Faculty Bibliography

OBJECTIVES/OBJECTIVE:To describe and compare perioperative complications in women undergoing combined ventral rectopexy with sacrocolpopexy compared with perineal rectopexy with vaginal apical suspension. METHODS:Current Procedural Terminology codes were used to identify women in the National Surgical Quality Improvement Program database who underwent ventral rectopexy with sacrocolpopexy or perineal rectopexy with vaginal apical suspension from 2006 to 2015. Perioperative complication was defined as any of the following within 30 days of surgery: death, return to the operating room, transfusion, or vascular, wound, respiratory, infectious, or renal morbidity. Secondary outcomes included length of hospital stay, operative time, blood loss, readmission, and rate of urinary tract infections. Modified Poisson regression was used to estimate the adjusted relative risks of complication associated with surgical approach, abdominal versus perineal. RESULTS:Of the 273 women included, 240 (88%) underwent surgery with an abdominal approach, and 33 (12%) underwent surgery with a perineal approach. Perioperative complications occurred in 24 (9%) patients; 19 (8%) in the abdominal group and 5 (15%) in the perineal group. The age-adjusted risk of perioperative complications was not significantly different between those with a perineal approach compared with those with an abdominal approach (adjusted relative risk, 1.78; 95% confidence interval, 0.73-4.33). CONCLUSIONS:Patients in this database who underwent surgery with a vaginal/perineal approach were not more likely to have a postoperative complication after adjusting for age compared with those undergoing an abdominal approach. Larger studies are needed to determine a more precise estimate of the impact of surgical approach on rates of perioperative complications.

BACKGROUND:While most known causes of infertility relate to the health of the woman and/or her partner, questions have been raised regarding the possible contributions of transgenerational or epigenetic factors. OBJECTIVE:The goal of this hypothesis-generating work was to examine whether Generation 1's (G1's) age at the delivery of G2 (Generation 2) was associated with G2's fertility in later life. METHODS:We conducted a retrospective cohort study of women (G2s) recruited online in 2016. A questionnaire queried G2s regarding demographics and fertility. The primary exposure was G1's age at G2's birth. Outcome measures included the following: 12-month infertility, time to pregnancy, and childlessness. The adjusted relative risk (RR) of G2 infertility and childlessness by G1 age at G2's birth was estimated through a modified Poisson regression approach. The fecundity odds ratio (FOR) for the association between G1's age at G2 birth and time to pregnancy for G2 was estimated by discrete-time survival models, with complementary log-log link. RESULTS:A total of 2,854 women enrolled. We found no association between G1 age at G2's birth and G2 infertility. Being born to a G1 aged 15-19 years was associated with a longer time to pregnancy for G2 (FOR 0.84, 95% confidence interval 0.72, 0.99), relative to being born to a G1 aged 20-24 years. We observed the suggestion of a possible increased risk of childlessness among G2s born to older G1s, but the estimate was imprecise. CONCLUSIONS:While being born to a G1 who was 15-19 years old was associated with an increase in G2 time to pregnancy, we found no association between G1 age at G2's birth and infertility and only the suggestion of a modest association with childlessness. These data suggest a possible subtle effect of G1 age at G2's birth on G2 fertility, which warrants further study.

BACKGROUND:Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. OBJECTIVE:To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy. MATERIALS AND METHODS:We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. RESULTS:Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P = .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm. CONCLUSION:Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

The Appalachian region experiences higher incidence and mortality due to cervical cancer compared with other regions of the United States. The goal of the Ohio State University Center for Population Health and Health Disparities (CPHHD), called the Community Awareness Resources and Education (CARE) project, was to understand reasons for this disparity. The first wave (2003-2008) of funding included three projects focusing on the known risk factors for cervical cancer, lack of screening, smoking, and infection with human papillomavirus (HPV). On the basis of the results of these projects, the second wave (2011-2017) included four projects, designed to address a multi-level model of factors contributing to cervical disparities in Appalachia. The results of these projects were then used to refine a multi-level model that explains cervical cancer disparities in Appalachia. Future funded projects will take these multi-level explanations for cervical disparities and focus on implementation science strategies to reduce the burden of cervical cancer morbidity and mortality in Appalachia.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.

Traditionally, children presenting with appendicitis are referred for urgent appendectomy. Recent improvements in the quality and availability of diagnostic imaging allow for better pre-operative characterization of appendicitis, including severity of inflammation; size of the appendix; and presence of extra-luminal inflammation, phlegmon, or abscess. These imaging advances, in conjunction with the availability of broad spectrum oral antibiotics, allow for the identification of a subset of patients with uncomplicated appendicitis that can be successfully treated with antibiotics alone. Recent studies demonstrated that antibiotics alone are a safe and efficacious treatment alternative for patents with uncomplicated appendicitis. The objective of this study is to perform a multi-institutional trial to examine the effectiveness of non-operative management of uncomplicated pediatric appendicitis across a group of large children's hospitals. A prospective patient choice design was chosen to compare non-operative management to surgery in order to assess effectiveness in a broad population representative of clinical practice in which non-operative management is offered as an alternative to surgery. The risks and benefits of each treatment are very different and a "successful" treatment depends on which risks and benefits are most important to each patient and his/her family. The patient-choice design allows for alignment of preferences with treatment. Patients meeting eligibility criteria are offered a choice of non-operative management or appendectomy. Primary outcomes include determining the success rate of non-operative management and comparing differences in disability days, and secondarily, complication rates, quality of life, and healthcare satisfaction, between patients choosing non-operative management and those choosing appendectomy.

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.

PURPOSE/OBJECTIVE:This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. METHODS:tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. RESULTS:Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between "Appalachian self-identity" variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. CONCLUSIONS:This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

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.

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.