Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

Clinical Presentation of COVID19 in Dementia Patients.

OBJECTIVE: No studies analyzing the role of dementia as a risk factor for mortality in patients affected by COVID-19. We assessed the prevalence, clinical presentation and outcomes of dementia among subjects hospitalized for COVID19 infection. DESIGN: Retrospective study. SETTING: COVID wards in Acute Hospital in Brescia province, Northern Italy. PARTICIPANTS: We used data from 627 subjects admitted to Acute Medical wards with COVID 19 pneumonia. MEASUREMENTS: Clinical records of each patients admitted to the hospital with a diagnosis of COVID19 infection were retrospectively analyzed. Diagnosis of dementia, modalities of onset of the COVID-19 infection, symptoms of presentation at the hospital and outcomes were recorded. RESULTS: Dementia was diagnosed in 82 patients (13.1%). The mortality rate was 62.2% (51/82) among patients affected by dementia compared to 26.2% (143/545) in subjects without dementia (p<0.001, Chi-Squared test). In a logistic regression model age, and the diagnosis of dementia resulted independently associated with a higher mortality, and patients diagnosed with dementia presented an OR of 1.84 (95% CI: 1.09-3.13, p<0.05). Among patients diagnosed with dementia the most frequent symptoms of onset were delirium, especially in the hypoactive form, and worsening of the functional status. CONCLUSION: The diagnosis of dementia, especially in the most advanced stages, represents an important risk factor for mortality in COVID-19 patients. The clinical presentation of COVID-19 in subjects with dementia is atypical, reducing early recognition of symptoms and hospitalization.

Diabetes as a risk factor for cognitive decline in older patients.

AIMS: To assess the role of type 2 diabetes as a risk factor for cognitive decline among elderly people. METHODS: Analyses were carried out on data from the Italian Longitudinal Study on Aging, a study on 5,632 subjects aged 65-84 years, with baseline in 1992 and follow-ups in 1996 and 2000. RESULTS: At baseline, diabetic women had significantly worse scores on all cognitive tests compared to nondiabetic women, but did not show worsening over time, whereas men with diabetes did not show worse scores on cognitive tests at baseline compared to nondiabetic males; however, diabetes in men was associated with a risk of cognitive decline over time, particularly in attention. Higher levels of HbA(1c) were associated with poorer performance on memory tests at follow-up in both sexes. CONCLUSION: The impact of diabetes on cognitive status might differ in older men and women, probably because of a survival effect, with a higher mortality at a younger age among diabetic men. The metabolic and cardiovascular abnormalities associated with diabetes might be responsible for the cognitive decline, at different rates and ages, in men and women. The routine assessment of diabetes complications in the elderly should include cognitive evaluation in both sexes.

Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.

BACKGROUND: Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific "confusion" regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. OBJECTIVE: We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. METHODS: The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. RESULTS: In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma, delirium, delirio, delirium tremens, délire, confusion mentale, delir, delier, Durchgangs-Syndrom, acute verwardheid, intensiv-psykose, IVA-psykos, IVA-syndrom, akutt konfusion/forvirring. Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. CONCLUSIONS: Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers.

Physical Performance Test and Activities of Daily Living scales in the assessment of health status in elderly people.

OBJECTIVE: To compare the ability of Basic Activities of Daily Living (BADL), Instrumental Activities of Daily Living (IADL), and the Physical Performance Test (PPT) to detect health status impairments. PATIENTS: Five hundred forty nine community-dwelling elders (89.8% of the eligible elderly population) aged 70 and over; mean age [was] 76.8 +/- 6.1; 179 were males and 370 females. SETTING: City of Ospitaletto, Brescia, Northern Italy. MEASUREMENTS: A multidimensional questionnaire assessing demographic variables, indicators of social activities, psychological function, and somatic health and functional status (BADL and IADL). Also, the PPT was administered. RESULTS: Cognitive and effective status were independently associated with BADL, IADL function, and age; number of drugs were also associated with IADL function. Other health variables (number of diseases, number of symptoms, and global health score) did not independently contribute to explaining the BADL and IADL variance. Cognitive status, number of symptoms, number of diseases, number of drugs, and global health were independently associated with PPT. CONCLUSIONS: Chronic diseases may affect functional status in a manner that is insensitive to traditional self-report ADL and IADL measures. Performance-based measures may capture this impairment before more severe functional loss emerges.

Nutritional intake, socioeconomic conditions, and health status in a large elderly population.

The nutritional intake of a large population of noninstitutionalized older people living in an urban area was studied in relation to socioeconomic conditions (living environment, income, and education) and health status (affective, functional, and physical health) to identify the subgroups at risk for malnutrition. Twenty-four-hour dietary recall was used to determine the percentage of older subjects with dietary intake of specific nutrients below two thirds of the 1980 Recommended Dietary Allowances. Ninety percent of the older people examined showed inadequate intake of thiamine and vitamin B6, and 30% to 40% demonstrated deficiencies of vitamin A, vitamin C, niacin, vitamin B12, calcium, and iron; only 10% of subjects had inadequate intake of protein. Poor nutritional intake was correlated more strongly with socioeconomic conditions, functional level, and affective status than with physical health status.

Good nutritional oral intake is associated with equal survival in demented and nondemented very old patients.

OBJECTIVE: To evaluate the association of oral food intake with survival in very old demented nursing home patients. DESIGN: A prospective cohort study. SETTING: A nursing home in northern Italy. MEASUREMENTS: Anthropometric and laboratory nutritional indicators and nutrient intake were assessed in 33 demented (age 85.7 +/- 5.7 years) and 25 nondemented (age 84.9 +/- 5.7 years) patients. Mortality data were collected over a 28-month follow-up period. Association of survival with dementia was estimated by Kaplan-Meyer analysis and multivariate Cox proportional hazard models. RESULTS: Nutrient intake and nutritional status were good compared with data in the literature and were similar in demented and nondemented patients, except for smaller triceps skinfold thickness in the demented. The cumulative annual death rate was 0.23 deaths per subject per year, similar in the demented (0.23) and the nondemented (0.22). Unadjusted survival by Kaplan-Meyer analysis was similar in the two groups, and correction for-age, gender, cognition, triceps skinfold thickness, and number of drugs in a Cox model did not alter the relationship. CONCLUSIONS: Dementia developing in very old age is not necessarily associated with malnutrition and decreased life expectancy.

A nutritional index predicting mortality in the nursing home.

OBJECTIVE: To define a sensitive and specific index, based on nutritional indicators, predicting mortality in nursing home patients. DESIGN: A prospective cohort study. SETTING: A nursing home. MEASUREMENTS: Anthropometric and laboratory nutritional indicators were assessed in 104 nursing home elderly residents (20 males, 84 females). Patients were aged 60 years and older and had relatively good somatic health and nutritional status. Mortality data were collected over an 18-month follow-up period. Discriminant analysis was used to compute an adimensional measure (index) that could predict mortality with the highest sensitivity and specificity. RESULTS: Mortality was 0.20/year. A nonlinear, "U-shaped" relationship of cholesterol levels with mortality was found. A prognostic index based on cholesterol, lymphocyte count, mid-arm circumference, hemoglobin, age, and gender was obtained. Higher values of this index were associated with progressively higher risks at 12 months and 18 months. Sensitivity and specificity calculated on 18-month mortality were 80% and 78.4%, respectively. CONCLUSIONS: This index, based on simple measures, can be a useful tool in the evaluation of health status of the elderly living in nursing homes.

The management of adverse clinical events in nursing homes: a 1-year survey study.

OBJECTIVE: In Italian nursing homes (NHs), care delivery at night and during holidays is not regulated by regional laws; some facilities employ staff physicians, others employ physicians engaged from year to year (temporary physicians), and others employ publicly funded National Health System (NHS) physicians. This study was designed to determine whether the use of different kinds of physicians leads to different outcomes with regard to the rate of hospitalization and appropriateness of the management of adverse clinical events. DESIGN: Prospective, nonrandomized-survey data collection. SETTING: Ten nonprofit nursing facilities in Italy. PARTICIPANTS: Three hundred and fifty-two NH residents, staff physicians, temporary physicians, and NHS physicians. MEASUREMENTS: Medical intervention during adverse clinical events occurring at night and during holidays. RESULTS: Three hundred and fifty-two residents experienced 551 adverse clinical events; 78 were hospitalized. The hospitalization rate of NHS physicians was about two times that of the temporary physicians and six times that of the staff physicians. Staff physicians' diagnoses and management were appropriate in the majority of cases; NHS diagnosis and management were doubtful or incorrect in about one-third of all cases. CONCLUSIONS: NH residents frequently experience adverse clinical events; physician characteristics influence the rate of hospitalization and the quality of medical interventions.

Protective effect of chronic NSAID use on cognitive decline in older persons.

OBJECTIVE: To verify whether chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect against cognitive decline in older persons. DESIGN: Prospective study with a 3-year observation period. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). SUBJECTS: A population-based sample of 7671 subjects who received an in-person interview at the sixth annual follow-up. Persons with documented NSAID use at the time of the interview and 3 years before were considered chronic users (21%), while all other persons were considered as nonusers. MAIN OUTCOME MEASURE: Change over time in cognitive function assessed as the number of correct answers to a 9-item version of the Short Portable Mental Status Questionnaire (SPMSQ). RESULTS: For every level of SPMSQ score measured at the beginning of the observation period, the mean SPMSQ score after 3 years was higher in chronic NSAID users than in nonusers. Cognitive function at the end of the observation period was significantly higher in chronic NSAID users than in controls, adjusting for initial SPMSQ score and potential confounders. Older age, female gender, education, and history of cerebrovascular disease were also independent predictors of lower SPMSQ score. In the multivariate analysis, the magnitude of the protective effect estimated for NSAID use was comparable to a difference in age of 3.5 years. The percentage of persons who started above a specific SPMSQ score cut-point and deteriorated below that cut-point over a 3-year period was significantly lower in chronic NSAID users than in nonusers (30.2% vs 34.3%, P = .03, for decline below SPMSQ score of 8 and 12.3% vs 14.4% for decline below SPMSQ score of 6, P = .04). After controlling for potential confounders, the relative risk of cognitive declining in chronic NSAID users compared with nonusers was 0.82 (95% Confidence Interval: 0.69-0.98) for a decline below a score of 8, and 0.80 (95% CI: 0.66-0.98) for a decline below a score of 6. CONCLUSIONS: These results support the association between NSAID use and reduction in cognitive decline in older persons. Ultimately, randomized controlled trials must be done to prove a beneficial effect definitively.

Atrial fibrillation and cognitive disorders in older people.

OBJECTIVES: To find a correlation between chronic nonrheumatic atrial fibrillation (CNRAF) and cognitive impairment in a group of older, nondemented patients. SETTING: Acute Care Unit for the Elderly, Poliambulanza Hospital, Brescia (Italy). METHODS: Two hundred fifty-five hospital in-patients older than 70 years (42 with CNRAF and 213 controls with normal sinus rhythm) were assessed by complete clinical history, physical examination, ECG, serum albumin levels, APACHE II score, mental status (Mini-Mental State Exam [MMSE] and Geriatric Depression Score [GDS]), functional status (Barthel Index and instrumental activities of daily living [IADL]), number of prescribed drugs, and comorbidity (Charlson Index). RESULTS: The group of patients with CNRAF had MMSE scores significantly lower than that of the reference group with normal sinus rhythm. Chronic nonrheumatic atrial fibrillation retained an independent relation to cognitive impairment also after adjusting for those variables associated with mental decline in univariate models (GDS, IADL, and APACHE II scores). CONCLUSIONS: The results of this study support the relationship between nonrheumatic atrial fibrillation and impaired cognitive function. Independent of etiopathogenetic mechanisms (thromboembolic or hemodynamic hypotheses), prevention of cognitive impairment in older persons should take into account the treatment of atrial fibrillation and its consequences.

Sensory impairment and quality of life in a community elderly population.

OBJECTIVE: To determine the association between quality of life measures and sensory impairment in aged individuals living at home. DESIGN: Survey SETTING: A community survey, carried out in the historical center of a town in Northern Italy. PATIENTS: 1191 non-institutionalized elders (age 70-75 years). MEASUREMENTS: Comprehensive QOL questionnaire, free-field voice testing, and Snellen eye chart. RESULTS: Single sensory impairments (either visual or auditory) were significantly and independently associated with increased risk for depression (odds ratio: 2.3, 95% confidence interval: 1.5-3.4; OR:1.8, CI:1.1-2.7, respectively) and decreased self-sufficiency in daily living activities (OR:1.7, CI:1.1-2.6; OR:2.1, CI:1.4-3.2, respectively). Visual dysfunction, but not hearing dysfunction, was independently associated with lower social relationships (OR:2.0, CI:1.3-3.1). CONCLUSION: The quality of life of community-dwelling elderly people is significantly linked to sensory impairment, which can be detected through simple physical examination. Mood level and social relationships are particularly affected by visual impairment, whereas self-sufficiency in daily living is more strongly related to hearing impairment.

Food intake and mortality in the frail elderly.

BACKGROUND: Adequate qualitative and quantitative food intake is a major determinant of health. However, nutritional requirements in the elderly are unknown, and even more so in the frail elderly. The aim of the study was to evaluate the influence of energy and macro-nutrients on health in the frail nursing home elderly. METHODS: Food intake of 72 not severely diseased elderly patients was assessed with direct weighing method. Outcome measure was survival over 28-month follow-up period. Confounders of the association of food intake with survival were: age, gender, body-mass index, daily function, somatic health, anergy, and nutritional status. Crude association of food intake with survival was assessed with Kaplan-Meyer method, and adjusted association with multiple Cox regression models. RESULTS: Patients of the study had good average food intake. Mortality rate was relatively low (.20 per year). Low levels of energy, protein, lipid, and carbohydrate intake were negatively associated with survival even after adjustment for confounders. When compared to high intake, adjusted relative risks for mortality of low intake were 4.74, 3.75, 4.71, and 2.04, respectively. Medium levels of energy, protein, and lipid, but not carbohydrate, intake yielded intermediate mortality risk. CONCLUSIONS: Food intake is a strong predictor of survival even in moderately diseased elderly patients, suggesting possible low-cost interventions.

Effects of acetyl-L-carnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors.

Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.

Co-occurrence of disadvantage conditions in elderly subjects with depressive symptoms.

The aim of this survey study is to describe the association of symptomatic depression with the co-occurrence of psycho-social, functional, and somatic disadvantage conditions in 390 over 70 subjects living at home. The most disadvantaged tertile of various conditions (age, social support, cognition, social interactions, self evaluation of health, disability, number of diseases, and somatic symptoms) was associated with greater risk of symptomatic depression. A subset of conditions that might be causally related to depression (age, social support, financial welfare, diseases, and disability) was used to divide subjects into five levels of increasing multiple disadvantage conditions (MDC). Increasing severity of MDC level was associated with greater risk of symptomatic depression even after adjustment for gender and all five conditions used to define MDC levels (odds ratios ranging from 2.7 to 11.3).

Correlation between beta-endorphin/beta-lipotropin-immunoreactivity and cortisol plasma concentrations.

Plasma Cortisol and Beta-Endorphin/Beta-Lipotropin-immunoreactivity concentrations were measured in 51 healthy aged subjects. A direct correlation was found between the plasma concentrations of the two hormones. The data suggest that beta-endorphin/beta-lipotropin is not only released during stress but also in resting conditions.

Venlafaxine-induced reset osmostat syndrome: case of a 79-year-old depressed woman.

The presence of hyponatremia, especially in a frail and very old patient, is associated with a greater morbidity and mortality rate. We report the case of a depressed 79-year-old woman who was treated with venlafaxine, in whom a drug-induced hyponatremia occurred in the absence of other possible causes. The case is discussed in the context of the multipotential factors that induce hyponatremia, with particular attention to the geriatric patient.

Assessment of alcohol consumption and alcoholism in the elderly.

This study evaluates characteristics associated with alcohol consumption or alcohol-related problems in an elderly population, as detected by CAGE questionnaire and self-reported alcohol intake respectively. Data were obtained from a multidimensional study carried out in a community-dwelling population aged 70-75 (n = 1205, 389 males and 816 females) living in the city center of Brescia, in northern Italy. All information was gathered by self-report. Male gender, better mood, daily function, somatic health, not living alone, and being married were significantly associated with self-reported alcohol consumption. Male gender, poorer cognitive function, and income dissatisfaction were significantly associated with alcohol problems as detected by CAGE. Data suggest that self-report of alcohol intake, though intrinsically loaded with imperfect internal consistency, does not necessarily indicate risk of alcoholism; on the contrary, it can reveal the positive psychological attitude of the drinking habit. CAGE questionnaire, which is sensitive to alcohol related problems, is associated with poor psychosocial conditions.

Italian community norms for the Brief Symptom Inventory in the elderly.

Italian community norms for the Brief Symptom Inventory (BSI) in the elderly are presented on 462 subjects. Means do not substantially differ from previously published US norms for the elderly. Higher scores were found in women and in subjects with social or distressing somatic conditions.

Primary carcinoid tumor of the ovary: report of an unusual case.

Carcinoid tumors are endocrine malignancies that are often associated with a characteristic syndrome, the malignant carcinoid syndrome, which is most common in patients with small bowel tumors and liver metastases. In the rare instances when the syndrome is present without liver metastases the primary tumor is usually localized to the bronchus or ovary and secretes hormones directly into the systemic circulation. About two thirds of patients with carcinoid syndrome have evidence of carcinoid heart disease. We report on a case of a primary ovarian carcinoid tumor with an unusual clinical presentation.