Faculty Bibliography

OBJECTIVE:To evaluate the effect of family attendance at inpatient rehabilitation therapy sessions on traumatic brain injury (TBI) patient outcomes at discharge and up to 9 months postdischarge. DESIGN:Propensity score methods are applied to the TBI Practice-Based Evidence database, a database consisting of multisite, prospective, longitudinal, and observational data. SETTING:Nine inpatient rehabilitation centers in the United States. PARTICIPANTS:Patients (N=1835) admitted for first inpatient rehabilitation after an index TBI. INTERVENTION:Family attendance during therapy sessions. MAIN OUTCOME MEASURES:Participation Assessment for Recombined Tools-Objective-17 (Total scores and subdomain scores of Productivity, Out and About, and Social Relations), Functional Independence Measure, Satisfaction with Life Scale, and Patient Health Questionnaire-9. RESULTS:Participants whose families were in attendance for at least 10% of the treatment time were more out and about in their communities at 3 and 9 months postdischarge than participants whose families attended treatment less than 10% of the time. Although findings varied by propensity score method, improved functional independence in the cognitive area at 9 months was also associated with increased family attendance. CONCLUSIONS:Family involvement during inpatient rehabilitation may improve community participation and cognitive functioning up to 9 months after discharge. Rehabilitation teams should engage patients' families in the rehabilitation process to maximize outcomes.

OBJECTIVE:To use causal inference methods to determine if receipt of a greater proportion of inpatient rehabilitation treatment focused on higher level functions, for example, executive functions, ambulating over uneven surfaces (advanced therapy [AdvTx]), results in better rehabilitation outcomes. DESIGN:A cohort study using propensity score methods applied to the traumatic brain injury practice-based evidence (TBI-PBE) database, a database consisting of multisite, prospective, longitudinal observational data. SETTING:Acute inpatient rehabilitation facilities. PARTICIPANTS:Patients enrolled in the TBI-PBE study (N=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, receiving their first inpatient rehabilitation facility admission to 1 of 9 sites in the United States, and consented to follow-up 3 and 9 months postdischarge from inpatient rehabilitation. INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Participation Assessment with Recombined Tools-Objective-17, FIM motor and cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. RESULTS:Controlling for measured potential confounders, increasing the percentage of AdvTx during inpatient TBI rehabilitation was found to be associated with better community participation, functional independence, life satisfaction, and decreased likelihood of depression during the year after discharge from inpatient rehabilitation. Participants who began rehabilitation with greater disability experienced larger gains on some outcomes than those who began rehabilitation with more intact abilities. CONCLUSIONS:Increasing the proportion of treatment targeting higher level functions appears to have no detrimental and a small, beneficial effect on outcome. Caution should be exercised when inferring causality given that a large number of potential confounders could not be completely controlled with propensity score methods. Further, the extent to which unmeasured confounders influenced the findings is not known and could be of particular concern due to the potential for the patient's recovery trajectory to influence therapists' decisions to provide a greater amount of AdvTx.

BACKGROUND:While the clinical trials and statistical methodology literature on sample size re-estimation (SSRE) is robust, evaluation of SSRE procedures following the completion of a clinical trial has been sparsely reported. In blinded sample size re-estimation, only nuisance parameters are re-estimated, and the blinding of the current trial treatment effect is preserved. Blinded re-estimation procedures are well-accepted by regulatory agencies and funders. We review our experience of sample size re-estimation in a large international, National Institutes of Health funded clinical trial for adjuvant breast cancer treatment, and evaluate our blinded sample size re-estimation procedure for this time-to-event trial. We evaluated the SSRE procedure by examining assumptions made during the re-estimation process, estimates resulting from re-estimation, and the impact on final trial results with and without the addition of participants, following sample size re-estimation. METHODS:We compared the control group failure probabilities estimated at the time of SSRE to estimates used in the original planning, to the final un-blinded control group failure probability estimates for those included in the SSRE procedure (SSRE cohort), and to the final total control group failure probability estimates. The impact of re-estimation on the final comparison between randomized treatment groups is evaluated for those in the originally planned cohort (n = 340) and for the combination of those recruited in the originally planned cohort and those added after re-estimation (n = 509). RESULTS:Very little difference is observed between the originally planned cohort and all randomized patients in the control group failure probabilities over time or in the overall hazard ratio estimating treatment effect (originally planned cohort HR 1.25 (0.86, 1.79); all randomized cohort HR 1.24 95% CI (0.91, 1.68)). At the time of blinded SSRE, the estimated control group failure probabilities at 3 years (0.24) and 5 years (0.40) were similar to those for the SSRE cohort once un-blinded (3 years, 0.22 (0.16, 0.30); 5 years, 0.33 (0.26, 0.41)). CONCLUSIONS:We found that our re-estimation procedure performed reasonably well in estimating the control group failure probabilities at the time of re-estimation. Particularly for time-to-event outcomes, pre-planned blinded SSRE procedures may be the best option to aid in maintaining power. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov, NCT00201851 . Registered on 9 September 2005. Retrospectively registered.

A lack of in-depth assessment of the nutritional status of homeless youth precludes interventions that achieve nutritional adequacy. We enrolled 118 unaccompanied homeless youth to obtain sociodemographic and health data along with dietary, anthropometric, biochemical, and clinical assessments. As a reference, homeless youth data were compared to a convenience sample of 145 college students. Obesity was prevalent among homeless youth than among college students (29% vs. 8% respectively (CI: 11.2, 29.9). Among homeless youth, 74% of females versus 41% of males were overweight/obese (CI: 14.9, 51.2). Homeless youth also had poor diet quality (44.37 (SD: 12.64)). Over 70% of homeless youth had inadequate intakes of vitamins A, C, D₃ and E, as well as calcium and magnesium. Our findings show increased weight, adiposity, and suboptimal intakes of essential nutrients among unaccompanied homeless youth. Further studies are needed to inform evidence-based nutrition interventions that will aid in improving their nutritional health.

OBJECTIVE:The impact of pathologic features of a cone biopsy on the management of women with early stage cervical cancer is understudied. Our objective was to evaluate the additive value of pathologic features of a cone biopsy toward identifying patients with high risk tumors for which adjuvant therapy may be indicated. METHODS:Patients with early stage cervical cancer undergoing a conization followed by radical hysterectomy from 1995 to 2016 were retrospectively identified. Clinical and pathologic data were abstracted from patient medical records. RESULTS:A total of 115 patients were identified. Based on final pathology, 70.5% were low risk, 10.4% intermediate risk, and 19.1% were high risk. The additive pathologic features of the conization specimen would have reclassified five patients from low into the intermediate risk group. Though depth of invasion did not correlate with final pathology results, when lymphovascular space invasion (LVSI) was present in the conization specimen, 51.2% of patients were noted to meet intermediate/high risk; compared to only 9.5% without LVSI. CONCLUSIONS:In women with early stage cervical cancer, additive pathology of the conization and hysterectomy specimen did not significantly impact risk stratification, only affecting 4.3% of patients. However, presence of LVSI in the conization was associated with intermediate risk criteria in 60% of cases and high risk criteria in 37% of cases. As patients with intermediate/high risk criteria would meet recommendations for adjuvant therapy, the evaluation of LVSI in conization specimens may influence the selection of primary treatment for women with cervical cancer.

OBJECTIVE:To evaluate the effect of providing a greater percentage of therapy as contextualized treatment on acute traumatic brain injury (TBI) rehabilitation outcomes. DESIGN:Propensity score methods are applied to the TBI Practice-Based Evidence (TBI-PBE) database, a database consisting of multi-site, prospective, longitudinal observational data. SETTING:Acute inpatient rehabilitation. PARTICIPANTS:Patients enrolled in the TBI-PBE study (N=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, received their first inpatient rehabilitation facility admission in the US, and consented to follow-up 3 and 9 months post discharge from inpatient rehabilitation. INTERVENTIONS:Not applicable. MAIN OUTCOME MEASURES:Participation Assessment with Recombined Tools-Objective (PART-O)-17, FIM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. RESULTS:Increasing the percentage of contextualized treatment during inpatient TBI rehabilitation leads to better outcomes, specifically in regard to community participation. CONCLUSIONS:Increasing the proportion of treatment provided in the context of real-life activities appears to have a beneficial effect on outcome. Although the effect sizes are small, the results are consistent with other studies supporting functional-based interventions effecting better outcomes. Furthermore, any positive findings, regardless of size or strength, are endorsed as important by consumers (survivors of TBI). While the findings do not imply that decontextualized treatment should not be used, when the therapy goal can be addressed with either approach, the findings suggest that better outcomes may result if the contextualized approach is used.

OBJECTIVE:To determine the Screening Tool for Early Predictors of Post-Traumatic Stress Disorder (STEPP) test accuracy in identifying children with new mental health diagnoses and psychotropic medications prescribed within 12 months after unintentional injuries in a managed-Medicaid population. STUDY DESIGN:We conducted a secondary analysis of a retrospective cohort that investigated mental health diagnoses and psychotropic medications pre- and post-injury in children ≤18 years of age treated at a pediatric trauma center from 2005 to 2015 (n = 2208). For this study, we analyzed children with STEPP scores from their injury admission (n = 85). For children without previous mental health diagnoses or psychotropic prescriptions, we calculated the sensitivity, specificity, and positive and negative predictive values for the child and parent STEPP. RESULTS:Of 78 children without previous diagnoses, 12 had post-injury mental health diagnoses. Of 68 children without previous psychotropic medication use, 10 had psychotropic medications prescribed. The child STEPP sensitivity was 8.3% for mental health diagnoses (95% CI 0.2, 38.5) and 10% for psychotropic medications (95% CI 0.3, 44.5). The child STEPP specificity was 77.3% for mental health diagnoses (95% CI 65.3, 86.7) and 75.9% for psychotropic medication (95% CI 62.8, 86.1). CONCLUSIONS:We found that the STEPP performed poorly in identifying children who received new mental health diagnoses and new psychotropic medications following injury.

OBJECTIVE:The aim of the study was to examine current patterns and factors associated with preoperative testing in patients undergoing midurethral sling and to compare 30-day outcomes in subjects. METHODS:This retrospective cohort study was performed using the National Surgery Quality Improvement Program database from 2005 to 2014. All women undergoing midurethral slings were identified by Current Procedural Terminology code. Clinical variables were abstracted and the incidence of preoperative serum labs was determined. Multivariable logistic regression was used to estimate associations between clinical factors and collection of preoperative serum labs and between 30-day outcomes and collection of labs. RESULTS:A total of 12,368 women underwent midurethral sling in the National Surgery Quality Improvement Program database during the study period. Preoperative serum testing within 30 days before surgery was observed in 9172 (74.2%) women. Age, American Society of Anesthesiologists class, diabetes, and hypertension were strongly associated with preoperative testing when modeling together in multivariable regression. Of the 543 women who had any complication, 410 (75.5%) received preoperative testing. Urinary tract infection was the most frequent complication (66.1%). Age, American Society of Anesthesiologists class, body mass index, and presence of any comorbidity were associated with the presence of any complication at 30 days. Adjusting for these factors, the odds of complications were not significantly different between those who did and did not have preoperative testing (adjusted odds ratio = 0.98, 95% confidence interval = 0.78-1.24). CONCLUSIONS:Most women who underwent midurethral sling procedures had preoperative testing. Major postoperative complications were uncommon, and there was no substantial difference in outcomes between women who underwent preoperative testing and those who did not. In the future, surgeons may consider eliminating preoperative testing in low-risk patients.

High-dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life-threatening infections and failure of ASCT. Granulocyte-colony stimulating factor (G-CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high-dose melphalan and G-CSF administration. The extended PK/PD model incorporated several covariates, including G-CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G-CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration.