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Aim: Biennial faecal occult blood testing (FOBT) is used to screen for colorectal cancer throughout the UK. Interval cancers are tumours that develop in patients between screening rounds who have had a negative FOBT. Through a multicentre study, we compared the demographics of patients with interval cancers, FOBT screen detected cancers and cancers that developed in patients who chose not to participate in the screening programme., Method: Five hundred and sixteen colorectal cancers were detected in the screening age group (60-74 years) population in three UK National Health Service hospitals over 2 years. One hundred and twenty seven (25%) were interval cancers, 161 (31%) were screen detected and 228 (44%) were cancers that developed in patients who had declined FOBT. The interval cancer group had a higher incidence of right-sided cancers (38% vs 29% and 24%), a higher proportion of high tumour stages (Dukes C and D) (70% vs 53% and 33%) and a shorter time from diagnosis to death (10 months vs 13 months and 24 months) compared to patients who had declined the FOBT and the FOBT screen detected cancers. Of all the patients studied, those with right-sided interval cancers had the worst outcome., Conclusion: A quarter of the colorectal cancers diagnosed in our study were interval cancers. Patients with right-sided interval cancers had the highest proportion of Dukes C and D tumours coupled with the shortest survival time after diagnosis compared with the other groups., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Answer questions and earn CME/CNE Each year, the American Cancer Society publishes a summary of its guidelines for early cancer detection, data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, the authors summarize current American Cancer Society cancer screening guidelines, describe an update of their guideline for using human papillomavirus vaccination for cancer prevention, describe updates in US Preventive Services Task Force recommendations for breast and colorectal cancer screening, discuss interim findings from the UK Collaborative Trial on Ovarian Cancer Screening, and provide the latest data on utilization of cancer screening from the National Health Interview Survey. CA Cancer J Clin 2017;67:100-121. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

We studied harms related to cervical cancer screening and management of screen-positive women in the United States (US) and the Netherlands. We utilized data from four US integrated health care systems (SEARCH), the US National Health Interview Survey, New Mexico state, the Netherlands national histopathology registry, and included studies on adverse health effects of cervical screening. We compared the number of Papanicolaou (Pap) smear tests, abnormal test results, punch biopsies, treatments, health problems (anxiety, pain, bleeding and discharge) and preterm births associated with excisional treatments. Results were age-standardized to the 2007 US population. Based on SEARCH, an estimated 36 million Pap tests were performed in 2007 for 91 million US women aged 21-65 years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3 million treatments for precancerous lesions, 5 thousand preterm births and over 8 million health problems. Under the Netherlands screening practice, fewer Pap tests (58%), abnormal test results (64%), punch biopsies (75%), treatment procedures (40%), preterm births (60%) and health problems (63%) would have occurred. The SEARCH data did not differ much from other US data for 2007 or from more recent data up to 2013. Thus compared to the less intensive screening practice in the Netherlands, US practice of cervical cancer screening may have resulted in two- to threefold higher harms, while the effects on cervical cancer incidence and mortality are similar. The results are also of high relevance in making recommendations for HPV screening. Systematic collection of harms data is needed for monitoring and for better incorporation of harms in making screening recommendations., (© 2016 UICC.)

Objective  To estimate the cumulative radiation exposure and lifetime attributable risk of cancer incidence associated with lung cancer screening using annual low dose computed tomography (CT). Design  Secondary analysis of data from a lung cancer screening trial and risk-benefit analysis. Setting  10 year, non-randomised, single centre, low dose CT, lung cancer screening trial (COSMOS study) which took place in Milan, Italy in 2004-15 (enrolment in 2004-05). Secondary analysis took place in 2015-16. Participants  High risk asymptomatic smokers aged 50 and older, who were current or former smokers (≥20 pack years), and had no history of cancer in the previous five years. Main outcome measures  Cumulative radiation exposure from low dose CT and positron emission tomography (PET) CT scans, calculated by dosimetry software; and lifetime attributable risk of cancer incidence, calculated from the Biological Effects of Ionizing Radiation VII (BEIR VII) report. Results  Over 10 years, 5203 participants (3439 men, 1764 women) underwent 42 228 low dose CT and 635 PET CT scans. The median cumulative effective dose at the 10th year of screening was 9.3 mSv for men and 13.0 mSv for women. According to participants' age and sex, the lifetime attributable risk of lung cancer and major cancers after 10 years of CT screening ranged from 5.5 to 1.4 per 10 000 people screened, and from 8.1 to 2.6 per 10 000 people screened, respectively. In women aged 50-54, the lifetime attributable risk of lung cancer and major cancers was about fourfold and threefold higher than for men aged 65 and older, respectively. The numbers of lung cancer and major cancer cases induced by 10 years of screening in our cohort were 1.5 and 2.4, respectively, which corresponded to an additional risk of induced major cancers of 0.05% (2.4/5203). 259 lung cancers were diagnosed in 10 years of screening; one radiation induced major cancer would be expected for every 108 (259/2.4) lung cancers detected through screening. Conclusion  Radiation exposure and cancer risk from low dose CT screening for lung cancer, even if non-negligible, can be considered acceptable in light of the substantial mortality reduction associated with screening., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Despite the US Preventive Services Task Force recommendation against screening mammography in women younger than 50 years, rates remain high, suggesting that screening recommendations may be motivated by other factors. The objective of this study was to understand provider-reported influences on screening recommendations for women 40 to 49 years old at average risk for breast cancer., Methods: An online survey of primary care providers was conducted at four health centers in Cleveland, Ohio in 2015. Provider-reported routine recommendation of mammography for women aged 40 to 49 at average risk for breast cancer was the primary outcome. The independent measures included influence of electronic health records, national guidelines, institutional policy, patient preferences, concerns about overtreatment, concerns about false-positives, and interest in early detection on screening recommendations. We used multivariable logistic regression to estimate the odds of recommending screening by potential influences, controlling for provider characteristics and provider-assessed balance of harms and benefits of screening in this age group., Results: Of 612 providers invited, 220 completed the survey (response rate 36%); 69% routinely recommended screening and 24% believed that the harms of screening in younger women outweighed the benefits. Being influenced by institutional policy was associated with higher odds of recommending screening (odds ratio [OR] 4.19, 95% confidence interval [CI] 1.35-12.9), as was interest in early detection (OR 4.19, 95% CI 1.31-12.9). Conversely, strong influence of national guidelines was associated with a lower odds of recommending screening (OR 0.25, 95% CI 0.09-0.71). The influence of patient preferences was not associated with screening recommendation., Conclusions: Providers face competing influences on screening recommendations for younger patients, some of which may be at odds with their beliefs. Institutional policy change allowing individually tailored screening discussions may improve patient-centered care.

The main harm of overdiagnosis is overtreatment. However a form of overdiagnosis also occurs when foci of cancer are found by imaging in addition to the symptomatic lesion when this leads to additional treatment which does not benefit the patient. Even if overtreatment is avoided, knowledge of the diagnosis can still cause psychological harm. Overdiagnosis is an inevitable effect of mammographic screening as the benefit comes from diagnosing breast cancer prior to clinical detectability. Estimates of the rate of overdiagnosis at screening are around 10%. DCIS represents 20% of cancers detected by screening and is the main focus in the overdiagnosis debate. Detection and treatment of low grade DCIS and invasive tubular cancer would appear to represent overdiagnosis in most cases. Supplementary screening with tomosynthesis or US are both likely to increase overdiagnosis as both modalities detect predominantly low grade invasive cancers. MRI causes overdiagnosis because it is so sensitive that it detects real tumour foci which after radiotherapy and systemic therapy do not, in many cases go on and cause local recurrence if the women had had no MRI and undergone breast conservation and adjuvant therapy with these small foci left in situ., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: No randomized, controlled trials of screening colonoscopy have been completed, and ongoing trials exclude persons aged 75 years or older. The Medicare program, however, reimburses screening colonoscopy without an upper age limit., Objective: To evaluate the effectiveness and safety of screening colonoscopy to prevent colorectal cancer (CRC) in persons aged 70 to 74 and those aged 75 to 79 years., Design: Large-scale, population-based, prospective study. The observational data were used to emulate a target trial with 2 groups: colonoscopy screening and no screening., Setting: United States., Participants: 1 355 692 Medicare beneficiaries (2004 to 2012) aged 70 to 79 years at average risk for CRC who used Medicare preventive services and had no previous diagnostic or surveillance colonoscopies in the past 5 years., Measurements: 8-year risk for CRC and 30-day risk for adverse events., Results: In beneficiaries aged 70 to 74 years, the 8-year risk for CRC was 2.19% (95% CI, 2.00% to 2.37%) in the screening colonoscopy group and 2.62% (CI, 2.56% to 2.67%) in the no-screening group (absolute risk difference, -0.42% [CI, -0.24% to -0.63%]). Among those aged 75 to 79 years, the 8-year risk for CRC was 2.84% (CI, 2.54% to 3.13%) in the screening colonoscopy group and 2.97% (CI, 2.92% to 3.03%) in the no-screening group (risk difference, -0.14% [CI, -0.41 to 0.16]). The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1000 individuals (CI, 4.4 to 6.8) in the 70- to 74-year age group and 10.3 per 1000 (CI, 8.6 to 11.1) in the 75- to 79-year age group., Limitation: CRC-specific mortality was not available, but CRC incidence and stage were studied at diagnosis., Conclusion: Screening colonoscopy may have had a modest benefit in preventing CRC in beneficiaries aged 70 to 74 years and a smaller benefit in older beneficiaries. The risk for adverse events was low but greater among older persons., Primary Funding Source: National Institutes of Health.

Diabetes mellitus is associated with an increased risk of coronary heart disease (CHD) morbidity and mortality. Although it frequently coexists with other cardiovascular disease (CVD) risk factors, it confers an increased risk for CVD events on its own. Coronary atherosclerosis is generally more aggressive and widespread in people with diabetes (PWD) and is frequently asymptomatic. Screening for silent myocardial ischaemia can be applied in a wide variety of ways. In nearly all asymptomatic PWD, however, the results of screening will generally not change medical therapy, since aggressive preventive measures, such as control of blood pressure and lipids, would have been already indicated, and above all, invasive revascularization procedures (either with percutaneous coronary intervention or coronary artery bypass grafting) have not been shown in randomized clinical trials to confer any benefit on morbidity and mortality. Still, unresolved issues remain regarding the extent of the underlying ischaemia that might affect the risk and the benefit of revascularization (on top of optimal medical therapy) in ameliorating this risk in patients with moderate to severe ischaemia. The issues related to the detection of coronary atherosclerosis and ischaemia, as well as the studies related to management of CHD in asymptomatic PWD, will be reviewed here.

Background: Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits., Objective: To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer., Design: Collaborative simulation modeling using national incidence, breast density, and screening performance data., Setting: United States., Patients: Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0., Intervention: Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years)., Measurements: Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false-positive results to breast cancer deaths averted., Results: Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained., Limitation: Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods., Conclusion: Average-risk women with low breast density undergoing triennial screening and higher-risk women with high breast density receiving annual screening will maintain a similar or better balance of benefits and harms than average-risk women receiving biennial screening., Primary Funding Source: National Cancer Institute.

The primary goal of cancer screening is to reduce cancer-related mortality without incurring significant harm. Screening efforts for solid tumors, therefore, have targeted the precursors of the most common and the most deadly cancers-breast, cervical, colorectal, lung and prostate cancer. Balancing risk and benefit has led to controversy regarding the timing of cancer screening-when to begin, how often to screen and when to stop-and the nature of the modality of cancer screening-invasive or noninvasive, laboratory-centered or imaging-centered. Evidence-based guidelines published by general medical societies, subspecialty societies and publicly funded task forces on population-based screening aid healthcare providers in making individualized decisions with their patients., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Dyslipidemia may occur in younger adults (defined as persons aged 21 to 39 years) and is an important risk factor for cardiovascular disease. Screening might identify younger adults with asymptomatic dyslipidemia who may benefit from lipid-lowering therapies., Purpose: To update the 2008 U.S. Preventive Services Task Force review on dyslipidemia screening in younger adults., Data Sources: The Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE through May 2016, and reference lists., Study Selection: Randomized, controlled trials; cohort studies; and case-control studies on screening for or treatment of asymptomatic dyslipidemia in adults aged 21 to 39 years., Data Extraction: The plan was for 1 investigator to abstract data and a second to check their accuracy, and for 2 investigators to independently assess study quality; however, no studies met the inclusion criteria., Data Synthesis: No study evaluated the effects of lipid screening versus no screening, treatment versus no treatment, or delayed versus earlier treatment on clinical outcomes in younger adults. In addition, no study evaluated the diagnostic yield of alternative screening strategies (such as targeted screening of persons with a family history of hyperlipidemia vs. general screening) in younger adults., Limitation: No direct relevant evidence., Conclusion: Direct evidence on the benefits and harms of screening for or treatment of dyslipidemia in younger adults remains unavailable. Estimating the potential effects of screening for dyslipidemia in this population requires extrapolation from studies performed in older adults., Primary Funding Source: Agency for Healthcare Research and Quality.

Importance: Familial hypercholesterolemia (FH) is characterized by elevated cholesterol concentrations early in life. Untreated FH is associated with premature cardiovascular disease in adulthood., Objective: To systematically review the evidence on benefits and harms of screening adolescents and children for heterozygous FH for the US Preventive Services Task Force (USPSTF)., Data Sources: MEDLINE, the Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF report were also searched. Surveillance was conducted through April 8, 2016., Study Selection: Fair- and good-quality studies in English with participants 0 to 20 years of age., Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized., Main Outcomes and Measures: Myocardial infarction and ischemic stroke in adulthood; lipid concentrations and atherosclerosis in childhood; diagnostic yield of screening; any harm of screening or treatment., Results: Based on 2 studies (n = 83,241), the diagnostic yield of universal screening for FH in childhood is 1.3 to 4.8 cases per 1000 screened. There was no eligible evidence on the benefits or harms of FH screening in childhood. Eight placebo trials of statin drugs (n = 1071, 6-104 weeks) found low-density lipoprotein cholesterol (LDL-C) decreases of 20% to 40%; 1 trial (n = 214) showed a 2.01% decrease in carotid intima-media thickness with statins, compared with 1.02% with placebo (P = .02). Three placebo trials of bile acid-sequestering agents (n = 332, 8-52 weeks) showed LDL-C reductions of 10% to 20%. In 1 trial (n = 248), ezetimibe with simvastatin resulted in greater LDL-C reductions compared with simvastatin alone at 33 weeks (mean, -54.0% [SD, 1.4%] vs -38.1% [SD, 1.4%]). One trial of ezetimibe monotherapy (n = 138) showed mean LDL-C decreases of 28% (95% CI, -31% to -25%) from baseline and negligible change with placebo at 12 weeks. Eighteen studies found statins generally well tolerated. One observational study found lower, but still normal, dehydroepiandrosterone sulfate concentrations in statin-treated males with FH at 10-year follow-up. Bile acid-sequestering agents were commonly associated with adverse gastrointestinal symptoms and poor palatability. There was no eligible evidence on the effect of FH treatment on myocardial infarction or stroke in adulthood., Conclusions and Relevance: Screening can detect FH in children, and lipid-lowering treatment in childhood can reduce lipid concentrations in the short term, with little evidence of harm. There is no evidence for the effect of screening for FH in childhood on lipid concentrations or cardiovascular outcomes in adulthood, or on the long-term benefits or harms of beginning lipid-lowering treatment in childhood.

Importance: Multifactorial dyslipidemia, characterized by elevated total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C), is associated with dyslipidemia and markers of atherosclerosis in young adulthood. Screening for dyslipidemia in childhood could delay or reduce cardiovascular events in adulthood., Objective: To systematically review the evidence on benefits and harms of screening adolescents and children for multifactorial dyslipidemia for the US Preventive Services Task Force (USPSTF)., Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and PubMed were searched for studies published between January 1, 2005, and June 2, 2015; studies included in a previous USPSTF evidence report and reference lists of relevant studies and ongoing trials were also searched. Surveillance was conducted through April 9, 2016., Study Selection: Fair- and good-quality studies in English with participants 0 to 20 years of age., Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data into evidence tables. Results were qualitatively summarized., Main Outcomes and Measures: Outcomes included dyslipidemia (TC≥200 mg/dL or LDL-C≥130 mg/dL) and atherosclerosis in childhood; myocardial infarction and ischemic stroke in adulthood; diagnostic yield (number of confirmed cases per children screened); and harms of screening or treatment. Simulated diagnostic yield was calculated as initial screening yield × positive predictive value from a study with confirmatory testing., Results: Screening of children for multifactorial dyslipidemia has not been evaluated in randomized clinical trials. Based on 1 observational study (n = 6500) and nationally representative prevalence estimates, the simulated diagnostic yield of screening for elevated TC varies between 4.8% and 12.3% (higher in obese children [12.3%] and at the ages when TC naturally peaks-7.2% at age 9-11 years and 7.2% at age 16-19 years). One good-quality randomized clinical trial (n = 663) found a modest effect of intensive dietary counseling for a low-fat, low-cholesterol diet on lipid levels at 1 year in children aged 8 to 10 years with mild to moderate dyslipidemia; mean between-group difference in TC change from baseline was -6.1 mg/dL (95% CI, -9.1 to -3.2 mg/dL; P < .001). Between-group differences dissipated by year 5. The intervention did not adversely affect nutritional status, growth, or development over the 18-year study period. One observational study (n = 9245) found that TC concentration at age 12 to 39 years was not associated with death before age 55 years., Conclusions and Relevance: The diagnostic yield of lipid screening varies by age and body mass index. No direct evidence was identified for benefits or harms of childhood screening or treatment on outcomes in adulthood. Intensive dietary interventions may be safe, with modest short-term benefit of uncertain clinical significance.

Importance: Elevations in levels of total, low-density lipoprotein, and non-high-density lipoprotein cholesterol; lower levels of high-density lipoprotein cholesterol; and, to a lesser extent, elevated triglyceride levels are associated with risk of cardiovascular disease in adults., Objective: To update the 2007 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in children, adolescents, and young adults., Evidence Review: The USPSTF reviewed the evidence on screening for lipid disorders in children and adolescents 20 years or younger--1 review focused on screening for heterozygous familial hypercholesterolemia, and 1 review focused on screening for multifactorial dyslipidemia., Findings: Evidence on the quantitative difference in diagnostic yield between universal and selective screening approaches, the effectiveness and harms of long-term treatment and the harms of screening, and the association between changes in intermediate outcomes and improvements in adult cardiovascular health outcomes are limited. Therefore, the USPSTF concludes that the balance of benefits and harms cannot be determined., Conclusions and Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger. (I statement).

Purpose: BRCA1 mutation carriers are offered screening with magnetic resonance imaging (MRI) and mammography. The aim of this study was to weigh benefits and risks of postponing mammographic screening until age 40., Methods: With the MISCAN microsimulation model two screening protocols were evaluated: 1) the current Dutch guidelines: annual MRI from age 25-60, annual mammography from age 30-60, and biennial mammography in the nationwide program from age 60-74, and 2) the modified protocol: with annual mammography postponed until age 40. A cost-effectiveness analysis was performed. The risks of radiation-induced breast cancer mortality were estimated with absolute and relative exposure-risk models of the 7th Biological Effects of Ionising Radiation Committee., Results: Current screening guidelines prevent 13,139 breast cancer deaths per 100,000 BRCA1 mutation carriers. Postponing mammography until age 40 would increase breast cancer deaths by 23 (0.17%), but would also reduce radiation-induced breast cancer deaths by 15 or 105 using the absolute and relative risk model respectively per 100,000 women screened. The estimated net effect is an increase of eight or a reduction of 82 breast cancer deaths per 100,000 women screened (depending on the risk model used). The incremental cost of mammograms between age 30-39 is €272,900 per life year gained., Conclusions: The modified protocol may be slightly less effective or even better than the current guidelines. The high cost-savings justify a possible small loss of effectiveness., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Communicating the harms and benefits of thyroid screening is necessary to help individuals decide on whether or not to undergo thyroid cancer screening. This study was conducted to assess changes in thyroid cancer screening intention in response to receiving information about overdiagnosis and to determine factors with the greatest influence thereon., Materials and Methods: Data were acquired from subjects included in the 2013 Korean National Cancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional survey. Of the 4,100 respondents in the 2013 KNCSS, women were randomly subsampled and an additional face-to-face interview was conducted. Finally, a total of 586 female subjects were included in this study. Intention to undergo thyroid cancer screening was assessed before and after receiving information on overdiagnosis., Results: Prior awareness of overdiagnosis in thyroid cancer screening was 27.8%. The majority of subjects intended to undergo thyroid cancer screening before and after receiving information on overdiagnosis (87% and 74%, respectively). Only a small number of subjects changed their intention to undergo thyroid cancer screening from positive to negative after receiving information on overdiagnosis. Women of higher education level and Medical Aid Program recipients reported being significantly more likely to change their intention to undergo thyroid cancer screening afterreceiving information on overdiagnosis,whilewomen with stronger beliefs on the efficacy of cancer screening were less likely to change their intention., Conclusion: Women in Korea appeared to be less concerned about overdiagnosis when deciding whether or not to undergo thyroid cancer screening.

This issue provides a clinical overview of breast cancer screening and prevention, focusing on risk assessment, screening, prevention, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

Background: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol., Methods: Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis., Results: In women aged 39-75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15-0.28) and it increased to 0.30 (95% CI 0.18-0.42) with deattenuation. In women aged 40-69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2-22.7%), deattenuation increased this to 29.7% (95% CI 17.8-41.5%)., Conclusions: Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography.

Background Previous research showed women experiencing false-positive mammograms to have greater anxiety about breast cancer than women with normal mammograms. To elucidate psychological effects of false-positive mammograms, we studied impact on drug intake. Methods We calculated the ratio of drug use for women with false-positive versus women with normal mammograms, before and after the event, using population-based registers, 1997-2006. The ratio of the ratios (RRR) assessed the impact. Results Before the test, 40.3% of women from the false-positive group versus 36.2% from the normal group used anxiolytic and antidepressant drugs. There was no difference in use of beta blockers. Hormone therapy was used more frequently by the false-positive, 36.6% versus 28.7%. The proportion of women using anxiolytic and antidepressant drugs increased with 19% from the before to the after period in the false-positive group, and with 16% in the normal group, resulting in an RRR of 1.02 (95% CI 0.92-1.14). RRR was 1.03 for beta blockers, 0.97 for hormone therapy. Conclusion(s) Drugs used to mitigate mood disorders were used more frequently by women with false-positive than by women with normal mammograms already before the screening event, while the changes from before to after screening were similar for both groups. The results point to the importance of control for potential selection in studies of screening effects.

Objective: We conducted a systematic review to assess the quality and limitations of published studies examining benefits and harms of screening mammography in relation to comorbidity and age., Methods: We searched MEDLINE and EMBASE from January 1980 through June 2013 for studies that examined benefits or harms of screening mammography in women aged 65 years or older in relation to comorbidity. For each study, we extracted data regarding setting, design, quality, screening schedule, measure of comorbidity, and estimates of benefits and/or harms. We reviewed 1760 titles, identifying 7 articles that met the inclusion criteria: prospective cohort (two studies), retrospective cohort (two studies), and decision analyses (three studies). No randomized controlled trials were identified., Results: At least one measure of life expectancy or reduction in the risk of breast cancer death as a marker of benefit was examined in four studies, whereas three studies addressed the harms of screening mammography, including false-positive results. Both cohort studies and decision analyses showed that screening benefits decreased with increasing age and comorbidity burden., Conclusions: The limited evidence currently available suggests that, apart from older women with severe comorbidity, women 65 and older may experience improvements in life expectancy from screening. Given the potential for harm, it is unclear whether the magnitude of the benefit is sufficient to warrant regular screening. Women, clinicians and policymakers should consider these factors in deciding whether continue screening., Competing Interests: The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. The authors declare that they do not have a conflict of interest.

Description: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for major depressive disorder (MDD) in children and adolescents., Methods: The USPSTF reviewed the evidence on the benefits and harms of screening; the accuracy of primary care-feasible screening tests; and the benefits and harms of treatment with psychotherapy, medications, and collaborative care models in patients aged 7 to 18 years., Population: This recommendation applies to children and adolescents aged 18 years or younger who do not have a diagnosis of MDD., Recommendation: The USPSTF recommends screening for MDD in adolescents aged 12 to 18 years. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for MDD in children aged 11 years or younger. (I statement).

Background: Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide., Purpose: To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings., Data Sources: Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature., Study Selection: Trials and recent systematic reviews of treatment, test-retest studies of screening, and trials and large cohort studies for harms., Data Extraction: Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality., Data Synthesis: Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms., Limitation: The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years., Conclusion: No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms., Primary Funding Source: Agency for Healthcare Research and Quality.

Background: Cancer prevention and screening guidelines are ideally suited to the task of providing high-quality benefit-harm information that informs clinical practice. We systematically examined how US guidelines present benefits and harms for recommended cancer prevention and screening interventions., Methods: We included cancer screening and prevention recommendations from: 1) the United States Preventive Services Task Force, 2) the American Cancer Society, 3) the American College of Physicians, 4) the National Comprehensive Cancer Network, and 5) other US guidelines within the National Guidelines Clearinghouse. Searches took place November 20, 2013, and January 1, 2014, and updates were reviewed through July 1, 2015. Two coders used an abstraction form to code information about benefits and harms presented anywhere within a guideline document, including appendices. The primary outcome was each recommendation's benefit-harm "comparability" rating, based on how benefits and harms were presented. Recommendations presenting absolute effects for both benefits and harms received a "comparable" rating. Other recommendations received an incomplete rating or an asymmetric rating based on prespecified criteria., Results: Fifty-five recommendations for using interventions to prevent or detect breast, prostate, colon, cervical, and lung cancer were identified among 32 guidelines. Thirty point nine percent (n = 17) received a comparable rating, 14.5% (n = 8) received an incomplete rating, and 54.5% (n = 30) received an asymmetric rating., Conclusions: Sixty-nine percent of cancer prevention and screening recommendation statements either did not quantify benefits and harms or presented them in an asymmetric manner. Improved presentation of benefits and harms in guidelines would better ensure that clinicians and patients have access to the information required for making informed decisions., (Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: Lung cancer screening with chest computed tomography (CT) is beneficial in smokers aged 55 to 74 years. We studied the risks, benefits and feasibility of early lung cancer diagnosis with CT in HIV-infected smokers., Design and Setting: French, multicentre, single round chest CT study in France, realized between February 2011 and June 2012., Participants: Patients were HIV-infected smokers at least 40 years, at least 20 pack-years, with a CD4 T-lymphocyte nadir count below 350 cells/μl., Intervention: Single chest CT with a proposed standardized workup algorithm of positive images., Main Outcome Measure: The outcome was the number of histologically proven lung cancers diagnosed by CT with a 2-year follow-up., Results: Median age of the 442 included patients was 49.8 years, 81.6% were under 55 years, 84% were men, median smoking was 30 pack-years, median nadir and last CD4 cell counts were 168 and 574 cells/μl, respectively, and 90% of patients had a plasma HIV RNA below 50 copies/ml. A positive image at baseline was reported in 94 (21%) patients, and 15 (3.4%) patients had 18 invasive procedures with no serious adverse events. Lung cancer was diagnosed in 10 patients (six at early stages), of which nine (2.0%, 95% confidence interval: 0.9-3.8) were CT detected, and eight in patients below 55 years., Conclusion: Early lung cancer diagnosis with CT in HIV-infected smokers was feasible, safe, and yielded a significant number of cancers. Lung cancer screening of HIV-infected smokers with an important history of immunodeficiency revealed a substantial number of cancers at younger ages than the targeted range in the general population.

Description: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for breast cancer., Methods: The USPSTF reviewed the evidence on the following: effectiveness of breast cancer screening in reducing breast cancer-specific and all-cause mortality, as well as the incidence of advanced breast cancer and treatment-related morbidity; harms of breast cancer screening; test performance characteristics of digital breast tomosynthesis as a primary screening strategy; and adjunctive screening in women with increased breast density. In addition, the USPSTF reviewed comparative decision models on optimal starting and stopping ages and intervals for screening mammography; how breast density, breast cancer risk, and comorbidity level affect the balance of benefit and harms of screening mammography; and the number of radiation-induced breast cancer cases and deaths associated with different screening mammography strategies over the course of a woman's lifetime., Population: This recommendation applies to asymptomatic women aged 40 years or older who do not have preexisting breast cancer or a previously diagnosed high-risk breast lesion and who are not at high risk for breast cancer because of a known underlying genetic mutation (such as a BRCA1 or BRCA2 gene mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age., Recommendations: The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. (B recommendation) The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging (MRI), DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

Background: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years., Purpose: To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure., Data Sources: MEDLINE and Cochrane databases through December 2014., Study Selection: English-language systematic reviews, randomized trials, and observational studies of screening., Data Extraction: Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus., Data Synthesis: Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer-specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100,000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone., Limitations: Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models., Conclusion: False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely., Primary Funding Source: Agency for Healthcare Research and Quality.

Background: Women screened with digital mammography may receive false-positive and false-negative results and subsequent imaging and biopsies. How these outcomes vary by age, time since the last screening, and individual risk factors is unclear., Objective: To determine factors associated with false-positive and false-negative digital mammography results, additional imaging, and biopsies among a general population of women screened for breast cancer., Design: Analysis of registry data., Setting: Participating facilities at 5 U.S. Breast Cancer Surveillance Consortium breast imaging registries with linkages to pathology databases and tumor registries., Patients: 405,191 women aged 40 to 89 years screened with digital mammography between 2003 and 2011. A total of 2963 were diagnosed with invasive cancer or ductal carcinoma in situ within 12 months of screening., Measurements: Rates of false-positive and false-negative results and recommendations for additional imaging and biopsies from a single screening round; comparisons by age, time since the last screening, and risk factors., Results: Rates of false-positive results (121.2 per 1000 women [95% CI, 105.6 to 138.7]) and recommendations for additional imaging (124.9 per 1000 women [CI, 109.3 to 142.3]) were highest among women aged 40 to 49 years and decreased with increasing age. Rates of false-negative results (1.0 to 1.5 per 1000 women) and recommendations for biopsy (15.6 to 17.5 per 1000 women) did not differ greatly by age. Results did not differ by time since the last screening. False-positive rates were higher for women with risk factors, particularly family history of breast cancer; previous benign breast biopsy result; high breast density; and, for younger women, low body mass index., Limitations: Confounding by variation in patient-level characteristics and outcomes across registries and regions may have been present. Some factors, such as numbers of first- and second-degree relatives with breast cancer and diagnoses associated with previous benign biopsy results, were not examined., Conclusion: False-positive mammography results and additional imaging are common, particularly for younger women and those with risk factors, whereas biopsies occur less often. Rates of false-negative results are low., Primary Funding Source: Agency for Healthcare Research and Quality and National Cancer Institute.

Background: Controversy persists about optimal mammography screening strategies., Objective: To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer., Design: Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality., Setting: United States., Patients: Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity., Intervention: Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years., Measurements: Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens., Results: Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years., Limitation: Other imaging technologies, polygenic risk, and nonadherence were not considered., Conclusion: Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening., Primary Funding Source: National Institutes of Health., Competing Interests: Potential Conflicts of Interest: None disclosed

Background: Estimates of risk for radiation-induced breast cancer from mammography screening have not considered variation in dose exposure or diagnostic work-up after abnormal screening results., Objective: To estimate distributions of radiation-induced breast cancer incidence and mortality from digital mammography screening while considering exposure from screening and diagnostic mammography and dose variation among women., Design: 2 simulation-modeling approaches., Setting: U.S. population., Patients: Women aged 40 to 74 years., Intervention: Annual or biennial digital mammography screening from age 40, 45, or 50 years until age 74 years., Measurements: Lifetime breast cancer deaths averted (benefits) and radiation-induced breast cancer incidence and mortality (harms) per 100,000 women screened., Results: Annual screening of 100,000 women aged 40 to 74 years was projected to induce 125 breast cancer cases (95% CI, 88 to 178) leading to 16 deaths (CI, 11 to 23), relative to 968 breast cancer deaths averted by early detection from screening. Women exposed at the 95th percentile were projected to develop 246 cases of radiation-induced breast cancer leading to 32 deaths per 100,000 women. Women with large breasts requiring extra views for complete examination (8% of population) were projected to have greater radiation-induced breast cancer risk (266 cancer cases and 35 deaths per 100,000 women) than other women (113 cancer cases and 15 deaths per 100,000 women). Biennial screening starting at age 50 years reduced risk for radiation-induced cancer 5-fold., Limitation: Life-years lost from radiation-induced breast cancer could not be estimated., Conclusion: Radiation-induced breast cancer incidence and mortality from digital mammography screening are affected by dose variability from screening, resultant diagnostic work-up, initiation age, and screening frequency. Women with large breasts may have a greater risk for radiation-induced breast cancer., Primary Funding Source: Agency for Healthcare Research and Quality, U.S. Preventive Services Task Force, National Cancer Institute.

Rapid diagnostic tests (RDTs) are routinely used in African blood centres. We analysed data from two cross-sectional studies representing 95 blood centres in 29 African countries. Standardized panels of sera containing varying concentrations of anti-human immunodeficiency virus (HIV) antibodies (Ab), hepatitis B virus antigen (HBsAg) and antihepatitis C virus (HCV) Ab were screened using routine operational testing procedures at the centres. Sensitivity of detection using RDTs was high for HIV Ab-positive samples, but low for intermediately HBsAg (51·5%) and HCV Ab (40·6%)-positive samples. These findings suggest that current RDT use in Africa could pose a hazard to blood safety., Competing Interests: Conflict of interests The authors declare no conflict of interests., (© 2015 International Society of Blood Transfusion.)

Importance: Depression is a source of substantial burden for individuals and their families, including women during the pregnant and postpartum period., Objective: To systematically review the benefits and harms of depression screening and treatment, and accuracy of selected screening instruments, for pregnant and postpartum women. Evidence for depression screening in adults in general is available in the full report., Data Sources: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials through January 20, 2015; references; and government websites., Study Selection: English-language trials of benefits and harms of depression screening, depression treatment in pregnant and postpartum women with screen-detected depression, and diagnostic accuracy studies of depression screening instruments in pregnant and postpartum women., Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and extracted data from fair- and good-quality studies. Random-effects meta-analysis was used to estimate the benefit of cognitive behavioral therapy (CBT) in pregnant and postpartum women., Main Outcomes and Measures: Depression remission, prevalence, symptoms, and related measures of depression recovery or response; sensitivity and specificity of selected screening measures to detect depression; and serious adverse effects of antidepressant treatment., Results: Among pregnant and postpartum women 18 years and older, 6 trials (n = 11,869) showed 18% to 59% relative reductions with screening programs, or 2.1% to 9.1% absolute reductions, in the risk of depression at follow-up (3-5 months) after participation in programs involving depression screening, with or without additional treatment components, compared with usual care. Based on 23 studies (n = 5398), a cutoff of 13 on the English-language Edinburgh Postnatal Depression Scale demonstrated sensitivity ranging from 0.67 (95% CI, 0.18-0.96) to 1.00 (95% CI, 0.67-1.00) and specificity consistently 0.87 or higher. Data were sparse for Patient Health Questionnaire instruments. Pooled results for the benefit of CBT for pregnant and postpartum women with screen-detected depression showed an increase in the likelihood of remission (pooled relative risk, 1.34 [95% CI, 1.19-1.50]; No. of studies [K] = 10, I2 = 7.9%) compared with usual care, with absolute increases ranging from 6.2% to 34.6%. Observational evidence showed that second-generation antidepressant use during pregnancy may be associated with small increases in the risks of potentially serious harms., Conclusions and Relevance: Direct and indirect evidence suggested that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population. Evidence for pregnant women was sparser but was consistent with the evidence for postpartum women regarding the benefits of screening, the benefits of treatment, and screening instrument accuracy.

Importance: Healthcare overuse, the delivery of low-value services, is increasingly recognized as a critical problem. However, little is known about the comparative effectiveness of alternate formats for presenting benefits and harms information to patients as a strategy to reduce overuse., Objective: To examine the effect of different benefits and harms presentations on patients' intentions to accept low-value or potentially low-value screening services (prostate cancer screening in men ages 50-69 years; osteoporosis screening in low-risk women ages 50-64 years; or colorectal cancer screening in men and women ages 76-85 years)., Design, Setting, and Participants: Randomized clinical trial of 775 individuals eligible to receive information about any 1 of the 3 screening services and scheduled for a visit with their clinician. Participants were randomized to 1 of 4 intervention arms that differed in terms of presentation format: words, numbers, numbers plus narrative, and numbers plus framed presentation. The trial was conducted from September 2012 to June 2014 at 2 family medicine and 2 internal medicine practices affiliated with the Duke Primary Care Research Consortium. The data were analyzed between May and September of 2015., Interventions: One-page evidence-based decision support sheets on each of the 3 screening services, with benefits and harms information presented in 1 of 4 formats: words, numbers, numbers plus narratives, or numbers plus a framed presentation., Main Outcomes and Measures: The primary outcome was change in intention to accept screening (on a response scale from 1 to 5). Our secondary outcomes included general and disease-specific knowledge, perceived risk and consequences of disease, screening attitudes, perceived net benefit of screening, values clarity, and self-efficacy for screening., Results: We enrolled and randomly allocated 775 individuals, aged 50 to 85 years, to 1 of 4 intervention arms: 195 to words, 192 to numbers, 196 to narrative, and 192 to framed formats. Intentions to accept screening were high before the intervention and change in intentions did not differ across intervention arms (words, -0.07; numbers, -0.05; numbers plus narrative, -0.12; numbers plus framed presentation, -0.02; P = .57 for all comparisons). Change in other outcomes also showed no difference across intervention arms. Results were similar when stratified by screening service., Conclusions and Relevance: Single, brief, written decision support interventions, such as the ones in this study, are unlikely to be sufficient to change intentions for screening. Alternate and additional interventions are needed to reduce overused screening services., Trial Registration: clinicaltrials.gov Identifier: NCT01694784.

Since population-based breast cancer screening was implemented in the Netherlands, the incidence of Ductal Carcinoma In Situ of the breast, regarded as a non-obligate precursor lesion of breast cancer, has strongly increased. However, the incidence of invasive breast cancer has not decreased. This suggests that a percentage of all the DCIS lesions would never have become symptomatic if no screening was performed. This phenomenon is known as 'overdiagnosis'. Nonetheless, almost all DCIS lesions are managed surgically, often followed by radiotherapy in those having breast-conserving treatment, to avoid potential progression to breast cancer. To prevent potential over- or undertreatment, further studies are required to distinguish low from high risk DCIS. Ultimately this could help avoid non-beneficial intensive treatment for women with low risk DCIS.

Purpose: The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening (ERSPC)., Experimental Design: We analyzed the absolute mortality reduction expressed as number needed to invite (NNI = 1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO = 1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers., Results: Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI, 200-7,000 and NNO, 16-69. Extent of overdiagnosis and mortality reduction was closely associated [correlation coefficient, r = 0.76; weighted linear regression coefficient, β = 33; 95% confidence interval (CI), 5-62; R(2) = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12 to 36 excess cases had to be detected in various centers., Conclusions: The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear., (©2015 American Association for Cancer Research.)

Background and Aims: Progress towards validating amyloid beta as an early indicator of Alzheimer's disease (AD) heightens the need for evaluation of stakeholders' perspectives of the benefits and harms of preclinical testing in asymptomatic individuals., Methods: Investigators conducted and analyzed 14 semi-structured interviews with family members of patients diagnosed with AD., Results: Participants reported benefits, including the potential to seek treatment, make lifestyle changes, and prepare for cognitive impairment. Participants identified harms, including social harms, adverse life decisions, and psychological harms. Nine participants reported either a "positive global perspective" or a "positive global perspective (qualified).", Conclusion: Results from this study characterized stakeholders' perspectives on the potential benefits and harms of clinical use of preclinical testing for AD. Investigators used data from this study to develop a framework that contributes to ongoing discussions that will evaluate widespread adoption of preclinical testing and will inform future research., (Copyright 2015 The Journal of Clinical Ethics. All rights reserved.)

Aim: Red reflex eye examinations often require opening the eyelids, risking infection. We evaluated links between this procedure and neonatal conjunctivitis., Methods: We divided 18 872 neonates of more than 35 weeks of gestation into two birth periods, 2008-2009 and 2010-2011, before and after red reflex examinations were carried out by our facility. The rates of clinical conjunctivitis, bacterial conjunctivitis and bacterial growth percentage were compared between the two periods., Results: The 2010-2011 period included more Caesarean deliveries and longer lengths of stay (LOS) than the 2008-2009 period. The clinical conjunctivitis rate increased significantly during 2010-2011 (p = 0.029), but the bacterial conjunctivitis and bacterial growth percentages did not differ between the two periods. Variables that were independently and significantly associated with clinical conjunctivitis included being born in 2010-2011, with an odds ratio (OR) of 1.22, male gender (OR 1.31) and LOS (OR 1.19). Bacterial conjunctivitis was associated with vaginal delivery (OR 3.65), males delivered by Caesarean (OR 2.68) and LOS (OR 1.37)., Conclusion: Clinical conjunctivitis was significantly associated with the later study period, male gender and LOS. Conjunctival swab sampling increased significantly following the implementation of red reflex examinations, but without changes in the bacterial conjunctivitis rate and the bacterial growth percentage., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Breast cancer screening programs are still object of harsh debate. In 2012, the Independent UK Panel reviewed the benefits and harms of mammography screening based on randomized trials and the EUROSCREEN Working Group reviewed European observational outcome studies. The conclusion was that screening programs should continue, while acknowledging that harms, such as the occurrence of false-positive results and overdiagnosis, can have a negative impact on a woman's life. Information on the balance sheet of the benefits and harms of breast cancer screening should help women and their physicians to make an informed choice. The future challenge for breast screening programs is to assess the feasibility, acceptability, effectiveness and impact of risk-based screening in order to maximize benefit-to-harm ratios.