Estimated Post-test Probability Research Articles

Clinical usefulness of scoring systems to predict severe acute pancreatitis: A systematic review and meta-analysis with pre and post-test probability assessment.

Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking. To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP. Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022. Retrospective, prospective, cross-sectional studies or clinical trials on patients with acute pancreatitis defined as Revised Atlanta Criteria, reporting rate of SAP and using at least one score among Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Examination (APACHE)-II, RANSON, and Systemic Inflammatory Response Syndrome (SIRS) with their sensitivity and specificity were included. Random effects model meta-analyses were performed. Pre-test probability and likelihood ratio (LR) were combined to estimate post-test probability on Fagan nomograms. Pooled severity rate was used as pre-test probability of SAP and pooled sensitivity and specificity to calculate LR and generate post-test probability. A priori hypotheses for heterogeneity were developed and sensitivity analyses planned. 43 studies yielding 14,116 acute pancreatitis patients were included: 42 with BISAP, 30 with APACHE-II, 27 with Ranson, 8 with SIRS. Pooled pre-test probability of SAP ranged 16.6%-25.3%. The post-test probability of SAP with positive/negative score was 47%/6% for BISAP, 43%/5% for APACHE-II, 48%/5% for Ranson, 40%/12% for SIRS. In 18 studies comparing BISAP, APACHE-II, and Ranson in 6740 patients with pooled pre-test probability of SAP of 18.7%, post-test probability when scores were positive was 48% for BISAP, 46% for APACHE-II, 50% for Ranson. When scores were negative, post-test probability dropped to 7% for BISAP, 6% for Ranson, 5% for APACHE-II. Quality, design, and country of origin of the studies did not explain the observed high heterogeneity. The most commonly used scoring systems to predict SAP perform poorly and do not aid in decision-making.

Validity assessment of the third molar maturity index (I3M) in a Lebanese sample of adolescents and young adults

ABSTRACT The validity of third molar index (I3 M = 0.08) for discriminating minors from adults was tested in a sample of 620 panoramic radiographs of Lebanese subjects (293 females and 327 males), aged between 14 and 23 years. The technical error of measurements (TEM), the relative technical error of measurements (rTEM), the coefficient of reliability (R) and the Intraclass Correlation Coefficient (ICC) were calculated for testing intra- and inter-observer agreement. The I3 M values gradually decreased as age (years) increased across all the age groups in both sexes. For females, the sensitivity and specificity of the test were 0.61 (95% CI: 0.53–0.69) and 0.97 (95% CI: 0.93–0.98), respectively. The sensitivity and specificity for males were 0.63 (95% CI: 0.56–0.70) and 0.89 (95% CI: 0.83–0.93), respectively. The accuracy values (number of correct assessments) were 0.79 (95% CI: 0.74–0.83) for females and 0.74 (95% CI: 0.70–0.79) for males. Estimated post-test probabilities were 0.97 (95% CI: 0.91–0.99) for females and 0.90 (95% CI: 0.83–0.94) for males. The I3 M was a useful further indicator for discriminating between adults and minors in this Lebanese sample of adolescents and young adults.

Cameriere's third molar maturity index in assessing age of majority: a study of a French sample.

Forensic age estimation is a challenging field in forensic sciences because of the increase of migratory flows. Medicolegal age assessment is a key point because it has many implications for authorities. Dental age estimation is an essential part of the global age assessment. The aim of this study was to evaluate and test the accuracy of Cameriere's cutoff values of the third molar maturity index (I3M) in assessing legal adult age of 18years in a French population. The sample was constituted of 431 orthopantomograms performed between January 2014 and August 2017 on patients aged between 14 and 22years. The reproducibility and repeatability of the method were high. Age distribution gradually decreases as I3M increases in both sexes. 0.08 seemed to be the best I3M cutoff. For females, the sensitivity and specificity of the test were 74.51% and 88.23%, respectively. The sensitivity and specificity for males were 92.19% and 88.35%, respectively. The accuracies were 80.74% for female, 90.57% for male. Estimated post-test probabilities were 0.879 for female and 0.899 for male. To conclude, the specific cutoff value of I3M ˂0.08 may be a useful additional tool in discriminating adults and minors in French population.

A cross-sectional analysis of Zika virus infection in symptomatic and asymptomatic non-pregnant travellers: Experience of a European reference center during the outbreak in the Americas.

Zika virus (ZIKV) infection a concern to travellers because of potential sexual transmission and adverse pregnancy outcomes. To describe our experience in diagnosing ZIKV in travellers returning from endemic territories. Travellers were evaluated for ZIKV at our clinic in a 12-month period during the outbreak, using ZIKV-specific RT-PCR and anti-ZIKV Immunoglobulin M/G ELISA when symptomatic, and ELISA only for asymptomatic travellers, preferably from 20 days after the last exposure. All positive ELISA results were subject to confirmation by Virus Neutralization Testing. We estimated post-test probabilities of ZIKV in asymptomatic travellers. Of 462 travellers, 227 reported symptoms and 235 did not. Asymptomatic travellers had similar baseline characteristics, but were younger (median age 31 vs. 33 years, p = 0.01) and had reproductive concerns more often (75.8% vs. 24.2%). ZIKV infection was confirmed in 49 cases: 46/227 (20.3%) were symptomatic and 3/235 (1.3%) asymptomatic. Rash (positive likelihood ratio (LRP) 5.6) and conjunctivitis (LRP 10.8) predicted ZIKV infection. The post-test probability of a negative ELISA-result at 20-25 days was below 0.1%. ZIKV infection was frequent in symptomatic, but not in asymptomatic travellers. We consider negative ELISA results at 20-25 days after exposure a safe strategy to rule out ZIKV infection. Testing for ZIKV-specific antibodies within this timeframe could be particularly valuable in the management of returning travellers who wish to conceive.

Assessment of second (I2M) and third (I3M) molar indices for establishing 14 and 16 legal ages and validation of the Cameriere’s I3M cut-off for 18 years old in Chilean population

This retrospective cross-sectional study has two-fold aims: the first is to assess new cut-offs at the legal age thresholds (LATs) of 14 and 16 years old and the second is to validate the cut-off of third molar index I3M=0.08 for 18 years of age in Chilean people. Orthopantomographs from 822 Chilean children aged from 11 to 22 (472 girls and 350 boys) were analysed. For LAT of 14 years, cut-offs were found using the ROC curves singly for boys and girls. The cut-offs for boys were I2M=0.16 and I3M=0.73 while for girls we obtained I2M=0.10 and I3M=0.77. For LAT of 16 years we obtained the same cut-offs regardless of gender, which were 0.06 and 0.36 for I2M and I3M respectively. Concerning the validity of I3M cut-off for 18 years old in Chilean population, the proportion of correctly classified individuals was 83% and estimated post-test probability, PPV, was 93.2%, with a 95% confidence interval equals to 91.3%, 94.6%. Hence, the probability that a subject positive on the test was 18 years of age or older was 93.2%, confirming the validation of the I3M cut-off for Chilean population.

Validation of third molar maturity index (I3M) for discrimination of juvenile/adult status in South Indian population

Deliberate falsification of age was considered to be one of the main reasons for forensic age estimation of the living individuals. This posed to be a challenging task during criminal and legal proceedings, and ultimate care must be taken not to classify juveniles as adults. Third molars are the only developing teeth during late adolescence and early adulthood. Our study was designed to analyze the usefulness of the third molar maturity index (I3M) specific cut-off value (I3M < 0.08) to discriminate adults (≥18 years) and juveniles (<18 years) in South Indian children.216 panoramic radiographs (114 females and 102 males) of living subjects aged between 14 and 21 years were analyzed. Our results demonstrated high sensitivity (83.3% and 90.2%) and specificity (98.3% and 95.1%) for females and males respectively. The positive likelihood ratios of being adult were 50.00 and 18.35 while the negative likelihood ratios were 0.17 and 0.10 in females and males respectively. The estimated posttest probability was 98.0% in females and 94.8% in males. The obtained results showed that the specific cut-off value of I3M < 0.08 may be a useful additional tool in discrimination of individuals who are around 18 years of age.

Third molar maturity index by measurements of open apices in a Libyan sample of living subjects

In most countries, forensic age estimation in living subjects has become increasingly important in the last few years. In addition, as the age of legal majority ranges from 14 to 18 in many countries, and in Libya it is 18 years, radiographic assessment of the degree of third molar development is essential for forensic age estimation of adolescents and young adults. The aim of this paper is to assess the accuracy of the cut-off value of 0.08, by measurements of third molar index (I3M), in determining if a subject is adult or not in Libyan population. Digital panoramic radiographs of 307 healthy subjects (163 girls, 144 boys), aged between 14 and 22, were analysed. The I3M, the age and the sex of the subjects were used as predictive variable for age estimation. Using a cut-off of 0.08, the sensitivity of the test for boys was 90.9% and the specificity 100%. The proportion of correctly classified individuals was 95.1% (95% CI: 91.5–98.7%). The sensitivity for girls was 90.6% and the specificity 100%. The proportion of correctly classified individuals was 94.5% (95% CI: 90.9–98.1%). Estimated post-test probability in boys and girls was 100%. Further analyses, performed using a cut-off of 0.09, do not affect the specificity (100%) while they improve the sensitivity for both boys and girls.

Internal Medicine residents use heuristics to estimate disease probability

Training in Bayesian reasoning may have limited impact on accuracy of probability estimates. In this study, our goal was to explore whether residents previously exposed to Bayesian reasoning use heuristics rather than Bayesian reasoning to estimate disease probabilities. We predicted that if residents use heuristics then post-test probability estimates would be increased by non-discriminating clinical features or a high anchor for a target condition. We randomized 55 Internal Medicine residents to different versions of four clinical vignettes and asked them to estimate probabilities of target conditions. We manipulated the clinical data for each vignette to be consistent with either 1) using a representative heuristic, by adding non-discriminating prototypical clinical features of the target condition, or 2) using anchoring with adjustment heuristic, by providing a high or low anchor for the target condition. When presented with additional non-discriminating data the odds of diagnosing the target condition were increased (odds ratio (OR) 2.83, 95% confidence interval [1.30, 6.15], p = 0.009). Similarly, the odds of diagnosing the target condition were increased when a high anchor preceded the vignette (OR 2.04, [1.09, 3.81], p = 0.025). Our findings suggest that despite previous exposure to the use of Bayesian reasoning, residents use heuristics, such as the representative heuristic and anchoring with adjustment, to estimate probabilities. Potential reasons for attribute substitution include the relative cognitive ease of heuristics vs. Bayesian reasoning or perhaps residents in their clinical practice use gist traces rather than precise probability estimates when diagnosing.

A Randomised Assessment of Trainee Doctors' Understanding and Interpretation of Diagnostic Test Results.

Doctors are unfamiliar with diagnostic accuracy parameters despite routine clinical use of diagnostic tests to estimate disease probability. Trainee doctors completed a questionnaire exploring their understanding of diagnostic accuracy parameters; ability to calculate post-test probability of a common surgical condition (appendicitis) and their perceptions on training in this area. To determine whether the method of information provision altered interpretation, trainees were randomised to receive diagnostic test information in three ways: positive test only; positive test with specificity and sensitivity; positive test with positive likelihood ratio in layman terms. 326 candidates were recruited across 30 training sessions. Trainees scored a median of three out of seven in questions concerning knowledge of diagnostic accuracy parameters. This was affected neither by training level (P = 0.737) nor by experience in acute general surgery (P = 0.738). 30 (11.8%) candidates correctly estimated post-test probability; with 86.6% overestimating this value. Neither level of training (P = 0.180) nor experience (P = 0.242) influenced the accuracy of the estimate. Provision of the ultrasound scan results in different ways was not associated with likelihood of a correct response (P = 0.857). This study highlights the deficiencies in trainee doctors' understanding and application of diagnostic tests results. Most trainees over-estimated disease probability, increasing the risk of unnecessary intervention and treatment.

How well do health professionals interpret diagnostic information? A systematic review

ObjectiveTo evaluate whether clinicians differ in how they evaluate and interpret diagnostic test information.DesignSystematic review.Data sourcesMEDLINE, EMBASE and PsycINFO from inception to September 2013; bibliographies of retrieved studies, experts and...

Cameriere's third molar maturity index in assessing age of majority

Estimation of chronological age of an individual is one of the main challenges in forensic science. Legally to be able to treat a person as a minor or an adult, it is necessary to determine whether their age of majority (if they are older or younger than 18, in most countries). Methods for estimating age are especially important when an individual in question lacks personal documents or other means of identification. As the dental age differs in various populations, the aim of this study was to evaluate applicability of third molar method for assessing age of majority in Croatia.Cameriere's third molar maturity index (I3M) value of 0.08, measured by the open apices of the teeth, was verified in sample of 1336 panoramic images aged between 14 and 23 years. Chronological age gradually decreased as I3M increased in both genders. Males showed statistically significant advanced maturation when I3M was between 0.0 and 0.3 value. The results indicate that the sensitivity of the test for 0.08 value was 84.3% (95%CI 80.6%, 87.5%) for females and 91.2% (95%CI 88.7%, 93.1) for males. Specificity was 95.4% (95%CI 92.5%, 97.5%) and 91.9% (95%CI 88.8%, 94.3%). The proportions of accurately classified males were 88.8% and that of females 91.5%. The estimated post-test probabilities, of individuals, in other word the probability that a Croatian individual with an I3M<0.08 is 18 years or older is 94.5% for females, and 96.5% for males.With high accuracy, the third molar maturity index should be used as a determinant of the age of majority in Croatia.

Pancreatic/Biliary.

Introduction: Chronic pancreatitis (CP) is a complex syndrome characterized by pancreatic fibrosis (PF), chronic inflammation, and progressive loss of glandular exocrine and endocrine function. The lack of a practical “gold standard” in the diagnosis of CP is a challenge, as direct biopsy of the pancreas to evaluate histology may not be feasible. Endoscopic pancreatic functional tests (ePFTs) can be used to predict PF, a key histologic component of CP. To construct a diagnostic tool based on Fagan’s nomogram for calculating post-test probability of pancreatic fibrosis (PF) utilizing the ePFT in subjects with and without known risk factors for CP. Methods: Exhaustive literature was conducted for review of PF data in surgical histology and autopsy studies. Step 1: Prevalence of PF in histopathology studies of subjects with and without major risk factors (smoking, alcohol abuse, neither smoking nor alcohol) was used to determine pre-test probability of PF. No data was available for subjects with both smoking and alcohol use. Step 2: Positive and negative likelihood ratios (LR) for secretin ePFT detection of PF were calculated based on sensitivity and specificity in literature using histopathology as gold standard (Table 1). Step 3: Fagan’s nomogram (Bayesian analysis) was used to determine the post-test probability of PF incorporating pre-test probability (risk factors) and positive/negative LR of ePFT.Table 1: Test Characteristics of ePFTResults: Based on histologic gold standards, a Fagan’s nomogram was constructed to estimate post-test probability of PF based on pre-test risk factors (smokers, alcoholics, and controls) and ePFT results (Table 2).Table 2: Posttest Pprobability of Pancreatic FibrosisConclusion: ePFT can assist in the assessment for PF, which is a key component of chronic pancreatitis. A negative ePFT (even in the setting of known CP risk factors) is a useful tool to rule out PF. On the other hand, a positive ePFT can predict PF, but should be interpreted in combination with other testing modalities (i.e., EUS, MRI) and clinical features (abdominal pain, recurrent pancreatitis) for a definitive diagnosis of chronic pancreatitis. While not all patients with PF will have clinical diagnosis of chronic pancreatitis, the presence of fibrosis in addition to other factors (exocrine insufficiency, abdominal pain, diabetes) can assist in the diagnostic evaluation.

Estimation of post-test probabilities by residents: Bayesian reasoning versus heuristics?

Although the process of diagnosing invariably begins with a heuristic, we encourage our learners to support their diagnoses by analytical cognitive processes, such as Bayesian reasoning, in an attempt to mitigate the effects of heuristics on diagnosing. There are, however, limited data on the use ± impact of Bayesian reasoning on the accuracy of disease probability estimates. In this study our objective was to explore whether Internal Medicine residents use a Bayesian process to estimate disease probabilities by comparing their disease probability estimates to literature-derived Bayesian post-test probabilities. We gave 35 Internal Medicine residents four clinical vignettes in the form of a referral letter and asked them to estimate the post-test probability of the target condition in each case. We then compared these to literature-derived probabilities. For each vignette the estimated probability was significantly different from the literature-derived probability. For the two cases with low literature-derived probability our participants significantly overestimated the probability of these target conditions being the correct diagnosis, whereas for the two cases with high literature-derived probability the estimated probability was significantly lower than the calculated value. Our results suggest that residents generate inaccurate post-test probability estimates. Possible explanations for this include ineffective application of Bayesian reasoning, attribute substitution whereby a complex cognitive task is replaced by an easier one (e.g., a heuristic), or systematic rater bias, such as central tendency bias. Further studies are needed to identify the reasons for inaccuracy of disease probability estimates and to explore ways of improving accuracy.

Accuracy of Cameriere's cut-off value for third molar in assessing 18 years of age

Due to increasingly numerous international migrations, estimating the age of unaccompanied minors is becoming of enormous significance for forensic professionals who are required to deliver expert opinions. The third molar tooth is one of the few anatomical sites available for estimating the age of individuals in late adolescence. This study verifies the accuracy of Cameriere's cut-off value of the third molar index (I3M) in assessing 18 years of age. For this purpose, a sample of orthopantomographs (OPTs) of 397 living subjects aged between 13 and 22 years (192 female and 205 male) was analyzed. Age distribution gradually decreases as I3M increases in both males and females. The results show that the sensitivity of the test was 86.6%, with a 95% confidence interval of (80.8%, 91.1%), and its specificity was 95.7%, with a 95% confidence interval of (92.1%, 98%). The proportion of correctly classified individuals was 91.4%. Estimated post-test probability, p was 95.6%, with a 95% confidence interval of (92%, 98%). Hence, the probability that a subject positive on the test (i.e., I3M<0.08) was 18 years of age or older was 95.6%.

The clinical diagnostic reasoning process determining the use of endoscopy in diagnosing peptic ulcer disease.

To evaluate the clinical diagnostic reasoning process as a tool to decrease the number of unnecessary endoscopies for diagnosing peptic ulcer disease. tudy Cross-sectional KAP study. Shifa College of Medicine, Islamabad, from April to August 2010. Two hundred doctors were assessed with three common clinical scenarios of low, intermediate and high pre-test probability for peptic ulcer disease using a questionnaire. The differences between the reference estimates and the respondents' estimates of pre-test and post test probability were used for assessing the ability of estimating the pretest probability and the post test probability of the disease. Doctors were also enquired about the cost-effectiveness and safety of endoscopy. Consecutive sampling technique was used and the data was analyzed using SPSS version 16. In the low pre-test probability settings, overestimation of the disease probability suggested the doctors' inability to rule out the disease. The post test probabilities were similarly overestimated. In intermediate pre-test probability settings, both over and under estimation of probabilities were noticed. In high pre-test probability setting, there was no significant difference in the reference and the responders' intuitive estimates of post test probability. Doctors were more likely to consider ordering the test as the disease probability increased. Most respondents were of the opinion that endoscopy is not a cost-effective procedure and may be associated with a potential harm. Improvement is needed in doctors' diagnostic ability by more emphasis on clinical decision-making and application of bayesian probabilistic thinking to real clinical situations.

Letter to the editor: Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer. Some considerations

Free AccessCorrespondenceLetter to the editor: Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer. Some considerationsP Cascales, J Gil and P ParrillaP CascalesSearch for more papers by this author, J GilSearch for more papers by this author and P ParrillaSearch for more papers by this authorPublished Online:28 Jan 2014https://doi.org/10.1259/bjr/26215328SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail AboutThe Editor,We read with interest the article by Chandrashekhara et al entitled “Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer“[1]. First we want to congratulate the authors for the in-depth analysis in relation to diagnostic tests (CT) used for the evaluation of patients with peritoneal carcinomatosis from ovarian origin before citoreductive surgery. The article evaluates the role of multidetector CT (MDCT) in identifying peritoneal deposits pre-operatively. However, we would like to make some comments on the results related to the evaluation of diagnostic tests in the published study.We believe that in addition to calculating sensitivity, specificity and predictive values, the coefficients of positive and negative probability (CPP and CPN, respectively) should have been calculated as well. This is because the sensitivity and specificity values, despite completely defining validity (the degree to which a test measures what it is supposed to measure) for the diagnostic test, have the disadvantage of not providing relevant information when it comes to making a clinical decision when faced with a certain test result. The CPP and CPN express a unified summary of sensitivity and specificity, and therefore do not depend on the disease prevalence in each location and permit comparison between different studies, unlike predictive values, which are only valid for the location at which they were calculated [2,3]. In addition, the authors believe that the point estimate of parameters (not including 95%) is valid. This is not entirely correct, since all specific determinations are subject to random error, whose magnitude depends on the sample size and dispersion of individual observations.When we refer to diagnostic test studies, parameters ≥80% are considered to be optimum or high. As we can see, these are optimal only for sensitivity for peritoneal implants or peritoneal thickening in the evaluation of two areas (umbilical and hypogastric region, the latter being at the limit of what may be considered optimum). The reported specificity is acceptable. We can not use the diagnostic test to confirm the presence of peritoneal disease with peritoneal thickening (positive predictive value), although there is a tendency to exclude the presence of disease (negative predictive value) with the information provided, within the margin of error. Based on data from the study, we could not recalculate the data with confidence intervals of 95%, which would be useful to contrast the presence of the null value (that percentage would be 50%) in some of them. This would be interesting for a correct analysis of the data. Nor can we calculate in this way the CPP and CPN, which in turn allow us to compare similar studies.To conclude, we must be careful and methodical with all details involved in a research study in order to contribute efficiently to its comprehensibility and usefulness to the researchers and clinicians for whom it is intended.Yours etc.,References1 Chandrashekhara SH , Thulkar S , Srivastava DN , Kumar L , Hariprasad R , Kumar S , Sharma MC . Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer. Br J Radiol 2011;84:38–43. Link ISI, Google Scholar2 Moreira J , Bisoffi Z , Narváez A , Van denEnde J . Bayesian clinical reasoning: does intuitive estimation of likelihood ratios on an ordinal scale outperform estimation of sensitivities and specificities? J Eval Clin Pract 2008;14:934–40. Crossref Medline ISI, Google Scholar3 Puhan MA , Steurer J , Bachmann LM , ter Riet G . A randomized trial of ways to describe test accuracy: the effect on physicians' post-test probability estimates. Ann Intern Med 2005;143:184–9. Crossref Medline ISI, Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byUse of 18 F-FDG PET/CT in the preoperative evaluation of patients diagnosed with peritoneal carcinomatosis of ovarian origin, candidates to cytoreduction and hipec. A pending issueEuropean Journal of Radiology, Vol. 85, No. 10 Volume 84, Issue 1004August 2011Pages: 677-e168 2011 The British Institute of Radiology History ReceivedJanuary 27,2011AcceptedMarch 07,2011Published onlineJanuary 28,2014 Metrics Download PDF

Post-test Probability According to Prevalence

Authors Reply: We described a scenario of a highly accurate screening test in which we randomly manipulated the prevalence of the disease (i.e. pre-test probability).1 The estimation of post-test probability was possible for all arms of the study except one, in which no information on prevalence was provided. As pointed out by Galen, the option “cannot be determined” was not proposed to that group, because we wanted to use the same response scale for all versions of the scenario. Instead, we expected a higher rate of missing answers, but this did not happen. In fact, for about 90% of physicians, the estimation of post-test probability was not influenced by disease prevalence, whether it was provided or not. We agree with Galen that computing the post-test probability of disease may be cumbersome and of limited usefulness for everyday diagnosis at the bedside. However, the aim of our study was not so much to test the exact arithmetic skills necessary for Bayesian calculations, for which many aids exist, but rather to assess whether physicians are aware of the relationship between pre-test and post-test probability when confronted with the result of a diagnostic test. We expected that respondents would adjust the range of their post-test estimation according to a prevalence varying between 1% and 95%. To our surprise, most physicians seemed to consider that diagnostic testing yields a fixed probability that characterizes the test’s performance. Ignoring the importance of pre-test probability when interpreting test results could result in unnecessary testing, patient anxiety, and even diagnostic errors. For example, without going as far as computing the exact post-test probability, it would be incorrect to rule out pulmonary embolism on the basis of a negative D-Dimer test when the pre-test probability is high.2 It is true that well conceived clinical guidelines can incorporate Bayesian principles into their proposed algorithms, but it is important that physicians remain aware of the reasons that underlie these recommendations. Moreover, this knowledge is crucial for the assessment of the numerous new diagnostic tests that are regularly brought to their attention. We believe that our results should prompt the exploration of new approaches for teaching Bayesian principles and their implementation in clinical practice. New didactic models have been proposed3, as well as a wider use of graphical reporting of diagnostic information.4 However these new decision aids will go to waste if doctors do not even realize that they may need them.

Bedside teaching of clinical reasoning and evidence-based physical examination

Context and setting Medical school physical examination (PE) education focuses on the acquisition of skills in three domains: psychomotor (motor skills); affective (interaction with examinees), and cognitive (interpretation). To reinforce learning in the cognitive domain, we currently offer an advanced physical diagnosis elective to senior medical students to teach the principles of evidence-based physical examination (EBPE). Why the idea was necessary Recent studies have emphasised a ‘synthetic’ domain: practising doctors must not only recognise findings and understand their evidence-based utility, but must also make optimal management decisions based on these findings. ‘Synthesis’ is rarely taught; rather, students are expected to become adept simply with experience. Consequently, as they make the transition to internship, students may be ill-prepared to apply EBPE in practice. What was done The existing elective includes an introduction to the principles of EBPE. We developed a 3-hour structured bedside rounding session to reinforce key EBPE skills, including: estimation of pre-test probability; recognition of PE findings; evidence-based estimation of post-test probability of the disease, and decision making based on this assessment. For example, in a patient with dyspnoea, elevated neck veins, S3 heart sound and abdominojugular reflux, students decide whether to prescribe diuretics or to order an echocardiogram. Each session is structured as follows: faculty staff preselect two to four patients to examine at the bedside; small groups of three or four students examine the patients and are given feedback by the faculty staff about their examination technique and findings; the students commit to a next step in management, and the faculty staff provide feedback on the students’ decision making. Students answered preand post-elective questionnaires that measured their confidence in their ability to perform EBPE, the perceived utility of PE, and the usefulness of elective activities. Clinical vignettes presenting practice choices were used to assess clinical reasoning. Evaluation of results and impact Three 2-week electives were offered between November 2009 and March 2010. Twenty-one students participated. On a Likert scale of 1–5 (1 = not at all confident, 5 = very confident), students showed increased confidence in: (i) their PE skills in general (mean ± standard deviation [SD] score: retrospective pre-elective 3.38 ± 0.50, post-elective 4.19 ± 0.40; p < 0.05); (ii) understanding the significance of findings (mean ± SD: retrospective pre-elective 2.86 ± 0.57, post-elective 4.23 ± 0.44; p < 0.05), and (iii) making management decisions based on findings (mean ± SD: retrospective pre-elective 2.90 ± 0.87, post-elective 4.57 ± 0.60; p < 0.05). Most students requested that more bedside rounds be included in the elective. Vignettes designed to assess clinical reasoning won high pre-elective scores that did not change appreciably in post-elective testing. Our pilot of structured bedside rounds to teach senior medical students to recognise findings, understand their evidence-based utility and use assessments to make optimal management decisions was well received and valued by students. Students reported increased confidence in making management decisions based on PE findings at the end of the elective. However, improvement in clinical reasoning could not be detected using our assessments, indicating that better calibrated instruments to measure the synthetic domain must be developed.

Clinical assessment incorporating a personal genome

The cost of genomic information has fallen steeply, but the clinical translation of genetic risk estimates remains unclear. We aimed to undertake an integrated analysis of a complete human genome in a clinical context. We assessed a patient with a family history of vascular disease and early sudden death. Clinical assessment included analysis of this patient's full genome sequence, risk prediction for coronary artery disease, screening for causes of sudden cardiac death, and genetic counselling. Genetic analysis included the development of novel methods for the integration of whole genome and clinical risk. Disease and risk analysis focused on prediction of genetic risk of variants associated with mendelian disease, recognised drug responses, and pathogenicity for novel variants. We queried disease-specific mutation databases and pharmacogenomics databases to identify genes and mutations with known associations with disease and drug response. We estimated post-test probabilities of disease by applying likelihood ratios derived from integration of multiple common variants to age-appropriate and sex-appropriate pre-test probabilities. We also accounted for gene-environment interactions and conditionally dependent risks. Analysis of 2.6 million single nucleotide polymorphisms and 752 copy number variations showed increased genetic risk for myocardial infarction, type 2 diabetes, and some cancers. We discovered rare variants in three genes that are clinically associated with sudden cardiac death-TMEM43, DSP, and MYBPC3. A variant in LPA was consistent with a family history of coronary artery disease. The patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, several variants associated with a positive response to lipid-lowering therapy, and variants in CYP4F2 and VKORC1 that suggest he might have a low initial dosing requirement for warfarin. Many variants of uncertain importance were reported. Although challenges remain, our results suggest that whole-genome sequencing can yield useful and clinically relevant information for individual patients. National Institute of General Medical Sciences; National Heart, Lung And Blood Institute; National Human Genome Research Institute; Howard Hughes Medical Institute; National Library of Medicine, Lucile Packard Foundation for Children's Health; Hewlett Packard Foundation; Breetwor Family Foundation.

Pretest expectations strongly influence interpretation of abnormal laboratory results and further management

BackgroundAbnormal results of diagnostic laboratory tests can be difficult to interpret when disease probability is very low. Although most physicians generally do not use Bayesian calculations to interpret abnormal results, their estimates of pretest disease probability and reasons for ordering diagnostic tests may - in a more implicit manner - influence test interpretation and further management. A better understanding of this influence may help to improve test interpretation and management. Therefore, the objective of this study was to examine the influence of physicians' pretest disease probability estimates, and their reasons for ordering diagnostic tests, on test result interpretation, posttest probability estimates and further management.MethodsProspective study among 87 primary care physicians in the Netherlands who each ordered laboratory tests for 25 patients. They recorded their reasons for ordering the tests (to exclude or confirm disease or to reassure patients) and their pretest disease probability estimates. Upon receiving the results they recorded how they interpreted the tests, their posttest probability estimates and further management. Logistic regression was used to analyse whether the pretest probability and the reasons for ordering tests influenced the interpretation, the posttest probability estimates and the decisions on further management.ResultsThe physicians ordered tests for diagnostic purposes for 1253 patients; 742 patients had an abnormal result (64%). Physicians' pretest probability estimates and their reasons for ordering diagnostic tests influenced test interpretation, posttest probability estimates and further management. Abnormal results of tests ordered for reasons of reassurance were significantly more likely to be interpreted as normal (65.8%) compared to tests ordered to confirm a diagnosis or exclude a disease (27.7% and 50.9%, respectively). The odds for abnormal results to be interpreted as normal were much lower when the physician estimated a high pretest disease probability, compared to a low pretest probability estimate (OR = 0.18, 95% CI = 0.07-0.52, p < 0.001).ConclusionsInterpretation and management of abnormal test results were strongly influenced by physicians' estimation of pretest disease probability and by the reason for ordering the test. By relating abnormal laboratory results to their pretest expectations, physicians may seek a balance between over- and under-reacting to laboratory test results.