J.D. Luna del Castillo

Sperm chromatin structure assay and classical semen parameters: systematic review

The present study is based on a PubMed search and compares the clinical validity of classical semen parameters (CSP) and the sperm chromatin structure assay (SCSA) in different clinical contexts. The PubMed database was searched using keywords on the sperm diagnostic test for pregnancy in three clinical scenarios: (i) couples attempting to conceive; (ii) couples who had been attempting to conceive for 12months without success; and (iii) couples treated with intrauterine insemination (IUI). There was a considerable heterogeneity among the studies included. For couples attempting to conceive following a SCSA that produced an abnormal result, the likelihood of male factor infertility ranged from a pre-test value of 7.5% to a post-test value of 32.1% [95% confidence interval (CI) 15.7-54.5], while after CSP with an abnormal result, the post-test probability was 17.3% (95% CI 11.8-24.5). For a pre-test prevalence of male factor infertility of 50%, the post-test probability of male factor infertility after an abnormal test is very similar for both SCSA and CSP. In couples treated with IUI, the clinical validity of SCSA is higher than that of sperm morphology alone, but not enough to introduce SCSA as a test in male infertility work-up.

Chitinase and peroxidase activities in sunflower hypocotyls: Effects of BTH and inoculation with Plasmopara halstedii

Systemic acquired resistance (SAR) can be induced in plants by incompatible pathogens, pathogen derived extracts, or certain chemicals as benzothiadiazole (BTH). The aim of this work was to compare changes in peroxidase and chitinase activities, enzymes considered as PR-proteins, caused by BTH and the pathogen Plasmopara halstedii. Hypocotyls from susceptible and resistant BTH-treated sunflower seedlings showed increased peroxidase and chitinase activities. Inoculation with P. halstedii increased chitinase and peroxidase activities in inoculated hypocotyls from susceptible but not from resistant sunflower seedlings.Systemic acquired resistance (SAR) can be induced in plants by incompatible pathogens, pathogen derived extracts, or certain chemicals as benzothiadiazole (BTH). The aim of this work was to compare changes in peroxidase and chitinase activities, enzymes considered as PR-proteins, caused by BTH and the pathogen Plasmopara halstedii. Hypocotyls from susceptible and resistant BTH-treated sunflower seedlings showed increased peroxidase and chitinase activities. Inoculation with P. halstedii increased chitinase and peroxidase activities in inoculated hypocotyls from susceptible but not from resistant sunflower seedlings.

Reacciones adversas a medicamentos en pacientes que acudieron a un hospital general: un meta-análisis de resultados

Objectives The aim of this study was to present the results of a meta-analysis on adverse drug reactions (ADR) in spanish patients admitted to hospital and presenting to emergency department over the past 20 years. Patients and methods An exhaustive review was undertaken of relevant articles in the IME (Spanish Medical Index) and MEDLINE databases and published between 1985 and 2006, rigorously selecting 12 out of 30 publications after applying inclusion and exclusion criteria. Information was required on: symptomatology, prognosis, type, drugs involved, imputability and admissions for ADR; and factors associated with ADR onset, e.g., age, sex, number of drugs, previous history of ADR, method used for ADR detection, and length of study period. A random-effects model (DerSimonian and Laird) and the STATA 9.1 programme were used for the meta-analysis. Results The combined estimation of the percentage of Spanish patients with ADR was 13% (95% CI); with severe ADR, 12 % (95% CI) and with fatal ADR, 0.1% (95% CI). ADR diagnosis was definite in 36% (95% CI), probable in 49.6% (95% CI), and type A in 71% (95% CI) of cases. Among patients in the Emergency Department for ADR, 5.1% (95% IC) were hospitalized. No association was found with number of prescriptions or previous history. Association was established with advanced age and female sex. Digestive, skin, nervous and cardiovascular systems were those most affected by ADR. The drugs most frequently implicated included NSAIDs, digoxin, IACE, calcium antagonists, furosemide, i.v. metamizol, antidiabetics, benzodiazepines, adrenergic bronchodilators and classic antipsychotics. Conclusions ADRs constitute a major medical and economic problem with aspects that have yet to be defined. Greater efforts are warranted to unify criteria for the publication of results in observational studies on ARD and to determine the role played by some factors associated with their onset, e.g., sex, previous history and comorbidities.

Influence of driver nationality on the risk of causing vehicle collisions in Spain.

Study objective: To estimate the association between driver nationality and the risk of causing a collision between vehicles in motion. Design: Retrospective, matched by collision, case-control study. Setting: Collisions that occurred in Spain during the period from 1990 to 1999 were studied. Participants: Responsible (case) and non-responsible (control) drivers identified in the databases of the Dirección General de Tráfico (General Traffic Directorate) who were involved in a collisions between two or more four wheeled vehicles in motion, in which only one of the drivers had committed a traffic violation. Main results: Crude odds ratios (ORs) for the effect of driver nationality on the risk of causing a collision were significantly higher for foreign drivers than for Spanish drivers, and ranged from a minimum of 1.19 (95% CI 1.09 to 1.29) for Portuguese drivers to a maximum of 2.06 (1.88 to 2.27) for British drivers. Corresponding adjusted ORs were slightly lower, but were still significantly higher than 1 for all nationalities except Italian, Belgian, and American (USA). Adjusted ORs were usually higher for collisions that occurred in urban areas than on open roads. Conclusions: Authorities responsible for traffic safety, and drivers in general, should consider foreign drivers in Spain at particularly high risk for causing collisions, especially in urban areas.

Confidence Intervals of Weighted Kappa Coefficient of a Binary Diagnostic Test

Sensitivity and specificity are classic parameters to assess the performance of a binary diagnostic test. Another useful parameter to measure the performance of a binary test is the weighted kappa coefficient, which is a measure of the classificatory agreement between the binary test and the gold standard. Various confidence intervals are proposed for the weighted kappa coefficient when the binary test and the gold standard are applied to all of the patients in a random sample. The results have been applied to the diagnosis of coronary artery disease.

Determining sample size to evaluate and compare the accuracy of binary diagnostic tests in the presence of partial disease verification

Calculating sample size to evaluate the accuracy of a binary diagnostic test and to compare the accuracy of two binary diagnostic tests is an important question in the study of diagnostic statistical methods. In the presence of partial disease verification, the disease status of some patients in the sample is unknown, so that the calculation of sample size can be complicated. A method to calculate sample size when evaluating the sensitivity and the specificity of a binary diagnostic test and when comparing the sensitivity and specificity of two binary tests in the presence of partial disease verification is proposed. The results obtained were applied to the diagnosis of coronary stenosis.

EM algorithm for comparing two binary diagnostic tests when not all the patients are verified

The comparison of the efficiency of two binary diagnostic tests is one of the most interesting problems in the study of the methods of diagnosis of disease. In the presence of partial disease verification, in the case of some patients, the true disease status is not known and, therefore, comparison of the accuracy of the two binary diagnostic tests cannot be carried out through the traditional method. In this study, an EM algorithm is proposed to compute the values of the maximum likelihood estimators of sensitivity, specificity and the predictive values of the diagnostic tests. Hypothesis tests have been deduced to compare these measurements in two diagnostic tests, estimating the variances–covariances by applying the SEM algorithm and the delta method. Simulation experiments have been carried out to study the asymptotic behaviour of the hypothesis tests obtained. The results have been applied to the diagnosis of coronary stenosis.The comparison of the efficiency of two binary diagnostic tests is one of the most interesting problems in the study of the methods of diagnosis of disease. In the presence of partial disease verification, in the case of some patients, the true disease status is not known and, therefore, comparison of the accuracy of the two binary diagnostic tests cannot be carried out through the traditional method. In this study, an EM algorithm is proposed to compute the values of the maximum likelihood estimators of sensitivity, specificity and the predictive values of the diagnostic tests. Hypothesis tests have been deduced to compare these measurements in two diagnostic tests, estimating the variances–covariances by applying the SEM algorithm and the delta method. Simulation experiments have been carried out to study the asymptotic behaviour of the hypothesis tests obtained. The results have been applied to the diagnosis of coronary stenosis.

Risk of Error and the Kappa Coefficient of a Binary Diagnostic Test in the Presence of Partial Verification

The accuracy of a binary diagnostic test is usually measured in terms of its sensitivity and its specificity, or through positive and negative predictive values. Another way to describe the validity of a binary diagnostic test is the risk of error and the kappa coefficient of the risk of error. The risk of error is the average loss that is caused when incorrectly classifying a non-diseased or a diseased patient, and the kappa coefficient of the risk of error is a measure of the agreement between the diagnostic test and the gold standard. In the presence of partial verification of the disease, the disease status of some patients is unknown, and therefore the evaluation of a diagnostic test cannot be carried out through the traditional method. In this paper, we have deduced the maximum likelihood estimators and variances of the risk of error and of the kappa coefficient of the risk of error in the presence of partial verification of the disease. Simulation experiments have been carried out to study the effect of the verification probabilities on the coverage of the confidence interval of the kappa coefficient.The accuracy of a binary diagnostic test is usually measured in terms of its sensitivity and its specificity, or through positive and negative predictive values. Another way to describe the validity of a binary diagnostic test is the risk of error and the kappa coefficient of the risk of error. The risk of error is the average loss that is caused when incorrectly classifying a non-diseased or a diseased patient, and the kappa coefficient of the risk of error is a measure of the agreement between the diagnostic test and the gold standard. In the presence of partial verification of the disease, the disease status of some patients is unknown, and therefore the evaluation of a diagnostic test cannot be carried out through the traditional method. In this paper, we have deduced the maximum likelihood estimators and variances of the risk of error and of the kappa coefficient of the risk of error in the presence of partial verification of the disease. Simulation experiments have been carried out to study the effect of the verification probabilities on the coverage of the confidence interval of the kappa coefficient.

The Effect of Verification Bias in the Naïve Estimators of Accuracy of a Binary Diagnostic Test

The assessment of a binary diagnostic test requires a knowledge of the disease status of all the patients in the sample through the application of a gold standard. In practice, the gold standard is not always applied to all of the patients, which leads to the problem of partial verification of the disease. When the accuracy of the diagnostic test is assessed using only those patients whose disease status has been verified using the gold standard, the estimators obtained in this way, known as Naïve estimators, may be biased. In this study, we obtain the explicit expressions of the bias of the Naïve estimators of sensitivity and specificity of a binary diagnostic test. We also carry out simulation experiments in order to study the effect of the verification probabilities on the Naïve estimators of sensitivity and specificity.

Computational methods for comparing two binary diagnostic tests in the presence of partial verification of the disease

In the presence of partial verification of the disease, confidence interval estimation for the difference of sensitivities and specificities cannot be carried out by applying confidence intervals for the difference of binomial proportions, and the comparison of the accuracy of the two binary tests cannot be carried out by applying McNemar’s test. In this article we propose two methods for comparing the accuracy of two binary tests in the presence of partial verification of the disease. The first method is based on the application of the EM and SEM algorithms, and the second method consists of the calculation of confidence intervals for the difference in sensitivities and specificities applying confidence intervals for the difference in the two binomial proportions from the last table obtained applying the EM algorithm. We carried out simulation experiments in order to study and compare the coverage of several confidence intervals for the difference of the sensitivities and specificities.