Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up.

BACKGROUND: Pneumonia with severe respiratory failure represents the principal cause of death in COVID-19, where hyper-inflammation plays an important role in lung damage. An effective treatment aiming at reducing the inflammation without preventing virus clearance is thus urgently needed. Tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, has been proposed for treatment of patients with COVID-19. METHODS: A retrospective cohort study at the Montichiari Hospital, Brescia, Italy, was conducted. We included consecutive patients with COVID-19 related pneumonia at the early stage of respiratory failure, all treated with a standard protocol (hydroxychloroquine 400 mg daily, lopinavir 800 mg plus ritonavir 200 mg per day). We compared survival rate and clinical status in a cohort of patients who received additional treatment with tocilizumab once (either 400 mg intravenous or 324 mg subcutaneous) with a retrospective cohort of patients who did not receive tocilizumab (referred to as the standard treatment group). All outcomes were assessed at the end of the follow-up, that correspond to death or complete recovery and discharge from the hospital. FINDINGS: 158 patients were included, 90 of which received tocilizumab. 34 out of 68 (50%) patients in the standard treatment group and 7 out of 90 (7.7%) in the tocilizumab group died. Tocilizumab significantly improved survival compared to standard care (multivariate HR: 0.057; 95% C.I = 0.017- 0.187, p < 0.001). No differences between the two administration routes of tocilizumab were observed. No tocilizumab-related infections and/or side effects were observed. INTERPRETATION: Early treatment with tocilizumab could be helpful to prevent excessive hyper-inflammation and death in COVID-19 related pneumonia. Low dose administration of tocilizumab is not associated with adverse events. FUNDING: none.

Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia.

BACKGROUND: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality. METHODS: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. RESULTS: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. CONCLUSIONS: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

Vitamin D and health status in elderly.

Recently, vitamin D has aroused considerable interest for several reasons. Many epidemiological studies have shown a widespread deficiency of vitamin D at all ages, and the recent finding that many organs and tissues have vitamin D receptors has fostered the clinical and biological relevance of vitamin D. Elderly people are at high risk for vitamin D deficiency if their life style entails few outdoor activities, their skin is thick and they exhibit impairment of renal function. In the elderly, vitamin D deficiency is very important because it can affect the function of many organs such as the muscle-skeletal, cardio-vascular systems and kidney, and may be involved in various diseases and pathological conditions including type II diabetes, cancer and cognitive decline. In the present review, the most relevant features of vitamin D are described as well as the clinical consequences of hypovitaminosis D in the elderly. Finally, the role of an adequate oral supplementation in the geriatric population is stressed.

Total lymphocyte count and in-hospital mortality in older persons with multimorbidity.

BACKGROUND AND AIMS: Low total lymphocyte count (TLC) has been found to be a poor prognostic factor in adults affected by heart diseases, malignancy, and renal failure. The aims of this study were to verify if a low TLC was associated with in-hospital mortality in older persons and to evaluate whether this association was independent of the presence of multiple co-existing diseases (multimorbidity). METHODS: The authors carried out a cross-section analysis of data of 65+ years old patients (n=596) admitted to a Geriatric Unit in Northern Italy. TLC, total white blood cell count (WBC) and serum albumin were assayed the day after admission. The presence and severity of diseases were evaluated with the Geriatric Index of Comorbidity (GIC). Other covariates included age, gender, cigarette smoking, cognition (Mini-Mental State Examination) and function (Activities of Daily Living). Logistic regression models were created to study factors affecting in-hospital death. RESULTS: TLC was inversely correlated with both age and multimorbidity. Patients in the lowest tertile of TLC had the highest association with death during hospitalization (OR 6.1, 95% CI 1.1-33.6) independently of multimorbidity and all the other covariates. Stratifying the sample by degree of multimorbidity, this association was clearest in patients with the least severe multimorbidity (GIC

Rehabilitation and nursing home admission after hospitalization in acute geriatric patients.

OBJECTIVES: This study explored the effect of multimorbidity, cognitive and physical impairment, and sociodemographic factors on the choice of allocation of geriatric patients at hospital discharge. DESIGN: Cross-sectional study SETTING AND PARTICIPANTS: Eight hundred thirty patients 65 years or older admitted into an acute geriatric ward in Italy were evaluated (1998-2000). MEASUREMENTS: Social characteristics before hospitalization, multimorbidity, physical functioning, and cognitive status were related to allocation of living place after hospitalization (home, rehabilitation unit, or nursing home). RESULTS: Most patients were discharged to their homes (85%); 7% of the younger patients (65-74 years) and 11% of the very old (75+ years) were referred to a rehabilitation unit, while only among the very old 4% were discharged to a nursing home. Worse functional status, longer hospitalization, and being affected by dementia and cerebrovascular diseases (CVD) were associated with the admission to both rehabilitation and nursing home. Cognitive impairment and multimorbidity played a role in discharge destination, but only in functionally impaired patients. Living alone before hospitalization was correlated only with being discharged to a rehabilitation unit. CONCLUSION: In geriatric patients, both medical and sociodemographic characteristics are key factors for referral to rehabilitation or nursing home at discharge.

Predictors of successful rehabilitation in geriatric patients: subgroup analysis of patients with cognitive impairment.

BACKGROUND AND AIMS: Understanding which patients benefit from rehabilitation programs may be useful in balancing resources and needs. The aim of this study was to evaluate whether cognitive and nutritional status are associated with functional improvement after rehabilitation in old persons. METHODS: 2650 patients (aged > or =60 years) consecutively admitted to a geriatric rehabilitation unit in Italy between August 2001 and December 2005, were included. Functional status was evaluated with the Tinetti scale, cognitive status with the Mini-Mental State Examination (MMSE), and nutritional status with the Mini-Nutritional Assessment Short Form (MNA-SF). To identify predictors of functional recovery, multiple logistic regression models were run, with improvement on the Tinetti scale score as dependent variable. RESULTS: Eighty per cent of old persons functionally improved after rehabilitation, ranges being 84% of those with MMSE> or =24 to 58% of those with MMSE<10. Persons with both good cognition and good nutritional status were most likely to improve [odds ratio (OR)=2.5; 95% confidence interval (95% CI)=1.9-3.2]. Stratifying the sample according to cognitive status, we found that in patients with MMSE> or =18 better nutritional status emerged as a factor associated with functional improvement, whereas in patients with severe cognitive impairment (MMSE<18), the only associated factor was a higher MMSE score. CONCLUSIONS: The results of the present study suggest that both good cognition and good nutritional status are associated with functional improvement in older persons. However, patients with poor cognition can also improve, depending on their degree of cognitive impairment, and they should not be routinely excluded from rehabilitation.

Homocysteine and disability in hospitalized geriatric patients.

Elevated total homocysteine (tHcy) concentrations have been found to be associated with cardiovascular disease and dementia in old age. The present study was performed to identify the prevalence of hyperhomocysteinemia (HHcy) and to analyze the association between tHcy concentration and sociodemographic characteristics, nutritional parameters, and cognitive and functional status in this sample of hospitalized geriatric patients. A total of 214 patients (77% females) 65+ years old admitted into an acute care geriatric ward of an internal medical department in the Northern Italy were studied. tHcy concentration was measured using a high-performance liquid chromatography with fluorescence detection (HPLC-F). Information about nutrition (body mass index [BMI], serum albumin, cholesterol, and transferrin) was collected on admission. Functional status was investigated with the Basic Activities of Daily Living scale (ADL) and the Instrumental Activities of Daily Living scale (IADL); cognitive and affective status were assessed by the Mini-Mental State Evaluation (MMSE) and the Geriatric Depression Scale (GDS). The mean tHcy concentration was 18.4 +/- 13.1 micromol/L; 74.2% of males and 68.9% of females had HHcy (> 12 micromol/L). Sixty-four percent of patients with normal serum vitamin B12 and folate concentrations had HHcy. Elevated tHcy concentrations were associated with older age, male gender, increasing serum creatinine, lower MMSE score, and disability. The mean tHcy concentration depended on the occurrence of different diseases. Patients affected by atherosclerotic diseases, such as ischemic heart diseases, cerebrovascular diseases, and dementia had higher mean tHcy concentration than those without diagnosed vascular diseases. In multivariate analysis, vitamin B12, folate, serum albumin, creatinine, and disability emerged as factors associated with tHcy, adjusted for age, gender, education, MMSE score, and atherosclerotic diseases. Our results suggest that the prevalence of HHcy in hospitalized patients is very high, even in subjects with normal cobalamin and folate concentrations. High Hcy concentration can be associated with functional impairment.

Poor mental and physical health differentially contributes to disability in hospitalized geriatric patients of different ages.

OBJECTIVE: To evaluate the relationship between depressive symptoms, cognition and somatic diseases on functional status of geriatric patients at hospital discharge. METHOD: Patients 65+ years consecutively admitted to the acute care geriatric ward of the Internal Medicine Department I, Civil Hospital of Brescia, Italy, from February 1998 to December 2000 (n = 830) were examined. Functional disability was defined as need of physical assistance in at least one of the basic Activities of Daily Living (ADL). The Greenfield Index of Disease Severity (IDS) and the Geriatric Index of Comorbidity (GIC) were used to measure number and severity of diseases. The Mini-Mental State Examination (MMSE) assessed cognitive status and the Geriatric Depression Scale (GDS) measured depressive symptoms. RESULTS: Prevalence of functional disability at discharge was 29.3% in the younger age group (65-74 years) and 55.2% in the older age group (75+ years). Using logistic regression models, older age, poorer cognitive status, and depressive symptoms were independently associated with functional disability in the younger and older age group, respectively. Additionally cognitive impairment and depressive symptoms showed an additive association with disability, especially in younger patients, while comorbidity was correlated with functional status only in the oldest old, in particular among those who were cognitively impaired. CONCLUSION: Functional disability after acute hospitalization is highly prevalent in geriatric patients. Depressive symptoms, comorbidity, and cognitive impairment often coexist, interact and are differentially associated with function depending on age. Considering that depressive symptoms are a modifiable problem, their detection in hospital settings may help clinicians in targeting subjects at high risk of functional disability.

Adverse outcomes in older hospitalized patients: the role of multidimensional geriatric assessment.

BACKGROUND AND AIMS: This study was carried out to detect the incidence of adverse outcomes in hospitalized older patients and the role of multidimensional assessment in identifying predictors of adverse outcomes, which include in-hospital mortality and the need for admission to rehabilitation units or nursing homes after hospital discharge. METHODS: 923 patients at least 65 years old (mean age 78.7 +/- 7.2, 49% women) admitted to the acute care geriatric ward of an internal medicine department were included in the study. On admission, each patient underwent a comprehensive medical, functional, neuropsychological, sociodemographic and nutritional assessment. RESULTS: Incidence of mortality and other adverse outcomes was 6 and 16%, respectively. In-hospital mortality was independently predicted by older age (OR per year: 1.07, 95% CI: 1.02-1.12), male gender (OR: 3.97, 1.99-7.95), higher comorbidity (OR: 2.09, 1.01-4.33), higher heart rate (OR: 2.87, 1.30-6.35), lower systolic blood pressure (OR: 2.22, 1.03-4.81), lower serum albumin values (OR: 3.20, 1.63-6.29) and a lower MMSE score at hospital admission (OR: 5.51, 2.34-12.9). Adverse outcomes were independently predicted by older age (OR per year: 1.03, 1.01-1.06), higher comorbidity (OR: 2.00, 1.35-2.94), lower serum albumin values (OR: 2.57, 1.69-3.90) and a lower admission MMSE score (OR: 2.49, 1.68-3.71). CONCLUSIONS: A multidimensional geriatric assessment should be comprised of simple parameters available early, like serum albumin and MMSE score, that are predictive of adverse outcomes in older hospitalized patients, along with other health Indicators (comorbidity, heart rate and blood pressure).

[Chronic obstructive lung disease. Systemic manifestations]. / Broncopneumopatia cronica ostruttiva. Le manifestazioni sistemiche.

Chronic obstructive lung diseases (COPD) are a complex disease state which not rarely can be associated with significant systemic manifestations. These alterations, though recognized since long time, are currently under extensive research, due to the increasing appreciation of their relevant negative role in the prognosis and health-related quality of life (Hr-QoL) of the COPD patients. The most clinically important are the decrease in body weight with loss of skeletal muscle mass (cachexia), osteoporosis, hypercapnia-induced peripheral edema, neuro-psychiatric disorders, such as oxygen-related cognitive impairment and depression, excessive polycytaemia and sleep disorders. Chronic systemic inflammation, oxidative stress and chronic hypoxia are believed as the main factors involved in the pathogenesis of systemic effects seen in COPD. Their adequate control with nutritional support, change of life-style and targeted pharmacological treatment is able to improve the prognosis and Hr-QoL among these COPD patients.

[Oxygen therapy. The new objectives: from survival to quality of life in correlation with state of health]. / Ossigenoterapia: i nuovi obiettivi. Dalla sopravvivenza alla qualità di vita correlata allo stato di salute.

The aim of this review is to give new insights on the effects, and consequently, on the prescription criteria of long-term oxygen therapy in chronic obstructive pulmonary disease (COPD), on the basis of the evidence accumulated in the recent past. Since the demonstration of the beneficial effect on survival offered by long-term oxygen therapy in severely hypoxemic COPD patients, further potential endpoints of this treatment in such subjects have been progressively evaluated. At present, knowledge of the favorable biochemical effects, especially on the skeletal muscles and brain tissue, and the widespread appreciation of the positive impact on the health-related quality of life parameters provided by long-term oxygen therapy in COPD patients should prompt us to reassess its indications in these subjects.

[Chronic obstructive pulmonary disease: brief review]. / Broncopneumopatia cronica ostruttiva: una breve rassegna.

The aim of this short review is to draw attention to chronic obstructive pulmonary disease (COPD), a clinical syndrome associated with emphysema and/or chronic bronchitis, in the light of the current scientific knowledge. The reason is that COPD has high socio-economic costs and the most recent projections place it among the first causes of mortality and morbidity due to chronic disease. The nosography, the clinical picture, including the systemic manifestations, the pathogenesis and the pathophysiological mechanisms, with special emphasis on expiratory flow limitation and pulmonary hyperinflation, leading to the most relevant symptoms and signs of the disease, have been reviewed. Finally a brief analysis of the costs due to the disease is also provided.