34 results on '"Adil SM"'
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2. A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA.
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Charalambous LT, Adil SM, Rajkumar S, Gramer R, Kirsch E, Liu B, Zomorodi A, McClellan M, and Lad SP
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- Humans, Retrospective Studies, Seizures, Postoperative Complications epidemiology, Postoperative Complications etiology, Subarachnoid Hemorrhage epidemiology, Subarachnoid Hemorrhage therapy, Subarachnoid Hemorrhage complications, Hyponatremia complications, Inappropriate ADH Syndrome complications
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Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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3. Treatment Patterns and Health Care Resource Utilization of Iatrogenic Spinal Cerebrospinal Fluid Leaks in the United States.
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Charalambous LT, Rajkumar S, Liu B, Adil SM, Wong M, Hodges S, Amrhein TJ, Leithe LG, Parente B, Lee HJ, and Lad SP
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- Adult, Humans, United States, Retrospective Studies, Delivery of Health Care, Patient Acceptance of Health Care, Treatment Outcome, Cerebrospinal Fluid Leak surgery, Iatrogenic Disease
- Abstract
Study Design: Retrospective cohort study., Objective: We aimed to characterize the treatment patterns and the associated costs in patients with cerebrospinal fluid (CSF) leak after spine procedures in the United States., Background: CSF leak is a common complication after spinal procedures. However, there is a little data regarding the national patterns of treatment choice and the associated health care resource utilization., Methods: We utilized the IBM MarketScan Research databases to retrospectively analyze adult US patients diagnosed with CSF leak within 30 days of spine procedures between 2001 and 2018. Treatment prevalence, treatment failure, and health care resource utilization data within 30 days of the CSF leak were collected. A subanalysis was performed on patients who received epidural blood patches (EBP) to better understand health care utilization attributable to this treatment modality., Results: Twenty one thousand four hundred fourteen patients were identified. The most common causes of CSF leak were diagnostic spinal tap (59.2%) and laminectomy/discectomy (18.7%). With regard to treatment prevalence, 40.4% of the patients (n=8651) had conservative medical management, 46.6% (n=9987) received epidural blood patch repair, 9.6% required surgical repair (n=2066), and 3.3% (n=710) had lumbar drain/puncture. Nine hundred sixty-seven (9.7%), 150 (21.1%), and 280 (13.5%) patients failed initial EBP, lumbar drain, and surgery, respectively, and the overall failure rate was 10.9% (n=1397). The median 30-day total cost across all groups was $5,101. Patients who received lumbar drain ($22,341) and surgical repair ($30,199) had higher 30-day median total costs than EBP ($8,140) or conservative management ($17,012). The median 30-day total cost for patients whose EBP failed ($8,179) was substantially greater than those with a successful EBP repair ($3,439)., Conclusions: National treatment patterns and costs for CSF leaks were described. When used in the correct patient cohort, EBP has the lower failure rates and costs than comparable alternatives. EBP may be considered more often in situations where conservative management or lumbar drains are currently being used., Competing Interests: The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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4. Deep Learning to Predict Traumatic Brain Injury Outcomes in the Low-Resource Setting.
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Adil SM, Elahi C, Patel DN, Seas A, Warman PI, Fuller AT, Haglund MM, and Dunn TW
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- Humans, Logistic Models, ROC Curve, Uganda epidemiology, Brain Injuries, Traumatic diagnosis, Brain Injuries, Traumatic therapy, Deep Learning
- Abstract
Objective: Traumatic brain injury (TBI) disproportionately affects low- and middle-income countries (LMICs). In these settings, accurate patient prognostication is both difficult and essential for high-quality patient care. With the ultimate goal of enhancing TBI triage in LMICs, we aim to develop the first deep learning model to predict outcomes after TBI and compare its performance with that of less complex algorithms., Methods: TBI patients' data were prospectively collected in Kampala, Uganda, from 2016 to 2020. To predict good versus poor outcome at hospital discharge, we created deep neural network, shallow neural network, and elastic-net regularized logistic regression models. Predictors included 13 easily acquirable clinical variables. We assessed model performance with 5-fold cross-validation to calculate areas under both the receiver operating characteristic curve and precision-recall curve (AUPRC), in addition to standardized partial AUPRC to focus on comparisons at clinically relevant operating points., Results: We included 2164 patients for model training, of which 12% had poor outcomes. The deep neural network performed best as measured by the area under the receiver operating characteristic curve (0.941) and standardized partial AUPRC in region maximizing recall (0.291), whereas the shallow neural network was best by the area under the precision-recall curve (0.770). In several other comparisons, the elastic-net regularized logistic regression was noninferior to the neural networks., Conclusions: We present the first use of deep learning for TBI prognostication, with an emphasis on LMICs, where there is great need for decision support to allocate limited resources. Optimal algorithm selection depends on the specific clinical setting; deep learning is not a panacea, though it may have a role in these efforts., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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5. Machine Learning to Predict Successful Opioid Dose Reduction or Stabilization After Spinal Cord Stimulation.
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Adil SM, Charalambous LT, Rajkumar S, Seas A, Warman PI, Murphy KR, Rahimpour S, Parente B, Dharmapurikar R, Dunn TW, and Lad SP
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- Analgesics, Opioid therapeutic use, Drug Tapering, Humans, Logistic Models, Machine Learning, Spinal Cord Stimulation
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Background: Spinal cord stimulation (SCS) effectively reduces opioid usage in some patients, but preoperatively, there is no objective measure to predict who will most benefit., Objective: To predict successful reduction or stabilization of opioid usage after SCS using machine learning models we developed and to assess if deep learning provides a significant benefit over logistic regression (LR)., Methods: We used the IBM MarketScan national databases to identify patients undergoing SCS from 2010 to 2015. Our models predict surgical success as defined by opioid dose stability or reduction 1 year after SCS. We incorporated 30 predictors, primarily regarding medication patterns and comorbidities. Two machine learning algorithms were applied: LR with recursive feature elimination and deep neural networks (DNNs). To compare model performances, we used nested 5-fold cross-validation to calculate area under the receiver operating characteristic curve (AUROC)., Results: The final cohort included 7022 patients, of whom 66.9% had successful surgery. Our 5-variable LR performed comparably with the full 30-variable version (AUROC difference <0.01). The DNN and 5-variable LR models demonstrated similar AUROCs of 0.740 (95% CI, 0.727-0.753) and 0.737 (95% CI, 0.728-0.746) ( P = .25), respectively. The simplified model can be accessed at SurgicalML.com ., Conclusion: We present the first machine learning-based models for predicting reduction or stabilization of opioid usage after SCS. The DNN and 5-variable LR models demonstrated comparable performances, with the latter revealing significant associations with patients' pre-SCS pharmacologic patterns. This simplified, interpretable LR model may augment patient and surgeon decision making regarding SCS., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)
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- 2022
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6. Palliative Care Consultations in Patients with Severe Traumatic Brain Injury: Who Receives Palliative Care Consultations and What Does that Mean for Utilization?
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Williamson TL, Adil SM, Shalita C, Charalambous LT, Mitchell T, Yang Z, Parente BA, Lee HJ, Ubel PA, Lemmon ME, Galanos AN, Lad SP, and Komisarow JM
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- Hispanic or Latino, Humans, Referral and Consultation, Retrospective Studies, Brain Injuries, Traumatic therapy, Palliative Care
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Background: Palliative care has the potential to improve goal-concordant care in severe traumatic brain injury (sTBI). Our primary objective was to illuminate the demographic profiles of patients with sTBI who receive palliative care encounters (PCEs), with an emphasis on the role of race. Secondary objectives were to analyze PCE usage over time and compare health care resource utilization between patients with or without PCEs., Methods: The National Inpatient Sample database was queried for patients age ≥ 18 who had a diagnosis of sTBI, defined by using International Classification of Diseases, 9th Revision codes. PCEs were defined by using International Classification of Diseases, 9th Revision code V66.7 and trended from 2001 to 2015. To assess factors associated with PCE in patients with sTBI, we performed unweighted generalized estimating equations regression. PCE association with decision making was modeled via its effect on rate of percutaneous endoscopic gastrostomy (PEG) tube placement. To quantify differences in PCE-related decisions by race, race was modeled as an effect modifier., Results: From 2001 to 2015, the proportion of palliative care usage in patients with sTBI increased from 1.5 to 36.3%, with 41.6% White, 22.3% Black, and 25% Hispanic patients with sTBI having a palliative care consultation in 2015, respectively. From 2008 to 2015, we identified 17,673 sTBI admissions. White and affluent patients were more likely to have a PCE than Black, Hispanic, and low socioeconomic status patients. Across all races, patients receiving a PCE resulted in a lower rate of PEG tube placement; however, White patients exhibited a larger reduction of PEG tube placement than Black patients. Patients using palliative care had lower total hospital costs (median $16,368 vs. $26,442, respectively)., Conclusions: Palliative care usage for sTBI has increased dramatically this century and it reduces resource utilization. This is true across races, however, its usage rate and associated effect on decision making are race-dependent, with White patients receiving more PCE and being more likely to decline the use of a PEG tube if they have had a PCE., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)
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- 2022
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7. Machine Learning for Predicting In-Hospital Mortality After Traumatic Brain Injury in Both High-Income and Low- and Middle-Income Countries.
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Warman PI, Seas A, Satyadev N, Adil SM, Kolls BJ, Haglund MM, Dunn TW, and Fuller AT
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- Adrenal Cortex Hormones, Hospital Mortality, Humans, Machine Learning, Prognosis, Brain Injuries, Traumatic diagnosis, Brain Injuries, Traumatic therapy, Developing Countries
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Background: Machine learning (ML) holds promise as a tool to guide clinical decision making by predicting in-hospital mortality for patients with traumatic brain injury (TBI). Previous models such as the international mission for prognosis and clinical trials in TBI (IMPACT) and the corticosteroid randomization after significant head injury (CRASH) prognosis calculators can potentially be improved with expanded clinical features and newer ML approaches., Objective: To develop ML models to predict in-hospital mortality for both the high-income country (HIC) and the low- and middle-income country (LMIC) settings., Methods: We used the Duke University Medical Center National Trauma Data Bank and Mulago National Referral Hospital (MNRH) registry to predict in-hospital mortality for the HIC and LMIC settings, respectively. Six ML models were built on each data set, and the best model was chosen through nested cross-validation. The CRASH and IMPACT models were externally validated on the MNRH database., Results: ML models built on National Trauma Data Bank (n = 5393, 84 predictors) demonstrated an area under the receiver operating curve (AUROC) of 0.91 (95% CI: 0.85-0.97) while models constructed on MNRH (n = 877, 31 predictors) demonstrated an AUROC of 0.89 (95% CI: 0.81-0.97). Direct comparison with CRASH and IMPACT models showed significant improvement of the proposed LMIC models regarding AUROC (P = .038)., Conclusion: We developed high-performing well-calibrated ML models for predicting in-hospital mortality for both the HIC and LMIC settings that have the potential to influence clinical management and traumatic brain injury patient trajectories., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)
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- 2022
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8. Corticosteroid Randomization after Significant Head Injury and International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury Models Compared with a Machine Learning-Based Predictive Model from Tanzania.
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Elahi C, Adil SM, Sakita F, Mmbaga BT, Hernandes Rocha TA, Fuller A, Haglund MM, Nickenig Vissoci JR, and Staton C
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- Adrenal Cortex Hormones, Humans, Machine Learning, Prognosis, Random Allocation, Tanzania epidemiology, Brain Injuries, Traumatic diagnosis
- Abstract
Hospitals in low- and middle-income countries (LMICs) could benefit from decision support technologies to reduce time to triage, diagnosis, and surgery for patients with traumatic brain injury (TBI). Corticosteroid Randomization after Significant Head Injury (CRASH) and International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) are robust examples of TBI prognostic models, although they have yet to be validated in Sub-Saharan Africa (SSA). Moreover, machine learning and improved data quality in LMICs provide an opportunity to develop context-specific, and potentially more accurate, prognostic models. We aim to externally validate CRASH and IMPACT on our TBI registry and compare their performances to that of the locally derived model (from the Kilimanjaro Christian Medical Center [KCMC]). We developed a machine learning-based prognostic model from a TBI registry collected at a regional referral hospital in Moshi, Tanzania. We also used the core CRASH and IMPACT online risk calculators to generate risk scores for each patient. We compared the discrimination (area under the curve [AUC]) and calibration before and after Platt scaling (Brier, Hosmer-Lemeshow Test, and calibration plots) for CRASH, IMPACT, and the KCMC model. The outcome of interest was unfavorable in-hospital outcome defined as a Glasgow Outcome Scale score of 1-3. There were 2972 patients included in the TBI registry, of whom 11% had an unfavorable outcome. The AUCs for the KCMC model, CRASH, and IMPACT were 0.919, 0.876, and 0.821, respectively. Prior to Platt scaling, CRASH was the best calibrated model (χ
2 = 68.1) followed by IMPACT (χ2 = 380.9) and KCMC (χ2 = 1025.6). We provide the first SSA validation of the core CRASH and IMPACT models. The KCMC model had better discrimination than either of these. CRASH had the best calibration, although all model predictions could be successfully calibrated. The top performing models, KCMC and CRASH, were both developed using LMIC data, suggesting that locally derived models may outperform imported ones from different contexts of care. Further work is needed to externally validate the KCMC model.- Published
- 2022
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9. Complementary and alternative medicine in children with diffuse intrinsic pontine glioma-A SIOPE DIPG Network and Registry study.
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El-Khouly FE, Adil SM, Wiese M, Hulleman E, Hendrikse NH, Kaspers GJL, Kramm CM, Veldhuijzen van Zanten SEM, and van Vuurden DG
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- Child, Humans, Registries, Retrospective Studies, Brain Stem Neoplasms therapy, Complementary Therapies, Diffuse Intrinsic Pontine Glioma therapy
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Introduction: Diffuse intrinsic pontine glioma (DIPG) is a rare and aggressive childhood brainstem malignancy with a 2-year survival rate of <10%. This international survey study aims to evaluate the use of complementary and alternative medicine (CAM) in this patient population., Methods: Parents and physicians of patients with DIPG were asked to participate in a retrospective online survey regarding CAM use during time of illness., Results: Between January and May 2020, 120 parents and 75 physicians contributed to the online survey. Most physicians estimated that <50% of their patients used CAM, whereas 69% of the parents reported using CAM to treat their child during time of illness. Cannabis was the most frequently used form of CAM, followed by vitamins and minerals, melatonin, curcumin, and boswellic acid. CAM was mainly used with the intention of direct antitumor effect. Other motivations were to treat side effects of chemotherapy or to increase comfort of the child. Children diagnosed from 2016 onwards were more likely to use CAM (χ
2 = 6.08, p = .014). No significant difference was found between CAM users and nonusers based on ethnicity (χ2 = 4.18, p = .382) or country of residence (χ2 = 9.37, p = .154). Almost 50% of the physicians do not frequently ask their patients about possible CAM use., Conclusion: This survey demonstrates that worldwide, a considerable number of patients with DIPG use CAM. Physicians should be more aware of potential CAM use and actively discuss the topic. In addition, more research is needed to gain knowledge about possible anticancer effects of CAM and (positive/negative) interactions with conventional therapies., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)- Published
- 2021
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10. Mobile Health Application for Patients Undergoing Breast Cancer Surgery: Feasibility Study.
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Ponder M, Venkatraman V, Charalambous L, Ansah-Yeboah AA, Adil SM, Antezana LA, Dharmapurikar R, Gellad ZF, Lad SP, Hwang ES, and Plichta JK
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- Feasibility Studies, Female, Humans, Mastectomy, Mastectomy, Segmental, Middle Aged, Breast Neoplasms surgery, Telemedicine
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Purpose: Contemporary breast cancer surgery often requires hospital stays of 1 day or less, presenting challenges to delivery of high-quality care. Without sufficient time for proper education and guidance, patients may delay seeking care, experience anxiety, or seek unnecessary care, leading to poorer outcomes and increased costs. To address this, we evaluated the feasibility of a planning-, outcomes-, and analytics-based mobile health application called Manage My Surgery (MMS) for patients undergoing elective breast cancer surgery., Methods: Patients undergoing breast cancer surgery at an academic health center were invited to use MMS. Those who used the application received pre- and postoperative surveys, which recorded and reported patient satisfaction and outcomes related to the application., Results: Thirty-three female patients undergoing elective breast cancer surgery used MMS. The median age was 58 years. Nineteen patients underwent lumpectomy, and 14 underwent mastectomy. Users logged on to the application an average of 3.5 times. The median number of questions viewed was 12 (range 2-35). Of 17 patients who completed the feedback survey, 100% said that MMS was helpful during preparation for surgery, 82.3% said that MMS was helpful postoperatively, and 94.1% would recommend MMS to others. Preliminary data on patient-reported outcomes collected by MMS suggest improvements in anxiety and depression over time., Conclusion: Implementation of a digital care navigation tool in breast cancer surgery patients is feasible. Patients found the tool helpful in both the pre- and postoperative period. Additional ongoing work will focus on patients' self-management skills, long-term outcomes, and health system costs., Competing Interests: Madison PonderEmployment: Higgs Boson HealthStock and Other Ownership Interests: Higgs Boson Health Lefko CharalambousConsulting or Advisory Role: Higgs Boson Health Abena A. Ansah-YeboahEmployment: Higgs Boson Health Syed M. AdilConsulting or Advisory Role: Higgs Boson Health Luis A. AntezanaEmployment: Higgs Boson Health LLC Rajeev DharmapurikarEmployment: Higgs Boson IncLeadership: Higgs Boson IncStock and Other Ownership Interests: Higgs Boson Inc Ziad F. GelladStock and Other Ownership Interests: Higgs Boson IncConsulting or Advisory Role: Merck, Novo Nordisk Shivanand P. LadStock and Other Ownership Interests: Higgs Boson Inc Jennifer K. PlichtaResearch Funding: Color GenomicsNo other potential conflicts of interest were reported.
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- 2021
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11. A high-resolution interactive atlas of the human brainstem using magnetic resonance imaging.
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Adil SM, Calabrese E, Charalambous LT, Cook JJ, Rahimpour S, Atik AF, Cofer GP, Parente BA, Johnson GA, Lad SP, and White LE
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- Autopsy, Humans, Atlases as Topic, Brain Stem anatomy & histology, Brain Stem diagnostic imaging, Diffusion Tensor Imaging, Gray Matter anatomy & histology, Gray Matter diagnostic imaging, White Matter anatomy & histology, White Matter diagnostic imaging
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Conventional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology, or the low spatial resolution of conventional magnetic resonance imaging (MRI). Postmortem high-resolution MRI circumvents the challenges associated with both modalities. A single human brainstem specimen extending from the rostral diencephalon through the caudal medulla was prepared for imaging after the brain was removed from a 65-year-old male within 24 h of death. The specimen was formalin-fixed for two weeks, then rehydrated and placed in a custom-made MRI compatible tube and immersed in liquid fluorocarbon. MRI was performed in a 7-Tesla scanner with 120 unique diffusion directions. Acquisition time for anatomic and diffusion images were 14 h and 208 h, respectively. Segmentation was performed manually. Deterministic fiber tractography was done using strategically chosen regions of interest and avoidance, with manual editing using expert knowledge of human neuroanatomy. Anatomic and diffusion images were rendered with isotropic resolutions of 50 μm and 200 μm, respectively. Ninety different structures were segmented and labeled, and 11 different fiber bundles were rendered with tractography. The complete atlas is available online for interactive use at https://www.civmvoxport.vm.duke.edu/voxbase/login.php?return_url=%2Fvoxbase%2F. This atlas presents multiple contrasting datasets and selected tract reconstruction with unprecedented resolution for MR imaging of the human brainstem. There are immediate applications in neuroanatomical education, with the potential to serve future applications for neuroanatomical research and enhanced neurosurgical planning through "safe" zones of entry into the human brainstem., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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12. Outcomes and Health Care Resource Utilization of Adult Bacterial Meningitis in the United States.
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Kiyani M, Hodges SE, Adil SM, Charalambous LT, Liu B, Lee HJ, Parente B, Perfect JR, and Lad SP
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Objective: To examine the longitudinal health care resource utilization, in-hospital mortality, and incidence of downstream complications of bacterial meningitis in the United States., Methods: Using IBM MarketScan, we retrieved data on adult patients with a diagnosis of bacterial meningitis admitted to a US hospital between 2008 and 2015. Patients were stratified into groups (1) with/without prior head trauma/neurosurgical complications, (2) nosocomial/community acquisition, and (3) Gram-negative/positive bacteria. Cost data were collected for up to 2 years and analyzed with descriptive statistics and longitudinal modeling., Results: Among 4,496 patients with bacterial meningitis, 16.5% and 4.6% had preceding neurosurgical complications and head injuries, respectively. Lumbar punctures were performed in 37.3% of patients without prior trauma/complications who went on to develop nosocomial meningitis, and those with prior head injuries or complications had longer initial hospital stays (17.0 days vs 8.0 days). Within a month of diagnosis, 29.2% of patients with bacterial meningitis had experienced downstream complications, most commonly hydrocephalus (12.7%). The worst 30-day mortality was due to tuberculous (12.3%) and streptococcal meningitis (7.2%). Overall, prior head trauma and complications were associated with higher costs. Community-acquired bacterial meningitis had lower median baseline costs relative to the nosocomial group (no head trauma/complication: $17,152 vs $82,778; head trauma/complication: $92,428 vs $168,309) but higher median costs within 3 months of diagnosis (no head trauma/complication: $47,911 vs $34,202; head trauma/complication: $89,207 vs $58,947). All costs demonstrated a sharp decline thereafter., Conclusions: Bacterial meningitis remains costly and devastating, especially for those who experience traumatic head injuries or have a complicated progress after neurosurgery., (© 2020 American Academy of Neurology.)
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- 2021
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13. Predicting the Individual Treatment Effect of Neurosurgery for Patients with Traumatic Brain Injury in the Low-Resource Setting: A Machine Learning Approach in Uganda.
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Adil SM, Elahi C, Gramer R, Spears CA, Fuller AT, Haglund MM, and Dunn TW
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- Adolescent, Adult, Brain Injuries, Traumatic epidemiology, Child, Female, Glasgow Coma Scale economics, Glasgow Coma Scale trends, Health Resources trends, Humans, Machine Learning trends, Male, Middle Aged, Neurosurgical Procedures trends, Predictive Value of Tests, Treatment Outcome, Uganda epidemiology, Young Adult, Brain Injuries, Traumatic economics, Brain Injuries, Traumatic surgery, Health Resources economics, Machine Learning economics, Neurosurgical Procedures economics
- Abstract
Traumatic brain injury (TBI) disproportionately affects low- and middle-income countries (LMICs). In these low-resource settings, effective triage of patients with TBI-including the decision of whether or not to perform neurosurgery-is critical in optimizing patient outcomes and healthcare resource utilization. Machine learning may allow for effective predictions of patient outcomes both with and without surgery. Data from patients with TBI was collected prospectively at Mulago National Referral Hospital in Kampala, Uganda, from 2016 to 2019. One linear and six non-linear machine learning models were designed to predict good versus poor outcome near hospital discharge and internally validated using nested five-fold cross-validation. The 13 predictors included clinical variables easily acquired on admission and whether or not the patient received surgery. Using an elastic-net regularized logistic regression model (GLMnet), with predictions calibrated using Platt scaling, the probability of poor outcome was calculated for each patient both with and without surgery (with the difference quantifying the "individual treatment effect," ITE). Relative ITE represents the percent reduction in chance of poor outcome, equaling this ITE divided by the probability of poor outcome with no surgery. Ultimately, 1766 patients were included. Areas under the receiver operating characteristic curve (AUROCs) ranged from 83.1% (single C5.0 ruleset) to 88.5% (random forest), with the GLMnet at 87.5%. The two variables promoting good outcomes in the GLMnet model were high Glasgow Coma Scale score and receiving surgery. For the subgroup not receiving surgery, the median relative ITE was 42.9% (interquartile range [IQR], 32.7% to 53.5%); similarly, in those receiving surgery, it was 43.2% (IQR, 32.9% to 54.3%). We provide the first machine learning-based model to predict TBI outcomes with and without surgery in LMICs, thus enabling more effective surgical decision making in the resource-limited setting. Predicted ITE similarity between surgical and non-surgical groups suggests that, currently, patients are not being chosen optimally for neurosurgical intervention. Our clinical decision aid has the potential to improve outcomes.
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- 2021
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14. Surgical intervention and patient factors associated with poor outcomes in patients with traumatic brain injury at a tertiary care hospital in Uganda.
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Spears CA, Adil SM, Kolls BJ, Muhumza ME, Haglund MM, Fuller AT, and Dunn TW
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Objective: The purpose of this study was to investigate whether neurosurgical intervention for traumatic brain injury (TBI) is associated with reduced risks of death and clinical deterioration in a low-income country with a relatively high neurosurgical capacity. The authors further aimed to assess whether the association between surgical intervention and acute poor outcomes differs according to TBI severity and various patient factors., Methods: Using TBI registry data collected from a national referral hospital in Uganda between July 2016 and April 2020, the authors performed Cox regression analyses of poor outcomes in admitted patients who did and did not undergo surgery for TBI, with surgery as a time-varying treatment variable. Patients were further stratified by TBI severity using the admission Glasgow Coma Scale (GCS) score: mild TBI (mTBI; GCS scores 13-15), moderate TBI (moTBI; GCS scores 9-12), and severe TBI (sTBI; GCS scores 3-8). Poor outcomes constituted Glasgow Outcome Scale scores 2-3, deterioration in TBI severity between admission and discharge (e.g., mTBI to sTBI), and death. Several clinical and demographic variables were included as covariates. Patients were observed for outcomes from admission through hospital day 10., Results: Of 1544 patients included in the cohort, 369 (24%) had undergone surgery. Rates of poor outcomes were 4% (n = 13) for surgical patients and 12% (n = 144) among nonsurgical patients (n = 1175). Surgery was associated with a 59% reduction in the hazard for a poor outcome (HR 0.41, 95% CI 0.23-0.72). Age, pupillary nonreactivity, fall injury, and TBI severity at admission were significant covariates. In models stratifying by TBI severity at admission, patients with mTBI had an 80% reduction in the hazard for a poor outcome with surgery (HR 0.20, 95% CI 0.04-0.90), whereas those with sTBI had a 65% reduction (HR 0.35, 95% CI 0.14-0.89). Patients with moTBI had a statistically nonsignificant 56% reduction in hazard (HR 0.44, 95% CI 0.17-1.17)., Conclusions: In this setting, the association between surgery and rates of poor outcomes varied with TBI severity and was influenced by several factors. Patients presenting with mTBI had the greatest reduction in the hazard for a poor outcome, followed by those presenting with sTBI. However, patients with moTBI had a nonsignificant reduction in the hazard, indicating greater variability in outcomes and underscoring the need for closer monitoring of this population. These results highlight the importance of accurate, timely clinical evaluation throughout a patient's admission and can inform decisions about whether and when to perform surgery for TBI when resources are limited.
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- 2021
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15. Inpatient mortality and healthcare resource utilization of nontraumatic intracerebral hemorrhage complications in the US.
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Park C, Charalambous LT, Yang Z, Adil SM, Hodges SE, Lee HJ, Verbick LZ, McCabe AR, and Lad SP
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Objective: Nontraumatic, primary intracerebral hemorrhage (ICH) accounts for 2 million strokes worldwide annually and has a 1-year survival rate of 50%. Recent studies examining functional outcomes from ICH evacuation have been performed, but limited work has been done quantifying the incidence of subsequent complications and their healthcare economic impact. The purpose of this study was to quantify the incidence and healthcare resource utilization (HCRU) for major complications that can arise from ICH., Methods: The IBM MarketScan Research databases were used to retrospectively identify patients with ICH from 2010 to 2015. Complications examined included cerebral edema, hydrocephalus, venous thromboembolic events (VTEs), pneumonia, urinary tract infections (UTIs), and seizures. For each complication, inpatient mortality and HCRU were assessed., Results: Of 25,322 adult patients included, 10,619 (42%) developed complications during the initial admission of ICH: 22% had cerebral edema, 11% hydrocephalus, 10% pneumonia, 6% UTIs, 5% seizures, and 5% VTEs. The inpatient mortality rates at 7 and 30 days for each complication of ICH ranked from highest to lowest were hydrocephalus (24% and 32%), cerebral edema (15% and 20%), pneumonia (8% and 18%), seizure (7% and 13%), VTE (4% and 11%), and UTI (4% and 8%). Hydrocephalus had the highest total cost (median $92,776, IQR $39,308-$180,716) at 7 days post-ICH diagnosis and the highest cumulative total cost (median $170,839, IQR $91,462-$330,673) at 1 year post-ICH diagnosis., Conclusions: This study characterizes one of the largest cohorts of patients with nontraumatic ICH in the US. More than 42% of the patients with ICH developed complications during initial admission, which resulted in high inpatient mortality and considerable HCRU.
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- 2021
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16. Paediatric bacterial meningitis in the USA: outcomes and healthcare resource utilization of nosocomial versus community-acquired infection.
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Adil SM, Hodges SE, Charalambous LT, Kiyani M, Liu B, Lee HJ, Parente BA, Perfect JR, and Lad SP
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- Adolescent, Bacteria classification, Bacteria genetics, Bacteria isolation & purification, Child, Child, Preschool, Community-Acquired Infections microbiology, Cross Infection microbiology, Female, Hospitals, Humans, Infant, Male, Meningitis, Bacterial microbiology, Pediatrics statistics & numerical data, United States, Community-Acquired Infections epidemiology, Cross Infection epidemiology, Meningitis, Bacterial epidemiology
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Introduction. Paediatric bacterial meningitis remains a costly disease, both financially and clinically. Hypothesis/Gap Statement . Previous epidemiological and cost studies of bacterial meningitis (BM) have largely focused on adult populations or single pathogens. There have been few recent, large-scale studies of pediatric BM in the USA. Aim. We examined healthcare resource utilization (HCRU) and associated morbidity and mortality of community-acquired versus nosocomial bacterial infections in children across the USA. Methodology. The IBM MarketScan Research databases were used to identify patients <18 years old admitted to USA hospitals from 2008 to 2015 with a primary diagnosis of BM. Cases were categorized as either community-acquired or nosocomial. HCRU, post-diagnosis neurosurgical procedures, 30-day in-hospital mortality, and complications were compared between groups. Multivariable regression adjusted for sex, age and Gram staining was used to compare costs of nosocomial versus community-acquired infections over time. Results. We identified 1928 cases of paediatric BM without prior head trauma or neurological/systemic complications. Of these, 15.4 % were nosocomial and 84.6 % were community-acquired infections. After diagnostic lumbar puncture (37.1 %), the most common neurosurgical procedure was placement of ventricular catheter (12.6 %). The 30-day complication rates for nosocomial and community-acquired infections were 40.5 and 45.9 %, respectively. The most common complications were hydrocephalus (20.8 %), intracranial abscess (8.8 %) and cerebral oedema (8.1 %). The 30-day in-hospital mortality rates for nosocomial and community-acquired infections were 2.7 and 2.8 %, respectively.Median length of admission was 14.0 days (Q1: 7 days, Q3: 26 days). Median 90-day cost was $40 861 (Q1: $11 988, Q3: $114,499) for the nosocomial group and $56 569 (Q1: $26 127, Q3: $142 780) for the community-acquired group. In multivariable regression, the 90-day post-diagnosis total costs were comparable between groups (cost ratio: 0.89; 95 % CI: 0.70 to 1.13), but at 2 years post-diagnosis, the nosocomial group was associated with 137 % higher costs (CR: 2.37, 95 % CI: 1.51 to 3.70). Conclusion. In multivariable analysis, nosocomial infections were associated with significantly higher long-term costs up to 2 years post-infection. Hydrocephalus, intracranial epidural abscess and cerebral oedema were the most common complications, and lumbar punctures and ventricular catheter placement were the most common neurosurgical procedures. This study represents the first nation-wide, longitudinal comparison of the outcomes and considerable HCRU of nosocomial versus community-acquired paediatric BM, including characterization of complications and procedures contributing to the high costs of these infections.
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- 2021
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17. Impact of Spinal Cord Stimulation on Opioid Dose Reduction: A Nationwide Analysis.
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Adil SM, Charalambous LT, Spears CA, Kiyani M, Hodges SE, Yang Z, Lee HJ, Rahimpour S, Parente B, Greene KA, McClellan M, and Lad SP
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- Adult, Female, Humans, Male, Middle Aged, Opioid-Related Disorders epidemiology, Retrospective Studies, Analgesics, Opioid therapeutic use, Chronic Pain therapy, Pain Management methods, Spinal Cord Stimulation methods
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Background: Opioid misuse in the USA is an epidemic. Utilization of neuromodulation for refractory chronic pain may reduce opioid-related morbidity and mortality, and associated economic costs., Objective: To assess the impact of spinal cord stimulation (SCS) on opioid dose reduction., Methods: The IBM MarketScan® database was retrospectively queried for all US patients with a chronic pain diagnosis undergoing SCS between 2010 and 2015. Opioid usage before and after the procedure was quantified as morphine milligram equivalents (MME)., Results: A total of 8497 adult patients undergoing SCS were included. Within 1 yr of the procedure, 60.4% had some reduction in their opioid use, 34.2% moved to a clinically important lower dosage group, and 17.0% weaned off opioids entirely. The proportion of patients who completely weaned off opioids increased with decreasing preprocedure dose, ranging from 5.1% in the >90 MME group to 34.2% in the ≤20 MME group. The following variables were associated with reduced odds of weaning off opioids post procedure: long-term opioid use (odds ratio [OR]: 0.26; 95% CI: 0.21-0.30; P < .001), use of other pain medications (OR: 0.75; 95% CI: 0.65-0.87; P < .001), and obesity (OR: 0.75; 95% CI: 0.60-0.94; P = .01)., Conclusion: Patients undergoing SCS were able to reduce opioid usage. Given the potential to reduce the risks of long-term opioid therapy, this study lays the groundwork for efforts that may ultimately push stakeholders to reduce payment and policy barriers to SCS as part of an evidence-based, patient-centered approach to nonopioid solutions for chronic pain., (Copyright © 2020 by the Congress of Neurological Surgeons.)
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- 2020
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18. A Smartphone App With a Digital Care Pathway for Patients Undergoing Spine Surgery: Development and Feasibility Study.
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Ponder M, Ansah-Yeboah AA, Charalambous LT, Adil SM, Venkatraman V, Abd-El-Barr M, Haglund M, Grossi P, Yarbrough C, Dharmapurikar R, Gellad Z, and Lad SP
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Background: There is a great unmet clinical need to provide patients undergoing spinal surgery and their caregivers with ongoing, high-quality care before and after surgery in an efficiency-focused health care environment., Objective: The objective of this study is to design, develop, and evaluate the acceptability and feasibility of a novel planning-, outcomes-, and analytics-based smartphone app called ManageMySurgery (MMS) in patients undergoing elective spine surgery (MMS-Spine)., Methods: The development process of the MMS app was conducted over 2 sequential stages: (1) an evidence-based intervention design with refinement from surgeon and patient feedback and (2) feasibility testing in a clinical pilot study. We developed a novel, mobile-based, Health Insurance Portability and Accountability Act-compliant platform for interventional and surgical procedures. It is a patient-centric mobile health app that streamlines patients' interactions with their care team. MMS divides the patient journey into phases, making it feasible to provide customized care pathways that meet patients' unique needs. Patient-reported outcomes are easily collected and conform to the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) standard., Results: We tested the feasibility of the MMS-Spine app with patients undergoing elective spine surgery at a large academic health system. A total of 47 patients undergoing elective spine surgery (26 cervical spine and 21 lumbar spine surgeries) downloaded and used MMS-Spine to navigate their surgical journey, quantify their baseline characteristics and postoperative outcomes, and provide feedback on the utility of the app in preparing for and recovering from their spinal surgery. The median age was 59.0 (range 33-77) years, 22 of the 47 patients (47%) were women, and 26 patients (55%) had commercial insurance. Of the 47 patients, a total of 33 (70%) logged in on an iOS device, 11 (23%) on an Android device, and 3 (6%) on a computer or tablet. A total of 17 of the 47 patients (36%) added a caregiver, of which 7 (41%) logged in. The median number of sign-ins was 2. A total of 38 of 47 patients (81%) completed their baseline preoperative PROMIS-29 outcomes, and 14 patients (30%) completed at least one PROMIS-29 survey during the postoperative period. Of the 24 patients who completed the MMS survey, 21 (88%) said it was helpful during preparation for their procedure, 16 (67%) said it was helpful during the postoperative period, and 23 (96%) said that they would recommend MMS to a friend or family member., Conclusions: We used a patient-centered approach based on proven behavior change techniques to develop a comprehensive smartphone app for patients undergoing elective spine surgery. The optimized version of the app is ready for formal testing in a larger randomized clinical study to establish its cost-effectiveness and effect on patients' self-management skills and long-term outcomes., (©Madison Ponder, Abena A. Ansah-Yeboah, Lefko T. Charalambous, Syed M. Adil, Vishal Venkatraman, Muhammad Abd-El-Barr, Michael Haglund, Peter Grossi, Chester Yarbrough, Rajeev Dharmapurikar, Ziad Gellad, Shivanand P. Lad. Originally published in JMIR Perioperative Medicine (http://periop.jmir.org), 16.10.2020.)
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- 2020
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19. Health care resource utilization and treatment of leptomeningeal carcinomatosis in the United States.
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Adil SM, Hodges SE, Edwards RM, Charalambous LT, Yang Z, Kiyani M, Musick A, Parente BA, Lee HJ, Peters KB, Fecci PE, and Lad SP
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Background: The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges., Methods: The IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis., Results: We identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%)., Conclusions: LC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2020
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20. Independent Association Between Type of Intraoperative Blood Transfusion and Postoperative Delirium After Complex Spinal Fusion for Adult Deformity Correction.
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Elsamadicy AA, Adil SM, Charalambous L, Drysdale N, Koo AB, Lee M, Kundishora AJ, Camara-Quintana J, Kolb L, Laurans M, Abbed K, and Karikari IO
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- Adolescent, Adult, Aged, Aged, 80 and over, Blood Transfusion trends, Cohort Studies, Delirium diagnosis, Delirium etiology, Elective Surgical Procedures adverse effects, Elective Surgical Procedures trends, Female, Humans, Male, Middle Aged, Postoperative Complications diagnosis, Postoperative Complications etiology, Retrospective Studies, Spinal Fusion trends, Young Adult, Blood Transfusion methods, Delirium prevention & control, Postoperative Complications prevention & control, Spinal Diseases surgery, Spinal Fusion adverse effects
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Study Design: Retrospective cohort study., Objective: To determine whether type of intraoperative blood transfusion used is associated with increased incidence of postoperative delirium after complex spine fusion involving five levels or greater., Summary of Background Data: Postoperative delirium after spine surgery has been associated with age, cognitive status, and several comorbidities. Intraoperative allogenic blood transfusions have previously been linked to greater complication risks and length of hospital stay. However, whether type of intraoperative blood transfusion used increases the risk for postoperative delirium after complex spinal fusion remains relatively unknown., Methods: The medical records of 130 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (more than or equal to five levels) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. We identified 104 patients who encountered an intraoperative blood transfusion. Of the 104, 15 (11.5%) had Allogenic-only, 23 (17.7%) had Autologous-only, and 66 (50.8%) had Combined transfusions. The primary outcome investigated was the rate of postoperative delirium., Results: There were significant differences in estimated blood loss (Combined: 2155.5 ± 1900.7 mL vs. Autologous: 1396.5 ± 790.0 mL vs. Allogenic: 1071.3 ± 577.8 mL vs. None: 506.9 ± 427.3 mL, P < 0.0001) and amount transfused (Combined: 1739.7 ± 1127.6 mL vs. Autologous: 465.7 ± 289.7 mL vs. Allogenic: 986.9 ± 512.9 mL, P < 0.0001). The Allogenic cohort had a significantly higher proportion of patients experiencing delirium (Combined: 7.6% vs. Autologous: 17.4% vs. Allogenic: 46.7% vs. None: 11.5%, P = 0.002). In multivariate nominal-logistic regression analysis, Allogenic (odds ratio [OR]: 24.81, 95% confidence interval [CI] [3.930, 156.702], P = 0.0002) and Autologous (OR: 6.43, 95% CI [1.156, 35.772], P = 0.0335) transfusions were independently associated with postoperative delirium., Conclusion: Our study suggests that there may be an independent association between intraoperative autologous and allogenic blood transfusions and postoperative delirium after complex spinal fusion. Further studies are necessary to identify the physiological effect of blood transfusions to better overall patient care and reduce healthcare expenditures., Level of Evidence: 3.
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- 2020
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21. Painful diabetic peripheral neuropathy: Health care costs and complications from 2010 to 2015.
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Kiyani M, Yang Z, Charalambous LT, Adil SM, Lee HJ, Yang S, Pagadala P, Parente B, Spratt SE, and Lad SP
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Objective: To quantify health care resource utilization and risk of complications in painful diabetic peripheral neuropathy (pDPN)., Methods: Adult patients diagnosed with diabetes mellitus or diabetic peripheral neuropathy (DPN) were identified in MarketScan from January 2010 to December 2015. Subgroups (pDPN and nonpainful DPN) were based on the use of pain medications 6 months before a new indexed diagnosis and 1 year thereafter. Health care costs were collected for up to 5 years, and complications charted for those with at least 1 and 2 years of follow-up. Complication comparisons were made using χ
2 or Fisher exact tests, and a multivariable regression cost model was fit with log link function using generalized estimating equations., Results: Among 360,559 patients with diabetes (62 ± 14 years; 54.3% female), 84,069 (23.3%) developed pDPN, 17,267 (4.8%) experienced nonpainful DPN, and the majority (259,223, 71.9%) were controls with diabetes without neuropathy. At baseline, costs associated with pDPN patients were 20% higher than diabetic controls (95% confidence interval [CI] [1.19, 1.21], p < 0.001), which increased to 31% in the 5th year (95% CI [1.27, 1.34], p < 0.001). Patients with pDPN had 200%, 356%, and 224% of the odds of using opioids, anticonvulsants, and antidepressants, respectively, compared with diabetic controls. The amputation risk in the pDPN subgroup was 16.24 times that of diabetic controls (95% CI [2.15, 122.72], p = 0.0003), and 87% more patients with pDPN experienced lower extremity infections (95% CI [1.43, 2.46], p < 0.0001) within a year. Within 2 years, 2.2% of patients with pDPN had falls and fall-related injuries compared with 1.1% of diabetic controls ( p < 0.0001)., Conclusions: Our study characterizes a substantial pDPN cohort in the United States, demonstrating considerable morbidity and economic costs., (© 2019 American Academy of Neurology.)- Published
- 2020
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22. The longitudinal health economic impact of viral encephalitis in the United States.
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Kiyani M, Liu B, Charalambous LT, Adil SM, Hodges SE, Yang S, Pagadala P, Perfect JR, and Lad SP
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- Adult, Aged, Encephalitis, Viral diagnosis, Encephalitis, Viral mortality, Encephalitis, Viral virology, Female, Health Care Costs, Humans, Male, Middle Aged, Retrospective Studies, United States, Young Adult, Encephalitis, Viral economics
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Introduction. Previous studies of viral encephalitis have focused on acute costs, estimating incidence at 7.3 per 100 000 and total US annual charges at $2 billion in 2010. Aim. We aim to quantify the most updated longitudinal health economic impact of viral encephalitis in the USA from 2008 to 2015. Methodology. Data on patients diagnosed with viral encephalitis were obtained from the Truven Health Analytics MarketScan database. Patients with a primary diagnosis of viral encephalitis, from herpetic viruses and other viral aetiologies (e.g. West Nile fever) were included in the analysis. Data concerning healthcare resource utilization, inpatient mortality, length of stay and accrued healthcare costs were collected for up to 5 years. Results. Among 3985 patients with continuous enrolment for 13 months prior to the encephalitis diagnosis, more non-herpes simplex encephalitis (61.7 %) than herpes simplex encephalitis (HSE; 38.3 %) cases were recorded, with the majority concentrated in the southern USA (29.2 %). One-year inpatient mortality was 6.2 %, which over a 5-year period rose to 8.9 % for HSE and 5.8 % for all other viral encephalitides. HSE resulted in longer cumulative stays in the hospital (11 days vs. 4 days; P =0.0025), and accrued 37 % higher first-year costs, after adjusting for known confounders [ P <0.001, cost ratio=1.37, 95 % confidence interval (1.20, 1.57)]. Additionally, HSE was associated with greater 5-year cumulative median charges ($125 338 vs. $82 317, P =0.0015). Conclusion. The health economic impact and long-term morbidity of viral encephalitis in the USA are substantial.
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- 2020
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23. Healthcare Economics of Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage in the United States.
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Adil SM, Liu B, Charalambous LT, Kiyani M, Gramer R, Swisher CB, Verbick LZ, McCabe A, Parente BA, Pagadala P, and Lad SP
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- Adult, Aged, Female, Health Care Costs, Health Resources statistics & numerical data, Humans, Hydrocephalus mortality, Length of Stay statistics & numerical data, Male, Middle Aged, Patient Readmission statistics & numerical data, Retrospective Studies, Subarachnoid Hemorrhage mortality, Subarachnoid Hemorrhage surgery, United States, Ventriculoperitoneal Shunt, Hydrocephalus economics, Hydrocephalus etiology, Patient Acceptance of Health Care statistics & numerical data, Subarachnoid Hemorrhage complications
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Hydrocephalus is one of the most common sequelae after aneurysmal subarachnoid hemorrhage (aSAH), and it is a large contributor to the condition's high rates of readmission and mortality. Our objective was to quantify the healthcare resource utilization (HCRU) and health economic burden incurred by the US health system due to post-aSAH hydrocephalus. The Truven Health MarketScan
® Research database was used to retrospectively quantify the prevalence and HCRU associated with hydrocephalus in aSAH patients undergoing surgical clipping or endovascular coiling from 2008 to 2015. Multivariable longitudinal analysis was conducted to model the relationship between annual cost and hydrocephalus status. In total, 2374 patients were included; hydrocephalus was diagnosed in 959 (40.4%). Those with hydrocephalus had significantly longer initial lengths of stay (median 19.0 days vs. 12.0 days, p < .001) and higher 30-day readmission rates (20.5% vs. 10.4%, p < .001). With other covariates held fixed, in the first 90 days after aSAH diagnosis, the average cost multiplier relative to annual baseline for hydrocephalus patients was 24.60 (95% CI, 20.13 to 30.06; p < .001) whereas for non-hydrocephalus patients, it was 11.52 (95% CI, 9.89 to 13.41; p < .001). The 5-year cumulative median total cost for the hydrocephalus group was $230,282.38 (IQR, 166,023.65 to 318,962.35) versus $174,897.72 (IQR, 110,474.24 to 271,404.80) for those without hydrocephalus. We characterize one of the largest cohorts of post-aSAH hydrocephalus patients in the USA. Importantly, the substantial health economic impact and long-term morbidity and costs from this condition are quantified and reviewed.- Published
- 2019
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24. Erratum to intraoperative ketamine may increase risk of post-operative delirium after complex spinal fusion for adult deformity correction.
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Elsamadicy AA, Charalambous LT, Sergesketter AR, Drysdale N, Adil SM, Freedman IG, Williamson T, Kundishora AJ, Camara-Quintana J, Abd-El-Barr MM, Goodwin CR, and Karikari IO
- Abstract
[This corrects the article DOI: 10.21037/jss.2018.12.10.]., (2019 Journal of Spine Surgery. All rights reserved.)
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- 2019
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25. Reduced Influence of Affective Disorders on 6-Week and 3-Month Narcotic Refills After Primary Complex Spinal Fusions for Adult Deformity Correction: A Single-Institutional Study.
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Elsamadicy AA, Charalambous L, Adil SM, Drysdale N, Lee M, Koo AB, Chouairi F, Kundishora AJ, Camara-Quintana J, Qureshi T, Kolb L, Laurans M, Abbed K, and Karikari IO
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- Adult, Drug Prescriptions, Elective Surgical Procedures adverse effects, Female, Humans, Male, Middle Aged, Narcotics administration & dosage, Pain Perception drug effects, Pain, Postoperative complications, Retrospective Studies, Spinal Diseases complications, Spine surgery, Mood Disorders complications, Narcotics therapeutic use, Pain, Postoperative drug therapy, Spinal Diseases surgery, Spinal Fusion adverse effects
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Objective: Previous studies have identified the impact of affective disorders on preoperative and postoperative perception of pain. However, there is a scarcity of data identifying the impact of affective disorders on postdischarge narcotic refills. The aim of this study was to determine whether patients with affective disorders have more narcotic refills after complex spinal fusion for deformity correction., Methods: The medical records of 121 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (≥5 level) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. Patient demographics, comorbidities, intraoperative and postoperative complication rates, baseline and postoperative patient-reported pain scores, ambulatory status, and narcotic refills were collected for each patient. The primary outcome was the rate of 6-week and 3-month narcotic refills., Results: Of the 121 patients, 43 (35.5%) had a clinical diagnosis of anxiety or depression (affective disorder) (AD n = 43; No-AD n = 78). Preoperative narcotic use was significantly higher in the AD cohort (AD 65.9% vs. No-AD 37.7%, P = 0.0035). The AD cohort had significantly higher pain scores at baseline (AD 6.5 ± 2.9 vs. No-AD 4.7 ± 3.1, P = 0.004) and at the first postoperative pain score reported (AD 6.7 ± 2.6 vs. No-AD 5.6 ± 2.9, P = 0.049). However, there were no significant differences in narcotic refills at 6 weeks (AD 34.9% vs. No-AD 25.6%, P = 0.283) and 3 months (AD 23.8% vs. No-AD 17.4%, P = 0.411) after discharge between the cohorts., Conclusions: Our study suggests that whereas spinal deformity patients with affective disorders may have a higher baseline perception of pain and narcotic use, the impact of affective disorders on narcotic refills at 6 weeks and 3 months may be minimal after complex spinal fusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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26. Structural mapping with fiber tractography of the human cuneate fasciculus at microscopic resolution in cervical region.
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Atik AF, Calabrese E, Gramer R, Adil SM, Rahimpour S, Pagadala P, Johnson GA, and Lad SP
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- Afferent Pathways anatomy & histology, Afferent Pathways diagnostic imaging, Humans, Male, Neural Pathways anatomy & histology, Neural Pathways diagnostic imaging, Cervical Cord anatomy & histology, Cervical Cord diagnostic imaging, Diffusion Tensor Imaging, Image Processing, Computer-Assisted methods, White Matter anatomy & histology, White Matter diagnostic imaging
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Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus., (Copyright © 2019. Published by Elsevier Inc.)
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- 2019
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27. Association Between Preoperative Narcotic Use with Perioperative Complication Rates, Patient Reported Pain Scores, and Ambulatory Status After Complex Spinal Fusion (≥5 Levels) for Adult Deformity Correction.
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Elsamadicy AA, Drysdale N, Adil SM, Charalambous L, Lee M, Koo A, Freedman IG, Kundishora AJ, Camara-Quintana J, Qureshi T, Kolb L, Laurans M, Abbed K, and Karikari IO
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- Adult, Aged, Bone Transplantation, Depression epidemiology, Female, Humans, Intraoperative Neurophysiological Monitoring, Laminectomy, Length of Stay, Male, Middle Aged, Osteotomy, Pain Measurement, Patient Readmission, Patient Reported Outcome Measures, Preoperative Period, Mobility Limitation, Narcotics therapeutic use, Pain drug therapy, Pain, Postoperative epidemiology, Postoperative Complications epidemiology, Spinal Diseases surgery, Spinal Fusion
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Objective: The widespread over-use of narcotics has been increasing. However, whether narcotic use impacts surgical outcomes after complex spinal fusion remains understudied. The aim of this study was to evaluate whether there is an association between preoperative narcotic use with perioperative complication rates, patient-reported pain scores, and ambulatory status after complex spinal fusions., Methods: The medical records of 134 adult (age ≥18 years) patients with spinal deformity undergoing elective, primary complex spinal fusion (≥5 levels) for deformity correction in a major academic institution from 2005-2015 were reviewed. Patient demographics, comorbidities, intraoperative and postoperative complication rates, pain scores, and ambulatory status were collected for each patient., Results: Patient demographics and comorbidities were similar between both cohorts, except that the Narcotic-User cohort had a greater mean age (57.5 years vs. 50.7 years; P = 0.045) and prevalence of depression (39.4% vs. 16.2%; P = 0.003). Complication rates were similar between both cohorts. The Narcotic-User cohort had significantly higher pain scores at baseline (6.7 ± 2.4 vs. 4.0 ± 3.4; P < 0.001) and at the first postoperative pain score reported (6.7 ± 2.8 vs. 5.3 ± 2.9; P = 0.013), but had a significantly greater improvement from baseline to last pain score (Narcotic-User: -2.5 ± 3.9 vs. Non-User: -0.5 ± 4.7; P = 0.031). The Narcotic-User cohort had significantly greater ambulation on the first postoperative ambulatory day compared with the Non-User cohort (103.8 ± 144.4 vs. 56.4 ± 84.0; P = 0.031)., Conclusions: Our study suggests that the preoperative use of narcotics may impact patient perception of pain and improvement after complex spinal fusions (≥5 levels). Consideration of patients' narcotic status preoperatively may facilitate tailored pain management and physical therapy regimens., (Copyright © 2019. Published by Elsevier Inc.)
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- 2019
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28. Intraoperative ketamine may increase risk of post-operative delirium after complex spinal fusion for adult deformity correction.
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Elsamadicy AA, Charalambous LT, Sergesketter AR, Drysdale N, Adil SM, Freedman IG, Williamson T, Kundishora AJ, Camara-Quintana J, Abd-El-Barr MM, Goodwin CR, and Karikari IO
- Abstract
Background: For complex surgery, intraoperative ketamine administration is readily used to reduce post-operative pain. However, there have been a few studies suggesting that intraoperative ketamine may have deleterious effects and impact post-operative delirium. Therefore, we sought to identify the impact that intraoperative ketamine has on post-operative outcomes after complex spinal surgery involving ≥5 level fusions., Methods: The medical records of 138 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (≥5 level) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. We identified 98 (71.0%) who had intraoperative ketamine administration and 40 (29%) who did not (Ketamine-Use: n=98; No-Ketamine: n=40). Patient demographics, comorbidities, intra- and post-operative complication rates were collected for each patient. The primary outcome investigated in this study was the rate of post-operative delirium. A multivariate nominal-logistic regression analysis was used to determine the independent association between intraoperative ketamine and post-operative delirium., Results: Patient demographics and comorbidities were similar between both cohorts, including age, gender, and BMI. The median number of fusion levels operated, length of surgery, estimated blood loss, and proportion of patients requiring blood transfusions were similar between both cohorts. Postoperative complication profile was similar between the cohorts, except for the Ketamine-Use cohort having significantly higher proportion of patients experiencing delirium (Ketamine-Use: 14.3% vs. No-Ketamine: 2.6%, P=0.047). In a multivariate nominal-logistic regression analysis, intraoperative Ketamine-Use was independently associated with post-operative delirium (OR: 9.475, 95% CI: 1.026-87.508, P=0.047)., Conclusions: Our study suggests that the intraoperative use of ketamine may increase the risk of post-operative delirium. Further studies are necessary to understand the physiological effect intraoperative ketamine has on patients undergoing complex spinal fusions in order to better overall patient care and reduce healthcare resources., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
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- 2019
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29. Neurological Outcomes After Surgical or Conservative Management of Spontaneous Spinal Epidural Abscesses: A Systematic Review and Meta-Analysis of Data From 1980 Through 2016.
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Wang TY, Harward SC 2nd, Tsvankin V, Bell H, Charalambous L, Adil SM, Englot DJ, Goodwin CR, Karikari IO, Isaacs RE, and Krucoff MO
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- Female, Humans, Male, Middle Aged, Time Factors, Conservative Treatment, Epidural Abscess surgery
- Abstract
Study Design: This is a meta-analysis., Objective: Perform a systematic review and quantitative meta-analysis of neurological outcomes from all available spinal epidural abscess (SEA) literature published between 1980 and 2016., Summary of Background Data: Current literature on SEAs lacks large-scale data characterizing prognostic factors and surgical indications., Materials and Methods: PubMed was queried for studies reporting neurological outcomes from patients undergoing conservative or surgical management for spontaneous SEA. Inclusion criteria included outcomes data measured ≥6 months after presentation, ≥10 human subjects, and diagnosis by magnetic resonance imaging or Computed tomography-myelogram. Where available, demographic data, abscess location, comorbidities, pretreatment neurological deficits, treatment methods, bacterial speciation, and complications were extracted from each study. Potential outcome predictors represented by continuous variables were compared using student t test and categorical variables were compared using the Pearson χ test. Variables identified as potentially associated with outcome (P≤0.05) were subjected to meta-analysis using Cochran-Mantel-Haenszel testing to calculate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: In total, 808 patients were analyzed from 20 studies that met inclusion criteria. 456 (56.3%) patients were treated with surgery and antibiotics, and 353 (43.7%) patients were managed with antibiotics alone. Neither surgical intervention (OR=1.01, 95% CI=0.40-2.59), lumbosacral location (OR=1.51, 95% CI=0.23-9.79), nor neurological deficit on presentation (OR=0.88, 95% CI=0.40-1.92) were significantly associated with good (stable or improved) or bad (worsened) neurological outcome, whereas delayed surgery was significantly associated with bad outcome (OR=0.01, 95% CI=0.02-0.62) and cervicothoracic location approached significance for predicting bad outcome (OR=0.41, 95% CI=0.15-1.09)., Conclusions: Current literature does not definitively support or oppose surgical intervention in all SEA cases. Therefore, until better evidence exists, the decision to operate must be made on an individual case-by-case basis with the goals of preventing neurological decline, obtaining source control after failed conservative treatment, or restoring spinal stability.
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- 2019
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30. Rate of instrumentation changes on postoperative and follow-up radiographs after primary complex spinal fusion (five or more levels) for adult deformity correction.
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Elsamadicy AA, Lubkin DT, Sergesketter AR, Adil SM, Charalambous LT, Drysdale N, Williamson T, Camara-Quintana J, Abd-El-Barr MM, Goodwin CR, and Karikari IO
- Subjects
- Adult, Aged, Female, Humans, Length of Stay, Male, Middle Aged, Postoperative Complications epidemiology, Radiography, Retrospective Studies, Spinal Fusion adverse effects, Time Factors, Postoperative Complications diagnostic imaging, Postoperative Complications surgery, Reoperation instrumentation, Spinal Diseases diagnostic imaging, Spinal Diseases surgery, Spinal Fusion instrumentation
- Abstract
OBJECTIVEIn the United States, healthcare expenditures have been soaring at a concerning rate. There has been an excessive use of postoperative radiographs after spine surgery and this has been a target for hospitals to reduce unnecessary costs. However, there are only limited data identifying the rate of instrumentation changes on radiographs after complex spine surgery involving ≥ 5-level fusions.METHODSThe medical records of 136 adult (≥ 18 years old) patients with spine deformity undergoing elective, primary complex spinal fusion (≥ 5 levels) for deformity correction at a major academic institution between 2010 and 2015 were reviewed. Patient demographics, comorbidities, and intra- and postoperative complication rates were collected for each patient. The authors reviewed the first 5 subsequent postoperative and follow-up radiographs, and determined whether revision of surgery was performed within 5 years postoperatively. The primary outcome investigated in this study was the rate of hardware changes on follow-up radiographs.RESULTSThe majority of patients were female, with a mean age of 53.8 ± 20.0 years and a body mass index of 27.3 ± 6.2 kg/m2 (parametric data are expressed as the mean ± SD). The median number of fusion levels was 9 (interquartile range 7-13), with a mean length of surgery of 327.8 ± 124.7 minutes and an estimated blood loss of 1312.1 ± 1269.2 ml. The mean length of hospital stay was 6.6 ± 3.9 days, with a 30-day readmission rate of 14.0%. Postoperative and follow-up change in stability on radiographs (days from operation) included: image 1 (4.6 ± 9.3 days) 0.0%; image 2 (51.7 ± 49.9 days) 3.0%; image 3 (142.1 ± 179.8 days) 5.6%; image 4 (277.3 ± 272.5 days) 11.3%; and image 5 (463.1 ± 525.9 days) 15.7%. The 3rd year after surgery had the highest rate of hardware revision (5.55%), followed by the 2nd year (4.68%), and the 1st year (4.54%).CONCLUSIONSThis study suggests that the rate of instrumentation changes on radiographs increases over time, with no changes occurring at the first postoperative image. In an era of cost-conscious healthcare, fewer orders for early radiographs after complex spinal fusions (≥ 5 levels) may not impact patient care and can reduce the overall use of healthcare resources.
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- 2019
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31. Spinal Cord Stimulation for Restless Legs Syndrome: Case Series and Mechanistic Hypothesis.
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Adil SM, Han JL, Parente BA, Hickey P, and Lad SP
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- Adult, Chronic Pain complications, Humans, Male, Middle Aged, Pain Management methods, Restless Legs Syndrome complications, Chronic Pain diagnostic imaging, Chronic Pain therapy, Restless Legs Syndrome diagnostic imaging, Restless Legs Syndrome therapy, Spinal Cord Stimulation methods
- Abstract
Background: Spinal cord stimulation (SCS) is a well-established therapy for chronic pain syndromes, with growing applicability to other conditions. Restless legs syndrome (RLS) is a widespread, chronic movement disorder managed primarily and incompletely by medication, and its etiology can be classified as idiopathic or secondary., Methods: Three patients underwent SCS implantation for chronic back and/or leg pain with concomitant targeting of RLS: (1) a 34-year-old man with sporadic RLS symptoms that strongly intensified after military-related spinal fractures, (2) a 54-year-old man with RLS likely secondary to meralgia paresthetica, and (3) a 42-year-old man with low back and right lower extremity pain after a military motor vehicle accident., Results: Continuing through 40-month, 2-month, and 28-month follow-ups, respectively, the patients experienced exemplary relief of their RLS symptoms. Notably in the case of patient 1, this benefit appears separate from his pain relief, as during the 5-month period directly after surgery but before adjusted targeting, he only experienced pain alleviation., Conclusions: To our knowledge, this is the first reported case of using SCS as a potentially long-lasting, safe, and highly effective therapy for RLS of mixed etiology. Additionally, 2 patients with RLS possibly secondary to chronic pain also benefited from the therapy. This success may be due to increased inhibition from hypothalamic cells controlling dopaminergic input to the spine., (© 2019 S. Karger AG, Basel.)
- Published
- 2019
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32. Postmortem diffusion MRI of the entire human spinal cord at microscopic resolution.
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Calabrese E, Adil SM, Cofer G, Perone CS, Cohen-Adad J, Lad SP, and Johnson GA
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- Cross-Sectional Studies, Diffusion Magnetic Resonance Imaging methods, Humans, Image Processing, Computer-Assisted methods, Male, Neuroimaging methods, Spinal Cord Diseases pathology, Gray Matter pathology, Magnetic Resonance Imaging methods, Spinal Cord pathology, White Matter pathology
- Abstract
The human spinal cord is a central nervous system structure that plays an important role in normal motor and sensory function, and can be affected by many debilitating neurologic diseases. Due to its clinical importance, the spinal cord is frequently the subject of imaging research. Common methods for visualizing spinal cord anatomy and pathology include histology and magnetic resonance imaging (MRI), both of which have unique benefits and drawbacks. Postmortem microscopic resolution MRI of fixed specimens, sometimes referred to as magnetic resonance microscopy (MRM), combines many of the benefits inherent to both techniques. However, the elongated shape of the human spinal cord, along with hardware and scan time limitations, have restricted previous microscopic resolution MRI studies (both in vivo and ex vivo ) to small sections of the cord. Here we present the first MRM dataset of the entire postmortem human spinal cord. These data include 50 μm isotropic resolution anatomic image data and 100 μm isotropic resolution diffusion data, made possible by a 280 h long multi-segment acquisition and automated image segment composition. We demonstrate the use of these data for spinal cord lesion detection, automated volumetric gray matter segmentation, and quantitative spinal cord morphometry including estimates of cross sectional dimensions and gray matter fraction throughout the length of the cord.
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- 2018
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33. Impact of patient selection and treatment strategies on outcomes after lobectomy for biopsy-proven stage IIIA pN2 non-small cell lung cancer.
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Yang CF, Adil SM, Anderson KL, Meyerhoff RR, Turley RS, Hartwig MG, Harpole DH Jr, Tong BC, Onaitis MW, D'Amico TA, and Berry MF
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- Aged, Biopsy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung therapy, Chemoradiotherapy, Adjuvant, Chemotherapy, Adjuvant, Evidence-Based Medicine methods, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms pathology, Lung Neoplasms therapy, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Pneumonectomy adverse effects, Pneumonectomy methods, Professional Practice trends, Retrospective Studies, Thoracic Surgery, Video-Assisted adverse effects, Thoracic Surgery, Video-Assisted trends, Treatment Outcome, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Patient Selection
- Abstract
Objectives: We evaluated the impact of patient selection and treatment strategies on long-term outcomes of patients who had lobectomy after induction therapy for stage IIIA pN2 non-small cell lung cancer (NSCLC)., Methods: The impact of various patient selection, induction therapy and operative strategies on survival of patients with biopsy-proven stage IIIA pN2 NSCLC who received induction chemotherapy ± radiation followed by lobectomy from 1995 to 2012 was assessed using Cox proportional hazards analysis., Results: From 1995 to 2012, 111 patients had lobectomy for stage IIIA pN2 NSCLC after chemotherapy ± radiation with an overall 5-year survival of 39%. The use of induction chemoradiation decreased over time; from 1996 to 2007, 46/65 (71%) patients underwent induction chemoradiation, whereas from 2007 to 2012, 36/46 (78%) patients underwent induction chemotherapy. The use of video-assisted thoracoscopic surgery (VATS) increased over the time period of the study, from 0/26 (0%) in 1996-2001, to 4/39 (10%) in 2002-07 to 33/46 (72%) in 2008-12. Compared with patients given induction chemotherapy alone, patients given additional induction radiation were more likely to have complete pathologic response (30 vs 11%, P = 0.01) but had worse 5-year survival in univariable analysis (31 vs 48%, log-rank P = 0.021). Patients who underwent pathologic mediastinal restaging following induction therapy but prior to resection had an improved overall survival compared with patients who did not undergo pathologic mediastinal restaging {5-year survival: 45.2 [95% confidence interval (CI): 33.9-55.9] vs 13.9% (95% CI: 2.5-34.7); log-rank, P = 0.004}. In multivariable analysis, the particular induction therapy strategy and the surgical approach used, as well as the extent of mediastinal disease were not important predictors of survival. However, pathologic mediastinal restaging was associated with improved survival (HR 0.39; 95% CI: 0.21-0.72; P = 0.003)., Conclusions: For patients with stage IIIA pN2 NSCLC, the VATS approach or the addition of radiation to induction therapy can be selectively employed without compromising survival. The strategy of assessing response to induction therapy with pathologic mediastinal restaging allows one to select appropriate patients for complete resection and is associated with a 5-year overall survival of 39% in this population., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
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- 2016
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34. Knock-in mouse model of alternating hemiplegia of childhood: behavioral and electrophysiologic characterization.
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Hunanyan AS, Fainberg NA, Linabarger M, Arehart E, Leonard AS, Adil SM, Helseth AR, Swearingen AK, Forbes SL, Rodriguiz RM, Rhodes T, Yao X, Kibbi N, Hochman DW, Wetsel WC, Hochgeschwender U, and Mikati MA
- Subjects
- Amygdala physiopathology, Animals, Convulsants, Disease Models, Animal, Electroencephalography, Electrophysiological Phenomena, Flurothyl, Gene Knock-In Techniques, Hemiplegia genetics, Kindling, Neurologic physiology, Learning, Locomotion, Memory, Mice, Mice, Transgenic, Seizures chemically induced, Sodium-Potassium-Exchanging ATPase genetics, Behavior, Animal, Brain physiopathology, Hemiplegia physiopathology, Seizures physiopathology
- Abstract
Objectives: Mutations in the ATP1α3 subunit of the neuronal Na+/K+-ATPase are thought to be responsible for seizures, hemiplegias, and other symptoms of alternating hemiplegia of childhood (AHC). However, the mechanisms through which ATP1A3 mutations mediate their pathophysiologic consequences are not yet understood. The following hypotheses were investigated: (1) Our novel knock-in mouse carrying the most common heterozygous mutation causing AHC (D801N) will exhibit the manifestations of the human condition and display predisposition to seizures; and (2) the underlying pathophysiology in this mouse model involves increased excitability in response to electrical stimulation of Schaffer collaterals and abnormal predisposition to spreading depression (SD)., Methods: We generated the D801N mutant mouse (Mashlool, Mashl+/-) and compared mutant and wild-type (WT) littermates. Behavioral tests, amygdala kindling, flurothyl-induced seizure threshold, spontaneous recurrent seizures (SRS), and other paroxysmal activities were compared between groups. In vitro electrophysiologic slice experiments on hippocampus were performed to assess predisposition to hyperexcitability and SD., Results: Mutant mice manifested a distinctive phenotype similar to that of humans with AHC. They had abnormal impulsivity, memory, gait, motor coordination, tremor, motor control, endogenous nociceptive response, paroxysmal hemiplegias, diplegias, dystonias, and SRS, as well as predisposition to kindling, to flurothyl-induced seizures, and to sudden unexpected death. Hippocampal slices of mutants, in contrast to WT animals, showed hyperexcitable responses to 1 Hz pulse-trains of electrical stimuli delivered to the Schaffer collaterals and had significantly longer duration of K+-induced SD responses., Significance: Our model reproduces the major characteristics of human AHC, and indicates that ATP1α3 dysfunction results in abnormal short-term plasticity with increased excitability (potential mechanism for seizures) and a predisposition to more severe SD responses (potential mechanism for hemiplegias). This model of the human condition should help in understanding the molecular pathways underlying these phenotypes and may lead to identification of novel therapeutic strategies of ATP1α3 related disorders and seizures., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)
- Published
- 2015
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