Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm® - and placebo-controlled trial (BRIDGE).

BACKGROUND: Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient. OBJECTIVES: To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm® , in adults with moderate-to-severe chronic plaque psoriasis. METHODS: In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of 'clear' or 'almost clear' in the Physician's Global Assessment (PGA) at week 16. RESULTS: In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm® ; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm® : P < 0·001). Overall, 33% of patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm® . Most treatment-related adverse events were classed as 'mild' in severity. CONCLUSIONS: LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.

Faecal carriage of oxyiminocephalosporin-resistant Enterobacteriaceae among paediatric units in different hospitals in the south of France.

The aim of this study was to determine the presence of oxyiminocephalosporin-resistant (OCR) Gram-negative bacilli and extended-spectrum ß-lactamase (ESBL)-producing isolates in stool specimens obtained from paediatric patients hospitalised for acute diarrhoea. We conducted a prospective, multicentre study over a period of 6 months in seven hospitals in the south of France. Samplings were carried out from infants admitted for acute diarrhoea with no previous antibiotic treatment in the last week. Bacteria in stool specimens were screened for the presence of OCR Gram-negative bacilli on Drigalski agar supplemented with ceftazidime and ESBL CHROMagar® media, and confirmed by the Rosco tablets test. Genetic detection was performed by the Check MDR® microarray and by polymerase chain reaction (PCR) and sequencing with bacterial DNA extracted from isolates. The presence of OCR enterobacteria was markedly high (177/1,118 patients, 15.2 %), with an important community origin (66.1 %). The majority of multidrug-resistant (MDR) bacteria were Enterobacter cloacae (106, 59.9 %) and Escherichia coli (61, 34.5 %). The prevalence of ESBL and CTX-M producers represented 5.2 and 4.3 % of the isolates, respectively. The main proportion of these ESBL carriers was found in children less than 1 year of age (53.4 %). One carbapenemase (IMP-1) was detected. The study revealed the wide dissemination of MDR bacteria in infants attending hospitals in the south of France during a non-outbreak situation, in particular, the spread of cefotaximase and the detection of a carbapenemase. This worrisome situation must reinforce the use of hygiene procedures and appropriate antibiotics to control the emergence and spread of OCR organisms.

Bronchodilatory effects of aclidinium bromide, a long-acting muscarinic antagonist, in COPD patients.

BACKGROUND: Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist bronchodilator currently in Phase III clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacodynamics, pharmacokinetics, safety and tolerability of ascending doses of aclidinium bromide in patients with COPD. METHODS: This double-blind, randomised, placebo-controlled, crossover study was conducted in patients with moderate to severe COPD (forced expiratory volume in 1s [FEV(1)] <65% predicted). Patients were randomly assigned to one of four treatment sequences of aclidinium bromide 100, 300, 900microg and placebo with a washout period between doses. The primary outcome was area under the FEV(1) curve over the 0-24h time interval. RESULTS: Seventeen patients with COPD were studied. Mean FEV(1) over 24h was 1.583L for placebo, and 1.727L, 1.793L and 1.815L for aclidinium bromide 100, 300 and 900microg, respectively (p<0.001 vs. placebo, all doses). Significant changes from baseline in FEV(1) were detected 15min post-dose for aclidinium bromide 300 and 900microg, with a peak effect 2h post-dose (all doses). Aclidinium bromide was undetected in plasma. The majority of adverse events was unrelated to study medication and did not result in discontinuation. CONCLUSION: Aclidinium bromide 100-900microg produced sustained bronchodilation over 24h in patients with COPD.

Aclidinium bromide provides long-acting bronchodilation in patients with COPD.

Aclidinium bromide is a novel, long-acting, muscarinic antagonist in phase III development for the maintenance treatment of COPD. This phase IIb study investigated the efficacy and safety of aclidinium for the treatment of moderate to severe COPD to establish the optimal dose for phase III studies. A total of 464 patients with moderate to severe stable COPD were randomised to double-blind, once-daily treatment with aclidinium (25, 50, 100, 200, or 400microg), placebo, or open-label tiotropium (18microg) for 4 weeks. Spirometric measurements were performed at 22-24h after the first dose and then at weekly intervals, and from 0.5 to 6h post-dose on day 1 and day 29. Compared with placebo, aclidinium 200microg and 400microg significantly increased trough FEV(1) on day 29 versus baseline. During the first 6h post-dose, the bronchodilatory effect of aclidinium (all doses) on day 1 was comparable to that on day 29. Time to peak FEV(1) was 3h for aclidinium 100-400microg. Aclidinium was well tolerated, with no dose-dependent effect on ECG, laboratory parameters, or adverse events. The incidence of AEs was generally comparable to placebo. Aclidinium produced sustained bronchodilation over 24h and was well tolerated during this short-term study. Based on these data, aclidinium 200microg was selected as the investigational dose for future clinical trials in COPD.

Safety and pharmacokinetics of single doses of aclidinium bromide, a novel long-acting, inhaled antimuscarinic, in healthy subjects.

OBJECTIVE: Aclidinium bromide is a novel antimuscarinic being developed for the treatment of chronic obstructive pulmonary disease. The objective of this Phase I study was to determine the maximum tolerated dose (MTD) as well as the tolerability, safety and pharmacokinetics of aclidinium in healthy subjects. MATERIALS AND METHODS: 16 healthy subjects were randomized to receive 5 single ascending doses of aclidinium 600 - 6,000 microg or placebo inhaled via dry powder inhaler, with 7 day washouts. Safety measurements included adverse events (AEs), physical examination, vital signs, pupillometry examination, clinical laboratory tests, and 12-lead electrocardiogram. Pharmacokinetic parameters of aclidinium and its metabolites were assessed. RESULTS: The incidence of AEs was comparable between aclidinium and placebo at all doses. Most AEs were mild to moderate with no dose-related or anticholinergic/cardiac AEs. At doses >or= 2,400 microg, only 13 AEs were considered treatment related. Aclidinium (600 - 6,000 microg) did not produce function-limiting or severe AEs in >or= 50% of subjects; hence, the prospectively-defined MTD was not established. Aclidinium was rapidly converted in plasma into alcohol and carboxylic acid metabolites, and was no longer detectable after 3 hours post-dose for all doses. At lower doses, aclidinium was quantifiable only up to 1 hour post-dose in the majority of subjects. Maximum plasma concentrations for aclidinium were reached within 5 - 7 minutes (all doses) and declined rapidly. Mean elimination half-lives of aclidinium > 2,400 microg were approximately 1 hour. AUC and Cmax increased proportionately up to 4,800 microg. CONCLUSIONS: Aclidinium appears to be safe and well tolerated in single doses of 600 - 6,000 microg.

Lung deposition of aclidinium bromide from Genuair, a multidose dry powder inhaler.

BACKGROUND: Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist currently in development for the treatment of chronic obstructive pulmonary disease (COPD). A next-generation multidose dry powder inhaler will be used for the delivery of aclidinium bromide. OBJECTIVES: To quantify whole lung deposition and regional lung deposition of aclidinium delivered by a multidose dry powder inhaler (Genuair) in healthy subjects. METHODS: A single dose (200 microg) of aclidinium bromide, radiolabelled with (99m)Tc, was administered from the multidose dry powder inhaler at a targeted peak inspiratory flow rate (PIFR) of 90 litres/min in 12 healthy males (18-63 years). Gamma scintigraphy was used to quantify drug deposition in the lungs and oropharynx, as well as amounts retained in the inhaler and exhaled. The quantities of drug deposited in 6 concentric regions within the lungs were also determined. RESULTS: The mean (+/- SD) PIFR was 79.0 +/- 9.4 litres/min. The mean (+/- SD) percentages of the metered dose deposited in the whole lung and oropharynx were 30.1 +/- 7.3 and 54.7 +/- 7.2%, respectively. Deposition of aclidinium occurred in all 6 lung zones, but was highest in the most central zone. CONCLUSIONS: These results demonstrated that the multidose dry powder inhaler delivered aclidinium efficiently to the lungs. The whole lung deposition seen in this study is an indication of the likely whole lung deposition in COPD patients who inhale with similar PIFRs; however, further studies in patients are required to confirm this.

Treatment and quality of life in patients with chronic obstructive pulmonary disease.

Treatments administered to patients with chronic obstructive pulmonary disease (COPD), especially when used in multiple combinations, are not free of interactions and side effects that can potentially impair health-related quality of life (HRQL). We studied HRQL and its relationship with treatment in a group of 441 patients with stage II or III COPD (age: 66.6 (SD: 8.3) years; FEV1: 32.4% (SD: 8.1%)) using the St George's Respiratory Questionnaire (SGRQ) and the 12-item short form (SF-12) Health Survey. The most prescribed drugs were ipratropium bromide (87.5%), inhaled corticosteroids (69.4%) and short-acting beta-2 agonists (64.9%). Patients with stage III of the disease were receiving more drugs, particularly short-acting beta-2 agonists (p = 0.002) and inhaled corticosteroids (p = 0.031). The use of theophyllines was associated with a worse total SGRQ score (beta = 4.49; p < 0.001), although this negative association decreased with advanced age. A trend towards worse SGRQ scores was observed with the use of high doses of long-acting beta-2 agonists (beta = 3.22; p = 0.072). Patients receiving three drugs or more presented worse total SGRQ scores than patients receiving fewer drugs (beta = 6.1, p < 0.001; and beta = 7.64, p < 0.001, respectively). These findings suggest that the use of multiple drugs in the treatment of patients with COPD is associated with worse total SGRQ scores. The effect of drugs, their dosages and associations with other drugs on HRQL merit further research.

Performance of a perceived health measure in different groups of the population: a comprehensive study in Spain.

The metric properties of health-related quality of life measures are typically evaluated on selected samples and assumed to hold across different population groups. We assessed the extent to which the measurement properties of the Spanish version of the Nottingham Health Profile (NHP) were stable across sociodemographic, clinical and geographical characteristics. We collected information from all available studies using the NHP in Spain (1986-1995), and obtained data from 9419 individuals. We examined data completeness and distribution, as well as reliability and construct validity. The percentage of missing dimensions was lower than 5%, but increased with age and poor health status. Large ceiling effects in scores were observed for social isolation and energy dimensions, being largest for younger ages and individuals reporting "very good/good" health. Reliability was higher than 0.7 in all population groups considered, except for social isolation and energy dimensions in some subgroups. Mean NHP scores correlated with self-rated overall health (r = 0.48), but they varied substantially by age among those rating their health as "very good/good." We conclude that NHP is adequate for all Spanish populations. Nevertheless, some caution is needed because the reliability of dimension scores is not sufficient for individual purposes. And also, because a non-negligible high ceiling effect renders the instrument inefficient to measure changes over time among healthy populations.

[Effectiveness and cost of total hip replacement in seven hospitals in Catalonia, Spain]. / Efectividad y costes de la intervención de prótesis total de cadera en siete hospitales de Cataluña.

BACKGROUND: To quantify short-term benefits of total hip replacement, prognostic factors of the outcome, and to assess hospital costs of this surgical procedure in Catalonia, Spain. PATIENTS AND METHODS: Multicentric prospective study in seven hospitals in Catalonia. All patients undergoing this procedure in one year were included. They were evaluated prior to the operation, and six months later. This evaluation involved: clinical assessment, the Hip Pain and Function Scale, the Nottingham Health Profile (NHP), and the EuroQol (EQ-5D), in order to measure cost-utility. Hospital costs were estimated by means of a specific questionnaire. RESULTS: Information was obtained for 332 patients. The mean age was 65 years (range: 27-89 years); 58% were women; the most common diagnosis was arthritis; 59% of patients had associated pathology and 13% presented some type of postoperative complication. The improvement in health status was important according to all instruments. An outcome of "excellent" or "good" was achieved by 70.8% of the patients, in terms of hip function and pain. The factors associated with not achieving an outcome of this level were: associated pathology, complications, diagnoses other than arthritis, and operation carried out in a tertiary hospital. The total cost of the procedure was 838,480 pesetas. This average varied significantly with the cost of the prosthesis, and as a function of the length of stay. The three-year cost-utility of the procedure was estimated as 507,500 pesetas. CONCLUSIONS: Total hip replacement greatly improves the pain, hip function and overall perceived health of the patient. This improvement is greater among patients with a diagnosis of arthritis, with good overall health, operated on by a surgeon experienced in this procedure. The benefit is high in relation to the cost, although there is a margin for improvement, reducing complications, shortening length of stay, and controlling the price of implants.

Evolution of self-rated health status in the elderly: cross-sectional vs. longitudinal estimates.

We assessed the perceived health status evolution among elderly subjects and examined the age-related differences in perceived health when comparing estimates obtained from cross-sectional and longitudinal approaches. Data come from a cohort of non-institutionalized individuals aged 65 years or older, living in Barcelona, Spain. One thousand three hundred fifteen (1315) elderly were successfully interviewed at baseline in 1986 and 754 (84.6% of the eligible) at the re-assessment (1993-1994). Estimates of change in perceived health status were calculated based on cross-sectional and longitudinal approaches. Cross-sectionally, no significant differences in the proportion of individuals with poor self-rated health were found (40.5 vs. 42.5%, P = 0.90). Among survivors, the proportion of individuals with poor health increased from 37.8% to 55.1% (P < 0.01), an 8.7-fold decline of perceived health when compared with the cross-sectional estimates. Comorbidity (aOR 2.1; 95%CI: 1.4-3.3) and no education (aOR 1.9; 95%CI: 1.1-3.2) were associated with a decline in health status after adjusting by baseline health status. We recommend the use of longitudinal studies to understand the evolution of perceived health in the elderly.

The pain and function of the hip (PFH) scale: a patient-based instrument for measuring outcome after total hip replacement.

The Pain and Function of the Hip (PFH) scale was developed following the recommendations of the Société International de Chirurgie Orthopedique et Traumatologie to assess the outcomes of total hip replacement (THR). This study evaluated metric properties of the PFH scale and its ability to measure clinical change (responsiveness) in consecutive patients undergoing THR. Patients were evaluated preoperatively and at 3 and at 12 months postoperatively. The PFH scale and the Nottingham Health Profile (NHP) were administered. Complete data were collected for 79 patients. Mean overall preoperative PFH score was 26.5 and mean overall PFH score 12 months postoperatively was 69.8 (P < .01). Correlation with the NHP was high (r = -0.64), and the magnitude of improvement (effect size) as assessed by the PFH scale was large (3.6 compared with 1.7 for the NHP). The PFH scale is simple and valid, and may complement routine clinical evaluation of hip replacement. Residual pain after hip replacement may have been previously underestimated.

[Factors predicting return home of hospitalized aged patients]. / Factores predictivos de retorno al domicilio en pacientes ancianos hospitalizados.

BACKGROUND: The identification of predictors of return home and nursing home placement in elderly patients, at the moment of admission to a Geriatric Convalescence Unit, may allow to make a discharge planning for these patients, and also may improve efficiency in the unit. PATIENTS AND METHODS: A number of 445 patients over 65 years were consecutively admitted to the unit. Analyzed variables at admission were; age, sex, diagnostic, comorbidity, functional status prior to admission, degree of independence in activities of daily living (Barthel index), cognitive function (Folstein Mini-Mental) and social support (modified version of social-familiar evaluation scale of Gijón). All these variables were used in two models of logistic regression analysis: 1 [symbol: see text] (dependent variable: return home after discharge versus other destinations), and 2 [symbol: see text] (dependent variable: nursing home placement on discharge versus other destinations). RESULTS: The variables significatively associated with greater probability of at home discharge were: moderate dependency for activities of daily living (Barthel index = 31-59), odds ratio (OR) = 2.46 (95% confidence interval: 1.43-4.22); mild dependency (Barthel index > or = 60), OR = 3.67 (1.96-6.87); normal cognitive function (Mini-Mental > or = 21), OR = 3.14 (1.76-5.60), and a favourable social support (social-familiar scale < 12), OR = 7.33 (3.18-16.91). The only variable significatively associated with the probability of nursing home placement after discharge was an impaired social function (social-familiar scale > or = 12), OR = 4.53 (2.25-9.12). CONCLUSIONS: Probability of return home after discharge is associated with functional status, cognitive function and social support. Definitively nursing home placement was only related with de degree of familiar support.

Comparison of performance-based and self-rated functional capacity in Spanish elderly.

Recent data have shown differences between Spain and the United States in the prevalence of reported disability among community elderly. Differences in reporting functional capacity by culture may contribute to these observed differences. The purpose of this study was to estimate the agreement between self-report of disability and performance-based measures for some basic mobility tasks in the community-dwelling elderly of a Mediterranean country. Interviews containing questions about difficulty for walking and rising from a chair, and performance-based measures (walking speed and chair stand tests) were carried out in 626 individuals aged 72 years and older in Barcelona, Spain. Kappa statistics were calculated, and logistic regression models were constructed to identify possible factors associated with under- and overreporting functional capacity. Moderate kappas (0.41-0.55) were found between self-report and performance-based measures. Patients who rated their health as "poor or very poor" were less likely to underreport disability (adjusted odds ratio (OR) = 0.2, 0.4) but more likely to overreport it (adjusted OR = 23.4, 9.9). No significant agreement differences by sex or informant source were found. These findings suggest that Spanish elderly self-report functional capacity accurately and that, contrary to previous results among US elderly, the direction of the observed disagreement is not systematic.

Rasch measurement for reducing the items of the Nottingham Health Profile.

The present study aimed to develop a short form of the Spanish version of the Nottingham Health Profile (NHP) by means of Rasch analysis. Data from several Spanish studies that included the NHP since 1987 were collected in a common database. Forty-five different studies were included, covering a total of 9,419 subjects both from the general population and with different clinical pathologies. The overall questionnaire (38 items) was simultaneously analyzed using the dichotomous response model. Parameter estimates, model-data fit and separation statistics were computed. The items of the NHP were additionally regrouped into two different scales: Physical (19 items) and Psychological (19 items). Separated Physical and Psychological parameter estimates were produced using the simultaneous item calibrations as anchor values. Misfitting items were deleted, resulting in a 22 item final short form (NHP22)-11 Physical and 11 Psychological-. The evaluation of the item hierarchies confirmed the construct validity of the new questionnaire. To demonstrate the invariance of the NHP22 item calibrations, Rasch analyses were performed separately for each study included in the sample and for several sociodemographic and health status variables. Results confirmed the validity of using the NHP22 item calibrations to measure different groups of people categorized by gender, clinical and health status.

Left-truncated data with age as time scale: an alternative for survival analysis in the elderly population.

BACKGROUND: The standard approach for survival analysis of the elderly population is to define the survival time as the elapsed time from entry into the study until death, and to adjust by age using stratification and regression procedures. However, the interest is in the study of the aging process and the risk factors related to it, not in the use of time-on-study as the time scale. Here, we present methods to use age as the time scale and compare inferences and interpretations with those obtained using the standard approach. METHODS: A total of 1,315 individuals aged 65 years or older from the city of Barcelona, Spain, were interviewed in 1986 (baseline). The vital status of the cohort was assessed in October 1994. To illustrate the usefulness of age as time scale (alternative approach) instead of time-on-study in the survival analysis of the elderly population, both methods were used to assess the relationship between baseline functional capacity and mortality. RESULTS: Using the alternative approach, we observed that 50% of the sample died at age 80.6 years; this information could not be estimated with the standard approach. Using age as a covariate in the standard analysis with time-on-study as the time scale and using age as the time scale in the alternative analysis, the association of functional capacity at baseline and mortality was of similar magnitude under both analyses. Nevertheless, using the alternative approach, relative risks were slightly lower, and the adjustment by age was tight and was not subject to the inherent assumptions in regression models of the functional relationship of independent variables with outcome. We illustrated the methods with fixed covariates (i.e., gender) and baseline values of time-dependent covariates (i.e., functional capacity), but we discussed the extension of our methods for the analysis of time-dependent covariates measured at several visits in a cohort study. Methods proposed here are easily implemented with widely available statistical software packages. CONCLUSIONS: Although the use of standard survival analysis generally produces correct estimates, the use of age as time scale is deemed more appropriate for survival analysis of the elderly: Inferences are easier to interpret and final models are simpler. We therefore recommend the use of age as time scale for survival analysis of the elderly population.

[Renal artery stenosis and chronic renal failure in NIDDM]. / Sténose de l'artère rénale et insuffisance rénale chronique chez le diabétique de type II.

The NIDDM patient, willingly with high blood pressure and atheroma, has frequently an abnormal renal function. Must a renal artery stenosis (RAS) be searched as a determining or favorising cause? We have searched RAS by color duplex scan, in 60 consecutive NIDDM patients with altered renal function (creatinine clearance < or = 60 mL/min). Metabolic blood pressure (ABPM), cardiovascular and renal investigations have been realised. The population was composed of 22F/38M with middle age: 70.7 +/- 6.2 yrs, diabetic duration: 11.6 +/- 8 yrs, the plasma creatinine was: 161 +/- 78 mumol/L and clearance: 40 +/- 13 mL/min. Thirty eight had albuminuria, 28 had plasma creatinine > or = 150 mumol/L. All patients had high blood pressure. Significative RAS (> or = 70%) was detected in 15 patients (25%) by color duplex scan and proved with arteriography (n = 10) or angio NMR (n = 5). Twelve (80%) had unilateral stenosis (4 thrombosis), 3 (20%) bilateral stenosis. Renal US lead the diagnosis in 10 patients (66%): unilateral or bilateral hypotrophy. Those 15 patients had these following characteristics: 4F/11M (sex R : 0.36), middle age: 70.8 +/- 7.2 yrs, diabetic duration: 14.3 +/- 7.5 yrs, HbA1c was at 8.4 +/- 2%, 8 (53%) patients require insuline and 5 have retinopathy, plasma creatinine was at 169 +/- 6 mumol/L; 32% of patients with plasma creatinine > or = 150 mumol/L had RAS (n = 9/60%), creatinine clearance was at 38 +/- 12 mL/min (7/47% < or = 30 mL/min), 9 (60%) had macroalbuminuria and 5 (33%) microalbuminuria. All hypertensive patients were treated (mean SBP: 148 +/- 16, mean DBP: 82 +/- 7 mmHg) and had 62 +/- 28% SBP escape and 33 +/- 19% DBP escape. Ten had severe hypertension (at least 3 hypotensive drugs), 12 received CEI; 8 (53%) were smokers; 14 (93%) had one or more macroangiopathies (10/66% coronary heart diseases, 7/46% lower limbs arteritis, 6/40% carotid atheroma); 13 of these macroangiopathies are severe. In conclusion, renal failure (especially evolutive and/or treated with CEI) in NIDDM must call up a RAS (25%) specially in elderly males with a long diabetes duration, severe hypertension and macroangiopathies. This patient profile must lead to a color duplex scan to confirm the diagnosis already suspected by the renal echography.

Smoking after age 65 years and mortality in Barcelona, Spain.

The objective of this study was to assess the risk of dying associated with smoking after the age of 65 years and the benefits of quitting smoking, taking into account baseline health status. The study was carried out in Barcelona, Spain, a southern European city with an increase in smoking prevalence and lifestyle different from those of other areas where hazards of smoking have been studied. A follow-up study begun in 1986 was carried out in 477 males (94.3% of the original cohort) who were randomly selected by census from members of the Barcelona general population aged > or =65 years. Vital status as of October 1994 and, where applicable, cause of death (cardiovascular disease, cancer, or respiratory disease) were assessed. The relative risk of dying was 2.11 (95% confidence interval (CI) 1.37-3.26) times higher in current smokers and 1.53 (95% CI 1.03-2.27) times higher in former smokers than in never smokers. Quitting smoking after the age of 65 years reduced the relative risk of dying to 0.77 (95% CI 0.51-1.16) in comparison with continuing to smoke, although persons who stopped smoking had poorer self-perceived health and were more frequently reported to suffer from cardiovascular disease (p < 0.05). This study confirms that the effects of smoking extend to later life in this elderly general population, with a magnitude as great as that seen in previous studies with different populations. In addition, it indicates that stopping smoking after age 65 reduces the risk of dying.