Sensitivity of regression calibration to non‐perfect validation data with application to the Norwegian Women and Cancer Study

Measurement error occurs when we observe error‐prone surrogates, rather than true values. It is common in observational studies and especially so in epidemiology, in nutritional epidemiology in particular. Correcting for measurement error has become common, and regression calibration is the most popular way to account for measurement error in continuous covariates. We consider its use in the context where there are validation data, which are used to calibrate the true values given the observed covariates. We allow for the case that the true value itself may not be observed in the validation data, but instead, a so‐called reference measure is observed. The regression calibration method relies on certain assumptions.This paper examines possible biases in regression calibration estimators when some of these assumptions are violated. More specifically, we allow for the fact that (i) the reference measure may not necessarily be an ‘alloyed gold standard’ (i.e., unbiased) for the true value; (ii) there may be correlated random subject effects contributing to the surrogate and reference measures in the validation data; and (iii) the calibration model itself may not be the same in the validation study as in the main study; that is, it is not transportable. We expand on previous work to provide a general result, which characterizes potential bias in the regression calibration estimators as a result of any combination of the violations aforementioned. We then illustrate some of the general results with data from the Norwegian Women and Cancer Study. Copyright © 2015 John Wiley & Sons, Ltd.     

Dietary patterns and lifestyle factors in the Norwegian EPIC cohort: the Norwegian Women and Cancer (NOWAC) study

OBJECTIVE: To identify different dietary patterns in Norway using a combination of cluster and factor analysis. DESIGN: Cross-sectional study. SETTING: Nation-wide, population-based study. SUBJECTS: The Norwegian EPIC cohort is a subcohort of the Norwegian Women and Cancer study (NOWAC), and consist 37.226 women aged 41-56 y who answered a food frequency questionnaire (FFQ) in 1998. INTERVENTIONS: The associations among 50 food variables were first investigated by using principal component analysis. Five important factors were found. The five principal components were then used as input in the cluster analysis. Different socioeconomic and lifestyle variables were examined. RESULTS: Six clusters of dietary patterns were found, and were labelled accordingly: 'traditional fish eaters', 'healthy eaters', 'average, less fish, less healthy', 'Western', 'traditional bread eaters', and 'alcohol users'. The traditional fish eaters and the traditional bread eaters were both highly represented in the north and west of Norway and were more likely to be present among persons with lower income and lower education. The healthy and the alcohol drinkers were found mostly in the south and east and were more likely to have higher income. Persons in the alcohol group were more likely to be current smokers. The western group had the highest percentage of three or more persons in the household and the shortest time since last birth, indicating that families with children dominate this group. CONCLUSION: Our data indicate six different dietary patterns in Norway, each with different socio-demographic and lifestyle characteristics. SPONSORSHIP: The Norwegian Cancer Society (E 04038/006).     

Low ploidy megakaryocytes in steady-state rat bone marrow

The amount of DNA in individual megakaryocytes (MK) was measured by Feulgen photometry performed on smears of steady-state rat bone marrow. The MK were identified by acetylcholinesterase (ACHE) staining. The method described is particularly suitable in the study of immature MK, hitherto difficult to examine for DNA content. The main MK ploidies were 8N, 16N, and 32N, comprising 33.4% +/- 1.4%, 40.8% +/- 1.4%, and 17.9% +/- 1.3%, respectively, of the total MK numbers. Only 6.7% +/- 1.7% had less than octoploid DNA content. Very few cells were found belonging to the 64N class. Among the immature MK, a relatively large fraction was found between the ploidy levels, indicating a rapid turnover within these ploidy classes. The demonstration of ACHE activity even in MK with a diploid DNA content indicates that the flow from the committed progenitors to differentiated MK occurs at the 2N level.     

Haemolytic complement in peripheral lymph of normal men.

The haemolytic activity of nine individual components of complement and the concentrations of C1q, C1s, C4, C3, C3PA and C9 proteins were measured in the leg lymph and serum of four normal men. The mean lymph/serum ratio for total haemolytic complement was 0.257, for C1H50 it was 0.138, for C4H50 0.105, for C2H50 0.279, for C3H50 0.063, for C5H50 0.266, for C6H50 0.145, for C7H50 0.25, for C8H50 0.244 and for C9H50 0.253. The mean lymph/serum ratio for complement proteins was: for C1q 0.048, for C1s 0.06, for C4 0.199, for C3 0.225, for C9 0.244 and for C3PA 0.263. The low haemolytic activity of total complement and of all components in lymph seems to be dependent on the low complement protein concentration. The remarkably low lymph C1q protein concentration may play a physiological role in controlling total complement activity in lymph and interstitial fluid. The total complement haemolytic activity in lymph exceeded the haemolytic activity of C1 and C3, which may indicate the possibility of independent activation of C5-7 and C8-9. The considerably low C3H50 level, with high C3 protein concentration, at present lacks a proper explanation.     

Axillofemoral bypass as a limb salvage procedure in high risk patients with aortoiliac disease

Thirty-eight patients presenting with severe limb ischaemia and considered unfit for major aortic reconstruction underwent axillofemoral bypass as a limb salvage procedure. Four patients (11 per cent) died, including two who had presented with bilateral ischaemia secondary to acute aortic occlusion. The operative mortality rate for patients presenting with rest pain or ulceration/gangrene was 6 per cent. Cumulative 5-year survival and limb salvage were 44 per cent and 86 per cent respectively. Graft occlusion was the principal cause of worsening symptoms during follow-up (5-year primary patency of 68 per cent) and accounted for all major amputations of the operated limb. Axillounifemoral grafts had a significantly worse 5-year patency (50 per cent) than axillobifemoral grafts (80 per cent, P less than 0.05) and three of five patients who developed worsening symptoms in the non-operated limb died or required a major limb amputation as a consequence. Axillofemoral bypass is a valuable alternative to major aortic reconstruction in elderly patients and allows a greater proportion to be offered reconstruction than would otherwise be possible.     

The Drinking Water Chlorination By-products 3,4-Dichloro-5-hydroxy-2[5H]-furanone (Mucochloric Acid) and 3-Chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone Do Not Induce Preneoplastic or Neoplastic Intestinal Lesions in F344 Rats,Balb/cA Mice or C57BL/6J-Min Mice

Abstract: Epidemiological studies indicate an association between exposure to chlorinated drinking water and risk of intestinal cancer. In order to study this experimentally, we have examined the effects of 3,4-dichloro-5-hydroxy-2[5H]-furanone (mucochloric acid, MCA) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), mutagenic and genotoxic compounds in drinking water, on aberrant crypt foci and tumours in the intestines of male F344 rats and Balb/cA mice, and C57BL/6J-Min (multiple intestinal neoplasia)/+ mice of both sexes, in six independent experiments. In some experiments the effects of MCA and MX on aberrant crypt foci induced by the colon carcinogens 1,2-dimethylhydrazine or its metabolite azoxymethane were also studied. Neither MCA nor MX alone induced aberrant crypt foci or intestinal tumours when given in drinking water. With this route of exposure neither MCA nor MX, when given in combination with 1,2-dimethylhydrazine or azoxymethane, had any effect on the induction or growth of the aberrant crypt foci. Drinking water exposure of MX did not affect the number or growth of aberrant crypt foci or intestinal tumours in the Min/+ mice. When administered intrarectally MCA had a weak inducing effect on aberrant crypt foci in the colons of Balb/cA mice. Exposure to MCA and MX intrarectally apparently promoted the growth of aberrant crypt foci both in rats and mice, increasing the crypt multiplicity, aberrant crypts/aberrant crypt foci. Based on an overall evaluation of these experiments, the intestinal tract, at least in rats and mice, seems not to be a main target organ for effects of MCA or MX on preneoplastic or neoplastic development.     

Consumption of meat and fish and risk of lung cancer: results from the European Prospective Investigation into Cancer and Nutrition

Evidence from case-control studies, but less so from cohort studies, suggests a positive association between meat intake and risk of lung cancer. Therefore, this association was evaluated in the frame of the European Prospective Investigation into Cancer and Nutrition, EPIC. Data from 478,021 participants, recruited from 10 European countries, who completed a dietary questionnaire in 1992-2000 were evaluated; 1,822 incident primary lung cancer cases were included in the present evaluation. Relative risk estimates were calculated for categories of meat intake using multi-variably adjusted Cox proportional hazard models. In addition, the continuous intake variables were calibrated by means of 24-h diet recall data to account for part of the measurement error. There were no consistent associations between meat consumption and the risk of lung cancer. Neither red meat (RR = 1.06, 95% CI 0.89-1.27 per 50 g intake/day; calibrated model) nor processed meat (RR = 1.13, 95% CI 0.95-1.34 per 50 g/day; calibrated model) was significantly related to an increased risk of lung cancer. Also, consumption of white meat and fish was not associated with the risk of lung cancer. These findings do not support the hypothesis that a high intake of red and processed meat is a risk factor for lung cancer.