Cost-effectiveness Of Screening Strategies Research Articles

A-354 Evaluating Emergent POC Technology for Sickle Cell Testing in Resource Limited Settings

Abstract Background Sickle cell disease (SCD) represents a collection of inherited hematological disorders characterized by abnormal sickle-shaped erythrocytes resulting in an increased risk of morbidity and mortality. SCD represents a significant global health burden, affecting more than 300,000 newborns per year. Most of these births occur in resource limited areas, including sub-Saharan Africa, where the mortality rate before the age of five is estimated to be as high as 50-80% and the existing infrastructure and resources cannot support most current and robust methods that offer hemoglobin variant detection and quantification for the diagnosis and monitoring of SCD. While newborn screening programs (NBS) to identify individuals affected with SCD have demonstrated efficacy in reducing morbidity and early mortality, NBS programs are limited outside of the US and Europe and face many practical challenges for universal implementation in a resource limited setting. The need for inexpensive and reliable hemoglobin variant detection and quantification at the Point of Care is essential to the diagnosis and management of SCD in resource limited settings with a high prevalence of SCD, and the expansion of NBS programs. This study aims to evaluate an inexpensive testing strategy using two methodologies for POC screening and confirmation of SCD that could be supported in a low resource setting. Methods The two-step testing strategy for evaluation of POC testing for hemoglobin variant detection and quantification included testing residual specimens from normal and known sickle cell patients by first screening with the HemoTypeSC, a qualitative lateral flow immunoassay (LFIA) that has improved sensitivity and specificity from other available LFIA methodologies given the use of monoclonal antibodies for the detection of hemoglobin variants. Confirmatory testing and quantification of hemoglobin variants was accomplished with the use of the Gazelle POC test a miniaturized chip-based cellulose acetate electrophoresis device capable of identification and quantification of normal and variant hemoglobin. Statistical evaluation of device performance and clinical agreement between the device and known disease status was achieved in EP evaluator. Results The two-tier testing strategy demonstrated effective and inexpensive mechanism for SCD screening and confirmation. Overall, the HemoTypeSC and Gazelle demonstrated 100% qualitative agreement between methods, with the total cost of the two-tiered testing strategy estimated at under $6 per sample. Conclusions In conclusion, the two-tiered approach using the HemoTypeSC and Gazelle yielded a practical and cost-effective strategy for screening and confirmation of hemoglobin variants for the detection and monitoring of SCD. Both the strip and chip-based methodologies provide rapid results, are accessible at the point-of-care, and require minimal sample volume, a feature ideal for use in a pediatric population in low resource settings. Overall, these methods show promise for the use and expansion of NBS programs to improve public health initiatives for the diagnosis of SCD.

Cost-effective endoscopic screening for gastric cancer in a cohort with low Helicobacter pylori prevalence.

Periodic endoscopic screening for gastric cancer (GC) is widely performed in East Asia; however, the optimal screening strategy remains unclear. This study aimed to determine the most cost-effective endoscopic screening strategy for the detection and treatment of GC in a cohort with a low Helicobacter pylori prevalence. The following data were retrospectively extracted from participants who received screening endoscopy between April 2019 and March 2023: age, H. pylori infection status, presence of intestinal metaplasia, pathological diagnosis of GC, and the interval between the most recent endoscopies. A Markov state transition model was constructed based on the cohort data. The cost-effectiveness of 15 strategies with different starting ages (40/50/60years) and screening intervals (1/2/3/4/5years) was compared. The net monetary benefit (NMB) and incremental cost-effectiveness ratio (ICER) of quality-adjusted life-years gained by treatment were used as outcomes. A simulation model was constructed based on the cohort data of 94 137 participants (mean age 54.5years, males 57.9%; 74.4% H. pylori-naïve, 94.2% intestinal metaplasia-negative). The results of the base-case analysis showed that the screening strategy of 4-year intervals starting at the age of 40years had the highest NMB (97 401 578 yen). In both the Monte Carlo simulation and one-way sensitivity analysis with a varying probability of H. pylori infection status transition, the ICER was superior in the screening strategy every 4years, starting at age 40years. Our simulation showed that endoscopic screening at 4-year intervals starting at the age of 40years was the most cost-effective method.

The Clinical Usefulness of a Glaucoma Polygenic Risk Score in 4 Population-Based European Ancestry Cohorts

ObjectiveWe used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts. DesignSecondary analysis of four prospective population-based studies. ParticipantsWe included four European-ancestry cohorts: the United States (US) based Nurses’ Health Study (NHS), NHS2, and the Health Professionals Follow-up Study, and the Rotterdam Study (RS) in the Netherlands. The US cohorts included female nurses and male health professionals aged 55+ years. The RS included residents aged 45 years or older living in Rotterdam, the Netherlands. MethodsPRS weights were estimated by applying the Lassosum method on imputed genotype and phenotype data from the UK-Biobank. This resulted in 144,020 variants, single nucleotide polymorphism (SNPs) and indels, with non-zero betas that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models’ concordance (Harrell’s C-statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits. Main Outcome MeasuresThe relative risk for POAG and Harrell’s C-statistic (the equivalent of an area-under-the-curve for longitudinal models). ResultsAmong 1,046 cases and 38,809‬ controls, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08, 5.18) in the US cohorts, and 4.89 (2.93, 8.17) in the Rotterdam Study, compared with participants with median genetic risk (3rd quintile). In restricted cubic spline analyses, the relation between continuous PRS and POAG risk increased exponentially in the US and Rotterdam cohorts (Pspline<0.05). Combining age, sex, intraocular pressure >25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (0.73, 0.75). Adding the PRS to this model improved the concordance to 0.82 (0.80, 0.84). In a meta-analysis of all cohorts, cases in the highest tertile had a larger cup-disc ratio at diagnosis, by 0.11 (0.07, 0.15), and a 2.07-fold increased risk of requiring glaucoma surgery (1.19, 3.60). ConclusionsIncorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

Chronic thromboembolic pulmonary hypertension is an uncommon complication of COVID-19: UK national surveillance and observational screening cohort studies.

Pulmonary embolism (PE) is a well-recognised complication of coronavirus disease 2019 (COVID-19) infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be established. We evaluated the CTEPD/CTEPH referral rate to the UK national multidisciplinary team (MDT) during the 2017-2022 period to establish the national incidence of CTEPD/CTEPH potentially attributable to COVID-19-associated PE with historical comparator years. All individual cases of suspected CTEPH were reviewed by the MDT for evidence of associated COVID-19. In a separate multicentre cohort, the risk of developing CTEPH following hospitalisation with COVID-19 was calculated using simple clinical parameters at a median of 5 months post-hospital discharge according to existing risk scores using symptoms, ECG and N-terminal pro-brain natriuretic peptide. By the second year of the pandemic, CTEPH diagnoses had returned to the pre-pandemic baseline (23.1 versus 27.8 cases per month; p=0.252). Of 334 confirmed CTEPD/CTEPH cases, four (1.2%) patients were identified to have CTEPH potentially associated with COVID-19 PE, and a further three (0.9%) CTEPD without PH. Of 1094 patients (mean age 58 years, 60.4% male) hospitalised with COVID-19 screened across the UK, 11 (1.0%) were at high risk of CTEPH at follow-up, none of whom had a diagnosis of CTEPH made at the national MDT. A priori risk of developing CTEPH following COVID-19-related hospitalisation is low. Simple risk scoring is a potentially effective way of screening patients for further investigation.

The Genetic Diagnostics of Hemochromatosis: Disparities in Low- Versus High-Income Countries.

This study provides a comprehensive overview of hereditary hemochromatosis (HH), a genetic condition characterized by iron overload due to excessive iron absorption. It elucidates diverse inheritance patterns and clinical manifestations by exploring mutations in critical genes such as HFE (hemochromatosis), HJV (hemojuvelin), HAMP (hepcidin antimicrobial peptide), TfR2 (transferrin receptor 2), and FP (ferroportin). The significance of early screening, diagnosis, and personalized management strategies based on genetic classification is emphasized, particularly in terms of high-income vs. low-income countries. Addressing challenges in diagnosis, genetic testing accessibility, and healthcare disparities, the study highlights the importance of early detection, cost-effective screening strategies, and enhancing healthcare outcomes globally. Advanced genetic testing in high-income countries facilitates early diagnosis and management, reducing complications such as liver disease and cardiomyopathy. In contrast, low-income populations face several barriers, including limited access to genetic testing, high costs, and inadequate healthcare infrastructure. Cost-effective serum ferritin (SF) and transferrin saturation (TS) tests and emerging point-of-care (POC) tests offer affordable diagnostic options for low-resource settings. Additionally, the ongoing development of hepcidin measurement methods holds promise for enhancing diagnostic capabilities. Implementing these strategies can aid healthcare providers in improving global HH management and reducing the burden of iron overload complications. Furthermore, the study underscores the need for public health initiatives to raise awareness about HH, promote routine screenings, and advocate for equitable healthcare policies. Collaborative efforts between governments, healthcare organizations, and research institutions are crucial in addressing the global burden of HH. By fostering international cooperation and resource-sharing, it is possible to bridge the gap between high-income and low-income countries, ensuring all individuals have access to the necessary diagnostic and treatment options. This holistic approach can ultimately lead to better health outcomes and improved quality of life for individuals affected by HH worldwide. This comprehensive examination of HH not only illuminates the genetic and clinical aspects of the condition but also provides a roadmap for addressing the multifaceted challenges associated with its diagnosis and management.

Development and Evaluation of Monoclonal Antibodies against CBPP Antigen with the End Goal of Developing an ELISA Kit.

Contagious bovine pleuropneumonia (CBPP) is an infectious and contagious bacterial respiratory disease that affects cattle with significant economic losses to the African animal industry. The use of ELISA kits based on monoclonal antibodies (mAbs) will aid in quick and precise diagnosis of CBPP, contributing to disease control and prevention in cattle. Thus, this research aims to develop and evaluate monoclonal antibodies against CBPP (T1/44) antigen for use in ELISA kits for CBPP diagnosis. Hybridoma technology was used to develop monoclonal antibodies that recognize and bind to the CBPP (T1/44) antigen. The antibody-secreting hybridomas were produced after immunizing mice with purified CBPP antigens. The hybridomas were screened for high sensitivity, specificity, and liking to the antigen. The selected mAbs were assessed for sensitivity and specificity against CBPP antigen using different immunoassays, dot-blot, ELISA, and mouse mAb isotyping. The monoclonal antibodies were profoundly specific, with a higher hindrance to CBPP antigen (<0.50 OD) while lacking cross-reactivity to other antigens. The monoclonal antibodies could distinguish CBPP antigen at low concentrations, showing their high sensitivity (>80% PI). The isotyped mAbs of intrigued appeared to have a place in the IgG class. These identified monoclonal antibodies can be utilized to develop an ELISA kit for CBPP diagnosis, which would give a fast, precise, and cost-effective strategy for screening and checking CBPP in cattle herds.

Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population.

There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea. A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model's variables. In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold. Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.

Barriers and Potential Solutions to Glaucoma Screening in the Developing World: A Review.

Glaucoma is a leading public health concern globally and its detection and management are way more complex and challenging in the developing world. This review article discusses barriers to glaucoma screening in developing countries from the perspective of different key stakeholders and proposes solutions. A literature search was carried out in the electronic catalogs of PubMed, Medline, and Cochrane database of systematic reviews to find studies that focused on barriers and enablers to glaucoma screening. The authors' interpretations were tabulated as descriptive and qualitative data and presented concisely from the point of view of key stakeholders such as the patients and their relatives, care providers, and system/governing bodies. Key barriers to glaucoma care identified are lack of awareness, poor accessibility to ophthalmic centers, inadequately trained human resources, unsatisfactory infrastructure, and nonavailability of financially viable screening programs. Educating care providers, as well as the public, providing care closer to where people live, and developing cost-effective screening strategies are needed to ensure proper identification of glaucoma patients in developing countries. The logistics of glaucoma detection and management are complex. Hence, glaucoma detection programs should be implemented only when facilities for glaucoma management are in place. Understanding the importance of glaucoma screening and its future implications, addressing the various roadblocks, empowering and efficiently implementing the existing strategies, and incorporating novel ones using Artificial Intelligence (AI) and deep learning (DL) will help in establishing a robust glaucoma screening program in developing countries.

Exploring Structural Uncertainty in Cost-Effectiveness Modeling of Gestational Diabetes Screening: An Application Example from Norway.

Screening pregnant women for gestational diabetes mellitus (GDM) has recently been expanded in Norway, although screening eligibility criteria continue to be debated. We aimed to compare the cost-effectiveness of alternative GDM screening strategies and explored structural uncertainty and the value of future research in determining the most cost-effective eligibility criteria for GDM screening in Norway. We developed a probabilistic decision tree to estimate the total costs and health benefits (i.e., quality-adjusted life-years; QALYs) associated with 4 GDM screening strategies (universal, current guidelines, high-risk, and no screening). We identified the most cost-effective strategy as the strategy with the highest incremental cost-effectiveness ratio below a Norwegian benchmark for cost-effectiveness ($28,400/QALY). We excluded inconclusive evidence on the effects of screening on later maternal type 2 diabetes mellitus (T2DM) in the primary analysis but included this outcome in a secondary analysis using 2 different sources of evidence (i.e., Cochrane or US Preventive Services Task Force). To quantify decision uncertainty, we conducted scenario analysis and value-of-information analyses. Current screening recommendations were considered inefficient in all analyses, while universal screening was most cost-effective in our primary analysis ($26,014/QALY gained) and remained most cost-effective when we assumed a preventive effect of GDM treatment on T2DM. When we assumed no preventive effect, high-risk screening was preferred ($19,115/QALY gained). When we assumed GDM screening does not prevent perinatal death in scenario analysis, all strategies except no screening exceeded the cost-effectiveness benchmark. In most analyses, decision uncertainty was high. The most cost-effective screening strategy, ranging from no screening to universal screening, depended on the source and inclusion of GDM treatment effects on perinatal death and T2DM. Further research on these long-term outcomes could reduce decision uncertainty. This article analyses the cost-effectiveness of 4 alternative gestational diabetes mellitus (GDM) screening strategies in Norway: universal screening, current (broad) screening, high-risk screening, and no screening.The current Norwegian screening recommendations were considered inefficient under all analyses.The most cost-effective screening strategy ranged from no screening to universal screening depending on the source and inclusion of GDM treatment effects on later maternal diabetes and perinatal death.The parameters related to later maternal diabetes and perinatal death accounted for most of the decision uncertainty.

The Cost Effectiveness of Newborn Hearing Screening Program: New Approach of Iran Ministry of Health and Medical Education in 2022

Background: In Iran’s newborn hearing screening (NHS) program, OAE and AABR are administered to early identify hearing impairment in the primary health care (PHC) system. Objectives: The aim of this study was to conduct a cost-effectiveness analysis of this program integrated into Iran's health system. Methods: We examined the cost-effectiveness of AABR and OAE screening procedures in infants less than 1 month old. TreeAge 2022 software was used for cost-effective modeling. In this study, QoL and QALY were considered as the outcome measures. To evaluate the robustness of the modeling results, we used one-way sensitivity analysis. A ± 20% variation was utilized to determine target variables and estimate the costs per identification. Results: In 2022, a total of 1,106,072 babies were born in Iran, of whom 1,006,293 underwent hearing impairment screening (coverage rate: 90.97%). Overall, 3,359 of the newborns screened were diagnosed with hearing problems, indicating a mean prevalence of 3.3 per 1000 births. The ICER was equal to 3297.2 US PPP (Purchasing Power Parity) per QALY. According to our results, the dominant cost-effective strategy for hearing impairment screening was OAE plus AABR. After 1000 iterations, the second cost-effective strategy was found to be OAE alone, according to Monte Carlo simulation modeling. Conclusions: In this study, we evaluated the cost-effectiveness of the NHS program for detecting hearing impairment in over a million births in Iran. A two-step screening approach, including OAE and AABR, was found to be the dominant cost-effective strategy to identify newborns with hearing impairment.

The impact of alternate HPV vaccination and cervical screening strategies in Japan: a cost-effectiveness analysis

The Japanese 2020 cervical screening guidelines recommend conventional cervical cytology screening every 2-years for women aged 20-69 years. The nonavalent human papillomavirus (HPV) vaccine has also recently been approved in Japan. We therefore evaluated the cost-effectiveness of cervical cancer screening strategies alongside universal nonavalent HPV vaccination of girls (12-16 years). A cost-effectiveness analysis was performed using an age-specific Markov microsimulation model for Japan to evaluate total costs, quality adjusted life-years (QALYs) gained, incremental cost-effectiveness ratios (ICER), colposcopies, biopsies, precancer and cervical cancer treatments for 29 combined vaccination and screening strategies (conventional cytology, liquid-based cytology (LBC), HPV testing, and HPV self-collection). A cohort of 100,000 girls (12-16 years old) over a lifetime offered the nonavalent HPV vaccine was used (current vaccination coverage=0.08%, current screening coverage=43.7%). A discount rate of 3% was applied to costs and QALYs. Univariate and probabilistic sensitivity analysis was performed to assess robustness of the findings. Costs were reported in US dollars (2023). Compared with conventional cytology, evaluated strategies would incur an additional cost of US$839,280-738,182,669 and gain 62,755-247,347 quality-adjusted-life-years. HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be most cost-effective (ICER= US$7511 per QALY gained). At a willingness-to-pay (WTP) of 1-times gross domestic product (GDP) per capita, the probability of it being cost-effective was 70%. At historically high vaccination coverage (70%) ICERs decreased overall but did not affect the ranking of the most cost-effective strategy. While a 5-yearly interval became more cost-effective than a 3-yearly interval. Including HPV self-collection for under-screened women made all strategies more cost-effective. At current cervical screening participation (43.7%) and low vaccination coverage (<1.0%), HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be the most cost-effective screening strategy compared to conventional cytology (2-yearly). Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17H03589) and Grants of the National Cancer Center Japan (Gan Kenkyu Kaihatsuhi 31-A-20 and 2023-A-23).

BRCA mutations: screening for germ-line founder mutations among early-onset Syrian breast cancer patients

BackgroundBreast cancer (BC) is the most common female cancers in many countries including Syria. Familial breast cancer or previous family cancer history are considered significant risk factors. Therefore, detecting the prevalence and founder mutations in the population facilitates genetic counselling, risk assessment and the development of a cost-effective screening strategy. In this study, we investigated the three germ-line founder mutations in the BRCA1/2 genes: [NM_007294.4 (BRCA1):c.68_69del (p.Glu23fs), NM_007294.4 (BRCA1):c.5266dup (p.Gln1756fs) and NM_000059.4 (BRCA2):c.5946del (p.Ser1982fs)], to examine their incidence and frequency in early-onset breast cancer cases and determine if they are connected to familial breast cancer. One hundred early diagnosed BC females (≤ 40 years old) with no other type of cancer were recruited. Genomic DNA was isolated from peripheral blood samples, and mutations were investigated using the Amplification-Created Restriction Site (ACRS) method.ResultsThe family history of cancer was observed in 61% of the cases, of which 35% were breast cancer; however, none of the screened mutations were detected among BC patients.ConclusionsThe investigated germ-line mutations were not common among Syrian female patients with early-onset BC and were not associated with familial BC. Other mutations in the BRCA1/2 genes or other genes may have a contributing role. Future studies and the need to launch nationwide mutation screening tests for BRCA 1/BRCA2 in the Syrian population are recommended.

Cost-Utility Analysis for Colorectal Cancer Screening According to the Initiating Age of National Cancer Screening Program in Korea.

This study aimed to identify the most cost-effective strategy for colorectal cancer screening using the fecal immunochemical test (FIT), focusing on screening initiation age in Korea. We designed Markov simulation models targeting individuals aged 40 years or older. Twelve strategies combining screening initiation ages (40, 45, or 50 years old), termination ages (80 or no limit), and intervals (1 or 2 years) were modeled, and the most cost-effective strategy was selected. The robustness of the results was confirmed using one-way and probabilistic sensitivity analyses. Furthermore, the cost-effectiveness of the qualitative and quantitative FIT methods was verified using scenario analysis. The 2-year interval strategy with a screening age range of 45-80 years was the most cost-effective (incremental cost-utility ratio = KRW 7,281,646/quality adjusted life years). The most sensitive variables in the results were transition rate from advanced adenoma to local cancer and discount rate. The uncertainty in the model was substantially low. Moreover, strategies starting at the age of 40 years were also cost-effective but considered suboptimal. The scenario analysis showed that there was no significant difference in cost-effectiveness between strategies with various relative screening ratio of quantitative and qualitative method. The screening method for advancing the initiation age, as presented in the 2015 revised national screening recommendations, was superior regarding cost-effectiveness. This study provides a new paradigm for the development of a national cancer screening system in Korea, which can be utilized as a scientific basis for economic evaluations.

Breast Cancer Screening in Georgia: Choosing the Most Optimal and Cost-Effective Strategy

ObjectivesTo define the optimal and cost-effective breast cancer screening strategy for Georgia. MethodsWe used the Microsimulation Screening Analysis-Breast (MISCAN-Breast) model that has been adapted to the Georgian situation to evaluate 736 mammography screening strategies varied by interval (biennial and triennial), starting ages (40-60 years), stopping ages (64-84 years), and screening modality (with and without clinical breast examination [CBE]). Quality-adjusted life-years (QALYs) and additional cost (healthcare perspective) compared with no screening per 1000 women were calculated with 3% discount. Major uncertainties (eg, costs) are addressed as sensitivity analyses. ResultsStrategies using a combination of mammography and CBE yielded in substantially higher costs with minimal differences in outcomes compared with mammography-only strategies. The current screening strategy, biennial mammography screening from the age of 40 until 70 years with CBE, is close to the frontier line but requires high additional cost given the QALY gains (€16 218/QALY), well above the willingness-to-pay threshold of €12 720. The optimal strategy in Georgia would be triennial mammography-only screening from age 45 to 66 years with an incremental cost-effectiveness ratio of €12 507. ConclusionsBiennial screening strategies are resource-intensive strategies and may not be feasible for Georgia. By switching to triennial mammography-only strategy from the age of 45 until 66 years, it is possible to offer screening to more eligible women while still gaining substantial screening benefits. This is to address capacity issues which is a common barrier for many Eastern European countries.

Cost-Effectiveness of Liquid Biopsy for Colorectal Cancer Screening in Patients Who Are Unscreened

Despite recommendations for universal screening, adherence to colorectal cancer screening in the US is approximately 60%. Liquid biopsy tests are in development for cancer early detection, but it is unclear whether they are cost-effective for colorectal cancer screening. To estimate the cost-effectiveness of liquid biopsy for colorectal cancer screening in the US. In this economic evaluation, a Markov model was developed to compare no screening and 5 colorectal cancer screening strategies: colonoscopy, liquid biopsy, liquid biopsy following nonadherence to colonoscopy, stool DNA, and fecal immunochemical test. Adherence to first-line screening with colonoscopy, stool DNA, or fecal immunochemical test was assumed to be 60.6%, and adherence for liquid biopsy was assumed to be 100%. For colonoscopy, stool DNA, and fecal immunochemical test, patients who did not adhere to testing were not offered other screening. In colonoscopy-liquid biopsy hybrid, liquid biopsy was second-line screening for those who deferred colonoscopy. Scenario analyses were performed to include the possibility of polyp detection for liquid biopsy. No screening, colonoscopy, fecal immunochemical test, stool DNA, liquid biopsy, and colonoscopy-liquid biopsy hybrid screening. Model outcomes included life expectancy, total cost, and incremental cost-effectiveness ratios. A strategy was considered cost-effective if it had an incremental cost-effectiveness ratio less than the US willingness-to-pay threshold of $100 000 per life-year gained. This study used a simulated cohort of patients aged 45 years with average risk of colorectal cancer. In the base case, colonoscopy was the preferred, or cost-effective, strategy with an incremental cost-effectiveness ratio of $28 071 per life-year gained. Colonoscopy-liquid biopsy hybrid had the greatest gain in life-years gained but had an incremental cost-effectiveness ratio of $377 538. Colonoscopy-liquid biopsy hybrid had a greater gain in life-years if liquid biopsy could detect polyps but remained too costly. In this economic evaluation of liquid biopsy for colorectal cancer screening, colonoscopy was a cost-effective strategy for colorectal cancer screening in the general population, and the inclusion of liquid biopsy as a first- or second-line screening strategy was not cost-effective at its current cost and screening performance. Liquid biopsy tests for colorectal cancer screening may become cost-effective if their cost is substantially lowered.

Sample Pooling: A Cost-Saving Strategy for SARS-CoV-2 Screening in Hospitalized Patients and Attending Relatives – Insights from a Secondary Care Hospital Amidst the Omicron Wave

Background: Pooled real-time reverse transcriptase polymerase chain reaction (rRT-PCR) for SARS-CoV-2 screening is cost- and labor-saving, but data during the Omicron wave are lacking. Objective: To examine a correlation between pooled rRT-PCR as a screening method for SARS-CoV-2 and community COVID-19 incidence. Materials and Methods: The authors retrospectively collected data on pooled rRT-PCR testing as a COVID-19 screening strategy between February 1 and April 30, 2022 in the present study center. Results: In comparison to performing single rRT-PCR testing, pooled rRT-PCR testing strategy reduced the numbers of rRT-PCR testing by 73.36%, 53.63%, and 54.7% in February, March, and April, respectively. The community COVID-19 incidence rate per day (CCIR) averaged 25.43, 48.12, and 80.96 per 100,000 population per day during February, March, and April, respectively. Conclusion: Small pooled rRT-PCR testing of up to five samples may be a cost-effective screening strategy among selected populations despite high CCIR during the Omicron wave. Keywords: Pooled rRT-PCR; Screening

Approach to Fatty Liver Disease in Patients with Type 2 Diabetes

Type 2 diabetes is a major risk factor for development and progression of non-alcoholic fatty liver disease (NAFLD). Fatty liver is prevalent in people with type 2 diabetes, and overweight or obesity in these patients aggravates insulin resistance and steatohepatitis, which appear to be drivers for the disease progression. The goal of screening is not to identify steatosis itself, but rather to identify patients at risk for adverse hepatic outcomes such as cirrhosis, hepatocellular carcinoma, and death from liver disease. The most important risk factors for disease progression are liver fibrosis and its severity. There is a consensus that the FIB-4 (fibrosis-4 index) is the most cost-effective strategy for initial screening of hepatic fibrosis in a clinical setting. At present, there are no approved drugs for the treatment of NAFLD. Clinically significant improvements in NAFLD are achieved with weight loss. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium glucose cotransporter 2 (SGLT2) inhibitors are effective for inducing weight loss in patients with type 2 diabetes, and some GLP-1 RAs and SGLT2 inhibitors have been shown to be effective for treating steatohepatitis. Therefore, GLP-1 RAs and SGLT2 inhibitors should be considered when choosing antidiabetic agents in patients with type 2 diabetes and NAFLD, especially in those who are overweight or obese.

A prospective study on the prevalence of MASLD in people with type-2 diabetes in the community. Cost effectiveness of screening strategies.

As screening for the liver disease and risk-stratification pathways are not established in patients with type-2 diabetes mellitus (T2DM), we evaluated the diagnostic performance and the cost-utility of different screening strategies for MASLD in the community. Consecutive patients with T2DM from primary care underwent screening for liver diseases, ultrasound, ELF score and transient elastography (TE). Five strategies were compared to the standard of care: ultrasound plus abnormal liver function tests (LFTs), Fibrosis score-4 (FIB-4), NAFLD fibrosis score, Enhanced liver fibrosis test (ELF) and TE. Standard of care was defined as abnormal LFTs prompting referral to hospital. A Markov model was built based on the fibrosis stage, defined by TE. We generated the cost per quality-adjusted life year (QALY) gained and calculated the incremental cost-effectiveness ratio (ICER) over a lifetime horizon. Of 300 patients, 287 were included: 64% (186) had MASLD and 10% (28) had other causes of liver disease. Patients with significant fibrosis, advanced fibrosis, and cirrhosis due to MASLD were 17% (50/287), 11% (31/287) and 3% (8/287), respectively. Among those with significant fibrosis classified by LSM≥8.1 kPa, false negatives were 54% from ELF and 38% from FIB-4. On multivariate analysis, waist circumference, BMI, AST levels and education rank were independent predictors of significant and advanced fibrosis. All the screening strategies were associated with QALY gains, with TE (148.73 years) having the most substantial gains, followed by FIB-4 (134.07 years), ELF (131.68 years) and NAFLD fibrosis score (121.25 years). In the cost-utility analysis, ICER was £2480/QALY for TE, £2541.24/QALY for ELF and £2059.98/QALY for FIB-4. Screening for MASLD in the diabetic population in primary care is cost-effective and should become part of a holistic assessment. However, traditional screening strategies, including FIB-4 and ELF, underestimate the presence of significant liver disease in this setting.

QSAR Classification of Beta-Secretase 1 Inhibitor Activity in Alzheimer's Disease Using Ensemble Machine Learning Algorithms

This study focuses on the development of a machine learning ensemble approach for the classification of Beta-Secretase 1 (BACE1) inhibitors in Quantitative Structure-Activity Relationship (QSAR) analysis. BACE1 is an enzyme linked to the production of amyloid beta peptide, a significant component of Alzheimer's disease plaques. The discovery of effective BACE1 inhibitors is difficult, but QSAR modeling offers a cost-effective alternative by predicting the activity of compounds based on their chemical structures. This study evaluates the performance of four machine learning models (Random Forest, AdaBoost, Gradient Boosting, and Extra Trees) in predicting BACE1 inhibitor activity. Random Forest achieved the highest performance, with a training accuracy of 98.65% and a testing accuracy of 82.53%. In addition, it exhibited superior precision, recall, and F1-score. Random Forest's superior performance was a result of its ability to capture a wide variety of patterns and its randomized ensemble approach. Overall, this study demonstrates the efficacy of ensemble machine learning models, specifically Random Forest, in predicting the activity of BACE1 inhibitors. The findings contribute to ongoing efforts in Alzheimer's disease drug discovery research by providing a cost-effective and efficient strategy for screening and prioritizing potential BACE1 inhibitors.

Cervical Cancer Screening and Prevention in Low- and Middle-Income Countries: A Perspective from Bangladesh

Cervical cancer is a major public health concern for women worldwide, particularly in low- and middle-come countries (LMICs). Despite a large number of women (nearly 58 million) are at risk of this preventable cancer, the issue of cervical cancer has not become a public health priority in Bangladesh. The understanding of the challenges and opportunities in Bangladesh about cervical cancer would provide valuable insights for other LMICs also. In this article, we review the epidemiology, risk factors, awareness and treatment of cervical cancer in the context of Bangladesh. Due to lack of awareness and an organized national screening program, the majority of patients are generally diagnosed at the advantaged stages of disease, in spite of having a big window of screening opportunity at precancer stage. Most LMICs lack resources for developing a parallel health service system dedicated for cancer prevention and management. In this context, we propose some recommendations including a cost-effective screening strategy by capitalizing available resources of COVID-19 diagnostic and GenXpert labs, and an innovative female-centric primary healthcare workers and high school-based approaches for generating awareness on cervical cancer risk factors, screening and vaccination. Our proposed strategy could also be effective for other similar settings in LMICs.&#x0D; Bangladesh J Microbiol, Volume 39, Number 2, December 2022, pp 76-82