Biomarkers in Environmental Epidemiology
Anthony P. DeCaprio in Toxicologic Biomarkers, 2006
An alternative to case–control studies is to establish prospective cohorts. A nested case–control study within the cohort limits the resources needed for the analysis. As all individuals are healthy at entry to the study when biological samples are collected, the problems of reverse causation are avoided and the design provides a measure of exposure prior to disease onset. In practice, the periods of follow-up still tend to encompass a relatively short fraction of the carcinogenic process (a few years rather than decades) and often involve only a single time-point (most often recruitment) for biological sampling. Nevertheless this design is more adapted to the type of exposure biomarker currently available. It is within this design that the most successful examples of biomarkers and disease outcome have been in evidence.
Causality Analysis of Climate and Ecosystem Time Series
Vyacheslav Lyubchich, Yulia R. Gel, K. Halimeda Kilbourne, Thomas J. Miller, Nathaniel K. Newlands, Adam B. Smith in Evaluating Climate Change Impacts, 2020
Identifying causal relationships among multiple variables and direction/strength of these causal links are key challenges in the analysis of complex dynamical systems. Statistical correlation and regression analysis have been important tools in understanding the relationships in social and environmental systems. However, these tools are not adequate for finding stimulusâĂŞresponse mechanisms. A well-known statement is that correlation does not imply causation. For example, correlation between variables A and B might be created in three scenarios of causal relationships, that is, A is a cause of B, B is a cause of A, or a third variable C is the cause of both A and B. If two variables are causally related (for example, A causes B: A → B), a change in A must produce a change in B. Unlike symmetry in correlation, the causal relation A → B does not imply B → A. Therefore, a statistical correlation is necessary but not sufficient to make a claim of causality.
Extreme Exercise and High Intensity Interval Training in Cardiac Rehabilitation
James M. Rippe in Lifestyle Medicine, 2019
A similar reverse J-shaped association was reported in a German cohort study of 1,038 subjects with stable CAD in which the frequency of strenuous leisure-time PA was assessed over a 10-year period after discharge from an inpatient rehabilitation clinic following an acute cardiovascular event or coronary revascularization procedure.39 Most subjects were ≥60 years of age (57%), male (85%), overweight or obese (76%), and had a history of AMI and hypertension. To reduce the likelihood of reverse causation bias, leading to an overestimation of the hazards in the inactive patient subset and an underestimation in the most physically active cohort, the investigators adjusted for potential confounders, including a baseline history of co-morbid conditions and for self-reported poor health. The highest hazards for cardiovascular and all-cause mortality were found in the least active patient group, as compared with the reference group of patients who were active two to four times per week. However, significantly increased hazards were also observed in the most physically active groups (i.e. daily vigorous exercise), indicating a reverse J-curve pattern of physical activity level with cardiovascular and all-cause mortality (Table 67.3).39 In fact, these hazard ratios were approximately twice those of the reference group.
Establishing target systolic and diastolic blood pressure in diabetic patients with hypertension: what do we need to consider?
Published in Expert Review of Cardiovascular Therapy, 2021
There are limitations to this evidence, firstly it is important to bear in mind that retrospective analysis and observational data is lower-level evidence. Secondly, is the possibility of reverse causation as the contributor to the J point phenomenon. Reverse causation refers to a direction of cause-and-effect contrary to a common presumption. Indeed, because EPHESUS was a trial of adults with systolic dysfunction after recent myocardial infarction and because the decision to revascularize or not was non-randomized, it is possible that the J curve was only seen in the non-revascularized group in this study because these persons were too sick or frail to undergo revascularization (noting that standard of care after MI with systolic dysfunction would be to pursue revascularization).
Dietary insulin index and insulin load in relation to glioma: findings from a case–control study
Published in Nutritional Neuroscience, 2021
Javad Anjom-Shoae, Mehdi Shayanfar, Minoo Mohammad-Shirazi, Omid Sadeghi, Giuve Sharifi, Fereydoun Siassi, Ahmad Esmaillzadeh
This study has several advantages. To the best of our knowledge, we conducted the first study to examine the association between DII and DIL and risk of glioma. Second, a wide range of confounders have been controlled for in the present study to reach an independent association. As a third strength, patients enrolled in the study were new cases of glioma who had been diagnosed with this malignancy in the past 1 month. This reduces the possibility of changing the usual dietary intakes. However, some limitations should be considered in this study. As in case–control studies data on exposure and outcome are gathered simultaneously in a specific time point, causality cannot be conferred. Reverse causation is always a concern in case–control studies that should also be taken into account in the interpretation of our findings. In addition, recall bias and selection bias in these studies might result in misleading findings. As with all epidemiologic studies, measurement error is always another concern. Moreover, due to the use of FFQ, misclassification of study participants cannot be excluded; however, FFQ used in this study was validated previously. We did not consider different stages of glioma in the current study; however, we enrolled newly diagnosed cases. Further studies that consider type, stage and grades of glioma might be useful to evaluate this relation more specifically. In addition, due to limited sample size, we were not able to do stratified analysis based on the age group. Given the contribution of age to glioma, we suggest future studies to enroll an adequate sample in any specific age group.
Vitamin D as disease-modifying therapy for multiple sclerosis?
Published in Expert Review of Clinical Immunology, 2021
Matthew R Lincoln, Raphael Schneider, Jiwon Oh
Observational studies are prone to confounding by unmeasured causal factors and to reverse causation. For example, people with MS may avoid sun exposure because heat exacerbates their symptoms. Thus, low serum vitamin D in MS patients may be a consequence of MS, rather than a cause. We lack large-scale randomized controlled trials (RCTs) of vitamin D in preventing MS. As vitamin D may act in concert with other genetic and environmental factors years before symptom onset, long-term studies of large cohorts would be required. A therapeutic dose or serum level has not been determined for vitamin D, and it is possible that exposure above a sufficient level has a smaller influence on risk, further decreasing power. Vitamin D is commonly used by MS patients, making recruitment and adherence major challenges. Given these challenges to RCT design, recent studies have used Mendelian randomization to demonstrate that insufficient vitamin D is a cause of MS [9,10]. These studies use genetic variants that influence serum vitamin D as instruments to assess vitamin D’s effect on MS risk. Because genetic variants are ‘randomized’ at meiosis, Mendelian randomization permits establishment of causality in a fashion analogous to RCTs. Genetically lowered vitamin D is thus shown to cause MS in both adult [9] and pediatric [10] populations.
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