Test Positivity Rate Research Articles

Salivary CD44 and Total Protein Levels to Detect Risk for Oral and Oropharyngeal Cancer Recurrence

Oral and oropharyngeal cancer have low survival rates, and incidence continues to increase. To determine whether soluble CD44 and total protein (TP) are useful for monitoring head and neck cancer recurrence, either used in a point-of-care (POC) test or as individual laboratory-based biomarkers. This multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay took place across the University of California, San Diego; Johns Hopkins University; the Greater Baltimore Medical Center; New York University; and the San Diego Veterans Affairs Hospital. Patients with newly biopsy-proven, untreated oral cavity and oropharyngeal cancer were enrolled. Patients were enrolled April 2017 to April 2019, and data were analyzed December 2022 to June 2023. POC salivary oral rinse test. Oral rinses were collected at pretreatment baseline and 3, 6, 12, and 18 months after completion of therapy; participants were then followed up for 3 years to define disease status. Associations of baseline characteristics with a positive test were evaluated by Fisher exact test. The association of a positive value on the CD44 or TP test with progression-free survival was evaluated in an adjusted multivariable proportional hazards model. Of 172 patients enrolled, the mean (SD) age was 62.5 (10.2) years, and 122 (70.9%) identified as male. Additionally, 92 patients (53.3%) had never smoked, 99 (57.6%) formerly or currently drank alcohol, and 113 (65.7%) presented with oropharyngeal cancers, which were positive for human papillomavirus in 95 (84.1%). Tumor site was associated with test results at baseline; patients with oral cavity cancer had a higher baseline positive POC test rate (47 of 51 [92.2%]) compared to patients with oropharyngeal cancer (85 of 110 [77.3%]). Using Cox regression models with CD44 or TP level as a time-varying covariate, a higher CD44 level showed a statistically significant association with a higher hazard of recurrence (hazard ratio, 1.06; 95% CI, 1.00-1.12), though the TP level was not statistically significant. In multivariate adjusted analysis, higher CD44 and TP levels were associated with increased hazard ratios of recurrence of 1.13 (95% CI, 1.04-1.22) and 3.51 (95% CI, 1.24-9.98), respectively. In this multi-institutional nonrandomized clinical trial of an assay, posttreatment longitudinal monitoring for elevated salivary CD44 and TP levels using an enzyme-linked immunosorbent assay-based laboratory test identified patients at increased risk of future cancer recurrence. The CD44 and TP rapid POC test holds some promise, but further development is needed for this indication. ClinicalTrials.gov Identifier: NCT03148665.

Short, stringent lockdowns halted SARS-CoV-2 transmissions in Danish municipalities

In late 2020, the focus of the global effort against the COVID-19 pandemic centered around the development of a vaccine, when reports of a mutated SARS-CoV-2 virus variant in a population of 17 million farmed mink came from Denmark, threatening to jeopardize this effort. Spillover infections of the new variant between mink and humans were feared to threaten the efficacy of upcoming vaccines. In this study the ensuing short-lived yet stringent lockdowns imposed in 7 of the countries 98 municipalities are analysed for their effectiveness to reduce SARS-CoV-2 infections. Synthetic counterfactuals are created for each of these municipalities using a weighted average combination of the remaining municipalities not targeted by the stringent measures. This allows for a clear overview regarding the development of test-positivity rates, citizen mobility behaviours and lastly daily infection numbers in response to the restrictions. The findings show that these targeted, short-term lockdowns significantly curtailed further infections, demonstrating a marked decrease, first in citizens mobility and then in daily cases when compared to their synthetic counterfactuals. Overall, the estimates indicate average reductions to infection numbers to be around 31%. This study underscores the potential of strict, yet severe lockdowns in breaking ongoing infection dynamics, by utilising a rare quasi-experimental design case that avoids bias introduced through treatment selection.

Cost analysis of cardiac MRI for cardiac transplant surveillance

National health expenditures in the United States have risen steadily since 1960. While lifesaving therapies exist for acquired and congenital heart diseases, for some children heart transplantation is their only chance for a period of durable survival. Like many advanced therapies, however, heart transplantation confers a significant cost to families and the health care system at large. Current heart transplant health surveillance relies on frequent cardiac catheterization with endomyocardial biopsy (cath-EMB) as periodic assessment of graft health and detection of possible life-threatening acute rejection. Cardiac magnetic resonance imaging (MRI) has emerged as a diagnostic tool which can characterize the myocardium, providing insights into graft health and potentially acute/chronic graft rejection. The PEACE study (R01-HL164995-02) aims to systematically evaluate the potential for using cardiac MRI parametric mapping as a pre-cath-EMB screening tool to alleviate both patient anxiety and discomfort, as well as the financial burden of cath-EMB. The PEACE trial aims to establish definitive evidence and criteria for determining when cath EMB is needed. For a technique to be practical in the real world, though, it must also be cost effective.Therefore, the goal of this current research is to determine a minimal set of measurement properties (positive predictive value (PPV), etc.) that cardiac MRI must attain to be cost-effective. These data will guide the decision-making for the PEACE trial results. Consistent with the recent emphasis on “Value MRI,” we sought to understand the potential Medicare savings, through economic cost analysis modeling, if cardiac MRI is used for cardiac transplant surveillance rather than cath-EMB surveillance. At even the most pessimistic positive test rate for MRI considered, these modeling results suggest substantial Medicare cost savings when using cardiac MRI parametric mapping as a screening tool for detecting acute cardiac rejection. Longitudinal cost savings are notable too.

Efficacy and safety of first-line anti-tuberculosis drugs combined with Linezolid for the treatment of pediatric tuberculous meningitis in real-word practice

Objective: To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM). Methods: A retrospective cohort study design was performed. Eight-nine Children diagnosed as TBM during January 1st 2016 and December 31st 2023 in Department of Infectious Disease, Children's Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results: The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions: The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

The Uganda housing modification study - association between housing characteristics and malaria burden in a moderate to high transmission setting in Uganda

BackgroundScale up of proven malaria control interventions has not been sufficient to control malaria in Uganda, emphasizing the need to explore innovative new approaches. Improved housing is one such promising strategy. This paper describes housing characteristics and their association with malaria burden in a moderate to high transmission setting in Uganda.MethodsBetween October and November 2021, a household survey was conducted in 1500 randomly selected households in Jinja and Luuka districts. Information on demographics, housing characteristics, use of malaria prevention measures, and proxy indicators of wealth were collected for each household. A finger-prick blood sample was obtained for thick blood smears for malaria from all children aged 6 months to 14 years in the surveyed households. Febrile children had a malaria rapid diagnostics test (RDT) done; positive cases were managed according to national treatment guidelines. Haemoglobin was assessed in children aged < 5 years. Households were stratified as having modern houses (defined as having finished materials for roofs, walls, and floors and closed eaves) or traditional houses (those not meeting the definition of modern house). Associations between malaria burden and house type were estimated using mixed effects models and adjusted for age, wealth, and bed net use.ResultsMost (65.5%) of the households surveyed lived in traditional houses. Most of the houses had closed eaves (85.5%), however, the use of other protective features like window/vent screens and installed ceilings was limited (0.4% had screened windows, 2.8% had screened air vents, and 5.2% had ceiling). Overall, 3,443 children were included in the clinical survey, of which 31.4% had a positive smear. RDT test positivity rate was 56.6% among children with fever. Participants living in modern houses had a significantly lower parasite prevalence by microscopy (adjusted prevalence ratio [aPR = 0.80]; 95% confidence interval [CI] 0.71 – 0.90), RDT test positivity rate (aPR = 0.90, 95%CI 0.81 – 0.99), and anaemia (aPR = 0.80, 95%CI 0.65 – 0.97) compared to those in traditional houses.ConclusionThe study found that even after adjusting for wealth, higher quality housing had a moderate protective effect against malaria, on top of the protection already afforded by recently distributed nets.

Current microbiological testing approaches and documented infections at febrile neutropenia onset in patients with hematologic malignancies

ObjectivesThis study aims to identify infection etiology in febrile neutropenia (FN) is vital. This study explores different microbiological approaches and their impact on diagnosing infections in patients with hematologic malignancies and FN. MethodsThis is a retrospective analysis conducted at the Hospital Clinic of Barcelona details microbiological testing strategies used to diagnose infections at FN onset between January 2020 and July 2022. ResultsA total of 4520 microbiological tests were ordered in 462 FN episodes, achieving a 10% test positivity rate, with 200 (43.3%) episodes showing microbiological documentation of infection. Blood cultures (40.4%), non-culture blood tests (21.2%), and respiratory tract samples (16.2%) were the most requested. Blood cultures exhibited the highest (16.9%) test positivity rates, whereas non-culture blood tests showed the lowest (3.3%). Bacterial infections were present in 149 of 462 (32.3%) FN episodes. Viral infections (66 of 462, 14.3%)—notably, respiratory viruses—were also frequent. Mortality rate at 60 days was 9.1%; documented infections were associated with a higher risk (15%). ConclusionsIn the current landscape of antimicrobial diagnostics, our findings revealed the highest reported rate of microbiologically documented infections at FN onset. Bacterial infections are common; however, our data reiterate the significance of viral infections in causing fever. Optimizing FN management during respiratory viral infections remains a challenge for antimicrobial de-escalation. The low positivity rates observed in certain diagnostic tests emphasize the need for cost-effective diagnostic stewardship.

Decreased Positive Fecal Occult Blood Tests and Delayed Medical Presentation for Colorectal Cancer during the Initial COVID-19 Pandemic Period: A Single-center Experience.

This study aimed to investigate the impact of the COVID-19 pandemic on the examination and treatment of colorectal cancer (CRC) and on the behaviors of patients and practitioners. This is a retrospective analysis of the CRC patients who presented to our department between April 2019 and March 2021 and underwent surgery. Clinical presentation of CRC and time from symptom onset to medical presentation were compared between the control (April 2019 to March 2020, n=124) and COVID-19 pandemic periods (April 2020 to March 2021, n=111). Two hundred and thirty-five patients were reviewed. The rate of positive fecal occult blood tests was significantly lower during the COVID-19 pandemic period (13.5 vs. 25.0%, P = 0.027). Among the symptomatic patients who had melena and abdominal symptoms, the time from symptom onset to medical presentation was significantly longer during the COVID-19 period (115 vs. 31 days, P < 0.001). In addition, the interval between presenting to a practitioner and being referred to our department was similar between the two periods (19 vs. 13 days, P = 0.092). There were no significant differences in the stage of cancer between the two periods. The rate of preoperative sub-obstruction was significantly higher during the COVID-19 period (41.4 vs 23.4%, P = 0.003). There was no significant difference in overall survival and recurrence-free survival between two periods. Hesitation to seek examination and treatment for CRC was observed in patients but not in practitioners during the COVID-19 pandemic period. The prognosis did not change.

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study.

Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Mitigating the Risk of Dengue Fever in Nagpur City, India: Insights from a Five-year Retrospective Study

Objectives: Dengue is a significant global threat, with millions of infections yearly, primarily transmitted by Aedes mosquitoes. Vector control is crucial as no specific treatment is available, and urbanisation has led to increased susceptibility to the disease. We aimed to study dengue fever’s incidence, mortality, and various determinants in Nagpur, India. Material and Methods: This was a retrospective record-based study conducted for the period between January 2018 and December 2022 in Nagpur, India. Results: During 2018–2022, 17,306 blood samples were tested for dengue immunoglobulin M antibodies by enzyme-linked immunosorbent assay method with 2470 positive results indicating an overall test positivity of 14.27%. A median of 27 samples was tested monthly (interquartile range [IQR]: 5–178.5) with seven dengue cases (IQR: 1–15) diagnosed per month, yielding a monthly median dengue test positivity rate of 15.3 % (IQR: 6.41–24.28). Median annual dengue incidence rate (per 1,00,000 population) was 20.12 (IQR: 21.46). The median dengue-attributable death yearly was 2 (IQR: 2.25), remaining stable over the study period. The mean annual case fatality rate (CFR) was 0.43% (standard deviation [SD]: 0.34%). During the same period, India’s mean annual dengue incidence rate (per 1,00,000 population) was 1.74 (SD: 0.81), and the mean annual CFR was 0.134 % (SD: 0.042). During the five years, action was taken on 194,698 containers. The median values of environmental factors and public health interventions, as calculated on a monthly basis, were as follows: Container index: 1.15 % (IQR: 0.7–1.98); action taken on containers: 3108.5 (IQR: 2436–4282); house index: 3.02 % (IQR: 2–4.07); guppy fishes introduced: 1736.5 (1005.5–1794.5) and rainfall (mm): 26.05 (1–69.11). The total number of dengue cases, incidence rate, and CFR showed an overall decline in year-wise evaluation. The important determinants identified were as follows: Higher container index, house index, and total blood samples tested for dengue were significant determinants of the total number of dengue cases, and environmental factors such as Aedes density, container index, and house index were significant determinants of dengue-related mortality. Introducing guppy fishes and taking action on containers successfully arrested the absolute number of dengue deaths. The container index, house index, and rainfall were significant determinants of Aedes’ density. Conclusion: Our study emphasises the effectiveness of public health interventions in reducing the incidence and fatality rate of dengue fever in Nagpur City over the past five years, particularly through introducing guppy fish and container management. Stagnant water around households has been identified as a significant risk factor for dengue transmission. Prevention strategies must prioritise tackling this issue, with enhanced monitoring during the wet season, and encourage community members to take personal responsibility for eliminating stagnant water sources in their households.

P-240 Is the intelligent Data Analysis Score (iDAScore) a reliable tool to predict pregnancy? Our center’s experience

Abstract Study question Is the intelligent Data Analysis Score (iDAScore) reliable in predicting a positive pregnancy test, clinical pregnancy and miscarriage rate after single vitrified-warmed blastocyst transfer (SVBT)? Summary answer There is a significant increase in positive pregnancy test and clinical pregnancy rates as iDAScore increases. The miscarriage rate is lower with increased iDAScore. What is known already With the improvement of assisted reproductive technology (ART), elective single embryo transfer has become a standard. Optimizing embryo selection is a major challenge to increase reproductive outcomes. The Gardner embryo grading system is widely adopted for the evaluation of blastocyst quality, but this tool is subject to inter- and intra-variability. In recent years, artificial intelligence has found diverse applications in healthcare. Based on time-laps sequences of &amp;gt; 180’000 developing embryos, iDAScore is a new deep-learning model for objective and standardized blastocyst scoring. However, its reliability in predicting pregnancy and miscarriage rates remains unknown. Study design, size, duration This monocentric retrospective pilot study was conducted from May 2023 to December 2023. A total of 206 homologous SVBT cycles from 206 patients were analyzed (one patient, one cycle). Exclusion criteria included: cycles involving preimplantation genetic testing, multiple and/or fresh blastocyst transfer, and blastocysts obtained after testicular sperm extraction. All vitrified-warmed blastocysts were scored using iDAScore version 1.0 model, ranging from 1 – 9.9. Participants/materials, setting, methods Scores were stratified into 3 groups: high-score (9.9 – 7.7), medium-score (7.6 – 5.5) and low-score (5.4 – 3.1). For each group, positive pregnancy test, clinical pregnancy and miscarriage rates were analyzed. SVBT cycles were then stratified into four maternal age groups (&amp;lt; 35, 35-37, 38-40, &amp;gt;41 years) and the same outcomes were analyzed. χ2 was used for statistics analysis. Main results and the role of chance Mean maternal age was 36.8 ± 4.9. Among the 206 vitrified-warmed blastocysts, 122 were scored as high-score, 57 as medium-score and 27 as low-score. Positive pregnancy test rate was significantly higher with increased iDAScore with 58% in the high-score group, 36.8% in the medium-score group and 17% in the low-score group (p &amp;lt; 0.0001). Clinical pregnancy rate, defined as the visualization of a fetal heartbeat at ultrasound scan, was also significantly higher with increased iDAScore, with 51.6% in the high-score group, 31.6% in the medium-score group and 17% in the low-score group (p &amp;lt; 0.0001). The miscarriage rate was lower with increased iDAScore, with 8.1% in the high-score group, 16.6% in the medium-score group and 50% in the low-score group, but this difference was not statistically significative (p 0.032). When adjusted to age group however, the miscarriage rate was found to be significantly lower in the high-score group when compared to the medium-score group (p &amp;lt; 0.0001); statistical analysis was not achieved in the low-score group due to the small sample size. Limitations, reasons for caution The major limitation of our study is its small sample size. Data collection is ongoing, to increase the study power. Additionally, many other factors, such as genetic, hormonal, metabolic and/or immunological, may play a role in achieving pregnancy. Wider implications of the findings Our results indicate that iDAScore may be a strong predictor of pregnancy and could be used as a complementary tool to the Gardner embryo grading system in the decision-making process of which blastocyst to transfer. Trial registration number N/A

P-579 Is the use of donated oocytes effective to reestablish live birth rates? Reproductive outcomes of 5313 euploid embryo transfers in autologous versus egg donation cycles

Abstract Study question Is live birth rate of autologous versus donor cycles similar after a euploid embryo transfer? Summary answer The live birth rate was significantly higher in autologous cycles after a euploid embryo transfer. What is known already Advanced maternal age (AMA) is a detrimental factor for patients to achieve a successful outcome in ART. Physiological ovarian aging negatively affects oocyte quality and quantity. Thus, the number of cycles with donated oocytes is increasing for AMA patients worldwide, with the perspective of surpass the oocyte factor and achieve a live birth in similar rates as younger patients. The goal of this study was to compare the live birth rates of autologous versus donor cycles after a euploid embryo transfer. Study design, size, duration Observational cohort study including all patients of IVF cycles with a euploid embryo transfer after PGT-A (NGS technology), according to medical referral between Jan/2016 and Dec/2020 (n = 3623 patients and 4025 cycles) in a private ART center. Participants/materials, setting, methods Reproductive outcomes between autologous and egg donation cycles were compared and data were analyzed in the follow subgroups: cycles with a fresh oocyte and fresh embryo transfer (FRESH), frozen embryo transfer (FET) and fresh embryo transfer from frozen oocytes (FOT). Positive pregnancy test (PPT), clinical pregnancy (CP), clinical miscarriage (CM) and live birth (LB) rates were compared. Kruskal-Wallis and Fisher test were applied for statistical analysis, significance was considered if p &amp;lt; 0,05. Main results and the role of chance In total, 3623 patients – 88.9% autologous and 11.1% with donated oocytes – were included. They performed 4025 ETs (3591/434) with 5313 biopsied blastocysts (4736/577) in a mean of 1,32/1,33 blastocysts per transfer in autologous/donated cycles respectively. The majority of patients using autologous and donated oocytes underwent a FET (97,2% and 63,1%), followed by FOT (1,5% and 34,7%) and FRESH (1,3% and 2,2%, respectively). Mean maternal age in autologous and donor cycles was 37,76±3,9yo and 43,47±4,26yo and oocyte donors were 24,99±3,86yo. In subgroups, autologous patients in FRESH were 38,33±2,69 yo, similar in FET (37,73±3,93 yo) and older in FOT, 39,25±3,93 yo (p = 0,03). Patients in donor cycles showed no difference in age. PPT and CP were similar in autologous and donated cycles (PPT: 59,2% vs 54,8%, p = 0.08; CP: 52,2% vs 48,2%, p = 0.11). In subgroup analysis, PPT and CP were higher in donated cycles vs autologous cycles for FOT (PPT: 50,7% vs 33,3%, p = 0.004; CP: 40,7% vs 20,8%, p = 0.01). Overall, CM were higher in donated cycles (15,5% vs 10,6%, p = 0.03), especially after FET (16,8% vs 10,6%, p = 0.025). LB rates were higher in autologous compared to donated cycles (37,8% vs 29,5%, p = 0.0007). There was no significant difference in LB rates in subgroup analysis. Limitations, reasons for caution This is a large cohort study; however, we cannot exclude potential bias due its retrospective nature. Including only euploid embryos, we excluded bias on ploidy status when comparing autologous versus donated oocytes cycles, yet the potential harmful of embryo biopsy may not be neglect. Wider implications of the findings Live birth rate was significantly higher in autologous cycles after a euploid embryo transfer, regardless of subgroups. AMA patients that choose to undergo an IVF treatment with donated oocytes should be aware that there are other important factors related to a successful reproductive outcome, including immunological adaptation and endometrial aging. Trial registration number Not applicable.

P-557 The contribution of PGT-A to PGT-M and PGT-SR clinical outcomes – A single centre retrospective analysis

Abstract Study question To determine if the introduction of concurrent testing with PGT-A has improved clinical outcomes for PGT-M/SR patients. Summary answer This study demonstrates that the introduction of concurrent testing may have improved clinical outcomes for this patient demographic irrespective of age. What is known already Preimplantation Genetic Testing (PGT) is utilised to investigate the genetic constitution of embryos. PGT-M (monogenic) and PGT-SR (structural rearrangements) are screening techniques considered in treatment for couples at risk of conceiving offspring with known genetic or structural chromosomal abnormalities respectively. Preimplantation Genetic testing for Aneuploidy (PGT-A) was developed in order to screen embryos for numerical chromosomal abnormalities, a leading cause of failed implantation. Nevertheless, routine use of PGT-A is discouraged due to lack of evidence regarding its efficacy. However, PGT-A is routinely used alongside PGT-M and PGT-SR despite the lack of evidence of its effectiveness in improving patient outcomes. Study design, size, duration The retrospective analysis of 496 PGT-M/SR single embryo transfer patient cycles between December 2013 and December 2021. Participants/materials, setting, methods The retrospective analysis of 496 PGT-M/SR single embryo transfer cycles at CRGH Portland was undertaken (single testing n = 77; concurrent testing n = 419). The clinical outcomes (positive urine pregnancy test, clinical pregnancy, live birth and miscarriage rates) were compared between groups using IBM SPSS Statistics (premium 27). Binary logistic regression was performed for statistical analysis, results with p &amp;lt; 0.05 were determined statistically significant. Main results and the role of chance Overall, concurrent testing was associated with statistically significant improved clinical outcomes compared to the reference group. Statistical significance was seen in positive urine pregnancy test (49% vs 68%, p = 0.012), clinical pregnancy (32.5% vs 63%; p = 0.000013), live birth rate (32.5% vs 59%; p = &amp;lt;0.00016) and miscarriage rates (34.2% vs 13%; p = 0.001). The results imply that the introduction of concurrent testing has improved the probability of obtaining a positive clinical outcome and has reduced the chance of miscarriage in this patient demographic. Further analysis showed concurrent testing improved the chances of obtaining a positive clinical outcome irrespective of the patients age or quality of the embryo. Limitations, reasons for caution This study has produced promising results. However, there are several limitations such as the small sample size, embryo biopsy techniques used, and the different molecular diagnostic techniques and providers utilised. Wider implications of the findings The results imply a justification for the use of PGT-A alongside PGT-M/SR screening techniques to improve embryo selection and clinical outcomes for this cohort of patients. Additionally, they demonstrate the efficacy of PGT-A in a previously underrepresented demographic. However, further research is required to confirm the clinical value of PGT-A. Trial registration number not applicable

Reducing Clostridioides difficile Infections in a Medical Intensive Care Unit: A Multimodal Quality Improvement Initiative.

Clostridioides difficile (C. diff) infection causes significant morbidity for hospitalized patients. A large medical intensive care unit had an increase in C. diff infection rates. The aim of this project was to reduce the C. diff polymerase chain reaction (PCR) test positivity rate and the rate of C. diff PCR tests ordered. Rates were compared between preintervention (July 2017 to December 2019) and postintervention (January 2021 to December 2022) timeframes. Unit leadership led a robust quality improvement project, including use of quality improvement tools such as A3, Gemba walks, and plan-do-study-act cycles. Interventions were tailored to the barriers identified, including standardization of in-room supply carts; use of single-packaged oral care kits; new enteric precautions signage; education to staff, providers, and visitors; scripting for patients and visitors; and use of a C. diff testing algorithm. Statistical process control charts were used to assess for improvements. The average rate of C. diff PCR test positivity decreased from 34.9 PCR positive tests per 10 000 patient days to 12.3 in the postintervention period, a 66% reduction. The average rate of PCR tests ordered was 28 per 1000 patient days in the preintervention period; this decreased 44% to 15.7 in the postintervention period. We found clinically significant improvements in the rate of C. diff infection and PCR tests ordered as a result of implementing tailored interventions in a large medical intensive care unit. Other units should consider using robust quality improvement methods and tools to conduct similar initiatives to reduce patient harm and improve care and outcomes.

Assessment of the FilmArray Gastrointestinal Pathogen PCR Panel at a Tertiary Cancer Center

Background: The FilmArray gastrointestinal (GI) pathogen panel (BioFire Diagnostics, Salt Lake City, UT) is a multiplex PCR assay for syndromic diagnosis of infectious gastroenteritis. This highly sensitive assay has been widely adopted as a preferred testing modality for infectious diarrhea among hospitalized patients. However, in the era of diagnostic stewardship, concerns have been raised that this approach risks unexpected findings of questionable significance. Following an increase in GI pathogen panel testing, the infection control department reviewed results among hospitalized patients at different stages of admission. Methods: From October 2022 to May 2023, we retrospectively reviewed all GI pathogen panels sent in a large tertiary cancer hospital. Count of tests ordered and positivity trends were studied by unit and organism among inpatients. We categorized an admission course into early (≤2 inpatient days) and late (≥3 inpatient days) stages and compared results across these stages. Finally, we compared reproducibility of multiple tests sent during a single admission. Results: From October 2022 to May 2023, a total of 2,763 tests were sent across the institution with 2,113 tests from inpatient units. Tests were most commonly sent on the Pediatrics and Hematology -Oncology inpatient units and together these units accounted for 60% of tests. These two units also had the highest rate of test positivity and together accounted for 60% of positive tests among hospitalized patients. The most frequently detected organisms were Norovirus (7%) and Enteropathogenic E. coli (3%) (Figure 1). Patients tested in the early stage of hospital admission were more likely to have a positive result for any target (93/509, 18.3%) compared to patients tested in the late stage (202/1604, 12.5%). Patients with a positive test in the early stage of admission were less likely to have a subsequent negative test (3/93, 3%) compared to patients who were positive in late stage of admission (39/202, 19.3% (Figure 2). Conclusions: Our findings suggest that the utility of the FilmArray GI PCR panel is highest in the early stages of a patient’s hospital admission. Testing of patients hospitalized ≥3 days is likely to be inappropriate. These findings support implementation of diagnostic stewardship standards on when syndromic testing for potentially infectious diarrhea is appropriate. Figure 1: FilmArray gastrointestinal pathogen PCR panel positivity by organism. Figure 2: FilmArray gastrointestinal pathogen PCR panel positivity by organism comparing early vs late stage of hospital admission.

Syndromic Surveillance Tracks COVID-19 Cases in University and County Settings: Retrospective Observational Study.

Syndromic surveillance represents a potentially inexpensive supplement to test-based COVID-19 surveillance. By strengthening surveillance of COVID-19-like illness (CLI), targeted and rapid interventions can be facilitated that prevent COVID-19 outbreaks without primary reliance on testing. This study aims to assess the temporal relationship between confirmed SARS-CoV-2 infections and self-reported and health care provider-reported CLI in university and county settings, respectively. We collected aggregated COVID-19 testing and symptom reporting surveillance data from Cornell University (2020-2021) and Tompkins County Health Department (2020-2022). We used negative binomial and linear regression models to correlate confirmed COVID-19 case counts and positive test rates with CLI rate time series, lagged COVID-19 cases or rates, and day of the week as independent variables. Optimal lag periods were identified using Granger causality and likelihood ratio tests. In modeling undergraduate student cases, the CLI rate (P=.003) and rate of exposure to CLI (P<.001) were significantly correlated with the COVID-19 test positivity rate with no lag in the linear models. At the county level, the health care provider-reported CLI rate was significantly correlated with SARS-CoV-2 test positivity with a 3-day lag in both the linear (P<.001) and negative binomial model (P=.005). The real-time correlation between syndromic surveillance and COVID-19 cases on a university campus suggests symptom reporting is a viable alternative or supplement to COVID-19 surveillance testing. At the county level, syndromic surveillance is also a leading indicator of COVID-19 cases, enabling quick action to reduce transmission. Further research should investigate COVID-19 risk using syndromic surveillance in other settings, such as low-resource settings like low- and middle-income countries.

Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer

BackgroundEsophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer.MethodsOverall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method.ResultsPreoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer.ConclusionPlasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.

Clinical audit of quality of care among patients with viral hepatitis in primary care in a low endemic region.

The current hepatitis B (HBV) and hepatitis C virus (HCV) screening practices may fail to detect many infected patients who could benefit from new therapeutic agents to limit progression to cirrhosis and hepatocellular carcinoma. This study assessed the test positivity rate and cascade of care of viral hepatitis patients in primary care in a low endemic region as well as the testing policy of abnormal alanine aminotransferase (ALT) level. This is a retrospective clinical audit among primary health care practices in Flanders, Belgium, assessing patients with an active medical file between 2019 and 2021. A total of 84/89 (94.4%) primary health care practices participated representing 621,573 patients of which 1069 patients (0.17%) were registered as having viral hepatitis, not further specified. Detailed information was available from 38 practices representing 243,723/621,573 (39.2%) patients of which 169 (0.07%) were HBsAg positive and 99 (0.04%) anti-HCV positive. A total of 96/134(71.6%) chronic HBV-infected and 31/77(40.3%) chronic HCV-infected patients were referred to a hepatologist. A total of 30,573/621,573(4.9%) patients had an abnormal ALT level, and by at random selection, more detailed information was obtained on 211 patients. Information on high-risk groups was missing in up to 60%. In patients with abnormal ALT level, HBsAg and anti-HCV testing were conducted in 37/211(17.5%) and 25/211(11.8%), respectively. In a low endemic region, the testing rate and cascade of care of HBV and HCV-infected patients can be improved in primary care, especially in high-risk groups and patients with abnormal ALT levels.

COVID-19 Vaccine Effectiveness and Digital Pandemic Surveillance in Germany (eCOV Study): Web Application-Based Prospective Observational Cohort Study.

The COVID-19 pandemic posed significant challenges to global health systems. Efficient public health responses required a rapid and secure collection of health data to improve the understanding of SARS-CoV-2 and examine the vaccine effectiveness (VE) and drug safety of the novel COVID-19 vaccines. This study (COVID-19 study on vaccinated and unvaccinated subjects over 16 years; eCOV study) aims to (1) evaluate the real-world effectiveness of COVID-19 vaccines through a digital participatory surveillance tool and (2) assess the potential of self-reported data for monitoring key parameters of the COVID-19 pandemic in Germany. Using a digital study web application, we collected self-reported data between May 1, 2021, and August 1, 2022, to assess VE, test positivity rates, COVID-19 incidence rates, and adverse events after COVID-19 vaccination. Our primary outcome measure was the VE of SARS-CoV-2 vaccines against laboratory-confirmed SARS-CoV-2 infection. The secondary outcome measures included VE against hospitalization and across different SARS-CoV-2 variants, adverse events after vaccination, and symptoms during infection. Logistic regression models adjusted for confounders were used to estimate VE 4 to 48 weeks after the primary vaccination series and after third-dose vaccination. Unvaccinated participants were compared with age- and gender-matched participants who had received 2 doses of BNT162b2 (Pfizer-BioNTech) and those who had received 3 doses of BNT162b2 and were not infected before the last vaccination. To assess the potential of self-reported digital data, the data were compared with official data from public health authorities. We enrolled 10,077 participants (aged ≥16 y) who contributed 44,786 tests and 5530 symptoms. In this young, primarily female, and digital-literate cohort, VE against infections of any severity waned from 91.2% (95% CI 70.4%-97.4%) at week 4 to 37.2% (95% CI 23.5%-48.5%) at week 48 after the second dose of BNT162b2. A third dose of BNT162b2 increased VE to 67.6% (95% CI 50.3%-78.8%) after 4 weeks. The low number of reported hospitalizations limited our ability to calculate VE against hospitalization. Adverse events after vaccination were consistent with previously published research. Seven-day incidences and test positivity rates reflected the course of the pandemic in Germany when compared with official numbers from the national infectious disease surveillance system. Our data indicate that COVID-19 vaccinations are safe and effective, and third-dose vaccinations partially restore protection against SARS-CoV-2 infection. The study showcased the successful use of a digital study web application for COVID-19 surveillance and continuous monitoring of VE in Germany, highlighting its potential to accelerate public health decision-making. Addressing biases in digital data collection is vital to ensure the accuracy and reliability of digital solutions as public health tools.

CtDNA for clinical decision support in pancreatic cancer.

e16354 Background: Circulating tumor DNA (ctDNA) is increasingly used to inform therapeutic decisions and its applicability to pancreatic cancer is emerging. We explore the adoption of ctDNA profiling in patients presenting to our pancreatic cancer clinic to help guide localized and metastatic pancreatic cancer treatment. Methods: This was an IRB-approved retrospective cohort study of Signatera ctDNA profiling among patients with pancreatic cancer at Northwell Health between October 2021 and September 2023. Patients received ctDNA testing at various treatment timepoints and were categorized according to clinical context: neoadjuvant, adjuvant, surveillance, radiographic relapse, and metastatic. Average ctDNA level and conversion rates were calculated for each group. Results: There were 203 tests completed among 59 patients representing the following clinical contexts: 36% metastatic disease, 27% in the adjuvant setting, 23% during surveillance, 7% prior to surgery, and 6% after relapse. 43 patients had ctDNA tests that were drawn but were cancelled or could not be performed due to inadequate tissue samples, of which 8 had at least one completed test and were included in final analysis. Of all 27 metastatic patients, 8 patients had tests that were never completed. 46% of all tests were positive, which ranged from 0.3 to 8089 MTM/mL, and averaged 196 MTM/mL. 51% of all patients had ctDNA results that remained positive, 34% remained negative, and 15% changed over time from either positive to negative or vice versa. Median ctDNA level was 0.1 MTM/mL or less for patients who were tested prior to surgery or during adjuvant treatment or surveillance and the median ranged from 0.0-67.1 for patients with metastatic disease or relapse. All ctDNA tests sent after radiographic relapse also tested positive. Conclusions: ctDNA testing was most commonly performed in patients with localized disease on adjuvant chemotherapy, and in those with metastatic disease at time of diagnosis, who also had the highest rates of positive tests by stage at diagnosis. Given all patients tested during relapse had positive tests, ctDNA may be an early predictor of disease progression in patients with negative tests on surveillance. When tissue is limited, such as in metastatic patients who are less likely to undergo surgery, production of the ctDNA assay may be hindered. A prospective, larger scale, and more longitudinal study would add greater power and clinical context.

The two-year epidemiological investigation of the COVID-19 pandemic in the nomadic population of Fars province, Southern Iran: An ecological study (February 20, 2020, to February 19, 2022)

BackgroundThe COVID-19 pandemic has highlighted the vulnerability of traveling populations, yet little is known about the health status of nomadic communities. This ecological study aimed to investigate the health status of the nomadic population in Fars Province, Iran, during the first two years of the COVID-19 pandemic. MethodsNomadic Information Registration System (NIRS) data were used to compare COVID-19 diagnostic tests, confirmed cases, referrals, hospital admissions, deaths, and vaccination coverage between the nomadic and general populations. Non-parametric chi-square test was used for data analysis. ResultsIn Fars Province, COVID-19 diagnostic tests were performed on 2.73 % of the nomadic population and 40 % of the general population. The test positivity rate was 23.91 % for the nomadic population and 29.3 % for the general population. The case fatality ratio (CFR) for COVID-19 was 9.24 % for the nomadic population and 1.29 % for the general population. Additionally, only 41.83 % and 24.35 % of the nomadic population had received the first and second doses of a COVID-19 vaccine, respectively, which were lower than the general population's rates of 65.65 % and 59.71 %. ConclusionThe nomadic population in Fars Province received suboptimal COVID-19 care compared to the general population.