Is the relationship among outcome variables shown in randomized trials?

BACKGROUND: Randomized controlled trials (RCTs) often have more than one primary outcome and frequently have secondary and harm outcomes. Comparison of outcomes between study arms is the primary focus of RCTs, but there are times when the relation between outcomes is important, such as determining whether an intermediate outcome and a clinical outcome have a strong association. We sought to determine how often reports of RCTs depict the relations among outcomes at the individual patient level and, for those studies that use composite outcomes, how often the relations between component elements are depicted. METHODS: We selected 20 general, specialty and subspecialty medical journals with high impact factors that publish original clinical research. We identified every RCT in the 2011 and 2012 issues and randomly selected 10 articles per journal. For each article we recorded the number of outcomes, the number of composite outcomes and how often the relations between outcomes or elements of composite outcomes were portrayed. RESULTS: All but 16 of the 200 RCTs had more than one outcome. Thus, outcomes could have been related in 92% of studies, but such relations were only reported in 2 (1%). A total of 33 (17%) investigations measured a composite outcome, 32 of which showed data for each component. None, however, showed cross-tabulation of the components. CONCLUSIONS: Readers are rarely shown the relation between outcomes. Mandatory posting of datasets or requirements for detailed appendices would allow readers to see these cross-tabulations, helping future investigators know which outcomes are redundant, which provide unique information and which are most responsive to changes in the independent variables. While not every relationship between outcomes requires depiction, at present such information is seldom portrayed

Failure of a patient-centered intervention to substantially increase the identification and referral for-treatment of ambulatory emergency department patients with occult psychiatric conditions: a randomized trial [ISRCTN61514736]

BACKGROUND: We previously demonstrated that a computerized psychiatric screening interview (the PRIME-MD) can be used in the Emergency Department (ED) waiting room to identify patients with mental illness. In that trial, however, informing the ED physician of the PRIME-MD results did not increase the frequency of psychiatric diagnosis, consultation or referral. We conducted this study to determine whether telling the patient and physician the PRIME-MD result would result in the majority of PRIME-MD-diagnosed patients being directed toward treatment for their mental illness. METHODS: In this single-site RCT, consenting patients with non-specific somatic chief complaints (e.g., fatigue, back pain, etc.) completed the computerized PRIME-MD in the waiting room and were randomly assigned to one of three groups: patient and physician told PRIME-MD results, patient told PRIME-MD results, and neither told PRIME-MD results. The main outcome measure was the percentage of patients with a PRIME-MD diagnosis who received a psychiatric consultation or referral from the ED. RESULTS: 183 (5% of all ED patients) were approached. 123 eligible patients consented to participate, completed the PRIME-MD and were randomized. 95 patients had outcomes recorded. 51 (54%) had a PRIME-MD diagnosis and 8 (16%) of them were given a psychiatric consultation or referral in the ED. While the frequency of consultation or referral increased as the intervention's intensity increased (tell neither = 11% (1/9), tell patient 15% (3/20), tell patient and physician 18% (4/22)), no group came close to the 50% threshold we sought. For this reason, we stopped the trial after an interim analysis. CONCLUSION: Patients willingly completed the PRIME-MD and 54% had a PRIME-MD diagnosis. Unfortunately, at our institution, informing the patient (and physician) of the PRIME-MD results infrequently led to the patient being directed toward care for their psychiatric condition

Peer Reviewed Evaluation of Registered End-Points of Randomised Trials (the PRE-REPORT study): a stepped wedge, cluster-randomised trial.

OBJECTIVE: To test whether providing relevant clinical trial registry information to peer reviewers evaluating trial manuscripts decreases discrepancies between registered and published trial outcomes. DESIGN: Stepped wedge, cluster-randomised trial, with clusters comprised of eligible manuscripts submitted to each participating journal between 1 November 2018 and 31 October 2019. SETTING: Thirteen medical journals. PARTICIPANTS: Manuscripts were eligible for inclusion if they were submitted to a participating journal during the study period, presented results from the primary analysis of a clinical trial, and were peer reviewed. INTERVENTIONS: During the control phase, there were no changes to pre-existing peer review practices. After journals crossed over into the intervention phase, peer reviewers received a data sheet describing whether trials were registered, the initial registration and enrolment dates, and the registered primary outcome(s) when enrolment began. MAIN OUTCOME MEASURE: The presence of a clearly defined, prospectively registered primary outcome consistent with the primary outcome in the published trial manuscript, as determined by two independent outcome assessors. RESULTS: We included 419 manuscripts (243 control and 176 intervention). Participating journals published 43% of control-phase manuscripts and 39% of intervention-phase manuscripts (model-estimated percentage difference between intervention and control trials = -10%, 95% CI -25% to 4%). Among the 173 accepted trials, published primary outcomes were consistent with clearly defined, prospectively registered primary outcomes in 40 of 105 (38%) control-phase trials and 27 of 68 (40%) intervention-phase trials. A linear mixed model did not show evidence of a statistically significant primary outcome effect from the intervention (estimated difference between intervention and control=-6% (90% CI -27% to 15%); one-sided p value=0.68). CONCLUSIONS: These results do not support use of the tested intervention as implemented here to increase agreement between prospectively registered and published trial outcomes. Other approaches are needed to improve the quality of outcome reporting of clinical trials. TRIAL REGISTRATION NUMBER: ISRCTN41225307

Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders

This is the author's final draft. Copyright 2014 ElsevierThe main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P < 0.0001) association between low-activity MAOA-uVNTR alleles and violent crime. This association was replicated in the group of Caucasian violent offenders (P < 0.01), but reached only a marginal trend (P = 0.08) in their African American counterparts. While violent crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P < 0.05) increase in BIS-11 total and attentional-impulsiveness scores. In summary, these findings support the role of MAOA gene as a prominent genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors

Meta-analyses and Forest plots using a microsoft excel spreadsheet: step-by-step guide focusing on descriptive data analysis

<p>Abstract</p> <p>Background</p> <p>Meta-analyses are necessary to synthesize data obtained from primary research, and in many situations reviews of observational studies are the only available alternative. General purpose statistical packages can meta-analyze data, but usually require external macros or coding. Commercial specialist software is available, but may be expensive and focused in a particular type of primary data. Most available softwares have limitations in dealing with descriptive data, and the graphical display of summary statistics such as incidence and prevalence is unsatisfactory. Analyses can be conducted using Microsoft Excel, but there was no previous guide available.</p> <p>Findings</p> <p>We constructed a step-by-step guide to perform a meta-analysis in a Microsoft Excel spreadsheet, using either fixed-effect or random-effects models. We have also developed a second spreadsheet capable of producing customized forest plots.</p> <p>Conclusions</p> <p>It is possible to conduct a meta-analysis using only Microsoft Excel. More important, to our knowledge this is the first description of a method for producing a statistically adequate but graphically appealing forest plot summarizing descriptive data, using widely available software.</p

Observer performance in Computed Tomography head reporting

Aim: To audit the reporting results of a cohort of radiographers (n=6) completing an accredited academic programme in clinical reporting of Computed Tomography (CT) head examinations. Methods: An audit of retrospective academic image case banks and prospective random clinical workload case banks. Both the academic test banks and clinical workload banks included a wide range of normal and abnormal cases of different levels of difficulty and pathology. Abnormalities included: haemorrhage, fractures, lesions, infarctions, degeneration, and normal variants from a variety of referral sources. True positive and negative, as well as false positive and negative fractions were used to mark the reports, which were analysed for accuracy against a reference standard. Further interobserver variability was assessed using Cohens Kappa, one-way analysis of variance and Tukey for multiple comparisons and significance testing at 95% confidence intervals. Results: The mean accuracy score for all radiographers (n=6) and reports (n=3,008) was 90.7% (95%CI 88.3%-93.0%). Mean sensitivity and specificity rate was 86.9% (95%CI 85.8%-88.2%), and 94% (95%CI 89.6%-98.3%) respectively. The most common errors were associated with herniation, lacunar infarctions and subtle fractures (false negatives) and involutional changes, subtle infarctions, and ventricular dilation (false positives). Conclusions: The results suggest appropriately trained radiographers can successfully undertake to report CT head examinations to a high standard. The adoption of both academic and clinical workload image banks that reflect disease examples and the prevalence that may logically be encountered in practice offers the potential for an accurate measure of performance of radiographer’s abilities

Impact of Patient Affect on Physician Estimate of Probability of Serious Illness and Test Ordering

Purpose The authors hypothesize patient facial affect may influence clinician pretest probability (PTP) estimate of cardiopulmonary emergency (CPE) and desire to order a computerized tomographic pulmonary angiogram (CTPA). Method This prospective study was conducted at three Indiana University–affiliated hospitals in two parts: collecting videos of patients undergoing CTPA for suspected acute pulmonary embolism watching a humorous video (August 2014–April 2015) and presenting the medical histories and videos to clinicians to determine the impact of patient facial affect on physicians’ PTP estimate of CPE and desire to order a CTPA (June–November 2015). Patient outcomes were adjudicated as CPE+ or CPE− by three independent reviewers. Physicians completed a standardized test of facial affect recognition, read standardized medical histories, then viewed videos of the patients’ faces. Clinicians marked their PTP estimate of CPE and desire for a CTPA before and after seeing the video on a visual analog scale (VAS). Results Fifty physicians completed all 73 videos. Seeing the patient’s face produced a > 10% absolute change in PTP estimate of CPE in 1,204/3,650 (33%) cases and desire for a CTPA in 1,095/3,650 (30%) cases. The mean area under the receiver operating characteristic curve for CPE estimate was 0.55 ± 0.15, and the change in CPE VAS was negatively correlated with physicians’ standardized test scores (r = −0.23). Conclusions Clinicians may use patients’ faces to make clinically important inferences about presence of serious illness and need for diagnostic testing. However, these inferences may fail to align with actual patient outcomes

A Bayesian decision support sequential model for severity of illness predictors and intensive care admissions in pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality in the USA. Our objective was to assess the predictive value on critical illness and disposition of a sequential Bayesian Model that integrates Lactate and procalcitonin (PCT) for pneumonia. METHODS: Sensitivity and specificity of lactate and PCT attained from pooled meta-analysis data. Likelihood ratios calculated and inserted in Bayesian/ Fagan nomogram to calculate posttest probabilities. Bayesian Diagnostic Gains (BDG) were analyzed comparing pre and post-test probability. To assess the value of integrating both PCT and Lactate in Severity of Illness Prediction we built a model that combined CURB65 with PCT as the Pre-Test markers and later integrated the Lactate Likelihood Ratio Values to generate a combined CURB 65 + Procalcitonin + Lactate Sequential value. RESULTS: The BDG model integrated a CUBR65 Scores combined with Procalcitonin (LR+ and LR-) for Pre-Test Probability Intermediate and High with Lactate Positive Likelihood Ratios. This generated for the PCT LR+ Post-test Probability (POSITIVE TEST) Posterior probability: 93% (95% CI [91,96%]) and Post Test Probability (NEGATIVE TEST) of: 17% (95% CI [15-20%]) for the Intermediate subgroup and 97% for the high risk sub-group POSITIVE TEST: Post-Test probability:97% (95% CI [95,98%]) NEGATIVE TEST: Post-test probability: 33% (95% CI [31,36%]) . ANOVA analysis for CURB 65 (alone) vs CURB 65 and PCT (LR+) vs CURB 65 and PCT (LR+) and Lactate showed a statistically significant difference (P value = 0.013). CONCLUSIONS: The sequential combination of CURB 65 plus PCT with Lactate yielded statistically significant results, demonstrating a greater predictive value for severity of illness thus ICU level care

Selection and Presentation of Imaging Figures in the Medical Literature

Background: Images are important for conveying information, but there is no empirical evidence on whether imaging figures are properly selected and presented in the published medical literature. We therefore evaluated the selection and presentation of radiological imaging figures in major medical journals. Methodology/Principal Findings: We analyzed articles published in 2005 in 12 major general and specialty medical journals that had radiological imaging figures. For each figure, we recorded information on selection, study population, provision of quantitative measurements, color scales and contrast use. Overall, 417 images from 212 articles were analyzed. Any comment/hint on image selection was made in 44 (11%) images (range 0–50% across the 12 journals) and another 37 (9%) (range 0–60%) showed both a normal and abnormal appearance. In 108 images (26%) (range 0–43%) it was unclear whether the image came from the presented study population. Eighty-three images (20%) (range 0–60%) had any quantitative or ordered categorical value on a measure of interest. Information on the distribution of the measure of interest in the study population was given in 59 cases. For 43 images (range 0–40%), a quantitative measurement was provided for the depicted case and the distribution of values in the study population was also available; in those 43 cases there was no over-representation of extreme than average cases (p = 0.37). Significance: The selection and presentation of images in the medical literature is often insufficiently documented; quantitative data are sparse and difficult to place in context