Testing Options Research Articles

Navigating an Uninformative Genomic Test Result: A Practical Guide.

Although genomic testing is increasingly standard of care for diagnosing children and adults with genetic conditions, over 50% of genomic testing will return an uninformative result. To provide a practical guide for paediatricians on how to approach an uninformative genomic test result, and the pathways which may be available to uncover a genetic diagnosis for their patients. Input from multiple genetics healthcare professionals including genetic counsellors, the literature, and a general paediatrician were used to construct this guide. We also provide a hypothetical case vignette, to further demonstrate the various options for a patient after receiving an uninformative result. There are several reasons why an underlying genetic diagnosis may not be diagnosed with current testing, including incomplete phenotyping, a different underlying genetic mechanism requiring specialised testing, and limitations in knowledge at the time of the test. Uninformative results are very common, and it is important to understand these results in the context of the limitations of genomic testing. General paediatricians play an important role in supporting families through their diagnostic odyssey, as well as reassessing the phenotype, referring for sub-specialty inputs, and discussion with local genetics services for consideration of alternative testing options or enrolment into research pathways.

Acceptability and Future Considerations for Telegenetic Counseling After the COVID Pandemic: Interviews with Genetic Counselors, Clinicians, and Patients.

While telegenetic counseling has increased substantially since the start of the COVID-19 pandemic, previous studies reported concerns around building rapport, nonverbal communication, and the patient-counselor relationship. This qualitative evaluation elicited feedback from genetic counselors, referring clinicians, and patients from a single healthcare organization to understand the user-driven reasons for overall satisfaction and experience. We conducted 22 in-depth, semi-structured interviews with participants from all 3 groups between February 2022 and February 2023. Interview recordings were transcribed and analyzed using a pragmatic thematic approach. Participants across all groups felt the style and content of the genetic counseling visit lent itself perfectly to telegenetics specifically because of no physical exam component. Most patient and counselor participants expressed having the genetic counseling over phone or video had no impact on the patient-counselor relationship or the amount of trust and emotional connection they were able to achieve remotely. Preference for visit type can be influenced by in-person masking requirements impeding full facial expressions or expressing strong emotions over phone. All respondents expressed strong support for all modalities going forward. Counselors with broad experience across platforms should be the focus of future recruitment as should patient education around the nature of the genetic counseling visit and the accuracy of various testing options. Telegenetic programs should consider perspectives from all 3 groups to ensure that specific needs of each are addressed.

P-1605. Matching the Right Test to the Right Patient: Building Probability-Based Decision Support into the Electronic Health Record to Guide Diagnosis of Community-Acquired Pneumonia (CAP) Among Hospitalized Patients

Abstract Background Respiratory infections are among the most common reasons antibiotics are prescribed. However, 30-50% of patients started on antibiotics for CAP do not have bacterial infections. Methods We implemented clinical decision support (CDS) in the electronic health record of two hospitals to support diagnosis of viral vs. bacterial CAP. The CDS (1) estimates the probability of bacterial CAP using logic from a publicly available calculator and (2) provides probability-based options for diagnostic testing. The CDS is triggered by an order for respiratory virus testing and can be dismissed if bacterial CAP is not suspected or the patient is not being admitted. Design of the CDS was refined iteratively in usability testing with frontline clinicians (Fig. 1). The final design was an order panel embedded within other order sets (Fig. 2). The CDS was activated on 11/1/2023. Impact of the CDS was assessed in a quasi-experiment comparing antibiotic use (AU) during the post-intervention respiratory virus season (10/2023 – 3/2024) to corresponding months in 2021-2022 and 2022-2023. AU was defined as days of therapy / 1000 patient bed-days (DOT/1000 BD) for antibiotics started on hospital day 0-7 for respiratory infection, regardless of whether the CDS triggered. AU categories, including extended-spectrum AU, were defined by pharmacy. Average quarterly AU was compared between the post-intervention respiratory virus season and preceding seasons using Student’s t-test. Results CDS guided test ordering in 890 of 3,201 eligible CAP patients (28% of appearances, Fig. 3) through 3/31/2024, with usage declining in February and March. Feedback from clinicians noted that the CDS is unobtrusive, but it does not apply to all patients, and recommended tests sometimes have longer turnaround times than alternatives. Overall AU for respiratory infections did not change in the post-intervention respiratory season (129.1 vs. 129.6 DOT/1000 BD, p = 0.94), but extended-spectrum AU decreased significantly (46.6 vs. 40.6 DOT/1kBD, p = 0.046, Fig. 4). Conclusion This project demonstrates use of CDS to guide diagnostic testing based on pre-test probability of bacterial CAP. An associated antimicrobial stewardship intervention is under investigation (NCT05976581). Disclosures Anthony Harris, MD, MPH, Innoviva: Advisor/Consultant|UpToDate: Infection Control Editor Kimberly C. Claeys, PharmD, PhD, bioMérieux: Advisor/Consultant|bioMérieux: Honoraria R. Gentry Wilkerson, MD, Beckton Dickinson: Grant/Research Support|CalciMedica: Grant/Research Support|CoapTech: Grant/Research Support|Eldon: Grant/Research Support|EndPoint Health, Inc: Grant/Research Support|Global Blood Therapeutics: Grant/Research Support|Novartis: Grant/Research Support|Pfizer: Grant/Research Support|Tonix: Grant/Research Support|Vapotherm: Grant/Research Support

P-920. Free-living Ameba Infections Diagnosed by Cell-free DNA Blood Testing – United States, 2018-2023

Abstract Background Free-living amebae (FLA) including Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri live in soil and water worldwide and cause severe infections in humans. Approximately 15 people in the United States are infected by FLA each year; most do not survive. Early diagnosis and treatment improve outcomes. Targeted testing options for FLA require tissue or cerebrospinal fluid (CSF) and are offered at < 5 laboratories in the U.S., making it challenging to diagnose infections quickly and non-invasively. Detection of FLA infections via cell-free DNA testing of blood (Karius Test®) has increased in recent years. Methods The Centers for Disease Control and Prevention (CDC) maintains a database of confirmed FLA cases reported through the CDC FLA Clinical Consultation Service or national surveillance efforts. This database was used to identify and describe cases in which a Karius Test® first detected an FLA infection. Results In 2018-2023, 9 U.S. FLA infections were diagnosed with Karius Test® and reported to CDC, including 4 Acanthamoeba, 4 Balamuthia, and 1 Naegleria case. These represent 10% of FLA cases reported to CDC in this timeframe (9/93). Four of these cases were reported in 2023 (22% of FLA cases in 2023), an increase over previous years. FLA had not been suspected in 8/9 cases before receiving results. Eight patients presented with meningitis or encephalitis; 1 had only skin findings. FLA diagnoses were subsequently confirmed by other methods in 7/7 cases for which tissue or CSF was available. Duration from hospitalization or symptom onset to Karius Test® result was 5-14 days. One patient was diagnosed postmortem; the others were initiated on anti-amebic therapy. No patients ultimately survived, though 3 patients were treated for several weeks. Conclusion Cell-free DNA testing (Karius Test®) of blood is increasingly being used to diagnose FLA infections. Nearly all patients described were diagnosed by Karius Tests® before FLA infections had been suspected. Early diagnosis can allow early treatment, inform clinical decision-making, and contribute to the further understanding of FLA infections through surveillance. In patients with suspected FLA infections or encephalitis of unknown etiology, Karius Test® may be useful, particularly when tissue or CSF is not available. Disclosures All Authors: No reported disclosures

Comparison of MIC Test Strip and reference broth microdilution method for amphotericin B and azoles susceptibility testing on wild type and non-wild type Aspergillus species.

This study was performed to evaluate whether the MIC Test Strip (MTS) quantitative assay for determining the minimum inhibitory concentration (MIC) correlated with the CLSI reference broth microdilution method (BMD) for antifungal susceptibility testing of wild-type and non-wild-type Aspergillus species isolated from cystic fibrosis patients against antifungal agents known to be usually effective against Aspergillus spp. This study was performed to assist in the decision-making process for possible deployment of the MTS assay for antimicrobial susceptibility testing of Aspergillus species into regional public health laboratories of Mycology due to difficulties in equipping the reference BMD methods in a laboratory routine. For this purpose, a set of 40 phenotypically diverse isolates (27 wild-type, 9 non-wild-type, and 4 species with reduced susceptibility to azoles and amphotericin B (AMB)) collected from clinical samples were tested. MICs were performed by both MTS and reference BMD for AMB, and azoles. MTS results for posaconazole correlated well with reference BMD rendering an almost perfect agreement (kappa value=1.000) by category interpretation (CI)/category distribution of MICs (CDM) (100%) while voriconazole MTS results yielded a substantial correlation with BMD (kappa value=0.788) by CI/CDM (97.5%). In contrast, itraconazole and AMB yielded the poorest correlation with BMD, rendering a moderate agreement (kappa values of 0.554 and 0.437, respectively) by CI/CDM (87.5% and 85%, respectively). In conclusion, the MTS method represents a valid option for antimicrobial susceptibility testing of Aspergillus species against posaconazole and voriconazole. Itraconazole and AMB MTS results showed some concerning lack of correlation with the corresponding reference BMD results.

A proposed screening strategy for evaluating the genotoxicity potential of botanicals and botanical extracts.

Botanicals have long been used to promote health and treat diseases, but the safety of many currently marketed botanicals has not been adequately evaluated. Given the chemical complexity of botanicals, which often contain numerous unknown constituents, and their widespread use, comprehensive toxicity assessments are needed. The Botanical Safety Consortium was established to address this challenge. This international group of experts in toxicology, chemistry, bioinformatics, and pharmacognosy is developing a toolkit of assays to generate reliable toxicological profiles for botanicals. Genotoxicity assessment is especially critical, because, unlike other toxicities, genotoxicity is not adequately identified by adverse event and history-of-use reports, and genotoxicity is directly linked to health consequences such as cancer and birth defects. The Consortium's Genotoxicity Technical Working Group is exploring a genotoxicity testing strategy based on the use of in silico modeling and the bacterial reverse mutation and in vitro micronucleus assays and including several options for additional tests to further characterize genotoxicity and mode of action when indicated. The effectiveness of this testing strategy is being evaluated using 13 well-characterized botanicals with existing toxicological data as case studies. A brief overview of each of these 13 botanicals is provided. The final strategy for developing comprehensive genotoxicity profiles of botanicals will incorporate published genotoxicity data, chemical composition information, in silico and in vitro test data, and human exposure data, reducing the need for animal testing.

Clinical Validation of MyProstateScore 2.0 Testing Using First-Catch, Non-DRE Urine.

The 18-gene MyProstateScore 2.0 (MPS2) test was previously validated for detection of Grade Group≥2 (GG≥2) prostate cancer using post-digital rectal examination (DRE) urine. To improve ease of testing, we validated MPS2 using first-catch, non-DRE urine. Patients provided first-catch urine prior to biopsy. MPS2 values were calculated using previously-validated models differing only by extent of clinical data included: biomarkers alone (BA; no clinical data), biomarkers and clinical factors (BA+CF), and biomarkers, clinical factors, and prostate volume (BA+CF+PV). The primary outcome was GG≥2 cancer on biopsy. MPS2 performance and clinical consequences of testing were compared to PSA and the Prostate Cancer Prevention Trial risk calculator (PCPTrc). The cohort included 266 men with median PSA 6.6 ng/mL (IQR 4.9-9.1), of which 103 (39%) had GG≥2 cancer on biopsy. The area under the curve for GG≥2 cancer was 57% for PSA, 62% for PCPTrc, and 71%, 74%, and 77% for MPS2 models. Under a testing approach detecting >90% of GG≥2 cancers, MPS2 testing would have avoided 36-42% of unnecessary biopsies, as compared to 13% using the PCPTrc. In patients with a prior negative biopsy, MPS2 testing would have avoided 44-53% of repeat biopsies, as compared to only 2.6% using PCPTrc. Using first-catch urine, MPS2 meaningfully improved the proportion of biopsies avoided relative to PCPTrc while maintaining highly-sensitive detection of GG≥2 cancer. Non-DRE testing provides a convenient, objective, and highly-accurate testing option to reduce the need for imaging and biopsy in men with elevated PSA.

Fetal Corpus Callosum Anomalies: A Review of Underlying Genetic Disorders and Prenatal Testing Options.

Anomalies of the corpus callosum (CC) are amongst the most common fetal Central Nervous System (CNS) anomalies detectable on ultrasound. Underlying genetic disease plays an important part in defining prognosis. Associations with aneuploidy and submicroscopic chromosomal deletions or duplications have been well demonstrated using chromosomal microarray analysis. Next-generation sequencing techniques such as exome sequencing, have revolutionized the ability to detect monogenic disease in these fetuses. In the context of important recent publications on exome sequencing in prenatal populations, an updated review of genetic testing options in CC anomalies is presented.

Exploring Literacy and Knowledge Gaps and Disparities in Genetics and Oncogenomics Among Cancer Patients and the General Population: A Scoping Review.

Genetic and genomic literacy is pivotal in empowering cancer patients and citizens to navigate the complexities of omics sciences, resolve misconceptions surrounding clinical research and genetic/genomic testing, and make informed decisions about their health. In a fast-evolving scenario where routine testing has become widespread in healthcare, this scoping review sought to pinpoint existing gaps in literacy and understanding among cancer patients and the general public regarding genetics and genomics. Adhering to the PRISMA framework, the review included 43 studies published between January 2018 and June 2024, which evaluated the understanding of genetics and genomics among cancer patients, caregivers, and citizens. Although the selected studies had significant heterogeneity in populations and evaluation tools, our findings indicate inadequate literacy levels, with citizens displaying lower proficiency than cancer patients and caregivers. This review highlighted consistent knowledge gaps in understanding the genetic and genomic underpinnings of diseases, encompassing misconceptions about mutation types and inheritance patterns, limited awareness of available genetic testing options, and difficulties in interpreting test results. Ethical and privacy concerns and the psychological impact of genetic testing were also common, highlighting the imperative need for effective communication between healthcare providers and patients. Given the dynamic nature of genomic science, the review underscores the need for continuously evolving educational programs tailored to diverse populations. Our findings could guide the development of educational resources addressed explicitly to cancer patients, caregivers, and the lay public.

Whole Exome Sequencing in a Population of Fetuses With Structural Anomalies.

To investigate the exome sequencing (ES) detection rate among fetuses with congenital anomalies and describe the rates in the setting of multiple versus isolated anomalies, perinatal autopsy, and family history of a previously affected child. A single-center retrospective chart review was conducted on 397 anomalous fetuses that underwent ES from May 2012 through December 2023. Medical record review included demographics, imaging, and genetic testing. The overall ES diagnostic rate was 34.3%. The rate of diagnosis was 31.6% in fetuses with a single anomaly and 42.6% in fetuses with 4 or more major organ systems involved. Of the fetuses with a single anomaly, lymphatic, craniofacial, skeletal, and neurological anomalies had the highest diagnostic rate on ES. 38.6% of deceased fetuses who underwent autopsy had a genetic diagnosis. Additionally, families who had a previously affected child had a 45.5% diagnostic rate. ES is an important tool that should be offered in pregnancies affected with congenital abnormalities or at the time of fetal demise or termination. The diagnostic rate of ES in the prenatal setting is also highly dependent on comprehensive phenotyping. With diagnostic ES results, reproductive technology and testing options are available in subsequent pregnancies.

A novel Schirmer strip-based tear matrix metalloproteinase measurement in dry eye evaluation.

The diagnosis and evaluation of dry eye require easy-to-use, precise, and consistent tools in clinical setting. Matrix metalloproteinase 9 (MMP-9) has been proven to be a reliable indicator of dry eye inflammation. The aim of this study is to establish an Eu-time resolved fluorescence immunochromatography (Eu-TRFICO) method for quantitative detection of MMP-9 in human tear based upon widely used Schirmer strips. The Eu-TRFICO method for Schirmer strip-based tear MMP-9 measurements were optimized and assembled. The sensitivity, repeatability and homogeneity were evaluated using MMP-9 standard dilutions. The diagnostic and treatment monitoring performance were evaluated in both dry eye patients and normal subjects. The standard curve equation was y=0.0037+8.0692/[1+ (x/188.322)-0.8972] (R2=0.99998), and the sensitivity was 0.25ng/mL. The Schirmer strip-based MMP-9 measurements showed acceptable repeatability and homogeneity with different saturation length in both low and high standard solutions. A total of 162 participants (162 eyes) were enrolled in this study, including 41 normal and 121 dry eye subjects. This method exhibited a sensitivity of 74.17% and specificity of 77.5% for dry eye diagnosis, with an AUC value of 0.8275, and cutoff value of 150.67ng/mL, using normal subjects as negative control. The tear MMP-9 concentrations monitored with this method correlated well with the therapeutic response in dry eye patients. This study developed Eu-TRFICO Schirmer strips with high sensitivity, specificity, precision, and satisfactory clinical testing performance, which provides a convenient and quantitative option for clinical testing of tear MMP-9 in dry eye patients.

New Option for Antibiotic Susceptibility Testing in Clinical Practice: Performance Evaluation of AutoMic-i600 Automatic System Based on Broth Microdilution Method.

The emergence of multidrug-resistant bacteria limits antibiotic efficacy, making accurate antimicrobial susceptibility testing (AST) essential for clinical decisions. Broth microdilution (BMD) is the gold standard but is impractical for routine application. Current automated AST systems improve efficiency but face accuracy or operational challenges, highlighting the need for reliable and user-friendly solutions. This study aims to evaluate the performance of a novel automated AST system (AutoMic-i600) based on the BMD method for AST of common clinical bacteria. A total of 229 clinical isolates (150 Gram-negative and 79 Gram-positive) were prospectively collected from microbiology laboratory between June 2023 and August 2023. We reported the comparison of the AutoMic-i600 and Vitek 2 systems for routine antibiotics, and also validated the detection performance of AutoMic-i600 for novel antibiotics, based on the BMD method. The overall essential agreement (EA) and categorical agreement (CA) between AutoMic-i600 and BMD were 93.2% and 93.5% for Gram-negative bacteria and 98.5% and 97.8% for Gram-positive bacteria, respectively. The overall EA and CA between Vitek 2 and BMD were 92.6% and 93.5% for Gram-negative bacteria and 97.9% and 97.4% for Gram-positive bacteria. Importantly, for drug-resistant bacteria, AutoMic-i600 demonstrated a higher overall agreement than Vitek 2 (EA: 98.1% vs 94.8%, CA: 97.5% vs 92.0%), especially in Gram-negative bacteria (EA: 97.7% vs 93.5%, CA: 97.7% vs 89.3%). The VME rate for Gram-negative bacteria using AutoMic-i600 was significantly lower than that of Vitek 2 (1.0% vs 2.9%).Novel antibiotics detected by AutoMic-i600 exhibited EA and CA rates exceeding 90.0%. Based on these findings, we recommend that the AutoMic-i600 system could be a new option for routine AST testing in a clinical setting. Particularly for drug-resistant bacteria and novel antibiotics, detection with AutoMic-i600 may be more reliable, which could further contribute to the prevention and treatment of drug-resistant bacteria.

The role of community pharmacists in point-of-care testing and treatment for influenza and Group A Streptococcus -a narrative review using Ecological Systems Theory.

Point-of-care testing (POCT) is a valuable diagnostic approach for identifying pathogens such as Group A Streptococcus (GAS) and influenza. Early detection through POCT allows for timely initiation of appropriate treatments improving public health outcomes and minimizing antibiotic misuse. Community pharmacists are well positioned to offer POCT and treatment, but they face significant system level barriers to widespread implementation and reach. This narrative review employs Ecological Systems Theory to examine the role of community pharmacists in the implementation of POCT and subsequent treatment for respiratory infections and synthesize findings from a range of studies at different levels of the system. Medline was used to identify articles with MESH headings of rapid diagnostic tests and community pharmacists. Articles were reviewed and used to inform the synthesis. Additional articles were identified using free-text search to fill gaps in the domains. The review indicates that community pharmacists are well-positioned to provide POCT for respiratory infections, addressing barriers such as appointment availability, scheduling difficulties, and distance to primary care facilities. The accessibility of neighborhood pharmacies can significantly reduce health disparities by offering timely testing and treatment options. Studies demonstrate that early intervention facilitated by POCT in pharmacies leads to better health outcomes and more efficient use of antibiotics and antivirals. Community pharmacists play a crucial role in expanding access to POCT and treatment for respiratory infections, particularly in underserved areas. Their involvement can lead to improved public health outcomes by ensuring early and appropriate treatment. Future research should focus on overcoming barriers to POCT implementation in pharmacies and further quantifying the impact on health disparities and treatment efficacy. The integration of POCT services in community pharmacies represents a significant advancement in public health strategy, enhancing the overall healthcare delivery system.

Technological Trends for Electrical Machines and Drives Used in Small Wind Power Plants—A Review

High-power-range wind generators mainly employ classical variants, with the advantages of low cost, high robustness and acceptable energetic performance, while for low-power applications, the available electrical drive solutions are more numerous. This paper investigates the current trend in this field, indicating simple or complex structures, with or without self-excitation and with or without mechanical or magnetic transmission. The discussed variants are compared in terms of complexity, cost, fault-tolerance capability and estimated energetic performances but also the grid connectivity for standard conditions. The review is completed by testing options and conditions, as well as the methods for parameter determination, which have an important effect on the controllability of the entire system.

The Role of Pharmacogenetic Testing in Optimizing Antipsychotic Therapy

Antipsychotic therapy in psychiatric practice can last from several months to many years, which requires the selection of drugs with the greatest effectiveness and the lowest risk of adverse drug reactions for the patient. According to experts, about a quarter of the total variability in response to antipsychotics is of genetic origin. This review analyzes and summarizes the results of domestic and foreign studies of the role of hereditary risk factors that cause a decrease in hepatic metabolism and efflux of antipsychotics due to polymorphism of genes encoding cytochrome P450 isoenzymes and transporter proteins. The key enzymes of antipsychotic metabolism registered for use in Russia and abroad are presented. The prospects of various options for pharmacogenetic testing in reducing the risk of potentially fatal complications in the selection of antipsychotic therapy in clinical practice are assessed.

Never tested for HIV among men who have sex with men, Hanoi, Vietnam: correlates and missed opportunities.

Introduction: Understanding levels of HIV testing among populations at risk for acquisition is essential to meeting the goal of the United Nations that 95% of individuals living with HIV know their status. This study assessed HIV testing prevalence among men who had sex with men (MSM), characteristics of MSM who have never tested for HIV, and missed testing opportunities in Hanoi, Vietnam.Methods: We measured the prevalence of never testing for HIV and missed opportunities for testing in the baseline data of a cohort study of MSM recruited in 2017-2019 in Hanoi. Logistic regression analysis characterized MSM who had never tested prior to cohort participation.Results: Of 1,893 MSM enrolled in the cohort, 39.4% had never previously tested for HIV. MSM with children (aOR 1.75, 95% CI 1.09-2.82) and those who did not know or remember having a male partner living with HIV (aOR 1.41, 95% CI 1.07-1.84) were more likely to have never tested. Older age, university education, higher income, and having a male partner living with HIV were associated with a lower likelihood of never having been tested. The most common missed testing opportunities to test MSM who had never been tested were when receiving free condoms from health educators (35.3%), testing for other sexually transmitted infections (STIs) (23.3%), reporting their MSM status to healthcare workers (16.4%), and receiving an STI diagnosis (13.0%). The most common barriers identified by MSM who had never tested were fear of seeking health care due to their sexual orientation (82.7%) and having been refused healthcare due to their sexual oreitnation (76.2%).Conclusions: Facilitating provider-initiated HIV testing in STI clinics and other healthcare services, community-based testing, and HIV self-test kits should enhance HIV testing options for young MSM, especially those with lower education and income.

Prevalence and Distribution of Unexpected Actionable Germline Pathogenic Variants Identified on Broad-Based Multigene Panel Testing Among Patients With Cancer.

In patients with a variety of malignancies undergoing multigene panel testing (MGPT), we examined the frequency of a pathogenic/likely pathogenic variant (PV) that would not have been predicted on the basis of the patient's personal and family history of cancer. This is a retrospective review of patients with cancer ascertained from a single academic cancer center who underwent broad-based MGPT of ≥20 cancer predisposition genes not selected on the basis of personal or family cancer history from 2015 to 2021. Low-penetrance variants and recessive inheritance genes were excluded. Deidentified pedigrees were analyzed to determine clinical suspicion of PV. MGPT was performed on 10,975 patients with cancer: 1,134 (10.3%) were found to have ≥1 PV in a moderate or highly penetrant cancer susceptibility gene. Three hundred seven (2.8%) of the PVs were not predicted on the basis of patient's personal cancer history alone, and 192 (1.7%) remained unsuspected after patient's cancer diagnosis and review of family cancer histories were considered. Unexpected PVs accounted for 16.9% of the 1,134 patients with a moderate- or high-penetrance PV. Most frequent unexpected variants were MITF (n = 18), PMS2 (n = 18), ATM (n = 17), BRIP1 (n = 17), HOXB13 (n = 14), SDHA (n = 12), CHEK2 (n = 11), BRCA2 (n = 7), MSH6 (n = 7), SDHC (n = 7), PALB2 (n = 6), and TP53 (n = 6). Low-penetrance or recessive variants were found in 519 (4.7%) patients. Variants of uncertain significance were found in 3,775 (34.4%). In patients with cancer, MGPT identified a rate of 1.7% PV in unexpected actionable cancer predisposition genes. Findings were more often unexpected (2.8%) when considering only the patient cancer history. These findings may justify consideration of broader MGPT panels in patients with cancer, given implications for subsequent surveillance, cascade testing, and treatment options dependent on specific findings.

Determining Filipinos’ Preferences for Colorectal Cancer Screening Tests: Insights From a Choice-Based Conjoint Analysis

Filipinos in the U.S. have worse colorectal cancer screening rates and outcomes than non-Hispanic Whites, despite 85% of Filipinos being proficient in English and having insurance rates, education, and incomes that exceed those of the general population. To begin to address this disparity, the authors used conjoint analysis-a method that assesses complex decision making-to better understand Filipinos' preferences for the different colorectal cancer screening test options. The authors conducted a conjoint analysis survey among unscreened Filipinos aged ≥40 years at average risk for colorectal cancer to determine the relative importance of screening test attributes in their decision making (e.g., modality, effectiveness at reducing colorectal cancer risk, bowel prep). The authors also performed simulations to estimate the proportion of people who would prefer to do an annual fecal immunochemical test or colonoscopy every 10 years for their screening. Overall, 105 Filipinos completed the survey; most respondents were female (74.3%) and aged 40-49 years (84.8%). The authors observed that test modality was the most important factor in respondents' decision making. After conducting simulations using the conjoint analysis data, the authors noted that 70 (66.7%) Filipinos preferred to do an annual fecal immunochemical test for their screening, whereas 35 (33.3%) wanted to do a colonoscopy every 10 years. The authors found that 2 in 3 Filipinos prefer fecal immunochemical test to colonoscopy for their colorectal cancer screening. To address colorectal cancer disparities in the Filipino community, investigators, health systems, public health agencies, and community organizations need to develop culturally tailored, sustainable interventions, and such programs may want to focus on improving education on and access to fecal immunochemical test.

Digital continuous glucose monitoring systems for patients with HIV-diabetes comorbidity in Ethiopia: a situational analysis

In patients with HIV-diabetes mellitus (DM) comorbidity, invasive blood glucose testing can increase the risk of HIV-related blood contamination and discourage regular glucose monitoring. Digital continuous glucose monitoring (CGM) systems may allow real-time glucose monitoring without the need for blood specimens. However, in high-burden HIV-DM countries, current glucose monitoring practices and their challenges are insufficiently explored to guide digital CGM research and developments. This study sought to explore the lived experiences of patients with HIV-DM comorbidity and their healthcare providers regarding glucose monitoring practices, and their openness to CGM and other digital technologies, to provide formative insights for a planned implementation trial of digital CGM in Ethiopia. A phenomenological qualitative study was conducted among patients with HIV-DM and their providers at the two largest public hospitals in Ethiopia. Both groups were interviewed face-to-face about DM clinic workflows, blood glucose monitoring and self-testing practices, and potential benefits and limitations of digital CGM systems. Interviews were audio-recorded, transcribed verbatim, and analyzed thematically. A total of 37 participants were interviewed, consisting of 18 patients with HIV-DM comorbidity and 19 healthcare providers. Patients had an average (min-max) duration of living with HIV and DM of 14 (8–31) and 6.6 (1–16) years, respectively, with 61% taking insulin—33% alone and 28% alongside oral hypoglycemic agents—and 79% having comorbid hypertension. The thematic analysis identified five main themes: “Diabetes routine clinical care and follow-up”, “Blood glucose monitoring practices”, “Perceptions about digital CGMs”, “Technology adoption”, and “Financial coverage”. Home self-testing was deemed beneficial, but the need for regular follow-ups, result cross-referencing, and glucometer reliability were emphasized. Patients performed fingerstick themselves or with family members, expressing concerns about waste disposal and the risk of HIV transmission. They rely mainly on health insurance for DM care. Patients and providers are happy with the quality of DM services but note a lack of integrated HIV-DM care. Very few providers and patients possessed background information about digital CGMs, and all have not yet utilized them in practice, but expressed keen interest in trying them, representing an important step for upcoming CGM clinical trials in these settings. Given the crucial role of regular glucose testing in managing HIV-DM comorbidity, it is essential to explore testing options that align with patient preferences and minimize the risk of HIV transmission.

Multi-faceted strategies to advance health equity in colorectal cancer screening in primary care setting: quality improvement project

BackgroundThe aim of this quality improvement (QI) project was to increase Colorectal Cancer (CRC) screening in patients ages 50–75 years from a baseline of 27–40% within 12 months in a primary care clinic in limited resource communities.MethodsThe multidisciplinary QI-team applied the Plan-Do-Study-Act method and developed stakeholder analysis, an Ishikawa fish bone diagram, a process flow map, and a driver diagram. Major barriers to suboptimal CRC screening included limited health literacy, language preferences, absence of stool test options, and knowledge gaps among patients and providers. The outcome measure was CRC screening rates, while stool test and colonoscopy completion rates served as process measures. Major interventions included the use of a patient-navigator, leveraging digital health technology to create a novel CRC screening data dashboard, educating patients and providers, patient centered-shared decision making, and creating messages and educational videos in patient’s preferred languages. We used monthly run charts and statistical process control charts (SPC) for data analysis.ResultsWe observed a sustainable, steady increase in CRC screening rates from baseline rates of 27.0–40.0% (n = 1304/3271) during the study period and 45.6% (n = 1493/3,271) six months post-study, with median rates of 34.0% in the run chart and mean rates of 43.0% in the SPC chart. Furthermore, we observed an increase in colonoscopy completion rates during the study and six months post-study to 65.0% (n = 411/631) and 72.9% (n = 461/631) respectively, from a baseline rate of 25.0%, with a median of 63.0% in the monthly run chart.ConclusionThe increase in CRC screening rates highlights the effectiveness of addressing barriers such as health literacy, language preferences, and knowledge gaps. This underscores the value of a multifaceted approach and the role of a patient navigator in enhancing preventive, patient-centered care. This project focused on population health and addressing social determinants of health to overcome disparities and improve CRC screening in a primary care setting. Continued emphasis on these strategies is likely to further advance colorectal cancer screening efforts.