Italian guidance on Dementia Day Care Centres: A position paper.

Dementia Day Care Centres (DDCCs) are defined as services providing care and rehabilitation to people with dementia associated with behavioural and psychological symptoms (BPSD) in a semi-residential setting. According to available evidence, DDCCs may decrease BPSD, depressive symptoms and caregiver burden. The present position paper reports a consensus of Italian experts of different disciplines regarding DDCCs and includes recommendations about architectural features, requirements of personnel, psychosocial interventions, management of psychoactive drug treatment, prevention and care of geriatric syndromes, and support to family caregivers. DDCCs architectural features should follow specific criteria and address specific needs of people with dementia, supporting independence, safety, and comfort. Staffing should be adequate in size and competence and should be able to implement psychosocial interventions, especially focused on BPSD. Individualized care plan should include prevention and treatment of geriatric syndromes, a targeted vaccination plan for infectious diseases including COVID-19, and adjustment of psychotropic drug treatment, all in cooperation with the general practitioner. Informal caregivers should be involved in the focus of intervention, with the aim of reducing assistance burden and promoting the adaptation to the ever-changing relationship with the patient.

Dietary acrylamide and incident osteoporotic fractures: an 8-year prospective cohort study.

BACKGROUND: Acrylamide, a component of fried foods, has been associated with several negative health outcomes. However, the relationship between dietary acrylamide and osteoporotic fractures has been explored by a few cross-sectional studies. AIMS: To investigate if dietary acrylamide is associated with the onset of fractures in North American participants at high risk/having knee osteoarthritis (OA), over 8 years of follow-up. METHODS: A Cox's regression analysis, adjusted for baseline confounders was run and the data were reported as hazard ratios (HRs) and 95% confidence intervals (CIs). Dietary acrylamide intake was assessed at the baseline using a food frequency questionnaire and categorized in tertiles (T), whilst fractures' history was recorded using self-reported information. RESULTS: Altogether, 4,436 participants were included. Compared to participants with lower acrylamide intake (T1; < 3,313 µg), those with a higher acrylamide intake (T3; > 10,180 µg) reported a significantly higher risk of any fracture (HR = 1.37; 95% CI 1.12-1.68; p for trend = 0.009), forearm (HR = 1.73; 95% CI 1.09-2.77; p for trend = 0.04), spine (HR = 2.21; 95% CI 1.14-4.31; p for trend = 0.04), and hip fracture (HR = 4.09; 95% CI 1.29-12.96; p for trend = 0.046). CONCLUSIONS: Our study is the first to report that high dietary acrylamide may be associated with an increased risk of osteoporotic fractures.

Innovative biomarkers in psychiatric disorders: a major clinical challenge in psychiatry.

INTRODUCTION: Currently, the diagnosis of psychiatric illnesses is based upon DSM-5 criteria. Although endophenotype-specificity for a particular disorder is discussed, the identification of objective biomarkers is ongoing for aiding diagnosis, prognosis, or clinical response to treatment. We need to improve the understanding of the biological abnormalities in psychiatric illnesses across conventional diagnostic boundaries. The present review investigates the innovative post-genomic knowledge used for psychiatric illness diagnostics and treatment response, with a particular focus on proteomics. Areas covered: This review underlines the contribution that psychiatric innovative biomarkers have reached in relation to diagnosis and theragnosis of psychiatric illnesses. Furthermore, it encompasses a reliable representation of their involvement in disease through proteomics, metabolomics/pharmacometabolomics and lipidomics techniques, including the possible role that gut microbiota and CYP2D6 polimorphisms may play in psychiatric illnesses. Expert opinion: Etiologic heterogeneity, variable expressivity, and epigenetics may impact clinical manifestations, making it difficult for a single measurement to be pathognomonic for multifaceted psychiatric disorders. Academic, industry, or government's partnerships may successfully identify and validate new biomarkers so that unfailing clinical tests can be developed. Proteomics, metabolomics, and lipidomics techniques are considered to be helpful tools beyond neuroimaging and neuropsychology for the phenotypic characterization of brain diseases.

How to define the therapeutic limits.

With the advance of technological progress and the increase in life expectancy, it is nowadays mandatory to define what is the therapeutic limit. Every day each physician must take therapeutic decisions on the basis of his scientific knowledge, but also of his own conscience and sense of limits. They can not avoid to consider the global risk of death, disability and morbidity in more advanced age, especially in the field of cardiology and cardiac surgery. In these subjects, both fit that frail, is necessary not only an evaluation for adequate risk assessment, but also a multidimensional assessment performed with advanced tools. The resilience of the subject, ability for which some patients considered out of therapy demonstrate the ability to adapt and overcome critical phases, must also be weighed. Where and what is the therapeutic limit should be evaluated individually with humility, competence and capacity for dialogue with other disciplines in a work team that respects the individual professionalism. In recent years, much has changed in the cardiology/cardiac surgery approach in old people. With the development of less or minimal invasive new techniques, there are no more insurmountable limits that can be connected only to the chronological age of the patients.

Effectiveness of switching to the rivastigmine transdermal patch from oral cholinesterase inhibitors: a naturalistic prospective study in Alzheimer's disease.

Oral donepezil and rivastigmine are two commonly used cholinesterase inhibitors (ChEIs) used in Alzheimer's disease (AD). The rivastigmine transdermal patch formulation has high tolerability profile, allowing patients to achieve optimal therapeutic doses and providing potential advantages over oral ChEIs. This is a 6-month, multicentre, observational efficacy and tolerability study of switching from oral ChEIs to rivastigmine patch in AD patients who failed to show benefit from previous treatment. The reasons of the switch were: (1) lack/loss of benefit from previous oral ChEI treatment; (2) tolerability problems. The primary outcome was cognitive changes measured with the mini-mental state examination (MMSE) test. Secondary outcomes were modifications of functional independence and behavioral disturbances and occurrence of adverse events (AEs) after switching. 174 patients, over 180 patients screened, entered the study (lack/loss of efficacy: 57 %, tolerability problems: 33 %, both reasons: 10 %). 6 months after switching 56 % of patients stabilized or increased the MMSE score respect to baseline. The only predictor of this outcome was the response at 3 months. In the group with lack/loss of response to oral ChEI, the decline of the MMSE score changed from -3.4 ± 2.5 points in the 6 months before switching to -0.5 ± 3.2 in the 6 months after the switch (p < 0.001). There were no significant changes in the IADL or NPI scores. Drug discontinuation rate was 20 %, due to AEs (18 %) and lack of compliance (2 %). Switching from an unsuccessful oral ChEI therapy to rivastigmine patch is effective and safe in more than half of the switched patients after a 6-month period.

miRNome Profiling Detects miR-101-3p and miR-142-5p as Putative Blood Biomarkers of Frailty Syndrome.

Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this study was to identify blood miRNAs that could serve as potential biomarkers and candidate mechanisms of frailty. Using the Fried index, we enrolled 22 robust and 19 frail subjects. Blood and urine samples were analysed for several biochemical parameters. We observed that sTNF-R was robustly upregulated in the frail group, indicating the presence of an inflammatory state. Further, by RNA-seq, we profiled 2654 mature miRNAs in the whole blood of the two groups. Expression levels of selected differentially expressed miRNAs were validated by qPCR, and target prediction analyses were performed for the dysregulated miRNAs. We identified 2 miRNAs able to significantly differentiate frail patients from robust subjects. Both miR-101-3p and miR-142-5p were found to be downregulated in the frail vs. robust group. Finally, using bioinformatics targets prediction tools, we explored the potential molecular mechanisms and cellular pathways regulated by the two miRNAs and potentially involved in frailty.

Efficacy of conservative treatments for hand osteoarthritis : An umbrella review of interventional studies.

BACKGROUND: Hand osteoarthritis (OA) is common, but the efficacy/safety of treatment interventions aimed to improve health outcomes in this population are not well understood. Therefore, the aim of this study was to map and grade the effect of interventions for health outcomes in hand OA. METHODS: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For outcomes with a p-value <0.05, the certainty of the evidence was evaluated using the grading of recommendations assessment, development and evaluation (GRADE) assessment. RESULTS: From 189 abstracts, 9 meta-analyses (24 outcomes) were included, with 8 reporting significant summary results. The use of splints was associated with reduced pain at medium term in thumb carpometacarpal OA (standardized mean difference [SMD] = -0.70; 95% confidence intervals [95% CI]: -1.05 to -0.35; low certainty), reduced pain in long follow-up RCTs in symptomatic hand OA (SMD = -0.80; 95% CI: -1.16; -0.45; moderate certainty), and better function (SMD = 0.42; 95% CI: 0.08; 0.70; low certainty). The use of resistance training (SMD = -0.27; 95% CI: -0.47; -0.07) or physical exercise (SMD = -0.23; 95% CI: -0.42; -0.04) in improving hand pain and in improving finger joint stiffness (SMD = -0.36; 95%CI: -0.58; -0.15) was supported by a moderate certainty of evidence. The use of intra-articular hyaluronic acid in improving function (MD = 1.12; 95% CI: 0.61; 1.64; moderate certainty of evidence) was the only statistically significant pharmacological intervention. CONCLUSION: Only some non-pharmacological interventions are effective in improving health outcomes in hand OA and this evidence is supported by a moderate/low certainty, indicating the necessity of further interventional research.

The Potential Role of miRNAs in Cognitive Frailty.

Frailty is an aging related condition, which has been defined as a state of enhanced vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Cognitive impairment is also frequent in older people, often accompanying frailty. Age is the main independent risk factor for both frailty and cognitive impairment, and compelling evidence suggests that similar age-associated mechanisms could underlie both clinical conditions. Accordingly, it has been suggested that frailty and cognitive impairment share common pathways, and some authors proposed "cognitive frailty" as a single complex phenotype. Nevertheless, so far, no clear common underlying pathways have been discovered for both conditions. microRNAs (miRNAs) have emerged as key fine-tuning regulators in most physiological processes, as well as pathological conditions. Importantly, miRNAs have been proposed as both peripheral biomarkers and potential molecular factors involved in physiological and pathological aging. In this review, we discuss the evidence linking changes of selected miRNAs expression with frailty and cognitive impairment. Overall, miR-92a-5p and miR-532-5p, as well as other miRNAs implicated in pathological aging, should be investigated as potential biomarkers (and putative molecular effectors) of cognitive frailty.

Stress Cardiomyopathy in COVID-19 Disease.

Patients affected by COVID-19 pneumonia may develop stress cardiomyopathy, also known as Takotsubo syndrome (TTS), at different stages during the disease and with different degrees of left ventricular dysfunction. We describe three cases of TTS in COVID-19-positive patients with different clinical presentations and outcomes. One of them died, while in the other two coronary angiography confirmed the diagnosis but was postponed until after pneumonia resolution because of the risk of virus spread. LEARNING POINTS: An association between COVID-19 and cardiac involvement is highlighted.The incidence of Takotsubo syndrome has increased during this pandemic, possibly because it is caused by acute stress.

Prospective associations of cardiovascular disease with physical performance and disability : A longitudinal cohort study in the Osteoarthritis Initiative.

BACKGROUND: Literature regarding cardiovascular disease (CVD) and incident physical performance limitations and disability in older people is equivocal. AIMS: This study aimed to investigate whether CVD is longitudinally associated with incident physical performance limitations and disability in a large population-based sample. METHODS: This was an 8­year prospective study using data collected as part of the Osteoarthritis Initiative. Participants were community-dwelling adults with knee osteoarthritis or at high risk for this condition. Diagnosed CVD was self-reported. Physical performance was assessed with measures of chair stand time and gait speed, whereas disability was assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Longitudinal associations between CVD and changes in physical performance tests (chair stand time and gait speed) and disability score were analyzed using generalized linear models with repeated measurements. RESULTS: The analyzed sample comprised 4796 adults (mean age 61.2 years, 58.5% female), of whom 313 people (6.5%) reported CVD at baseline. During 8 years of follow-up, after adjustment for 11 potential confounders measured at baseline, those with CVD experienced a worse profile in chair stand time over the 8­year follow-up period than those without CVD (p = 0.006). CONCLUSION: In a cohort of middle-aged and older adults with knee osteoarthritis or at high risk for this condition those with CVD experienced a worse profile in chair stand time over the 8­year follow-up period than those without CVD; however, CVD was not significantly associated with an increased incidence of poor gait speed and disability over 8 years of follow-up. Importantly, no associations were observed when utilizing propensity score matching.

Factors Associated With Loneliness: An Umbrella Review Of Observational Studies.

BACKGROUND: Evidence provides inconsistent findings on risk factors and health outcomes associated with loneliness. The aim of this work was to grade the evidence on risk factors and health outcomes associated with loneliness, using an umbrella review approach. METHODS: For each meta-analytic association, random-effects summary effect size, 95% confidence intervals (CIs), heterogeneity, evidence for small-study effect, excess significance bias and 95% prediction intervals were calculated, and used to grade significant evidence (p<0.05) from convincing to weak. For narrative systematic reviews, findings were reported descriptively. RESULTS: From 210 studies initially evaluated, 14 publications were included, reporting on 18 outcomes, 795 studies, and 746,706 participants. Highly suggestive evidence (class II) supported the association between loneliness and incident dementia (relative risk, RR=1.26; 95%CI: 1.14-1.40, I2 23.6%), prevalent paranoia (odds ratio, OR=3.36; 95%CI: 2.51-4.49, I2 92.8%) and prevalent psychotic symptoms (OR=2.33; 95%CI: 1.68-3.22, I2 56.5%). Pooled data supported the longitudinal association between loneliness and suicide attempts and depressive symptoms. In narrative systematic reviews, factors cross-sectionally associated with loneliness were age (in a U-shape way), female sex, quality of social contacts, low competence, socio-economic status and medical chronic conditions. LIMITATIONS: Low quality of the studies included; mainly cross-sectional evidence. CONCLUSIONS: This work is the first meta-evidence synthesis showing that highly suggestive and significant evidence supports the association between loneliness and adverse mental and physical health outcomes. More cohort studies are needed to disentangle the direction of the association between risk factors for loneliness and its related health outcomes.

The Relationship between Dietary Vitamin K and Depressive Symptoms in Late Adulthood: A Cross-Sectional Analysis from a Large Cohort Study.

Few studies assessed the associations between dietary vitamin K and depressive symptoms. We aimed to investigate the association between dietary vitamin K and depressive symptoms in a large cohort of North American People. In this cross-sectional analysis, 4,375 participants that were aged 45⁻79 years from the Osteoarthritis Initiative were included. Dietary vitamin K intake was collected through a semi-quantitative food frequency questionnaire and categorized in quartiles. Depressive symptoms were diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16. To investigate the associations between vitamin K intake and depressive symptoms, logistic regression analysis were run, which adjusted for potential confounders. Overall, 437 (=10%) subjects had depressive symptoms. After adjusting for 11 confounders, people with the highest dietary vitamin K intake had lower odds of having depressive symptoms (OR = 0.58; 95%CI: 0.43⁻0.80). This effect was only present in people not taking vitamin D supplementation. In conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders. Future longitudinal research is required to explore the directionality of the association.

The relationship between different settings of medical service and incident frailty.

BACKGROUND: Some studies have reported a potential association between usual source of health care and disability, but no one has explored the association with frailty, a state of early and potential reversible disability. We therefore aimed to explore the association between older persons' self-reported usual source of health care at baseline and the onset of frailty. METHODS: Information regarding usual source of health care was captured through self-report and categorized as 1) private doctor's office, 2) public clinic, 3) Health Maintenance Organization (HMO), or 4) hospital clinic/emergency department (ED). Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (i) weight loss ≥5% between baseline and any subsequent follow-up visit; (ii) inability to do five chair stands; and (iii) low energy level according to the SOF definition. Multivariable Cox's regression analyses, calculating hazard ratios (HRs) with 95% confidence intervals (CIs), were undertaken. RESULTS: Of the 4292 participants (mean age: 61.3), 58.7% were female. During the 8-year follow-up, 348 subjects (8.1% of the baseline population) developed frailty. Cox's regression analysis, adjusting for 14 potential confounders showed that, compared to those using a private doctor's office, people using a public clinic for their care had a significantly higher risk of developing frailty (HR = 1.56; 95%CI: 1.07-2.70), similar to those using HMO (HR = 1.48; 95%CI: 1.03-2.24) and those using a hospital/ED (HR = 1.76; 95%CI: 1.03-3.02). CONCLUSION: Participants receiving health care from sources other than private doctors are at increased risk of frailty, highlighting the need for screening for frailty in these health settings.

Low-dose vitamin D supplementation and incident frailty in older people: An eight year longitudinal study.

Hypovitaminosis D is associated with frailty, but if vitamin D supplementation may prevent the onset of frailty is poorly known. Therefore, we aimed to investigate whether vitamin D supplementation is associated with a lower risk of frailty. In this longitudinal study, 4,421 individuals at high risk or having knee osteoarthritis free from frailty at baseline (mean age: 61.3, females=58.0%) were followed for 8 years. Details regarding vitamin D supplementation were captured by asking whether the participant took vitamin D during the previous year, at least once per month. Frailty was defined using the Study of Osteoporotic Fracture (SOF) index as the presence of at least two of the following criteria: (i) weight loss≥5% between baseline and any subsequent follow-up visit; (ii) inability to do five chair stands; (iii) low energy level according to the SOF definition. Multivariable Cox's regression analyses, calculating hazard ratios (HRs) with 95% confidence intervals (CIs), were undertaken. At baseline 69.7% took vitamin D supplements in the previous year, with a mean dose of 384±157 IU per day. During the 8-year follow-up, no difference in the incidence of frailty was evident by vitamin D supplementation status at baseline, even after adjusting for 13 baseline confounders (HR=0.95; 95% CI: 0.72-1.25). Similar results were obtained using the propensity score (HR=0.95; 95% CI: 0.71-1.25) or age- and sex-matched controls (HR=1.00; 95% CI: 0.75-1.33). In conclusion, low-dose vitamin D supplementation was not associated with any decreased risk of frailty during eight years of follow-up in a large cohort of North American people. Future large-scale trials with high doses of oral vitamin D and longer follow-up are needed to confirm/refute our findings.

[Healthcare delivery to patients with heart failure: from healthcare networks to management of end-stage disease]. / Assistenza allo scompenso cardiaco cronico: dalla rete assistenziale alla gestione della terminalità

In geriatrics, end-stage chronic heart failure, old age and death are often an almost obliged clinical and existential continuum. Accompanying these patients to death with dignity and relief is an issue deserving a high degree of cultural attention not only by our discipline, but also by all other specialties and scientific societies that are devoted to the management of terminal illness. Involved professionals are too often in troubles in identifying the conditions that mark the boundary between continuing or stopping the specific treatments. Management of terminal illness requires the ability to identify and treat the complexity of patient's frailty; to discern when continuing therapy is still appropriate; to prepare young physicians in the soft communicative modalities needed to cope with such delicate problems; to face with patient's family expectations in front of death. It is also necessary to distinguish technocratic medicine from humanistic medicine, including human, cultural and overall coordinating capabilities and sharing these capabilities with all actors involved, focusing attention mainly on patient's dignity. Advanced or end-stage chronic heart failure is a peculiar clinical arena that requires close interaction among hospitals, outpatient health district services, and families' needs, expectations and support. Multidimensional assessment teams, firstly introduced into daily clinical practice by geriatricians, address individualized choices and share part of knowledge with cardiology teams. Dichotomy and cultural and scientific debate between aggressive treatment and euthanasia should not prevent from discussing crucial issues such as therapy withdrawal.