The predictive effect of body mass index on type 2 diabetes in the Norwegian women and cancer study

Background Several studies have analyzed the association of body mass index (BMI) with either the prevalence or incidence of type 2 diabetes (T2D), but no study from Europe or North America has yet analyzed and compared the association of BMI with both incident and prevalent T2D cases. Methods Stratified logistic regression was used to calculate odds ratios (OR), and stratified Cox proportional hazards regression was used to calculate hazard ratios (HR) of the effect of BMI on the prevalence, and incidence of T2D. Wald chi-square statistics were applied when comparing the risk estimates. Results Among prevalent T2D cases, overweight women (BMI 25–29.9 kg/m2) had an OR of 2.83 (95% confidence interval [CI], 1.92-4.18) and obese women (BMI ≥30 kg/m2) had an OR of 12.12 (95% CI, 8.32-17.68) when compared with normal weight women (BMI <25 kg/m2). Among incident T2D cases, overweight women had a HR of 5.01 (95% CI, 3.59-6.98) and obese women had a HR of 15.99 (95% CI, 11.39-22.46) when compared with normal weight women. After stratification by level of physical activity, and adjustment for age, smoking status, and education level, the Wald chi-square statistic for BMI was 180.90 for prevalent T2D cases, and 262.03 for incident T2D cases. Conclusion The predictive effect of BMI was found to be stronger for T2D incidence than T2D prevalence

Optimal starting point for antiretroviral HIV treatment in a town in Cameroon: a randomised controlled study

BACKGROUND: Optimal starting point for antiretroviral treatment (ART) has been uncertain. METHODS: Parallel group, single blind, randomised controlled study of adult HIV positive patients consulting at the Protestant Hospital, Ngaoundere, Cameroon in 2007-8. Simple randomisation of patients in WHO clinical stage 1-2 to start of ART early or deferred, i.e. when CD4 counts dropped below 350 versus 250 cells/mm(3), or when they reached clinical stage 3-4. Clinical follow-up every three months were offered for all patients. Main outcomes were clinical stage, CD4 differences and mortality. Of 424 consulting patients, most were excluded, mainly because they were already in WHO stage 3-4. Forty-four patients were randomised. RESULTS: In the ‘early’ group two patients died and five were lost to follow-up. In the ‘deferred’ group, six patients died and nine were lost to follow-up (Hazard ratio for death by early compared to deferred treatment 0.26, 95% confidence interval 0.05-1.29). Of the patients lost to follow-up, three patients in the ‘early’ group and four patients in the ‘deferred’ group were known to be alive when the study ended. Fourteen patients in the early group and 11 in the deferred group started ART. Twenty-two patients were evaluated clinically six to seven months after the study period was terminated. Except for one patient with AIDS, these were all still in clinical stage 1-2. CONCLUSIONS: In our small sample, relative risk for death did not differ significantly, but deferred treatment seemed to carry no increased survival or other clinical advantage. During the study period, other studies made WHO change its guidelines to conform to our early treatment. The tendency in our study lends support to this policy. TRIAL REGISTRATION: ISRCTN22114173 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2458-14-828) contains supplementary material, which is available to authorized users

Physical activity and mortality among Norwegian women – the Norwegian Women and Cancer Study

Physical activity (PA) and its relationship with all-cause mortality suggest a strong and consistent inverse association. This study prospectively investigated the association between PA level and mortality among participants of the Norwegian Women and Cancer (NOWAC) Study. A total of 66,136 NOWAC participants were followed-up until December 31st 2008. PA level and possible confounding factors were obtained through a self-administered questionnaire at enrolment. Cox proportional hazards regression was used to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD) and cancer mortality and PA levels defined from 1 to 10 on a global scale. PA levels 1–4 were associated with a significantly increased risk of all-cause mortality (level 1 RR = 2.35; 95% CI: 1.94–2.84, level 2 RR = 1.71; 95% CI: 1.45–2.00, level 3 RR = 1.30; 95% CI: 1.14–1.49, level 4 RR = 1.07; 95% CI: 0.95–1.22), compared with PA level 5. CVD mortality risk increased in PA levels 1–3 (level 1 RR = 3.50; 95% CI: 2.41–5.10, level 2 RR = 1.50; 95% CI: 0.99–2.25, level 3 RR = 1.12; 95% CI: 0.79–1.60) as did cancer mortality risk (RR = 1.32; 95% CI: 0.96–1.81, RR = 1.48; 95% CI: 1.19–1.84, RR = 1.26; 95% CI: 1.06–1.50, respectively). The magnitude of the associations was consistent across strata of age, smoking, and body mass index. The population attributable fractions for PA levels 1–4 were: all-cause mortality, 11.5%; CVD mortality, 11.3%; cancer mortality, 7.8%. There is a significant trend of increased risk of all-cause, CVD and cancer mortality in relation to low PA levels among Norwegian women

Lifestyle risk factors of self-reported fibromyalgia in the Norwegian Women and Cancer (NOWAC) study

Background While the aetiology of fibromyalgia syndrome (FM) remains unknown, lifestyle factors have been linked to the disorder. However, there are few studies on the association between lifestyle factors and FM, thus we examine the risk of self-reported fibromyalgia given selected lifestyle factors. Methods We used data from 75,485 participants in the Norwegian Women and Cancer study. Information on FM and the lifestyle factors body mass index (BMI), physical activity level, smoking status/intensity, and alcohol consumption were obtained from baseline and follow-up questionnaires. We used Cox proportional hazards model to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Results After a median follow-up time of 10 years, we observed 2,248 cases of self-reported fibromyalgia. Overweight (BMI 25-29.9 kg/m2 ) and obese (BMI≥30 kg/m2 ) women had a relative risk of 1.34 (95% CI 1.21–1.47) and 1.62 (95% CI 1.41–1.87), respectively, compared to women with normal weight (BMI 18.5–24.9 kg/m2 ). Very low physical activity level (1–2) was associated with a 31% higher risk of self-reported fibromyalgia (HR 1.31, 95% CI 1.09–1.57) when compared to moderate physical activity level (5–6). There was a strong dose-response relationship between smoking status/intensity and self-reported fibromyalgia (p for trend<0.001). Compared with moderate alcohol consumption (4.0–10 g/day), the risk of self-reported FM was 72% (HR 1.72; 95% CI 1.45–2.03) higher among teetotallers, and 38% (HR 1.38, 95% CI 1.23–1.54) higher among those with low consumption (0.1–3.9 g/day). Conclusions Overweight and obesity, very low physical activity level, smoking, and alcohol consumption were associated with an increased risk of self-reported FM

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian women and cancer study: A population-based prospective study

Source at https://doi.org/10.1186/1472-6874-14-48. Background: Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. Methods: A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. Results: During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. Conclusions: These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.<p

Coffee consumption and overall and cause-specific mortality: the Norwegian Women and Cancer Study (NOWAC)

Coffee consumption has previously been reported to reduce overall and cause-specific mortality. We aimed to further investigate this association by coffee brewing methods and in a population with heavy coffee consumers. The information on total, filtered, instant, and boiled coffee consumption from self-administered questionnaires was available from 117,228 women in the Norwegian Women and Cancer (NOWAC) Study. We used flexible parametric survival models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular, and cancer mortality by total coffee consumption and brewing methods, and adjusted for smoking status, number of pack-years, age at smoking initiation, alcohol consumption, body mass index, physical activity, and duration of education. During 3.2 million person-years of follow-up, a total of 16,106 deaths occurred. Compared to light coffee consumers (≤ 1 cup/day), we found a statistically significant inverse association with high-moderate total coffee consumption (more than 4 and up to 6 cups/day, HR 0.89; 95% CI 0.83–0.94) and all-cause mortality. The adverse association between heavy filtered coffee consumption (> 6 cups/day) and all-cause mortality observed in the entire sample (HR 1.09; 95% CI 1.01–1.17) was not found in never smokers (HR 0.85; 95% CI 0.70–1.05). During the follow-up, both high-moderate total and filtered coffee consumption were inversely associated with the risk of cardiovascular mortality (HR 0.79; 95% CI 0.67–0.94; HR 0.80; 95% CI 0.67–0.94, respectively). The association was stronger in the analyses of never smokers (> 6 cups of filtered coffee/day HR 0.20; 95% CI 0.08–0.56). The consumption of more than 6 cups/day of filtered, instant, and coffee overall was found to increase the risk of cancer deaths during the follow-up. However, these associations were not statistically significant in the subgroup analyses of never smokers. The data from the NOWAC study indicate that the consumption of filtered coffee reduces the risk of cardiovascular deaths. The observed adverse association between coffee consumption and cancer mortality is most likely due to residual confounding by smoking

Risk of lung cancer and physical activity by smoking status and body mass index, the Norwegian Women and Cancer Study

We aimed to investigate physical activity (PA) and risk of different histological subtypes of lung cancer according to smoking status and body mass index using repeated measurements in a large cohort of women in Norway. The study sample for the multiple imputation analyses consisted of 86,499 and for the complete-case analysis 80,802 women. Repeated measurements of PA level, smoking habits, weight, and height were available for 54,691 women (63.2%), who were included in repeated measurement analyses combined with multiple imputation to address attrition. Cox proportional hazards regression models were used to calculate hazard ratios with 95% confidence intervals. During a median follow-up of 12.9years, 866 cases of primary lung cancer were identified. We found an inverse association between PA and lung cancer overall. The results were consistent from multiple imputed data analysis to complete-case analysis of PA and possible confounders. We observed a similar trend for adenocarcinoma, but not for squamous cell or small cell carcinomas. Our findings suggest a more pronounced association between lung cancer overall and PA levels in current and former smokers, and in normal-weight and overweight participants with increasing PA levels. The potential of a modifiable lifestyle factor as PA to reduce the risk of lung cancer independently of smoking status is important in public health.Peer reviewe

Greedy knot selection algorithm for restricted cubic spline regression

Non-linear regression modeling is common in epidemiology for prediction purposes or estimating relationships between predictor and response variables. Restricted cubic spline (RCS) regression is one such method, for example, highly relevant to Cox proportional hazard regression model analysis. RCS regression uses third-order polynomials joined at knot points to model non-linear relationships. The standard approach is to place knots by a regular sequence of quantiles between the outer boundaries. A regression curve can easily be fitted to the sample using a relatively high number of knots. The problem is then overfitting, where a regression model has a good fit to the given sample but does not generalize well to other samples. A low knot count is thus preferred. However, the standard knot selection process can lead to underperformance in the sparser regions of the predictor variable, especially when using a low number of knots. It can also lead to overfitting in the denser regions. We present a simple greedy search algorithm using a backward method for knot selection that shows reduced prediction error and Bayesian information criterion scores compared to the standard knot selection process in simulation experiments. We have implemented the algorithm as part of an open-source R-package, knutar