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Biomedical subjects

S E Vollset

Publications and source records attributed to S E Vollset.

At least 19 recordsLinked to original sources

Plasma homocysteine levels and mortality in patients with coronary artery disease.

BACKGROUND: Elevated plasma homocysteine levels are a risk factor for coronary heart disease, but the prognostic value of homocysteine levels in patients with established coronary artery disease has not been defined. METHODS: We prospectively investigated the relation between plasma total homocysteine levels and mortality among 587 patients with angiographically confirmed coronary artery disease. At the time of angiography in 1991 or 1992, risk factors for coronary disease, including homocysteine levels, were evaluated. The majority of the patients subsequently underwent coronary-artery bypass grafting (318 patients) or percutaneous transluminal coronary angioplasty (120 patients); the remaining 149 were treated medically. RESULTS: After a median follow-up of 4.6 years, 64 patients (10.9 percent) had died. We found a strong, graded relation between plasma homocysteine levels and overall mortality. After four years, 3.8 percent of patients with homocysteine levels below 9 micromol per liter had died, as compared with 24.7 percent of those with homocysteine levels of 15 micromol per liter or higher. Homocysteine levels were only weakly related to the extent of coronary artery disease but were strongly related to the history with respect to myocardial infarction, the left ventricular ejection fraction, and the serum creatinine level. The relation of homocysteine levels to mortality remained strong after adjustment for these and other potential confounders. In an analysis in which the patients with homocysteine levels below 9 micromol per liter were used as the reference group, the mortality ratios were 1.9 for patients with homocysteine levels of 9.0 to 14.9 micromol per liter, 2.8 for those with levels of 15.0 to 19.9 micromol per liter, and 4.5 for those with levels of 20.0 micromol per liter or higher (P for trend=0.02). When death due to cardiovascular disease (which occurred in 50 patients) was used as the end point in the analysis, the relation between homocysteine levels and mortality was slightly strengthened. CONCLUSIONS: Plasma total homocysteine levels are a strong predictor of mortality in patients with angiographically confirmed coronary artery disease.

Adult

Infant mortality in Norway and Sweden 1975-88: a cause-specific analysis of an increasing difference.

In a previous article, a high infant mortality was reported in the 1980s in Norway compared with Sweden. The aim of the present study was to assess secular trends in this difference, and to clarify whether the difference was confined to particular causes of death. Mortality rates, ratios of mortality rates and numbers of excess deaths were calculated on the basis of birth records comprising all livebirths in Norway and Sweden during the two periods 1975-79 and 1985-88. From the first to the second period, the infant mortality ratio for Norway to Sweden increased from 1.22 to 1.45 for single births, and from 1.23 to 1.54 for twin births. Increasing mortality ratios were observed for all ages at death. These were lowest in the early neonatal period (1.09 and 1.20 respectively) and highest in the postneonatal period (1.53 and 1.78 respectively). Within each cause of death category, the mortality rate in Norway was equal to or higher than the rate in Sweden. The highest mortality rate ratios were observed for sudden infant death syndrome (SIDS), 2.44 and 2.46 respectively, for the two time periods. SIDS was also the single cause of death that gave the largest contribution to the Norwegian excess mortality (45% and 53% overall, 65% and 78% for postneonatal deaths, and 65% and 79% for birthweights above 2500 g). In the second period, the excess SIDS mortality in Norway pertained mainly to infants of young mothers, infants of birth order two or more and twin births. An adverse trend for infants of young mothers in Norway was also observed in non-SIDS deaths. This suggests that in Norway, preventive health care should be improved, particularly for young mothers and their infants.

Birth Order

Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study.

The health consequences of coffee drinking remain controversial. We report on an association between coffee consumption and the concentration of total homocysteine (tHcy) in plasma, a risk factor for cardiovascular disease and for adverse pregnancy outcome. The study population consisted of 7589 men and 8585 women 40-67 y of age and with no history of hypertension, diabetes, ischemic heart disease, or cerebrovascular disease. They were recruited from Hordaland county of western Norway in 1992-1993. Daily use of coffee was reported by 89.1% of the participants, of whom 94.9% used caffeinated filtered coffee. There was a marked positive dose-response relation between coffee consumption and plasma tHcy, which was stronger than the relation between coffee and total serum cholesterol. In 40-42-y-old men, mean tHcy was 10.1 mumol/L for nonusers and 12.0 mumol/L for drinkers of > or = 9 cups of coffee/d. Corresponding tHcy concentrations in 40-42-y-old women were 8.2 and 10.5 mumol/L, respectively. Although coffee drinking was associated with smoking and lower intake of vitamin supplements and fruit and vegetables, the coffee-tHcy association was only moderately reduced after these variables were adjusted for. The combination of cigarette smoking and high coffee intake was associated with particularly high tHcy concentrations. A strong inverse relation between tea and tHcy concentration in univariate analysis was substantially attenuated after smoking and coffee drinking were adjusted for. The results of the present report should promote future studies on tHcy as a possible mediator of adverse clinical effects related to heavy coffee consumption.

Adult

Elevated plasma total homocysteine and C677T mutation of the methylenetetrahydrofolate reductase gene in patients with spina bifida.

Total plasma homocysteine (tHcy) was significantly higher in 28 children with spina bifida (median 6.05 mumol/l) as compared with 76 controls (median 4.94 mumol/l). This difference was confined to a subgroup of patients (16/28) with one or two C677T-mutated alleles in the methylenetetrahydrofolate reductase gene. Since we found no significant difference between patients and controls in serum folate, erythrocyte folate, serum cobalamin or serum methylmalonic acid, which were within the normal range for both patients and controls, the elevated tHcy could not be attributed to vitamin deficiencies. Our findings point to an additional genetic defect involving folate-dependent enzymes in a subgroup of patients with neural-tube defects.

5,10-Methylenetetrahydrofolate Reductase (FADH2)

Smoking and ulcer perforation.

BACKGROUND: The use of ulcerogenic drugs is the only well documented risk factor for peptic ulcer perforation, but accounts for only a quarter of the events. Smoking is a well known risk factor for uncomplicated ulcer disease, and patients with ulcer bleeding have increased death rates from smoking related disorders. AIM: To assess the role of smoking in ulcer perforation. SUBJECTS: A total of 168 consecutive patients with gastroduodenal ulcer perforation and 4469 control subjects from a population based health survey. METHODS: The association between ulcer perforation and smoking habits was analysed by logistic regression while adjusting for age and sex. RESULTS: Current smoking increased the risk for ulcer perforation 10-fold in the age group 15-74 years (OR 9.7, 95% CI 5.9 to 15.8) and there was a highly significant dose-response relationship (p < 0.001). The results were similar in men (OR 9.3, 95% CI 4.9 to 17) and women (OR 11.6, 95% CI 5.3 to 25), and for gastric (OR 10.5, 95% CI 4.5 to 25) and duodenal (OR 8.6, 95% CI 4.9 to 15.4) ulcer perforation. No increase in risk was found in previous smokers (OR 0.8, 95% CI 0.2 to 2.2). CONCLUSION: Our findings suggest that smoking is a causal factor for ulcer perforation and accounts for a major part of ulcer perforations in the population aged less than 75 years.

Adolescent

Antibiotic prophylaxis in total hip arthroplasty. Review of 10,905 primary cemented total hip replacements reported to the Norwegian arthroplasty register, 1987 to 1995.

We have assessed the effect of different regimes of antibiotic prophylaxis on the survival of total hip implants, comparing antibiotics administered both systemically and in the bone cement, systemically only, in the bone cement only and with no antibiotics given. We studied 10,905 primary cemented total hip replacements, performed for osteoarthritis of the hip and reported to the Norwegian arthroplasty register between 1987 and 1995. Cox-estimated failure-rate ratios (FRR) are presented with adjustment for gender, age, the brand of cement, the prosthesis, the type of operating theatre and the operating time. For revisions performed for infection (39 operations), the lowest rate of revision was found among patients receiving antibiotic-containing cement plus systemic antibiotics (n = 5804). The revision rate for the 4586 patients receiving systemic antibiotics only was 4.3 times greater (95% CI 1.7 to 11.0, p = 0.001); in 239 with antibiotics in the bone cement only it was 6.3 times greater (CI 1.6 to 25.0, p = 0.003); and in the 276 who did not receive antibiotics it was by 11.5 times greater (CI 2.1 to 63.0, p = 0.002). Adjustment for the total amount of systemic antibiotic administered did not change the results. We also observed an increased revision rate for aseptic loosening (109 operations) comparing the systemic-only (FRR = 1.8, CI 1.1 to 2.9, p = 0.01) and the cement-only regimes (FRR = 2.6, CI 1.2 to 5.9, p = 0.02) with the combined dosage. Our findings show that systemic antibiotics combined with antibiotic-containing bone cement led to fewer revisions than the other methods.

Antibiotic Prophylaxis

Patient-related risk factors for early revision of total hip replacements. A population register-based case-control study of 674 revised hips.

In this population register-based, matched case-control study, we assessed patient-related factors and early risk of revision after total hip replacement (THR). Information was obtained via a mall survey among patients reported to the Norwegian Arthroplasty Register during the period 1987-1993. The study included 674 revised hips, as cases, and 1,343 hips with a primary operation only, as controls. Completed questionnaires were received from 81% of the 2,017 individual cases and controls. We identified a set of patient-related factors associated with poor THR prognosis. Increasing weight was a risk factor among male patients older than 67 years who were more than 1.77 m tall (p = 0.01). Smoking had no overall effect, but former heavy smokers had an increased risk of 2.8 compared to never-smokers. Alcohol intake was associated with an increased risk of dislocation. Revision due to infection was commoner among patients taking anti-diabetic drugs (OR = 14) than among patients taking no medication. An increased overall revision risk was found among patients using systemic steroids (OR = 2.8) or local pulmonary steroids (OR = 6.0). The risk also increased in male patients performing regular exercise before the primary operation (OR = 2.6), and in female patients of working-age doing heavy work (OR = 1.9).

Adolescent

Determinants and vitamin responsiveness of intermediate hyperhomocysteinemia (> or = 40 micromol/liter). The Hordaland Homocysteine Study.

From 1992-93, we screened 18,043 subjects, aged 40-67 yr, and found 67 cases (0.4%) with total plasma homocysteine (tHcy) > or = 40 micromol/liter. Compared to 329 controls, the cases had lower plasma folate and cobalamin levels, lower intake of vitamin supplements, consumed more coffee, and were more frequently smokers. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase gene was observed in 73.1% of the cases and 10.2% of the controls. Only seven cases with cobalamin deficiency and one with homocystinuria received specific therapeutic instructions. 2 yr after the screening, 58 subjects were reinvestigated. 41 still had tHcy > 20 micromol/liter, and in 37 of these, intervention with low dose folic acid (0.2 mg/d) was started. Notably, 34 of 37 (92%) had homozygosity for the C677T mutation. Plasma tHcy was reduced in all but two after 7 wk, and became normal within 7 mo in 21 of 37 subjects. Most of the remaining subjects obtained a normal tHcy level with 5 mg/d of folic acid. We conclude that most subjects with hyperhomocysteinemia > or = 40 micromol/liter in the general population have the C677T mutation combined with low folate status. Daily supplement of low dose folic acid will reduce and often normalize their tHcy level.

Adult

[The hip registry. Good economy for society].

As many as 33,656 total hip arthroplasties (THA) have been recorded in the Norwegian Arthtroplasty Register from the start in September 1987 until January 1994. The annual costs for the about 5,500 THA performed in Norway (4.2 million inhabitants) are 72 million USD. We have documented before that some types of uncemented prostheses (Ti-Fit/ Bio-Fit (cup/stem) and Coxa/Femora) and types of cements (low-viscosity and Boneloc) show higher revision rates than others do. In this paper the costs of these "inferior" implants are estimated. The "inferior" implants were compared with a reference-THA (the Charnley prosthesis with antibiotic-containing high viscosity cement and with systemic antibiotic-prophylaxis (n = 4,970)). In addition, based on data in the literature, comparisons have been made for two earlier commonly used prostheses in Norway: The Christiansen prosthesis (n = 6,500) and the Wagner double-cup prosthesis (n = 2,200). For the period 1987-93, the annual over-all extra cost of using other implants than the reference-THA was 1.71 mill. USD for the first 3-5 years postoperatively. For the Christiansen and the Wagner prostheses the annual extra costs were estimated to 2.65 and 2.38 mill. USD respectively. By documenting poor results early the Register helps to stop the use of the inferior prostheses and cements, and thus reduce both the number of revisions, and, most important, the suffering of the patients.

Costs and Cost Analysis

The Hordaland homocysteine study: the opposite tails odds ratios reveal differential effects of gender and intake of vitamin supplements at high and low plasma total homocysteine concentrations.

Both female sex and intake of vitamin supplements are known to be associated with a low mean plasma homocysteine level. In the present study, we used multiple logistic regression analyses to investigate the relation between these two variables and plasma homocysteine at the extreme ends of the plasma homocysteine distribution curve. We propose that the obtained set of odds ratios for hyper- and hypohomocysteinemia, referred to as the opposite tails odds ratios, may be an alternative approach to study determinants of plasma homocysteine.

Adult

The economic impact of failures in total hip replacement surgery: 28,997 cases from the Norwegian Arthroplasty Register, 1987-1993.

The Norwegian Arthroplasty Register was established in 1987. Until January 1994, approximately 200 different implant combinations had been used in total hip replacements (THR) in Norway. About 5,500 THR were performed each year in this period with a total cost of 70 million USD per year. We analyzed the economic consequences related to the use of some inferior primary hip arthroplasties in this period. As the reference arthroplasty, we chose the most commonly used prosthesis in Norway, i.e., the Charnley prosthesis fixed with high viscosity cement containing antibiotic and with systemic antibiotic prophylaxis (n 4,970). We compared this reference group to all other primary THR registered in the same time period (n 24,027), and to the following sub-groups of primary THR: 1) uncemented Ti-Fit/ Bio-Fit (acetabulum/femur) combination (n 173), 2) uncemented Coxa/Femora combination (n 153), 3) THR with low-viscosity cement (n 1,807) and 4) THR with Boneloc cement (n 1,250). We estimated the number of additional revisions compared to the reference arthroplasty after a follow-up of 3-5 years in the different groups, with adjustment for age, sex and diagnosis. The direct extra revision costs were calculated. Compared to the reference arthroplasty, the group of all other primary THR gave an extra revision cost estimated at about 1.7 million USD per year. About 1,000 uncemented Bio-Fit femoral prostheses have been applied in Norway, including those implanted before the registration started (1985-1987). The extra revision costs the first postoperative years for these 1,000 prostheses amount to about 0.7 million USD per year. Corresponding figures in the Coxa/ Femora group were 0.08 million USD, in the group with low-viscosity cement, 0.3 million USD and in the Boneloc group, 0.4 million USD per year.

Aged

Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study.

OBJECTIVE: To estimate the relations between established cardiovascular risk factors and total homocysteine (tHcy) in plasma. DESIGN: Health examination survey by the Norwegian Health Screening Service in 1992 and 1993. SETTING: General community, Hordaland County of Western Norway. PARTICIPANTS: A total of 7591 men and 8585 women, 40 to 67 years of age, with no history of hypertension, diabetes, coronary heart disease, or cerebrovascular disease were included. MAIN OUTCOME MEASURE: Plasma tHcy level. RESULTS: The level of plasma tHcy was higher in men than in women and increased with age. In subjects 40 to 42 years old, geometric means were 10.8 mumol/L for 5918 men and 9.1 mumol/L for 6348 women. At age 65 to 67 years, the corresponding tHcy values were 12.3 mumol/L (1386 men) and 11.0 mumol/L (1932 women). Plasma tHcy level increased markedly with the daily number of cigarettes smoked in all age groups. Its relation to smoking was particularly strong in women. The combined effect of age, sex, and smoking was striking. Heavy-smoking men aged 65 to 67 years had a mean tHcy level 4.8 mumol/L higher than never-smoking women aged 40 to 42 years. Plasma tHcy level also was positively related to total cholesterol level, blood pressure, and heart rate and inversely related to physical activity. The relations were not substantially changed by multivariate adjustment, including intake of vitamin supplements, fruits, and vegetables. CONCLUSIONS: Elevated plasma tHcy level was associated with major components of the cardiovascular risk profile, ie, male sex, old age, smoking, high blood pressure, elevated cholesterol level, and lack of exercise. These findings should influence future studies on the etiology and pathogenesis of cardiovascular disease.

Adult

Exact power computation for dose-response studies.

The toxicity of an agent or the therapeutic effect of a drug may be assessed by a dose-response study. We present a method for computing the exact power of exact and large sample statistical tests employed for binary response data from such a study. This method, based on recursive polynomial multiplications, enables fast computation of exact power for studies with up to a moderately large sample size. We demonstrate the efficiency of our method using three examples. The method is suitable for the design and power analysis of dose-response studies in which the usual asymptotic approximations are suspect.

Adenoma

Do reproductive factors influence colorectal cancer survival?

During 29 years follow up of 63,090 Norwegian women, 1347 women had a diagnosed cancer of the colon or rectum. Seven hundred and fifty-five of these women (56%) subsequently died of colorectal cancer. We investigated possible relationships between reproductive history and cancer survival and found little evidence that reproductive history is of prognostic value for colorectal cancer survival.

Adult

The effect of the type of cement on early revision of Charnley total hip prostheses. A review of eight thousand five hundred and seventy-nine primary arthroplasties from the Norwegian Arthroplasty Register.

We studied the survival of 8579 Charnley prostheses, in 7922 patients, according to the different types of cement that had been used. All of the patients had had a primary total hip replacement for primary coxarthrosis. The mean duration of follow-up was 3.2 years (range, zero to 6.4 years). The data were collected from the national Norwegian Arthroplasty Register. The duration of survival was defined as the time to revision due to aseptic loosening. The Kaplan-Meier estimate of survival at 5.5 years for the 1226 femoral components that had been implanted with low-viscosity cement was 94.1 per cent (95 per cent confidence interval, 92.1 to 96.2 per cent), compared with 98.1 per cent (95 per cent confidence interval, 97.5 to 98.6 per cent) for the 6589 components that had been implanted with high-viscosity cement (p < 0.0001). The remaining 764 femoral components had been implanted with Boneloc cement, which was classified as neither high nor low-viscosity, and these components were considered as a separate group in the analyses. The Boneloc cement had been used for only three years, and the two-year survival rate of these prostheses was 95.5 per cent (p < 0.0001). The cement contained an antibiotic in 2801 (42 per cent of the hips in which the femoral component had been implanted with high-viscosity cement, compared with only thirty (2 per cent) of those in which it had been implanted with low-viscosity cement.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetabulum

Early revision among 12,179 hip prostheses. A comparison of 10 different brands reported to the Norwegian Arthroplasty Register, 1987-1993.

On the basis of data from the Norwegian Arthroplasty Register during the period 1987-1993, we have compared times to revision for 10 different cemented total hip prostheses. A total of 11,169 patients, with 12,179 primary total hip replacements (THRs), performed with high viscosity cement for primary arthrosis and followed for a maximum of 6.4 years, were included in this study. The Kaplan-Meier estimate of the overall percentage revised after 5 years was 2.5 (95% Confidence Interval: 2.1-3.0). For the Charnley prosthesis (n 6,694), 2.9% were revised after 5 years (95% CI: 2.3-3.4). Using Cox regression to adjust for gender, age, type of cement and use of systemic antibiotic prophylaxis, the Charnley prosthesis was compared with the 9 other brands. The revision rate for the Spectron/ITH combination (Spectron acetabulum, ITH femur) (n 1,034) was only 0.35 (p 0.04) times that of the Charnley prostheses. The Elite/Charnley combination (Elite acetabulum, Charnley femur) (n 507) and the Müller Type prosthesis (n 116) showed poorer results with failure rates 2.3 (p 0.01) and 2.7 times (p 0.04) that of Charnley, respectively. Although the overall results for cemented THRs in general were good, clinically important differences in revision rates were demonstrated among the cemented prosthesis brands. Our findings underline the need for careful evaluation of different total hip replacements.

Hip Prosthesis

Revision for aseptic loosening of uncemented cups in 4,352 primary total hip prostheses. A report from the Norwegian Arthroplasty Register.

From September 1987 until January 1994 the Norwegian Arthroplasty Register recorded 5,021 primary total hip replacements performed with uncemented acetabular components. We compared the survival until revision for aseptic loosening of the cup, in the 11 commonest types (n 4,352). The overall cumulative revision rate for the acetabular components was 3.2% after 5 years and 7.1% after 6 years, with large differences among the designs. With the hydroxyapatite (HA)-coated cups and the hemispheric porous-coated cups, the failure rate was less than 0.1%. Of the unthreaded hemispheric porous-coated cups, Harris-Galante and Gemini (n 626), none had been revised, and of the HA-coated cups, Atoll and Tropic (n 1,943), only 1 had been revised. For the threaded uncoated metal-backed cups, the results varied from no revisions of the PM cups (n 148) to a cumulative 6-year revision rate of 21% for the Ti-Fit (n 300). The all-polyethylene Endler cups (n 334) had a cumulative revision rate of 14%. Women and patients with inflammatory arthritis had poorer results. However, the type and the design of the cups were of far greater importance for the results than patient-related factors.

Acetabulum