Clinical profile of trazodone users in a multisetting older population: data from the Italian GeroCovid Observational study.

BACKGROUND AND OBJECTIVES: Depression is highly prevalent in older adults, especially in those with dementia. Trazodone, an antidepressant, has shown to be effective in older patients with moderate anxiolytic and hypnotic activity; and a common off-label use is rising for managing behavioral and psychological symptoms of dementia (BPSD). The aim of the study is to comparatively assess the clinical profiles of older patients treated with trazodone or other antidepressants. METHODS: This cross-sectional study involved adults aged ≥ 60 years at risk of or affected with COVID-19 enrolled in the GeroCovid Observational study from acute wards, geriatric and dementia-specific outpatient clinics, as well as long-term care facilities (LTCF). Participants were grouped according to the use of trazodone, other antidepressants, or no antidepressant use. RESULTS: Of the 3396 study participants (mean age 80.6 ± 9.1 years; 57.1% females), 10.8% used trazodone and 8.5% others antidepressants. Individuals treated with trazodone were older, more functionally dependent, and had a higher prevalence of dementia and BPSD than those using other antidepressants or no antidepressant use. Logistic regression analyses found that the presence of BPSD was associated with trazodone use (odds ratio (OR) 28.4, 95% confidence interval (CI) 18-44.7 for the outcome trazodone vs no antidepressants use, among participants without depression; OR 2.17, 95% CI 1.05-4.49 for the outcome trazodone vs no antidepressants use, among participants with depression). A cluster analysis of trazodone use identified three clusters: cluster 1 included mainly women, living at home with assistance, multimorbidity, dementia, BPSD, and depression; cluster 2 included mainly institutionalized women, with disabilities, depression, and dementia; cluster 3 included mostly men, often living at home unassisted, with better mobility performance, fewer chronic diseases, dementia, BPSD, and depression. DISCUSSION: The use of trazodone was highly prevalent in functionally dependent and comorbid older adults admitted to LTCF or living at home. Clinical conditions associated with its prescription included depression as well as BPSD.

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study.

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

Clinical Features of SARS-CoV-2 Infection in Older Adults.

Covid-19 clinical presentation is extremely heterogenous, especially in older patients due to the possible presence of atypical symptoms, such as delirium, hyporexia and falls. The clinical characteristics at onset are influenced by the presence of common health-related conditions in older people, such as comorbidity, disability and frailty, and not simply by chronological age. Few studies investigated the tendency of Covid-19 symptoms to aggregate in cluster and the use of cluster approach might better describe the clinical complexity of the acute disease. Concerning the prognostic significance of Covid-19 clinical presentation in older people, the available literature still provides discordant results.

Presepsin levels and COVID-19 severity: a systematic review and meta-analysis.

Plasmatic presepsin (PSP) is a novel biomarker reported to be useful for sepsis diagnosis and prognosis. During the pandemic, only few studies highlighted a possible correlation between PSP and COVID-19 severity, but results remain inconsistent. The present study aims to establish the correlation between PSP and COVID-19 severity. English-language papers assessing a correlation between COVID-19 and PSP from MEDLINE, PubMed, Google Scholar, Cochrane Library, MeSH, LitCovid NLM, EMBASE, CINAHL Plus and the World Health Organization (WHO) website, published from January 2020 were considered with no publication date limitations. Two independent reviewers performed data abstraction and quality assessment, and one reviewer resolved inconsistencies. The protocol was registered on PROSPERO (CRD42022325971).Fifteen articles met our eligibility criteria. The aggregate study population included 1373 COVID-19 patients who had undergone a PSP assessment. The random-effect meta-analysis was performed in 7 out of 15 selected studies, considering only those reporting the mean PSP levels in low- and high-severity cases (n = 707).The results showed that the pooled mean difference of PSP levels between high- and low-severity COVID-19 patients was 441.70 pg/ml (95%CI: 150.40-732.99 pg/ml).Our data show that presepsin is a promising biomarker that can express COVID-19 severity.

Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-Term Care Facilities: Data From the GeroCovid Vax Study.

OBJECTIVE: Type 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment. RESEARCH DESIGN AND METHODS: For this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents). RESULTS: The mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (ß = -0.20; 95% CI -0.34, -0.06) and 6 months (ß = -0.22; 95% CI -0.37, -0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (ß = -0.24; 95% CI -0.43, -0.05 and ß = -0.30; 95% CI -0.50, -0.10, respectively), whereas no differences were observed for those using insulin. CONCLUSIONS: Older residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.

Determinants of Cause-Specific Mortality and Loss of Independence in Older Patients following Hospitalization for COVID-19: The GeroCovid Outcomes Study.

Hospitalization for acute SARS-CoV-2 infection confers an almost five-fold higher risk of post-discharge, all-cause mortality compared to controls from the general population. A negative impact on the functional autonomy of older patients, especially in cases of severe disease and prolonged hospitalization, has been recently described. However, little is known about the determinants of cause-specific mortality and loss of independence (LOI) in the activities of daily living (ADL) following COVID-19 hospitalization. Thus, the current prospective, multicenter study is aimed at identifying the determinants of post-discharge cause-specific mortality and the loss of autonomy in at least one ADL function. Older patients hospitalized for a SARS-CoV-2 infection were consecutively enrolled in an e-Registry from 1 March 2020, until 31 December 2020. After at least six months from discharge, patients were extensively re-evaluated according to a common protocol at the outpatient clinic of eight tertiary care Italian hospitals. Of 193 patients [109 (56.4%) men, mean age 79.9 ± 9.1 years], 43 (22.3%) died during follow-up. The most common causes of death were cardiovascular diseases (46.0%), respiratory failure (26.5%), and gastrointestinal and genitourinary diseases (8.8% each). Pre-morbid ADLs qualified as an independent mortality risk factor [adjusted HR 0.77 (95%CI: 0.63-0.95)]. Of 132 patients, 28 (21.2%) lost their independence in at least one ADL. The adjusted risk of LOI declined with a lower frailty degree [aOR 0.03 (95%CI: 0.01-0.32)]. In conclusion, at long-term follow-up after hospitalization for acute SARS-CoV-2 infection, more than 40% of older patients died or experienced a loss of functional independence compared to their pre-morbid condition. Given its high prevalence, the loss of functional independence after hospitalization for COVID-19 could be reasonably included among the features of the "Long COVID-19 syndrome" of older patients.

Strategies and Tools for Supporting the Appropriateness of Drug Use in Older People.

Through this structured review of the published literature, we aimed to provide an up-to-date description of strategies (human-related) and tools (mainly from the digital field) facilitating the appropriateness of drug use in older adults. The evidence of each strategy and tool's effectiveness and sustainability largely derives from local and heterogeneous experiences, with contrasting results. As a general framework, three main steps should be considered in implementing measures to improve appropriateness: prescription, acceptance by the patient, and continuous monitoring of adherence and risk-benefit profile. Each step needs efforts from specific actors (physicians, patients, caregivers, healthcare professionals) and dedicated supporting tools. Moreover, how to support the appropriateness also strictly depends on the particular setting of care (hospital, ambulatory or primary care, nursing home, long-term care) and available economic resources. Therefore, it is urgent assigning to each approach proposed in the literature the following characteristics: level of effectiveness, strength of evidence, setting of implementation, needed resources, and issues for its sustainability.

COVID-19 Signs and Symptom Clusters in Long-Term Care Facility Residents: Data from the GeroCovid Observational Study

Background: Long-term care facility (LTCF) residents often present asymptomatic or paucisymptomatic features of SARS-CoV-2 infection. We aimed at investigating signs/symptoms, including their clustering on SARS-CoV-2 infection and mortality rates associated with SARS-CoV-2 infection in LTCF residents. Methods: This is a cohort study of 586 aged ≥60 year-old residents at risk of or affected with COVID-19 enrolled in the GeroCovid LTCF network. COVID-19 signs/symptom clusters were identified using cluster analysis. Cluster analyses associated with SARS-CoV-2 infection and mortality were evaluated using logistic regression and Cox proportional hazard models. Results: Cluster 1 symptoms (delirium, fever, low-grade fever, diarrhea, anorexia, cough, increased respiratory rate, sudden deterioration in health conditions, dyspnea, oxygen saturation, and weakness) affected 39.6% of residents and were associated with PCR swab positivity (OR = 7.21, 95%CI 4.78–10.80;p < 0.001). Cluster 1 symptoms were present in deceased COVID-19 residents. Cluster 2 (increased blood pressure, sphincter incontinence) and cluster 3 (new-onset cognitive impairment) affected 20% and 19.8% of residents, respectively. Cluster 3 symptoms were associated with increased mortality (HR = 5.41, 95%CI 1.56–18.8;p = 0.008), while those of Cluster 2 were not associated with mortality (HR = 0.82, 95%CI 0.26–2.56;p = 730). Conclusions: Our study highlights that delirium, fever, and low-grade fever, alone or in clusters should be considered in identifying and predicting the prognosis of SARS-CoV-2 infection in older LTCF patients.

Clinical features of SARS-CoV-2 infection in older adults

Synopsis The heterogeneity of Covid-19 clinical presentation is extremely diversified, especially in older patients due to possible presence of atypical symptoms at disease onset, such as delirium, hyporexia and falls. Despite this findings, even in older people the typical clinical presentation with fever and respiratory symptoms remains the most probable. The clinical characteristic at Covid-19 onset are influenced by the presence of common health-related conditions in geriatric subjects, such as comorbidity, disability and frailty, and not simply by chronological age. Moreover, few studies investigated the tendency of Covid-19 symptoms to aggregate in cluster and the use of cluster approach might better describe the clinical complexity of the acute disease. Finally, concerning the prognostic significance of Covid-19 clinical presentation in older people, the available literature still provides discordant results: currently, patients with atypical symptoms report a higher risk to adverse outcomes, such as severity of acute illness and death.

Computed tomography findings and prognosis in older COVID-19 patients.

BACKGROUND: In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. METHODS: Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. RESULTS: 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24-3.06) for pleural effusion and 13 (95%CI 6.41-27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion ("LH"), respectively. Out of the three CT based clusters, "LH" was the only independent predictor in the multivariable model. CONCLUSIONS: Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04379440.

Monitoring COVID-19 vaccine use in Italian long term care centers: The GeroCovid VAX study.

The COVID-19 pandemic has changed routine care practice for older persons, especially in those with frailty living in long term care (LTC) facilities. Due to the high mortality rates of Nursing home (NH) residents during the first wave of the COVID-19 pandemic, priority for COVID-19 vaccinations was given to this vulnerable population. However, the safety and efficacy of such vaccines in older frail elders remains questionable due to the fact that initial randomized clinical trials (RCTs) for such vaccines did not include this population. This type of discrimination in patient participation in RCTs continues and has been recognized in the literature. Nevertheless, in the context of a worldwide emergency, COVID-19 vaccination in older persons living in LTC facilities may provide a solid basis to protect against negative outcomes, such as COVID-19 infection and death. In this report, we present the protocol of the GeroCovid Vax study, an Italian study that began in February 2021 which is aimed at investigating the safety and efficacy of the anti-SARS-CoV-2 vaccinations in older persons living in LTCs. This protocol specially aims to continuously and closely monitor events related to- and following- the anti-SARS-CoV-2 vaccination in elderly living in LTC facilities. In this report, we will provide information related to the study protocol and describe baseline characteristics of the sample.

Atrial fibrillation and COVID-19 in older patients: how disability contributes to shape the risk profile. An analysis of the GeroCovid registry.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is often complicated by disabling conditions in the elderly. COVID-19 has high mortality in older people. This study aimed at evaluating the relationship of pre-infection AF with characteristics and survival of older COVID-19 patients. METHODS: We retrospectively analyzed inpatients aged ≥ 60 years enrolled in GeroCovid Observational, a multicenter registry endorsed by the Italian and the Norwegian Societies of Gerontology and Geriatrics. Pre-COVID-19 sociodemographic, functional, and medical data were systematically collected, as well as in-hospital mortality. RESULTS: Between March and June 2020, 808 COVID-19 subjects were enrolled (age 79 ± 9 years; men 51.7%). The prevalence of AF was 21.8%. AF patients were older (82 ± 8 vs. 77 ± 9 years, p < 0.001), had a higher CHA2DS2-VASc score (4.1 ± 1.5 vs. 3.2 ± 1.5, p < 0.001) and were more likely to present almost all comorbidities. At multivariable analysis, advanced age, white blood cell count, the presence of heart and peripheral artery diseases were significantly associated with the presence of AF. In-hospital mortality was higher in AF patients (36.9 vs. 27.5%; OR = 1.55, 95% CI = 1.09-2.20; p = 0.015). A decision tree analysis showed that, in AF subjects, preserved functional status at admission was the most important factor associated with survival. In patients without AF, baseline COVID-19 severity was the most relevant variable related to clinical prognosis. CONCLUSIONS: AF is frequent in older patients with COVID-19, in whom it associates with clinical complexity and high mortality. Pre-infection disability shapes the prognosis of this extremely vulnerable segment of hospitalized subjects. CLINICAL TRIAL REGISTRATION: GeroCovid Observational was registered at www.clinicaltrials.gov (NCT04379440).

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 < 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.

Management of Older Outpatients during the COVID-19 Pandemic: The GeroCovid Ambulatory Study.

OBJECTIVES: The GeroCovid Study is a multi-setting, multinational, and multi-scope registry that includes the GeroCovid home and outpatients' care cohort. The present study aims to evaluate whether outpatient and home care services with remote monitoring and consultation could mitigate the impact of the COVID-19 pandemic on mental and affective status, perceived well-being, and personal capabilities of outpatients and home care patients with cognitive disorders. METHODS: Prospectively recorded patients in an electronic web registry provided by BlueCompanion Ltd. Up to October 31, 2020, the sample included 90 patients receiving regular care from the Center for Cognitive Disorders and Dementia in Catanzaro Lido, Italy. It was made of 52 ambulatory outpatients and 38 home care patients, mean age 83.3 ± 7.54 years. Participants underwent a multidimensional assessment at baseline (T0) and after 90 days (T1). For each patient, we administered the Mini-Mental State Examination (MMSE) for cognitive functions, the Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales for functional capabilities, the Cumulative Illness Rating Scale (CIRS) for comorbidities and their impact on patients' health, the 5-items Geriatric Depression Scale (GDS) for mood, and the Euro Quality of Life (EuroQoL) for perceived quality of life. Contacts with both ambulatory and home care patients were managed in person or via telephone, preferably through video calls (WhatsApp or FaceTime). RESULTS: Contacts with patients were kept at T0 through telephone. At T1, visits were made in person for over 95% out of the cases. The ADL, IADL, CIRS, GDS, MMSE, and EuroQoL changed slightly between T0 and T1. Most of the patients were clinically stable over time on the majority of the scales explored, but behavioral changes were found in 24.4% of patients and anxiety and insomnia in 17.7% of patients. CONCLUSION: Our study suggests that contacts through telephone and video consultations are likely associated with a health status preservation of the patients.

COVID-19 and Atrial Fibrillation in Older Patients: Does Oral Anticoagulant Therapy Provide a Survival Benefit?-An Insight from the GeroCovid Registry.

INTRODUCTION: Atrial fibrillation (AF), the most frequent arrhythmia of older patients, associates with serious thromboembolic complications and high mortality. Coronavirus disease 2019 (COVID-19) severely affects aged subjects, determining an important prothrombotic status. The aim of this study was to evaluate mortality-related factors in older AF patients with COVID-19. METHODS: Between March and June 2020, we enrolled ≥60 year-old in-hospital COVID-19 patients (n = 806) in GeroCovid, a multicenter observational study promoted by the Italian Society of Gerontology and Geriatric Medicine. 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). At admission, 51.7, 10.2, and 38.1% of AF cases were taking, respectively, oral anticoagulants (OACs), antiplatelet agents, and no antithrombotic therapy. During hospitalization, 51% patients switched to low-molecular-weight heparins. AF patients who survived were younger (81 ± 8 vs. 84 ± 7 years; p = 0.002) and had a lower CHA2DS2-VASc score (3.9 ± 1.6 vs. 4.4 ± 1.3; p = 0.02) than those who died. OAC use before (63.1 vs. 32.3%; p < 0.001) and during hospitalization (34.0 vs. 12.7%; p = 0.002) was higher among survivors. At multivariable analysis, lower age, higher self-sufficiency, less severe initial COVID-19 presentation, and the use of vitamin K antagonists (odds ratio [OR] = 0.16, 95% confidence interval [CI]: 0.03-0.84) or direct OACs (OR = 0.22, 95% CI: 0.08-0.56) at admission, or the persistence of OAC during hospitalization (OR = 0.05, 95% CI: 0.01-0.24), were associated with a lower chance of in-hospital death. CONCLUSION: AF is a prevalent and severe condition in older COVID-19 patients. Advanced age, dependency, and relevant clinical manifestations of disease characterized a worse prognosis. Preadmission and in-hospital anticoagulant therapies were positively associated with survival.

Assessing the impact of COVID-19 on the health of geriatric patients: The European GeroCovid Observational Study.

BACKGROUND: Despite the growing evidence on COVID-19, there are still many gaps in the understanding of this disease, especially in individuals in advanced age. We describe the study protocol of GeroCovid Observational, a multi-purpose, multi-setting and multicenter initiative that aims at investigating: risk factors, clinical presentation and outcomes of individuals affected by COVID-19 in acute and residential care settings; best strategies to prevent infection in long-term care facilities; and, impact of the pandemic on neuropsychologic, functional and physical health, and on medical management in outpatients and home care patients at risk of COVID-19, with a special focus on individuals with dementia. METHODS: GeroCovid involves individuals aged ≥60 years, at risk of or affected by COVID-19, prospectively or retrospectively observed since March 1st, 2020. Data are collected in multiple investigational sites across Italy, Spain and Norway, and recorded in a de-identified clinical e-Registry. A common framework was adapted to different care settings: acute wards, long-term care facilities, geriatric outpatient and home care, and outpatient memory clinics. RESULTS: At September 16th, 2020, 66 investigational sites obtained their Ethical Committee approval and 1618 cases (mean age 80.6 [SD=9.0] years; 45% men) have been recorded in the e-Registry. The average inclusion rate since the study start on April 25th, 2020, is 11.2 patients/day. New cases enrollment will ended on December 31st , 2020, and the clinical follow-up will end on June 30th, 2021. CONCLUSION: GeroCovid will explore relevant aspects of COVID-19 in adults aged ≥60 years with high-quality and comprehensive data, which will help to optimize COVID-19 prevention and management, with practical implications for ongoing and possible future pandemics. TRIAL REGISTRATION: NCT04379440 (clinicaltrial.gov).