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Smith, Timothy

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Smith

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Timothy

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Smith, Timothy
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Now showing 1 - 9 of 9
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    Venous thromboembolism and intracranial hemorrhage after craniotomy for primary malignant brain tumors: a National Surgical Quality Improvement Program analysis
    (Springer US, 2017) Senders, Joeky; Goldhaber, Nicole; Cote, David; Muskens, Ivo S.; Dawood, Hassan Y.; De Vos, Filip Y. F. L.; Gormley, William; Smith, Timothy; Broekman, Marike L. D.
    Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), frequently complicates the postoperative course of primary malignant brain tumor patients. Thromboprophylactic anticoagulation is commonly used to prevent VTE at the risk of intracranial hemorrhage (ICH). We extracted all patients who underwent craniotomy for a primary malignant brain tumor from the National Surgical Quality Improvement Program (NSQIP) registry (2005–2015) to perform a time-to-event analysis and identify relevant predictors of DVT, PE, and ICH within 30 days after surgery. Among the 7376 identified patients, the complication rates were 2.6, 1.5, and 1.3% for DVT, PE, and ICH, respectively. VTE was the second-most common major complication and third-most common reason for readmission. ICH was the most common reason for reoperation. The increased risk of VTE extends beyond the period of hospitalization, especially for PE, whereas ICH occurred predominantly within the first days after surgery. Older age and higher BMI were overall predictors of VTE. Dependent functional status and longer operative times were predictive for VTE during hospitalization, but not for post-discharge events. Admission two or more days before surgery was predictive for DVT, but not for PE. Preoperative steroid usage and male gender were predictive for post-discharge DVT and PE, respectively. ICH was associated with various comorbidities and longer operative times. This multicenter study demonstrates distinct critical time periods for the development of thrombotic and hemorrhagic events after craniotomy. Furthermore, the VTE risk profile depends on the type of VTE (DVT vs. PE) and clinical setting (hospitalized vs. post-discharge patients).
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    Ethical considerations of neuro-oncology trial design in the era of precision medicine
    (Springer US, 2017) Gupta, Saksham; Smith, Timothy; Broekman, Marike L.
    The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.
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    Validation of an International Classification of Disease, Ninth Revision coding algorithm to identify decompressive craniectomy for stroke
    (BioMed Central, 2017) Dasenbrock, Hormuzdiyar; Cote, David; Pompeu, Yuri Andreiw; Vasudeva, Viren; Smith, Timothy; Gormley, William
    Background: Although International Classification of Disease, Ninth Revision, Clinical Modification (ICD9-CM) coding is the basis of administrative claims data, no study has validated an ICD9-CM algorithm to identify patients undergoing decompressive craniectomy for space-occupying supratentorial infarction. Methods: Patients who underwent decompressive craniectomy for stroke at our institution were retrospectively identified and their associated ICD9-CM codes were extracted from billing data. An ICD9-CM algorithm was generated and its accuracy compared against physician review. Results: A total of 10,925 neurosurgical operations were performed from December 2008 to March 2015, of which 46 (0.4%) were decompressive craniectomy for space-occupying stroke. The ICD9-CM procedure code for craniectomy (01.25) was only encoded in 67.4% of patients, while craniotomy (01.24) was used in 19.6% and lobectomy (01.39, 01.53, 01.59) in 13.1%. The ICD-9-CM algorithm included patients with a diagnosis codes for cerebral infarction (433.11, 434.01, 434.11, and 434.91) and a procedure code for craniotomy, craniectomy, or lobectomy. Patients were excluded with an ICD9-CM diagnosis code for brain tumor, intracranial abscess, subarachnoid hemorrhage, vertebrobasilar infarction, intracranial aneurysm, Moyamoya disease, intracranial venous sinus thrombosis, vertebral artery dissection, congenital cerebrovascular anomaly, head trauma or an ICD9-CM procedure code for laminectomy. This algorithm had a sensitivity of 97.8%, specificity of 99.9%, positive predictive value of 88.2%, and negative predictive value of 99.9%. The majority of false-positive results were patients who underwent evacuation of a primary intracerebral hematoma. Conclusion: An ICD-9-CM algorithm based on diagnosis and procedure codes can effectively identify patients undergoing decompressive craniectomy for supratentorial stroke.
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    Stereotactic radiosurgery versus whole-brain radiotherapy after intracranial metastasis resection: a systematic review and meta-analysis
    (BioMed Central, 2017) Lamba, Nayan; Muskens, Ivo S.; DiRisio, Aislyn C.; Meijer, Louise; Briceno, Vanessa; Edrees, Heba; Aslam, Bilal; Minhas, Sadia; Verhoeff, Joost J. C.; Kleynen, Catharina E.; Smith, Timothy; Mekary, Rania A.; Broekman, Marike L.
    Background: In patients with one to three brain metastases who undergo resection, options for post-operative treatments include whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) of the resection cavity. In this meta-analysis, we sought to compare the efficacy of each post-operative radiation modality with respect to tumor recurrence and survival. Methods: Pubmed, Embase and Cochrane databases were searched through June 2016 for cohort studies reporting outcomes of SRS or WBRT after metastasis resection. Pooled effect estimates were calculated using fixed-effect and random-effect models for local recurrence, distant recurrence, and overall survival. Results: Eight retrospective cohort studies with 646 patients (238 with SRS versus 408 with WBRT) were included in the analysis. Comparing SRS to WBRT, the overall crude risk ratio using the fixed-effect model was 0.59 for local recurrence (95%-CI: 0.32–1.09, I2: 3.35%, P-heterogeneity = 0.36, 3 studies), 1.09 for distant recurrence (95%-CI: 0.74–1.60, I2: 50.5%, P-heterogeneity = 0.13; 3 studies), and 2.99 for leptomeningeal disease (95% CI 1.55–5.76; I2: 14.4% p-heterogeneity: 0.28; 2 studies). For the same comparison, the risk ratio for median overall survival was 0.47 (95% CI: 0.41–0.54; I2: 79.1%, P-heterogeneity < 0.01; 4 studies) in a fixed-effect model, but was no longer significant (0.63; 95%-CI: 0.40–1.00) in a random-effect model. SRS was associated with a lower risk of leukoencephalopathy (RR: 0.15, 95% CI: 0.07–0.33, 1 study), yet with a higher risk of radiation-necrosis (RR: 19.4, 95% CI: 1.21–310, 1 study). Conclusion: Based on retrospective cohort studies, the results of this study suggest that SRS of the resection cavity may offer comparable survival and similar local and distant control as adjuvant WBRT, yet may be associated with a higher risk for developing leptomeningeal disease. Future research on SRS should focus on achieving a better understanding of the various factors that may favor SRS over WBRT.
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    Defensive medicine among neurosurgeons in the Netherlands: a national survey
    (Springer Vienna, 2017) Yan, Sandra C.; Hulsbergen, Alexander F. C.; Muskens, Ivo S.; van Dam, Marjel; Gormley, William; Broekman, Marike L. D.; Smith, Timothy
    Objective: In defensive medicine, practice is motivated by legal rather than medical reasons. Previous studies have analyzed the correlation between perceived medico-legal risk and defensive behavior among neurosurgeons in the United States, Canada, and South Africa, but not yet in Europe. The aim of this study is to explore perceived liability burdens and self-reported defensive behaviors among neurosurgeons in the Netherlands and compare their practices with their non-European counterparts. Methods: A survey was sent to 136 neurosurgeons. The survey included questions from several domains: surgeon characteristics, patient demographics, type of practice, surgeon liability profile, policy coverage, defensive practices, and perception of the liability environment. Survey responses were analyzed and summarized. Results: Forty-five neurosurgeons filled out the questionnaire (response rate of 33.1%). Almost half (n = 20) reported paying less than 5% of their income to annual malpractice premiums. Nearly all respondents view their insurance premiums as a minor or no burden (n = 42) and are confident that in their coverage is sufficient (n = 41). Most neurosurgeons (n = 38) do not see patients as “potential lawsuits”. Conclusions: Relative to their American peers, Dutch neurosurgeons view their insurance premiums as less burdensome, their patients as a smaller legal threat, and their practice as less risky in general. They are sued less often and engage in fewer defensive behaviors than their non-European counterparts. The medico-legal climate in the Netherlands may contribute to this difference.
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    Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results
    (Springer Vienna, 2016) Senders, Joeky T.; Muskens, Ivo S.; Schnoor, Rosalie; Karhade, Aditya; Cote, David; Smith, Timothy; Broekman, Marike L. D.
    Background: Fluorescence-guided surgery (FGS) is a technique used to enhance visualization of tumor margins in order to increase the extent of tumor resection in glioma surgery. In this paper, we systematically review all clinically tested fluorescent agents for application in FGS for glioma and all preclinically tested agents with the potential for FGS for glioma. Methods: We searched the PubMed and Embase databases for all potentially relevant studies through March 2016. We assessed fluorescent agents by the following outcomes: rate of gross total resection (GTR), overall and progression-free survival, sensitivity and specificity in discriminating tumor and healthy brain tissue, tumor-to-normal ratio of fluorescent signal, and incidence of adverse events. Results: The search strategy resulted in 2155 articles that were screened by titles and abstracts. After full-text screening, 105 articles fulfilled the inclusion criteria evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44 studies, including three randomized control trials), fluorescein (11), indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical testing phase (30). Three meta-analyses were also identified. Conclusions: 5-ALA is the only fluorescent agent that has been tested in a randomized controlled trial and results in an improvement of GTR and progression-free survival in high-grade gliomas. Observational cohort studies and case series suggest similar outcomes for FGS using fluorescein. Molecular targeting agents (e.g., fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre-clinical phase, but offer promising results and may be valuable future alternatives.
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    Visual outcomes after endoscopic endonasal pituitary adenoma resection: a systematic review and meta-analysis
    (Springer US, 2017) Muskens, Ivo S.; Zamanipoor Najafabadi, Amir H.; Briceno, Vanessa; Lamba, Nayan; Senders, Joeky; van Furth, Wouter R.; Verstegen, Marco J. T.; Smith, Timothy; Mekary, Rania; Eenhorst, Christine A. E.; Broekman, Marike L. D.
    Purpose Patients with pituitary adenomas often present with visual deficits. While the aim of endoscopic endonasal transsphenoidal surgery (EETS) is to improve these deficits, permanent worsening is a possible outcome. The aim of this meta-analysis was to evaluate the effect of EETS for pituitary adenomas on visual outcomes. Methods: A meta-analysis was conducted according to the PRISMA guidelines. Pooled prevalence was calculated for complete recovery, improvement, and deterioration of visual field deficits, visual acuity and unspecified visual function in fixed- and random-effect models, including assessment of heterogeneity (I2) and publication bias (Begg’s test). Results: Out of 2636 articles, 35 case series were included in the meta-analysis. Results are described for fixed-effect models. For patients with impaired visual acuity, only one study reported complete recovery (27.2%). Pooled prevalence for improvement was 67.5% (95% CI = 59.1–75.0%), but with considerable heterogeneity (I2: 86.0%), and 4.50% (95% CI = 1.80–10.8%) for patients experiencing deterioration. For patients with visual field deficits, the prevalence was 40.4% (95% CI = 34.8–46.3%) for complete recovery, 80.8% (95% CI = 77.7–83.6%) for improvement, and 2.3% (95% CI = 1.1–4.7%) for deterioration. For the unspecified visual outcomes, pooled prevalence of complete recovery was 32.9% (95% CI: 28.5–37.7%), but with considerable heterogeneity (I2 = 84.2%). The prevalence was 80.9% (95% CI = 77.9–83.6) for improvement and 2.00% (95% CI = 1.10–3.40%) for deterioration. Random-effect models yielded similar results. Publication bias was non-significant for all the outcomes. Conclusion: While visual deficits improved after EETS in the majority of patients, complete recovery was only achieved in less than half of the patients and some patients even suffered from visual deterioration. Electronic supplementary material The online version of this article (doi:10.1007/s11102-017-0815-9) contains supplementary material, which is available to authorized users.
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    Health-related quality of life of cranial WHO grade I meningioma patients: are current questionnaires relevant?
    (Springer Vienna, 2017) Zamanipoor Najafabadi, Amir H.; Peeters, Marthe C. M.; Lobatto, Daniel J.; Broekman, Marieke L. D.; Smith, Timothy; Biermasz, Nienke R.; Peerdeman, Saskia M.; Peul, Wilco C.; Taphoorn, Martin J. B.; van Furth, Wouter R.; Dirven, Linda
    Background: The clinical relevance of Health-Related Quality of Life (HRQoL) in meningioma patients has been increasingly acknowledged in recent years. Various questionnaires have been used. However, almost none of these questionnaires has been particularly developed for and/or validated in this patient group. Therefore, the aim of this study was to assess the relevance and comprehensiveness of existing HRQoL questionnaires used in meningioma research and to assess the agreement between patients and health care professionals (HCPs) on the most relevant and important HRQoL issues. Methods: A systematic literature search, following the PRISMA statement, was conducted to identify all HRQoL questionnaires used in meningioma research. Semi-structured interviews were organized with patients and HCPs to (1) assess the relevance of all issues covered by the questionnaires (score 0–3: not relevant–highly relevant), (2) assess the ten most important issues, and (3) identify new relevant HRQoL issues. Results: Fourteen different questionnaires were found in the literature, comprising 140 unique issues. Interviews were conducted with 20 patients (median age 57, 71% female) and 10 HCPs (4 neurosurgeons, 2 neurologists, 2 radiotherapists, 1 rehabilitation specialist, 1 neuropsychologist; median experience 13 years). Meningioma patients rated 17–80% of the issues in each of the questionnaires as relevant, HCPs 90–100%. Patients and HCPs agreed on the relevance of only 49 issues (35%, Cohen’s kappa: 0.027). Both patients and HCPs considered lack of energy the most important issue. Patients and HCPs suggested five additional relevant issues not covered by current HRQoL questionnaires. Conclusions: Existing HRQoL questionnaires currently used in meningioma patients do not fully cover all relevant issues to these patients. Agreement between patients and HCPs on the relevance of issues was poor. Both findings support the need to develop and validate a meningioma-specific HRQoL questionnaire. Electronic supplementary material The online version of this article (10.1007/s00701-017-3332-8) contains supplementary material, which is available to authorized users.
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    The endoscopic endonasal approach is not superior to the microscopic transcranial approach for anterior skull base meningiomas—a meta-analysis
    (Springer Vienna, 2017) Muskens, Ivo S.; Briceno, Vanessa; Ouwehand, Tom L.; Castlen, Joseph P.; Gormley, William; Aglio, Linda; Zamanipoor Najafabadi, Amir H.; van Furth, Wouter R.; Smith, Timothy; Mekary, Rania; Broekman, Marike L. D.
    Object In the past decade, the endonasal transsphenoidal approach (eTSA) has become an alternative to the microsurgical transcranial approach (mTCA) for tuberculum sellae meningiomas (TSMs) and olfactory groove meningiomas (OGMs). The aim of this meta-analysis was to evaluate which approach offered the best surgical outcomes. Methods: A systematic review of the literature from 2004 and meta-analysis were conducted in accordance with the PRISMA guidelines. Pooled incidence was calculated for gross total resection (GTR), visual improvement, cerebrospinal fluid (CSF) leak, intraoperative arterial injury, and mortality, comparing eTSA and mTCA, with p-interaction values. Results: Of 1684 studies, 64 case series were included in the meta-analysis. Using the fixed-effects model, the GTR rate was significantly higher among mTCA patients for OGM (eTSA: 70.9% vs. mTCA: 88.5%, p-interaction < 0.01), but not significantly higher for TSM (eTSA: 83.0% vs. mTCA: 85.8%, p-interaction = 0.34). Despite considerable heterogeneity, visual improvement was higher for eTSA than mTCA for TSM (p-interaction < 0.01), but not for OGM (p-interaction = 0.33). CSF leak was significantly higher among eTSA patients for both OGM (eTSA: 25.1% vs. mTCA: 10.5%, p-interaction < 0.01) and TSM (eTSA: 19.3%, vs. mTCA: 5.81%, p-interaction < 0.01). Intraoperative arterial injury was higher among eTSA (4.89%) than mTCA patients (1.86%) for TSM (p-interaction = 0.03), but not for OGM resection (p-interaction = 0.10). Mortality was not significantly different between eTSA and mTCA patients for both TSM (p-interaction = 0.14) and OGM resection (p-interaction = 0.88). Random-effect models yielded similar results. Conclusion: In this meta-analysis, eTSA was not shown to be superior to mTCA for resection of both OGMs and TSMs. Electronic supplementary material The online version of this article (10.1007/s00701-017-3390-y) contains supplementary material, which is available to authorized users.