Cumulative Detection Rate Research Articles

Participation and Yield in Multiple Rounds of Colorectal Cancer Screening Based on Fecal Immunochemical Test: A Systematic Review and Meta-Analysis.

The evidence on the cumulative participation and yield in multiple rounds of colorectal cancer (CRC) screening based on fecal immunochemical test is sparse. We aimed to assess the trends in participation and detection for advanced colorectal neoplasm under different screening intervals in multiround fecal immunochemical testing-based CRC screening by synthesizing the current available evidence. PubMed, Embase, and Cochrane were retrieved from January 1, 2002, to April 16, 2024, for potential eligible studies, and then, we synthesized participation and advanced colorectal neoplasm detection rates for each screening round, along with their respective 95% confidence intervals (CIs). Nineteen studies involving a total of 2,296,071 individuals were included. As screening rounds increased, participation exhibited a gradual consistent increase, reaching 78.45% and 74.97% for annual and biennial screening strategies. For annual screening, the cumulative detection rates for 3 rounds were 1.38% (95% CI: 1.18%-1.63%), 1.95% (95% CI: 1.72%-2.21%), and 2.50% (95% CI: 2.29%-2.72%), respectively. For biennial screening, the cumulative detection rates for 4 rounds were 2.22% (95% CI: 1.22%-3.22%), 3.44% (95% CI: 2.06%-4.82%), 4.26% (95% CI: 2.70%-5.83%), and 5.10% (95% CI: 3.28%-7.29%), respectively. Notably, the per-round detection rate of advanced colorectal neoplasms declined yet as the screening progressed. In population-based CRC screening programs, the participation exhibited a slow upward trend for both screening strategies, but the incremental benefits in CRC detection gradually diminished. Tailored strategies, such as extending intervals for individuals with multiple negative fecal immunochemical testing results, might optimize effectiveness and cost-efficiency in population-based CRC screening.

Screening and Diagnostic Mammography During Pregnancy and Lactation: A Systematic Review of the Literature.

In recent years, the age of childbearing has been increasing in Western countries, and consequently the need to conduct mammography during pregnancy and lactation is also increasing. The aim of the present study was to systematically review the existing evidence regarding the overall use of mammographyduring pregnancy and lactation. A systematic review of the literature was conducted in PubMed, Epistemonikos, and clinicaltrials.gov, by using the search terms "pregnancy" AND "mammography", and "lactation" AND "mammography". The review protocol was prospectively registered in PROSPERO (CRD42024543971). Initially, 1,038 articles were identified; the titles and abstracts of 441 studies were screened; 40 studies were retrieved; after assessment of full texts, 20 studies were included for data extraction and further analysis. All 20 studies were retrospective; 14 studies included women with pregnancy-associated breast cancer, five studies included women with breast symptoms during pregnancy and/or lactation and one study included young breast cancer patients under age 40. Overall, 420 diagnostic and one incidental screening mammography examinations were performed during pregnancy and/or lactation with a 78.6% cumulative detection rate of breast cancer. The role of mammography was confounded by the use of breast ultrasound in most studies. In conclusion, the use of mammography during pregnancy and lactation is based on empirical data from retrospective studies, not directly addressing this issue. Hence, well-designed, focused, prospective clinical studies are needed in order to improve existing evidence regarding the use of diagnostic and screening mammography during pregnancy and lactation.

MRI-guided in-bore biopsy of the prostate – defining the optimal number of cores needed

BackgroundNumerous studies have shown that magnetic resonance imaging (MRI)-targeted biopsy approaches are superior to traditional systematic transrectal ultrasound guided biopsy (TRUS-Bx). The optimal number of biopsy cores to be obtained per lesion identified on multiparametric MRI (mpMRI) images, however, remains a matter of debate. The aim of this study was to evaluate the incremental value of additional biopsy cores in an MRI-targeted “in-bore”-biopsy (MRI-Bx) setting.Patients and methodsTwo hundred and forty-five patients, who underwent MRI-Bx between June 2014 and September 2021, were included in this retrospective single-center analysis. All lesions were biopsied with at least five biopsy cores and cumulative detection rates for any cancer (PCa) as well as detection rates of clinically significant cancers (csPCa) were calculated for each sequentially labeled biopsy core. The cumulative per-core detection rates are presented as whole numbers and as proportion of the maximum detection rate reached, when all biopsy cores were considered. CsPCa was defined as Gleason Score (GS) ≥ 7 (3 + 4).ResultsOne hundred and thirty-two of 245 Patients (53.9%) were diagnosed with prostate cancer and csPCa was found in 64 (26.1%) patients. The first biopsy core revealed csPCa/ PCa in 76.6% (49/64)/ 81.8% (108/132) of cases. The second, third and fourth core found csPCa/ PCa not detected by previous cores in 10.9% (7/64)/ 8.3% (11/132), 7.8% (5/64)/ 5.3% (7/132) and 3.1% (2/64)/ 3% (4/132) of cases, respectively. Obtaining one or more cores beyond the fourth biopsy core resulted in an increase in detection rate of 1.6% (1/64)/ 1.5% (2/132).ConclusionWe found that obtaining five cores per lesion maximized detection rates. If, however, future research should establish a clear link between the incidence of serious complications and the number of biopsy cores obtained, a three-core biopsy might suffice as our results suggest that about 95% of all csPCa are detected by the first three cores.

Associated factors, incidence, and management of gestational and congenital syphilis in a Brazilian state capital: a cross-sectional study.

Maternal and child health remains an enduring global challenge, having occupied a prominent position on international agendas since the dawn of the 21st century. During pregnancy, syphilis emerges as the second most prevalent cause of stillbirth on a global scale, potentially leading to a range of adverse outcomes. This study aimed to describe the clinical and epidemiological profile of cases of gestational and congenital syphilis and the hospital care provided for newborns in Campo Grande municipality, Mato Grosso do Sul State, Brazil, from 2013 to 2018. This is a cross-sectional study based on data from Brazilian Notifiable Diseases Surveillance System (SINAN) and hospital medical records. Chi-square or Fisher's exact test and logistic regression analysis were used to assess the associations and relationships between the child's clinical outcome at birth and the mother's clinical-obstetric and epidemiological characteristics. Cumulative detection rate of gestational syphilis was 174.3 cases per 1,000 live births and cumulative incidence of congenital syphilis was 47.7 cases per 1,000 live births. Alcoholism, prenatal care, number of prenatal visits, maternal treatment regimen, and timing of maternal diagnosis were associated with child's clinical outcome at birth and considered in the regression model. Prenatal visits showed a protective effect against the signs and symptoms of congenital syphilis (odds ratio = 0.37; 95% confidence interval = 0.17-0.77). Medical assistance was considered inadequate in 62.3% of cases. Prenatal consultations should be encouraged among pregnant women. There is a need for better education of health personnel on the treatment and diagnosis of syphilis.

Unraveling the potential clinical utility of circulating tumor DNA detection in colorectal cancer—evaluation in a nationwide Danish cohort

Increasingly, circulating tumor DNA (ctDNA) is proposed as a tool for minimal residual disease (MRD) assessment. Digital PCR (dPCR) offers low analysis costs and turnaround times of less than a day, making it ripe for clinical implementation. Here, we used tumor-informed dPCR for ctDNA detection in a large colorectal cancer (CRC) cohort to evaluate the potential for post-operative risk assessment and serial monitoring, and how the metastatic site may impact ctDNA detection. Additionally, we assessed how altering the ctDNA-calling algorithm could customize performance for different clinical settings. Stage II-III CRC patients (N= 851) treated with a curative intent were recruited. Based on whole-exome sequencing on matched tumor and germline DNA, a mutational target was selected for dPCR analysis. Plasma samples (8 ml) were collected within 60 days after operation and-for a patient subset (n= 246)-every 3-4 months for up to 36 months. Single-target dPCR was used for ctDNA detection. Both post-operative and serial ctDNA detection were prognostic of recurrence [hazard ratio (HR)= 11.3, 95% confidence interval (CI) 7.8-16.4, P < 0.001; HR= 30.7, 95% CI 20.2-46.7, P < 0.001], with a cumulative ctDNA detection rate of 87% at the end of sample collection in recurrence patients. The ctDNA growth rate was prognostic of survival (HR= 2.6, 95% CI 1.5-4.4, P= 0.001). In recurrence patients, post-operative ctDNA detection was challenging for lung metastases (4/21 detected) and peritoneal metastases (2/10 detected). By modifying the cut-off for calling a sample ctDNA positive, we were able to adjust the sensitivity and specificity of our test for different clinical contexts. The presented results from 851 stage II-III CRC patients demonstrate that our personalized dPCR approach effectively detects MRD after operation and shows promise for serial ctDNA detection for recurrence surveillance. The ability to adjust sensitivity and specificity shows exciting potential to customize the ctDNA caller for specific clinical settings.

Cumulative Detection of Anal High-Grade Squamous Intraepithelial Lesions Over 2-Year Follow-up in Men Who Have Sex With Men Living With Human Immunodeficiency Virus in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSILs) in men who have sex with men living with human immunodeficiency virus and who underwent 3 visits over 2 years, with cytology and high-resolution anoscopy, within the ANRS-EP57-APACHES study. The cumulative HSIL detection rate was 33% (134 of 410), of which 48% HSILs were detected at baseline. HSIL detection varied considerably by center (from 13% to 51%). The strongest HSIL determinants were baseline human papillomavirus 16 (adjusted odds ratio, 8.2; 95% confidence interval, 3.6-18.9) and p16/Ki67 (4.6 [2.3-9.1]). Repeated annual cytology and high-resolution anoscopy improved HSIL detection but did not fully compensate for between-center heterogeneity.

Intra-urban differences underlying leprosy spatial distribution in central Brazil: geospatial techniques as potential tools for surveillance.

This ecological study identified an aggregation of urban neighbourhoods spatial patterns in the cumulative new case detection rate (NCDR) of leprosy in the municipality of Rondonópolis, central Brazil, as well as intra-urban socioeconomic differences underlying this distribution. Scan statistics of all leprosy cases reported in the area from 2011 to 2017 were used to investigate spatial and spatiotemporal clusters of the disease at the neighbourhood level. The associations between the log of the smoothed NCDR and demographic, socioeconomic, and structural characteristics were explored by comparing multivariate models based on ordinary least squares (OLS) regression, spatial lag, spatial error, and geographically weighted regression (GWR). Leprosy cases were observed in 84.1% of the neighbourhoods of Rondonópolis, where 848 new cases of leprosy were reported corresponding to a cumulative NCDR of 57.9 cases/100,000 inhabitants. Spatial and spatiotemporal high-risk clusters were identified in western and northern neighbourhoods, whereas central and southern areas comprised low-risk areas. The GWR model was selected as the most appropriate modelling strategy (adjusted R²: 0.305; AIC: 242.85). By mapping the GWR coefficients, we identified that low literacy rate and low mean monthly nominal income per household were associated with a high NCDR of leprosy, especially in the neighbourhoods located within high-risk areas. In conclusion, leprosy presented a heterogeneous and peripheral spatial distribution at the neighbourhood level, which seems to have been shaped by intra-urban differences related to deprivation and poor living conditions. This information should be considered by decision-makers while implementing surveillance measures aimed at leprosy control.

Genome sequencing identifies coding and non-coding variants for non-syndromic hearing loss.

Hearing loss (HL) is a common heterogeneous trait that involves variants in more than 200 genes. In this study, we utilized exome (ES) and genome sequencing (GS) to effectively identify the genetic cause of presumably non-syndromic HL in 322 families from South and West Asia and Latin America. Biallelic GJB2 variants were identified in 58 probands at the time of enrollment these probands were excluded. In addition, upon review of phenotypic findings, 38/322 probands were excluded based on syndromic findings at the time of ascertainment and no further evaluation was performed on those samples. We performed ES as a primary diagnostic tool on one or two affected individuals from 212/226 families. Via ES we detected a total of 78 variants in 30 genes and showed their co-segregation with HL in 71 affected families. Most of the variants were frameshift or missense and affected individuals were either homozygous or compound heterozygous in their respective families. We employed GS as a primary test on a subset of 14 families and a secondary tool on 22 families which were unsolved by ES. Although the cumulative detection rate of causal variants by ES and GS is 40% (89/226), GS alone has led to a molecular diagnosis in 7 of 14 families as the primary tool and 5 of 22 families as the secondary test. GS successfully identified variants present in deep intronic or complex regions not detectable by ES.

Learning curve and factors influencing successful robot-assisted bilateral sentinel lymph node mapping in early-stage cervical cancer: an observational cohort study

ABSTRACT Objectives To evaluate whether a learning curve affects the bilateral sentinel lymph node (SLN) detection in early-stage cervical cancer. Methods All patients with FIGO (2018) stage IA1-IB2 or IIA1 cervical cancer who had undergone robot-assisted SLN mapping performed with a combination of preoperative technetium-99m nanocolloids (including preoperative imaging) and intraoperative blue dye were retrospectively included. Risk-adjusted cumulative sum (RA-CUSUM) analysis was used to determine if a learning curve based on bilateral SLN detection existed in this cohort. Results A total of 227 cervical cancer patients were included. In 98.2% of patients (223/227) at least one SLN was detected. The bilateral SLN detection rate was 87.2% (198/227). Except for age (OR 1.06 per year, 95%CI 1.02–1.09), no significant risk factors for non-bilateral SLN detection were found (e.g., prior conization, BMI or FIGO stage). The RA-CUSUM analysis showed no clear learning phase during the first procedures and cumulative bilateral detection rate remained at least 80% during the entire inclusion period. Conclusions In this single-institution experience, we observed no learning curve affecting robot-assisted SLN mapping using a radiotracer and blue dye in early-stage cervical cancer patients, with stable bilateral detection rates of at least 80% when adhering to a standardized methodology.

Atrial fibrillation detection using insertable cardiac monitor after stroke: A real-world cohort study.

This study aimed to report the real-world atrial fibrillation (AF) diagnostic yield of the implantable cardiac monitor (ICM) in patients with stroke or transient ischemic attack (TIA), and compare it to patients with an ICM for unexplained syncope. We used patient data from device clinics across the United States of Americawith ICM remote monitoring via PaceMate™, implanted for stroke or TIA, and unexplained syncope. Patients with known AF or atrial flutter were excluded. The outcome was AF lasting ≥2 min, adjudicated by International Board of Heart Rhythm Examiners certifiedcardiac device specialists. We included a total of 2469 patients, 51.1% with stroke or TIA (mean age: 69.7 [SD: 12.2] years, 41.1% female) and 48.9% with syncope (mean age: 67.0 [SD: 17.1] years, 59.4% female). The cumulative AF detection rate in patients with stroke or TIA was 5.5%, 8.9%, and 14.0% at 12, 24, and 36 months, respectively. The median episode duration was 73 (interquartile range: 10-456) min, ranging from 2 min to 40.9 days, with 52.3%, 28.6%, and 4.4% of episodes lasting at least 1, 6, and 24 h, respectively. AF detection was increased by age (adjusted hazard ratio [for every 1-year increase]: 1.024, 95% confidence interval: 1.008-1.040; p = .003), but was not influenced by sex (p = .089). For comparison, the cumulative detection rate at 12, 24, and 36 months were, respectively, 2.4%, 5.2%, and 7.4% in patients with syncope. Patients with stroke or TIA have a higher rate of AF detection. However, this real-world study shows significantly lower AF detection rates than what has been previously reported.

Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

Clinical criteria for Mucosal Leishmaniasis diagnosis in rural South America: A systematic literature review.

BackgroundMucosal Leishmaniasis (ML), a neglected tropical disease caused by Leishmania parasites, impairs the quality of life of under-resourced populations in South America. If not treated promptly, this disease progresses to facial deformities and death. The low sensitivity of microscopy results and the unavailability of other accurate tests hamper the diagnosis. As clinical criteria are readily available in any setting, these may be combined in a syndromic algorithm, which in turn can be used as a diagnostic tool. We explore potential clinical criteria for a syndromic diagnostic algorithm for ML in rural healthcare settings in South America.Methodology/Principal findingsThe protocol for this systematic review was pre-registered in PROSPERO with the number: CRD42017074148. In patients with ML, described in case series identified through a systematic retrieval process, we explored the cumulative ML detection rates of clinical criteria. Participants: all patients with active mucosal disease from an endemic area in South America. Any original, non-treatment study was eligible, and case reports were excluded. PUBMED, EMBASE, Web of Science, SCIELO, and LILACS databases were searched without restrictions. The risk of bias was assessed with the JBI checklist for case series. We included 10 full texts describing 192 ML patients. Male gender had the highest detection rate (88%), followed by ulcer of the nasal mucosa (77%), age >15 (69%), and symptom duration >4 months (63%).SignificanceWithin this selection of patients, we found that the male gender, ulcer of the nasal mucosa, age >15, and symptom duration >4 months lead to the highest detection rates. However, higher detection comes -naturally- with a higher rate of false positives as well. As we only included ML patients, this could not be verified. Therefore, the criteria that we found to be most promising should be validated in a well-designed prospective study.

Safety, Efficacy and High-Quality Standards of Gastrointestinal Endoscopy Procedures in Personalized Sedoanalgesia Managed by the Gastroenterologist: A Retrospective Study.

Performing GI endoscopy under sedoanalgesia improves the quality-indices of the examination, in particular for cecal intubation and adenoma detection rates during colonoscopy. The implementation of procedural sedoanalgesia in GI endoscopy is also strongly recommended by the guidelines of the major international scientific societies. Nevertheless, there are regional barriers that prevent the widespread adoption of this good practice. A retrospective monocentric analytic study was performed on a cohort of 529 patients who underwent EGDS/Colonoscopy in sedoanalgesia, with personalized dosage of Fentanyl and Midazolam. ASA class, age and weight were collected for each patient. The vital parameters were recorded during, pre- and post-procedure. The rates of cecal intubation and of procedure-related complications were entered. The VAS scale was used to evaluate the efficacy of sedoanalgesia, and the Aldrete score was used for patient discharge criteria. No clinically significant differences were found between vital signs pre- and post-procedure. Both anesthesia and endoscopic-related complications occurring were few and successfully managed. At the end of examination, both the mean Aldrete score (89.56), and the VAS score (<4 in 99.1%) were suitable for discharge. For the colonoscopies, the cumulative adenoma detection rate (25%) and the cecal intubation rate in the general group (98%) and in the colorectal cancer screening group (100%) were satisfying. Pain control management is an ethical and medical issue aimed at increasing both patient compliance and the quality of the procedures. The findings of this work underscore that in selected patients personalized sedoanalgesia in GI endoscopy can be safely managed by gastroenterologists.

Serum human chorionic gonadotropin ratios for the detection of etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine resistance in high-risk gestational trophoblastic neoplasia.

AimsThis study aimed to identify the optimal human chorionic gonadotropin (hCG) ratio in predicting etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine resistance in women diagnosed with high‐risk gestational trophoblastic neoplasia (GTN) and to compare the chemoresistant disease detection rate by using the optimal hCG ratio and traditional criteria.MethodsSeventy‐six women with primary high‐risk GTN treated with etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine in a tertiary‐care center were included. The hCG ratio was determined by its serum pretreatment level divided by that before each cycle of chemotherapy. The traditional criteria for chemoresistance included plateau or rising of hCG or presence of new metastasis. The optimal hCG ratio was determined using receiver operating characteristics (ROC) curve analysis.ResultsAmong the specificities of 90%, 92.5%, and 95%, the 90% specificity yielded the best ROC curve. At 90% specificity, the best area under curve value was at the fourth cycle with 75% sensitivity. The hCG ratio at the fourth cycle was 31.92. Using the ratio at the fourth cycle, chemoresistant disease was detected in six out of eight patients, compared to one in the traditional criteria. When combining the two diagnostic tools, the cumulative detection rate in the fourth cycle was 10/12 (83.3%) of total drug resistance. Among patients who developed drug resistance at the fourth cycle or thereafter, the use of the ratio at the fourth cycle could diagnose chemoresistance approximately two cycles earlier than that with the traditional criteria.ConclusionsA hCG ratio of <31.9 at the fourth cycle should be considered a high‐risk for etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine resistance and may need second‐line chemotherapy. The ratio increases the detection rate of resistance to these drugs more than the traditional criteria.

Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening: A multicenter randomized controlled trial in different resource settings in China.

We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

640. Development of a Laboratory Verification Protocol for Concurrent Detection of Bacterial, Fungal, and Antimicrobial Resistance Genes in a Multiplex Syndromic Joint Infection Panel

Abstract Background Verification is a critical component of implementing a diagnostic test in a clinical lab and can be time consuming and costly. A verification protocol and organism panel were developed in collaboration with ZeptoMetrix®, LLC to verify all analyte detections for the BioFire® Joint Infection (JI) Panel*. The BioFire JI Panel detects 31 pathogens and 8 antimicrobial resistance (AMR) genes associated with joint infections from synovial fluid specimens. Methods A protocol was developed using prototype NATtrol™ controls from ZeptoMetrix®, synovial fluid, and the BioFire® FilmArray® 2.0 and the BioFire® FilmArray® Torch Systems. Control materials were tested in the presence of synovial fluid from pooled human donors. The 32 targets required for all analyte detections were divided into 5 pools of 6-7 analytes and then tested over multiple days on several systems. Results Preliminary outcomes were good with a cumulative positive detection rate of 100% (310/310) and expected negative detections of 99.3% (1182/1190) from 50 prototype BioFire JI Panel test runs. AMRs were correctly identified in 50/50 (100%) replicates when a correlated bacterium was present. Unexpected detections of Streptococcus spp. (7/50) and Staphylococcus lugdunensis (1/50) were likely due to contaminants in the synovial fluid; Streptococcus spp. was confirmed by testing the synovial fluid in isolation. Conclusion Efficient performance verification may be achieved by combining 32 organisms/8 AMR into 5 pools and can be completed with 20 test runs in 4 days. The pooling scheme provides multiple positive/negative detections per analyte and accurately detects AMR. The protocol and controls serve as a useful tool for providing reliable detections of targets over multiple days, operators and systems and offers a flexible solution for supporting verification needs. *The BioFire® Joint Infection Panel is currently pending US FDA De Novo review. This product has not been evaluated by other global regulatory agencies for in vitro diagnostic use. Not available for sale. Panel menu subject to change. Disclosures Monica Cronin, MS, BioFire Diagnostics, LLC (Employee) Taylor K. Fadgen, Bachelor of Science, BioFire Diagnostics, LLC (Employee) Lisa Ogden, BS, BioFire Diagnostics, LLC (Employee) Jeremy P. Green, BS, BioFire Diagnostics, LLC (Employee, Shareholder) Stephanie A. Thatcher, MS, BioFire Diagnostics (Employee) Rebecca C. Young, MS, BioFire Diagnostics, LLC (Employee) Brandon Hoelcle, BS, ZeptoMetrix, LLC (Employee)

Assessment of a Program for SARS-CoV-2 Screening and Environmental Monitoring in an Urban Public School District

Scalable programs for school-based SARS-CoV-2 testing and surveillance are needed to guide in-person learning practices and inform risk assessments in kindergarten through 12th grade settings. To characterize SARS-CoV-2 infections in staff and students in an urban public school setting and evaluate test-based strategies to support ongoing risk assessment and mitigation for kindergarten through 12th grade in-person learning. This pilot quality improvement program engaged 3 schools in Omaha, Nebraska, for weekly saliva polymerase chain reaction testing of staff and students participating in in-person learning over a 5-week period from November 9 to December 11, 2020. Wastewater, air, and surface samples were collected weekly and tested for SARS-CoV-2 RNA to evaluate surrogacy for case detection and interrogate transmission risk of in-building activities. SARS-CoV-2 detection in saliva and environmental samples and risk factors for SARS-CoV-2 infection. A total of 2885 supervised, self-collected saliva samples were tested from 458 asymptomatic staff members (mean [SD] age, 42.9 [12.4] years; 303 women [66.2%]; 25 Black or African American [5.5%], 83 Hispanic [18.1%], 312 White [68.1%], and 35 other or not provided [7.6%]) and 315 students (mean age, 14.2 [0.7] years; 151 female students [48%]; 20 Black or African American [6.3%], 201 Hispanic [63.8%], 75 White [23.8%], and 19 other race or not provided [6.0%]). A total of 46 cases of SARS-CoV-2 (22 students and 24 staff members) were detected, representing an increase in cumulative case detection rates from 1.2% (12 of 1000) to 7.0% (70 of 1000) among students and from 2.1% (21 of 1000) to 5.3% (53 of 1000) among staff compared with conventional reporting mechanisms during the pilot period. SARS-CoV-2 RNA was detected in wastewater samples from all pilot schools as well as in air samples collected from 2 choir rooms. Sequencing of 21 viral genomes in saliva specimens demonstrated minimal clustering associated with 1 school. Geographical analysis of SARS-CoV-2 cases reported district-wide demonstrated higher community risk in zip codes proximal to the pilot schools. In this study of staff and students in 3 urban public schools in Omaha, Nebraska, weekly screening of asymptomatic staff and students by saliva polymerase chain reaction testing was associated with increased SARS-CoV-2 case detection, exceeding infection rates reported at the county level. Experiences differed among schools, and virus sequencing and geographical analyses suggested a dynamic interplay of school-based and community-derived transmission risk. Collectively, these findings provide insight into the performance and community value of test-based SARS-CoV-2 screening and surveillance strategies in the kindergarten through 12th grade educational setting.

Lower Serum Angiotensin-Converting Enzyme Level in Relation to Hyperinflammation and Impaired Antiviral Immune Response Contributes to Progression of COVID-19 Infection.

IntroductionAs a homologue of the angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2) has been identified as the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion. We aimed to investigate the role of serum ACE in predicting the coronavirus disease 2019 (COVID-19) disease progression and the underlying mechanisms.MethodsWe retrospectively enrolled 120 patients with confirmed COVID-19 who underwent serum ACE detection on admission. The clinical characteristics and laboratory findings during hospitalization were evaluated dynamically to identify the potential risk factors for disease progression.ResultsACE level was demonstrated as one of the independent risk factors. Patients with ACE level ≤ 33.5 U/L showed a higher cumulative virus RNA detection rate, elevated pro-inflammatory mediators levels, declined lymphocyte count, and decreased SARS-CoV-2-specific antibodies than those with ACE level > 33.5 U/L.ConclusionLower serum ACE levels in relation to delayed virus elimination, hyperinflammatory condition, and impaired host antiviral immune responses contribute to disease progression of COVID-19.

Burden of Leprosy Patients at Post-Elimination Stage: Evidence from Bangladesh

Introduction: There has been a marked decline in the prevalence rate of leprosy in Bangladesh, but understanding the current magnitude is important for both the service providers and the community. Therefore, the present study is undertaken to describe the pattern and prevalence of leprosy at post-elimination stage. Materials and Methods: This is a descriptive retrospective cross-sectional study carried out using the register records of patients attending the leprosy clinic in Chittagong Medical College Hospital (CMCH) during the period 2004 and 2019. Results: Among a total of 865 patients, males 631 (72.95%) outnumbered females 234 (27.05%). There were 259 (29.59%) paucibacillary (PB) and 606 (70.05%) multibacillary (MB) cases. Smear positive cases were only 218 (25.20%). Of the 865 patients, 515 (59.54%) were BT, which was higher compared to other forms of leprosy. Four age groups were computed. The calculated age-specific cumulative detection rates showed that the highest case detection was in 26- 40 years group 324 (37.46%) patients. A total of 388 (44.87%) patients developed leprosy reactions and 149 (17.22%) patients presented with grade 2 deformities. The LRs comprised of 212 (24.50%) Type 1 Reaction, 74 (8.55%) Type 2 Reaction and 102 (11.79%) neuritis patients. From all, 865 new leprosy patients only 115 (13.29%) had presented with limb deformity, 61 (7.05%) had a trophic ulcer and 29 (3.35%) patients presented with ocular complication. Among the 115 (13.29%) patients with limb deformity 75 (8.67%) had a claw hand followed by foot drop 20 (2.31%), wrist drop 17 (1.96%) and nerve abscess 3 (0.35%). Conclusions: The study shows that new case detection rate is declining but burden of leprosy in the community has not changed significantly. MB (70.05%) patients with grade 2 deformities (17.22%) are still high. Although leprosy has been eliminated globally on paper, the disease continues to be significant cause of peripheral neuropathy, deformity, disability and disfigurement in some developing countries like Bangladesh. Keywords: Leprosy, Reactions, Deformity, Chittagong, Bangladesh. Read more →

Follicular development during hormone replacement therapy in patients with premature ovarian insufficiency.

PurposeTo provide information about the relationship between follow‐up period and follicular development in patients with infertility due to premature ovarian insufficiency (POI) who are undergoing hormone replacement therapy (HRT). It is necessary to detect follicle development for artificial insemination or in vitro fertilization.MethodsThis retrospective cohort study was conducted at a university hospital in Tokyo, Japan, from April 2014 to February 2019 in 20 patients [follicular development group, 11 women (55%); non‐follicular development group, 9 women (45%)] with POI; their follicular development was followed up weekly. Background characteristics, including age, follicle‐stimulating hormone (FSH) and anti‐Mullerian hormone levels (AMH), the period from the last spontaneous menstruation to hormone replacement therapy initiation, and follow‐up period during HRT were investigated. The period without follicular development was tabulated, and the subsequent cumulative follicular development detection rate was calculated.ResultsAt least 1‐year follow‐up, the cumulative follicular development rate was 70%; follicular development was observed with a probability of 49.1% at 3 months, 33.4% at 6 months, and 8.3% at 12 months in the follow‐up period.ConclusionsThe results show that the longer the non‐follicle development period, the lower the probability of subsequent follicular development in patients with POI during HRT.