Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis.

OBJECTIVES: Cocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness. AIMS: We conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs. MATERIALS AND METHODS: Quality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline. RESULTS: On a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively. CONCLUSIONS: We find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.

Deep Brain Stimulation Results in Greater Symptomatic Improvement in Tourette Syndrome than Conservative Measures: A Meta-Analysis.

INTRODUCTION: Deep brain stimulation (DBS) has emerged as a safe and effective therapy for refractory Tourette syndrome (TS). Recent studies have identified several neural targets as effective in reducing TS symptoms with DBS, but, to our knowledge, none has compared the effectiveness of DBS with conservative therapy. METHODS: A literature review was performed to identify studies investigating adult patient outcomes reported as Yale Global Tic Severity Scale (YGTSS) scores after DBS surgery, pharmacotherapy, and psychotherapy. Data were pooled using a random-effects model of inverse variance-weighted meta-analysis (n = 168 for DBS, n = 131 for medications, and n = 154 for behavioral therapy). RESULTS: DBS resulted in a significantly greater reduction in YGTSS total score (49.9 ± 17.5%) than pharmacotherapy (22.5 ± 15.2%, p = 0.001) or psychotherapy (20.0 ± 11.3%, p < 0.001), with a complication (adverse effect) rate of 0.15/case, 1.13/case, and 0.60/case, respectively. CONCLUSION: Our data suggest that adult patients with refractory TS undergoing DBS experience greater symptomatic improvement with surprisingly low morbidity than can be obtained with pharmacotherapy or psychotherapy.

Comparative effectiveness of neuroablation and deep brain stimulation for treatment-resistant obsessive-compulsive disorder: a meta-analytic study.

BACKGROUND: The safety and efficacy of neuroablation (ABL) and deep brain stimulation (DBS) for treatment refractory obsessive-compulsive disorder (OCD) has not been examined. This study sought to generate a definitive comparative effectiveness model of these therapies. METHODS: A EMBASE/PubMed search of English-language, peer-reviewed articles reporting ABL and DBS for OCD was performed in January 2018. Change in quality of life (QOL) was quantified based on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the impact of complications on QOL was assessed. Mean response of Y-BOCS was determined using random-effects, inverse-variance weighted meta-analysis of observational data. FINDINGS: Across 56 studies, totalling 681 cases (367 ABL; 314 DBS), ABL exhibited greater overall utility than DBS. Pooled ability to reduce Y-BOCS scores was 50.4% (±22.7%) for ABL and was 40.9% (±13.7%) for DBS. Meta-regression revealed no significant change in per cent improvement in Y-BOCS scores over the length of follow-up for either ABL or DBS. Adverse events occurred in 43.6% (±4.2%) of ABL cases and 64.6% (±4.1%) of DBS cases (p<0.001). Complications reduced ABL utility by 72.6% (±4.0%) and DBS utility by 71.7% (±4.3%). ABL utility (0.189±0.03) was superior to DBS (0.167±0.04) (p<0.001). INTERPRETATION: Overall, ABL utility was greater than DBS, with ABL showing a greater per cent improvement in Y-BOCS than DBS. These findings help guide success thresholds in future clinical trials for treatment refractory OCD.

Awake versus asleep deep brain stimulation for Parkinson's disease: a critical comparison and meta-analysis.

OBJECTIVE: No definitive comparative studies of the efficacy of 'awake' deep brain stimulation (DBS) for Parkinson's disease (PD) under local or general anaesthesia exist, and there remains significant debate within the field regarding differences in outcomes between these two techniques. METHODS: We conducted a literature review and meta-analysis of all published DBS for PD studies (n=2563) on PubMed from January 2004 to November 2015. Inclusion criteria included patient number >15, report of precision and/or clinical outcomes data, and at least 6 months of follow-up. There were 145 studies, 16 of which were under general anaesthesia. Data were pooled using an inverse-variance weighted, random effects meta-analytic model for observational data. RESULTS: There was no significant difference in mean target error between local and general anaesthesia, but there was a significantly less mean number of DBS lead passes with general anaesthesia (p=0.006). There were also significant decreases in DBS complications, with fewer intracerebral haemorrhages and infections with general anaesthesia (p<0.001). There were no significant differences in Unified Parkinson's Disease Rating Scale (UPDRS) Section II scores off medication, UPDRS III scores off and on medication or levodopa equivalent doses between the two techniques. Awake DBS cohorts had a significantly greater decrease in treatment-related side effects as measured by the UPDRS IV off medication score (78.4% awake vs 59.7% asleep, p=0.022). CONCLUSIONS: Our meta-analysis demonstrates that while DBS under general anaesthesia may lead to lower complication rates overall, awake DBS may lead to less treatment-induced side effects. Nevertheless, there were no significant differences in clinical motor outcomes between the two techniques. Thus, DBS under general anaesthesia can be considered at experienced centres in patients who are not candidates for traditional awake DBS or prefer the asleep alternative.

Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor.

BACKGROUND: Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options. METHODS: Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques. RESULTS: Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery. CONCLUSIONS: Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.

Elevated Red Cell Distribution Width is Associated with Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated red blood cell distribution width (RDW) has been associated with thrombotic disorders including myocardial infarction, venous thromboembolism, and ischemic stroke, independent of other inflammatory and coagulation biomarkers. The purpose of this study was to determine whether elevated RDW is associated with cerebral infarction and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective single-center cohort of aSAH patients (October 2009-September 2014), elevated RDW was defined as a mean RDW >14.5 % during the first 14 days after aSAH. Outcomes included cerebral infarction (CI) by any mechanism and poor functional outcome, defined as discharge modified Rankin Scale (mRS) >4, indicating severe disability or death. RESULTS: Of 179 patients, 27 % had a high Hunt-Hess grade (IV-V), and 76 % were women. Twenty-four patients (13.4 %) underwent red blood cell (RBC) transfusion and compared to patients with normal RDW, patients with an elevated RDW were at greater odds of RBC transfusion (OR 2.56 [95 % CI, 1.07-6.11], p = 0.035). In univariate analysis, more patients with elevated RDW experienced CI (30.8 vs. 13.7 %, p = 0.017). In the multivariable model, elevated RDW was significantly associated with CI (OR 3.08 [95 % CI, 1.30-7.32], p = 0.011), independent of known confounders including but not limited to age, sex, race, high Hunt-Hess grade, and RBC transfusion. In multivariable analysis, RDW elevation was also associated with poor functional outcome (mRS > 4) at discharge (OR 2.59 [95 % CI, 1.04-629], p = 0.040). CONCLUSIONS: RDW elevation is associated with cerebral infarction and poor outcome after aSAH. Further evaluation of this association is warranted as it may shed light on mechanistic relations between anemia, inflammation, and thrombosis after aSAH.

Thromboelastography defines late hypercoagulability after TBI: a pilot study.

INTRODUCTION: Traumatic brain injury (TBI) is associated with a hypercoagulable state, the mechanism and duration of which remain unclear. We sought to determine whether thromboelastography (TEG) analysis could identify the hypercoagulable state after TBI, as defined by elevations in maximal amplitude (MA), thrombus generation (TG), G value (G), and alpha angle (αA). METHODS: Patients with moderate-severe TBI, defined primarily as a GCS <12, admitted between 1/2012 and 8/2013 were eligible for enrolment in this prospective cohort study. TEG profiles were obtained between 0-24 h (T1), 24-48 h (T2), 48-72 h (T3), 72-96 h (T4), and 96-120 h (T5) after admission. Early TEG was defined as 0-48 h, and late TEG was defined as >48 h. RESULTS: Twenty five patients (80 % men) and 7 age- and sex-matched control subjects were studied. Median age was 38 years (range 18-85). Early MA was [63.6 mm (60.5, 67.4)] versus late MA [69.9 mm (65.2,73.9); p = 0.02], early TG was [763.3 mm/min (712.8, 816.2)] versus late TG [835.9 mm/min (791.2,888.3); p = 0.02], and early G was [8.8 d/cm(2) (7.7,10.4)] versus late G [11.6 d/cm(2) (9.4,14.1); p = 0.02]. Study patients had higher MA (p = 0.02), TG (p = 0.03), and G (p = 0.02) values at T5 compared to controls. There was a linear increase per day of MA by 2.6 mm (p = 0.001), TG 31.9 mm/min (p ≤ 0.001), and G value by 1.3 d/cm(2) (p ≤ 0.001) when clustered by pairs in regression analysis. Lower MA values trended toward home discharge (p = 0.08). CONCLUSION: The data suggest a progressive and delayed hypercoagulable state observed days after initial TBI. The hypercoagulable state may reflect excess platelet activity.

Optimal approach to circumferential decompression and reconstruction for thoracic spine metastatic disease.

BACKGROUND: Circumferential decompression has been demonstrated to be the first-line therapy for patients with metastatic tumors in the thoracic spine requiring surgical intervention. However, there is significant debate regarding whether these tumors are best accessed anteriorly utilizing a thoracotomy or posteriorly. We used decision analysis to determine which approach yields greater health-related quality of life (QOL). METHODS: We searched Medline, Embase, and the Cochrane Library for relevant articles published between 1990 and 2011 on anterior and posterior approaches to metastatic disease in the thoracic spine. QOL values for major treatment outcomes were determined using the existing literature. Separate models were created for ambulatory and nonambulatory patients. A Monte Carlo simulation and sensitivity analyses were used to determine which treatment strategy resulted in the highest QOL. RESULTS: For ambulatory patients, an anterior approach resulted in a slightly higher QOL, and for nonambulatory patients, a posterior approach was favored, but these differences were not statistically significant. CONCLUSIONS: Using a decision-analytic model, we found no significant difference in QOL resulting from anterior versus posterior approaches to metastatic lesions in the thoracic spine. Decisions should instead be based on surgeon comfort, tumor characteristics, anatomy of the lesion, patient-related factors, and goals of the operation.

Pediatric intracranial arachnoid cysts: comparative effectiveness of surgical treatment options.

PURPOSE: A variety of surgical approaches for the treatment of pediatric intracranial arachnoid cysts exist. In an effort to identify the optimal surgical treatment for this disorder, we developed a decision analytic model to evaluate outcomes of four surgical approaches in children. These included open craniotomy for cyst excision, open craniotomy for cyst fenestration, endoscopic cyst fenestration, and cystoperitoneal shunting. METHODS: Pooled data were used to create evidence tables, from which we calculated incidence, relative risks, and summary outcomes in quality-adjusted life years (QALYs) for the four surgical treatments. Our study incorporated data up to 5 years postsurgery. RESULTS: We analyzed 1,324 cases from 36 case series. There were no significant differences in outcome among the four surgical strategies. The QALYs (maximum of 5) for surgical approaches resulted in a range from 4.79 (for open craniotomy and excision) to 4.92 (for endoscopic fenestration). CONCLUSIONS: Overall quality of life is comparable between patients undergoing open craniotomy for cyst excision or fenestration, endoscopic fenestration, and cystoperitoneal shunting up to 5 years after surgery. While each approach offers unique advantages and disadvantages, an individualized treatment strategy should be employed in the setting of surgical outcome equipoise.

Systematic review of outcome after ischemic stroke due to anterior circulation occlusion treated with intravenous, intra-arterial, or combined intravenous+intra-arterial thrombolysis.

BACKGROUND AND PURPOSE: The optimal approach to recanalization in acute ischemic stroke is unknown. We performed a literature review and meta-analysis comparing the relative efficacy of 6 reperfusion strategies: (1) 0.9 mg/kg intravenous tissue-type plasminogen activator; (2) intra-arterial chemical thrombolysis; (3) intra-arterial mechanical thrombolysis; (4) intra-arterial combined chemical/mechanical thrombolysis; (5) 0.6 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis; and (6) 0.9 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis. METHODS: A literature search in Medline, Embase, and the Cochrane database identified case series, observational studies, and treatment arms of randomized trials of anterior circulation arterial occlusion treated with thrombolytic therapy. Included studies had ≥10 subjects, mean time to treatment <6 hours, and treatment specific reporting of disability, death, and intracerebral hemorrhage. Multivariable metaregression evaluated the effects of treatment group on outcome at the same time as accounting for differences in baseline covariates. RESULTS: A total of 2986 abstracts were identified from which 54 studies (5019 subjects) were included. There were significant differences across groups in age (P=0.0008), baseline National Institutes of Health Stroke Scale (P=0.0002), and time to treatment initiation (P<0.0001). There were also differences in mean modified Rankin Scale (P<0.0001), mortality (P=0.0024), and symptomatic intracerebral hemorrhage (P=0.0305). Differences in modified Rankin Scale were not significant in the metaregression and likely attributable to differences in baseline covariates between studies. CONCLUSIONS: This study found no evidence that one reperfusion strategy is superior with respect to efficacy or safety, supporting clinical equipoise between reperfusion strategies. Intravenous tissue-type plasminogen activator remains the standard of care for acute ischemic stroke. Randomized clinical trials are necessary to determine the efficacy of alternative reperfusion strategies. Participation in such trials is strongly recommended.

Durability of Roux-en-Y gastric bypass surgery: a meta-regression study.

OBJECTIVE: The present meta-regression pools data from reports of long-term follow-up (>2 years) to assess durability of the efficacy associated with Roux-en-Y gastric bypass (RYGB) surgery. DATA SOURCES: Medline and PubMed searches for articles pertaining to long-term weight loss after RYGB surgery were performed. BACKGROUND: Various studies have consistently shown short-term (<2 years) efficacy of RYGB surgery for morbid obesity, corroborated by meta-analytic techniques. Relatively few studies have assessed efficacy over longer periods of time. This is the first meta-analysis to analyze long-term effects of RYGB surgery on weight loss. METHODS: Twenty-two reports with a total of 4206 patient cases were included. Sixteen of the 22 studies had multiple follow-up times, ranging from 2 to 12.3 years (mean: 3.6 years). An inverse variance weighted model and meta-regression were used to generate the pooled percent mean excess weight loss (EWL) and the durability of EWL over time, respectively. RESULTS: Meta-regression did not reveal any significant change in EWL over time. Pooled mean EWL was 66.5%, and there was no significant association between EWL and length of follow-up. CONCLUSIONS: Pooling data from multiple studies meta-analytically revealed that weight loss after RYGB is maintained over the long-term. Further investigation would be necessary to ascertain similar durability in comorbidity reduction after RYGB surgery.

Comparative effectiveness in neurosurgery: what it means, how it is measured, and why it matters.

Comparative effectiveness research has recently been the subject of intense discussion. With congressional support, there has been increasing funding and publication of studies using comparative effectiveness and related methodology. The neurosurgical field has been relatively slow to accept and embrace this approach. The author outlines the procedures and rationale of comparative effectiveness, illustrates how it applies to neurosurgical topics, and explains its importance.

Cost-effectiveness of confirmatory techniques for the placement of lumbar pedicle screws.

OBJECT: There is considerable variation in the use of adjunctive technologies to confirm pedicle screw placement. Although there is literature to support the use of both neurophysiological monitoring and isocentric fluoroscopy to confirm pedicle screw positioning, there are no studies examining the cost-effectiveness of these technologies. This study compares the cost-effectiveness and efficacy of isocentric O-arm fluoroscopy, neurophysiological monitoring, and postoperative CT scanning after multilevel instrumented fusion for degenerative lumbar disease. METHODS: Retrospective data were collected from 4 spine surgeons who used 3 different strategies for monitoring of pedicle screw placement in multilevel lumbar degenerative disease. A decision analysis model was developed to analyze costs and outcomes of the 3 different monitoring strategies. A total of 448 surgeries performed between 2005 and 2010 were included, with 4 cases requiring repeat operation for malpositioned screws. A sample of 64 of these patients was chosen for structured interviews in which the EuroQol-5D questionnaire was used. Expected costs and quality-adjusted life years were calculated based on the incidence of repeat operation and its negative effect on quality of life and costs. RESULTS: The decision analysis model demonstrated that the O-arm monitoring strategy is significantly (p < 0.001) less costly than the strategy of postoperative CT scanning following intraoperative uniplanar fluoroscopy, which in turn is significantly (p < 0.001) less costly than neurophysiological monitoring. The differences in effectiveness of the different monitoring strategies are not significant (p = 0.92). CONCLUSIONS: Use of the O-arm for confirming pedicle screw placement is the least costly and therefore most cost-effective strategy of the 3 techniques analyzed.

Endoscopic versus open resection of tuberculum sellae meningiomas: a decision analysis.

BACKGROUND/AIMS: Tuberculum sellae meningiomas (TSMs) are challenging tumors for surgical resection. Endoscopic endonasal (EE) approaches to these lesions have not been directly compared to open craniotomy in a controlled trial. METHODS: We searched Medline and Embase online databases for English-language articles containing key words related to TSMs. Data were pooled, including 5 of our own patients reported here for the first time. Metaregression was used and a decision-analytical model was constructed to compare outcomes between open microsurgery and EE approaches. RESULTS: The overall quality of life (QOL) was not significantly different between the approaches (p = 0.410); however, there were large differences in individual complication rates. The Monte Carlo simulation yielded an overall average QOL in craniotomy patients of 0.915 and in endoscopic patients of 0.952. Endoscopy had a higher CSF leak rate (26.8 vs. 3.5%, p < 0.001) but a lower rate of injury to the optic apparatus (1.4 vs. 9.2%, p < 0.001) compared with craniotomy. The 3-year recurrence rates were not statistically different (p = 0.529). CONCLUSION: EE resection of TSMs appears to be a comparable alternative to traditional open microsurgical resection with respect to overall QOL based on available publications. A meaningful comparison of recurrence rates will require a longer follow-up.

Decompressive hemicraniectomy for pediatric traumatic brain injury: long-term outcome based on quality of life.

AIMS: The impact of decompressive hemicraniectomy (DCH) on the overall outcome of pediatric brain injury patients has not been fully determined. In this paper, the authors performed a systematic review of patient outcome based on quality of life following DCH in a pediatric population. METHODS: We describe our experience with decompressive craniectomy in pediatric patients and perform a literature review and pooled outcomes analysis to supplement these findings. A total of 13 children underwent DCH for intractable intracranial pressure in our institution from 2000 to 2008. Follow-up was available in 11 patients with 1 death (9%) and 7 survivors (70%) obtaining a favorable outcome (Glasgow Outcome Scale, GOS, scores = 4-5). RESULTS: A literature review to determine the usefulness of DCH identified 17 articles that, when combined with our series, resulted in 186 pediatric DCH cases. Pooled outcomes found 42 deaths and 112 patients who had favorable outcomes at 6 months. The average 6-month mortality was 21.1%, and the pooled mean quality of life among survivors 0.75 (0.68-0.82), midway between moderate disability and good outcome. CONCLUSIONS: Based on our findings, DCH results in a majority of pediatric patients having a good outcome based on the GOS score.

Bilateral Deep Brain Stimulation is the Procedure to Beat for Advanced Parkinson Disease: A Meta-Analytic, Cost-Effective Threshold Analysis for Focused Ultrasound.

BACKGROUND: Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective. OBJECTIVE: To (1) quantify the utility (functional disability metric) imparted by DBS and radiofrequency ablation (RF), (2) compare cost-effectiveness of DBS and RF, and (3) establish a preliminary success threshold at which FUS would be cost-effective compared to these procedures. METHODS: We performed a meta-analysis of articles (1998-2018) of DBS and RF targeting the globus pallidus or subthalamic nucleus in PD patients and calculated utility using pooled Unified Parkinson Disease Rating Scale motor (UPDRS-3) scores and adverse events incidences. We calculated Medicare reimbursements for each treatment as a proxy for societal cost. RESULTS: Over a 22-mo mean follow-up period, bilateral DBS imparted the most utility (0.423 quality-adjusted life-years added) compared to (in order of best to worst) bilateral RF, unilateral DBS, and unilateral RF, and was the most cost-effective (expected cost: $32 095 ± $594) over a 22-mo mean follow-up. Based on this benchmark, FUS would need to impart UPDRS-3 reductions of ∼16% and ∼33% to be the most cost-effective treatment over 2- and 5-yr periods, respectively. CONCLUSION: Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS's cost-effectiveness from a societal cost perspective.

Signaling, delivery and age as emerging issues in the benefit/risk ratio outcome of tPA For treatment of CNS ischemic disorders.

Stroke is a leading cause of morbidity and mortality. While tissue-type plasminogen activator (tPA) remains the only FDA-approved treatment for ischemic stroke, clinical use of tPA has been constrained to roughly 3% of eligible patients because of the danger of intracranial hemorrhage and a narrow 3 h time window for safe administration. Basic science studies indicate that tPA enhances excitotoxic neuronal cell death. In this review, the beneficial and deleterious effects of tPA in ischemic brain are discussed along with emphasis on development of new approaches toward treatment of patients with acute ischemic stroke. In particular, roles of tPA-induced signaling and a novel delivery system for tPA administration based on tPA coupling to carrier red blood cells will be considered as therapeutic modalities for increasing tPA benefit/risk ratio. The concept of the neurovascular unit will be discussed in the context of dynamic relationships between tPA-induced changes in cerebral hemodynamics and histopathologic outcome of CNS ischemia. Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals.

Predicting intracranial lesions by antiplatelet agents in subjects with mild head injury.

BACKGROUND: The effect of pre-injury antiplatelet treatment in the risk of intracranial lesions in subjects after mild head injury (Glasgow Coma Scale (GCS) 14-15) is uncertain. METHODS: The potential risk was determined, considering its increasing use in guidelines on cardiovascular disease prevention, and ageing of the trauma population in Europe. PATIENTS: The interaction of antiplatelet therapy with the prediction variables of main decision aids was analysed in 14,288 consecutive adolescent and adult subjects with mild head injury. MEASUREMENTS: Any intracranial lesion at CT scan was selected as an outcome measure in a multivariable logistic regression analysis. RESULTS: Intracranial lesions were demonstrated in 880 cases (6.2%), with an unfavourable outcome at 6 months in 86 (0.6%). Antiplatelet drugs were recorded in 10% of the entire cohort (24.7% in the group over 65 years). They increased the risk of intracranial lesions in the univariate analysis (OR 2.6; 95% CI 2.2 to 3.1), interacting with age in the multivariate analysis (antiplatelet OR 2.7 (1.9 to 3.7); age ≥75 years 1.4 (1.0 to 1.9)). The inclusion of these two variables with those included in previous decision aids for CT scanning (GCS, neurodeficit, post-traumatic seizures, suspected skull fracture, vomiting, loss of consciousness, coagulopathy) predicted intracranial lesions with a sensitivity of 99.7% (95% CI 98.9 to 99.8) and a specificity of 54.0% (95% CI 53.1 to 54.8), with a CT ordering rate of 49.3% (undetermined events 0.2:1000). INTERPRETATION: Antiplatelet drugs need to be considered in future prediction models on mild head injury, considering their increasing use and progressive ageing of the trauma population.

Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study.

OBJECT: Roux-en-Y gastric bypass is the gold standard treatment for morbid obesity, although failure rates may be high, particularly in patients with a BMI > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of obesity, deep brain stimulation (DBS) offers a less invasive and reversible alternative to available surgical treatments. In this decision analysis, the authors determined the success rate at which DBS would be equivalent to the two most common bariatric surgeries. METHODS: Medline searches were performed for studies of laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB), and DBS for movement disorders. Bariatric surgery was considered successful if postoperative excess weight loss exceeded 45% at 1-year follow-up. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment by LAGB, LRYGB, DBS, or no surgical treatment. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. RESULTS: Fifteen studies involving 3489 and 3306 cases of LAGB and LRYGB, respectively, and 45 studies involving 2937 cases treated with DBS were included. The operative successes were 0.30 (95% CI 0.247-0.358) for LAGB and 0.968 (95% CI 0.967-0.969) for LRYGB. Sensitivity analysis revealed utility of surgical complications in LRYGB, probability of surgical complications in DBS, and success rate of DBS as having the greatest influence on outcomes. At no values did LAGB result in superior outcomes compared with other treatments. CONCLUSIONS: Deep brain stimulation must achieve a success rate of 83% to be equivalent to bariatric surgery. This high-threshold success rate is probably due to the reported success rate of LRYGB, despite its higher complication rate (33.4%) compared with DBS (19.4%). The results support further research into the role of DBS for the treatment of obesity.

A critical comparison of clinical decision instruments for computed tomographic scanning in mild closed traumatic brain injury in adolescents and adults.

STUDY OBJECTIVE: A number of clinical decision aids have been introduced to limit unnecessary computed tomographic scans in patients with mild traumatic brain injury. These aids differ in the risk factors they use to recommend a scan. We compare the instruments according to their sensitivity and specificity and recommend ones based on incremental benefit of correctly classifying patients as having surgical, nonsurgical, or no intracranial lesions. METHODS: We performed a secondary analysis of prospectively collected database from 7,955 patients aged 10 years or older with mild traumatic brain injury to compare sensitivity and specificity of 6 common clinical decision strategies: the Canadian CT Head Rule, the Neurotraumatology Committee of the World Federation of Neurosurgical Societies, the New Orleans, the National Emergency X-Radiography Utilization Study II (NEXUS-II), the National Institute of Clinical Excellence guideline, and the Scandinavian Neurotrauma Committee guideline. Excluded from the database were patients for whom the history of trauma was unclear, the initial Glasgow Coma Scale score was less than 14, the injury was penetrating, vital signs were unstable, or who refused diagnostic tests. Patients revisiting the emergency department within 7 days were counted only once. RESULTS: The percentage of scans that would have been required by applying each of the 6 aids were Canadian CT head rule (high risk only) 53%, Canadian (medium & high risk) 56%, the Neurotraumatology Committee of the World Federation of Neurosurgical Societies 56%, New Orleans 69%, NEXUS-II 56%, National Institute of Clinical Excellence 71%, and the Scandinavian 50%. The 6 decision aids' sensitivities for surgical hematomas could not be distinguished statistically (P>.05). Sensitivity was 100% (95% confidence interval [CI] 96% to 100%) for NEXUS-II, 98.1% (95% CI 93% to 100%) for National Institute of Clinical Excellence, and 99.1% (95% CI 94% to 100%) for the other 4 clinical decision instruments. Sensitivity for any intracranial lesion ranged from 95.7% (95% CI 93% to 97%) (Scandinavian) to 100% (95% CI 98% to 100%) (National Institute of Clinical Excellence). In contrast, specificities varied between 30.9% (95% CI 30% to 32%) (National Institute of Clinical Excellence) and 52.9% (95% CI 52% to 54) (Scandinavian). CONCLUSION: NEXUS-II and the Scandinavian clinical decision aids displayed the best combination of sensitivity and specificity in this patient population. However, we cannot demonstrate that the higher sensitivity of NEXUS-II for surgical hematomas is statistically significant. Therefore, choosing which of the 2 clinical decision instruments to use must be based on decisionmakers' attitudes toward risk.