Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland.

BACKGROUND: Screening for colorectal cancer (CRC) with guaiac-based faecal occult-blood test (FOBT) has been reported to reduce CRC mortality in randomised trials in the 1990s, but not in routine screening, so far. In Finland, a large randomised study on biennial FOB screening for CRC was gradually nested as part of the routine health services from 2004. We evaluate the effectiveness of screening as a public health policy in the largest population so far reported. METHODS: We randomly allocated (1:1) men and women aged 60-69 years to those invited for screening and those not invited (controls), between 2004 and 2012. This resulted in 180 210 subjects in the screening arm and 180 282 in the control arm. In 2012, the programme covered 43% of the target age population in Finland. RESULTS: The median follow-up time was 4.5 years (maximum 8.3 years), with a total of 1.6 million person-years. The CRC incidence rate ratio between the screening and control arm was 1.11 (95% CI 1.01 to 1.23). The mortality rate ratio from CRC between the screening and control arm was 1.04 (0.84 to 1.28), respectively. The CRC mortality risk ratio was 0.88 (0.66 to 1.16) and 1.33 (0.94 to 1.87) in males and females, respectively. CONCLUSIONS: We did not find any effect in a randomised health services study of FOBT screening on CRC mortality. The substantial effect difference between males and females is inconsistent with the evidence from randomised clinical trials and with the recommendations of several international organisations. Even if our findings are still inconclusive, they highlight the importance of randomised evaluation when new health policies are implemented. TRIAL REGISTRATION: 002_2010_august.

Economic evaluation of cancer registration in Europe.

BACKGROUND: Little has been reported on costs of cancer registration, and standard indicators have not yet been identified. This study investigated costs and outcomes of a sample of 18 European registries covering a population of 58.8 million inhabitants. METHODS: Through a questionnaire, we asked registries for real cost data including personnel, information technology (IT), and infrastructure. Staff costs were grouped by professional position and by activity performed. As outcomes, besides the production of current data, we considered publications in peer-reviewed journals (last 5 years' impact factor [IF]) and characteristics of registry websites. RESULTS: In our sample, the average cost of cancer registration per inhabitant was €0.27 at purchasing power standard (PPS) (range €0.03-€0.97), while the mean cost per case registered was €50.71 PPS (range €6-€213). Personnel costs accounted for an average of 79 percent of total resources. Resources spent in routine activities (an average of 51 percent, range 28 percent-87 percent) were predominant with respect to those allocated to research, with a few exceptions. Website quality seemed to be independent of total registry budget. CONCLUSIONS: The variance in costs of cancer registration across Europe can be attributed mainly to the type of registry (whether national or regional), the size of the covered population, and the national economic profile, expressed as gross domestic product.

Study populations for period analyses of cancer survival.

BACKGROUND: Period analysis is increasingly used to compute long-term cancer survival, as it provides better prediction of survival of newly diagnosed patients than traditional cohort analysis. However, the patient population to which period survival estimates best pertain to and which should be described in a study is less obvious. METHODS: Using Finnish Cancer Registry data on 23 common cancer sites, age-standardized period estimates of 5-, 10-, 15-, and 20-year relative survival were computed for each 2-, 5-, and 10-year calendar period in 1954-2003 and compared with survival estimates for two cohorts by means of mean, mean absolute and mean squared differences: a full cohort of all patients potentially contributing some data to the survival analysis and a restricted cohort of patients diagnosed in the period of interest. RESULTS: In most computations, survival estimates for the full cohorts were on average closer to the period estimates for the majority of cancer sites. For 10-year survival, results were less obvious with respect to the mean difference. However, mean squared and mean absolute differences were smaller for the majority of cancers when using the full cohort. CONCLUSION: Our results suggest that the full cohort should be described in reports of period survival analysis.

Testicular cancer in Europe and the USA: survival still rising among older patients.

BACKGROUND: Despite high curability, some testicular cancer (TC) patient groups may have increased mortality. We provide a detailed age- and histology-specific comparison of population-based relative survival of TC patients in Europe and the USA. Design Using data from 12 European cancer registries and the USA Surveillance, Epidemiology and End Results 9 database, we report survival trends for patients diagnosed with testicular seminomas and nonseminomas between 1993-1997 and 2003-2007. Additionally, a model-based analysis was used to compare survival trends and relative excess risk (RER) of death between Europe and the USA adjusting for differences in age and histology. RESULTS: In 2003-2007, the 5-year relative survival of patients with testicular seminoma was at least 98% among those aged <50 years, survival of patients with nonseminoma remained 3%-6% units lower. Despite improvements in the relative survival of nonseminoma patients aged ≥ 50 years by 13%-18% units, survival remained markedly lower than the survival of seminoma patients of the same age. Model-based analyses showed increased RERs for nonseminomas, older, and European patients. CONCLUSIONS: There remains little room for survival improvement among testicular seminoma patients, especially for those aged <50 years. Older TC patients remain at increased risk of death, which seems mainly attributable to the lower survival among the nonseminoma patients.

Population-based survival of penile cancer patients in Europe and the United States of America: no improvement since 1990.

INTRODUCTION: Penile cancer is a rare neoplasm in Western countries, and detailed studies on trends in population-based survival of penile cancer have never been published before. We examined population-based trends in survival in Europe and the United States of America (USA). METHODS: Data from 3297 European and 1820 American penile cancer patients, contributed by 12 European cancer registries and the Surveillance, Epidemiology, and End Results (SEER) Program of the USA were included in this study. Period analysis techniques were used to examine relative survival trends overall, as well as for four geographic regions in Europe, and for the age groups 15-54, 55-64, 65-74 and 75+ for both populations between 1990-1995 and 2002-2007. Survival trends were assessed in a multiple regression model of relative excess risk including period of diagnosis, age and continent. RESULTS: The 5-year relative survival of penile cancer patients increased statistically non-significantly from 65% to 70% in Europe and decreased (significantly) from 72% to 63% in the USA. Trends in age-specific 5-year relative survival did not find any significant improvement in either Europe or the USA. The multiple regression analysis confirmed the lack of survival trend, and found significantly higher relative excess risk with age, and, apparently due to lower survival before 2002-2007, higher risk in Europe. CONCLUSION: Survival for penile cancer patients has not improved in either Europe or the USA since at least 1990. The reasons for the decrease of survival in the USA remain unknown and to be explored. Stronger international cooperation in clinical research may be important to facilitate clinical progress in treatment and thereby improvement of survival of this rare malignancy.

Avoidable deaths and random variation in patients' survival.

BACKGROUND: Random error in the numbers of avoidable deaths among cancer patients has not been considered in earlier studies. METHODS: Methods to obtain valid confidence intervals (CIs) for numbers of avoidable deaths were developed. The excess mortality rates were estimated for patients diagnosed with colon cancer in five cancer control regions in Finland during 2000-2007 using a relative survival regression model. Numbers of avoidable deaths due to colon cancer and other causes, respectively, were estimated in different scenarios. RESULTS: Altogether, 4139 and 1335 out of 10 772 patients under 90 years at diagnosis were estimated to have died due to colon cancer and other causes, respectively, during the first 5 years after diagnosis. If all the patients had shared the relative survival of the largest cancer control region to which the country capital belongs, the estimated number of avoidable deaths would have been 146 (95% CI 3-290). CONCLUSION: Random error in numbers of avoidable deaths, often substantial, can be quantified by realistic error margins, based on appropriate statistical methods.

Standard errors of non-standardised and age-standardised relative survival of cancer patients.

BACKGROUND: Relative survival estimates cancer survival in the absence of other causes of death. Previous work has shown that standard errors of non-standardised relative survival may be substantially overestimated by the conventionally used method. However, evidence was restricted to non-standardised relative survival estimates using Hakulinen's method. Here, we provide a more comprehensive evaluation of the accuracy of standard errors including age-standardised survival and estimation by the Ederer II method. METHODS: Five- and ten-year non-standardised and age-standardised relative survival was estimated for patients diagnosed with 25 common forms of cancer in Finland in 1989-1993, using data from the nationwide Finnish Cancer Registry. Standard errors of mutually comparable non-standardised and age-standardised relative survival were computed by the conventionally used method and compared with bootstrap standard errors. RESULTS: When using Hakulinen's method, standard errors of non-standardised relative survival were overestimated by up to 28%. In contrast, standard errors of age-standardised relative survival were accurately estimated. When using the Ederer II method, deviations of the standard errors of non-standardised and age-standardised relative survival were generally small to negligible. CONCLUSION: In most cases, overestimations of standard errors are effectively overcome by age standardisation and by using Ederer II rather than Hakulinen's method.

Pregnancy incidence and outcome among patients with cervical intraepithelial neoplasia: a retrospective cohort study.

OBJECTIVE: To investigate the effect of cervical intraepithelial neoplasia (CIN) treatment on incidence of pregnancy and pregnancy outcome. DESIGN: Retrospective cohort study. SETTING: Helsinki University Central Hospital, Finland, the sole reference centre in the Helsinki-Uusimaa region for women referred for colposcopy. POPULATION: A cohort of 6179 women treated for CIN between 1974 and 2001, and a randomly selected, age- and municipality-matched, reference population of 30,436 women. METHODS: Based on nationwide registers, all women were followed-up for pregnancy outcomes until death, emigration, sterilization, or until the end of 2004. MAIN OUTCOME MEASURES: Incidence of any pregnancy, livebirths, miscarriages, extrauterine pregnancies, molar pregnancies, and terminations of pregnancies (TOPs) before and after CIN treatment, estimated by calculating hazard ratios (HRs) with stratified Cox regression and Poisson regression. RESULTS: After CIN treatment, both incidence of pregnancy (HR 1.20; 95% CI 1.15-1.26; P < 0.001) and incidence of livebirths (HR 1.12; 95% CI 1.06-1.18; P < 0.001) were higher among the treated women than among the reference population. Before treatment, only incidence of pregnancy had been elevated among those treated (HR 1.06; 95% CI 1.04-1.09; P < 0.001). The incidence of extrauterine pregnancies and of TOPs was significantly elevated among those treated both before and after CIN treatment. CONCLUSIONS: No clear evidence emerged of adverse effects resulting from the CIN treatment itself, because the women treated had more pregnancies and more children than their reference population. TOPs and extrauterine pregnancies were more common among the treated women already before the CIN treatment.

Maternal food consumption during pregnancy and risk of advanced ß-cell autoimmunity in the offspring.

BACKGROUND: Evidence for a putative role of maternal diet during pregnancy in the development of ß-cell autoimmunity in the child is scarce. The authors study the association of food consumption during pregnancy and the development of ß-cell autoimmunity in the offspring. SUBJECTS AND METHODS: A prospective Finnish birth cohort of 4297 infants with human leukocyte antigen (HLA)-DQB1-conferred susceptibility to type 1 diabetes and their mothers. Blood samples were collected from the children at 3-12 months intervals to measure type 1 diabetes-associated antibodies: antibodies against islet cells (ICA), insulin, glutamate dehydroxylase, and islet antigen 2. The mothers completed a validated food frequency questionnaire. The end-point was repeated positivity for ICA together with at least one of the other three antibodies. Piecewise-exponential survival models were used. The effective sample size was 3723, with 138 end-points. The median follow-up time was 4.4 years. RESULTS: Maternal consumption of butter, low-fat margarines, berries, and coffee were inversely associated with the development of advanced ß-cell autoimmunity in the offspring, adjusted for genetic risk group and familial diabetes. These associations for low-fat margarines (use vs. non-use HR 0.60, 95% CI: 0.38-0.93, p = 0.02), berries (continuous variable HR 0.90, 95% CI: 0.83-0.98, p = 0.02) and coffee (highest quarter vs. lowest HR 0.62, 95% CI: 0.40-0.97, p = 0.04), remained significant when adjusting for potential confounding sociodemographic, perinatal, and other dietary factors. CONCLUSIONS: In this study assessing total food consumption of the mother during pregnancy, only few among the 27 food groups tested were weakly related to the development of advanced ß-cell autoimmunity in Finnish children.

The effect of hospital volume on the outcome of breast cancer surgery.

BACKGROUND: This study was conducted to investigate whether annual surgical unit caseload affects extent of breast cancer surgery, breast cancer recurrence or breast cancer-specific survival. METHODS: In a population-based cohort study, 12,604 women diagnosed with breast cancer in Finland during the years 1998-2001 were followed up until the end of year 2008. Surgical units were divided into subgroups: >200, 100-200, 50-99 or <50 breast cancer operations per year. Information on patients, treatment, and follow-up was obtained from two national registries. The analyses were adjusted for age and disease stage. The reliability of the registry information was validated by comparison with information from one hospital area. Cox proportional hazard and logistic regression models were employed in the analyses. RESULTS: Validation of the registry data showed that date of diagnosis, age, stage, extent of surgery, and date and cause of death were reliably recorded in the registers. Information on radiotherapy was obtained by combining different registry data. Data on local and distant recurrences were not reliable enough to allow analyses. Patients in hospitals with smaller caseloads underwent mastectomy more often than those operated in hospitals with higher caseloads (P < 0.001). Higher caseloads were also related to improved survival (P = 0.031). CONCLUSIONS: National registries should include information on both local and distant recurrences in order to provide reliable population-based data for evaluation of treatment results. Centralization of surgery to high-volume centers is supported by a higher incidence of conservative surgery and better survival.

Education, survival and avoidable deaths in cancer patients in Finland.

BACKGROUND: Relative survival after cancer in Finland is at the highest level observed in Europe and has, in general, been on a steady increase. The aim of this study is to assess whether the high survival is equally shared by different population subgroups and to estimate the possible gains that might be achieved if equity prevailed. MATERIALS AND METHOD: The educational level and occupation before the cancer diagnosis of patients diagnosed in Finland in 1971-2005 was derived from an antecedent population census. The cancers were divided into 27 site categories. Cancer (cause)-specific 5-year survival proportions were calculated for three patient categories based on the educational level and for an occupational group of potentially health-conscious patients (physicians, nurses, teachers etc.). Proportions of avoidable deaths were derived by assuming that the patients from the two lower education categories would have the same mortality owing to cancer, as those from the highest educational category. Estimates were also made by additionally assuming that even the mortalities owing to other causes of death were all equal to those in the highest category. RESULTS: For almost all the sites considered, survival was consistently highest for patients with the highest education and lowest for those with only basic education. The potentially health-conscious patients had an even higher survival. The differences were, in part, attributable to less favourable distributions of tumour stages in the lower education categories. In 1996-2005, 4-7% of the deaths in Finnish cancer patients could have potentially been avoided during the first 5-year period after diagnosis, if all the patients had the same cancer mortality as the patients with the highest educational background. The proportion would have also been much higher, 8-11%, if, in addition, the mortality from other causes had been the same as that in the highest educational category. INTERPRETATION: Even in a potentially equitable society with high health care standards, marked inequalities persist in cancer survival. Earlier cancer diagnosis and the ability to cope within the health care system may be a partly relevant explanation, but personal habits and lifestyles also have a role, particularly for the cancer patients' mortality from other causes of death than cancer.

Early detection of colorectal cancer with faecal occult blood test screening.

BACKGROUND: Faecal occult blood test (FOBT) screening has been shown to decrease the incidence and mortality from colorectal cancer. This study compared the stage profile of patients with colorectal cancer diagnosed at the first FOBT screening round with that of an unscreened control group. METHODS: Subjects aged 60-64 years were allocated randomly to biennial FOBT screening (52 998 subjects) or a control group (53 002) in a Finnish prospective public health policy in 2004-2006. FOBT was performed with a guaiac test. At the end of 2007 the screened and control populations were linked to the Finnish Cancer Registry database, and the colonoscopic findings in the screen positives were analysed. RESULTS: Early-stage colorectal cancer was observed in 52 per cent of the FOBT-positive subjects, in 42.2 per cent of the total screened population and in 38 per cent of the control population (P = 0.191 for FOBT positives, P = 0.592 for total screened population). The prevalence of adenomas and colorectal cancer was 31.5 and 8.2 per cent respectively among the 806 subjects with a positive FOBT. Some 27.3 per cent of all colorectal tumours in the screened population were interval cancers. The tumour was located in the right colon in 28.9 per cent of the screened subjects and 22 per cent of controls (P = 0.255). CONCLUSION: Biennial FOBT screening improves detection of colorectal cancer at the first screening round, but the high percentage of interval cancers is a cause for concern.

Coffee consumption and risk of colorectal cancer.

BACKGROUND/OBJECTIVES: The possible association between coffee consumption and risk of colorectal cancer has been extensively studied in the many populations. The aim of this study is to examine this relationship among Finns, who are the heaviest coffee consumers in the world. SUBJECTS/METHODS: A total of 60 041 Finnish men and women who were 26-74 years of age and without history of any cancer at baseline were included in the present analyses. Their coffee consumption and other study characteristics were determined at baseline, and they were prospectively followed up for onset of colon and rectal cancer, emigration, death or until 30 June 2006. RESULTS: During a mean follow-up period of 18 years, 538 cases of colorectal cancer (304 cases of colon cancer and 234 cases of rectal cancer) were diagnosed. The multivariate-adjusted hazard ratio of colorectal cancer incidence for > or =10 cups of coffee per day compared with non-drinkers was 0.98 (95% CI, 0.47-2.03) for men (P for trend=0.86), 1.24 (95% CI, 0.49-3.14) for women (p for trend=0.83) and 1.03 (95% CI, 0.58-1.83) for men and women combined (P for trend=0.61). CONCLUSIONS: In this study, we found no association between coffee consumption and the risk of colorectal, colon and rectal cancer.

What if cancer survival in Britain were the same as in Europe: how many deaths are avoidable?

OBJECTIVE: To estimate the number of deaths among cancer patients diagnosed in Great Britain that would be avoidable within 5 years of diagnosis if the mean (or highest) survival in Europe for patients diagnosed during 1985-1989, 1990-1994 and 1995-1999 were achieved. DESIGN: Five-year relative survival for cancers in Great Britain compared with that from other countries in the EUROCARE-2, -3 and -4 studies. Calculation of excess deaths (those more than expected from mortality in the general population) that would be avoidable among cancer patients in Britain if relative survival were the same as in Europe. SETTING: Great Britain (England, Wales, Scotland) and 13 other European countries. SUBJECTS: 2.8 million adults diagnosed in Britain with 1 of 39 cancers during 1985-1989 (followed up to 1994), 1990-1994 (followed up to 1999) and 1995-1999 (followed up to 2003). MAIN OUTCOME MEASURE: Annual number of avoidable deaths within 5 years of diagnosis. Percentage of the excess (cancer-related) deaths among cancer patients that would be avoidable. RESULTS: Compared with the mean European 5-year relative survival, the largest numbers of avoidable deaths for patients diagnosed during 1985-1989 were for cancers of the breast (about 18% of the excess mortality from this cancer, 7541 deaths), prostate (14%, 4285), colon (9%, 4090), stomach (8%, 3483) and lung (2%, 3548). For 1990-1994, the largest numbers of avoidable deaths were for cancers of the prostate (20%, 7335), breast (15%, 6165), colon (9%, 4376), stomach (9%, 3672), lung (2%, 3735) and kidney (22%, 2644). For 1995-1999, most of the avoidable deaths were for cancers of the prostate (17%, 5758), breast (15%, 5475), lung (3%, 4923), colon (10%, 4295), stomach (9%, 3137) and kidney (21%, 2686).Overall, some 6600-7500 premature deaths would have been avoided each year among cancer patients diagnosed in Britain during 1985-1999 if the mean survival in Europe had been achieved. This represents 6-7% of cancer-related mortality. Compared with the highest European survival, avoidable premature mortality among cancer patients fell from about 12 800 deaths a year (12.2% of cancer-related mortality) to about 11 400 deaths a year (10.6%) over the same period.A large component of the avoidable mortality is due to prostate cancer: excluding this cancer from comparison with the European mean survival reduces the annual number of avoidable deaths by 1000-1500, and the percentage of excess mortality by up to 1%. Compared with the highest survival, the annual number of avoidable deaths would be 1500-2000 fewer, and 1-2% lower as a percentage of excess mortality, but the overall trend in avoidable premature mortality among cancer patients would be similar, falling from 11.4% (1985-1989) to 10.3% (1990-1994) and 9.7% for those diagnosed during 1995-1999.For several cancers, survival in Britain was slightly higher than the mean survival in Europe; this represented some 110-180 premature deaths avoided each year during the period 1985-2003. CONCLUSIONS: Avoidable premature mortality among cancer patients diagnosed in Britain during 1985-1999 has represented 6-7% of cancer-related mortality compared with the mean survival in Europe. Compared with the highest levels of survival in Europe, the reduction from 12.2% to 10.6% of cancer-related mortality reflects small but steady progress over the period 1985-2003.

Trends in cancer survival in 11 European populations from 1990 to 2009: a model-based analysis.

BACKGROUND: The timely provision and interpretation of trends in population-based cancer survival estimates is an important clinical and public health priority. MATERIALS AND METHODS: We examined survival trends between 1990-1994 and 2000-2004 for 15 common cancers in 10 countries from diverse areas of Europe and provide projected survival estimates for 2005-2009, using novel techniques of model-based period analysis. RESULTS: Between 1990-1994 and 2000-2004, the 5-year relative survival increased significantly in all participating registries among patients with prostate, breast, and colorectal cancers and in at least 7 of 11 registries for stomach, corpus uteri, ovarian, kidney, and thyroid cancers, as well as for non-Hodgkin's lymphoma. Projections suggest further substantial increases in survival in the calendar period 2005-2009. For most cancer sites amenable to effective early detection and treatment, major geographical differences persist with lower survival in Eastern European countries. CONCLUSIONS: Model-based period analysis may be useful in providing population-based cancer survival estimates for currently diagnosed cancer patients. Concerted efforts in the organisation and quality control of cancer care will be very important to achieving further improvements in cancer control in Europe, and improving outcomes in Eastern European populations remains a priority.

Recent trends in cancer survival across Europe between 2000 and 2004: a model-based period analysis from 12 cancer registries.

BACKGROUND: Monitoring population-based cancer survival is an essential component in the evaluation of cancer control, but subject to an inherent delay in the reporting of the most recent survival estimates with traditional techniques of analysis. METHODS: We examined survival trends between the years 2000 and 2004 for 20 common cancers based on follow-up data from 12 cancer registries from diverse areas of Europe using model-based period analysis techniques. RESULTS: Between 2000 and 2004, marked rises were seen in 5-year relative survival amongst patients with prostate, breast and colorectal cancer, which were statistically significant in 10, 8 and 7 of the 12 participating cancer registries, respectively. For cancer sites amenable to effective early detection and treatment, major geographical differences in patient prognosis still persisted, with a lower survival generally observed in Eastern European countries. CONCLUSION: Model-based period analysis enables the timely monitoring of recent trends in population-based cancer survival. For colorectal and breast cancers, the identified rises in survival are probably (at least partly) explained by the improvements in clinical care and the management of the disease. Nevertheless, persisting geographic differences do point to the potential for a further reduction in the burden of cancer throughout Europe, towards which improvements in diverse areas of care, including secondary prevention, access to advances in treatment as well as subspecialisation and regionalisation of oncologic care may all contribute.

Age at introduction of new foods and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes.

AIMS/HYPOTHESIS: Evidence for the role of infant feeding in the development of beta cell autoimmunity is inconsistent. We set out to study the effects of breastfeeding and of age at introduction of supplementary foods on the development of beta cell autoimmunity. SUBJECTS AND METHODS: A prospective birth cohort of 3,565 infants with HLA-DQB1-conferred susceptibility to type 1 diabetes was recruited between 1996 and 2001 from two university hospital areas in Finland. Blood samples were collected at 3- to 12-month intervals to measure antibodies against islet cells, insulin, glutamate dehydroxylase and islet antigen 2. The families kept a record on the age at introduction of new foods, and for each visit completed a structured dietary questionnaire. The endpoint was repeated positivity for islet cell antibodies together with at least one of the other three antibodies. RESULTS: The overall or exclusive duration of breastfeeding was not associated with the risk of developing the endpoint. An early age at introduction of fruits and berries (< or =4 months) was related to increased risk of developing positivity for the endpoint (hazard ratio [95% CI] for earliest tertile 2.02 [1.03-3.95] and for midtertile 1.97 [1.06-3.64] compared with latest tertile >4 months). Also, introducing roots between 3 and 3.9 months (midtertile) was related to increased risk of the endpoint (hazard ratio [95% CI] for the earliest tertile 1.04 [0.57-1.90] and for midtertile 1.82 [1.19-2.79] compared with latest tertile). These associations were independent of several putative socio-demographic and perinatal confounding factors. CONCLUSIONS/INTERPRETATION: Our findings suggest that an early age at introduction of fruits and berries and roots associates independently with beta cell autoimmunity, contradicting earlier findings from smaller birth cohort studies.

Age adjustment of cancer survival rates: methods, point estimates and standard errors.

We empirically evaluated the performance of a new method for age adjustment of cancer survival compared to traditional age adjustment using data from the Finnish Cancer Registry. We find that both methods provide almost identical results for absolute survival but the new method generally provides more meaningful estimates of relative survival with often a smaller standard error.

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study.

AIMS/HYPOTHESIS: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. METHODS: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. RESULTS: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). CONCLUSIONS/INTERPRETATION: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

The influence of mammographic screening on national trends in breast cancer incidence.

Introducing an organized mammographic screening programme affects the breast cancer incidence rate in a population. The diagnosis is advanced in time, and initially, an increase will occur in the number of cases, followed by a drop in the rate when women leave the programme. The aim of this study was to quantify the potential effects that mammographic screening programmes have on breast cancer incidence. In addition, we wanted to investigate how the incidence of breast cancer varies between different birth cohorts, age groups and time periods in the five Nordic countries Finland, Denmark, Iceland, Norway and Sweden, adjusting for the effects of the screening programmes. Time trends were analysed over the period 1978-1997, using age-period-cohort models. In Sweden, the rates more than doubled (relative risk (RR)=2.20, 95% confidence interval (CI) 1.8-2.6) in women offered screening for the first time compared with women not offered screening. The risk remained elevated (RR=1.34, 95% CI 1.2-1.6) for women who were continued to be offered screening, compared with women who were not offered screening. Finally, the rates dropped (RR=0.68, 95% CI 0.6-0.8) when the women left the programme. This indicates that screening advances the time of diagnosis, which is a prerequisite to subsequent reduction in mortality. Analysis of secular trends, corrected for the influence of screening, showed that the rates in Finland increased by 13% per 5-year period, with a more modest increase in the other countries. There were strong cohort effects in all Nordic countries, and the risk seemed to be flattening for the youngest cohorts in most of the countries.