Risultati per: Le campagne di screening come strumento di prevenzione oncologica tra dubbi e certezze

In Reply I thank Elwood et al for highlighting their previous efforts to develop more robust evidence to guide melanoma screening efforts. However, their work found similar findings as Matsumoto et al, with increased thin melanoma ascertainment in patients who had undergone screening skin examinations. While they modeled possible associations with mortality based on thickness data, their work did not look at actual mortality, either all cause or melanoma related.

This Viewpoint discusses the role of the International Patient Decision Aid Standards Collaboration in emphasizing the importance of shared decision-making facilitated by trained individuals and the use of decision aids that meet minimal quality standards when counseling patients for lung cancer screening.

To the Editor We agree with the title of the Editorial by Swerlick, but it omits the considerable efforts to mount a randomized clinical trial in Australia. We assessed melanoma screening in 1992, recommending a randomized clinical trial at ages 45 to 69 years to assess mortality. Subsequently, a similar trial based on whole-body examinations by primary care practitioners (PCPs) was proposed. A pilot phase showing that screening increased enough to allow detection of a 20% reduction in mortality over 15 years was reported in 2002. The trial cost approximately $8.4 million; after national and international peer review, the research costs were approved, which were approximately half the total. However, the other costs, including payments to PCPs for the screening examinations, were not funded. Thus, the full trial was not conducted.

Objective
There is a concern about performance of the screening approaches, where information on the quality of novel and affordable screening approaches that will perform well in remote areas is warranted. This lack of information makes it difficult to prioritise resource use in efforts to improve cervical cancer outcomes. We aimed to compare the diagnostic value of human papillomavirus (HPV) testing on self-collected samples, Pap smear and visual inspection of the cervix with acetic acid (VIA) tests for detection of high-grade cervical intraepithelial neoplasia or worse (CIN2+).

Design
A combined cross-sectional and cohort study.

Setting
Three primary healthcare centres in Kilimanjaro region, Tanzania.

Participants
1620 women undergoing cervical cancer screening from December 2018 to September 2021. Inclusion criteria were being aged 25–60 years, and no history of premalignant or cervical cancer. Exclusion criteria were overt signs of cancer and previous hysterectomy.

Interventions
Participants underwent HPV self-sampling with Evalyn Brush and Care HPV kit assay was used to determine prevalence of high-risk HPV infection. Women with positive HPV test were together with a random sample of HPV negative women scheduled for follow-up where VIA was performed, and Pap smear and cervical biopsies obtained.

Results
Of 1620 women enrolled, 229 (14.1%) were HPV positive and 222 of these attended follow-up together with 290 (20.8%) women with negative HPV test. On VIA, 17.6% were positive. On Pap smear, 8.0% were classified as high-grade squamous intraepithelial lesion. The sensitivity and specificity, respectively, of the various tests, compared with histopathology for the detection of CIN2+ were: HPV test 62.5%, 59.3%; Pap smear 82.8%, 82.1% and; VIA 48.4%, 56.8%. When combined, the sensitivity and specificity for HPV and Pap smear were 90.6%, 70.6% while HPV and VIA were 65.6% and 75.5% for the detection of CIN2+.

Conclusions
The performance of care HPV testing on self-collected samples opens the possibility of increasing coverage and early detection in resource-constrained settings.

Circulation, Volume 146, Issue Suppl_1, Page A10105-A10105, November 8, 2022. Introduction:Hypercholesterolemia is often asymptomatic and requires cholesterol screening to be identified. Current guidelines recommend adults at low risk for cardiovascular disease (CVD) to receive cholesterol screening at least every 5 years with more frequent screenings in older adults and/or at higher CVD risk. Yet, currently, about 25% of Americans do not meet the every-5-year screening recommendations. While disparities in the prevention and treatment of hypercholesterolemia continue to rise, little is known regarding factors influencing cholesterol screening among older Americans in the past 10 years.Methods:This longitudinal analysis used data from the Health and Retirement Study (HRS). HRS is a nationally representative survey of older adults in the U.S. The current study focused on data collected from 2008 (Wave 9) to 2018 (Wave 14). Participants who passed away by 2019, ever had CVD or stroke, were under age 55 at baseline, had more than 3 waves of missing data in self-reported cholesterol screening, or any missing data in covariates were excluded from the current analysis. In total, 7643 participants were included. Meeting cholesterol screening recommendations was defined as those reporting more than two cholesterol screenings between waves 9-14. Poisson regression and logistic regression were used for data analysis.Results:Compared to Black, Indigenous, and People of Color (BIPOC), White older Americans were more likely to meet cholesterol screening recommendations (odds ratio= 1.60; p

Circulation, Volume 146, Issue Suppl_1, Page A13225-A13225, November 8, 2022. Introduction:Frailty is a major risk factor for adverse health events in older adults with cardiovascular disease.Hypothesis:We sought to develop and validate a predictive model leveraging data available in the electronic health record to screen for frailty as defined by a prospective reference standard.Methods:We conducted a population-based cohort study using data from the Canadian Longitudinal Study of Aging (CLSA). From 2010-2015, the CLSA enlisted a diverse and multi-ethnic sample of community-dwelling adults 45-85 years of age. Comprehensive phenotyping was performed through interviews at participants’ homes and assessments at data collection sites. Frailty was quantified by the 47-item Frailty Index (FI) Examination, consisting of tests for age-related deficits in physical performance, body composition, cardiovascular and pulmonary physiology, cognitive and sensory function. After dividing our sample into training (80%) and test (20%) sets, we compared machine learning and linear regression models to predict the FI based on age, sex, comorbidities, and blood test results. We used the H2O AutoML platform (DAI 1.10.2) to iteratively determine the optimal model.Results:The cohort consisted of 30,097 adults with a mean age of 63±10 years and 51% females. The mean FI score was 0.28±0.08 (best-worst 0.07-0.70). The gradient-boosted machine learning model achieved an R2of 0.512 and a root mean squared error (RMSE) of 0.058 to regress FI scores, and an area under the curve of 0.766 to classify FI quintiles, selecting the following 10 variables in descending order of importance: age, chronic heart failure, hypertension, glycated hemoglobin, high-sensitivity C-reactive protein, high-density lipoprotein, red cell distribution width, vitamin D, female sex, and diabetes. The linear regression model achieved a similar R2and RMSE with all 62 input variables and a modest decline after selecting the top 10 input variables using a leaps-and-bounds algorithm.Conclusions:Frailty screening can be performed at scale for clinical or research purposes using common clinical and biochemical inputs. Our machine learning model predicted frailty with a manageable number of inputs and yielded pathophysiological insights about their relative importance.

Circulation, Volume 146, Issue Suppl_1, Page A14675-A14675, November 8, 2022. Introduction:Genome-wide association studies (GWAS) have discovered >300 associations for CAD. Few loci are functionally characterized and may represent new mechanisms of disease.Hypothesis:Can a high-throughput, unbiased transcriptional screen for all candidate GWAS genes identify the causal genes and biological pathways at CAD GWAS loci in endothelial cells (ECs)?Methods:We applied CRISPRi-Perturb-seq to knock down the expression of all genes within 500 Kb of coronary artery disease GWAS loci (2,300 genes in total) and measure their effects on the transcriptome using single-cell RNA-seq.Results:We identified 60 programs of co-expressed genes, which represent core cellular pathways (i.e. ribosome biogenesis) and EC-specific pathways such as flow response and angiogenesis. The EC-specific programs show the greatest contribution to CAD heritability. 6 EC-specific programs have the greatest number of CAD GWAS candidate genes. One of the EC-specific programs had genes regulated byKLF-transcription factors and was enriched for shear-stress response genes. The novel CAD candidate genes in this program included multiple known mediators of the cerebral cavernous malformation (CCM)-signaling complex. 9 known members of the CCM-signaling cascade and several potentially novel mediators of CAD clustered together in theKLFPerturb-seq topic. These included genetic variants in theCCM2,KLF4,RAC1, andHEG1loci as well as genes will a similar transcriptional profile but no prior connection to the CCM-signaling complex.Conclusions:High-throughput functional analysis of 2,300 genes proximal to CAD GWAS loci prioritized pathways—such as angiogenesis and EC migration—that are regulated by multiple risk SNPs. Our study identifies new genes that likely influence risk for CAD, identifies convergence of CAD genes into certain pathways in endothelial cells, and demonstrates a generalizable strategy to connect disease variants to functions.

Circulation, Volume 146, Issue Suppl_1, Page A10137-A10137, November 8, 2022. Introduction:Clinical practice guidelines recommend regular chronic kidney disease (CKD) screening after a diagnosis of hypertension (HTN) or type 2 diabetes (T2DM). Annual monitoring of kidney function increases early detection of CKD and improves quality of life. However, disparities in neighborhood characteristics can impact access to routine care, including CKD screening.Hypothesis:We hypothesize area deprivation index (ADI), a national ranking of neighborhood sociodemographic disadvantage would predict annual CKD screening and CKD development among newly diagnosed HTN or T2DM patients.Methods:Electronic health records of patients (n=235,208) with an new HTN or T2DM diagnosis between 2015-2018 were abstracted using International Classification Codes. Patients were followed for three years to assess annual CKD screening (one estimated glomerular filtration rate and urinary albumin-to-creatine ratio) and CKD development (CKD or end stage renal disease). ADI ranks (1-100) were divided into quintiles (Q1=least deprived, Q5=most deprived). Multivariable logistic regression models evaluated associations between ADI quintiles with CKD screening and CKD development.Results:Most patients were White (57%) females (55%) with solely HTN (65%). Few with only T2DM (9%) and 26% had both. Screening was highest for patients who developed HTN and T2DM during the study (44%) compared to only T2DM (38%) or HTN (4%). CKD developed for 9% of patients with HTN and T2DM, but 0% for only HTN or T2DM. Compared to the least deprived patients, the most deprived were less likely to not be screened in the first year of HTN or T2DM diagnosis (Odds Ratio (OR)= 0.77; 95% confidence interval (CI): 0.73, 0.80). The most deprived patients were more likely to develop CKD compared to the least deprived patents (OR=1.98, 95%CI: 1.75, 2.23).Conclusions:The most deprived patients were more likely to be screened annually and almost twice as likely to develop CKD compared to the least deprived. Although an increase in deprivation is associated with poor lifestyle choices which can lead to an increase in CKD, it’s possible early diagnosis is due to an increase in screening, thus leading to an increase in quality of life through monitoring kidney function.

Circulation, Volume 146, Issue Suppl_1, Page A9447-A9447, November 8, 2022. Introduction:Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF) among patients aged > 60 years. While the V122I variant that is associated with hereditary ATTR-CM is present in 3.4% of self-identified Black individuals in the US (or 1.5 million people), the phenotypic penetrance of this allele remains incompletely defined owing to age-dependent expression and limited methods for disease ascertainment.Methods:The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study is a currently accruing multisite cohort designed to determine the prevalence of ATTR-CM using Tc-99m-Pyrophosphate imaging in older (age > 60 years) Black and Hispanic individuals with HF.TTRgenotype is determined by 4-exon targeted PCR, while functional, biochemical, and echocardiographic testing is performed. Data are presented here as an interim analysis performed using Kruskal-Wallis testing for the first 240 self-identified Black participants.Results:The prevalence of V122I was 6.7% (n=16 carriers of whom 7 had ATTR-CM), yielding a phenotypic penetrance of 44% (95% CI 20%, 70%) at a median age of 82 (IQR 74, 85) years. Allele carriers with ATTR-CM (Group 3) were older and more likely male, with lower 6-minute walk distance and LVEF, when compared to carriers without ATTR-CM (Group 2, Table) or wild-type, non-amyloid HF controls (Group 1). Other functional, biochemical, and echocardiographic parameters were predictably different between Group 3 and the other groups but similar between Groups 1 and 2 except for prealbumin levels (Group 1: 25 mg/dl vs. Group 2: 20.5 mg/dl, p < 0.05).Conclusion:The clinical penetrance of V122I among elderly Black individuals with HF and a median age of 82 years was 44%, suggesting that genotype alone is insufficient to infer ATTR-CM as the cause of HF in this clinical context. Prealbumin concentration may be useful to identify ATTR-CM in V122I carriers.

Circulation, Volume 146, Issue Suppl_1, Page A15026-A15026, November 8, 2022. Introduction:A novel technology utilizing artificial intelligence (AI) to provide real-time image-acquisition guidance, enabling novices to obtain diagnostic echocardiographic (echo) images holds promise to expand the reach of echo screening for rheumatic heart disease (RHD). We evaluated the ability of non-experts to obtain diagnostic quality images in patients with RHD using AI guidance (Caption Health) with color Doppler.Methods:This study was performed in Kampala, Uganda at the Uganda Heart Institute. Nurses and nursing students with no prior echo experience underwent one-day training in the use of AI guidance, which included a 7-view screening protocol with 2D and color Doppler images. Following training, all participants scanned 8-10 patients using AI guidance, half RHD and half normal. The same patients were scanned by two expert sonographers without the use of AI guidance. Each echo was evaluated by a panel of 4 expert echocardiographers blinded to the identity of the scanner (novice/exert) and diagnosis of the patient to provide quality assessment including (1) diagnostic quality to determine presence/absence of RHD, (2) more detailed valvular assessment, and (3) ACEP score 1-5 for each view.Results:Thirty-six novice scanners scanned a total of 50 patients, 25 with RHD and 25 controls. A total of 462 echocardiogram studies were obtained, 351 obtained by non-experts using AI guidance and 111 obtained by expert sonographers without AI guidance. Preliminary analysis of 394 interpretations showed that 95% of non-expert studies were of diagnostic quality to assess for RHD and mitral valve disease (vs 100% by experts, p=0.03), but only 56% of non-expert studies were of diagnostic quality to assess aortic valve disease (vs 97% by experts, p

Circulation, Volume 146, Issue Suppl_1, Page A10257-A10257, November 8, 2022. Introduction:Transthyretin cardiac amyloidosis (ATTR-CA) has been associated with severe aortic stenosis (AS), with some studies finding up to 20% of patients who undergo transcatheter aortic replacement (TAVR) have ATTR-CA. New therapies for ATTR-CA have brought significant interest in identifying patients at high risk for this disease. The purpose of this study was to prospectively evaluate the yield of universal testing for ATTR-CA in older patients with severe AS.Methods:All patients ≥ 70 years with severe, native, and degenerative AS seen in valve clinic for evaluation of TAVR were referred for technetium-99m pyrophosphate cardiac scintigraphy (PYP scan). Diagnosis was made via a combination of planar grade, heart to contralateral lung ratio, and single positron emission computed tomography/computed tomography. Patients with a positive PYP scan were referred for appropriate laboratory testing to rule out AL amyloidosis. Clinical and echocardiographic factors were correlated with the PYP result.Results:Over a 12-month period, 787 patients with severe AS were screened of which 543 met the inclusion criteria. Of these patients, 298 underwent a PYP scan with 232 not undergoing the scan for logistical and scheduling issues during the pandemic. The positivity rate was 4.3% (13/298). Patients with a positive PYP scan had higher rates of carpal tunnel syndrome (54% vs 14%, p -18%) (100% vs 69%, p=0.044), low stroke volume index (≤35 ml/m2) (92% vs 42%, p

Circulation, Volume 146, Issue Suppl_1, Page A10253-A10253, November 8, 2022. Introduction:Multi-dimensional assessments of patient reported outcomes (PROs) are becoming increasingly important in optimizing patient-centered care for chronic conditions such as peripheral artery disease (PAD). We aimed to demonstrate the feasibility of a health system integrated workflow to incorporate mental health screenings into the outpatient PAD clinic workflow.Methods:In a large academic center, we administered three validated psychological assessments to consecutive outpatients between March 3, 2021 and July 7, 2021. Assessments were administered as part of an in-person patient navigation system (Yale PRO-QI) and was supported by online data collection. Assessments included the Patient Health Questionnaire-8 (PHQ-8) for depression, the Generalized Anxiety Disorder-7 (GAD-7) for anxiety, and the Perceived Stress Scale-4 (PSS-4) for stress. Validated cutoffs were used to screen for depression and anxiety ( >10 = depression or anxiety, respectively) and stress ( >6 = high stress).Results:There were 104 assessments collected for 98 participants with a mean age of 68.6+12.0 years old, 38.8% female, 86.7% White, 9.1% Black and 2.0% Asian or American Indian. The majority (72.5%) were seen for a routine follow-up visit. Two participants (2.0%) screened positive for generalized anxiety disorder. For depression, 12.2% screened positive. Almost half of all participants (47.9%) had higher levels of stress compared with a normative population. There were no statistically significant associations between the risk of positive screening and visit type.Conclusions:Measurement-based care metrics are becoming a standard best practice in routine clinical operations. Psychosocial screening instruments can be integrated in PAD outpatient care and highlight opportunities to improve integrated behavioral care pathways to provide the best care for this vulnerable population.

Circulation, Volume 146, Issue Suppl_1, Page A11770-A11770, November 8, 2022. Background:Association of cardiovascular disease with cancer is caused by an increased risk of coronary artery disease (CAD), in part attributable to the association of standard risk factors with both coronary disease and cancer. In addition to these drivers of accelerated plaque formation, treatment used in breast cancer therapy is associated with CAD.Purpose:Cancer patients require an individualised approach for managing CAD and there is an unmet need to define the benefit of CAD screening on outcomes in cancer survivors and the cost-effectiveness of this approach is unknown.Methods:A Markov model was assembled using three states; well, myocardial infarction and death. Base case scenario was a 55 year old female treated for breast cancer, followed up 10 years post treatment. Costs, utilities, and transition probabilities were derived from published literature. Costs are in 2021 AUD$ and calculated from a societal perspective. Costs and utilities were discounted at 3% per annum. Sensitivity analyses were performed on key inputs including transition probabilities of well state and MI, costs of CAD and screening test. Willing-to-pay threshold of AUD$50,000 was selected.Results:Screening cancer survivors for CAD dominated no screening, providing cost savings of $1916 and QALY savings of 5.9 QALYs per-patient. Major determinants were probabilities of MI, death and costs of screening and MI. There was no change in life expectancy.Conclusion:Screening for CAD provided an increase in long-term QALY and reduction in healthcare costs in breast cancer survivors at least 10 years post treatment. ​

Circulation, Volume 146, Issue Suppl_1, Page A11554-A11554, November 8, 2022. Introduction:Familial Hypercholesterolemia (FH) is a common genetic disorder resulting in elevated low-density lipoprotein cholesterol (LDL-C) causing premature atherosclerosis. Despite guidelines, universal screening rates remain low. Newborn screening could increase FH diagnostic rates.Hypothesis:Biochemical newborn screening for LDL-C, total cholesterol (TC), and apolipoprotein B (apoB) followed by selective molecular testing identifies pathogenic and likely pathogenic variants causing FH.Methods:De-identified, residual newborn screening bloodspots collected for routine screening at 24-48 hours of life were analyzed for LDL-C, TC, and apoB. Values are expressed as multiples of median (MoM). Mahalanobis distance, measuring how far MoM values differed positively from 1, was computed. Samples with the most extreme Mahalanobis distance were selected for molecular testing (panel includesLDLR,APOB,PCSK9,LDLRAP1,APOE,STAP1,LIPA,ABCG5, andABCG8).Results:Distributions of apoB, TC, and LDL-C from 5,248 samples are shown below (figure). ApoB followed a Gamma distribution; TC and LDL-C followed non-normal but symmetric distributions. ApoB and LDL-C accounted for 93% of variance among biomarkers. Of the first 2500 samples, 192 samples were selected for molecular testing; a pathogenic variant for monogenic FH was detected in 1 sample and risk factors for polygenic FH in 4 samples (table below).Conclusions:Pathogenic or likely pathogenic variants for FH were identified with an incidence of 1 in 500 in the first 2500 newborn specimens tested. Further study will determine if this two-tiered screening strategy adequately detects FH in newborns.

Circulation, Volume 146, Issue Suppl_1, Page A14935-A14935, November 8, 2022. Introduction:The electrocardiogram (ECG) contains information about age-related changes in cardiovascular physiology, which have been linked with the frailty syndrome.Hypothesis:We sought to develop and validate a predictive model leveraging the 12-lead ECG to screen for frailty as defined by a prospective reference standard.Methods:We conducted a population-based cohort study using data from the Canadian Longitudinal Study of Aging (CLSA). From 2010-2015, the CLSA enlisted a diverse and multi-ethnic sample of community-dwelling adults 45-85 years of age. Comprehensive phenotyping was performed through interviews at participants’ homes and assessments at data collection sites. Frailty was quantified by the 110-item Frailty Index (FI) Composite, consisting of self-reported comorbidities, blood tests, physical performance tests, body composition tests, cardiovascular and pulmonary tests, cognitive and sensory tests. After dividing our sample into training (80%) and test (20%) sets, we developed an end-to-end deep neural network to predict the FI score based on the 12-lead ECG time series.Results:A total of 26,700 ECGs with paired FI scores were evaluated. For classification of FI quintiles, a bidirectional long short-term memory (BiLSTM) neural network with a cross-entropy loss function achieved a 5-fold mean area under the receiver operating characteristics curve (AUROC) of 0.70 and area under the precision-recall curve (AUPRC) of 0.36. Predictive performance was superior for classification of the first (most robust) quintile that had AUROC 0.79 and AUPRC 0.46, and the fifth (most frail) quintile that had AUROC 0.79 and AUPRC 0.56, as compared to the middle quintiles that had AUROC 0.60-0.69 and AUPRC 0.27-0.29.Conclusions:Our deep learning model can be used to screen for high or low levels of frailty based on the readily available 12-lead ECG. Additional research is underway to gain insights into other representations of the ECG signal and relative importance of the ECG features.

Circulation, Volume 146, Issue Suppl_1, Page A14221-A14221, November 8, 2022. Introduction:Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure. Novel therapies for transthyretin (TTR) CA elevate the need for early identification when treatment has the greatest efficacy. The TTR CA score (TCAS) was recently developed to predict the likelihood of TTR CA in patients undergoing 99mTc-pyrophosphate scintigraphy (PYP) scanning. Its simple inputs could be easily extracted from the electronic health record (EHR), suggesting possible use as a quick, EHR-based screening tool. We perform the first external validation of the TCAS using only EHR-extracted data. We hypothesized that a screening algorithm like TCAS could be generalizable and feasible to implement using our EHR.Methods:EHR data were extracted on all patients at a large academic medical center who underwent PYP scans between 2017 and 2022. PYP scan was considered positive if the patient was part of our institution’s registry of patients with confirmed CA. Inputs – age, sex, echocardiogram wall thickness and ejection fraction, and hypertension diagnosis codes – were converted to TCAS scores. Area under the receiver operating characteristic curve (AUROC) was calculated to analyze predictive performance. Using a TCAS ≥6 as the threshold for high-risk, performance characteristics were calculated.Results:Of 365 patients who underwent PYP scan, 335 had sufficient records to calculate a TCAS. Of these 335 patients, 69 (20.6%) had positive PYP scans. Median TCAS was 5 (interquartile range 4,7). The AUROC was 0.826, with a sensitivity of 87.0%, specificity of 63.9%, positive predictive value of 38.5%, and negative predictive value (NPV) of 95.0%.Conclusions:External validation of the TCAS supports its strong predictive performance with comparable AUROCs to the initial study (0.84-0.89). Clinically, with its high NPV, the TCAS has potential to serve as a simple, low-cost screen to avoid costly PYP scans. We demonstrate the ability to extract all inputs from the EHR, without need for manual chart review or calculation, suggesting that the TCAS could function as an EHR-based screening tool. Low-cost screening tools are needed to identify patients who would benefit from TTR CA workup with PYP scanning, facilitating treatment at earlier disease stages.