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Introduction: Guideline-discordant low-dose computed tomography (LDCT) screening may cause lung cancer (LC) overdiagnosis, but its extent and consequences are unclear. This study aimed to investigate the prevalence of self-initiated, non-reimbursed LDCT screening in a predominantly non-smoking population and its impact on LC epidemiology and healthcare utilization., Methods: This nationwide cohort study analyzed data from Korea's National Health Information Database and 11 academic hospital screening centers (1999-2022). The overall analysis encompassed the entire Korean population. For non-reimbursed LDCT screening prevalence, which the National Health Information Database does not capture, a separate analysis was conducted on a cohort of 1.7 million adults to extrapolate nationwide rates. Outcomes included trends in self-initiated, non-reimbursed LDCT screening, LC incidence, mortality, stage and age at diagnosis, 5-year survival, and LC-related healthcare utilization, including surgeries and biopsies. Joinpoint regression assessed trend changes., Results: Self-initiated, non-reimbursed LDCT screening during health check-ups increased from 29% to 60% in men and 7% to 46% in women, despite only 2.4% of men and 0.04% of women qualifying for risk-based screening. In women, localized-stage LC incidence nearly doubled (age-standardized incidence rate: from 7.6 to 13.7 per 100,000), whereas distant-stage incidence decreased (age-standardized incidence rate: from 16.1 to 15.0 per 100,000). LC mortality declined (age-standardized mortality rate: from 23.3 to 19.8 per 100,000), whereas 5-year survival rates improved substantially. LC diagnoses in women shifted towards earlier stages and younger ages. Lung surgeries for both malignant and benign lesions, frequently lacking nonsurgical biopsies, increased sharply in women., Conclusions: Widespread guideline-discordant LDCT screening correlates with LC overdiagnosis and increased healthcare utilization, particularly in women. Randomized controlled trials are needed to assess the risks and benefits of screening in low-risk populations to determine its efficacy and consequences., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Asymptomatic patients with moderate functional capacity do not require Coronary Artery Disease (CAD) workup in the preoperative period of non-cardiac surgeries, especially when scheduled for minor and intermediate-risk surgeries. The workup is inappropriate because it promotes over diagnosing and pointless treatments. Moreover, those patients usually undergo cardiology assessment, in addition to pre-anesthetic evaluation. Objective: Investigate the role of cardiology consultation as mediator in inappropriate assessment of CAD for preoperative of non-cardiac surgeries. Method: Retrospective study performed in a private anesthesia service using medical charts of asymptomatic patients with a history of controlled systemic disease and moderate functional capacity, submitted to pre-anesthetic consultation for minor and intermediate risk surgeries. Cardiology consultations were identified by the presence of a consultation report by a cardiologist. CAD workup was defined as undergoing cardiac stress tests. Results: We included 390 medical charts of patients with mean age of 48.6 ± 15.4 years, 67% women and 69% intermediate risk surgeries. CAD workup was infrequent and performed in 3.9% of patients. Besides, pre-anesthetic evaluation, 93 (24%) patients had a cardiology consultation. Among those patients, 15.1% were submitted to CAD workup, compared to 0.34% of patients without cardiology assessment (p

Worldwide, lung cancer is the most common killer among cancers, advanced disease has worse outcomes, earlier stage detection leads to better outcomes, and high-quality screening has a favorable net benefit. With the mortality reduction recognized from annual low-radiation dose computed tomography by screening those at high risk, there has been consideration that this benefit could translate to those who have never smoked. There have been several large-scale, single-arm, observational trials in Asia in persons with light to no smoking histories, with or without a family history of lung cancer, which have revealed high or higher lung cancer detection rates than previously reported in high-risk persons who currently or formerly smoked. The Early Detection Program for Lung Cancer in Taiwan, of nearly 50,000 persons, revealed that the cancer detection rate for those screened with low-radiation dose computed tomography was more than twofold higher in light- or never-smokers with a family history of lung cancer compared with high-risk persons with more than 30 or more pack-years exposure and meeting U.S. Preventative Services Task Force criteria for screening. In addition, more than 90% of the cancers detected in those with a family history were in early stage. On the basis of those findings, the researchers concluded that screening first-degree relatives of those with a family history of lung cancer, irrespective of smoking history, would lead to a decrease in lung cancer mortality. We believe that the findings in this cohort and others like it represent substantial overdiagnosis and that the harms associated with screening a population that has a low likelihood of developing lethal cancers have not been thoroughly considered. Here, we provide our perspective and consider the potential benefits and harms of screening populations outside those currently eligible using the U.S. Preventative Services Task Force criteria., Competing Interests: Disclosure Dr. Silvestri reports research relationships with Delfi, Nucleix and Freenome and research and consulting relationship with Biodesix. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Digital pathology solutions are increasingly implemented for primary diagnostics in departments of pathology around the world. This has sparked a growing engagement on validation studies to evaluate the diagnostic performance of whole slide imaging (WSI) regarding safety, reliability, and accuracy. The aim of this review was to evaluate the performance of digital pathology for diagnostic purposes compared to light microscopy (LM) in human pathology, based on validation studies designed to assess such technologies. Methods: In this systematic review based on PRISMA guidelines, we analyzed validation studies of WSI compared with LM. We included studies of diagnostic performance of WSI regarding diagnostic test accuracy (DTA) indicators, degree of overdiagnosis, diagnostic concordance, and observer variability as a secondary outcome. Overdiagnosis is (for example) detecting a pathological condition that will either not progress or progress very slowly. Thus, the patient will never get symptoms from this condition and the pathological condition will never be the cause of death. From a search comprising four databases: PubMed, EMBASE, Cochrane Library, and Web of Science, encompassing the period 2010–2021, we selected and screened 12 peer-reviewed articles that fulfilled our selection criteria. Risk of bias was conducted through QUADAS-2 tool, and data analysis and synthesis were performed in a qualitative format. Results: We found that diagnostic performance of WSI was not inferior to LM for DTA indicators, concordance, and observer variability. The degree of overdiagnosis was not explicitly reported in any of the studies, while the term itself was used in one study and could be implicitly calculated in another. Conclusion: WSI had an overall high diagnostic accuracy based on traditional accuracy measurements; however, the degree of overdiagnosis is unknown.

Resumen: Los médicos de familia atendemos una gran variedad de pacientes, con un amplio rango de complejidad, en poco tiempo y con pocos medios diagnósticos. Esta situación hace más vulnerables a los profesionales de atención primaria a los errores diagnósticos (EEDD). Por ello, un adecuado proceso de razonamiento clínico es la herramienta más potente con la que contamos para orientar con seguridad el proceso asistencial de los pacientes. El hecho de considerar estos errores como oportunidades perdidas de un diagnóstico correcto, que pueden producir daño al paciente, nos lleva como profesionales a revisar cómo mejorar dicho proceso. La revisión incluye, entre otros aspectos, identificar sesgos cognitivos, analizar las formas de organización del trabajo en los equipos de atención primaria y situaciones del contexto asistencial que pueden contribuir a dichos errores. En este artículo describimos los EEDD y sus factores causales más frecuentes en atención primaria, el impacto que tienen los fallos de los procesos cognitivos, las situaciones de sobrediagnóstico y las cascadas diagnósticas y terapéuticas asociadas a estos. Finalmente, proponemos un conjunto de herramientas para mejorar la toma de decisiones en el proceso diagnóstico en atención primaria. Abstract: Family doctors see a wide range of patients, with a wide range of complexity, in a short time and with few diagnostic resources. This situation makes primary care professionals more vulnerable to diagnostic errors. For this reason, an adequate clinical reasoning process is the most powerful tool family doctors have to safely guide the patient care process. Considering these errors as missed opportunities for a correct diagnosis, which may cause harm to the patient, leads us as professionals to review how to improve this process. The review includes, among other aspects, identifying cognitive biases, analysing the ways in which work is organised in primary care teams, and situations in the care context that may contribute to such errors. In this article we describe the most frequent diagnostic errors and their causal factors in primary care, the impact of cognitive process failures, situations of overdiagnosis and the diagnostic and therapeutic cascades associated with them. Finally, we propose a set of tools to improve decision-making in the diagnostic process in primary care.

Objectives: Film mammography has been replaced by digital mammography in breast screening programs globally. This led to a small increase in the rate of detection, but whether the detection of clinically important cancers increased is uncertain. We aimed to assess the impact on tumor characteristics of screen-detected and interval breast cancers., Study Design and Setting: We searched seven databases from inception to October 08, 2023, for publications comparing film and digital mammography within the same population of asymptomatic women at population (average) risk of breast cancer. We recorded reported tumor characteristics and assessed risk of bias using the Risk Of Bias In Non-randomised Studies - of Interventions tool. We synthesized results using meta-analyses of random effects., Results: Eighteen studies were included in the analysis from 8 countries, including 11,592,225 screening examinations (8,117,781 film; 3,474,444 digital). There were no differences in tumor size, morphology, grade, node status, receptor status, or stage in the pooled differences for screen-detected and interval invasive cancer tumor characteristics. There were statistically significant increases in screen-detected ductal carcinoma in situ (DCIS) across all grades: 0.05 (0.00-0.11), 0.14 (0.05-0.22), and 0.19 (0.05-0.33) per 1000 screens for low, intermediate, and high-grade DCIS, respectively. There were similar (non-statistically significant) increases in screen-detected invasive cancer across all grades., Conclusion: The increased detection of all grades of DCIS and invasive cancer may indicate both increased early detection of more aggressive disease and increased overdiagnosis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Although three randomized control trials have proven mortality benefit of CT lung cancer screening (CTLS),

Chest pain is a common clinical condition in the emergency department. A high sensitive (hs) troponin test assay may help to identify patients with acute coronary syndrome earlier compared to conventional tests but also entails the risk of a high proportion of positive test results in patients without cardiac disease. We assessed the impact of the introduction of the hs-troponin test in clinical practice in an emergency department.We compared December 1, 2009 until November 30, 2010 (standard test period) to December 1, 2010 – the date of the introduction of the hs-troponin assay – until December 31, 2011 (hs troponin test period) of patients presenting with chest pain to one of the ten largest hospitals in Switzerland.We identified electronic health records using the following ICD-10 codes: R06.4 (hyperventilation), R07.1 (chest pain when breathing), R07.2 (precordial pain), R07.3 (other chest pain), and R07.4 (chest pain not specified), I20 (angina pectoris), I21 (acute MI), I22 (recurrent MI), I23 (complications after acute MI), and I24 (other acute ischemic heart disease).Included were all medical records of adult patients (≥18 years) presenting to the ED with chest pain and with ≥1 troponin test. Excluded were records without troponin test, pregnancy, trauma patients/life-threatening conditions, malignant disease, current fracture, renal replacement therapy/severe kidney failure (creatinine clearance 3 months due to chest pain were defined as a new index visit of a second episode. The extraction form with predefined variables was pilot-tested in 20 records. Additional diagnostic tests were ECG, treadmill test, coronary angiography, MIBI scintigraphy, echocardiography, chest X-ray, computer tomography (CT) of the chest or abdomen, sonography of the abdomen or pleura, gastroscopy, and lung function tests.We compared the number of non-invasive / invasive cardiac diagnostic tests in troponin positive and negative patients and the number of diagnostic tests after the exclusion of patients with STEMI diagnosis. Non-invasive / invasive cardiac tests included treadmill test, coronary angiography, MIBI scintigraphy, and echocardiography. We calculated average monthly tests per patient and compared mean tests per patient between groups. We used a t-test to quantify the evidence for differential number of diagnostic tests per patient in each period. Between-group differences were estimated with 95% confidence intervals. All analyses were performed with the statistical software R for windows [1].Interpretation of this data can be found in a research article titled Impact of the introduction of high-sensitive troponin assay on the evaluation of chest pain patients in the emergency department: a retrospective study [2]).

Objectives: Thyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence., Methods: PATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States., Results: PATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases., Conclusions: PATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs., Competing Interests: Author Disclosures Links to the disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The quality of e-Consultations in the COPD is unknown. The objectives of this study were (i) to evaluate the quality of referrals; (ii) to define the characteristics of patients referred from Primary Care (PC) to the Unit of Pulmonology; and (iii) to describe differences between accepted and rejected patients., Methods: A retrospective, observational study of e-Consultations requested by PC for suspected COPD throughout 2022. To quantify the quality of the e-Consultations, an arbitrary scale of 12 variables (score 0-10) was created., Results: In total, 384 e-Consultations were reviewed, of which 167 (43.5 %) resulted in a face-to-face visit, and 217 (56.5 %) were rejected. No differences were observed between the two types of patients, except for confirmations of diagnostic suspicion of COPD [significantly higher in accepted patients (p = 0.042)]; physical examination data of rejected patients (more data provided; p = 0.015); and lung function (significantly better in rejected patients). The mean quality of referrals was acceptable (5.6 ± 2.1 score): 121 (31.3 %) had insufficient quality; 118 (30.5 %) acceptable; 75 (19.4 %) good, and 30 (7.8 %) excellent. Quality was low in half of the variables analyzed (6/12); acceptable in 3, and good in another 3. The capacity of resolution of referrals was good (one e-Consultation) in 199 requests (66.1 %); deficient (two e-Consultations) in 72 (23.9 %), and poor (≥3 e-Consultations) in 30 (10 %). Overdiagnosis was 40.2 % (86/214 e-Consultations). The risk could be classified in 247 patients (64.3 %; 135 low-risk; 90 high-risk)., Conclusions: When adequate information is provided, e-Consultations help identify different levels of severity. However, the quality and capacity of resolution of referrals were suboptimal, with a high percentage of overdiagnoses., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication. We confirm that the manuscript has not been published elsewhere in any other language and is not currently being considered for publication in another journal., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: To evaluate the strength of the evidence for, and the extent of, overdiagnosis in noncancer conditions., Study Design and Setting: We systematically searched for studies investigating overdiagnosis in noncancer conditions. Using the 'Fair Umpire' framework to assess the evidence that cases diagnosed by one diagnostic strategy but not by another may be overdiagnosed, two reviewers independently identified whether a Fair Umpire-a disease-specific clinical outcome, a test result or risk factor that can determine whether an additional case does or does not have disease-was present. Disease-specific clinical outcomes provide the strongest evidence for overdiagnosis, follow-up or concurrent tests provide weaker evidence, and risk factors provide only weak evidence. Studies without a Fair Umpire provide the weakest evidence of overdiagnosis., Results: Of 132 studies, 47 (36%) did not include a Fair Umpire to adjudicate additional diagnoses. When present, the most common Umpire was a single test or risk factor (32% of studies), with disease-specific clinical outcome Umpires used in only 21% of studies. Estimates of overdiagnosis included 43-45% of screen-detected acute abdominal aneurysms, 54% of cases of acute kidney injury, and 77% of cases of oligohydramnios in pregnancy., Conclusion: Much of the current evidence for overdiagnosis in noncancer conditions is weak. Application of the framework can guide development of robust studies to detect and estimate overdiagnosis in noncancer conditions, ultimately informing evidence-based policies to reduce it., Competing Interests: Declaration of competing interest All authors are part of Wiser Healthcare—a research collaboration for reducing overdiagnosis and overtreatment: https://www.wiserhealthcare.org.au., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Examine how women aged 35-50 respond to messages about limiting cancer screening., Methods: A national sample of women aged 35-50 (n = 983) were randomly assigned to read one of four media vignettes: three provided information about potential harms of mammograms using evidence, norms, or an anecdote strategy, and one provided no such information. Participants listed thoughts they had about the message, and after coding these themes, we tested for associations between the themes evoked, message exposure, and mammogram history., Results: Thematic categories included emotions (8 %); behavioral intentions (14 %); and cognitions, attitudes, and beliefs (67 %). Pro-screening attitudes, questioning, and cues to get screened were most prevalent. The anecdote message often elicited pro-screening attitudes, while the evidence message often elicited negative emotions and anger, as well as questioning or skeptical responses. Those with a history of mammograms expressed more pro-screening attitudes and disagreed with the message more often., Conclusions: Media messaging about guideline-supported care, especially when it involves reducing a clinical service that is routine and valued by patients, may evoke counterarguing, skepticism, and other negative responses., Practice Implications: Clinicians should recognize the role of the media in potentially shaping women's attitudes, beliefs, and intentions when it comes to breast cancer screening., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Medical imaging plays an essential role in healthcare. As a diagnostic test, imaging is prone to substantial overuse and potential overdiagnosis, with dire consequences to patient outcomes and health care costs. Clinical decision support systems (CDSSs) were developed to guide referring physicians in making appropriate imaging decisions. This study will evaluate the effect of implementing a CDSS (ESR iGuide) with versus without active decision support in a physician order entry on the appropriate use of imaging tests and ordering behaviour., Methods: A protocol for a multi-center cluster-randomized trial with departments acting as clusters, combined with a before-after-revert design. Four university hospitals with eight participating departments each for a total of thirty-two clusters will be included in the study. All departments start in control condition with structured data entry of the clinical indication and tracking of the imaging exams requested. Initially, the CDSS is implemented and all physicians remain blinded to appropriateness scores based on the ESR imaging referral guidelines. After randomization, half of the clusters switch to the active intervention of decision support. Physicians in the active condition are made aware of the categorization of their requests as appropriate, under certain conditions appropriate, or inappropriate, and appropriate exams are suggested. Physicians may change their requests in response to feedback. In the revert condition, active decision support is removed to study the educational effect., Results/conclusions: The main outcome is the proportion of inappropriate diagnostic imaging exams requested per cluster. Secondary outcomes are the absolute number of imaging exams, radiation from diagnostic imaging, and medical costs., Trial Registration Number: Approval from the Medical Ethics Review Committee was obtained under protocol numbers 20-069 (Augsburg), B 238/21 (Kiel), 20-318 (Lübeck) and 2020-15,125 (Mainz). The trial is registered in the ClinicalTrials.gov register under registration number NCT05490290., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Dijk receives research funding from the Gordon and Betty Moore Foundation Dr. Kröncke receives (or received within the past 36 months) research funding outside the submitted work from The Bavarian Centre for Cancer Research, the national Network University Medicine (NUM) and Siemens Healthineers, has received honoraria for educational symposia from SIRTEX Medical, Boston Scientific and Abbott Medical GmbH and re-imbursements of expenses related to his work in the executive committee and congressional events of the Cardiovascular and Interventional Radiological Society of Europe. Dr. Claudia Wollny has no conflicts of interest to report. Dr. Halfmann has no conflicts of interest to report Dr. Jansen receives (or received within the past 36 months) research funding outside the submitted work from DFG (German scientific society), has received speaker fee from Philips Medical, Rapid AI, mRAY, Boehringer and Bayer and has received consultant honoraria from TÜV Süd, Radiologie Holding and Stryker. Dr. Hunink receives (or received in the past 36 months) Royalties from Cambridge University Press for a textbook on Medical Decision Making, reimbursement of expenses from the European Society of Radiology (ESR) for work on the ESR guidelines for imaging referrals, reimbursement of expenses from the European Institute for Biomedical Imaging Research (EIBIR) for membership of the Scientific Advisory Board, and research funding from the American Diabetes Association, the Netherlands Organization for Health Research and Development, Netherlands Educational Grant (“Studievoorschotmiddelen”), and the Gordon and Betty Moore Foundation., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Adequate methods to promptly translate digital health innovations for improved patient care are essential. Advances in Artificial Intelligence (AI) and Machine Learning (ML) have been sources of digital innovation and hold the promise to revolutionize the way we treat, manage and diagnose patients. Understanding the benefits but also the potential adverse effects of digital health innovations, particularly when these are made available or applied on healthier segments of the population is essential. One of such adverse effects is overdiagnosis., Objective: to comprehensively analyze quantification strategies and data-driven definitions for overdiagnosis reported in the literature., Methods: we conducted a scoping systematic review of manuscripts describing quantitative methods to estimate the proportion of overdiagnosed patients., Results: we identified 46 studies that met our inclusion criteria. They covered a variety of clinical conditions, primarily breast and prostate cancer. Methods to quantify overdiagnosis included both prospective and retrospective methods including randomized clinical trials, and simulations., Conclusion: a variety of methods to quantify overdiagnosis have been published, producing widely diverging results. A standard method to quantify overdiagnosis is needed to allow its mitigation during the rapidly increasing development of new digital diagnostic tools., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel Capurro reports a relationship with Medical Research Future Fund that includes: funding grants. Corresponding author is a member of the journal’s Editorial Board, (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Thyroid cancer incidence in France has increased rapidly in recent decades. Most of this increase has been attributed to overdiagnosis, the major consequence of which is overtreatment. We aimed to estimate the cost of thyroid cancer management in France and the corresponding cost proportion attributable to the treatment of overdiagnosed cases., Methods: Multiple data sources were integrated: the mean cost per patient with thyroid cancer was estimated by using the Echantillon Généraliste des Bénéficiaires data set; thyroid cancer cases attributable to overdiagnosis were estimated for 21 departments using data from the French network of cancer registries and extrapolated to the whole country; medical records from 6 departments were used to refine the diagnosis and care pathway., Results: Between 2011 and 2015, 33 911 women and 10 846 men in France were estimated to be diagnosed of thyroid cancer, with mean cost per capita of €6248. Among those treated, 8114 to 14 925 women and 1465 to 3626 men were due to overdiagnosis. The total cost of thyroid cancer patient management was €203.5 million (€154.3 million for women and €49.3 million for men), of which between €59.9 million (or 29.4% of the total cost, lower bound) and €115.9 million (or 56.9% of the total cost, upper bound) attributable to treatment of overdiagnosed cases., Conclusions: The management of thyroid cancer represents not only a relevant clinical and public health problem in France but also a potentially important economic burden. Overdiagnosis and corresponding associated treatments play an important role on the total costs of thyroid cancer management., (Copyright © 2023. Published by Elsevier Inc.)

The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration's risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Overdiagnosis of lung cancer by low-dose CT (LDCT) screening has raised concerns globally. LDCT screening has been used widely in employee health examinations in China since 2011., Research Question: Has the increasing use of LDCT in low-risk populations in China led to lung cancer overdiagnosis?, Study Design and Methods: A total of 34,152 incident cases of and 27,208 deaths resulting from lung cancer in a population of approximately 3 million were derived from the Cancer Surveillance of Shanghai between 2002 and 2017. Changes in stage-specific and histologic type-specific incidence and mortality and incidence rate ratio (IRR) relative to the base year 2002 or to the period 2002 through 2005 were calculated by sex and were used to evaluate potential overdiagnosisve of lung cancer., Results: In men, both age-adjusted incidence of and mortality as a result of lung cancer decreased significantly up to 2008 and thereafter remained stable; in women, the incidence increased rapidly from 2011 (annual percentage change, 11.98%; 95% CI, 9.57%-14.45%), whereas the mortality declined persistently. The upward trend of incidence mainly was observed in lung adenocarcinoma in both sexes, with a sharper increase from 2012 through 2017. In men, the incidence of early-stage cancer increased 6.9 per 100,000 (95% CI, 5.1-8.7 per 100,000) and was accompanied by 5.5 per 100,000 (95% CI, -9.2 to -1.7 per 100,000) decline in late-stagecancer from 2002 through 2017. In women, early-stage incidence rose 16.1 per 100,000 (95% CI, 14.0-18.3 per 100,000), but no significant decline in late-stage cancer was found (absolute difference, -0.6 per 100,000; 95% CI, -2.8 to 1.7 per 100,000). The IRR was highest in most recent period and increased most in young women, mainly for early-stage cancer or lung adenocarcinoma., Interpretation: The results provide evidence at a population level for lung cancer overdiagnosis in Chinese women resulting from increasing LDCT screening in the low-risk populations. Criteria for LDCT screening and management of screening-detected nodules need to be addressed fully for expanded application of LDCT screening in China., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with epidemiology and challenges in the management of thyroid nodules., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The appropriate age at which to perform endometrial biopsy for abnormal uterine bleeding (AUB) is controversial. This study aimed to determine the prevalence of malignant and premalignant pathologies in women aged 41-49 years with AUB and without risk factors for endometrial cancer. Records of women who had undergone a biopsy at the gynaecology clinic of the Centre hospitalier de l'Université de Montréal between 2014 and 2018 were reviewed. Of the 209 women included in the study, 2 had atypical hyperplasia, which resolved without treatment, and 3 had hyperplasia without atypia. The remaining women had benign results, showing that the prevalence of malignant and premalignant endometrial pathologies is low in this subgroup of patients., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. All rights reserved.)

Background: Georgia is an upper middle-income country, which has lower cancer survival rates than most of the countries in the World Health Organization European region, as well as compared to many other post-Soviet states and upper middle-income countries. The purpose of our study was to analyse the cancer stage distribution data of Georgia as a first step towards identifying the areas of early cancer detection in the country that might need improvement or require further research., Methods: Descriptive analysis of the population-based cancer registry of Georgia was performed using the data for the period of 01.01.2018-31.12.2019., Results: Around 57 % of cancers in males and 56 % of cancers in females were amenable to early detection. At least 35.7 % of these cancers in males and 44.2 % in females were detected early. 15.2 % (n = 964) of male and 35.3 % (n = 3179) of female cancer patients met the age criteria for the respective cancer screening programmes. Breast, colorectal, cervical and stomach cancers contributed to 58.7 % of all late-stage cancers in females. Lung, prostate, colorectal, laryngeal and stomach cancers made up 72.4 % of all late-stage cancer cases among males. At least 83.8 % (n = 1438) of thyroid cancers in females and 84.2 % (n = 246) of thyroid cancers in males were diagnosed at stage I. Moreover, stage I thyroid cancer cases made up 50.7 % of all stage I cancer cases detected in women and 25.6 % of all stage I cancers in men. At least 42.4 % of stage I thyroid cancers in females and 37.4 % of stage I thyroid cancers in males were papillary microcarcinomas., Conclusion: The potential of early cancer detection is underutilised in Georgia and there is a need to strengthen screening and especially early diagnosis in the country. The possibility of thyroid cancer overdiagnosis requires further investigation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: This study explores the validity of Paget's disease of bone (PDB) reported in unpublished skeletal reports, based on macroscopic analysis alone., Materials: The high prevalence of 'suspected' Paget's disease (10.7%) in an early modern sample from St John's the Evangelist Church in Redhill, Surrey is reassessed., Methods: Signs of PDB were examined in 53 well-preserved adults aged 35 + years using macroscopic, radiographic and histological techniques., Results: Macroscopic features of PDB were identified in 8 individuals (15%), with 5 individuals later rejected using radiography. Two individuals showed classic radiographic features of PDB, with a third presenting possible features in radiography (5.7%). These three cases were confirmed by histological analysis., Conclusions: PDB should not be suggested as a single diagnosis in cases of bone hypertrophy without confirmation using radiography., Significance: The growing popularity of 'big data' projects and limited collections access means that unpublished cases of PDB are often included in large scale analyses, impacting our understanding of the evolution of this disease. Using macroscopic analysis alone leads to overdiagnosis. Histological analysis is unnecessary when radiographic features are present, but provides a useful diagnostic step in long bones in advanced cases of PBD., Limitations: The radiographic sample in this study was limited to three individuals., Suggestions for Further Research: The conclusion that radiography alone can be used to identify PDB in archaeological cases merits further research on a larger number of cases., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Methods to quantify overdiagnosis of screen detected cancer have been developed, but methods for quantifying overdiagnosis of noncancer conditions (whether symptomatic or asymptomatic) have been lacking. We aimed to develop a methodological framework for quantifying overdiagnosis that may be used for asymptomatic or symptomatic conditions and used gestational diabetes mellitus as an example of how it may be applied., Study Design and Setting: We identify two earlier definitions for overdiagnosis, a narrower prognosis-based definition and a wider utility-based definition. Building on the central importance of the concepts of prognostic information and clinical utility of a diagnosis, we consider the following questions: within a target population, do people found to have a disease using one diagnostic strategy but found not to have the disease using another diagnostic strategy (so called 'additional diagnoses'), have an increased risk of adverse clinical outcomes without treatment (prognosis evidence), and/or a decreased risk of adverse outcomes with treatment (utility evidence)?, Results: Using Causal Directed Acyclic Graphs and fair umpires, we illuminate the relationships between diagnostics strategies and the frequency of overdiagnosis. We then use the example of gestational diabetes mellitus to demonstrate how the Fair Umpire framework may be applied to estimate overdiagnosis., Conclusion: Our framework may be used to quantify overdiagnosis in noncancer conditions (and in cancer conditions) and to guide further studies on this topic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Most authorities define childhood overweight/obesity as a BMI exceeding the same high centile cutoff at all ages, but it seems unlikely that true obesity prevalence (excess body fat) is constant throughout childhood., Objectives: We investigated how fat mass (FM) and lean mass (LM), adjusted for height, relate to BMI and each other across childhood, using a uniquely large database of body composition measures, estimated using gold standard methods., Methods: Cross-sectional and cohort data were collated from representative samples of healthy children aged 6 wk to 20 y and children attending obesity clinics aged 7-16 y. Body composition was measured by deuterium dilution up to age 4 y, and by either deuterium or the criterion 4-component model from 4 to 20 y. FM and LM were expressed, respectively, as fat mass index (FMI; FM/height2) and lean mass index (LMI; LM/height2)., Results: There were 2367 measurements of weight, height, and body composition from 1953 individuals. Before age 6 y, the variability in FMI, LMI, and BMI was much less than after; FMI was low (mainly <8 kg/m2) and FMI and LMI were weakly negatively correlated. From mid-childhood, upper limits for both BMI and FMI rose, but FMI in children with BMI <91st centile still rarely exceeded 8. With increasing age, the correlation of FMI with LMI rose to 0.5-0.7, driven mainly by children with a high FMI also having a high LMI., Conclusions: Raised fat levels are much less common at younger than older ages, and young children with a high BMI centile have lower FMI than older children with the same BMI centile. Current BMI centile cutoffs thus overdiagnose obesity in younger groups. More stringent cutoffs are required for children aged <6 y, matching the WHO recommendation for 0-5 y., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The primary cause of the increase in melanoma incidence in the United States has been suggested to be overdiagnosis. We used Surveillance, Epidemiology, and End Result Program data from 1975 to 2017 to examine epidemiologic trends of melanoma incidence and mortality and better characterize overdiagnosis in white Americans. Over the 43-year period, incidence and mortality showed discordant temporal changes across population subgroups; trends most suggestive of overdiagnosis alone were present in females aged 55-74. Other groups showed mixed changes suggestive of overdiagnosis plus changes in underlying disease risk (decreasing risk in younger individuals and increasing risk in older males). Cohort effects were identified for male and female mortality and male incidence but were not as apparent for female incidence, suggesting that period effects have had a greater influence on changes in incidence over time in females. Encouraging trends included long-term declines in mortality in younger individuals and recent stabilization of invasive incidence in individuals aged 15-44 years and males aged 45-54 years. Melanoma in situ incidence, however, has continued to increase throughout the population. Overdiagnosis appears to be relatively greater in American females and for melanoma in situ., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the impact of test measurement variation on misclassification of prediabetes and diabetes in the US adult population., Study Design and Setting: Data from adults with no prior diagnosis of diabetes in the 2015 to 2016 National Health and Nutrition Examination Survey (NHANES) were used to simulate populations of US adults eligible for screening. Estimates of measurement variation were applied to each simulated individual's true values to generate observed values for up to five repeated screens., Results: UNDERDIAGNOSIS: For 100,000 people assessed according to ADA or USPSTF guidelines, no people with true values in the diabetes range would be underdiagnosed as normal after one screen, and between 64 and 138 people would be misclassified with prediabetes after five re-screens (depending on guideline and test used)., Overdiagnosis: For 100,000 people assessed according to the guidelines, between 1,602 and 2,233 people with true values in the normal range would be over diagnosed with prediabetes after 3 re-screens. A further 627 to 1,672 people with true values in the prediabetes range would be over diagnosed with diabetes after 5 re-screens., Conclusion: Measurement variation may cause overdiagnosis of prediabetes and diabetes, as well as apparent "progression" or "regression" of either condition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Population trends in PSA testing and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA testing, prostate cancer incidence and mortality in Australia and factors that influence them., Methods: We calculated and described standardised time trends in PSA tests, prostate biopsies, treatment of benign prostatic hypertrophy (BPH) and prostate cancer incidence and mortality in Australia in men aged 45-74, 75-84, and 85 + years., Results: PSA testing increased from its introduction in 1989 to a peak in 2008 before declining in men aged 45-84 years. Prostate biopsies and cancer incidence fell from 1995 to 2000 in parallel with decrease in trans-urethral resections of the prostate (TURP) and, latterly, changes in pharmaceutical management of BPH. After 2000, changes in biopsies and incidence paralleled changes in PSA screening in men 45-84 years, while in men ≥85 years biopsy rates stabilised, and incidence fell. Prostate cancer mortality in men aged 45-74 years remained low throughout. Mortality in men 75-84 years gradually increased until mid 1990s, then gradually decreased. Mortality in men ≥ 85 years increased until mid 1990s, then stabilised., Conclusion: Age specific prostate cancer incidence largely mirrors PSA testing rates. Most deviation from this pattern may be explained by less use of TURP in management of BPH and consequent less incidental cancer detection in TURP tissue specimens. Mortality from prostate cancer initially rose and then fell below what it was when PSA testing began. Its initial rise and fall may be explained by a possible initial tendency to over-attribute deaths of uncertain cause in older men with a diagnosis of prostate cancer to prostate cancer. Decreases in mortality rates were many fold smaller than the increases in incidence, suggesting substantial overdiagnosis of prostate cancer after introduction of PSA testing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Limited evidence exists on the impact of age and comorbidity on biopsy rates and findings among older women., Materials and Methods: We used data from 170,657 women ages 66-94 enrolled in the United States Breast Cancer Surveillance Consortium (BCSC). We estimated one-year rates of biopsy by type (any, fine-needle aspiration (FNA), core or surgical) and yield of the most invasive biopsy finding (benign, ductal carcinoma in situ (DCIS) and invasive breast cancer) by age and comorbidity. Statistical significance was assessed using Wald statistics comparing coefficients estimated from logistic regression models adjusted for age, comorbidity, BCSC registry, and interaction between age and comorbidity., Results: Of 524,860 screening mammograms, 9830 biopsies were performed following 7930 exams (1.5%) within one year, specifically 5589 core biopsies (1.1%), 3422 (0.7%) surgical biopsies and 819 FNAs (0.2%). Biopsy rates per 1000 screens decreased with age (66-74:15.7, 95%CI:14.8-16.8), 75-84:14.5(13.5-15.6), 85-94:13.2(11.3,15.4), p trend  < 0.001) and increased with Charlson Comorbidity Score (CCS = 0:14.4 (13.5-15.3), CCS = 1:16.6 (15.2-18.1), CCS ≥2:19.0 (16.9-21.5), p trend  < 0.001).Biopsy rates increased with CCS at ages 66-74 and 75-84 but not 85-94. Core and surgical biopsy rates increased with CCS at ages 66-74 only. For each biopsy type, the yield of invasive breast cancer increased with age irrespective of comorbidity., Discussion: Women aged 66-84 with significant comorbidity in a breast cancer screening population had higher breast biopsy rates and similar rates of invasive breast cancer diagnosis than their counterparts with lower comorbidity. A considerable proportion of these diagnoses may represent overdiagnoses, given the high competing risk of death from non-breast-cancer causes among older women., Competing Interests: Declaration of Competing Interest Dr. Braithwaite reports grants from National Cancer Institute (NCI) during the conduct of the study. Dr. Lee reports grants from NCI during the conduct of the study. Dr. Lee also reports grants from GE Healthcare to his institution, research consulting fees from GRAIL, Inc., personal fees for editorial board work from American College of Radiology, and textbook royalties from McGraw Hill, Inc., Oxford University Press, and UpToDate, Inc.; all outside the submitted work. Ms. Abraham reports grants from NCI during the conduct of the study. Dr. Buist reports grants from NCI during the conduct of the study. Dr. Miglioretti reports grants from NIH/NCI during the conduct of the study. Dr. O'Meara reports grants from NIH/NCI, during the conduct of the study. Dr. Sprague reports grants from NIH during the conduct of the study., (Published by Elsevier Ltd.)