Pedro Saavedra

A bedside scoring system ("Candida score") for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization.

Objective:To obtain a score for deciding early antifungal treatment when candidal infection is suspected in nonneutropenic critically ill patients. Design:Analysis of data collected from the database of the EPCAN project, an ongoing prospective, cohort, observational, multicenter surveillance study of fungal infection and colonization in intensive care unit (ICU) patients. Setting:Seventy-three medical-surgical ICUs of 70 teaching hospitals in Spain. Patients:A total of 1,699 ICU patients aged 18 yrs and older admitted for at least 7 days between May 1998 and January 1999 were studied. Interventions:Surveillance cultures of urine, tracheal, and gastric samples were obtained weekly. Patients were grouped as follows: neither colonized nor infected (n = 719), unifocal or multifocal Candida colonization (n = 883), and proven candidal infection (n = 97). The odds ratio (OR) for each risk factor associated with colonization vs. proven candidal infection was estimated. A logistic regression model was performed to adjust for possible confounders. The “Candida score” was obtained according to the logit method. The discriminatory power was evaluated by the area under the receiver operating characteristics curve. Measurements and main results:In the logit model, surgery (OR = 2.71, 95% confidence interval [CI], 1.45–5.06); multifocal colonization (OR = 3.04, 95% CI, 1.45–6.39); total parenteral nutrition (OR = 2.48, 95% CI, 1.16–5.31); and severe sepsis (OR = 7.68, 95% CI, 4.14–14.22) were predictors of proven candidal infection. The “Candida score” for a cut-off value of 2.5 (sensitivity 81%, specificity 74%) was as follows: parenteral nutrition, +0.908; surgery, +0.997; multifocal colonization, +1.112; and severe sepsis, +2.038. Central venous catheters were not a significant risk factor for proven candidal infection (p = .292). Conclusions:In a large cohort of nonneutropenic critically ill patients in whom Candida colonization was prospectively assessed, a “Candida score” >2.5 accurately selected patients who would benefit from early antifungal treatment.

Usefulness of the "Candida score" for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study.

Objective:To assess the usefulness of the “Candida score” (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate of IC <5% in patients with CS <3 was the primary end point. Design:Prospective, cohort, observational study. Setting:Thirty-six medical-surgical intensive care units of Spain, Argentina, and France. Patients:A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007. Measurements and Main Results:Clinical data, surveillance cultures for fungal growth, and serum levels of (1–3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1): total parenteral nutrition ×1, plus surgery ×1, plus multifocal Candida colonization ×1, plus severe sepsis ×2. A CS ≥3 accurately selected patients at high risk for IC. The colonization index was registered if ≥0.5. The rate of IC was 2.3% (95% confidence interval [CI] 1.06–3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p ≤ 0.001). The area under the receiver operating characteristic curve for CS was 0.774 (95% CI 0.715–0.832) compared with 0.633 (95% CI 0.557–0.709) for CI. (1–3)-Beta-d-glucan was also an independent predictor of IC (odds ratio 1.004, 95% CI 1.0–1.007). The relative risk for developing IC in colonized patients without antifungal treatment was 6.83 (95% CI 3.81–12.45). Conclusions:In this cohort of colonized patients staying >7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.

Quantitative Ultrasound Calcaneus Measurements: Normative Data and Precision in the Spanish Population

Abstract:Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain.

Differences in cardiovascular risk profile of diabetic subjects discordantly classified by diagnostic criteria based on glycated hemoglobin and oral glucose tolerance test

OBJECTIVE To characterize the cardiovascular risk profile of subjects categorized differently by A1C- and oral glucose tolerance test (OGTT)-based diagnostic criteria for diabetes according to the recommendations of the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS An OGTT, A1C, and several cardiovascular risk factors were assessed in 964 individuals without known diabetes participating in a cross-sectional epidemiological survey in Gran Canaria, Spain. RESULTS Taking the OGTT as the gold standard, the sensitivity and specificity of an A1C value ≥6.5% were 38.7 and 99.6%, respectively. Subjects who fulfilled A1C-based criterion presented greater measures of BMI and waist circumference, lower values for HDL cholesterol, and higher values for fasting plasma glucose, homeostasis model assessment of insulin resistance, and fibrinogen than subjects with diabetic OGTT but A1C <6.5%. CONCLUSIONS Newly diagnosed diabetic individuals who fulfill A1C-based diagnostic criterion for the disease display a more unfavorable cardiovascular risk profile than individuals who only meet the glucose-based criteria.

Assessment of candidemia-attributable mortality in critically ill patients using propensity score matching analysis

IntroductionCandidemia in critically ill patients is usually a severe and life-threatening condition with a high crude mortality. Very few studies have focused on the impact of candidemia on ICU patient outcome and attributable mortality still remains controversial. This study was carried out to determine the attributable mortality of ICU-acquired candidemia in critically ill patients using propensity score matching analysis.MethodsA prospective observational study was conducted of all consecutive non-neutropenic adult patients admitted for at least seven days to 36 ICUs in Spain, France, and Argentina between April 2006 and June 2007. The probability of developing candidemia was estimated using a multivariate logistic regression model. Each patient with ICU-acquired candidemia was matched with two control patients with the nearest available Mahalanobis metric matching within the calipers defined by the propensity score. Standardized differences tests (SDT) for each variable before and after matching were calculated. Attributable mortality was determined by a modified Poisson regression model adjusted by those variables that still presented certain misalignments defined as a SDT > 10%.ResultsThirty-eight candidemias were diagnosed in 1,107 patients (34.3 episodes/1,000 ICU patients). Patients with and without candidemia had an ICU crude mortality of 52.6% versus 20.6% (P < 0.001) and a crude hospital mortality of 55.3% versus 29.6% (P = 0.01), respectively. In the propensity matched analysis, the corresponding figures were 51.4% versus 37.1% (P = 0.222) and 54.3% versus 50% (P = 0.680). After controlling residual confusion by the Poisson regression model, the relative risk (RR) of ICU- and hospital-attributable mortality from candidemia was RR 1.298 (95% confidence interval (CI) 0.88 to 1.98) and RR 1.096 (95% CI 0.68 to 1.69), respectively.ConclusionsICU-acquired candidemia in critically ill patients is not associated with an increase in either ICU or hospital mortality.

Influence of genetic variability at the surfactant proteins A and D in community-acquired pneumonia: a prospective, observational, genetic study

IntroductionGenetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24. The objective of this study was to evaluate the existence of linkage disequilibrium (LD) among these genes, and the association of variability at these genes with susceptibility and outcome of community-acquired pneumonia (CAP). We also studied the effect of genetic variability on SP-D serum levels.MethodsSeven non-synonymous polymorphisms of SFTPA1, SFTPA2 and SFTPD were analyzed. For susceptibility, 682 CAP patients and 769 controls were studied in a case-control study. Severity and outcome were evaluated in a prospective study. Haplotypes were inferred and LD was characterized. SP-D serum levels were measured in healthy controls.ResultsThe SFTPD aa11-C allele was significantly associated with lower SP-D serum levels, in a dose-dependent manner. We observed the existence of LD among the studied genes. Haplotypes SFTPA1 6A2(P = 0.0009, odds ration (OR) = 0.78), SFTPA2 1A0(P = 0.002, OR = 0.79), SFTPA1-SFTPA2 6A2-1A0(P = 0.0005, OR = 0.77), and SFTPD-SFTPA1-SFTPA2 C-6A2-1A0(P = 0.00001, OR = 0.62) were underrepresented in patients, whereas haplotypes SFTPA2 1A10(P = 0.00007, OR = 6.58) and SFTPA1-SFTPA2 6A3-1A (P = 0.0007, OR = 3.92) were overrepresented. Similar results were observed in CAP due to pneumococcus, though no significant differences were now observed after Bonferroni corrections. 1A10and 6A-1A were associated with higher 28-day and 90-day mortality, and with multi-organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) respectively. SFTPD aa11-C allele was associated with development of MODS and ARDS.ConclusionsOur study indicates that missense single nucleotide polymorphisms and haplotypes of SFTPA1, SFTPA2 and SFTPD are associated with susceptibility to CAP, and that several haplotypes also influence severity and outcome of CAP.

The range of bone mineral density in healthy Canarian women by dual X-ray absorptiometry radiography and quantitative computer tomography.

Bone mass measurements play a crucial role in the diagnosis of osteoporosis. According to a World Health Organization (WHO) Working Group, osteoporosis in women can be diagnosed if the value for bone mineral density (BMD) is 2.5 or more standard deviations below the mean value of a young reference population. This definition obviously requires the availability of normal data, which should ideally be obtained locally. The objective was establish normal values of BMD in the female Canarian population, by dual X-ray absorptiometry (DXA) in the lumbar spine and the proximal femur, and by quantitative computed tomography (QCT) in the lumbar spine, and to study the correlation between the results of both techniques and the changes with age. Seven hundred forty-four Healthy Canarian women, from 20-80 yr old were examined. Measurement of bone density was performed by an Hologic QDR 1000 densitometer (DXA) in the lumbar spine and proximal femur, and by a Toshiba scanner model 600 HQ in the lumbar spine. Both methods show that the peak bone mass is achieved in the fourth decade (30-39 yr). Bone density decreases thereafter with age in the lumbar spine (r = -0.3364 DXA and r = -0.6988 for QCT) and in the femoral neck (r = -0.3988). Bone density mean values obtained by DXA are very similar to those described in Spain and in other European female populations, using the same densitometer. The correlations between both techniques (DXA and QCT) were high and statistically significant (p < 0.001 in every case). Normal values in the normal Canarian women for DXA and QCT are provided. Our results are very similar to those previously described. These two techniques have a close correlation.

Bone mineral density and risk of fractures in aging, obese post-menopausal women with type 2 diabetes. The GIUMO Study.

Background and aims: Type 2 diabetes mellitus (DM) has a high prevalence in aging obese postmenopausal women. It is not clear whether or not diabetes produces an increase in bone mineral density or an increase in fracture rates. Objective: The main objective of this study was to investigate whether type 2 DM produces a higher prevalence of vertebral, hip and non-vertebral fractures in obese postmenopausal Caucasian women. A secondary objective was to study the influence of DM in quantitative ultrasound measurements of the heel (QUS) and bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), in both lumbar spine (L2–L4) and proximal femur. Method: This study was a prospective cohort of 111 patients with type 2 DM and 91 control individuals (CTR) over age 65 and obese, recruited from 16 centers in Spain. Main Outcome Measures: Lateral dorsal and lumbar X-rays were performed to assess vertebral fractures. Hip and non-vertebral fractures were noted from medical records, written reports or X-ray studies. QUS measurements were made of the calcaneus and BMD measurements of the lumbar spine (L2–L4) and proximal femur. Results: Patients had higher BMD in the lumbar spine (L2–L4) than controls (0.979 g/cm2 vs 0.927 g/cm2, p=0.035), but we found no statistically significant differences in the proximal femur. QUS measurements showed similar values in both groups: BUA (69.3 dB/Mhz vs 66.7 dB/Mhz, p=0.291), SOS (1537 m/sg vs 1532 m/sg, p=0.249) and QUI (87.5 vs 83.7, p=0.153). No statistically significant differences were found in any case. There was no association between vertebral, hip and non-vertebral fractures and DM. The crude odds ratio, without adjusting was 1.045 (CI 957o 0.531; 2.059), and the adjusted odds ratio was 0.927 (CI 95% 0.461; 1.863). Conclusions: In obese postmenopausal Caucasian women, type 2 DM produces an increase in BMD of the lumbar spine without changes in BMD of the proximal femur or in QUS measurements of the heel. The prevalence of vertebral, hip and non-vertebral fractures did not increase in type 2 DM.

Osteoporosis and metabolic syndrome according to socio‐economic status, contribution of PTH, vitamin D and body weight: The Canarian Osteoporosis Poverty Study (COPS)

Poverty is associated with a great number of diseases, but the prevalence of vitamin D deficiency, secondary hyperparathyroidism and the potential association of osteoporosis, osteoporotic fractures and metabolic syndrome in this situation are less well known.

Disproportionately high incidence of diabetes-related end-stage renal disease in the Canary Islands. An analysis based on estimated population at risk

BACKGROUND An exceptionally high incidence of diabetes-related end-stage renal disease (DM-ESRD) has been reported in the Canary Islands. This phenomenon was attributed to an increased prevalence of diabetes in this community. We compared the incidence of DM-ESRD in the Canary Islands with the rest of Spain among the estimated number of individuals at risk (people with diabetes in the population). METHODS The population-at-risk was calculated using census population figures and estimates of self-reported diabetes prevalence from the Spanish National Health Survey in the years 2003 and 2006. The incidence of DM-ESRD for the same years was obtained through Spanish regional registries. The independent effect of age, community of residence and calendar year was estimated with a Poisson regression model. Age-standardized acceptance rate ratios were calculated for each community. RESULTS Overall DM-ESRD incidence in the Canary Islands population-at-risk was 1209.9 per million population (pmp) in 2003 and 1477.3 pmp in 2006. Rates for the remaining Spanish regions ranged from 177.3-984.9 pmp. The incidence was higher in the Canary Islands across all age groups, but was most striking for patients > or =75 years. Diabetes prevalence in the general population was greater in the two youngest age strata and diminished from 75 years on in the Canary Islands, in comparison with other areas of Spain. Using a cluster of three communities with the lowest incidence as a reference, the relative risk of DM-ESRD in the Canary Islands population-at-risk was 3.88 [95% confidence interval (CI): 3.07-4.89]. Age-standardized acceptance ratios (95% CI) in the Canary Islands were 2.21 (1.85-2.61) in 2003 and 2.73 (2.34-3.17) in 2006. CONCLUSIONS Individuals with diabetes in the Canary Islands present a disproportionately high incidence of ESRD. Diabetic Canary inhabitants are exposed to the disease for a longer time and therefore, may be more vulnerable to the development of chronic diabetes complications, including ESRD.