Elisa L. Priest

Associations Between Cardiorespiratory Fitness and C-Reactive Protein in Men

Objective—This study examined the association between cardiorespiratory fitness and C-reactive protein (CRP), with adjustment for weight and within weight categories. Methods and Results—We calculated median and adjusted geometric mean CRP levels, percentages of individuals with an elevated CRP (≥2.00 mg/L), and odds ratios of elevated CRP across 5 levels of cardiorespiratory fitness for 722 men. CRP values were adjusted for age, body mass index, vitamin use, statin medication use, aspirin use, the presence of inflammatory disease, cardiovascular disease, and diabetes, and smoking habit. We found an inverse association of CRP across fitness levels (P for trend<0.001), with the highest adjusted CRP value in the lowest fitness quintile (1.64 [1.27 to 2.11] mg/L) and the lowest adjusted CRP value in the highest fitness quintile (0.70 [0.60 to 0.80] mg/L). Similar results were found for the prevalence of elevated CRP across fitness quintiles. We used logistic regression to model the adjusted odds for elevated CRP and found that compared with the referent first quintile, the second (odds ratio [OR] 0.43, 95% CI 0.22 to 0.85), third (OR 0.33, 95% CI 0.17 to 0.65), fourth (OR 0.23, 95% CI 0.12 to 0.47), and fifth (OR 0.17, 95% CI 0.08 to 0.37) quintiles of fitness had significantly lower odds of elevated CRP. Similar results were found when examining the CRP-fitness relation within categories of body fatness (normal weight, overweight, and obese) and waist girth (<102 or ≥102 cm). Conclusions—Cardiorespiratory fitness levels were inversely associated with CRP values and the prevalence of elevated CRP values in this sample of men from the Aerobics Center Longitudinal Study.

Exercise without weight loss does not reduce C-reactive protein: the INFLAME study.

PURPOSE Numerous cross-sectional studies have observed an inverse association between C-reactive protein (CRP) and physical activity. Exercise training trials have produced conflicting results, but none of these studies was specifically designed to examine CRP. The objective of the Inflammation and Exercise (INFLAME) study was to examine whether aerobic exercise training without dietary intervention can reduce CRP in individuals with elevated CRP. METHODS The study was a randomized controlled trial of 162 sedentary men and women with elevated CRP (> or = 2.0 mg·L(-1)). Participants were randomized into a nonexercise control group or an exercise group that trained for 4 months. The primary outcome was change in CRP. RESULTS The study participants had a mean (SD) age of 49.7 (10.9) yr and a mean body mass index of 31.8 (4.0) kg·m(-2). The median (interquartile range (IQR)) and mean baseline CRP levels were 4.1 (2.5-6.1) and 4.8 (3.4) mg·L(-1), respectively. In the exercise group, median exercise compliance was 99.9%. There were no differences in median (IQR) change in CRP between the control and exercise groups (0.0 (-0.5 to 0.9) vs 0.0 (-0.8 to 0.7) mg·L(-1), P = 0.4). The mean (95% confidence interval) change in CRP adjusted for gender and baseline weight was similar in the control and exercise groups, with no significant difference between groups (0.5 (-0.4 to 1.3) vs 0.4 (-0.5 to 1.2) mg·L(-1), P = 0.9). Change in weight was correlated with change in CRP. CONCLUSIONS Exercise training without weight loss is not associated with a reduction in CRP.

Obesity, macrophage migration inhibitory factor, and weight loss.

OBJECTIVE:Elevated macrophage migration inhibitory factor (MIF) has been implicated as a causal mechanism in a number of disease conditions including cardiovascular disease (CVD), diabetes, and cancer. Excess body fat is associated with an increased risk of numerous health conditions including CVD, diabetes, and cancer. To our knowledge, the association between MIF and obesity status and the effect of weight loss on serum MIF concentrations have not been reported. In this study, we examined the effects of participation in a behavior-based weight loss program on MIF concentrations in obese individuals.SUBJECTS:Study participants were 71 men and women enrolled in The Cooper Institute Weight Management Program. Participants were predominantly female (68%, n=48), middle-aged (46.5±9.8 y), and severely obese (BMI=43.0±8.6).METHOD:Plasma MIF concentrations and other standard risk factors were measured before and after participation in a diet and physical activity based weight management program.RESULTS:The mean follow-up was 8.5±3.0 months with an average weight loss of 14.4 kg (P<0.001). The majority of clinical risk factors significantly improved at follow-up. Median levels of plasma MIF concentration were significantly lower at follow-up (median [IQR]; 5.1[3.6–10.3]) compared to baseline (8.4 [4.3–48.8]; P=0.0005). The percentage of participants with plasma MIF concentration ≥19.5 mg/nl (highest tertile at baseline) decreased from 33.8 to 5.6% (P<0.001). Further, elevated baseline plasma MIF concentration was associated with markers of β-cell dysfunction and reductions in MIF were associated with improvements in β-cell function.CONCLUSIONS:Circulating MIF concentrations are elevated in obese but otherwise healthy individuals; however, this elevation in MIF is not uniform across individuals. In obese individuals with elevated circulating MIF concentrations, participation in physical activity and a dietary-focused weight management program resulted in substantial reduction in MIF.

A randomized clinical trial to determine the efficacy of regimens containing clarithromycin, metronidazole, and amoxicillin among histologic subgroups for Helicobacter pylori eradication in a developing country.

Background: Most treatments deemed effective for Helicobacter pylori eradication in developed countries are less effective in developing countries. Regimens containing clarithromycin, metronidazole, and amoxicillin seem efficacious despite antibiotic resistance, and may be a viable option in developing countries.

Association of White Blood Cell Subfraction Concentration with Fitness and Fatness

Objective To examine the association between fitness, BMI, and neutrophil, lymphocyte, monocyte, basophil, and eosinophil concentrations in apparently healthy, non-smoking men. Design Cross-sectional study of 452 men from the Aerobics Center Longitudinal Study examining the resting concentration of white blood cell subfractions across fitness (maximal METs during a treadmill exercise test) and fatness (BMI) categories after adjusting for age. Results Fitness was inversely associated with all WBC subfraction concentrations. After further adjustment for BMI, only total WBC, neutrophil, and basophil concentrations remained significantly associated with fitness. BMI was directly associated with total WBC, neutrophil, lymphocyte, monocyte, and basophil concentrations and, when fitness was added to the model, only monocytes lost significance. Conclusion Fitness (inversely) and fatness (directly) are associated with WBC subfraction populations.

Assessing Trends in Tobacco Cessation in Diverse Patient Populations.

INTRODUCTION This study examined change in tobacco use over 4 years among the general population of patients in six diverse health care organizations using electronic medical record data. METHODS The study cohort (N = 34 393) included all patients age 18 years or older who were identified as smokers in 2007, and who then had at least one primary care visit in each of the following 4 years. RESULTS In the 4 years following 2007, this patient cohort had a median of 13 primary care visits, and 38.6% of the patients quit smoking at least once. At the end of the fourth follow-up year, 15.4% had stopped smoking for 1 year or more. Smokers were more likely to become long-term quitters if they were 65 or older (OR = 1.32, 95% CI = [1.16, 1.49]), or had a diagnoses of cancer (1.26 [1.12, 1.41]), cardiovascular disease (1.22 [1.09, 1.37]), asthma (1.15 [1.06, 1.25]), or diabetes (1.17 [1.09, 1.27]). Characteristics associated with lower likelihood of becoming a long-term quitter were female gender (0.90 [0.84, 0.95]), black race (0.84 [0.75, 0.94]) and those identified as non-Hispanic (0.50 [0.43, 0.59]). CONCLUSIONS Among smokers who regularly used these care systems, one in seven had achieved long-term cessation after 4 years. This study shows the practicality of using electronic medical records for monitoring patient smoking status over time. Similar methods could be used to assess tobacco use in any health care organization to evaluate the impact of environmental and organizational programs.

Increased Reflux Symptoms After Calcium Carbonate Supplementation and Successful Anti-Helicobacter pylori Treatment

We used data from a randomized placebo-controlled clinical trial to examine the relationship between Helicobacter pylori and reflux symptoms in nonulcer dyspepsia patients randomly assigned anti-Helicobacter pylori triple therapy alone, calcium carbonate alone, or in combination with triple therapy, tetracycline, or placebo. We compared risk differences for posttreatment Helicobacter pylori status and increased reflux symptoms from crude, multivariable and stratified multivariable analyses. In crude analyses, 54% of subjects without Helicobacter pylori after-treatment reported an increase in reflux compared to 41% of those with persistent infection (risk difference = 13%; P = 0.07). Only subjects with multifocal atrophic gastritis assigned to calcium carbonate reported an increase in reflux symptoms more frequently when Helicobacter pylori was absent versus when it persisted (risk difference = 52%; P = 0.0001). Therefore, the interaction of calcium carbonate use, chronic multifocal atrophic gastritis, and the absence of Helicobacter pylori may increase reflux symptoms.

Analytical Methods for a Learning Health System: 3. Analysis of Observational Studies

The third paper in a series on how learning health systems can use routinely collected electronic health data (EHD) to advance knowledge and support continuous learning, this review describes how analytical methods for individual-level electronic health data EHD, including regression approaches, interrupted time series (ITS) analyses, instrumental variables, and propensity score methods, can also be used to address the question of whether the intervention “works.” The two major potential sources of bias in non-experimental studies of health care interventions are that the treatment groups compared do not have the same probability of treatment or exposure and the potential for confounding by unmeasured covariates. Although very different, the approaches presented in this chapter are all based on assumptions about data, causal relationships, and biases. For instance, regression approaches assume that the relationship between the treatment, outcome, and other variables is properly specified, all of the variables are available for analysis (i.e., no unobserved confounders) and measured without error, and that the error term is independent and identically distributed. The instrumental variables approach requires identifying an instrument that is related to the assignment of treatment but otherwise has no direct on the outcome. Propensity score methods approaches, on the other hand, assume that there are no unobserved confounders. The epidemiological designs discussed also make assumptions, for instance that individuals can serve as their own control. To properly address these assumptions, analysts should conduct sensitivity analyses within the assumptions of each method to assess the potential impact of what cannot be observed. Researchers also should analyze the same data with different analytical approaches that make alternative assumptions, and to apply the same methods to different data sets. Finally, different analytical methods, each subject to different biases, should be used in combination and together with different designs, to limit the potential for bias in the final results.

Analytical Methods for a Learning Health System: 1. Framing the Research Question

Learning health systems use routinely collected electronic health data (EHD) to advance knowledge and support continuous learning. Even without randomization, observational studies can play a central role as the nation’s health care system embraces comparative effectiveness research and patient-centered outcomes research. However, neither the breadth, timeliness, volume of the available information, nor sophisticated analytics, allow analysts to confidently infer causal relationships from observational data. However, depending on the research question, careful study design and appropriate analytical methods can improve the utility of EHD. The introduction to a series of four papers, this review begins with a discussion of the kind of research questions that EHD can help address, noting how different evidence and assumptions are needed for each. We argue that when the question involves describing the current (and likely future) state of affairs, causal inference is not relevant, so randomized clinical trials (RCTs) are not necessary. When the question is whether an intervention improves outcomes of interest, causal inference is critical, but appropriately designed and analyzed observational studies can yield valid results that better balance internal and external validity than typical RCTs. When the question is one of translation and spread of innovations, a different set of questions comes into play: How and why does the intervention work? How can a model be amended or adapted to work in new settings? In these “delivery system science” settings, causal inference is not the main issue, so a range of quantitative, qualitative, and mixed research designs are needed. We then describe why RCTs are regarded as the gold standard for assessing cause and effect, how alternative approaches relying on observational data can be used to the same end, and how observational studies of EHD can be effective complements to RCTs. We also describe how RCTs can be a model for designing rigorous observational studies, building an evidence base through iterative studies that build upon each other (i.e., confirmation across multiple investigations).