Javier Llorca

Impact of the Surviving Sepsis Campaign protocols on hospital length of stay and mortality in septic shock patients: Results of a three-year follow-up quasi-experimental study

Objectives:To describe the effectiveness of the Surviving Sepsis Campaign bundles with regard to both implementation and outcome in patients with septic shock and to determine the contribution of the various elements of the bundles to the outcome. Design:Quasi-experimental study with a historical comparison group. Setting:The three medical–surgical intensive care units of an academic tertiary care center. Patients:A total of 384 adult patients in septic shock were enrolled after the educational intervention (September 2005–August 2008) and 96 patients in the historical group (June 2004–May 2005). Intervention:A hospital-wide quality improvement program based on the implementation of the Surviving Sepsis Campaign guidelines performed between June 2005 and August 2005. Measurements and Results:In-hospital mortality was reduced from 57.3% in the historical group to 37.5% in the intervention group (p = .001). This difference remained significant after controlling for confounding factors (odds ratio, 0.50; 95% confidence interval, 0.28–0.89). The intervention group had also lower length of stay for survivors in the hospital (36.2 ± 34.8 days vs. 41.0 ± 26.3 days; p = .043) and in the intensive care units (8.4 ± 9.8 days vs. 11.0 ± 9.5 days; p = .004). Improvements in survival were related to the number of bundle interventions completed (p for trend <.001). Compliance with six or more interventions of the 6-hr resuscitation bundle was an independent predictor of survival (adjusted odds ratio, 0.30; 95% confidence interval, 0.17–0.53; p <.001). The only single intervention with impact on mortality was the achievement of ScvO2 ≥70% (adjusted odds ratio, 0.62; 95% confidence interval, 0.38–0.99; p = .048). Conclusions:The implementation of the Surviving Sepsis Campaign guidelines was associated with a significant decrease in mortality. The benefits depend on the number of interventions accomplished within the time limits. The 6-hr resuscitation bundle showed greater compliance and effectiveness than the 24-hr management bundle. (Crit Care Med 2010; 38:1036–1043)

Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients.

Giant cell (temporal) arteritis (GCA) is the most common systemic vasculitis in Western countries. It involves large and medium-sized vessels with predisposition to the cranial arteries in the elderly. Cranial ischemic complications, in particular permanent visual loss, constitute the most feared aspects of this vasculitis. Although the use of corticosteroids and a higher physician awareness may have contributed to a decrease in the frequency of severe ischemic complications, permanent visual loss is still present in 7%-14% of patients. To investigate further the incidence, trends, and clinical spectrum of visual manifestations in patients with GCA, we examined the features of patients with biopsy-proven GCA diagnosed at the single reference hospital for a defined population in northwestern Spain during an 18-year period. Predictive factors for the development of any visual manifestation, not only permanent visual loss, were also examined. Between 1981 and 1998, 161 patients were diagnosed with biopsy-proven GCA. Visual ischemic complications were observed in 42 (26.1%), and irreversible blindness, mainly due to anterior ischemic optic neuropathy and frequently preceded by amaurosis fugax, was found in 24 (14.9%). Despite a progressive increase in the number of new cases diagnosed, there was not a significant change in the proportion of patients with visual manifestations during the study period (p = 0.37). Patients with visual ischemic complications had lower clinical and laboratory biologic markers of inflammation. Indeed, during the last years of the study, anemia was associated with a very low risk of visual complications. Also, HLA-DRB1*04-positive patients had visual manifestations more commonly. Patients with other ischemic complications developed irreversible blindness more frequently. The best predictors of any visual complication were HLA-DRB1*04 phenotype (odds ratio [OR] 7.47) and the absence of anemia at the time of admission (OR for patients with anemia = 0.07). The best predictors of irreversible blindness (permanent visual loss) were amaurosis fugax (OR 12.63) and cerebrovascular accidents (OR 26.51). The present study supports the claim that ocular ischemic complications are still frequent in biopsy-proven GCA patients from southern Europe. The presence of other ischemic complications constitutes an alarm for the development of irreversible blindness. In contrast, a higher inflammatory response may be a protective factor against the development of cranial ischemic events.

Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease.

We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound.Patients had greater carotid IMT (0.779 ± 0.164 mm) than did controls (0.699 ± 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 ± 0.116 mm) than those without plaques (0.739 ± 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease.The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.

Carotid Intima-Media Thickness Predicts the Development of Cardiovascular Events in Patients with Rheumatoid Arthritis

OBJECTIVE To establish whether carotid intima-media wall thickness (IMT) may be a good predictor for the development of cardiovascular (CV) events in patients with rheumatoid arthritis (RA). METHODS A series of 47 RA patients who at the time of recruitment did not have traditional CV risk factors or CV disease were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were measured in the right common carotid artery. Then, a prospective assessment of the CV outcome was performed over a 5-year period. Logistic regression models and receiver operating characteristic curves were performed to evaluate the ability of different variables to predict CV events. RESULTS Carotid IMT was greater in RA patients who over the extended follow-up experienced CV events (1.01 +/- 0.16 mm) compared with the remaining RA patients who did not have CV complications (0.74 +/- 0.12 mm) (P < 0.001). Also, carotid IMT categorized in quartiles was strongly associated with CV events. In this regard, none of the patients with carotid IMT less than 0.77 mm had CV events. However, 6 of the 10 patients with carotid IMT greater than 0.91 mm experienced CV events (P value for the trend <0.001). Carotid IMT yielded a high predictive power for the development of CV events over the 5-year follow-up period. The area under the receiver operating characteristic curve was 0.93 for a model that only included carotid IMT and 0.90 for carotid plaque. CONCLUSIONS The results from the present study support the use of carotid ultrasonography as a predictor of CV events in RA.

Giant Cell Arteritis: Disease Patterns of Clinical Presentation in a Series of 240 Patients

Abstract: 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. Abbreviations: ALP = alkaline phosphatase, CI = confidence intervals, ESR = erythrocyte sedimentation rate, GCA = giant cell arteritis, IFN = interferon, IL = interleukin, OR = odds ratio, PMR = polymyalgia rheumatica, SD = standard deviation, TAB = temporal artery biopsy.

Henoch-Schönlein purpura in children from northwestern Spain: a 20-year epidemiologic and clinical study.

IntroductionHenoch-Schonlein purpura (HSP) is a systemic vasculitis characterized by purpuric skin lesions unrelated to any underlying coagulopathy, gastrointestinal manifestations, arthritis, and renal involvement (25,51). Infiltration of small blood vessels with polymorphonuclear leukocytes a

HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis.

PURPOSE To examine endothelial function in rheumatoid arthritis patients and to assess whether clinical or genetic factors affect the development of endothelial dysfunction. METHODS Fifty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for rheumatoid arthritis were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with one or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, or cardiovascular disease were excluded. Thirty-one age-, sex-, and ethnically matched controls were also studied. Endothelium-dependent (postischemia) and -independent (postnitroglycerin) vasodilatation were measured by brachial ultrasonography. Patients were genotyped for human leukocyte antigen (HLA)-DRB1. RESULTS Patients had decreased endothelium-dependent vasodilatation (mean [+/- SD], 3.8% +/- 4.9%) compared with controls (8.0% +/- 4.5%; P <0.001). There were no differences in endothelium-independent vasodilatation. Clinical features were not associated with endothelial dysfunction. Endothelium-dependent vasodilatation was lower in the 30 rheumatoid arthritis patients with the HLA-DRB1*04 shared epitope alleles (2.4% +/- 4.1%) than in the remaining patients (5.5% +/- 5.3%; P = 0.01). Similar results were seen for patients with the HLA-DRB1*0404 shared epitope allele (-0.4% +/- 2.5%) compared with other patients (4.4% +/- 4.9%; P = 0.01). CONCLUSION Patients with chronically treated rheumatoid arthritis had evidence of endothelial dysfunction, especially those with certain HLA-DRB1 genotypes. If confirmed, our results suggest that HLA-DRB1 status may be a predictor of cardiovascular risk in these patients.

Adherence to Highly Active Antiretroviral Therapy (HAART): A Meta-Analysis

This meta-analysis synthesizes eighty-four observational studies, conducted across twenty countries, to determine the mean proportion of people who reported ≥90% adherence to prescribed highly active antiretroviral therapy (HAART) and to identify the factors associated with high levels of adherence. Eight electronic databases were searched to locate all relevant studies available by January 2010, which were then coded for sample characteristics and adherence levels. The average rate of reporting ≥90% adherent HAART adherence is 62%. However, this proportion varies greatly across studies. In particular, a greater proportion of individuals maintaining ≥90% adherence to HAART is more likely in studies with higher proportions of men who have sex with men (MSM) and lower proportions of injection drug users (IDU), with participants in an earlier stage of infection, and in studies conducted in countries characterized by lower Human Development Index (HDI) scores.ResumenEste metaanálisis sintetiza ochenta y cuatro estudios observacionales, realizados en veinte países, para determinar la proporción media de personas que informan de la adherencia a la Terapia Antirretroviral Altamente Activa ≥90% e identificar los factores relacionados con los niveles elevados de adherencia. Para localizar los estudios relevantes disponibles hasta enero de 2010 accedimos a ocho bases de datos electrónicas. Los estudios seleccionados se codificaron según las características de la muestra y los niveles de adherencia. Los resultados obtenidos indican que una media del 62% de las personas que tomaban Terapia Antirretroviral Altamente Activa eran adherentes en un ≥90%. Sin embargo, esta proporción varía enormemente entre los estudios. En particular, una mayor proporción de individuos que muestran una adherencia a la Terapia Antirretroviral Altamente Activa ≥90% es más frecuente en estudios con altas proporciones de hombres que mantienen relaciones sexuales con hombres y con menores proporciones de usuarios de drogas parenterales, con los participantes en un estadio más temprano de la infección y en estudios llevados a cabo en países caracterizados con puntuaciones más bajas en el índice de desarrollo humano.

Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study.

Abstract: Most classical manifestations of giant cell arteritis (GCA) are the result of occlusive vascular involvement. However, unlike ischemic manifestations, aortic aneurysmal disease in patients with GCA has been less well described. We assessed the incidence and predictors of aortic aneurysm and dissection in patients with biopsy-proven GCA from the Lugo region of northwestern Spain and compared the results with those in a 2003 report from Olmsted County, MN. We performed a retrospective study of biopsy-proven GCA patients diagnosed from 1981 to 2001 at the single hospital for a well-defined population of almost 250,000 people. Twenty (9.5%) of the 210 biopsy-proven GCA patients diagnosed during the study period developed aortic aneurysmal disease. Sixteen of the 20 patients had thoracic aneurysms and 6 had abdominal aneurysms. The incidence of aortic aneurysm and/or dissection in Lugo (18.9 per 1000 person years at risk) was similar to that reported in Olmsted County (18.7 per 1000 person years at risk). Hypertension (hazard ratio: 4.73) and polymyalgia rheumatica with a marked acute inflammatory response at the time of diagnosis of GCA (hazard ratio: 3.71) were the best predictors of aortic aneurysmal disease. Our present observations suggest that a severe inflammatory response associated with hypertension at the time of diagnosis of GCA may promote the development of aortic aneurysmal disease. GCA patients having these features should be monitored for the existence of aortic aneurysm and dissection. Abbreviations: CI = confidence intervals, ESR = erythrocyte sedimentation rate, GCA = giant cell arteritis, OR = odds ratio, PMR = polymyalgia rheumatica.

Trend in hip fracture epidemiology over a 14-year period in a Spanish population

Spain lacks detailed data on hip fracture trends despite being the country with the greatest increase in the pensioner-to-provider ratio in Europe. We reproduced a study on hip fracture incidence in a region of northern Spain (Cantabria) carried out 14 years ago to determine whether a secular trend to change is taking place. If such a trend could be found, our objective was to determine whether the effect is solely due to ageing or whether additional variables are involved. We assessed the incidence of hip fracture in patients aged ≥50 years through clinical records from Emergency Units and Orthopedic Surgical Units of all hospitals in the region of Cantabria in 1988 and 2002. A total of 318 new cases of hip fracture were recorded in 1988 and 490 in 2002 (54% increase; p<0.001). No significant changes were noticed following an adjustment for age. Women accounted for the increase in crude hip fracture incidence [246 women and 72 men suffered a hip fracture in 1988 compared to 404 women and 86 men in 2002 (64% increase in women and 19% increase in men; p<0.005 and not significant, respectively)]. The female:male ratio was 3.4 in 1988 versus 4.7 in 2002; following age-adjustment, no significant changes were found (1.8 in 1988 and 1.9 in 2002). The increase in crude hip fracture incidence was greater at cervical (versus trochanteric) sites. Patient residence, time of the year, site of fracture, kind of injury, previous contralateral hip fracture, length of stay, and peri-operative mortality did not differ significantly. In conclusion, a crude hip fracture incidence increase of about 50% in the northern Spanish region of Cantabria has taken place over the last 14 years. This effect does not persist after adjustments have been made for age. The crude rate increase occurred mainly at the expense of women, with a more noticeable rise in cervical fractures as opposed to trochanteric lesions.