Is Metformin Use Associated with a More Favorable COVID-19 Course in People with Diabetes?

Background: Diabetes Mellitus (DM) has been associated with a higher Coronavirus disease-19 (COVID-19) mortality, both in hospitalized patients and in the general population. A possible beneficial effect of metformin on the prognosis of COVID-19 has been reported in some observational studies, whereas other studies disagree. Methods: To investigate the possible effect of metformin on COVID-19 in-hospital mortality, we performed a retrospective study that included all SARS-CoV-2-positive patients with DM who were admitted to two Italian hospitals. In order to adjust for possible confounders accounting for the observed reduction of mortality in metformin users, we adopted the COVID-19 Mortality Risk Score (COVID-19 MRS) as a covariate. Results: Out of the 524 included patients, 33.4% died. A binomial logistic regression showed that metformin use was associated with a significant reduction in case fatality (OR 0.67 [0.45-0.98], p = 0.039), with no significant effect on the need for ventilation (OR 0.75 [0.5-1.11], p = 0.146). After adjusting for COVID-19 MRS, metformin did not retain a significant association with in-hospital mortality [OR 0.795 (0.495-1.277), p = 0.342]. Conclusions: A beneficial effect of metformin on COVID-19 was not proven after adjusting for confounding factors. The use of validated tools to stratify the risk for COVID-19 severe disease and death, such as COVID-19 MRS, may be useful to better explore the potential association of medications and comorbidities with COVID-19 prognosis.

Are enhanced recovery protocols after pancreatoduodenectomy still efficient when applied in elderly patients? A systematic review and individual patient data meta-analysis.

BACKGROUND: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD). METHODS: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included. The main outcomes were postoperative morbidity, length of stay, readmission and postoperative functional recovery elements. To assess an age-dependent effect, the group was divided in septuagenarians (70-79 years) and older patients (≥80 years). RESULTS: IPD were obtained from 15 of 31 eligible studies comprising 1109 patients. The overall complication and major complication rates were comparable in both groups (OR 0.92 [95% CI: 0.65-1.29], p = .596 and OR 1.22 [95% CI: 0.61-2.46], p = .508). Length of hospital stay tended to be shorter in the ERAS group compared to the conventional care group (-0.14 days [95% CI: -0.29 to 0.01], p = .071) while readmission rates were comparable and the total length of stay including days in hospital after readmission tended to be shorter in the ERAS group (-0.28 days [95% CI: -0.62 to 0.05], p = .069). In the subgroups, the length of stay was shorter in octogenarians treated with ERAS (-0.36 days [95% CI: -0.71 to -0.004], p = .048). The readmission rate increased slightly but not significantly while the total length of stay was not longer in the ERAS group. CONCLUSION: ERAS in the elderly is safe and its benefits are preserved in the care of even in patients older than 80 years. Standardized care protocol should be encouraged in all pancreatic centers.

The interplay of post-acute COVID-19 syndrome and aging: a biological, clinical and public health approach.

The post-acute COVID-19 syndrome (PACS) is characterized by the persistence of fluctuating symptoms over three months from the onset of the possible or confirmed COVID-19 acute phase. Current data suggests that at least 10% of people with previously documented infection may develop PACS, and up to 50-80% of prevalence is reported among survivors after hospital discharge. This viewpoint will discuss various aspects of PACS, particularly in older adults, with a specific hypothesis to describe PACS as the expression of a modified aging trajectory induced by SARS CoV-2. This hypothesis will be argued from biological, clinical and public health view, addressing three main questions: (i) does SARS-CoV-2-induced alterations in aging trajectories play a role in PACS?; (ii) do people with PACS face immuno-metabolic derangements that lead to increased susceptibility to age-related diseases?; (iii) is it possible to restore the healthy aging trajectory followed by the individual before pre-COVID?. A particular focus will be given to the well-being of people with PACS that could be assessed by the intrinsic capacity model and support the definition of the healthy aging trajectory.

Role of new drug therapies and innovative procedures in older patients with heart failure: from trials to clinical practice.

During earliest years, new drug-therapies and novel interventional therapies have been tested to modify the detrimental effect of secondary valve diseases, adverse ventricular remodelling and persistent fluid overload in HF patients. However, the increased prevalence of older or very old patients with HF has made their widespread implementation more problematic due to complex comorbidity, frailty, or overt disability. This growing older population, often excluded by randomized trials, but with elevated risk of hospitalization, required a different clinical and management approach that allows clinicians to take full advantage in reducing mortality and morbidity from these new pharmacological and instrumental therapies. In this perspective, the role of multidisciplinary Heart Team is mandatory for better define a correct decision-making process and tailoring the best pharmacological therapy in each patient and to program a continuum care in a post-acute phase of treatment. In addition, the possibility to plan multicentre registries of several complex cases evaluated by Heart Team could become a very important source of real world data to further refine indications and contraindications of different highly technological therapeutic approach, today based often on randomized clinical trials that do not represent faithfully the current clinical practice population.

The older patient with cardiovascular disease: background and clinical implications of the comprehensive geriatric assessment.

Principles and processes of comprehensive geriatric assessment (CGA) are increasingly being applied to subspecialties and subspecialty conditions, including cardiovascular patients (i.e., infective endocarditis; considerations of surgery or transcatheter aortic valve replacement, TAVR, for patients with aortic stenosis; vascular surgery) and postoperative mortality risk. In cardiovascular field CGA has mainly the aim to define ideal management according to the different typology of older adult patients (e.g., robust versus intermediate versus physical and cognitively disabled versus end-stage or dying), allowing physicians to select different therapeutic goals according to life expectancy; Aspect to be valued are by CGA are global health status and patient's decision-making capacity: CGA allows the individualized treatment definition and optimize the preprocedure condition.

Dementia Clinical Care in Relation to COVID-19.

PURPOSE OF REVIEW: This review discusses the complex relationship between COVID-19 and dementia and how the pandemic has affected the management of patients with dementia. This population resulted particularly susceptible to SARS-CoV-2 infection and its effects and also to the negative effects of the measures taken worldwide to control the spread of the virus. RECENT FINDINGS: Patients with dementia were at increased risk for COVID-19 compared to patients without dementia, and diagnosis of dementia represents an independent risk factor for hospitalization in COVID-19 patients. Mortality due to SARS-CoV2 infection in subjects with dementia is 2-5 times higher than in the general population. Cognitive impairment and delirium have been described in COVID-19 survivors. SARS-COV2 pandemic exacerbates the vulnerability of dementia patients and their caregivers, due to the morbidity and mortality from COVID-19, the indirect effects of the pandemic on the social supports, and the effects on healthcare system on which they depend. SUMMARY: The COVID-19 pandemic requires people with dementia to move from traditional models of health care to innovative models for home care, to support caregivers' burden, and to improve long term care.

Hypertension in the elderly: why one size does not fit all.

Over recent years, managing hypertension in older people has gained increasing attention, with reference to very old, frailer individuals. In these patients, hypertension treatment may be challenging due to a higher risk of hypotension-related adverse events which commonly overlaps with a higher cardiovascular risk. Additionally, frailer older adults rarely satisfy inclusion criteria of randomized clinical trials, which determines a substantial lack of scientific data. Although limited, available evidence suggests that the association between blood pressure and adverse outcomes significantly varies at advanced age according to frailty status. In particular, the negative prognostic impact of hypertension seems to attenuate or even revert in individuals with older biological age, e.g., patients with disability, cognitive impairment, and poor physical performance. Consequently, "one size does not fit all" and personalized treatment strategies are needed, customized to individuals' frailty and functional status. Similar to other cardiovascular diseases, hypertension management in older people should be characterized by a geriatric approach based on biological rather than chronological age and a geriatric comprehensive evaluation including frailty assessment is required to provide the most appropriate treatment, tailored to patients' prognosis and health care goals. The aim of this review was to illustrate the importance of a patient-centered geriatric approach to hypertension management in older people with the final purpose to promote a wider implementation of frailty assessment in routine practice.

Evidence and uncertainties in the management of atrial fibrillation in the elderly.

Atrial fibrillation (AF) is the most common cardiac sustained arrhythmia, whose incidence and prevalence increase with age, representing a significant burden for health services in western countries. Older people contribute to most patients affected from AF. Although oral anticoagulant therapy represents the cornerstone for the prevention of ischemic stroke and its disabling consequences, several other interventions - including left atrial appendage occlusion (LAAO), catheter ablation (CA) of AF, and rhythm control strategy (RCS) - have proved to be potentially effective in reducing the incidence of AF-associated clinical complications. Scientific literature focused on the three items will be discussed. Practical treatment of older AF patients is presented, including approach and management of patients with geriatric syndromes, selection of the most appropriate individualized drug treatment, clinical indications, and potential clinical benefit of LAAO and CA in selected older AF patients. Older people carry the greatest burden of AF in real world practice. Within a shared decision-making process, the patient centered approach needs to be put in the context of a comprehensive assessment, in order to gain maximal net clinical benefit and avoid futility or harm.

Severe aortic stenosis and transcatheter aortic valve replacement in elderly patients: utility vs. futility.

Recently, transcatheter aortic valve replacement (TAVR) has emerged as established standard treatment for symptomatic severe aortic stenosis, providing an effective, less-invasive alternative to open cardiac surgery for inoperable or high-risk older patients. In order to assess the anticipated benefit of aortic replacement, considerable interest now lies in better identifying factors likely to predict outcome. In the elderly population frailty and medical comorbidities have been shown to significantly predict mortality, functional recovery and quality of life after transcatheter aortic valve replacement. Scientific literature focused on the three items will be discussed. High likelihood of futility is described in patients with severe chronic lung, kidney, liver disease and/or frailty. The addition of frailty components to conventional risk prediction has been shown to result in improved discrimination for death and disability following the procedure and identifies those individuals least likely to derive benefit. Several dedicated risk score have been proposed to provide new insights into predicted "futile" outcome. However, assessment of frailty according to a limited number of variables is not sufficient, while a multi-dimensional geriatric assessment significantly improves risk prediction. A multidisciplinary heart team that includes geriatricians can allow the customization of therapeutic interventions in elderly patients to optimise care and avoid futility.

Predicting Mortality Risk in Older Hospitalized Persons With COVID-19: A Comparison of the COVID-19 Mortality Risk Score with Frailty and Disability.

OBJECTIVES: To assess the association of pre-morbid functional status [Barthel Index (BI)] and frailty [modified Frailty Index (mFI)] with in-hospital mortality and a risk scoring system developed for COVID-19 in patients ≥75 years diagnosed with COVID-19. DESIGN: Retrospective bicentric observational study. SETTING AND PARTICIPANTS: Data on consecutive patients aged ≥75 years admitted with COVID-19 at 2 Italian tertiary care centers were collected from February 22 to May 30, 2020. METHODS: Overall, 221 consecutive patients with COVID-19 aged ≥75 years were admitted to 2 hospitals in the study period and were included in the analysis. Clinical, functional (BI), frailty (mFI), laboratory, and imaging data were collected. Mortality risk on admission was assessed with the COVID-19 Mortality Risk Score (COVID-19 MRS), a dedicated score developed for hospital triage. RESULTS: Ninety-seven (43.9%) patients died. BI, frailty, age, dementia, respiratory rate, Pao2/Fio2 ratio, creatinine, and platelet count were associated with mortality. Analysis of the area under the receiver operating characteristic (AUC) indicated that the predictivity of age was modest and the combination of BI, mFI, and COVID-19 MRS yielded the highest prediction accuracy (AUCCOVID-19MRS+BI+mFI vs AUCAge: 0.87 vs 0.59; difference: +0.28, lower bound-upper bound: 0.17-0.34, P < .001). CONCLUSIONS AND IMPLICATIONS: Premorbid BI and mFI are associated with mortality and improved the accuracy of the COVID-19 MRS. Functional status may prove useful to guide clinical management of older individuals.

Effect of Corticosteroids on Mortality in Hospitalized COVID-19 Patients Not Receiving Invasive Mechanical Ventilation.

The most beneficial effect of corticosteroid therapy in COVID-19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single-center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID-19) patients who did not receive IMV (OSCI 3-5). Included were 1,311 COVID-19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. The median daily dose was of 8 mg of dexamethasone or equivalent, with a mean therapy duration of 5 (3-9) days. The indication to administer or withhold corticosteroids was given by the treating physician. In-hospital mortality was similar between the two cohorts after adjusting for possible confounders (adjusted odds ratio (ORadj) 1.04, 95% confidence interval (CI), 0.81-1.34, P = 0.74). There was also no difference in Intensive Care Unit (ICU) admission (ORadj 0.81, 95% CI, 0.56-1.17, P = 0.26). COVID-19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35-0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID-19 with OSCI 3-5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.

Delirium in Patients with SARS-CoV-2 Infection: A Multicenter Study.

OBJECTIVES: The aims of this study are to report the prevalence of delirium on admission to the unit in patients hospitalized with SARS-CoV-2 infection, to identify the factors associated with delirium, and to evaluate the association between delirium and in-hospital mortality. DESIGN: Multicenter observational cohort study. SETTINGS: Acute medical units in four Italian hospitals. PARTICIPANTS: A total of 516 patients (median age 78 years) admitted to the participating centers with SARS-CoV-2 infection from February 22 to May 17, 2020. MEASUREMENTS: Comprehensive medical assessment with detailed history, physical examinations, functional status, laboratory and imaging procedures. On admission, delirium was determined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition) criteria, 4AT, m-Richmond Agitation Sedation Scale, or clinical impression depending on the site. The primary outcomes were delirium rates and in-hospital mortality. RESULTS: Overall, 73 (14.1%, 95% confidence interval (CI) = 11.0-17.3%) patients presented delirium on admission. Factors significantly associated with delirium were dementia (odds ratio, OR = 4.66, 95% CI = 2.03-10.69), the number of chronic diseases (OR = 1.20, 95% CI = 1.03; 1.40), and chest X-ray or CT opacity (OR = 3.29, 95% CI = 1.12-9.64 and 3.35, 95% CI = 1.07-10.47, for multiple or bilateral opacities and single opacity vs no opacity, respectively). There were 148 (33.4%) in-hospital deaths in the no-delirium group and 43 (58.9%) in the delirium group (P-value assessed using the Gray test <.001). As assessed by a multivariable Cox model, patients with delirium on admission showed an almost twofold increased hazard ratio for in-hospital mortality with respect to patients without delirium (hazard ratio = 1.88, 95% CI = 1.25-2.83). CONCLUSION: Delirium is prevalent and associated with in-hospital mortality among older patients hospitalized with SARS-CoV-2 infection.

Delirium: Clinical Presentation and Outcomes in Older COVID-19 Patients.

The aim of the study is to describe the clinical characteristics and outcomes of a series of older patients consecutively admitted into a non-ICU ward due to SARS-CoV-2 infection (14, males 11), developing delirium. Hypokinetic delirium with lethargy and confusion was observed in 43% of cases (6/14 patients). A total of eight patients exhibited hyperkinetic delirium and 50% of these patients (4/8) died. The overall mortality rate was 71% (10/14 patients). Among the four survivors we observed two different clinical patterns: two patients exhibited dementia and no ARDS (acute respiratory distress syndrome), while the remaining two patients exhibited ARDS and no dementia. The observed different clinical patterns of delirium (hypokinetic delirium; hyperkinetic delirium with or without dementia; hyperkinetic delirium with or without ARDS) identified patients with different prognosis: we believe these observations may have an impact on the management of older subjects with delirium due to COVID-19.

Clinical risk score to predict in-hospital mortality in COVID-19 patients: a retrospective cohort study.

OBJECTIVES: Several physiological abnormalities that develop during COVID-19 are associated with increased mortality. In the present study, we aimed to develop a clinical risk score to predict the in-hospital mortality in COVID-19 patients, based on a set of variables available soon after the hospitalisation triage. SETTING: Retrospective cohort study of 516 patients consecutively admitted for COVID-19 to two Italian tertiary hospitals located in Northern and Central Italy were collected from 22 February 2020 (date of first admission) to 10 April 2020. PARTICIPANTS: Consecutive patients≥18 years admitted for COVID-19. MAIN OUTCOME MEASURES: Simple clinical and laboratory findings readily available after triage were compared by patients' survival status ('dead' vs 'alive'), with the objective of identifying baseline variables associated with mortality. These were used to build a COVID-19 in-hospital mortality risk score (COVID-19MRS). RESULTS: Mean age was 67±13 years (mean±SD), and 66.9% were male. Using Cox regression analysis, tertiles of increasing age (≥75, upper vs <62 years, lower: HR 7.92; p<0.001) and number of chronic diseases (≥4 vs 0-1: HR 2.09; p=0.007), respiratory rate (HR 1.04 per unit increase; p=0.001), PaO2/FiO2 (HR 0.995 per unit increase; p<0.001), serum creatinine (HR 1.34 per unit increase; p<0.001) and platelet count (HR 0.995 per unit increase; p=0.001) were predictors of mortality. All six predictors were used to build the COVID-19MRS (Area Under the Curve 0.90, 95% CI 0.87 to 0.93), which proved to be highly accurate in stratifying patients at low, intermediate and high risk of in-hospital death (p<0.001). CONCLUSIONS: The COVID-19MRS is a rapid, operator-independent and inexpensive clinical tool that objectively predicts mortality in patients with COVID-19. The score could be helpful from triage to guide earlier assignment of COVID-19 patients to the most appropriate level of care.

The impact of COVID-19 on health status of home-dwelling elderly patients with dementia in East Lombardy, Italy: results from COVIDEM network.

BACKGROUND: COVID-19 outbreak has led to severe health burden in the elderly. Age, morbidity and dementia have been associated with adverse outcome. AIMS: To evaluate the impact of COVID-19 on health status in home-dwelling patients. METHODS: 848 home-dwelling outpatients with dementia contacted from April 27 to 30 and evaluated by a semi-structured interview to evaluate possible health complication due to COVID-19 from February 21 to April 30. Age, sex, education, clinical characteristics (including diagnosis of dementia) and flu vaccination history were obtained from previous medical records. Items regarding change in health status and outcome since the onset of the outbreak were collected. COVID-19 was diagnosed in patients who developed symptoms according to WHO criteria or tested positive at nasal/throat swab if hospitalized. Unplanned hospitalization, institutionalization and mortality were recorded. RESULTS: Patients were 79.7 years old (SD 7.1) and 63.1% were females. Ninety-five (11.2%) patients developed COVID-19-like symptoms. Non COVID-19 and COVID-19 patients differed for frequency of diabetes (18.5% vs. 37.9%, p < 0.001), COPD (7.3% vs. 18.9%, p < 0.001), and previous flu vaccination (56.7% vs. 37.9%, p < 0.001). Diabetes and COPD were positively associated with COVID-19, whereas higher dementia severity and flu vaccination showed an inverse association. Among COVID-19 patients, 42 (44.2%) were hospitalized while 32 (33.7%) died. Non COVID-19 patients' hospitalization and mortality rate were 1.9% and 1.2%, respectively. COVID-19 and COPD were significantly associated with the rate of mortality. DISCUSSION/CONCLUSIONS: A high proportion of adverse outcome related to COVID-19 was observed in home-dwelling elderly patients with dementia. Active monitoring though telehealth programs would be useful particularly for those at highest risk of developing COVID-19 and its adverse outcomes.

Improving the care of older patients during the COVID-19 pandemic.

The SARS-CoV-2 pandemic has led to a dramatic crisis of Health Care Systems worldwide, and older people have been among the most disadvantaged. Specific recommendations and reports have been released both at International and National level, regarding the diagnosis and management of COVID-19 in the elderly. However, little has been proposed for an appropriate response to older, frail and multimorbid patients in different settings of care (acute care units, long term care facilities, nursing homes and primary care) and for the management of geriatric syndromes (i.e. delirium, sarcopenia, falls). We presume that the current pandemic of will leads to substantial changes in health care systems, and we suggest some key guide principles that could inspire the provision of healthcare services to older people and their families. These principles are primarily directed to physicians and nurses working in the geriatric field but could also be useful for other specialists.