Substantial rise in the lifetime risk of primary total knee replacement surgery for osteoarthritis from 2003 to 2013: an international, population-level analysis.

OBJECTIVE: To estimate and compare the lifetime risk of total knee replacement surgery (TKR) for osteoarthritis (OA) between countries, and over time. METHOD: Data on primary TKR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of TKR was calculated for 2003 and 2013 using registry, life table and population data. RESULTS: Marked international variation in lifetime risk of TKR was evident, with females consistently demonstrating the greatest risk. In 2013, Finland had the highest lifetime risk for females (22.8%, 95%CI 22.5-23.1%) and Australia had the highest risk for males (15.4%, 95%CI 15.1-15.6%). Norway had the lowest lifetime risk for females (9.7%, 95%CI 9.5-9.9%) and males (5.8%, 95%CI 5.6-5.9%) in 2013. All countries showed a significant rise in lifetime risk of TKR for both sexes over the 10-year study period, with the largest increases observed in Australia (females: from 13.6% to 21.1%; males: from 9.8% to 15.4%). CONCLUSIONS: Using population-based data, this study identified significant increases in the lifetime risk of TKR in all five countries from 2003 to 2013. Lifetime risk of TKR was as high as 1 in 5 women in Finland, and 1 in 7 males in Australia. These risk estimates quantify the healthcare resource burden of knee OA at the population level, providing an important resource for public health policy development and healthcare planning.

Efficacy of a pneumococcal conjugate vaccine against acute otitis media.

BACKGROUND: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. METHODS: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. RESULTS: Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. CONCLUSIONS: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.

Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial.

BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene may each influence the development of prostate cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation, separately or together, on prostate cancer in male smokers. METHODS: A total of 29133 male smokers aged 50-69 years from southwestern Finland were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects were estimated by a proportional hazards model, and two-sided P values were calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47% to -12%) in the incidence of prostate cancer was observed among the subjects receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n = 14569). The reduction was evident in clinical prostate cancer but not in latent cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n = 14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n = 14573). Neither agent had any effect on the time interval between diagnosis and death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially reduced prostate cancer incidence and mortality in male smokers. Other controlled trials are required to confirm the findings.

Prognosis of patients with lung cancer found in a single chest radiograph screening.

BACKGROUND: The prognosis of patients with lung cancer is better when the diagnosis is made early; the disease is localized, and radical surgery is possible. Screening for lung cancer with mass radiography or sputum cytology should contribute to a more favorable prognosis. Large-scale screening studies have improved the survival rates for lung cancer but have yielded no reduction in mortality rates. METHODS: The histologic types, stages, treatments, and survival rates were studied in 93 men who were found to have lung cancer in a single chest radiograph screening of more than 33,000 men who smoked and were 50 to 69 years old ("screened cases"), and in 239 men of the same age range whose lung cancer was detected through ordinary health care system ("other cases") during the screening period. RESULTS: The distribution of the histology was similar in the two groups, but screening detected more instances of early-stage disease that were resectable more often than in the other group (37 vs 19%). The 5-year survival rate for men in the screened cases was 19%, and that of men in the other cases was 10% (relative risk, 0.65; 95% confidence interval [CI], 0.50 to 0.84). The survival rate of men in the screened cases remained significantly higher than that of men in the other cases even after adjustments for age, smoking status, histology, stage of the disease, and resectability of the disease (relative risk, 0.74; 95% CI, 0.55 to 1.00). CONCLUSIONS: According to this study, chest radiograph screening might improve the prognosis of lung cancer. Our results are, however, subject to many factors that were only partially controlled for, and they should be interpreted cautiously.

Validity of diagnoses of major coronary events in national registers of hospital diagnoses and deaths in Finland.

We validated diagnoses of acute myocardial infarction (AMI) and death from coronary heart disease (CHD) found in the Finnish National Hospital Discharge Register and the Register of Causes of Death from a sample of the 29,133 men participating in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cases were traced to hospitals and institutes performing medico-legal death cause examinations and all relevant information was collected. The cardiac events were re-evaluated according to the diagnostic criteria of the Finnish contribution to the WHO MONICA project, i.e. the FINMONICA criteria. Altogether 408 cases of non-fatal AMI (n = 217) and death from CHD (n = 191) were reviewed. In the re-evaluation 94% of them (95% confidence interval 92-96%) were diagnosed as either definite (57%) or possible (37%) AMI. Non-fatal cases were more often classified definite AMI in the review, whereas fatal cases were more often classified possible AMI. Age or trial supplementation group did not affect classification, and no secular trend was observed. In conclusion, the diagnoses of AMI and death from CHD in the registers were highly predictive of a true major coronary event defined by strict criteria, thus their use in endpoint assessment in epidemiological studies and clinical trials is justified.

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance.

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.

Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study.

The Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study was a placebo-controlled, randomized intervention trial testing the hypothesis that beta-carotene and alpha-tocopherol (vitamin E) supplements prevent lung and other cancers. The study is predicated on a substantial body of evidence supporting a role in cancer prevention for these micronutrients. Based on the 2 x 2 factorial study design, 29,133 eligible male cigarette smokers aged 50-69 y were randomly assigned to receive beta-carotene (20 mg), alpha-tocopherol (50 mg), beta-carotene and alpha-tocopherol, or placebo daily for 5-8 y. Capsule compliance was high (median = 99%). beta-Carotene treatment did not result in a decrease in cancer at any of the major sites but rather in an increase at several sites, most notably lung, prostate, and stomach (number of cases 474 compared with 402, 138 compared with 112, and 70 compared with 56, respectively). The vitamin E group had fewer incident cancers of the prostate and colorectum compared with the group not receiving vitamin E (number of cases 99 compared with 151 and 68 compared with 81, respectively), but more cancers of the stomach (70 compared with 56). In contrast to these intervention-based findings for beta-carotene and vitamin E supplements, we observed lower lung cancer rates in men with higher amounts of both serum and dietary beta-carotene and vitamin E at baseline.

Reproducibility and validity of dietary assessment instruments. II. A qualitative food frequency questionnaire.

The reproducibility and validity of a food frequency questionnaire designed to measure intakes of total fat, saturated and polyunsaturated fats, vitamins A, C, and E, selenium, and dietary fiber were tested from March to October 1984 among 297 Finnish men aged 55-69 years. The questionnaire asked about consumption of 44 food items. In the reproducibility study, 107 subjects filled in the questionnaire three times, at three-month intervals. Intraclass correlations varied from 0.52 for vitamin A to 0.85 for polyunsaturated fat. In the validity study, 190 subjects kept food consumption records for 12 two-day periods distributed evenly over a period of six months and filled in the questionnaire both before and after this period. Correlations between the nutrient intake values from the food records and those from the food frequency questionnaires ranged from 0.33 for selenium to 0.68 for polyunsaturated fat. On the average, 40-45% of the subjects in the lowest and highest quintiles based on food records were in the same respective quintiles when assessed by the food frequency questionnaire, and 70-75% were in the two lowest and two highest questionnaire quintiles, respectively. The food frequency questionnaire and a quantitative food use questionnaire tested in the same study were compared. Use of these two instruments in large-scale epidemiologic studies is discussed.

Reproducibility and validity of dietary assessment instruments. I. A self-administered food use questionnaire with a portion size picture booklet.

A self-administered food use questionnaire which included 276 food items and mixed dishes and a portion size picture booklet with 122 photographs was developed for a large lung cancer intervention trial among approximately 27,000 Finnish men aged 50-69 years. The reproducibility and validity of this questionnaire were studied from March to October 1984. In the reproducibility study, 121 men aged 55-69 years completed the questionnaire three times, at three-month intervals. The intraclass correlations varied from 0.56 for vitamin A to 0.88 for alcohol, with most falling between 0.60 and 0.70. In the validity study, 190 men of similar age kept food consumption records for 12 two-day periods, distributed evenly over a period of six months, and filled in the questionnaire both before and after this period. Correlations between nutrient intake values from the food records and the food use questionnaires ranged from 0.40 for selenium to 0.80 for alcohol. Among subjects who belonged to the lowest quintile on the basis of the food record measurement, an average of 51 per cent fell into the same quintile and 76 per cent fell into the lowest two quintiles when they were categorized on the basis of the food use questionnaire. Findings were similar for the upper tail of the distribution. These data indicate that the self-administered food use questionnaire is useful for measuring individual or group intakes for a variety of nutrients.

The mortality and case fatality rates in acute myocardial infarction in Finland. The results of Helsinki Coronary Register during 1970-1977.

In 1970 the Helsinki Coronary Register gathered data on 1191 AMI cases and 470 deaths from AMI of Helsinki residents under 65 years of age. Since then the mortality (deaths within the first 28 days per 1000 habitants of Helsinki) from AMI declined by 1.8% a year during the period 1970-1977, and there were no statistically significant differences in trends between women and men, or between different age groups (P greater than 0.10). The case fatality rate varied from 39% in 1970 to 35% in 1977, and the statistical analysis could not reveal any significant permanent decreasing trend in any age or sex group. These results, together with our previously reported AMI incidence trends, show that at least in 1970-1977 the declining trend in mortality from AMI was due to an equal fall in the incidence of AMI. Therefore there is reason to think that the effect is due to the prevention of AMI, rather than to more effective acute care.

Usefulness of QTc interval on the discharge electrocardiogram for predicting survival after acute myocardial infarction.

The corrected QT (QTc) interval was measured on the discharge electrocardiogram of 457 consecutive patients who had survived the first 28 days after a first acute myocardial infarction (AMI). The patients were followed for 4 years. The QTc interval was not related to long-term survival after the acute phase of AMI. Sixteen percent of the patients had a QTc interval above the normal upper limit of 440 ms. Of them, 71% survived 4 years and 77% with a shorter QTc interval survived (p = 0.31). When mortality per 100 patient-years was calculated for different QTc intervals, with 10 ms accuracy, no consistent relation between the 2 variables was seen. Results that indicate a strong relation between QTc-interval prolongation and sudden death after AMI should be reevaluated. The QTc interval is not a useful prognostic tool after AMI.

The declining trend in the incidence of acute myocardial infarction in Finland. The results of Helsinki Coronary Register during 1970-1977.

The results from Helsinki Coronary Register during the period 1970-1977 show that the incidence of acute myocardial infarction (AMI) among people under 65 years of age reached its peak in 1972 and declined annually by 2.8% from 1972 to 1977. The trend was clearest in patients under 50 years, but statistical analysis showed that no 5-year age group, either in women or men, differed statistically significantly from the general declining trend.

The mortality predictive power of discharge electrocardiogram after first acute myocardial infarction.

The prognostic value of discharge ECG was studied in 457 patients after their first acute myocardial infarction. Thirteen different ECG variables were studied on the discharge ECG. When cumulative 4-year survival rates were calculated by standard life-table method for each variable individually, the following variables had statistically significant prognostic power: PTF (P terminal force), PTFA (P terminal frontal axis), AF (atrial fibrillation), ST depression, ST elevation, QRS duration, and the combination block (LBBB/RBBB + LAHB/LPHB). The variables with no statistically significant predictive power were: QTc, LBBB or RBBB, LAHB or LPHB, AV block, T wave angle, T negativity, and sigma R. The relative risks for the most important variables in the discrete life-table model were: PTF 3.4, QRS duration 3.3, ST depression 2.6, PTFA 2.5, and ST elevation 2.2. In further analysis a model with only three ECG variables (PTF, ST depression, and ST elevation) was developed which stratified the study population in categories with 1.9% to 75.5% estimated 4-year survival rates.

Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data.

Relative risk (RR) and cumulative risk of gastric cancer (GCA) were calculated for different grades of atrophic gastritis (AG) of the antrum and body. Cross-sectional data on the occurrence of AG in a representative population sample (371 subjects), and Finnish Cancer Registry data on GCA were used in the calculations. The RR was increased significantly in severe AG of the antrum and the body (18.1 and 4.6 times, respectively), but not significantly in the less severe grades of AG. As a risk factor, severe antral and body gastritis were independent of each other. The cumulative risk, i.e., the probability of contracting GCA within the following 10 years in age groups 50-54 . . . 70-74 years was calculated to vary from 2.3% to 9.3% and from 8.7% to 31.9% in severe antral AG and from 0.9% to 4.5% and from 3.6% to 16.6% in severe body AG in males and females, respectively.

Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9 1/2-year follow-up of the Helsinki Policemen Study population.

In the Helsinki Policemen Study based on a cohort of 982 men aged 35-64 years and free of coronary heart disease (CHD) at entry plasma insulin level (fasting, 1-hour and 2-hour plasma insulin after oral glucose load) showed during a 9 1/2-year follow-up a non-linear association to the incidence of "hard criteria" CHD events (CHD death or non-fatal myocardial infarction) with highest incidence in the top decile of plasma insulin. Plasma insulin levels showed positive correlations, besides to blood glucose levels, to body mass index, plasma triglyceride level and blood pressure and inverse correlations to leisure time physical activity and objectively measured physical fitness. In multivariate analyses the predictive value of high plasma insulin with respect to CHD risk was found to be independent of other risk factors, including blood glucose levels.

Socio-economic conditions in childhood and mortality and morbidity caused by coronary heart disease in adulthood in rural Finland.

In this study, the hypothesis that bad socio-economic conditions in childhood may increase the probability of coronary heart disease in adulthood is examined. The study is based partly on the data of the East-West Study in Finland, which is part of the Seven Countries Study. The study began with 823 men in Eastern Finland and 888 men in Western Finland in 1959. The mortality and morbidity of the cohorts were followed from 1959 to 1974. Risk factors were measured in medical examinations in 1959, 1964, 1969 and 1974. Parents of those included in the sample were traced by using parish registers from 1900 to 1919. Over 90% of those in the East-West Study were found. The parents' socio-economic position (socio-economic conditions in childhood) was determined. According to our findings, the relative risks of coronary death, myocardial infarction and ischemic heart disease are systematically increased for those born landless in East Finland. Variables partly explaining the increased risk were body height and smoking. The effect of cholesterol was negligible.

A multivariate analysis of the risk indicators of reduction limb defects.

In order to evaluate associations of various selected risk indicators with reduction limb defects, data on 453 cases of reduction limb defects and their time-area matched pair controls from the Finnish Registry of Congenital Malformations was studied. A multivariate analysis of the earlier reported associations was performed. This analysis showed that the following risk indicators were associated with the defects: high birth order, threatened abortion, low placental weight, low birth weight, previous malformations in the family, influenza during early pregnancy, other infectious diseases, and mother's alcohol consumption during pregnancy.