External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens.

PURPOSE: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. METHODS AND MATERIALS: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. RESULTS: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. CONCLUSIONS: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.

Rehabilitation following pediatric traumatic brain injury: variability in adherence to psychosocial quality-of-care indicators.

OBJECTIVE: To examine variations in processes of pediatric inpatient rehabilitation care related to family-centered care, management of neurobehavioral and psychosocial needs, and community reintegration after traumatic brain injury. SETTING: Nine acute rehabilitation facilities from geographically diverse areas of the United States. PARTICIPANTS: A total of 174 children with traumatic brain injury. DESIGN: Retrospective chart review. MAIN MEASURES: Adherence to care indicators (the number of times recommended care was delivered or attempted divided by the number of times care was indicated). RESULTS: Across facilities, adherence rates (adjusted for difficulty of delivery) ranged from 33.6% to 73.1% (95% confidence interval, 13.4-53.9, 58.7-87.4) for family-centered processes, 21.3% to 82.5% (95% confidence interval, 6.6-36.1, 67.6-97.4) for neurobehavioral and psychosocial processes, and 22.7% to 80.3% (95% confidence interval, 5.3-40.1, 68.1-92.5) for community integration processes. Within facilities, standard deviations for adherence rates were large (24.3-34.9, family-centered domain; 22.6-34.2, neurobehavioral and psychosocial domain; and 21.6-40.5, community reintegration domain). CONCLUSION: The current state of acute rehabilitation care for children with traumatic brain injury is variable across different quality-of-care indicators addressing neurobehavioral and psychosocial needs and facilitating community reintegration of the patient and the family. Individual rehabilitation facilities demonstrate inconsistent adherence to different indicators and inconsistent performance across different care domains.

Medicaid status is associated with higher complication rates after spine surgery.

STUDY DESIGN: Multivariate analysis of prospectively collected registry data. OBJECTIVE: To determine the effect of payor status on complication rates after spine surgery. SUMMARY OF BACKGROUND DATA: Understanding the risk of perioperative complications is an essential aspect in improving patient outcomes. Previous studies have looked at complication rates after spine surgery and factors related to increased perioperative complications. In other areas of medicine, there has been a growing body of evidence gathered to evaluate the role of payor status on outcomes and complications. Several studies have found increased complication rates and inferior outcomes in the uninsured and Medicaid insured. METHODS: The Spine End Results Registry (2003-2004) is a collection of prospectively collected data on all patients who underwent spine surgery at our 2 institutions. Extensive demographic data, including payor status, and medical information were prospectively recorded as described previously by Mirza et al. Medical complications were defined in detail a priori and were prospectively recorded for at least 2 years after surgery. Using univariate and multivariate analysis, we determined risk of postoperative medical complications dependent on payor status. RESULTS: A total of 1591 patients underwent spine surgery in 2003 and 2004 that met our criteria and were included in our analysis. With the multivariate analysis and by controlling for age, patients whose insurer was Medicaid had a 1.68 odds ratio (95% confidence interval: 1.23-2.29; P = 0.001) of having any adverse event when compared with the privately insured. CONCLUSION: After univariate and multivariate analyses, Medicaid insurance status was found to be a risk factor for postoperative complications. This corresponds to an ever-growing body of medical literature that has shown similar trends and raises the concern of underinsurance.

Variations in the quality of inpatient rehabilitation care to facilitate school re-entry and cognitive and communication function for children with TBI.

OBJECTIVE: To examine variations in processes of paediatric inpatient rehabilitation care related to school re-entry and management of cognitive and communication impairments after traumatic brain injury. DESIGN: Retrospective cohort study. METHODS: Adherence to care processes recommended for children (aged 0-17) with moderate-to-severe traumatic brain injury and admitted for inpatient rehabilitation was assessed. Quality-of-care indicators for processes supporting school re-entry and cognitive and communication rehabilitation were applied to measure variations in care delivered to 174 children across nine facilities using medical record review. MAIN OUTCOMES AND RESULTS: Adherence rates (the number of times recommended care was delivered or attempted divided by the number of times care was indicated) were calculated, revealing substantial variations in care within and between facilities. Overall, children received 51.3% (95% CI = 31.9-70.7) and 72.3% (95% CI = 61.1-83.5), of the care recommended for school re-entry and cognitive and communication rehabilitation, respectively. CONCLUSION: Substantial variations exist in the delivery of paediatric inpatient rehabilitation care processes for managing school re-entry and cognitive and communication impairments after traumatic brain injury. Measures of association of these care processes with patient outcomes are necessary. Reduction in this variation is essential to improving quality of care.

Risk factors for medical complication after cervical spine surgery: a multivariate analysis of 582 patients.

STUDY DESIGN: Multivariate analysis of prospectively collected registry data. OBJECTIVE: Using multivariate analysis to determine significant risk factors for medical complication after cervical spine surgery. SUMMARY OF BACKGROUND DATA: Several studies have examined the occurrence of medical complication after spine surgery. However, many of these studies have been done using large national databases. While these allow for analysis of thousands of patients, potentially influential covariates are not accounted for in these retrospective studies. Furthermore, the accuracy of these retrospective data collection in these databases has been called into question. METHODS: The Spine End Results Registry (2003-2004) is a repository of prospectively collected data on all patients who underwent spine surgery at our 2 institutions. Extensive demographic and medical information was prospectively recorded. Complications were defined in detail a priori and were prospectively recorded for at least 2 years after surgery. We analyzed risk factors for medical complication after lumbar spine surgery, using univariate and multivariate analyses. RESULTS: We analyzed data from 582 patients who met our inclusion criteria. The cumulative incidences of complication after cervical spine surgery per organ system are as follows: cardiac, 8.4%; pulmonary, 13%; gastrointestinal, 3.9%; neurological, 7.4%; hematological, 10.8%; and urologic complications, 9.2%. The occurrence of cardiac or respiratory complication after cervical spine surgery was significantly associated with death within 2 years (relative risk, 4.32, 6.43, respectively). Relative risk values with 95% confidence intervals and P values are reported. CONCLUSION: Risk factors identified in this study can be beneficial to clinicians and patients alike when considering surgical treatment of the cervical spine. Future analyses and models that predict the occurrence of medical complication after cervical spine surgery may be of further benefit for surgical decision making.

Risk factors for unintended durotomy during spine surgery: a multivariate analysis.

BACKGROUND CONTEXT: Incidental durotomy during spine surgery is a common occurrence, with a reported incidence ranging from 3% to 16%. Risk factors identified by prior studies include age, type of procedure, revision surgery, ossification of the posterior longitudinal ligament, gender, osteoporosis, and arthritis. However, these studies are largely univariate analyses using retrospectively recorded data. PURPOSE: To identify and quantify statistically significant risk factors for inadvertent durotomy during spine surgery. STUDY DESIGN: Multivariate analysis of prospectively collected registry data. The University of Washington Spine End Results Registry 2003 and 2004 is a compilation of prospectively collected detailed data on 1,745 patients who underwent spine surgery during 2003 to 2004. PATIENT SAMPLE: One thousand seven hundred forty-five patients underwent spine surgery from 2003 to 2004 at our two institutions. OUTCOME MEASURES: Cardiac, pulmonary, gastrointestinal, neurologic, renal, and urologic complications defined a priori data collection. METHODS: Using these data, univariate and multivariate statistical analyses were performed to identify and quantify risk factors for incidental durotomy during spine surgery. Relative risk (RR) values with valid confidence intervals and p values were determined using these data. RESULTS: Our multivariate analysis demonstrated that age, lumbar surgery, revision surgery, and elevated surgical invasiveness are significant risk factors for unintended durotomy. Of these, revision surgery was the strongest risk factor for dural tear (RR, 2.21). Diabetes was a significant risk factor in the univariate analysis but not in the multivariate analysis. CONCLUSIONS: Revision surgery, age, lumbar surgery, degenerative disease, and elevated surgical invasiveness are significant risk factors for unintended durotomy during spine surgery. These data can be useful to surgeons and patients when considering surgical treatment.

Risk factors for medical complication after spine surgery: a multivariate analysis of 1,591 patients.

BACKGROUND CONTEXT: Several studies have examined the occurrence of medical complication after spine surgery. However, many of these studies have been done using large national databases. Although these allow for analysis of thousands of patients, potentially influential covariates are not accounted for in these retrospective studies. Furthermore, the accuracy of these retrospective data collection in these databases has been called into question. PURPOSE: Using multivariate analysis on a prospectively collected data registry to determine significant risk factors for medical complication after spine surgery. STUDY DESIGN: Retrospective multivariate analysis of prospectively collected registry data. The registry is a prospectively collected database of all patients who underwent spine surgery in our two institutions from January 1, 2003 to December 31, 2004. METHODS: Extensive demographic and medical information were prospectively recorded as described previously by Mirza et al. Complications were defined in detail a priori, and they were prospectively recorded for at least 2 years after surgery. We analyzed risk factors for medical complication after spine surgery using univariate and multivariate analyses. RESULTS: We analyzed data from 1,591 patients who met out inclusion criteria. The cumulative incidences of complication after spine surgery per organ system are as follows: cardiac, 8.4%; pulmonary, 13%; gastrointestinal, 3.9%; neurological, 7.35%; hematological, 10.75%; and urological complications, 9.18%. The occurrence of cardiac or respiratory complication after spine surgery was significantly associated with death within 2 years (relative risk, 4.11 and 10.76, respectively). Surgical invasiveness and age were significant risk factors for complications in five of the six organ systems evaluated. Individual organ system-specific elative risk values with 95% confidence intervals and p values are listed in Tables 3 and 4. CONCLUSIONS: Risk factors identified in this study can be beneficial to clinicians and patients alike when considering surgical treatment of the spine. Future analyses and models that predict the occurrence of medical complication after spine surgery may be of further benefit for surgical decision making.

Risk factors for medical complication after lumbar spine surgery: a multivariate analysis of 767 patients.

STUDY DESIGN: Multivariate analysis of prospectively collected registry data. OBJECTIVE: Using multivariate analysis to determine significant risk factors for medical complication after lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Several studies have examined the occurrence of medical complication after spine surgery. However, many of these studies have been done utilizing large national databases. Although these allow for analysis of thousands of patients, potentially influential covariates are not accounted for in these retrospective studies. Furthermore, the accuracy of these retrospective data collection in these databases has been called into question. METHODS: The Spine End Results Registry (2003­2004) is a collection of prospectively collected data on all patients who underwent spine surgery at our two institutions. Extensive demographic and medical information were prospectively recorded as described previously by Mirza et al. Complications were defined in detail a priori and were prospectively recorded for at least 2 years after surgery. We analyzed risk factors for medical complication after lumbar spine surgery using univariate and multivariate analysis. RESULTS: We analyzed data from 767 patients who met out inclusion criteria. The cumulative incidences of complication after lumbar spine surgery per organ system are as follows: cardiac, 13%; pulmonary, 7%; gastrointestinal, 6.7%; neurological, 8.2%; hematological, 17.5%; and urologic complications, 10.3%. The occurrence of cardiac or respiratory complication after lumbar spine surgery was significantly associated with death within 2 years (relative risk: 6.09 and 10.9, respectively). Several significant risk factors were identified for organ-specific complications. Among these, surgical invasiveness appeared to be the largest risk factor for cardiac, pulmonary, neurological, and hematological complications. CONCLUSION: Risk factors identified in this study can be beneficial to clinicians and patients alike when considering surgical treatment of the lumbar spine. Future analyses and models that predict the occurrence of medical complication after lumbar spine surgery may be of further benefit for surgical decision making.

Development of an index to characterize the "invasiveness" of spine surgery: validation by comparison to blood loss and operative time.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To create and validate an index describing the extent of spine surgical intervention to allow fair comparisons of complication rates among patients treated by different surgeons, devices, or hospitals. SUMMARY OF BACKGROUND DATA: Safety comparisons in spine surgery are limited by lack of methods that adjust for important variations in the surgical "case-mix." Among other factors, the magnitude of an operation is likely to have a substantial influence on the likelihood of complications. METHODS: We created a spine surgery invasiveness index defined as the sum, across all vertebral levels, of 6 possible interventions on each operated vertebra: anterior decompression, anterior fusion, anterior instrumentation, posterior decompression, posterior fusion, and posterior instrumentation. We assessed the validity of this index by examining its association with blood loss and surgery duration in 1723 spine surgeries, adjusting for important factors including age, gender, body mass index, diagnosis, neurologic deficit, revision surgery, and vertebral level of surgery. RESULTS: Blood loss increased by 11.5% and surgery duration increased by 12.8 minutes for each unit increase in the invasiveness index. The invasiveness index explained 44% of the variation in blood loss and 52% of the variation in surgery duration. For specific surgical components, blood loss increased by 9.4% and surgery duration by 11.4 minutes for each vertebral level of anterior decompression, 19.4% and 33.8 minutes for each segment of anterior instrumentation, 12.9% and 22.7 minutes for each level of posterior decompression, and 25.1% and 18.8 minutes for each segment of posterior instrumentation. CONCLUSION: An "invasiveness" index based on the number of vertebrae decompressed, fused, or instrumented showed the expected associations with both blood loss and surgery duration. This quantitative description of surgery invasiveness may be useful to adjust for surgical variations when making safety comparisons in spine surgery.

Neural space integrity of the lower cervical spine: effect of anterior lesions.

STUDY DESIGN: A repeated measures study design was used to evaluate intervertebral foramen and spinal canal neural space integrity subsequent to sequential surgical anterior lesions of the lower cervical spine in a human cadaver model. OBJECTIVE: To investigate the degree to which sequential ablation of anterior vertebral elements places the neural structures at risk of injury. SUMMARY OF BACKGROUND DATA: Classic instability management utilizing functional-structural criteria has been widely examined associating specific lesions or pathologies to a degree of mechanical instability. Unfortunately, these studies have not assessed the neuroprotective role of the vertebral column. METHODS: Eight human cadaveric lower cervical spines were instrumented with transducers to measure geometrical changes in the intervertebral foramen and spinal canal. Sequential lesions were performed anteriorly on the anterior and middle column structures (C4-C5 disc and C5 vertebra), and their effects on neural space integrity and range of motion were measured under physiologic loading. RESULTS: Range of motion significantly increased with successively more destructive lesions, whereas the spinal canal exhibited few changes. Intervertebral foramen integrity was statistically reduced for corpectomy (66% intact), hemivertebrectomy (62% intact) and full vertebrectomy (57% intact) lesions when loaded in concomitant extension and ipsilateral bending (4 Nm). CONCLUSIONS: Lesions more extensive than a surgical discectomy have significant effects on the cervical neural foramens specifically when the spine is placed in extension, ipsilateral bending, and coupled ipsilateral bending and extension. Our study establishes a quantitative relationship between the risk of neural structure compression and anterior lesions of the spinal column under physiologic loading.

Neural space integrity of the lower cervical spine: effect of normal range of motion.

STUDY DESIGN: An experimental investigation of intervertebral foramen and spinal canal neural space integrity was performed throughout physiologic range of motion of the lower cervical spine in intact human cadaver specimens. OBJECTIVE: To investigate cervical positions that might place the neural tissues of the spine in heightened risk of injury. To meet this objective the following hypotheses were tested: 1) spinal canal integrity varies with specific normal range of motion positions of the lower cervical spine, and 2) intervertebral foramen integrity is dependent on and unique for different physiologic positions of the lower cervical spine. SUMMARY OF BACKGROUND DATA: Cervical spine injuries are frequently associated with compressive damage to neurologic tissues and consequently poor clinical outcomes. Neurologic injury typically occurs from disc, ligamentous, or bony occlusion of the spinal canal and intervertebral foraminal spaces dynamically during an injury event or with abnormal alignment and position after the injury event. Prior studies have shown pressure and geometric changes in cervical spine neural spaces in certain cervical spine positions. However, to the authors' knowledge, this is the first research effort aimed at elucidating the integrity of the cervical spine neural spaces throughout the normal physiologic range of motion. METHODS: The authors instrumented 17 fresh-frozen unembalmed cadaveric human cervical spines (C3-C7) with specially designed intervertebral foramen occlusion transducers and a spinal canal occlusion transducer. The specimens were loaded with pure bending moments to produce simulated physiologic motions of the lower cervical spine. The resulting occlusion profiles for the intervertebral foramen and spinal canal were recorded along with the 6-degree of freedom position of the cervical spine. Because these occlusion measurements describe the ability of the spine to preserve the space for the neural structures, the authors define this neuroprotective role of the vertebral column as neural space integrity. RESULTS: The range of motion developed experimentally in this study compared well with published reports of normal cervical motion. Thus, subsequent changes in neural space integrity may be regarded as resulting from normal human cervical spine motion. No significant change in the spinal canal space was detected for any physiologic motion; however, intervertebral foramen integrity was significantly altered in extension, ipsilateral bending, combined ipsilateral bending and extension, and combined contralateral bending with extension when compared with intact upright neutral position. CONCLUSIONS: This study defines the range of neural space integrity associated with simulated physiologic motion of the lower cervical spine in an experimental setting. This information may be useful in comparing neural space changes in pathologic conditions and may enhance refinement of neurologic injury prevention strategies.