Increase Test Sensitivity Research Articles

HEART + score: integrating carotid ultrasound to chest pain assessment in the emergency department.

The HEART score is a clinical decision tool that stratifies patients into categories of low, moderate, and high-risk of major adverse cardiac events in the emergency department (ED) but cannot identify underlying cardiovascular disease in patients without prior history. The presence of atherosclerosis can easily be detected at the bedside using carotid ultrasound. Plaque quantification is well established, and plaque composition can be assessed using ultrasound grayscale pixel distribution analysis. This study aimed to determine whether carotid plaque burden and/or composition correlated with risk of events and could improve the sensitivity of the HEART score in risk stratifying ED patients with chest pain. The HEART score was calculated based on history, electrocardiogram, age, risk factors, and initial troponin in patients presenting to the ED with chest pain (n = 321). Focused carotid ultrasound was performed, and maximum plaque height and total plaque area were used to determine plaque burden (quantity). Plaque composition (% blood, fat, muscle, fibrous, calcium-like tissue) was assessed by pixel distribution analysis. Carotid plaque height and area increased with HEART score (p < 0.0001). Carotid plaque % fibrous and % calcium also increased with HEART score. The HEART score had a higher area under the curve (AUC = 0.84) in predicting 30-day events compared to the plaque variables alone (AUCs < 0.70). Integrating plaque quantity into the HEART score slightly increased test sensitivity (62-69%) for 30-day events and reclassified 11 moderate-risk participants to high-risk (score 7-10). Plaque burden with advanced composition features (fibrous and calcium) was associated with increased HEART score. Integrating plaque assessment into the HEART score identified subclinical atherosclerosis in moderate-risk patients.

New light on an old syndrome: Role of Api g 7 in mugwort pollen–related celery allergy

BackgroundCelery root is known to cause severe allergic reactions in patients sensitized to mugwort pollen. ObjectiveTo study clinically well-characterized patients with celery allergy by IgE testing with a comprehensive panel of celery allergens to disentangle the molecular basis of the “celery-mugwort-syndrome”. MethodsPatients with suspected food allergy to celery underwent a standardized interview. Main inclusion criteria were a positive food challenge with celery or an unambiguous case history of severe anaphylaxis. IgE to celery allergens (rApi g 1.01, rApi g 1.02, rApi g 2, rApi g 4, nApi g 5, rApi g 6, rApi g 7), and to mugwort allergens (rArt v 1, rArt v 3, rArt v 4) were determined by ImmunoCAP. IgE levels ≥ 0.35kUA/L were regarded positive. ResultsSeventy-nine patients with allergy to celery were included. Thirty patients suffered from mild oral or rhino-conjunctival symptoms and 49 from systemic reactions. Sixty-eight % had IgE to celery extract, 80% to birch pollen and 77% to mugwort pollen. A combination of Api g 1.01, 1.02, 4, 5, and 7 increased diagnostic sensitivity for celery allergy to 92%. The LTPs Api g 2 and Api g 6 were not relevant in our celery allergic population. IgE to Api g 7, detected in 52% of patients, correlated closely (r=0.86) to Art v 1 from mugwort pollen. Eleven out of 12 patients with monosensitization to Api g 7 were IgE negative to celery extract. The odds ratio for developing a severe anaphylactic reaction rather than only mild oral symptoms was about 6 times greater (odds ratio 5.87; 95% CI 1.08-32.0, p=0.0410) for Api g 7 sensitized versus Api g 7 non-sensitized subjects. ConclusionThere is an urgent need for routine diagnostic tests to assess sensitization to Api g 7 not only to increase test sensitivity, but also to identify celery allergic patients at risk of a severe allergic reaction to celery.

Characterization of morphological structures of Fe3O4/SiO2/ZnO composite

The coprecipitation method has been successfully used for the synthesis and characterization of composite Fe3O4/SiO2/ZnO. The purpose of this research was to lower the concentrations of heavy metals in the water in an effort to restore natural functioning of the water. Because of its excellent chemical properties and high biocompatibility, silica is an intriguing and renewable material. The mixing magnetic materials Fe3O4 and ZnO can provide efficient separation effects, increase test sensitivity, and reduce detection time. The modification Fe3O4 with %wt ZnO (5; 10; 15;20) uses rice husk ash as a substitute for SiO2 in the application of heavy metal ion wastewater absorption, the aim is to minimize the composition of recyclable metal ion content which is environmentally friendly. The characterization of composite Fe3O4/SiO2/ZnO using SEM-EDS for morphological analysis and mapping of the elements that make up the sample The composite Fe3O4/SiO2/ZnO has gaps between its particles and a homogeneous shape, as seen by the SEM images.

Testing of worn face mask and saliva for SARS-CoV-2.

Exhaled SARS-CoV-2 can be detected on face masks. We compared tests for SARS-CoV-2 RNA on worn face masks and matched saliva samples. We conducted this prospective, observational, case-control study between December 2021 and March 2022. Cases comprised 30 in-center hemodialysis patients with recent COVID-19 diagnosis. Controls comprised 13 hemodialysis patients and 25 clinic staff without COVID-19 during the study period and the past 2 months. Disposable 3-layer masks were collected after being worn for 4 hours together with concurrent saliva samples. ThermoFisher COVID-19 Combo Kit (A47814) was used for RT-PCR testing. Mask and saliva testing specificities were 99% and 100%, respectively. Test sensitivity was 62% for masks, and 81% for saliva (p = 0.16). Median viral RNA shedding duration was 11 days and longer in immunocompromised versus non-immunocompromised patients (22 vs. 11 days, p = 0.06, log-rank test). While SARS-CoV-2 testing on worn masks appears to be less sensitive compared to saliva, it may be a preferred screening method for individuals who are mandated to wear masks yet averse to more invasive sampling. However, optimized RNA extraction methods and automated procedures are warranted to increase test sensitivity and scalability. We corroborated longer viral RNA shedding in immunocompromised patients.

From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer.

Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments.

Rapid detection of nicotine and benzoic acid in e-liquids with surface-enhanced Raman scattering and artificial intelligence-assisted spectrum interpretation

Electronic cigarettes have rapidly gained acceptance recently. Nicotine-containing electronic cigarette liquids (e-liquids) are prohibited in some countries, but are permitted and simply available online in others. A rapid detection method is therefore required for on-site inspection or screening of a large amount of samples. Our previous study demonstrated a surface-enhanced Raman scattering (SERS)-based approach to identify nicotine-containing e-liquids; without any pre-treatment, e-liquid can be directly tested on our solid-phase SERS substrates, made of silver nanoparticle arrays embedded in anodic aluminium oxide nanochannels (Ag/AAO). However, this approach required manual determination of spectral signatures and negative samples should be validated in the second round detection. Here, after examining 406 commercial e-liquids, we refined this approach by developing artificial intelligence (AI)-assisted spectrum interpretations. We also found that nicotine and benzoic acid can be simultaneously detected in our platform. This increased test sensitivity because benzoic acid is usually used in nicotine salts. Around 64% of nicotine-positive samples in this study showed both signatures. Using either cutoffs of nicotine and benzoic acid peak intensities or a machine learning model based on the CatBoost algorithm, over 90% of tested samples can be correctly discriminated with only one round of SERS measurement. False negative and false positive rates were 2.5–4.4% and 4.4–8.9%, respectively, depending on the interpretation method and thresholds applied. The new approach takes only 1 microliter of sample and can be performed in 1–2 min, suitable for on-site inspection with portable Raman detectors. It could also be a complementary platform to reduce samples that need to be analyzed in the central labs and has the potential to identify other prohibited additives.

Aided Cortical Auditory Evoked Potentials in Infants With Frequency-Specific Synthetic Speech Stimuli: Sensitivity, Repeatability, and Feasibility.

The cortical auditory evoked potential (CAEP) test is a candidate for supplementing clinical practice for infant hearing aid users and others who are not developmentally ready for behavioral testing. Sensitivity of the test for given sensation levels (SLs) has been reported to some degree, but further data are needed from large numbers of infants within the target age range, including repeat data where CAEPs were not detected initially. This study aims to assess sensitivity, repeatability, acceptability, and feasibility of CAEPs as a clinical measure of aided audibility in infants. One hundred and three infant hearing aid users were recruited from 53 pediatric audiology centers across the UK. Infants underwent aided CAEP testing at age 3 to 7 months to a mid-frequency (MF) and (mid-)high-frequency (HF) synthetic speech stimulus. CAEP testing was repeated within 7 days. When developmentally ready (aged 7-21 months), the infants underwent aided behavioral hearing testing using the same stimuli, to estimate the decibel (dB) SL (i.e., level above threshold) of those stimuli when presented at the CAEP test sessions. Percentage of CAEP detections for different dB SLs are reported using an objective detection method (Hotellings T 2 ). Acceptability was assessed using caregiver interviews and a questionnaire, and feasibility by recording test duration and completion rate. The overall sensitivity for a single CAEP test when the stimuli were ≥0 dB SL (i.e., audible) was 70% for the MF stimulus and 54% for the HF stimulus. After repeat testing, this increased to 84% and 72%, respectively. For SL >10 dB, the respective MF and HF test sensitivities were 80% and 60% for a single test, increasing to 94% and 79% for the two tests combined. Clinical feasibility was demonstrated by an excellent >99% completion rate, and acceptable median test duration of 24 minutes, including preparation time. Caregivers reported overall positive experiences of the test. By addressing the clinical need to provide data in the target age group at different SLs, we have demonstrated that aided CAEP testing can supplement existing clinical practice when infants with hearing loss are not developmentally ready for traditional behavioral assessment. Repeat testing is valuable to increase test sensitivity. For clinical application, it is important to be aware of CAEP response variability in this age group.

Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10mg or leflunomide (any dose) or steroids (≥ 7.5mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

PMON93 Adenoma Size &amp; Inferior Petrosal Sinus Sampling in Cushing's Disease Diagnosis - Smoke &amp; Mirrors?

Abstract Background The current guidelines on Cushing's Disease management recommend surgically resecting adenomas larger than 10 mm in size.1 For smaller adenomas, inferior petrosal sinus sampling (IPSS) is considered the gold standard to distinguish between Cushing's disease and ectopic ACTH production. We report a case where IPSS testing and the size of the adenoma on MRI were misleading in determining the final diagnosis, prompting us to challenge the existing guidelines. Clinical Case A 40-year-old female with a past medical history of hyperlipidemia, obesity (BMI 42) and prediabetes presented with secondary infertility, galactorrhea, headaches, blurred vision and weight gain (30 lbs) over the past year. Physical examination was notable for acanthosis nigricans of the neck and bilateral milky nipple discharge. Prolactin level was elevated to 46.9 ng/ml (n 4.8-23.3 ng/mL). ACTH was elevated to 83.5 pg/mL (n 7.2-63.3 pg/mL) and cortisol to 17.4 ug/dL (n 2.7-10.5 ug/dL). Salivary cortisol was elevated to 0.216 ug/dL (n &amp;lt;0.112 ug/dL), 24-hour urinary cortisol elevated to 60.2 ug (n &amp;lt;45 ug) and on 1 mg dexamethasone suppression testing, morning cortisol was elevated to 7.2 ug/dL (n &amp;lt;1.8 ug/dL). MRI revealed a 6×7×7 mm right sided pituitary mass. Referral to Neurosurgery for resection was made. Neurosurgery recommended bilateral IPSS for pre-operative tumour lateralisation. 10 ug of DDAVP was used to increase test sensitivity. Central to peripheral ACTH ratio was 1: 1. No significant laterality was noted. In the absence of other identifiable sources on CT imaging, endoscopic endonasal surgical resection was pursued. On pathology, the adenoma was immunoreactive for ACTH, confirming Cushing's Disease. Post-operative morning cortisol was 1.3 ug/dL. The patient was started on hydrocortisone 50 mg in the morning and 20 mg in the afternoon with outpatient taper two weeks following discharge to prednisone 10 mg daily. Conclusion Current guidelines recommend surgery for adenomas &amp;gt;10 mm in size, IPSS for adenomas &amp;lt; 6 mm and further diagnostics (IPSS or serum CRH and DDAVP stimulation tests plus whole-body CT) for those 6-9 mm. IPSS is strongly preferred. 1 IPSS is operator dependent and has low efficacy in tumour lateralisation. With the advent of high-resolution CT imaging and emerging data corroborating non-invasive stimulation tests,2 it may be time to shift away from IPSS as a first line test for adenomas irrespective of size. IPSS can present a costly, invasive, oft misleading, and hence superfluous testing strategy; it is high time the medical community re-evaluates its reliance on it.

The Effect Of Mouth Breathing On Exercise Induced Bronchoconstriction In Children

BACKGROUND: Exercise induced bronchoconstriction (EIB) is a common finding in the pediatric population. Nose breathing is considered to decreases hyper-responsiveness of the airways. Therefore, nose clip (NC) is used during exercise challenge test (ECT) in adults to increase test sensitivity. Data on the need for NC during ECT in children is scarce. Our aim was to evaluate the effect of breathing with and without NC on EIB in children. METHODS: A prospective study evaluating two ECT’s with/without NC within a month period. Demographic, clinical data, Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) were recorded. RESULTS: Fifty-four children (mean age 16.7 ± 1.2 y/o, 39% Female) were evaluated. Forty-four returned to visit 2. At Visit 1 (with NC) baseline FEV1 was 92.8 ± 11.0%pred and 27/44 (61%) had positive ECT (decline≥12% in FEV1) with mean FEV1 drop of 14.7 ± 11.3%pred. At visit 2 ,8.7 ± 7.7 days post visit 1 (without NC), baseline FEV1 was 88.9 ± 11.3%pred (p < 0.001), mean FEV1 drop was 9.0 ± 10.1%pred (p < 0.0001) and only 14/44 (32%) had positive ECT (p < 0.0001). A total of 14/44 (32%) of children with a positive ECT with a NC turned negative without a NC. CONCLUSIONS: Use of NC during ECT increases the rate of positive tests thus possibly improving the yield of EIB diagnosis in children. Optional physiologic mechanisms could be humidification and warming of the inhaled air through the nose cavity. The findings strengthen the recommendation of nasal blockage during ECT. Larger randomized studies are needed to unfold the full effect of nose breathing during exercise.

Perinatal COVID-19.

Perinatal COVID-19.

Multiple diagnostic tests demonstrate an increased risk of canine heartworm disease in northern Queensland, Australia

BackgroundCanine heartworm (Dirofilaria immitis) is a life-threatening infection of dogs with a global distribution. Information on the prevalence of D. immitis and associated risk factors for canine heartworm antigen positivity—and thus disease—in Australia is scarce or outdated. The current reference method for D. immitis diagnosis in dogs is via the detection of heartworm antigen in blood using commercially available microwell-based enzyme-linked immunosorbent assays (ELISAs). Heat treatment of canine plasma prior to testing has been suggested to increase test sensitivity. The aim of the current study was to estimate the prevalence of D. immitis in dogs confined to shelters in Queensland, Australia. The impact of heat treatment on antigen test results was also assessed.MethodsBlood samples (n = 166) were collected directly from dogs in seven shelters across Queensland (latitudinal span of approx. 1700 km) into EDTA blood collection tubes. A commercially available ELISA (DiroCHEK®) was used to detect canine heartworm antigen in untreated and heat-treated plasma. Whole blood was concurrently tested for the presence of microfilariae and D. immitis DNA using a modified Knott’s test and real-time PCR, respectively. Risk factors (age, gender, source, location) associated with the odds of positivity for canine heartworm were assessed using binary logistic regression models.ResultsA total of 16 dogs (9.6%; 95% confidence interval [CI]: 5.9–15.2%) were positive for canine heartworm based on combined test results. Heat treatment did not impact on the positivity of D. immitis antigen within samples (Cohen’s kappa = 0.98), but the optical density was significantly increased in paired plasma samples for D. immitis antigen-positive samples (Wilcoxon matched-pairs signed rank test, two-tailed P < 0.01). Location of the dog in a shelter in northern Queensland was the only risk factor significantly associated with the odds of a dog being more likely to be D. immitis antigen positive (odds ratio: 4.39; 95% CI: 1.26–13.51). All samples positive for the modified Knott’s test were also positive for D. immitis DNA by PCR.ConclusionsThis study demonstrated the presence of heartworm-positive dogs in shelters in Queensland, with positive animals significantly more likely to occur in northern Queensland than southern Queensland. Sustained testing for the presence of D. immitis microfilariae and antigen remain important diagnostic tools in areas with known and re-emerging canine heartworm activity.Graphical

Refinement of an open-microcavity optical biosensor for bacterial endotoxin test

The Limulus Amebocyte Lysate (LAL) test is an in vitro assay widely used in the pharmaceutical and biotechnology industries to detect bacterial endotoxins. Endotoxin is a structural component of the cell wall of Gram-negative bacteria, which has serious pathogenic effects in the body and may cause dysfunction of multiple organ systems and increased risk of mortality. To address the growing need for LAL assays due to the increased demand from drug and vaccine manufacturers, we have developed a new LAL assay approach. Our detection mechanism is different and improved from those currently used in the industry, leading to increased test sensitivity and reduced assay time. Our study utilizes an open-microcavity photonic-crystal biosensor to quantify endotoxin concentrations. It has demonstrated an improved LAL assay sensitivity by 10 fold compared to the commercial standard methods and reduced the time needed for the assay by more than half. In addition, this approach requires as little as 5 μL of LAL reagent per test, thereby decreasing costs and conserving horseshoe crabs. The results reported in this paper indicate the possibility of using the photonic-crystal biosensor based approach for significant enhancements of endotoxin testing.

Bronchoalveolar lavage in suspected COVID-19 cases with a negative nasopharyngeal swab: a retrospective cross-sectional study in a high-impact Northern Italy area.

COVID-19 diagnosis relies on molecular testing for SARS-CoV-2 via nasopharyngeal swab in the presence of suggestive clinical, radiological and laboratory findings. Since bronchoalveolar lavage liquid (BAL) collected during fibrobronchoscopy may increase test sensitivity compared to nasopharyngeal swabs, it was performed during the 2020 pandemic in clinically or radiologically suspected cases. Our aim was to determine whether clinical features, chest computed tomography (CT) findings or laboratory tests may predict patients testing positive for SARS-CoV-2 at BAL after a negative nasopharyngeal swab. We performed a retrospective cross-sectional study with multivariable analysis of suspected patients who were tested for SARS-CoV-2 at BAL after at least one negative nasopharyngeal swab. Univariable logistic regression for odds ratio and multivariate models was calculated to determine clinical, radiological and laboratory predictors. 32/198 (16%) patients had BAL positive for SARS-CoV-2, while 65/198 tested positive for other pathogens at BAL. Of the 32 patients positive for COVID, 4 had a coinfection at BAL, being thus positive both for COVID as well as for another pathogen while the remaining 105 patients were negative for COVID and other pathogens at BAL. COVID-19 patients had more often highly suggestive CT findings, higher number of involved lobes, more often ground glass opacity of more than 50% of lung parenchyma, and less frequently other radiologically suspected infections. At multivariate model, temperature also predicted BAL positivity. The procedure was well tolerated—with only one desaturation episode—while no healthcare worker was infected. In conclusion, when nasopharyngeal swabs are negative but there is clinical or imaging suspicion of COVID-19, BAL represents a complementary diagnostic tool, particularly in conjunction with suggestive/more extensive lung involvement at CT scan. The procedure did not carry increased risks for patients nor for operators, while allowing to free hospital resources, avoiding unnecessary isolations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11739-021-02714-y.

Field Postmortem Rabies Rapid Immunochromatographic Diagnostic Test for Resource-Limited Settings with Further Molecular Applications.

Functional rabies surveillance systems are crucial to provide reliable data and increase the political commitment necessary for disease control. To date, animals suspected as rabies-positive must be submitted to a postmortem confirmation using classical or molecular laboratory methods. However, most endemic areas are in low- and middle-income countries where animal rabies diagnosis is restricted to central veterinary laboratories. Poor availability of surveillance infrastructure leads to serious disease underreporting from remote areas. Several diagnostic protocols requiring low technical expertise have been recently developed, providing opportunity to establish rabies diagnosis in decentralized laboratories. We present here a complete protocol for field postmortem diagnosis of animal rabies using a rapid immunochromatographic diagnostic test (RIDT), from brain biopsy sampling to the final interpretation. We complete the protocol by describing a further use of the device for molecular analysis and viral genotyping. RIDT easily detects rabies virus and other lyssaviruses in brain samples. The principle of such tests is simple: brain material is applied on a test strip where gold conjugated antibodies bind specifically to rabies antigens. The antigen-antibody complexes bind further to fixed antibodies on the test line, resulting in a clearly visible purple line. The virus is inactivated in the test strip, but viral RNA can be subsequently extracted. This allows the test strip, rather than the infectious brain sample, to be safely and easily sent to an equipped laboratory for confirmation and molecular typing. Based on a modification of the manufacturer's protocol, we found increased test sensitivity, reaching 98% compared to the gold standard reference method, the direct immunofluorescence antibody test. The advantages of the test are numerous: rapid, easy-to-use, low cost and no requirement for laboratory infrastructure, such as microscopy or cold-chain compliance. RIDTs represent a useful alternative for areas where reference diagnostic methods are not available.

Diagnostic accuracy and utility of three dengue diagnostic tests for the diagnosis of acute dengue infection in Malaysia

BackgroundDengue is an emerging infectious disease that infects up to 390 million people yearly. The growing demand of dengue diagnostics especially in low-resource settings gave rise to many rapid diagnostic tests (RDT). This study evaluated the accuracy and utility of ViroTrack Dengue Acute - a new biosensors-based dengue NS1 RDT, SD Bioline Dengue Duo NS1/IgM/IgG combo - a commercially available RDT, and SD Dengue NS1 Ag enzyme-linked immunosorbent assay (ELISA), for the diagnosis of acute dengue infection.MethodsThis prospective cross-sectional study consecutively recruited 494 patients with suspected dengue from a health clinic in Malaysia. Both RDTs were performed onsite. The evaluated ELISA and reference tests were performed in a virology laboratory. The reference tests comprised of a reverse transcription-polymerase chain reaction and three ELISAs for the detection of dengue NS1 antigen, IgM and IgG antibodies, respectively. The diagnostic performance of evaluated tests was computed using STATA version 12.ResultsThe sensitivity and specificity of ViroTrack were 62.3% (95%CI 55.6–68.7) and 95.0% (95%CI 91.7–97.3), versus 66.5% (95%CI 60.0–72.6) and 95.4% (95%CI 92.1–97.6) for SD NS1 ELISA, and 52.4% (95%CI 45.7–59.1) and 97.7% (95%CI 95.1–99.2) for NS1 component of SD Bioline, respectively. The combination of the latter with its IgM and IgG components were able to increase test sensitivity to 82.4% (95%CI 76.8–87.1) with corresponding decrease in specificity to 87.4% (95%CI 82.8–91.2). Although a positive test on any of the NS1 assays would increase the probability of dengue to above 90% in a patient, a negative result would only reduce this probability to 23.0–29.3%. In contrast, this probability of false negative diagnosis would be further reduced to 14.7% (95%CI 11.4–18.6) if SD Bioline NS1/IgM/IgG combo was negative.ConclusionsThe performance of ViroTrack Dengue Acute was comparable to SD Dengue NS1 Ag ELISA. Addition of serology components to SD Bioline Dengue Duo significantly improved its sensitivity and reduced its false negative rate such that it missed the fewest dengue patients, making it a better point-of-care diagnostic tool. New RDT like ViroTrack Dengue Acute may be a potential alternative to existing RDT if its combination with serology components is proven better in future studies.

Social Restrictions Versus Testing Campaigns in the COVID-19 Crisis: A Predictive Model Based on the Spanish Case

Background: The global COVID-19 spread has forced countries to implement different nonpharmacological interventions (NPI) to preserve their health systems. Spain was one of the first and most severely impacted countries, both clinically and economically. In an effort to support policy decision-making, we aimed to assess the impacts of different NPI on COVID-19 epidemiology, healthcare costs and Gross Domestic Product (GDP). Methods: A modified Susceptible-Exposed-Infectious-Removed epidemiological model was created to simulate the pandemic evolution. Its output was then used to populate an economic model to predict healthcare costs and Q4 2020 GDP decline, estimated through a multiple linear regression model based on NPIs and GDP decline from 42 countries during Q2 2020. Thirteen scenarios combining different NPI were consecutively simulated in the epidemiological and economic models. Findings: With no changes in testing rate or stringency (lockdown), 2·38 million new exposed cases in the subsequent 90 days were estimated in Spain. Both increased testing and stringency could reduce cases, hospitalizations and deaths. While policies based on increased testing rates led to higher healthcare costs, increased stringency led to greater GDP declines with differences of up to 4·4% points. Increased test sensitivity may lead to a reduction of cases, hospitalizations and deaths and to the implementation of pooling techniques that can increase throughput testing capacity. Interpretation: Alternative strategies for controlling the COVID-19 spread lead to differing economic outcomes. Decision-makers may utilize this tool to identify the most suitable strategy considering epidemiological and economic outcomes. Funding: This study is funded by Grifols S.A.Declaration of Interests: EV is employee from Grifols S.A. FJC, JS-R-M, RR, PB and MMC received honoraria from Grifols S.A. for their participation in the study as subject experts, within the Fair Market Value range. DC and AK are employees from IQVIA, which was the Clinical Research Organization hired by Grifols S.A. for the implementation of this study and medical writing support. MCR is employee from Grifols S.S.N.A.

Effect of a Single Aspirin Dose Prior to Fecal Immunochemical Testing on Test Sensitivity for Detecting Advanced Colorectal Neoplasms

Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men. To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling. A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017). Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test. The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-μg Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma). Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, -3.1% to 22.2%, P = .14) at cutoff 10.2-μg Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, -5.7% to 17.5%, P = .32) at cutoff 17-μg Hb/g stool. Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test. Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE.

Low accuracy of Bayesian latent class analysis for estimation of herd-level true prevalence under certain disease characteristics—An analysis using simulated data

Estimation of the true prevalence of infected individuals involves the application of a diagnostic test to a population and adjusting according to test performance, sensitivity and specificity. Bayesian latent class analysis for the estimation of herd and animal-level true prevalence, has become increasingly used in veterinary epidemiology and is particularly useful in incorporating uncertainty and variability into analyses in a flexible framework. However, the approach has not yet been evaluated using simulated data where the true prevalence is known. Furthermore, using this approach, the within-herd true prevalence is often assumed to follow a beta distribution, the parameters of which may be modelled using hyperpriors to incorporate both uncertainty and variability associated with this parameter. Recently however, the authors of the current study highlighted a potential issue with this approach, in particular, with fitting the distributions and a tendency for the resulting distribution to invert and become clustered at zero. Therefore, the objective of the present study was to evaluate commonly specified models using simulated datasets where the herd-level true prevalence was known. The specific purpose was to compare findings from models using hyperpriors to those using a simple beta distribution to model within-herd prevalence. A second objective was to investigate sources of error by varying characteristics of the simulated dataset. Mycobacterium avium subspecies paratuberculosis infection was used as an example for the baseline dataset. Data were simulated for 1000 herds across a range of herd-level true prevalence scenarios, and models were fitted using priors from recently published studies. The results demonstrated poor performance of these latent class models for diseases characterised by poor diagnostic test sensitivity and low within-herd true prevalence. All variations of the model appeared to be sensitive to the prior and tended to overestimate herd-level true prevalence. Estimates were substantially improved in different infection scenarios by increasing test sensitivity and within-herd true prevalence. The results of this study raise questions about the accuracy of published estimates for the herd-level true prevalence of paratuberculosis based on serological testing, using latent class analysis. This study highlights the importance of conducting more rigorous sensitivity analyses than have been carried out in previous analyses published to date.

Preferences for Surveillance of Barrett’s Oesophagus: a Discrete Choice Experiment

PurposeEndoscopic surveillance for Barrett’s oesophagus is undertaken to detect dysplasia and early cancer, and to facilitate early intervention. Evidence supporting current practice is of low quality and often influenced by opinion. This study investigated the preferences of patients for surveillance of Barrett’s oesophagus in an Australian cohort. MethodsFour Barrett’s oesophagus surveillance characteristics/attributes were evaluated within a discrete choice experiment based on literature and expert opinion: (1) surveillance method (endoscopy vs a blood test vs a novel breath test), (2) risk of missing a cancer over a 10-year period, (3) screening interval, and (4) out-of-pocket cost. The data from the discrete choice experiment was analysed within the framework of random utility theory using a mixed logit regression model. ResultsThe study sample comprised patients (n = 71) undergoing endoscopic surveillance for Barrett’s oesophagus of whom n = 65 completed the discrete choice experiment. The sample was predominantly male (77%) with average age of 65 years. All attributes except surveillance method significantly influenced respondents’ preference for Barrett’s oesophagus surveillance. Policy analyses suggested that compared to the reference case (i.e. endoscopy provided annually at no upfront cost and with a 4% risk of missing cancer), increasing test sensitivity to 0.5% risk of missing cancer would increase participation by up to 50%; surveillance every 5 years would lead to 26% reduction, while every 3 to 3.5 years would result in 7% increase in participation. Respondents were highly averse to paying A$500 for the test, resulting in 48% reduction in participation. None of the other surveillance methods was preferred to endoscopy, both resulting in 11% reduction in participation. ConclusionTest sensitivity, test frequency and out-of-pocket cost were the key factors influencing surveillance uptake. Patients prefer a test with the highest sensitivity, offered frequently, that incurs no upfront costs.