OBJECTIVES:This is a protocol for a Cochrane review (intervention). The objectives are as follows: To evaluate the benefits and harms of whole-body magnetic resonance imaging (MRI) or computed tomography (CT) scans for screening in asymptomatic adults, compared with no intervention, usual care, or alternative screening strategies not involving whole-body MRI or whole-body CT.

OBJECTIVES:Although the concept of overdiagnosis was first referenced in MEDLINE 100 years ago, consensus on a clear definition has been lacking. In 2021, the MeSH term "Overdiagnosis" was officially introduced, which defined the concept. A key goal of the new term is to improve the reliability of literature searches and enhance the conceptual understanding of overdiagnosis. METHODS:We conducted a systematic bibliometric review of all citations indexed under the MeSH term for "Overdiagnosis" in MEDLINE. We compared the citations with citations identified through a text-word search for overdiagnosis not indexed under the MeSH term. Searches were performed on 15 September 2024. RESULTS:We found that a higher percentage of citations indexed under the new MeSH term used it according to the definition compared with the text-word search (73.2% vs. 49.5%). The remainder used the term to describe misdiagnosis, false positives, and overtreatment. The citations indexed under the MeSH term were primarily descriptive in nature (68.7%), focusing on oncology (54.2%) and screening practices (31.2%). DISCUSSION:Despite advancements, the field of overdiagnosis is still in its early stages, with potential for expansion into studies addressing prevention and mitigation strategies. The introduction of the MeSH term has facilitated some degree of conceptual alignment. CONCLUSION:Our review provides insights into the current state of the overdiagnosis literature, emphasising prevalent themes and areas for further research, and improvements in MeSH indexing accuracy. Residual conceptual ambiguity surrounding overdiagnosis terminology and indexing practices may explain discrepancies in MeSH categorisation and definition adherence.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of using NGS techniques compared to conventional newborn screening alone for pre-symptomatic identification of genetic diseases in newborns. SECONDARY OBJECTIVES:to explore equity and ethical issues in the application of the new techniques, to inform healthcare decisions by families, carers, and policymakers.

Breast cancer screening effectiveness is measured by its ability to reduce breast cancer mortality in real world settings. A viewpoint issued by the International Agency for Research on Cancer (IARC) in 2015 considered that observational studies (cohort and case-control) are the preferred methods to evaluate the effectiveness of mammography screening. A statistical method was deemed to correct for differences in personal characteristics between women choosing to attend or to not attend screening (self-selection bias). But we showed in a systematic review of observational studies that, compared to women who never attend screening, attenders have a 45 % reduction in their risk of breast cancer death (95 % CI: 40-50 %) and a 46 % reduction (95 % CI: 42-50 %) in their risk of death from a cause other than breast cancer. Screening mammography has no known beneficial influence on causes of death other than breast cancer. If screening mammography reduced the risk of breast cancer death, one would expect a much greater percentage reduction in the risk of breast cancer death than in the risk of all-cause death. Our results suggest that screening mammography attendance is an indicator of personal characteristics associated with a lower risk of dying from any cause, including from breast cancer, which observational studies have misinterpreted as a screening effect. This paper calls into question the IARC 2015 recommendations and advocates the reinstatement of recommendations made by the IARC in 2002 which were based on the use of descriptive and comparative studies.

Authors of a matched cohort study claimed the NHS Health Check programme reduced total mortality 23

Background A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been published and national policies vary. This is an update of a review previously updated 2013 and originally published 2001. Objectives To assess the effect of screening for breast cancer with mammography on mortality and morbidity. Search methods For this 2023 update, we searched PubMed, CENTRAL, the Cochrane Breast Cancer Group Specialised Register, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov up to 28 February 2023. Selection criteria Randomised clinical trials (RCTs) comparing mammographic screening with no mammographic screening. Data collection and analysis Two authors independently extracted data. Study authors were contacted for additional information. Our main outcomes of interest were deaths due to breast cancer, any cancer, and due to any cause, and harms measured as overdiagnosis, number of mastectomies, lumpectomies, use of radiotherapy and of chemotherapy. Certainty of evidence was assessed with GRADE. Main results Eight eligible trials from Europe and North America that compared women offered screening mammography with women not offered screening were included. We excluded a trial because the randomisation failed to produce comparable groups. The eligible trials included 600,000 women in the age range 39 to 74 years. The trials with adequate randomisation did not show a benefit in terms of a reduction in breast cancer mortality at 13 years (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02; 33 vs 30 deaths from breast cancer per 10,000 women; 3 RCTs; 292,153 participants). The findings at 24 years were similar to those at 13 years. Our certainty in both estimates was downgraded 1 level to 'low' due to changes in technology and treatment (indirectness) and due to imprecision. The trials with suboptimal randomisation showed a reduction in breast cancer mortality at 13 years with an RR of 0.75 (95% CI 0.67 to 0.83; 4 RCTs; 306,937 participants; very low certainty evidence). In women below age 50 years, the results from adequately randomised trials did not show a reduction in breast cancer mortality at 13 years of follow-up (RR 0.87, CI 0.73 to 1.03; 28 vs 24 deaths from breast cancer per 10,000 women; 3 RCTs; 218,697 participants, low certainty evidence), nor for women at least 50 years (RR 0.94, CI 0.77 to 1.15; 53 vs 50 deaths from breast cancer per 10,000 women; 2 RCTs; 74,261 participants, low certainty evidence). Only one trial included women aged 70 years and above and could not provide a reliable effect estimate.We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly because of the risk of differential misclassification of cause of death. The trials with adequate randomisation did not find an effect of screening on total cancer mortality, including breast cancer, (RR 1.00, 95% CI 0.96 to 1.04; 288 vs 288 cancer deaths per 10,000 women; 3 RCTs; 292,954 participants; moderate certainty evidence; the follow-up was 10.5 years for Canada, 9 years for Malmo and 23 years for the UK age trial). All-cause mortality was not reduced (RR 0.98, 95% CI 0.94 to 1.03 after 7 years; RR 0.99, 95% CI 0.95 to 1.03 after 13 years; 324 vs 328 deaths per 10,000 women; and RR 1.01, 95% CI 0.99 to 1.04 after 24 years; 773 vs 765 deaths per 10,000 women; 2 RCTs; 250,671 participants; moderate certainty evidence) in the adequately randomised trials. There were more lumpectomies and mastectomies combined in the screened groups, likely reflecting overtreatment (RR 1.31, 95% CI 1.22 to 1.42; 164 vs 214 operations per 10,000 women; 2 RCTs; 132,321 participants; moderate certainty evidence), as were the number of mastectomies alone (RR 1.20, 95% CI 1.08 to 1.32; 122 vs 102 per 10,000 women; 2 RCTs; 132,321; moderate certainty evidence). The use of radiotherapy was similarly increased whereas there was no difference in the use of chemotherapy (data for each outcome available from only one adequately randomised trial; low certainty evidence). Breast screening increased the number of breast cancer diagnoses (overdiagnosis)(RR 1.25, CI 1.18 to 1.34, 142 vs 113 diagnoses at 7 to 9 years of follow-up; 3 RCTs, 292,979 participants; moderate certainty evidence) in trials that did not screen the control group after the intervention phase. Authors' conclusions Because of substantial changes in screening technology, treatment, and breast cancer awareness since the trials were done, the estimates from the trials are uncertain in today's setting. As breast cancer mortality is an unreliable outcome that is biased in favour of screening, it is noteworthy that screening did not reduce total cancer mortality or total mortality. Breast screening does not meet the criteria that population screening should be based on rigorously performed randomised trials that show that the benefits outweigh the harms. No studies have been completed in low income countries and one small study from Colombia has yet to provide data on long term outcomes. Women, clinicians and policy makers should consider the trade-offs and the uncertainties carefully when they decide whether or not to attend or support breast screening programmes.

Background: Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. Objective: To estimate overdiagnosis associated with breast cancer screening among older women by age. Design: Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. Setting: Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. Patients: Women 70 years and older who had been recently screened. Measurements: Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. Results: This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. Limitations: This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. Conclusion: Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question.

OBJECTIVES:Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING:We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS:Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION:Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

RATIONALE:Postpartum iron deficiency anaemia is caused by antenatal iron deficiency or excessive blood loss at delivery and might affect up to 50% of labouring women in low- and middle-income countries. Effective and safe treatment during early motherhood is important for maternal well-being and newborn care. Treatment options include oral iron supplementation, intravenous iron, erythropoietin, and red blood cell transfusion. OBJECTIVES:To assess the benefits and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. These include intravenous iron, oral iron supplementation, red blood cell transfusion, and erythropoietin. SEARCH METHODS:A Cochrane Information Specialist searched for all published, unpublished, and ongoing trials, without language or publication status restrictions. We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, LILACS, WHO ICTRP, and ClinicalTrials.gov, together with reference checking, citation searching, and contact with study authors to identify eligible studies. We applied date limits to retrieve new records since the last search on 9 April 2015 until 11 April 2024. ELIGIBILITY CRITERIA:We included published, unpublished, and ongoing randomised controlled trials (RCTs) that compared treatments for postpartum iron deficiency anaemia with placebo, no treatment, or alternative treatments. Cluster-randomised trials were eligible for inclusion. We included RCTs regardless of blinding. Participants were women with postpartum haemoglobin ≤ 12 g/dL, treated within six weeks after childbirth. We excluded non-randomised, quasi-randomised, and cross-over trials. OUTCOMES:The critical outcomes of this review were maternal mortality and fatigue. The important outcomes included persistent anaemia symptoms, persistent postpartum anaemia, psychological well-being, infections, compliance with treatment, breastfeeding, length of hospital stay, serious adverse events, anaphylaxis or evidence of hypersensitivity, flushing/Fishbane reaction, injection discomfort/reaction, constipation, gastrointestinal pain, number of red blood cell transfusions, and haemoglobin levels. RISK OF BIAS:We assessed risk of bias in the included studies using the Cochrane RoB 1 tool. SYNTHESIS METHODS:Two review authors independently performed study screening, risk of bias assessment, and data extraction. We contacted trial authors for supplementary data when necessary. We screened all trials for trustworthiness and scientific integrity using the Cochrane Trustworthiness Screening Tool. We conducted meta-analyses using a fixed-effect model whenever feasible to synthesise outcomes. In cases where data were not suitable for meta-analysis, we provided a narrative summary of important findings. We evaluated the overall certainty of the evidence using GRADE. INCLUDED STUDIES:We included 33 RCTs with a total of 4558 postpartum women. Most trials were at high risk of bias for several risk of bias domains. SYNTHESIS OF RESULTS:Most of the evidence was of low or very low certainty. Imprecision due to few events and risk of bias due to lack of blinding were the most important factors. Intravenous iron versus oral iron supplementation The evidence is very uncertain about the effect of intravenous iron on mortality (risk ratio (RR) 2.95, 95% confidence interval (CI) 0.12 to 71.96; P = 0.51; I² = not applicable; 3 RCTs; 1 event; 572 women; very low-certainty evidence). One woman died of cardiomyopathy, and another developed arrhythmia, both in the groups treated with intravenous iron. Intravenous iron probably results in a slight reduction in fatigue within 8 to 28 days (standardised mean difference -0.25, 95% CI -0.42 to -0.07; P = 0.006; I² = 47%; 2 RCTs; 515 women; moderate-certainty evidence). Breastfeeding was not reported. Oral iron probably increases the risk of constipation compared to intravenous iron (RR 0.12, 95% CI 0.06 to 0.21; P < 0.001; I² = 0%; 10 RCTs; 1798 women; moderate-certainty evidence). The evidence is very uncertain about the effect of intravenous iron on anaphylaxis or hypersensitivity (RR 2.77, 95% CI 0.31 to 24.86; P = 0.36; I² = 0%; 12 RCTs; 2195 women; very low-certainty evidence). Three women treated with intravenous iron experienced anaphylaxis or hypersensitivity. The trials that reported on haemoglobin at 8 to 28 days were too heterogeneous to pool. However, 5 of 6 RCTs favoured intravenous iron, with mean changes in haemoglobin ranging from 0.73 to 2.10 g/dL (low-certainty evidence). Red blood cell transfusion versus intravenous iron No women died in the only trial that reported on mortality (1 RCT; 7 women; very low-certainty evidence). The evidence is very uncertain about the effect of red blood cell transfusion on fatigue at 8 to 28 days (mean difference (MD) 1.20, 95% CI -2.41 to 4.81; P = 0.51; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence) and breastfeeding more than six weeks postpartum (RR 0.43, 95% CI 0.12 to 1.57; P = 0.20; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence). Constipation and anaphylaxis were not reported. Red blood cell transfusion may result in little to no difference in haemoglobin within 8 to 28 days (MD -1.00, 95% CI -2.02 to 0.02; P = 0.05; I² = not applicable; 1 RCT; 12 women; low-certainty evidence). Intravenous iron and oral iron supplementation versus oral iron supplementation Mortality and breastfeeding were not reported. One trial reported a greater improvement in fatigue in the intravenous and oral iron group, but the effect size could not be calculated (1 RCT; 128 women; very low-certainty evidence). Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone (RR 0.21, 95% CI 0.07 to 0.69; P = 0.01; I² = not applicable; 1 RCT; 128 women; low-certainty evidence). There were no anaphylaxis or hypersensitivity events in the trials (2 RCTs; 168 women; very low-certainty evidence). Intravenous iron and oral iron may result in little to no difference in haemoglobin (g/dL) at 8 to 28 days (MD 0.00, 95% CI -0.48 to 0.48; P = 1.00; I² = not applicable; 1 RCT; 60 women; low-certainty evidence). Red blood cell transfusion versus no transfusion Mortality, fatigue at day 8 to 28, constipation, anaphylaxis, and haemoglobin were not reported. Red blood cell transfusion may result in little to no difference in breastfeeding more than six weeks postpartum (RR 0.91, 95% CI 0.78 to 1.07; P = 0.24; I² = not applicable; 1 RCT; 297 women; low-certainty evidence). Oral iron supplementation versus placebo or no treatment Mortality, fatigue, breastfeeding, constipation, anaphylaxis, and haemoglobin were not reported. Two trials reported on gastrointestinal symptoms, but did not report results by study arm. AUTHORS' CONCLUSIONS:Intravenous iron probably reduces fatigue slightly in the early postpartum weeks (8 to 28 days) compared to oral iron tablets, but probably results in little to no difference after four weeks. It is very uncertain if intravenous iron has an effect on mortality and anaphylaxis/hypersensitivity. Breastfeeding was not reported. Intravenous iron may increase haemoglobin slightly more than iron tablets, but the data were too heterogeneous to pool. However, changes in haemoglobin levels are a surrogate outcome, and treatment decisions should preferentially be based on patient-relevant outcomes. Iron tablets probably result in a large increase in constipation compared to intravenous iron. The effect of red blood cell transfusion compared to intravenous iron on mortality, fatigue, and breastfeeding is very uncertain. No studies reported on constipation or anaphylaxis/hypersensitivity. Red blood cell transfusion may result in little to no difference in haemoglobin at 8 to 28 days. The effect of intravenous iron and oral iron supplementation on mortality, fatigue, breastfeeding, and anaphylaxis/hypersensitivity is very uncertain or unreported. Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone, and in little to no difference in haemoglobin. The effect of red blood cell transfusion compared to non-transfusion on mortality, fatigue, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. Red blood cell transfusion may result in little to no difference in breastfeeding. The effect of oral iron supplementation on mortality, fatigue, breastfeeding, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol and previous versions are available: Protocol (2013) [DOI: 10.1002/14651858.CD010861] Original review (2004) [DOI: 10.1002/14651858.CD004222.pub2] Review update (2015) [DOI: 10.1002/14651858.CD010861.pub2].

OBJECTIVES:Observational cohort studies are used to evaluate the effectiveness of screening mammography in women offered screening. Because screening mammography has no effect on causes of death other than breast cancer (BC), cohort studies should show reductions in the risk of BC death substantially greater than possible reductions in the risk of all-cause death. We assessed the risk of BC deaths and of all-cause (or of nonBC) deaths associated with screening mammography attendance reported in cohort studies. STUDY DESIGN AND SETTING:Cohort studies published from 2002 to 2022 on women invited to screening mammography were searched in PubMed, Web of Sciences, Scopus, and in review articles. Random effect meta-analyses were performed using relative risks (RRs) of death between women who attended screening compared to women who did not attend screening. RESULTS:Eighteen cohort studies were identified, nine that reported RRs of BC deaths only, five that reported RRs of all-cause deaths only, and four that reported RRs for both BC deaths and all-cause deaths. The latter four cohort studies reported 12-76 times more all-cause deaths than BC deaths. The random-effect summary of RR for BC mortality in screening attendees vs nonattendees was 0.55 (95% CI: 0.50-0.60) in 13 cohort studies. The summary of RR for all-cause mortality was 0.54 (0.50-0.58) in 10 cohort studies. In the four cohort studies that evaluated both outcomes, the summary of RRs were 0.63 (0.43-0.83) for BC mortality and of 0.54 (0.44-0.64) for all-cause mortality. CONCLUSION:The similar relative reductions in breast- and all-cause (or nonBC) mortality indicates that screening mammography attendance is an indicator of characteristics associated with a lower risk of dying from any cause, including from BC, which observational studies have falsely interpreted as a screening effect.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of immune checkpoint inhibitors (single-agent or combination therapy) in people with advanced malignant pleural mesothelioma in a first-line or salvage setting.

This study examines the content, including mention of benefits and harms of testing and treatment, and funding of disease awareness campaign websites recognized by major noncommercial institutions.

Tackling overdiagnosis will create more sustainable healthcare for people and the planet