Testing Options Research Articles

Hereditary Hemorrhagic Telangiectasia - a literature review

Introduction and purpose: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and complex vascular disorder characterized by abnormal blood vessel formation. It can present significant challenges in diagnosis and management, as it is currently estimated up to 90% of those affected are never diagnosed. Despite its rarity, HHT can carry substantial implications for patients and their families, at times requiring comprehensive medical care and support. This paper aims to provide an in-depth exploration of HHT, encompassing its epidemiology, genetics, clinical manifestations, diagnostic approaches, and current management strategies. Moreover, we hope to point out possible areas in need of future research.
 Description of the state knowledge: HHT is an autosomal dominant genetic disorder that affects 1 in 5-10,000 people. Its most prominent symptoms include telangiectasia of skin and mucous membranes, recurrent epistaxis, gastrointestinal bleeding and arteriovenous malformations in vital organs. In the vast majority of cases, it is caused by a mutation in one of the following genes: ENG, ACVRL1, SMAD4; however, mutations in other genes have been described to cause a similar or much the same constellation of symptoms. Treatment options are focused on managing symptoms and improving quality of life, but possible new treatment options are being researched that could change the landscape of HHT management.
 Summary: HHT is a severely underdiagnosed disease that has seen a surge of researchers’ interest in recent years. We firmly believe that, combined with plummeting costs of genetic testing and possible new treatment options, means that HHT will become increasingly important in physicians’ everyday practice.

Abstract LB095: ASPYRE-Lung addresses critical gaps in NGS-based biomarker testing: Robust variant calling from NGS QC fails

Abstract Advanced NSCLC treatment guidelines recommend testing patients for genomic biomarkers to utilize over 30 FDA-approved targeted therapies. A major challenge with current NGS-based testing methods is that ~45% of patient samples fail NGS quality control (QC), leading to inadequate patient care. The ASPYRE® technology addresses the urgent need for rapid, accessible and affordable diagnostics informing actionable genomic target variants. The ASPYRE-Lung® panel covers 114 variants in 11 genes (ALK, BRAF, EGFR, ERBB2, KRAS, RET, ROS1, MET & NTRK1/2/3) to robustly inform clinical management, based on clinical practice guidelines. The assay concurrently detects single nucleotide variants, insertions, deletions, and gene fusions from NSCLC tissue-derived DNA and RNA. In this study, we investigated an NSCLC patient sample set from Precision for Medicine, including biobanked clinical specimens that had previously failed NGS QC, and for which genomic biomarker data were unavailable. 120 matched DNA and RNA biobanked NSCLC FFPE patient samples previously analyzed by Illumina TSO 500 were tested using ASPYRE-Lung in Biofidelity’s CLIA laboratory, including 94 samples which failed NGS QC parameters for DNA, RNA, or both, and 26 control samples which passed NGS QC. Samples were tested by ASPYRE-Lung using an input of 20 ng DNA and 6 ng RNA, except for 5 patient samples that were run at lower inputs, ranging from 4.25 to 14 ng DNA. Key findings:•Of the 94 patient samples that failed NGS QC, 98% of samples (92/94) passed ASPYRE-Lung QC and could inform patient care.•In the 92 patient samples that passed ASPYRE-Lung QC, 47% (43/92) had a detectable variant identified by ASPYRE-Lung.•All 26 control samples that passed NGS QC also passed ASPYRE-Lung QC.•Of the 5 samples with 4.25 to 14 ng DNA inputs to ASPYRE-Lung, data were generated on 4/5 samples and 2/4 had a detectable variant.•ASPYRE-Lung has the potential to provide actionable clinical information on patient samples deemed to be of insufficient quantity for NGS testing.ASPYRE-Lung has a high success rate, is easily adoptable and cost effective making it suitable as a first-line testing option, or for samples that are either QNS or fail NGS QC, and can provide a large fraction of NSCLC patients with actionable biomarker information, with potentially smaller tissue requirements. ASPYRE-Lung genomic testing is transformative for cancer care management, and allows more patients with NSCLC to benefit from effective and better tolerated therapies. Citation Format: Ryan T. Evans, Elyse Shapiro, Elizabeth Gillon-Zhang, Julia N. Brown, Candace King, Cory Kiser, Mary Beth Rossi, Darren Davis, Michelle L. Taylor, Jennifer Clower, Jian Yang, Cullen A. Taylor, Robert W. Snyder, Wendy J. Levin. ASPYRE-Lung addresses critical gaps in NGS-based biomarker testing: Robust variant calling from NGS QC fails [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB095.

Correlation Between Serum and Fecal Biomarkers and Patient-Reported Outcomes in Patients with Crohn's Disease and Ulcerative Colitis.

Patient-reported outcomes (PROs), such as the short CD activity index (sCDAI) and partial Mayo Score (PMS), are used to define clinical remission in IBD, but may not represent the true degree of inflammation and endoscopy is invasive. Non-invasive testing options include c-reactive protein (CRP) and fecal calprotectin (FCP). The aim of this study was to assess the degree of correlation of non-invasive biomarkers with PROs and the impact other clinical variables can have on their levels. We reviewed data collected from the prospective cohort, Study of a Prospective Adult Research Cohort with IBD (SPARC-IBD), comprised of over 3000 patients from 17 tertiary referral centers. Demographic and clinical variables were analyzed by disease type, disease severity was based on PROs, and baseline CRP and FCP were measured. For comparative analysis, we performed Fisher's exact test and Welch's t test, where p < 0.05 was significant. 1547 patients were included; 63% had CD, 56% were female, with an average disease duration of 13.6years. CRP and FCP were associated with symptom severity in inflammatory CD. CRP was useful to differentiate symptoms across different disease locations in CD, whereas FCP was associated with symptom severity in Crohn's colitis only. For UC, FCP was able to distinguish symptom severity better in distal UC, whereas in extensive or pancolitis, it was useful only to distinguish severe symptoms from other categories of symptom severity. PROs correlate with CRP and FCP; however, disease location and phenotype impact their ability to distinguish symptom severity.

Skin tests, serological IgE detection, basophil test—what is available, useful and helps to clarify a mold allergy?

AbstractThe prevalence of sensitization to molds is low in healthy people, but significant in asthmatics. As it has not yet been possible to establish a cause-and-effect relationship between the presence of mold allergens and the occurrence of allergic symptoms, there is a great deal of uncertainty. The update of the S2k guideline “Medical–clinical diagnostics for indoor mold exposure” should help to objectify the topic. Based on the recommendations listed there for the diagnosis of suspected IgE-mediated mold allergy, this article presents the possibilities of skin tests, IgE determinations, and other in vitro test options, but also their limitations in clarifying the cause. Potential possibilities include component-resolved allergy diagnostics, while the limitations include the difficult standardization of test allergen extracts due to the complex allergen source and the insufficient commercial availability of the test extracts. A diagnostic algorithm is presented as a tool for a systematic approach to patients with suspected mold-associated respiratory allergy.

Biological Testing and Interpretation of Laboratory Results Associated with Detecting Newborns with Substance Exposure.

Substance use during pregnancy is common, as is biological testing that is intended to help identify prenatal exposures. However, there is no standardized requirement for biological testing with either maternal or newborn specimens, nor is there standardization related to when testing occurs, how frequently testing occurs, what specimen(s) to test, what substances to test for, or how to perform testing. We review common specimen types tested to detect maternal and newborn substance exposure with a focus on urine, meconium, and umbilical cord tissue. We also review common analytical methods used to perform testing, including immunoassay, and mass spectrometry platforms. Considerations regarding the utilization of testing relative to the purpose of testing, the drug analyte(s) of interest, the specific testing employed, and the interpretation of results are emphasized to help guide decisions about clinical utilization of testing. We also highlight specific examples of unexpected results that can be used to guide interpretation and appropriate next steps. There are strengths and limitations associated with all approaches to detecting substance exposure in pregnant persons as well as biological testing to evaluate a newborn with possible substance exposure. Standardization is needed to better inform decisions surrounding evaluation of substance exposures in pregnant people and newborns. If biological sampling is pursued, testing options and results must be reviewed in clinical context, acknowledging that false-positive and -negative results can and do occur.

Expanding options for HIV testing: A process evaluation of a community-led HIV self-testing intervention among men who have sex with men in Kenya.

Men who have sex with men (MSM) in Kenya continue to face barriers to HIV testing, which leads to delays in HIV prevention and care. An HIV self-testing (HIVST) intervention was implemented in three Kenyan counties to increase coverage and frequency of HIV testing among MSM communities with high HIV prevalence. The evaluation study examined how HIVST can increase testing among MSM who are unaware of their status by increasing coverage, frequency, and early uptake of testing and support linkages to prevention and treatment. We share results from the process evaluation of the intervention implemented in partnership with MSM-led organizations. For a 12-month period between August 2019 and July 2020, the project team conducted in-depth interviews with HIVST users, monthly meetings with programme implementation teams, and monthly monitoring data reviews. Polling booth surveys were also conducted with participants. The process evaluation explored the fidelity, feasibility, coverage, acceptability, quality, and effectiveness of the HIVST intervention. An average of 793 MSM received 1,041 HIVST kits on a monthly basis through different distribution channels. Of those who received HIVST kits, 67% were distributed to infrequent testers and non-testers. Testing frequency among users increased to 82% for those who had a recent test during the previous three months, compared to 58% of HIVST non-users. There was a high linkage to care and treatment services (84%) among those who tested reactive for HIV at endline. MSM shared preferring HIVST kits because of its convenience and privacy. During the COVID-19 pandemic, adaptations to the intervention were made to support ongoing HIV testing and linkages to services. The introduction of HIVST in MSM-led HIV prevention programmes was feasible with high acceptability. The involvement of the MSM community in the design, implementation and evaluation of the intervention was a key factor to intervention success.

Abstract 4787: Preference for multi-target stool DNA for colorectal cancer screening among Alaska Native people in rural/remote communities

Abstract Background: The Alaska Tribal Health System is working on increasing colorectal cancer (CRC) screening rates among Alaska Native people, who have the highest CRC rates in the world. Most remote Alaska Native communities are not connected to the road system, which severely limits access to screening colonoscopy. As part of a clinical trial, Alaska Native patients were offered either colonoscopy or the at-home multi-target stool DNA test (mt-sDNA; Cologuard®). Patients had never been offered mt-sDNA before and it was unknown what they would think about the new test option. Both tests were provided at no cost to patients. Methods: From April 2022 to July 2023, 194 patients who chose mt-sDNA for screening received a follow-up phone survey asking whether they were aware that they could have had colonoscopy instead, their reasons for choosing mt-sDNA, and the factors influencing their choice of mt-sDNA over colonoscopy. Patients answered the survey before receiving results of their mt-sDNA test in order to capture initial screening test preferences. Results: A total of 115 (59%) Alaska Native patients participated in the survey; 56% men and 44% women. About 70% were ages 45 to 60 years while the remaining 30% were 61 to 75 years old. The majority (80%) were aware that they had the option to undergo colonoscopy for CRC screening instead of mt-sDNA. Key themes for mt-sDNA preference included not having to travel, less time commitment, and greater convenience. Many patients expressed financial concerns arising from the costs of air travel and accommodation required to access screening colonoscopy even though the procedure itself was covered. Additionally, patients highlighted existing obligations such as childcare and work responsibilities which made the use of mt-sDNA at home more appealing. Many respondents also shared negative perceptions of colonoscopy procedure including fear, embarrassment, and discomfort as reasons why they preferred mt-sDNA instead. Conclusions: These findings demonstrate the multifaceted factors influencing the preference for at-home mt-sDNA CRC screening among Alaska Native individuals. Challenges such as limited access to medical facilities, financial burdens, and personal commitments have significant bearing on the screening decision-making process. Moreover, the emotional aspect of fear and discomfort associated with colonoscopy plays a role in shaping these preferences. CRC screening programs need to be aware of patient needs and preferences when deciding which screening methods to offer to increase screening rates and result in improved colorectal health outcomes. Citation Format: Diana Redwood. Preference for multi-target stool DNA for colorectal cancer screening among Alaska Native people in rural/remote communities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4787.

Abstract 783: Early impact assessment of in-house EGFR testing for NSCLC in Kenya

Abstract Introduction: Quality of life and survival among non-small cell lung cancer (NSCLC) patients have improved in the last two decades owing mainly to use of tyrosine kinase inhibitors (TKIs) and other targeted therapies. Low and middle-income countries (LMICs) especially in Africa, are lagging in realizing these benefits largely due to hurdles in molecular testing. In addition, quality histology and molecular data from LMICs is deficient. The aim of this study is to assess the immediate impact of improved access to epidermal growth factor receptor (EGFR) testing in Kenya, and to establish a long term-lung cancer data base. Methods: Staring mid-June 2023, an in-house PCR-based method was adopted for EGFR testing of NSCLC in order to side step the challenges of out-of-country send outs which was until then, the only option for EGFR testing. Further, a sponsored access program was created. From prospectively accrued samples, we performed a before-and-after assessment of the number of NSCLC cases intercepted, cost and turnaround times (TAT) as measures of impact. Demographic, histopathology, and EGFR mutation profiles were analyzed in comparison to Asia, USA and European data. Whole slide histology scanned images are made to compliment the database. Results: Over the four-month period, 62 NSCLC cases were accrued, median age at diagnosis was 63 with a range of 24 - 93. The male to female ratio was 1: 1.5. Adenocarcinomas comprised 89%, squamous cell carcinoma 5% and 3% were not classifiable. Metastatic disease was reported in 14 (22%) with the brain being the commonest site. EGFR mutations were identified in 16 (25%) with exon 19 deletions and L858R mutations constituting 94% of them. Monthly requisitions for EGFR have increased 3-fold, and the average TAT has been halved to 7 days. Conclusion: Similarities between our data and global patterns are noted; median age is in the seventh decade, NSCLC is more common in women, and so are the rates of EGFR mutations, adenocarcinomas are the predominant type, and there are high rates of brain metastasis at diagnosis. EGFR mutation rates appear to be higher than USA and European data but lower than Asian data. In-house and sponsored testing has had an immediate impact in reduction of costs and TAT and increased requisitions. Assessment of access to targeted therapy, clinical outcome, survival, expansion of molecular profiling beyond EGFR, and build-up of the database including virtual histology images for exploring artificial intelligence algorithms are our next steps. Citation Format: Allan Njau, Samuel Nguku, Joseph Abuodha. Early impact assessment of in-house EGFR testing for NSCLC in Kenya [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 783.

Abstract 7288: Evaluation of silica spin-column and bead formats for rapid promoter DNA methylation analysis by qMSP in clinical and point-of-care settings

Abstract Late-stage cancers often lack effective management and treatment options, emphasizing the importance of early diagnosis for better prognosis and lower mortality rates. Molecular markers, such as DNA methylation tests, have shown promise in predicting and detecting cancer at its earliest stages. The COVID-19 post-pandemic scenario is providing a one in one-hundred-year opportunity of utilizing the excess installed PCR capacity world-wide to develop novel Quantitative Methylation Specific PCR (qMSP) screening strategies for cervical cancer screening in low-resource settings. This study aimed to compare the use of commercial bisulfite conversion kits in cervical epithelium liquid cytology samples (liquid cytology) from cancer screening clinics in the United States. Commercially available rapid bisulfite conversion protocols using silica spin column and magnetic beads were compared with conventional DNA extraction followed by bisulfite conversion protocols to profile DNA methylation by qMSP in a panel of methylated genes we previously developed to distinguish normal and cervical cancer patient samples. The results revealed that small sample volumes are suitable for methylation studies. Comparisons among four spin-column kits showed no significant differences in β-actin Cycle Threshold (Cts) values between Abcam, Epigentek, QIAGEN and Zymo D5021 kits. Zymo The best performing spin-column kit was compared with manual and automated versions of magnetic bead kits using a 96-well plate format for higher throughput. Methylation profiling of three genes (β-actin ZNF516, and FKBP6) with manual and automated magnetic bead kits revealed that automation increases throughput without a reduction in amplification efficiency in open PCR systems. Cost analysis showed that the direct kits 96-well plate format were more affordable compared to the Gold Standard manual protocol that uses spin-columns. An optimized version of Zymo D5046 magnetic bead kit provides the fastest turnaround time with similar amplification efficiency, when compared to spin-column or other magnetic bead kits. The test cost per sample is $5.41 dollars to process 83 samples in a 96 well-plate format in less than 2 hours. Another significant finding was showing the feasibility of using as low as 12µL of liquid cytology samples for DNA methylation testing, proving that bodily fluids are a liquid biopsy alternative to plasma. Overall, this comprehensive comparison is useful in determining optimal options for efficient and cost-effective cancer DNA methylation diagnostic tests, particularly in low-resource settings. Citation Format: Fernando Zamuner, Ashley Ramos-Lopez, Amanda Garcia-Negron, Ana Purcell-Wiltz, Andrea Cortes-Ortiz, Aniris Roman, Keerthana Gosala, Eli Winkler, David Sidransky, Mariana Brait, Rafael E. Guerrero-Preston. Evaluation of silica spin-column and bead formats for rapid promoter DNA methylation analysis by qMSP in clinical and point-of-care settings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7288.

Accurate and reproducible enumeration of CD4 T cell counts and Hemoglobin levels using a point of care system: Comparison with conventional laboratory based testing systems in a clinical reference laboratory in Cameroon.

Measurements of CD4 T cells and hemoglobin (Hb) are conventionally used to determine the immunological state and disease progression for HIV-infected patients. We obtained a small lightweight point-of-care device, the BD FACSPrestoTM in order to demonstrate its ability to deliver CD4 and Hb analysis in comparison with two larger clinical machines the BDFACSCantoTM analyzer and Sysmex XN 1000 haematology analyzer. The advantages of using the POC device include access to HIV patient data in remote and in resource limited settings. The analytical performance of the BD FACSPrestoTM, compared with the FACSCantoTM II flow cytometer and the Sysmex XN 1000 haematology analyzer was evaluated by testing 241 routine clinical specimens collected in EDTA tubes from patients attending the Immunology and Microbiology laboratory of Chantal BIYA International Reference Centre (Yaounde, Cameroon) between January and May 2016. The mean in absolute counts and percentage of CD4 T cells was 606 cells/mL and 25% respectively via the FACSPrestoTM, and 574 cells/mL and 24% respectively via the BD FACSCantoTM II. The mean concentration of Hb levels was 11.90 on the Sysmex XN 1000 and 11.45 via the BD FACSPrestoTM, A high correlation (R2 = 0.95, P < 0.001) of Hb level measurements was noted between the BD FACSPrestoTM and Sysmex XN 1000 hematology analyzer. Overall, a Bland-Altman plot of the differences between the two methods showed an excellent agreement for absolute and percentage CD4 counts and hemoglobin measurements between POC and conventional methods evaluated here. Furthermore, the study demonstrated the ease of use of the BD FACSPrestoTM POC technology in remote areas. The BD FACPrestoTM is a suitable tool for CD4 enumeration in resource-limited settings, specifically providing a deployable, reliable POC testing option. The BD FACSPrestoTM performed appropriately in comparison to the conventional reference standard technologies. The BD FACSPrestoTM, system provides accurate, reliable, precise CD4/%CD4/Hb results on venous blood sampling. The data showed good agreement between the BD FACSPrestoTM, BD FACSCantoTM II and Sysmex XN 1000 XN 1000 systems.

Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence

ObjectiveWe evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters....

The Importance of Community-Based and Community-Partnered COVID-19 Testing for Reducing Disparities Among African American Populations.

Health inequalities in African American communities have been further exacerbated by COVID-19. Public health departments and other safety-net providers across the United States have partnered with community-based organizations to address barriers to COVID-19 testing in disproportionately impacted communities. This narrative review summarizes lessons learned from published examples of these community-based COVID-19 testing efforts. We searched online databases for peer-reviewed articles on community-based COVID-19 testing interventions in the United States aimed at increasing COVID-19 testing among African American populations. We abstracted information about each example and synthesized the primary lessons learned and key aspects that contributed to their success. Seven examples of community-based COVID-19 testing aimed at increasing testing among African Americans and other underserved populations were identified and described, across various U.S. locations and involving multiple types of partners (1) St. Paul, MN (faith, health centers, Mayo Clinic); (2) Chicago, IL (university hospital and health centers); (3) NC (health centers, Community Advisory Board); (4) Baltimore, MD (hospitals, community clinic, mobile clinic); (5) Marion County, FL (health department and community partners); (6) New Orleans, LA (health department and health system); and (7) New York City, NY health and hospital system, mobile clinic). Several key aspects of the COVID-19 testing models included the following: (1) close proximity of the testing site to affected communities and availability of walk-up and drive-through testing options; (2) partnerships between safety-net providers and broad community networks, which facilitated outreach and trust; (3) increased resources for safety-net providers; and (4) the use of data to identify areas of need and track impact. The merging of resources and relationships among well-equipped, safety-net providers and other health care institutions and culture-rich, community-centered organizations, to jointly address structural and systemic inequities, is key to cultivating health equity in the distribution of COVID-19 testing and other essential public health services.

Practical approach to testing the imported dog for parasites

Background: Despite the Covid‐19 pandemic and Brexit, the number of dogs being imported into the UK remains high. At the same time there are a variety of factors driving global parasite distributions, increasing the likelihood that imported pets will be infected with exotic parasites. Therefore, early diagnosis of exotic infections is important, both in dogs with clinical signs but also those that are subclinical carriers. Detecting infections allows us to minimise the potential zoonotic exposure, plan for treatment of any pathogens present and maintain UK biosecurity.Aim of the article: This article summarises the clinical signs and testing options for the key parasites that imported dogs may be infected with.

Comparative effectiveness of two interventions to increase colorectal cancer screening among females living in the rural Midwest.

To assess the comparative effectiveness of a tailored, interactive digital video disc (DVD) intervention versus DVD plus patient navigation (PN) intervention versus usual care (UC) on the uptake of colorectal cancer (CRC) screening among females living in Midwest rural areas. As part of a larger study, 663 females (ages 50-74) living in rural Indiana and Ohio and not up-to-date (UTD) with CRC screening at baseline were randomized to one of three study groups. Demographics , health status/history, and beliefs and attitudes about CRC screening were measured at baseline. CRC screening was assessed at baseline and 12 months from medical records and self-report. Multivariable logistic regression was used to determine whether females in each group were UTD for screening and which test they completed. Adjusted for covariates, females in the DVD plus PN group were 3.5× more likely to complete CRC screening than those in the UC group (odds ratio [OR] 3.62; 95% confidence interval [CI]: 2.09, 6.47) and baseline intention to receive CRC screening (OR 3.45, CI: 2.21,5.42) at baseline. Adjusting for covariates, there was no difference by study arm whether females who became UTD for CRC screening chose to complete a colonoscopy or fecal occult blood test/fecal immunochemical test. Many females living in the rural Midwest are not UTD for CRC screening. A tailored intervention that included an educational DVD and PN improved knowledge, addressed screening barriers, provided information about screening test options, and provided support was more effective than UC and DVD-only to increase adherence to recommended CRC screening.

Characteristics and courses of COVID-19 in patients from the first through fifth waves of the disease: Focused on a single public health center in Tokyo, Japan

Objective Coronavirus disease 2019 (COVID-19) became a global public health threat, and local public health centers in Japan implemented an infectious disease response to support patients. The response was subsequently modified to meet the needs for each of the five waves of infection. The study aim was to analyze the characteristics and courses of the disease in patients with COVID-19 at a single public health center. The study period included the first through fifth waves of the disease.Methods We utilized a descriptive epidemiological design in this study and data of patients with COVID-19 from one administrative district in Tokyo, Japan. We analyzed age, gender, nationality, symptoms at diagnosis, the route of infection, the recovery environment, and associated morbidity intervals, including case fatality rate, days from symptom onset to diagnosis, days from diagnosis to hospitalization, and recovery time for each of the first through fifth waves.Results From February 2020 to November 2021, 11,252 patients were diagnosed with COVID-19. Specifically, in the first wave, 151 patients were diagnosed, followed by 803 in the second wave, 2,406 in the third wave, 1,480 in the fourth wave, and 6,412 in the fifth wave. Hospitalization was the primary recovery environment during the first wave, while home recovery became the primary approach from the third wave onward. The case fatality rate was highest during the first wave, likely because of limited testing and treatment options for severe cases. The median time from onset to diagnosis was seven days in the first wave, significantly longer than for the other waves. The median time from diagnosis to hospitalization was one day in the first through fourth waves but three days in the fifth wave. The extension of this interval suggests that hospitalization was delayed in this wave as the number of severe patients increased rapidly, likely because of the novel COVID-19 variant.Conclusion This study of patients testing positive for COVID-19 provides valuable insights into the characteristics and courses of the pandemic within this district. These findings can inform regarding the development of effective strategies to manage the ongoing COVID-19 pandemic and other future emerging infectious diseases.

Helicobacter pylori Infection and Complications of Cirrhosis.

Helicobacter pylori is a significant contributor to conditions such as peptic ulcer disease, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and colorectal cancer. Recent studies have suggested a potential link between H. pylori and cirrhosis. However, the impact of H. pylori on cirrhosis-related mortality, inpatient outcomes, and decompensating events remains unclear. Considering the widespread availability of H. pylori testing and effective treatment options, there is a potential rationale for eradicating H. pylori in cirrhotic patients to mitigate the morbidity and mortality associated with cirrhosis. This study aims to investigate the association between H. pylori and inpatient outcomes and complications related to cirrhosis. The National Inpatient Sample (NIS) database, a part of the Healthcare Cost & Utilization Project, was utilized for this study. Inpatient data from the years 2016 through 2019 were extracted for patients with a primary discharge diagnosis of cirrhosis and a concurrent diagnosis of H. pylori infection. The primary outcomes included inpatient mortality, length of stay, and cost of care. Secondary outcomes involved cirrhosis-related complications during hospitalization, such as gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome. Over the years 2016 to 2019, 416,410 patients received a primary discharge diagnosis of cirrhosis. Among them, 990 patients (0.2%) had a secondary diagnosis of H. pylori infection. Those with both cirrhosis and H. pylori tended to be younger on average (mean age 54.25 vs. 57.18 years, p=0.01) and more frequently fell within the age range of 18-49 (33.84% vs. 24.71%, P=0.01). H. pylori-infected patients were also more likely to be male (70.71% vs. 63.11%, P<0.028), of Hispanic race (36.4% vs. 18.6%, p< 0.1), and of Black race (20.2% vs. 8.1%, p< 0.1). While H. pylori-exposed patients had lower in-hospital mortality (0.51% vs. 4.44%, p=0.007), their mean length of stay was higher (6.97 days vs. 5.75, p=0.002). The overall cost of care was comparable between the H. pylori-exposed and non-exposed groups (mean USD18,106.18 vs. $16,543.49, P=0.160). H. pylori-exposed patients had a higher overall rate of cirrhosis-related complications (84.85% vs. 67.59%, p< 0.001), gastrointestinal bleeding (48.48% vs. 27.34%, p< 0.001), and hepatorenal syndrome (70.71% vs. 46.99%, p< 0.001), and these differences persisted in multivariable analysis. Initially, rates of hepatic encephalopathy were higher in H. pylori non-exposed patients (21.57% vs. 15.66%, p=0.04), but this discrepancy was corrected after adjusting for potential confounders. While patients in this study were diagnosed with both H. pylori and cirrhosis by discharge, it cannot be definitively concluded that H. pylori was the direct cause of cirrhosis complications. Recognizing this uncertainty, further studies are needed better to understand the associations between cirrhosis and H. pylori complications. Distinguishing the causes of cirrhosis and its relationship with H. pylori may offer deeper insights into whether H. pylori is a causative factor or merely correlated in its effects on patients with cirrhosis.

A Multimodal Intervention to Reduce C. difficile Infections and Stool Testing.

The introduction of multiplex gastrointestinal panels at our institution resulted in increased Clostridioides difficile (C. difficile) detection and stool test utilization. We aimed to reduce hospital-onset C. difficile infections (HO-CDIs), C. difficile detection, and overall stool testing by 20% within 1 year. We conducted a quality improvement project from 2018 to 2020 at a large children's hospital. Interventions included development of a C. difficile testing and treatment clinical care pathway, new options for gastrointestinal panel testing with or without C. difficile (results were suppressed if not ordered), clinical decision support tool to restrict testing, and targeted prevention efforts. Outcomes included the rate of HO-CDI (primary), C. difficile detection, and overall stool testing. All measures were evaluated monthly among hospitalized children per 10 000 patient-days (PDs) using statistical process-control charts. For balancing measures, we tracked suppressed C. difficile results that were released during real-time monitoring because of concern for true infection and C. difficile-related adverse events. HO-CDI decreased by 55%, from 11 to 5 per 10 000 PDs. C. difficile detection decreased by 44%, from 18 to 10 per 10 000 PDs, and overall test utilization decreased by 29%, from 99 to 70 per 10 000 PDs. The decrease in stool tests resulted in annual savings of $55 649. Only 2.3% of initially suppressed positive C. difficile results were released, and no patients had adverse events. Diagnostic stewardship strategies, coupled with an evidence-based clinical care pathway, can be used to decrease C. difficile and improve overall test utilization.

A67 REDUCING INAPPROPRIATE GAMMA-GLUTAMYL TRANSFERASE TESTING FOR INPATIENTS: A QUALITY IMPROVEMENT INITIATIVE IN LAB WASTE REDUCTION APPLYING THE MODEL FOR CONTINUOUS IMPROVEMENT

Abstract Background Review of the literature identifies a rising trend in laboratory testing, with over 30% of tests estimated to be inappropriately repeated. Laboratory overutilization increases healthcare costs, and can lead to overdiagnosis, overtreatment and negative health outcomes. Indications for repeat Gamma Glutamyl Transferase (GGT) testing in adults are limited, particularly repeat testing within the same admission. Aims Our aim was to reduce the inappropriate ordering of repeat GGT testing by 25% for all inpatients at the London Health Sciences Centre (LHSC) over a one-year study period. Methods An interprofessional team was created to help engage relevant stakeholders, collect baseline data and reassess the indications for GGT testing. A combination of root cause analysis tools, specifically the Ishikawa diagram and Pareto chart, were employed to identify potential factors contributing to the overutilization of GGT testing. After prioritizing potential solutions, intervention bundles were developed, and Plan-Do-Study-Act (PDSA) cycles were created to target correctable factors. In PDSA cycle #1, the process started by eliminating GGT as a laboratory testing option in the three most commonly used admission order care sets. Considering the hierarchy of intervention effectiveness, PDSA cycle #2 involved implementing a computerized Clinical Decision Support (CDS) system to restrict the reordering of GGT tests within 72 hours of the same admission. Results Baseline data showed that in 2022, a total of 62,542 GGT tests were ordered, with an average of approximately 5,200 GGT tests ordered per month. Of these, 16.4% were ordered through the top 3 most prevalent admission order care sets, and around 25% of all GGT tests were repeats within 72 hours of admission. Referring to Figure 1, PDSA cycle #1 yielded no significant reduction in GGT testing. PDSA cycle #2 successfully reduced the proportion of repeat GGT tests ordered by 12% within two months of implementation, leading to an estimated annualized cost savings of approximately $37,440. Conclusions Our results establish the effectiveness of CDS systems in reducing laboratory testing overutilization, suggesting their superiority to individual care set targeting interventions, and emphasize the potential for cost-effective CDS development in contemporary healthcare. Funding Agencies None

Evaluating the Intensity of Exposure to MTV Shuga, an Edutainment Program for HIV Prevention: Cross-Sectional Study in Eastern Cape, South Africa.

MTV Shuga is an edutainment campaign designed to equip young people with knowledge, motivation, and informed choices to protect themselves from HIV infection. From 2019 to 2020, a total of 10 episodes of a new dramatic series, MTV Shuga "Down South 2" (DS2), were broadcast via television and the internet, alongside complementary media activities. This study aims to investigate whether the intensity of DS2 exposure was linked with positive HIV prevention outcomes in a setting with high HIV prevalence and relatively low levels of HIV testing. We analyzed data from a web-based survey of participants aged 15 to 24 years in South Africa in 2020. The survey was promoted via social media platforms of schools, universities, and communities in Eastern Cape, South Africa. The primary exposure of interest was the intensity of exposure to DS2, measured by the number of episodes of DS2 watched on the television or the internet or listened to on the radio (out of 10 episodes). Individuals who had not watched or listened to any DS2 episode were classified according to other MTV Shuga content that they had accessed. We estimated associations between the intensity of DS2 exposure and HIV-related outcomes, including knowledge of HIV status, awareness of HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP), uptake of HIVST, and demand for HIVST and PrEP, adjusting for potential confounders using multivariable logistic regression. Among the 3431 survey participants, 827 (24.1%) were exposed to DS2. Specifically, 18.1% (622/3431) watched or listened to only 1 DS2 episode, and 2.4% (82/3431), 1.7% (58/3431), and 1.8% (62/3431) watched or listened to 2 to 4, 5 to 7, and 8 to 10 DS2 episodes, respectively. Increasing the exposure to DS2 was associated with improvements in most outcomes. Exposure to multiple episodes (eg, 2-4, 5-7, and 8-10) was associated with successively higher odds of knowing one's HIV status, awareness of PrEP and HIVST, and uptake of HIVST compared with no MTV Shuga exposure, albeit with statistical uncertainty around some estimates. The interest in using HIVST or PrEP was high overall (>80%), with no measurable differences by DS2 intensity. We found evidence consistent with a dose-response relationship between MTV Shuga DS2 exposure and outcomes, including knowledge of HIV status, awareness and uptake of HIVST, and awareness of PrEP among young people in Eastern Cape. This indicates that greater engagement with a youth-focused edutainment campaign can improve HIV testing and prevention options in a setting and population with high need. However, only a few participants accessed multiple DS2 episodes despite its availability on multiple media platforms. We conclude that there is potential to benefit more young people by increasing access to and interest in the show.

Experience on postmortem minimally invasive tissue sampling to ascertain the cause of death determination in South African children: A case for implementing as standard of care

Determining the death burden for prioritising public health interventions necessitates detailed data on the causal pathways to death. Postmortem minimally invasive tissue sampling (MITS), incorporating histology, molecular and microbial culture diagnostics, enhances cause-of-death attribution, particularly for infectious deaths. MITS proves a valid alternative to full diagnostic autopsies, especially in low- and middle-income countries. In Soweto, South Africa (SA), the Child Health and Mortality Prevention Surveillance (CHAMPS) programme has delineated over 1 000 child and stillbirth deaths since 2017. This SA CHAMPS site supports advocating for the use of postmortem MITS as routine practice, for more granular insights into under-5 mortality causes. This knowledge is crucial for SA’s pursuit of Sustainable Development Goal 3.2, targeting reduced neonatal and under-5 mortality rates. This commentary explores the public health advantages and ethicolegal considerations surrounding implementing MITS as standard of care for stillbirths, neonatal and paediatric deaths in SA. Furthermore, based on the data from CHAMPS, we present three pragmatic algorithmic approaches to the wide array of testing options for cost-effectiveness and scalability of postmortem MITS in South African state facilities.