Low Prevalence Populations Research Articles

Rapid rule-out of acute myocardial infarction using the 0/1-hour algorithm for cardiac troponins in emergency primary care: the OUT-ACS implementation study

Abstract Background Acute chest pain in primary care often results in defensive and unnecessary hospital referrals due to the limited ability to rule out an acute myocardial infarction (AMI) outside of hospital. In a previous prospective observational study (OUT-ACS; One-hoUr Troponin in a low-prevalence population of Acute Coronary Syndrome), we demonstrated that the ESC 0/1-hour algorithm for high-sensitivity cardiac troponin T (hs-cTnT) would be safe and cost-effective if implemented to assess low-risk patients with chest pain in emergency primary care. Purpose We evaluated the real-world applicability, personnel adherence, and disposition of low-risk patients with chest pain following the implementation of the ESC 0/1-hour algorithm in emergency primary care. Methods In April 2023, the ESC 0/1-hour algorithm for hs-cTnT was implemented at a large emergency primary care clinic in Norway. The clinic is located close to a hospital, enabling the patient to wait at the clinic while blood samples are analysed for hs-cTnT at the hospital laboratory. For the following six months, all patients ≥18 years with acute non-traumatic chest discomfort, offered hs-cTnT measurements at the clinic, were anonymously registered, including their discharge diagnoses and disposition from the clinic. By applying the ESC 0/1-hour algorithm, patients were assigned to rule-out, rule-in or further observation. Patients in the observation group were offered a 4-hour hs-cTnT measurement before a final decision. Results During the six-month period, 10.3% (n=3,053/29,631) of the clinic's consultations involved chest complaints. Hs-cTnT measurements were conducted in 32.6% (n=995/3,053) with a median age of 58 years (IQR 45-68), 50.6% being female. A single hs-cTnT <5 ng/L, sampled ≥3 hours since symptom onset, triaged 24.1% (n=240/995) of the patients towards the rule-out group, increasing to 63.8% after adding a 1-hour measurement. In the rule-in group (n=42/995, 4.2%), 16 patients were diagnosed with an AMI. The intermediate observation group (n=318/995, 32.0%, 4 AMIs) was reduced to 23.0 % after a 4-hour hs-cTnT measurement. Healthcare personnel adhered well to the algorithm, with a median sampling interval of 63 minutes (IQR 60-66) and 4.5 hours (IQR 4.1-5.5) for the 1- and 4-hour measurements, respectively. The algorithm was misinterpreted or overruled in 8.8% of the cases. Ultimately, only 14.8% required hospital transfer following troponin assessment at the clinic. The remaining patients were sent home or managed in the outpatient setting. Conclusions The OUT-ACS strategy, utilizing a 0/1/4-hour algorithm for hs-cTnT measurements in emergency primary care, is safe, effective and applicable, and the strategy contributes to reduced hospital referrals for low-risk patients with chest pain.0/1/4-hour algorithm for hs-cTnTDisposition

Performance of post-mortem diagnostic tests for tuberculosis in wild ungulates at low and high prevalence assessed using Bayesian latent class models.

Animal tuberculosis (TB) is often maintained by multi-host communities, including livestock and wildlife. Quantitative studies of such communities require estimating the true prevalence of TB, correcting the apparent prevalence by the diagnostic sensitivity (Se) and specificity (Sp) of the test. The goal of this study was to lay the foundations for estimating the true prevalence of TB in wild ungulate populations (wild boar and two cervids: red deer and fallow deer). We used Bayesian latent class models to assess the Se and Sp of gross pathology, IS6110 real-time PCR in tissues, bacteriological culture, and P22 indirect ELISA. We analyzed 308 harvested wild ungulates (211 wild boar and 97 cervids: 92 red deer and 5 fallow deer). The Se of bacteriological culture (80.4%, CI95 61.0-96.3%) and gross pathology (87.9%, CI95 69.5-99.9%) was reasonably good in wild boar. These tests showed lower Se in cervids: 60.2% (CI95 38.3-82.3%) for bacteriological culture and 81.5% (CI95 63.6-96.2%) for gross pathology. The Se of the real-time PCR was low (50.7% in wild boar and 53.0% in cervids). These tests showed Sp between 95.2 and 99.1% in both taxa. The P22 ELISA performed reasonably well in wild boar (Se = 71.9%, CI95 59.2-83.4%; Sp = 98.8%, CI95 96.9-99.9%) but lacked Sp in cervids (Se = 77.1%, CI95 62.9-89.7%; Sp = 74.5%, CI95 65.7-83.3%). The real-time PCR in wild boar and cervids and bacteriological culture in cervids tended to show higher Se in low-prevalence populations, possibly due to a higher proportion of early-stage TB lesions. In cervids, the parallel interpretation of gross pathology and bacteriological culture significantly improved the diagnostic performance (Se = 93.1%, CI95 84.7-98.9%; Sp = 92.9%, CI95 86.0-98.3%). Our results allow the estimation of true prevalence from the results of a single diagnostic test applied to harvested wild boar, red deer, and fallow deer, paving the way for more precise quantitative ecological studies of the multi-host TB maintenance community.

Variance Between Clinical Guidance and Real-world Management of Metabolic Dysfunction-associated Steatotic Liver Disease in the United States

Clinical practice guidelines can facilitate diagnosis and management of patients with metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction associated steatohepatitis (MASH), although their implementation to date has been suboptimal.1,2 Using recently published 2023 American Association for the Study of Liver Diseases (AASLD) practice guidance-based recommendations as a reference,3 we assessed current real-world management of patients with MASH to identify gaps in clinical practice. We extracted data from the Adelphi Real World MASH Disease Specific Programme, a cross-sectional survey with retrospective data capture (from 85 hepatologists, gastroenterologists, and endocrinologists [Supplementary Table1] and 633 patients [Supplementary Table2] in the United States between January and June 2022). Two key goals of the AASLD guidance algorithm served as reference points: exclude fibrosis in low-prevalence populations (Goal A) and identify/manage people with 'at-risk' MASH or cirrhosis (Goal B).3 Patients were split into 2 groups: Goal A comprised 100 patients initially diagnosed by primary care physicians (PCPs)/endocrinologists, and Goal B included 533 patients managed by gastroenterologists/hepatologists.

Strategic Implementation of Fragile X Carrier Screening in China: A Focused Pilot Study

Fragile X syndrome (FXS) is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus.. Given the relatively low prevalence but large population, the distinct healthcare system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1/850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1/356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies—no screening, population-based screening, targeted screening, and our pilot screening—indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening due to their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China.

Association of ambient air pollution and pesticide mixtures on respiratory inflammatory markers in agricultural communities

Air pollution exposure is associated with adverse respiratory health outcomes. Evidence from occupational and community-based studies also suggests agricultural pesticides have negative health impacts on respiratory health. Although populations are exposed to multiple inhalation hazards simultaneously, multidomain mixtures (e.g. environmental and chemical pollutants of different classes) are rarely studied. We investigated the association of ambient air pollution-pesticide exposure mixtures with urinary leukotriene E4 (LTE4), a respiratory inflammation biomarker, for 75 participants in four Central California communities over two seasons. Exposures included three criteria air pollutants estimated via the Community Multiscale Air Quality model (fine particulate matter, ozone, and nitrogen dioxide) and urinary metabolites of organophosphate (OP) pesticides (total dialkyl phosphates (DAPs), total diethyl phosphates (DE), and total dimethyl phosphates (DM)). We implemented multiple linear regression models to examine associations in single pollutant models adjusted for age, sex, asthma status, occupational status, household member occupational status, temperature, and relative humidity, and evaluated whether associations changed seasonally. We then implemented Bayesian kernel machine regression (BKMR) to analyse these criteria air pollutants, DE, and DM as a mixture. Our multiple linear regression models indicated an interquartile range (IQR) increase in total DAPs was associated with an increase in urinary LTE4 in winter (β: 0.04, 95% CI: [0.01, 0.07]). Similarly, an IQR increase in total DM was associated with an increase in urinary LTE4 in winter (β:0.03, 95% CI: [0.004, 0.06]). Confidence intervals for all criteria air pollutant effect estimates included the null value. BKMR analysis revealed potential non-linear interactions between exposures in our air pollution-pesticide mixture, but all confidence intervals contained the null value. Our analysis demonstrated a positive association between OP pesticide metabolites and urinary LTE4 in a low asthma prevalence population and adds to the limited research on the joint effects of ambient air pollution and pesticides mixtures on respiratory health.

The Echocardiographic Diagnosis of Rheumatic Heart Disease: A Review of the Performance of the World Heart Federation Criteria 2012-2023.

The World Heart Federation (WHF) published the first evidence-based guidelines on the echocardiographic diagnosis of rheumatic heart disease (RHD) in 2012. These guidelines have since been applied internationally in research and clinical practice. Substantial research has assessed the utility of the 2012 WHF criteria, including its applicability in low-resource settings. This article summarises the evidence regarding the performance of the guidelines. A scoping review assessing the performance of the guidelines was performed. Cochrane, Embase, Medline, PubMed Lilacs, Sielo, and Portal BVS databases were searched for studies on the performance of the guidelines between January 2012-March 2023, and 4047 manuscripts met the search criteria, of which 34 were included. This included papers assessing the specificity, inter-rater reliability, application using hand-carried ultrasound, and modification of the criteria for simplicity. The review followed the PRISMA Extension for Scoping Reviews guideline. The WHF 2012 criteria were 100% specific for definite RHD when applied in low-prevalence populations. The criteria demonstrated substantial and moderate inter-rater reliability for detecting definite and borderline RHD, respectively. The inter-rater reliability for morphological features was lower than for valvular regurgitation. When applied to hand-carried ultrasound performed by an expert, modified versions of the criteria demonstrated a sensitivity and specificity range of 79-90% and 87-93% respectively for detecting any RHD, performing best for definite RHD. The sensitivity and the specificity were reduced when performed in task-sharing but remains moderately accurate. The WHF 2012 criteria provide clear guidance for the echocardiographic diagnosis of RHD that is reproducible and applicable to a range of echocardiographic technology. Furthermore, the criteria are highly specific and particularly accurate for detecting definite RHD. There are limitations in applying all aspects of the criteria in specific settings, including task-sharing. This summary of evidence can inform the updated version of the WHF guidelines to ensure improved applicability in all RHD endemic regions.

Single-test syphilis serology: A case of not seeing the forest for the trees

Introduction There have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening. Methods Between August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma. Results Of the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants. Conclusion Use of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

Diagnostic accuracy of a novel lateral flow assay for histoplasmosis.

Antigen testing is an important diagnostic tool for histoplasmosis but has limited availability globally. We evaluated the OIDx urine lateral flow antigen assay among 204 persons suspected to have histoplasmosis. Among patients with proven histoplasmosis, sensitivity was 33.3% (3/9, 95% CI 7.5%-70.1%) and specificity 80.5% (157/195, 95% CI 74.3%-85.8%). The MiraVista urine antigen test had better specificity (96.9%) and equal sensitivity. The OIDx test demonstrated 33.3% (3/9) positive agreement and 84.0% (163/194) negative agreement with the MiraVista test. These results should be considered in the context of our low HIV prevalence population with a mixture of pulmonary and disseminated disease.

Treatment patterns and persistence on disease modifying therapies for multiple sclerosis and its associated factors

Background Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown.Objectives To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS.MethodsWe conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan–Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality.ResultsSeven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01–1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs.ConclusionsA majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.

A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay

IntroductionInternational guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the “gold standard” treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM).Method1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers’ instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics).Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated.ResultsOut of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22–26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5–100), and the specificity was 99.4% (95% CI: 98.7–99.7). The ROC area values were 0.996 (95% CI: 0.992–0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1–99.2; NPV 99.9%, 95% CI: 99.5–100).ConclusionsThe ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.

Fishing for the evidence on community water fluoridation: a commentary on the CATFISH study.

Goodwin M, Emsley R, Kelly M P et al. Evaluation of water fluoridation scheme in Cumbria: the CATFISH prospective longitudinal cohort study. Southampton: National Institute for Health and Care Research, 2022. This longitudinal, prospective cohort study, recruited two populations - a birth cohort and older school cohort - assessing the effects of community water fluoridation (CWF) over a five-year period. The control group received non-fluoridated drinking water in the East of Cumbria, while the intervention group received fluoridated drinking water in the West of Cumbria. The primary outcome measures were the presence or absence of decay into dentine in primary and permanent teeth. Cost effectiveness was assessed by quality-adjusted life-years. Birth Cohort: Modest beneficial effect (17.4% with decay, 21.4% in control). Adjusted Odd Ratios (AOR): 0.74 (95% CI: 0.56 to 0.98). Older Cohort: Insufficient evidence of difference (19.1% with decay and 21.9% in control). AOR: 0.80 (95% CI: 0.58 to 1.09). The authors concluded that CWF was effective in the birth cohort and that the modest absolute reduction in caries should be considered in the context of other preventive measures. A longer follow-up period was recommended to fully understand the benefits and risks of CWF in contemporary low-prevalence populations.

The Effect of Accuracy and Uncertainty in Test Performance on Optimal Early Detection Survey Budget Allocations

Early detection of pests at a low population prevalence is a key pillar of surveillance for plant health. A novel pest is expected to undergo exponential growth when it first occurs in a host population. This allows for the use of mathematical rules of thumb for the number of samples required to detect presence before it reaches a target prevalence given the diagnostic performance of the tests used. Previous work assumes that pest presence is diagnosed by applying a single diagnostic test to each sample. However, diagnostic decisions are often made based on outcomes of multiple tests applied to the same sample in a consistent test program; for example, an assessment of symptoms followed by a PCR test applied to samples for which symptoms were observed. Each test can have different testing costs, as well as distinct and independent diagnostic performance and uncertainty values. A framework to optimize early detection surveys by minimizing overall costs for test programs that apply up to three diagnostic tests has been developed. The framework assesses the consequences of the test order and logical rule by which diagnoses are determined on costs across a range of pest prevalence. Explicit definitions of uncertainty in key parameters are incorporated to assess the consequences of uncertainty about their true value. Use of the framework is exemplified with two hypothetical case studies exploring the potential impact of selecting a suboptimal test program (based on Xylella fastidiosa) and investment in test improvements (based on lateral flow devices applied to Phytophthora pluvialis). [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Adherence to Selected Pillars of Lifestyle Medicine in the United States: A Cross-Sectional Analysis

Background: The American College of Lifestyle Medicine proposed 6 evidenced-based pillars to tackle the increasing burden from chronic non-communicable diseases, including regular physical activity, 7+ hours of restorative sleep, a whole-food plant-based diet, stress management, avoidance of risky substances and positive social connections. Methods: We used cross-sectional nationally representative data from the National Health and Nutrition Examination Surveys to analyze the degree of adherence to 4 of these pillars in the US general population. Results: We analyzed data from n = 1217 participants (representing n = 64,468,933 US adults). Results suggested a low population prevalence of established lifestyle medicine behaviors. Less than 50% of the population met the minimal weekly physical activity goal of 150 minutes of moderate intensity activity. We observed a high prevalence of risky substances (excessive alcohol and tobacco) in younger participants aged 20-38 years. Only .52% met common indicators of a whole-food plant-based diet. We found substantial differences between sexes and age groups, with an alarmingly low percentage of young adults achieving optimal levels of common lifestyle practices. Conclusions: Lifestyle medicine as a cost-effective strategy to reduce premature mortality is widely established. Our findings reiterate the required shift from symptom management via interventions towards “tackling the cause” of chronic diseases.

Evaluation of a two-test strategy for HIV screening in a low-prevalence setting and the indications for optimizing clinical management

ObjectivesTo evaluate a two-test strategy for HIV screening in the low-prevalence population and to assess the feasibility of utilizing the optimal signal-to-cutoff (S/CO) threshold on the chemiluminescence immunoassay(CMIA) and an additional rapid test on the gold immune-chromatography assay (GICA) for screening positive patients and optimization of clinical management. MethodsWe conducted a retrospective study of samples analyzed by the fourth-generation Architect HIV Ag/Ab combo assay (CMIA) in a large medical center between June 2017 and August 2020. Reactive samples underwent a second screening test using the rapid test GICA, followed by Western blot (WB) as the confirmatory test. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal S/CO. We calculated sensitivity, specificity, and predictive value based on our population. The performance of the single-test strategy (CMIA) was compared with that of the two-test strategy (CMIA and GICA). Logistic regression was used to analyze the factors of clinical characteristics leading to false positive results. ResultsA total of 220558 samples were screened by CMIA, and 429 patients met the inclusion criteria. Of these, CMIA produced 199 false-positive results with a median S/CO of 1.93(IQR1.45–3.68) and 230 positive results with a median S/CO of 455.1 (IQR169.3–709.7). The optimal S/CO of the single-test strategy was 8.82, which achieved a sensitivity of 100% and a positive predictive value (PPV) of 90.9%. The two-test strategy (CMIA and GICA) provided a sensitivity of 100% and a PPV of 98.7%, which best correlated with the confirmatory test WB. The combination of S/CO 8.82 on the CMIA assay and additional test results of GICA can be defined as four types used to interpret HIV serostatus. The false positive rate (FPR) was high in the female, the age≤18 group, the pre-operative patients, and the patients from the clinical departments of Pediatrics, Gynecology and Obstetrics, and Oncology, etc. ConclusionsThe false positive rate is high in the low-prevalence setting by using CMIA. The two-test strategy (CMIA and GICA) is recommended for HIV screening in hospitals. Hopefully, the clinicians will be able to interpret HIV serostatus and facilitate clinical decision-making while waiting for the confirmatory results.

Evaluation of high-risk human papillomavirus in sinonasal papillomas and squamous cell carcinomas.

The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous cell carcinomas (SCCs) and 38% of papillomas. There is limited data from geographical regions with low prevalence of high-risk (HR)-HPV on the association of HR-HPV in sinonasal neoplasms and on utility of p16 as a surrogate marker.p16 immunohistochemistry, HR-HPV mRNA ISH and quantitative real-time PCR (qPCR) were performed on a retrospective cohort of sinonasal papillomas and SCCs. KRAS mutation analysis was done in oncocytic papillomas.p16 positivity was present in 22/142 cases (15.5%) including eight inverted papillomas, one oncocytic papilloma (OP), and 13 SCC. Among these, mRNA ISH showed HR-HPV in the OP and two SCC, while another SCC was found to harbour HPV18 by qPCR. Two HPV-associated SCCs had foci of OP. mRNA ISH was negative in all p16 negative cases. p16 immunohistochemistry showed 68% concordance with mRNA ISH, and had sensitivity and negative predictive value of 100%; specificity was 67%, and positive predictive value was 14.3%.Association with HR-HPV in sinonasal papillomas and SCC is rare, and may be seen in cases demonstrating oncocytic morphology. p16 immunohistochemistry has low specificity and positive predictive value in low-prevalence populations; thus, reflex direct HR-HPV testing should be performed in p16 immunopositive cases. This two-step approach is viable in resource-limited settings, as the proportion of p16 positive cases is small.

Clinical testing of pediatric mpox specimens: Unique features and challenges in a low prevalence population.

Pediatric mpox cases comprise less than 0.3% of the total cases reported in the United States during the global 2022 outbreak. As a result, relatively little is known about the epidemiology or performance characteristics of clinical testing in this group. We retrospectively extracted and analyzed results for pediatric mpox specimens tested at a national reference laboratory from July to December 2022. During our study period 13.4% (2,063/15,385) of specimens were from individuals <18 years of age. The positivity rate of pediatric specimens was significantly lower than in adults (1.3% vs 22.3%). The pediatric cohort also consisted of a higher percentage of females (42.7% vs 31.0%) and lower percentage of specimens from genital sources (9.0% vs 19.7%) as compared to adults. In children, specimens were most frequently collected from 1-year-olds (10.1%) and least frequently from 11-year-olds (3.5%). Positivity rates were disproportionately elevated in the less than 1-year-old and 17-year-old age groups (7.8% and 6.4%, respectively). Ct values of positive cases were not statistically different between pediatric and adult cohorts (25.2vs 22.2, p>0.05). When all pediatric cases with an initial positive mpox result were examined, 5/26 were classified as inconclusive and 2/26 were determined to be false positives. The positive predictive value of monkeypox virus detection was 90.5% (95% CI: 70.4-97.4%) in children. These results highlight important differences between pediatric and adult mpox populations and reinforce the need for clinical correlation when reporting positive results from a low prevalence population.

SAT-462 - Diagnostic performance of fibrosis-4 index and NAFLD fibrosis score in at-risk group from low prevalence population

SAT-462 - Diagnostic performance of fibrosis-4 index and NAFLD fibrosis score in at-risk group from low prevalence population

Evaluating the utility of a two-assay serological algorithm for hepatitis C screening in a low prevalence population.

Screening for hepatitis C virus (HCV) is performed by testing for anti-HCV antibodies, which may yield false-positive results leading to additional testing and other downstream consequences for the patient. We report our experience in a low prevalence population (<0.05%) using a two-assay algorithm aimed at testing specimens with borderline or weak positive anti-HCV reactivity in the screening assay by a second anti-HCV assay prior to confirming positive anti-HCV results with RT-PCR. Retrospective analysis of 58,908 plasma samples was obtained over a 5-year period. Samples were initially tested using the Elecsys Anti-HCV II assay (Roche Diagnostics), with borderline or weakly positive results (defined in our algorithm as a Roche cutoff index of 0.9-19.99) reflexively analyzed using the Architect Anti-HCV assay (Abbott Diagnostics). The Abbott anti-HCV results dictated the final anti-HCV interpretation for reflexed samples. Our testing algorithm resulted in 180 samples requiring second-line testing, with final anti-HCV results interpreted as 9% positive, 87% negative, and 4% indeterminate. The positive predictive value (PPV) of a weakly positive Roche result was 12%, which was significantly lower than the PPV using our two-assay approach (65%). The incorporation of a two-assay serological testing algorithm in a low prevalence population provides a cost-effective method of improving the PPV of HCV screening in specimens with borderline or weakly positive anti-HCV results.

The Vaping and Patterns of e-Cigarette Use Research Study: Protocol for a Web-Based Cohort Study.

In total, 3.2% of American adults report using e-cigarettes every day or some days. The Vaping and Patterns of E-cigarette Use Research (VAPER) Study is a web-based longitudinal survey designed to observe patterns in device and liquid use that suggest the benefits and unintended consequences of potential e-cigarette regulations. The heterogeneity of the e-cigarette devices and liquids on the market, the customizability of the devices and liquids, and the lack of standardized reporting requirements result in unique measurement challenges. Furthermore, bots and survey takers who submit falsified responses are threats to data integrity that require mitigation strategies. This paper aims to describe the protocols for 3 waves of the VAPER Study and discuss recruitment and data processing experiences and lessons learned, including the benefits and limitations of bot- and fraudulent survey taker-related strategies. American adults (aged ≥21 years) who use e-cigarettes ≥5 days per week are recruited from up to 404 Craigslist catchment areas covering all 50 states. The questionnaire measures and skip logic are designed to accommodate marketplace heterogeneity and user customization (eg, different skip logic pathways for different device types and customizations). To reduce reliance on self-report data, we also require participants to submit a photo of their device. All data are collected using REDCap (Research Electronic Data Capture; Vanderbilt University). Incentives are US $10 Amazon gift codes delivered by mail to new participants and electronically to returning participants. Those lost to follow-up are replaced. Several strategies are applied to maximize the odds that participants who receive incentives are not bots and are likely to possess an e-cigarette (eg, required identity check and photo of a device). In total, 3 waves of data were collected between 2020 and 2021 (wave 1: n=1209; wave 2: n=1218; wave 3: n=1254). Retention from waves 1 to 2 was 51.94% (628/1209), and 37.55% (454/1209) of the wave 1 sample completed all 3 waves. These data were mostly generalizable to daily e-cigarette users in the United States, and poststratification weights were generated for future analyses. Our data offer a detailed examination of users' device features and specifications, liquid characteristics, and key behaviors, which can provide more insights into the benefits and unintended consequences of potential regulations. Relative to existing e-cigarette cohort studies, this study methodology has some advantages, including efficient recruitment of a lower-prevalence population and collection of detailed data relevant to tobacco regulatory science (eg, device wattage). The web-based nature of the study requires several bot- and fraudulent survey taker-related risk-mitigation strategies, which can be time-intensive. When these risks are addressed, web-based cohort studies can be successful. We will continue to explore methods for maximizing recruitment efficiency, data quality, and participant retention in subsequent waves. DERR1-10.2196/38732.

Mortality Prediction of COVID-19 in Hospitalized Patients Using the 2020 Diagnosis Procedure Combination Administrative Database of Japan.

Objectives Numerous people have died from coronavirus disease 2019 (COVID-19) infection. Identifying crucial predictive biomarkers of disease mortality is critical to support decision-making and logistic planning in healthcare systems. This study investigated the association between mortality and medical factors and prescription records in 2020 in Japan, where COVID-19 prevalence and mortality remain relatively low. Methods This retrospective cohort study analyzed anonymous administrative data from the Diagnosis Procedure Combination (DPC) database in Japan. Results A total of 22,795 patients were treated in DPC hospitals in 2020 in Japan, and of these, 5,980 patients over 50 years old were hospitalized, with 299 (5.0%) dying. There were 2,399 severe patients among 11,440 total hospitalized patients (all ages). The results of a logistic model analysis revealed that an older age, male sex, Parkinson's disease, cerebrovascular diseases, and chronic kidney diseases were risk factors for mortality. A machine learning analysis identified an older age, male sex (mortality), pneumonia, drugs for acid-related disorders, analgesics, anesthesia, upper respiratory tract disease, drugs for functional gastrointestinal disorders, drugs for obstructive airway diseases, topical products for joint and muscular pain, diabetes, lipid-modifying agents, calcium channel blockers, drugs for diabetes, and agents acting on the renin-angiotensin system as risk factors for a severe status. Conclusions This COVID-19 mortality risk tool is a well-calibrated and accurate model for predicting mortality risk among hospitalized patients with COVID-19 in Japan, which is characterized by a relatively low COVID-19 prevalence, aging society, and high population density. This COVID-19 mortality prediction model can assist in resource utilization and patient and caregiver education and be useful as a risk stratification instrument for future research trials.