Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Systemic and Mucosal Humoral Immune Response Induced by Three Doses of the BNT162b2 SARS-CoV-2 mRNA Vaccines

BNT162b2 (BioNTech/Pfizer) was the first SARS-CoV-2 mRNA vaccine approved by the European Medicines Agency. We monitored the long-term humoral responses of healthcare workers (HCWs) who received three vaccine doses. A total of 59 healthcare workers were studied: 47 were never SARS-CoV-2-infected (naïve-HCWs), and 12 (infected-HCWs) recovered from COVID-19 before the first vaccine. Serum and saliva were collected at baseline (before the first dose), just before the second dose, 1, 3, 6, and 9 months after the second dose, and 10 days after the third vaccine. SARS-CoV-2-specific IgG and IgA were evaluated in serum and saliva, respectively, and the presence of neutralizing antibodies (NAb) was analyzed in serum. SARS-CoV-2-specific IgG peaked one month after the second vaccine in naïve-HCWs but right before this timepoint in infected-HCWs. IgG titers significantly decreased during follow-up and at month 9 were still detectable in 50% of naïve-HCWs and 90% of infected-HCWs. NAb were significantly decreased 6 months after the second vaccine in naïve-HCWs and 9 months after this dose in infected-HCWs. Salivary SARS-CoV-2-specific IgA titers were significantly higher in infected-HCWs and were undetectable 9 months after the second vaccine in 43% of the naïve-HCWs alone. The third vaccine greatly increased humoral IgG and mucosal IgA in both groups. Two BNT162b2 doses induced strong systemic and humoral immune responses; to note, these responses weakened over time, although they are more prolonged in individuals who had recovered from COVID-19. The third vaccine dose quickly boosts systemic and mucosal humoral responses

Il vaccino anti-rotavirus:raccomandazioni, modalità di gestione e proposte per l’offerta vaccinale, in Health Technology Assessment della vaccinazione anti-rotavirus con il vaccino Rotarix

mary Secondo le ultime raccomandazioni della World Health Organization, i vaccini antirotavirus dovrebbero essere inclusi in tutti i programmi di immunizzazione delle nazioni, specialmente nei Paesi con un alto tasso di mortalit\ue0 da gastroenteriti da rotavirus come il Sud-Est asiatico e l\u2019Africa sub-sahariana. L\u2019utilizzo della vaccinazione anti-rotavirus dovrebbe altres\uec essere parte di una pi\uf9 completa strategia per controllare la malattia diarroica, insieme ad altri provvedimenti di igiene e sanit\ue0 pubblica, reidratazione, allattamento materno. I piani per l'introduzione di vaccini contro il rotavirus dovrebbero considerare una serie di aspetti, quali l'epidemiologia della malattia per et\ue0, l\u2019impatto di sanit\ue0 pubblica, una stima dei potenziali rischi, valutazioni di costo-efficacia, accessibilit\ue0 del vaccino, impatto finanziario e operativo sul sistema di erogazione. L\u2019introduzione del vaccino antirotavirus dovrebbe inoltre essere accompagnata da misure per garantire un'alta copertura vaccinale e la somministrazione tempestiva di ogni dose in base all'et\ue0 consigliata. La European Society for Paediatric Infectious Disease (ESPID) e la European Society for Paediatric Gastroenterology, Haepatology and Nutrition (ESPGHAN) raccomandano la vaccinazione anti-rotavirus a tutti i neonati sani in Europa (alto livello delle evidenze, beneficio netto, raccomandazione di grado 1A) con uno dei due vaccini licenziati dalla European Medicines Agency in Europa (Rotarix\u2122 o RotaTeq\u2122), entrambi vaccini mucosali a somministrazione orale caratterizzati da alta efficacia e buon profilo di sicurezza. Rotarix\u2122 \ue8 un vaccino vivo monovalente, derivato dal pi\uf9 frequente ceppo di rotavirus umano, il G1P8, attenuato attraverso una serie di passaggi in coltura. Rotateq\u2122 \ue8 un vaccino vivo attenuato pentavalente, derivato da un ceppo bovino (WC- 3) sottoposto al riassortimento con segmenti di RNA provenienti dai rotavirus umani. Il ciclo completo di vaccinazione prevede 2 dosi con Rotarix\u2122 e 3 con Rotateq\u2122, somministrate a distanza di almeno 4 settimane l'una dall'altra. La prima dose pu\uf2 essere somministrata a partire dalla sesta settimana di et\ue0 e il ciclo della vaccinazione dovrebbe essere effettuato preferibilmente entro la 16\ub0 settimana di et\ue0, ma in ogni caso deve essere completato entro le 24 settimane di et\ue0. Rotarix e Rotateq possono essere somministrati ai neonati prematuri con la medesima posologia e alla stessa et\ue0 cronologica dei bambini nati a termine. Entrambi i vaccini sono pronti all\u2019uso e pertanto non necessitano di ricostituzione o diluizione e devono essere somministrati oralmente senza mescolarli con nessun altro vaccino o soluzione. Quando una tipologia di vaccino viene somministrato al bambino come prima dose, si raccomanda che venga somministrato lo stesso vaccino (e non un altro vaccino anti-rotavirus) anche come dose/i successiva/e. Per quanto riguarda il contesto italiano, la Commissione Federazione Italiana Medici Pediatri (FIMP)/Societ\ue0 Italiana di Pediatria (SIP) sottolinea la necessit\ue0 di introdurre la vaccinazione contro il rotavirus e promuovere la sua offerta attiva nei tempi pi\uf9 brevi, compatibilmente con le altre priorit\ue0 nelle strategie vaccinali sul territorio nazionale, nonch\ue9 quella di promuovere le iniziative pi\uf9 efficaci per rendere accessibile la vaccinazione ai bambini dei Paesi poveri. Analoga risulta essere l\u2019opinione della Societ\ue0 Italiana di Igiene, Medicina Preventiva e Sanit\ue0 Pubblica (SitI) che, in collaborazione con la Federazione Italiana Medici di Medicina Generale (FIMMG),con la Federazione Italiana Medici Pediatri (FIMP) e con la SIP stessa, ha riportato la vaccinazione anti-RV nel recente aggiornamento del Calendario Vaccinale per la Vita. Ad oggi, il Piano Nazionale Prevenzione Vaccinale (PNPV) 2012-2014 non fa riferimento specifico alla vaccinazione anti-rotavirus e, dagli ultimi dati disponibili, il quadro italiano risulta essere alquanto frammentario, caratterizzato da una disomogeneit\ue0 determinata dalla presenza di un gran numero regioni in cui la vaccinazione non \ue8 prevista. Alla luce delle raccomandazioni disponibili ed a partire dal calendario vaccinale completo, la somministrazione di Rotarix\u2122 potrebbe avvenire contestualmente alla vaccinazione esavalente (DTPa, IPV, EpB, Hib) al terzo e al quinto mese d\u2019et\ue0. Rispettando le indicazioni sui tempi di somministrazione, tale schedula, aggiungerebbe una serie di vantaggi di tipo logistico/economico, derivanti dal fatto che entrambe le somministrazioni avverrebbero contemporaneamente alle vaccinazioni tradizionali, senza comportare disagi per i genitori/caregiver, n\ue9 la necessit\ue0 di sedute aggiuntive per gli operatori. I Sistemi Sanitari Regionali, cui \ue8 demandata nel nostro Paese la responsabilit\ue0 in ambito di processi vaccinali, devono farsi garanti di standard di qualit\ue0 omogenei in qualsiasi articolazione del processo di vaccinazione. Il perseguimento di modelli organizzativi basati su logiche di rete e sulla definizione di standard e sistemi di misurazione e valutazione \ue8 pertanto auspicabile in quanto presupposto basilare per il miglioramento continuo della qualit\ue0 dei processi assistenziali e per il successo dei programmi vaccinali

miR-23a-3p and miR-181a-5p modulate SNAP-25 expression.

SNAP-25 protein is a key protein of the SNARE complex that is involved in synaptic vesicles fusion with plasma membranes and neurotransmitter release, playing a fundamental role in neural plasticity. Recently the concentration of three specific miRNAs-miR-27b-3p, miR-181a-5p and miR-23a-3p -was found to be associated with a specific SNAP-25 polymorphism (rs363050). in silico analysis showed that all the three miRNAs target SNAP-25, but the effect of the interaction between these miRNAs and the 3'UTR of SNAP-25 mRNA is currently unknown. For this reason, we verified in vitro whether miR-27b-3p, miR-181a-5p and miR-23a-3p modulate SNAP-25 gene and protein expression. Initial experiments using miRNAs-co-transfected Vero cells and SNAP-25 3'UTR luciferase reporter plasmids showed that miR-181a-5p (p≤0.01) and miR-23a-3p (p<0.05), but not miR-27b-3p, modulate the luciferase signal, indicating that these two miRNAs bind the SNAP-25 3'UTR. Results obtained using human oligodendroglial cell line (MO3.13) transfected with miR-181a-5p or miR-27b-3p confirmed that miR-181a-5p and miR-23a-3p regulate SNAP-25 gene and protein expression. Interestingly, the two miRNAs modulate in an opposite way SNAP-25, as miR-181a-5p significantly increases (p<0.0005), whereas miR-23a-3p decreases (p<0.0005) its expression. These results for the first time describe the ability of miR-181a-5p and miR-23a-3p to modulate SNAP-25 expression, suggesting their possible use as biomarkers or as therapeutical targets for diseases in which SNAP-25 expression is altered