Optimal Screening Strategies Research Articles

Changes in Staging and Management of Non-Small Cell Lung Cancer (NSCLC) Patients Following the Implementation of Low-Dose Chest Computed Tomography (LDCT) Screening at Kaohsiung Medical University Hospital

Background: Low-dose computed tomography (LDCT) has been widely adopted for lung cancer screening due to its proven ability to reduce lung cancer mortality, especially among high-risk populations. Methods: This retrospective study aims to evaluate the impact of LDCT screening on non-small cell lung cancer (NSCLC) staging at Kaohsiung Medical University Hospital (KMUH) from 2011 to 2020, following the introduction of LDCT in 2013. The study examines the correlation between LDCT screening volume and changes in the distribution of NSCLC stages, particularly early-stage (stages 0 and I) and late-stage (stage IV) diagnoses. Additionally, it explores the differences in histopathological subtypes, focusing on adenocarcinoma and squamous cell carcinoma, and assesses the impact of early detection on five-year survival rates. Results: The results show a significant increase in early-stage NSCLC diagnoses, particularly in adenocarcinoma cases, where early-stage diagnoses rose from 10.4% in 2010 to 38.7% in 2019. However, the number of stage IV cases remained stable, indicating that LDCT may not substantially reduce late-stage diagnoses. Pearson’s correlation analysis demonstrated a strong positive correlation between LDCT screening and early-stage NSCLC detection, particularly for adenocarcinoma (p < 0.001), though the early detection of squamous cell carcinoma and small cell carcinoma remained limited. Conclusions: The study concludes that LDCT screening plays a crucial role in improving early NSCLC detection and five-year survival rates. Future research should focus on optimizing screening strategies to capture more at-risk populations and enhance the detection of harder-to-diagnose subtypes like squamous cell carcinoma.

Prevalence of Human Papillomavirus (HPV) Infection and its Association With Pap Smear Findings Among Women Attending a Gynecology Clinic in Khorasan Razavi-Iran.

Human papillomavirus (HPV) infection is the most common sexual transmitted disease and Pap smears and HPV testing are crucial for early detection. Advancements in HPV testing improve accuracy, but optimal screening strategies are still debated. This cross-sectional study explores HPV genotypes and predictors of infection among Iranian women undergoing gynecological screening. Study Design: A retrospective cross-sectional study. Women undergoing their initial cervical screening enrolled in this study. Cervical cytology samples for Pap smear analysis were collected from women referred to the genetic laboratory of Academic Center for Education Culture and Research (ACECR), Khorasan Razavi, during gynecological visits, adhering to standardized liquid-based cytology protocols. These samples were obtained over a one-year period since January 2023. Statistical analyses were conducted using SPSS version 21.0, with a significance level set at P<0.05. A total of 328 women enrolled in this study. The mean age of participants was 36±11 years and the overall HPV prevalence was 37.5% (n=123). Among HPV-positive women, nearly half (48.7%) had a single HPV genotype. Genotypes 6 (13%), 16 (12.3%), and 53 (6.7%) were the most prevalent types. Notably, high-risk HPV genotypes (16 and 18 among all) were identified in one-fourth of the study population. Women with endocervical/transformation zone cells had 25% higher odds of having HPV infection, and having mild, moderate, and severe inflammation increased the odds of having HPV infection by 14%, 11%, and 20%, respectively. The considerably high prevalence of HPV infection highlights the significance of HPV prevention programs in this population. Neither bacterial vaginosis nor candida infection showed a direct link to HPV positivity.

Synthesized economic evidence on the cost-effectiveness of screening familial hypercholesterolemia

BackgroundFamilial hypercholesterolemia (FH) is a prevalent genetic disorder with global implications for severe cardiovascular diseases. Motivated by the growing recognition of the need for early diagnosis and treatment of FH to mitigate its severe consequences, alongside the gaps in understanding the economic implications and equity impacts of FH screening, this study aims to synthesize the economic evidence on the cost-effectiveness of FH screening and to analyze the impact of FH screening on health inequality.MethodsWe conducted a systematic review on the economic evaluations of FH screening and extracted information from the included studies using a pre-determined form for evidence synthesis. We synthesized the cost-effectiveness components involving the calculation of synthesized incremental cost-effectiveness ratios (ICERs) and net health benefit (NHB) of different FH screening strategies. Additionally, we applied an aggregate distributional cost-effectiveness analysis (DCEA) to assess the impact of FH screening on health inequality.ResultsAmong the 19 studies included, over half utilized Markov models, and 84% concluded that FH screening was potentially cost-effective. Based on the synthesized evidence, cascade screening was likely to be cost-effective, with an ICER of $49,630 per quality-adjusted life year (QALY). The ICER for universal screening was $20,860 per QALY as per evidence synthesis. The aggregate DCEA for six eligible studies presented that the incremental equally distributed equivalent health (EDEH) exceeded the NHB. The difference between EDEH and NHB across the six studies were 325, 137, 556, 36, 50, and 31 QALYs, respectively, with an average positive difference of 189 QALYs.ConclusionsOur research offered valuable insights into the economic evaluations of FH screening strategies, highlighting significant heterogeneity in methods and outcomes across different contexts. Most studies indicated that FH screening is cost-effective and contributes to improving overall population health while potentially reducing health inequality. These findings offer implications that policies should promote the implementation of FH screening programs, particularly among younger population. Optimizing screening strategies based on economic evidence can help identify the most effective measures for improving health outcomes and maximizing cost-effectiveness.

Lung cancer screening in never smokers.

Low-dose computed tomography (LDCT) lung cancer screening has been established in smokers, but its role in never smokers remains unclear. The differences in lung cancer biology between smokers and nonsmokers highlight the importance of a discriminated approach. This overview focuses on the emerging data and implementation challenges for LDCT screening in nonsmokers. The first LDCT screening study in nonsmokers enriched with risk factors demonstrated a lung cancer detection rate double that of the phase 3 trials in smokers. The relative risk of lung cancer detected by LDCT has also been found to be similar amongst female never smokers and male ever smokers in Asia. Majority of lung cancers detected through LDCT screening are stage 0/1, leading to concerns of overdiagnosis. Risk prediction models to enhance individual selection and nodule management could be useful to enhance the utility of LDCT screening in never smokers. With appropriate risk stratification, LDCT screening in never smokers may attain similar efficacy as compared to smokers. A global effort is needed to generate evidence surrounding optimal screening strategies, as well as health and economic benefits to determine the suitability of widespread implementation.

HIV-1 residual risk and pre-treatment drug resistance among blood donors: A sentinel surveillance from Gabon.

Surveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon. A sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance. Five HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02_AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02_AG, P = 0.3 and Recombinants, P = 0.5). This sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors.

Optimal malarial screening strategy in Australian blood donors: A cost-effectiveness analysis.

The risk of transfusion-transmitted malaria (TTM) infections is extremely low in Australia, and the cost-effectiveness of the current screening strategy has not been assessed. This study aims to conduct a cost-effectiveness analysis of different malaria screening strategies in blood donors as part of the risk-based decision-making framework. A decision tree model was developed to assess the cost-effectiveness of five alternative malaria screening strategies from a healthcare sector perspective. Screening strategies combining total or partial removal of malaria testing with different deferral periods were considered. The probabilities of developing severe and uncomplicated TTM were based on a literature review of cases in non-endemic areas since 2000. The health outcomes were quantified using disability-adjusted life years. The costs of non-returning donors due to deferral were also included. Deterministic and probabilistic sensitivity analyses were conducted to account for data uncertainty. The residual risks for all strategies were so low that the costs, mortality and morbidity associated with TTM are almost negligible. The overall costs were predominantly influenced by the costs of non-returning blood donors. As a result, removal of malaria testing and applying a 28-day deferral for at-risk donors were the least costly and most cost-effective of all the options considered. The current screening strategy for malaria in blood donors in Australia is not an efficient use of healthcare resources. Partial or total removal of malaria testing would bring significant cost savings without significantly compromising blood safety.

A mathematical simulation model to determine the optimal endoscopic screening strategy for detection of H. pylori-naïve gastric neoplasms.

The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs). EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50years) and intervals (2/5/10years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes. Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20mm in size, and the deep submucosal invasion rate was less than 30%. A mathematical simulation model revealed that screening every 5years starting at 45years of age could efficiently assist in identifying HpNGNs at an early stage.

Screening for chronic kidney disease: change of perspective and novel developments.

Chronic kidney disease (CKD) is a serious health issue because of its rising global prevalence and its complications, such as kidney failure and cardiovascular disease (CVD). CKD is mainly diagnosed late or undiagnosed, delaying or missing the initiation of preventive interventions. Screening can prevent or delay progressive kidney function decline and CVD. This article reviews diagnostic tests and risk prediction developments for patients with CKD, highlights key evidence for targeted screening, and provides new insights into population-wide screening. Large cohort studies and clinical trial data established the strong association of albuminuria with CKD outcomes, supporting the role of albuminuria as target of CKD screening and treatment. Significant advances in both risk prediction of CKD and CVD in CKD patients and treatment options provided new evidence for the relevance and implications of CKD screening. Guidelines recommend targeted screening in high-risk patients, but evidence suggests limited adherence to guideline recommendations. More recently, population-wide screening has been investigated as another approach, showing potential effectiveness and cost-effectiveness. There is increasing evidence for the methods, implications, and effectiveness of CKD screening. Implementing and optimizing screening strategies requires enhanced awareness and understanding of the possibilities for CKD screening within different healthcare systems.

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.

Strategic Implementation of Fragile X Carrier Screening in China: A Focused Pilot Study

Fragile X syndrome (FXS) is the leading genetic cause of intellectual disability and autism spectrum disorders. Female premutation carriers exhibit no obvious symptoms during reproductive age, but the premutation allele can expand to full mutation when transmitted to the fetus.. Given the relatively low prevalence but large population, the distinct healthcare system, the middle-income economic status, and low awareness among public and medical professionals, the optimal genetic screening strategy remains unknown. We conducted a pilot study of Fragile X carrier screening in China, involving 22,245 pregnant women and women with childbearing intentions, divided into control and pilot groups. The prevalence of Fragile X carriers in the control group was 1/850, similar to East Asian populations. Strikingly, the prevalence of Fragile X carriers in the pilot group was 1/356, which can be attributed to extensive medical training, participant education, and rigorous genetic counseling and testing protocols. Cost-effectiveness analyses of four strategies—no screening, population-based screening, targeted screening, and our pilot screening—indicated that our pilot screening was the most cost-effective option. A follow-up survey revealed that 55% of respondents reported undergoing screening due to their family history. We have successfully established a standardized system, addressing the challenges of low prevalence, limited awareness, and genetic testing complexities. Our study provides practical recommendations for implementing Fragile X carrier screening in China.

#2205 Varying practice patterns in prevention, screening and treatment of diabetes early after kidney transplantation: a European survey

Abstract Background and Aims Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there is no consensus on preventive measures, nor on the optimal screening and treatment strategy. Method The European Renal Association—DESCARTES working group—distributed a web-based survey to transplant centers across Europe to gather information on the risk assessment, screening procedures and management practices for the prevention and treatment of PTDM in kidney-transplant recipients. Results Answers were obtained from 121 transplant centers across 15 European countries. Screening practices for pre-existing diabetes during the transplant work-up varied considerably, with only 13% of centers using the recommended oral glucose tolerance test (OGTT), while 14% did not screen at all. At transplantation, 19% (n = 23) of centers tailored the immunosuppressive regimen based on perceived PTDM risk, employing strategies like cyclosporin use (12/23), or early steroid withdrawal (2/23). Fifty-two percent adopted strict glycemic control with long-acting insulin in the first days post-transplant. Sixty-eight percent had defined screening protocols for early PTDM (45 days—six months), mostly based on fasting glycemia and/or HbA1c, while only 8/82 incorporated an OGTT. Changes in immunosuppression were considered by 41% in cases of early hyperglycemia (&amp;lt;45 days) and by 58% in established PTDM (&amp;gt;45 days). Besides insulin therapy, dipeptidyl peptidase-4 (DPP4) inhibitors and metformin were most frequently used to manage early hyperglycemia (&amp;lt;45 days) and PTDM (&amp;gt;45 days). Conclusion This European survey underscores significant variation in PTDM prevention, screening, and treatment practices, emphasizing the imperative for clearer guidance in approaching this complication.

Unawareness of partner risk factors thwarts implementation of USPSTF recommendations for HIV pre-exposure prophylaxis in primary care

ABSTRACT The United States Preventive Services Task Force recommends pre-exposure chemoprophylaxis for persons at high risk of HIV exposure. The optimal screening strategy for at-risk individuals in primary care is not known. We evaluated the strategy of universal screening and discussed challenges to the implementation of this recommendation in primary care. Around 430 of 500 (86%) screening surveys were completed. Mutual monogamy was common but monogamous partners with recent negative HIV testing were uncommon. Likewise, among heterosexually active men and women, inconsistent condom use was common. Such individuals would be on guideline for HIV pre-exposure prophylaxis (PrEP) if their partner was at risk for HIV exposure. None of these potentially at-risk individuals met the criteria for PrEP, but 13% lacked knowledge of their partners' sexual and behavioral risk factors, preventing a clear decision on whether PrEP should be used. Our screen identified no individuals who clearly met the guideline criteria for HIV PrEP. We conclude that universal screening for HIV PrEP in primary care is unlikely to be an efficient strategy; targeted screening is likely more appropriate. Moreover, the 2019 guidelines for heterosexually active men and women rely on information that is often unknown to the patient, which makes these guidelines difficult to implement. Future guidelines should address these problems.

Evaluation of reticulocyte indices and mathematical formulas for beta-thalassemia carriers screening among Egyptian beta-thalassemia patients’ families

Background Egypt lies within the global thalassemia belt, where beta-thalassemia presents a notable socioeconomic burden. Patients and methods One hundred fifty-seven relatives of beta-thalassemia patients were included in this cross-sectional study. It aimed to ascertain a cost-efficient and accurate screening approach for identifying beta-thalassemia carriers (BTC) by evaluating some erythrocyte and reticulocyte parameters measured on Advia 2120 analyzer (Siemens) and assessing four mathematical Formulas (Metzner index, Green and King et al., Roth et al., and Vicinanza et al. formulas). Results Participants were stratified into distinct categories: BTC (42%), normal (24.2%), mild iron-deficiency anemia (IDA) (17.2%), severe IDA (3.8%), and a subset with both IDA and BTC (mix group) accounting for 12.7%. Receiver operating characteristic curve analysis identified absolute reticulocyte count as the optimal discriminator (area under a curve=0.837) between BTC and IDA. The Mentzer index and Green and King et al. formula demonstrated superior diagnostic utility among the evaluated formulas. However, none of the formulas effectively distinguished between BTC and the mix group, a frequently overlooked and challenging group for diagnosis. Interestingly, our data highlighted absolute reticulocyte count and percentage as the sole parameters capable of distinguishing BTC from the mix group. Consequently, two algorithms were developed. The first one had a good agreement (κ=0.62) with 77.3% concordance, while the second one demonstrated improved screening performance (κ=0.66) with 79.8% agreement. Conclusion The optimal screening strategy involves distinguishing between various categories of both IDA and BTC. Our algorithms, designed as a low-cost and user-friendly mass screening tool, may serve this purpose effectively.

Establishing a screening strategy for non-discriminatory reactive blood donors by constructing a predictive model of hepatitis B virus infection status from a single blood center in China.

When employing the transcription-mediated amplification method for screening blood donors, there are some non-discriminatory reactive results which are screening assay reactive but HBV-DNA discriminatory assay negative. This raises concerns regarding the possibility of false positives among donors, which may lead to permanent deferral of blood donors and affect blood supply. This study aimed to elucidate the infection status of these non-discriminatory reactive blood donors and develop and validate a model to predict individualized hepatitis B status to establish an optimal screening strategy. Supplementary tests were conducted on initial non-discriminating reactive donations to determine their HBV infection status, including repeat testing, viral load, serological marker detection, and follow-up. Primary clinical variables of the donors were recorded. Based on the Akaike information criterion, a stepwise forward algorithm was used to identify the predictive factors for information and construct a predictive model. The optimal screening strategy was determined through cost-effectiveness analysis. At the Blood Center of Zhejiang Province, 435 cases of initial non-discriminatory reactive donations were collected over two successive periods and sub-categorized through repeated testing into the following three groups: non-repeated positive group, non-discriminated positive group, and non-repeated HBV-DNA positive group. The HBV discriminatory rate increased after repeated testing (110/435, 25.29%). According to supplementary tests, the HBV-DNA positivity rate was 65.52% (285/435), and occult HBV infection was a significantly different among groups (χ2 = 93.22, p < 0.01). The HBV serological markers and viral load in the non-repeated positive group differed from those in the other two groups, with a lower viral load and a higher proportion of false positives. The predictive model constructed using a stepwise forward algorithm exhibited high discrimination, good fit, high calibration, and effectiveness. A cost-effectiveness analysis indicated that utilizing repeated discriminatory testing and the predictive model is an extremely beneficial screening approach for non-discriminatory reactive blood donors. Nearly two-third (65.52%) of the non-discriminatory reactive blood donors were HBV-DNA positive. Our innovative approach of constructing a predictive model as a supplementary screening strategy, combined with repeated discriminatory experiments, can effectively identify the infection status of non-discriminatory reactive blood donors, thereby increasing the safety of blood transfusions.

The risk-based breast screening (RIBBS) study protocol: a personalized screening model for young women.

The optimal mammography screening strategy for women aged 45-49years is a matter of debate. We present the RIBBS study protocol, a quasi-experimental, prospective, population-based study comparing a risk- and breast density-stratified screening model (interventional cohort) with annual digital mammography (DM) screening (observational control cohort) in a real-world setting. The interventional cohort consists of 10,269 women aged 45years enrolled between 2020 and 2021 from two provinces of the Veneto Region(northen Italy). At baseline, participants underwent two-view digital breast tomosynthesis (DBT) and completed the Tyrer-Cuzick risk prediction model. Volumetric breast density (VBD) was calculated from DBT and the lifetime risk (LTR) was estimated by including VBD among the risk factors. Based on VBD and LTR, women were classified into five subgroups with specific screening protocols for subsequent screening rounds: (1) LTR ≤ 17% and nondense breast: biennial DBT; (2) LTR ≤ 17% and dense breast: biennial DBT and ultrasound; (3) LTR 17-30% or LTR > 30% without family history of BC, and nondense breast: annual DBT; (4) LTR 17-30% or > 30% without family history of BC, and dense breast: annual DBT and ultrasound; and (5) LTR > 30% and family history of BC: annual DBT and breast MRI. The interventional cohort is still ongoing. An observational, nonequivalent control cohort of 43,000 women aged 45years participating in an annual DM screening programme was recruited in three provinces of the neighbouring Emilia-Romagna Region. Cumulative incidence rates of advanced BC at three, five, and ten years between the two cohorts will be compared, adjusting for the incidence difference at baseline.Trial registration This study is registered on Clinicaltrials.gov (NCT05675085).

Analysis of the current state of cervical cancer prevention awareness and its influencing factors among rural women in Luohe City.

The purpose of this cross-sectional study was to identify the current awareness about cervical cancer prevention among rural women in Luohe City as well as its potential influencing factors. Meanwhile, these data were expected to provide a theoretical basis for Luohe future cervical cancer prevention and therapy. Based on geographical distribution, 40 villages in Luohe City were randomly selected, and questionnaires were given to women in each village. In this study, a total of 4665 questionnaires were distributed, and 4561 valid questionnaires were returned, with a recovery rate of 97.98%. The average score was 4.06 ± 2.46 out of 10. It was found that women had a high awareness rate of cervical cancer screening (55.25%) but a low awareness rate of human papillomavirus (HPV) and HPV vaccine (10.17%). Moreover, univariate and multivariable analyses showed that age > 45 years, low household income, low education level, being a farmer, spouse unemployment, no pregnancy or birth delivery history, no family or personal history of cervical disease, and no previous complimentary 2-cancer screening (i.e., breast cancer and cervical cancer) were all factors influencing the cognitive level of rural women in Luohe City (P < .05). However, ethnicity, marital status, and spouse education level were not correlated with cognitive level (P > .05). In conclusion, low awareness of cervical cancer prevention among rural women in Luohe was correlated with individual, family, and social factors. So it was recommended to cultivate the rural population knowledge, optimize screening strategies, and conduct targeted cervical cancer prevention and treatment in rural regions.

A cost-effectiveness analysis of lung cancer screening with low-dose computed tomography and a polygenic risk score

IntroductionSeveral studies have proved that Polygenic Risk Score (PRS) is a potential candidate for realizing precision screening. The effectiveness of low-dose computed tomography (LDCT) screening for lung cancer has been proved to reduce lung cancer specific and overall mortality, but the cost-effectiveness of diverse screening strategies remained unclear.MethodsThe comparative cost-effectiveness analysis used a Markov state-transition model to assess the potential effect and costs of the screening strategies incorporating PRS or not. A hypothetical cohort of 300,000 heavy smokers entered the study at age 50–74 years and were followed up until death or age 79 years. The model was run with a cycle length of 1 year. All the transition probabilities were validated and the performance value of PRS was extracted from published literature. A societal perspective was adopted and cost parameters were derived from databases of local medical insurance bureau. Sensitivity analyses and scenario analyses were conducted.ResultsThe strategy incorporating PRS was estimated to obtain an ICER of CNY 156,691.93 to CNY 221,741.84 per QALY gained compared with non-screening with the initial start age range across 50–74 years. The strategy that screened using LDCT alone from 70–74 years annually could obtain an ICER of CNY 80,880.85 per QALY gained, which was the most cost-effective strategy. The introduction of PRS as an extra eligible criteria was associated with making strategies cost-saving but also lose the capability of gaining more LYs compared with LDCT screening alone.ConclusionThe PRS-based conjunctive screening strategy for lung cancer screening in China was not cost-effective using the willingness-to-pay threshold of 1 time Gross Domestic Product (GDP) per capita, and the optimal screening strategy for lung cancer still remains to be LDCT screening for now. Further optimization of the screening modality can be useful to consider adoption of PRS and prospective evaluation remains a research priority.

Gestational diabetes mellitus in Cameroon: prevalence, risk factors and screening strategies.

The burden of gestational diabetes (GDM) and the optimal screening strategies in African populations are yet to be determined. We assessed the prevalence of GDM and the performance of various screening tests in a Cameroonian population. We carried out a cross-sectional study involving the screening of 983 women at 24-28 weeks of pregnancy for GDM using serial tests, including fasting plasma (FPG), random blood glucose (RBG), a 1-hour 50g glucose challenge test (GCT), and standard 2-hour oral glucose tolerance test (OGTT). GDM was defined using the World Health Organization (WHO 1999), International Association of Diabetes and Pregnancy Special Group (IADPSG 2010), and National Institute for Health Care Excellence (NICE 2015) criteria. GDM correlates were assessed using logistic regressions, and c-statistics were used to assess the performance of screening strategies. GDM prevalence was 5·9%, 17·7%, and 11·0% using WHO, IADPSG, and NICE criteria, respectively. Previous stillbirth [odds ratio: 3·14, 95%CI: 1·27-7·76)] was the main correlate of GDM. The optimal cut-points to diagnose WHO-defined GDM were 5·9 mmol/L for RPG (c-statistic 0·62) and 7·1 mmol/L for 1-hour 50g GCT (c-statistic 0·76). The same cut-off value for RPG was applicable for IADPSG-diagnosed GDM while the threshold was 6·5 mmol/L (c-statistic 0·61) for NICE-diagnosed GDM. The optimal cut-off of 1-hour 50g GCT was similar for IADPSG and NICE-diagnosed GDM. WHO-defined GDM was always confirmed by another diagnosis strategy while IADPSG and GCT independently identified at least 66·9 and 41·0% of the cases. GDM is common among Cameroonian women. Effective detection of GDM in under-resourced settings may require simpler algorithms including the initial use of FPG, which could substantially increase screening yield.

Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors.

Genetic, lifestyle, reproductive, and anthropometric factors are associated with the risk of developing breast cancer. However, it is not yet known whether polygenic risk score (PRS) and absolute risk based on a combination of risk factors are associated with the risk of progression of breast cancer. This study aims to estimate the distribution of sojourn time (pre-clinical screen-detectable period) and mammographic sensitivity by absolute breast cancer risk derived from polygenic profile and the other risk factors. The authors used data from a population-based case-control study. Six categories of 10-year absolute risk based on different combinations of risk factors were derived using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm. Women were classified into low, medium, and high-risk groups. The authors constructed a continuous-time multistate model. To calculate the sojourn time, they simulated the trajectories of subjects through the disease states. There was little difference in sojourn time with a large overlap in the 95% confidence interval (CI) between the risk groups across the six risk categories and PRS studied. However, the age of entry into the screen-detectable state varied by risk category, with the mean age of entry of 53.4years (95% CI, 52.2-54.1) and 57.0years (95% CI, 55.1-57.7) in the high-risk and low-risk women, respectively. In risk-stratified breast screening, the age at the start of screening, but not necessarily the frequency of screening, should be tailored to a woman's risk level. The optimal risk-stratified screening strategy that would improve the benefit-to-harm balance and the cost-effectiveness of the screening programs needs to be studied.

Optimal Screening and Detection Strategies for Cervical Lesions: A Retrospective Study.

Background: Cervical cancer is the fourth most common cancer among women worldwide. Cervical cancer usually develops from human papillomavirus (HPV) infection, which leads to cervical intraepithelial neoplasia (CIN1/2/3) and eventually invasive cervical cancer. Therefore, early-screening and detection of cervical lesions are crucial for preventing and treating cervical cancer. However, different regions have different levels of medical resources and availability of diagnostic methods. There is a need to compare the efficiency of different methods and combinations for detecting cervical lesions and provide recommendations for the optimal screening and detection strategies. Methods: The current clinical methods for screening and detection of cervical lesions mainly include TruScreen (TS), Thinprep cytologic test (TCT), HPV testing, and colposcopy, but their sensitivity and specificity vary and there is no standard protocol recommended. In this study, we retrospectively reviewed 2286 female samples that underwent cervical biopsy and compared the efficiency of different methods and combinations for detecting cervical lesions. Results: HPV screening showed the highest sensitivity for identifying women with CIN2+ cervical lesions compared with other single methods. Our results also showed the importance and necessary of the secondary diagnostic test like TCT and TS as a triage method before colposcopy examination and guided biopsy. Conclusions: Our study provides recommendations for the optimal screening and detection strategies for cervical lesions in different regions with different levels of development. As a non-invasive, easily operated, and portable device, TS is a promising tool to replace TCT for detecting cervical lesions in the health care center with insufficient medical resources.