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.

Body mass index and mortality among hospitalized patients.

BACKGROUND: Body mass index (weight in kilograms divided by the square of the height in meters [BMI]) is known to be associated with overall mortality. However, the effect of age on excess mortality from all causes associated with obesity is controversial. The aim of the present study is to determine the effect of age on the relationship between BMI and mortality. METHODS: We analyzed data from a large collaborative observational study group, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), that collected data on hospitalized patients. A total of 18,316 patients consecutively admitted to 79 clinical centers during 5 different surveys in 1998, 1991, 1993, 1995, and 1997 were enrolled in the present study. The main outcome measure was the relative hazard ratio of death for different levels of BMI. RESULTS: Mortality rate was lowest among men and women with BMIs from 25.0 through 27.4 kg/m(2) (relative risk, 0.24; 95% confidence interval, 0.15-0.38). The graphed relationship between BMI and mortality in younger patients was hyperbolic, with increased death rates at the lowest and highest BMI rankings. On the contrary, the older patients showed an increased death rate at the lowest BMIs with only a slight elevation at the highest BMIs (>35 kg/m(2)). CONCLUSIONS: Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among young and old hospitalized patients. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival. Furthermore, the finding of the high BMI associated with minimum hazard in elderly subjects supports some past findings and opposes others and, if confirmed, has important implications for geriatric clinical guidelines.

Prevalence, clinical correlates, and treatment of hypertension in elderly nursing home residents. SAGE (Systematic Assessment of Geriatric Drug Use via Epidemiology) Study Group.

BACKGROUND: Hypertension is prevalent in the elderly, but an information gap remains regarding the old, frail, individuals with complex conditions living in long-term care. OBJECTIVE: To analyze the patterns of antihypertensive drug therapy among elderly patients living in nursing homes to elucidate their conformity with consensus guidelines. SUBJECTS AND METHODS: We used a long-term care database that merged sociodemographic, functional, clinical, and treatment information on nearly 300000 patients admitted to the facilities of 5 US states between 1992 and 1994. RESULTS: Hypertension was diagnosed in 80206 patients (mean age, 82.7+/-7.8 years). The prevalence was higher among women and among blacks. About one fourth of patients had 6 or more comorbid conditions; 26%, 22%, and 29% had concomitant diagnoses of coronary heart disease, congestive heart failure, and cerebrovascular disease, respectively. Seventy percent of patients were treated pharmacologically. Calcium channel blockers were the most common agents (26%), followed by diuretics (25%), angiotensin-converting enzyme inhibitors (22%), and beta-blockers (8%). The relative use of these drugs changed according to the presence of other cardiovascular conditions. Adjusting for potential confounders, the relative odds of receiving antihypertensive therapy were significantly decreased for the oldest subjects (> or =85 years old: odds ratio, 0.85; 95% confidence interval, 0.81-0.89) and those with marked impairment of physical (odds ratio, 0.77; 95% confidence interval, 0.73-0.81) and cognitive (odds ratio, 0.67; 95% confidence interval, 0.64-0.70) function. CONCLUSIONS: Among very old, frail hypertensive patients living in nursing homes, the pattern of treatment seems not to follow recommended guidelines; age, functional status, and comorbidity appear to be important determinants of treatment choice.

Effects of angiotensin-converting enzyme inhibitors and digoxin on health outcomes of very old patients with heart failure. SAGE Study Group. Systematic Assessment of Geriatric drug use via Epidemiology.

BACKGROUND: Randomized trials have shown that angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity, and improve symptoms and exercise tolerance in selected patients with congestive heart failure (CHF). There is, however, no evidence on the effectiveness of ACE inhibitors in the typical, very old and frail patients with CHF. OBJECTIVE: To compare the effects of ACE inhibitors and digoxin on 1-year mortality, morbidity, and physical function among patients aged 85 years. METHODS: We conducted a retrospective cohort study using the SAGE database, a long-term care database linking patient information with drug utilization data. Among 64637 patients with CHF admitted to all nursing homes in 5 states between 1992 and 1995, we identified 19492 patients taking either an ACE inhibitor (n = 4911) or digoxin (n = 14890). Record of date of death was derived from Medicare enrollment files, and we used the part A Medicare files to identify hospital admissions and discharge diagnoses. As a measure of physical function, we used a scale for activities of daily living performance. The effect of ACE inhibitors was estimated using Cox proportional hazards models with digoxin users as the reference group. RESULTS: The overall mortality rate among ACE inhibitor recipients was more than 10% less than that of digoxin users (relative rate, 0.89; 95% confidence interval, 0.83-0.95). Mortality was equally reduced regardless of concomitant cardiovascular conditions and baseline physical function. Treatment with ACE inhibitors was associated with a tendency toward reduced hospital admissions that was more evident among patients with greater functional impairment. The adjusted relative rate for hospitalization for any reason was 0.96 (95% confidence interval, 0.91-1.01). The rate of functional decline was greatly reduced among ACE inhibitor recipients (relative rate, 0.74; 95% confidence interval, 0.69-0.80), and this effect was consistent and independent of background comorbidity and baseline physical function. CONCLUSIONS: These data suggest that survival and functional benefits of ACE inhibitor therapy extend to patients with CHF 85 years and older, and mostly women, both systematically underrepresented in randomized trials. Alternatively, digoxin has a detrimental effect in this population.

Temperature modulates calcium homeostasis and ventricular arrhythmias in myocardial preparations.

OBJECTIVE: The aim was to evaluate the effect of temperature on reoxygenation induced ventricular arrhythmias in isolated hearts, on delayed afterdepolarisations and Iti current in Purkinje fibres, and on sarcoplasmic reticular function and Ca2+ handling of single cardiac myocytes. METHODS: Isolated guinea pig hearts were retrogradely perfused at 37 degrees C with a hypoxic medium for 15 min and reoxygenated for 10 min either at 33 degrees C or at 37 degrees C. Intracellular microelectrodes were used to assess the presence of delayed afterdepolarisations and triggered activity in sheep Purkinje fibres exposed to strophanthidin at different temperatures. Iti current was evaluated in voltage clamp experiments. In rat cardiomyocytes, loaded with the fluorescent Ca2+ dye, indo-1, the sarcoplasmic reticular Ca2+ content was assessed at 30 degrees C and at 37 degrees C, either by a caffeine spritz puffed onto a cell from a patch pipette or by a post-rest contraction. RESULTS: Hypothermic reoxygenation reduced the incidence of ventricular arrhythmias in isolated hearts (30%, n = 10, at 33 degrees C and 75%, n = 30, at 37 degrees C, p < 0.05). In Purkinje fibres, hypothermia decreased the amplitude of delayed afterdepolarisations. Moreover, at 32 degrees C, the amplitude of Iti current was decreased to 59.2(SEM 2.6)% of the normothermic value [27.5(6.7) nA, n = 4, p < 0.005] and time to peak increased to 159.7(10.2)% [value at 37 degrees C = 470(41) ms, n = 4, p < 0.01]. In cardiac cells, sarcoplasmic reticular Ca2+ release induced by caffeine spritz or by post-rest contraction was increased at 30 degrees C. However, following a pacing period at 1 Hz, hypothermia prolonged the time to onset of the first spontaneous Ca2+ oscillation [59(14) s at 30 degrees C and 27(9) s at 37 degrees C, n = 5, p < 0.05] and reduced the oscillation frequency [1.1(0.4) min-1 at 30 degrees C and 3.1(0.9) min-1 at 37 degrees C, n = 5, p < 0.05]. CONCLUSIONS: Mild hypothermia increases sarcoplasmic reticular Ca2+ content but decreases the likelihood of spontaneous Ca2+ release. This may explain the reduction of delayed afterdepolarisations and Iti current amplitude in Purkinje fibres and it could represent a mechanism for the protection provided by hypothermia against ventricular arrhythmias.

Enalapril prevents cardiac fibrosis and arrhythmias in hypertensive rats.

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 mg/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199 +/- 3 mm Hg (treated) versus 237 +/- 3 mm Hg (controls) (p less than 0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively; p less than 0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p less than 0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p less than 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p less than 0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (p less than 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.

Use of calcium antagonists and hemoglobin loss in hospitalized elderly patients: a cohort study. Gruppo Italiano di Farmacoepidemiologia nell'Anziano (GIFA) investigators.

OBJECTIVE: To assess the association between in-hospital use of calcium antagonists and incident reduction in hemoglobin levels, as well as the impact of individual baseline risk for gastrointestinal bleeding on such an association. METHODS: The association between calcium antagonists and hemoglobin decrease > 1.2 g/dL was examined in 6,721 patients enrolled in a collaborative pharmacoepidemiology study who did not take calcium antagonists before admission and with baseline hemoglobin > or =12 g/dL. Among these participants, 1,076 patients started taking calcium antagonists during their hospital stays. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hemoglobin loss in separate age- and sex-adjusted logistic regression models were examined as potential confounders in a summary model. Higher risk for gastrointestinal bleeding was defined by diagnosis, treatment for peptic disease, or both. RESULTS: Hemoglobin decrease was detected in 24% of participants who started treatment with calcium antagonists and in 19% of other patients (P < .0001). In addition, use of calcium antagonists was independently associated with increased probability of hemoglobin loss (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.03 to 1.45; P = .018) after adjusting for potential confounders. Treatment with calcium antagonists was associated with hemoglobin loss in patients with higher baseline risk for gastrointestinal bleeding (OR, 1.67; 95% CI, 1.26 to 2.22; P < .0001) but not among other participants (OR, 1.02; 95% CI, 0.82 to 1.25). CONCLUSION: Starting treatment with calcium antagonists is associated with a reduction in hemoglobin levels during a hospital stay. However, the increased risk of hemoglobin loss seems to be limited to patients with diagnosis or symptoms of peptic disease.

Immune parameters in a population of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations.

Twenty-six institutionalized elderly subjects, selected as healthy according to the SENIEUR protocol, were compared to adult controls to establish correlations between affective disorders and immune abnormalities and to investigate underlying neuroendocrine mechanisms. After an extensive psychodiagnostic examination, 35% of the aged subjects were classified as depressed. Cutaneous delayed hypersensitivity tests showed reduced responses in the aged, but no correlation was found with the psychological status. Examination of the peripheral blood lymphocyte subsets revealed no imbalance in the percentages of CD3+, CD4+, CD8+ cells in the aged. A slight reduction in the CD4+/CD8+ cell ratio could however be detected in the non-depressed aged, as compared to adult controls. The CD4+/CD45R+ cell subset was reduced in non-depressed aged. The percentage of B lymphocytes was reduced in the aged, mostly in the non-depressed subjects. No changes were detected in the percent of OKDR+ cells. The percentage of CD16+ cells was found unchanged, while that of Leu7+ cells was significantly higher in the aged than in the adults and in the non-depressed than in the depressed aged. Leu7+ cell levels were negatively correlated with the depression score. On double labelling, the percent of CD16+/Leu7+ cells appears increased in the subgroup of depressed aged and positively correlated with age. Plasmatic and urinary cortisol levels were both positively correlated with depression score. Urinary cortisol level was higher in the depressed aged. These parameters, as well as plasmatic ACTH, beta-endorphin and urinary catecholamines, were not correlated with immune responses. Based on these findings, we recommend that the neuroendocrinological conditions should be taken into account when healthy subjects are examined in studies of immune senescence.

Impairment of lymphocyte activities in depressed aged subjects.

Lymphocyte activities were determined in a population of 26 institutionalized aged subjects, selected as healthy according to the SENIEUR protocol and previously reported to display immunological and endocrinological abnormalities correlated with depressive disorders. The lymphocyte mitotic response to PHA, which was reduced in aged as compared to adult subjects, was found to be significantly lower and negatively correlated with the depression score in the elderly subjects. In supernatants of PHA-stimulated lymphocyte culture from aged subjects, IL-2, IL-4 and gamma-IFN levels were very low and more severely affected in the depressed aged group. Each cytokine production was negatively correlated with age and depression score. NK activity was lower in the aged and it could be augmented by the addition of IL-2 or alpha-IFN, even though to a lesser extent than in the adult subjects. The nondepressed aged displayed higher levels of IL-2 inducible NK activity than the depressed aged subjects. IL-2 and alpha-IFN stimulated NK activities were negatively correlated with depression score. The present work indicates that the psychological status could affect lymphocyte reactivity in the aged. Given the relatively high frequency of affective disorders in these subjects, the psychological status should be considered in studies of immune senescence.

A controlled trial of verapamil in patients after acute myocardial infarction: results of the calcium antagonist reinfarction Italian study (CRIS)

A multicenter, double-blind, randomized, placebo-controlled trial was conducted to assess the effects of verapamil on total mortality, cardiac mortality, reinfarction, and angina after an acute myocardial infarction. All patients, aged 30 to 75 years, consecutively admitted for acute myocardial infarction between 1985 and 1987 to the participating centers, and without contraindications to verapamil or history of severe heart failure were enrolled. Seven to 21 days (mean 13.8) after myocardial infarction, 531 patients were randomized to verapamil retard 360 mg/day, and 542 patients to placebo. At baseline, the 2 groups of patients had similar characteristics. Mean age was 55.5 years and 91% were men. During a mean follow-up of 23.5 months, 5.5% of the patients died. No differences between verapamil and placebo were observed in total mortality (n = 30 and 29, respectively) and cardiac death (n = 21 and 22, respectively). The verapamil group had nonsignificant lower reinfarction rates (n = 39 vs 49). The number of patients developing angina was significantly less in the verapamil group (n = 100 vs 132, RR = 0.8, 95% confidence interval 0.5 to 0.9). There were no differences in discontinuation of therapy caused by adverse reactions. This trial showed no effect of verapamil on mortality. The lower reinfarction rates found in the verapamil group are in agreement with the results of other studies.

Electrophysiological mechanisms for the antiarrhythmic action of mexiletine on digitalis-, reperfusion- and reoxygenation-induced arrhythmias.

The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.

Electrophysiological mechanism for the antiarrhythmic action of propafenone: a comparison with mexiletine.

1. The antiarrhythmic potency of propafenone was evaluated in the guinea-pig isolated heart; arrhythmias were induced with (a) digitalis intoxication and (b) hypoxia followed by reoxygenation. 2. Propafenone, 0.5 microM, was found to be the minimal but effective antiarrhythmic concentration. The antiarrhythmic activity of propafenone developed slower than that of 10 microM mexiletine, which was the lowest effective concentration under the same experimental conditions. 3. The electrophysiological effects of propafenone were then studied on sheep cardiac Purkinje fibres (manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin) and compared with those of 10 microM mexiletine. 4. Both 0.5 microM propafenone and 10 microM mexiletine consistently blocked triggered activity in sheep Purkinje fibres. The onset of the effect of propafenone was slower than that of mexiletine. 5. Unlike mexiletine, propafenone did not reduce the amplitude of oscillatory afterpotentials. 6. In contrast, propafenone significantly reduced Vmax in barium- and strophanthidin-treated preparations. 7. It is concluded that the antiarrhythmic action of propafenone on digitalis- and reoxygenation-induced arrhythmias is probably due to an electrophysiological mechanism different from that of mexiletine. Mexiletine, by reducing the amplitude of oscillatory afterpotentials, prevents the attainment of the threshold; propafenone, by reducing the excitability of the cell, increases the threshold and consequently an oscillatory afterpotential of the same amplitude will not generate arrhythmias.

Lack of correlation between the antiarrhythmic effect of L-propionylcarnitine on reoxygenation-induced arrhythmias and its electrophysiological properties.

1. The antiarrhythmic effect of L-propionylcarnitine (L-PC) was evaluated in the guinea-pig isolated heart; arrhythmias were induced with hypoxia followed by reoxygenation and by digitalis intoxication. 2. L-PC 1 microM, was found to be the minimal but effective antiarrhythmic concentration against reoxygenation-induced ventricular fibrillation. No antiarrhythmic effect was observed against digitalis-induced arrhythmias. D-Propionylcarnitine, L-carnitine and propionic acid did not exert antiarrhythmic effects. 3. During hypoxia and reoxygenation L-PC consistently prevented the rise of the diastolic left ventricular pressure, and significantly reduced the release of the cardiac enzymes creatine kinase (CK) and lactic dehydrogenase (LDH). 4. The electrophysiological effects of L-PC were then studied on either normal sheep cardiac Purkinje fibres or those manifesting oscillatory after potentials induced by barium or strophanthidin. 5. L-PC (1 and 10 microM) did not significantly modify action potential characteristics and contractility of normal Purkinje fibres, or the amplitude of OAP induced by strophanthidin or barium. 6. It is concluded that the antiarrhythmic action of L-PC on reoxygenation-induced arrhythmias is not correlated with its direct electrophysiological effects studied on normoxic preparations.

Cardiac aging, calcium overload, and arrhythmias.

The effect of aging was tested on experimental ventricular arrhythmias in isolated heart preparations from normal Wistar rats (NWR), Wistar Kyoto rats (WKY), and spontaneously hypertensive rats (SHR). Delayed afterdepolarizations and triggered activity induced by high-calcium perfusion (16 mM) in isolated papillary muscles were more frequent in the 24-month-old than in 6-month-old NWR. Reperfusion-VA were more severe in 14-month-old SHR than in WKY. The authors have previously shown that: (1) reperfusion- and reoxygenation-induced VA, in the isolated Langendorff perfused heart, were significantly more severe and frequent in 24-month-old than in 6-month-old NWR; (2) no age-related difference in the incidence of programmed electrical stimulation (PES, train of stimuli + 1 or 2 extrastimuli)-induced VA was observed in isolated NWR hearts during control perfusion, after coronary artery ligation or during hypoxia; (3) on the contrary, the incidence of PES-induced VA was significantly higher in isolated hearts from 14-month-old SHR than from 3-month-old SHR, and 3-month-old and 14-month-old WKY. It was concluded that "physiological" aging is associated with a higher propensity to calcium-related VA, while "pathological" aging characterized by hypertension of long duration increases the incidence of PES-induced VA, probably caused by myocardial fibrosis, which could facilitate reentry.

The impact of age on risk of adverse drug reactions to digoxin. For The Gruppo Italiano di Farmacovigilanza nell' Anziano.

To assess the association of age and other potential risk factors with digoxin toxicity, adverse drug reactions to digoxin (ADRDIG) were studied in all patients (n = 1338) on digoxin therapy consecutively admitted to 41 clinical wards throughout Italy during 4 months in 1988. At the time of admission, 28 patients (2.1%) had evidence of ADRDIG. In multivariate logistic regression analysis, significant associations with ADRDIG were found for age > or = 80 years compared to age 65-79 years (OR = 2.75, 95% CI = 1.17-6.45), daily digoxin dosage of > or = 0.25 mg (OR = 2.51, 95% CI = 1.16-5.47), serum creatinine > or = 120 mumol/L (OR = 3.75, 95% CI = 1.69-8.32), and for treatment with amiodarone, propafenone, quinidine or verapamil (OR = 2.60, 95% CI = 1.07-6.30). Those aged < 65 years had a similar risk of digoxin toxicity as those aged 65-79 years (OR = 1.07, 95% CI = 0.28-4.12). Adverse drug reactions to digoxin were found in 1 in 50 patients hospitalized on digoxin therapy. Patients aged 65-79 years were not at increased risk for digoxin toxicity compared to younger patients, while advanced age (> or = 80 years) was an independent risk factor for this outcome.

Age and severe adverse drug reactions caused by nifedipine and verapamil. Gruppo Italiano di Farmacovigilanza nell' Anziano (GIFA).

The association of age with risk for severe adverse drug reactions (SADRs) was studied in 2371 and 862 hospitalized patients taking nifedipine and verapamil, respectively. Nifedipine caused hypotension (n = 22), tachycardia (n = 3), and acute renal failure (n = 1) (total SADR rate, 1.1%, 26/2371). Verapamil caused hypotension (n = 3), bradycardia (n = 9), and atrioventricular blocks (n = 2) (total SADR rate, 1.6%, 14/862). The mean age of patients with and without SADRs was for nifedipine 77.1 +/- 1.7 and 71.8 +/- 0.8 years, respectively (p < 0.05), and for verapamil 73.4 +/- 2.9 and 73.1 +/- 0.4 years, respectively. Sex, length of stay, comorbidity, polypharmacy, intake of slow-release preparations, daily dosage, and new intake of calcium antagonists were examined as potential confounders of the age-SADR association. After adjusting for potential confounders, age was significantly and independently associated with SADRs caused by nifedipine, but not with SADRs caused by verapamil (OR = 1.69, 95% CI = 1.05-2.72 and OR = 1.06, 95% CI = 0.63-1.68 for 10-year increase, respectively). Although nifedipine and verapamil did not have significantly different rates of SADRs, an age-related gradient was found only for nifedipine.

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.

Is age an independent risk factor of adverse drug reactions in hospitalized medical patients?

OBJECTIVE: To study the incidence and the risk factors of adverse drug reactions. DESIGN: Multicenter survey. SETTING: Hospitalized care: 22 internal medicine and 19 geriatric wards. PATIENTS: All patients (n = 9,148) consecutively admitted during two observation periods of 2 months. MAIN OUTCOME MEASURE: Incidence of adverse drug reactions. RESULTS: The mean age was 67.1 +/- 0.17 years (median 72); the mean duration of hospital stay was 18.1 +/- 0.19 days (median 14). Each patient was administered 5.1 +/- 0.03 (median 5) drug prescriptions. The incidence of probable or definite adverse drug reactions was 5.8% (532/9,148). In univariate analysis, the incidence of adverse drug reactions increased from 3.3% at under age 50 to 6.5% at age 70-79 and decreased over age 80 (5.8%). In multivariate logistic regression, taking more than four drugs (OR = 2.94, CI = 2.38-3.62), staying in hospital more than 14 days (OR = 2.82, CI = 2.26-3.52), having more than 4 active medical problems (OR = 1.78, CI = 1.29-2.45), staying in a medical ward instead of geriatric ward (OR = 1.33, CI = 1.09-1.63), and drinking alcohol (OR = 1.28, CI = 1.03-1.58) were positively correlated with adverse drug reactions occurrence (P less than 0.05). Age, gender, and smoking cigarettes were not significant predictors of adverse drug reactions. CONCLUSION: Age is not an independent risk factor of adverse drug reactions, and good geriatric care can reduce the incidence of adverse drug reactions.

Ostium secundum atrial septal defect in the elderly.

Atrial septal defect (ASD) is one of the most common congenital cardiac anomalies in adults. Life expectancy is shortened, and almost 90% of patients die by the age of 60 years. The progression of this congenital disease to congestive heart failure has been related to several factors such as the onset of pulmonary hypertension, arrhythmias, bronchopulmonary infections, or the development of other cardiovascular disease. We describe three cases of very old patients with significant ASDs and late development of symptoms. Given the higher risks and poorer long-term results of surgical closure of the defect in advanced age, the indications for such an intervention in elderly patients should be carefully evaluated.

Long-term survival and use of antihypertensive medications in older persons.

OBJECTIVE: To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors have a different risk of mortality than those using beta-blockers. DESIGN: A prospective cohort study continuing from 1988 through 1992. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Hypertensive participants aged > or = 71 years (n = 906) who had no evidence of congestive heart failure and who were using either beta-blockers (n = 515), verapamil (n = 77), diltiazem (n = 92), nifedipine (n = 74), or ACE inhibitors (n = 148). Nifedipine was of the short acting variety. MEASUREMENTS: The main outcome measure was all-cause mortality. Age, gender, smoking, HDL-cholesterol, blood pressure, intake of digoxin and diuretics, physical disability, self-perceived health, and comorbid conditions were examined as confounders. RESULTS: During 3538 person-years of follow-up, 188 participants died (53 deaths per 1000 person-years). Compared with beta-blockers, after adjusting for age, gender, comorbid conditions and other health-related factors, the relative risks (95% confidence interval) for mortality associated with use of verapamil, diltiazem, nifedipine, and ACE inhibitors were 0.8 (0.4-1.4), 1.3 (0.8-2.1), 1.7 (1.1-2.7), and 0.9 (0.6-1.4), respectively. The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics. Higher doses of nifedipine were associated with higher mortality. CONCLUSION: Compared with beta-blockers, use of short acting nifedipine was associated with decreased survival in older hypertensive persons. However, selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted, and final conclusions will depend on clinical trials.