The Prognostic Value of Hyponatremia for Predicting Poor Outcome in Patients With COVID-19: A Systematic Review and Meta-Analysis

Background: This meta-analysis aimed to assess the prognostic value of hyponatremia in patients with COVID-19.Methods: We performed a systematic literature search on PubMed, Scopus, ScienceDirect, and Wiley up until January 26, 2021. The key exposure was hyponatremia, defined as sodium level below the reference level. The outcome of interest was poor outcome, which was a composite of mortality, severe COVID-19, and prolonged hospitalization. Severe COVID-19 was defined severe CAP or needing ICU care or IMV. The pooled effect estimate was odds ratio (OR). Sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic OR (DOR), and area under curve (AUC) were generated.Results: There were 11,493 patients from eight studies included in this systematic review and meta-analysis. The incidence of hyponatremia was 24%, and incidence of poor outcome was 20%. Hyponatremia was associated with poor outcome in COVID-19 (OR 2.65 [1.89, 3.72], p < 0.001; I2: 67.2%). Meta-regression analysis showed that the association between hyponatremia and poor outcome was reduced by age (OR 0.94 [0.90, 0.98], p = 0.006) and hypertension (OR 0.96 [0.93, 0.94], p < 0.001). Hyponatremia has a sensitivity of 0.37 [0.27, 0.48], specificity of 0.82 [0.72, 0.88], PLR of 2.0 [1.5, 2.7], NLR of 0.77 [0.69, 0.87], DOR of 3 [2, 4], and AUC of 0.62 [0.58, 0.66] for predicting poor outcome. In this pooled analysis, hyponatremia has a 33% posttest probability for poor outcome, and absence of hyponatremia confers to a 16% posttest probability.Conclusion: Hyponatremia was associated with poor outcome in patients with COVID-19.Systematic Review Registration: PROSPERO, CRD42021233592.

Validity and Diagnostic Accuracy of Clarke's Angle in Determining Paediatric Flexible Flatfoot Using Radiographic Findings as a Criterion Standard Measure: A Cross-Sectional Study

Background: Clinical diagnosis of Paediatric flexible flatfoot is still a challenging issue for the healthcare professionals. Clarke's Angle (CA) is frequently used clinically for assessing foot posture; however there is still a debate about its validity and diagnostic accuracy in evaluation of static foot posture especially in Paediatric population with some previous studies supporting, while the others are refuting its validity. The current study aimed to investigate validity and diagnostic accuracy of CA using radiographic findings as a criterion standard measure to determine flexible flatfoot between ages of 6-18 years. Methods: A cross-sectional study conducted on 612 participants (1224 feet) with flexible flatfoot aged 6-18 years (12.36 {plus minus}3.39) was recruited. The clinical measures results were compared to the criterion standard radiographic measures and displayed on the receiver operating characteristic curve (ROC) and the area under ROC curve (AUC) was computed. Intra-rater reliability, sensitivity, specificity, predictive values, and likelihood ratios were calculated for CA. Fagan nomogram was used to detect the posttest probability. Results: Clarke's angle (CA) demonstrated higher intra-rater reliability (ICC=0.99). CA showed higher sensitivity (98.4%), specificity (98.8), positive predictive value (97.3), negative predictive value (99.3), positive likelihood ratio (84) and negative likelihood ratio (0.02). AUC was 0.98[95%CI= 0095-1.00]. The positive likelihood ratio (LR+) yielded a posttest probability of 97%, while the negative likelihood ratio (LR−) yielded a posttest probability of 0.02. Conclusions: CA is a valid with high diagnostic accuracy in diagnosis of flexible flatfoot between the ages of 6-18 years.

Diagnosis of optic nerve head drusen using enhanced depth imaging optical coherence tomography

Purpose: To evaluate the efficacy of Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) in differentiating between optic nerve head drusen (ONHD) and optic disc oedema (ODE). Methods: This was a cross-sectional study of 140 patients: 83 patients with ONHD (49 hidden and 34 visible), 20 patients with pseudopapilloedema (without drusen), and 37 patients with ODE. EDI-OCT of the optic nerve was performed, selecting one high-resolution line from the HD 5-line raster protocol. Two observers blindly evaluated the presence of a hyporeflective core surrounded by a hyperreflective margin or border. The sensitivity, specificity, predictive values and posttest probability were evaluated as well as the inter-observer agreement (k). Results: EDI-OCT demonstrated a sensitivity of 92% (95% CI: 83%–96%), a specificity of 96% (95% CI: 87%–99%), with a positive predictive value of 97% and a negative predictive value of 89%. The inter-observer agreement was as remarkable as k = 0.8985 (95% CI 0.8252–0.9718). A positive EDI OCT increases the posttest probability to 97% (95% CI: 91%–99%); when negative, the posttest probability is reduced to 12% (95% CI: 6%–21%). Conclusion: EDI-OCT allowed for differentiation between ONHD and ODE with high sensitivity and specificity.

Evidence-Based Physical Examination for the Diagnosis of Subscapularis Tears: A Systematic Review

Context: There is a renewed interest in diagnosing and treating subscapularis tears, but there is a paucity of clinical guidance to optimize diagnostic decision-making. Objective: To perform a literature review to evaluate advanced maneuvers and special tests in the diagnosis of subscapularis tears and create a diagnostic algorithm for subscapularis pathology. Data Sources: PubMed, MEDLINE, Ovid, and Cochrane Reviews databases. Study Selection: Inclusion criteria consisted of level 1 and 2 studies published in peer-reviewed scientific journals that focused on physical examination. Study Design: Systematic review. Level of Evidence: Level 2. Data Extraction: Individual test characteristics (bear hug, belly press, lift-off, Napoleon, and internal rotation lag sign) were combined in series and in parallel to maximize clinical sensitivity and specificity for any special test evaluated in at least 2 studies. A secondary analysis utilized subjective pretest probabilities to create a clinical decision tree algorithm and provide posttest probabilities. Results: A total of 3174 studies were identified, and 5 studies met inclusion criteria. The special test combination of the bear hug and belly press demonstrated the highest positive likelihood ratio (18.29). Overall, 3 special test combinations in series demonstrated a significant impact on posttest probabilities. With parallel testing, the combination of bear hug and belly press had the highest sensitivity (84%) and lowest calculated negative likelihood ratio (0.21). Conclusion: The combined application of the bear hug and belly press physical examination maneuvers is an optimal combination for evaluating subscapularis pathology. Positive findings using this test combination in series with a likely pretest probability yield a 96% posttest probability; whereas, negative findings tested in parallel with an unlikely pretest probability yield a 12% posttest probability.

Multicenter Validation of the DETAIL Questionnaire for the Screening of Spondyloarthritis in Patients With Inflammatory Bowel Diseases

Objective Spondyloarthritis (SpA) is among the most frequent extraintestinal manifestations of inflammatory bowel diseases (IBD). In this study, we aimed to validate the DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire in a multicenter cohort of patients with IBD enrolled at 11 gastroenterology units. Methods From October 2018 to March 2019, consecutive adult patients with IBD, either Crohn disease or ulcerative colitis, independently filled out the DETAIL questionnaire in the outpatient waiting room. Within 2 weeks a blinded rheumatologist assessed all the patients, irrespective of the DETAIL results, and classified them to be affected or not by SpA. The performance of the questions was evaluated through Bayesian analysis. Results Overall, 418 patients with IBD filled out the DETAIL questionnaire. Upon rheumatological evaluation, 102 (24.4%) patients received a diagnosis of SpA. Of the 6 questions, the best performances were found in question 6 [positive likelihood ratio (LR)+ 3.77], reporting inflammatory back pain at night, and in question 3 (LR+ 3.31), exploring Achilles enthesitis. The presence of back pain lasting > 3 months (LR+ 2.91), back pain with inflammatory features (LR+ 2.55), and a history of dactylitis (LR+ 2.55), also showed a fairly good performance, whereas a history of peripheral synovitis was slightly worse (LR+ 2.16). The combination of at least 3 questions answered affirmatively yielded a posttest probability of SpA of 80% or more. The presence of alternative diagnoses, such as osteoarthritis or fibromyalgia, represented a minor confounder. Conclusion The DETAIL questionnaire is a useful tool for the early detection of SpA in IBD.

Interpretable Clinical Genomics with a Likelihood Ratio Paradigm

Human Phenotype Ontology (HPO)-based analysis has become standard for genomic diagnostics of rare diseases. Current algorithms use a variety of semantic and statistical approaches to prioritize the typically long lists of genes with candidate pathogenic variants. These algorithms do not provide robust estimates of the strength of the predictions beyond the placement in a ranked list, nor do they provide measures of how much any individual phenotypic observation has contributed to the prioritization result. However, given that the overall success rate of genomic diagnostics is only around 25–50% or less in many cohorts, a good ranking cannot be taken to imply that the gene or disease at rank one is necessarily a good candidate. Likelihood ratios (LR) are statistics for summarizing diagnostic accuracy, providing a measure of how much more (or less) a patient with a disease has a particular test result compared to patients without the disease. Here, we present an approach to genomic diagnostics that exploits the LR framework to provide an estimate of (1) the posttest probability of candidate diagnoses; (2) the LR for each observed HPO phenotype, and (3) the predicted pathogenicity of observed genotypes. LIkelihood Ratio Interpretation of Clinical AbnormaLities (LIRICAL) placed the correct diagnosis within the first three ranks in 92.9% of 384 cases reports comprising 262 Mendelian diseases, with the correct diagnosis having a mean posttest probability of 67.3%. Simulations show that LIRICAL is robust to many typically encountered forms of genomic and phenomic noise. In summary, LIRICAL provides accurate, clinically interpretable results for phenotype-driven genomic diagnostics.

How to Teach Laboratory Stewardship in the Undergraduate Medical Curriculum?

Objectives Promotion of high-quality care at a lower cost requires educational initiatives across the continuum of medical education. A needs assessment was performed to inform the design of an educational tool with the goal of teaching laboratory stewardship to medical students. Methods The needs assessment consisted of semistructured interviews with core clerkship directors and residency program directors at our institution, a national survey to the Undergraduate Medical Educators Section (UMEDS) of the Association of Pathology Chairs, and a review of existing online resources that teach high-value care. Results Two major themes emerged regarding opportunities to enhance laboratory stewardship education: appropriate ordering (knowledge of test indications, pretest/posttest probability, appropriateness criteria, recognition of unnecessary testing) and correct interpretation (understanding test specifications, factors that affect the test result, recognizing inaccurate results). Conclusions The online educational tool will focus on the curricular needs identified, using a multidisciplinary approach for development and implementation.

The Jumping Up (J-Up) Test: Making the Diagnosis of Acute Appendicitis Easier in Children

We evaluate a new clinical test, jumping up (J-up) test, to diagnose easier appendicitis in children. A total of 407 patients, aged 5 to16 years, with right lower quadrant abdominal pain were asked to jump rising both hands and trying to reach a toy hanging down from the ceiling of the examination room. Bieri pediatric Face Pain Scale was used for recording the pain response. J-up test has sensitivity of 87% and specificity of 70%. A positive J-up test combined with leukocytosis (white blood cells count >12 000/mm3), neutrophilia >75%, neutrophil/lymphocyte >2, and C-reactive protein >5 mg/dL, achieved a posttest probability of appendicitis of 85%. A negative J-up test combined with the aforementioned blood markers within normal range had a posttest probability for non-appendicitis of 92%. J-up test is a reliable clinical test, which could be used even by an inexperienced doctor. Combined with classical blood markers, it could successfully predict which child is in urgent need or not of surgery.

Differential diagnostic utilities of combined testing for islet cell antibody, glutamic acid decarboxylase antibody, and tyrosine phosphatase antibody

Background. Beta-cell antibody tests are used for the differential diagnosis of diabetes mellitus. They permit to discriminate between the type 1 diabetes (T1D) and non-autoimmune diabetes types. To choose an appropriate test for ruling in or ruling out the T1D a physician needs to know how conclusive test results are. The most powerful estimate of test conclusiveness is its likelihood ratio (LHR). The higher LHR of a positive result (LHR+), the more posttest probability of T1D; the lower LHR of a negative result (LHR), the less posttest probability of T1D. Aims. To compare conclusiveness of single and combined tests for antibodies to islet cells (ICA), glutamate decarboxylase (GADA), and tyrosine phosphatase IA-2 (IA-2A), and to evaluate posttest probabilities of T1D at various pretest probabilities. Methods. All antibodies were tested in parallel in 169 children and adolescents with a new-onset T1D, and in 169 persons without this disease. ICA, GADA, and IA-2A were determined by indirect immunofluorescence, radioimmune assay, and ELISA, respectively. LHR+ and LHR were calculated with the MedCalc Statistical Software. Posttest T1D probabilities were calculated from Bayes theorem-based equation. Results. Among single tests, an ICA test had the greatest LHR+ and the smallest LHR, and consequently was the most reliable either for ruling in or ruling out the T1D. Among test combinations, an ICAGADA combination had the greatest LHR+ and was the most suitable for T1D confirmation. The triple combination ICAGADAIA-2A had the smallest LHR and was the most suitable for T1D exclusion. Conclusions. In the differential diagnosis of diabetes, the most appropriate test for ruling in the T1D is the double combination ICAGADA. With both antibodies positive, this combination provides the highest posttest T1D probabilities at any pretest probability. The most appropriate test for ruling out the T1D is the triple combination ICAGADAIA-2A. With all three antibodies negative, this combination provides the lowest posttest T1D probabilities.

The Possible Use of Preoperative Natriuretic Peptides for Discriminating Low Versus Moderate-High Surgical Risk Patient

Perioperative risk scores for patients undergoing noncardiac surgery are generally considered inaccurate, poor, or, at best, modest. We propose estimating a patient’s pretest and posttest probability of cardiac morbidity and death using the preoperative scoring system plus the negative likelihood ratio from brain natriuretic peptide (BNP) or N-terminal proB-type natriuretic peptide (NT-proBNP) plasma levels. Our clinical challenge scenario showed a pretest probability of postoperative major cardiac complications with the patient risk factor as 6.6% for the Revised Cardiac Risk Index and between 1% and 5% (intermediate risk) per the recent European Society of Cardiology and the European Society of Anesthesiologist guidelines for surgical risk estimation. In fact, the American College of Cardiology and the American Heart Association guidelines consider the same surgical procedure for elevated risk. The posttest probability takes advantage of a negative likelihood ratio from BNP plasma levels, with patient risk factor reduced to 0.8% and surgical risk to 1.1%. In the same way, the pretest American College of Surgeons National Surgical Quality Improvement Program score decreased from 18.8% to 3.5% for severe complications and from 0.9% to 0.1% for death at ≤90 days. Following noncardiac surgery, postoperative complications and mortality are often cardiac in nature. The negative likelihood ratio of BNP and NT-proBNP plasma levels provides a quick, low-cost tool for recognizing and reclassifying the cardiovascular risk of those undergoing noncardiac surgery, thereby singling out low- versus moderate-high-risk surgical patients.