Maria M. Ciarleglio

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

BACKGROUND The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). METHODS AND RESULTS We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. CONCLUSION Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.

Effect of a Zoster Vaccine on Herpes Zoster–Related Interference with Functional Status and Health‐Related Quality‐of‐Life Measures in Older Adults

OBJECTIVE: To determine the efficacy of a zoster vaccine on herpes zoster (HR)‐related interference with activities of daily living (ADLs) and health‐related quality of life (HRQL).

Surgical Residency and Attrition: Defining the Individual and Programmatic Factors Predictive of Trainee Losses

BACKGROUND Voluntary resident attrition remains problematic despite recent changes in postgraduate general surgery training, including reduction of work hours. STUDY DESIGN We conducted a prospective study of all postgraduate year (PGY)-1 and -2 trainees on the 2008 American Board of Surgery resident roster (ABS-RR) who completed the National Study of Expectations and Attitudes of Residents in Surgery (NEARS) survey after the American Board of Surgery In-Training Examination (ABSITE) in 2008 or 2009. RESULTS Among 2,222 PGY-1 and -2 residents on the 2008 ABS-RR, 2,033 completed the NEARS survey in 2008 or 2009 (91.5%). The only demographic or programmatic variables associated with voluntary attrition on univariate analysis were PGY-1 status (9.4% risk vs 4.5% risk for PGY-2, p < 0.001) and program location (p = 0.03). Response differences (p < 0.01) were noted in 23 survey items. In multivariate modeling, PGY-2 status was protective against voluntary attrition (p < 0.001, hazard ratio [HR] 0.41), while programs located outside of the South (Northeast: p = 0.006, HR 2.39; Midwest: p = 0.01, HR 2.37; West: p = 0.10, HR 1.76) were associated with higher attrition. The attrition group more frequently reported that they had considered leaving training (p < 0.001, HR 2.59), that the personal cost of training was too great (p < 0.001, HR 2.89), that they were dissatisfied with their operative experience (p = 0.002, HR 1.89), and that they were not committed to completing their training (p < 0.001, HR 3.96). Using the estimated regression coefficient for each variable in the multivariate models, we calculated a risk score for individual residents; these scores were used to construct covariate-adjusted survivorship functions. CONCLUSIONS Resident attitudes, PGY-1 status, and program location are most frequently associated with voluntary attrition. Our risk score calculation represents a novel potential tool for programs to quantify deficiencies in the training experience of residents, and develop targeted strategies to limit disaffection and improve resident retention.

Postoperative Complications After Gynecologic Surgery

OBJECTIVE: To estimate the association of age, medical comorbidities, functional status, and unintentional weight loss (as a marker of frailty) with postoperative complications in women undergoing major gynecologic surgery. METHODS: We conducted a cross-sectional analysis of the American College of Surgeons National Surgical Quality Improvement Program 2005–2009 participant use data files to analyze gynecologic procedures. The primary outcome was a composite of 30-day major postoperative complications. RESULTS: A total of 22,214 women were included in our final analysis. The overall prevalence of composite 30-day major postoperative complications was 3.7% (n=817). Age 80 years or older (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 1.25–2.58), dependent functional status (adjusted OR 2.37, 95% CI 1.53–3.68), and unintentional weight loss (adjusted OR 2.49, 95% CI 1.48–4.17) were significantly associated with postoperative morbidity after adjusting for diabetes mellitus (adjusted OR 1.44, 95% CI 1.15–1.79), known bleeding disorder (adjusted OR 2.29, 95% CI 1.49–3.52), morbid obesity (adjusted OR 1.77, 95% CI 1.45–2.17), ascites (adjusted OR 3.27, 95% CI 2.18–4.90), preoperative systemic infection (adjusted OR 3.02, 95% CI 2.03–4.48), procedures for gynecologic cancer (adjusted OR 1.60, 95% CI 1.27–2.0), disseminated cancer (adjusted OR 2.57, 95% CI 1.64–4.03), emergency procedures (adjusted OR 1.82, 95% CI 1.18–2.79), operative time more than 4 hours compared with less than 1 hour (adjusted OR 2.91, 95% CI 2.18–3.89), and wound class 4 compared with wound class 1 (adjusted OR 4.28, 95% CI 1.82–10.1). CONCLUSION: Age 80 years or older, medical comorbidities, dependent functional status, and unintentional weight loss are associated with increased major postoperative complications after gynecologic procedures. LEVEL OF EVIDENCE: III

The association between urinary and fecal incontinence and social isolation in older women

OBJECTIVE To describe the association between social isolation and urinary incontinence and fecal incontinence in older women. METHODS We conducted a secondary database analysis of the National Social Life, Health and Aging Project for women aged 57 to 85 years old. Our primary outcome was self-report of often feeling isolated. We explored self-report of daily urinary incontinence and weekly fecal incontinence. Two logistic regression analyses were performed to assess the association between often feeling isolated and (1) daily urinary incontinence and (2) weekly fecal incontinence. RESULTS A total of 1412 women were included in our analysis. Daily urinary incontinence was reported by 12.5% (177/1412) of community-dwelling older women. More women with daily urinary incontinence reported often feeling isolated (6.6%; 95% confidence interval [CI], 1.3-11.9 vs 2.6%; 95% CI, 1.7-3.5; P = .04) compared with women without daily urinary incontinence. Women with daily urinary incontinence had 3.0 (95% CI, 1.1-7.6) increased odds of often feeling isolated after adjusting for depressive symptoms, age, race, education, and overall health. Weekly fecal incontinence was reported by 2.9% (41/1412) of women. Weekly fecal incontinence and often feeling isolated were associated on univariable analysis (crude odds ratio, 4.6; 95% CI, 1.4-15.1). However, after adjusting for depressive symptoms, age, race, education, and overall health the association between weekly fecal incontinence and often feeling isolated was not significant (adjusted odds ratio, 0.65; 95% CI, 0.1-5.3; P = .65). CONCLUSION After adjusting for confounders, daily urinary incontinence was significantly associated with often feeling isolated. Weekly fecal incontinence was not found to be associated with often feeling isolated on multivariable logistic regression.

Nurse Observation During Colonoscopy Increases Polyp Detection: A Randomized Prospective Study

OBJECTIVES:To determine whether a second observer during colonoscopy increases adenoma detection.METHODS:Consecutive patients undergoing screening colonoscopy were prospectively randomized to routine colonoscopy or physician and nurse observation during withdrawal.RESULTS:Of 502 patients, 249 were randomized to routine colonoscopy, and 253 to physician plus nurse observation during withdrawal. A total of 592 polyps were detected, 40 identified by the endoscopy nurse only. With nurse observation, 1.32 polyps and 0.82 adenomas were found per colonoscopy, vs. 1.03 polyps and 0.64 adenomas in the routine group, demonstrating a 1.29-fold and a 1.28-fold increase in the average number of polyps and of adenomas detected, respectively. The overall adenoma detection rate (ADR) was 44.1%, with trends toward increased ADR and all-polyp detection rate with nurse observation.CONCLUSIONS:Nurse observation during colonoscopy resulted in an increase in the number of polyps and adenomas found per colonoscopy, along with a trend toward improved overall ADR and all-polyp detection rate.

Model for End-Stage Liver Disease Score Predicts Adverse Events Related to Ventricular Assist Device Therapy

BACKGROUND The Model for End-stage Liver Disease (MELD) score is a marker of multisystem organ dysfunction. It has been used to predict outcomes in patients undergoing hepatic and nonhepatic interventions. End-stage heart disease exhibits a varying degree of multiorgan dysfunction, which impacts the adverse events related to ventricular assist device (VAD) therapy. Our aim for the present study was to investigate the value of MELD score in predicting adverse events related with VAD therapy. METHODS Data were collected on demographics, clinical characteristics, MELD score; Interagency Registry for Mechanically Assisted Circulatory Support-defined VAD adverse events within the first 6 months, and survival from VAD recipients (n=286; from 1996 to 2009). Univariable, multivariable, and Cox regression analyses were performed using SAS software (SAS Institute, Cary, NC). RESULTS The mean MELD score was 14.4±5.9. Actuarial incidence of infections, bleeding events, and cardiovascular dysfunction at 6 months was 65.4%, 52.1%, and 45.6%, respectively. Multivariable Cox proportional hazards model (controlling for gender, type of device, diagnosis, intention to treat, urgency, and inotropic use) confirmed that MELD score predicted mortality, respiratory, and renal dysfunction at 6 months (p<0.01). CONCLUSIONS Preoperative MELD score is predictive of mortality, respiratory, and renal dysfunction at 6 months after controlling for gender, type of device, diagnosis, intention to treat, urgency, and inotropic use. The MELD score may be used as a quantitative tool to assess the adverse events associated with VAD therapy.

Institutional Variation in the Promotion of Racial/Ethnic Minority Faculty at US Medical Schools

OBJECTIVES We compared faculty promotion rates by race/ethnicity across US academic medical centers. METHODS We used the Association of American Medical Colleges 1983 through 2000 faculty roster data to estimate median institution-specific promotion rates for assistant professor to associate professor and for associate professor to full professor. In unadjusted analyses, we compared medians for Hispanic and Black with White faculty using the Wilcoxon rank sum test. We compared institution-specific promotion rates between racial/ethnic groups with data stratified by institutional characteristic (institution size, proportion racial/ethnic minority faculty, and proportion women faculty) using the χ(2) test. Our sample included 128 academic medical centers and 88, 432 unique faculty. RESULTS The median institution-specific promotion rates for White, Hispanic, and Black faculty, respectively, were 30.2%, 23.5%, and 18.8% (P < .01) from assistant to associate professor and 31.5%, 25.0%, and 16.7% (P < .01) from associate to full professor. CONCLUSIONS At most academic medical centers, promotion rates for Hispanic and Black were lower than those for White faculty. Equitable faculty promotion rates may reflect institutional climates that support the successful development of racial/ethnic minority trainees, ultimately improving healthcare access and quality for all patients.

Small Intestinal Transit Time Is Delayed in Small Intestinal Bacterial Overgrowth

Background: Altered small intestinal motility is thought to contribute to the development of small intestinal bacterial overgrowth (SIBO). The clinical manifestations of SIBO and consequent malabsorption are wide ranging and include abdominal pain, bloating, diarrhea, weight loss, and nutritional deficiencies. However, due to the nonspecific nature of symptoms, the diagnosis may often be overlooked. To date, few studies have illustrated a direct relationship between impaired small intestinal motility and SIBO. In addition, further study has been limited by the technical challenges and lack of widespread availability of antroduodenal manometry. The development of a wireless motility capsule (WMC) (SmartPill) that evaluates pressure, pH, and temperature throughout the GI tract offers the potential to identify patients with small bowel transit delays who may be at risk for bacterial overgrowth. Aims: The primary aims of this study were to: (1) characterize the relationship of prolonged small bowel transit time (SBTT) in patients undergoing WMC with SIBO as based on a positive lactulose breath testing (LBT); and (2) to assess the relationship of prolonged gastric, colonic, and whole gut transit times (WGTT) and additional motility parameters with SIBO (positive LBT). We also sought to evaluate the relationship of small bowel motility parameters (SB motility index, contractions per minute, and SB peak amplitudes) with LBT results. Methods: We performed a retrospective study of consecutive patients who were referred for wireless motility testing at a single, tertiary care institution from April 2009 to December 2012. Of the 72 total patients identified, 34 underwent both WMC and LBT. Gastric, small bowel, colonic, WGTT, and SB motility parameters were measured and correlated with LBT results. Statistical methods utilized for data analysis include ANOVA, 2-sample t tests, nonparametric Kruskal Wallis test, Wilcoxon rank-sum test, and the Fisher exact test. Results: Of the 37 patients who underwent both WMC and LBT, 24 (65%) were LBT positive. The mean SBTT among those who were LBT positive was 6.6 hours as compared with 4.2 hours in those who were LBT negative (P=0.04). Among patients who were LBT positive, 47.6% had prolonged SBTT (≥6 h), whereas only 7.7% of those who were LBT negative had a delay in their SBTT (P=0.01). In addition, patients who were LBT positive were more likely to have prolongation of both colonic and WGTT versus those who were LBT negative (CTT: positive LBT=64.4 h vs. negative LBT=35.5 h, P=0.02; WGTT: positive LBT=70.5 h vs. negative LBT=44.1 h, P=0.02). However, there were no statistical differences observed between the groups for gastric emptying times or other small intestinal motility parameters (SB motility index, contractions per minute, and peak amplitudes) between the 2 groups. Conclusions: Patients with underlying SIBO have significant delays in SBTT as compared with those without. The association between prolonged SBTT and positive LBT may be useful in identifying those patients with SIBO diagnosed by LBT and potentially target therapeutic options for those refractory to standard therapy. Interestingly, patients with positive LBT did not necessarily have a generalized gastrointestinal motility (similar GETs among groups), suggesting that small bowel transit specifically predisposes to the development of SIBO. Future, prospective studies are needed to further characterize intestinal dysmotility and other contributing pathophysiological mechanisms in SIBO and to investigate the potential benefits of prokinetics in this challenging patient population.

Drug Authorization for Sofosbuvir/Ledipasvir (Harvoni) for Chronic HCV Infection in a Real-World Cohort: A New Barrier in the HCV Care Cascade

Background New treatments for hepatitis C (HCV) infection hold great promise for cure, but numerous challenges to diagnosing, establishing care, and receiving therapy exist. There are limited data on insurance authorization for these medications. Materials and Methods We performed a retrospective chart review of patients receiving sofosbuvir/ledipasvir (SOF/LED) from October 11-December 31, 2014 to determine rates and timing of drug authorization. We also determined predictors of approval, and those factors associated with faster decision and approval times. Results Of 174 patients prescribed HCV therapy during this period, 129 requests were made for SOF/LED, of whom 100 (77.5%) received initial approval, and an additional 17 patients (13.9%) ultimately received approval through the appeals process. Faster approval times were seen in patients with Child-Pugh Class B disease (14.4 vs. 24.7 days, p = 0.048). A higher proportion of patients were initially approved in those with Medicare/Medicaid coverage (92.2% vs. 71.4%, p = 0.002) and those with baseline viral load ≥6 million IU/mL (84.1% vs. 62.5%, p = 0.040). Linear regression modeling identified advanced fibrosis, high Model of End Stage Liver Disease (MELD) score, and female gender as significant predictors of shorter decision and approval times. On logistic regression, Medicare/Medicaid coverage (OR 5.96, 95% CI 1.66–21.48) and high viral load (OR 4.52, 95% CI 1.08–19.08) were significant predictors for initial approval. Conclusions Early analysis of real-world drug authorization outcomes between October-December 2014 reveals that nearly one in four patients are initially denied access to SOF/LED upon initial prescription, although most patients are eventually approved through appeal, which delays treatment initiation. Having Medicare/Medicaid and advanced liver disease resulted in a higher likelihood of approval as well as earlier decision and approval times. More studies are needed to determine factors resulting in higher likelihood of denial and to evaluate approval rates and times after implementation of restrictive prior authorization guidelines.