Heart Failure and Biomarkers. Unravelling new pathophysiological pathways, outcome predictors, and therapeutic targets.

The present thesis, result of the international experience I had during the last 3 years in the context of the International Philosophiæ Doctor programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh), disserts on the known and unknown role of biomarkers in HF. The thesis is divided in several chapter, each of them dwelling upon specific aspects that have been investigated during the 3 years of my PhD curriculum. After a generalist paragraph dwelling upon the use of biomarkers in HF, its associated diseases, and the argument around the dilemma of racial differences (chapter 2), the important and emerging role of hormone deficiencies (HD), alone ore combined in the multiple hormone deficiency syndrome (MHDS) is discussed (chapter 3), together with the presentation of the results of the main project of my PhD, the T.O.S.CA. project, an international effort aimed to investigate the role of MHDS in HF. The following chapter (chapter 4) is based on the even strong relationship between the heart and the gut (the so-called Gut Axis), followed by a chapter showing the possible role of novel biomarkers in HF (chapter 5). In conclusion, a last chapter about my other HF research activity (not strictly related to biomarkers) is present

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register.

BACKGROUND: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. METHODS: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. RESULTS: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, depression, and diverticulitis disease were more common in women. Severity and comorbidity indexes according to the Cumulative Illness Rating Scale (CIRS-s and CIRS-c) were higher in men, while cognitive impairment, mood disorders, and disability in daily life measured by the Barthel Index (BI) were worse in women. In the multivariate analysis, BI, CIRS, and malignancy significantly increased the risk of death in men at the 1-year follow-up, while age was independently associated with mortality in women. CONCLUSIONS: Our study highlighted the relevance and the validity of our previous predictive model in the identification of sex dimorphism in hospitalised elderly patients underscoring the need of sex-personalised health-care

Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards.

BACKGROUND: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic. OBJECTIVE: We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards. METHODS: Taking advantage of the "REgistro POliterapie Società Italiana Medicina Interna" (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain. RESULTS: Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p < .0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p < .0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p = .172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p < .0001). CONCLUSIONS: Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge

Use of non-steroidal anti-inflammatory drugs and analgesics in a cohort of hospitalized elderly patients: Results from the REPOSI study.

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Disability, and not diabetes, is a strong predictor of mortality in oldest old patients hospitalized with pneumonia

Background: Pneumonia causes more deaths than any other infectious disease, especially in older patients with multiple chronic diseases. Recent studies identified a low functional status as prognostic factor for mortality in elderly patients with pneumonia while contrasting data are available about the role of diabetes. The aim of this study was to evaluate the in-hospital, 3-month and 1-year mortality in elderly subjects affected by pneumonia enrolled in the RePoSi register.Methods: We retrospectively analyzed the data collected on hospitalized elderly patients in the frame of the REPOSI project. We analyzed the socio-demographic, laboratory and clinical characteristics of subjects with pneumonia. Multivariate logistic analysis was used to explore the relationship between variables and mortality.Results: Among 4714 patients 284 had pneumonia. 52.8% were males and the mean age was 80 years old. 19.8% of these patients had a Barthel Index &lt;= 40 (p &lt; 0.0001), as well as 43.2% had a short blessed test &gt;= 10 (p &lt; 0.0117). In these subjects a significant CIRS for the evaluation of severity and comorbidity indexes (p &lt; 0.0001) were present. Although a higher fasting glucose level was identified in people with pneumonia, in the multivariate logistic analysis diabetes was not independently associated with in-hospital, 3-month and 1-year mortality, whereas patients with lower Barthel Index had a higher mortality risk (odds ratio being 9.45, 6.84, 19.55 in hospital, at 3 and 12 months).Conclusion: Elderly hospitalized patients affected by pneumonia with a clinically significant disability had a higher mortality risk while diabetes does not represent an important determinant of short and long-term outcome

Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients.

The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from "Registro Politerapia Società Italiana di Medicina Interna (REPOSI)". Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR < 60 ml/min/1.73 m2 was associated with unfavorable outcomes, although with a poor level of accuracy (AUC 0.60-0.66). No difference in predictive power between different equations was found. Physicians should be aware of the prognostic role of eGFR in a comprehensive assessment of elderly in-patients

Prevalence and Determinants of the Use of Lipid-Lowering Agents in a Population of Older Hospitalized Patients: the Findings from the REPOSI (REgistro POliterapie Società Italiana di Medicina Interna) Study.

Older patients are prone to multimorbidity and polypharmacy, with an inherent risk of adverse events and drug interactions. To the best of our knowledge, available information on the appropriateness of lipid-lowering treatment is extremely limited

Antibiotic use and associated factors in a large sample of hospitalised older people

Objectives: The aims of this study were to assess (i) the prevalence of antibiotic use, (ii) factors associated with their use and (iii) the association with in-hospital mortality in a large sample of hospitalised older people in Italy. Methods: Data were obtained from the 2010\u20132017 REPOSI register held in more than 100 internal medicine and geriatric wards in Italy. Patients aged 6565 years with at least one antibiotic prescription during their hospitalisation were selected. Multivariable logistic regression models were used to determine factors associated with antibiotic use. Results: A total of 5442 older patients were included in the analysis, of whom 2786 (51.2%) were prescribed antibiotics during their hospitalisation. The most frequently prescribed antibiotic class was \u3b2- lactams, accounting for 50% of the total prescriptions. Poor physical independence, corticosteroid use and being hospitalised in Northern Italy were factors associated with a higher likelihood of being prescribed antibiotics. Antibiotic use was associated with an increased risk of in-hospital mortality (odds ratio = 2.52, 95% confidence interval 1.82\u20133.48) also when accounting for factors associated with their use. Conclusion: Hospitalised older people are often prescribed antibiotics. Factors related to poor physical independence and corticosteroid use are associated with increased antibiotic use. Being prescribed antibiotics is also associated with an increased risk of in-hospital death. These results demand the implementation of specific stewardship programmes to improve the correct use of antibiotics in hospital settings and to reduce the risk of antimicrobial resistance

Prevalence and Determinants of the Use of Lipid-Lowering Agents 3 in a Population of Older Hospitalized Patients: the Findings 4 from the REPOSI (REgistro POliterapie Societa` Italiana di 5 Medicina Interna) Study

Background Older patients are prone to multimorbidity and polypharmacy, with an inherent risk of adverse events and drug interactions. To the best of our knowledge, available information on the appropriateness of lipid-lowering treatment is extremely limited. Aim The aim of the present study was to quantify and characterize lipid-lowering drug use in a population of complex in-hospital older patients. Methods We analyzed data from 87 units of internal medicine or geriatric medicine in the REPOSI (Registro Politerapie della SocietA Italiana di Medicina Interna) study, with reference to the 2010 and 2012 patient cohorts. Lipid-lowering drug use was closely correlated with the clinical profiles, including multimorbidity markers and polypharmacy. Results 2171 patients aged > 65 years were enrolled (1057 males, 1114 females, mean age 78.6 years). The patients treated with lipid-lowering drugs amounted to 508 subjects (23.4%), with no gender difference. Atorvastatin (39.3%) and simvastatin (34.0%) were the most widely used statin drugs. Likelihood of treatment was associated with polypharmacy (>= 5 drugs) and with higher Cumulative Illness Rating Scale (CIRS) score. At logistic regression analysis, the presence of coronary heart disease, peripheral vascular disease, and hypertension were significantly correlated with lipid-lowering drug use, whereas age showed an inverse correlation. Diabetes was not associated with drug treatment. Conclusion In this in-hospital cohort, the use of lipid-lowering agents was mainly driven by patients' clinical history, most notably the presence of clinically overt manifestations of atherosclerosis. Increasing age seems to be associated with lower prescription rates. This might be indicative of cautious behavior towards a potentially toxic treatment regimen

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

Objectives: We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes.Design: Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged &gt;= 65 years.Setting and Participants: Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD.Measures: We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence.Results: At hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (&gt;= 5 drugs) at admission [odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81], a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90).Conclusions/Implications: COPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine