Iatrogenic Delirium in an Elderly Patient: When Drugs are Harmful

Delirium is a global disorder of cognition that represents a medical emergency and, particularly in elderly, is often unrecognized or misdiagnosed and commonly mistaken for dementia, depression, mania, or an acute schizophrenic reaction. Drug-induced delirium is a common matter in the elderly and in this paper we report the onset of delirium induced by -drug interaction in a previously health elderly patient

Antiabsence effects of carbenoxolone in two genetic animal models of absence epilepsy (WAG/Rij rats and lh/lh mice)

Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. We have tested its possible effects upon two genetic animal models of epilepsy (WAG/Rij rats and lethargic (lh/lh) mice). Systemic administration of CBX was unable to significantly affect the occurrence of absence seizures in WAG/Rij rats. In particular, intravenous (5-40 mg/kg) or intraperitoneal (i.p.; 10-80 mg/kg) administration of CBX was unable to significantly modify the number and duration of spike-wave discharges (SWDs) in WAG/Rij rats, whereas the bilateral microinjection (0.05, 0.1, 0.5 and 1 microg/0.5 microl) of CBX into nucleus reticularis thalami (NRT) and nucleus ventralis posterolateralis (VPL) thalami produced a decrease in the duration and the number of SWDs. Bilateral microinjection of CBX into nucleus ventroposteromedial (VPM) thalami did not produce any significant decrease in the number and duration of SWDs. On the contrary, i.p. (5-40 mg/kg) or intracerebroventricular (0.5, 1, 2 and 4 microg/2 microl) administration of CBX in lh/lh mice induced a marked decrease in the number and duration of SWDs in a dose-dependent manner. At the doses used no movement disorders, or other behavioural changes, were recorded in both WAG/Rij rats and lh/lh mice. No effects were observed in both animal models following systemic or focal administration of glycyrrhizin into the same brain areas where CBX was shown to be effective

Oral anticoagulant therapy at hospital admission associates with lower mortality in older COVID-19 patients with atrial fibrillation. An insight from the Covid Registry

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. ONBEHALF: the GeroCovid Investigators Introduction. Atrial fibrillation (AF), the arrhythmia most frequently diagnosed in older patients, associates with serious, thrombo-embolic, complications and high mortality. COVID-19 severely affects aged subjects, determining an important prothrombotic status. Purpose. Aim of this study was to evaluate mortality-related factors in older AF patients with COVID-19.  Methods. We included 806 in-hospital COVID-19 patients aged 60 years or more hospitalized between March 1st and June 6th 2020 and enrolled in a multicenter observational study. Results. The prevalence of AF was 21.8%. In-hospital mortality was higher in the AF group (36.9 vs. 27.5%; p = 0.015). Among AF patients, those who survived were younger (81 ± 8 vs. 84 ± 7 years; p = 0.002), had a lower CHA2DS2-VASc score (3.9 ± 1.6 vs. 4.4 ± 1.3; p = 0.02) and were more frequently treated with oral anticoagulants at admission (63.1 vs. 32.3%; p < 0.001) than those who died in hospital. At multivariable logistic regression analysis, lower age (p = 0.042), a better functional profile (p = 0.007), less severe COVID-19 manifestations at admission (p = 0.001), and the use of Vitamin K antagonists (OR = 0.16, 95%CI: 0.03-0.84; p = 0.031) or DOACs (OR = 0.22, 95%CI: 0.08-0.56; p = 0.002), compared to antiplatelet therapy or no treatment at all, were associated with a lower chance of in-hospital death. Conclusions. AF is a prevalent condition and a severity factor in older COVID-19 patients. Advanced age, dependency and severe clinical manifestations of disease characterized older AF subjects with a worse prognosis. Interestingly, pre-admission anticoagulant therapy correlated positively with in-hospital survival

Postępowanie w niewydolności serca u osób starszych

Wstęp: Celem pracy był przegląd aktualnie dost&#234;pnej wiedzy dotyczącej objawów oraz cech klinicznych i post&#234;powania w niewydolności serca (HF) u osób starszych. Metody: Autorzy dokładnie przeszukali kilka źródeł informacji opartych na dowodach naukowych, obejmujących Cochrane Database of Systemic Reviews, Clinical Evidence, wytyczne oparte na dowodach naukowych z National Guidelines Clearinghouse, zaś w bazie MEDLINE sprawdzili takie terminy, jak "niewydolność serca", "osoby starsze" oraz "postępowanie". Wyniki: Różne cechy związane z procesem starzenia mogą predysponowa&#230; osoby starsze do HF i upośledzać ich zdolność do reakcji na uszkodzenie. Inną cechą charakterystyczną u starszych pacjentów jest rosnąca częstość występowania wielu towarzyszących chorób przewlekłych i zespołów geriatrycznych, które mogą wikłać obraz kliniczny i rozwój HF. Kryteria diagnostyczne nie zmieniają się u osób starszych, mimo że rozpoznanie może stanowić wyzwanie z powodu często atypowych objawów i manifestacji klinicznej, a choroby towarzyszące mogą naśladować lub wikłać obraz kliniczny. Farmakoterapia nie różni się znacząco od tej zalecanej u młodszych pacjentów i w dużym stopniu pozostaje empiryczna, ponieważ zwykle wyklucza się osoby starsze oraz osoby z chorobami współistniejącymi z prób klinicznych. Programy postępowania mogą potencjalnie przyczynią się do zmniejszenia chorobowości i śmiertelności pacjentów z HF. Wnioski: Niewydolność serca jest najczęstszą przyczyną hospitalizacji i rehospitalizacji osób starszych. Wykazuje ona szczególne cechy u starszych pacjentów i jest zwykle powikłana chorobami towarzyszącymi, stanowiąc na całym świecie ogromne obciążenie finansowe. Pomimo to osoby starsze zwykle wykluczano z prób klinicznych i dlatego postępowanie w dużym stopniu pozostaje empiryczne i oparte na dowodach naukowych dotyczących osób z młodszych grup wiekowych

Psychological Well-Being of Older Adults With Cognitive Deterioration During Quarantine: Preliminary Results From the GeroCovid Initiative

Objectives: The spread of COVID-19 has undeniably unsettled the social, psychological and emotional life of the entire world population. Particular attention should be paid to older adults with dementia, given their vulnerability to emotional stressors. The aim of this retrospective study is to evaluate the impact of the first wave quarantine related to Covid-19 on psychological and affective well-being of older adults with mild/major neurocognitive disorders and of their caregivers.Methods: Data on participants' assessment before the quarantine (PREQ) were retrospectively collected. Patients with Mild Cognitive Impairment (MCI) or dementia were recruited from different Centers for Cognitive Decline and Dementia in Italy. During the quarantine, psychological and affective well-being were evaluated by phone through the administrations of scales measuring anxiety and depression (DASS), perceived stress (PSS), coping strategies (COPE) and the caregivers' burden (CBI). The scales' results were compared across participants' PREQ cognitive level (Mini Mental State Examination, MMSE ≥25, 23–24, and ≤ 22) with multiple linear regression models.Results: The sample included 168 patients (64% women) with a mean age of 79 ± 7 years. After adjusting for potential confounders, more severe cognitive impairment was independently associated with higher DASS and PSS score, and poorer coping strategies (p &lt; 0.05). Cognitive functioning was also inversely associated with CBI.Conclusions: The impact of the quarantine on the psycho-affective well-being of individuals with MCI and dementia and on caregivers' burden varies according to the PREQ cognitive functioning with more severely impaired patients having worse outcomes

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs