Bonita S. Agee

A Phase 1 Trial of Oncolytic HSV-1, G207, Given in Combination With Radiation for Recurrent GBM Demonstrates Safety and Radiographic Responses

G207, a mutant herpes simplex virus (HSV) type 1, is safe when inoculated into recurrent malignant glioma. We conducted a phase 1 trial of G207 to demonstrate the safety of stereotactic intratumoral administration when given 24 hours prior to a single 5 Gy radiation dose in patients with recurrent malignant glioma. Nine patients with progressive, recurrent malignant glioma despite standard therapy were included. Patients received one dose of G207 stereotactically inoculated into the multiple sites of the enhancing tumor margin and were then treated focally with 5 Gy radiation. Treatment was well tolerated, and no patient developed HSV encephalitis. The median interval between initial diagnosis and G207 inoculation was 18 months (mean: 23 months; range: 11-51 months). Six of the nine patients had stable disease or partial response for at least one time point. Three instances of marked radiographic response to treatment occurred. The median survival time from G207 inoculation until death was 7.5 months (95% confidence interval: 3.0-12.7). In conclusion, this study showed the safety and the potential for clinical response of single-dose oncolytic HSV therapy augmented with radiation in the treatment of malignant glioma patients. Additional studies with oncolytic HSV such as G207 in the treatment of human glioma are recommended.

Predictors of delayed recovery following pediatric sports-related concussion: a case-control study

OBJECT Pediatric sports-related concussions are a growing public health concern. The factors that determine injury severity and time to recovery following these concussions are poorly understood. Previous studies suggest that initial symptom severity and diagnosis of attention deficit hyperactivity disorder (ADHD) are predictors of prolonged recovery (> 28 days) after pediatric sports-related concussions. Further analysis of baseline patient characteristics may allow for a more accurate prediction of which patients are at risk for delayed recovery after a sports-related concussion. METHODS The authors performed a single-center retrospective case-control study involving patients cared for at the multidisciplinary Concussion Clinic at Childrens of Alabama between August 2011 and January 2013. Patient demographic data, medical history, sport concussion assessment tool 2 (SCAT2) and symptom severity scores, injury characteristics, and patient balance assessments were analyzed for each outcome group. The control group consisted of patients whose symptoms resolved within 28 days. The case group included patients whose symptoms persisted for more than 28 days. The presence or absence of the SCAT2 assessment had a modifying effect on the risk for delayed recovery; therefore, stratum-specific analyses were conducted for patients with recorded SCAT2 scores and for patients without SCAT2 scores. Unadjusted ORs and adjusted ORs (aORs) for an association of delayed recovery outcome with specific risk factors were calculated with logistic regression analysis. RESULTS A total of 294 patients met the inclusion criteria of the study. The case and control groups did not statistically significantly differ in age (p = 0.7). For the patients who had received SCAT2 assessments, a previous history of concussion (aOR 3.67, 95% CI 1.51-8.95), presenting SCAT2 score < 80 (aOR 5.58, 95% CI 2.61-11.93), and female sex (aOR 3.48, 95% CI 1.43-8.49) were all associated with a higher risk for postconcussive symptoms lasting more than 28 days. For patients without SCAT2 scores, female sex and reporting a history of ADHD significantly increased the odds of prolonged recovery (aOR 4.41, 95% CI 1.93-10.07 and aOR 3.87, 95% CI 1.13-13.24, respectively). Concussions resulting from playing a nonhelmet sport were also associated with a higher risk for prolonged symptoms in patients with and without SCAT2 scores (OR 2.59, 95% CI 1.28-5.26 and OR 2.17, 95% CI 0.99-7.73, respectively). Amnesia, balance abnormalities, and a history of migraines were not associated with symptoms lasting longer than 28 days. CONCLUSIONS This case-control study suggests candidate risk factors for predicting prolonged recovery following sports-related concussion. Large prospective cohort studies of youth athletes examined and treated with standardized protocols will be needed to definitively establish these associations and confirm which children are at highest risk for delayed recovery.

Migration patterns following HIV diagnosis among adults residing in the nonurban Deep South.

Abstract Health care needs of those infected with the human immunodeficiency virus (HIV) and subsequent transmission dynamics are altered by migration after infection. We interviewed 760 HIV-infected persons attending HIV-specialty clinics living in non-urban Alabama and Mississippi to ascertain the likely geographic origins of their infections, determine their post-HIV diagnosis mobility, and identify predictors of this mobility. Most subjects (81%) were living in these two states when diagnosed and have not moved since learning of their HIV status (70%). Of those who moved their primary residence post-HIV diagnosis (25% of the entire study population), the majority in-migrated to Alabama or Mississippi from elsewhere. Persons who had moved post-HIV diagnosis were more likely to be male, an injection drug user, an urban resident at HIV diagnosis, have an AIDS-defining condition, and have moved prior to HIV diagnosis. We conclude that most HIV transmission in non-urban Alabama and Mississippi is acquired locally. These results underline the need to expand HIV prevention programs in the Deep South.

Validation and modification of a predictive model of postresection hydrocephalus in pediatric patients with posterior fossa tumors

OBJECT Postresection hydrocephalus is observed in approximately 30% of pediatric patients with posterior fossa tumors. However, which patients will develop postresection hydrocephalus is not known. The Canadian Preoperative Prediction Rule for Hydrocephalus (CPPRH) was developed in an attempt to identify this subset of patients, allowing for the optimization of their care. The authors sought to validate and critically appraise the CPPRH. METHODS The authors conducted a retrospective chart review of 99 consecutive pediatric patients who presented between 2002 and 2010 with posterior fossa tumors and who subsequently underwent resection. The data were then analyzed using bivariate and multivariate analyses, and a modified CPPRH (mCPPRH) was applied. RESULTS Seventy-six patients were evaluated. Four variables were found to be significant in predicting postresection hydrocephalus: age younger than 2 years, moderate/severe hydrocephalus, preoperative tumor diagnosis, and transependymal edema. The mCPPRH produced observed likelihood ratios of 0.737 (95% CI 0.526-1.032) and 4.688 (95% CI 1.421-15.463) for low- and high-risk groups, respectively. CONCLUSIONS The mCPPRH utilizes readily obtainable and reliable preoperative variables that together stratify children with posterior fossa tumors into high- and low-risk categories for the development of postresection hydrocephalus. This new predictive model will aid patient counseling and tailor the intensity of postoperative clinical and radiographic monitoring for hydrocephalus, as well as provide evidence-based guidance for the use of prophylactic CSF diversion.

Large-scale clinical endodontic research in the national dental practice-based research network: Study overview and methods

INTRODUCTION This article reports on the feasibility of conducting a large-scale endodontic prospective cohort study in The National Dental Practice-Based Research Network. This study was designed to measure pain and burden associated with initial orthograde root canal therapy (RCT) and to explore potential prognostic factors for pain outcomes. The main objectives of this first report in a series are to describe the projects feasibility and methods and the demographics of the sample obtained. METHODS Sixty-two dentist practitioner-investigators (ie, 46 generalists and 16 endodontists) in 5 geographic areas were certified within the network and trained regarding the standardized study protocol. Enrollment and baseline data collection occurred over 6 months with postobturation follow-up for another 6 months. Patients and dentists completed questionnaires before and immediately after treatment visits. Patients also completed questionnaires at 1 week, 3 months, and 6 months after obturation. RESULTS Enrollment exceeded target expectations, with 708 eligible patient-participants. Questionnaire return rates were good, ranging between 90% and 100%. Patient demographics were typical of persons who receive RCT in the United States (ie, mean age = 48 years [standard deviation = 13 years], with most being female [59%], college educated [81%], white non-Hispanic [86%], and having dental insurance [81%]). The tooth types being treated were also typical (ie, 61% molars, 28% premolars, and 11% anteriors, with maxillary teeth being predominant [59%]). CONCLUSIONS This study shows the feasibility of conducting large-scale endodontic prospective cohort studies in the network. Patients were rapidly recruited with high levels of compliance in data collection.

Observer reliability of arteriovenous malformations grading scales using current imaging modalities

OBJECT The aim of this study was to examine observer reliability of frequently used arteriovenous malformation (AVM) grading scales, including the 5-tier Spetzler-Martin scale, the 3-tier Spetzler-Ponce scale, and the Pollock-Flickinger radiosurgery-based scale, using current imaging modalities in a setting closely resembling routine clinical practice. METHODS Five experienced raters, including 1 vascular neurosurgeon, 2 neuroradiologists, and 2 senior neurosurgical residents independently reviewed 15 MRI studies, 15 CT angiograms, and 15 digital subtraction angiograms obtained at the time of initial diagnosis. Assessments of 5 scans of each imaging modality were repeated for measurement of intrarater reliability. Three months after the initial assessment, raters reassessed those scans where there was disagreement. In this second assessment, raters were asked to justify their rating with comments and illustrations. Generalized kappa (κ) analysis for multiple raters, Kendalls coefficient of concordance (W), and interclass correlation coefficient (ICC) were applied to determine interrater reliability. For intrarater reliability analysis, Cohens kappa (κ), Kendalls correlation coefficient (tau-b), and ICC were used to assess repeat measurement agreement for each rater. RESULTS Interrater reliability for the overall 5-tier Spetzler-Martin scale was fair to good (ICC = 0.69) to extremely strong (Kendalls W = 0.73) on initial assessment and improved on reassessment. Assessment of CT angiograms resulted in the highest agreement, followed by MRI and digital subtraction angiography. Agreement for the overall 3-tier Spetzler-Ponce grade was fair to good (ICC = 0.68) to strong (Kendalls W = 0.70) on initial assessment, improved on reassessment, and was comparable to agreement for the 5-tier Spetzler-Martin scale. Agreement for the overall Pollock-Flickinger radiosurgery-based grade was excellent (ICC = 0.89) to extremely strong (Kendalls W = 0.81). Intrarater reliability for the overall 5-tier Spetzler-Martin grade was excellent (ICC > 0.75) in 3 of the 5 raters and fair to good (ICC > 0.40) in the other 2 raters. CONCLUSION The 5-tier Spetzler-Martin scale, the 3-tier Spetzler-Ponce scale, and the Pollock-Flickinger radiosurgery-based scale all showed a high level of agreement. The improved reliability on reassessment was explained by a training effect from the initial assessment and the requirement to defend the rating, which outlines a potential downside for grades determined as part of routine clinical practice to be used for scientific purposes.

Recurrent laryngeal nerve injury following reoperative anterior cervical discectomy and fusion: a meta-analysis

OBJECTIVE Recurrent laryngeal nerve (RLN) injury is one of the most frequent complications of anterior cervical discectomy and fusion (ACDF) procedures. The frequency of RLN is reported as 1%-11% in the literature. (4 , 15) The rate of palsy after reoperative ACDF surgery is not well defined. This meta-analysis was performed to review the current medical evidence on RLN injury after ACDF surgery and to determine a relative rate of RLN injury after reoperative ACDF. METHODS MEDLINE, PubMed, and Google Scholar searches were performed using several key words and phrases related to ACDF surgery. Included studies were written in English, addressed revisionary ACDF surgery, and studied outcomes of RLN injury. Statistical analysis was then performed using a random-effects model to calculate a pooled rate of RLN injury. The heterogeneity of the studies was assessed using Cochrans Q statistic and I(2) statistic, and a funnel plot was constructed to evaluate publication bias. RESULTS The search initially identified 345 articles on this topic. Eight clinical articles that met all inclusion criteria were included in the meta-analysis. A total of 238 patients were found to have undergone reoperative ACDF. Thirty-three of those patients experienced an RLN injury. This analysis identified a rate of RLN injury in the literature after reoperative ACDF of 14.1% (95% confidence interval [CI] 9.8%-19.1%). CONCLUSIONS The rate of RLN palsy of 14.1% was greater than any published rate of RLN injury after primary ACDF operations, suggesting that there is a greater risk of hoarseness and dysphagia with reoperative ACDF surgeries than with primary procedures as reported in these studies.

Assessment of driving outcomes after epilepsy surgery

INTRODUCTION Driving is an important factor contributing to good quality of life in patients with epilepsy. Little work has been undertaken to explore the details of driving experience alone in this patient population. We assessed the driving status of our patients prior to and following surgery for epilepsy. We also sought to determine what associations exist between patient characteristics and postoperative driving status. METHODS The participants were selected from those adult patients with epilepsy who have required surgical treatment at our home institution between 2006 and 2010. Each participant received a questionnaire asking about driving and seizure status before and after surgery. The surveys were distributed using a modified Dillman approach. Perioperative patient data were obtained from the electronic medical record system in addition to a previously assembled epilepsy database from the Neurology Department at our institution. Independent variables were analyzed to look for significant associations with driving outcomes. RESULTS One hundred forty eligible patients were included in the survey population; 78 patients returned a questionnaire for a response rate of 55.7%. Eighty percent of patients experienced driving as a regular part of life at some point prior to surgery. At the time of the questionnaire distribution, 68% of patients had returned to regular driving. Demographic characteristics did not play a significant role in whether or not the patient had a favorable driving outcome after surgery. However, patients who had a history of driving on a regular basis prior to surgery and those who had an Engel Class I outcome after surgery had significantly higher rates of good driving outcomes. Also, patients with an unfavorable preoperative driving status were more likely to have a favorable driving outcome after surgery if they had an Engel Class I outcome. Patients in whom intracranial electroencephalography (EEG) was utilized prior to resection had worse driving outcomes. CONCLUSIONS A surprisingly high percentage of patients with epilepsy have experienced driving on a regular basis prior to surgery. We can assume that most patients were not driving immediately prior to surgery, given the fact that they had progressed to requiring surgery for treatment of their epilepsy. Thus, a driving rate of 68% after surgery can be considered good. We found that a patients preoperative driving history, the use of intracranial EEG before surgical resection, and Engel classification were significant predictors of postoperative driving outcomes. These data provide patients with assistance in preoperative counseling. More investigation needs to be completed in other patient variables - such as seizure types, magnetic resonance imaging (MRI) findings, and patient motivators for driving - as possible predictors of driving outcomes.

Implications of transitioning to a resident night float system in neurosurgery: mortality, length of stay, and resident experience.

OBJECTIVE Many neurosurgical training programs have moved from a 24-hour resident call system to a night float system, but the impact on outcomes is unclear. Here, the authors compare length of stay (LOS) for neurosurgical patients admitted before and after initiation of a night float system at a tertiary care training hospital. METHODS The neurosurgical residency at the University of Alabama at Birmingham transitioned from 24-hour call to a night float resident coverage system in July 2013. In this cohort study, all patients admitted to the neurosurgical service for 1 year before and 1 year after this transition were compared with respect to hospital and ICU LOSs, adjusted for potential confounders. RESULTS A total of 4619 patients were included. In the initial bivariate analysis, night float was associated with increased ICU LOS (p = 0.032) and no change in overall LOS (p = 0.65). However, coincident with the transition to a night float system was an increased frequency of resident service transitions, which were highly associated with hospital LOS (p < 0.01) and ICU LOS (p < 0.01). After adjusting for resident service transitions, initiation of the night float system was associated with decreased hospital LOS (p = 0.047) and no change in ICU LOS (p = 0.35). CONCLUSIONS This study suggests that a dedicated night float resident may improve night-to-night continuity of care and decrease hospital LOS, but caution must be exercised when initiation of night float results in increased resident service transitions.

Effect of resident handoffs on length of hospital and intensive care unit stay in a neurosurgical population: a cohort study.

OBJECT Handoffs and services changes are potentially modifiable sources of medical error and delays in transition of care. This cohort study assessed the relationship between resident service handoffs and length of stay for neurosurgical patients. METHODS All patients admitted to the University of Alabama at Birmingham neurosurgical service between July 1, 2012, and July 1, 2014, were retrospectively identified. A service handoff was defined as any point when a resident handed off coverage of a service for longer than 1 weekend. A conditional probability distribution was constructed to adjust length of stay for the increasing probability of a random handoff. The Student t-test and ANCOVA were used to assess relationships between resident service handoffs and length of hospital stay, adjusted for potential confounders. RESULTS A total of 3038 patients met eligibility criteria and were included in the statistical analyses. Adjusted length of hospital stay (5.32 vs 3.53 adjusted days) and length of ICU stay (4.38 vs 2.96 adjusted days) were both longer for patients who experienced a service handoff, with no difference in mortality. In the ANCOVA model, resident service handoff remained predictive of both length of hospital stay (p < 0.001) and length of ICU stay (p < 0.001). CONCLUSIONS Occurrence of a resident service handoff is an independent predictor of length of hospital and ICU stay in neurosurgical patients. This finding is novel in the neurosurgical literature. Future research might identify mechanisms for improving continuity of care and mitigating the effect of resident handoffs on patient outcomes.