Concurrent Testing Research Articles

HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

Efficacy and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) in the treatment of paediatric drug-resistant epilepsy: A retrospective analysis.

This investigation evaluates the effectiveness and safety of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) as a treatment modality for drug-resistant epilepsy. A retrospective review of clinical data from 40 paediatric patients with drug-resistant epilepsy, who underwent SEEG-guided RF-TC at our Epilepsy Center between 2020 and 2022, was conducted. This review included the patients' medical history, imaging and electroencephalography results, surgical procedures, and follow-up outcomes. The duration of SEEG monitoring, accompanied by concurrent electrical stimulation tests, varied from 3 days to 4 weeks. Following RF-TC surgery, 4 patients demonstrated temporary neurological impairments, including central facial and tongue weakness, reduced limb strength, and challenges in fine motor hand movements. All these symptoms were related to lesions in the central region, but showed improvement within 2 weeks to 3 months post-surgery. There were no reported instances of status epilepticus, intracranial haemorrhage, or infections. During a follow-up period of 6 months to 2.5 years, seizure control was achieved in 25 patients (62.5%) at 6 months post-surgery, and a > 50% decrease in seizure frequency was observed in 10 patients. In 5 patients where seizure control was not achieved, the management of epilepsy seemed to be independent of factors such as age at surgery, duration of preoperative disease, seizure type, or negative MRI findings ( p > 0.05). Patients with controlled epilepsy exhibited cognitive improvement, with some demonstrating no EEG abnormalities upon follow-up and a decrease in antiepileptic medication. SEEG-guided RF-TC appears to be a potentially effective and safe therapeutic approach for paediatric patients with drug-resistant epilepsy.

Pengaruh Faktor Pola Asuh Orang Tua, Kompetensi Pedagogik Guru dan Motivasi Berprestasi terhadap Prestasi Belajar Siswa di SMA Negeri Satu Atap Lembongan

The research in this thesis is motivated by the many teacher competencies that have not been achieved in accordance with the National Education System Law No. 20 of 2003 Article 39 Paragraph 2. And also the parenting style of parents who tend not to support children's education because they have to help parents because of work and economic demands. The type of research used by this research is quantitative research with an "ex-post facto" approach. Data collection is carried out by questionnaire instrument. Data analysis and hypothesis testing in this study used multiple regression. The results showed (1) There is a significant influence between parenting style on student achievement at SMA Negeri Satu Atap Lembongan as shown from tcalculate > ttable (3,840 > 1.972), the significance value of t for the parenting variable is 0.000 and the value is smaller than the probability of 0.05 (0.000 < 0.05) (2) There is a significant influence between teacher pedagogic competence on student achievement at SMA Negeri Satu Atap Lembongan Shown from tcount > ttable (2.920 > 1.972). The significance value of t for the teacher's pedagogic competency variable is 0.004 and the value is smaller than the probability of 0.05 (0.004 < 0.05). (3) There is a significant influence between achievement motivation on student achievement at SMA Negeri Satu Atap Lembongan as shown from the ttable > (2,314 > 1,972). The significance value of t for the motivational variable is 0.021 and the value is smaller than the probability of 0.05 (0.021 < 0.05). (4) There is a significant influence between parenting, teacher pedagogic competence and achievement motivation on student achievement at SMA Negeri Satu Atap Lembongan as shown from Fhitung > Ftabel (11,975> 2.65). The significance value of the concurrent test (F test) is 0.000 and the value is smaller than the probability of 0.05 (0.000 < 0.05).

The Finger Dexterity Test: Validation study of a smartphone-based manual dexterity assessment

Background: The Nine-Hole Peg Test (9HPT) is the golden standard to measure manual dexterity in people with multiple sclerosis (MS). However, administration requires trained personnel and dedicated time during a clinical visit. Objectives: The objective of this study is to validate a smartphone-based test for remote manual dexterity assessment, the icompanion Finger Dexterity Test (FDT), to be included into the icompanion application. Methods: A total of 65 MS and 81 healthy subjects were tested, and 20 healthy subjects were retested 2 weeks later. Results: The FDT significantly correlated with the 9HPT (dominant: ρ = 0.62, p < 0.001; non-dominant: ρ = 0.52, p < 0.001). MS subjects had significantly higher FDT scores than healthy subjects (dominant: p = 0.015; non-dominant: p = 0.013), which was not the case for the 9HPT. A significant correlation with age (dominant: ρ = 0.46, p < 0.001; non-dominant: ρ = 0.40, p = 0.002), Expanded Disability Status Scale (EDSS, dominant: ρ = 0.36, p = 0.005; non-dominant: ρ = 0.31, p = 0.024), and disease duration for the non-dominant hand (ρ = 0.31, p = 0.016) was observed. There was a good test–retest reliability in healthy subjects (dominant: r = 0.69, p = 0.001; non-dominant: r = 0.87, p < 0.001). Conclusions: The icompanion FDT shows a moderate-to-good concurrent validity and test–retest reliability, differentiates between the MS subjects and healthy controls, and correlates with clinical parameters. This test can be implemented into routine MS care for remote follow-up of manual dexterity.

Research on multi-dimensional reconstruction mechanism of cloud native full link in the metaverse scenario

Recently, the Microservices whole link whole life cycle optimization framework has been a research hotspot in the academic and engineering fields, especially how to encapsulate the component security mechanism and conduct high concurrency testing based on the existing active framework. The whole link delay, load, and cost have always been the key optimization goals of Microservices splitting and deployment logic. Based on this, this paper proposes a multi-objective optimization Microservices framework that takes into account the security mechanism, Define the fitness function, define the upper and lower limits, and perform multi-dimensional constraints to filter for global and local optima. At the same time, reconstruct the circuit breaker current limiting mechanism, dynamically detect protocol parameters, and perceive the logical relationship of heartbeat status in real-time. Experimental results have shown that this innovative framework can solve scenarios such as high concurrency, high reliability, and high availability Performance bottleneck, business degradation, especially in financial and securities scenarios.

#318 : Embryomap: A Flexible Tool for Preimplantation Biopsy Samples

EmbryoMap is a streamlined workflow for chromosome copy number variation analysis and has been optimised and analytically validated to maximise the accuracy of results and reproducibility in the users’ hands. EmbryoMap’s improved chemistry enables increased assay flexibility by allowing various sample input types. Users can adapt EmbryoMap to lab requirements, including starting material of blastomere, blastocyst, polar body biopsies or various other sample input alternatives. EmbryoMap DNA libraries can also be used as starting material for concurrent testing in complementary workflows, increasing the capacity to perform testing from a single sample. In this study, we demonstrated EmbryoMap’s flexibility by performing concurrent CNV analysis followed by linkage-based haplotyping using the EmbryoMap library product as input for KaryoMap v2.0. Genomic DNA from commercial cell lines were used to evaluate the platform performance. EmbryoMap sequencing-ready libraries were used as input for Infinium KaryoMap v2.0 BeachChip arrays. EmbryoMap CNV analysis was performed with eMap software. KaryoMap v2.0 analysis was performed with kMap software. Sample performance was assessed using default QC settings for each platform. The reproducibility of haplotyping between the EmbryoMap libraries and bulk genomic DNA was evaluated. All samples passed EmbryoMap QC and produced karyotype matched CNV charts, qualifying the EmbryoMap libraries for KaryoMap v2.0 analysis. All samples passed the KaryoMap v2.0 QC metrics. The haplotyping result from EmbryoMap samples was highly concordant with the expected inheritance pattern derived from bulk genomic DNA. QC parameters for ADO and miscalls were within the expected range. This proof of concept demonstrates that EmbryoMap libraries are suitable for linkage-based analysis using KaryoMap v2.0. Additional experiments show these libraries can be used in additional workflows such as PGT-SR, and STR PGT-M, amongst others.

Distributed Accelerated Concurrency Testing Method for Automated Driving System

Distributed Accelerated Concurrency Testing Method for Automated Driving System

Next-Generation Sequencing Testing and Triaging of Bone Marrow Samples: Indications, Pre-authorization and Medical Necessity for Patient Care

Abstract Introduction/Objective Bone marrow biopsy (BMBx) is an invasive procedure and samples are usually obtained for diagnosis, staging and prognosis of hematolymphoid disorders (HDs). Given the need for WHO and ICC classification of HDs; the Next Generation Sequencing (NGS) testing (in addition to other esoteric testing) has become relevant and medically necessary. It is important to triage BMBx in real-time based on clinical indications; however, pathologists are challenged by limited published guidelines as well as need for pre-authorization (PA) thus resulting in claim denials. Methods/Case Report Retrospective analysis was performed (2018 to 2022) on 1610 BMBx submitted for various clinical indications. These were categorized as follows: Cytopenias 220 (MDS); Cytosis 250 (MPN); Lymphomas work-up 350 (LY), acute leukemias 440 (AL) and plasma cell disorders 350 (PCD). In addition to esoteric testing; the decision was made to perform NGS testing based on preview of aspirate slides, clinical history and CBC. Results (if a Case Study enter NA) Providers initially ordered NGS in 10% of cases; however, NGS was added later by pathologists in 30% of BMBx samples. Abnormal NGS results were obtained as follows: MDS (70%); MPN (75%); LY (15%); AL (90%) and PCD (40%). NGS testing provided clinically useful data for MDS, MPN and AL groups. Even though LY and PCD groups also yielded positive results; the concurrent esoteric testing (Flow, FISH and Cytogenetics) was useful thus making indication of NGS in these two subset groups less indicated. Conclusion Appropriate triaging of BMBx for NGS testing is medically necessary for following reasons: 1) Enables precise diagnosis in a timely manner; 2) to avoid repeat BMBx if triaging guidelines are followed; and 3) decision to order NGS is made in real-time as BMBx are time sensitive samples thus eliminating the need for PA as this study emphasize that NGS has become standard of care in the work-up of HDs.

A Sticky Situation: Diagnosing Post-Transfusion Purpura in the Setting of Longstanding, Transfusion-Dependent AML

Background Post-transfusion purpura (PTP), a commonly underreported adverse transfusion event. It is defined as severe thrombocytopenia with related sequelae occurring 5-10 days of transfusion where both transfused and autologous platelets are destroyed. Low cell counts may be masked by other conditions (i.e. AML) and there is a paucity of literature on cases of PTP especially in concurrent pancytopenia. Swift diagnosis is critical for management. This case presents a unique opportunity to examine PTP in a patient with a complex hematopathologic malignancy history. Methods Relevant clinical data was obtained through examination of available medical records, concurrent ancillary diagnostic testing, and serological send-out testing was performed. Appropriate investigation and evaluation of repeated transfusion reactions with clinical symptomatology in accordance with available bio-vigilance surveillance guidelines aided in the diagnosis. Findings A 73-year-old female patient presented to the emergency department with acute, worsening fatigue, lethargy, pallor, and shortness of breath. She was found at home by emergency medical services with bright red blood covering her legs, originating from the rectum, several longstanding pressure ulcers, and an oxygen saturation in the 80s. The initial physical exam revealed a cachectic, ill-appearing woman who was tachypneic, wheezing, with new and old blood at anus, generalized weakness, fatigue, shortness of breath, cough, myalgias, and diffuse bruising of various sizes. There was no loss of consciousness or history of anticoagulant therapy. The patient had a complex medical history which included acute myeloid leukemia with concurrent chemotherapy complicated by longstanding, transfusion-dependent pancytopenia, lung adenocarcinoma status-post radiation therapy now in remission, congestive heart failure, chronic obstructive pulmonary disease on continuous home oxygen, chronic intermittent bilateral lower extremity rashes secondary to adult-onset Still's disease, and multiple visits to the emergency department, inpatient admissions, and numerous outpatient infusions for the management of pancytopenia. The patient's initial laboratory workup in the emergency room setting demonstrated clear, previously known, pancytopenia along with severe acidosis, marked anemia, and derangements of coagulation testing. With numerous visits to both the emergency department and outpatient infusion centers, the patient had previous transfusion reactions which ranged from mild allergic to repeating patterns of fulminant weakness, lethargy, and confusion relating to the timing of transfusions. With increasing skin manifestations of purpuric skin lesions, severely acute thrombocytopenia regardless of HLA matched or compatible platelet units, and results of send-out serology demonstrating 100% reactivity to all platelets and specific HPA antibodies, the diagnosis of post-transfusion purpura was made. Conclusion Despite this patient succumbing to diffuse hypoxic anemia and suffering a fatal cardiac dysrhythmia, the results of reference laboratory send-out serology revealed positivity in 100% of platelets crossmatched and the presence of antibodies to HLA Class I and HPA-2b, which satisfy the clinical and serologic criteria for post-transfusion purpura and represent a rare diagnostic finding.

Concurrent Testing of Spatially Separated Tissue Samples and Circulating Tumor DNA Reveals Substantial Intra-Patient Genetic Heterogeneity in Relapsed/Refractory Follicular Lymphoma

Background: Scrutiny of genetic heterogeneity in follicular lymphoma (FL) patients has been mainly limited to the investigation of single-site biopsies in previous studies, while the potential of circulating cell-free DNA (cfDNA) to resolve intra-patient heterogeneity has not been fully exploited in FL. Therefore, we aimed to characterize spatiotemporal heterogeneity in relapsed/refractory (R/R) FL by performing comprehensive genomic profiling of spatially separated tissue samples with matching cfDNA samples collected throughout the disease course. Methods: We performed ultra-deep targeted sequencing of 63 tumor tissue DNA (tisDNA), 28 cfDNA and paired germline DNA samples collected from 22 R/R FL patients. Sequencing libraries were prepared using a SureSelectXT HS (Agilent, USA) panel encompassing 173 genes recurrently mutated in FL, as well as rearrangement regions for immunoglobulin V(D)J repertoire profiling. Sequencing was performed on a NovaSeq6000 or NextSeq2000 (Illumina, USA) platform reaching a median deduplicated depth of 5,419x and 1,695x for cfDNA and tisDNA samples, respectively. We called short somatic variants using GATK Mutect2 (v.4.1.7.0), copy number alterations using PureCN (v.1.20.0) and CNVKit (v.0.9.9), as well as immunoglobulin repertoire using the whole-mark module of ARResT/Interrogate. Results: Median 6 and 8 non-silent variants were detected in cfDNA and tisDNA samples, respectively, affecting KMT2D (52%), CREBBP (45%) and TNFRSF14 (33%) most frequently in both sample types. Non-silent variants were detected in 21 of 24 (87.5%) pretreatment cfDNA samples. Comparing tisDNA samples with matching pretreatment cfDNA samples median 63.6% of variants were shared, yet unique variants were identified in cfDNA in 13/20 sample pairs, involving a median 14.3% of the variants. Studying the phylogenetic evolution of tumor samples pointed to early branching in majority of the patients, with ubiquitously present mutations detected in all samples constituting a median 24.3% of variants, although late branching was also observed in a subset (2/22) of the patients with at least 50% of variants detected in all samples. Most conserved variants were detectable in KMT2D and CREBBP, with notable exceptions of a lower mutation prevalence, but a high conservation rate in ATP6V1B2 and STAT6 genes. Subclonal clustering of variants and hierarchy analysis of samples from patients (n=5) with 2 tisDNA collected at separate lymphoma sites and a matching pretreatment cfDNA indicated that spatially discordant variants formed the same subclone, that could be also recovered in cfDNA in 4/5 patients (80%). An additional patient presented with almost identical tisDNA samples, but further unique mutations in cfDNA (PAT-FL-20)(Figure 1.). Investigating the prognostic significance of ctDNA level in the relapsed setting revealed that higher ctDNA levels were significantly associated with poor response to therapy (p=0.023, Kruskal-Wallis test), yet when we stratified patients by the median pretreatment ctDNA level (1.44x10 5 haploid genome equivalent/mL plasma) progression free survival in the subsequent treatment line was not substantially different between the two arms (p=0.11, log-rank test). Conclusion: Based on our results, R/R FL is characterized by remarkable intra-patient genetic heterogeneity. Although the founder clone harboring pathogenic KMT2D and CREBBP mutations can be identified in majority of the samples, expansion of tumor subclones between lymphoma sites confers divergent evolution, leaving genetic alterations unidentified during single-site based genetic testing. We also provide preliminary evidence, that multitarget high-throughput sequencing of cfDNA can uncover spatially restricted subclones that play a role in disease progression in R/R FL and that pretreatment ctDNA level might have a predictive value in the relapsed setting of FL. Figure 1. Molecular alterations in FL patients with tisDNA samples from two separate lymphoma sites and a matching cfDNA. KMT2D and CREBBP variants show high conservation, yet further variants are often spatially restricted, which can be resolved by cfDNA profiling. Copy number alterations (CNA) show lower concordance, yet recurrent CNA-s can be recovered in a subset of the cases. Identical immunoglobulin heavy and light chain usage can be detected in all samples of 3 patients and in paired tisDNA in 2 patients.

2682. Opt-Out Syphilis Screening in an Urgent Care Center Increases Recognition and Treatment of Asymptomatic Syphilis Infection and Uptake of HIV Pre-Exposure Prophylaxis

Abstract Background Atlanta, Georgia has an extremely high burden of both HIV and early syphilis. This syndemic is driven by a complex set of structural factors that result in striking healthcare inequities, further burdening communities with low access to primary care. These populations may instead utilize emergency departments and urgent care centers (UC) for medical care. UC visits represent a crucial opportunity for recognition and treatment of syphilis as well as connection to HIV prevention services. We describe a novel pilot of a universal, opt-out syphilis screening program offered to all adults in the Grady Urgent Care Center in Atlanta. Methods A retrospective chart review was performed on all patients 18 years and older who had a rapid plasma reagin (RPR) test collected from 9/1/21 to 12/31/21. Demographic data, syphilis diagnosis, syphilis treatment, and HIV testing and serostatus were abstracted from the electronic health record. Patients with reactive RPRs were contacted by a physician for diagnosis and potential syphilis treatment, sexual health counseling, and referral for HIV pre-exposure prophylaxis (PrEP) or HIV care. Results From 9/1/21 to 12/31/21, 5794 patients were triaged and 1381 underwent RPR screening (23.8%). Eighty (5.8%) had reactive RPRs, and 42 (52.5%) had active syphilis infection. Of those with active syphilis, 39 (92.9%) received treatment, and 35 (83.3%) completed treatment. Among all undergoing RPR screening, 37 (2.7%) were living with HIV. Of those who were not previously diagnosed with HIV, 1279 (93.9%) underwent concurrent HIV testing. Among all undergoing RPR screening, 41 expressed interest in PrEP, and 7 completed PrEP clinic intake. Of those with reactive RPRs, 16 expressed interest in PrEP, and 6 completed PrEP clinic intake. Syphilis Testing and Treatment Among Patients 18 Years of Age and Older Who Had an RPR Collected in the Grady Urgent Care Center, 9/1/2021-12/31/2021 HIV Testing and PrEP Among Patients 18 Years of Age and Older Who Had an RPR Collected in the Grady Urgent Care Center, 9/1/2021-12/31/2021 Conclusion Routine, opt-out syphilis testing was used to identify a substantial number of patients with active syphilis and connect a majority to treatment, underscoring the need for universal syphilis screening in this setting. It also provided an opportunity to deliver sexual health counseling and offer PrEP, although few patients completed PrEP clinic intake, suggesting that a more targeted approach to PrEP referral may be more effective. Disclosures All Authors: No reported disclosures

Concurrent Validity and Test–Retest Reliability of the 3-Meter Backward Walk Test in Stroke Survivors

In the context of evaluating physical function in individuals with stroke, the 3-Meter Backward Walk Test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test–retest reliability and concurrent validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) under the supervision of different physiotherapists. The results indicate that the 3MBWT demonstrated high reliability, with an Intraclass Correlation Coefficient of 0.97 (95% CI: 0.95, 0.98). It also showed significant concurrent validity with other established walking tests like the 6MWT (r = −0.78) and 10MWT (r = 0.71), with a moderate correlation with the FGA (r = −0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and agrees well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.

Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy in Patients Clinically Suspected of FSHD Using Optical Genome Mapping.

Facioscapulohumeral muscular dystrophy (FSHD) represents the third most common muscular dystrophy in the general population and is characterized by progressive and often asymmetric muscle weakness of the face, upper extremities, arms, lower leg, and hip girdle. In FSHD type 1, contraction of the number of D4Z4 repeats to 1-10 on the chromosome 4-permissive allele (4qA) results in abnormal epigenetic derepression of the DUX4 gene in skeletal muscle. In FSHD type 2, epigenetic derepression of the DUX4 gene on the permissive allele (4qA) with normal-sized D4Z4 repeats (mostly 8-20) is caused by heterozygous pathogenic variants in chromatin modifier genes such as SMCHD1, DNMT3B, or LRIF1. We present validation of the optical genome mapping (OGM) platform for accurate mapping of the D4Z4 repeat size, followed by diagnostic testing of 547 cases with a suspected clinical diagnosis of FSHD and next-generation sequencing (NGS) of the SMCHD1 gene to identify cases with FSHD2. OGM with Bionano Genomics Saphyr and EnFocus FSHD analysis software was used to identify FSHD haplotypes and D4Z4 repeat number and compared with the gold standard of Southern blot-based diagnosis. A custom Agilent SureSelect enrichment kit was used to enrich SMCHD1, followed by NGS on an Illumina system with 100-bp paired-end reads. Copy number variants were assessed using NxClinical software. We performed OGM for the diagnosis of FSHD in 547 patients suspected of FSHD between December 2019 and December 2022, including 301 male (55%) and 246 female patients (45%). Overall, 308 of the referred patients were positive for D4Z4 contraction on a permissive haplotype, resulting in a diagnosis of FSHD1. A total of 252 of 547 patients were referred for concurrent testing for FSHD1 and FSHD2. This resulted in the identification of FSHD2 in 9/252 (3.6%) patients. In our FSHD2 cohort, the 4qA allele size ranged from 8 to 18 repeats. Among FSHD1-positive cases, 2 patients had biallelic contraction and 4 patients had homozygous contraction and showed early onset of clinical features. Nine of the 308 patients (3%) positive for 4qA contraction had mosaic 4q alleles with contraction on at least one 4qA allele. The overall diagnostic yield in our cohort was 58%. A combination of OGM to identify the FSHD haplotype and D4Z4 repeat number and NGS to identify sequence and copy number variants in the SMCHD1 gene is a practical and cost-effective option with increased precision for accurate diagnosis of FSHD types 1 and 2.

Accuracy of QuantiFERON in active tuberculosis suspects with comorbidities and nontuberculous mycobacterial infection in Northern California.

The QuantiFERON-TB Gold (QFT) is routinely utilized in North American health systems to detect a cellular immune response to Mycobacterium tuberculosis antigens in symptomatic and asymptomatic patients. The sensitivity of QFT in tuberculosis (TB) patients with comorbidities is not well established and the specificity of QFT in patients with nontuberculous mycobacteria (NTM) infections is incompletely understood. Between 2012 and 2023, all patients with culture-positive TB and patients with NTM infection per the expert diagnostic guidelines or biopsy-proven NTM infection who had a concurrent QFT test were included in this study. The sensitivity and specificity of QFT were measured in TB and NTM patients, respectively. In 109 patients with active TB, the overall sensitivity of QFT was 78.0% (85/109; 95% CI: 70.1, 85.7). The sensitivity was 86.0% (49/57; 95% CI: 76.6, 94.8) and 69.2% (36/52; 95% CI: 56.7, 81.8) in immunocompetent and immunocompromised patients, respectively. The overall specificity of QFT in 88 patients with NTM infection was 76.1% (67/88; 95% CI: 67.2, 85.0). After the exclusion of 17 NTM patients with risk factors for latent TB infection, the specificity was 94.4% (67/71; 95% CI: 89.1, 99.7). Two patients had NTM species known to cross-react with QFT. In two NTM patients infected with species (Mycobacterium intracellulare subsp. intracellulare and Mycobacterium intracellulare subsp. chimaera) not known to cross-react, whole genome sequencing did not detect ESAT-6 or CFP-10. In Northern California, the QFT assay demonstrated moderately low to moderately high sensitivity in TB patients and very high specificity in NTM patients, thus ruling out concerns for cross-reactivity with NTM.

Evidence for overdiagnosis in noncancer conditions was assessed: a metaepidemiological study using the ‘Fair Umpire’ framework

ObjectivesTo evaluate the strength of the evidence for, and the extent of, overdiagnosis in noncancer conditions. Study Design and SettingWe systematically searched for studies investigating overdiagnosis in noncancer conditions. Using the ‘Fair Umpire’ framework to assess the evidence that cases diagnosed by one diagnostic strategy but not by another may be overdiagnosed, two reviewers independently identified whether a Fair Umpire—a disease-specific clinical outcome, a test result or risk factor that can determine whether an additional case does or does not have disease—was present. Disease-specific clinical outcomes provide the strongest evidence for overdiagnosis, follow-up or concurrent tests provide weaker evidence, and risk factors provide only weak evidence. Studies without a Fair Umpire provide the weakest evidence of overdiagnosis. ResultsOf 132 studies, 47 (36%) did not include a Fair Umpire to adjudicate additional diagnoses. When present, the most common Umpire was a single test or risk factor (32% of studies), with disease-specific clinical outcome Umpires used in only 21% of studies. Estimates of overdiagnosis included 43–45% of screen-detected acute abdominal aneurysms, 54% of cases of acute kidney injury, and 77% of cases of oligohydramnios in pregnancy. ConclusionMuch of the current evidence for overdiagnosis in noncancer conditions is weak. Application of the framework can guide development of robust studies to detect and estimate overdiagnosis in noncancer conditions, ultimately informing evidence-based policies to reduce it.

Development and clinimetric assessment of a performance-based functional vision tool in visually impaired children.

Appropriate functional vision is vital for the development of visually impaired (VI) children. However, the literature currently lacks a performance-based tool for assessing functional vision, unlike the existing self-reported tools. The objective of this study is to develop and conduct a clinimetric study on a Performance-Based Functional Vision Tool (PB-FVT) specifically designed for VI children aged 3-7 and 7-10 years old. This methodological study was conducted to assess the clinimetric properties of the PB-FVT. The assessment included face validity (evaluated through cognitive interviews and an Impact Score >1.5), content validity (with criteria including content validity ratio >0.63, item content validity index >0.78, scale content validity index or average >0.8, and Kappa value >0.7), criterion validity (assessed through a concurrent test using visual acuity scores), construct validity (utilizing the known group method), relative reliability (measured by the intra-class correlation coefficient), absolute reliability (determined by the standard error of measurement and minimal detectable changes), interpretability, responsiveness, sensitivity, and specificity (analyzed via ROC curve analysis). The PB-FVT was developed with 32 items, divided into five components: activities of daily living, instrumental activities of daily living, education, play, and social interaction. The results indicate that the scale demonstrates suitability in terms of validity, reliability, and other measurement characteristics. The valid and reliable PB-FVT may accurately assess the level of functional vision during early childhood, helping to prevent negative impacts on a child's overall development. By utilizing the PB-FVT, any functional vision impairments can be identified appropriately, enabling the planning and implementation of effective rehabilitation interventions.

Comprehensive molecular testing prior to first treatment among patient with metastatic non-small cell lung cancer.

431 Background: Nearly 60% of patients with non-small cell lung cancer will have actionable mutations identified via molecular testing. Of these patients, those treated with targeted therapy had longer overall survival than those who did not. Therefore, it is imperative molecular testing is both sent and resulted at time of first treatment. Despite this, multiple barriers remain with reported community rates of &lt;50% with comprehensive molecular testing. We sought to understand testing practices at our institution. Methods: In this retrospective chart review, patients with stage IV, non-small cell, non-squamous cell lung cancer treated at Orlando Regional Medical Center between 1/2021-5/31/2022 were identified. Primary endpoints included rate of comprehensive molecular testing (EGFR, ALK, ROS1, RET, MET, BRAF, KRAS, ErbB2 and NTRK, either tissue or plasma) available prior to first line treatment. Results: Of the 73 patients who were included, 69 patients (94.8%) had comprehensive molecular testing results available prior to first line treatment. 48 (65.8%) patients had tissue testing results prior to first treatment. 44 (60.2%) patients had plasma testing results prior to first treatment. 14 (19.2%) patients had tissue testing sent, without results at time of first treatment. Conclusions: The comprehensive molecular testing rate at a large tertiary hospital is 94.8%, substantially higher than the rates reported in the literature. Despite this, 19.2% of patients had tissue testing sent but not resulted at time of first treatment. Future studies are needed to improve turnaround time of tissue based molecular testing results and evaluate concurrent versus sequential tissue and plasma testing.

The Stability and Validity of Automated Indices of Vocal Development in Infants With Autistic and Non-Autistic Siblings.

This study evaluates the extent to which automated indices of vocal development are stable and valid for predicting language in infants at increased familial likelihood for autism and/or language impairment and relatively lower likelihood infants. A group of infants with autistic siblings (Sibs-autism; 20 infants) and a comparison group of infants with non-autistic siblings (Sibs-NA; 20 infants) wore Language ENvironment Analysis (LENA) recording devices for 16 hr on 2 days within a 1-week period. Extant software was used to derive several putative indices of vocal development from these recordings. Stability of these variables was examined across and within groups. Expressive and receptive language aggregates were calculated for each participant. Multiple regression analyses were used to (a) evaluate zero-order correlations for variables derived from LENA recordings with concurrent and future language and (b) test whether those associations were moderated by group status. Both stability and validity differed by variable and group status. All variables reached acceptable stability in the Sibs-autism group within two to three observations, whereas stability of most variables was attenuated in the Sibs-NA group. No variables were associated with concurrent language in the theoretically motivated direction across groups, but two variables were strongly associated with concurrent expressive language in only the Sibs-NA group. Additionally, two variables were associated with later expressive language, though these correlations were again stronger in the Sibs-NA versus Sibs-autism group. Although selected automated indices of vocal development were stable in Sibs-autism and/or valid for predicting expressive language within Sibs-NA, no scores showed strong, theoretically motivated associations with language within the Sibs-autism group. Automated indices of vocal development may, thus, have limited validity or clinical utility for predicting language development in infants at elevated familial likelihood for autism. https://doi.org/10.23641/asha.24415735.

Concurrent Testing for COVID-19 and HIV Infection at 6 High-Volume Emergency Departments in a Priority Jurisdiction for Ending the HIV Epidemic in the United States.

The COVID-19 pandemic caused disruptions in access to routine HIV screening. We assess HIV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing across 6 emergency departments (EDs) in Cook County, Illinois. We retrospectively analyzed the number of SARS-CoV-2 tests, HIV screens, and the proportion of concurrent tests (encounters with both SARS-CoV-2 and HIV testing), correlating with diagnoses of new and acute HIV infection. Five sites reported data from March 1, 2020, to February 28, 2021, and 1 site from September 1, 2020, to February 28, 2021. A total of 1,13,645 SARS-CoV-2 and 36,094 HIV tests were performed; 17,469 of these were concurrent tests. There were 102 new HIV diagnoses, including 25 acute infections. Concurrent testing proportions ranged from 6.7% to 37% across sites (P < 0.001). HIV testing volume correlated with the number of new diagnoses (r = 0.66, P < 0.01). HIV testing with symptomatic SARS-CoV-2 testing was strongly correlated with diagnosis of acute infections (r = 0.87, P < 0.001); this was not statistically significant when controlling for HIV testing volumes (r = 0.59, P = 0.056). Acute patients were more likely to undergo concurrent testing (21/25) versus other new diagnoses (29/77; odds ratio = 8.69, 95% CI: 2.7 to 27.8, P < 0.001). Incorporating HIV screening into SARS-CoV-2 testing in the ED can help maintain HIV screening volumes. Although all patients presenting to the ED should be offered opt-out HIV screening, testing individuals with symptoms of COVID-19 or other viral illness affords the opportunity to diagnose symptomatic acute and early HIV infection, rapidly link to care, and initiate treatment.

Physiological characterization of gastric emptying using high-resolution antropyloroduodenal manometry.

Delayed gastric emptying (GE) has been associated with antral and pyloric dysmotility. We aimed to characterize differences in the antral, duodenal, and pyloric motility profiles associated with delayed GE, using high-resolution antropyloroduodenal manometry (HR-ADM). Patients referred for HR-ADM for dyspeptic symptoms performed a concurrent GE breath test (NCT01519180 and NCT04918329). HR-ADM involved 36 sensors 1 cm apart, placed across the pylorus. Interdigestive and postprandial periods were identified. Antral, pyloric, and duodenal motor profiles were analyzed recording the frequency, amplitude, and propagative nature of contractions for each period. Plots of patients with normal and delayed GE were compared. Sixty patients underwent both HR-ADM and GE tests. Twenty-five and 35 patients had delayed and normal GE, respectively. Antral and duodenal motor profiles were not different between the two groups during the interdigestive period. During the postprandial period, a lower frequency of antral contractions was associated with delayed GE (2.22 vs. 1.39 contractions/min; P = 0.002), but no difference in mean contraction amplitude was observed. The pyloric region was identified in all the patients and pylorospasms, defined as 3 min of repeated isolated pyloric contractions, were more frequent in patients with delayed GE (32.0% vs. 5.7%; P = 0.02) during the postprandial period. No difference in duodenal contraction profiles was observed. Manometric profile alterations were observed in 72% of the patients with delayed GE, with 56% having a low frequency of antral contractions. Using HR-ADM, patients with delayed GE displayed different postprandial antropyloric motility as compared with patients with normal GE.NEW & NOTEWORTHY High-resolution antropyloroduodenal manometry (HR-ADM) allows precise characterization of antral, pyloric, and duodenal motility, although its association with gastric emptying (GE) has been poorly investigated. Concurrent HR-ADM with GE measurement showed a lower frequency of antral postprandial contractions and an increased frequency of postprandial pylorospasms in patients with delayed GE. HR-ADM could, therefore, be useful in the future to better select patients for treatments targeting the pylorus.