Improving Anesthesia Start Time Documentation Through a Departmental Education Initiative at Yale New Haven Hospital, New Haven, United States.

Background Reimbursement for anesthetic services in the United States utilizes a formula that incorporates procedural and patient factors with total anesthesia time. According to the Centers for Medicare & Medicaid Services and the American Society of Anesthesiologists, the period of billable time starts when the anesthesia practitioner assumes care of the patient and may include transport to the operating room from the preoperative holding area. In this report on a quality improvement effort, we implemented a departmental education initiative aimed at improving the accuracy of anesthesia start-time documentation. Methods Utilizing de-identified, internal data on surgical procedures at Yale New Haven Hospital (YNHH), New Haven, United States, the difference between documented anesthesia start and patient in-room time was determined for all cases. Those with a difference between 0-1 minute were assumed "likely underbilled," and the total revenue lost for these cases was estimated using a weighted average of institutional reimbursement per unit of time. A monthly, department-wide educational email was then introduced to inform practitioners about the guidelines around start-time documentation, and the percentage of "likely underbilled" cases and lost revenue estimates trended over a one-year period. Results Baseline data in December 2020 showed that of the 6,877 total surgical cases requiring anesthesia at YNHH, 55.1% (N=3,790) had an anesthesia start to in-room time of 0-1 minute, which were considered "likely underbilled." The average start-to-in-room time for properly recorded cases (44.9%, N=3,087) was 4.42 minutes. The baseline revenue lost in December 2020 for underbilled cases was estimated at $52,302. Over the one-year quality improvement initiative, the proportion of underbilled cases showed a downward trend, decreasing to 29.2% of total cases by November 2021. The estimate of revenue lost due to underbilling also showed a downward trend, decreasing to $29,300 in November 2021. Conclusion This quality improvement study demonstrated that a relatively simple, department-wide educational email sent monthly correlated with an improvement in anesthesia start-time documentation accuracy and a reduction in estimated revenue lost to underbilling over a one-year period.

Smooth versus Textured Tissue Expanders: Comparison of Outcomes and Complications in 536 Implants.

Background Increasing concerns regarding the safety of textured surface implants have resulted in surgeons transitioning from textured tissue expanders (TEs) to smooth TEs. Given this change has only recently occurred, this study evaluated outcomes between smooth and textured TEs. Methods Women who underwent two-stage breast reconstruction using TEs from 2013 to 2022 were included. TE-specific variables, perioperative information, pain scores, and complications were collected. Chi-squared, t -test, and linear regression analyses were performed. Results A total of 320 patients received a total of 384 textured and 152 smooth TEs. Note that 216 patients received bilateral reconstruction. TEs were removed in 9 cases. No significant differences existed between groups regarding comorbidities. Smooth TEs had a higher proportion of prepectoral placement ( p < 0.001). Smooth TEs had less fills (3 ± 1 vs. 4 ± 2, p < 0.001), shorter expansion periods (60 ± 44 vs. 90 ± 77 days, p < 0.001), smaller expander fill volumes (390 ± 168 vs. 478 ± 177 mL, p < 0.001), and shorter time to exchange (80 ± 43 vs. 104 ± 39 days, p < 0.001). Complication rates between textured and smooth TEs were comparable. Smooth TE had a greater proportion of TE replacements ( p = 0.030). On regression analysis, pain scores were more closely associated with age ( p = 0.018) and TE texture ( p = 0.046). Additional procedures at time of TE exchange ( p < 0.001) and textured TE ( p = 0.017) led to longer operative times. Conclusion As many surgeons have transitioned away from textured implants, our study shows that smooth TEs have similar outcomes to the textured alternatives.

Assessment of disparities in timely diagnosis and comprehensive workup of cognitive impairment between English and Spanish speakers.

BACKGROUND: Previous studies have examined disparities in dementia care that affect the U.S. Hispanic/Latino population, including clinician bias, lack of cultural responsiveness, and less access to health care. However, there is limited research that specifically investigates the impact of language barriers to health disparities in dementia diagnosis. METHODS: In this retrospective cross-sectional study, 12,080 English- or Spanish- speaking patients who received an initial diagnosis of mild cognitive impairment (MCI) or dementia between July 2017 and June 2019 were identified in the Yale New Haven Health (YNHH) electronic medical record. To evaluate the timeliness of diagnosis, an initial diagnosis of MCI was classified as "timely", while an initial diagnosis of dementia was considered "delayed." Comprehensiveness of diagnosis was assessed by measuring the presence of laboratory studies, neuroimaging, specialist evaluation, and advanced diagnostics six months before or after diagnosis. Binomial logistic regressions were calculated with and without adjustment for age, legal sex, ethnicity, neighborhood disadvantage, and medical comorbidities. RESULTS: Spanish speakers were less likely to receive a timely diagnosis when compared with English speakers both before (unadjusted OR, 0.65; 95% CI, 0.53-0.80, p <0.0001) and after adjusting for covariates (adjusted OR, 0.55; 95% CI, 0.40-0.75, p = 0.0001). Diagnostic services were provided equally between groups, except for referrals to geriatrics, which were more frequent among Spanish-speaking patients. A subgroup analysis revealed that Spanish-speaking Hispanic/Latino patients were less likely to receive a timely diagnosis compared to English-speaking Hispanic/Latino patients (adjusted OR, 0.53; 95% CI, 0.38-0.73, p = 0.0001). CONCLUSIONS: Non-English language preference is likely to be a contributing factor to timely diagnosis of cognitive impairment. In this study, Spanish language preference rather than Hispanic/Latino ethnicity was a significant predictor of a less timely diagnosis of cognitive impairment. Policy changes are needed to reduce barriers in cognitive disorders care for Spanish-speaking patients.

Domestic Violence-Related Ocular Injuries Among Adult Patients: Data from the Nationwide Emergency Department Sample, 2008-2017.

PURPOSE: To investigate domestic violence (DV)-related ocular injuries among adult emergency department (ED) patients in the US. METHODS: This was a retrospective, cross-sectional study of patients with a diagnosis of DV and diagnosis of ocular injury in the Nationwide Emergency Department Sample (NEDS) from 2008-2017. We identified patient- and hospital-level variables associated with DV-related ocular injuries. We calculated annual incidence rates using US Census data. Adjusting for inflation using the Consumer Price Index, we calculated mean and total charges. RESULTS: From 2008-2017, there were 26,215 ED visits for ocular injuries related to DV with an average incidence of 1.09 per 100,000 adult population (female patients, 84.5%; mean age [SE], 34.3 [0.2]). DV-related ocular injuries were most prevalent among patients in the lowest income quartile (39.1%) and on Medicaid (37.4%). Most ED visits presented to metropolitan teaching (55.4%), non-trauma (46.7%), and south regional (30.5%) hospitals. The most common ocular injury was contusion of eye/adnexa (61.1%). The hospital admission rate was 5.2% with a mean hospital stay of 2.9 [0.2]. The inflation-adjusted mean cost for medical services was $38,540 [2,310.8] per encounter with an average increase of $2,116 per encounter, annually. The likelihood of hospital admission increased for patients aged ≥60 years old, on Medicare, and with open globes or facial/orbital fractures (all p < .05). CONCLUSION: Contusion of the eye/adnexa was the most common ocular injury among patients with DV-related ED visits. To better facilitate referrals to social services, ophthalmologists should utilize DV screenings, especially towards women and patients of less privileged socioeconomic status.

Epidemiologic trends of domestic violence-related ocular injuries among pediatric patients: data from the Nationwide Emergency Department Sample 2008-2017.

PURPOSE: To study the epidemiology of all domestic violence (DV)-related ocular injuries among pediatric emergency department (ED) patients in the United States. METHODS: This is a retrospective, cross-sectional study of isolated children (<18 years of age) with a diagnosis of DV and primary or secondary diagnosis of ocular injuries in the Nationwide Emergency Department Sample, 2008-2017. We calculated annual incidence of DV-related ocular injuries and prevalence by demographic variables, including age, sex, and income quartile. Median charges, median length of inpatient hospital stay, and factors associated with hospitalization were also measured. RESULTS: From 2008 to 2017, there were 4,125 ED encounters, with an average incidence of 0.56 per 100,000 population (males, 50.0%; mean age [SE], 9.2 [0.3]). Patients in the lowest income quartile (42.6%) and with Medicaid insurance (63.2%) were the most prevalent. The most common known perpetrator was a family member (29.4%). Most ED encounters took place at southern regional (28.6%), metropolitan teaching (67.1%) and designated trauma hospitals (57.8%). Contusion of the eye/adnexa and being struck by or against an object were the most common ocular diagnosis and known mechanism of injury, respectively. An estimated 12.4% of patients were admitted with a median hospital stay of 4 (IQR, 2-6). Median charges during the study period were $27,415.10 (IQR, $13,142.70-$54,454.90). CONCLUSIONS: DV-related ocular injuries were most prevalent among patients with a low socioeconomic status. Given the historical underreporting of DV, future studies are warranted to identify more specific social determinants of health that contribute to such presentations.

Emergency Department Presentations of Acute Primary Angle Closure in the United States from 2008 to 2017.

Purpose: Acute primary angle closure (APAC) is an ophthalmologic emergency. Nationwide data on the epidemiology and clinical characteristics of APAC are lacking despite the associated visual morbidity. Patients and Methods: A retrospective cross-sectional study using the Nationwide Emergency Department Sample (NEDS). The NEDS was queried by ICD-9/10 code for cases of APAC presenting to the United States emergency departments over a ten-year period from 2008 to 2017. All identified cases were included to produce nationally representative estimates. Linear regression and seasonality tests were used to identify trends. Reported outcomes include the incidence, demographics, seasonality, and economic impact of APAC regionally and nationwide. Results: A total of 23,203 APAC-related ED visits were identified. The mean (SD) and median ages were 58.8 (16.2) and 60 years, respectively. Females (59.4%, p < 0.01), those in the lowest income quartile (6983, 30.1%, p < 0.01), and those in the seventh decade of life (5599, 24.1%) presented more frequently with APAC. The incidence of ED presentations within each age group rose with age and increased significantly over the study period (p < 0.01). The Northeast region had the highest average incidence (0.93 per 100,000 population). Significant seasonal variation was seen regionally and nationally (p < 0.01), with the highest average incidence in December and lowest in April. Median inflation adjusted charge per ED visit was $2496.10, and the total inflation adjusted charges equaled $101.5 million. Conclusion: The incidence of APAC-related ED visits continues to rise in the United States. High-risk groups include women, individuals of low socioeconomic status, and those between ages 50 and 70. Significant seasonal and regional trends were observed in ED presentations of APAC.

Association of the Affordable Care Act with Eye-Related Emergency Department Utilization in the United States.

PURPOSE: To investigate the association of the Affordable Care Act (ACA) with nationwide eye-related emergency department (ED) use. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: All patients who presented to the ED with an eye-related primary diagnosis were eligible for inclusion. METHODS: Nationally representative data from the US Nationwide Emergency Department Sample were used to analyze eye-related ED visits before (2010-2013) and after (2014-2017) the ACA was mandated. All ED visits were categorized as emergent or nonemergent or could not be determined. MAIN OUTCOME MEASURES: The primary outcome was to compare the nationwide and regional incidence of eye-related ED visits per 100 000 US population before (2010-2013) and after (2014-2017) the ACA was mandated. Secondary outcome measures included change in payor status, proportion of urgent versus nonurgent visits, proportion of visits at teaching versus nonteaching hospitals, associated charges, and discharge disposition. RESULTS: A total of 16 808 343 eye-related ED visits occurred in the United States during the study period from 2010 to 2017. Of these, 8 088 203 ED visits occurred before the ACA was mandated (2010-2013), and 8 720 766 ED visits occurred after the ACA was mandated (2014-2017). After the ACA was mandated in 2014, there was an initial decline in incidence of eye-related ED visits from 652.4 per 100 000 population in 2013 to 593.0 per 100 000 population in 2014, followed by a rapid increase in incidence to 658.5 per 100 000 population in 2015, with a further increase to 746.6 per 100 000 population in 2016. The percentage of uninsured patients decreased from 19.0% to 14.3%. The increase in ED use was greatest for individuals in the lowest income quartile (895.1 per 100 000 population in 2013 to 964.0 per 100 000 in 2017). Overall, 44.8% of ED visits were due to nonemergent eye conditions. CONCLUSIONS: Although the ACA increased insurance coverage for Americans, theoretically increasing access to outpatient ophthalmic care, this did not decrease ED reliance for management of ophthalmic conditions. Additional measures beyond expanding insurance coverage may be necessary to provide high-quality, efficient, and equitable outpatient ophthalmic care to all Americans.

Robotic Cholecystectomies: What Are They Good for? - A Retrospective Study - Robotic versus Conventional Cases.

INTRODUCTION: Robot-assisted cholecystectomies are often criticized as expensive with uncertain benefit to patients. Characterization of robotic surgery benefits, as well as specific factors that drive cost, has the potential to shape the current debate. METHODS: The surgical cost and outcomes among patients who underwent robotic (n = 283) or non-robotic (n = 1438) laparoscopic cholecystectomies between 2012 and 2018 at a single academic institution were examined retrospectively. All cholecystectomies were primary surgical procedures with no secondary procedures. We also examined the subset of robotic (n = 277) and non-robotic (n = 1108) outpatient procedures. RESULTS: Robotic cholecystectomies were associated with higher median total cost compared to conventional procedures, largely attributable to variable costs and surgical costs. Patients who underwent conventional cholecystectomy had longer mean lengths of stays (1.7 versus 1.1 days) compared to robotic procedures-with over 10 times as many requiring hospital admission. CONCLUSIONS: At present, robotic cholecystectomies have a little value to patients and institutions outside of surgical training. Prior to narrowing the analysis to outpatient cases, difference in total cost between procedures was less pronounced due to more frequent inpatient management following conventional procedures. Future optimization of robotic consumables and free market competition among system manufacturers may increase financial feasibility by decreasing variable costs associated with robotic surgery.

Comparison of Autologous Breast Reconstruction Complications by Type of Neoadjuvant Chemotherapy Regimen.

BACKGROUND: Neoadjuvant chemotherapy before mastectomy helps reduce tumor burden and pathologic response in breast cancer. Limited evidence exists regarding how neoadjuvant chemotherapy impacts outcomes following microvascular breast reconstruction. This study examines the effects of neoadjuvant chemotherapy regimens and schedules on microvascular breast reconstruction complication rates and also assesses the effects of neoadjuvant chemotherapy on circulating immune cells related to wound healing. METHODS: Patients who underwent neoadjuvant chemotherapy and microvascular breast reconstruction at Yale New Haven Hospital between 2013 and 2018 were identified. Demographic variables, oncologic history, chemotherapy regimens, and complication profiles were collected. Chemotherapy regimens were stratified by inclusion of anthracycline and order of taxane administration. Chi-square, Fisher's exact, and t tests were used for univariate analysis. Multivariate binary logistic regression was used to control for covariates. RESULTS: One hundred patients met inclusion criteria. On multivariate analysis, the administration of taxane first in an anthracycline-containing chemotherapy sequence was associated with increased complications (OR, 3.521; p = 0.012), particularly fat necrosis (OR, 2.481; p = 0.040). In the logistic regression model evaluating the effect of the taxane-first regimen on complication rates, the area under the curve was estimated to be 0.760 (p < 0.0001), particularly fat necrosis 0.635 (p < 0.05). The dosage of chemotherapy, number of days between neoadjuvant chemotherapy completion and surgery, and number of circulating immune cells did not significantly differ among patients who experienced complications. CONCLUSIONS: Taxane-first, anthracycline-containing neoadjuvant chemotherapy regimens were associated with increased complications, particularly fat necrosis. The increased postreconstruction complication risk must be weighed against the benefits of taxane-first regimens in improving tumor outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Effectiveness of Thermal Ablation and Stereotactic Radiotherapy Based on Stage I Lung Cancer Histology.

PURPOSE: To assess whether the effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) as initial treatments for stage I lung cancer varies depending on the histological subtype. MATERIALS AND METHODS: The 2004-2016 National Cancer Database was queried for patients with American Joint Committee on Cancer stage I lung cancer treated with TA or SBRT. Patients <18 years, those treated with surgery or chemotherapy, or those with unknown survival and follow-up were excluded. TA and SBRT patients were 1:5 propensity score matched separately for each histological subtype to adjust for confounders. Overall survival (OS) was assessed using Cox models. RESULTS: A total of 28,425 patients were included (SBRT, n = 27,478; TA, n = 947). TA was more likely to be used in Caucasian patients, those with more comorbidities and smaller neuroendocrine tumors (NETs) of the lower lobe, and those whose treatment had taken place in the northeastern United States. After propensity score matching, a cohort with 4,085 SBRT and 817 TA patients with balanced confounders was obtained. In this cohort, OS for TA and SBRT was comparable (hazard ratio = 1.07; 95% confidence interval,0.98-1.18; P = .13), although it varied by histological subtypes: higher OS for TA was observed in patients with non-small cell NETs (vs SBRT hazard ratio = 0.48; 95% confidence interval, 0.24-0.95; P = .04). No significant OS differences between TA and SBRT were noted for adenocarcinomas, squamous cell carcinomas, small cell carcinomas, and non-neuroendocrine large cell carcinomas (each, P > .1). CONCLUSIONS: OS following TA and SBRT for stage I lung cancer is comparable for most histological subtypes, except that OS is longer after TA in non-small cell NETs.

Abdominal subcutaneous fat thickness as a substitute for BMI in predicting complications in abdominally-based autologous breast reconstruction.

INTRODUCTION: Patient selection for autologous tissue transfer for postmastectomy breast reconstruction often utilizes body mass index (BMI) to risk stratify patients, though it only estimates fat content and does not address fat distribution. This study aims to identify a measurement of abdominal subcutaneous fat thickness (ASFT) from preoperative computed tomography (CT) angiography imaging to better predict complications. METHODS: A retrospective review of patients who underwent an abdominal microvascular free flap breast reconstruction was performed. The average of the bilateral distances from the lateral border of the rectus abdominus to the most proximal point of the dermis at the L4-L5 space was measured on preoperative imaging to estimate ASFT. This measurement was compared to BMI in regards to correlation with any complication, major or minor complications, and donor or recipient site complications. Statistical analysis utilized point-biserial correlations and multivariable logistic regression analyses. RESULTS: Three hundred and nine cases comprising a total of 496 breast reconstructions were identified. BMI did not correlate with any of the grouped complications, while ASFT correlated with occurrence of any complication (p = .003), minor complications (p = .001), and recipient site complications (p = .001). Further analysis revealed ASFT is specifically correlated with fat necrosis (p = .005). In independent multivariable regression models, both BMI (p = .011) and ASFT (p = .001) were significant predictors of fat necrosis. The ASFT model had a BIC of 335.42 compared to the BMI model with a value of 340.89, with smaller numbers representing more predictive models. CONCLUSION: Estimation of ASFT is easily performed and is a significantly better predictor of flap fat necrosis than BMI.

Does Surgical Specialty Impact Mandibular Fracture Outcomes?

PURPOSE: Maxillofacial trauma is treated by two medical specialties, plastic surgery (PRS) and otolaryngology (ENT). Differences in training exposure and practice patterns exist between specialties, but their respective outcomes have never been compared. METHODS: Mandible fracture data were reviewed from the National Surgical Quality Improvement Program from 2005 to 2016. Demographics variables, repair types, and adverse outcomes were compared between PRS and ENT. RESULTS: From 2005 to 2016, one thousand two hundred eighty-two cases were identified with 756 cases managed by ENT and 526 cases managed by PRS. Mean patient age was 34.6 years for both specialties (P = 0.95). Patient demographics between both cohorts were not statistically different except for higher rates of hypertension among ENT patients (10.2% for ENT versus 6.7% for PRS, P = 0.027) and higher rates of smoking history among PRS patients (46.8% versus 52.3%, P = 0.055). Mean operative time (131.3 versus 124.0 min, P = 0.090) had a trend toward being longer for ENT and mean length of stay (1.3 versus 2.0, P = 0.002) was significantly longer for PRS. Despite a greater proportion of high ASA class patients in the ENT group (P = 0.012) and patients with dirty/infected wounds in the PRS group (P = 0.013), there were no significant differences in 30-day readmission rates, 30-day reoperation rates, or wound infection rates. CONCLUSIONS: No significant differences in 30-day readmission rates, reoperation rates, or wound infection rates for mandible fracture management exist between specialties. Despite differences in training between PRS and ENT, both specialties have comparable perioperative outcomes for mandible fracture management.

Worse overall health status negatively impacts satisfaction with breast reconstruction.

BACKGROUND: BREAST-Q is a validated measure of patient satisfaction and health-related quality of life following breast surgery. Limited evidence exists with regard to the influence of preoperative overall health status on BREAST-Q outcomes. The American Society of Anesthesiologists (ASA) physical status classification is representative of preoperative overall health and its impact on patient-reported outcomes can be assessed. METHODS: Patients who received breast reconstruction at Yale New Haven Hospital between 2013 and 2018 and completed the BREAST-Q were enrolled in the study. Associations between BREAST-Q scores within modules and between modules and ASA were analyzed. Pearson's correlation and Spearman's Rho were used to characterize correlations between patient factors and BREAST-Q scores. Significantly correlated factors were entered into a general linear model (GLM) to control for confounding variables and isolate the effect of ASA on BREAST-Q scores. RESULTS: A total of 1136 patients underwent breast reconstruction of whom 489 patients completed the BREAST-Q. Increasing ASA indicative of worsening overall health was associated with a decreased BREAST-Q score for all modules except Physical Well-being of the Abdomen (p<0.01 to p = 0.029). In a GLM controlling for relevant covariates, ASA remained a significant contributor for all modules except Physical Well-being of the Chest (p<0.01 to p = 0.021). BREAST-Q scores decreased by approximately twice as much from ASA 1 to 2 compared to ASA 2 to 3. CONCLUSION: ASA classification is an independent predictor of BREAST-Q patient-reported outcomes following breast reconstruction. Communicating the potential impact of overall health may help reduce the discrepancy in postoperative satisfaction across ASA classifications.

Patients with psychiatric illness report worse patient-reported outcomes and receive lower rates of autologous breast reconstruction.

Psychiatric well-being impacts on general satisfaction and quality of life. This study explored how the presence of psychiatric diagnoses affects patient-reported outcomes in breast reconstruction and on selection of reconstructive modality. Patients who received breast reconstruction at a tertiary hospital between 2013 and 2018 and completed the BREAST-Q survey were included. BREAST-Q module scores were compared between patients who had a psychiatric diagnosis at presentation and the remaining cohort using t tests. General linear models (GLMs) were used to control for confounding factors. A chi-squared test was used to assess the effect on reconstructive modality, and binary logistic regression was used to control for confounding factors. Of the 471 patients included, 93 (19.7%) had at least one psychiatric diagnosis. Cohorts did not differ significantly by age, BMI, race, ASA classification, or insurance status. Patients with a psychiatric diagnosis experienced a decrease in BREAST-Q scores for the Psychosocial Wellbeing (B = 9.16, P = .001) and Sexual Wellbeing (B = 9.29, P = .025) modules. On binary logistic regression, patients with a psychiatric diagnosis were less likely to receive autologous reconstruction compared with implant reconstruction (OR = 0.489, P = .010). The presence of psychiatric diagnoses is an independent predictor of decreased BREAST-Q. Furthermore, there is a significant disparity in modality of reconstruction given to patients with psychiatric diagnoses. Further study is needed to evaluate interventions to improve satisfaction among at-risk populations and evaluate the reason for low autologous reconstruction in this population.

Preresidency Publication Productivity of U.S. Neurosurgery Interns.

BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized. OBJECTIVE: In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs. CONCLUSIONS: Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.

Improving Viscosity and Stability of a Highly Concentrated Monoclonal Antibody Solution with Concentrated Proline.

PURPOSE: To explain the effects of the osmolyte proline on the protein-protein interactions (PPI), viscosity and stability of highly concentrated antibody solutions in contrast to other neutral osmolytes. METHODS: The viscosity of ~225 mg/mL mAb solutions was measured with proline, glycine and trehalose as a function of pH and co-solute concentration up to 1.3 M. The stability was assessed via turbidity as well as size exclusion chromatography after 4 weeks storage at 40°C. The PPI strength was assessed qualitatively via the high concentration diffusion rate by dynamic light scattering. RESULTS: Increasing proline significantly reduced the mAb viscosity and increased the colloidal stability at pH 6, but not at pH 5 further from the mAb pI. In contrast, glycine and trehalose did not improve the viscosity nor stability. The normalized diffusion coefficient at high concentration, which is inversely proportional to the attractive PPI strength, increased with proline concentration but decreased with increasing glycine. CONCLUSIONS: Proline demonstrated greater efficacy for improving mAb viscosity and stability in contrast to glycine and trehalose due to its amphipathic structure and partial charge on the pyrrolidine side chain. These properties likely allow proline to screen the attractive electrostatic and hydrophobic interactions that promote self-association and high viscosities. Binary proline-histidine formulations also demonstrated greater viscosity reduction effects than histidine alone at the same total co-solute concentration, while maintaining a lower total solution osmolarity.