Search

BackgroundColorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity.MethodsA hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant.ResultsAmong 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals).ConclusionsA regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

BackgroundHousehold contact investigations are effective for finding tuberculosis (TB) cases but are hindered by low referral uptake for clinic-based evaluation and testing. We assessed the acceptability and feasibility of in-home testing of household contacts (HHC) using the GeneXpert Edge platform.MethodsWe conducted a 2-arm, randomized study in Eastern Cape, South Africa. HHCs were verbally assessed using the World Health Organization-recommended 4-symptom screen. Households with ≥1 eligible symptomatic contact were randomized. Intervention households received in-home GeneXpert MTB/RIF molecular testing. GeneXpert-positive HHCs were referred for clinic-based treatment. Standard-of-care households were referred for clinic-based sputum collection and testing. We defined acceptability as agreeing to in-home testing and feasibility as generation of valid Xpert MTB/RIF results. The proportion and timeliness of test results received was compared between groups.ResultsEighty-four households were randomized (n = 42 per arm). Of 100 eligible HHCs identified, 98/100 (98%) provided consent. Of 51 HHCs allocated to the intervention arm, all accepted in-home testing; of those, 24/51 (47%) were sputum productive and 23/24 (96%) received their test results. Of 47 HCCs allocated to standard-of-care, 7 (15%) presented for clinic-based TB evaluation, 6/47 (13%) were tested, and 4/6 (67%) returned for their results. The median (interquartile range) number of days from screening to receiving test results was 0 (0) and 16.5 (11-15) in the intervention and standard-of-care arms, respectively.ConclusionsIn-home testing for TB was acceptable, feasible, and increased HHCs with a molecular test result. In-home testing mitigates a major limitation of household contact investigations (dependency on clinic-based referral), revealing new strategies for enhancing early case detection.

Screening for psychosis spectrum disorders in primary care could improve early identification and reduce the duration of untreated psychosis. However, the accuracy of psychosis screening in this setting is unknown. To address this, we conducted a diagnostic accuracy study of screening for psychosis spectrum disorders in eight behavioral health services integrated into primary care clinics. Patients attending an integrated behavioral health appointment at their primary care clinic completed the Prodromal Questionnaire - Brief (PQ-B) immediately prior to their intake assessment. This was compared to a diagnostic phone interview based on the Structured Interview for Psychosis Risk Syndromes (SIPS). In total, 145 participants completed all study procedures, of which 100 screened positive and 45 negative at a provisional PQ-B threshold of ≥20. The PQ-B was moderately accurate at differentiating psychosis spectrum from no psychosis spectrum disorders; a PQ-B distress score of ≥27 had a sensitivity and specificity of 71.2 % and 57.0 % respectively. In total, 66 individuals (45.5 %) met criteria for a psychosis spectrum disorder and 24 (16.7 %) were diagnosed with full psychosis, indicating a high prevalence of psychosis in the sample. Overall, screening for psychosis spectrum disorders in an IBH primary care setting identified a relatively high number of individuals and may identify people that would otherwise be missed. The PQ-B performed slightly less well than in population-based screening in community mental health settings. However, the findings suggest this may represent an effective way to streamline the pathway between specialty early psychosis programs and primary care clinics for those in need.

BackgroundRecently-updated global guidelines for cervical cancer screening incorporated new technologies-most significantly, the inclusion of HPV DNA detection as a primary screening test-but leave many implementation decisions at countries' discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening.MethodsUsing a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing "triage" approaches-i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software.ResultsThermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach.ConclusionsThese results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.

ObjectiveDetermine diagnostic yield of chest, abdomen, and 4-site screening to diagnose metastatic disease and secondary diseases of prognostic significance in dogs with oral cancer.SampleMedical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.ResultsThoracic metastasis was diagnosed in 4.9% (0.9% odontogenic, 6.5% nonodontogenic) of oral tumors. Oral malignant melanoma and multilobular osteochondrosarcoma were most at risk. Abdominal metastasis was diagnosed in 2% of oral tumors (0% odontogenic, 3.1% nonodontogenic) and cytologically confirmed in 2 cases (0.6% [2/295)] of all abdominal ultrasounds (AUS) 5.5% [2/36] of all AUS that had cytology). Both cases had oral malignant melanoma. Incidental disease was diagnosed in 53.1% and 81.3% of thoracic and abdominal screenings, respectively. Major findings were more common in AUS (7.8%) compared to thoracic screening (1.9%). The prevalence of incidental findings was similar for odontogenic and nonodontogenic tumors. Both metastasis and major findings were diagnosed more commonly with thoracic CT compared to radiographs. Metastasis or a major finding of prognostic significance was diagnosed in at least 1 test in 27.8% of patients that had head CT, lymph node cytology, thoracic screening, and AUS (n = 115).Clinical relevanceMajor incidental findings were more commonly detected with AUS and were diagnosed in 1 in every 12 patients. However, metastatic disease was most commonly detected with thoracic screening. When all 4 screening tests are performed, there is an approximately 1 in 4 chance of diagnosing metastasis or major significant disease regardless of tumor type.

Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information. We conducted an embedded Ethical, Legal, and Social Implications (ELSI) study to examine if and how unaffected participants in a US population breast cancer screening trial understood and utilized PRS, as part of a multifactorial risk score combining traditional risk factors with a genetic risk assessment, to make screening and risk-reduction decisions. Semi-structured qualitative interviews were conducted with 24 trial participants who were designated at elevated risk for breast cancer due to their combined risk score. Interviews were analyzed using a grounded theory approach. Participants understood PRS conceptually and accepted it as one of many risk factors to consider, yet the value and meaning they ascribed to this risk estimate varied. Most participants reported financial and insurance barriers to enhanced screening with MRI and were not interested in taking risk-reducing medications. These findings contribute to our understanding of how PRS may be best translated from research to clinical care. Furthermore, they illuminate ethical concerns about identifying risk and making recommendations based on polygenic risk in a population screening context where many may have trouble accessing appropriate care.

Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.

IntroductionLimited data exists on the effectiveness of organized outreach campaigns on CRC screening completion for patients who are newly eligible for such screening.MethodsWe conducted an analysis of an existing clinical trial dataset of a publicly funded safety-net health system serving low-income populations.ResultsA total of 619 patients aged 50-51 received the outreach intervention and 3108 patients aged greater than 51 years old who had no prior history of FIT testing similarly received the outreach intervention. Patients newly eligible for FIT were more likely to complete a FIT test compared with older patients who had yet to complete a FIT test (58.3% vs 40.5%, p

BackgroundHepatocellular carcinoma (HCC) incidence and mortality continue to rise worldwide. Society guidelines recommend HCC screening for patients with chronic hepatitis B (CHB) or cirrhosis. Unfortunately, HCC screening rates remain relatively low, and the performance characteristics of current screening modalities are suboptimal.AimThe aim of the study was to discuss the current state of HCC screening and imaging diagnosis utilising standard and emerging imaging modalities in addition to outlining areas of need and ongoing study.MethodsA review of the field was performed combining literature searches and expert opinion.ResultsThe development of the Liver Imaging Reporting and Data System (LI-RADS version 2018) algorithms have advanced and standardised the imaging diagnosis of HCC. While guidelines recommend US for HCC screening, the sensitivity of ultrasound is highly variable for the detection of early-stage HCC with sensitivity reports ranging from 40% to 80%. Biomarker-based scores such as GALAD and alternative imaging modalities such as abbreviated MRI are promising tools to improve HCC early detection. Patients with non-alcoholic fatty liver disease (NAFLD) and patients hepatitis C (HCV) who have achieved sustained virologic response (SVR) can present a clinical dilemma regarding the need for HCC screening. Biomarkers and elastography can aid in identification of individuals at high risk for HCC in these populations.ConclusionsThe LI-RADS system has standardised the imaging interpretation and diagnosis of HCC. Work remains regarding screening in special populations and optimization of screening modalities.

IntroductionOrganized outreach to increase CRC screening using mailed FIT tests has been shown to be effective, but durable changes to screening behavior after cessation of screening is not known.MethodsIn this study, after cessation of funding for an organized cancer screening outreach program, we evaluated whether adherence to screening remained elevated. Patients aged 50-75 years eligible for CRC screening from eight safety net clinics were randomly assigned to outreach intervention vs usual care alone in 2016 to 2018; the primary outcome analyzed was the difference in the cumulative proportion of completed FIT screening between study assignments 1 year after study cessation.ResultsDespite higher rates of FIT screening for patients who were randomly assigned to the outreach intervention, FIT completion was not significantly different between the group that received the outreach services versus the usual care group (28.3% vs 29.8%, p = 0.158).ConclusionOutreach campaigns and their activities must be sustained to maintain improved rates of screening participation.

PurposeProstate cancer (PCa) screening, which relies on prostate-specific antigen (PSA) testing, is a contentious topic that received negative attention due to the low sensitivity and specificity of PSA to detect clinically significant PCa. In this context, due to the higher sensitivity and specificity of magnetic resonance imaging (MRI), several trials investigate the feasibility of "MRI-only" screening approaches, and question if PSA testing may be replaced within prostate cancer screening programs.MethodsThis narrative review discusses the current literature and the outlook on the potential of MRI-based PCa screening.ResultsSeveral prospective randomized population-based trials are ongoing. Preliminary study results appear to favor the "MRI-only" approach. However, MRI-based PCa screening programs face a variety of obstacles that have yet to be fully addressed. These include the increased cost of MRI, lack of broad availability, differences in MRI acquisition and interpretation protocols, and lack of long-term impact on cancer-specific mortality. Partly, these issues are being addressed by shorter and simpler MRI approaches (5-20 min bi-parametric MRI), novel quality indicators (PI-QUAL) and the implementation of radiomics (deep learning, machine learning).ConclusionAlthough promising preliminary results were reported, MRI-based PCa screening still lack long-term data on crucial endpoints such as the impact of MRI screening on mortality. Furthermore, the issues of availability, cost-effectiveness, and differences in MRI acquisition and interpretation still need to be addressed.

Current colorectal cancer (CRC) screening recommendations take a "one-size-fits-all" approach using age as the major criterion to initiate screening. Precision screening that incorporates factors beyond age to risk stratify individuals could improve on current approaches and optimally use available resources with benefits for patients, providers, and health care systems. Prediction models could identify high-risk groups who would benefit from more intensive screening, while low-risk groups could be recommended less intensive screening incorporating noninvasive screening modalities. In addition to age, prediction models incorporate well-established risk factors such as genetics (eg, family CRC history, germline, and polygenic risk scores), lifestyle (eg, smoking, alcohol, diet, and physical inactivity), sex, and race and ethnicity among others. Although several risk prediction models have been validated, few have been systematically studied for risk-adapted population CRC screening. In order to envisage clinical implementation of precision screening in the future, it will be critical to develop reliable and accurate prediction models that apply to all individuals in a population; prospectively study risk-adapted CRC screening on the population level; garner acceptance from patients and providers; and assess feasibility, resources, cost, and cost-effectiveness of these new paradigms. This review evaluates the current state of risk prediction modeling and provides a roadmap for future implementation of precision CRC screening.

BackgroundThrough adequate screening and follow-up, cervical cancer can be prevented or detected at early-stage (stage I), which is related to excellent survival. Current guidelines recommend discontinuing screening for women ≥65 years with history of normal Pap and/or HPV tests, potentially leaving this age group vulnerable. This study examined late-stage disease in a population-based cohort.MethodsUsing California Cancer Registry data, we identified 12,442 patients ages ≥21 years with a first primary cervical cancer diagnosed during 2009-2018. Proportions of late-stage disease (stages II-IV) and early- and late-stage 5-year relative survival are presented by the age group. Among patients ages ≥65 years, multivariable logistic regression estimated associations of sociodemographic and clinical characteristics with late-stage cervical cancer.ResultsNearly one fifth of patients (n = 2,171, 17.4%) were ≥65 years. More women ages ≥65 years (71%) presented with late-stage disease than younger women (48% in patients ages

To reach the millions of people with tuberculosis (TB) undiagnosed each year, there is an important need to provide people-centered screening and testing services. Despite people-centered care being a key pillar of the WHO END-TB Strategy, there have been few attempts to formally characterize and integrate the preferences of people most affected by TB - including those who have increased exposure to TB, limited access to services, and/or are at increased risk for TB - into new tools and strategies to improve screening and diagnosis. This perspective emphasizes the importance of preference research among people most affected by TB, provides an overview of qualitative preference exploration and quantitative preference elicitation research methods, and outlines how preferences can be applied to improve the acceptability, accessibility, and appropriateness of TB screening and testing services via four key opportunities. These include the following: (1) Defining the most preferred features of novel screening, triage, and diagnostic tools, (2) exploring and prioritizing setting-specific barriers and facilitators to screening and testing, (3) understanding what features of community- and facility-based strategies for improving TB detection and treatment are most valued, and (4) identifying the most relevant and resonant communication strategies to increase individual- and community-level awareness and demand. Preference research studies and translation of their findings into policy/guidance and operationalization have enormous potential to close the existing gaps in detection in high burden settings by enhancing the people-centeredness and reach of screening and diagnostic services to people most affected by TB who are currently being missed and left behind.

BackgroundDynamic hyperpolarized (HP)-13C MRI has enabled real-time, non-invasive assessment of Warburg-related metabolic dysregulation in glioma using a [1-13C]pyruvate tracer that undergoes conversion to [1-13C]lactate and [13C]bicarbonate. Using a multi-parametric 1H/HP-13C imaging approach, we investigated dynamic and steady-state metabolism, together with physiological parameters, in high-grade gliomas to characterize active tumor.MethodsMulti-parametric 1H/HP-13C MRI data were acquired from fifteen patients with progressive/treatment-naïve glioblastoma [prog/TN GBM, IDH-wildtype (n = 11)], progressive astrocytoma, IDH-mutant, grade 4 (G4AIDH+, n = 2) and GBM manifesting treatment effects (n = 2). Voxel-wise regional analysis of the cohort with prog/TN GBM assessed imaging heterogeneity across contrast-enhancing/non-enhancing lesions (CEL/NEL) and normal-appearing white matter (NAWM) using a mixed effects model. To enable cross-nucleus parameter association, normalized perfusion, diffusion, and dynamic/steady-state (HP-13C/spectroscopic) metabolic data were collectively examined at the 13C resolution. Prog/TN GBM were similarly compared against progressive G4AIDH+ and treatment effects.ResultsRegional analysis of Prog/TN GBM metabolism revealed statistically significant heterogeneity in 1H choline-to-N-acetylaspartate index (CNI)max, [1-13C]lactate, modified [1-13C]lactate-to-[1-13C]pyruvate ratio (CELval > NELval > NAWMval); [1-13C]lactate-to-[13C]bicarbonate ratio (CELval > NELval/NAWMval); and 1H-lactate (CELval/NELval > NAWMundetected). Significant associations were found between normalized perfusion (cerebral blood volume, nCBV; peak height, nPH) and levels of [1-13C]pyruvate and [1-13C]lactate, as well as between CNImax and levels of [1-13C]pyruvate, [1-13C]lactate and modified ratio. GBM, by comparison to G4AIDH+, displayed lower perfusion %-recovery and modeled rate constants for [1-13C]pyruvate-to-[1-13C]lactate conversion (kPL), and higher 1H-lactate and [1-13C]pyruvate levels, while having higher nCBV, %-recovery, kPL, [1-13C]pyruvate-to-[1-13C]lactate and modified ratios relative to treatment effects.ConclusionsGBM consistently displayed aberrant, Warburg-related metabolism and regional heterogeneity detectable by novel HP-13C/1H imaging techniques.

BackgroundPeople living with HIV (PLHIV) have an increased risk of developing active tuberculosis (TB). To reduce the burden of TB among PLHIV, the World Health Organization (WHO) recommends systematic TB screening followed by (1) confirmatory TB testing for all who screen positive and (2) TB preventive therapy (TPT) for all TPT-eligible PLHIV who screen negative. Symptom-based screening remains the standard of care in most high TB burden settings, including Uganda. Despite having high sensitivity for active TB among antiretroviral-naïve PLHIV, symptom screening has poor specificity; as such, many high-risk PLHIV without active TB are not referred for TPT. C-reactive protein (CRP) is a promising alternative strategy for TB screening that has comparable sensitivity and higher specificity than symptom screening, and was endorsed by WHO in 2021. However, the impact of CRP-based TB screening on TB burden for PLHIV remains unclear.MethodsTB SCRIPT (TB Screening Improves Preventive Therapy Uptake) is a phase 3, multi-center, single-blinded, individual (1:1) randomized controlled trial evaluating the effectiveness of CRP-based TB screening on clinical outcomes of PLHIV. The trial aims to compare the effectiveness of a TB screening strategy based on CRP levels using a point-of-care (POC) assay on 2-year TB incidence and all-cause mortality (composite primary trial endpoint) and prevalent TB case detection and uptake of TPT (intermediate outcomes), relative to symptom-based TB screening (current practice).DiscussionThis study will be critical to improving selection of eligible PLHIV for TPT and helping guide the scale-up and integration of TB screening and TPT activities. This work will enable the field to improve TB screening by removing barriers to TPT initiation among eligible PLHIV, and provide randomized evidence to inform and strengthen WHO guidelines.Trial registrationClinicalTrials.gov NCT04557176. Registered on September 21, 2020.

IntroductionDespite the increased risk of cervical cancer among HIV-positive women, many HIV-care programs do not offer integrated cervical cancer screening. Incorporating self-collected Human Papillomavirus (HPV) testing into HIV programs is a potential strategy to identify women at higher risk for cervical cancer while leveraging the staffing, infrastructure and referral systems for existing services. Community-based HIV and HPV testing has been effective and efficient when offered in single-disease settings.MethodsThis cross-sectional study was conducted within a community outreach and multi-disease screening campaigns organized by the Family AIDS Care and Education Services in Kisumu County, Kenya. In addition to HIV testing, the campaigns provided screening for TB, malaria, hypertension, diabetes, and referrals for voluntary medical male circumcision. After these services, women aged 25-65 were offered self-collected HPV testing. Rates and predictors of cervical cancer screening uptake and of HPV positivity were analyzed using tabular analysis and Fisher's Exact Test. Logistic regression was performed to explore multivariate associations with screening uptake.ResultsAmong the 2016 women of screening age who attended the outreach campaigns, 749 women (35.6%) were screened, and 134 women (18.7%) were HPV-positive. In bivariate analysis, women who had no children (p

In 2020, Centers for Disease Control and Prevention (CDC) released guidelines recommending HCV screening in all adults 18 years and older. In the current study, we aimed to identify risk factors for HCV infection in an ED population. We performed a retrospective analysis of ED patients ≥ 18 years who were screened for HCV between 28 November 2018, and 27 November 2019, at a single urban, quaternary referral academic hospital. An HCV-antibody immunoassay (HCV-Ab) was used for screening; positive results were confirmed by measuring HCV ribonucleic acid (RNA). The outcome of interest was the number of new HCV diagnoses (presence of viremia by HCV RNA testing). Multiple logistic regression models were used to identify risk factors associated with a new HCV diagnosis. 16,722 adult patients were screened for HCV (mean age: 46 ± 15 years; 51% female). HCV seroprevalence was 5%. Independent risk factors for HCV included increasing age [10-year aOR 1.26 (95% CI 1.23, 1.30)], male sex [aOR 1.25 (95% CI 1.03, 1.51)], undomiciled housing status [aOR 2.8 (95% CI 2.3, 3.5)], history of tobacco use [aOR 3.0 (95% CI 2.3, 3.9)], history of illicit drug use [aOR 3.6 (95% CI 2.9, 4.5)], Medicaid insurance status [aOR 4.0 (95% CI 2.9, 5.5)] and Medicare insurance status [aOR 1.6 (95% CI 1.1, 2.2)].The ED services a high-risk population with regards to HCV infection. These data support universal screening of ED patients for HCV. Risk factor profiles could improve targeted screening at institutions without universal testing protocols.

BACKGROUND: Xpert® MTB/RIF, a rapid, molecular TB diagnostic assay, can detect Mycobacterium tuberculosis and rifampin resistance directly from clinical sputum samples in

Screening tests are widely recommended for the early detection of disease among asymptomatic individuals. While detecting disease at an earlier stage has the potential to improve outcomes, screening also has negative consequences, including false positive results which may lead to anxiety, unnecessary diagnostic procedures, and increased healthcare costs. In addition, multiple false positive results could discourage participating in subsequent screening rounds. Screening guidelines typically recommend repeated screening over a period of many years, but little prior research has investigated how often individuals receive multiple false positive test results. Estimating the cumulative risk of multiple false positive results over the course of multiple rounds of screening is challenging due to the presence of censoring and competing risks, which may depend on the false positive risk, screening round, and number of prior false positive results. To address the general challenge of estimating the cumulative risk of multiple false positive test results, we propose a nonhomogeneous multistate model to describe the screening process including competing events. We developed alternative approaches for estimating the cumulative risk of multiple false positive results using this multistate model based on existing estimators for the cumulative risk of a single false positive. We compared the performance of the newly proposed models through simulation studies and illustrate model performance using data on screening mammography from the Breast Cancer Surveillance Consortium. Across most simulation scenarios, the multistate extension of a censoring bias model demonstrated lower bias compared to other approaches. In the context of screening mammography, we found that the cumulative risk of multiple false positive results is high. For instance, based on the censoring bias model, for a high-risk individual, the cumulative probability of at least two false positive mammography results after 10 rounds of annual screening is 40.4.

Germline testing is becoming increasingly relevant in prostate cancer (PCa) screening, prognosis, and management. A subset of patients with PCa harbor pathogenic/likely pathogenic variants (P/LPVs) in genes mediating DNA-repair processes, and these P/LPVs have implications for cancer screening, treatment, and cascade testing. As a result, it is recommended that all men with high-risk localized and metastatic PCa undergo routine germline testing. As more PCa patients undergo germline testing, it is important that clinicians and genetics experts recognize current disparities in germline testing rates among racial/ethnic minorities in the United States. The reasons for these disparities are multiple and require similarly manifold consideration to close the germline testing gap and reduce inequities in PCa screening, management, and treatment.

Patients experiencing homelessness face significant barriers to screening and treatment for colorectal cancer, leading to worse outcomes. In this perspective, we use an exemplar patient case to highlight potential policy solutions for reducing this health care disparity by increasing access to early detection and treatment in this population.

Background & aimsReports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics.MethodsA total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time up-to-date, consistency of adherence, and frequency of abnormal FIT.ResultsThe cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs 55.1%; P < .001). The proportion of time covered by screening was higher in the intervention group (46.8% vs 27.3%; Δ19.6%; 95% confidence interval, 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs 21.8%; P < .001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs 4.1% Usual Care; P < .01).ConclusionsOrganized mailed FIT outreach significantly increased colorectal cancer screening over multiple years in this safety-net health system. Although mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260).

BackgroundEstimating advanced breast cancer risk in women undergoing annual or biennial mammography could identify women who may benefit from less or more intensive screening. We developed an actionable model to predict cumulative 6-year advanced cancer (prognostic pathologic stage II or higher) risk according to screening interval.MethodsWe included 931 186 women aged 40-74 years in the Breast Cancer Surveillance Consortium undergoing 2 542 382 annual (prior mammogram within 11-18 months) or 752 049 biennial (prior within 19-30 months) screening mammograms. The prediction model includes age, race and ethnicity, body mass index, breast density, family history of breast cancer, and prior breast biopsy subdivided by menopausal status and screening interval. We used fivefold cross-validation to internally validate model performance. We defined higher than 95th percentile as high risk (>0.658%), higher than 75th percentile to 95th or less percentile as intermediate risk (0.380%-0.658%), and 75th or less percentile as low to average risk (

ObjectiveGiven that cervical cancer incidence rates do not decline in women >65, there is generally limited screening, and these women have a poor prognosis, it is imperative to better understand this population. We aim to describe the characteristics, treatment, and survival of women >65 diagnosed with cervical cancer.MethodsSEER-Medicare 2004-2013 data was used to describe 2274 patients >65 diagnosed with cervical cancer. Five-year cancer-specific survival was estimated using the Kaplan-Meier method. Multivariable Poisson and Cox regression analyses identified characteristics associated with treatment and mortality.ResultsThe median age was 76.1 years, with nearly one-third of cases occurring in women >80 years. Most patients were non-Hispanic White (64.8%), had comorbidity scores ≥ 1 (53.9%) and squamous histology (66.3%). Most women were diagnosed at stage II or higher (62.7%), including nearly one-quarter at Stage IV (23.1%). Nearly 15% of patients were not treated (14.6%). Lack of treatment was associated with oldest age (>80), comorbidity scores ≥3, and stage IV disease. Five-year cancer-specific survival was 50%. Increasing age and stage at diagnosis were significantly associated with lower cancer-specific survival whereas treatment was strongly associated with increased survival.ConclusionMost women >65 with cervical cancer are diagnosed with locally advanced or metastatic disease and many do not receive treatment. Survival is improved with early-stage diagnosis and treatment. These findings, coupled with the fact that women >65 constitute an increasing proportion of the population, highlight the need to re-evaluate screening and treatment practices in this population to detect cervical cancer at earlier stages and increase survival.Novelty and impact statementIn SEER-Medicare linked data from 2004 to 2013, most women >65 with cervical cancer were diagnosed with locally advanced or metastatic disease. Both receipt of treatment and survival decreased with increasing age. These findings, coupled with the fact that women aged >65 constitute an increasing proportion of the population, highlight the need to re-evaluate screening and treatment practices in older women to detect cervical cancer at earlier stages and increase survival.

BackgroundMammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.ObjectiveTo estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.DesignBayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.SettingBreast Cancer Surveillance Consortium (BCSC) facilities.ParticipantsWomen aged 50 to 74 years at first mammography screen between 2000 and 2018.MeasurementsScreening mammograms and screen-detected or interval breast cancer.ResultsThe cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.LimitationsExclusion of women with first mammography screen outside BCSC.ConclusionOn the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.Primary funding sourceNational Cancer Institute.

Opinion statementColorectal cancer (CRC) imposes significant morbidity and mortality, yet it is also largely preventable with evidence-based screening strategies. In May 2021, the US Preventive Services Task Force updated guidance, recommending screening begin at age 45 for average-risk individuals to reduce CRC incidence and mortality in the United States (US). The Task Force recommends screening with one of several screening strategies: high-sensitivity guaiac fecal occult blood test (HSgFOBT), fecal immunochemical test (FIT), multi-target stool DNA (mt-sDNA) test, computed tomographic (CT) colonography (virtual colonoscopy), flexible sigmoidoscopy, flexible sigmoidoscopy with FIT, or traditional colonoscopy. In addition to these recommended options, there are several emerging and novel CRC screening modalities that are not yet approved for first-line screening in average-risk individuals. These include blood-based screening or "liquid biopsy," colon capsule endoscopy, urinary metabolomics, and stool-based microbiome testing for the detection of colorectal polyps and/or CRC. In order to maximize CRC screening uptake in the US, patients and providers should engage in informed decision-making about the benefits and limitations of recommended screening options to determine the most appropriate screening test. Factors to consider include the invasiveness of the test, test performance, screening interval, accessibility, and cost. In addition, health systems should have a programmatic approach to CRC screening, which may include evidence-based strategies such as patient education, provider education, mailed screening outreach, and/or patient navigation, to maximize screening participation.

BackgroundInterstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILA are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral.Research questionCan consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs?Study design and methodsPulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement.ResultsFifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System "S-modifier" [Lung-RADS; which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD.InterpretationGuidance was established for identifying clinically relevant ILA, subsequent referral, and follow-up. These results lay the foundation for developing practical guidance on managing patients with ILA.

PurposeThe Breast Cancer Surveillance Consortium (BCSC) model is a widely used risk model that predicts 5- and 10-year risk of developing invasive breast cancer for healthy women aged 35-74 years. Women with high BCSC risk may also be at elevated risk to develop interval cancers, which present symptomatically in the year following a normal screening mammogram. We examined the association between high BCSC risk (defined as the top 2.5% by age) and breast cancers presenting as interval cancers.MethodsWe conducted a case-case analysis among women with breast cancer in which we compared the mode of detection and tumor characteristics of patients in the top 2.5% BCSC risk by age with age-matched (1:2) patients in the lower 97.5% risk. We constructed logistic regression models to estimate the odds ratio (OR) of presenting with interval cancers, and poor prognosis tumor features, between women from the top 2.5% and bottom 97.5% of BCSC risk.ResultsOur analysis included 113 breast cancer patients in the top 2.5% of risk for their age and 226 breast cancer patients in the lower 97.5% of risk. High-risk patients were more likely to have presented with an interval cancer within one year of a normal screening, OR 6.62 (95% CI 3.28-13.4, p

Tuberculosis (TB) is one of the leading causes of mortality in people living with HIV (PLHIV) and contributes to up to a third of deaths in this population. The World Health Organization guidelines aim to target early detection and treatment of TB among PLHIV, particularly in high-prevalence and low-resource settings. Prevention plays a key role in the fight against TB among PLHIV. This review explores TB screening tools available for PLHIV, including symptom-based screening, chest radiography, tuberculin skin tests, interferon gamma release assays, and serum biomarkers. We then review TB Preventive Treatment (TPT), shown to reduce the progression to active TB and mortality among PLHIV, and available TPT regimens. Last, we highlight policy-practice gaps and barriers to implementation as well as ongoing research needs to lower the burden of TB and HIV coinfection through preventive activities, innovative diagnostic tests, and cost-effectiveness studies.

BackgroundPoorly controlled diabetes mellitus (DM) increases the risk for periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). While institutional protocols include hemoglobin A1c (HbA1c) screening in TJA patients, the costs and benefits of routine preoperative screening have not been described.MethodsThe authors created a decision tree model to evaluate short-term costs and risk reduction for PJIs with routine screening of primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. Probabilities and costs were obtained from published sources. They calculated net costs and absolute risk reduction in PJI for routine screening versus no screening. The authors also performed sensitivity analyses of model inputs including probabilistic sensitivity analyses (PSAs) consisting of 10,000 Monte Carlo simulations.ResultsIn patients with DM, routine screening before THA resulted in net cost savings of $81 per patient with 286 patients needing to be screened to prevent 1 PJI, while screening before TKA incurred net additional costs of $25,810 per PJI prevented. Routine screening in patients with DM undergoing THA or TKA was cost-saving across 75.5% or 21.8% of PSA simulations, respectively. In patients with no history of DM, routine screening before THA or TKA incurred net additional costs of $24,583 or $87,873 per PJI prevented, respectively.ConclusionsRoutine HbA1c screening in patients with DM prior to THA with referral of patients with elevated HbA1c for glycemic optimization may prevent PJI and reduce healthcare costs. In contrast, routine screening in patients with DM prior to TKA or in patients with no history of DM is not cost-saving.Level of evidenceEconomic Level IV.

PurposeAdjunct cervical cancer screening methods are under evaluation to improve the diagnostic accuracy of human papillomavirus (HPV)-based screening in low- and middle-income countries. We evaluated the feasibility and acceptability of smartphone-based cervicography among HPV-positive women living with HIV (WLWH) in Western Kenya.MethodsHPV-positive WLWH of 25-49 years of age enrolled in a clinical trial (ClinicalTrials.gov identifier: NCT04191967) had digital images of the cervix taken using a smartphone by a nonphysician provider following visual inspection with acetic acid. All participants had colposcopy-directed biopsy before treatment. Cervical images were evaluated by three off-site colposcopists for quality, diagnostic utility, and assigned a presumed diagnosis. We determined the proportion of images rates as low, medium, or high quality, interobserver agreement using Cohen's Kappa statistic, and the off-site colposcopist's sensitivity and specificity for diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with histopathology. Acceptability was evaluated using a questionnaire.ResultsOne hundred sixty-four HPV-positive WLWH underwent cervicography during the study period. Mean age was 37.3 years. Images from the first 94 participants were evaluated by off-site colposcopists, with a majority (70.9%) rated as high quality. Off-site colposcopists had a sensitivity ranging from 21.4% (95% CI, 0.06 to 0.43) to 35.7% (95% CI, 0.26 to 0.46) and a specificity between 85.5% (95% CI, 0.81 to 0.90) to 94.9% (95% CI, 0.92 to 0.98) for diagnosis of CIN2+ based compared with histopathology. The majority of women, 99.4%, were comfortable having an image of their cervix taken as part of screening.ConclusionCervicography by a nonphysician provider as an adjunct to HPV-based screening among WLWH in a low- and middle-income country setting is feasible and acceptable. However, low sensitivity for diagnosis of CIN2+ by off-site expert colposcopists highlights the limitations of cervicography.

ObjectiveDigital health care offers an opportunity to scale and personalize cancer screening programs, such as mailed outreach for colorectal cancer (CRC) screening. However, studies that describe the patient selection strategy and process for CRC screening are limited. Our objective was to evaluate implementation strategies for selecting patients for CRC screening programs in large health care systems.MethodsWe conducted a systematic review of 30 studies along with key informant surveys and interviews to describe programmatic implementation strategies for selecting patients for CRC screening. PubMed and Embase were searched since inception through December 2018, and hand searches were performed of the retrieved reference lists but none were incorporated (n = 0). No language exclusions were applied.ResultsCommon criteria for outreach exclusion included: being up-to-date with routine CRC screening (n = 22), comorbidities (n = 20), and personal history (n = 22) or family history of cancer (n = 9). Key informant surveys and interviews were performed (n = 28) to understand data sources and practices for patient outreach selection, and found that 13 studies leveraged electronic medical care records, 10 studies leveraged a population registry (national, municipal, community, health), 4 studies required patient opt-in, and 1 study required primary care provider referral. Broad ranges in fecal immunochemical test completion were observed in community clinic (n = 8, 31.0-59.6%), integrated health system (n = 5, 21.2-82.7%), and national regional CRC screening programs (n = 17, 23.0-64.7%). Six studies used technical codes, and four studies required patient self-reporting from a questionnaire to participate.ConclusionThis systematic review provides health systems with the diverse outreach practices and technical tools to support efforts to automate patient selection for CRC screening outreach.

Although colorectal cancer (CRC) screening is highly effective, screening rates lag far below recommended levels, particularly for low-income people. The Colorectal Cancer Control Program (CRCCP) funded $100 million in competitively awarded grants to 25 states from 2009-2015 to increase CRC screening rates among low-income, uninsured populations, in part by directly providing and paying for screening services. Using data from the 2001-2015 Behavioral Risk Factor Surveillance System (BRFSS) and a difference-in-differences strategy, we find no effects of CRCCP on the use of relatively cheap fecal occult blood tests (FOBT). We do, however, find that the CRCCP significantly increased the likelihood that uninsured 50-64-year-olds report ever having a relatively expensive endoscopic CRC screening (sigmoidoscopy or colonoscopy) by 2.9 percentage points, or 10.7%. These effects are larger for women, minorities, and individuals who did not undertake other types of preventive care. We do not find that the CRCCP led to significant changes in CRC cancer detection. Our results indicate that the CRCCP was effective at increasing CRC screening rates among the most vulnerable.

Ovarian cancer is one of the leading causes of cancer related deaths affecting United States women. Early-stage detection of ovarian cancer has been linked to increased survival, however, current screening methods, such as biomarker testing, have proven to be ineffective in doing so. Therefore, further developments are necessary to be able to achieve positive patient prognosis. Ongoing efforts are being made in biomarker discovery towards clinical applications in screening for early-stage ovarian cancer. In this perspective, we discuss and provide examples for several workflows employing mass spectrometry-based proteomics towards protein biomarker discovery and characterization in the context of ovarian cancer; workflows include protein identification and characterization as well as intact protein profiling. We also discuss the opportunities to merge these workflows for a multiplexed approach for biomarkers. Lastly, we provide our insight as to future developments that may serve to enhance biomarker discovery workflows while also considering translational potential.

Background & aimsReports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics.MethodsA total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time up-to-date, consistency of adherence, and frequency of abnormal FIT.ResultsThe cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs 55.1%; P < .001). The proportion of time covered by screening was higher in the intervention group (46.8% vs 27.3%; Δ19.6%; 95% confidence interval, 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs 21.8%; P < .001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs 4.1% Usual Care; P < .01).ConclusionsOrganized mailed FIT outreach significantly increased colorectal cancer screening over multiple years in this safety-net health system. Although mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260).

ObjectivesThe goal of this study was to assess the utility of a genetic risk score (GRS) in targeted coronary artery calcium (CAC) screening among young individuals.BackgroundEarly CAC screening and preventive therapy may reduce long-term risk of a coronary heart disease (CHD) event. However, identifying younger individuals at increased risk remains a challenge. GRS for CHD are age independent and can stratify individuals on various risk trajectories.MethodsUsing 142 variants associated with CHD events, we calculated a GRS in 1,927 individuals in the CARDIA (Coronary Artery Risk Development in Young Adults) cohort (aged 32 to 47 years) and 6,600 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (aged 44 to 87 years). We assessed GRS utility to predict CAC presence in the CARDIA cohort and stratify individuals of varying risk for CAC presence over the lifetime in both cohorts.ResultsThe GRS predicted CAC presence in CARDIA males. It was not predictive in CARDIA females, which had a CAC prevalence of 6.4%. In combined analysis of the CARDIA and MESA cohorts, the GRS was predictive of CAC in both males and females and was used to derive an equation for the age at which CAC probability crossed a predetermined threshold. When assessed in combination with traditional risk factors, the GRS further stratified individuals. For individuals with an equal number of traditional risk factors, probability of CAC reached 25% approximately 10 years earlier for those in the highest GRS quintile compared to the lowest.ConclusionsThe GRS may be used to target high-risk younger individuals for early CAC screening.

ObjectiveAssess the quality of critical congenital heart disease (CCHD) screening data reports in California, where CCHD screening is not mandatory but reporting is.Study designRetrospective review of California hospital-level CCHD screening data to evaluate data reliability and adherence to state screening and reporting recommendations. Data were evaluated for internal consistency and compared to two databases.ResultsOver one-third of hospitals did not submit data. Only 70.7% of the Vital Records live births were reported in CCHD screening data. Only 46% of reporting hospitals submitted data with matching numbers of completed screens and results, and 22% matched their respective live births in a second database.ConclusionCCHD data reporting in California is incomplete, which may miss 359 CCHD cases/year from non-reporting. Data inconsistencies may miss additional cases. Mandatory screening, reporting, and improvements in data reliability are urgently needed to inform screening modifications and enhance timely detection and disease surveillance.

The purpose of this study was to first characterize the prevalence of recall, recognition, and knowledge of colon cancer screening tests and guidelines (collectively, "awareness") among non-Hispanic black (NHB) and NH white (NHW) urban colon cancer patients. Second, we sought to examine whether awareness was associated with mode of cancer detection. Low awareness regarding colon cancer screening tests and guidelines may explain low screening rates and high prevalence of symptomatic detection. We examined recall, recognition, and knowledge of colorectal cancer (CRC) screening tests and guidelines and their associations with mode of cancer detection (symptomatic versus screen-detected) in 374 newly diagnosed NHB and NHW patients aged 45-79. Patients were asked to name or describe any test to screen for colon cancer (recall); next, they were given descriptions of stool testing and colonoscopy and asked if they recognized each test (recognition). Lastly, patients were asked if they knew the screening guidelines (knowledge). Overall, awareness of CRC screening guidelines was low; just 20% and 13% of patients knew colonoscopy and fecal test guidelines, respectively. Awareness of CRC screening tests and guidelines was especially low among NHB males, socioeconomically disadvantaged individuals, and those diagnosed at public healthcare facilities. Inability to name or recall a single test was associated with reduced screen-detected cancer compared with recall of at least one test (36% vs. 22%, p = 0.01). Low awareness of CRC screening tests is a risk factor for symptomatic detection of colon cancer.

Oral cancer (OC) is the sixth most commonly reported malignant disease globally, with high rates of disease-related morbidity and mortality due to advanced loco-regional stage at diagnosis. Early detection and prompt treatment offer the best outcomes to patients, yet the majority of OC lesions are detected at late stages with 45% survival rate for 2 years. The primary cause of poor OC outcomes is unavailable or ineffective screening and surveillance at the local point-of-care level, leading to delays in specialist referral and subsequent treatment. Lack of adequate awareness of OC among the public and professionals, and barriers to accessing health care services in a timely manner also contribute to delayed diagnosis. As image analysis and diagnostic technologies are evolving, various artificial intelligence (AI) approaches, specific algorithms and predictive models are beginning to have a considerable impact in improving diagnostic accuracy for OC. AI based technologies combined with intraoral photographic images or optical imaging methods are under investigation for automated detection and classification of OC. These new methods and technologies have great potential to improve outcomes, especially in low-resource settings. Such approaches can be used to predict oral cancer risk as an adjunct to population screening by providing real-time risk assessment. The objective of this study is to (1) provide an overview of components of delayed OC diagnosis and (2) evaluate novel AI based approaches with respect to their utility and implications for improving oral cancer detection.

Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.

ObjectiveTo evaluate access to treatment after community-based HPV testing as testing within screen-and-treat programs has the potential to lower mortality from cervical cancer in low-resource settings.MethodsA prospective cohort study was conducted in western Kenya in 2018. Women aged 25-65 years underwent HPV self-testing. HPV-positive women were referred for cryotherapy. Participant data were obtained from questionnaires during screening and treatment. The proportion successfully accessing treatment and variables associated with successful treatment was determined.ResultsOf the 750 women included, 140 (18.6%) tested positive for HPV. Of them, 135 were notified of their results, of whom 77 (59.2%) sought treatment and 73 (52.1%) received cryotherapy. Women who received treatment had a shorter time from screening to result notification (median 92 days, interquartile range [IQR] 84-104) compared to those who did not (97 days, IQR 89-106; P=0.061). In adjusted analyses, women with a history of cervical cancer screening (odds ratio [OR] 11, 95% confidence interval [CI] 1.42-85.20) and those electing result notification through a home visit (OR 4, 95% CI 1.23-14.17) were significantly more likely to acquire treatment at follow-up.ConclusionLinkage to treatment after community-based HPV screening in this population was low, highlighting the need for strategies aimed at strengthening treatment linkage in similar settings.

PurposeWomen with a first-degree family history of breast cancer (FHBC) are sometimes advised to initiate screening mammography when they are 10 years younger than the age at which their youngest relative was diagnosed, despite a lack of unambiguous evidence that this is an effective strategy. It is unknown how often this results in women initiating screening earlier (< 40 years) than screening guidelines recommend for average-risk women.MethodsWe examined screening initiation age by FHBC and age at diagnosis of the youngest relative using data collected by the Breast Cancer Surveillance Consortium on 74,838 first screening mammograms performed between 1996 and 2016.ResultsOf the 74,838 women included in the study, nearly 9% reported a FHBC. Approximately 16.8% of women who initiated mammography before 40 years reported a FHBC. More women with a FHBC than without initiated screening < 40 years (48% vs. 23%, respectively). Among women with a FHBC who initiated screening < 40 years, 65% were 10 years younger than the age at which their relative was diagnosed.ConclusionWomen with a first-degree relative diagnosed with breast cancer were more likely to start screening before 40 years than women reporting no FHBC, especially if their relative was diagnosed before 50 years.

Population screening played a substantial role in safely reopening the economy and avoiding new outbreaks of COVID-19. PCR-based pooled screening makes it possible to test the population with limited resources by pooling multiple individual samples. Our study compared different population-wide screening methods as transmission-mitigating interventions, including pooled PCR, individual PCR, and antigen screening. Incorporating testing-isolation process and individual-level viral load trajectories into an epidemic model, we further studied the impacts of testing-isolation on test sensitivities. Results show that the testing-isolation process could maintain a stable test sensitivity during the outbreak by removing most infected individuals, especially during the epidemic decline. Moreover, we compared the efficiency, accuracy, and cost of different screening methods during the pandemic. Our results show that PCR-based pooled screening is cost-effective in reversing the pandemic at low prevalence. When the prevalence is high, PCR-based pooled screening may not stop the outbreak. In contrast, antigen screening with sufficient frequency could reverse the epidemic, despite the high cost and the large numbers of false positives in the screening process.

BackgroundFetal Alcohol Spectrum Disorders (FASD) are a global health concern. Early intervention mitigates deficits, yet early diagnosis remains challenging. We examined whether children can be screened and meet diagnoses for FASD at 1.5 years compared to 5 years post-birth.MethodsA population cohort of pregnant women in 24 neighborhoods (N = 1258) was recruited and 84.5 %-96 % were reassessed at two weeks post-birth, 0.5 years, 1.5 years, 3 years, and 5 years later. A two-step process was followed to diagnose FASD; first, a paraprofessional screened the children and then a physician evaluated the child. We evaluated FASD symptoms at 1.5 vs. 5 years. We also examined maternal differences in children receiving a positive FASD screening (n = 160) with those who received a negative FASD screening.ResultsScreening positive for FASD more than doubled from 1.5 years to 5 years (from 6.8 % to 14.8 %). About one quarter of children who screened positive and were evaluated by a physician, were diagnosed as having a FASD. However, half did not complete the 2nd stage screening. Compared to mothers of children with a negative FASD screening, mothers of children with a positive FASD screening were less likely to have a high school education and more likely to have lower incomes, have experienced interpersonal partner violence, and have a depressed mood. Mothers of children who did not follow up for a 2nd stage physician evaluation were more like to live in informal housing compared to those who followed-up (81.3 % vs. 62.5 %, p = 0.014).ConclusionsWe found that children can be screened and diagnosed for FASD at 1.5 and 5 years. As FASD characteristics develop over time, repeated screenings are necessary to identify all affected children and launch preventive interventions. Referrals for children to see a physician to confirm diagnosis and link children to care remains a challenge. Integration with the primary healthcare system might mitigate some of those difficulties.

BackgroundPhysiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM.MethodsInclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), Ktrans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria.ResultsOut of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, Ktrans, Vp, and Ve were not indicative of treatment response within 6 months.ConclusionsIn patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment.Key points• In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response.• Interval change in rADC can be used as an imaging biomarker to determine PFS6.• Interval change in MR perfusion and permeability measures do not suggest ICI treatment response.

Screening for cancer is a proven and recommended approach to prevent deaths from cancer; screening can locate precursor lesions and/or cancer at early stages when it is potentially curable. Racial and ethnic minorities and other medically underserved populations exhibit lower uptake of cancer screening than nonminorities in the United States. The COVID-19 pandemic, which disproportionately affected minority communities, has curtailed preventive services including cancer screening to preserve personal protective equipment and prevent spread of infection. While there is evidence for a rebound from the pandemic-driven reduction in cancer screening nationally, the return may not be even across all populations, with minority population screening that was already behind becoming further behind as a result of the community ravages from COVID-19. Fear of contracting COVID-19, limited access to safety-net clinics, and personal factors like, financial, employment, and transportation issues are concerns that are intensified in medically underserved communities. Prolonged delays in cancer screening will increase cancer in the overall population from pre-COVID-19 trajectories, and elevate the cancer disparity in minority populations. Knowing the overall benefit of cancer screening versus the risk of acquiring COVID-19, utilizing at-home screening tests and keeping the COVID-19-induced delay in screening to a minimum might slow the growth of disparity.

Immigration-related concerns can impact health and are an important consideration while caring for a multinational Latinx immigrant community. Patients and caregivers waiting for a non-urgent clinic appointment were randomly screened with one of two social risk screening tools. One tool included a question about "any health or stability concerns related to immigration status." The other tool did not include an immigration health question. Immediately following, respondents were invited to participate in a semi-structured interview regarding their social risk screening experience. 201 screens were completed, and 20 patients agreed to an interview. There were no significant sociodemographic differences between groups. Of those screened for immigration, 11% reported a concern. In both arms, interviewees felt that social risk screening was acceptable in a clinic setting. Questions about immigration are timely, important, and relevant, and can be considered when implementing social assessments in communities where there are high levels of trust in providers.

IntroductionThe majority of blindness worldwide could be prevented or reversed with early diagnosis and treatment, yet identifying at-risk and prevalent cases of eye disease and linking them with care remain important obstacles to addressing this burden. Leading causes of blindness like glaucoma, diabetic retinopathy and age-related macular degeneration have detectable early asymptomatic phases and can cause irreversible vision loss. Mass screening for such diseases could reduce visual impairment at the population level.Methods and analysisThis protocol describes a parallel-group cluster-randomised trial designed to determine whether community-based screening for glaucoma, diabetic retinopathy and age-related macular degeneration reduces population-level visual impairment in Nepal. A door-to-door population census is conducted in all study communities. All adults aged ≥60 years have visual acuity tested at the census visit, and those meeting referral criteria are referred to a local eye care facility for further diagnosis and management. Communities are subsequently randomised to a community-based screening programme or to no additional intervention. The intervention consists of a single round of screening including intraocular pressure and optical coherence tomography assessment of all adults ≥60 years old with enhanced linkage to care for participants meeting referral criteria. Four years after implementation of the intervention, masked outcome assessors conduct a repeat census to collect data on the primary outcome, visual acuity. Individuals with incident visual impairment receive a comprehensive ophthalmological examination to determine the cause of visual impairment. Outcomes are compared by treatment arm according to the originally assigned intervention.Ethics and disseminationThe trial has received ethical approval from the University of California San Francisco Institutional Review Board, Nepal Netra Jyoti Sangh and the Nepal Health Research Council. Results of this trial will be disseminated through publication in peer-reviewed journals and presentation at local and international meetings.Trial registration numberNCT03752840.

Public health newborn screening (NBS) programs provide population-scale ascertainment of rare, treatable conditions that require urgent intervention. Tandem mass spectrometry (MS/MS) is currently used to screen newborns for a panel of rare inborn errors of metabolism (IEMs)1-4. The NBSeq project evaluated whole-exome sequencing (WES) as an innovative methodology for NBS. We obtained archived residual dried blood spots and data for nearly all IEM cases from the 4.5 million infants born in California between mid-2005 and 2013 and from some infants who screened positive by MS/MS, but were unaffected upon follow-up testing. WES had an overall sensitivity of 88% and specificity of 98.4%, compared to 99.0% and 99.8%, respectively for MS/MS, although effectiveness varied among individual IEMs. Thus, WES alone was insufficiently sensitive or specific to be a primary screen for most NBS IEMs. However, as a secondary test for infants with abnormal MS/MS screens, WES could reduce false-positive results, facilitate timely case resolution and in some instances even suggest more appropriate or specific diagnosis than that initially obtained. This study represents the largest, to date, sequencing effort of an entire population of IEM-affected cases, allowing unbiased assessment of current capabilities of WES as a tool for population screening.