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Mammography screening may save women from dying of breast cancer, although it has not been shown to reduce all-cause mortality. Screening also leads to overdiagnosis and many false positive mammograms aggravating women's quality-of-life. Quality adjusted life years (QALY) analyses of mammography screening have so far, calculated life years gained assuming that all prevented breast cancer deaths translate into a reduction in all-cause mortality. We calculated net QALYs in two hypothesized cohorts of 100,000 Norwegian women; one screened biennially from age 50 to 69 years and one not screened. We followed both cohorts to age 85 years. We used EQ-5D and an alternative equity weighted QALY instrument to estimate utility losses. In the screening cohort, we assumed 20% false positive tests during screening, different levels of overdiagnosis (20-75%) and different levels of breast cancer mortality reduction (10-30%). We assumed that reductions in breast cancer mortality only to a limited extent (20, 50 or 80%), resulted in reductions in all-cause mortality. We calculated both undiscounted and discounted (4%) QALYs. Assuming that 50% of the reduction in breast cancer mortality translated to a reduction in all-cause mortality and using estimated levels of benefits and harms in modern screening programs (50-75% overdiagnosis and 10% reduction in breast cancer mortality), undiscounted equity weighted QALY loss varied from 437 to 875 per 100,000 women. Using the levels of benefit and harms as reported in 30-40 years old randomized trials (30% overdiagnosis and 15% reduction in breast cancer mortality), undiscounted equity weighted QALY gain was 535 per 100,000. Net QALY in modern mammography screening in Norway is negative. Results could also be representative for Sweden, Denmark, UK and the US.

Summary Background Large reductions in the incidence of abdominal aortic aneurysm (AAA) and AAA-related mortality mean that results from randomised trials of screening for the disorder might be out-dated. The aim of this study was to estimate the effect of AAA screening in Sweden on disease-specific mortality, incidence, and surgery. Methods Individual data on the incidence of AAA, AAA mortality, and surgery for AAA in a cohort of men aged 65 years who were invited to screening between 2006 and 2009, were compared with data from an age-matched contemporaneous cohort of men who were not invited for AAA screening. We also analysed national data for all men aged 40–99 years between Jan 1, 1987, and Dec 31, 2015, to explore background trends. Adjustment for confounding was done by weighting the analyses with a propensity score obtained from a logistic regression model on cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline. Adjustment for differential attrition was also done by weighting the analyses with the inverse probability of still being in the cohort 6 years after screening. Generalised estimating equations were used to adjust the variance for repeated measurement and in response to the weighting. Findings AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65–74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio [aOR] 0·76, 95% CI 0·38–1·51), which means that two men (95% CI −3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1·52, 95% CI 1·16–1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20–2·10; p=0·001), such that for every 10 000 men offered screening, 49 men (95% CI 25–73) were likely to be overdiagnosed, 19 of whom (95% CI 1–37) had avoidable surgery that increased their risk of mortality and morbidity. Interpretation AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question. Funding Research Unit and Section for General Practice, FoUU-centrum Fyrbodal, Sweden, and the region of Vastra Gotaland, Sweden.

Updated guidelines on breast cancer screening have been published by several major organisations over the past five years. Recommendations vary regarding both age range, screening interval, and even on whether breast screening should be offered at all. The variation between recommendations reflects substantial differences in estimates of the major benefit (breast cancer mortality reduction) and the major harm (overdiagnosis). Estimates vary considerably among randomised trials, as well as observational studies: from no benefit to large reductions, and from no overdiagnosis to substantial levels. The estimates vary according to the methodology of the randomised trials, and the design of the observational studies. Guideline recommendations reflect the choice of evidence informing them. While there are well-developed tools to deal with randomised trials in guideline work, these are not always used, or they may not be followed as recommended. Further, results of trials performed decades ago may no longer be applicable. For observational studies, the framework for inclusion in guidelines is not similarly well-developed and there are methodological concerns specific to screening interventions, such as small effects in absolute terms. There is a need for agreement on a hierarchy of observational study designs to quantify the major benefit and harm of cancer screening. This review provides a summary of recent guidelines on breast cancer screening and their major strengths and weaknesses, as well as a short overview of the major strengths and limitations of observational study designs. There is a need for agreement on a hierarchy of observational study designs in this field.

Background: A 68-year-old man died of cerebral arterial embolism 6 days after transrectal prostate biopsy with a single p.o. dose of trimethoprim sulfamethoxazole (TMP-SMX) as prophylaxis. The case precipitated analysis of local antibiotic resistance and complication rates. Materials and methods: Data on E. coli resistance from Oslo University Hospital and national data on hospitalizations and mortality after biopsy were retrieved from local microbiology files and the Norwegian Patient Registry (NPR) 2011–2017. Results: Urine E. coli resistance against TMP-SMX increased from 35% in 2013 to more than 60% in 2015. For ciprofloxacin, the resistance increased from 15% in 2013 to about 45% in 2016. The highest annual E. coli resistance in blood cultures for TMP-SMX and ciprofloxacin was 37% and 28%, respectively. 10% of patients were hospitalized with a diagnosis of infection within the first 60 days after biopsy and there was a relative increase in mortality rate of 261% within the first 30 days. Due to the severity of the figures, the story and the NPR data were published in Norway’s leading newspaper and were succeeded by a series of chronicles and commentaries. Conclusions: Several critical points of the biopsy procedure were not performed according to current standards. We believe that the patient might have died of septic embolism after biopsy. As a result of the findings and the debate, local practice was changed from transrectal to transperineal prostate biopsies.

Background National mortality statistics should be comparable between countries that use the World Health Organization’s International Classification of Diseases. Distinguishing between manners of death, especially suicides and accidents, is a challenge. Knowledge about accidents is important in prevention of both accidents and suicides. The aim of the present study was to assess the reliability of classifying deaths as accidents and undetermined manner of deaths in the three Scandinavian countries and to compare cross-national differences. Methods The cause of death registers in Norway, Sweden and Denmark provided data from 2008 for samples of 600 deaths from each country, of which 200 were registered as suicides, 200 as accidents or undetermined manner of deaths and 200 as natural deaths. The information given to the eight experts was identical to the information used by the Cause of Death Register. This included death certificates, and if available external post-mortem examinations, forensic autopsy reports and police reports. Results In total, 69 % (Sweden and Norway) and 78 % (Denmark) of deaths registered in the official mortality statistics as accidents were confirmed by the experts. In the majority of the cases where disagreement was seen, the experts reclassified accidents to undetermined manner of death, in 26, 25 and 19 % of cases, respectively. Few cases were reclassified as suicides or natural deaths. Among the extracted accidents, the experts agreed least with the official mortality statistics concerning drowning and poisoning accidents. They also reported most uncertainty in these categories of accidents. In a second re-evaluation, where more information was made available, the Norwegian psychiatrist and forensic pathologist increased their agreement with the official mortality statistics from 76 to 87 %, and from 85 to 88 %, respectively, regarding the Norwegian and Swedish datasets. Among the extracted undetermined deaths in the Swedish dataset, the two experts reclassified 22 and 51 %, respectively, to accidents. Conclusion There was moderate agreement in reclassification of accidents between the official mortality statistics and the experts. In the majority of cases where there was disagreement, accidents were reclassified as undetermined manner of death, and only a small proportion as suicides.

BACKGROUND In 2011, following a period with delivery problems, the only registered digitoxin drug in Norway was replaced with digoxin. As a result, approximately 21 000 patients had to replace digitoxin with digoxin. There are important pharmacokinetic differences between digitoxin and digoxin (the general term for both drugs is digitalis), which must be taken into account when changing therapy. The aim of this study was to investigate compliance of drug security, during the transition from digitoxin to digoxin in Norway.MATERIAL AND METHOD Enquiries addressed to the Norwegian Poison Information Centre and reports of fatal adverse effects to the Regional Drug Information Centres (RELIS) regarding intake of digitalis were analysed. Serum concentrations of digitoxin and digoxin analyzed at Oslo University Hospital were reviewed. All data sources were reviewed for the years 2010-2014 and patients > 20 years were included.RESULTS The total number of enquiries addressed to the Norwegian Poison Information Centre, fatal adverse drug reactions reported to RELIS, and patient samples in the toxic range analyzed at Oslo University Hospital increased from 2012, timewise related to the transition to digoxin.INTERPRETATION Despite extensive information from the Norwegian Medicines Agency, a small, transient increase was observed in the number of overdoses and reported deaths from digitalis related to change in therapy. The cause of the overdose was in many cases unknown. This study revealed several cases of incorrect dosage, simultaneous use of digitoxin and digoxin, and washout time that was insufficient or lacking before initiation of digoxin.

Background Suicide prevention is a core task in mental health services. Our objective was to determine whether Collaborative Assessment and Management of Suicidality (CAMS) reduced suicidal thoughts and behaviors and mental health distress more effectively than treatment as usual (TAU) in a heterogeneous patient population within specialized mental health care services. Methods In this observer-blinded pragmatic randomized controlled trial participants who scored 13 or above on Beck's Scale for Suicide Ideation-Current (BSSI-C) were included from seven in- and outpatient units. Primary outcome was suicidal ideation (BSSI-C). Secondary outcomes were mental health distress measured by the Outcome Questionnaire–45, and suicidal behaviors measured by the Suicide Attempt Self-Injury Count. Patients were assessed at baseline and after 6 and 12 months. Results The final intent-to-treat analyses included 78 participants (mean age 35.9 years, SD = 14.5, 41 females). The majority were depressed (65%), had a secondary diagnosis (73%) and 32% suffered from borderline personality disorder or borderline traits. After 6 months, CAMS participants reported lower levels of suicidal ideation compared to TAU (β = −4.29, 95% CI = −8.32 to −0.27, p = .036). Larger changes in mental health distress were observed for CAMS participants after 6 months (β = −11.87, 95% CI = −22.99 to −0.76, p = .036) and 12 months (β = −13.70, 95% CI = −24.88 to −2.51, p = .017). Limitations The modest sample size rendered the trial unable to detect small between-group differences. Conclusions CAMS reduced suicidal ideation and mental health distress more efficiently than TAU in a heterogeneous patient population within specialized care.

Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Using unique data from screening programs launched in Denmark from 1991 to 2007, the authors assesse...

Background Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant). Design Cohort study. Setting Denmark from 1980 to 2010. Participants Women aged 35 to 84 years. Intervention Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times. Measurements Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas. Results Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]). Limitation Regional differences complicate interpretation. Conclusion Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%). Primary funding source None.

Lead-time can mean two different things: Clinical lead-time is the lead-time for clinically relevant tumors; that is, those that are not overdiagnosed. Model-based lead-time is a theoretical construct where the time when the tumor would have caused symptoms is not limited by the person’s death. It is the average time at which the diagnosis is brought forward for both clinically relevant and overdiagnosed cancers. When screening for breast cancer, clinical lead-time is about 1 year, while model-based lead-time varies from 2 to 7 years. There are two different methods to calculate overdiagnosis in cancer screening—the excess-incidence approach and the lead-time approach—that rely on two different lead-time definitions. Overdiagnosis when screening with mammography has varied from 0 to 75 %. We have explained that these differences are mainly caused by using different definitions and methods and not by variations in data. High levels of overdiagnosis of cancer have usually been explained by detection of many slow-growing tumors with long lead-times. This theory can be tested by studying if slow-growing tumors accumulate in the absence of screening, which they don’t. Thus, it is likely that the natural history of many subclinical cancers is spontaneous regression.

BACKGROUND In 2011, following a period with delivery problems, the only registered digitoxin drug in Norway was replaced with digoxin. As a result, approximately 21 000 patients had to replace digitoxin with digoxin. There are important pharmacokinetic differences between digitoxin and digoxin (the general term for both drugs is digitalis), which must be taken into account when changing therapy. The aim of this study was to investigate compliance of drug security, during the transition from digitoxin to digoxin in Norway.MATERIAL AND METHOD Enquiries addressed to the Norwegian Poison Information Centre and reports of fatal adverse effects to the Regional Drug Information Centres (RELIS) regarding intake of digitalis were analysed. Serum concentrations of digitoxin and digoxin analyzed at Oslo University Hospital were reviewed. All data sources were reviewed for the years 2010-2014 and patients20 years were included.RESULTS The total number of enquiries addressed to the Norwegian Poison Information Centre, fatal adverse drug reactions reported to RELIS, and patient samples in the toxic range analyzed at Oslo University Hospital increased from 2012, timewise related to the transition to digoxin.INTERPRETATION Despite extensive information from the Norwegian Medicines Agency, a small, transient increase was observed in the number of overdoses and reported deaths from digitalis related to change in therapy. The cause of the overdose was in many cases unknown. This study revealed several cases of incorrect dosage, simultaneous use of digitoxin and digoxin, and washout time that was insufficient or lacking before initiation of digoxin.

Background Collaborative Assessment and Management of Suicidality (CAMS) is a therapeutic framework that appears promising to reduce suicidal ideation and suicidal cognition. CAMS has not previously been evaluated in a standard specialized mental health care setting for patients with suicidal problems in general. In this pragmatic randomized controlled trial (RCT) we will investigate if CAMS is more effective than treatment as usual (TAU) in reducing suicidal thoughts and behaviors. Effects will also be investigated on mental health and symptom relief in general and upon readmissions to inpatient units. Methods/design The study is a multicenter, observer-blinded, superiority, two-armed RCT which will include patients from four clinical departments at Vestre Viken Hospital Trust, Norway. We aim to include 100 patients with moderate to strong suicidal problems, as defined by a score of 13 or more on Beck’s Scale for Suicide Ideation - Current. Patients are included regardless of diagnosis. Randomization will be performed using a stratified four-block procedure with treatment unit as the stratification variable. The duration of treatment will vary depending on patients’ needs and clinical assessments. Patients are interviewed by research staff at four checkpoints: baseline, 2 weeks, 6 months, and 12 months. Central outcome measures are the Beck Scale for Suicide Ideation - Current, Outcome Questionnaire – 45, and Suicide Attempt Self-Injury Count. Discussion This pragmatic trial is effectuated within the Public Health Care System in Norway, where patients have multiple problems and diagnoses and therapists have a high work load. Results from this trial are highly generalizable to a typical everyday clinical setting, and one should expect similar results if CAMS is implemented in the future as a standard component in specialized mental health care systems. Trial registration Open Science Framework: DOI 10.17605/OSF.IO/JHRM2 . Registered 5 July 2015. ClinicalTrials.gov: NCT02685943 . Registered on 8 February 2016.

Abstract. Background: There may be various reasons for differences in suicide rates between countries and over time within a country. One reason can be different registration practices. Aims: The purpose of this study was to describe and compare the present procedures for mortality and suicide registration in the three Scandinavian countries and to illustrate potential sources of error in the registration of suicide. Method: Information about registration practices and classification procedures was obtained from the cause of death registers in Norway, Sweden, and Denmark. In addition, we received information from experts in the field in each country. Results: Sweden uses event of undetermined intent more frequently than Denmark does, and Denmark more frequently than Norway. There seems to be somewhat more uncertainty among deaths classified as ill-defined and unknown cause of mortality in Norway, compared with the other two countries. Sweden performs more forensic autopsies than Norway, and Norway more than Denmark. In Denmark, in cases of a suspected unnatural manner of death, a thorough external examination of the deceased is performed. Conclusion: Differences in the classification of causes of death and in postmortem examinations exist in Scandinavian countries. These differences might influence the suicide statistics in Scandinavia.

Solveig Hofvind and colleagues have compared incidence rates of breast cancer by tumour stages and size, and of treatment of breast cancer detected in attendees versus nonattendees who were invited to the Norwegian breast cancer screening programme [1]. Hofvind and colleagues found that advanced stage breast cancers were less common in attendees than in nonattendees and concluded that this ‘‘...possibly suggest[s] an overall mortality benefit from screening’’ [1]. Further, the authors concluded that more research is needed to determine whether the differences they found in the stage distribution leads to ‘‘...a clinically significant mortality benefit’’ [1]. However, their study design (a comparison of attendees with non-attendees) cannot clarify whether the screening programme leads to more favourable prognostic features or reduced mortality because of two major sources of bias: First, self-selection bias (also called the healthy screenee effect) means that those who attend are different from those who do not attend, and that their characteristics and outcomes therefore cannot usefully be compared directly, as they were in the present paper [1]. This bias is due to the fact that attendees are predominantly resourceful and health-aware, which will skew results for both prognostic criteria and cause specific mortality in favour of screening. Second, overdiagnosis of carcinoma in situ and small invasive cancers will also skew results for both diagnostic criteria and survival rates in favour of screening. These overdiagnosed lesions are predominantly early stage and, per definition, have an excellent prognosis and would not lead to death. These biases are both of unknown size and differ between populations and over time. Therefore, they cannot be compensated for, which also prohibit the use of case– control studies to assess the effects of breast screening [2, 3]. The paper also contain a third study group, which the authors labelled ‘‘before invitation’’ [1]. This group includes only women in areas that invited to screening, but who were not yet invited themselves (Hofvind, personal communication). This is a small subset of all Norwegian women not yet invited to screening. The agedistribution of this selected study group prohibits meaningful comparisons with the invited women, as those not yet invited were about 3 years younger on average at the time of diagnosis [1]. K. J. Jorgensen (&) The Nordic Cochrane Centre, Rigshospitalet, Department 7811, Blegdamsvej 9, 2100 Copenhagen, Denmark e-mail: kj@cochrane.dk

Mammography screening and postmenopausal hormone therapy (HT) both influence breast cancer incidence. While breast cancer incidence increased by around 50% during the introduction of screening, a smaller decline in incidence has been reported in several countries after 2002 when the sales of HT started to decline. Data suggest that HT increases the risk of the second most common type of breast cancer, invasive lobular carcinoma (ILC) but not the most common, invasive ductal carcinoma (IDC). Breast cancer incidences stratified on histological subtypes were obtained from the national cancer registries. HT sales data from drug consumption statistics and information on the county-level introduction of mammography screening were combined, and breast cancer incidence trends were estimated using Poisson regression models, focusing on the period after 2002. From 2002 to 2007 the annual decrease in breast cancer incidence rates for women aged 50–69 was 1.5% (95% CI −2.3% to −0.7%) in Sweden and 0.8% (95% CI −2.8% to 1.2%) in the part of Norway not confounded by prevalence screening. Most of the decline was in the rates of ILC which dropped by 4.7% (95% CI −6.6% to −2.7%) and 7.0% (95% CI −12.8% to −0.9%) per year, respectively. The rates of IDC were stable in this period. Breast cancer incidence has declined in Sweden and Norway since 2002, but the reduction is moderate compared with the large increase that occurred during the introduction of mammography screening. Declining rates of ILC, but not of IDC, support the hypothesis that the drop in breast cancer incidence is associated with reduced HT use.

BACKGROUND In 2004 we wrote in Tidsskriftet that mammography screening resulted in massive over-diagnosis and over-treatment of breast cancer. Our study was criticised because we had only five years of follow-up time and did not take account of the fact that increased use of hormone replacement therapy could lead to more breast cancer. We have now been screening women for 14 years, and during a period when the use of hormones has fallen by 70 %. MATERIAL AND METHOD Age-specific incidence rates, detection rates and interval rates for breast cancer in the period 1991-2009 have been computed for 40-79 year-old women. Incidence trends have been calculated using Poisson regression. RESULTS The incidence of breast cancer in the age group 40-49 was stable throughout the period, but rose by 50 % in the age group 50-69 years immediately after the start of screening. There was no significant reduction in the incidence of breast cancer in the age group 70-74. The number of new cases of breast cancer in the period increased from around 2000 to 2750. About 300 cases of ductal carcinoma in situ (DCIS) were also diagnosed. Today a total of some 1050 more women have been diagnosed than before screening started. Our calculations indicate that in the absence of screening, around 800 of these women would never have become breast cancer patients. INTERPRETATION The figures from 14 years of mammography screening indicate that all increase in the incidence of breast cancer is due to over-diagnosis: findings of tumours that in the absence of screening would never have given rise to clinical illness.

We analysed the relation between tumour sizes and stages and the reported effects on breast cancer mortality with and without screening in trials and observational studies. The average tumour sizes in all the trials suggest only a 12% reduction in breast cancer mortality, which agrees with the 10% reported in the most reliable trials. Recent studies of tumour sizes and tumour stages show that screening has not lowered the rate of advanced cancers. In agreement with this, recent observational studies of breast cancer mortality have failed to find an effect of screening. In contrast, screening leads to serious harms in healthy women through overdiagnosis with subsequent overtreatment and false-positive mammograms. We suggest that the rationale for breast screening be urgently reassessed by policy-makers. The observed decline in breast cancer mortality in many countries seems to be caused by improved adjuvant therapy and breast cancer awareness, not screening. We also believe it is more important to reduce the incidence of cancer than to detect it 'early.' Avoiding getting screening mammograms reduces the risk of becoming a breast cancer patient by one-third.

During the past decades, extensive reformatory changes in institutional psychiatric care have been implemented in Norway. The objective of the present study was to investigate whether these changes have resulted in shortened length of psychiatric hospital stays for suicide attempters. Further, to examine if length of hospital stay and time period in which the patients received treatment were related to the risk of a repeated suicide attempt and/or committing suicide. All cases of suicide attempters hospitalised between 1984 and 2006 in the municipality of Baerum, a suburb outside Oslo, were examined. The period of observation was further subdivided in two time intervals on the basis of the de-institutionalisation of psychiatric care, which started to plateau in 1996. Among 1,574 patients consecutively admitted to the local general hospital after a suicide attempt, 330 were admitted to inpatient psychiatric care. Patients admitted in the period 1996–2006 had significantly shorter hospital stays than patients in the preceding period 1984–1995 (Log Rank P

Objective Valid mortality statistics are important for healthcare planning and research. Suicides and accidents often present a challenge in the classification of the manner of death. The aim of this study was to analyse the reliability of the national suicide statistics by comparing the classification of suicide in the Scandinavian cause of death registers with a reclassification by 8 persons with different medical expertise (psychiatry, forensic pathology and public health) from each of the 3 Scandinavian countries. Methods The cause of death registers in Norway, Sweden and Denmark retrieved available information on a sample of 600 deaths in 2008 from each country. 200 were classified in the registers as suicides, 200 as accidents or undetermined and 200 as natural deaths. The reclassification comprised an assessment of the manner and cause of death as well as the level of certainty. Results In total, 81%, 88% and 90% of deaths registered as suicide in the official mortality statistics were confirmed by experts using the Swedish, Norwegian and Danish data sets, respectively. About 3% of deaths classified as accidents or natural deaths in the cause of death registers were reclassified as suicides. However, after a second reclassification based on additional information, 9% of the natural deaths and accidents were reclassified as suicides in the Norwegian data set, and 21% of the undetermined deaths were reclassified as suicides in the Swedish data set. In total, the levels of certainty of the experts were 87% of suicides in the Norwegian data set, 77% in the Swedish data set and 92% in Danish data set; the uncertainty was highest in poisoning suicides. Conclusions A high percentage of reported suicides were confirmed as being suicides. Few accidents and natural deaths were reclassified as suicides. Hence, reclassification did not increase the overall official suicide statistics of the 3 Scandinavian countries.

Background During the period 1985-2000 the breast cancer incidence rates increased 50% in the age group invited to mammography screening in Norway and Sweden. Simultaneously, use of hormone replacement treatment therapy (HT) increased 5 times. Several influential observational studies showed that HT was associated with 50% to 100% increased risk of breast cancer and most for those using combined (estrogen plus progestin) hormone replacement therapy (CHT). In contrast, the randomized WHI trial reported that CHT increased the risk by 10% for those not having previously used hormones and 24% when including previous users in the analyses. In another randomized trial, estrogen use only was not associated with any increased risk at all. After the WHI trial was published in 2003, use of HT dropped 70% within 5 years in Norway and Sweden while breast cancer rates were essentially unchanged. After 2008, HT use has dropped further and breast cancer incidence rates have started increasing again. The study objective is to calculate and to explain potential bias in the observational study design. Methods and Findings Here we use data from the randomized WHI trial and analyze these data as done in the observational studies to calculate the magnitude of the potential biases in the observational study design. Time varying effect of hormones and categorization of the follow-up time may increase the hazard ratio for long-term users from 1.10 to 1.48. Selective retrospective reporting of hormone use may further increase the hazard ratio to 1.68. Conclusions We suggest that the mechanism causing higher hazard ratio of breast cancer (compared to the observational studies) is the time-varying effect of CHT on the breast cancer risk and selective retrospective reporting of hormone use. Other risk factors for the increase in breast cancer risk in the age group 50-69 years should be considered, for example, overdiagnosis.

Background: The aim of this paper was to measure socio-economic inequalities in mortality over a 27-year period, and estimate the simultaneous effects of education and income adjusted for changing proportions and potential confounders. Methods: Census data in 1970, 1980 and 1990 with information about income, educational level and household size were linked to mortality records at the individual level and analysed with absolute mortality rates, Poisson regression (univariate and multivariate) and Relative Index of Inequality (RII). Results: Mortality differences increased between income quartiles and educational groups as well as between singles and non-singles. RII between income quartiles increased from 1.6 to 3.6 for men and 1.7 to 2.7 for women while RII between the educational groups increased from 1.6 to 2.8 for men and 1.5 to 2.1 for women. However, RII derived from the adjusted multivariate regression analysis was 1.8 (men) and 1.9 (women) between the income groups in 1990 and 2.2 (men) and 1.7 (women) between the educational groups. In the 1990s current income was more important than previous income, and the rate ratios (RR) increased for groups dropping into the lowest income quartile between two censuses. Conclusion: Low education and single status have become relatively more important risk factors for mortality over time. Confounder effects of education and household size could partly explain the seemingly large increase in inequalities between income groups. Results may also indicate a stronger reverse causation (poor health causing low income) over time.

A positive relationship has been found between high levels of education and breast cancer mortality. The aim of our study is to determine if the educational gradient in breast cancer mortality persists after adjustment for reproductive history. Register data including the total adult population in Norway were used. A total of 512,353 Norwegian women 35-54 years of age at the Norwegian Census in 1990 were followed with respect to breast cancer deaths until December 31, 2001. The analysis included 2,052 breast cancer deaths in 5.6 million person years. Educational differences in breast cancer mortality were analysed using Cox regression. The age adjusted relative risk of dying from breast cancer for women with >12 years of education compared to women with

Objective To determine whether any increase in the incidence of breast cancer in women detected by mammography is compensated for by a drop in the incidence after age 69, years when women are no longer invited for screening. Design Population based cohort study of incidence of breast cancer during the introduction of nationwide screening programmes. Setting Norway and Sweden. Participants All women aged above 30 years (1.4 and 2.9 million, respectively, in 2000). Main outcome measures Changes in age specific incidence rates of invasive breast cancer associated with the introduction of the screening programmes. Results As a result of screenin creening is defined as the detection of low malignancy lesions that otherwise would not be detected in a patient9s lifetime. It is often argued that overdiagnosis is not a problem for screening in breast cancer.1 – 3 For example, Boer et al predicted a 31% increase in incidence of breast cancer in the Dutch mass screening programme that would be nearly fully compensated for by a strong drop in the incidence after age 69 years conclusion Without screening one third of all invasive breast cancers in the age group 50-69 years would not have been detected in the patients9 lifetime. This level of overdiagnosis is larger than previously reported

By analysing a theoretical cohort, Duffy and Parmar [1] find 0% overdiagnosis when screening for breast cancer in the UK. The fundamental assumption in their calculation is that the average lead time is 40 months, and this estimate relies on a method proposed by Walter and Day [2] for calculating lead time. Clinical lead time and statistical lead time are two fundamentally different concepts. Clinical lead time is the time diagnosis of a clinical relevant disease is moved by screening [3]. Statistical lead time is the time diagnosis is being moved by screening when all tumours grow and there are no competing causes of death [2]. It is a theoretical concept including both clinical cancers that are detected earlier and overdiagnosed tumours. Statistical lead time for breast cancer varies between 2 and 7 years (depending on the level of overdiagnosis), while the clinical lead time is about 1 year [3]. If you adjust the incidence increase when screening for statistical lead time, it will always give estimates of overdiagnosis close to zero because you subtract all clinical cancers that are diagnosed earlier as well as all overdiagnosed cancers from the incidence increase during screening [3]. In my opinion, the authors incorrectly assume that lead time is 40 months and postulate an 86% reduction in breast cancer rate between the first two screening rounds [1]. The literature on estimates of breast cancer rates between two screening rounds (so-called interval cancer rate), which reflects the clinical lead time, reports that the decline was 48% based on a small data set [4] and close to 0% in a large British data set [5]. Tables two and three in [1] do not represent real breast cancer data. It is a constructed data set that, by definition, yields 0% overdiagnosis. Ten years after screening they postulate a 7% reduction in incidence. However, after 20 years with overdiagnosis and overtreatment, a small reduction in breast cancer incidence is expected simply because many healthy women have lost their breast and are using anti-oestrogens, both of which reduce the numbers of women at risk of breast cancer. The reduction is not the effect of early diagnosis but of overtreatment or, at best, what could be called prophylactic treatment. Finally in Table four in [1], the authors argue that the level of overdiagnosis adjusted for statistical lead time varies with length of screening as well as the length of follow-up after last screening (because the denominator varies). This is actually an argument for not using this method. Overdiagnosis adjusted for clinical lead time is insensitive to these effects [3].

Cancer incidence rates for Swedish twins born between 1928 and 1965 and who both were alive at age 30 are studied by means of bivariate frailty models. Altogether, 7,280 fraternal (DZ) and 4,699 identical (MZ) twin pairs were followed up through December 31, 1995, for cancer status. The association between cancer incidence rates was statistically greater among the MZ than among the DZ pairs and stronger between women than between men; however, the magnitude of this association is relatively small and decreases over time. The relative decrease in dependency (association) is most easily detected using shared frailty models but may also be demonstrated, at least for women, using correlated frailty models. We also demonstrate that estimates of the correlation coefficient are similar when using any correlated frailty models derived from the power variance family but that these estimates disagree regarding the age at which the dependence is most important. The relative importance of dependence across age may sometimes be more interesting than the correlation coefficient itself. The latter may usually be estimated using alternative methods. Furthermore, when estimating correlation coefficients close to the boundary of the parameter space, simulation studies indicate that the correlated inverse Gaussian frailty model is more robust than the gamma frailty model.

Purpose To investigate the survival of patients with capsular or simple glaucoma compared with that of the common population, with particular attention to the impact of sex and use of acetazolamide (Diamox). Methods The 30 year survival of 1147 patients with capsular or simple glaucoma who were finally hospitalized at the Eye Department, Rikshospitalet, Oslo, from 1961 to 1970, are analysed, using log rank tests. The time varying impacts of sex and acetazolamide on survival are also studied using a regression model. Results There was a significant increased mortality for patients with acetazolamide, and for men also those not using it. The observed mortality for men was initially lower than the average Norwegian population, but later the mortality increased more rapidly in the glaucoma group. This may be explained by a selection of the healthiest patients to Rikshospitalet, and actually indicates that the excess mortality is even higher than calculated here. Conclusion The analysis of data indicated increased mortality for glaucoma patients when the disease had lasted for some time. This was especially pronounced for men using acetazolamide. A similar study from a period when acetazolamide was not in common use and an analysis of causes of death is also asked for.

Survival curves may be adjusted for covariates using Aalen's additive risk model. Survival curves may be compared by taking the ratio of two adjusted survival curves; the ratio is denoted the generalized relative survival rate. Adjusting both survival curves for all but one of a common set of covariates gives the partial relative survival rate, which measures the covariate-specific contribution to the generalized relative survival rate. The generalized and partial relative survival rates have interpretations similar to the traditional relative survival rates frequently used in cancer epidemiology. In fact, the traditional relative survival rate can be generalized to a regression context using the additive risk model. This population-adjusted relative survival rate is an alternative and useful method for removing confounding effects of age, cohorts, and sex. The authors use a data set of malignant melanoma patients diagnosed from 1965 to 1974 in Norway. The 25-year survival of 1967 individuals is studied.