Alfonso Muriel

Meta-DiSc: a software for meta-analysis of test accuracy data

BackgroundSystematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis.ResultsMeta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities.ConclusionMeta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at http://www.hrc.es/investigacion/metadisc_en.htm.

Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism.

BACKGROUND The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute pulmonary embolism (PE). We constructed a simplified version of the PESI. METHODS The study retrospectively developed a simplified PESI clinical prediction rule for estimating the risk of 30-day mortality in a derivation cohort of Spanish outpatients. Simplified and original PESI performances were compared in the derivation cohort. The simplified PESI underwent retrospective external validation in an independent multinational cohort (Registro Informatizado de la Enfermedad Tromboembólica [RIETE] cohort) of outpatients. RESULTS In the derivation data set, univariate logistic regression of the original 11 PESI variables led to the removal of variables that did not reach statistical significance and subsequently produced the simplified PESI that contained the variables of age, cancer, chronic cardiopulmonary disease, heart rate, systolic blood pressure, and oxyhemoglobin saturation levels. The prognostic accuracy of the original and simplified PESI scores did not differ (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305 of 995 patients (30.7%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%-13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106 patients (36.2%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the high-risk group. CONCLUSION The simplified PESI has similar prognostic accuracy and clinical utility and greater ease of use compared with the original PESI.

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

RATIONALE Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Troponin-Based Risk Stratification of Patients With Acute Nonmassive Pulmonary Embolism: Systematic Review and Metaanalysis

BACKGROUND Controversy exists regarding the usefulness of troponin testing for the risk stratification of patients with acute pulmonary embolism (PE). We conducted an updated systematic review and a metaanalysis of troponin-based risk stratification of normotensive patients with acute symptomatic PE. The sources of our data were publications listed in Medline and Embase from 1980 through April 2008 and a review of cited references in those publications. METHODS We included all studies that estimated the relation between troponin levels and the incidence of all-cause mortality in normotensive patients with acute symptomatic PE. Two reviewers independently abstracted data and assessed study quality. From the literature search, 596 publications were screened. Nine studies that consisted of 1,366 normotensive patients with acute symptomatic PE were deemed eligible. Pooled results showed that elevated troponin levels were associated with a 4.26-fold increased odds of overall mortality (95% CI, 2.13 to 8.50; heterogeneity chi(2) = 12.64; degrees of freedom = 8; p = 0.125). Summary receiver operating characteristic curve analysis showed a relationship between the sensitivity and specificity of troponin levels to predict overall mortality (Spearman rank correlation coefficient = 0.68; p = 0.046). Pooled likelihood ratios (LRs) were not extreme (negative LR, 0.59 [95% CI, 0.39 to 0.88]; positive LR, 2.26 [95% CI, 1.66 to 3.07]). The Begg rank correlation method did not detect evidence of publication bias. CONCLUSIONS The results of this metaanalysis indicate that elevated troponin levels do not adequately discern normotensive patients with acute symptomatic PE who are at high risk for death from those who are at low risk for death.

Mapping of the IgE and IgG4 sequential epitopes of milk allergens with a peptide microarray–based immunoassay

BACKGROUND Peptide microarray analysis is a novel method that can provide useful information on the nature of specific allergies. OBJECTIVE We sought to determine the specificity and diversity of IgE and IgG4 antibodies binding to sequential epitopes of alpha(s1)-, alpha(s2)-, beta-, and kappa-caseins and beta-lactoglobulin by using a peptide microarray-based immunoassay. METHODS A microarray immunoassay was performed with sera from 31 children with IgE-mediated milk allergy (16 with positive oral milk challenge results [ie, the reactive group] and 15 with negative oral milk challenge results [ie, the tolerant group]). A library of peptides, consisting of 20 amino acids (AAs) overlapping by 17 (3-offset), corresponding to the primary sequences of alpha(s1)-, alpha(s2)-, beta-, and kappa-caseins and beta-lactoglobulin was printed on epoxy-coated slides. A region was defined as an epitope if it was statistically associated with reactive groups and recognized by at least 75% of reactive patients. RESULTS By using this method, a total of 10 epitopes were identified: alpha(s1), AAs 28 to 50, 75% reactive and 26.7% tolerant; alpha(s2), AAs 1 to 20, 75% reactive and 13.3% tolerant; AAs 13 to 32, 75% reactive and 26.7% tolerant; AAs 67 to 86, 75% reactive and 33.3% tolerant; and AAs 181 to 207, 75% reactive and 20% tolerant; beta-casein, AAs 25 to 50, 75% reactive and 33.3% tolerant, AAs 52 to 74, 81.3% reactive and 26.7% tolerant; and AAs 154 to 173, 75% reactive and 33.3% tolerant; beta-lactoglobulin, AAs 58 to 77, 81.3% reactive and 40% tolerant; and kappa-casein, AAs 34 to 53, 87.5% reactive and 40% tolerant. CONCLUSION Several regions have been defined as epitopes, which showed differential recognition patterns between reactive and tolerant patients. Further studies are needed to validate the utility of this assay in clinical practice.

Oral desensitization as a useful treatment in 2-year-old children with cow's milk allergy: Oral desensitization to cow's milk allergy

Background Limited published evidence shows oral desensitization to be a potential intervention option for cows milk protein (CMPs) allergy.

Long-term functional evolution after an acute kidney injury: a 10-year study

BACKGROUND Data on long-term effects of acute kidney injury (AKI) on renal function (RF) are scarce and factors implicated in the functional outcome are not established. Our aim was to investigate these aspects. METHODS At hospital discharge and annually for 10 years, we retrospectively reviewed RF of 187 patients surviving AKI. Glomerular filtration rates estimated with MDRD equation (eGFR) and KDOQI stages were used to evaluate RF. Only 34.8% of patients had pre-existing renal dysfunction (KDOQI-3). Variables determining long-term RF were collected during AKI and at discharge and analysed with a regression model. RESULTS At discharge no patient necessitated dialysis, but eGFR was lower than baseline (47.5 +/- 23.3 ml/min/ 1.73 m(2) versus 75.8 +/- 25.4 ml/min/1.73 m(2)); 38.4% of survivors had recovered basal RF: 26% of those with previous normal RF and 61% of those in KDOQI-3, respectively. At 1 year, eGFR increased to 61.9 +/- 24.4 ml/min/1.73 m(2) and remained stable later. During an 8-year median follow-up (P25:2; P75:10), 31% improved RF, 50% remained stable and 19% deteriorated. In total only 46% (n = 82) definitively recovered RF. Finally, at the end of the study period 61.6% presented some degree of renal dysfunction: 40% of those with previous normal RF developed moderate-severe renal dysfunction and 37% KDOQI-3 progressed into more severe renal failure. Only two patients needed dialysis. Regression model identified age, co-morbidities, discharge eGFR and follow-up time as independent predictors of long-term RF. CONCLUSIONS AKI carries implication for long-term RF even in patients without pre-existing renal dysfunction. Ageing, co-morbidities and RF at discharge are determinants of the long-term functional outcome.

Artificial anal sphincter : complications and functional results of a large personal series

AbstractPURPOSE: This study was undertaken to evaluate the technique of artificial sphincter for fecal incontinence, with its complications and risk factors, the functional results, and which variables derived from demographic data, preoperative studies, device characteristics, technical details, perioperative findings, and complications could influence the outcome. METHODS: The Acticon Neosphincter® was implanted in 53 patients (35 females), median age 46 years, with total anal incontinence not amenable to sphincter repair or after failed sphincteroplasty. In females with associated rectocele, this was synchronously corrected. Six (11 percent) patients already had a colostomy, but no proximal stoma was constructed at the time of implantation. Causes of incontinence were congenital, 13; iatrogenic, 13; obstetric, 10; neurogenic, 9; trauma, 4; idiopathic, 2; and perineal colostomy, 2. Physiologic testing before and after the operation and preoperative endosonography were done when they were available. Quality of life was assessed in 25 patients. Mean follow-up was 26.5 (range, 7–55) months. RESULTS: Perioperative events occurred in 14 (26 percent) patients: abnormal bleeding, 7; vaginal perforation, 4; rectal perforation without apparent contamination, 2; and unobserved urethral perforation, 1. Early complications were mainly related to sepsis in 8 (15 percent) patients and wound complication in 8 (15 percent). Sepsis could not be statistically associated with any of the variables studied here. Wound separation was associated with fibrosis (P = 0.003) and tension of the wound (P = 0.001). Late complications were: cuff and/or pump erosion, 9 (18 percent) patients; infection, 3 (6 percent); impaction, 11 (22 percent); pain, 4 (8 percent); and mechanical failures, 2 (4 percent). None of those complications showed a statistical association with any of the variable studied here. There were 10 (19 percent) definitive explants caused by septic or skin complications. Only 26 (60 percent) of 43 patients with the device in action use the pump (patients’ decision). Normal continence was achieved in 65 percent of patients and continence to solid stool in 98 percent. The Cleveland Clinic score of incontinence (0–20, maximal incontinence) changed from 17 ± 3 preoperatively to 4 ± 3 postoperatively (P = 0.000). An early complication of the perianal wound influenced the functional results: postimplant score > 4 vs. ≤ 4 (P = 0.009). Resting and squeeze pressures changed significantly after activation (P = 0.000). Quality of life measured in four subscales changed significantly in all the subscales (P = 0.000). CONCLUSIONS: The artificial anal sphincter restores continence to solid stool in almost all severely incontinent patients, two-thirds of whom achieve practically normal continence. Quality of life improves significantly. Infection and skin erosion are the cause of the majority of explants. No predictable factors of functional success could be found in this study.

Survival effects of inferior vena cava filter in patients with acute symptomatic venous thromboembolism and a significant bleeding risk.

OBJECTIVES The purpose of this study was to investigate the survival effects of inferior vena cava filters in patients with venous thromboembolism (VTE) who had a significant bleeding risk. BACKGROUND The effectiveness of inferior vena cava filter use among patients with acute symptomatic VTE and known significant bleeding risk remains unclear. METHODS In this prospective cohort study of patients with acute VTE identified from the RIETE (Computerized Registry of Patients With Venous Thromboembolism), we assessed the association between inferior vena cava filter insertion for known significant bleeding risk and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, and VTE rates through 30 days after the initiation of VTE treatment. Propensity score matching was used to adjust for the likelihood of receiving a filter. RESULTS Of the 40,142 eligible patients who had acute symptomatic VTE, 371 underwent filter placement because of known significant bleeding risk. A total of 344 patients treated with a filter were matched with 344 patients treated without a filter. Propensity score-matched pairs showed a nonsignificant trend toward lower risk of all-cause death for filter insertion compared with no insertion (6.6% vs. 10.2%; p = 0.12). The risk-adjusted PE-related mortality rate was lower for filter insertion than no insertion (1.7% vs. 4.9%; p = 0.03). Risk-adjusted recurrent VTE rates were higher for filter insertion than for no insertion (6.1% vs. 0.6%; p < 0.001). CONCLUSIONS In patients presenting with VTE and with a significant bleeding risk, inferior vena cava filter insertion compared with anticoagulant therapy was associated with a lower risk of PE-related death and a higher risk of recurrent VTE. However, study design limitations do not imply a causal relationship between filter insertion and outcome.

Psychometric Characteristics of the Spanish Version of the FAB Questionnaire

Study Design. Validation of a translated, culturally adapted questionnaire. Objectives. To translate and culturally adapt the Spanish version of the Fear Avoidance Beliefs Questionnaire (FABQ), and to validate its use in Spanish-speaking patients with low back pain (LBP). Summary of Background Data. The FABQ is a reliable evaluation instrument for fear avoidance beliefs, which includes two subscales (FAB-Work and FAB-Phys). No validated Spanish version was available. Methods. Translation/retranslation of the English version of the FABQ was done blindly and independently by a multidisciplinary team. The study was done in 12 primary care centers and 9 hospital outpatient clinics from seven regions in Spain, with 209 acute, subacute, and chronic patients who visited their physician for LBP: 53 in the pilot phase and 156 in the validation phase. Subjects were given the FABQ, two VAS for LBP and referred pain, and the Roland-Morris and SF-12 Questionnaires on their first visit and 14 days later. In the pilot phase, on day 1 test-retest reliability was estimated by giving a second FABQ in which the name and order of the items had been changed. Results. Time necessary to complete the FABQ was [median, P25, P75] 10 minutes (5,15). FABQ values were not normally distributed. Comprehensibility: No request for aid in interpretation was made during the validation phase and no item was left unanswered by ≥ 10% of patients. Reliability: Scores [median, P25, P75] of the two FABQ were: 72.00 (47.25, 82.00) and 72.00 (49.50, 83.75), with an intraclass correlation coefficient of 0.9668 (95% confidence interval, 0.9421,0.9823). Mean of kappa values for all items was 0.743. Internal Consistency: Cronbachs α was 0.9337. Validity: Values of FAB and FAB-Work were >37% higher for patients on sick leave. For FAB-Phys differences were below 8%. FABQ, FAB-Work and FAB-Phys strongly correlated with disability on days 1 and 15. Conclusions. The Spanish version of the FABQ has good comprehensibility, internal consistency, and reliability. It cannot be analyzed parametrically, but only nonparametrically. The total FABQ is at least as valid as its subscales and simpler to score, making it more suitable for routine clinical use.