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Purpose: There is a need to balance the benefits and risks associated with strong anticholinergic medications in older adults, particularly among those with frailty and cognitive impairment. This study explored the international prevalence of strong anticholinergic medication use in residents of nursing homes with and without cognitive impairment and frailty., Methods: Secondary, cross-sectional analyses of data from 5,800 residents of 106 nursing homes in Australia, China, Czech Republic, England, Finland, France, Germany, Israel, Italy, Japan, Netherlands, and Spain were conducted. Strong anticholinergic medications were defined as medications with a score of 2 or 3 on the Anticholinergic Cognitive Burden scale. Dementia or cognitive impairment was defined as a documented diagnosis or using a validated scale. Frailty was defined using the FRAIL-NH scale as 0-2 (non-frail), 3-6 (frail) and 7-14 (most-frail). Data were analyzed using descriptive statistics., Results: Overall, 17.4 % (n = 1010) residents used ≥1 strong anticholinergic medication, ranging from 1.3 % (n = 2) in China to 27.1 % (n = 147) in Italy. The most prevalent strong anticholinergics were quetiapine (n = 290, 5.0 % of all residents), olanzapine (132, 2.3 %), carbamazepine (102, 1.8 %), paroxetine (88, 1.5 %) and amitriptyline (87, 1.5 %). Prevalence was higher among residents with cognitive impairment (n = 602, 17.9 %) compared to those without (n = 408, 16.8 %), and among residents who were most frail (n = 553, 17.9 %) compared to those who were frail (n = 286, 16.5 %) or non-frail (n = 171, 17.5 %)., Conclusions: One in six residents who were most frail and living with cognitive impairment used a strong anticholinergic. However, there was a 20-fold variation in prevalence across the 12 countries. Targeted deprescribing interventions may reduce potentially avoidable medication-harm., Competing Interests: Declaration of competing interest A.J.C. has received grant or consulting funds from the Medical Research Future Fund, Dementia Australia Research Foundation and the Pharmaceutical Society of Australia. All these funds were paid to the administering University. A.J.C. is also a national board director for the Pharmaceutical Society of Australia. S.H. belongs to an endowed chair funded by donations from Hakue technology, PROUMED, Japan Bio Products, Towa Pharmaceutical, Yellow Eight and Sugi Holdings and received research funding from SOMPO Care Inc. outside of this work. N.M.V. has received grant or consulting funds from UCB Biopharma, Nestlé and Vegenat. R.V. was previously on the board of Resthaven and the board governance committee. Visvanathan is co-founder and chair of the clinical advisory group for a wearable sensor technology start-up HealthVibes.ai. J.S.B. has received grant or consulting funds from the NHMRC, Medical Research Future Fund, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Australian Commission on Safety and Quality in Health Care, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations. All these funds were paid to the administering University. All other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Cardiovascular diseases (CVDs) are the most common cause of mortality and morbidity in Western countries, thus representing a global health concern. CVDs show different patterns in terms of the prevalence and presentation in men and women. The role of sex hormones has been extensively implicated in these sex-specific differences, due to the presence of the menstrual cycle and menopause in women. Moreover, the gut microbiota (GM) has been implicated in cardiovascular health, considering the growing evidence that it is involved in determining the development of specific diseases. In particular, gut-derived metabolites have been linked to CVDs and kidney disorders, which can in turn promote the progression of CVDs. Considering the differences in the composition of GM between men and women, it is possible that gut microbiota act as a mediator in regard to the sex disparities in CVDs. This narrative review aims to comprehensively review the interplay between sex, GM, and CVDs, discussing potential mechanisms and therapeutic options.

Background: Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear., Aims: To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population., Methods: Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) population., Results: Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m 2 vs. 8.92 ± 4.83 kg/m 2 , p = 0.135), SMI (7.38 ± 1.01 kg/m 2 vs. 7.46 ± 2.77 kg/m 2 , p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m 2 vs. 8.11 ± 4.29 kg/m 2 , p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older., Conclusions: Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interventions targeting the skeletal muscle to prevent or treat sarcopenia., (© 2024. The Author(s).)

Background: Frailty, disability, and polypharmacy are prevalent in nursing home (NH) residents, often co-occurring with multimorbidity. There may be a complex interplay among them in terms of outcomes such as mortality. Aims of the study were to (i) assess whether nursing home residents with polypharmacy (5-9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified by the co-presence of frailty or disability., Methods: Cohort study with longitudinal mortality data including 4,023 residents from 50 European and 7 Israeli NH facilities (mean age = 83.6 years, 73.2% female) in The Services and Health for Elderly in Long Term care (SHELTER) cohort study. Participants were evaluated with the interRAI-LongTerm Care assessment tool. Frailty was evaluated with the FRAIL-NH scale. Hazard ratio (HR) of death over 12 months was assessed with stratified Cox proportional hazards models adjusted for demographics, facilities, and cognitive status., Results: 1,042 (25.9%) participants were not on polypharmacy, 49.8% ( n = 2,002) were on polypharmacy, and 24.3% ( n = 979) on hyperpolypharmacy. Frailty and disability mostly increased risk of death in the study population (frailty: HR = 1.85, 95%CI 1.49-2.28; disability: HR = 2.10, 95%CI 1.86-2.47). Among non-frail participants, multimorbidity (HR = 1.34, 95%CI = 1.01-1.82) and hyperpolypharmacy (HR = 1.61, 95%CI = 1.09-2.40) were associated with higher risk of death. Among frail participants, no other factors were associated with mortality. Polypharmacy and multimorbidity were not associated with mortality after stratification for disability., Conclusions: Frailty and disability are the strongest predictors of death in NH residents. Multimorbidity and hyperpolypharmacy increase mortality only in people without frailty. These findings may be relevant to identify patients who could benefit from tailored deprescription., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zazzara, Villani, Palmer, Fialova, Corsonello, Soraci, Fusco, Cipriani, Denkinger, Onder and Liperoti.)

Purpose: Up to 26% of residents in nursing homes (NHs) are affected by cancer. Their care represents a challenge, because NHs are not usually considered a setting focused on oncologic management and care. The aim of this paper is to describe socio-demographic and clinical features of patients with cancer residing in European NHs., Methods: Cross-sectional study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. Participants were assessed through the interRAI-LTCF, which includes cancer assessment., Results: Among 4140 participants (mean age 83.4 years; female 73%), 442 (10.7%) had cancer. Patients with cancer had a higher prevalence of do-not-resuscitate directives compared to those without cancer (21.1% vs 16.5%, p = 0.019). Variables directly associated with cancer were male sex (adj OR 1.67, 95% CI 1.36-2.05), pain (adj OR 1.43, 95% CI 1.16-1.77), fatigue (adj OR 1.25, 95% CI 1.01-1.55), polypharmacy (adj OR 1.59, 95% CI 1.21-2.08) and falls (adj OR. 1.30, 95% CI 1.01-1.67). Dementia was inversely associated with cancer (adj OR 0.74, 95% CI 0.58-0.94). Symptomatic drugs such as opioids (23.5% vs 12.2, p < .001), NSAIDS (7.2% vs 3.9%, p = 0.001), antidepressants (39.1% vs 33.8%, p = 0.026) and benzodiazepines (40.3% vs 34.3, p = 0.012) were all prescribed more in participants with cancer compared to those without cancer., Conclusions: Cancer patients are prevalent in European NHs and they show peculiar characteristics. Studies are needed to evaluate the impact of a supportive care approach on the management of NHs residents with cancer throughout all its phases, until the end-of-life care., (© 2021. The Author(s).)

Head trauma and delirium are two common conditions in the elderly population. They both carry a heavy burden in terms of mortality and morbidity and are associated with one another through several environmental and clinical factors, such as comorbidities, age, and sex. One factor that may play a role in both these conditions is inflammation, which might also represent a link between them. In particular, head trauma can cause both systemic and neuroinflammation, while delirium appears to be precipitated by inflammatory conditions, while also involving a number of inflammatory pathways in its pathogenesis. Interleukin 6 and tumor necrosis factor α are only two of the main actors in this crosstalk, which also involves microglia and immune cells. An indirect proof is that anti-inflammatory drugs have proven effective in reducing post-traumatic delirium, thus demonstrating the importance of inflammation in the pathophysiology of this disease. In this paper, we have revised the available literature exploring the links between inflammation, head trauma and delirium and we will discuss the mechanisms of this relationship, paying particular attention to the possible future implications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: 1.5-8% of older adults live in nursing homes (NHs), presenting a high prevalence of frailty and polypharmacy., Aims: To investigate the association of frailty with polypharmacy and drug prescription patterns in a sample of European Nursing Home (NH) residents., Methods: Cross-sectional study based on the data from the Services and Health for Elderly in Long TERm care (SHELTER) study. 4121 NH residents in Europe and Israel. Residents' clinical, cognitive, social, and physical status were evaluated with the InterRAI LTCF tool, which allows comprehensive, standardized evaluation of persons living in NH. Polypharmacy and hyperpolypharmacy were defined as the concurrent use of ≥ 5 and ≥ 10 medications. Frailty was defined according to the FRAIL-NH scale., Results: Of 4121 participants, 46.6% were frail (mean age 84.6 ± 9.2 years; 76.4% female). Polypharmacy and hyperpolypharmacy were associated with a lower likelihood of frailty (Odds Ratio = 0.72; 95% CI = 0.59-0.87 and OR = 0.75; 95% CI = 0.60-0.94, respectively). Patterns of drug prescriptions were different between frail and non-frail residents. Symptomatic drugs (laxatives, paracetamol, and opioids) were more frequently prescribed among frail residents, while preventive drugs (bisphosphonates, vitamin D, and acetylsalicylic acid) were more frequently prescribed among non-frail residents., Conclusions: Frailty is associated with less polypharmacy and with higher prevalence of symptomatic drugs use among NH residents. Further studies are needed to define appropriateness of drug prescription in frail individuals., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Background: Population of oldest old will grow dramatically in the next future and cancer, physiologically related to aging, will be very prevalent among them. Lack of evidence is a huge problem to manage cancer in oldest old and will be more and more in the next years., Aims: Our purpose was to investigate the characteristics of a population of oldest old patients with cancer treated in the Radiation Oncology Unit of Fondazione Policlinico A. Gemelli IRCCS., Methods: We conducted a retrospective study. The primary outcome was to evaluate which characteristics of the population could influence the choice of oncological treatment (with radical or non-radical intent)., Results: We identified a total of 348 patients: 140 were on follow-up; 177 were under treatment; 31 were considered not eligible for treatments. Patients under treatment had a high comorbidity index (mean Charlson Comorbidity Index 5.4), and a high prevalence of polypharmacy (mean number of drugs 5.6). More than half (53.1%) was treated with radical intent. Patients treated with radical intent were 1 year younger (87.1 years old vs 88.1 years old), more performant (ECOG 0.7 vs 1.3), and had less prevalence of metastatic neoplasia (6.4% vs 34.9%); comorbidities and drugs did not show differences in the two groups., Conclusion: Oldest old, usually not considered in international guidelines, are treated for oncological disease, often with radical intent. The treatment seems not to be tailored considering comorbidities but on performance status., (© 2021. The Author(s).)

Background: Frailty is increasingly reported among older adults with cardiovascular diseases and it has been demonstrated to increase negative health outcomes and mortality. To date, no systematic review of the evidence is available regarding the association between frailty and ischemic heart disease (IHD). We performed a systematic review of literature and a meta-analysis to assess the association between frailty and IHD., Methods: We selected all the studies that provided information on the association between frailty and IHD, regardless of the study setting, study design, or definition of IHD and frailty. PubMed, Web of Science and Embase were searched for relevant papers. Studies that adopted the Fried definition for frailty were included in the meta-analyses. For each measure of interest (proportions and estimates of associations), a meta-analysis was performed if at least three studies used the same definition of frailty. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting., Results: Thirty-seven studies were included. Of these, 22 adopted the Fried criteria to define frailty and provided estimates of prevalence and therefore they were included in meta-analyses. The pooled prevalence of IHD in frail individuals was 17% (95% Confidence Interval [95%CI] 11-23%) and the pooled prevalence of frailty in individuals with IHD was 19% (95% CI 15-24%). The prevalence of frailty among IHD patients ranged from 4 to 61%. Insufficient data were found to assess longitudinal association between frailty and IHD., Conclusions: Frailty is quite common in older persons with IHD. The identification of frailty among older adults with IHD should be considered relevant to provide individualized strategies of cardiovascular prevention and care. Further research should specifically explore the association between frailty and IHD and investigate the potential common biological ground.

Background: Older adults are a complex population, at risk of adverse events during and after hospital stay., Aim: To investigate the association of walking speed (WS) and grip strength (GS) with adverse outcomes, during and after hospitalization, among older individuals admitted to acute care wards., Methods: Multicentre observational study including 1123 adults aged ≥ 65 years admitted to acute wards in Italy. WS and GS were measured at admission and discharge. Outcomes were length-of-stay, in-hospital mortality, 1-year mortality and rehospitalisation. Length-of-stay was defined as a number of days from admission to discharge/death., Results: Mean age was 81 ± 7 years, 56% were women. Compared to patients with WS ≥ 0.8 m/sec, those unable to perform or with WS < 0.8 m/sec had a higher likelihood of longer length-of-stay (OR 2.57; 95% CI 1.63-4.03 and 2.42; 95% CI 1.55-3.79) and 1-year mortality and rehospitalization (OR 1.47, 95% CI 1.07-2.01; OR 1.57, 95% CI 1.04-2.37); those unable to perform WS had a higher likelihood of in-hospital mortality (OR 9.59; 95% CI 1.23-14.57) and 1-year mortality (OR 2.60; 95% CI 1.37-4.93). Compared to good GS performers, those unable to perform had a higher likelihood of in-hospital mortality (OR 17.43; 95% CI 3.87-28.46), 1-year mortality ( OR 3.14; 95% CI 1.37-4.93) and combination of 1-year mortality and rehospitalisation (OR 1.46; 95% CI 1.01-2.12); poor GS performers had a higher likelihood of 1-year mortality (OR 1.39; 95% CI 1.03-2.35); participants unable to perform GS had a lower likelihood of rehospitalisation (OR 0.59; 95% CI 0.39-0.89)., Conclusion: Walking speed (WS) and grip strength (GS) are easy-to-assess predictors of length-of-stay, in-hospital and post-discharge death and should be incorporated in the standard assessment of hospitalized patients.

Background: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19., Methods: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample., Results: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129)., Conclusions: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed., (© 2020 Wiley Periodicals LLC.)

People with Down Syndrome (DS) have a high prevalence of physical and psychiatric comorbidities and experience early-onset dementia. With the outbreak of CoVID-19 pandemic, strict social isolation measures have been necessary to prevent the spreading of the disease. Effects of this lockdown period on behavior, mood and cognition in people with DS have not been assessed so far. In the present clinical study, we investigated the impact of CoVID-19-related lockdown on psychosocial, cognitive and functional well-being in a sample population of 46 adults with DS. The interRAI Intellectual Disability standardized assessment instrument, which includes measures of social withdrawal, functional impairment, aggressive behavior and depressive symptoms, was used to perform a three time-point evaluation (two pre-lockdown and one post-lockdown) in 37 subjects of the study sample, and a two time point evaluation (one pre- and one post-lockdown) in 9 subjects. Two mixed linear regression models - one before and one after the lockdown - have been fitted for each scale in order to investigate the change in the time-dependent variation of the scores. In the pre-lockdown period, significant worsening over time (i.e., per year) was found for the Depression Rating Scale score (β = 0.55; 95% CI 0.34; 0.76). In the post-lockdown period, a significant worsening in social withdrawal (β = 3.05, 95% CI 0.39; 5.70), instrumental activities of daily living (β = 1.13, 95% CI 0.08; 2.18) and depression rating (β = 1.65, 95% CI 0.33; 2.97) scales scores was observed, as was a significant improvement in aggressive behavior (β = -1.40, 95% CI -2.69; -0.10). Despite the undoubtful importance of the lockdown in order to reduce the spreading of the CoVID-19 pandemic, the related social isolation measures suggest an exacerbation of depressive symptoms and a worsening in functional status in a sample of adults with DS. At the opposite, aggressive behavior was reduced after the lockdown period. This finding could be related to the increase of negative and depressive symptoms in the study population. Studies with longer follow-up period are needed to assess persistence of these effects., (Copyright © 2020 Villani, Vetrano, Damiano, Paola, Ulgiati, Martin, Hirdes, Fratiglioni, Bernabei, Onder and Carfì.)

Background: Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available., Methods: A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex., Results: Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90)., Conclusions: Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.

Data on clinical characteristics of adults with Down syndrome (DS) are limited and the clinical phenotype of these persons is poorly described. This study aimed to describe the occurrence of chronic diseases and pattern of medication use in a population of adults with DS. Participants were 421 community dwelling adults with DS, aged 18 years or older. Individuals were assessed through a standardized clinical protocol. Multimorbidity was defined as the occurrence of two or more chronic conditions and polypharmacy as the concomitant use of five or more medications. The mean age of study participants was 38.3 ± 12.8 years and 214 (51%) were women. Three hundred and seventy-four participants (88.8%) presented with multimorbidity. The most prevalent condition was visual impairment (72.9%), followed by thyroid disease (50.1%) and hearing impairment (26.8%). Chronic diseases were more prevalent among participants aged >40 years. The mean number of medications used was 2.09 and polypharmacy was observed in 10.5% of the study sample. Psychotropic medications were used by a mean of 0.7 individuals of the total sample. The high prevalence of multimorbidity and the common use of multiple medications contributes to a high level of clinical complexity, which appears to be similar to the degree of complexity of the older non-trisomic population. A comprehensive and holistic approach, commonly adopted in geriatric medicine, may provide the most appropriate care to persons with DS as they grow into adulthood., (© 2020 Wiley Periodicals, Inc.)

Coronavirus disease 2019 (COVID-19) is the respiratory disease caused by the novel severe acute respiratory syndrome-coronavirus-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms to severe respiratory insufficiency and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high mortality risk. Also, thrombotic complications such as pulmonary embolisms and disseminated intravascular coagulation are frequent in these patients. Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its life-threatening complication. Immunomodulatory drugs, such as hydroxychloroquine and interleukin-6 inhibitors, as well as antithrombotic drugs such as heparin and low molecular weight heparin, are currently being administered with some benefit. Ozone therapy consists in the administration of a mixture of ozone and oxygen, called medical ozone, which has been used for over a century as an unconventional medicine practice for several diseases. Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent. Thus, medical ozone could help to decrease lung inflammation, slow down viral growth, regulate lung circulation and oxygenation and prevent microvascular thrombosis. Ozone-therapy could be considered a feasible, cost-effective and easy to administer adjuvant therapy while waiting for the synthesis of a therapy or the development of the vaccine., Competing Interests: None

Objective: Bevacizumab maintenance following platinum-based chemotherapy is an effective treatment for epithelial ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition., Methods: This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (<65 years, group 1) and elderly (≥65 years, group 2). A binary logistic model was applied to correlate clinical variables and severe (grade ≥3) toxicity risk., Results: Overall, 283 patients with EOC were included, with 72 (25.4%) older patients compared with 211 (74.6%) younger women. Bevacizumab had been administered to 234 patients (82.7%) as first-line treatment and in 49 (17.3%) with recurrent disease. At diagnosis, elderly patients presented with at least one comorbidity and were taking at least 1 medication in 84.7% and 80.6% of the cases respectively, compared with correspondingly 47.4% and 37.4% in group 1 (p<0.001). Nonetheless, the occurrence of serious (grade ≥3) adverse events did not increase among the older group. Creatinine serum levels >1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity., Conclusions: Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2020. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objectives: To assess 1-year incidence and factors related to deprescribing in nursing home (NH) residents in Europe., Design: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study., Setting: NHs in Europe and Israel., Participants: 1843 NH residents on polypharmacy., Methods: Polypharmacy was defined as the concurrent use of 5 or more medications. Deprescribing was defined as a reduction in the number of medications used over the study period. Residents were followed for 12 months., Results: Residents in the study sample were using a mean number of 8.6 (standard deviation 2.9) medications at the baseline assessment. Deprescribing was observed in 658 residents (35.7%). Cognitive impairment (mild/moderate impairment vs intact, odds ratio [OR] 1.41, 95% confidence interval [CI] 1.11-1.79; severe impairment vs intact, OR 1.60, 95% CI 1.23-2.09), presence of the geriatrician within the facility staff (OR 1.41, 95% CI 1.15-1.72), and number of medications used at baseline (OR 1.10, 95% CI 1.06-1.14) were associated with higher probabilities of deprescribing. In contrast, female gender (OR 0.76, 95% CI 0.61-0.96), heart failure (OR 0.69, 95% CI 0.53-0.89), and cancer (OR 0.64, 95% CI 0.45-0.90) were associated with a lower probability of deprescribing., Conclusions and Implications: Deprescribing is common in NH residents on polypharmacy, and it is associated with individual and organizational factors. More evidence is needed on deprescribing, and clear strategies on how to withdraw medications should be defined in the future., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Down syndrome (DS) is characterised by premature ageing that affects selected organ systems, and persons with this condition can present patterns of co-morbidities and deficits often observed in the older population without DS. However, information on the characteristics of adult persons with DS is limited. The objective of the study is to describe characteristics of adults with DS collected with a standardised, comprehensive assessment instrument., Methods: Cross-sectional study. Four hundred thirty adults with DS (age range 18/75 years) from three countries (Italy, n = 95; USA, n = 175; and Canada, n = 160). A standardised assessment instrument (interRAI intellectual disability) was used to assess sample characteristics., Results: Mean age ranged from 35.2 (standard deviation 12.0) years in the US sample to 48.8 (standard deviation 9.0) years in the Canadian sample. Most participants in the Italian and US sample were living in private homes, while more than half of those in the Canadian sample were institutionalised. Prevalences of geriatric conditions, including cognitive deficits, disability in the common activities of daily living, symptoms of withdrawal or anhedonia, aggressive behaviour, communication problems, falls and hearing problems were high in the study sample. Gastrointestinal symptoms, skin and dental problems and obesity were also frequently observed., Conclusions: Adults with DS present with a high level of complexity, which may suggest the need for an approach based on a comprehensive assessment and management that can provide adequate care. Further research is needed to understand better the effectiveness of such an approach in the DS population., (© 2019 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: People with Down syndrome (DS) experience premature aging. Whether this accelerated aging also involves early declines in muscle mass, strength and physical performance is presently unclear. The present study investigated the prevalence of sarcopenia parameters in adults with DS. In addition, the relationship between well-established muscle mass indexes and a set of body composition, functional, biological, and clinical parameters was explored., Methods: One hundred-five adults with DS participated in the study. Demographic, clinical, anthropometric, and functional parameters were assessed. Lean body mass (LBM) was estimated using bioelectrical impedance analysis. Bone mineral density (BMD) of the hip and the spine was measured through dual X-ray absorptiometry. For the analysis, participants were categorized into two subgroups (i.e., low and high) for each LBM-related measurement (i.e., crude LBM, LBM to body mass index ratio, and skeletal muscle index) according to their median values., Results: The mean age of participants was 38.4 ± 12.1 years, with 43 men (41%). Muscle mass, handgrip strength, and gait speed were lower than established cutoffs for sarcopenia. All muscle mass indexes were negatively correlated with age. However, only crude LBM and the skeletal muscle index were correlated with a set of anthropometric parameters and BMD., Conclusion: Findings from this exploratory study indicate that adults with DS show muscle mass indexes and physical performance levels similar to or lower than older adults with sarcopenia. The assessment of muscle mass and functional status should therefore be included in the routine evaluation of this population starting at young age., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate: (1) the cross-sectional association between polypharmacy, hyperpolypharmacy and presence of prefrailty or frailty; (2) the risk of incident prefrailty or frailty in persons with polypharmacy, and vice versa., Methods: A systematic review and meta-analysis was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/1998 to 5/2/2018. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I 2 statistic and publication bias with Egger's and Begg's tests., Results: Thirty-seven studies were included. The pooled proportion of polypharmacy in persons with prefrailty and frailty was 47% (95% CI 33-61) and 59% (95% CI 42-76), respectively. Increased odds ratio of polypharmacy were seen for prefrail (pooled OR = 1.52; 95% CI 1.32-1.79) and frail persons (pooled OR = 2.62, 95% CI 1.81-3.79). Hyperpolypharmacy was also increased in prefrail (OR = 1.95; 95% CI 1.41-2.70) and frail (OR = 6.57; 95% CI 9.57-10.48) persons compared to robust persons. Only seven longitudinal studies reported data on the risk of either incident prefrailty or frailty in persons with baseline polypharmacy. A significant higher odds of developing prefrailty was found in robust persons with polypharmacy (pooled OR = 1.30; 95% CI 1.12-1.51). We found no papers investigating polypharmacy incidence in persons with prefrailty/frailty., Conclusions: Polypharmacy is common in prefrail and frail persons, and these individuals are also more likely to be on extreme drug regimens, i.e. hyperpolypharmacy, than robust older persons. More research is needed to investigate the causal relationship between polypharmacy and frailty syndromes, thereby identifying ways to jointly reduce drug burden and prefrailty/frailty in these individuals., Prospero Registration Number: CRD42018104756.

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril ( n = 8) or placebo ( n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA 4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA 4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging., Competing Interests: authors declare no conflict of interest.

Atrial fibrillation (AF) is a common cardiac arrhythmia and its prevalence increases with age. There is a significant correlation between frailty, morbidity and mortality in elderly patients with cardiovascular disease, but the relation between AF and frailty is still under debate. The aim of this study is to systematically review evidence on the association between AF and frailty. A systematic review of articles published between 02/01/2002 and 09/28/2017 according to PRISMA recommendations was carried out. PubMed, Web of Science, and Embase were searched for relevant articles. 11 studies were included; one longitudinal, 10 cross-sectional. Only 4 studies assessed the association of frailty with AF, while 7 studies were performed in a sample of participants with AF and did not provide any measure of association between these two conditions. The prevalence of frailty in AF patients ranged from 4.4%-75.4% while AF prevalence in the frail population ranged from 48.2%-75.4%. Selected studies enrolled an overall sample of 9420 participants. Among them, 2803 participants were diagnosed with AF and of these 1517 (54%) were frail and 1286 (46%) were pre-frail or robust. The four studies assessing the association of AF and frailty provided conflicting results. Evidence suggests that frailty is common in persons with AF. More research is needed to better assess the association of these conditions and to identify the optimal therapeutic approach to AF in persons with frailty., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objectives: To test the association between polypharmacy and 1-year change in physical and cognitive function among nursing home (NH) residents., Design: Longitudinal multicenter cohort study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study., Setting: NH in Europe (n = 50) and Israel (n = 7)., Participants: 3234 NH older residents., Measurements: Participants were assessed through the interRAI long-term care facility instrument. Polypharmacy was defined as the concurrent use of 5 to 9 drugs and excessive polypharmacy as the use of ≥10 drugs. Cognitive function was assessed through the Cognitive Performance Scale (CPS). Functional status was evaluated through the Activities of Daily Living (ADL) Hierarchy scale. The change in CPS and ADL score, based on repeated assessments, was the outcome, and their association with polypharmacy was modeled via linear mixed models. The interaction between polypharmacy and time was reported [beta and 95% confidence intervals (95% CIs)]., Results: A total of 1630 (50%) residents presented with polypharmacy and 781 (24%) excessive polypharmacy. After adjusting for potential confounders, residents on polypharmacy (beta 0.10, 95% CI 0.01-0.20) and those on excessive polypharmacy (beta 0.13, 95% CI 0.01-0.24) had a significantly higher decline in CPS score compared to those using <5 drugs. No statistically (P > .05) significant change according to polypharmacy status was shown for ADL score., Conclusions: Polypharmacy is highly prevalent among older NH residents and, over 1 year, it is associated with worsening cognitive function but not functional decline., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing evidence that frailty may play a role in chronic diseases, but the associations with specific chronic disorders are still unclear., Objectives: To conduct a systematic review and meta-analysis assessing the association of anaemia and frailty in observational studies., Methods: The review was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/2002-10/09/2017. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I2 statistic. Publication bias was assessed with Egger's and Begg's tests., Results: Nineteen studies were included; two longitudinal, seventeen cross-sectional. All studies except three reported an association between anaemia and frailty. The pooled prevalence of prefrailty in individuals with anaemia was 49% (95% CI=38-59%; I2=89.96%) and 24% (95% CI=17-31%; I2= 94.78%) for frailty. Persons with anaemia had more than a twofold odds of frailty (pooled OR=2.24 95% CI=1.53-3.30; I2=91.8%). Only two studies longitudinally examined the association between anaemia and frailty, producing conflicting results., Conclusions: Frailty and prefrailty are common in anaemic persons. Older persons with anaemia have more than a two-fold increased odds of frailty. These results may have clinical implications, as they identify the need to assess frailty in anaemic people and investigate any potential negative effects associated with the co-occurrence of both conditions. Longitudinal research that examines temporal changes in anaemia and effect of treatment are needed to further clarify the relationship between anaemia and frailty., Competing Interests: None

This study analyzed data of bone mineral density (BMD) from a large cohort of adults with Down syndrome (DS). BMD was found to decrease with age more rapidly in these subjects than in the general population, exposing adults with DS to an increased risk of osteoporosis and bone fracture., Introduction: Down syndrome (DS) in adulthood presents with a high prevalence of osteoporosis. However, in DS, bone mineral density (BMD) can be underestimated due to short stature. Furthermore, the rate of age-related decline in BMD and its association with gender in DS has been rarely evaluated or compared with the general population. The present study is aimed at assessing the variation of BMD with age and gender in a sample of adults with DS and to compare these data with those of the general population, after adjusting for anthropometric differences., Methods: Adults with DS, aged 18 or older, were assessed dual-energy-X-ray-absorptiometry (DXA) at the femoral neck and at the lumbar spine. They were compared with the general population enrolled in the National Health and Nutrition Examination Survey (NHANES) 2009-2010 dataset. Bone mineral apparent density (BMAD) was calculated for each individual., Results: DXA was evaluated in 234 subjects with DS (mean age 36.93 ± 11.83 years, ranging from 20 to 69 years; 50.4% females). In the lumbar spine both mean BMD (DS 0.880 ± 0.141 vs. NHANES 1.062 ± 0.167, p < 0.001) and BMAD (DS 0.138 ± 0.020 vs. NHANES 0.152 ± 0.020, p < 0.001) were significantly lower in the DS sample than in the NAHNES cohort. The same trend was observed at the femoral neck in both BMD (DS 0.658 ± 0.128 vs. NHANES 0.835 ± 0.137, p < 0.001) and BMAD (DS 0.151 ± 0.030 vs. NHANES 0.159 ± 0.028, p<0.001). Age was associated with lower femoral neck BMAD in both samples; importantly, this association was significantly stronger in the DS sample. In the lumbar spine region, no significant association between BMAD and age could be observed in both samples., Conclusions: Adults with DS have lower bone mineral density compared to the general population and they experience a steeper decline with age. Early screening programs are needed in DS population.

People with Down syndrome (DS) show lower bone mass density (BMD) and a higher prevalence of hypothyroidism compared to general population. Furthermore, DS is a well-known high oxidative stress (OS) condition because genes involved in OS map on chromosome 21. Thyroid function too is involved in OS. Since both thyroid function and OS lead to lower BMD and osteoporotic fractures, we have explored correlations among BMD, thyroid hormones, and parameters of OS in DS adults. A total of 105 DS patients (48 males; 21-71 years; mean BMI 28.88±7.12 kg/m(2)) were enrolled in a cohort study, 48 of them undergoing thyroid replacement therapy. We evaluated thyroid function, BMD, and total antioxidant capacity (TAC) in blood plasma. TAC was assayed by H2O2-metmyoglobin system, as source of radicals, and by the chromogenous ABTS, with a latency time (LAG) in the appearance of its cation ABTS+proportional to antioxidant concentration. BMD was evaluated with DEXA, using WHO criteria to classify osteoporosis. Low BMD was found in 83.78% of patients. TSH and LAG did not correlate with BMD. Nevertheless, LAG significantly correlates to Z-scores estimated at the lumbar spine (r(2)=0.558; p=0.03) in hypothyroid patients. Our data show that low TAC could be more associated with reduced BMD rather than TSH itself in DS patients and that the OS could have a role in the pathogenesis of osteoporosis regarding the hypothyroid subgroup., (© Georg Thieme Verlag KG Stuttgart · New York.)