Douglas Gunzler

Introduction to mediation analysis with structural equation modeling

In mediation, we consider an intermediate variable, called the mediator, that helps explain how or why an independent variable influences an outcome. In the context of a treatment study, it is often of great interest to identify and study the mechanisms by which an intervention achieves its effect. By investigating mediational processes that clarify how the treatment achieves the study outcome, not only can we further our understanding of the pathology of the disease and the mechanisms of treatment, but we may also be able to identify alternative, more efficient, intervention strategies. For example, a tobacco prevention program may teach participants how to stop taking smoking breaks at work (the intervention) which changes their social norms about tobacco use (the intermediate mediator) and subsequently leads to a reduction in smoking behavior (study outcome).

Fish consumption, mercury exposure, and their associations with scholastic achievement in the Seychelles Child Development Study §

Studies of neurodevelopmental outcomes in offspring exposed to MeHg from maternal consumption of fish have primarily measured cognitive abilities. Reported associations have been subtle and in both adverse and beneficial directions. Changes in functional outcomes such as school achievement and behavior in exposed children and adolescents have not been examined. We undertook an assessment of school success of children in the Seychelles Child Development Study (SCDS) main cohort to determine if there were any associations with either prenatal or recent postnatal MeHg exposure. The primary endpoints were Seychelles nationally standardized end-of-year examinations given when the cohort children were 9 and 17 years of age. A subgroup (n=215) from the main cohort was also examined at 9 years of age using a regional achievement test called SACMEQ. Prenatal MeHg exposure was 6.8 ppm in maternal hair; recent postnatal exposure was 6.09 ppm at 9 years and 8.0 ppm at 17 years, measured in child hair. Multiple linear regression analyses showed no pattern of associations between prenatal or postnatal exposure, and either the 9- or 17-year end-of-year examination scores. For the subgroup of 215 subjects who participated in the SACMEQ test, there were significant adverse associations between examination scores and postnatal exposure, but only for males. The average postnatal exposure level in child hair for this subgroup was significantly higher than for the overall cohort. These results are consistent with our earlier studies and support the interpretation that prenatal MeHg exposure at dosages achieved by mothers consuming a diet high in fish are not associated with adverse educational measures of scholastic achievement. The adverse association of educational measures with postnatal exposure in males is intriguing, but will need to be confirmed by further studies examining factors that influence scholastic achievement.

A laparoscopic approach does reduce short-term complications in patients undergoing ileal pouch-anal anastomosis.

BACKGROUND: Studies to date examining the impact of laparoscopy in the IPAA have failed to demonstrate a significant, consistent benefit in terms of a reduction in short-term morbidity or length of stay. OBJECTIVE: The aim of this study was to establish the impact of the operative approach (laparoscopic or open) on outcomes after IPAA formation. DESIGN, SETTING, AND PATIENTS: With use of the American College of Surgeons National Surgical Quality Improvement Program participant use file (2005–2008), the records of patients who underwent open or laparoscopic IPAA with diverting ileostomy were examined. MAIN OUTCOME MEASURES: Risk-adjusted 30-day outcomes and length of stay were assessed by use of regression modeling, adjusting for patient characteristics, comorbidities, and operative approach. RESULTS: Six hundred seventy-six cases were included, of which 339 (50.1%) were laparoscopic procedures. After adjustment, a laparoscopic approach was associated with a lower rate of major (OR = 0.67, 95% CI: 0.45–0.99, P = .04) and minor (OR = 0.44, 95% CI: 0.27–0.70, P = .01) complications. Laparoscopy was not associated with a significant reduction in length of postoperative stay compared with open pouch formation (laparoscopic vs open approach, −0.05 ± 0.30 d (P = .87)). LIMITATIONS: The sampling strategy used by the National Surgical Quality Improvement Program means that only a proportion of all relevant cases would have been analyzed and no data are available about the potential impact of surgeon experience on outcome. CONCLUSIONS: A laparoscopic approach to ileal pouch formation was associated with a significant reduction in both major and minor complications compared with the traditional open approach. Given the high financial costs associated with complications arising from this procedure, this study provides support for the adoption of the laparoscopic approach in the formation of an IPAA.

Factors Independently Associated With Complications and Length of Stay after Hip Arthroplasty : Analysis of the National Surgical Quality Improvement Program

By analysis of the American College of Surgeons National Surgical Quality Improvement Program database, we identified factors associated with postoperative complications and increased hospital stay after total hip arthroplasty in 4281 patients. There was a minor complication rate of 2.7%, a major complication rate of 4.2%, and a mortality rate of 0.26% within 30 days of the procedure. After adjusted analysis, obesity, preoperative anemia, and longer operative time were all associated with wound complications. Preoperative anemia, higher American Society of Anesthesiologists class, and prolonged operative time were associated with development of a major complication. A predischarge major complication resulted in an increased length of stay of 6.248 days (±0.286, P < .0001). One in 25 hip arthroplasty patients developed a major postoperative complication, and 1 in 16, a medical complication after elective hip arthroplasty.

Randomized Controlled Trial of Surface Peroneal Nerve Stimulation for Motor Relearning in Lower Limb Hemiparesis

OBJECTIVE To compare the motor relearning effect of a surface peroneal nerve stimulator (PNS) versus usual care on lower limb motor impairment, activity limitation, and quality of life among chronic stroke survivors. DESIGN Single-blinded randomized controlled trial. SETTING Teaching hospital of academic medical center. PARTICIPANTS Chronic stroke survivors (N=110; >12wk poststroke) with unilateral hemiparesis and dorsiflexion strength of ≤4/5 on the Medical Research Council scale. INTERVENTIONS Subjects were stratified by motor impairment level and then randomly assigned to ambulation training with either a surface PNS device or usual care (ankle-foot orthosis or no device) intervention. Subjects were treated for 12 weeks and followed up for 6 months posttreatment. MAIN OUTCOME MEASURES Lower limb portion of the Fugl-Meyer (FM) Assessment (motor impairment), the modified Emory Functional Ambulation Profile (mEFAP) performed without a device (functional ambulation), and the Stroke Specific Quality of Life (SSQOL) scale. RESULTS There was no significant treatment group main effect or treatment group by time interaction effect on FM, mEFAP, or SSQOL raw scores (P>.05). The time effect was significant for the 3 raw scores (P<.05). However, when comparing average change scores from baseline (t1) to end of treatment (t2, 12wk), and at 12 weeks (t3) and 24 weeks (t4) after end of treatment, significant differences were noted only for the mEFAP and SSQOL scores. The change in the average scores for both mEFAP and SSQOL occurred between t1 and t2, followed by relative stability thereafter. CONCLUSIONS There was no evidence of a motor relearning effect on lower limb motor impairment in either the PNS or usual-care groups. However, both the PNS and usual-care groups demonstrated significant improvements in functional mobility and quality of life during the treatment period, which were maintained at 6-month follow-up.

A laparoscopic approach reduces short-term complications and length of stay following ileocolic resection in Crohn's disease: An analysis of outcomes from the NSQIP database

Aim  Studies to date examining the impact of laparoscopy in resection for Crohns disease on short‐term morbidity have been limited by small study populations. The aim of this study was to establish the impact of the operative approach (laparoscopic or open) on outcomes after ileocolic resection for Crohn’s disease.

Peripheral nerve stimulation compared with usual care for pain relief of hemiplegic shoulder pain: a randomized controlled trial.

ObjectiveThis study sought to establish the efficacy of single-lead, 3-wk peripheral nerve stimulation (PNS) therapy for pain reduction in stroke survivors with chronic hemiplegic shoulder pain. DesignThis study is a single-site, pilot, randomized controlled trial of adults with chronic shoulder pain after stroke. Participants were randomized to receive a 3-wk treatment of single-lead PNS or usual care. The primary outcome was the worst pain in the last week (Brief Pain Inventory, Short Form, question 3) measured at baseline and weeks 1, 4, 12, and 16. The secondary outcomes included pain interference (Brief Pain Inventory, Short Form, question 9), pain measured by the ShoulderQ Visual Graphic Rating Scales, and health-related quality-of-life (Short-Form 36 version 2). ResultsTwenty-five participants were recruited, 13 to PNS and 12 to usual care. There was a significantly greater reduction in pain for the PNS group compared with the controls, with significant differences at 6 and 12 wks after treatment. Both PNS and usual care were associated with significant improvements in pain interference and physical health-related quality-of-life. ConclusionsShort-term PNS is a safe and efficacious treatment of shoulder pain. Pain reduction is greater compared with usual care and is maintained for at least 12 wks after treatment.

Longitudinal changes in infant body composition: association with childhood obesity

Rapid weight gain in infancy has been established as a risk factor for the development of later obesity.

Modeling longitudinal binomial responses: implications from two dueling paradigms

The generalized estimating equations (GEEs) and generalized linear mixed-effects model (GLMM) are the two most popular paradigms to extend models for cross-sectional data to a longitudinal setting. Although the two approaches yield well-interpreted models for continuous outcomes, it is quite a different story when applied to binomial responses. We discuss major modeling differences between the GEE- and GLMM-derived models by presenting new results regarding the model-driven differences. Our results show that GLMM induces some artifacts in the marginal models at assessment times, making it inappropriate when applied to such responses from real study data. The different interpretations of parameters resulting from the conceptual difference between the two modeling approaches also carry quite significant implications and ramifications with respect to data and power analyses. Although a special case involving a scale difference in parameters between GEE and GLMM has been noted in the literature, its implications in real data analysis has not been thoroughly addressed. Further, this special case has a very limited covariate structure and does not apply to most real studies, especially multi-center clinical trials. The new results presented fill a substantial gap in the literature regarding the model-driven differences between the two dueling paradigms.

Test of a Clinical Model of Drinking and Suicidal Risk

BACKGROUND There are few data on the role of drinking patterns in suicidal thoughts or behavior among alcohol-dependent individuals (ADIs) and meager data on variables that may influence the role of drinking in suicidal thoughts and behavior. This study tested a heuristic model that predicts that drinking promotes suicidal thoughts and behavior, the association is mediated (accounted for) by depressive symptoms, and that anger moderates (increases) the risk associated with intense drinking. METHODS Data from Project MATCH, a multisite alcohol use disorders treatment trial, were analyzed using structural equation modeling. There were 1,726 participants including 24% women and a mean age of 40.2 ± 11.0 years. Subjects were assessed at baseline and at 3-, 9-, and 15-month follow-up. Two categorical measures (presence/absence) of suicidal ideation (SI) were used that were analyzed in separate models. Predictors of interest were continuous assessments of average drinking intensity (i.e., drinks per drinking day or DDD), drinking frequency (i.e., percent days abstinent or PDA), depression, and anger. RESULTS Both DDD and PDA were associated with SI at a statistically significant level, with PDA showing an inverse association. Depression scores served as a partial mediator or a full mediator of the drinking-SI relationship depending on the measure of SI used in the analysis. The models testing anger scores as a moderator fit the data poorly and did not support that anger serves as a moderator of the drinking-SI association. CONCLUSIONS Greater drinking intensity and drinking frequency predict SI among ADIs and depression serves as a mediator of these associations, but anger does not appear to serve as a moderator. Further research is required to clarify whether depression serves as a partial or full mediator and to see whether the results herein extend to suicidal behavior (i.e., suicide attempt, suicide).