Clinical presentation and prognosis of COVID-19 in older adults with hypothyroidism: data from the GeroCovid observational study.

BACKGROUND: The prevalence of hypothyroidism among older patients hospitalized for COVID-19 and its association with mortality is unclear. This study aims to investigate the prevalence of hypothyroidism in older COVID-19 inpatients and verify if this comorbidity is associated with a specific pattern of onset symptoms and a worse prognosis. METHODS: COVID-19 inpatients aged ≥ 60 years, participating in the GeroCovid acute wards cohort, were included. The history of hypothyroidism was derived from medical records and the use of thyroid hormones. Sociodemographic data, comorbidities, symptoms/signs at the disease onset and inflammatory markers at ward admission were compared between people with vs without history of hypothyroidism. The association between hypothyroidism and in-hospital mortality was tested through Cox regression. RESULTS: Of the 1245 patients included, 8.5% had a history of hypothyroidism. These patients were more likely to present arterial hypertension and obesity compared with those without an history of hypothyroidism. Concerning COVID-19 clinical presentation, patients with hypothyroidism had less frequently low oxygen saturation and anorexia but reported muscle pain and loss of smell more commonly than those without hypothyroidism. Among the inflammatory markers, patients with hypothyroidism had higher lymphocytes values. At Cox regression, hypothyroidism was associated with reduced in-hospital mortality only in the univariable model (HR = 0.66, 95% CI 0.45-0.96, p = 0.03); conversely, no significant result were observed after adjusting for potential confounders (HR = 0.69, 95% CI 0.47-1.03, p = 0.07). CONCLUSIONS: Hypothyroidism does not seem to substantially influence the prognosis of COVID-19 in older people, although it may be associated with peculiar clinical and biochemical features at the disease onset.

Association between reduced pulmonary diffusing capacity and cardiac autonomic dysfunction in Type 1 diabetes.

BACKGROUND: In Type 1 diabetes mellitus (DM), it has been suggested that autonomic nervous system dysfunction (NAD) impairs lung diffusion capacity. Heart rate variability (HRV), a measure of cardiac autonomic function, is a sensitive method of detecting NAD. To our knowledge, no previous study has assessed whether cardiac sympatho-vagal balance is associated with lung diffusion capacity in diabetes. METHODS: Twenty Type 1 DM patients without pulmonary abnormalities and systemic NAD underwent measurement of lung diffusion capacity for carbon monoxide (DLCO) by single-breath method and assessment of cardiac autonomic function by HRV analysis on 24-h electrocardiographic Holter recordings. RESULTS: Standard respiratory function tests and peripheral autonomic tests were normal in all patients. DLCO was lower than normal reference values in six patients (30%). DLCO correlated significantly with most HRV variables, independent of the clinical and laboratory variables. The strongest correlation was found with standard deviation of all RR intervals (SDNN; r = 0.62, P = 0.003) in the time domain and low frequency (LF) power (r = 0.73, P < 0.001) in the frequency domain. CONCLUSIONS: In Type 1 diabetes, a significant association exists between cardiac NAD and reduced DLCO in the absence of clinical respiratory and autonomic abnormalities. Thus, NAD may be involved in the early reduction of DLCO in these patients, possibly through abnormalities in the regulation of pulmonary blood flow at the microvascular level.

Use of ACE-inhibitors and Quality of Life in an Older Population.

BACKGROUND: Improved ability to treat chronic diseases have increased the interest in measuring health-related quality of life (HRQoL) in older adults. Hypertension and heart failure have been associated with decreased HRQoL. HYPOTHESIS: The aim of this study was to assess the association between health-related quality of life and use of angiotensin converting enzyme inhibitors in unselected community-dwelling elderly. METHODS: We analyzed data of all 387 subjects aged 75+ living in a rural Italian town, without exclusion criteria. HRQoL was assessed using the Health Utility Index Mark 3, which allows formal cost-effectiveness calculations. The association of the HRQoL score with use of ACE-I was analyzed by multivariable linear and logistic regression. RESULTS: The median HUI3 score was 0.31, and 186 participants (48%) reported a score above the median value. Use of ACE-I was reported by 34 (9%) participants, and confirmed by general practitioners. Use of these agents was associated with significantly better HRQoL (B=.16, 95% CI=.02 - .30; P=.025). Also, use of ACE-I was associated with increased probability of better HRQoL in logistic regression (OR=2.83; 95% CI=1.03 - 7.78; P=.044) after adjusting. No associations were found between the HRQoL score and use of calcium antagonists or beta-blockers. CONCLUSIONS: Use of ACE-I, but not of other antihypertensives, is associated with better HRQoL among community-dwelling older adults. ACE-inhibitors might therefore present with the best cost-effectiveness ratio for the treatment of older populations.

Energy intake and in-hospital starvation. A clinically relevant relationship.

BACKGROUND: Malnutrition is a common finding in the acute-care hospital. OBJECTIVES: To assess the adequacy of nutritional intake to individual needs and the effects of the hospitalization on nutritional status and to identify the reasons for inadequate energy intake. METHODS: A total of 286 patients with a mean ( +/- SD) age of 79 +/- 6 years (range, 70 to 99 years), consecutively admitted to the geriatrics and internal medicine wards of an acute-care university hospital, underwent multidisciplinary assessment on admission and at discharge and daily dietary data collection. The needed, prescribed, and actual daily energy intake for each individual was measured. Nutritional depletion was diagnosed if midarm circumference decreased by 3.6% or more from admission to discharge. RESULTS: Nutritional depletion occurred in 27% of the patients and correlated with anorexia (86.4% vs 65.5% and 40% in patients whose midarm circumference was unchanged and increased, respectively; P < .001), Mini-Mental State Examination score (21.6 +/- 8.3 vs 23 +/- 6.9 and 26.5 +/- 3.6; P < .05), simplified premorbid Activities of Daily Living score (4.4 +/- 2.2 vs 5.1 +/- 1.8 and 5.0 +/- 1.8; P < .03), lymphocyte count (1.32 +/- 0.63 x 10(9)/L vs 1.62 +/- 0.88 x 10(9)/L and 1.47 +/- 0.50 x 10(9)/L; P < .03), serum albumin level (38 +/- 5g/L vs 40 +/- 4 g/L and 39 +/- 8 g/L; P < .002), ratio of actual to needed energy intake (56.9% +/- 22.1% vs 69.3% +/- 30.4% and 60.0% +/- 14.1%; P < .01), ratio of actual to prescribed energy intake (50.5% +/- 16.9% vs 60.5% +/- 20.%% and 65.5% +/- 15.7%; P < .001). Patients who consumed less than 40% of the prescribed food complained of anorexia and masticatory inefficiency and were unsatisfied with quality and timing of meals compared with other patients. CONCLUSIONS: In-hospital starvation affects mainly patients with baseline nutritional, functional, and cognitive deficits and is strongly related to the inadequate energy intake.

Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease.

PURPOSE: To identify factors affecting the short-term prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the kappa coefficient and Spearman's rho for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. RESULTS: The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR] 1.07; 95% confidence interval [CI] 1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). CONCLUSIONS: Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model.

Verbal memory impairment in COPD: its mechanisms and clinical relevance.

STUDY OBJECTIVES: Identification of mechanisms accounting for verbal memory impairment in patients with severe COPD; assessing the relationship between verbal memory and the overall cognitive performance; verifying if verbal memory impairment affects medication adherence. DESIGN: Case-comparison study. SETTING: Outpatient Departments of Pneumology and Neurology, Day Hospital of General Surgery. PATIENTS: Forty-two COPD ambulatory patients, age 70+/-9.7 years, with hypoxemia and hypercarbia (group A); 27 normal subjects of comparable age and educational level (group B); 31 patients with Alzheimer's disease (group C); and 26 older normal subjects (group D). MEASUREMENTS AND RESULTS: The overall cognitive function and verbal memory were evaluated by the Mental Deterioration Battery and 14 indexes of verbal memory. Defective retrieval and recognition mechanisms distinguished group A from group B. According to discriminant analysis, verbal memory profile of COPD patients was group specific in 38.1% of cases and conformed to that of group B, C, and D in 19%, 16.7%, and 26.2% of cases, respectively. In COPD patients, both immediate and delayed recall, the strongest determinants of the discriminant function, were significantly correlated with the overall cognitive performance (rho=0.64, p=0.001; rho=0.61, p=0.001, respectively). Poor adherence to medication regimen was significantly associated with abnormal delayed recall score (82.3% vs 36% in subjects with normal delayed recall, p<0.008). CONCLUSIONS: Decline of verbal memory parallels that of the overall cognitive function in COPD patients and is due to the impairment of both active recall and passive recognition of learned material. It could be an important determinant of the level of medication adherence.

Acute oxygen supplementation does not relieve the impairment of respiratory muscle strength in hypoxemic COPD.

STUDY OBJECTIVES: To verify whether hypoxemia affects respiratory muscle strength in the absence of malnutrition and whether such effect, if present, is reversible with an acute oxygen supplementation. DESIGN: Case series analysis, before-after trial. SETTING: Outpatient pneumology departments of two university hospitals. PATIENTS: One hundred twenty patients affected by COPD in stable conditions having actual to ideal body weight ratio of > or =90%. MEASUREMENTS AND RESULTS: Maximal inspiratory pressure (MIP) was measured at functional residual capacity level in the whole sample of subjects and during oxygen supplementation in 58 patients having a PaO2< or =60 mm Hg when breathing in room air. Predictors of MIP were assessed by a multivariate analysis. MIP values before and after oxygen supplementation were compared by a paired t test. MIP was independently correlated with FVC (p<0.001), PaO2 (p<0.01), and age (p<0.01). In the subgroup of hypoxemic patients, MIP values did not change significantly after oxygen supplementation (3.08+/-1.74 vs 3.03+/-1.91 kPa, t=0.43, not significant). CONCLUSIONS: Hypoxemia is an important negative correlate of MIP even in well-nourished COPD patients. Its effect is not reversible with an acute oxygen supplementation.

Cardiac arrhythmias and left ventricular function in respiratory failure from chronic obstructive pulmonary disease.

In 22 patients with COPD, we studied the relationship between left ventricular function and cardiac arrhythmias. Ventricular arrhythmias were detected on a 24-h ECG recorded at the beginning of the observation period and after a stable improvement of RF. Left ventricular function was evaluated by equilibrium-gated radionuclide angiocardiography measuring LVEF, PER and PFR. We found a significant decrease in the arrhythmia score after improvement of RF; LVEF and PFR were slightly depressed in six and nine patients, respectively. A "step-up" multiple regression analysis revealed a significant inverse correlation between PFR and ventricular arrhythmias during worsened RF, whereas LVEF, arterial blood gases and clinical data were not significantly predictive variables. Thus, a depressed left ventricular diastolic performance seems to be a predictive factor for arrhythmias during RF from COPD. The poor definition of the statistical model suggests that other presently unknown factors contribute to the genesis of ventricular arrhythmias.

Evaluation of health outcomes in elderly patients with asthma and COPD using disease-specific and generic instruments: the Salute Respiratoria nell'Anziano (Sa.R.A.) Study.

OBJECTIVES: To compare the effects of asthma and COPD on health status (HS) in elderly patients, and to assess the correlation between disease-specific and generic instruments assessing HS. DESIGN: Multicenter, cross-sectional, observational study. SETTING: The Salute Respiratoria nell'Anziano (respiratory health in the elderly) Study network of outpatient departments. PATIENTS: One hundred ninety-eight asthma patients and 230 COPD patients > or = 65 years old. MEASUREMENTS: HS was assessed by the Saint George's Respiratory Questionnaire (SGRQ) and five generic outcomes: Barthel's index, 6-min walk test, mini mental state examination, geriatric depression scale (GDS), and quality-of-sleep index. Independent correlates of SGRQ scores were assessed by logistic regression. Patients were considered to have a "good" HS or "poor" HS according to whether they did or did not perform worse than 75% of the corresponding population of asthma or COPD patients, on at least two of the five generic outcomes. RESULTS: On average, COPD patients had poorer HS than asthma patients on the SGRQ. Only polypharmacy (more than three respiratory drugs) and diagnosis of COPD qualified as independent correlates of the SGRQ score. The SGRQ "Activity" and "Impacts" scores shared the following independent correlates: polypharmacy, Barthel's index < 92, and GDS > 6. Further correlates were waist/hip ratio > 1 for the Activity score, and age and occiput-wall distance > 9 cm for the Impacts score. All sections of the SGRQ except for the Symptoms score could significantly distinguish patients with good HS and poor HS. CONCLUSIONS: Individual dimensions of HS recognize different determinants. COPD outweighs asthma as a cause of distressing respiratory symptoms. A high degree of concordance exists between SGRQ and generic health outcomes, except for the Symptoms dimension in COPD patients.

Body mass index and mortality among older people living in the community.

OBJECTIVES: To determine if body mass index (BMI = weight/height2), predictive of mortality in seriously ill hospitalized and institutionalized patients, is also predictive of mortality in a longitudinal epidemiologic study. DESIGN: A prospective cohort study. SETTING: Rovereto, a town in northern Italy. PARTICIPANTS: A consecutive sample of 214 patients aged 81.2 +/- 7.3 years receiving community care services. MAIN OUTCOME MEASURES: Malnutrition and mortality. RESULTS: According to logistic regression analysis, malnutrition status, expressed by a BMI < 22 Kg/m2, was correlated with dependency in Activity of Daily Living (odds ratio 1.21; 95% confidence interval (CI) 1.01-1.45). Only a low BMI was associated with 1-year survival in Cox regression analysis, after adjusting for potential confounders (relative risk 0.85; 95%CI, 0.74-0.97). A high BMI (>27 Kg/m2) was not significantly related to risk of mortality. CONCLUSIONS: Nutrition variables are a cardinal component of comprehensive geriatric assessment. Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among older people living in the community. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival.

Reasons prompting digitalis therapy in the acute care hospital.

BACKGROUND: The choice of administering digitalis to older patients with congestive heart failure (CHF) cannot be made on the account of univocally defined criteria because of uncertainty about efficacy and concern about safety of digitalis in this population. The purpose of this study was to verify whether the clinical characteristics on admission to the acute care hospital determine the use of digitalis therapy in elderly patients. METHODS: A total of 1239 patients (mean age 77.8 +/- 7.1 years, range 65-100 years, males 49.8%) consecutively admitted to 69 General Medicine and Geriatrics wards over a 4-month period were grouped by combining two dichotomous factors (Carlson's score > 4: definite or possible diagnosis of CHF; Carlson's score < 5: unlikely diagnosis of CHF; in-hospital adoption of digitalis therapy: yes or no) as follows: Group A: Carlson's score > 4, digitalis (n = 413); Group B: Carlson's score > 4, no digitalis (n = 260); Group C: Carlson's score < 5, digitalis (n = 104); Group D: Carlson's score < 5, no digitalis (n = 462). Variables significantly distinguishing groups were entered into a discriminant analysis aimed at assessing the group specificity of individual clinical profiles. RESULTS: Use of digoxin at home, atrial fibrillation, older age, and comorbidity (mainly COPD and chronic renal failure) characterized most of the patients given digoxin with or without a definite diagnosis of CHF. Clinical profiles of groups A, B, and C largely overlapped. CONCLUSION: Age, historical use of digitalis, and comorbidity might lead to seemingly incongruous digitalis prescription. The choice of adopting digitalis therapy cannot be reliably predicted on the basis of clinical variables only. Presently unexplored physician-related factors, such as cultural background, likely outweigh clinical variables in prompting digitalis prescription.

Predicting cognitive decline in patients with hypoxaemic COPD.

The objective was to identify predictors of cognitive decline in patients with hypoxaemic COPD on continuous oxygen therapy. Eighty-four consecutive ambulatory hypoxaemic COPD patients in stable clinical conditions were prospectively studied over the course of 2 yr. Baseline multidimensional assessment included respiratory function tests, blood gas analysis, Mini Mental Status (MMS) test, Geriatric Depression Scale (GDS), Activities of Daily Living (ADLs) and Charlson's index of comorbidity. Reassessments were made 1 yr and 2 yr thereafter. Sequential changes in MMS, GDS and ADLs were assessed by Friedman's ANOVA by rank test. Forty patients completed the study (group A), while 44 died or were lost to follow-up (group B). Group B was characterized by more severe respiratory function impairment and worse performances on ADLs and GDS. In group A, MMS deteriorated from baseline to the 1 yr and 2 yr reassessments (27 +/- 2.9 vs. 25.8 +/- 4.1 and 25.4 +/- 4, P < 0.005), whereas GDS and ADLs did not change significantly; the 23 patients experiencing a decline of MMS had baseline lower percentage predicted FVC (52.3 +/- 17.1 vs. 66.9 +/- 13.4, P < 0.03) and FEV1 (27.2 +/- 8.6 vs. 44 +/- 26.8, P < 0.02) values and better affective status (GDS score: 11.9 +/- 7.7 vs. 16.5 +/- 5.6, P < 0.04). Two-year changes in MMS and in GDS scores were inversely correlated (Spearman's p = -0.32, P = 0.04). Cognitive decline is faster in the presence of severe bronchial obstruction and parallels the worsening of the affective status in COPD patients on oxygen therapy. The onset of depression rather than baseline depressive symptoms seems to be a risk factor for cognitive decline.

Correlates of osteoporosis in chronic obstructive pulmonary disease.

The aim of this study was to analyse the correlates of reduced bone mineral density in patients with chronic obstructive pulmonary disease (COPD), with special regard to a possible protective role of hypercapnia. One hundred and four consecutive COPD inpatients in stabilized respiratory conditions underwent a comprehensive assessment of their health status. Bone mineral density was measured by X-ray absorptiometry at the lumbar site and at the femoral neck site. Differences in health-related variables between patients with (group O, n=62) and without (group N, n=42) lumbar and/or femoral neck osteoporosis were assessed first by univariate analysis and then by logistic regression analysis aimed to identify independent correlates of osteoporosis. Group O was characterized by worse nutritional status, as reflected by indices exploring either lean or fat mass, and by a trend towards lower forced expiratory volume in 1 sec/forced vital capacity ratio. Arterial tension of carbon dioxide lacked any correlation with bone mineral density. According to the logistic regression analysis, body mass index < or = 22 kg m(-2) qualified as the only and positive independent correlate of osteoporosis (odds ratio=4.18; 95% confidence intervals=1.19-14.71). In conclusion, malnutrition characterizes COPD patients with osteoporosis, while mild to moderate hypercapnia lacks either a positive or negative effect on bone mineral density. Longitudinal studies are needed to identify predictors rather than correlates of bone mineral density.

The effects of chronic hypoxia on left ventricular peak filling rate evaluated by equilibrium radionuclide angiocardiography.

Left ventricular peak filling rate (PFR) was measured by equilibrium radionuclide angiocardiography (ERNA) in 15 patients with Stage II stabilized chronic respiratory failure (CRF) without evidence of coexisting heart diseases and in 18 patients with coronary artery disease (CAD) without myocardial infarction. The study was designed to assess the effects of severe hypoxia and of ischaemia on the calcium-dependent early diastolic filling. PFR was found to be impaired in both groups of patients (mean = 1.72 EDVs-1 and S.E.M. = 0.07 in CAD; mean = 2.35 EDVs-1 and S.E.M. = 0.14 in CRF) but significantly less (p less than 0.001) in CRF patients while the left ventricular ejection fraction (LVEF) values were not significantly different between the two groups (mean = 60.0% and S.E.M. = 1.4 in CAD; mean = 62.0% and S.E.M. = 1.6 in CRF). As PFR is known to be a sensitive index of left ventricular performance the results obtained in this human model are consistent with findings obtained in animal models suggesting that hypoxia is less efficient than ischaemia in depressing left ventricular function.

[The orthopedic-geriatric unit: a new model of hospital care]. / L'unità ortogeriatrica: un nuovo modello di assistenza ospedaliera.

We describe here the basic characteristics and operative modalities of the acute care orthopedic-geriatric unit, an innovative model of health care for elderly trauma patients. This new unit offers several advantages over traditional models: decreased patient mortality and length of hospital stay, a lower incidence of complications, and less need for specialist consultations. No particular organizational or management problems have arisen, and the cost/benefit ratio is very low. This model has also become a valuable teaching tool and a rich source of pathophysiological and clinical data for geriatric research.

Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions.

Aging is known to be associated with an increased prevalence of multiple chronic diseases, which frequently causes the use of complex therapeutic regimens. The aging process is characterized by relevant changes in drug handling, physiological reserve, and pharmacodynamic response. Hepatic drug clearance of several drugs decreases with aging, mainly due to reduced blood flow, and hepatocyte mass. Renal function also declines with aging, mainly due to sclerotic changes in the glomeruli. Furthermore, due to reduced muscle mass, older subjects frequently have depressed glomerular filtration rate despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly the clearance of hydrosoluble drugs. Changes in pharmacodynamics are also well documented in the cardiovascular and nervous system. Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for adverse drug reactions, which in turn are cause of relevant health burden and costs. Selected measures can assist in preventing or detecting timely such adverse events.