribed and delivered, vascular access management, general criteria, timing of initiation and cessation of CRRT, and initiation of renal replacement therapy for nonrenal indications. with AKI and/or sepsis.

Artificial intelligence informing clinical decision making on the risk of hospital readmissions in multi-morbid patients: a systematic review

Abstract Introduction Multi-morbid patients have complex care needs and are more likely to utilise healthcare services, which represents a financial burden on healthcare organisations. 30-day readmission of patients is a method of measuring the quality of the services provided within healthcare.[1] Artificial intelligence (AI) models can flag multi-morbidity patients at increased risk of readmission.[2] However, it is unclear which common predictors have been used to develop these models. Aim To systematically review the medical literature to identify predictors that have been used to develop AI models that predicted unplanned 30-day hospital readmissions of multi-morbid patients, and whether these predictors were modifiable or non-modifiable. Methods Four large databases: Medline, Embase, Web of Science and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched on 15th November 2022. Only publications that developed a machine learning algorithm to predict unplanned 30-day hospital readmission for patients with multi-morbidity were included. Articles published in English language were eligible for inclusion. A narrative synthesis of all eligible studies was undertaken. Key findings were identified through inductive strategy, which includes simplifying raw data in the included articles into a comprehensive format. This systematic review was registered with the PROSPRO database (CRD42022373937) and followed PRISMA guidelines. Results There were 1,906 articles extracted from all databases, 18 of which met our inclusion criteria. A total of 669 predictors of hospital readmission were found, and were divided into 103 modifiable (i.e., action could be taken to change the outcome) and 566 non-modifiable (i.e. age, gender, number of previous emergency admissions. The average number of modifiable predictors per prediction model was six, with the most common being length of hospital stay, multi-morbidity, obesity, hypertension, diabetes, depression, and anaemia. The most commonly used AI algorithm was the gradient boosting algorithm. This algorithm generally showed a better performance than other models reported. The performance of all models in the included studies was compared; 13 studies showed an average sensitivity of 72%. The average specificity was calculated at 73% from 11 studies. The highest AUC reported was above 0.9, which demonstrates an excellent performing model, while five models did not report a value for the AUC. Conclusion We identified modifiable and non-modifiable predictors used in previously developed AI algorithms that predict 30-day hospital readmissions of multi-morbid patients. Modifiable predictors in particular can help guide clinical decision-making by allowing early actions to be taken in primary care to potentially reduce the risk of readmission. However, one limitation of this review is that some included studies used balanced (i.e. synthetic) data which could have introduced a level of bias.

Multimorbidity disease clusters are associated with venous thromboembolism: an extended cross-sectional national study

Multimorbidity, i.e., two or more non-communicable diseases (NCDs), is an escalating challenge for society. Venous thromboembolism (VTE) is a common cardiovascular disease and it is unknown which multimorbidity clusters associates with VTE. Our aim was to examine the association between different common disease clusters of multimorbidity and VTE. The study is an extended (1997–2015) cross-sectional Swedish study using the National Patient Register and the Multigeneration Register. A total of 2,694,442 Swedish-born individuals were included in the study. Multimorbidity was defined by 45 NCDs. A principal component analysis (PCA) identified multimorbidity disease clusters. Odds ratios (OR) for VTE were calculated for the different multimorbidity disease clusters. There were 16% (n = 440,742) of multimorbid individuals in the study population. Forty-four of the individual 45 NCDs were associated with VTE. The PCA analysis identified nine multimorbidity disease clusters, F1-F9. Seven of these multimorbidity clusters were associated with VTE. The adjusted OR for VTE in the multimorbid patients was for the first three clusters: F1 (cardiometabolic diseases) 3.44 (95%CI 3.24–3.65), F2 (mental disorders) 2.25 (95%CI 2.14–2.37) and F3 (digestive system diseases) 4.35 (95%CI 3.63–5.22). There was an association between multimorbidity severity and OR for VTE. For instance, the occurrence of at least five diseases was in F1 and F2 associated with ORs for VTE: 8.17 (95%CI 6.32–10.55) and 6.31 (95%CI 4.34–9.17), respectively. In this nationwide study we have shown a strong association between VTE and different multimorbidity disease clusters that might be useful for VTE prediction.Graphical abstract

Is there a “renal-pulmonary syndrome” in rheumatoid arthritis?

Objective: to compare the course of “rheumatoid disease” in multimorbid patients with and without interstitial lung disease (ILD).Material and methods. Two groups were formed of 1034 patients with active rheumatoid arthritis (RA) who met the 2010 ACR/EULAR criteria: one group with ILD identified by high-resolution computed tomography of the lungs (n=82) and another – without ILD (n=900). In all patients, estimated glomerular filtration rate (eGFR) was determined using the Cockroft–Gault formula. The presence and stage of chronic kidney disease (CKD) was assessed depending on the eGFR level: stage I CKD was diagnosed in eGFR &lt;89 ml/min, stage II (subclinical) – 60&lt;eGFR &lt;89 ml/min, stage IIIa (clinical) – 45&lt;eGFR&lt;59 ml/min and IIIb – 30&lt;eGFR&lt;45 ml/min.Results and discussion. Arterial hypertension (p=0.004), cerebrovascular disease (p=0.0001), diabetes mellitus (p=0.04), obesity, psoriasis (p=0.009) and stage II–III CKD (p=0.04) were more frequently observed in the group with ILD.Conclusion. The combination of CKD and ILD frequently found in patients with RA and the known similarity and close interrelationship of the pathogenesis of these diseases, suggest a type of “renal-pulmonary syndrome” associated with a specific variant of RA.

Treatment Nonadherence among Multimorbid Chronic Disease Patients: Evidence from 3515 Subjects in Indonesia.

Background and Objectives: Multimorbid patients require intensive treatment for their diseases. However, little research has been given to their treatment adherence as part of its management. This study aims to determine the prevalence and characteristics of chronic disease multimorbidity in Indonesia, alongside its treatment nonadherence. Materials and Methods: We conducted a cross-sectional study using the fifth Indonesian Family Life Survey database among adult subjects aged ≥ 15 years with multimorbidity. Our descriptive and multivariate analyses include sex, age, formal education, ethnicity, geographic residence, demographic residence, household size, insurance ownership, annual income, current self-perceived health status, missing active days, smoking behavior, and body mass index. Results: We identified 3515 multimorbid patients, constituting 30.8% prevalence across chronic disease patients. Hypertension was found to be a prevalent component of multimorbidity (61.2%), followed by digestive diseases (44.5%) and arthritis (30.3%). We identified that 36.4% of the subjects were nonadherent to their chronic disease treatment. Characteristics associated with nonadherence were found to be a good self-perception of health (aOR 1.79, 95% CI 1.54-2.08), active smoking behavior (aOR 1.51, 95% CI 1.14-1.99), no smoking behavior (aOR 1.44, 95% CI 1.08-1.90), missing seven active/productive days or less in the past month due to poor health (aOR 1.36, 95% CI 1.10-1.68), no insurance ownership (aOR 1.20, 95% CI 1.04-1.39), age of 15-65 years (aOR 1.25, 95% CI 1.01-1.55), income below IDR 40 million (aOR 1.23, 95% CI 1.04-1.46), and household size of 2-6 people (aOR 1.17, 95% CI 1.01-1.36). Conclusions: While the prevalence of multimorbidity in Indonesia is generally similar to that observed in previous studies, we have identified patient characteristics related to nonadherence. We suggest that patient's nonadherence was primarily dictated by their self-perception of health and treatment complexity. With the longstanding issue of nonadherence, this study indicated the need to consider creating patient-tailored treatment programs in clinical practice to improve adherence by considering individual patients' characteristics.

Health economic evaluation of blended collaborative care for older multimorbid heart failure patients: study protocol

BackgroundIntegrated care, in particular the ‘Blended Collaborative Care (BCC)’ strategy, may have the potential to improve health-related quality of life (HRQoL) in multimorbid patients with heart failure (HF) and psychosocial burden at no or low additional cost. The ESCAPE trial is a randomised controlled trial for the evaluation of a BCC approach in five European countries. For the economic evaluation of alongside this trial, the four main objectives were: (i) to document the costs of delivering the intervention, (ii) to assess the running costs across study sites, (iii) to evaluate short-term cost-effectiveness and cost-utility compared to providers’ usual care, and (iv) to examine the budgetary implications.MethodsThe trial-based economic analyses will include cross-country cost-effectiveness and cost-utility assessments from a payer perspective. The cost-utility analysis will calculate quality-adjusted life years (QALYs) using the EQ-5D-5L and national value sets. Cost-effectiveness will include the cost per hospital admission avoided and the cost per depression-free days (DFD). Resource use will be measured from different sources, including electronic medical health records, standardised questionnaires, patient receipts and a care manager survey. Uncertainty will be addressed using bootstrapping.DiscussionThe various methods and approaches used for data acquisition should provide insights into the potential benefits and cost-effectiveness of a BCC intervention. Providing the economic evaluation of ESCAPE will contribute to a country-based structural and organisational planning of BCC (e.g., the number of patients that may benefit, how many care managers are needed). Improved care is expected to enhance health-related quality of life at little or no extra cost.Trial registrationThe study follows CHEERS2022 and is registered at the German Clinical Trials Register (DRKS00025120).

Closed-incision negative pressure therapy as a strategy to reduce sternal wound infection in identified high-risk patients: a multicentre propensity matched study.

The premise of this retrospective study was to evaluate the intraoperative use of closed-incision negative pressure therapy (ciNPT) to help reduce the incidence of postoperative sternal wound infections in multimorbid patients with an elevated risk of developing a sternal wound infection post cardiac surgery versus a cohort that received standard-of-care dressings. Data for all adult patients were collected from each cardiothoracic surgery unit across 3 hospitals in the United Kingdom. High-risk patients had 2 or more recognized risk factors. Fisher's exact test (two-tailed) and unpaired t-test were used to help analyse categorical and continuous data. Propensity matching was performed to compare the 2 groups. A total of 5,288 patients who had cardiac surgery were included. Propensity matching led to 766 matched cases. There were significantly fewer sternal wound infections in the ciNPT group [43 (5.6%) vs 119 (15.5%) cases; P = 0.0001], as well as fewer deep sternal wound infections [14 (1.8%) vs 31 (4.0%) cases; P = 0.0149] and superficial sternal wound infections [29 (3.8%) vs 88 (11.4%) cases; P = 0.0001]. A higher mean length of stay in the ciNPT group was statistically significant (11.23 ± 13 vs 9.66 ± 10 days; P = 0.0083) as was a significantly higher mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (11.143 ± 13 vs 8.094 ± 11; P = 0.0001). A statistically significant higher readmission to the intensive care unit due to sternal wound infection was noted for the controls [16 (2.08%) vs 3 (0.39%) readmissions; P = 0.0042]. The ciNPT appears to be an effective intervention to help reduce the incidence of sternal wound infection in high-risk individuals undergoing cardiac surgery.

Study protocol for two stepped-wedge interventional trials evaluating the effects of holistic information technology-based patient-oriented management in older multimorbid patients with cancer: The GERONTE trials

IntroductionCurrent hospital-based care pathways are generally single-disease centred. As a result, coexisting morbidities are often suboptimally evaluated and managed, a deficiency becoming increasingly apparent among older patients who exhibit heterogeneity in health status, functional abilities, frailty, and other geriatric impairments. To address this issue, our study aims to assess a newly developed patient-centred care pathway for older patients with multimorbidity and cancer.The new care pathway was based on currently available evidence and co-designed by end-users including health care professionals, patients, and informal caregivers.Within this care pathway, all healthcare professionals involved in the care of older patients with multimorbidity and cancer will form a Health Professional Consortium (HPC). The role of the HPC will be to centralise oncologic and non-oncologic treatment recommendations in accordance with the patient's priorities. Moreover, an Advanced Practice Nurse will act as case-manager by being the primary point of contact for the patient, thus improving coordination between specialists, and by organising and leading the consortium. Patient monitoring and the HPC collaboration will be facilitated by digital communication tools designed specifically for this purpose, with the added benefit of being customisable for each patient. Materials and MethodsThe GERONTE study is a prospective international, multicentric study consisting of two stepped-wedge trials performed at 16 clinical sites across three European countries. Each trial will include 720 patients aged 70 years and over with a new or progressive cancer (breast, lung, colorectal, prostate) and at least one moderate or severe multimorbidity. The patients in the intervention group will receive the new care pathway whereas patients in the control group will receive usual oncologic care. DiscussionGERONTE will evaluate whether this kind of holistic, patient-oriented healthcare management can improve quality of life (primary outcome) and other valuable endpoints in older patients with multimorbidity and cancer. An ancillary study will assess in depth the socio-economic impact of the intervention and deliver concrete implementation guidelines for the GERONTE intervention care pathway.Trial registration: FRONE: NCT05720910TWOBE: NCT05423808

Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages

Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear. In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages. We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n=858/1082) and K. variicola (15.7%, n=170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n=270/1082) but 78.9% (n=213/270) were not MDR, and 53.7% (n=145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n=21; aHR 1.86, CI 1.10-3.17, p=0.02), and global MDR-associated Kp CGs (CFR 17.0%, n=36; aHR 1.52, CI 0.98-2.38, p=0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n=46). Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.

Clozapine to treat aggression and agitation in advanced dementia

IntroductionAgitation and aggression are a serious problem in clinical psychiatry, especially in multimorbid patients of advanced age, including those with dementia.ObjectivesWe wanted to investigate to what extent clozapine could be an option in the treatment of selected refractory patients.MethodsA retrospective study included patients with a diagnosis of dementia who were treated with clozapine in a specialist geriatric psychiatry unit between August 2018 and February 2022, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used for the assessment of improvement and the Pittsburgh Agitation Scale for the assessment of symptom reduction. In addition, there was detailed documentation of side effects and clinical features.Results A total of 31 patients with a median age of 82 years were identified.Conclusions In conclusion, clozapine was effective and well tolerated in 23 patients. This suggests that low-dose clozapine may help alleviate the suffering of difficult-to-treat multimorbid patients with advanced dementia and their carers. However, adverse effects, particularly in patients with cardiovascular and pulmonary impairment, should be carefully monitored.Disclosure of InterestNone Declared

Multimorbidity healthcare expenditure in Belgium: a 4-year analysis (COMORB study)

BackgroundThe complex management of health needs in multimorbid patients, alongside limited cost data, presents challenges in developing cost-effective patient-care pathways. We estimated the costs of managing 171 dyads and 969 triads in Belgium, taking into account the influence of morbidity interactions on costs.MethodsWe followed a retrospective longitudinal study design, using the linked Belgian Health Interview Survey 2018 and the administrative claim database 2017–2020 hosted by the Intermutualistic Agency. We included people aged 15 and older, who had complete profiles (N = 9753). Applying a system costing perspective, the average annual direct cost per person per dyad/triad was presented in 2022 Euro and comprised mainly direct medical costs. We developed mixed models to analyse the impact of single chronic conditions, dyads and triads on healthcare costs, considering two-/three-way interactions within dyads/triads, key cost determinants and clustering at the household level.ResultsPeople with multimorbidity constituted nearly half of the study population and their total healthcare cost constituted around three quarters of the healthcare cost of the study population. The most common dyad, arthropathies + dorsopathies, with a 14% prevalence rate, accounted for 11% of the total national health expenditure. The most frequent triad, arthropathies + dorsopathies + hypertension, with a 5% prevalence rate, contributed 5%. The average annual direct costs per person with dyad and triad were €3515 (95% CI 3093–3937) and €4592 (95% CI 3920–5264), respectively. Dyads and triads associated with cancer, diabetes, chronic fatigue, and genitourinary problems incurred the highest costs. In most cases, the cost associated with multimorbidity was lower or not substantially different from the combined cost of the same conditions observed in separate patients.ConclusionPrevalent morbidity combinations, rather than high-cost ones, made a greater contribution to total national health expenditure. Our study contributes to the sparse evidence on this topic globally and in Europe, with the aim of improving cost-effective care for patients with diverse needs.

Healthcare needs in elderly patients with chronic heart failure in view of a personalized blended collaborative care intervention: a cross sectional study.

Few studies explored healthcare needs of elderly heart failure (HF) patients with comorbidities in view of a personalized intervention conducted by Care Managers (CM) in the framework of Blended Collaborative Care (BCC). The aims of the present study were to: (1) identify perceived healthcare needs/preferences in elderly patients with HF prior to a CM intervention; (2) investigate possible associations between healthcare needs/preferences, sociodemographic variables (age; sex) and number of comorbidities. Patients aged 65 years or more affected by HF with at least 2 medical comorbidities were enrolled in the study. They were assessed by structured interviewing with colored cue cards that represented six main topics including education, individual tailoring of treatment, monitoring, support, coordination, and communication, related to healthcare needs and preferences. Thirty-three patients (Italy = 21, Denmark = 7, Germany = 5; mean age = 75.2 ± 7.7 years; males 63.6%) were enrolled from June 2021 to February 2022. Major identified needs included: HF information (education), patients' involvement in treatment-related management (individual tailoring of treatment), regular checks of HF symptoms (monitoring), general practitioner update by a CM about progression of symptoms and health behaviors (coordination), and telephone contacts with the CM (communication). Regarding communication modalities with a CM, males preferred phone calls (χ2 = 6.291, p = 0.043) and mobile messaging services (χ2 = 9.647, p = 0.008), whereas females preferred in-person meetings and a patient dashboard. No differences in needs and preferences according to age and number of comorbidities were found. The findings highlight specific healthcare needs and preferences in older HF multimorbid patients, allowing a more personalized intervention delivered by CM in the framework of BCC.

Personalized, interdisciplinary patient pathway for cross-sector care of multimorbid patients (eliPfad trial): study protocol for a randomized controlled trial

BackgroundMultimorbid and frail elderly patients often carry a high burden of treatment. Hospitalization due to the onset of an acute illness can disrupt the fragile balance, resulting in further readmissions after hospital discharge. Current models of care in Germany do not meet the needs of this patient group. Rather lack of coordination and integration of care combined with a lack of interdisciplinary approaches result in fragmented and inadequate care and increase the burden of treatment even more.MethodseliPfad is a randomized controlled trial conducted in 6 hospitals in Germany. Multimorbid elderly patients aged 55 or older are randomly assigned to the intervention or control group. Patients in the intervention group receive the eliPfad intervention additional to standard care. The core components of eliPfad are:Early assessment of patients’ individual treatment burden and support through a specially trained case managerInvolvement of the patient’s general practitioner (GP) right from the beginning of the hospital stayPreparation of an individual, cross-sectoral treatment plan through the interdisciplinary hospital team with the involvement of the patient’s GPEstablishment of a cross-sectoral electronic patient record (e-ePA) for documentation and cross-sectoral exchangeSupport/Promote patient adherenceTailored early rehabilitation during the hospital stay, which is continued at homeClose-tele-monitoring of medically meaningful vital parameters through the use of tablets, digital devices, and personal contacts in the home environmentThe intervention period begins in the hospital and continues 6 weeks after discharge. Patients in the control group will be treated according to standard clinical care and discharged according to current discharge management. The primary aim is the prevention/reduction of readmissions in the first 6 months after discharge. In addition, the impact on health-related quality of life, the burden of treatment, survival, self-management, medication prescription, health literacy, patient-centered care, cost-effectiveness, and process evaluation will be examined. Nine hundred forty-eight patients will be randomized 1:1 to intervention and control group.DiscussionIf eliPfad leads to fewer readmissions, proves (cost-)effective, and lowers the treatment burden, it should be introduced as a new standard of care in the German healthcare system.Trial registrationThe trial was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 08/14/2023 under the ID DRKS00031500.