Jesse Y. Hsu

Pre- to postoperative changes in physical activity: report from the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2)

BACKGROUND Numerous studies have reported that bariatric surgery patients report more physical activity (PA) after surgery than before; however, the quality of the PA assessment has been questionable. METHODS The longitudinal assessment of bariatric surgery-2 is a 10-center longitudinal study of adults undergoing bariatric surgery. Of 2458 participants, 455 were given an activity monitor, which records the steps per minute, and an exercise diary before and 1 year after surgery. The mean number of steps/d, active min/d, and high-cadence min/wk were calculated for 310 participants who wore the monitor ≥10 hr/d for ≥3 days at both evaluations. Pre- and postoperative PA were compared for differences using the Wilcoxon signed-rank test. Generalized estimating equations were used to identify independent preoperative predictors of postoperative PA. RESULTS PA increased significantly (P < .0001) from before to after surgery for all PA measures. The median values before and after surgery were 7563 and 8788 steps/d, 309 and 340 active min/d, and 72 and 112 high-cadence min/wk, respectively. However, depending on the PA measure, 24-29% of participants were ≥5% less active postoperatively than preoperatively. Controlling for surgical procedure, gender, age, and body mass index, more PA preoperatively independently predicted for more PA postoperatively (P < .0001, for all PA measures). Less pain, not having asthma, and the self-report of increasing PA as a weight loss strategy preoperatively also independently predicted for more high-cadence min/wk postoperatively (P < .05). CONCLUSIONS The majority of adults increase their PA level after bariatric surgery. However, most remain insufficiently active, and some become less active. Increasing PA, addressing pain, and treating asthma before surgery might have a positive effect on postoperative PA.

Hepatic Pathology among Patients without Known Liver Disease Undergoing Bariatric Surgery: Observations and a Perspective from the Longitudinal Assessment of Bariatric Surgery (LABS) Study

Liver biopsy is not routine during bariatric surgery. Alanine aminotransferase (ALT) is widely used to screen for liver disease. We assessed the relationship between ALT and pathology in biopsies from Longitudinal Assessment of Bariatric Surgery (LABS) patients with normal preoperative ALTs. Biopsies from the LABS-1 and LABS-2 studies were scored using the NASH CRN and Ishak systems. Diagnosis and histology were examined in relation to alanine aminotransferase (ALT) values. Six-hundred ninety-three suitable biopsies were evaluated. Biopsied patients had a median age of 45 years; 78.6% were female and 35.1% diabetic; median body mass index was 46 kg/m(2). Six-hundred thirty-five biopsied patients had preoperative ALTs. Median ALT was 25 IU/L (interquartile range [IQR] 19-36 IU/L); 26.6% had an ALT > 35 IU/L and 29.9% exceeded the more restrictive Prati criteria for normal. Using the Prati criteria, 7.9% of participants with normal ALT had steatohepatitis and 5.3% had ≥ stage 2 fibrosis. Logistic regression models were used to predict the probabilities of having bridging fibrosis/cirrhosis or a diagnosis of borderline/definite steatohepatitis in the unbiopsied LABS-2 sample. The proportion of biopsied participants with these findings was very similar to the modeled results from the unbiopsied cohorts. We estimated that 86.0% of participants with advanced fibrosis and 88.1% of participants with borderline/definite steatohepatitis were not biopsied and went undiagnosed. As ALT did not reliably exclude significant obesity-related liver disease in bariatric surgery patients, consideration should be given to routine liver biopsy during bariatric surgery and medical follow-up of significant hepatic pathology.

Reporting weight change: Standardized reporting accounting for baseline weight

BACKGROUND Although it is recognized that a standardized approach to reporting weight change is essential to meaningful comparisons among cohorts and across studies, consensus is lacking. This study aimed to propose a method of reporting weight change that would allow meaningful comparisons among studies of patients who underwent bariatric surgery and to demonstrate its utility using an example from the Longitudinal Assessment of Bariatric Surgery (LABS). METHODS Relationships among several measures of weight change are described. Results from an observational, longitudinal cohort study of adults undergoing bariatric surgery and from simulation studies are used to illustrate the proposed method. RESULTS Baseline weight is a critical parameter when assessing weight change. Men undergoing a bariatric procedure other than gastric bypass or adjustable band tended to have greater weight loss 12 months after surgery than men undergoing gastric bypass when not accounting for baseline weight, but the opposite was found when results were adjusted for baseline weight. Simulation results show that with relatively modest sample sizes, the adjusted weight loss was significantly different between the 2 groups of men. CONCLUSION A consistent metric for reporting weight loss after bariatric surgery is essential to interpret outcomes across studies and among subgroups. The baseline weight adjusted percent of weight loss (A%WL) uses a standard population (e.g., the LABS cohort) to account for differences between cohorts with respect to baseline weight, and its use can change the interpretation of results compared with an unadjusted measure.

Effect Modification and Design Sensitivity in Observational Studies

In an observational study of treatment effects, subjects are not randomly assigned to treatment or control, so differing outcomes in treated and control groups may reflect a bias from nonrandom assignment rather than a treatment effect. After adjusting for measured pretreatment covariates, perhaps by matching, a sensitivity analysis determines the magnitude of bias from an unmeasured covariate that would need to be present to alter the conclusions of the naive analysis that presumes adjustments eliminated all bias. Other things being equal, larger effects tend to be less sensitive to bias than smaller effects. Effect modification is an interaction between a treatment and a pretreatment covariate controlled by matching, so that the treatment effect is larger at some values of the covariate than at others. In the presence of effect modification, it is possible that results are less sensitive to bias in subgroups experiencing larger effects. Two cases are considered: (i) an a priori grouping into a few categories based on covariates controlled by matching and (ii) a grouping discovered empirically in the data at hand. In case (i), subgroup specific bounds on p-values are combined using the truncated product of p-values. In case (ii), information that is fixed under the null hypothesis of no treatment effect is used to partition matched pairs in the hope of identifying pairs with larger effects. The methods are evaluated using an asymptotic device, the design sensitivity, and using simulation. Sensitivity analysis for a test of the global null hypothesis of no effect is converted to sensitivity analyses for subgroup analyses using closed testing. A study of an intervention to control malaria in Africa is used to illustrate.

Calibrating Sensitivity Analyses to Observed Covariates in Observational Studies

In medical sciences, statistical analyses based on observational studies are common phenomena. One peril of drawing inferences about the effect of a treatment on subjects using observational studies is the lack of randomized assignment of subjects to the treatment. After adjusting for measured pretreatment covariates, perhaps by matching, a sensitivity analysis examines the impact of an unobserved covariate, u, in an observational study. One type of sensitivity analysis uses two sensitivity parameters to measure the degree of departure of an observational study from randomized assignment. One sensitivity parameter relates u to treatment and the other relates u to response. For subject matter experts, it may be difficult to specify plausible ranges of values for the sensitivity parameters on their absolute scales. We propose an approach that calibrates the values of the sensitivity parameters to the observed covariates and is more interpretable to subject matter experts. We will illustrate our method using data from the U.S. National Health and Nutrition Examination Survey regarding the relationship between cigarette smoking and blood lead levels.

Statistical Methods for Cohort Studies of CKD: Survival Analysis in the Setting of Competing Risks

Survival analysis is commonly used to evaluate factors associated with time to an event of interest (e.g., ESRD, cardiovascular disease, and mortality) among CKD populations. Time to the event of interest is typically observed only for some participants. Other participants have their event time censored because of the end of the study, death, withdrawal from the study, or some other competing event. Classic survival analysis methods, such as Cox proportional hazards regression, rely on the assumption that any censoring is independent of the event of interest. However, in most clinical settings, such as in CKD populations, this assumption is unlikely to be true. For example, participants whose follow-up time is censored because of health-related death likely would have had a shorter time to ESRD, had they not died. These types of competing events that cause dependent censoring are referred to as competing risks. Here, we first describe common circumstances in clinical renal research where competing risks operate and then review statistical approaches for dealing with competing risks. We compare two of the most popular analytical methods used in settings of competing risks: cause-specific hazards models and the Fine and Gray approach (subdistribution hazards models). We also discuss practical recommendations for analysis and interpretation of survival data that incorporate competing risks. To demonstrate each of the analytical tools, we use a study of fibroblast growth factor 23 and risks of mortality and ESRD in participants with CKD from the Chronic Renal Insufficiency Cohort Study.

Relation of Aortic Valve Calcium to Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort Study)

Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p<0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and nonblack patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors.

Perioperative Timing of Infliximab and the Risk of Serious Infection After Elective Hip and Knee Arthroplasty

The optimal timing of tumor necrosis factor antagonists before elective surgery is unknown. This study evaluated the association between infliximab timing and serious infection after elective hip or knee arthroplasty.

CKD Progression and Mortality among Hispanics and Non-Hispanics

Although recommended approaches to CKD management are achieved less often in Hispanics than in non-Hispanics, whether long-term outcomes differ between these groups is unclear. In a prospective longitudinal analysis of participants enrolled into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC Studies, we used Cox proportional hazards models to determine the association between race/ethnicity, CKD progression (50% eGFR loss or incident ESRD), incident ESRD, and all-cause mortality, and linear mixed-effects models to assess differences in eGFR slope. Among 3785 participants, 13% were Hispanic, 43% were non-Hispanic white (NHW), and 44% were non-Hispanic black (NHB). Over a median follow-up of 5.1 years for Hispanics and 6.8 years for non-Hispanics, 27.6% of all participants had CKD progression, 21.3% reached incident ESRD, and 18.3% died. Hispanics had significantly higher rates of CKD progression, incident ESRD, and mean annual decline in eGFR than did NHW (P<0.05) but not NHB. Hispanics had a mortality rate similar to that of NHW but lower than that of NHB (P<0.05). In adjusted analyses, the risk of CKD progression did not differ between Hispanics and NHW or NHB. However, among nondiabetic participants, compared with NHB, Hispanics had a lower risk of CKD progression (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.95) and incident ESRD (hazard ratio, 0.50; 95% confidence interval, 0.30 to 0.84). At higher levels of urine protein, Hispanics had a significantly lower risk of mortality than did non-Hispanics (P<0.05). Thus, important differences in CKD progression and mortality exist between Hispanics and non-Hispanics and may be affected by proteinuria and diabetes.

Failure to rescue in trauma: coming to terms with the second term

INTRODUCTION The failure to rescue (FTR) rate is the probability of death after a major complication and was defined in elective surgical cohorts. In elective surgery, the precedence rate (proportion of deaths preceded by major complications) approaches 100%, but recent studies in trauma report rates of only 20-25%. We hypothesised that use of high quality data would result precedence rates in higher than those derived from national datasets, and we further sought to characterise the nature of those deaths not preceded by major complications. METHODS Prospectively collected data from 2006 to 2010 from a single level I trauma centre were used. Patients age >16 years with AIS ≥2 who survived beyond the trauma bay were included. Complications, mortality, FTR, and precedence rates were calculated. Chart abstraction was performed for registry deaths without recorded complications to verify the absence of complications and determine the cause of death, after which outcomes were re-calculated. RESULTS A total of 8004 patients were included (median age 41 (IQR 25-75), 71% male, 82% blunt, median ISS 10 (IQR 5-18)). Using registry data the precedence rate was 55%, with 132/293 (45%) deaths occurring without antecedent major complications. On chart abstraction, 11/132 (8%) patients recorded in the registry as having no complication prior to death were found to have major complications. Complication and FTR rates after chart abstraction were statistically significantly different than those derived from registry data alone (complications 16.5% vs. 16.3, FTR 12.3 vs.13, p=0.001), but this difference was unlikely to be clinically meaningful. Patients dying without complications predominantly (87%) had neurologic causes of demise. CONCLUSIONS Use of data with near-complete ascertainment of complications results in precedence rates much higher than those from national datasets. Patients dying without precedent complications at our centre largely succumbed to progression of neurologic injury. Attempts to use FTR to compare quality between centres should be limited to high quality data. LEVEL OF EVIDENCE Level III. RETROSPECTIVE COHORT STUDY Outcomes.