High-risk Screening Research Articles

Aberrant right subclavian artery in the absence of other prenatal ultrasound findings: Should we still be concerned?

To analyze the value of prenatal diagnostic genetic testing in cases with isolated aberrant right subclavian artery (ARSA). This is a retrospective cohort study, conducted between January 2015-January 2022 in a fetal medicine center. Women who had an ultrasound scan and diagnosed with fetal ARSA were included. Ultrasonographic characteristics, genetic, obstetric, and neonatal outcomes were collected and analyzed. A total of 240 fetuses with ARSA were identified and included to the analysis. Eighty-two of the group had isolated ARSA (34.2%, 82/240), 57 had additional soft markers (23.8%, 57/240) and 101 had additional major ultrasonographic abnormalities (42.1%, 101/240). Genetic results were available in 196 cases (81.7%, 196/240). Seventy-four of isolated ARSA cases underwent genetic testing (90.2%, 74/82). A chromosomal abnormality was present in 60 cases; 54 (22.5%, 54/240) aneuploidies and 6 (2.5%, 6/240) copy number variants. Five (6.1%) of the isolated ARSA cases had chromosomal abnormalities. All of these five cases had prenatal genetic testing due to high-risk aneuploidy screening fetuses who had ARSA with at least one additional anomaly had the highest chromosomal abnormality rate (38.6%, 39/101). Seventy-seven of isolated ARSA cases were liveborn (93.9%, 77/82). Our results supports the evidence from the literature that isolated ARSA confers a very low-risk for aneuploidy, if the aneuploidy screening tests are low-risk. Also, chromosomal microarray analysis did not yield any extra information in isolated ARSA.

Prospective Study of Supplemental Screening With Contrast-Enhanced Mammography in Women With Elevated Risk of Breast Cancer: Results of the Prevalence Round.

Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients. A prospective, single-institution, institutional review board-approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months. Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2-, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM. A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.

The Impact of a Nurse-Led High-Risk Referral Protocol Implemented in a Comprehensive Breast Center.

This quality improvement project implemented a nurse-led high-risk screening referral protocol for earlier identification of women at increased risk for breast cancer. The Breast Cancer Risk Assessment Tool was used at the ma.

How many future dementia cases would be missed by a high-risk screening program? A retrospective cohort study in a population-based cohort.

Risk prediction models aim to identify those at high risk to receive targeted interventions. We aimed to identify the proportion of future dementia cases that would be missed by a high-risk screening program. We identified validated dementia risk prediction models from systematic reviews. We applied these to European Prospective Investigation of Cancer Norfolk, a large population-based cohort of 30,387 individuals with 29 years of linked healthcare data. A maximum of 16.0% (14.7,17.2) and 31.9% (30.2,33.5) of cases arose from the highest risk decile and quintiles, respectively. For every 1000 people considered to be at high risk, a maximum of 235 (215, 255) developed dementia. Seven in every 10 cases of dementia arose from people at normal risk, and eight in every 10 people at high risk did not develop dementia. Individual-level prevention approaches targeted at high-risk groups are unlikely to produce large reductions in disease incidence at the population level. Dementia, a significant public health challenge, is not an inevitability of aging; risk reduction is possible. Several dementia risk prediction models have been validated in the general population, and these aim to identify people at high risk of the disease who can then be targeted with primary prevention interventions. An alternative prevention approach is to focus on interventions that reduce risk across the population, irrespective of risk status. In our study, seven out of every ten people who developed dementia during 29 year follow-up were classed as 'normal-risk' (rather than 'high risk') at baseline. Eight out of every ten people who were at high risk at baseline did not go on to develop dementia. Even if effective, dementia risk reduction efforts based upon targeted high-risk approaches are unlikely to reduce incidence of disease at the population level.

Chromosomal abnormalities detected by chromosomal microarray analysis and pregnancy outcomes of 4211 fetuses with high-risk prenatal indications

With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.

Sex-based differences in the lung immune microenvironment are associated with an increased risk of lung cancer in women

ObjectiveLung cancer remains a major cause of mortality worldwide, necessitating further understanding of carcinogenesis and its driving factors, including those influenced by sex-dependent variables. We hypothesized that sex-specific lung immune composition may contribute to a greater risk of lung cancer in women. MethodsData from 1056 lung cancer screenings were examined for an association between sex and lung cancer risk using time-to-event analyses. Immune profiling by flow cytometry was performed on male and female lungs of 3 independent mouse models: nontumor bearing, KRAS mutated, and urethane-exposed carcinogenic. A comparable analysis was performed on human bronchoalveolar lavage samples (n = 81) from patients with lung cancer. ResultsOf the high-risk screening cohort examined, 60 patients (5.7%) developed lung cancer during median follow-up of 43.4 months. Multivariable stepwise modeling retained female sex (hazard ratio, 1.56; P < .01) and age (P < .01) as prognostic indicators for lung cancer development. Female lung immune profiles in patients included T-cell phenotypes consistent with exhaustion (eg, higher proportions of PD-1+ Ki67–; P = .02), an expanded pool of regulatory T-cells (P = .03), reduced effector T-cell frequencies (P = .008), and enhancements in suppressive myeloid populations (P = .02) versus male patients, and this is recapitulated in mouse studies. ConclusionsFemale smokers display higher risk for lung cancer. In murine models and humans, female sex is associated with robust immunosuppression within the lung. Further examination of this link will be important in developing immune-based approaches to lung cancer interception and their optimal application across the sexes.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients: A prospective phase II study.

Definitive chemoradiotherapy (dCRT) is the standard treatment for unresectable locally advanced esophageal cancer. However, this treatment is associated with substantial toxicity, and most malnourished or elderly patients are unable to complete this therapy. Therefore, there is a need for a more suitable radiotherapy combination regimen for this population. This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002 (NRS-2002) score. Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled. They were treated with S-1 and nimotuzumab with concurrent radiotherapy, followed by surgery or definitive radiotherapy. The primary endpoint was the locoregional control (LRC) rate. A total of 55 patients who met the study criteria were enrolled. After completion of treatment, surgery was performed in 15 patients and radiotherapy was continued in 40 patients. The median follow-up period was 33.3 [95% confidence interval (95% CI), 31.4-35.1)] months. The LRC rate was 77.2% (95% CI, 66.6%-89.4%) at 1 year in the entire population. The overall survival (OS) rate and event-free survival (EFS) rate were 57.5% and 51.5% at 3 years, respectively. Surgery was associated with better LRC [hazard ratio (HR)=0.16; 95% CI, 0.04-0.70; P=0.015], OS (HR=0.19; 95% CI, 0.04-0.80; P=0.024), and EFS (HR=0.25; 95% CI, 0.08-0.75; P=0.013). Most adverse events were of grade 1 or 2, and no severe adverse events occurred. For malnourished or elderly patients with locally advanced esophageal cancer, radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Development of an artificial intelligent model for pre-endoscopic screening of precancerous lesions in gastric cancer

BackgroundGiven the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy.MethodsFrom December 2022 to December 2023, a large-scale screening study was conducted in Fujian, China. Based on traditional Chinese medicine theory, we simultaneously collected tongue images and inquiry information from 1034 participants, considering the potential of these data for PLGC screening. Then, we introduced inquiry information for the first time, forming a multimodality artificial intelligence model to integrate tongue images and inquiry information for pre-endoscopic screening. Moreover, we validated this approach in another independent external validation cohort, comprising 143 participants from the China-Japan Friendship Hospital.ResultsA multimodality artificial intelligence-assisted pre-endoscopic screening model based on tongue images and inquiry information (AITonguequiry) was constructed, adopting a hierarchical prediction strategy, achieving tailored endoscopic recommendations. Validation analysis revealed that the area under the curve (AUC) values of AITonguequiry were 0.74 for overall PLGC (95% confidence interval (CI) 0.71–0.76, p < 0.05) and 0.82 for high-risk PLGC (95% CI 0.82–0.83, p < 0.05), which were significantly and robustly better than those of the independent use of either tongue images or inquiry information alone. In addition, AITonguequiry has superior performance compared to existing PLGC screening methodologies, with the AUC value enhancing 45% in terms of PLGC screening (0.74 vs. 0.51, p < 0.05) and 52% in terms of high-risk PLGC screening (0.82 vs. 0.54, p < 0.05). In the independent external verification, the AUC values were 0.69 for PLGC and 0.76 for high-risk PLGC.ConclusionOur AITonguequiry artificial intelligence model, for the first time, incorporates inquiry information and tongue images, leading to a higher precision and finer-grained pre-endoscopic screening of PLGC. This enhances patient screening efficiency and alleviates patient burden.

Participation in a High-Risk Program Is Associated with a Diagnosis of Earlier-Stage Disease Among Women at Increased Risk for Breast Cancer Development.

High-risk programs provide recommendations for surveillance/risk reduction for women at elevated risk for breast cancer development. This study evaluated the impact of high-risk surveillance program participation on clinicopathologic breast cancer features at the time of diagnosis. Women followed in the authors' high-risk program (high-risk cohort [HRC]) with a diagnosis of breast cancer from January 2015 to June 2021 were identified and compared with the general population of women undergoing breast cancer surgery at Memorial Sloan Kettering Cancer Center (MSK; general cohort [GC]) during the same period. Patient and tumor factors were collected. Clinicopathologic features were compared between the two cohorts and in a subset of women with a family history of known BRCA mutation. The study compared 255 women in the HRC with 9342 women in the GC. The HRC patients were slightly older and more likely to be white and have family history than the GC patients. The HRC patients also were more likely to present with DCIS (41 % vs 23 %; p < 0.001), to have smaller invasive tumors (pT1: 100 % vs 77 %; p < 0.001), and to be pN0 (95 % vs 81 %; p < 0.001). The HRC patients had more invasive triple-negative tumors (p = 0.01) and underwent less axillary surgery (p < 0.001), systemic therapy (p < 0.001), and radiotherapy (p = 0.002). Among those with a known BRCA mutation, significantly more women in the HRC underwent screening mammography (75 % vs 40 %; p < 0.001) or magnetic resonance imaging (MRI: 82 % vs 9.9 %; p < 0.001) in the 12 months before diagnosis. Women followed in a high-risk screening program have disease diagnosed at an earlier stage and therefore require less-intensive breast cancer treatment than women presenting to a cancer center at the time of diagnosis. Identification of high-risk women and implementation of increased surveillance protocols are vital to improving outcomes.

Public Preferences for Genetic and Genomic Risk-Informed Chronic Disease Screening and Early Detection: A Systematic Review of Discrete Choice Experiments.

Genetic and genomic testing can provide valuable information on individuals' risk of chronic diseases, presenting an opportunity for risk-tailored disease screening to improve early detection and health outcomes. The acceptability, uptake and effectiveness of such programmes is dependent on public preferences for the programme features. This study aims to conduct a systematic review of discrete choice experiments assessing preferences for genetic/genomic risk-tailored chronic disease screening. PubMed, Embase, EconLit and Cochrane Library were searched in October 2023 for discrete choice experiment studies assessing preferences for genetic or genomic risk-tailored chronic disease screening. Eligible studies were double screened, extracted and synthesised through descriptive statistics and content analysis of themes. Bias was assessed using an existing quality checklist. Twelve studies were included. Most studies focused on cancer screening (n = 10) and explored preferences for testing of rare, high-risk variants (n = 10), largely within a targeted population (e.g. subgroups with family history of disease). Two studies explored preferences for the use of polygenic risk scores (PRS) at a population level. Twenty-six programme attributes were identified, with most significantly impacting preferences. Survival, test accuracy and screening impact were most frequently reported as most important. Depending on the clinical context and programme attributes and levels, estimated uptake of hypothetical programmes varied from no participation to almost full participation (97%). The uptake of potential programmes would strongly depend on specific programme features and the disease context. In particular, careful communication of potential survival benefits and likely genetic/genomic test accuracy might encourage uptake of genetic and genomic risk-tailored disease screening programmes. As the majority of the literature focused on high-risk variants and cancer screening, further research is required to understand preferences specific to PRS testing at a population level and targeted genomic testing for different disease contexts.

Disparities in breast cancer prevention initiatives at a comprehensive cancer center: Who are we serving?

1615 Background: Despite advances in personalized breast cancer risk assessment and screening, populations at highest risk for cancer-related mortality are often excluded. At the IU Simon Comprehensive Cancer Center, a high-risk screening program (HRSP) identifies and serves women at increased risk of breast cancer. Risk assessment using Tyrer Cuzick v.8 and Gail models is performed in mammography; women at increased risk are navigated to a clinic appointment to discuss individualized screening and prevention services including MRI, chemoprevention, and/or genetic testing. We hypothesize gaps in the demographic and socioeconomic (SES) characteristics of women seen for a HRSP appointment, compared to women receiving a cancer diagnosis at the same mammography sites. Methods: Retrospective review was performed of women who met criteria for the HRSP (age ≤65 and Gail 5 yr risk ≥3% or TC v.8 10-yr risk ≥8%, or recommended by the radiologist) and subsequently accepted, scheduled, and attended an appointment from 6/2020 to 6/2022 (n=233). This population was compared to women who were diagnosed with breast cancer at the same clinical sites over the same dates, without history of being evaluated in the HRSP. Age was restricted to ≤65 to match the HRSP population (n=685). Zip codes were used to calculate area-based SES by median household income and percent poverty. CDC social vulnerability index (SVI) was evaluated using the U.S. Census Bureau and American Community Survey (0=least vulnerable, 1=most vulnerable). Comparisons across groups by age, race, insurance status, area SES and SVI were made using the Wilcoxon or Chi-square test. Results: Cancer cases were significantly older than those attending the HRSP (median age 54 vs 49 p &lt; 0.001). Black patients represented 19.4% of participants diagnosed with cancer, versus 10.8% of participants attending the HRSP (p=0.0032). There was also a disparity in insurance coverage, with 83.8% of women seen in the HRSP being privately insured, versus 75.6% of women diagnosed with cancer (p=0.011). There was no statistical difference in SVI (0.64 vs 0.66 p=0.11) or area poverty rate (11.2 vs 12.0 p=0.26) between the groups; cancer cases came from areas with lower household income (69,611 vs 73,165 p=0.04). Conclusions: Women seen in the HRSP were more likely to be younger, White, privately insured, and from an area with higher household income, compared to women diagnosed with cancer in the same health system at the same mammography sites. This highlights disparities in access to individualized breast cancer interception such as chemoprevention, high-risk screening, and genetic testing, which may further existing disparities in breast cancer-related mortality based on race and SES. Further studies will investigate barriers and motivators to personalized breast cancer prevention in high-risk groups, and utilize community partnerships to develop equitable interventions.

Clinico-Biochemical Spectrum of Pakistani Patients with Glutaric Aciduria Type 1 (GA1): Experience from a Specialised Biochemical Genetics Laboratory in Pakistan.

To evaluate the clinical, radiological, and biochemical features of glutaric aciduria Type 1 (GA1) patients identified through urine organic acid testing at a biochemical genetics laboratory (BGL) in Pakistan. Observational study. Place and Duration of the Study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, Pakistan, from January 2013 to December 2022. Medical charts and urine organic acid (UOA) chromatograms of the patients presenting at the BGL from January 2013 to December 2022 were reviewed. Brain imaging was obtained where available. Variables were noted as per the objective and descriptive statistics were obtained. GA1 was found in 64 (0.4%) patients out of a total of 16,094 UOA requests for high-risk screening cases. The age of diagnosis ranged between one month and three years. The brain MRI findings revealed characteristic abnormalities such as cerebral atrophy, expanded CSF spaces, white matter abnormalities, and a distinct bat wings appearance, in cohesion with the results of biochemical testing. Sixty-four cases of GA1 from a single centre indicate a high frequency of the disorder in Pakistan. Late diagnosis emphasises the need for increased clinical awareness and preferably newborn screening to ensure optimal outcomes. Glutaric aciduria Type 1 (GA1), Brain imaging, UOA analysis, Glutaryl-CoA dehydrogenase (GCDH), Pakistan.

Effectiveness of high-risk human papillomavirus genotyping for cervical cancer screening. A multicentre screening cohort study in rural China.

This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.

Characteristics of Patients Receiving Complex Case Management in an Acute Care Hospital.

Improving transitions in care is a major focus of health care planning. In the research team's prior intervention study, the length of stay (LOS) was reduced when patients at high risk for readmission were identified early in their acute care stay and received complex management. This study will describe the characteristics of patients receiving complex case management in an urban acute care hospital. Acute care hospital. This was a retrospective chart review of patients in a previous quality assurance study. A random selection of patients who previously underwent high-risk screening using the LACE (Length of stay; Acuity of the admission; Comorbidity of the patient; Emergency department use) index and received complex case management (the intervention group) were reviewed. The charts of a random selection of patients from the previous comparison group were also reviewed. Patient characteristics were collected and compared using descriptive statistics. In the intervention group, more patients had their family physicians (FPs) documented (93.1% [81/87] vs. 89.2% [66/74]). More patients in the intervention group (89.7% [77/87] vs. 85.1% [63/74]) lived at home prior to admission. More patients in the intervention group had a family caregiver involved (44.8% [39/87] vs. 41.9% [31/74]). At discharge, more patients in the intervention group (87.1% [74/85]) were discharged home compared with the comparison group (78.4% [58/74]). (1) Having an identified FP, living at home, and having family caregiver(s) characterized those with lower LOS and discharged home. (2) Case management, risk screening, and discharge planning improve patient outcomes. (3) This study identified the importance of having a FP and engaged family caregivers in improving care outcomes.

#2617 Impact of CKD screening in high‑risk populations and guideline-directed therapy on RRT, CV events, and mortality in Europe: an IMPACT CKD analysis

Abstract Background and Aims Despite the rising and substantial burden of chronic kidney disease (CKD), there is a lack of recognition of CKD as a health priority in Europe. This contributes to underdiagnosis of CKD despite the potential for early detection and effective intervention to delay progression to late-stages (associated with costly and resource-intensive renal replacement therapy [RRT; i.e., dialysis and transplantation]). Further, diagnosed patients are undertreated when compared to current and upcoming CKD guidelines, leading to increased risk for progression to RRT and cardiovascular (CV) or other events. Early detection and intervention in high-risk populations, such as those with diabetes mellitus (DM) and hypertension (HTN) have shown cost-effectiveness; however, the broader implications of these strategies on CKD progression and clinical outcomes in a European context remains underexplored. Our study aims to illustrate the clinical benefit of targeted screening followed by an optimal compliance to guideline-directed treatment use to provide insight into potential CKD policies across Europe. Method Four country populations (Germany, Netherlands, Spain, United Kingdom [UK]) were simulated for 10-years (baseline: 2022; simulated years: 2023-2032) using the validated IMPACT CKD model to compare two scenarios: targeted screening for people with DM and/or HTN followed by 90% compliance to guideline-directed therapy versus current practice (i.e., underdiagnosis without screening and low treatment rates). Annual targeted screening was modelled using estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing. Initiation of therapies for people with diagnosed CKD was based on Kidney Disease Improving Global Outcomes guidelines. A 90% compliance to guideline-directed therapies was assumed to approximate maximum clinical benefit. Current practice was modelled based on the observed diagnosed rate without screening and the observed treatment rate in each country. The incremental population initiated on recommended therapies were modelled to experience a multiplicative treatment effect on GFR decline, CV events, and acute kidney injury (AKI) events. The model projected CKD and RRT prevalence, incidence of CV and AKI events with results shown for year 10 (2032), as well as cumulative all-cause mortality over the simulated 10-years. Results Results compare the high-risk population screening followed by guideline-directed treatment scenario to continuation of current practices for the four countries (Fig. 1). The identification of undiagnosed CKD, as well as lower rates of progression due to guideline-directed treatment was associated with a small rise in the number of total CKD patients, with increases in stage 1-2 by 3.5% to 5.0%, and stage 3-5 by 0.2% to 1.2%. There was a reduction in the number of undiagnosed CKD stage 1-2 patients by 49.2% to 71.6%, and stage 3-5 by 60.2% to 69.8%. The largest reductions were predicted for CV events (44.6% to 49.1%) followed by dialysis (22.6% to 41.9%). The strategy resulted in a decrease in cumulative 10-year all-cause mortality between 4.5% to 9.1% in CKD patients. Conclusion The study predicted significant clinical benefits from targeted CKD screening followed by guideline-directed interventions across all four European countries. Notably, this approach was forecasted to reduce undiagnosed CKD cases, dialysis, CV events, and mortality. These findings underscore the potential of acting earlier on CKD to mitigate the future CKD burden.

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM): a decade follow-up of individuals at high-risk for pancreatic cancer

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29–83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.

Towards Comprehensive Newborn Hearing and Genetic Screening in Russia: Perspectives of Implementation

The universal newborn hearing screening (NHS) program was implemented in Russia in 2008 to replace the high-risk newborn hearing screening. More than 95% coverage and significant improvement in early detection and intervention is achieved. Meanwhile, it was shown that current OAE-based hearing screening missed 13% of newborns with genetically ascertained hereditary sensorineural hearing loss (SNHL). The aim of the study is to assess the results of genetic investigation and NHS in a large cohort of Russian children with bilateral SNHL and to study the feasibility of implementation of combined hearing and genetic screening in Russia. Genetic, audiological and NHS data of 1292 pediatric patients with bilateral SNHL born in 2008–2021 were analyzed. GJB2 sequencing was performed for all subjects, 644 patients had pathological GJB2 genotype, 406 of them were homozygous for c.35delG variant. The group of 155 GJB2-negative patients were searched for other SNHL genes, The pathological genotypes were identified at 87 patients. The most frequent genes were STRC (21.8%), USH2A (16.1%), OTOF (8%) and SLC26A4 (6.9%). Children with confirmed genetic etiology passed NHS in 21% of cases. The perspectives of implementation of national comprehensive newborn hearing and genetic screening including whole exome sequencing technologies are discussed.

Expert consensus on the classification and management in eye disease screening high risk neonatal (2024)

Expert consensus on the classification and management in eye disease screening high risk neonatal (2024)

Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center.

Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care. Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. Outcomes included rates of completion of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and NCCN risk-reducing and age-dependent screening guidelines (version 3.2019). Multivariable logistic regression analyses were used to evaluate potential predictors of these outcomes. Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) underwent RRSO and 77 (60%) had RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. Women with a history of breast or ovarian cancer were more likely to have RRM (OR = 4.38; 95% CI 1.80-11.51; p = 0.002). Increasing age was associated with an increased likelihood of RRSO (OR = 1.05; 95% CI 1.01-1.09; p = 0.019) and decreased likelihood for RRM (OR = 0.95; 95% CI 0.92-0.99; p = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 2.81; 95% CI 1.10-7.44; p = 0.025). Women who had genetic testing after June 2013 were less likely to have RRM than those tested before June 2013 (OR = 0.42; 95% CI 0.18-0.95; p = 0.040. None of the other measured factors were associated with rates of RRSO, RRM or follow through with NCCN recommendations. There was near universal (127/129) reported disclosure of genetic test results to family members, resulting in the discovery of a median of 1 relative with a pathogenic variant (range = 0-8). An evaluation of follow up practice in a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of reported completion of screening and surgical risk-reducing recommendations. Educational efforts should continue to reinforce the importance of follow-through with guideline recommended care among this high-risk group.

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.