Evaluating the Efficacy of a Screening Protocol for Severe Acute Respiratory Syndrome Coronavirus 2 Virus in Asymptomatic Preoperative/Preprocedural Patients at a Military Hospital

ABSTRACT Introduction Facing the COVID-19 pandemic, many hospitals implemented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening protocols before aerosol-generating procedures (AGPs) in an effort to protect patients and health care workers. Given the limited prior evidence on the effectiveness of such protocols, we report the process improvement experience at a military treatment facility. Materials and Methods We evaluated the outcomes of patients undergoing AGPs from March to September 2020, divided into three cohorts: a preprotocol (PP) cohort who did not receive screening, an early testing (ET) cohort representing the early months of the screening protocol, and a late testing (LT) cohort managed under adaptive modifications to the screening protocol. We recorded identifiable post-procedure COVID-19 diagnoses. The study was approved as a process improvement protocol and was determined not to meet criteria for human subject research through an institutional approval process. Results Across the three cohorts, 4520 procedures were performed: 422 PP, 1297 ET, and 2801 LT. Among 4098 procedures in the ET and LT cohorts, 12 asymptomatic patients tested positive for SARS-CoV-2 (0.29% positivity rate). One left the health system before completing the procedure and another proceeded urgently under COVID precautions, while 10 were rescheduled and completed at a later date; 7 were cleared using a test-based strategy, while 3 were cleared using a time-based strategy. Of 445 patients who had SARS-CoV-2 tests performed within 30 days following their procedures, three patients with negative preoperative tests had a positive test within 30 days, all in the LT cohort but had evidence of acquiring the infection after the procedure or had a false-positive test. Conclusions Our strategy of preprocedural SARS-CoV-2 testing successfully identified asymptomatic infected patients before surgery. Care was delayed for most of these patients without apparent detriment. Adaptation to a time-based strategy for clearance might reduce such delays, but other considerations may still influence how soon procedures should be completed after a positive test.

Prioritizing interventions for preventing COVID-19 outbreaks in military basic training

Like other congregate living settings, military basic training has been subject to outbreaks of COVID-19. We sought to identify improved strategies for preventing outbreaks in this setting using an agent-based model of a hypothetical cohort of trainees on a U.S. Army post. Our analysis revealed unique aspects of basic training that require customized approaches to outbreak prevention, which draws attention to the possibility that customized approaches may be necessary in other settings, too. In particular, we showed that introductions by trainers and support staff may be a major vulnerability, given that those individuals remain at risk of community exposure throughout the training period. We also found that increased testing of trainees upon arrival could actually increase the risk of outbreaks, given the potential for false-positive test results to lead to susceptible individuals becoming infected in group isolation and seeding outbreaks in training units upon release. Until an effective transmission-blocking vaccine is adopted at high coverage by individuals involved with basic training, need will persist for non-pharmaceutical interventions to prevent outbreaks in military basic training. Ongoing uncertainties about virus variants and breakthrough infections necessitate continued vigilance in this setting, even as vaccination coverage increases.

Qualitative Evaluation of Causes for Routine Salmonella Monitoring False-Positive Test Results in Dutch Poultry Breeding Flocks

The Salmonella monitoring program, as outlined in the EU Commission regulation 200/2010, asks for repeated sampling in order to ascertain progress in achievement of the EU target. According to Article 2.2.2.2.c of this regulation, the competent authority may decide to do a resample and retest when it has reasons to question the results of initial testing. In the Netherlands, the competent authorities have been resampling and retesting all initial positive samplings for several years because of doubts about false positive initial test results. An analysis of population data in the period 2015–2019 indicates that 48% of initial samplings at the farm were classified as false positive after resampling and retesting by the competent authorities. A qualitative analysis, assessing factors that could be associated with the occurrence of false positives, indicates that cross-contamination during the sampling process by the poultry farmer is probably the most likely source. Cross-contamination of samples during transport from the farm to the laboratory and/or cross-contamination at the laboratory are also considered possible sources. Given the slightly non-optimal system-specificity of the Salmonella monitoring program, there is good reason to make, or consider, standard resampling and retesting of initial positive results by the competent veterinary authorities possible within the EU.

The Likelihood Difference Heuristic and Binary Test Selection Given Situation-Specific Utilities

Consider the task of selecting a medical test to determine whether a patient has a particular disease. Normatively, this requires taking into account (i) the prior probability of the disease, (ii) the likelihood---for each available test---of obtaining a positive result if the medical condition is present or absent, respectively, and (iii) the utilities for both correct and incorrect treatment decisions based upon each possible test result. But these quantities may not be precisely known. Are there strategies that could help identify the test with the highest utility given incomplete information? Here we consider the Likelihood Difference Heuristic (LDH), a simple heuristic that selects the test with the highest difference between the likelihood of obtaining a true positive and a false positive test result, ignoring all other information. We prove that the LDH is optimal when the probability of the disease equals the therapeutic threshold, the probability for which treating the patient and not treating the patient have the same expected utility. By contrast, prominent models of the value of information from the literature, such as information gain, probability gain, and Bayesian diagnosticity, are not optimal under these circumstances. Further results show how, depending on the relationship of the therapeutic threshold and prior probability of the disease, it is possible to determine which likelihoods are more important for assessing tests' expected utilities. Finally, to illustrate the potential relevance for real-life contexts, we show how the LDH might be applied to choosing tests for screening of latent tuberculosis infection.

Proteinuria in hospitalised internal medicine adult patients

RationaleDipstick proteinuria may be a sign of a renal disorder, false-positive or associated with acute disease, and consequently, transient in hospitalised patients.ObjectiveTo assess (a) the prevalence of proteinuria in hospitalised patients; (b) its association with estimated glomerular filtration rate (eGFR), findings known to cause false-positive test results and indicators of acute disease and (c) the need for follow-up after discharge.Setting and participantsAll patients who had a dipstick urinalysis on admission to medical wards of a 400-bed regional hospital in 2018–2019.Outcome variableProteinuria.Independent variables(a) Other findings on dipstick urinalysis; (b) patients’ age, gender, presence of urinary catheter and eGFR and (c) white blood cell count (WBC) and fever.ResultsOf 22 329 patients, 6609 (29.6%) had urinalysis. Of those, 2973 patients (45.0%) had proteinuria of ≥+1 (≥0.30 g/L). The variables independently associated with proteinuria were other dipstick findings known to cause false-positive test results, elevated WBC, fever on presentation, presence of a urethral catheter and a low eGFR. eGFR alone was a poor predictor of proteinuria (c-stat 0.62); however, addition of the remaining independent variables to the model significantly improved its predictive ability (c-stat 0.80).ConclusionsDipstick proteinuria is common in hospitalised patients. Although weakly associated with eGFR, proteinuria is mainly associated with confounding factors that may result in false-positive test results. The need for follow-up of proteinuria after discharge has questionable clinical utility and its high frequency would entail a considerable cost.

Zinc transporter 8 autoantibody testing requires age-related cut-offs

IntroductionZinc transporter 8 autoantibodies (ZnT8A) are biomarkers of beta cell autoimmunity in type 1 diabetes that have become more widely available to clinicians in recent years. Robust control population-defined thresholds are essential to ensure high clinical specificity in islet autoantibody testing. We aimed to determine the optimal cut-offs for ZnT8A testing.Research design and methods97.5th and 99th centile cut-offs were determined using residual clinical sera from 1559 controls aged between 0 and 83 years with no history of diabetes and a hemoglobin A1c level of less than 6.0% (<42 mmol/mol). ZnT8A were measured by ELISA (RSR, Cardiff, UK) on a Dynex DS2 ELISA robot (Dynex, Preston, UK). We assessed the impact of age-related cut-offs in comparison with the manufacturer’s recommended threshold in a mixed cohort of young-onset (<age 30) diabetes (UNITED study (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes), n=145).ResultsUsing the manufacturer’s limit of detection, 6 WHO U/mL, 16.2% of people in the control cohort had detectable levels of ZnT8A and those who had detectable ZnT8A were much more likely to be younger (p<0.0001). The 97.5th and 99th centile thresholds were substantially higher in younger participants: 18 and 127 WHO U/mL (tested under 30 years) in comparison with 9 and 21 WHO U/mL (tested 30 years and over). In the UNITED cohort some of those found to be ZnT8A-positive by the manufacturer’s threshold but negative using the appropriate 99% centile cut-off (127 WHO U/mL) displayed characteristics suggestive of type 2 diabetes.ConclusionsAge-related thresholds are needed for ZnT8A testing. In those aged <30 years, use of manufacturers’ recommended cut-offs may result in low test specificity and potentially high rates of false positive test results in patients who do not have autoimmune diabetes.

Cost-effectiveness of dengue vaccination in Puerto Rico

An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue virus infection. However, in vaccinees who had no prior dengue virus infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 0.057 (0.045–0.073) additional hospitalizations could occur for every 1,000 people in Puerto Rico due to DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13–24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.

The “false positive paradox” and the risks of testing asymptomatic people for COVID-19

Widespread screening of asymptomatic people leads to high numbers of false positives when background prevalence is low, even with accurate tests. During the Covid-19 pandemic, not only has the background prevalence been low (vaccine clinical trial baseline testing finds 0.5-0.6% even during periods of higher prevalence), but the various COVID-19 tests are not very accurate. When inaccurate tests are combined with a low background prevalence, this results in a massive and unacknowledged problem of far more false positive test results than true positive test results, leading also to inaccurate characterization of COVID-19 hospitalizations and deaths.

Autoimmune Antibody in Encephalopathic Patients: A Pilot Study

Objective: To investigate the specificity of the antibodies related to autoimmune encephalitis and to identify possible associated factors with the false-positive result. Materials and Methods: The present study was a prospective observational study, conducted at the Ramathibodi Hospital between June and December 2019. All patients, who had acute to subacute encephalopathy from any causes, were recruited to the study. Their serum or cerebrospinal fluid (CSF) were taken to analyze for autoimmune encephalitis assays and anti-thyroid antibodies. The authors did not interfere with the primary physicians on any management of the patients. Clinical and laboratory data were systematically reviewed and collected from medical records. The clinical outcome was evaluated one month after the onset. Results: Fifty-one patients were recruited. Only one patient had autoimmune encephalitis related to anti-CV2/CRMP5 antibody. Seventeen out of the remaining fifty patients had positive tests for anti-thyroid antibodies of which five had Hashimoto’s thyroiditis and one of them did not have the document of thyroid status. Eleven remaining patients appeared to have false-positive test since their medical conditions were all clearly explained by other causes. Comparison of clinical and laboratory data between patients with false-positive test and patients with true negative test did not show any significant difference except the duration of the symptoms, which was significantly shorter in the false-positive group. Conclusion: False-positive anti-thyroid antibodies appear to be common in patients with acute encephalopathy. The occurrence of serum/CSF antibody in acute encephalopathy may be a true association, but it may not be the cause of encephalopathy. Therefore, the diagnosis of autoimmune encephalopathy based on anti-thyroid antibodies should be carefully made and excluded from all other possible causes. Keywords: Autoimmune encephalitis; Metabolic encephalopathy; Hashimoto’s encephalopathy; False positive