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.

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.

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.

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.

Isolated PACNS-like presentation of a systemic vasculitis complicating a myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a series of haematological malignancies ranging from chronic refractory anaemia to leukaemia. There is increasing recognition of immunological abnormalities in patients with MDS, including few reports of cutaneous vasculitis; in no instance, a cerebral localization has been ascertained. Here, the case of a patient with MDS who presented exclusively with neurological signs that were considered indicative of a primary, isolated central nervous system vasculitis (PACNS) is reported. Although histological findings on brain tissue confirmed a small-vessel vasculitis, this had to be considered in the context of a systemic vasculitis. In fact, at autopsy, an involvement of skin, myocardium, lungs, liver, kidney and bone marrow was also found. An autoimmune vasculitis should be included in the differential diagnosis of acute-onset, isolated, cerebral symptoms complicating the course of MDS.

Reversible bronchial obstruction and disease-related health status in COPD.

We aimed to assess whether partially reversible and fixed airway obstructions are associated with different health status profiles of chronic obstructive pulmonary disease (COPD) patients. We characterized health status profiles of outpatients over 64 years suffering from COPD with fixed (n = 181) or partially reversible obstruction (n = 95) and from chronic bronchitis with forced expiratory volume in the first second (FEV1) > 69% of that predicted (n = 109) on the basis of the Saint George Respiratory Questionnaire (SGRQ) and indexes assessing cognitive (Mini Mental State), affective (15-item Geriatric Depression Scale) and physical status (Index of Barthel, six-minute walking test) and quality of sleep (Index of disturbed sleep). The degree of group-specificity of health status profiles was assessed by discriminant analysis. The 54.1% of COPD patients with partially reversible obstruction were recognized to have a distinctive health status profile characterized by a moderate to severe impairment of all components ('Symptoms', 'Activity', 'Impacts') of the SGRQ and of select indexes of performance. According to logistic regression analysis, this health status profile was associated with FEV < 46% of that predicted (odds ratio (OR): 1.6, 95% confidence interval (CI): 1.07-2.38), the use of at least three respiratory drugs (OR: 2.28, CI: 1.46-3.57) and living alone (OR: 2.01, 95% CI: 1.3-2.29). COPD patients with fixed obstruction had a very heterogeneous health status. Research is needed to verify whether the unfavorable health status profile typical of a subset of COPD patients is associated with a distinctive prognosis and can be improved by dedicated therapeutic interventions.

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.

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 length of stay of older patients with exacerbated chronic obstructive pulmonary disease.

Our study objective was to identify factors predicting length of hospital stay of older patients with exacerbated chronic obstructive pulmonary disease (COPD) through a multicenter, cross-sectional, retrospective study. We examined 3789 patients aged 74.3+/-11.1 years (mean+/-SD), 66.1% males, consecutively hospitalized in 32 wards of General Medicine and 31 of Geriatrics in acute care hospitals for exacerbated COPD in 10 bimonthly periods between 1988 and 1997. On admission, patients underwent a structured assessment of demographic data, nutritional status, cognitive and physical functions, comorbidity, and pharmacological therapy in the two weeks prior to admission. Patients were grouped according to whether their length of stay exceeded or not the 75th percentile of stay distribution in each bimonthly period. Variables univariately distinguishing groups were entered into a logistic regression analysis having long-stay as the dependent variable. Living alone (Odds Ratio 1.33, 95% Confidence Limits 1.03-1.70), use of more than 3 drugs prior to admission (OR 1.29, CL 1.09-1.51), use of drugs with respiratory depressant properties prior to admission (OR 1.24, CL 1.05-1.46), and the presence of more than 3 comorbid diseases (OR 1.88, CL 1.61-2.19) were independent correlates of long-stay. Age did not predict length of stay. In conclusion, selected health outcomes and indicators of disease severity, but not age, target COPD patients at risk of long-stay. Research is needed to verify whether these data can help program interventions aimed at shortening length of stay and, thus, at reducing annual hospitalization costs of the elderly.

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.

Life-threatening subcutaneous hematoma caused by an axillary pad in an anticoagulated patient.

A large subcutaneous hematoma extending from the left axillary region to the left flank developed in a 70-year-old man receiving anticoagulant therapy. The cause was repeated microtrauma caused by the axillary pad on a walker. Physicians and physiotherapists should be aware that rehabilitation devices causing pressure on the skin increase hemorrhagic risk in patients taking anticoagulants. Accordingly, these patients should systematically be checked for hemorrhagic complications, and the use of such devices should be limited.

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.

Electrocardiographic signs of chronic cor pulmonale: A negative prognostic finding in chronic obstructive pulmonary disease.

BACKGROUND: Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. METHODS AND RESULTS: Two hundred sixty-three patients (217 men) with COPD, mean age 67+/-9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or >/=1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3. 45 years, respectively; Mantel-Cox test, 9.58; P=0.002). The Cox regression analysis identified S1S2S3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (PAO2-PaO2) >48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S1S2S3 pattern and RAO (n=14) and of patients having either S1S2S3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively (P=0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their PAO2-PaO2 during oxygen therapy was or was not >48 mm Hg. CONCLUSIONS: Some ECG signs of CCP and PAO2-PaO2 >48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis.