Bayesian updating and sequential testing: overcoming inferential limitations of screening tests

Background Bayes’ theorem confers inherent limitations on the accuracy of screening tests as a function of disease prevalence. Herein, we establish a mathematical model to determine whether sequential testing with a single test overcomes the aforementioned Bayesian limitations and thus improves the reliability of screening tests. Methods We use Bayes’ theorem to derive the positive predictive value equation, and apply the Bayesian updating method to obtain the equation for the positive predictive value (PPV) following repeated testing. We likewise derive the equation which determines the number of iterations of a positive test needed to obtain a desired positive predictive value, represented graphically by the tablecloth function. Results For a given PPV ($$\rho$$ ρ ) approaching k, the number of positive test iterations needed given a prevalence of disease ($$\phi$$ ϕ ) is: $$n_i =\lim _{\rho \rightarrow k}\left\lceil \frac{ln\left[ \frac{\rho (\phi -1)}{\phi (\rho -1)}\right] }{ln\left[ \frac{a}{1-b}\right] }\right\rceil \qquad \qquad (1)$$ n i = lim ρ → k l n ρ ( ϕ - 1 ) ϕ ( ρ - 1 ) l n a 1 - b ( 1 ) where $$n_i$$ n i = number of testing iterations necessary to achieve $$\rho$$ ρ , the desired positive predictive value, ln = the natural logarithm, a = sensitivity, b = specificity, $$\phi$$ ϕ = disease prevalence/pre-test probability and k = constant. Conclusions Based on the aforementioned derivation, we provide reference tables for the number of test iterations needed to obtain a $$\rho (\phi )$$ ρ ( ϕ ) of 50, 75, 95 and 99% as a function of various levels of sensitivity, specificity and disease prevalence/pre-test probability. Clinical validation of these concepts needs to be obtained prior to its widespread application.

A prospective comparative analysis of the survival rates of conventional vs no-prep/minimally invasive veneers over a mean period of 9 years

Objectives The present study compares the survival rates of 186 conventional and no-prep/minimally invasive porcelain veneers in 35 patients over a mean period of 9 years. Materials and methods The veneers were placed on the incisors, canines, and premolars in 35 patients between January 2009 and December 2010. Fourteen patients received 84 conventional veneers, and 21 patients received 102 no-prep/minimally invasive veneers. The restorations were evaluated at baseline and after every 6 months until June 2019 based on modified United States Public Health Service criteria. The data was analyzed by using Wilcoxon–Breslow–Gehan and Taron–Ware tests. Kaplan–Meier survival and success curves were plotted for two groups of veneers. The results were compared by using the log rank test. A test probability of P < .05 was regarded as significant, while a test probability of P < .01 was considered to be statistically significant. Results The mean survival rate, according to the Kaplan–Meier estimator, was 9.67% for conventional veneers and 100% for the no-prep or minimal prep veneers. A total of ten absolute failures were observed in six patients: eight restoration chipping/fractures, one debonding, and one fracturing of the tooth. Mean success rate time for conventional veneers without absolute or relative failures was 9.32 years, and 10.28 years for no-prep/minimally invasive veneers. Conclusions Over a mean observation period of 9 years, the survival rate of no-prep/minimally invasive veneers exceed that of conventional veneers. Clinical relevance No-prep/minimally invasive veneers appear very effective and should always be considered in certain clinical situations.

Testing for Heparin Induced Thrombocytopenia in Hospitalized Patients: In Line with Evidence?

Background: Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Both clinical probability and laboratory testing are needed for establishing a diagnosis of HIT. The 4Ts clinical scoring system, due to a very high negative predictive value when low, offers a robust means to exclude a diagnosis of HIT. However, these strategies are under-employed in clinical practice and limited evidence indicates a high prevalence of over-testing for HIT. Methods: This retrospective analysis was conducted to identify patients who underwent heparin/PF4 antibody testing over a period of 12 months. The testing was performed using an ELISA-based IgG anti-heparin/PF4 antibody assay and an optical density (OD) of 0.4 was used as a cut-off for a positive value. Electronic medical records were reviewed for 4T score documentation, anti-PF4 results, SRA testing and 4T scores were retrospectively calculated for all the patients. SAS v9.4 (Cary, NC) was used for statistical analysis. Results: A total of 105 patients who underwent anti-PF4 antibody testing were included for analysis. Majority of the patients in our cohort were admitted in an intensive care unit setting (75/105,71.4%). On chart review, only 17 patients (16.2%) were noted to have documentation of 4T score. Based on the retrospectively calculated 4T scores, 60 patients (57.1%) had low pre-test probability, 41 (39%) had intermediate pre-test probability and 4 (3.8%) patients were noted to have high pre-test probability. Anti-PF4/heparin antibodies were positive in 9 patients, of which 5 (55.5%) patients did not undergo concomitant SRA testing. Out of 9, 4 (44.4%) had weakly positive (0.4-1.0 OD units), 2 (21.1%) had strongly positive (1.0-2.0 OD units) and 2 (21.1%) patients had very strongly positive (&gt;2 OD units) anti-PF4 antibody titers. Out of 105 patients, SRA was tested in 11 patients (10.5%) and was noted to be positive in 1 (0.95%). Overall, 2 patients were diagnosed and treated for HIT, out of which the diagnosis was not confirmed with SRA in 1 patient (due to high pre-test probability and very strong anti-PF4 titers). In the remaining patients, sepsis (48, 46.6%) and drug-induced thrombocytopenia (29, 28.2%) emerged as the most common possible causes of thrombocytopenia. Conclusion: Among hospitalized patients, over-testing for HIT is common. Practices to promote 4T score documentation and evidence-based anti-PF4 testing may help prevent unnecessary costs associated with serological testing and costly alternate anticoagulants. To improve overall outcomes, clinicians should also attempt to identify and treat other more likely causes of thrombocytopenia, especially in patients with low pre-test probability for HIT. Disclosures No relevant conflicts of interest to declare.

Satellite Observations Show Reductions in Light Emissions at International Dark Sky Places During 2012-2020

Hyde et al. previously examined the trends in light emission measured by satellite for 98 communities located in or near areas certified as “International Dark Sky Places” (IDSP), and did not find evidence of a difference in trends in comparison to 98 communities of similar size located further away. Here we re-examine the satellite dataset, making use of a newly available correction for the radiance of atmospheric airglow, and extending the analysis period by an additional two years. The new dataset is consistent with the hypothesis that light emissions tend to decrease in communities in or near certified IDSP (median value of -1.6% per year), and is in tension with the hypothesis that there is no difference between these communities and others located further away (median increase of +0.1% per year). While the null hypothesis of no difference in the certified regions still cannot be entirely ruled out (Kolmogorov-Smirnov test probability of 2.5%), it appears likely that IDSP certification is associated with changes in light emissions.

Coronary computed tomographic angiography as gatekeeper for new-onset stable angina

Patients with new-onset stable angina constitute a substantial part of the population seen by cardiologists. Currently, the diagnostic workup of these patients depends on the pre-test probability of having obstructive coronary artery disease. It consists of either functional testing for myocardial ischaemia or anatomical testing by using coronary computed tomographic angiography (CCTA) or invasive coronary angiography. In case the pre-test probability is > 5%, the current guidelines for the management of chronic coronary syndromes do not state a clear preference for one of the noninvasive techniques. However, based on the recently published cost-effectiveness analysis of the PROMISE trial and considering the diagnostic yield in patients with angina and nonobstructive coronary artery disease, we argue a more prominent role for CCTA as a gatekeeper for patients with new-onset stable angina.

Performance of the 2016 diagnostic criteria for fibromyalgia in a tertiary care pain rehabilitation setting: a diagnostic accuracy study

Objectives With the International Classification of Diseases 11th revision (classifying fibromyalgia as a primary pain disorder) soon to be implemented, the importance of pain physicians being able to identify patients with fibromyalgia is emphasized. The diagnostic criteria proposed in 2016 are based on self-reported pain distribution and symptom severity. The study aimed to evaluate the diagnostic accuracy of the 2016 diagnostic criteria for fibromyalgia applied in a population of patients with high impact chronic pain referred for pain rehabilitation. Methods The study was performed as a diagnostic accuracy study at two Danish interdisciplinary pain rehabilitation centers, including 215 participants. All participants were evaluated clinically to identify patients with fibromyalgia. The diagnosis was based on expert opinion, but the minimum requirements were: (1) pain in all four body quadrants and axially for at least three months and (2) minimum 8 of 18 positive tender points. Participants filled in the fibromyalgia survey questionnaire, the patient version of the 2016 diagnostic criteria. Sensitivity, specificity, likelihood ratios, and positive and negative post-test probabilities were calculated using a clinical diagnosis of fibromyalgia as the reference standard. Results Based on clinical diagnosis 45% of the participants were diagnosed with fibromyalgia; of these, only 19% had been diagnosed previously. The 2016 diagnostic criteria demonstrated a sensitivity of 88.5%, a specificity of 81.5%, a positive likelihood ratio of 4.79, a negative likelihood ratio of 0.14, a positive post-test probability of 79.4%, and a negative post-test probability of 10.2%. Conclusions Fibromyalgia was severely under-diagnosed among patients with high impact chronic pain referred to tertiary care in two pain rehabilitation centers in Denmark. The 2016 diagnostic criteria showed sufficient discriminatory properties suggesting that the fibromyalgia survey questionnaire can be used as a screening tool assisting the identification of fibromyalgia in this patient population.

The Value of a Systematic Protocol Using Endobronchial Ultrasound and Endoscopic Ultrasound in Staging of Lung Cancer for Patients with Imaging iN0–N1 Disease

<b><i>Introduction:</i></b> We hypothesize that systematic, combined, and multidisciplinary study of the mediastinum (endobronchial ultrasound [EBUS] and endoscopic ultrasound [EUS]) in patients with NSCLC with radiologically normal mediastinum improves the results of mediastinal staging obtained with EBUS alone. <b><i>Material and Methods:</i></b> A retrospective study of the prospective database collected on the patients with NSCLC with a radiologically normal mediastinum and an indication for systematic staging with EBUS and EUS. EBUS staging was followed by EUS in patients in which the results from the pathological analysis of EBUS were negative. <b><i>Results:</i></b> Forty-five patients were included in the analysis. The combination of EBUS followed by EUS provided better results than EBUS alone: sensitivity (S) 95% versus 80%, negative predictive value (NPV) 96.15% versus 86.21%, negative likelihood ratio 0.05 versus 0.20, and post-test probability 3.8% versus 13.8%. This represents an increase in S (15%), the validity index (6.6%), and NPV (9.9%) compared to EBUS alone. There were 4 false negatives (FNs) (8.8%) with the EBUS test alone. After adding EUS, 3 more cases were positive (6.6%) and only 1 FN (2.2%). <b><i>Conclusions:</i></b> In patients with NSCLC and a radiographically normal mediastinum, a systematic and combined staging with EBUS and EUS show higher sensitivity in the detection of mediastinal metastasis than with the use of EBUS alone. The high accuracy of the test means that the use of mediastinoscopy is not necessary to confirm the results in these patients. Since the availability of EUS is low, it may be advisable for the interventional pulmonologist to receive training in EUS-b.

Bayesian Updating and Sequential Testing: Overcoming Inferential Limitations of Screening Tests

Background: Bayes’ Theorem confers inherent limitations on the accuracy of screening tests as a function of disease prevalence. Herein, we establish a mathematical model to determine whether sequential testing with a single test overcomes the aforementioned Bayesian lim- itations and thus improves the reliability of screening tests. Methods: We use Bayes’ Theorem to derive the positive predictive value equation, and apply the Bayesian updating method to obtain the equation for the positive predictive value (PPV) following repeated testing. We likewise derive the equation which determines the number of iterations of a positive test needed to obtain a desired positive pre- dictive value, represented graphically by the tablecloth function. Results: For a given PPV ρ approaching k, the number of positive test iterations given a prevalence φ needed is: [see equation], where ni = number of testing iterations necessary to achieve ρ, the desired positive predictive value, ln = the natural logarithm, a = sensitivity, b = specificity, φ = disease prevalence/pre-test probability and k = constant. Conclusions: Based on the aforementioned derivation, we provide reference tables for the number of test iterations needed to obtain a ρ(φ) of 50, 75, 95 and 99% as a function of various levels of sensitivity, specificity and disease prevalence/pre-test probability. Clinical vali- dation of these concepts needs to be obtained prior to its widespread application.