Primary Screening Test Research Articles

Accuracy of alternative PHQ-9 scoring algorithms to screen for depression in people living with HIV in Sub-Saharan Africa.

Screening for depression remains a priority for people living with HIV (PLWH) accessing care. The nine-item Patient Health Questionnaire (PHQ-9) is a widely used depression screening tool, but has limited accuracy when applied across various cultural contexts. We aimed to evaluate the performance of alternative PHQ-9 scoring algorithms in sub-Saharan African PLWH. five HIV programs in Cameroon, Côte d'Ivoire, Kenya, Senegal and the Republic of Congo. Adult PLWH were screened for depression during the 2018-2022 period. Diagnosis confirmation was done by psychiatrist blinded clinical evaluation (gold standard). Diagnostic performances, including sensitivity, and area under the curve (AUC)) of the traditional PHQ-9 scoring (positive screening - score≥10) was compared to alternative scoring algorithms including: i) the presence of ≥1 mood symptom (PHQ-9 items 1&2) combined with ≥2 other symptoms listed in the PHQ-9, and ii) a simplified recoding of each 4-response item into two categories (absence/presence). A total of 735 participants were included (54% female, median age 42 years [IQR 34-50]). Depression was diagnosed by a psychiatrist in 95(13%) participants. Alternative scoring sensitivities (0.59 to 0.74) were higher than that of the traditional score's (0.39). Compared to traditional scoring, AUC were significantly higher for PHQ-9 alternative scoring. Across settings, alternative scoring algorithms increased sensitivity and reduced variability. As a primary screening test, new scoring algorithms appeared to improve the PHQ-9 sensitivity in identifying depression and reduce heterogeneity across settings. This alternative might be considered to identify PLWH in need of referral for further diagnostic evaluations.

Interpretable diagnosis of breast lesions in ultrasound imaging using deep multi-stage reasoning

Objective.Ultrasound is the primary screening test for breast cancer. However, providing an interpretable auxiliary diagnosis of breast lesions is a challenging task. This study aims to develop an interpretable auxiliary diagnostic method to enhance usability in human-machine collaborative diagnosis.Approach.To address this issue, this study proposes the deep multi-stage reasoning method (DMSRM), which provides individual and overall breast imaging-reporting and data system (BI-RADS) assessment categories for breast lesions. In the first stage of the DMSRM, the individual BI-RADS assessment network (IBRANet) is designed to capture lesion features from breast ultrasound images. IBRANet performs individual BI-RADS assessments of breast lesions using ultrasound images, focusing on specific features such as margin, contour, echogenicity, calcification, and vascularity. In the second stage, evidence reasoning (ER) is employed to achieve uncertain information fusion and reach an overall BI-RADS assessment of the breast lesions.Main results.To evaluate the performance of DMSRM at each stage, two test sets are utilized: the first for individual BI-RADS assessment, containing 4322 ultrasound images; the second for overall BI-RADS assessment, containing 175 sets of ultrasound image pairs. In the individual BI-RADS assessment of margin, contour, echogenicity, calcification, and vascularity, IBRANet achieves accuracies of 0.9491, 0.9466, 0.9293, 0.9234, and 0.9625, respectively. In the overall BI-RADS assessment of lesions, the ER achieves an accuracy of 0.8502. Compared to independent diagnosis, the human-machine collaborative diagnosis results of three radiologists show increases in positive predictive value by 0.0158, 0.0427, and 0.0401, in sensitivity by 0.0400, 0.0600 and 0.0434, and in area under the curve by 0.0344, 0.0468, and 0.0255.Significance.This study proposes a DMSRM that enhances the transparency of the diagnostic reasoning process. Results indicate that DMSRM exhibits robust BI-RADS assessment capabilities and provides an interpretable reasoning process that better suits clinical needs.

Severe hydronephrosis complicated with primary aldosteronism: a case report and review of the literature

BackgroundPrimary aldosteronism is characterized by high plasma aldosterone and low renin. The plasma aldosterone-to-renin ratio is recommended for screening. Severe hydronephrosis leads to renal parenchymal ischemia, resulting in increased renin secretion. Since nonsuppression of renin may cause a negative result in the aldosterone-to-renin ratio test, severe hydronephrosis and primary aldosteronism occurring simultaneously in a patient are challenging to diagnose.Case presentationA 54-year-old Chinese man of Han ethnicity was diagnosed with hypertension and severe hypokalemia (minimum 1.57 mmol/L) 13 years prior, and was also diagnosed with severe hydronephrosis due to congenital ureteral stenosis on the left side. His clinical features suggested primary aldosteronism, but the aldosterone-to-renin ratio result of the patient was negative every time he underwent the primary aldosteronism screening test. No further treatment for primary aldosteronism was performed, which led the patient to suffer from severe hypokalemia, such that he was taking 12–15 g/day potassium chloride orally to keep his blood potassium between 3.0 and 3.5 mmol/L (reference value, 3.5–5.5 mmol/L) for 13 years, and the patient needed to be hospitalized in the intensive care unit for rescue several times. At admission, although the aldosterone-to-renin ratio result of the patient was negative, we still did the saline stress test and captopril inhibition test, and the results showed that the plasma aldosterone level was not lower after the test than before the test. Adrenal enhanced computed tomography suggested an adenoma in the left adrenal gland, and the results of adrenal vein sampling suggested that the left side was the dominant side. Therefore, laparoscopic total resection of the left adrenal gland was performed, and 2 weeks later, the patient developed short-term renal function impairment and hyperkalemia, but his renal function and blood potassium returned to normal after treatment that included fluid rehydration. The patient’s biochemical test results and clinical symptoms were completely normal after 1 year.ConclusionWe suggest that for patients with a high suspicion of primary aldosteronism in the clinic, comprehensive analysis must be performed in combination with clinical characteristic assessments, such as severe hydronephrosis, if renin is within the normal range or if the aldosterone-to-renin ratio result is negative at screening and diagnostic tests, and adrenal vein sampling should be performed if necessary. It can help avoid misdiagnoses and contribute to the treatment of patients with severe hydronephrosis and primary aldosteronism.

A dual-center study: can ultrasound radiomics differentiate type I and type II epithelial ovarian cancer patients with normal CA125 levels?

CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients. We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour's region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram. Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort. Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels. This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.

Self-performed Rh typing: a cross-sectional study

ObjectiveTo evaluate whether patients are capable and willing to self-administer and interpret an EldonCard test to determine their Rh status.MethodsThis was a cross-sectional study in Honolulu, HI, USA of pregnancy-capable...

Cost-effectiveness of approaches to cervical cancer screening in Malawi: comparison of frequencies, lesion treatment techniques, and risk-stratified approaches

BackgroundRecently-updated global guidelines for cervical cancer screening incorporated new technologies—most significantly, the inclusion of HPV DNA detection as a primary screening test—but leave many implementation decisions at countries’ discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening.MethodsUsing a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing “triage” approaches—i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software.ResultsThermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach.ConclusionsThese results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.

Eosinophilic Cells in Ovarian Borderline Serous Tumors as a Predictor of BRAF Mutation.

According to recent reports, ovarian serous borderline tumor (SBT) harboring the BRAF V600E mutation is associated with a lower risk of progression to low-grade serous carcinoma. Preliminary observations suggest that there may be an association between eosinophilic cells (ECs) and the above-mentioned mutation, so this study aimed to evaluate interobserver reproducibility for assessing ECs. Forty-two samples of SBTs were analyzed for ECs with abundant eosinophilic cytoplasm. Immunohistochemical staining and genetic pro-filing were performed in all cases to verify the BRAF V600E mutation. A BRAF V600E mutation was found in 19 of 42 (45%) cases. Inter-observer reproducibility in the assessment of ECs was substantial (κ = 0.7). The sensitivity and specificity for predicting the mutation were 79% and 91%, respectively. Patients with BRAF-mutated SBTs were significantly younger than those without mutation (p = 0.005). SBTs with BRAF mutation were less likely to be accompanied by non-invasive implants than wild-type SBT: 12% (2/17) versus 33% (6/18). Seven cases were excluded due to incomplete cytoreductive surgery. Nevertheless, Fisher's exact test showed no significant differences between the two groups (p = 0.228). Overall, this study strengthens the idea that ECs in ovarian SBTs may represent a mutation with prognostic significance, which can serve as a primary screening test for BRAF V600E mutation in this pathologic entity.

Novel Deep Learning Neural Networks for Breast Cancer Malignancy Estimation

Medicine has become one of the huge fields which has its own growth each and every day. Few diseases are still a threat to medical field. Because of its destructive nature, cancer is a disease that causes fear in many people throughout the world. However, most cancers are curable if detected early and treated with the right medical care and computer-assisted diagnosis. These days, diagnosis is more popular because it works well as a primary screening test for many diseases, particularly cancer. Deep learning is a method of artificial intelligence where the computer is given intelligence that attempts to emulate the way a human brain thinks. This research focuses on creating a deep neural network that can accurately predict the malignancy of breast cancer up to 98%, allowing medical personnel to diagnose patients more quickly and administer therapy more effectively.

Clinical Outcomes from the Alaska Native Tribal Health Consortium Colorectal Cancer Control Program: 2009-2015.

The Alaska Native Tribal Health Consortium (ANTHC) participated in the United States Centers for Disease Control and Prevention Colorectal Cancer Control Program (CRCCP) from 2009 to 2015. We conducted a descriptive evaluation of ANTHC CRCCP demographics, quality measures, and clinical outcomes, including screening methods employed within the program and screening outcomes. There were 6981 program screenings completed, with the majority (81.3%) of people screened in the 50-75 year age group. Colonoscopy was the primary screening test used, accounting for 6704 (96.9%) of the screening tests. Quality of colonoscopy was high: adequate bowel preparation was reported in 98.2% of colonoscopies, cecal intubation rate was 98.9%, and the adenoma detection rate was 38.9%. A high proportion (58.9%) of colonoscopies had an initial finding of polyps or lesions suspicious for cancer; 41.2% of all colonoscopies had histological confirmation of either adenomatous polyps (40.6%) or cancer (0.5%). The ANTHC CRCCP successfully increased CRC screening among American Indian and Alaska Native peoples living in Alaska; this was achieved primarily through high-quality colonoscopy metrics. These data support a continued focus by the Alaska Native Tribal Health Consortium and its tribal health partners on increasing CRC screening and reducing cancer mortality among Alaska Native peoples.

The association between organised colorectal cancer screening strategies and reduction of its related mortality: a systematic review and meta-analysis

BackgroundTo assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality.MethodsWe systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results.ResultsWe summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years.ConclusionsA CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

The Contemporary Role of Antinuclear Antibodies in Early Diagnosis of Autoimmune Rheumatic Diseases

Antinuclear antibodies (ANA) in blood serum remain the primary diagnostic screening test for systemic connective tissue diseases. This article presents recent literature findings concerning the utilization of ANA in clinical practice. Specifically, it focuses on interpreting analysis positivity, identifying clinically significant types of fluorescence, and categorizing ANA patterns according to specific nosologies. Recommendations for using the name HEp-2-IIF instead of ANA and reporting the results of indirect immunofluorescence analysis for antinuclear antibodies on HEp-2 cell substrates are described in a standardized way, presenting immunofluorescence patterns together with the nomenclature of antibodies and informing about the subsequent management of the patient. Changes made to pattern classification to distinguish between competent and expert level patterns and to improve the visual separation between nuclear and cytoplasmic HEp-2 patterns are discussed. The need for further study of the prevalence and clinical significance of rare ANA patterns, particularly those directed at the mitotic spindle apparatus (NuMA and MSA-2), is emphasized. Prospects for the study and use of autoantibodies against double-stranded DNA not only in diagnosis but also in the treatment of patients with SLE are noted. It was concluded that there is a need for further clinical research, collection, and arrangement of various models of HEp-2 IIF to facilitate the accurate determination of «criterion level» patterns, increase the possibilities of early diagnosis of rheumatological diseases, and improve the management tactics of patients in this category.

Evaluating the economic screening of cervical cancer using IVA, HPV DNA, and histology methods: Systematic review

Background: Cervical cancer is a common malignancy causing cancer-related deaths worldwide. Evidence suggests that adequate screening can reduce cervical cancer-related deaths. Screening for cervical cancer can be done using Visual Inspection of Acetic Acid (VIA), HPV DNA and cytology. The economic burden of cancer patients is substantial ranging from US$8,066 to 22,888 per patient. Health cost effectiveness was comparative in the analysis of costs and consequences for the three screening methods. VIA is the most cost-effective primary screening test for cervical cancer. Purpose: To review the research results of a full economic evaluation to encourage the specific cervical cancer screening methods used to enhance the detection of precancerous lesions in women's cervix. Method: This systematic review used the PRISMA ScR framework with a literature search using 3 databases, namely Pubmed, Wiley, and Google Scholar, with years of publication from 2009 – 2023. The data that has been obtained is carried out by critical appraisal using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results: Based on the search for 3,973 selected articles, 7 match the inclusion criteria. This systematic review discovered three major themes: the utility value of health status, cost and analysis. Conclusion: The most cost-effective cervical cancer screening is by VIA. HPV DNA and pap smear based cytology techniques have been reported to show high sensitivity and specificity respectively including being expensive and resource intensive. In contrast the VIA technique has moderate sensitivity and specificity but is less expensive Various developed countries have used Pap or HPV DNA cytology tests as the main screening method, which can lead to a 50-70% reduction in cervical cancer incidence, while in developing countries using VIA tests as a cervical cancer screening method.

Practical recommendations for antihypertensive therapy during the primary aldosteronism screening test.

The aldosterone-to-renin activity ratio (ARR) is recommended as a screening test for primary aldosteronism (PA). The use of antihypertensive medication is one of the most important factors to take into account when interpreting the ARR. The goal of this study was to compare the effect of various antihypertensive drug classes on biochemical testing and provide practical recommendations for antihypertensive medication regimens in patients suspected of having PA. We retrospectively investigated 4218 hypertensive patients who underwent PA detection between January 2020 and February 2023. Finally, 25 patients with essential hypertension (EH) and 39 with PA were involved. The enrolled EH patients were selected from EH patients with at least two screening tests with interfering medication changes for at least 4 weeks. A total of 2/18 (11.1%) EH patients had opposite screening results after angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine-calcium channel blockers (DHP-CCBs) and diuretics were withdrawn. A total of 3/3 (100%) of the patients were initially screened as positive but had results that tested negative after β-blockers withdrawal. A total of 3/39 (7.7%) PA patients were misdiagnosed with EH with drug effects. Only plasma renin activity was markedly reduced after antihypertensive medication washout (P = 0.0173). Not every patient receiving β-blockers, ACEIs, ARBs and DHP-CCBs with negative reports needed withdrawal or switching antihypertensive drugs. We recommend that patients be left on a regimen that includes β-blockers, ACEIs, ARBs, DHP-CCBs and spironolactone when determining the ARR during the initial test.

B-208 Correlation Studies of Human Papillomavirus DNA on Roche Cobas vs Human Papillomavirus mRNA on Hologic Panther

Abstract Background Molecular testing, specifically HPV DNA has revolutionised the screening and management of cervical cancer. WHO in 2021 has recommended HPV DNA as the primary screening test and also the newer technology HPV mRNA as alternative assay. This evaluation aims to study the result concordance between HPV DNA and mRNA assay. Methods The evaluation was conducted on Roche Cobas 4800 (HPV DNA) and Hologic Panther (HPV mRNA) at NHGD IMH lab in 2021. Both instruments underwent precision studies and carryover test to ascertain its performance prior to the concordance study. 64 samples were used in the correlation against the reference method- HPV DNA testing on Roche Cobas 6800. Results Both Cobas 4800 and Hologic Panther demonstrated acceptable performance in precision, carryover and LoD (for Hologic only). However closer result agreement is observed in Roche 4800 results to the testing laboratory, Quest which is using Roche 6800. Conclusion The disconcordance between cobas 6800 vs cobas 4800 came from the negative samples in cobas 4800 in which their Ct value were found to be near to the detection limit. Similar to Cobas 4800, the discordance observed in Hologic came from the negative samples. However, HPV mRNA screening has been recognized for its higher specificity at baseline in the recent studies which improve clinical outcomes and reduce colposcopy referrals by 14%. Unfortunately, this could not be verified in our evaluation as colposcopy results for those HPV DNA positive sample were not available.

HPV Testing and its Role in Cervical Cancer Screening.

The recognition that persistent infection with carcinogenic human papillomavirus (HPV) is a necessary cause of cervical precancer and cancer has led to the introduction of HPV testing into cervical cancer screening, either as a primary screening test or in conjunction with cervical cytology (i.e., co-testing). HPV testing has much higher sensitivity for detection of cervical precancer and provides greater long-term reassurance if negative compared to cytology. However, most HPV infections are transient, and do not progress to invasive cancer, thus triage tests are required to identify individuals who should be referred to colposcopy for diagnostic evaluation. This chapter begins with a description of the biology, natural history, and epidemiology of HPV as a foundation for understanding the role of HPV in cervical carcinogenesis. This section is followed by a detailed discussion regarding the introduction of HPV-based testing and triage into cervical cancer screening and management. Summarized triage tests include cervical cytology, HPV genotyping, p16/Ki-67 dual stain, and HPV and cellular methylation markers. The final section of this chapter includes an important discussion on cervical cancer disparities, particularly within the United States, followed by concluding remarks.

The Accuracy of Transcutaneous Bilirubin as a Screening Test in Preterm Infants.

To determine the accuracy of transcutaneous bilirubin (TcB) to predict total serum bilirubin (TSB) in preterm infants across gestational age (GA) ranges and to calculate the cost-effectiveness of TcB as the primary screening test of choice for neonatal jaundice in neonatal intensive care unit (NICU) settings. Single-center retrospective study of infants aged ≤ seven days admitted to the NICU over a six-month period with a paired TSB and TcB, with or without phototherapy as part of their routine clinical care. Infants were divided into GA-specific groups asterm, late preterm, moderate preterm, and very preterm. Measurement bias (bias=TSB-TcB) was calculated on the paired TSB and TcB values, and a Bland-Altman analysis was carried out. The impacts of additional infant-specific variables on the bias were assessed with univariate and multivariate linear regression techniques. The potential direct cost savings associated with the use of TcB as the primary screening test were calculated. A total of 263 paired TSB and TcB samples from 95 patients were included (130 paired samples from term (n=60), 75 from late preterm (n=21), 27 from moderate preterm (n=7), and 31 from very preterm (n=7)). The mean paired measurement bias across all the GA groups was -0.9 ± 2.9 mg/dL. The sensitivity and specificity of TcB in GA < 35 weeks were 92% and 62%, respectively. A conservative estimate of a one-third reduction in TSB measurement by using TcB as the primary screening test will have a direct cost saving of $3,148 over a six-month period. Our data suggest that TcB is a safe and potentially cost-effective screening test for jaundice across GA groups.

Integrating human papillomavirus testing as a point-of care service using GeneXpert platforms: Findings and lessons from a Kenyan pilot study (2019-2020).

Globally, cervical cancer is a major public health problem, with about 604,000 new cases and over 340,000 deaths in 2020. In Kenya, it is the leading cause of cancer deaths, with over 3,000 women dying in 2020 alone. Both the Kenyan cancer screening guidelines and the World Health Organization's Global Cervical Cancer Elimination Strategy recommend human papillomavirus (HPV) testing as the primary screening test. However, HPV testing is not widely available in the public healthcare system in Kenya. We conducted a pilot study using a point of care (POC) HPV test to inform national roll-out. The pilot was implemented from October 2019 to December 2020, in nine health facilities across six counties. We utilized the GeneXpert platform (Cepheid, Sunnyvale, CA, USA), currently used for TB, Viral load testing and early infant diagnosis for HIV, for HPV screening. Visual inspection with acetic acid (VIA) was used for triage of HPV-positive women, as recommended in national guidelines. Quality assurance (QA) was performed by the National Oncology Reference Laboratory (NORL), using the COBAS 4800 platform (Roche Molecular System, Pleasanton, CF, USA). HPV testing was done using either self or clinician-collected samples. We assessed the following screening performance indicators: screening coverage, screen test positivity, triage compliance, triage positivity and treatment compliance. Test agreement between local GeneXpert and central comparator high-risk HPV (hrHPV) testing for a random set of specimens was calculated as overall concordance and kappa value. We conducted a final evaluation and applied the Nominal Group Technique (NGT) to identify implementation challenges and opportunities. The screening coverage of target population was 27.0% (4500/16,666); 52.8% (2376/4500) were between 30-49 years of age. HPV positivity rate was 22.8% (1027/4500). Only 10% (105/1027) of HPV positive cases were triaged with VIA/VILI; 21% (22/105) tested VIA/VILI positive, and 73% (16/22) received treatment (15 received cryotherapy, 1 was referred for biopsy). The median HPV testing turnaround time (TAT) was 24 hours (IQR 2-48 hours). Invalid sample rate was 2.0% (91/4500). Concordance between the Cepheid and COBAS was 86.2% (kappa value = 0.71). Of 1042 healthcare workers, only 5.6% (58/1042) were trained in cervical cancer screening and treatment, and only 69% (40/58) of those trained were stationed at service provision areas. Testing capacity was identifed as the main challenge, while the community strategy was the main opportunity. HPV testing can be performed on GeneXpert as a near point of care platform. However, triage compliance and testing TAT were major concerns. We recommend strengthening of the screening-triage-treatment cascade and expansion of testing capacity, before adoption of a GeneXpert-based HPV screening among other near point of care platforms in Kenya.

Abstract 4193: N-NOSE technology based on C. elegans olfaction. Multi-cancer early detection with high sensitivity using urine. Pancreatic-cancer-specific early detection with high sensitivity using urine

Abstract N-NOSE (Nematode Nose) is a cancer screening test based on the chemotactic characteristics of the nematode C. elegans. C. elegans shows avoidance of the urine of healthy individuals while displaying a chemotactic attraction toward the urine of patients with 15 types of cancer (stomach, colon-rectum, lung, breast, pancreas, liver, prostate, uterus, esophagus, gallbladder, bile duct, kidney, urinary bladder, ovary, oropharynx) rendering N-NOSE a primary multi-cancer screening test. N-NOSE has a high sensitivity of 87.5% and 90.2% specificity, on average, from early stage 0-I. N-NOSE is non-invasive because it relies on a urine sample and is affordable (JPY 13,800, ~USD 100).N-NOSE by Hirotsu Bio Science has been available in Japan since late 2020 and is a commercial hit with over 250,000 screenings performed, rapidly increasing. In this presentation, we outline the N-NOSE technology and business in Japan. We review N-NOSE clinical research and critical findings compared to competitors that highlight its excellent performance as a non-invasive primary cancer screening for early detection. N-NOSE is a multi-cancer early detection test. Next, we introduce an evolution of N-NOSE for identifying the cancer type. Pancreatic cancer is the 12th most common cancer worldwide but remains one the deadliest cancer with a 5-year relative survival rate at only 11%, all stages combined. An affordable, non-invasive, and highly sensitive early-stage pancreatic cancer screening test is sorely needed. As an evolution of N-NOSE we genetically engineered C. elegans by knocking out in AWC olfactory neurons a specific olfactory receptor (GPCR), triggering a chemotactic response particular to the only pancreatic cancer urine specimen at an early stage. In this study, we outline, for the first time, the critical discovery of cr-4 GPCR in AWC, which is crucial for a specific chemotaxis response to the urine of patients with pancreatic cancer. Next, we briefly conclude by outlining the link between N-NOSE primary cancer screening followed by N-NOSE cancer type identification, effectively completing the whole cancer screening and identification process in a non-invasive way. Citation Format: Eric Di Luccio, Takaaki Hirotsu. N-NOSE technology based on C. elegans olfaction. Multi-cancer early detection with high sensitivity using urine. Pancreatic-cancer-specific early detection with high sensitivity using urine. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4193.

Clinical application of noninvasive prenatal testing in twin pregnancies: a single-centre experience

Objectives To evaluate the clinical efficiency of non-invasive prenatal testing (NIPT) for fetal chromosomal aneuploidy screening in twin pregnancies. Methods A total of 1650 women with twin pregnancies were enrolled in the study, which underwent NIPT at the Southwest Hospital, Army Medical University, Chongqing, China from January 2013 to June 2022. Fetal karyotyping analysis was conducted in high-risk patients, with subsequent follow-up on pregnancy outcomes. Results In 1650 pregnancies, NIPT results showed ten cases of the fetal chromosome aneuploidy, of which six cases were true positive and four cases were false positive. The sensitivity, specificity, positive predictive value (PPV), and false-positive rate (FPR) of trisomy 21 were 100%, 99.79%, 57.14%, and 0.18%, respectively. Sensitivity, specificity, PPV, and FPR of trisomy 18 were 100%, 99.94%, 50%, and 0.06%, respectively. The sensitivity, specificity, PPV, and FPR of trisomy 13 were 100%, 100%, 100%, and 0%, respectively. No false negatives were detected and the negative predictive value (NPV) was 100% of the total. Eleven pregnancies failed the NIPT test with no-call due to the low fetal fraction (< 4%). Conclusions NIPT is a high-performing routine primary prenatal screening test in twin pregnancies, with high sensitivity and specificity in screening for fetal aneuploidy.

Indication for molecular testing by multiplex ligation-dependent probe amplification in parkinsonism.

The monogenic forms of Parkinson's disease represent less than 10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. We aim to establish the interest of multiplex ligation-dependent probe amplification as a primary screening test and to propose clinical criteria to guide genetic diagnostic tests for patients with suspected Mendelian Parkinson's disease. We recruited 567 patients with parkinsonism from 547 unrelated families and performed two multiplex ligation-dependent probe amplifications for each. We confirmed all pathogenic G2019S variants in the LRRK2 gene by Sanger sequencing and screened the PRKN gene for a second mutation in cases of one heterozygous structural variant in the PRKN gene. The performance of multiplex ligation-dependent probe amplifications was 51/567 (9%) for the entire cohort and included 27 (4.8%) LRRK2 G2019S mutations, 19 (3.4%) PRKN mutations, and 5 (0.9%) SNCA locus duplications. The variables significantly associated with a positive test in the total cohort were North African ancestry (p < 0.0001), female sex (p = 0.004), and younger age at onset (p < 0.0008). Retrospective analysis allowed us to refine our indication criteria: (i) North African ancestry, (ii) an age at onset < 40, or (iii) a familial history of parkinsonism with at least one affected first-degree relative. Our study highlights the interest of MLPA testing for other parkinsonisms cases with a family history, especially for patients with dementia with Lewy bodies or a multiple system atrophy-like phenotype.