The cost-utility of CT angiography and conventional angiography for people presenting with intracerebral hemorrhage.

OBJECTIVE: To determine the optimal imaging strategy for ICH incorporating CTA or DSA with and without a NCCT risk stratification algorithm. METHODS: A Markov model included costs, outcomes, prevalence of a vascular lesion, and the sensitivity and specificity of a risk stratification algorithm from the literature. The four imaging strategies were: (a) CTA screening of the entire cohort; (b) CTA only in those where NCCT suggested a high or indeterminate likelihood of a lesion; (c) DSA screening of the entire cohort and (d) DSA only for those with a high or indeterminate suspicion of a lesion following NCCT. Branch d was the comparator. RESULTS: Age of the cohort and the probability of an underlying lesion influenced the choice of optimal imaging strategy. With a low suspicion for a lesion (<12%), branch (a) was the optimal strategy for a willingness-to-pay of $100,000/QALY. Branch (a) remained the optimal strategy in younger people (<35 years) with a risk below 15%. If the probability of a lesion was >15%, branch (b) became preferred strategy. The probabilistic sensitivity analysis showed that branch (b) was the optimal choice 70-72% of the time over varying willingness-to-pay values. CONCLUSIONS: CTA has a clear role in the evaluation of people presenting with ICH, though the choice of CTA everyone or CTA using risk stratification depends on age and likelihood of finding a lesion.

Reading a cost-effectiveness or decision analysis study: Five things to consider.

Cost-effectiveness studies and decision analyses of neurologic practices, treatments, and technologies are increasing in the literature and have an emerging role within both medicine and neurology. Knowledge about these research approaches, how to interpret the results of such studies, as well as an understanding of their limitations will be of growing importance for the practicing neurologist. We discuss 5 aspects of these analyses to increase awareness about the uses and limitations of cost-effectiveness articles in everyday practice.

Prediction of postdischarge venous thromboembolism using a risk assessment model.

OBJECTIVE: The risk of postdischarge venous thromboembolism (VTE) (either deep vein or pulmonary embolism) is increasingly recognized yet the prescription of postdischarge thromboprophylaxis is inconsistent. There is a paucity of information to aid clinicians in identifying surgical patients who are at increased risk for postdischarge VTE. This study aimed to determine the incidence and risk factors associated with symptomatic postdischarge VTE and develop a risk score to identify patients who may benefit from extended duration thromboprophylaxis. METHODS: This was a retrospective study. All nonorthopedic cases in which the patient was discharged alive without inpatient VTE were selected from the 2005-2009 National Surgical Quality Improvement Program database. A multivariate logistic regression was used to create a risk score for postdischarge VTE prediction. The dataset was split into two-thirds for risk score development and validated in the remaining one-third. RESULTS: The overall incidence of early postdischarge VTE for 2005-2009 National Surgical Quality Improvement Program was 0.3%. The risk score stratified patients into low, moderate, and high risk for postdischarge VTE with the incidence based on the risk score ranging from 0.07% to 2.2%. The risk score had good predictive ability with c-statistic = 0.72 for model development and c-statistic = 0.71 in the validation dataset. Factors associated with postdischarge VTE on multivariate analysis included race, increasing age, steroid use, body mass index ≥30, malignancy, higher American Society of Anesthesiologists class, increasing operative time, length of postsurgical stay, and major postoperative complication. CONCLUSIONS: This novel postdischarge VTE prediction score utilizes patient, operative, and early outcome factors to accurately identify patients at increased risk of a postdischarge thromboembolic event. The development of a patient- specific postdischarge VTE risk profile may help address the challenge of determining postdischarge prophylaxis requirements.

Carotid endarterectomy and carotid artery stenting utilization trends over time.

BACKGROUND: Carotid endarterectomy (CEA) has been the standard in atherosclerotic stroke prevention for over 2 decades. More recently, carotid artery stenting (CAS) has emerged as a less invasive alternative for revascularization. The purpose of this study was to investigate whether an increase in stenting parallels a decrease in endarterectomy, if there are specific patient factors that influence one intervention over the other, and how these factors may have changed over time. METHODS: Using a nationally representative sample of US hospital discharge records, data on CEA and CAS procedures performed from 1998 to 2008 were obtained. In total, 253,651 cases of CEA and CAS were investigated for trends in utilization over time. The specific data elements of age, gender, payer source, and race were analyzed for change over the study period, and their association with type of intervention was examined by multiple logistic regression analysis. RESULTS: Rates of intervention decreased from 1998 to 2008 (P < 0.0001). Throughout the study period, endarterectomy was the much more widely employed procedure. Its use displayed a significant downward trend (P < 0.0001), with the lowest rates of intervention occurring in 2007. In contrast, carotid artery stenting displayed a significant increase in use over the study period (P < 0.0001), with the highest intervention rates occurring in 2006. Among the specific patient factors analyzed that may have altered utilization of CEA and CAS over time, the proportion of white patients who received intervention decreased significantly (P < 0.0001). In multivariate modeling, increased age, male gender, white race, and earlier in the study period were significant positive predictors of CEA use. CONCLUSIONS: Rates of carotid revascularization have decreased over time, although this has been the result of a reduction in CEA despite an overall increase in CAS. Among the specific patient factors analyzed, age, gender, race, and time were significantly associated with the utilization of these two interventions.

Evidence-based treatment of carotid artery stenosis.

Carotid atheromatous disease is an important cause of stroke. Carotid endarterectomy (CEA) is a well-established option for reducing the risk of subsequent stroke due to symptomatic stenosis (> 50%). With adequately low perioperative risk (< 3%) and sufficient life expectancy, CEA may be used for asymptomatic stenosis (> 60%). Recently, carotid angioplasty and stent placement (CAS) has emerged as an alternative revascularization technique. Trial design considerations are discussed in relation to trial results to provide an understanding of why some trials were considered positive whereas others were not. This review then addresses both the original randomized studies showing that CEA is superior to best medical management and the newer studies comparing the procedure to stent insertion in both symptomatic and asymptomatic populations. Additionally, recent population-based studies show that improvements in best medical management may be lowering the stroke risk for asymptomatic stenosis. Finally, the choice of revascularization technique is discussed with respect to symptom status. Based on current evidence, CAS should remain limited to specific indications.

Transesophageal echocardiography screening in subjects with a first cerebrovascular ischemic event.

Our goal was to develop decision guides to predict the presence of a high-risk source of embolus and to predict a change in management following transesophageal echocardiography (TEE) in subjects who present with a first cerebral ischemic event. We conducted a retrospective review of subjects age ≥18 years who underwent TEE after a first ischemic event and were admitted to our stroke service between 2004 and 2007 (n = 287). A high-risk source of embolus and a change in clinical management (including medication changes or subsequent testing) were analyzed as separate endpoints, using multivariate techniques and receiver operating characteristic curves. We found that 14.3% of the subjects had a high-risk source, and an additional 61.3% had a potential (or low-risk) source of embolus. Increasing age and no history of diabetes mellitus were independently associated with a high-risk source of embolus. TEE would be recommended for nondiabetic individuals age ≥66 years (sensitivity, 68%; specificity, 76%). The area under the curve (AUC) for detecting a high-risk source was 0.773. TEE results changed medications or clinical management in 30.3% of the subjects. Current smokers were less likely to undergo a change in management. The AUC was uninformative (0.56) for predicting changes in management. Subjects presenting with a first ischemic event age ≥66 years may benefit from TEE. Although changes in management occurred in at least 30% of our cohort, no factors that predicted a change in management better than chance alone could be identified.

Cost-effectiveness of multimodal CT for evaluating acute stroke.

OBJECTIVE: Multimodal CT, including noncontrast CT (NCCT), CT with contrast, CT angiography (CTA), and perfusion CT (CTP), is increasingly used in acute stroke patients to identify candidates for endovascular therapy. Our goal is to explore the cost-effectiveness of multimodal CT as a diagnostic test. METHODS: A Markov model compared multimodal CT to NCCT in a hypothetical cohort of nonhemorrhagic stroke patients presenting within 3 hours of symptom onset who were potential IV tPA candidates. Patients who failed to improve after IV tPA or in whom IV tPA was contraindicated were candidates for endovascular therapy. Direct costs (2008 USD), outcomes, and probabilities were obtained from the literature. RESULTS: For the 3-month time horizon, multimodal CT had lower costs (-$1,716), had greater quality-adjusted life-years (QALYs, 0.004), and was the cost-effective choice 100% of the time for a willingness-to-pay of $100,000/QALY (probabilistic sensitivity analysis). The number needed to screen with multimodal CT to avoid 1 diagnostic angiogram was 2. Over a lifetime, multimodal CT had lower costs (-$2,058), had greater QALYs (0.008), and was cost-effective, with a 90.1% likelihood, for a willingness-to-pay of $100,000/QALY. CONCLUSIONS: Multimodal CT appears to be a cost-saving screening tool over the short term. However, additional data regarding clinical outcomes following multimodal CT-guided intra-arterial treatment are needed before the long-term cost-effectiveness can be suitably addressed. This analysis can be incorporated into future discussions of multimodal CT as a diagnostic test for unselected patients, within and beyond the 3-hour IV tPA time window.

A cost-effectiveness analysis of carotid artery stenting compared with endarterectomy.

Endarterectomy and angioplasty with stenting have emerged as 2 alternative treatments for carotid artery stenosis. This study's objective was to determine the cost-effectiveness of carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) in symptomatic subjects who are suitable for either intervention. A Markov analysis of these 2 revascularization procedures was conducted using direct Medicare costs (2007 US$) and characteristics of a symptomatic 70-year-old cohort over a lifetime. In the base case analysis, CAS produced 8.97 quality-adjusted life-years, compared with 9.64 quality-adjusted life-years for CEA. The incremental cost of stenting was $17,700, and thus CAS was dominated by CEA. Sensitivity analyses show that the long-term probabilities of major stroke or mortality influenced the results. In the base case analysis, CEA for patients with symptomatic stenosis has a greater benefit than CAS, with lower direct costs. With 59% probability, CEA will be the optimal intervention when all of the model assumptions are varied simultaneously.

How much do we need to worry about venous thromboembolism after hospital discharge? A study of colorectal surgery patients using the National Surgical Quality Improvement Program database.

PURPOSE: It is well recognized that the increased risk of a postoperative venous thrombotic event extends beyond the inpatient treatment period. The purpose of this study was to determine the 30-day incidence and risk factors associated with the occurrence of early postdischarge symptomatic venous thromboembolic events in patients who have undergone major colorectal surgery. METHODS: The National Surgical Quality Improvement Program database was queried for patients who had undergone a colon or rectal resection during the study period (2005-2008). Patient demographics, preoperative risk factors, and operative variables were recorded. The primary outcomes were occurrence of deep venous thrombosis requiring therapy or pulmonary embolism within 30 days after initial surgery. The occurrence of postdischarge venous thromboembolic events was calculated from the days to primary outcome and days from operation to discharge. Univariate and multivariate linear regression models incorporating pre- and intraoperative variables as well as the occurrence of a major or minor complication were used to evaluate the effect of these clinical factors on the early postdischarge venous thromboembolic event rate. RESULTS: A total of 52,555 patients were included in the initial analysis. A total of 240 deep venous thromboses were diagnosed in the postdischarge setting giving a postdischarge incidence of 0.47%. One hundred thirty cases of a pulmonary embolus were diagnosed (0.26% incidence) with 30 patients having a concurrent deep venous thrombosis and pulmonary embolus. The overall cumulative postdischarge symptomatic venous thromboembolic incidence was 0.67% (n = 340). Obesity, preoperative steroid use, "bleeding disorder," ASA class III, and postoperative (major and minor) complications were all independently associated with an increased risk of an early postdischarge venous thromboembolic event. CONCLUSION: This study has identified risk factors that may help stratify patients into different risk profiles and offer prolonged prophylaxis to patients at increased risk on the basis of preoperative risk factors and postoperative complications.

Hospital resource use following carotid endarterectomy in 2006: analysis of the nationwide inpatient sample.

To explore the relationships among patient age and length of stay (LOS), hospital costs, and discharge disposition following carotid endarterectomy (CEA), we identified discharge records from the 2006 Nationwide Inpatient Sample (NIS). The primary outcome was LOS from the surgical procedure to discharge. We examined LOS from procedure to discharge because the time from procedure to discharge may better reflect hospital stay due to the procedure itself for subjects with symptomatic carotid artery disease compared with the inclusion of days hospitalized for stroke recovery. Secondary endpoints included total LOS, discharge disposition, and cost of hospitalization. More than 90% of the 118,218 discharge records for CEA examined were for patients with asymptomatic carotid disease. The LOS from procedure to discharge and total LOS increased per decade, starting at age 70-79 years. Age per decade increased the likelihood of needed an LOS from procedure to discharge of >1 day. The same trend was seen for the likelihood of needing a >2-day postoperative stay; patients age ≥80 years required the longest postoperative LOS (odds ratio [OR]=1.45 for >1 day and 1.45 for >2 days; both P<.001). Total hospital costs averaged $10,965 for all discharges. For age dichotomized at 80 years, the average cost increased by $845. Age≥80 years also was independently associated with discharge to a skilled nursing facility (SNF) (OR=2.4; 95% confidence interval=2.09-2.76). Hospital LOS and costs following CEA increased with increasing patient age. Morbidity after CEA should be discussed with patients in whom revascularization for asymptomatic disease is being considered.

Cost-effectiveness of abdominal aortic aneurysm repair based on aneurysm size.

OBJECTIVE: To evaluate the cost-effectiveness of endovascular repair (EVAR) for small abdominal aortic aneurysms (AAA). METHODS: We developed a Markov model of a hypothetical 68-year-old cohort to determine the cost-effectiveness of early EVAR for "small" AAAs (4.0 cm-5.4 cm) compared with elective repair (open or endovascular) at the traditional cut-off of 5.5 cm. Repair options for 5.5-cm AAAs include both endovascular and open procedures. Probabilities were obtained from the literature. Costs reflected direct costs in 2007 dollars. Outcomes were reported as quality-adjusted life-years (QALYs). RESULTS: The model demonstrated that early EVAR for 4.0 cm-5.4 cm AAAs led to fewer QALYs at greater costs when compared with observational management with elective repair at 5.5 cm. Sensitivity analyses suggested that early EVAR of 4.6 cm-4.9 cm AAAs can be cost-effective if the long-term mortality rate after EVAR is or=4.6 cm may be cost-effective. With a >70% probability, observational management until AAA diameter is 5.5 cm will be the cost-effective option. CONCLUSIONS: This analysis demonstrated that early EVAR for AAAs <5.5 cm is not likely to be cost-effective compared with elective repair at 5.5 cm. However, EVAR for small AAAs may become cost-effective when differences in quality of life and mortality are considered.

Cost-effectiveness of treating resistant hypertension with an implantable carotid body stimulator.

The purposes of this study are to investigate the cost-effectiveness of an implantable carotid body stimulator (Rheos; CVRx, Inc, Minneapolis, MN) for treating resistant hypertension and determine the range of starting systolic blood pressure (SBP) values where the device remains cost-effective. A Markov model compared a 20-mm Hg drop in SBP from an initial level of 180 mm Hg with Rheos to failed medical management in a hypothetical 50-year-old cohort. Direct costs (2007$), utilities, and event rates for future myocardial infarction, stroke, heart failure, and end-stage renal disease were modeled. Sensitivity analyses tested the assumptions in the model. The incremental cost-effectiveness ratio (ICER) for Rheos was $64,400 per quality-adjusted life-years (QALYs) using Framingham-derived event probabilities. The ICER was <$100,000 per QALYs for SBPs > or =142 mm Hg. A probability of device removal of <1% per year or SBP reductions of > or =24 mm Hg were variables that decreased the ICER below $50,000 per QALY. For cohort characteristics similar to Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm (ASCOT-BPLA) participants, the ICER became $26,700 per QALY. Two-way sensitivity analyses demonstrated that lowering SBP 12 mm Hg from 220 mm Hg or 21 mm Hg from 140 mm Hg were required. Rheos may be cost-effective, with an ICER between $50,000 and $100,000 per QALYs. Cohort characteristics and efficacy are key to the cost-effectiveness of new therapies for resistant hypertension .

Glutamate receptor expression and chronic glutamate toxicity in rat motor cortex.

In addition to the loss of spinal motor neurons, amyotrophic lateral sclerosis (ALS) is also associated with degeneration of corticospinal layer V pyramidal neurons and decreased glutamate transport in the cortex. We characterized the glutamate receptors on corticospinal neurons in acutely isolated rat motor cortex slices and found that the synaptic inputs to the corticospinal layer V neurons had a lesser proportional contribution from NMDA receptors relative to AMPA receptors than did layer II/III pyramidal neurons. The synaptic I(AMPA) was also more inwardly rectified, indicating a greater Ca(2+)-permeable component, in layer V. In a cortical organotypic slice culture model, blockade of glutamate transporters elevated glutamate in the media and led to pyramidal neuron loss in both layers. The loss of layer V pyramidal neurons was attenuated by antagonists of AMPA/kainate or Ca(2+)-permeable AMPA receptors, suggesting their therapeutic potential in the protection of the motor cortex in ALS.

The voltage gates of connexin channels are sensitive to CO(2).

Cx45 channel sensitivity to CO(2), transjunctional voltage (V(j)) and inhibition of calmodulin (CaM) expression was tested in oocytes by dual voltage-clamp. Cx45 channels are very sensitive to V(j) and close preferentially by the slow gate, likely the same as the chemical gate. With CO(2)-induced drop in junctional conductance (G(j)), the speed of V(j)-dependent inactivation of junctional current (I(j)) and V(j) sensitivity increased. With 40 mV V(j), the tau of single exponential I(j) decay reversibly decreased by approximately 40% with CO(2), and G(j steady state)/G(j peak) decreased multiphasically, indicating that kinetics and V(j) sensitivity of chemical/slow-V(j) gating are altered by changes in [H(+)](i) and/or [Ca(2+)](i). With 15 min exposure to CO(2), G(j) dropped to 0% in controls and by approximately 17% following CaM expression inhibition; similarly, V(j) sensitivity decreased significantly. This indicates that the speed and sensitivity of V(j)-dependent inactivation of Cx45 channels are increased by CO(2), and that CaM plays a role in gating. Cx32 channels behaved similarly, but the drop in both G(j steady state)/G(j peak) and tau with CO(2) matched more closely that of G(j peak). In contrast, sensitivity and speed of V(j) gating of Cx40 and Cx26 channels decreased, rather than increased, with CO(2) application.