Biomedical subjects

M Hakama

Publications and source records attributed to M Hakama.

At least 19 recordsLinked to original sources

PubMed2007

Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial.

Specificity constitutes a component of validity for a screening test. The number of false-positive (FP) results has been regarded as one of major shortcomings in prostate cancer screening. We estimated the specificity of serum prostate-specific antigen (PSA) determination in prostate cancer screening using data from a randomised, controlled screening trial conducted in Finland with 32 000 men in the screening arm. We calculated the specificity as the proportion of men with negative findings (screen negatives, SN) relative to those with negative and FP results (SN/(SN+FP)). A SN finding was defined as either PSA</=4 ng ml(-1) or PSA 3.0-3.9 ng ml(-1) combined with a negative ancillary test (digital rectal examination, DRE or free/total, F/T PSA ratio). False positives were those with positive screening test followed by a negative diagnostic examination. Of the 30 194 eligible men, 20 794 (69%) attended the first screening round and 1968 (9.5%) had a screen-positive finding. A total of 508 prostate cancers were detected at screening (2.4%). Hence, the number of SN findings was 18 825 and the number of FP results 1358. Specificity was estimated as 0.933 (18 825 out of 20 183) with 95% confidence interval (CI) 0.929-0.936. Specificity decreased with age. Digital rectal examination as ancillary examination had similar or higher specificity than F/T PSA. In the second screening round, specificity was slightly lower (0.912, 95% CI 0.908-0.916). The specificity of PSA screening in the Finnish screening trial is acceptable. Further improvement in specificity could, however, improve acceptability of screening and decrease screening costs.

Aged↗

PubMed2006

Erectile dysfunction influences the subsequent incidence of lower urinary tract symptoms and bother.

It is unclear whether lower urinary tract symptoms (LUTS) cause erectile dysfunction (ED) independently or through common underlying pathophysiology and shared risk factors. The aim of this study was to investigate the effect of ED on the incidence of frequency and bother of LUTS. Target population consisted of men aged 50, 60 or 70 years residing in the study area in Finland in 1994. Questionnaires were mailed to 3143 men in 1994 and to 2837 of them 5 years later. The follow-up sample comprised 1683 men who responded to both baseline and follow-up surveys. ED was assessed by two questions on subject's ability to achieve or maintain an erection sufficient for intercourse and LUTS by the Danish Prostatic Symptom Score questionnaire. A dose-response relation was found between the severity of ED at baseline and the incidence of LUTS or bother during follow-up. After adjustment for the confounders, the incidence rate ratio (RR) of LUTS was higher in men with moderate (RR 1.5, 95% confidence interval (CI) 1.0-2.3) or severe ED (RR 2.3, 95% CI 1.4-3.8) than in those free of ED at entry. Compared with men free of ED at baseline, the RRs of urinary bother were 1.6 (95% CI 1.1-2.4), 1.9 (95% CI 1.1-3.2) and 2.2 (95% CI 1.1-4.3) for minimal, moderate or severe ED, respectively. In summary, ED is associated with an increased incidence of LUTS and bother. ED and LUTS may have a common underlying pathophysiology or shared risk factors.

Aged↗

PubMed2006

Cardiovascular drug use and the incidence of erectile dysfunction.

It is unclear whether high blood pressure per se or antihypertensive drug use causes erectile dysfunction (ED). The aim of this study was to investigate the effect of cardiovascular diseases and their concomitant medications use on the incidence of ED. The target population consisted of men aged 55, 65 or 75 years old residing in the study area in Finland in 1999. Questionnaires were mailed to 2837 men in 1999 and to 2510 of them 5 years later. The follow-up sample consisted of 1665 men (66% of those eligible) who responded to both baseline and follow-up questionnaires. Men free of moderate or severe ED at baseline (N=1000) were included in the study. ED was assessed by two questions on subject ability to achieve or maintain an erection sufficient for intercourse. Poisson regression model was used in the multivariable analyses. The risk of ED was higher in men suffering from treated hypertension or heart disease than in those with the untreated condition. The risk of ED was higher in men using calcium channel inhibitor (adjusted relative risk (RR)=1.6, 95% confidence interval (CI) 1.0-2.4), angiotensin II antagonist (RR=2.2, 95% CI 1.0-4.7), non-selective beta-blocker (RR=1.7, 95% CI 0.9-3.2) or diuretic (RR=1.3, CI 0.7-2.4) compared with non-users. ED was not associated with using organic nitrates, angiotensin-converting enzyme inhibitors, selective beta-blockers and serum lipid-lowering agents. In summary, calcium channel inhibitors, angiotensin II antagonists, non-selective beta-blockers and diuretics may increase the risk of ED.

Aged↗

PubMed2006

Effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile dysfunction.

PURPOSE: We estimated the effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile dysfunction. MATERIALS AND METHODS: The target population consisted of men 50, 60 or 70 years old residing in the study area in Finland in 1994. Questionnaires were mailed to 3,143 men in 1994 and to 2,864 men 5 years later. The followup sample consisted of 1,683 men who responded to baseline and followup questionnaires. We estimated the effect of NSAIDs on the incidence of ED in men free from moderate or complete ED at baseline (in 1,126). ED was assessed by 2 questions on subject ability to achieve or maintain an erection sufficient for intercourse. Confounding was assessed by stratification and by adjustment in multivariate Poisson regression model. RESULTS: The incidence of ED was 93 cases per 1,000 person-years in men who used and 35 in those who did not use NSAIDs. Among men with arthritis, the most common indication for NSAID use, ED incidence was 97 cases per 1,000 in those using and 52 in men who did not use NSAIDs. Compared with men who did not use NSAIDs and were free from arthritis, the relative risk of ED after controlling for the effects of age, smoking, and other medical conditions and medications was higher in men who used NSAIDs but were free of arthritis (IDR 2.0, 95% CI 1.2-3.5) and in those who used NSAIDs and had arthritis (IDR 1.9, 95% CI 1.2-3.1). The relative risk was only somewhat higher in men who had arthritis but did not use NSAIDs (IDR 1.3, 95% CI 0.9-1.8). CONCLUSIONS: The use of nonsteroidal anti-inflammatory drugs increases the risk of ED and the effect is independent of indication.

Aged↗

PubMed2006

The effects of parity, oral contraceptive use and hormone replacement therapy on the incidence of varicose veins.

Three population-based age cohorts (40-, 50- and 60-years old) of women (n = 3,590) were followed up to find out if pregnancies, use of oral contraceptives (OCs) or hormone replacement therapy (HRT) affect the appearance of varicose veins. Results were presented as odds ratios (OR) of prevalences at entry (POR) and as incidence odds ratios (IOR) during the 5-year follow-up. Parity with three or more births was an independent risk factor for varicose veins IOR 2.0 (95% confidence interval (CI), 1.0 - 3.9). OC use showed a small and not significant protective effect for varicose veins, both POR and IOR equal to 0.9. HRT use indicated an increased risk of varicose veins, with POR 1.3 (1.0 - 1.7), but in the follow-up, the effect disappeared, IOR 1.0 (0.5 - 1.9). As a conclusion, higher age and high parity are characteristic for varicose veins. The use of HRT or OCs do not increase the risk.

Adult↗

PubMed2005

Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting.

The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present report on first-year results was to assess the cross-sectional relative validity parameters for routine hrHPV screening, in comparison with conventional screening. An equal number of women invited to routine screening was randomly allocated to primary hrHPV screening (n=7060) and to cytological screening (n=7089). In the hrHPV screening arm, after a single positive hrHPV test result, the need of colposcopy referral was determined by a cytological triage test. Compared with the conventional arm, more colposcopy referrals were made in the hrHPV screening arm (relative risk 1.51, confidence interval 95% 1.03-2.22). Specificity of the primary screening with sole hrHPV test (91.5-92.1%) was much lower than that with the cytology triage (98.7-99.3%), which was not quite as specific as screening with conventional cytology (99.2-99.6%). Compared with conventional cytology, primary screening with hrHPV test results in increased cross-sectional relative sensitivity at the level of all positive lesions at the cost of substantial loss in specificity. With cytology triage, the specificity improves to the level of conventional cytology.

Adult↗

PubMed2005

Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.

OBJECTIVES: To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. DESIGN: Multinational retrospective cohort study of cancer mortality. SETTING: Cohorts of workers in the nuclear industry in 15 countries. PARTICIPANTS: 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. MAIN OUTCOME MEASUREMENTS: Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. RESULTS: The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. CONCLUSIONS: These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study.

Dose-Response Relationship, Drug↗

PubMed2005

Follow-up cost of breast cancer patients with localized disease after primary treatment: a randomized trial.

We studied the cost of follow-up of 472 breast cancer patients without distant metastasis after primary treatment in four different schedules in a randomized trial. The mean follow-up was 4.2 years. The four schedules differed in frequency of follow-up visits (every third or sixth month) and in intensity of diagnostic examinations (routine or on clinical grounds). Neither the frequency of visits nor the intensity of diagnostic examinations had any effect on disease-free or overall survival of patients. The total costs of follow-up, however, were different in the four follow-up schedules and varied between arms per patient from 1050 to 2269 euros and per detected recurrence from 4166 to 9149 euros. Outpatient visits every third month compared to every sixth month and routine examinations in the follow-up of asymptomatic primary breast cancer patients do not improve patient disease-free or overall survival, but increase the costs of follow-up 2.2 times.

Aftercare↗

PubMed2005

Validity of process indicators of screening for breast cancer to predict mortality reduction.

The aim of the study was to empirically assess the acceptable levels of process indicators as described in the European Community Guidelines using materials from the mammography service screening programmes. The Finnish programme was evaluated for effectiveness with a prior estimate of 0.74 for RR in Finland and 0.81 in Helsinki. Hence, the Finnish programme was likely to be somewhat less effective in terms of reduction in mortality than implied on the basis of early randomized trials, but probably approaching the same level of effectiveness. Finland therefore provides background data on the applicability of the process indicators that are indicators of performance and surrogates for effectiveness. The performance data on 10 Finnish screening centres at subsequent screens were used. These centres invited 687,000 women aged 50-64 years in 1991-2000. The mean compliance was 93% and the corresponding recall rate was 2.3%. The benign to malignant biopsy ratio was 0.43:1. The average breast cancer detection rate was 0.36%, 2.1 compared with the background incidence. The proportion of screen-detected stage II+ cancers was 26%. Most, but not all, of these process indicators met the desirable reference values of the European Community. The specific criteria of the European Community on stage distribution, rates of screen-detected cancers by stage and detection rate to background incidence may need reconsideration.

Biopsy↗

PubMed2004

Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies.

OBJECTIVE: To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gas. DESIGN: Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. SETTING: Nine European countries. SUBJECTS: 7148 cases of lung cancer and 14,208 controls. MAIN OUTCOME MEASURES: Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic metre (Bq/m3) of household air. RESULTS: The mean measured radon concentration in homes of people in the control group was 97 Bq/m3, with 11% measuring > 200 and 4% measuring > 400 Bq/m3. For cases of lung cancer the mean concentration was 104 Bq/m3. The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m3 increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m3 increase in usual radon--that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P = 0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m3. The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m3 would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. CONCLUSIONS: Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe.

Air Pollutants, Radioactive↗

PubMed2004

Cervical cancer screening programmes and policies in 18 European countries.

A questionnaire survey was conducted by the Epidemiology Working Group of the European Cervical Cancer Screening Network, and the International Agency for Research on Cancer, IARC, between August and December 2003 in 35 centres in 20 European countries with reliable cervical cancer incidence and/or mortality data in databanks held at IARC and WHO. The questionnaire was completed by 28 centres from 20 countries. The final tables included information on 25 centres from 18 countries. Six countries had started screening in the 1960s, whereas 10 countries or regions had started at least a pilot programme by 2003. There were six invitational and nine partially invitational programmes, the rest employing opportunistic screening only. Recommended lifetime number of smears varied from seven to more than 50. Coverage of smear test within the recommended screening interval (usually 3 or 5 years) was above 80% in three countries. Screening registration took place in 13 programmes. Eight programmes reported the rates of screen-detected cervical cancers and precursor lesions. There was wide variation in the CIN3 detection rates. International guidelines and quality assurance protocols are useful for monitoring and evaluating screening programmes systematically. Our survey indicated that the recommendations as currently given are met in only few European countries. Health authorities need to consider stronger measures and incentives than those laid out in the current set of recommendations.

Adolescent↗

PubMed2004

Loss-adjusted survival of cervix cancer in Khon Kaen, Northeast Thailand.

For incident cancers of the cervix uteri (601 cases) registered in the population-based cancer registry of Khon Kaen province, Northeast Thailand, in 1985-1990 loss-adjusted survival probabilities were estimated by a logistic regression model with four prognostic factors (age at diagnosis, stage of disease, place of residence and treatment), and compared with observed survival, estimated by the actuarial method. All patients were followed up for a minimum of 5 years, using both passive and active methods. In all, 27.6% of patients were lost to follow-up within 5 years of the index date. The overall observed survival at 5 years was 56.8% and loss-adjusted survival was 54.7%. The difference between the loss-adjusted and observed survival at 5 years was small: 2.1% overall, varying between 0.8 and 3.5 percent units for any prognostic group. The assumption of independence of loss to follow-up and death in the calculation of survival by the actuarial method in this, and probably in other, population-based series, is reasonable and leads to no material bias in the estimates.

Adult↗

PubMed2004

Joint effects of different human papillomaviruses and Chlamydia trachomatis infections on risk of squamous cell carcinoma of the cervix uteri.

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.

Adult↗

PubMed2004

Process indicators from ten centres in the Finnish breast cancer screening programme from 1991 to 2000.

The aim of this study was to evaluate the quality of the Finnish mammography programme by assessing process indicators from 10 screening centres using data from the first and subsequent screens. We compared these screen-specific indicators with European standards and results from countries with similar screening protocols. Ten Finnish centres invited approximately 1,000,000 women from 1991-2000. Women were mainly 50-64 years old. Mean compliance amongst this age group was 90% at the first and 93% at subsequent screens. The corresponding recall rates were 4.6% and 2.3%, respectively. The average breast cancer detection rates were 0.44% and 0.36%, respectively. The positive predictive values (PPVs) of mammography at the first and subsequent screens were 10% (range 7-20%) and 16% (range 12-31%), and the corresponding benign to malignant (B:M) biopsy ratios were 1:1 (range 0.5-1.8:1) and 0.4:1 (range 0.3-0.8:1). The PPV of mammography increased significantly during the study period, and the average process indicators fulfilled the criteria of the European community for the most part. However, the variation in PPVs was wide, as has been seen for other European mammography programmes, indicating meaningful differences in diagnostic criteria and potential adverse effects.

Adult↗

PubMed2004

Sheep and goats: separating cervix and corpus uteri from imprecisely coded uterine cancer deaths, for studies of geographical and temporal variations in mortality.

Analysing time trends in mortality from cancers of the cervix and corpus uteri using routine data sources (such as the World Health Organisation mortality database) involves two major problems: deaths certified as "uterus, unspecified site", and the presence of a combined category comprising unspecified and corpus uteri cancer deaths. To avoid misleading interpretations, the unspecified and the misclassified data must be incorporated into the analysis to produce rates that allow meaningful comparisons between populations and over time. Reallocation methods based on age- and time-specific distributions of cervix and corpus uteri cancer are applied to the unspecified deaths, while for those in the combined category, the age- and time-specific distributions of unspecified and corpus uteri cancer are considered. Adjustments of the general strategies for reallocation were developed to take into account the different quality of the data. Results from eight European countries with different degrees of coding precision are presented. The reallocation methods bring the cervix and corpus uteri mortality trends more in line with the trends for countries with more precise data while keeping the country-specific characteristics. In addition, the methods ensured the availability of time trends for corpus uteri cancer in women age 50 years and older, which were completely missing without reallocation. We propose generally applicable reallocation methods that allow valid time trend analysis of cervix and corpus uteri cancer mortality using datasets of varying precision. Our results show that any sensible analysis of time trends must involve procedures for correcting for unspecified and misclassified uterine cancer deaths. The modified data are available at .

Age Distribution↗

PubMed2004

Incidence of varicose veins in Finland.

BACKGROUND: Incidence of varicose veins in the population is unknown. The study aimed at estimating the incidence of varicose veins in complete cohorts of 40-60 year-olds in a general population. PATIENTS AND METHODS: The study was conducted in the city of Tampere, Finland. A validated questionnaire (with 93% sensitivity and 92% specificity) was used in a general population of 6874 individuals (aged 40, 50 or 60). Initially, 3065 of them had no varicose veins and 78% were followed-up for 5 years. RESULTS: 157 individuals reported new varicose veins during the follow-up. The overall incidence was 13.5 per 1000 person years (8.5 for men and 19.2 for women). Female sex was an independent and statistically significant risk indicator of varicose veins (adjusted odds ratio, OR 2.4). The incidence was significantly higher at the age of 50-55 years (OR 1.6). Higher body mass index seemed to be related to higher risk of new varicose veins (OR 1.2-1.8), but the association failed to reach statistical significance. The level of education did not affect the incidence. CONCLUSIONS: New varicose veins appear also in the middle-aged population, and the rate is linked with the female gender, especially at the beginning of the 6th decade.

Adult↗

PubMed2004

Effect of life-style factors on incidence of erectile dysfunction.

We estimated the incidence of erectile dysfunction (ED) in a population-based sample during 5-y follow-up and determined how the rate was affected by sociodemographic and life-style factors. The target population comprised all men aged 50, 60 or 70 y residing in the city of Tampere or 11 surrounding municipalities in Finland at the start of follow-up. A questionnaire was mailed to 3143 men in 1994 and to 2864 in 1999. The follow-up sample consisted of 1442 men who responded to both baseline and follow-up questionnaires. We estimated the effect of sociodemographic and life-style factors on the incidence of ED among the 1130 men free of ED at baseline. We found no differences in the incidence of ED by the level of education, marital status, urban/rural place of residence, amount of alcohol and coffee consumption. Obesity (rate ratio (RR)=1.7, 95% confidence interval (CI): 1.1-2.5) and current smoking (RR=1.5, 95% CI: 0.9-2.2) increased the incidence of ED. Current smokers free of comorbidity were also at higher risk of ED (RR=1.3, 95% CI: 0.8-2.1), but no effect was observed among past smokers. Our results indicate that sociodemographic and life-style factors, except age and obesity, have little influence on ED.

Aged↗

PubMed2004

A randomized trial of choice of treatment in prostate cancer: the effect of intervention on the treatment chosen.

OBJECTIVE: To determine whether different approaches in the choice of treatment affect the treatment chosen by the patient for prostate cancer. PATIENTS AND METHODS: We conducted a randomized trial with 210 men who had a histologically confirmed diagnosis of prostate cancer in 1993-94 at four major hospitals in Finland. After obtaining informed consent the men were randomized either to an intervention arm, in which there was greater patient participation in the choice of treatment following a structured procedure, or a control arm in which the standard approach, i.e. a standardized treatment protocol, was used. The main outcome measure of the analysis was the primary treatment chosen for prostate cancer. RESULTS: In the enhanced participation arm patients not eligible for radical prostatectomy chose orchidectomy less frequently and favoured nonsurgical endocrine treatment than in the treatment protocol arm. Radical prostatectomy was the most commonly chosen treatment option in both arms among men with operable cancer. The way treatment options were presented affected the treatment chosen for prostate cancer. CONCLUSION: Patients with prostate cancer are willing and able to take an active role in making decisions. The preferences of patients with prostate cancer in the choice of treatment may differ from the priorities of the physicians.

Adult↗