Recommended confidence intervals for two independent binomial proportions

Abstract The relationship between two independent binomial proportions is commonly estimated and presented using the difference between proportions, the number needed to treat, the ratio of proportions or the odds ratio. Several different confidence intervals are available, but they can produce markedly different results. Some of the traditional approaches, such as the Wald interval for the difference between proportions and the Katz log interval for the ratio of proportions, do not perform well unless the sample size is large. Better intervals are available. This article describes and compares approximate and exact confidence intervals that are -with one exception -easy to calculate or available in common software packages. We illustrate the performances of the intervals and make recommendations for both small and moderate-to-large sample sizes

Classification of comorbidity in trauma: agreement and reliability of the pre-injury ASA-PS Scale

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Are symptoms assessed differently for schizophrenia and other psychoses in legal insanity evaluations of violent crimes?

Background: Forensic evaluations of legal insanity include the experts’ assessment of symptoms present at the mental state examination (MSE) and the mental state at the time of offense (MSO). Delusions and hallucinations are most important. We explored how often symptoms were recorded in written forensic reports. Design: This exploratory, cross-sectional study included 500 reports of legal insanity written in 2009–2018 from cases of violent crimes in Norway. The first author read all reports and coded symptoms recorded from the experts’ assessments of the offenders. Two co-authors repeated this procedure for 50 randomly selected reports. Interrater reliability was calculated with Gwet’s AC1. Generalized Linear Mixed Models with Wald tests for fixed effects and Risk Ratios as effect sizes were used for the statistical analyses. Results: Legal insanity was the main conclusion in 23.6% of the reports; 71.2% of these were diagnosed with schizophrenia while 22.9% had other psychotic disorders. Experts recorded few symptoms from MSO, but more from MSE, although MSO is important for insanity. We found a significant association between delusions and hallucinations recorded present in the MSO and legal insanity for defendants with other psychotic disorders, but no association for defendants with schizophrenia. The differences in symptom recordings between diagnoses were significant. Conclusion: Few symptoms were recorded from the MSO. We found no association between presence of delusions or hallucinations and legal insanity for defendants with schizophrenia. This may indicate that a schizophrenia diagnosis is more important to the forensic conclusion than the symptoms recorded in the MSO. Keywords: delusions, hallucinations, forensic, insanity, bias, stigmapublishedVersio

Categorisation of continuous exposure variables revisited. A response to the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study

Background Although the general statistical advice is to keep continuous exposure variables as continuous in statistical analyses, categorisation is still a common approach in medical research. In a recent paper from the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study, categorisation of body mass index (BMI) was used when analysing the effect of BMI on adverse pregnancy outcomes. The lowest category, labelled "underweight", was used as the reference category. Methods The present paper gives a summary of reasons for categorisation and methodological drawbacks of this approach. We also discuss the choice of reference category and alternative analyses. We exemplify our arguments by a reanalysis of results from the HAPO paper. Results Categorisation of continuous exposure data results in loss of power and other methodological challenges. An unfortunate choice of reference category can give additional lack of precision and obscure the interpretation of risk estimates. A highlighted odds ratio (OR) in the HAPO study is the OR for birth weight >90th percentile for women in the highest compared to the lowest BMI category ("obese class III" versus "underweight"). This estimate was OR = 4.55 and OR = 3.52, with two different multiple logistic regression models. When using the "normal weight" category as the reference, our corresponding estimates were OR = 2.03 and OR = 1.62, respectively. Moreover, our choice of reference category also gave narrower confidence intervals. Summary Due to several methodological drawbacks, categorisation should be avoided. Modern statistical analyses should be used to analyse continuous exposure data, and to explore non-linear relations. If continuous data are categorised, special attention must be given to the choice of reference category

Regression analysis with categorized regression calibrated exposure: some interesting findings

BACKGROUND: Regression calibration as a method for handling measurement error is becoming increasingly well-known and used in epidemiologic research. However, the standard version of the method is not appropriate for exposure analyzed on a categorical (e.g. quintile) scale, an approach commonly used in epidemiologic studies. A tempting solution could then be to use the predicted continuous exposure obtained through the regression calibration method and treat it as an approximation to the true exposure, that is, include the categorized calibrated exposure in the main regression analysis. METHODS: We use semi-analytical calculations and simulations to evaluate the performance of the proposed approach compared to the naive approach of not correcting for measurement error, in situations where analyses are performed on quintile scale and when incorporating the original scale into the categorical variables, respectively. We also present analyses of real data, containing measures of folate intake and depression, from the Norwegian Women and Cancer study (NOWAC). RESULTS: In cases where extra information is available through replicated measurements and not validation data, regression calibration does not maintain important qualities of the true exposure distribution, thus estimates of variance and percentiles can be severely biased. We show that the outlined approach maintains much, in some cases all, of the misclassification found in the observed exposure. For that reason, regression analysis with the corrected variable included on a categorical scale is still biased. In some cases the corrected estimates are analytically equal to those obtained by the naive approach. Regression calibration is however vastly superior to the naive method when applying the medians of each category in the analysis. CONCLUSION: Regression calibration in its most well-known form is not appropriate for measurement error correction when the exposure is analyzed on a percentile scale. Relating back to the original scale of the exposure solves the problem. The conclusion regards all regression models

Test-retest reproducibility of a food frequency questionnaire (FFQ) and estimated effects on disease risk in the Norwegian Women and Cancer Study (NOWAC)

BACKGROUND: The Norwegian Women and Cancer Study (NOWAC) is a national population-based cohort study with 102 443 women enrolled at age 30–70 y from 1991 to 1997. The present study was a methodological sub-study to assess the test-retest reproducibility of the NOWAC food frequency questionnaire (FFQ), and to study how measurement errors in the data can affect estimates of disease risk. METHODS: A random sample of 2000 women aged 46–75 y was drawn from the cohort in 2002. A self-instructive health and lifestyle questionnaire with a FFQ section was mailed to the same subjects twice (test-retest), about three months apart, with a response rate of 75%. The FFQ was designed to assess habitual diet over the past year. We assess the reproducibility of single questions, food groups, energy, and nutrients with several statistical measures. We also demonstrate the method of regression calibration to correct disease risk estimates for measurement error. Alcohol intake (g/day) and high blood pressure (yes/no) is used in the example. RESULTS: For single foods there were some indications of seasonal reporting bias. For food groups and nutrients the reliability coefficients ranged from 0.5–0.8, and Pearson's r, Spearman's r(s), and two intraclass correlation coefficients gave similar results. Although alcohol intake had relatively high reproducibility (r = 0.72), odds ratio estimates for the association with blood pressure were attenuated towards the null value compared to estimates corrected by regression calibration. CONCLUSION: The level of reproducibility observed for the FFQ used in the NOWAC study is within the range reported for similar instruments, but may attenuate estimates of disease risk

Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers

Background Plant-based diets rich in fruit and vegetables can prevent development of several chronic age-related diseases. However, the mechanisms behind this protective effect are not elucidated. We have tested the hypothesis that intake of antioxidant-rich foods can affect groups of genes associated with cellular stress defence in human blood cells. Trial registration number: NCT00520819 http://clinicaltrials.gov. Methods In an 8-week dietary intervention study, 102 healthy male smokers were randomised to either a diet rich in various antioxidant-rich foods, a kiwifruit diet (three kiwifruits/d added to the regular diet) or a control group. Blood cell gene expression profiles were obtained from 10 randomly selected individuals of each group. Diet-induced changes on gene expression were compared to controls using a novel application of the gene set enrichment analysis (GSEA) on transcription profiles obtained using Affymetrix HG-U133-Plus 2.0 whole genome arrays. Results Changes were observed in the blood cell gene expression profiles in both intervention groups when compared to the control group. Groups of genes involved in regulation of cellular stress defence, such as DNA repair, apoptosis and hypoxia, were significantly upregulated (GSEA, FDR q-values < 5%) by both diets compared to the control group. Genes with common regulatory motifs for aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (AhR/ARNT) were upregulated by both interventions (FDR q-values < 5%). Plasma antioxidant biomarkers (polyphenols/carotenoids) increased in both groups. Conclusions The observed changes in the blood cell gene expression profiles suggest that the beneficial effects of a plant-based diet on human health may be mediated through optimization of defence processes