In the current landscape of evidence-based medicine, prospective clinical trials are an important avenue through which to establish the efficacy and safety of biomedical treatments compared with standard-of-care interventions. Depending on their scope and aims, clinical trials can be extremely costly and time intensive, and significant coordination is needed to ensure optimal utilization of healthcare resources, adherence to the principles of biomedical ethics, and appropriate interpretation of study results. This review highlights the core principles for designing and implementing clinical trials within neurosurgery, with the aim to provide clinicians with a framework for implementing both investigator-initiated and industry-sponsored trials.
Adrian E. Jimenez, Rupesh Kotecha, and Debraj Mukherjee
Michael T. C. Poon
Adham M. Khalafallah, Sakibul Huq, Adrian E. Jimenez, Henry Brem, and Debraj Mukherjee
Health measures such as the Charlson Comorbidity Index (CCI) and the 11-factor modified frailty index (mFI-11) have been employed to predict general medical and surgical mortality, but their clinical utility is limited by the requirement for a large number of data points, some of which overlap or require data that may be unavailable in large datasets. A more streamlined 5-factor modified frailty index (mFI-5) was recently developed to overcome these barriers, but it has not been widely tested in neuro-oncology patient populations. The authors compared the utility of the mFI-5 to that of the CCI and the mFI-11 in predicting postoperative mortality in brain tumor patients.
The authors retrospectively reviewed a cohort of adult patients from a single institution who underwent brain tumor surgery during the period from January 2017 to December 2018. Logistic regression models were used to quantify the associations between health measure scores and postoperative mortality after adjusting for patient age, race, ethnicity, sex, marital status, and diagnosis. Results were considered statistically significant at p values ≤ 0.05. Receiver operating characteristic (ROC) curves were used to examine the relationships between CCI, mFI-11, and mFI-5 and mortality, and DeLong’s test was used to test for significant differences between c-statistics. Spearman’s rho was used to quantify correlations between indices.
The study cohort included 1692 patients (mean age 55.5 years; mean CCI, mFI-11, and mFI-5 scores 2.49, 1.05, and 0.80, respectively). Each 1-point increase in mFI-11 (OR 4.19, p = 0.0043) and mFI-5 (OR 2.56, p = 0.018) scores independently predicted greater odds of 90-day postoperative mortality. Adjusted CCI, mFI-11, and mFI-5 ROC curves demonstrated c-statistics of 0.86 (CI 0.82–0.90), 0.87 (CI 0.83–0.91), and 0.87 (CI 0.83–0.91), respectively, and there was no significant difference between the c-statistics of the adjusted CCI and the adjusted mFI-5 models (p = 0.089) or between the adjusted mFI-11 and the adjusted mFI-5 models (p = 0.82). The 3 indices were well correlated (p < 0.01).
The adjusted mFI-5 model predicts 90-day postoperative mortality among brain tumor patients as well as our adjusted CCI and adjusted mFI-11 models. The simplified mFI-5 may be easily integrated into clinical workflows to predict brain tumor surgery outcomes in real time.
Holly Dickinson, Christine Carico, Miriam Nuño, Debraj Mukherjee, Alicia Ortega, Keith L. Black, and Chirag G. Patil
Research on readmissions has been influenced by efforts to reduce hospital cost and avoid penalties stipulated by the Centers for Medicare and Medicaid Services. Less emphasis has been placed on understanding these readmissions and their impact on patient outcomes. This study 1) delineates reasons for readmission, 2) explores factors associated with readmissions, and 3) describes their impact on the survival of glioblastoma patients.
The authors conducted a retrospective review of 362 cases involving patients with glioblastoma undergoing biopsy or tumor resection at their institution between 2003 and 2011. Reasons for re-hospitalization were characterized according to whether or not they were related to surgery and considered preventable. Multivariate analyses were conducted to identify the effect of readmission on survival and determine factors associated with re-hospitalizations.
Twenty-seven (7.5%) of 362 patients experienced unplanned readmissions within 30 days of surgery. Six patients (22.2%) were readmitted by Day 7, 14 (51.9%) by Day 14, and 20 (74.1%) by Day 21. Neurological, infectious, and thromboembolic complications were leading reasons for readmission, accounting for, respectively, 37.0%, 29.6%, and 22.2% of unplanned readmissions. Twenty-one (77.8%) of the 27 readmissions were related to surgery and 19 (70.4%) were preventable. The adjusted hazard ratio of mortality associated with a readmission was 2.03 (95% CI 1.3–3.1). Higher-functioning patients (OR 0.96, 95% CI 0.9–1.0) and patients discharged home (OR 0.21, 95% CI 0.1–0.6) were less likely to get readmitted.
An overwhelming fraction of documented unplanned readmissions were considered preventable and related to surgery. Patients who were readmitted to the hospital within 30 days of surgery had twice the risk of mortality compared with patients who were not readmitted.
Debraj Mukherjee and Chirag G. Patil
Miriam Nuño, Christine Carico, Debraj Mukherjee, Diana Ly, Alicia Ortega, Keith L. Black, and Chirag G. Patil
The Agency for Healthcare Research and Quality patient safety indicators (PSIs) and the Centers for Medicare and Medicaid Services hospital-acquired conditions (HACs) are administrative data-based metrics. The use of these outcomes as standard performance measures has been discussed in previous studies. With the objective of determining the applicability of these events as performance metrics among patients undergoing brain tumor surgery, this study had 2 aims: 1) to evaluate the association between PSIs, HACs, and in-hospital mortality rates; and 2) to determine a correlation between hospital volume, PSIs, and HACs.
Patients with brain tumors treated between 1998 and 2009 were captured in the Nationwide Inpatient Sample database. Hospitals were categorized into groups according to surgical volume. Associations between PSIs, HACs, and in-hospital mortality rates were studied. Factors associated with a PSI, HAC, and mortality were evaluated in a multivariate setting.
A total of 444,751 patients with brain tumors underwent surgery in 1311 hospitals nationwide. Of these, 7.4% of patients experienced a PSI, 0.4% an HAC, and 1.9% died during their hospitalization. The occurrence of a PSI was strongly associated with mortality. Patients were 7.6 times more likely to die (adjusted odds ratio [aOR] 7.6, CI 6.7–8.7) with the occurrence of a PSI in a multivariate analysis. Moderate to strong associations were found between HACs, PSIs, and hospital volume. Patients treated at the highest-volume hospitals compared with the lowest-volume ones had reduced odds of a PSI (aOR 0.9, CI 0.8–1.0) and HAC (aOR 0.5, CI 0.5–0.08).
Patient safety-related adverse events were strongly associated with in-hospital mortality. Moderate to strong correlations were found between PSIs, HACs, and hospital procedural volume. Patients treated at the highest-volume hospitals had consistently lower rates of mortality, PSIs, and HACs compared with those treated at the lowest-volume facilities.
Kaisorn L. Chaichana, Debraj Mukherjee, Owoicho Adogwa, Joseph S. Cheng, and Matthew J. McGirt
Lumbar discectomy is the most common surgical procedure performed in the US for patients experiencing back and leg pain from herniated lumbar discs. However, not all patients will benefit from lumbar discectomy. Patients with certain psychological predispositions may be especially vulnerable to poor clinical outcomes.
The goal of this study was therefore to determine the role that preoperative depression and somatic anxiety have on long-term back and leg pain, disability, and quality of life (QOL) for patients undergoing single-level lumbar discectomy.
In 67 adults undergoing discectomy for a single-level herniated lumbar disc, the authors determined quantitative measurements of leg and back pain (visual analog scale [VAS]), quality of life (36-Item Short Form Health Survey [SF-36]), and disease-specific disability (Oswestry Disability Index) preoperatively and at 6 weeks, 3, 6, and 12 months after surgery. The degree of preoperative depression and somatization was assessed using the Zung Self-Rating Depression Scale and a modified somatic perception questionnaire (MSPQ). Multivariate regression analyses were performed to assess associations between Zung Scale and MSPQ scores with achievement of a minimum clinical important difference (MCID) in each outcome measure by 12 months postoperatively.
All patients completed 12 months of follow-up. Overall, a significant improvement in VAS leg pain, VAS back pain, Oswestry Disability Index, and SF-36 Physical Component Summary scores was observed by 6 weeks after surgery. Improvements in all outcomes were maintained throughout the 12-month follow-up period. Increasing preoperative depression (measured using the Zung Scale) was associated with a decreased likelihood of achieving an MCID in disability (p = 0.006) and QOL (p = 0.04) but was not associated with VAS leg pain (p = 0.96) or back pain (p = 0.85) by 12 months. Increasing preoperative somatic anxiety (measured using the MSPQ) was associated with decreased likelihood of achieving an MCID in disability (p = 0.002) and QOL (p = 0.03) but was not associated with leg pain (p = 0.64) or back pain (p = 0.77) by 12 months.
The Zung Scale and MSPQ are valuable tools for stratifying risk in patients who may not experience clinically relevant improvement in disability and QOL after discectomy. Efforts to address these confounding and underlying contributors of depression and heightened somatic anxiety may improve overall outcomes after lumbar discectomy.
Sakibul Huq, Adham M. Khalafallah, David Botros, Adrian E. Jimenez, Shravika Lam, Judy Huang, and Debraj Mukherjee
Debraj Mukherjee, Barry D. Pressman, Deborah Krakow, David L. Rimoin, and Moise Danielpour
Achondroplasia may be associated with compression at the cervicomedullary junction. Determining which patients are at greatest risk for neurological complications of cervicomedullary compression can be difficult. In the current study the authors reviewed their records to determine the incidence and clinical significance of dynamic cervicomedullary stenosis and obstruction of CSF flow along with surgical outcomes following posterior fossa decompression.
The authors reviewed 34 consecutive cases involving symptomatic children with achondroplasia undergoing cervicomedullary decompression performed by a single surgeon over 11 years. Of these patients, 29 had undergone preoperative dynamic MRI of the cervicomedullary junction with cine (cinema) CSF flow studies; 13 of these patients underwent postoperative dynamic MRI studies. Clinical outcomes included changes in polysomnography, head circumference percentile, and fontanel characteristics. Radiographic outcomes included changes in dynamic spinal cord diameter, improvement in CSF flow at the foramen magnum, and change in the Evans ratio.
Patients were predominantly female, with a mean age at presentation of 6.6 years and mean follow-up of 3.7 years (range 1–10 years).
All patients had moderate to excellent improvement in postoperative polysomnography, slight decrease in average head circumference percentile (from 46.9th percentile to 45.7th percentile), and no subjective worsening of fontanel characteristics. The Evans ratio decreased by 2%, spinal cord diameter increased an average of 3.1 mm, 5.2 mm, and 0.2 mm in the neutral, flexed, and extended positions, respectively, and CSF flow improved qualitatively in all 3 positions. There were no postoperative infections, CSF leaks, or other major complications. None of the patients undergoing initial foramen magnum decompression performed at our medical center required reoperation.
Patients with achondroplasia and symptomatic cervicomedullary compression have increased risk of dynamic stenosis at the foramen magnum evident upon dynamic cine MRI. Operative decompression may be offered with low risk of complications or need for reoperation.