t-tests, non-parametric tests, and large studies—a paradox of statistical practice?

Background During the last 30 years, the median sample size of research studies published in high-impact medical journals has increased manyfold, while the use of non-parametric tests has increased at the expense of t-tests. This paper explores this paradoxical practice and illustrates its consequences. Methods A simulation study is used to compare the rejection rates of the Wilcoxon-Mann-Whitney (WMW) test and the two-sample t-test for increasing sample size. Samples are drawn from skewed distributions with equal means and medians but with a small difference in spread. A hypothetical case study is used for illustration and motivation. Results The WMW test produces, on average, smaller p-values than the t-test. This discrepancy increases with increasing sample size, skewness, and difference in spread. For heavily skewed data, the proportion of p<0.05 with the WMW test can be greater than 90% if the standard deviations differ by 10% and the number of observations is 1000 in each group. The high rejection rates of the WMW test should be interpreted as the power to detect that the probability that a random sample from one of the distributions is less than a random sample from the other distribution is greater than 50%. Conclusions Non-parametric tests are most useful for small studies. Using non-parametric tests in large studies may provide answers to the wrong question, thus confusing readers. For studies with a large sample size, t-tests and their corresponding confidence intervals can and should be used even for heavily skewed data

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

Assessing the cumulative effect of long-term training load on the risk of injury in team sports

Objectives: Determine how to assess the cumulative effect of training load on the risk of injury or health problems in team sports. Methods: First, we performed a simulation based on a Norwegian Premier League male football dataset (n players=36). Training load was sampled from daily session rating of perceived exertion (sRPE). Different scenarios of the effect of sRPE on injury risk and the effect of relative sRPE on injury risk were simulated. These scenarios assumed that the probability of injury was the result of training load exposures over the previous 4 weeks. We compared seven different methods of modelling training load in their ability to model the simulated relationship. We then used the most accurate method, the distributed lag non-linear model (DLNM), to analyse data from Norwegian youth elite handball players (no. of players=205, no. of health problems=471) to illustrate how assessing the cumulative effect of training load can be done in practice. Results: DLNM was the only method that accurately modelled the simulated relationships between training load and injury risk. In the handball example, DLNM could show the cumulative effect of training load and how much training load affected health problem risk depending on the distance in time since the training load exposure. Conclusion: DLNM can be used to assess the cumulative effect of training load on injury risk.publishedVersio

The longitudinal association between objectively measured physical activity and mental health among Norwegian adolescents

Background: Mental health among young people in many countries, including Norway, seems to be deteriorating. Physical activity (PA) has been positively associated with mental health. However, methodological issues related to study design and measurement of PA and mental health outcomes currently limits our understanding of the relationship. The purpose of the present study is to explore the prospective relationship between objectively measured PA and mental health outcomes. More specifically, volume (total PA), intensity (moderate-to-vigorous PA [MVPA]) and sedentary behaviour (SED) were explored in relation to mental health problems (MHP) and mental wellbeing (MWB). Methods: Data from 599 adolescents (54.4% female, mean age at baseline ±SD 13.3 ± 0.3 years) were collected annually during their 3 years (T1, T2 and T3) at lower secondary school. PA was measured using accelerometry. MWB was measured using the ‘Warwick-Edinburgh Mental Wellbeing Scale’ and MHP by the ‘Strengths and Difficulties Questionnaire’. Multiple linear regression was performed to explore relationships between changes in PA/SED (between T1-T3) and MWB/MHP (at T3). The term ‘movement categories’ was used to refer to components on the movement continuum and includes volume (total PA), intensity (MVPA) and SED. Results: Among boys, any increase in SED was positively associated with MWB (β = 0.05, 95% CI: 0.01 to 0.10), whereas a small positive association between an increase in total PA (volume) and MWB was found among girls (β = 1.13, 95% CI: 0.05 to 2.21). There were no associations between changes in any movement categories [total PA (volume), MVPA, SED] and score on MHP at T3, neither for girls nor boys. Conclusion: This study provided no clear evidence of any association between change in volume or intensity of PA and MHP among an overall healthy adolescent study sample. There was, however, evidence of a relationship between increased SED and MWB among boys and increased volume of PA and MWB among girls. The relationship between movement categories and mental health may depend on the measurement used to assess both PA/SED and variables of mental health. Future research would be strengthened by researchers clarifying what construct of mental health is being used and measured.publishedVersio

A new statistical approach to training load and injury risk: separating the acute from the chronic load

The relationship between recent (acute) training load relative to long-term (chronic) training load may be associated with sports injury risk. We explored the potential for modelling acute and chronic loads separately to address current statistical methodology limitations. We also determined whether there was any evidence of an interaction in the association between acute and chronic training loads and injury risk in football. A men’s Qatar Stars League football cohort (1 465 players, 1 977 injuries), where training load was defined as the number of minutes of activity, and a Norwegian elite U-19 football cohort (81 players, 60 injuries), where training load was defined as the session rating of perceived exertion (sRPE). Mixed logistic regression was run with training load on the current day (acute load) and cumulative past training load estimated by distributed lag non-linear models (chronic load) as independent variables. Injury was the outcome. An interaction between acute and chronic training load was modelled. In both football populations, we observed that the risk of injury on the current day for different values of acute training load was highest for players with low chronic load, followed by high and then medium chronic load. The slopes varied substantially between different levels of chronic training load, indicating an interaction. Modelling acute and chronic loads separately in regression models is a suitable statistical approach for analysing the association between relative training load and injury risk in injury prevention research. Sports scientists should also consider the potential for interactions between acute and chronic load.publishedVersio

Parametric methods outperformed non-parametric methods in comparisons of discrete numerical variables

<p>Abstract</p> <p>Background</p> <p>The number of events per individual is a widely reported variable in medical research papers. Such variables are the most common representation of the general variable type called discrete numerical. There is currently no consensus on how to compare and present such variables, and recommendations are lacking. The objective of this paper is to present recommendations for analysis and presentation of results for discrete numerical variables.</p> <p>Methods</p> <p>Two simulation studies were used to investigate the performance of hypothesis tests and confidence interval methods for variables with outcomes {0, 1, 2}, {0, 1, 2, 3}, {0, 1, 2, 3, 4}, and {0, 1, 2, 3, 4, 5}, using the difference between the means as an effect measure.</p> <p>Results</p> <p>The Welch U test (the T test with adjustment for unequal variances) and its associated confidence interval performed well for almost all situations considered. The Brunner-Munzel test also performed well, except for small sample sizes (10 in each group). The ordinary T test, the Wilcoxon-Mann-Whitney test, the percentile bootstrap interval, and the bootstrap-<it>t </it>interval did not perform satisfactorily.</p> <p>Conclusions</p> <p>The difference between the means is an appropriate effect measure for comparing two independent discrete numerical variables that has both lower and upper bounds. To analyze this problem, we encourage more frequent use of parametric hypothesis tests and confidence intervals.</p

Small- and large-fiber neuropathy after 40 years of type 1 diabetes associations with glycemic control and advanced protein glycation: the Oslo Study

OBJECTIVE To study large- and small-nerve fiber function in type 1 diabetes of long duration and associations with HbA1c and the advanced glycation end products (AGEs) N-&#949-(carboxymethyl)lysine (CML) and methylglyoxal-derived hydroimidazolone. RESEARCH DESIGN AND METHODS In a long-term follow-up study, 27 persons with type 1 diabetes of 40 &#177 3 years duration underwent large-nerve fiber examinations, with nerve conduction studies at baseline and years 8, 17, and 27. Small-fiber functions were assessed by quantitative sensory thresholds (QST) and intraepidermal nerve fiber density (IENFD) at year 27. HbA1cwas measured prospectively through 27 years. Serum CML was measured at year 17 by immunoassay. Serum hydroimidazolone was measured at year 27 with liquid chromatography– mass spectrometry. RESULTS Sixteen patients (59%) had large-fiber neuropathy. Twenty-two (81%) had smallfiber dysfunction by QST. Heat pain thresholds in the foot were associated with hydroimidazolone and HbA1c. IENFD was abnormal in 19 (70%) and significantly lower in diabetic patients than in age-matched control subjects (4.3 &#177 2.3 vs. 11.2 &#177 3.5 mm, P , 0.001). IENFD correlated negatively with HbA1c over 27 years (r = 20.4, P = 0.04) and CML (r = 20.5, P = 0.01). After adjustment for age, height, and BMI in a multiple linear regression model, CML was still independently associated with IENFD. CONCLUSIONS Small-fiber sensory neuropathy is a major manifestation in type 1 diabetes of 40 years duration and more prevalent than large-fiber neuropathy. HbA1c and the AGEs CML and hydroimidazolone are important risk factors in the development of large- and small-fiber dysfunction in long-term type 1 diabetes

Low level of MAp44, an inhibitor of the lectin complement pathway, and long-term graft and patient survival; a cohort study of 382 kidney recipients

© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Higher incidence of malignancy and infectious diseases in kidney transplant recipients is related to immunosuppressive treatment after transplantation and the recipient’s native immune system. The complement system is an essential component of the innate immunity. The aim of the present study was to investigate the association of effector molecules of the lectin complement pathway with graft and patient survival after kidney transplantation. Methods: Two mannan-binding lectin (MBL) associated proteases, MASP-2 and MASP-3 (activators of the lectin pathway) and two MBL-associated proteins, MAp44 and MAp19 (inhibitors of the lectin pathway) were measured at the time of transplantation in 382 patients (≥17 years old) transplanted in 2000–2001. The cohort was followed until December 31, 2014. Data on patient and graft survival were obtained from the Norwegian Renal Registry. Cox proportional hazard regression models were performed for survival analyses. Results: Low MAp44 level (1st versus 2–4 quartile) was significantly associated with overall mortality; HR 1.52, 95 % CI 1.08–2.14, p = 0.017. In the sub analyses in groups below and above median age (51.7 years), low MAp44 as a predictor of overall mortality was statistically significant only in recipients of ≤51.7 years; HR 2.57, 95 % CI 1.42–4.66, p = 0.002. Furthermore, low MAp44 was associated with mortality due to infectious diseases; HR 2.22, 95 % CI 1.11–4.41, p = 0.023. There was no association between MASP-2, MASP-3 or MAp19 levels and patient mortality. No association between any measured biomarkers and death censored graft loss was found. Conclusions: Low MAp44 level at the time of transplantation was associated with increased overall mortality in kidney recipients of median age of 51.7 years or below and with mortality due to infectious diseases in the whole patient cohort after nearly 14-years of follow up after transplantation. No associations between other effector molecules; MASP-2, MASP-3 or MAp19 and recipient mortality were found, as well as no association of any biomarker with death censored graft loss

Impact of White Matter Lesions on Cognition in Stroke Patients Free from Pre-Stroke Cognitive Impairment: A One-Year Follow-Up Study

Background/Aim: Post-stroke cognitive impairment and dementia may be caused by pure vascular, pure degenerative or mixed disease. The relation between post-stroke cognitive impairment and the combination of vascular pathology and degenerative changes is less evaluated. We aimed to evaluate the associations between white matter lesions (WMLs) and patient performance 1 year after stroke on tests of executive functioning, memory and visuospatial function, adjusted for the effects of lifestyle and disease-related factors, including medial temporal lobe atrophy (MTLA). Methods: Patients with a first-ever stroke or transient ischemic attack were invited to participate in the study. The associations between the cognitive test performances and WMLs were studied using linear regression [Trail Making Test B (TMT B) and 10-word test] and logistic regression (Clock Drawing Test). Results: In total, 199 patients completed the follow-up. The TMT B (p = 0.029) and the 10-word test (p = 0.014) were significantly associated with WMLs; however, the Clock Drawing Test (p = 0.19) was not. The TMT B (p = 0.018) and the 10-word test (p ≤ 0.001) were both significantly associated with MTLA. Conclusion: Impaired executive functioning and memory are significantly associated with WMLs and MTLA. The mechanisms explaining post-stroke cognitive impairment are multifactorial, including different types of vascular pathology and coexisting vascular and degenerative changes