Quality-of-life effects of screening mammography in Norway.

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.

Antibiotic resistance, hospitalizations, and mortality related to prostate biopsy: first report from the Norwegian Patient Registry.

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.

Benefits and harms of screening men for abdominal aortic aneurysm in Sweden: a registry-based cohort study.

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 Västra Götaland, Sweden.

Statistical analysis of early cancer diagnosis requires new methods. / Statistisk analyse av tidligdiagnostikk av kreft krever nye metoder.

The methods for diagnosing cancer have traditionally been based on the concept that everything grows. However, immunotherapy and screening trials show that some tumours resolve spontaneously.

Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis.

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.

Accidents and undetermined deaths: re-evaluation of nationwide samples from the Scandinavian countries.

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.

[Drug safety associated with the change of digitalis drug in Norway]. / Legemiddelsikkerhet ved bytte av digitalispreparat i Norge.

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.