The impact of frailty on intra-hospital survival in older patients with COVID-19 infection: the importance of early identification. SEMI-COVID National Registry.

BACKGROUND: Emerging evidence suggests that frailty may be a significant predictor of poor outcomes in older individuals hospitalized due to COVID-19. This study aims to determine the prognostic value of frailty on intrahospital patient survival. METHODS: This observational, multicenter, nationwide study included patients aged 70 years and older who were hospitalized due to COVID-19 in Spain between March 1 and December 31, 2020. Patient data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine. Frailty was assessed using the Clinical Frailty Scale. The primary outcome was hospital survival. Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 1,878 participants (52% men and 48% women) were included, with 1,351 (71.9%) survivors and 527 (28.1%) non-survivors. The non-survivor group had higher mean age (83.5 vs. 81 years), comorbidities (6.3 vs. 5.3 points on the Charlson index), degree of dependency (26.8% vs. 12.4% severely dependent patients), and frailty (34.5% vs. 14.7% severely frail patients) compared to survivors. However, there were no differences in terms of sex. Our results demonstrate that a moderate-severe degree of frailty is the primary factor independently associated with shorter survival [HR 2.344 (1.437-3.823; p<0.001) for CFS 5-6 and 3.694 (2.155-6.330; p<0.001) for CFS 7-9]. CONCLUSION: Frailty is the main predictor of adverse outcomes in older patients with COVID-19. The utilization of tools such as the Clinical Frailty Scale is crucial for early detection in this population.

[Detecting adverse drug events during the hospital stay]. / Detección de acontecimientos adversos producidos por medicamentos durante la estancia hospitalaria.

INTRODUCTION: The principal objective was to determine the incidence rate of adverse drug events (ADEs) in hospitalised patients and evaluate the event prevention percentage. METHODS: Multi-centre, prospective observational study lasting four months, performed in five hospitals providing different levels of care. We included all adult patients who were admitted to one of the selected centres for longer than 48 hours and who required pharmacological treatment. ADEs were identified by direct observation and the use of previously defined alarm signals. The Karch-Lasagna scale was used to determine the causality relationship, and the Schumock and Thornton questionnaire adapted by Otero was used to evaluate ADE preventability. Preventable drug-induced adverse events were classified according to the taxonomy that the Ruiz-Jarabo 2000 group defined, and coordinated by ISMP-Spain. RESULTS: We included 1,550 patients, 159 of whom experienced at least one ADE (10.3 %). The preventability percentage was 51.6 %, which represented 5.3 % of the total sample. The endocrine system (34.8 %) and the cardiovascular system (20.7 %) were the most affected by preventable ADEs. Antibiotics were responsible for 16.5 % of all ADEs. 9.3 % of all preventable ADEs were triggered by use of opiates. The vast majority of preventable ADEs (36.3 %) resulted from omitting a necessary medication. Only 4.4 % of preventable ADEs are considered to be serious. CONCLUSIONS: There is a high incidence rate of ADEs during patients' hospital stay (10.3 %), and half of them (51.6 %) could have been prevented. Implementation of an automatic alarm system and certain best practices for problem spots along the care circuit will help detect and avoid preventable ADEs.

High alcohol intake as a risk and prognostic factor for community-acquired pneumonia.

OBJECTIVE: To evaluate whether high alcohol intake is an independent risk factor for community-acquired pneumonia in middle-aged people and whether it confers a poor prognosis. METHODS: A two-phase study was performed. Risk factors for community-acquired pneumonia were evaluated in a case-control study of 50 patients and 50 controls. Prognostic factors and microbiologic and clinical features were then evaluated in a cohort study of the 50 middle-aged patients with community-acquired pneumonia. RESULTS: In the first study, the only independent risk factor for community-acquired pneumonia was high alcohol intake (P < .02). In the second study, patients with chronic alcoholism had a higher incidence of pneumonia caused by gram-negative bacilli (P < .03), as well as a higher incidence of Candida albicans (P < .03), Staphylococcus aureus (P < .0001), and gram-negative bacilli (P < .001) in the cultures of pharyngeal smears than did the nonalcoholics. Compared with nonalcoholic patients, alcoholic patients with pneumonia showed more severe clinical symptoms (P < .02), required longer intravenous treatment (P < .02) and longer hospital stay (P < .01), and had multilobar involvement and pleural effusion (both P < .01), as well as slower resolution of pulmonary infiltrates. The only prognostic factor for mortality was high alcohol intake (P < .03). CONCLUSIONS: High alcohol intake is the main risk factor for developing community-acquired pneumonia in middle-aged people. This situation also confers a worse prognosis in these patients, who should be treated with broad-spectrum antibiotics for a longer period.

Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring.

Several studies have shown that cessation of alcohol drinking reduces blood pressure (BP). However, attempts to reproduce these findings by ambulatory BP monitoring (ABPM) have shown inconsistent results. The aim of the present study was to assess the effect of 1 month of proven abstinence from alcohol on the 24-hour BP profile in heavy alcohol drinkers. Forty-two men who were heavy drinkers (>100 g of pure ethanol per day) were consecutively admitted to a general ward for voluntary alcohol detoxification. On the day of admission, they received a total dose of 2 g/kg of ethanol diluted in orange juice in 5 divided doses, and a 24-hour ABPM was performed. A new 24-hour BP monitoring in the same environmental conditions was performed after 1 month of proven alcohol abstinence while the subjects were receiving the same amount of fluid but without the addition of alcohol. After 1 month of proven alcohol abstinence, BP and heart rate (HR) significantly decreased. The reduction was 7.2 mm Hg for 24-hour systolic BP (SBP) (95% CI, 4.5 to 9.9), 6.6 mm Hg for 24-hour diastolic BP (DBP) (95% CI, 4.2 to 9.0), and 7.9 bpm for HR (95% CI, 5.1 to 10.7). The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence. Abstinence did not modify either the long-term BP variability, assessed by SD of 24-hour BP, or its circadian profile. We conclude that abstinence in heavy alcohol drinkers significantly reduces BP assessed by 24-hour ABPM and that this reduction is clinically relevant. These results show that heavy alcohol consumption has an important effect on BP, and thus cessation of alcohol consumption must be recommended as a priority for hypertensive alcohol drinkers.

Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease.

Different abnormalities in mitochondrial electron transport chain activity have been demonstrated in muscle and other tissues of patients with idiopathic Parkinson's disease (PD). We studied eight Spanish patients with PD to evaluate the functional activity of the electron transport chain in muscle mitochondria from patients of this country. We found lower complex I activity (nmol.min-1.mg-1) in patients (245.8 +/- 42.8) than in controls (331.6 +/- 60.1) (p = 0.004) and lower complex IV activity in patients (46.1 +/- 9) than in controls (144.1 +/- 42.3) (p = 0.00001). Complex V activity was also decreased in two patients and complex II and III activities were normal in all of them. Although these results strongly suggest an alteration in mitochondrial DNA in PD, the various electron transport chain defects in different tissues seem to be nonspecific.

Differential effects of moderate or heavy alcohol consumption on circulating adhesion molecule levels.

Epidemiological studies suggest that moderate but not heavy alcohol consumption provides protection against coronary heart disease. We assessed the relationship between alcohol consumption and serum levels of adhesion molecules involved in the pathogenesis of early atherosclerosis. One-hundred apparently healthy men with similar cardiovascular risk factors were divided into four groups according to ethanol intake. Moderate drinkers (20-40 g/day) showed lower serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels than abstainers (p < 0.05; both), as well as lower serum ICAM-1, VCAM-1 and E-selectin levels than heavy drinkers (p = 0.01; all). The latter also showed higher serum ICAM-1 and E-selectin levels than abstainers (p < 0.001; both). We conclude that moderate drinkers show a significant reduction of soluble endothelial adhesion molecule levels compared to abstainers and heavy drinkers, that may contribute to the protective effect of moderate alcohol consumption against atherosclerosis.

Comparison of alcoholic cardiomyopathy in women versus men.

To compare the prevalence and cardiac status of male and female alcoholics with alcoholic cardiomyopathy during a 5-year period, all chronic alcoholics with dilated cardiomyopathy who had clinical symptoms of heart failure were included. Alcoholic cardiomyopathy was diagnosed in 10 chronic alcoholic women and in 26 men; the prevalence of alcoholic cardiomyopathy was similar in both sexes. No significant differences were observed in age, nutritional parameters, and clinical and radiologic data of heart failure between the 2 groups. Alcoholic women reported a significantly lower daily dose of ethanol (p = 0.002), a shorter duration of alcoholism (p = 0.017), and a lower total lifetime dose of ethanol consumption (p = 0.001), and had a lower New York Heart Association functional class than men. Women also had lesser ventricular dysfunction than men. In a multivariate analysis, left ventricular systolic dysfunction was related to the total lifetime dose of ethanol consumption (p <0.04), but not to gender. Finally, when patients were matched for left ventricular ejection fraction, women had consumed a lower total lifetime dose of ethanol than men (p <0.001). The prevalence of alcoholic women with dilated cardiomyopathy was found to be similar to that of alcoholic men, although women required a lower total lifetime dose of ethanol to develop the disease.

Microvascular changes in skeletal muscle in idiopathic inflammatory myopathy.

Open deltoid muscle biopsy specimens from patients with idiopathic adult dermatomyositis, paraneoplastic dermatomyositis, childhood dermatomyositis, and idiopathic polymyositis, and from control patients were studied. Qualitative and morphometric capillary analysis by phase and electron microscopy was carried out. In the morphologic analysis the most striking difference was the presence of capillary damage and a higher capillary depletion in dermatomyositis as well as a higher capillary density in polymyositis. By electron microscopy, capillaries from patients with dermatomyositis showed mainly microtubuloreticular structures, loss of endothelial plasma membranes, and the appearance of abnormal cytoplasmic organelles. In contrast, capillaries from patients with polymyositis exhibited only minimal changes. By morphometric analysis, muscle capillaries in dermatomyositis had a significantly higher mean endothelial thickness than those in polymyositis. Finally, a significant topographic association between capillary damage and muscle fiber changes was observed only in patients with dermatomyositis. On the other hand, paraneoplastic dermatomyositis showed fewer structural and morphometric capillary changes than the other forms of dermatomyositis. We conclude that dermatomyositis is characterized by microvascular alterations that are absent in polymyositis. The topographic proximity of capillary changes to muscle fiber injury suggests that capillary damage may play a role in the pathogenesis of the muscle lesions observed in patients with dermatomyositis.

Low-dose ethanol consumption allows strength recovery in chronic alcoholic myopathy.

Chronic skeletal myopathy may affect one third of chronic alcohol misusers. It is generally accepted that abstinence allows partial recovery, and that continued high-dose ethanol consumption progressively deteriorates muscle function. However, the effect of low-dose ethanol consumption in alcoholic myopathy has not been studied. We studied 58 chronic alcoholic male patients with biopsy-proven chronic alcoholic myopathy over 5 years. We evaluated ethanol intake, biochemical and nutritional parameters, and assessed muscle strength. Eighteen patients who remained abstinent showed marked improvement in muscle strength. As expected, the 19 patients who persisted in high-dose ethanol consumption further diminished in their muscle strength. In the 11 patients who maintained low-dose (

Chronic alcoholic myopathy: diagnostic clues and relationship with other ethanol-related diseases.

We report the clinical, laboratory, functional and histological features of 100 male alcoholic patients of whom 44 had chronic alcoholic myopathy (CAM). We evaluated the use of non-invasive tests in detecting CAM, and examined its relationship with other ethanol-related diseases such as cirrhosis and cardiomyopathy. Of the CAM patients, 24 (55%) presented clinical symptoms of myopathy, whereas proximal muscle atrophy was observed in 15 patients (35%). Thirty-seven (80%) had significantly decreased muscle strength by myometric measurement and 27 (60%) had abnormally increased serum muscle enzymes. In most of these patients, the myopathy was classified as mild. The most frequent histological findings were myocytolysis, fibre size variability and type II fibre atrophy. As there was a good correlation between clinical symptoms, decreased muscle strength on myometry and histological evidence of CAM, muscle biopsy may be avoidable in some of these patients. Cardiomyopathy and liver cirrhosis were more frequent in patients with CAM, and should be checked for in chronic alcoholics with skeletal myopathy.

High ethanol intake and malnutrition in alcoholic cerebellar shrinkage.

To determine the influence of chronic ethanol intake and nutritional status on cerebellar shrinkage in alcoholism, we studied 12 undernourished patients with acute Wernicke's encephalopathy (WE), 12 undernourished and 24 well-nourished asymptomatic chronic alcoholics, and 24 age-matched well-nourished controls, using morphometric analysis of MRI scans with volumetry of the cerebellum. Alcoholics reported a mean daily intake of ethanol of 177+/-8 g over a period of 27+/-1 years. Most undernourished alcoholics and half of the well-nourished alcoholics, compared to one-tenth of the controls, showed a significant reduction in cerebellar volume (p< or =0.01, both). Alcoholics with cerebellar shrinkage (n=33) were older (p=0.05) and tended to report greater daily ethanol intake than alcoholics without cerebellar shrinkage (n=15), although not significantly so (p=0.09). Cerebellar volume correlated negatively with age in controls and asymptomatic alcoholics (r> or =0.52, p< or =0.01, both), with a significantly greater shrinkage for age in the latter (p=0.003). Logistic regression analysis showed that malnutrition (OR 6.6 [95%CI 1.7-25.6], p=0.005) and a daily ethanol intake of more than 140 g over ten years (OR 6.1 [95%CI 1.8-20.5], p=0.003) were independently associated with the development of cerebellar shrinkage.

Significance of type II fiber atrophy in chronic alcoholic myopathy.

To determine the significance of type II fiber atrophy in alcoholic myopathy and its relationship with ethanol-related diseases a prospective study was carried out in 100 chronic alcoholics who showed clinical suspicion of skeletal myopathy. Measurement of muscle strength, laboratory analysis, nutritional assessment and open biopsy of deltoid muscle were performed in each case, as well as electrophysiological testing for peripheral neuropathy. Hepatic ultrasonography and liver biopsy, echocardiography and radionuclide cardiac scanning were carried out in selected subjects. According to histomorphometric analysis, type II fiber atrophy was found in 33 cases (33%), being selective for type II B fiber in 23 (70%). Skeletal myopathy was diagnosed in 61 cases, alcoholic cardiomyopathy in 26, peripheral neuropathy in 23 and cirrhosis in 12. Patients with type II fiber atrophy had a significantly higher total lifetime dose of ethanol, presented a greater incidence of skeletal myopathy and peripheral neuropathy, and exhibited significantly lower values of percentage of ideal body weight and lean body mass than their counterparts. However, the only independent factors for developing type II fiber atrophy were the coexistence of caloric malnutrition (p = 0.004) and the presence of skeletal myopathy (p = 0.043). Selective type II fiber atrophy is a non-specific finding in alcohol-induced muscle damage appearing, overall, in the patients with caloric malnutrition as well as in those with histologic evidence of myopathy.

Patients with chronic glucocorticoid treatment develop changes in muscle glycogen metabolism.

High dose glucocorticoid may induce a significant myopathy with loss of thick myofilament from muscle, particularly if administered in conjunction with depolarizing drugs. Remarkably, the effect of chronic low dose glucocorticoid in muscle is vastly different, although it may induce changes in muscle glycogen metabolism as evidenced in animal experimental trials. However, there is no clear confirmation that these changes could develop similarly in patients. We evaluate clinical, functional, histological and metabolic muscle changes during chronic low-dose glucocorticoid treatment in 11 asthmatic patients. Remarkably, these patients did not develop clinical symptoms of myopathy nor significant muscle weakness or morphological changes in muscle histology. However, glycogen concentration and the activity of the main regulatory enzymes of glycogen metabolism, aldolase and creatine kinase were modified in comparison with controls. An increase in the synthesis and muscle cell deposition of glycogen and a decrease in the muscle glycogen degradation process have been suggested. These changes were not related with malnutrition. There was not correlation between histological and biochemical changes. We conclude that chronic treatment with glucocorticoid causes clear changes in glycogen metabolism in the skeletal muscle, resulting in glycogen muscle storage. The significance of these biochemical changes is unknown, but it can be well an associated phenomenon with glucocorticoid treatment.

Lack of muscle toxicity with didanosine (ddI). Clinical and experimental studies.

Currently, 2',3'-dideoxyinosine (ddI) is used in AIDS therapy. To investigate the possible myotoxicity of ddI in patients infected with human immunodeficiency virus (HIV), we examined the effect of ddI in vitro in tissue cultures of skeletal muscles of rats exposed to ddI at doses equivalent to plasma ddI levels obtained in the treatment of HIV patients. Control cultures were exposed to normal saline and zidovudine (AZT). After 4 weeks no changes were noted in the ddI and normal saline cultures, but AZT cultures showed abnormal accumulation of mitochondria. The creatine kinase values in culture supernatants were all normal. We also reviewed the clinical, nutritional and biological parameters, AZT and ddI dosage, and histochemical findings in muscle specimens of 14 HIV patients receiving ddI therapy. All patients had previously received AZT. The mean cumulative dose of ddI was 91.6 gm. Two patients had myalgia, 9 muscle atrophy, and 13 weakness. All patients were malnourished. Five patients had mitochondrial myopathy related to AZT, 4 had ddI-associated neuropathy and 2 patients had only selective type 2 fiber atrophy. One patient had necrotizing vasculitis, one had scattered necrotic fibers and type 2 fiber atrophy and 2 had a normal muscle biopsy. On the basis of the results, we have been unable to implicate ddI as a cause of skeletal myopathy.

Atrophy of the corpus callosum in chronic alcoholism.

To determine the prevalence of corpus callosum atrophy in chronic alcoholics and its relationship to cognitive function and brain atrophy, a prospective clinicoradiologic study was carried out in 28 right-handed male patients with chronic alcoholism and 14 age- and sex-matched right-handed control subjects. Clinical evaluation, neuropsychological testing and measurement of the midsagittal corpus callosum area and thickness (genu, truncus and splenium), as well as the frontal lobe index and the width of the cortical sulci on T1- and T2-weighted magnetic resonance images were performed. Compared to controls, alcoholics had significantly decreased corpus callosum area and thickness, mainly in the genu. Two-thirds had a corpus callosum area 2 SD below the mean of the control group. The sagittal area of the corpus callosum body correlated negatively with the degree of frontal and cortical atrophies (r = -0.5579 and -0.6853, respectively p < 0.01, both). Alcoholics with corpus callosum atrophy exhibited impairment of visual and logical memories (p < 0.05 both) and those with reduced thickness of the genu showed impairment of frontal lobe tasks (p < 0.05). The reduction of corpus callosum indices (age-corrected) also correlated with the total lifetime dose of ethanol consumed (r = 0.6107, p < 0.001), but was not related to nutritional status or electrolyte imbalance. Atrophy of the corpus callosum is common among alcoholic patients and may reflect the severity and pattern of cortical damage. The degree of this atrophy also correlated with the severity of ethanol intake.

Chronic fatigue syndrome: studies on skeletal muscle.

Chronic fatigue syndrome represents a poorly defined disease with protean clinical manifestations, the majority of them expressed as a muscle fatigue or as inability to maintain the expected muscle strength. In the present work we studied muscle function and muscle histopathology in 20 patients fulfilling the proposed criteria for chronic fatigue syndrome. Special interest is directed towards the immunoreactive expression of class I MHC molecules comparing some inflammatory and virus-related myopathies with muscles from chronic fatigue syndrome. Only minor morphological changes were detected in 9 out of 20 patients of the series. The nonspecific morphological changes in muscle tissue and the lack of class I MHC expression does not support the viral etiology of muscle fatigue in chronic fatigue syndrome. In contrast with the reported clinical improvement with high doses of essential fatty acids, our patients' clinical condition did not improve after three months of L-carnitine therapy.

Idiopathic inflammatory myopathies. Immunohistochemical analysis of the major histocompatibility complex antigen expression, inflammatory infiltrate phenotype and activation cell markers.

Muscle biopsies from 21 dermatomyositis (DM) and 7 polymyositis (PM) patients were studied by conventional histoenzymatic reactions and immunoreacted with antibodies against T cells and subsets, B cells, macrophages, activated T cells, proliferating cells, transferrin and IL-2 receptors, and natural killer cells. The expression of both class I and II molecules from the major histocompatibility complex (MHC) was also tested. As control groups we used muscle biopsies from normal healthy people, from chronic alcoholics and from a cohort of HIV-1 infected patients. In DM cases, severe muscle fiber necrosis, predominant perivascular infiltrates, fibrosis and perifascicular atrophy were the rule whereas in PM cases, endomysial infiltrates and the existence of partially invaded non-necrotic cells were more frequent. Perivascular B cells were found only in some DM cases. Transferrin and IL-2 receptors, proliferating cells and NK cells were detected in some cases from both diseases. MHC class I molecules were detected mainly in perifascicular fibres in DM while in PM the stronger expression was demonstrated in non-necrotic partially invaded cells, suggesting for the latter a MHC-restricted T-cell cytotoxicity. MHC Class II molecules expression in endothelial cells was detected in a variable fashion in both diseases, probably reflecting different stages of activation of such cells.

[Tracheobronchomegaly associated with light chain deposition disease]. / Traqueobroncomegalia asociada a enfermedad por depósito de cadenas ligeras.

Tracheobronchomegaly, also known as Mounier-Kühn's Syndrome, is characterized by market dilation of the trachea and main bronchi and has been reported in association with several conditions, particularly connective tissue disease. The pathogenesis and clinical signs of light chain deposition disease are similar to those of light chain amyloidosis, in which these chains are deposited as amorphous material lacking the tinctorial features of the amyloid. We present a case involving both entities, an association that has not been previously reported, and we review the main characteristics of both diseases.

[Hypothyroid myopathy. A clinical and histologic prospective study of 19 patients]. / Miopatía hipotiroidea. Estudio prospectivo clínico e histológico de 19 pacientes.

Nineteen patients with primary hypothyroidism were prospectively studied before starting replacement therapy with thyroid hormones. Most patients had mild to moderate muscle symptoms: generalized muscle weakness, myalgia and cramps, and increased serum levels of muscle enzymes. In two patients these features were the motive for consulting the physician. The patients with muscular features had significantly higher plasma levels of lactic dehydrogenase and aldolase than asymptomatic patients. The major histological muscle findings were atrophy of type II fibers, abnormalities in the oxydative pattern of muscle cells, and glycogen deposition. In the biochemical investigations an increased muscle glycogen with reduced activity of the glycolysis and glucogenolysis enzymes were found. The patients with more marked histological abnormalities had lower levels of thyroid hormones, but the differences did not reach significant values. Five patients in euthyroid status after 12 months of therapy underwent a new biopsy. Although the remaining clinical and laboratory parameters had returned to normal, some of the histological muscle abnormalities persisted. This finding leads to the suspicion that the lack of thyroid hormones may induce irreversible structural damage in skeletal muscle.