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Biomedical subjects

Javier Llorca

Publications and source records attributed to Javier Llorca.

At least 37 records · Page 2Linked to original sources

Mortality of multiple sclerosis in Spain: demonstration of a north-South gradient.

OBJECTIVE: To analyse the geographical distribution of multiple sclerosis in Spain from 1975 to 1998. METHODS: Age-adjusted mortality rates by province were obtained by the indirect method using the whole Spanish population as the reference. Then, standardised mortality ratios (SMRs) and their 95% confidence intervals were estimated. RESULTS: For both men and women, provinces with SMRs higher than the mean tended to be in the northern third of Spain, whilst those with SMRs lower than the mean were mostly located in the southern half. A linear regression analysis showed a significant positive association between mortality and latitude. CONCLUSION: A north-south gradient in age-adjusted multiple sclerosis mortality exists in Spain.

Adult↗

Survival analytical techniques were used to assess agreement of a quantitative variable.

BACKGROUND AND OBJECTIVE: Survival-agreement plots have been suggested as a new graphical approach to assess agreement in quantitative variables. We propose that survival analytical techniques can complement this method, providing a new analytical insight for agreement. METHODS: Two survival-agreement plots are used to detect the bias between to measurements of the same variable. The presence of bias is tested with log-rank test, and its magnitude with Cox regression. RESULTS: An example on C-reactive protein determinations shows how survival analytical methods would be interpreted in the context of assessing agreement. CONCLUSION: Log-rank test, Cox regression, or other analytical methods could be used to assess agreement in quantitative variables; correct interpretations require good clinical sense.

Bias↗

Reoperations after tricuspid valve repair.

OBJECTIVE: The objective was to analyze the short- and long-term results of patients with previous tricuspid valve repair who had valve dysfunction and required cardiac reoperations. METHODS: Between 1976 and 2002, 74 patients with a mean age of 53.8 +/- 12.2 years underwent valve reoperations for dysfunction of previous tricuspid valve repair. Mitral and tricuspid lesions were diagnosed in 40 patients (54%), triple valve disease (mitral, aortic, tricuspid) was diagnosed in 26 patients (35.1%), isolated tricuspid disease was diagnosed in 6 patients (8.1%), and aortic and tricuspid lesions were diagnosed in 2 patients (2.7%). Reoperations included tricuspid valve replacement in 43 patients (58.1%) and a new tricuspid valve repair procedure in the remaining 31 patients (41.9%). RESULTS: Hospital mortality (30-day or within first admission) was 35.1% (n = 26). In the multivariate analysis, risk factors for hospital mortality included body mass index less than 20 kg/m2 and greater than 24 kg/m2 , triple valve disease, use of intra-aortic balloon counterpulsation, and presence of postoperative complications. The follow-up was complete in 100% of patients, with a mean follow-up of 14.2 years (range 4 months to 26 years). The late mortality was 40.5% (n = 30). Predictors of late mortality were body mass index less than 20 kg/m2 , cardiac surgery before 1991, and development of dysfunction early after tricuspid valve repair. At the follow-up closing date, 19 patients are alive (25.7%). The actuarial survival was 11.8% +/- 4.9% at 26 years. CONCLUSIONS: Patients with failure of a tricuspid valve repair procedure requiring reoperation have a poor prognosis with a high mortality rate both in-hospital and in the long-term.

Adult↗

Quality of controlled clinical trials on glaucoma and intraocular high pressure.

AIM: To study the quality of controlled clinical trials on glaucoma. METHODS: Two hundred and twenty-six clinical trials published between 1980 and 1999 were selected from seven international ophthalmological journals. Their quality was assessed by four researchers with epidemiological skills using a structured questionnaire. RESULTS: Sample size was pre-estimated in 34 (15.0%) papers, which were of greater size (P = 0.05). Randomization was performed in 98.2% of the trials, although the procedure of randomization was scarcely reported. Masking was reported in 56.6% of the papers, and was more frequent in medical treatments (P < 0.001). The basal characteristics of the groups were compared in 139 papers (61.5%). Patient losses during the follow-up period were fully described in only 27 trials. Intention-to-treat analysis was used in 17 (7.7%) papers. Most trials reported P values, but a measure of effect (mean, proportion, or relative risk) appeared in only 16 trials (7.7%). Trials performed in the US more frequently compared baseline characteristics of the groups (P = 0.03), described the patient flow (P = 0.04), and used adequate statistical procedures (P = 0.03). Those trials that included a statistician or an epidemiologist among the authors were more commonly blinded (P = 0.06) and they always avoided the analyses of subgroups (P = 0.006). Several methodological issues have improved throughout the studied period. CONCLUSIONS: Several methodological characteristics should be improved when reporting a clinical trial on glaucoma. Using a checklist like that suggested by the CONSORT can help to achieve this.

Controlled Clinical Trials as Topic↗

Giant cell arteritis: disease patterns of clinical presentation in a series of 240 patients.

Classically, patients with giant cell arteritis (GCA) present with cranial ischemic manifestations that are directly related to vascular involvement. However, a variable proportion of GCA patients may present without obvious vascular manifestations. Since a high index of suspicion of this condition in individuals over the age of 50 years is needed to prevent the development of severe complications, we have studied the different patterns of disease presentation in a series of 240 patients with biopsy-proven GCA diagnosed at the single hospital for the well-defined population of Lugo, Spain, between January 1, 1981, and June 15, 2004. During the study period, 203 (86.4%) GCA patients presented with headache. Patients with headache were found to have an abnormal temporal artery on physical examination more commonly than the other GCA patients (79.8% versus 35.1%; p < 0.001). Compared with the other GCA patients, those who presented with polymyalgia rheumatica (PMR) were younger (73.4 +/- 6.3 versus 75.6 +/- 6.9 yr; p = 0.013) and had a longer delay to diagnosis (13.4 +/- 12.2 versus 8.3 +/- 10.0 wk; p = 0.013). One hundred thirty-one (54.6%) patients presented with severe ischemic manifestations. Abnormal temporal artery on physical examination (odds ratio, 2.25) and anemia at the time of disease diagnosis (odds ratio, 0.53) were found to be the best predictors for severe ischemic manifestations of GCA. Eighteen (7.5%) patients presented without overt ischemic manifestations of GCA. Patients younger than 70 years of age at the time of diagnosis had a longer delay to diagnosis and exhibited PMR more commonly than older patients. Our observations confirm the presence of different disease patterns of clinical presentation in GCA and emphasize the importance of an abnormal temporal artery on physical examination and anemia as factors that may predict the risk of severe ischemic complications related to GCA.

Age Factors↗

Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients.

The outcome of a patient with giant cell arteritis (GCA) is closely related to the development of severe ischemic manifestations. In the current study we analyzed the implications of routine laboratory tests obtained at the time of diagnosis in the clinical spectrum of a series of 240 consecutive patients with biopsy-proven GCA at the single hospital for a defined population. We also examined whether the laboratory markers of inflammation may be predictors of severe ischemic manifestations (visual ischemic events, cerebrovascular accidents, jaw claudication, or large-artery stenosis of the extremities of recent onset), and their potential correlation. Anemia (hemoglobin <12 g/dL) was observed in 131 (54.6%) and thrombocytosis in 117 (48.8%) patients. Sixty-eight (28.3%) patients had leukocytosis. The percentage of patients showing a significant increase of alkaline phosphatase and hypoalbuminemia was similar (25% and 27.8%, respectively). The mean values of erythrocyte sedimentation rate (ESR) and C-reactive protein were 93 +/- 23 mm/h and 94 +/- 63 mg/L, respectively. A strong correlation among most laboratory markers of inflammation was observed. Anemia was more commonly observed in patients without severe ischemic manifestations (61.5% versus 48.9% in those with severe ischemic manifestation; p = 0.05) and in patients with constitutional syndrome or fever (p < 0.001). Patients with ESR greater than 100 mm/h exhibited more commonly constitutional syndrome (p < 0.001) and had a statistically significant reduction in the incidence of visual ischemic events (p < 0.025). Only 7 (22.6%) of the 31 patients who suffered permanent visual loss had an ESR at the time of disease diagnosis greater than 100 mm/h. However, in a multivariate logistic regression analysis, only anemia was found to be a negative predictor for the development of severe ischemic manifestations of GCA (odds ratio, 0.53; 95% confidence intervals, 0.30-0.94; p = 0.03). In conclusion, our results suggest that some laboratory markers of inflammation, in particular the presence of anemia, may negatively predict the risk of severe ischemic complications in GCA patients.

Aged↗

Ischemic heart disease in patients from Northwest Spain with biopsy proven giant cell arteritis. A population based study.

OBJECTIVE: To assess the incidence, mortality, and predictors of ischemic heart disease (IHD) in patients from the Lugo region of Northwest Spain with biopsy-proven giant cell arteritis (GCA). METHODS: Retrospective study of patients with biopsy-proven GCA diagnosed from 1981 to 2001 at the single hospital for a population of 250,000 people. A survival analysis was performed. Hazard ratios and standardized mortality ratio (SMR) as well as predictors of IHD in patients with biopsy-proven GCA were also assessed. RESULTS: Nineteen (9%) of the 210 patients with biopsy-proven GCA diagnosed during the period of study had IHD. The incidence of IHD in patients with GCA was 12.6/1000 person-years at risk (95% CI 6.9-21.0). During the study period 1981-2000 the population aged > or = 50 years in Lugo was roughly 100,000, and the mortality rate due to IHD in patients with GCA for that population was 8/100,000. The SMR in patients with GCA due to IHD was 1.62 (95% CI 0.70-3.20). Mortality in patients with GCA who had IHD was higher than in those patients without IHD (age and sex adjusted hazard ratio 2.81, 95% CI 1.51-5.21; p = 0.001). Age (hazard ratio 1.15), hypertension (hazard ratio 2.51), and abnormal temporal artery on physical examination (hazard ratio 0.36) at the time of diagnosis of GCA were the best predictors of IHD over the followup period in patients with biopsy-proven GCA. CONCLUSION: Our observations suggest that mortality due to IHD in patients from Lugo with GCA is not much higher than that reported in the Spanish population aged 50 years and older. However, mortality in patients with GCA with IHD is higher than in GCA patients without IHD.

Aged↗

High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at greater risk of developing cardiovascular events compared with individuals without RA. Increased risk for cardiovascular disease in these patients is a consequence of atherosclerosis. Case-control studies have shown that increased intima-media thickness (IMT) of the common carotid artery is an indicator of generalized atherosclerosis. Some investigators have suggested that the development of atherosclerosis in RA may be related to the magnitude and chronicity of the systemic inflammation. We examined the relationship between carotid IMT to C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are the most commonly assessed markers of inflammatory response in patients with RA. METHODS: Retrospective review of CRP and ESR values in 47 patients with longterm actively treated (at least 5 years) RA without clinically evident atherosclerosis or its complications, who had been studied for carotid IMT with high resolution B-mode ultrasound. RESULTS: No correlation between ESR and carotid IMT was observed. However, a correlation was found between the maximum CRP values and the carotid IMT (p = 0.009). The distribution of patients in 4 quartiles according to the average CRP values showed significant differences in the carotid IMT (p = 0.03). Those exhibiting the highest mean CRP values (quartile 4) had greater carotid IMT. There was no correlation between CRP at the time of disease diagnosis or at the time of the ultrasound study and the carotid IMT. CONCLUSION: Our study confirms that the magnitude and chronicity of the inflammatory response measured by CRP correlates directly with the presence of atherosclerosis in patients with RA.

Arthritis, Rheumatoid↗

Nitrogen dioxide increases cardiorespiratory admissions in Torrelavega (Spain).

The objective of the study reported here was to analyze relationships between levels of air pollutants and emergency admissions for cardiorespiratory disease. Admission data from January 1, 1992, to December 31, 1995, were obtained from the Marques de Valdecilla University Hospital Admission Service; meteorological data (rainfall, temperatures wind speed, wind direction) were obtained from the National Meteorology Institute in Santander. Pollutant data on sulfur dioxide (SO2), hydrogen sulfide (H2S), total suspended particles (TSP), nitrogen oxide (NO), and nitrogen dioxide (NO2) were provided by the secretary of environment for the Cantabrian Regional Government. Rate ratios were estimated for each pollutant by Poisson regression; they were adjusted for meteorological variables. It was found that elevated NO2 increased by 20 percent the risk of having an admission for cardiorespiratory diseases; this effect was mainly due to respiratory diseases (rate ratio = 1.7, p < .001) and was negligible for cardiac diseases (rate ratio = 1.1, p = .28). In the one-pollutant model, elevated particulates and nitrogen monoxide were also related to admissions, but this effect disappeared when a five-pollutant model was used (p = .21 and p = 0.36, respectively. SO2 and SH2 did not show any relationship with admissions. Thus, nitrogen dioxide was the only pollutant the authors found to be related to emergency admissions for cardiorespiratory diseases. It is difficult to generalize from these results because of the small number of daily admissions and the variability in pollutant levels; therefore, more studies are necessary to improve knowledge about the relationship between air pollution and health in small towns.

Air Pollutants↗

Mortality trends of multiple sclerosis in Spain, 1951-1997: an age-period-cohort analysis.

Trends of multiple sclerosis mortality in Spain from 1951 to 1997 are examined. Age-adjusted mortality strongly decreased from 3.08 per 100,000 women in 1951-1967 to 0.59 in 1968-1980 (similar figures were obtained for men). This decrease seems to be due to an artifact produced by changes in codification of causes of death. An age-period-cohort analysis, limited to the period 1968-1997, showed that the mortality trend in Spain cannot be fully explained by year of death (period effect), but that a cohort (year of birth) effect is also necessary. An increase in mortality related with the cohort of birth was detected: people born after 1953 had double the risk of those born between 1938 and 1947, and four times the risk of those born between 1923 and 1932. Regarding the period effect, there is a decrease in mortality, probably due to improvements in life expectancy of multiple sclerosis patients.

Adult↗

The chemokine receptor CCR5-Delta32 gene mutation is not protective against Alzheimer's disease.

Chronic local inflammatory reaction involving reactive microglia is one of the major pathological events in Alzheimer's disease (AD). There is growing evidence that the chemokine receptor CCR5 is up-regulated in AD brain and plays a role in the recruitment and accumulation of microglia in senile plaques. A 32-base pair deletion in the CCR5 gene (CCR5-Delta32 mutant allele) confers resistance to HIV-1 infection by preventing expression of the receptor on the cell surface. Several other reports have shown a similar protective effect of CCR5-Delta32 mutation towards certain chronic inflammatory diseases. Given the potential importance of CCR5 in brain inflammation, we hypothesized that individuals carrying the CCR5-Delta32 allele would show a reduced risk of AD. So, we performed a case-control study in 376 Spanish AD patients and 369 healthy controls. The frequency of the CCR5-Delta32 allele in our AD sample was 7.8%, not significantly different from our control sample group (5.8%). The present study indicates that the CCR5-Delta32 allele is not a preventive factor for AD.

Aged↗

Fever in biopsy-proven giant cell arteritis: clinical implications in a defined population.

OBJECTIVE: To assess the frequency and clinical features of biopsy-proven giant cell arteritis (GCA) patients who had fever at the time of diagnosis of the disease, and the relationship between fever, ischemic complications, and the systemic inflammatory response in GCA. METHODS: A retrospective study of biopsy-proven GCA patients diagnosed between 1981 and 2001 was performed at the single referral hospital for a well-defined population in the Lugo region of northwest Spain. Patients were considered as having fever if the axillary temperature at the time of admission or during the followup prior to the onset of corticosteroid therapy was > or =38 degrees C. RESULTS: During the period of study, 21 (10%) of the 210 biopsy-proven GCA patients had fever. Two of them fulfilled criteria for fever of unknown origin. Patients with fever had a lower frequency of severe ischemic manifestations than the rest of biopsy-proven GCA patients. They also exhibited a more severe inflammatory disease, with significant abnormality in most laboratory variables, including higher elevation of erythrocyte sedimentation rate, lower values of hemoglobin, and higher proportion of patients with increased alkaline phosphatase. By logistic regression analysis, we observed that patients with fever had an increased risk of developing anemia (odds ratio [OR] 12.24). In contrast, a negative association between severe ischemic manifestations and fever was found (OR 0.41). CONCLUSION: Biopsy-proven GCA patients with fever constitute a subgroup of patients with more severe inflammatory response and less ischemic disease.

Aged↗

Genetic association of CYP46 and risk for Alzheimer's disease.

An increasing number of studies suggest that cholesterol plays an important role in regulating beta-amyloid (Abeta) metabolism in Alzheimer's disease (AD). One of the most important mechanisms for the elimination of excess brain cholesterol is its conversion into the 24S-hydroxycholesterol catalyzed by cholesterol 24S-hydroxylase (CYP46). Preliminary evidence indicates that an intron 2 CYP46 T/C gene polymorphismis associated with increased brain Abeta load and higher risk of AD. A case-control study utilizing a clinically well-defined group of 321 sporadic AD patients and 315 control subjects was performed to test this association. Our results indicate that the intron 2 CYP46 C/C genotype may predispose to AD, and this association is independent of the apolipoprotein E genotype.

Aged↗

Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor alpha antibody.

OBJECTIVE: Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA). Atherosclerosis and RA share similar inflammatory mechanisms that include involvement of tumor necrosis factor alpha (TNF alpha). Anti-TNF alpha antibody improved endothelial function in RA patients after a 12-week treatment. The aim of the present study was to assess whether improvement of endothelial function is still effective in long-term infliximab-treated RA patients. METHODS: Seven RA patients (5 women; age range 25-73 years) were studied. They had been treated with infliximab for at least 1 year and were currently being treated with this drug every 8 weeks. Endothelial-dependent and independent vasodilatation were measured by brachial ultrasonography. RESULTS: Following infliximab infusion, a rapid increase in the percentage of endothelial-dependent vasodilatation was found in all patients (mean +/- SD 9.4 +/- 5.5% 2 days postinfusion compared with 2.8 +/- 2.5% 2 days before infusion). However, values returned to baseline by 4 weeks after infusion. There were no differences in the percentage of endothelial-independent vasodilatation prior to and after infusion. A decrease in the individual disease activity score for each patient was observed at day 7 postinfusion (P = 0.02). CONCLUSION: Our study confirms an active but transient effect of infliximab on endothelial function in RA patients treated periodically with this drug. It may support long-term use of drugs that block TNF alpha function to reduce the high incidence of cardiovascular complications in RA.

Adult↗