A plea for more careful scholarship in reviewing evidence: the case of mammographic screening.

Objectives: To identify issues of principle and practice giving rise to misunderstandings in reviewing evidence, to illustrate these by reference to the Nordic Cochrane Review (NCR) and its interpretation of two trials of mammographic screening, and to draw lessons for future reviewing of published results. Methods: A narrative review of the publications of the Nordic Cochrane Review of mammographic screening (NCR), the Swedish Two-County Trial (S2C) and the Canadian National Breast Screening Study 1 and 2 (CNBSS-1 and CNBSS-2). Results: The NCR concluded that the S2C was unreliable, despite the review's complaints being shown to be mistaken, by direct reference to the original primary publications of the S2C. Repeated concerns were expressed by others about potential subversion of randomisation in CNBSS-1 and CNBSS-2; however, the NCR continued to rely heavily on the results of these trials. Since 2022, however, eyewitness evidence of such subversion has been in the public domain. Conclusions: An over-reliance on nominal satisfaction of checklists of criteria in systematic reviewing can lead to erroneous conclusions. This occurred in the case of the NCR, which concluded that mammographic screening was ineffective or minimally effective. Broader and more even-handed reviews of the evidence show that screening confers a substantial reduction in breast cancer mortality. Advances in knowledge: Those carrying out systematic reviews should be aware of the dangers of over-reliance on checklists and guidelines. Readers of systematic reviews should be aware that a systematic review is just another study, with the capability that all studies have of coming to incorrect conclusions. When a review seems to overturn the current position, it is essential to revisit the publications of the primary research.

Smoking cessation advice from healthcare professionals helps those in the contemplation and preparation stage: An application with transtheoretical model underpinning in a community-based program.

INTRODUCTION: The efficacy of smoking cessation intervention has been proven with randomized controlled trials. Our study aims to elucidate the effects of the delivery method of smoking cessation advice on the process of stage of changes with transtheorectical model underpinning in a community setting. METHODS: A total of 436 subjects were recruited in a quasi-experimental untreated control design study, with 46 receiving advice from healthcare professionals (HCP group) and 390 in the control group, in 2003, Nantou, Taiwan. A discrete time Markov model was used to quantify the multi-state process of smoking cessation in light of the transtheorectical model. Multiple polytomous logistic regression models were simultaneously applied to different transitions. RESULTS: The estimated forward transition probabilities were higher in the HCP group compared to their counterparts in the control group. On the other hand, the backward transition probabilities were smaller in the HCP group. After adjusting for confounding factors, HCP had a 4.3-fold (95% CI: 2.21-8.46) odds ratio of moving forward from the contemplation stage, and 2.4-fold odds ratio (95% CI: 1.03-4.42) from the preparation stage. Elderly people were more reluctant to change from precontemplation (AOR=0.50; 95% CI: 0.34-0.74) and contemplation (AOR=0.58; 95% CI: 0.44-0.84), but once in the preparation stage, they were more likely to take action (AOR=1.28; 95% CI: 1.01-1.83). For those in the preparation stage, longer smoking years had a negative effect on taking action (AOR=0.74; 95% CI: 0.52-0.99), but cessation advice from others enhanced the likelihood to take action (AOR=1.36; 95% CI: 1.01-1.99). CONCLUSIONS: The direct advice on smoking cessation from healthcare professionals enforced the net forward transition towards smoking cessation, especially the transition from contemplation and preparation. The proposed Markov regression model assessed the net effect of different intervention approaches allowing for the simultaneous consideration of multiple transitions and the effects of other confounders.

A Proposal to Unify the Classification of Breast and Prostate Cancers Based on the Anatomic Site of Cancer Origin and on Long-term Patient Outcome.

The similarity between the structure and function of the breast and prostate has been known for a long time, but there are serious discrepancies in the terminology describing breast and prostate cancers. The use of the large, thick-section (3D) histology technique for both organs exposes the irrationality of the breast cancer terminology. Pathologists with expertise in diagnosing prostate cancer take the anatomic site of cancer origin into account when using the terms AAP (acinar adenocarcinoma of the prostate) and DAP (ductal adenocarcinoma of the prostate) to distinguish between the prostate cancers originating primarily from the fluid-producing acinar portion of the organ (AAP) and the tumors originating either purely from the larger ducts (DAP) or from both the acini and the main ducts combined (DAP and AAP). Long-term patient outcome is closely correlated with the terminology, because patients with DAP have a significantly poorer prognosis than patients with AAP. The current breast cancer terminology could be improved by modeling it after the method of classifying prostate cancer to reflect the anatomic site of breast cancer origin and the patient outcome. The long-term survival curves of our consecutive breast cancer cases collected since 1977 clearly show that the non-palpable, screen-detected breast cancers originating from the milk-producing acini have excellent prognosis, irrespective of their histologic malignancy grade or biomarkers. Correspondingly, the breast cancer subtypes of truly ductal origin have a significantly poorer outcome, despite recent improvements in diagnosis and therapy. The mammographic appearance of breast cancers reflects the underlying tissue structure. Addition of these "mammographic tumor features" to the currently used histologic phenotypes makes it possible to distinguish the breast cancer cases of ductal origin with a poor outcome, termed DAB (ductal adenocarcinoma of the breast), from the more easily managed breast cancers of acinar origin, termed AAB (acinar adenocarcinoma of the breast), which have a significantly better outcome. This simple and easily communicable terminology could lead to better communication between the diagnostic and therapeutic team members and result in more rational treatment planning for the benefit of their patients.

Analytical decision model for sample size and effectiveness projections for use in planning a population-based randomized controlled trial of colorectal cancer screening.

RATIONALE, AIMS AND OBJECTIVES: Population-based randomized controlled trials (RCTs) often involve enormous costs and long-term follow-up to evaluate primary end points. Analytical decision-simulated model for sample size and effectiveness projections based on primary and surrogate end points are necessary before planning a population-based RCT. METHOD: Based on the study design similar to two previous RCTs, transition rates were estimated using a five-state natural history model [normal, preclinical detection phase (PCDP) Dukes' A/B, PCDP Dukes' C/D, Clinical Dukes' A/B and Clinical Dukes' C/D]. The Markov cycle tree was assigned transition parameters, variables related to screening and survival rate that simulated results of 10-year follow-up in the absence of screening for a hypothetical cohort aged 45-74 years. The corresponding screened arm was to simulate the results after the introduction of population-based screening for colorectal cancer with fecal occult blood test with stop screen design. RESULTS: The natural course of mean sojourn time for five-state Markov model were estimated as 2.75 years for preclinical Dukes' A/B and 1.38 years for preclinical Dukes' C/D. The expected reductions in mortality and Dukes' C/D were 13% (95% confidence intervals: 7-19%) and 26% (95% confidence intervals: 20-32%), respectively, given a 70% acceptance rate and a 90% colonoscopy referral rate. Sample sizes required were 86,150 and 65,592 subjects for the primary end point and the surrogate end point, respectively, given an incidence rate up to 0.0020 per year. CONCLUSIONS: The sample sizes required for primary and surrogate end points and the projection of effectiveness of fecal occult blood test for colorectal cancer screening were developed. Both are very important to plan a population-based RCT.

Kinetic epidemiological model for elucidating sexual difference of hypertension (KCIS no.20).

BACKGROUND: Woman have lower rate of hypertension than man but it is still elusive how such gender difference can be explained by kinetic epidemiological curves. OBJECTIVE: The aim of this paper was to develop a multi-state model for delineating the kinetic epidemiology of hypertension according to the Seventh Report of the Joint National Committee (JNC 7) classification criteria by gender, and to derive gender-specific kinetic curves. METHODS: We used data from a population-based screening programme with 42,027 participants to fit a four-state Markov model corresponding to the classification of hypertension from the JNC 7. RESULTS: The young man had higher progression rate but lower regression rate for the movement between normal and pre-hypertension than the young woman. Such gender difference disappeared after 50 years old. The mean sojourn time of pre- and stage 1 hypertension for man and stage 1 for woman was approximately 5 years. However, the corresponding figure for pre-hypertension for woman was 25 years at age 30, 10 years at age 40 and 5 years afterwards. CONCLUSION: Elucidating the kinetic epidemiological curves of hypertension explains higher prevalence rate in young man than woman. These findings fit with the role of sex hormones regulating blood pressure demonstrated in the animal model.

Decision modelling of economic evaluation of intervention programme of breast cancer.

OBJECTIVES: Economic appraisal of an intervention is a complex and multivariable problem, with probabilistic issues related not only to clinical outcomes but also to costs and willingness to pay. METHODS: We provide a comprehensive framework for economic appraisal of a health intervention to prevent beast cancer mortality, involving probabilistic model of costs as well as of aspects of the disease process. The economic appraisal can give a range of probabilities of cost-effectiveness depending on willingness or ability to pay. RESULTS: We apply the method to the example of polychemotherapy for early breast cancer. Results indicate a 30% probability of cost-effectiveness for a willingness to pay of $ 60,000 per quality-adjusted life-year and around 50% for a threshold of $ 100,000. CONCLUSION: The comprehensive economic appraisal model is a powerful tool for decision making over a range of economic environments.

Incorporating frailty in a multi-state model: application to disease natural history modelling of adenoma-carcinoma in the large bowel.

Homogeneous multi-state models of disease progression have been widely used for designing and evaluating cancer screening programs. However, in screening for premalignant conditions of the cervix or large bowel, it is unlikely that all premalignant lesions have the same underlying propensity for progression. Incorporating frailty into multi-state models raises practical difficulties as it precludes the derivation of finite transition probabilities by matrix solution of the Kolmogorov equations. We address this problem by formulating a heterogeneous process as a series of homogeneous processes linked by transitions which are subject to heterogeneity (frailty). Continuous frailty and discrete mover-stayer models were developed. We applied these to the example of progression of adenoma to colorectal cancer in a three-state model and to a five-state model including consideration of adenoma size. Results were compared with those of purely homogeneous models in a previous study in terms of cumulative risk of malignant transformation from adenoma to invasive colorectal cancer.

Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England.

OBJECTIVES: To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50-69 years. SETTING: The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50-69 years. METHODS: We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974-2004 and 1974-2003, respectively). We used Poisson regression for statistical inference. RESULTS: A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. CONCLUSIONS: The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.

The influence of media coverage of a celebrity suicide on subsequent suicide attempts.

OBJECTIVE: To investigate the impact of media reporting of a celebrity suicide on subsequent suicide attempts. METHOD: A Poisson time series autoregression analysis was conducted to examine whether there was a significant increase in suicide attempts during the 3-week period after the start of extensive media reporting of a celebrity suicide. The reporting began on May 2, 2005, and lasted about 17 days. To investigate the influence of media reporting on suicide attempts, a structured interview was conducted with 124 suicide attempters identified from 2 counties in Mid Taiwan who had exposure to the media reporting. RESULTS: After controlling for seasonal variation, calendar year, temperature, and humidity, there was a marked increase in the number of suicide attempts during the 3-week period after media reporting began (adjusted relative risk = 1.55, 95% CI = 1.26 to 1.91). Among 124 suicide attempters exposed to the media reports, 23.4% reported an influence from them. There was no relationship between the attempters' ages and the age of the celebrity or the method, but male attempters had a significantly higher risk for such influence. A considerably higher risk for such influence was found among subjects with a history of suicide attempt(s) in the previous year (odds ratio = 52.3, 95% CI = 5.96 to 459.1). CONCLUSIONS: The extensive media reporting of the suicide of a celebrity was followed by an increase in suicide attempts. The effect was particularly marked in individuals with a recent history of a suicide attempt. The results provide further support for the need for more restrained reporting of suicides as part of suicide prevention strategies and for special vigilance for contagious effects of such reporting on people who have carried out recent suicidal acts.

The influence of media reporting of a celebrity suicide on suicidal behavior in patients with a history of depressive disorder.

BACKGROUND: Few studies have directly assessed the impact of a specific media report in vulnerable people. This study investigates possible influences of media reporting of a celebrity suicide on subsequent suicidal behaviors and associated risk factors among depressive patients. METHODS: Depressive patients (N=461) were assessed through a structured interview soon after extensive media reporting of a celebrity suicide. RESULTS: Among 438 depressive patients exposed to the media report, 38.8% reported an influence on subsequent suicidal behaviors, including 24 (5.5%) with a suicide attempt. The risk of such influence was highest among patients in a severe depressive state just prior to the media report (adjusted OR 7.81, 95% CI 3.28-18.59). Such influence on a subsequent suicide attempt was highest in patients with a most recent suicide attempt within one month prior to the media reports (adjusted hazard ratio 11.91, 95% CI 3.76-37.72). LIMITATIONS: Our finding of the significant media influence may reflect adverse thoughts among more suicidal and depressed individuals. The possible influence of other factors on the findings cannot be ruled out. CONCLUSIONS: This study has provided more convincing evidence suggesting negative influences of media reporting of a celebrity suicide on subsequent suicidal behaviors among depressive patients. Particular attention in terms of potential negative media influences should be paid to patients who are younger and currently depressed and have made a recent suicide attempt.

Screening for breast cancer.

Strong evidence supports the value of breast cancer screening with mammography, and high-quality mammography screening can be considered a major public health achievement. As noted earlier in the discussion about the evaluation of service screening, the group of women who did not participate in mammographic screening in the decades after screening had been introduced had essentially unchanged or only minor improvements in mortality compared with the pattern before the introduction of screening, despite widespread use of adjuvant chemotherapy or hormonal therapy. Breast cancer should be treated in its preclinical phase if we are to save the lives of women with this disease, and a considerable body of evidence outlines best practices that, with broader adherence, would result in greater breast cancer mortality reductions than have been observed to date.

The randomized trials of breast cancer screening: what have we learned?

Eight randomized controlled trials of mammography screening have been conducted to date. In addition to evaluating the efficacy of screening with an experimental design, the trials provided investigators with access to information about breast cancers much earlier in their development than had previously been available. The trials of mammographic screening provide conclusive evidence that the policy of offering screening is associated with a significant and substantial reduction in breast cancer mortality.