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Biomedical subjects

Håkon K Gjessing

Publications and source records attributed to Håkon K Gjessing.

11 recordsLinked to original sources

Smoking and deaths between 40 and 70 years of age in women and men.

BACKGROUND: The vast scientific literature on smoking and health contains few large studies with direct estimates of long-term mortality by smoking habits. Data have been lacking, particularly for women. OBJECTIVE: To study smoking and deaths and causes of death in women and men of middle age (40 to 70 years of age). DESIGN: Population-based cohort study. SETTING: Norway (the Norwegian Counties Study). PARTICIPANTS: 24,505 women and 25,034 men who were born between 1925 and 1941. MEASUREMENTS: Initial information on smoking habits was collected between 1974 and 1978. Smoking status was also assessed about 5 years and 10 years after the first examination. Death during 1974 to 2000 was studied by using death certificate information. RESULTS: During follow-up, 2333 women and 4680 men died in middle age. Among women and men, 9% and 14% of never smokers, respectively, and 26% and 41% of continuing heavy smokers (> or =20 cigarettes per day), respectively, died in middle age. Years of life lost among heavy smokers between 40 and 70 years of age were 1.4 years in women and 2.7 years in men, compared with never smokers. Rates of smoking-associated lung cancer were similar in women and men, while lower cardiovascular mortality rates in women explained most of the difference in smoking-associated all-cause mortality between men and women. LIMITATIONS: Data on changes in smoking habits after the baseline examination were not available for all participants and for the last 15 years of follow-up. Mortality levels in middle age may not apply to non-Norwegian populations. CONCLUSIONS: Continuing smoking strongly increased and smoking cessation decreased the risk for death between 40 and 70 years of age for both women and men. Despite similar rates for lung cancer death, women who smoked had lower mortality rates in middle age than men with similar smoking histories due to fewer cardiovascular deaths in women.

Adult↗

Likelihood ratio tests in behavioral genetics: problems and solutions.

The likelihood ratio test of nested models for family data plays an important role in the assessment of genetic and environmental influences on the variation in traits. The test is routinely based on the assumption that the test statistic follows a chi-square distribution under the null, with the number of restricted parameters as degrees of freedom. However, tests of variance components constrained to be non-negative correspond to tests of parameters on the boundary of the parameter space. In this situation the standard test procedure provides too large p-values and the use of the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC) for model selection is problematic. Focusing on the classical ACE twin model for univariate traits, we adapt existing theory to show that the asymptotic distribution for the likelihood ratio statistic is a mixture of chi-square distributions, and we derive the mixing probabilities. We conclude that when testing the AE or the CE model against the ACE model, the p-values obtained from using the chi(2)(1 df) as the reference distribution should be halved. When the E model is tested against the ACE model, a mixture of chi(2)(0 df), chi(2)(1 df) and chi(2)(2 df) should be used as the reference distribution, and we provide a simple formula to compute the mixing probabilities. Similar results for tests of the AE, DE and E models against the ADE model are also derived. Failing to use the appropriate reference distribution can lead to invalid conclusions.

Analysis of Variance↗

Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study.

BACKGROUND: Plasma total homocysteine (tHcy) has been associated with hip fracture but not directly with bone mineral density (BMD). We examined the association of hip BMD with levels of plasma tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C polymorphisms. METHODS: Bone mineral density was measured between 1997 and 2000 in 2268 men and 3070 women, aged 47 to 50 and 71 to 75 years, from the Hordaland Homocysteine Study cohort. Low BMD was defined as BMD in the lowest quintile for each sex and age group. Linear, logistic, and generalized additive regression models were used. RESULTS: Plasma levels of tHcy were inversely related to BMD among middle-aged and elderly women (P<.001) but not among men. The multiple adjusted odds ratio for low BMD among subjects with high (>or=15 micromol/L [>or=2.02 mg/L]) compared with low (<9 micromol/L [<1.22 mg/L]) tHcy level was 1.96 (95% confidence interval, 1.40-2.75) for women and was not significant for men. Additional adjustments for plasma folate level or intake of calcium and vitamin D did not substantially alter the results. Plasma folate level was associated with BMD in women only. We observed no association between BMD and vitamin B12 level or the MTHFR polymorphisms. CONCLUSIONS: Elevated tHcy and low folate levels were associated with reduced BMD in women but not in men. These findings suggest that tHcy may be a potential modifiable risk factor for osteoporosis in women.

Age Distribution↗

Patterns and predictors of folic acid supplement use among pregnant women: the Norwegian Mother and Child Cohort Study.

BACKGROUND: Patterns and predictors of maternal folic acid supplement use have not been examined in large prospective studies of pregnant women. OBJECTIVE: We examined the patterns and predictors of maternal folic acid supplement use from 2 mo before pregnancy through the eighth month of pregnancy. DESIGN: Data from 22 500 women in the Norwegian Mother and Child Cohort Study with deliveries recorded in 2000-2003 were analyzed. RESULTS: Folic acid supplement use increased from 11.8% at 2 mo before pregnancy to 46.9% at gestational month 3, but decreased to 26.0% at gestational month 8. Of 16 116 women (71.6%) who had taken folic acid supplements at some time before or during pregnancy, 72.4% had started use after becoming pregnant. Ten percent of the women had used supplements regularly from 1 mo before pregnancy throughout the first trimester. These women more frequently reported higher maternal and paternal education, planned pregnancies, infertility treatments, or chronic diseases. They were also more likely to be older, married, and nonsmokers and to have higher income and lower parity. CONCLUSIONS: Most women started folic acid supplementation too late with respect to the prevention of neural tube defects. More effective intervention programs to improve periconceptional intakes of folic acid are needed and should consider both demographic and socioeconomic factors.

Adult↗

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

BACKGROUND: A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma. OBJECTIVES: To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk. METHODS: We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif). RESULTS: ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027). CONCLUSION: Variation in arginase genes may contribute to asthma and atopy in children.

Adolescent↗

Folate supplementation and twin pregnancies.

BACKGROUND: Women in many countries are advised to increase their folate intake to lower the risk of neural tube defects. For this purpose several countries add folate to the flour. Therefore, it is important to monitor possible adverse effects of this B vitamin. We have assessed the effect of folate on twin pregnancies. METHODS: We conducted a retrospective, population-register based study of 176,042 women who gave birth from December 1998 through the end of 2001. Use of folate and multivitamin supplements was recorded on the mandatory birth notification form of the Medical Birth Registry of Norway. Pregnancies after in vitro fertilization (IVF) were reported separately. RESULTS: With adjustment for maternal age and parity, we observed an increased risk of twin pregnancies associated with preconceptional use of folate (odds ratio = 1.59; 95% confidence interval = 1.41-1.78). This association was largely explained by confounding with IVF pregnancies, which were strongly associated both with twin pregnancies and folate use. After exclusion of known IVF pregnancies, and accounting for underreporting of both IVF pregnancies and folate use, the risk was no longer elevated (1.02; 0.85-1.24). Weak associations with twin pregnancies were observed for use of multivitamins and folate during pregnancy, but could be due to increased use of vitamins after a recognized twin pregnancy. CONCLUSIONS: The association between preconceptional folate use and twin pregnancies was strongly confounded by IVF. After accounting for IVF pregnancies and underreporting, we found no evidence for an association between preconceptional folate supplements and twinning.

Adult↗

Dependency issues in survival analyses of 55,782 primary hip replacements from 47,355 patients.

Artificial hip joints are used in only one hip for about 85 per cent of the patients and in both hips (bilateral) for about 15 per cent of the patients. The occurrence of bilateral prostheses and the influence they have in survival analyses of joint arthroplasties are seldom considered. In this study we therefore focus on issues related to bilateral primary hip prostheses, time to revision surgery, and some commonly used statistical methods. We used information from 47,355 patients with 55,782 primary hip prostheses reported to the Norwegian Arthroplasty Register between 1987 and 2000. Due to the large number of diagnoses, fixation techniques for the prostheses, and combination of prostheses brands, we furthermore considered a 'homogeneous' subset of 8703 prostheses from 7930 patients with primary osteoarthritis, and Charnley prosthesis fixed with antibiotic-containing Palacos cement. Kaplan-Meier curves for all prostheses, ignoring that some patients have bilateral prostheses, were compared with Kaplan-Meier curves using only the first inserted prostheses, and with survival curves modified for patients with bilateral prostheses. Cox regression analyses were used to assess explanatory variables and to adjust for confounding factors. The results from the ordinary Cox regression analyses were compared with results from a marginal model, a shared gamma frailty model, and a model using a time dependent covariate to condition on failures in the opposite hip. We found no practical difference between the three calculated survival curves for the hip replacement data. The ordinary Cox-model and the marginal model gave equivalent results. In the shared gamma frailty model estimates for the risk factors were comparable with the former two approaches. The estimated frailty variance was higher when all data were used, even after adjustment for confounding factors. For the 'homogeneous' data the estimated frailty variance was negligible. Using a time dependent covariate to condition on previous revisions in the opposite hip, we found a higher risk of revision for the remaining primary hip prosthesis if the opposite hip had been revised (RR = 3.49, p < 0.0001). There was no difference in risk for revision between right and left hip prostheses. If the time interval between the two primary operations was more than two years, for the full data, the first hip prosthesis had an increased risk of revision compared to prostheses in patients with only one prosthesis (RR = 1.25, p = 0.01). For the 'homogeneous' data no statistically significant difference was found between unilateral and bilateral prostheses. A revision in one hip, for patients with bilateral prostheses, is a risk factor for revision of the other hip. Thus, in analyses of prostheses survival, dependencies between two hip prostheses from one patient should be considered. However, ignoring possible dependencies does not necessarily have an impact on the results on standard risk factors.

Aged↗

Analysis of testicular cancer data using a frailty model with familial dependence.

Previously published papers have indicated a fairly strong familial dependence intesticular cancer patients. This is particularly evident in brothers. We have applied a frailty model with familial dependence to family data on brothers of testicular cancer patients from the Norwegian Radium Hospital. The model is a two-level frailty, with variation in susceptibility at both the family and the individual level. Specifically, the frailty variable is assumed to be compound Poisson distributed to allow individuals to be non-susceptible. The underlying Poisson parameter is gamma distributed to model how testicular cancer is distributed among families. This is an extension of a previous compound Poisson frailty model developed for individual testicular cancer data, and an alternative to traditional modelling of survival time family data. The likelihood construction and ascertainment problems are looked at in detail. To avoid ascertainment bias, the likelihood is based on the probability of observing the disease status for each brother in a family, given that at least one brother is ascertained. The estimated relative risk for brothers is 7.4. This paper expands on a previous analysis of the data by using a frailty model, which makes it possible to examine how the cancer is distributed among families. The estimated gamma-shaped parameter is 0.151 (95 per cent confidence interval 0.078-0.294), and this indicates that in order to obtain the high relative risks observed for brothers of testicular cancer patients, the distribution of susceptibility has to be strongly skewed among the families. The vast majority of families have a very low risk and a small proportion have a high risk. In addition, a quantity similar to the relative risk is derived to show that the susceptibility is skewly distributed also if the Poisson parameter is Bernoulli or stable distributed. This indicates that the results are valid also if other distributions are used to model familial dependence in the compound Poisson frailty model.

Genetic Predisposition to Disease↗

Survival models based on the Ornstein-Uhlenbeck process.

When modelling survival data it may be of interest to imagine an underlying process leading up to the event in question. The Ornstein-Uhlenbeck process is a natural model to consider in a biological context because it stabilizes around some equilibrium point. This corresponds to the homeostasis often observed in biology, and also to some extent in the social sciences. First, we study the first-passage time distribution of an Ornstein-Uhlenbeck process, focussing especially on what is termed quasi-stationarity and the various shapes of the hazard rate. Next, we consider a model where the individual hazard rate is a squared function of an Ornstein-Uhlenbeck process. We extend known results on this model. The results on quasi-stationarity are relevant for recent discussions about mortality plateaus. In addition, we point out a connection to models for short-term interest rates in financial modeling.

Humans↗

Protection from natural infections with enterotoxigenic Escherichia coli: longitudinal study.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhoea and diarrhoeal deaths in children living in developing countries and of travellers' diarrhoea. During the past 25 years, vaccine development efforts have been focused on induction of protective immunity against surface colonisation factors (CFs) and the heat-labile enterotoxin. Although vaccines that induce immunity to heat-labile toxin offer protection against diarrhoea from ETEC that produce this toxin, the benefit of including CF antigens remains uncertain. We aimed to estimate the protection that natural ETEC infections induce against new infections. METHODS: In Guinea-Bissau, we followed up 200 neonates until up to age 2 years, most of whom were breastfed throughout the study. We collected stool specimens from the children every week irrespective of whether they had diarrhoea. As a measure of protection, we used Cox regression models to estimate the change in infection rates after a primary ETEC infection. We thus estimated the protection attributable to CFs, toxins, and to any other factors that could be shared by ETEC with the same toxin-CF profile. FINDINGS: ETEC infections induced a 47% (95% CI 12 to 69) protection against new infections with ETEC that had the same toxin-CF profile; the corresponding estimate attributable to CFs was -1% (-40 to 27). Infection with heat-labile toxin-positive ETEC conferred a 45% (-1 to 70) protection against symptomatic infections with ETEC positive for this toxin. INTERPRETATION: For breastfed children living in endemic areas, other antigens are substantially more important than CFs for induction of protective immunity against ETEC infection.

Diarrhea↗