Socio-economic inequality of utilization of cancer testing in Europe: A cross-sectional study.

There are currently screening programmes for breast, cervical and colorectal cancer in many European countries. However, the uptake of cancer screening in general may vary within and between countries. The aim of this study is to assess the inequalities in testing utilization by socio-economic status and whether the amount of inequality varies across European regions. We conducted an analysis based on cross-sectional data from the second wave of the European Health Interview Survey from 2013 to 2015. We analysed the use of breast, cervical, and colorectal cancer testing by socio-economic position (household income, educational level and employment status), socio-demographic factors, self-perceived health and smoking behaviour, by using multinomial logistic models, and inequality measurement based on the Slope index of inequality (SII) and Relative index of inequality (RII). The results show that the utilization of mammography (Odds Ratio (OR) = 0.55, 95% confidence interval (95%CI):0.50-0.61), cervical smear tests (OR = 0.60, 95%CI:0.56-0.65) and colorectal testing (OR = 0.82, 95%CI:0.78-0.86) was overall less likely among individuals within a low household income compared to a high household income. Also, individuals with a non-EU country of birth, low educational level and being unemployed (or retired) were overall less likely to be tested. The income-based inequality in breast (SII = 0.191;RII = 1.260) and colorectal testing utilization (SII = 0.161;RII = 1.487) was the greatest in Southern Europe. For cervical smears, this inequality was greatest in Eastern Europe (SII = 0.122;RII = 1.195). We concluded that there is considerable inequality in the use of cancer tests in Europe, with inequalities associated with household income, educational level, employment status, and country of birth.

Prostate and breast cancer in four Nordic countries: A comparison of incidence and mortality trends across countries and age groups 1975-2013.

In recent decades, management of prostate and breast cancer patients has changed considerably. The purpose of our study is to interpret patterns of prostate and breast cancer incidence and mortality in four Nordic countries across age groups and time periods. Prostate and breast cancer incidence and mortality data (1975-2013) were obtained from the NORDCAN database. Joinpoint regression models were used to identify changes in the trends. A more prominent increase in prostate than breast cancer incidence was observed. From the mid-1990s, mortality rates in patients below 75 years of age have decreased for both cancers in all four countries. The relative decline in breast cancer mortality from 1985-1989 to 2009-2013 were largest in women under 50 years of age, with reductions in mortality rates ranging from 38% in Finland to 55% in Denmark. In the age group 55-74 years, mortality rates for prostate cancer declined more than for breast cancer in all countries except Denmark, ranging from 14% in Denmark to 39% in Norway. The substantial decrease in breast cancer mortality in women below regular screening age and the reductions in mortality from both cancers in Denmark from the mid-1990s are consistent with beneficial contributions from improved treatment besides mammography screening and increased PSA testing. Alongside similar mortality decreases, the larger increases in prostate cancer incidence as compared to breast cancer indicate that a higher proportion of prostate cancer cases are overdiagnosed.

Determinants of non-participation in a mass screening program for colorectal cancer in Finland.

BACKGROUND: For an effective colorectal cancer (CRC) screening program, high participation rate is essential. However, non-participation in CRC screening program has increased in Finland. MATERIAL AND METHODS: The study was based on a population-based nationwide cohort of persons invited for CRC screening in 2004-2011. Information on the first round of the CRC screening participation and related background factors was obtained from the Finnish Cancer Registry, and information about health behavior factors from the Health Behavior Survey (HBS) in 1978-1999. Non-participation in CRC screening was analyzed with Poisson regression as incidence rate ratios (IRR) with 95% confidence intervals (95% CI). RESULTS: Of all persons invited for CRC screening (79 871 men and 80 891 women) 35% of men and 21% of women refused. Of those invited for screening, 2456 men (3.1%) and 2507 women (3.1%) were also invited to the HBS. Persons, who declined HBS, were also more likely to refuse CRC screening (men IRR 1.40, 95% CI 1.26-1.56, women 1.75, 1.52-2.02) compared to HBS participants. Never married persons had about a 75% higher risk for refusing than married ones. The youngest age group (60 years) was more likely to refuse screening than the older age groups (62 or >64 years). Smoking was associated with non-participation in screening (current smokers, men: IRR 1.32, 95% CI 1.05-1.67, women: 2.10, 1.61-2.73). CONCLUSIONS: Participation in CRC screening was affected by gender, age, and marital status. Persons, who refused the HBS, were also more likely to refuse CRC screening. Smoking was a risk factor for non-participation in CRC screening.

Mammography screening in three Finnish residential areas: comprehensive population-based study of breast cancer incidence and incidence-based mortality 1976-2009.

BACKGROUND: The aim of this study was to evaluate the effectiveness of a large-scale screening programme for breast cancer (BC) in Turku, Finland. Incidence and incidence-based mortality (IBM) figures were compared with the areas applying different screening policies. METHODS: Deaths and person-time of women aged 40-84 were assessed for the period 1976-1986 (prescreening era) and the periods 1987-1997 and 1998-2009 (screening periods) using incidence and IBM by age at diagnosis and at death. There was a total of 40.7 million women-years, 83 497 invasive BCs obtained from the Finnish Cancer Registry; 17 508 BC deaths were linked with the data from Statistics Finland. RESULTS: In Turku, a significant (> 20%) reduction in IBM occurred during 1987-2009 among women aged 60-74 years at diagnosis compared with Helsinki (IBMRR: 0.75, 95% CI: 0.57-1.00), and in women aged 75-84 years at death compared with the rest of Finland (IBMRR: 0.72, 95% CI: 0.53-0.96). CONCLUSIONS: The wide mammography screening programme in Turku was effective in decreasing BC mortality in the elderly age groups. These results support the implementation of BC screening from age 50 up to 74 years.

Overdiagnosis due to breast cancer screening: updated estimates of the Helsinki service study in Finland.

BACKGROUND: Overdiagnosis is the most important adverse event of breast cancer screening with the estimates ranging from 0% to 40-50% depending on invitational age and methods. We updated the estimates of overdiagnosis in Helsinki service screening study in Finland by comparing the observed and expected cumulative incidence of all breast carcinomas and invasive breast carcinomas. METHODS: Women aged 50-59 years have been invited to Helsinki service screening since 1986. The incidence of breast carcinoma in the first invited birth cohorts born in 1935-1939 was compared with older, non-invited cohorts. The minimum follow-up time of the invitees after the last screening round was 14 years. Expected cumulative incidence rates were estimated with two alternative approaches. RESULTS: For both any breast carcinoma and invasive breast carcinoma, the estimates of overdiagnosis varied from 5% (95% CI=-1, 11%) to 7% (95% CI=1, 13%) depending on the approach. CONCLUSIONS: Our estimates of overdiagnosis are of the same magnitude than other plausible estimates in Europe. Both alternative approaches produced similar estimates for the expected cumulative incidence, which increased the confidence in the estimates of overdiagnosis.

Search for clastogenic factors in the plasma of locally irradiated individuals.

In studies reported in the 1960s and in several investigations since, plasma from irradiated individuals was shown to induce chromosomal aberrations when transferred into normal blood cultures. In the present study, the aim was to investigate the occurrence of these clastogenic factors (CF) using markers representing DNA damage produced in reporter lymphocytes that are treated with plasma from locally exposed individuals. Blood plasma was obtained from clinical patients with benign conditions before and after they had received radiation to small treatment volumes. Three patient groups were studied: (I) marginal resected basal cell carcinoma, (II) painful osteoarthritis of the knee, and (III) painful tendinitis of the elbow or the heel. Patients in each treatment group obtained the same fractionated treatment regimen, ranging from a total dose of 40 Gy (8 × 5 Gy, 2 factions/week) to a very small volume (1-3.5 cm³) in group I to a total dose of 6 Gy (6 × 1 Gy, 2 fractions/week) for groups II and III (treatment volumes 800-1150 cm³ and 80-160 cm³, respectively). The presence of CF in the plasma was investigated through cytogenetic (chromosomal aberrations, micronuclei) assays and kinetics of early DNA damage (γ-H2AX foci) in reporter cells. With the experimental settings applied, local radiation exposure had no apparent effect on the induction of CF in patient plasma; no deviations in chromosomal aberrations or micronucleus or focus induction were observed in reporter cells treated with postexposure plasma with respect to pre-exposure samples when the mean values of the groups were compared. However, there was a large interindividual variation in the plasma-induced DNA-damaging effects. Steroid treatment of patients was demonstrated to be the most influential factor affecting the occurrence of plasma factors; plasma from patients treated with steroids led to significant reductions of γ-H2AX foci and reduced numbers of chromatid aberrations in reporter cells. In addition to the locally exposed patients, newly obtained plasma samples from three radiological accident victims exposed in 1994 were examined. In contrast to the patient data, a significant increase in chromosomal aberrations was induced with plasma from two accident victims.

Meningioma and mobile phone use--a collaborative case-control study in five North European countries.

BACKGROUND: Use of mobile telephones has been suggested as a possible risk factor for intracranial tumours. To evaluate the effect of mobile phones on risk of meningioma, we carried out an international, collaborative case-control study of 1209 meningioma cases and 3299 population-based controls. METHODS: Population-based cases were identified, mostly from hospitals, and controls from national population registers and general practitioners' patient lists. Detailed history of mobile phone use was obtained by personal interview. Regular mobile phone use (at least once a week for at least 6 months), duration of use, cumulative number and hours of use, and several other indicators of mobile phone use were assessed in relation to meningioma risk using conditional logistic regression with strata defined by age, sex, country and region. RESULTS: Risk of meningioma among regular users of mobile phones was apparently lower than among never or non-regular users (odds ratio, OR = 0.76, 95% confidence interval, CI 0.65, 0.89). The risk was not increased in relation to years since first use, lifetime years of use, cumulative hours of use or cumulative number of calls. The findings were similar regardless of telephone network type (analogue/digital), age or sex. CONCLUSIONS: Our results do not provide support for an association between mobile phone use and risk of meningioma.

Breast cancer mortality with varying invitational policies in organised mammography.

We examined the effect of different invitational policies on the reduction of breast cancer mortality at 60-79 years of age within the Finnish mammography programme in 1992-2003, which varied in its coverage at 60-69 years of age. The data from 260 municipalities were grouped into three categories: regular invitations at 50-59 years of age only, regular invitations at 50-69 years of age, and regular invitations at 50-59 years of age with irregular invitations at 60-69 years of age. Observed deaths from breast cancer were compared to those expected without screening among all women and among the screened and non-screened women. Observed deaths were obtained from population data and from a cohort follow-up in 1992-2003. Expected deaths were derived by modelling breast cancer mortality at population level in 1974-1985 and 1992-2003. The reduction in breast cancer mortality was strongest, 28% (0.72, 0.51-0.97), in municipalities with regular invitations at 50-69 years of age. No overall effect at 60-79 years of age was observed with regular invitations at 50-59 years of age. The study confirms a reduction by screening of breast cancer mortality in Finland. Uniform extension of invitations to 60-69 years of age would increase the number of prevented breast cancer deaths among the elderly.

Activity concentrations of 226Ra and 228Ra in drilled well water in Finland.

The activity concentrations of (226)Ra and (228)Ra in drinking water were determined in water samples from 176 drilled wells. (226)Ra activity concentrations were in the range of <0.01-1.0 Bq l(-1) and (228)Ra activity concentrations in the range of <0.03-0.3 Bq l(-1). The mean activity concentration of (226)Ra and (228)Ra were 0.041 and 0.034 Bq l(-1), respectively. High radium activity concentrations in drinking water were rare. Only 2-4% of the drilled wells exceeded a (226)Ra concentration of 0.5 Bq l(-1) and 1-2% of the wells exceeded a (228)Ra concentration of 0.2 Bq l(-1). These are the activity concentrations that cause a 0.1 mSv annual effective dose for users of drinking water. The maximum annual effective doses from (226)Ra and (228)Ra for users of drilled wells were 0.21 mSv, and 0.16 mSv respectively. The elevated activity concentrations of (226)Ra and (228)Ra did not occur simultaneously in the same groundwaters and the correlation between (226)Ra and (228)Ra was small.

Cancer-specific survival of patients with multiple cancers: an application to patients with multiple breast cancers.

In the analysis of cause-specific survival, the causes of death must be known. For single-cancer patients with a known cause of death, the estimation of the cause-specific survival rate is straightforward. For multiple-cancer patients with two primary cancers, however, the analysis of cause-specific survival rates is more complex, particularly if the cancers are of the same primary site. In these situations, a concept of cancer-specific survival may also be distinguished from cause-specific survival. Cancer-specific survival rates are studied here by introducing two models, the primary one where the death from cancer is attributed to one of the cancers, and an alternative where such an attribution is not necessary. The models are illustrated using data on patients with multiple breast cancers. The model-based survival rates are compared with each other and with the corresponding relative survival rates based on analogous modelling of relative survival. The results show that for the subsequent breast cancer, the cancer-specific survival rates based on the alternative, where the distinction between the cancers as a cause of death was not necessary, tended to be higher than those based on that distinction. It is thus possible that the subsequent cancer was too often coded as a cause of death, particularly when being localized at diagnosis.

Relative survival of patients with subsequent cancer.

BACKGROUND: With the increasing numbers of patients with multiple primary cancers, survival from subsequent cancers is of growing interest. The majority of the analyses on the subject so far have, however, suffered from methodological difficulties. METHODS: A new model is now proposed for estimating relative survival of patients with subsequent primary cancer. The model is an extension to that proposed earlier by Estève et al. for estimating relative survival using individual patient data. The model is illustrated with real data on patients with one or two primary breast cancers and used in comparing the excess hazards between first and subsequent breast cancer. RESULTS: For patients with multiple cancers, the traditional analysis of relative survival can be made cancer-specific. The excess hazards are different between the first and subsequent breast cancer: The excess hazard of the subsequent breast cancer tends to decrease with increasing age when compared to the corresponding hazard of the first breast cancer. CONCLUSIONS: Relative survival of patients with subsequent cancer can be modelled facilitating studies on different hypothesis on the excess hazards of a first and subsequent cancer.

Parametric mixture model for analysing relative survival of patients with multiple cancers.

BACKGROUND: This study aimed to provide a parametric mixture model for analysing relative survival and cure rates of patients with multiple cancers. METHODS: A new model was introduced by extending a parametric mixture model on relative survival of patients with a single cancer. The model was applied to empirical data on lung cancer as a first and second tumour after a first localised colorectal cancer. RESULTS: Survival and cure from subsequent cancer are estimatable with the parametric mixture model on relative survival of patients with multiple cancers. Survival from lung cancer does not differ between the first and second tumour, but there is suggestive evidence that survival from second lung cancer is higher than that from the first lung cancer. DISCUSSION: Relative survival analysis of patients with multiple cancers can be extended to incorporate cure rates and excess hazards related to the individual cancers. Prognostic factors can be included in the model.

Endothelial and epithelial expression of sialyl Lewis(x) in squamous carcinoma of the tongue.

In this retrospective study we describe the immunohistochemical expression pattern of sLe(x) epitopes in endothelial and epithelial cells of 59 squamous carcinomas of the tongue, and relate this to the relative survival rates of the patients. Endothelial sLe(x) expression was significantly elevated in malignant lesions compared to normal tissues, but did not have any prognostic value for the relative survival rate. In contrast, epithelial sLe(x) expression was decreased in carcinomas compared to normal tongue. The patients whose carcinoma showed only moderate epithelial HECA-452 reactivity had a significantly better relative survival rate than the patients with tumor specimens with neglible or very high HECA-452 reactivity. The epithelial staining with the two other anti-sLe(x) antibodies (CSLEX-1 and 2F3) did not correlate with the survival rates of tongue carcinoma patients.

What do Danes know about naevi, skin cancer and melanoma? Experience from a dermatological out-patient clinic.

A survey of public knowledge about naevi, melanoma/ skin cancer and sunscreens was undertaken in Denmark at a time when no public awareness campaign had taken place. A total of 339 study subjects, aged 18-79 years, was recruited at our dermatology outpatient clinic, and data were collected by a self-administered questionnaire. The study group differed from the population in that females and the younger age groups were over-represented. A knowledge score was calculated. Males, the oldest age group and those with shortest school education were less knowledgeable. The study revealed several points of public uncertainty and ignorance with regard to early signs of melanoma and risk factors, which need to be emphasized in future public education.

Effect of entacapone, a COMT inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of controlled-release levodopa-carbidopa in volunteers.

We studied the effect of entacapone, a catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of a controlled-release (CR) levodopa-carbidopa preparation (Sinemet CR) in an open, randomized trial in 12 healthy male volunteers. The inhibition of soluble COMT (S-COMT) in red blood cells (RBCs) was also measured. Single graded doses of entacapone (100-800 mg) were administered concomitant with a single oral dose of CR levodopa, or CR levodopa was given without entacapone (control treatment), at least 1 week apart. Plasma concentrations of levodopa, 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), carbidopa, and entacapone were determined for pharmacokinetic calculations. Entacapone decreased dose-dependently the activity of S-COMT in RBCs with a maximal inhibition of 66% after the highest dose (800 mg). Entacapone increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was highest (33%) after the 400-mg dose. Entacapone did not influence time to maximal concentration (Tmax) of levodopa. Entacapone was absorbed faster than levodopa from the CR preparation. The AUCs of 3-OMD and HVA decreased and that of DOPAC increased dose-dependently after entacapone, maximally by 69, 38, and 74%, respectively. Higher doses of entacapone (400 mg and 800 mg) decreased the AUC, but not Tmax of carbidopa. Over the dose range studied, entacapone was well tolerated. Entacapone is an effective COMT inhibitor. It improves the pharmacokinetic profile of levodopa when used in combination with a CR levodopa preparation, as it does with a standard levodopa preparation. The results justify further clinical studies with entacapone in combination with CR preparations of levodopa.

COMT inhibition by high-dose entacapone does not affect hemodynamics but changes catecholamine metabolism in healthy volunteers at rest and during exercise.

We studied the effects of catechol-O-methyltransferase (COMT) inhibition with entacapone on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during a bicycle exercise test. Entacapone was given orally during two periods of seven days each to eleven healthy male volunteers; on the first period 400 mg t.i.d. and on the second 800 mg t.i.d. A submaximal exercise test giving a heart rate of about 163-167 beats/min with the highest predetermined work load was performed on a bicycle ergometer, and blood pressure, heart rate and ECG were recorded. The concentrations of adrenaline, noradrenaline, 3,4-dihydroxyphenylglycol (DHPG), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC) in plasma were determined. Blood pressure, heart rate, ECG, and plasma concentrations of unconjugated adrenaline and noradrenaline were not influenced after single and repeated dosing of entacapone. The plasma concentrations of DHPG (a monoamine oxidase (MAO)-dependent metabolite) increased maximally by 245% compared to the control day. DOPAC (a MAO-dependent metabolite) increased maximally by 144% and MHPG (a COMT-dependent metabolite) decreased by 54%. The increase in DHPG and DOPAC was significantly greater with the 800 mg dose than with the 400 mg dose. The decrease in MHPG was significantly greater with the repeated dosing than with the single dose of entacapone. COMT inhibition by entacapone seems not to affect hemodynamics or plasma concentrations of unconjugated adrenaline and noradrenaline in healthy volunteers either at rest or during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival of breast cancer patients after subsequent term pregnancy: "healthy mother effect".

OBJECTIVE: A population-based matched survival study was conducted to assess the risk of death for breast cancer patients in relation to whether they were delivered of a live born child subsequent to the cancer diagnosis. STUDY DESIGN: Among the 2548 women < 40 years old diagnosed with carcinoma of the breast in 1967 to 1989 in Finland there were 91 eligible patients with subsequent deliveries (> or = 10 months after the diagnosis) for whom 471 controls were matched for stage, age, and year of breast cancer diagnosis. The controls had to have survived at least the interval between the diagnosis and the delivery of their matched counterparts. The follow-up started from the date of the first delivery after the diagnosis or after the corresponding interval for the matched controls. A stratified Cox proportional hazards survival analysis was performed. RESULTS: The controls had a 4.8-fold (95% confidence interval 2.2 to 10.3) risk of death compared with those who were delivered after the diagnosis of breast cancer. CONCLUSION: Our interpretation of this result is a "healthy mother effect" (i.e., that only women who feel healthy give birth and those who are affected by the disease do not). Nevertheless, six of eight deaths among the 91 patients who did give birth were related to breast cancer.