Interactions between patterns of multimorbidity and functional status among hospitalized older patients: a novel approach using cluster analysis and association rule mining.

BACKGROUND: Multimorbidity (MM) is generally defined as the presence of 2 or more chronic diseases in the same patient and seems to be frequently associated with frailty and poor quality of life. However, the complex interplay between MM and functional status in hospitalized older patients has not been fully elucidated so far. Here, we implemented a 2-step approach, combining cluster analysis and association rule mining to explore how patterns of MM and disease associations change as a function of disability. METHODS: This retrospective cohort study included 3366 hospitalized older patients discharged from acute care units of Ancona and Cosenza sites of Italian National Institute on Aging (INRCA-IRCCS) between 2011 and 2017. Cluster analysis and association rule mining (ARM) were used to explore patterns of MM and disease associations in the whole population and after stratifying by dependency in activities of daily living (ADL) at discharge. Sensitivity analyses in men and women were conducted to test for robustness of study findings. RESULTS: Out of 3366 included patients, 78% were multimorbid. According to functional status, 22.2% of patients had no disability in ADL (functionally independent group), 22.7% had 1 ADL dependency (mildly dependent group), and 57.4% 2 or more ADL impaired (moderately-severely dependent group). Two main MM clusters were identified in the whole general population and in single ADL groups. ARM revealed interesting within-cluster disease associations, characterized by high lift and confidence. Specifically, in the functionally independent group, the most significant ones involved atrial fibrillation (AF)-anemia and chronic kidney disease (CKD) (lift = 2.32), followed by coronary artery disease (CAD)-AF and heart failure (HF) (lift = 2.29); in patients with moderate-severe ADL disability, the most significant ARM involved CAD-HF and AF (lift = 1.97), thyroid dysfunction and AF (lift = 1.75), cerebrovascular disease (CVD)-CAD and AF (lift = 1.55), and hypertension-anemia and CKD (lift = 1.43). CONCLUSIONS: Hospitalized older patients have high rates of MM and functional impairment. Combining cluster analysis to ARM may assist physicians in discovering unexpected disease associations in patients with different ADL status. This could be relevant in the view of individuating personalized diagnostic and therapeutic approaches, according to the modern principles of precision medicine.

Blood circulating bacterial DNA in hospitalized old COVID-19 patients.

BACKGROUND: Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. RESULTS: BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65-99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. CONCLUSIONS: The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Diabetes mellitus increases risk of adverse drug reactions and death in hospitalised older people: the SENATOR trial.

PURPOSE: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, especially in older people. Older people with diabetes mellitus may be at especially high risk of ADRs but this risk has not been well studied. This study aimed to compare severity and type of ADRs in hospitalised, multimorbid older people with and without diabetes and secondly to assess the impact of ADRs on mortality, rehospitalisation and length of stay. METHODS: Participants in the SENATOR (Software Engine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons) trial were assessed for 12 common and 'other' prevalent and incident adverse drug reactions using a blinded end-point adjudication process. Descriptive analyses, logistic regression and mediation analyses were undertaken. RESULTS: Of 1537 people in the SENATOR trial, 540 (35.1%) had diabetes mellitus (mean age 77.4 ± 7.3 years, 58.5% male). In the total population, 773 prevalent and 828 incident ADRs were reported. Both prevalent and incident symptomatic hypoglycaemia and incident acute kidney injury (AKI) were significantly more common in people with diabetes (p < 0.05). Patients with diabetes had higher all-cause mortality at 12 weeks than those without (9.1% vs 6.3%, p = 0.04). Mediation analysis revealed that mortality was significantly higher (OR = 1.43, Sobel test p = 0.048) in people with diabetes and ADRs causing AKI. CONCLUSIONS: Older multimorbid people with diabetes presenting to hospital with acute illness have significantly more ADRs than those without, and a significantly higher mortality that is mediated by medication-associated AKI and poorer renal function.

The Association of Dementia With Incident Adverse Drug Reactions in Hospitalized Older Adults.

BACKGROUND: Older adults with dementia commonly receive multiple medications and have higher hospitalization rates, elevating the risk of potentially inappropriate prescribing and in-hospital adverse drug reactions (ADRs). There is limited evidence examining ADRs in older adults with dementia during hospitalization. OBJECTIVES: Our aim was to assess the association between dementia and incidence of ADRs during hospitalization and to identify prevalent types of ADRs and medications linked to ADRs. DESIGN: Secondary analysis of the SENATOR trial database, which was a randomized controlled trial of an intervention to reduce ADRs in older inpatients with multimorbidity. SETTING AND PARTICIPANTS: A total of 1537 patients (47.2% females) with a mean age of 78.1 years were recruited from 6 European hospitals. METHODS: Sociodemographic data, functional status, cognitive status, clinical information, and ADR-related outcomes were extracted from the SENATOR database. Inpatients with dementia were identified based on prior International Classification of Diseases, Tenth Revision (ICD-10), dementia diagnosis, receiving acetylcholinesterase inhibitors or memantine, or a Mini-Mental State Examination score ≤24 at admission without concurrent delirium. RESULTS: Among participants, 392 (25.5%) were identified as having dementia. The proportion of patients with probable or certain incident in-hospital ADRs was similar between the groups with and without dementia (22.4% vs 25.4%, P > .05). However, in-hospital rates of probable or certain ADRs from 12 common categories were less frequently identified in patients with dementia compared to those without (19.4% vs 23%, P = .025). Major constipation (6.4% vs 9.9%, P = .03) and acute dyspepsia, nausea, or vomiting (2.8% vs 5%, P = .03) were less commonly observed ADRs in patients with dementia. CONCLUSIONS AND IMPLICATIONS: We did not observe an increased risk of in-hospital ADRs among inpatients with dementia. However, ADRs related to the gastrointestinal tract and identified by subjective symptoms were less frequently identified in this group. This study lays the groundwork for developing new tools for ADR diagnosis for older patients with dementia.

Constipation: a neglected condition in older emergency department patients.

Constipation and fecal impaction are common issues with the potential for significant morbidity in older people presenting to the Emergency Department (ED). While many of these patients present with classical symptoms of constipation or fecal impaction, atypical presentations are also frequent. These atypical presentations may include paradoxical diarrhea, fecal incontinence, urinary retention or overflow incontinence, hyperactive or hypoactive delirium, anorexia/dysphagia, and syncope. In addition, various clinical conditions (such as dementia, Parkinson's disease, dehydration, and hypothyroidism) and medications (such as opiate analgesics, anticholinergics, diuretics, calcium channel blockers, anti-parkinsonian drugs, and oral iron supplements) are associated with constipation and should be considered during the diagnostic process in the ED. This narrative review specifically focuses on the prevalence, presentation, diagnoses, and management of constipation in older ED patients.

Sex differences in patterns of potentially inappropriate prescribing and adverse drug reactions in hospitalized older people: Findings from the SENATOR trial.

BACKGROUND: Older women experience more adverse drug reactions (ADRs) than older men. However, the underlying basis for this sex difference is unclear. Sex (biological status) and/or gender (sociocultural constructs) influences on patterns of inappropriate prescribing in multimorbid older adults may be one reason for this ADR sex difference. In this secondary analysis, we examined whether incident ADR sex differences could be related to concurrent sex differences in potentially inappropriate prescribing. DESIGN AND SETTING: A retrospective secondary analysis of sex differences in the prevalence of potentially inappropriate medications (PIMs), potential prescribing omissions (PPOs), and ADRs among the 1537 participants (47.2% female, median [IQR] age 78 [72-84] years) was undertaken in the SENATOR clinical trial database, conducted in six large European medical centers. PARTICIPANTS AND METHODS: We looked specifically for male/female differences relating to PIMs and PPOs (defined by STOPP/START version 2 criteria) identified within 48 h of acute hospitalization. We also assessed sex differences for ADRs identified at 14 days from admission or discharge, whichever came first. ADRs were assessed by blinded endpoint adjudication panel consensus. RESULTS: During hospitalization, significantly more females experienced ≥1 ADR compared to males (28% and 21%, respectively; odds ratio 1.40, 95% CI 1.10-1.78, p < 0.005). Nine of the 11 STOPP-criteria PIMs showing a significant sex difference occurred more often in females. Of the four START-criteria PPOs showing a significant sex difference, all occurred more often in females. Some sex-associated PIMs reflect higher prevalence of related conditions in older women. CONCLUSION: We conclude that specific STOPP-criteria PIMs and START-criteria PPOs were identified more frequently in older women than older men during acute hospitalization, possibly contributing to higher ADR incidence in older women. Prescribers should appreciate sex differences in exposure to potentially inappropriate prescribing and ADR risk, given the preponderance of older women over older men in most clinical settings.

A descriptive analysis of drug-drug interactions and corresponding adverse drug reactions in multimorbid older inpatients: findings from the SENATOR trial.

PURPOSE: Drug-drug interactions (DDIs) are prevalent among multimorbid and polymedicated older adults and can increase the risk of adverse drug reactions (ADRs), hospital admissions, and mortality. This study describes the incidence and prevalence of 66 clinically relevant DDIs and analyses the occurrence of 12 corresponding predefined ADRs in older inpatients enrolled in the SENATOR trial. METHODS: The sub-study of the SENATOR trial that involved 1537 multimorbid older inpatients, recruited from 2016 to 2018 in six academic teaching hospitals in Belgium, Iceland, Ireland, Italy, Scotland, and Spain respectively, and analysed 66 potentially clinically significant DDIs. Descriptive analysis determined DDI and corresponding ADR prevalence/incidence. RESULTS: At baseline (median age: 78 [72, 84], 52.8% male), the prevalence of patients with DDIs was high (50.9%), increased during hospitalisation (55.2%) and reduced to 49.7% after 12 weeks. The most common DDIs were: ≥ 2 potassium reducing drugs (17.1%), ≥ 3 centrally acting drugs (9.0%), and SSRI + loop/thiazide diuretic (7.2%). Of all participants, one-third experienced a prevalent (36.6%)/incident (35.8%) ADR. Major serum electrolyte disturbance had the highest incidence (10.7%)/prevalence (11.5%). Incident ADRs were more common in patients with DDIs (p = 0.013). A higher prevalence of new onset falls (p = 0.013), major constipation (p = 0.004), and major serum electrolyte disturbances (p = 0.006) was observed in patients with related and thus potentially causal DDIs. CONCLUSIONS: Clinicians should, be aware of DDIs and the involved drug classes that can lead to an increased rate of ADRs in older multimorbid inpatients. Regularly reevaluating the appropriateness of the frequently prescribed drug classes and initiating judicious deprescribing is recommended.

Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.

Background: Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning. Materials and methods: A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification. Results: Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687-0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001). Conclusion: Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.

Plasma cfDNA abundance as a prognostic biomarker for higher risk of death in geriatric cardiovascular patients.

The management of geriatric cardiovascular disease (CVD) patients with multimorbidity remains challenging and could potentially be improved by integrating clinical data with innovative prognostic biomarkers. In this context, the analysis of circulating analytes, including cell-free DNA (cfDNA), appears particularly promising. Here, we investigated circulating cfDNA (measured through the quantification of 247 bp and 115 bp Alu genomic fragments) in a cohort of 244 geriatric CVD patients with multimorbidity hospitalised for acute CVD or non-CVD events. Survival analysis showed a direct association between Alu 247 cfDNA abundance and risk of death, particularly evident in the first six months after admission for acute CVD events. Higher plasma cfDNA concentration was associated with mortality in the same period of time. The cfDNA integrity (Alu 247/115), although not associated with outcome, appeared to be useful in discriminating patients in whom Alu 247 cfDNA abundance is most effective as a prognostic biomarker. The cfDNA parameters were associated with several biochemical markers of inflammation and myocardial damage. In conclusion, an increase in plasma cfDNA abundance at hospital admission is indicative of a higher risk of death in geriatric CVD patients, especially after acute CVD events, and its analysis may be potentially useful for risk stratification.

Relationship between imaging-derived parameters and circulating microRNAs to study the degree of lung involvement in hospitalized geriatric patients with COVID-19 pneumonia.

AIM: Chest computed tomography (CT) scan is useful to evaluate the type and extent of lung lesions in coronavirus disease 2019 (COVID-19) pneumonia. This study explored the association between radiological parameters and various circulating serum-derived markers, including microRNAs, in older patients with COVID-19 pneumonia. METHODS: A retrospective analysis was designed to study geriatric patients (≥75 years) with COVID-19 pneumonia, who underwent chest CT scan on admission, and for whom clinical data and serum samples were obtained. To quantify the extent of lung involvement, CT-score, the percentage of healthy lung (HL%), the percentage of ground glass opacity (GGO%), and the percentage of lung consolidation were assessed using computer-aided tools. The association of these parameters with two circulating microRNAs, miR-483-5p and miR-320b, previously identified as biomarkers of mortality risk in COVID-19 geriatric patients, was tested. RESULTS: A total of 73 patients with COVID-19 pneumonia were evaluable (median age 85 years; interquartile range 82-90 years). Among chest CT-derived parameters, the percentage of lung consolidation (HR 1.08, 95% CI 1.02-1.14), CT-score (HR 1.14, 95% CI 1.03-1.25), and HL% (HR 0.97, 95% CI 0.95-0.99) emerged as significant predictors of mortality, whereas non-significant trends toward increased mortality were observed in patients with higher GGO%. We also found a significant positive association between serum miR-483-5p and GGO% (correlation coefficient 0.28; P = 0.018) and a negative association with HL% (correlation coefficient -0.27; P = 0.023). CONCLUSIONS: Overall, the extent of lung consolidation can be confirmed as a prognostic parameter of COVID-19 pneumonia in older patients. Among various serum-derived markers, miR-483-5p can help in exploring the degree of lung involvement, due to its association with higher GGO% and lower HL%. Geriatr Gerontol Int 2024; ••: ••-••.

A Modified Corona Score Using Lung Ultrasound to Identify COVID-19 Patients.

BACKGROUND: COVID-19 continues to circulate around the world with multiple different strains being active at once. While diagnosis with antigen and molecular testing is more readily available, there is still room for alternative methods of diagnosis, particularly in out-of-hospital settings, e.g., home or nursing homes, and in low-medium income countries, where testing may not be readily available. STUDY OBJECTIVES: To evaluate the performance of two modified corona score methods compared with a traditional corona score approach to identify patients with COVID-19. METHODS: This was a retrospective multicenter study performed to compare the ability to predict SARS-CoV-2 test results on a nasopharyngeal swab between the corona scores and two novel corona scores (modified 1 corona score (M1CS) and modified 2 corona score (M2CS)). The M1CS included lung ultrasound (LUS) and chest X-ray (CXR) results, while the M2SC only utilized LUS findings without CXRs. Emergency physicians performed point-of-care LUS and a physical examination upon admission to the emergency department. RESULTS: Subjects positive for SARS-CoV-2 were older and had higher ferritin levels and temperature and lower diastolic blood pressure and oxygen saturation. The two groups differed on corona score and modified corona scores (p < 0.001 for all). SARS-CoV-2-positive patients had fewer pleural line irregularities (p = 0.025) but presented more frequently with an interstitial pattern on CXRs (p < 0.001). CONCLUSIONS: In our study, LUS alone provided a valuable contribution to the corona score and improved its performance more than when CXR results were included. These results suggest that resource-limited areas where CXRs may be unavailable or prohibitively expensive can utilize an ultrasound as the sole imaging modality without a loss of diagnostic performance for SARS-CoV-2 pneumonia diagnosis.