The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer’s Disease

According to the World Alzheimer’s report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer’s disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer’s disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and nonpharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents

Exploring Cost-Effectiveness of the Comprehensive Geriatric Assessment in Geriatric Oncology: A Narrative Review

: The Comprehensive Geriatric Assessment (CGA) and the corresponding geriatric interventions are beneficial for community-dwelling older persons in terms of reduced mortality, disability, institutionalisation and healthcare utilisation. However, the value of CGA in the management of older cancer patients both in terms of clinical outcomes and in cost-effectiveness remains to be fully established, and CGA is still far from being routinely implemented in geriatric oncology. This narrative review aims to analyse the available evidence on the cost-effectiveness of CGA adopted in geriatric oncology, identify the relevant parameters used in the literature and provide recommendations for future research. The review was conducted using the PubMed and Cochrane databases, covering published studies without selection by the publication year. The extracted data were categorised according to the study design, participants and measures of cost-effectiveness, and the results are summarised to state the levels of evidence. The review conforms to the SANRA guidelines for quality assessment. Twenty-nine studies out of the thirty-seven assessed for eligibility met the inclusion criteria. Although there is a large heterogeneity, the overall evidence is consistent with the measurable benefits of CGA in terms of reducing the in-hospital length of stay and treatment toxicity, leaning toward a positive cost-effectiveness of the interventions and supporting CGA implementation in geriatric oncology clinical practice. More research employing full economic evaluations is needed to confirm this evidence and should focus on CGA implications both from patient-centred and healthcare system perspectives

Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?

Background: Hypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection. Methods: The aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available. Results: Sixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9–45.6) vs. 12.9 (8.7–21.1) pg/ml, p = 0.02], CRP [10.7 (4.2–19.2) vs. 5.9 (1.6–8.1) mg/dl, p = 0.003], TNF-a [8.9 (6.0–14.8) vs. 4.4 (1.5–10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25–0.72) vs. 0.22 (0.17–0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8–6.9) vs. 2.3 (0.5–5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p < 0.001), and 25OHD levels were lower in nonsurvivor patients. Conclusions: The relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated

Effetti collaterali e interazione tra farmaci nel paziente anziano che accede al Pronto Soccorso

Nei Paesi occidentali le reazioni avverse ai farmaci (ADR) causano circa il 2-5% di tutti i ricoveri ospedalieri e costituiscono un enorme capitolo di spesa per il SSN. Nella popolazione anziana questo dato risulta notevolmente più elevato. Poche informazioni sono disponibili sulla reale epidemiologia della patologia iatrogena nei soggetti anziani nel nostro Paese, soprattutto nell’area critica. Questa tesi ha l’obiettivo di valutare la prevalenza della patologia iatrogena nei pazienti anziani che accedono al Pronto Soccorso (PS) e le potenziali reazioni avverse ai farmaci attese sulla base di quanto riportato in scheda tecnica. Inoltre, questo studio ha lo scopo di descrivere e valutare eventuali fattori associati allo sviluppo di ADR. Sono stati arruolati i pazienti afferenti all’area triage del PS di Pisa di età superiore a 65 anni che presentavano un codice di gravità giallo/verde da Giugno 2012 a Luglio 2014. Un geriatra e un farmacologo hanno condotto l’anamnesi farmacologica all’ingresso del PS e valutato la correlazione tra il motivo dell’accesso e una potenziale reazione avversa ai farmaci assunti, analizzando anche le possibili interazioni. Le banche dati utilizzate sono state Micromedex® 2.0, Farmadati Italia e Pubmed. Il numero totale di pazienti inseriti nell'analisi è stato di 3260 pazienti. Il principale motivo di accesso in PS è stato la caduta seguita dalle patologie respiratorie. La maggior parte dei pazienti poli-trattati presentava una potenziale interazione farmacologica in base alla consultazione di banche dati. In questa coorte la prevalenza delle ADR è stata circa il 5% di tutti gli accessi. I dati raccolti confermano che le ADR sono un problema sanitario potenzialmente molto rappresentato nelle popolazioni a rischio come i pazienti anziani e molti di questi assumono farmaci che possono interagire negativamente tra di loro incrementando il rischio di ADR. Il precoce riconoscimento di una potenziale reazione avversa potrebbe essere di aiuto agli operatori sanitari sia nella diagnosi differenziale che nella terapia

Efficacia del Multidimensional Prognostic Index nella stratificazione dei pazienti anziani affetti da neoplasia avanzata candidati a immunoterapia

I pazienti di età superiore ai 65 anni affetti da neoplasia avanzata rappresentano una parte importante di candidati all'immunoterapia, rendendo necessaria una stratificazione del rischio pre-trattamento attraverso un'adeguata valutazione multidimensionale geriatrica (VMDG). Infatti, in questi pazienti l'efficacia delle tradizionali terapie antiblastiche può essere influenzata da diversi fattori limitanti come le comorbidità, lo stato cognitivo e funzionale, la malnutrizione e il contesto sociale. Il Multidimensional-Prognostic Index (MPI) è un valido strumento basato sulla valutazione multidimensionale geriatrica, rivelatosi efficace nel predire la mortalità a breve e lungo termine anche in ambito oncologico. Tuttavia, ad oggi, non sono stati ancora validati test affidabili per la stratificazione del rischio di mortalità nei pazienti oncologici anziani candidati a trattamento immunoterapico. Scopo della presente tesi è stato quello di valutare l’efficacia del MPI nella stratificazione del rischio e nella conseguente pianificazione del trattamento nei pazienti anziani con neoplasia avanzata/metastatica candidati ad immunoterapia

Why are so few antipsychotic drugs licensed for Alzheimer's disease related behavioral and psychological symptoms?

Alzheimer’s disease is the most common type of dementia. The progressive nature of the disease represents a challenge for clinicians, aiming to ensure an adequate treatment and support to the patient and the caregivers. Together with the impairment in several cognitive domains, progressively worsening, behavioral symptoms frequently occur. Among them, agitation and aggression pose great management difficulty; the therapeutic approach could be nonpharmacological and/or pharmacological. Unfortunately, even though the non-pharmacological approach is safer for the patient, the data about efficacy are sparse and limited. The pharmacological approach with antipsychotic drugs, together with heterogeneous results about efficacy, leads to higher rate of complications. For this reason, antipsychotic drugs are not licensed for the use in behavioral disturbances in dementia, apart from Risperidone; other drugs are usually prescribed off-label. All considered, the treatment of behavioral symptoms in dementia represents a great challenge for clinicians, especially when treating complex or frail patients

Exploring Cost-Effectiveness of the Comprehensive Geriatric Assessment in Geriatric Oncology: A Narrative Review

The Comprehensive Geriatric Assessment (CGA) and the corresponding geriatric interventions are beneficial for community-dwelling older persons in terms of reduced mortality, disability, institutionalisation and healthcare utilisation. However, the value of CGA in the management of older cancer patients both in terms of clinical outcomes and in cost-effectiveness remains to be fully established, and CGA is still far from being routinely implemented in geriatric oncology. This narrative review aims to analyse the available evidence on the cost-effectiveness of CGA adopted in geriatric oncology, identify the relevant parameters used in the literature and provide recommendations for future research. The review was conducted using the PubMed and Cochrane databases, covering published studies without selection by the publication year. The extracted data were categorised according to the study design, participants and measures of cost-effectiveness, and the results are summarised to state the levels of evidence. The review conforms to the SANRA guidelines for quality assessment. Twenty-nine studies out of the thirty-seven assessed for eligibility met the inclusion criteria. Although there is a large heterogeneity, the overall evidence is consistent with the measurable benefits of CGA in terms of reducing the in-hospital length of stay and treatment toxicity, leaning toward a positive cost-effectiveness of the interventions and supporting CGA implementation in geriatric oncology clinical practice. More research employing full economic evaluations is needed to confirm this evidence and should focus on CGA implications both from patient-centred and healthcare system perspectives

The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals