Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma-induced hypergastrinemia causing excessive gastric acid secretion. Secretin stimulation tests (SSTs) are required for diagnosis in the ...majority of patients. Two case reports suggest that proton pump inhibitors (PPIs) cause false SST results. Consequently, PPIs are discontinued to allow hyperchlorhydria to recur; however, uncontrolled acidity can cause life-threatening complications in those with underlying undiagnosed ZES. The aim of this study was to determine whether PPIs influence the validity of SSTs for the diagnosis of ZES.
A retrospective chart review was performed. Charts of patients who underwent SSTs were reviewed to determine whether they were performed on or off PPI and the test's accuracy by comparing the results with gold standard tests (diagnostic laboratory testing performed off PPI or surgical pathology consistent with gastrinoma). Sensitivity, specificity, and positive predictive value (PPV) of SST on PPI were calculated and results compared with SST off PPI using noninferiority analyses.
Twenty-eight patients corresponding to 29 SSTs were performed on PPI, and 70 patients corresponding to 107 SSTs were performed off PPI. Most of them were female and white and had multiple endocrine neoplasia type 1. We found no false-positive or false-negative SSTs on PPI. Sensitivity, specificity, and PPV of SSTs on PPI were determined to be noninferior to SSTs off PPI (P ≤ 0.05 for all).
In our cohort, SSTs on PPI compared with SSTs off PPI were noninferior for sensitivity, specificity, and PPV. These results suggest that PPI withdrawal before SSTs may not be necessary.
Abstract Objective When studies report proportions such as sensitivity or specificity, it is customary to meta-analyze them using the DerSimonian and Laird random effects model. This method ...approximates the within-study variability of the proportion by a normal distribution, which may lead to bias for several reasons. Alternatively an exact likelihood approach based on the binomial within-study distribution can be used. This method can easily be performed in standard statistical packages. We investigate the performance of the standard method and the alternative approach. Study Design and Setting We compare the two approaches through a simulation study, in terms of bias, mean-squared error, and coverage probabilities. We varied the size of the overall sensitivity or specificity, the between-studies variance, the within-study sample sizes, and the number of studies. The methods are illustrated using a published meta-analysis data set. Results The exact likelihood approach performs always better than the approximate approach and gives unbiased estimates. The coverage probability, in particular for the profile likelihood, is also reasonably acceptable. In contrast, the approximate approach gives huge bias with very poor coverage probability in many cases. Conclusion The exact likelihood approach is the method of preference and should be used whenever feasible.
Herpes simplex virus (HSV)-1 and HSV-2 are common infections affecting the global population, with HSV-1 estimated to affect 67% of the global population. HSV can have rare but severe manifestations, ...such as encephalitis and neonatal herpes, necessitating the use of reliable and accurate diagnostic tools for the detection of the viruses. Currently used HSV diagnostic tools require highly specialized skills and availability of a laboratory setting but may lack sensitivity. The numerous recently developed HSV diagnostic tools need to be identified and compared in a systematic way to make the best decision about which diagnostic tool to use. The diagnosis of HSV is essential for prompt treatment with antivirals. To select the best test for a patient, knowledge of the performance and limitations of each test is critical.
This systematic review has summarized recent studies evaluating HSV-1 and HSV-2 diagnostic tools.
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, selection criteria, data extraction, and data analysis were determined before the commencement of the study. Studies assessing the specificity/sensitivity of HSV-1 or HSV-2 diagnostic tools published between 2012 and 2018 were included. Quality assessment of included studies was performed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool.
Searches of the PubMed database yielded 264 studies; 11 studies included 11 molecular assays, and 8 studies included 19 different serological assays for the detection of HSV-1, HSV-2, or both. A greater proportion of molecular assay-based tools are being developed by commercial entities. Studies that tested molecular assays mostly focused on cutaneous and mucosal HSV infections (n=13); 2 studies focused on ocular disease, whereas only 1 study focused on the central nervous system manifestations. The Simplexa HSV 1 & 2 Direct is currently the only Food and Drug Administration-approved device for use on cerebrospinal fluid. No tools focused on prenatal screening. We also present performance metrics of tests for benchmarking of future technology. Most of the included studies had a high risk of bias rating in half of the QUADAS-2 tool risk of bias domains.
The use of serologic tests to diagnose genital lesions is inappropriate because positive results may be due to chronic infection, whereas negative results may overlook recent infection. The incidence of acute infections is rising. As these infections present the greatest risk to fetuses, work needs to be done to prevent vertical transfer. Prenatal screening for primary infection and subsequent medical intervention will assist in lowering the rate of neonatal herpes. In conclusion, HSV diagnosis is moving away from culture-based methods to serology-based or polymerase chain reaction-based methods. Sensitive, rapid, and efficient HSV diagnostic tools should be adopted for the prevention of acute infections and neonatal herpes.
Metabolomics-based strategies have become an integral part of modern clinical research, allowing for a better understanding of pathophysiological conditions and disease mechanisms, as well as ...providing innovative tools for more adequate diagnostic and prognosis approaches. Metabolomics is considered an essential tool in precision medicine, which aims for personalized prevention and tailor-made treatments. Nevertheless, multiple pitfalls may be encountered in clinical metabolomics during the entire workflow, hampering the quality of the data and, thus, the biological interpretation. This review describes the challenges underlying metabolomics-based experiments, discussing step by step the potential pitfalls of the analytical process, including study design, sample collection, storage, as well as preparation, chromatographic and electrophoretic separation, detection and data analysis. Moreover, it offers practical solutions and strategies to tackle these challenges, ensuring the generation of high-quality data.
A Brief Resolved Unexplained Event (BRUE) can be a sign of occult physical abuse.
To identify rates of diagnostic testing able to detect physical abuse (head imaging, skeletal survey, and liver ...transaminases) at BRUE presentation. The secondary objective was to estimate the rate of physical abuse diagnosed at initial BRUE presentation through 1 year of age.
Infants who presented with a BRUE at one of 15 academic or community hospitals were followed from initial BRUE presentation until 1 year of age for BRUE recurrence or revisits.
This study was part of the BRUE Research and Quality Improvement Network, a multicenter retrospective cohort examining infants with BRUE. Generalized estimating equations assessed associations with performance of diagnostic testing (adjusted odds ratio (aOR)).
Of the 2036 infants presenting with a BRUE, 6.2 % underwent head imaging, 7.0 % skeletal survey, and 12.1 % liver transaminases. Infants were more likely to undergo skeletal survey if there were physical examination findings concerning for trauma (aOR 8.23, 95 % CI 1.92, 35.24, p < 0.005) or concerning social history (aOR 1.89, 95 % CI 1.13, 3.16, p = 0.015). There were 7 (0.3 %) infants diagnosed with physical abuse: one at BRUE presentation, one <3 days after BRUE presentation, and five >30 days after BRUE presentation.
There were low rates of diagnostic testing and physical abuse identified in infants presenting with BRUE. Further study including standardized testing protocols is warranted to identify physical abuse in infants presenting with a BRUE.
•Rates of diagnostic testing to detect physical abuse were low in infants with BRUE.•Child physical abuse did not differ between lower- and higher-risk BRUE designations.•The rate of physical abuse detected in infants with BRUE was low.
US Food and Drug Administration (FDA)‐approved diagnostic assays play an increasingly common role in managing patients to prolong lifespan while also enhancing quality of life. Diagnostic assays can ...be essential for the safe and effective use of therapeutics (companion diagnostic), or may inform on improving the benefit/risk ratio without restricting drug access (complementary diagnostic). This tutorial reviews strategic considerations for drug and assay development resulting in FDA‐approved companion or complementary diagnostic status.
Dystonia is the third most common movement disorder, characterized by abnormal, frequently twisting postures related to co-contraction of agonist and antagonist muscles. Diagnosis is challenging. We ...provide a comprehensive appraisal of the epidemiology and an approach to the phenomenology and classification of dystonia, based on the clinical characteristics and underlying etiology of dystonia syndromes. We discuss the features of common idiopathic and genetic forms of dystonia, diagnostic challenges, and dystonia mimics. Appropriate workup is based on the age of symptom onset, rate of progression, whether dystonia is isolated or combined with another movement disorder or complex neurological and other organ system features. Based on these features, we discuss when imaging and genetic should be considered. We discuss the multidisciplinary treatment of dystonia, including rehabilitation and treatment principles according to the etiology, including when pathogenesis-direct treatment is available, oral pharmacological therapy, chemodenervation with botulinum toxin injections, deep brain stimulation and other surgical therapies, and future directions.
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