Javier Zamora

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.

Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles

BACKGROUND While live birth is the principal clinical outcome following in vitro fertilization (IVF) treatment, the number of eggs retrieved following ovarian stimulation is often used as a surrogate outcome in clinical practice and research. The aim of this study was to explore the association between egg number and live birth following IVF treatment and identify the number of eggs that would optimize the IVF outcome. METHODS Anonymized data on all IVF cycles performed in the UK from April 1991 to June 2008 were obtained from the Human Fertilization and Embryology Authority (HFEA). We analysed data from 400 135 IVF cycles. A logistic model was fitted to predict live birth using fractional polynomials to handle the number of eggs as a continuous independent variable. The prediction model, which was validated on a separate HFEA data set, allowed the estimation of the probability of live birth for a given number of eggs, stratified by age group. We produced a nomogram to predict the live birth rate (LBR) following IVF based on the number of eggs and the age of the female. RESULTS The median number of eggs retrieved per cycle was 9 [inter-quartile range (IQR) 6-13]. The overall LBR was 21.3% per fresh IVF cycle. There was a strong association between the number of eggs and LBR; LBR rose with an increasing number of eggs up to ∼15, plateaued between 15 and 20 eggs and steadily declined beyond 20 eggs. During 2006-2007, the predicted LBR for women with 15 eggs retrieved in age groups 18-34, 35-37, 38-39 and 40 years and over was 40, 36, 27 and 16%, respectively. There was a steady increase in the LBR per egg retrieved over time since 1991. CONCLUSION The relationship between the number of eggs and live birth, across all female age groups, suggests that the number of eggs in IVF is a robust surrogate outcome for clinical success. The results showed a non-linear relationship between the number of eggs and LBR following IVF treatment. The number of eggs to maximize the LBR is ∼15.

The educational effects of portfolios on undergraduate student learning: A Best Evidence Medical Education (BEME) systematic review. BEME Guide No. 11

Introduction: In recent years, the use of portfolios as learning and assessment tools has become more widespread across the range of health professions. Whilst a growing body of literature has accompanied these trends, there is no clear collated summary of the evidence for the educational effects of the use of portfolios in undergraduate education. This systematic review is the result of our work to provide such a summary. Methods: We developed a protocol based on the recommendations of the Best Evidence Medical Education (BEME) collaboration. Citations retrieved by electronic searches of 10 databases were assessed against pre-defined inclusion/exclusion criteria by two independent reviewers and full texts of potentially relevant articles were obtained. Studies were identified for inclusion in the review by examination of full text articles by two independent reviewers. At all stages, discrepancies were resolved by consensus. Data relating to characteristics of the student population, intervention, outcome measures, study design and outcomes were collected using a piloted data extraction form. Each study was assessed against 11 quality indicators designed to provide information about how well it was designed and conducted; and against the Kirkpatrick hierarchy as modified for educational settings. Comparisons between different groups were carried out using the Kruskal–Wallis test (non-parametric ANOVA) or the Mann–Whitney U test as appropriate. Results: Electronic searches yielded 2,348 citations. A further 23 citations were obtained by hand searching of reference lists. Five hundred and fifty four full articles were retrieved and assessed against our inclusion criteria. Of the 69 studies included in our review, 18 were from medicine, 32 from nursing and 19 from other allied health professions, including dentistry, physiotherapy and radiography. In all professional groups, portfolios were used mainly in the clinical setting, completion was mostly compulsory, reflection required and assessment (either formative, summative or a combination of both) the norm. Three studies used electronic portfolios. Whilst many studies used a combination of data collection methods, over half of all included studies used questionnaires, a third used focus group interviews and another third used direct assessment of portfolios. Most studies assessed student or tutor perceptions of the effect of the use of portfolios on their learning. Five studies used a comparative design, one of which was a randomized controlled trial. Studies were most likely to meet the quality indicators relating to appropriateness of study subjects, clarity of research question and completeness of data. However, in many studies, methods were not reported in sufficient detail to allow a judgement to be made. Nineteen of the 69 included studies (27%) met seven or more quality indicators. Across all professions, such ‘higher quality’ studies were more likely to have been published recently. The median ‘quality score’ (number of indicators met) rose from two for studies published in 2000 or earlier to seven for studies published in 2005 or later. Significant differences were observed between the quality scores for studies published in or before 2000 and those published between 2001 and 2004 (p = 0.027), those published in or before 2000 and those published in 2005 or later (p = 0.002) and between all studies (p = 0.004). Similar trends were seen in all professional groups. Fifty nine (85%) of the included studies were assessed at level 1 of the modified Kirkpatrick hierarchy (i.e. ‘participation’ effects, including ‘post hoc’ evaluations of student perceptions of the effects of keeping a portfolio on their learning). Nine (13%) of the studies reported direct measurement of changes in student skills or attitudes and one study reported a change in student behaviour. The main effects of portfolio use identified by the included studies were: Improvement in student knowledge and understanding (28 studies, six at Kirkpatrick level 2 or above), greater self-awareness and encouragement of reflection (44 studies, seven at Kirkpatrick level 2 or above) and the ability to learn independently (10 studies, one at Kirkpatrick level 2). The findings of higher quality studies also identified benefits in these areas. They reported improved student knowledge and understanding, particularly the ability to integrate theory with practice, although a correlation with improved scores in other assessments was not always apparent. Greater self-awareness and engagement in reflection were also noted, although some studies questioned the quality of the reflection undertaken. Higher quality studies also suggest that use of portfolios improves feedback to students and gives tutors a greater awareness of students’ needs, may help students to cope with uncertain or emotionally demanding situations and prepares students for postgraduate settings in which reflective practice is required. Time commitment required to collate a portfolio was the major drawback identified. In two of the studies, this was found to detract from other clinical learning. Conclusions: At present, the strength and extent of the evidence base for the educational effects of portfolios in the undergraduate setting is limited. However, there is evidence of an improving trend in the quality of reported studies. ‘Higher quality’ papers identify improvements in knowledge and understanding, increased self-awareness and engagement in reflection and improved student–tutor relationships as the main benefits of portfolio use. However, they also suggest that whilst portfolios encourage students to engage in reflection, the quality of those reflections cannot be assumed and that the time commitment required for portfolio completion may detract from other learning or deter students from engaging with the process unless required to do so by the demands of assessment. Further work is needed to strengthen the evidence base for portfolio use, particularly comparative studies which observe changes in student knowledge and abilities directly, rather than reporting on their perceptions once a portfolio has been completed.

The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review

BACKGROUND The prevalence of congenital uterine anomalies in high-risk women is unclear, as several different diagnostic approaches have been applied to different groups of patients. This review aims to evaluate the prevalence of such anomalies in unselected populations and in women with infertility, including those undergoing IVF treatment, women with a history of miscarriage, women with infertility and recurrent miscarriage combined, and women with a history of preterm delivery. METHODS Searches of MEDLINE, EMBASE, Web of Science and the Cochrane register were performed. Study selection and data extraction were conducted independently by two reviewers. Studies were grouped into those that used ‘optimal’ and ‘suboptimal’ tests for uterine anomalies. Meta-analyses were performed to establish the prevalence of uterine anomalies and their subtypes within the various populations. RESULTS We identified 94 observational studies comprising 89 861 women. The prevalence of uterine anomalies diagnosed by optimal tests was 5.5% [95% confidence interval (CI), 3.5–8.5] in the unselected population, 8.0% (95% CI, 5.3–12) in infertile women, 13.3% (95% CI, 8.9–20.0) in those with a history of miscarriage and 24.5% (95% CI, 18.3–32.8) in those with miscarriage and infertility. Arcuate uterus is most common in the unselected population (3.9%; 95% CI, 2.1–7.1), and its prevalence is not increased in high-risk groups. In contrast, septate uterus is the most common anomaly in high-risk populations. CONCLUSIONS Women with a history of miscarriage or miscarriage and infertility have higher prevalence of congenital uterine anomalies compared with the unselected population.

A Systematic Review of Kidney Transplantation From Expanded Criteria Donors

BACKGROUND During the past few years, there has been renewed interest in the use of expanded criteria donors (ECD) for kidney transplantation to increase the numbers of deceased donor kidneys available. More kidney transplants would result in shorter waiting times and limit the morbidity and mortality associated with long-term dialysis therapy. STUDY DESIGN Systematic review of the literature. SETTING & POPULATION Kidney transplantation population. SELECTION CRITERIA FOR STUDIES Studies were identified by using a comprehensive search through MEDLINE and EMBASE databases. Inclusion criteria were case series, cohort studies, and randomized controlled trials assessing kidney transplantation in adult recipients using ECDs. PREDICTOR A special focus was given to studies comparing the evolution of kidney transplantation between standard criteria donors (defined as a donor who does not meet criteria for donation after cardiac death or ECD) and ECDs (defined as any brain-dead donor aged > 60 years or a donor aged > 50 years with 2 of the following conditions: history of hypertension, terminal serum creatinine level >or= 1.5 mg/dL, or death resulting from a cerebrovascular accident). OUTCOMES Criteria used to define and select ECDs, practice patterns, long-term outcomes, early complications, and some patient issues, such as selection criteria and immunosuppressive management. RESULTS ECD kidneys have worse long-term survival than standard criteria donor kidneys. The optimal ECD kidney for donation depends on adequate glomerular filtration rate and acceptable donor kidney histological characteristics, albeit the usefulness of biopsy is debated. LIMITATIONS This review is based mainly on data from observational studies, and varying amounts of bias could be present. We did not attempt to quantitatively analyze the effect of ECD kidneys on kidney transplantation because of the huge heterogeneity found in study designs and definitions of ECD. CONCLUSIONS Based on the available evidence, we conclude that patients younger than 40 years or scheduled for kidney retransplantation should not receive an ECD kidney. Patients 40 years or older, especially with diabetic nephropathy or nondiabetic disease, but a long expected waiting time for kidney transplantation, show better survival receiving an ECD kidney than remaining on dialysis therapy.

Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis

BACKGROUND Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. We assessed the performance of pulse oximetry as a screening method for the detection of critical congenital heart defects in asymptomatic newborn babies. METHODS In this systematic review, we searched Medline (1951-2011), Embase (1974-2011), Cochrane Library (2011), and Scisearch (1974-2011) for relevant citations with no language restriction. We selected studies that assessed the accuracy of pulse oximetry for the detection of critical congenital heart defects in asymptomatic newborn babies. Two reviewers selected studies that met the predefined criteria for population, tests, and outcomes. We calculated sensitivity, specificity, and corresponding 95% CIs for individual studies. A hierarchical receiver operating characteristic curve was fitted to generate summary estimates of sensitivity and specificity with a random effects model. FINDINGS We screened 552 studies and identified 13 eligible studies with data for 229,421 newborn babies. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76·5% (95% CI 67·7-83·5). The specificity was 99·9% (99·7-99·9), with a false-positive rate of 0·14% (0·06-0·33). The false-positive rate for detection of critical congenital heart defects was particularly low when newborn pulse oximetry was done after 24 h from birth than when it was done before 24 h (0·05% [0·02-0·12] vs 0·50 [0·29-0·86]; p=0·0017). INTERPRETATION Pulse oximetry is highly specific for detection of critical congenital heart defects with moderate sensitivity, that meets criteria for universal screening. FUNDING None.

Correlation Between Pain, Disability, and Quality of Life in Patients With Common Low Back Pain

Study Design. Correlation among previously validated questionnaires. Objectives. To determine the correlation between pain, disability, and quality of life in patients with low back pain. Summary of Background Data. The Visual Analogue Scale (VAS), and the Roland-Morris (RMQ), Oswestry (OQ), and EuroQol (EQ) Questionnaires are validated instruments to assess pain, low back pain-related disability, and quality of life. Methods. The study was done in the primary care setting, in Mallorca, with 195 patients who visited their physician for LBP. Individuals were given the VAS, RMQ, OQ, and EQ on their first visit and 14 days later. Results. Median duration of pain when entering the study was 10 days (P25,P75: 3, 40). On day 1, simple correlation was r = 0.347 between VAS and RMQ, r = −0.422 between VAS and EQ, and r = −0.442 between RMQ and EQ. On day 15, simple correlation was r = 0.570 between VAS and RMQ, r = −0.672 between VAS and EQ, and r = −0.637 between RMQ and EQ. Multiple linear regression models showed that, on day 1, the VAS score explains 12% of the RMQ score and the VAS and RMQ scores explain 27% of the EQ score. On day 15, the VAS score explains 33% of the RMQ score, and the VAS and RMQ scores explain 58% of the EQ score. On day 1, a 10% increase in VAS worsens disability by 3.3% and quality of life by 2.65%. On day 15, a 10% increase in VAS worsens disability by 4.99% and quality of life by 3.80%. Prestudy duration of pain had no influence on any model. All these correlation coefficients and models are significant at the P < 0.001 level. The OQ had lower correlation values with the other three scales, and only two of them were significant. Conclusion. Clinically relevant improvements in pain may lead to almost unnoticeable changes in disability and quality of life. Therefore, these variables should be assessed separately when evaluating the effect of any form of treatment for low back pain. The influence of pain and disability on quality of life progresses while they last, and doubles in 14 days. In acute and subacute patients, this increase is not dependent on the previous duration of pain.

Prognosis for the co‐twin following single‐twin death: a systematic review

Background  Following single‐twin death, the perinatal mortality and morbidity for the surviving co‐twin is increased but difficult to quantify. We present data on prognosis from a systematic review.

Immunosuppression With Calcineurin Inhibitors With Respect to the Outcome of HCV Recurrence After Liver Transplantation: Results of a Meta-analysis

A controversy exists over whether the outcome of a hepatitis C virus (HCV)‐infection‐related liver transplant differs based on the calcineurin inhibitor (CNI) used. We have performed a systematic review and a subsequent meta‐analysis evaluating tacrolimus (Tac)‐based vs. cyclosporine A‐based immunosuppression in HCV‐infected liver transplant recipients. Searches were conducted to locate randomized controlled trials comparing Tac vs. cyclosporine A. Data on HCV liver transplant recipients were obtained, independently of whether the study was specifically designed for patients with this disease or not. A fixed effects model was used for statistical pooling of the relative risks (RR) for the different outcomes. A total of 5 articles (366 patients) fulfilled the inclusion criteria. Statistically significant differences between Tac‐based vs. cyclosporine A‐based therapies were not found for mortality (P = 0.11; RR = 0.72; 95% confidence interval [CI], 0.49‐1.08), graft survival (P = 0.37; RR = 0.86; 95% CI, 0.61‐1.21), biopsy‐proven acute rejection (P = 0.65; RR = 0.91; 95% CI, 0.61‐1.36), corticoresistant acute rejection (P = 0.26; RR = 2.25; 95% CI, 0.55‐9.29), and fibrosing cholestatic hepatitis (P = 0.92; RR = 0.96; 95% CI, 0.41‐2.26). In 1 study, no differences were detected regarding severe fibrosis at 1 yr. In conclusion, patient and graft survivals in HCV‐positive liver transplant patients are similar independently of the CNI selected as basic immunosuppressant. Unfortunately, data on the severity of recurrence and effect on viremia are scarce. Well‐designed randomized prospective studies are needed to determine whether there are differences between the 2 CNIs regarding these specific variables. Liver Transpl 13:21–29, 2007.

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.