Clinical benefits of vortioxetine 20 mg/day in patients with major depressive disorder.

BACKGROUND: Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. METHODS: Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). RESULTS: After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. CONCLUSION: Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

Deviations from evidence-based clinical management guidelines increase mortality in critically injured trauma patients*.

OBJECTIVES: The effect of treatment guidelines on clinical outcomes in general and specifically for trauma patients has not been well-studied. We hypothesized that better compliance with guidelines would be associated with improved clinical outcomes. DESIGN: Prospective, randomized, double-blinded, multicentered, placebo-controlled study of recombinant factor VII in severe trauma that utilized guidelines for damage control, transfusions, and mechanical ventilation. Vanderbilt Coordinating Center reviewed compliance in near real-time and reported deviations classified as minor, moderate, or major to investigators. Multivariate regression analysis measured the association between outcomes (30-day and 90-day mortality, development of multiple organ failure, ventilator-free days, renal failure-free days, and blood products transfused) and compliance with each guideline, as well as a composite assessment of overall compliance. SETTING: One hundred hospitals in 26 countries. PATIENTS: Blunt and/or penetrating trauma patients aged 18-70 yrs who had received 4-8 units of red blood cells for active torso and/or proximal lower extremity bleeding despite standard interventions. MEASUREMENTS AND MAIN RESULTS: When assessed as composite end point, major deviations from guidelines were associated with significantly higher mortality at 30 and 90 days after injury and fewer renal failure-free days. Moderate deviations were associated with a significantly higher risk of multiple organ failure and fewer ventilator-free days. Moderate and major deviations from damage control and ventilation guidelines were also significantly associated with higher risk of death at days 30 and 90. Within the ventilation protocol, noncompliance with tidal volume and plateau pressure targets was associated with significantly higher mortality at days 30 and 90 and fewer ventilator-free days, whereas noncompliance with weaning guideline was only associated with significantly fewer ventilator-free days. CONCLUSIONS: : In a clinical trial of trauma patients, higher compliance with guidelines for damage control, transfusion, and ventilation management is associated with lower mortality and improved outcomes.

Neurological Impairment Among Survivors of Intracerebral Hemorrhage: The FAST Trial.

BACKGROUND: Intracerebral hemorrhage (ICH) is the deadliest and most disabling form of stroke. Little is known about the causes of persistent neurological impairment among ICH survivors. METHODS: Factor seven for acute hemorrhagic stroke (FAST) was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 122 sites in 22 countries. Neurological impairment was evaluated according to the NIHSS in all patients at hospital admission, and at days 1, 2, 3, 15 and day 90 after ICH onset. Multivariate stepwise logistic regression was applied to identify predictors of neurological impairment 90 days after hospital admission. RESULTS: A total of 821 patients were enrolled; 638 survivors were evaluated with the NIHSS at day 90. Mean NIHSS score at admission was 13.2 (SD 6.6), decreasing to 9.6 (SD 7.7) at day 15 and 5.1 (SD 5.5) at day 90. Twenty-five percent of patients had severe neurological impairment (NIHSS ≥ 15) at baseline compared to 6% of those alive at day 90. Neurological worsening within the first 72 h (defined as worsening of GCS of two or more points or increase in NIHSS score ≥ 4) predicted greater neurological impairment at day 90 in all models. A decrease of <10% in systolic blood pressure (SBP) within the first 24 h was significantly associated with less severe neurologic impairment compared to more severe reductions. CONCLUSION: Neurological deterioration within 24 h of ICH onset is a powerful determinant of persistent neurological impairment. Careful reduction of the SBP by 1­10% in the first 24 h may lower the risk.

Increased chest tube drainage is independently associated with adverse outcome after cardiac surgery.

OBJECTIVE: To investigate the clinical relevance of specific volume criteria for hemorrhage in a patient population undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A retrospective analysis; postoperative hemorrhage was defined by a fixed set of criteria ≥200 mL/h in any 1 hour or part thereof, or (2) ≥2 mL/kg/h for 2 consecutive hours in the first 6 hours after surgery. Classification and regression tree (CART) analysis were used to validate the results of the specific volume criteria. Multivariate regression analysis was applied to investigate the association of specific volume criteria for hemorrhage with clinical outcomes. SETTING: A university hospital. PARTICIPANTS: All adult cardiac surgery patients undergoing surgery with CPB at the authors' center in 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,188 patients underwent cardiac surgery, and 76 patients (6.4%) experienced postoperative hemorrhage according to the fixed criteria for blood loss. Blood loss as measured by these criteria was associated with a higher 30-day mortality (odds ratio [OR] = 2.9, p < 0.001), incidence of stroke (OR = 3.3, p = 0.0033), re-exploration (OR = 103.655, p < 0.0001), intensive care unit stay >72 hours (OR = 1.3, p < 0.0001), and mechanical ventilation >24 hours (OR = 3.4, p = 0.0002). The clinical relevance of these criteria is supported by CART analysis. CONCLUSIONS: Postoperative hemorrhage (drainage loss) exceeding 200 mL/h in 1 hour or 2 mL/kg for 2 consecutive hours occurring within 6 hours after cardiac surgery is associated with higher 30-day mortality and other postoperative complications. Further research is needed to validate these results.

Quality of life after severe trauma: results from the global trauma trial with recombinant Factor VII.

BACKGROUND: Physical disability and psychologic morbidity are frequent and important complications of severe trauma injury with serious consequences for long-term health-related quality of life (HRQOL). Little prospective data exist, however, in a global trauma population on the risk factors for poor HRQOL. METHODS: The CONTROL trial was a prospective, randomized, double-blinded, multicenter, placebo-controlled trial conducted from August 2005 to September 2008. HRQOL was assessed 3 months after injury using the Polytrauma Outcome Chart (Glasgow Outcomes Scale, Short Form 36, European Quality of Life-5 Dimensions (EQ-5D), and Trauma Outcome Profile). Multivariate stepwise regression analysis identified predictors of poor HRQOL. RESULTS: Three hundred forty-seven (72%) patients completed at least one HRQOL instrument. Three percent had an EQ-5D score <0 (worse than death); 92% had a score <0.87 (average score in the general population). All HRQOL instruments identified physical functioning and activities of daily living as the dimensions of health most significantly affected by trauma injury. Mental functioning was also significantly affected according to the Trauma Outcome Profile. Independent predictors of poor HRQOL were higher age, female gender, extremity injury, blunt injury, intensive care unit stay >3 days, repeated nonadherence to transfusion guidelines, and inability to work postinjury. CONCLUSIONS: Three months after severe trauma injury, survivors report very poor HRQOL. Physical wellbeing is generally more negatively affected than mental wellbeing. A trauma-specific HRQOL instrument reveals more diverse mental health problems than generic instruments. In a global trauma population, postinjury HRQOL is predicted by demographic and socioeconomic characteristics, type of injury, and treatment received.

Neurosurgical outcomes after intracerebral hemorrhage: results of the Factor Seven for Acute Hemorrhagic Stroke Trial (FAST).

The value of neurosurgical interventions after spontaneous intracerebral hemorrhage (SICH) is uncertain. We evaluated clinical outcomes in patients diagnosed with SICH within 3 hours of symptom onset who underwent hematoma evacuation or external ventricular drainage (EVD) of the hematoma in the Factor Seven for Acute Hemorrhagic Stroke Trial (FAST). FAST was a randomized, multicenter, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. Neurosurgical procedures (hematoma evacuation and external ventricular drainage) performed at any point after hospital admission were prospectively recorded. Clinical outcomes evaluated were post-SICH disability, as assessed by the modified Rankin Scale; neurologic impairment, as assessed by the National Institutes of Health Stroke Scale; and mortality at 90 days after SICH onset. The impact of neurosurgical procedures on clinical outcomes was evaluated using multivariate logistic regression analysis, controlling for relevant baseline characteristics. Fifty-five of 821 patients underwent neurosurgery. Patients who underwent hematoma evacuation or EVD were on average younger, had greater baseline neurologic impairment, and lower levels of consciousness compared with patients who did not undergo neurosurgery. After adjusting for these differences and other relevant baseline characteristics, we found that neurosurgery was generally associated with unfavorable outcomes at day 90. Among the patients who underwent hematoma evacuation, those with lobar ICH had less ICH expansion than those with deep gray matter ICH, and the smaller expansion was associated with lower mortality. ICH volume was substantially decreased in patients who underwent hematoma evacuation between 24 and 72 hours after hospital admission, and this was associated with better clinical outcome. In conclusion, a small number of patients who underwent neurosurgery in FAST exhibited no overall clinical benefit from neurosurgical intervention, although outcomes varied by type of surgery, time of surgery, and hematoma location. Our findings support the need for further research into the value of neurosurgery in patients with SICH.

Global differences in causes, management, and survival after severe trauma: the recombinant activated factor VII phase 3 trauma trial.

BACKGROUND: Little is known about international variation in mortality after severe trauma. This study examines variation in mortality, injury severity, and case management among countries from a recent prospective multinational trauma trial. METHODS: This trauma trial was a prospective, randomized, double-blinded, multicenter comparison of recombinant activated factor VII versus placebo in severely injured bleeding trauma patients. Differences in baseline patient characteristics, case management, and clinical outcomes were examined for the 11 countries recruiting most patients. Between-country differences in mortality were examined using regression analysis adjusting for case mix and case management differences. Global predictors of mortality were also identified using multivariate regression analysis. RESULTS: Significant differences were observed between countries in unadjusted mortality rates at 24 hours (p = 0.025) and 90 days (p < 0.0001). When adjusting for differences in case mix and case management, the between country differences in mortality at 24 hours and 90 days remained significant. Consistent independent predictors of 24-hour, 24-hour to 90-day, and 90-day mortality were admission lactate >or=5 mmol/L (odds ratio: 9.06, 3.56, and 5.39, respectively) and adherence to clinical management guidelines (odds ratio: 4.92, 5.90, and 3.26, respectively). On average, the damage control surgery guideline was less well adhered to than the RBC transfusion and ventilator guidelines. There was statistically significant variation between countries with respect to adherence to the RBC transfusion guideline. CONCLUSIONS: Considering international variation in mortality when designing or interpreting results from multinational trauma studies is important. Significant differences in mortality persisted between patients from different countries after case mix and case management adjustment. Adherence to clinical guidelines was associated with improved survival. Stratification, case mix adjustment, and use of guidelines on damage control surgery, transfusion, and ventilation may mitigate country-driven variation in mortality.

Information and communications technology in U.S. health care: why is adoption so slow and is slower better?

Politicians across the political spectrum support greater investment in health care information and communications technology (ICT) and expect it to significantly decrease costs and improve health outcomes. We address three policy questions about adoption of ICT in health care: First, why is there so little adoption? Second, what policies will facilitate and accelerate adoption? Third, what is the best pace for adoption? We first describe the unusual economics of ICT, particularly network externalities, and then determine how those economics interact with and are exacerbated by the unusual economics of health care. High replacement costs and the need for technical compatibility are general barriers to ICT adoption and often result in lock-in to adopted technologies. These effects are compounded in health care because the markets for health care services, health insurance, and labor are interlinked. In addition, the government interacts with all markets in its role as an insurer. Patient heterogeneity further exacerbates these effects. Finally, ICT markets are often characterized by natural monopolies, resulting in little product diversity, an effect ill-suited to patient heterogeneity. The ongoing process for setting technical standards for health care ICT is critical but needs to include all relevant stakeholders, including patient groups. The process must be careful (i.e., slow), flexible, and allow for as much diversity as possible. We find that waiting to adopt ICT is a surprisingly wise policy.

Costs of excessive postoperative hemorrhage in cardiac surgery.

BACKGROUND: Excessive postoperative hemorrhage in cardiac surgery is a serious clinical complication placing substantial demands on hospital resources. This study quantifies the exact impact of postoperative hemorrhage on hospital costs in Germany. METHODS: We retrospectively analyzed data collected prospectively in the Quality Assurance Database at the Heart Center of the Klinikum Augsburg, Germany. All relevant perioperative data for resources consumption were analyzed and compared in patients with and without excessive postoperative hemorrhage in cardiac surgery. Multivariate regression analysis identified the incremental costs of postoperative hemorrhage while adjusting for potential confounding. RESULTS: A total of 1118 patients had cardiac surgery between January and December 2006. Six percent were identified with excessive postoperative hemorrhage. The risk of experiencing a postoperative complication (including death) (P < .0001), returning to operating room for reexploration (P < .0001), staying in intensive care unit for longer than 72 hours (P < .0001), receiving ventilation for longer than 24 hours (P < .0001), and receiving any kind of postoperative blood transfusion (P < .0001) was significantly higher in patients with excessive postoperative hemorrhage. Twenty-two percent of patients with excessive postoperative hemorrhage died compared with 6% of the patients without excessive postoperative hemorrhage (P < .0001). When adjusting for potential confounding factors, the incremental costs of excessive postoperative hemorrhage was euro6251 (95% confidence interval, 4594-7909). CONCLUSIONS: The average hospital costs related to excessive postoperative hemorrhage in cardiac surgery in Germany are substantial and associated with a significant risk of postoperative complications and death. Clinical interventions that can effectively prevent or address excessive postoperative hemorrhage in cardiac surgery are likely to have substantial cost-effectiveness potential.

Global differences in patient characteristics, case management and outcomes in intracerebral hemorrhage: the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial.

BACKGROUND: The outcomes after stroke vary considerably between countries, yet the extent of the variation after intracerebral hemorrhage (ICH) remains unknown. This study examines differences in outcomes after ICH in a recent multinational trial, and explores the effect of differences in patient severity and case management for the variations observed. METHODS: Factor Seven for Acute Hemorrhagic Stroke was a randomized, multinational, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. We investigated differences in baseline patient characteristics, case management and clinical outcomes across the 14 highest recruiting countries. Between-country differences in mortality and functional outcomes were examined using regression analysis while adjusting for differences in observed patient severity (case mix) and case management. RESULTS: Eight hundred and one patients had complete data on baseline characteristics, case management and clinical outcomes and were recruited in a country that contributed >or=20 patients to the trial. Significant differences were observed between the countries in unadjusted mortality rates (p = 0.001) and functional outcomes (p = 0.001) at 90 days after ICH onset. When first adjusting for differences in case mix, and secondly differences in case management, the differences in outcomes remained significant, yet the variation between countries was reduced with each level of adjustment. Significant determinants of mortality were age, baseline ICH and intraventricular hemorrhage volume, baseline neurological deficit, smoking status, use of mechanical ventilation, total length of hospital stay, reduction in blood pressure between 1 and 20% during the first 24 h of admission and edema management. Poor functional outcomes were also determined by age, baseline ICH volume and baseline neurological deficit as well as neurosurgical procedures performed and sedation during the first 5 days of admission. CONCLUSION: Significant global differences exist in the clinical outcomes after ICH, even after comprehensively adjusting for differences in case mix and case management. This is most likely due to unmeasured variation in case mix and case management. Similar research is encouraged in data sets of other multinational stroke trials to further investigate country-level and regional differences in clinical outcomes.

Quality of life after intracerebral hemorrhage: results of the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial.

BACKGROUND AND PURPOSE: Neurological impairment and physical disability are frequent and important complications of stroke with serious consequences for health-related quality of life (HRQOL). Little data exist, however, on the risk factors for poor HRQOL after intracerebral hemorrhage, the deadliest and most disabling form of stroke. METHODS: Factor Seven for Acute Hemorrhagic Stroke (FAST) was an international, randomized, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. All patients were followed for 3 months after stroke onset and HRQOL was assessed using the EuroQoL. Multivariate stepwise logistic regression was used to identify predictors of poor HRQOL based on demographic and clinical baseline characteristics and in-hospital complications. RESULTS: Six hundred fifty-seven patients survived until 3 months after stroke onset, and 621 (95%) completed the EuroQoL. Two percent had a utility score <0 (HRQOL worse than death), 15% a utility score <0.2, 32% a utility score <0.5, and 87% a score <0.87 (average score in the general population). At the other end of the scale, 13% had a utility score of 1 (perfect HRQOL). Independent predictors of poor HRQOL were advanced age (OR, 1.80; P<0.0001), higher baseline National Institutes of Health Stroke Scale score (OR, 1.11; P<0.0001), higher systolic blood pressure (OR, 1.05; P=0.0039), higher baseline intracerebral hemorrhage volume (OR, 1.11; P=0.015), deep (versus lobar) hematoma location (OR, 3.05; P=0.003), and increase in neurological deficit in first 72 hours after ICH onset (Delta Glasgow Coma Scale >or=2 or Delta National Institutes of Health Stroke Scale >or=4; OR, 2.04; P=0.006). The model explained a large amount of the variation in the utility score (C-statistic 0.77). CONCLUSIONS: The vast majority of survivors after intracerebral hemorrhage have very poor HRQOL. Critical care interventions designed to control blood pressure or prevent neuroworsening may improve HRQOL in intracerebral hemorrhage survivors.

Depressed mood after intracerebral hemorrhage: the FAST trial.

BACKGROUND AND PURPOSE: Depression is a frequent and important complication of stroke. Few data exist on the prevalence of depression/depressed mood after intracerebral hemorrhage (ICH) and the relationship between depression/depressed mood and the quality of life (QoL) more generally experienced by survivors of ICH. METHODS: Factor Seven for Acute Hemorrhagic Stroke (FAST) was a randomized, multicenter, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. All patients were evaluated at day 90 after ICH onset for depressed mood and QoL with the Hamilton Depression Rating Scale (HDRS) and the EuroQoL, respectively. Multivariate stepwise logistic regression was used to develop a predictive model for depressed mood at day 90. Relationships between HDRS and EuroQoL scores at day 90 were evaluated with Spearman correlation coefficients. RESULTS: 657 patients were alive at 3 months after ICH onset; 596 (91%) completed the HDRS. Twenty percent reported an HDRS score >10, indicating at least a minor degree of depressed mood; 6% endorsed symptoms of severely depressed mood. Significant predictors of depressed mood included comorbidities (p = 0.0022), moderate to severe neurological impairment according to the National Institutes of Health Stroke Scale (NIHSS) at day 15 (p = 0.0097), physical disability as measured by the Barthel Index (BI) at day 15 (p = 0.0486), and female gender (p = 0.04), but not hemorrhage severity or a history of depression. Irrespective of the presence of post-ICH disability and impairment, the severity of depressed mood at day 90 was significantly correlated with poor QoL. CONCLUSION: Depressed mood affects approximately 20% of ICH survivors and adversely affects QoL. Physicians should be vigilant to ensure that chronically ill and severely impaired survivors of ICH are adequately monitored and treated for depression after ICH.

Acute treatment costs of stroke in Brazil.

BACKGROUND AND PURPOSE: Although stroke is the leading cause of death in Brazil, little information exist on the acute treatment provided for stroke and its associated costs. This study addresses this gap by both clinically and economically characterizing the acute treatment of first-ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Brazil. METHODS: Retrospective medical chart review using data from two high-volume stroke centers in São Paulo, Brazil. Clinical and resource utilization data for all patients admitted to the stroke centers with a first-ever stroke between January 1, 2006 and May 31, 2007 were collected and the mean acute treatment costs per person were calculated by assigning appropriate unit cost data to all resource use. Cost estimates in Brazilian reals (BRL) were converted to US dollars (USD) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of mean cost estimate per person to national incidence data for the two types of stroke. The mean costs of acute treatment on a national scale were examined in sensitivity analysis. RESULTS: A total of 316 stroke patients were identified and their demographic and clinical characteristics, patterns of care, and outcomes were examined. Mean length of hospital stay was 12.0 +/- 8.8 days for ICH and 13.3 +/-23.4 days for IS. Ninety-one percent of the ICH patients and 68% of the IS patients were admitted to an intensive care unit (ICU). Mean total costs of initial hospitalization were USD 4,101 (SD +/-4,254) for ICH and USD 1,902 (SD +/-1,426) for IS. In multivariate analysis, hemorrhagic stroke, development of pneumonia, neurosurgical intervention, stay in ICU, and physical therapy were all significant independent predictors of acute treatment costs. Aggregate national health care expenditures for acute treatment of incident ICH were USD 122.4 million (range 30.8-274.2) and USD 326.9 million for IS (range 82.4-732.2). CONCLUSION: Acute treatment costs of incident ICH and IS in Brazil are substantial and primarily driven by the intensity of hospital treatment and in-hospital complications. With the expected increase in the incidence of stroke in Brazil over the coming decades, these results emphasize the need for effective preventive and acute medical care.

Cost-Drivers in Acute Treatment of Severe Trauma in Europe: A Systematic Review of Literature.

INTRODUCTION: Throughout the world, trauma is a leading cause of morbidity and mortality in the young and most active group of society. While specialist trauma centers play a critical role in the survival after severe trauma, the assessment of trauma-related costs, budgeting for adequate trauma capacity, and determining the cost-effectiveness of interventions in critical care are fraught with difficulties. Through a systematic review of the European literature on severe trauma, we aimed to identify the key elements that drive the costs of acute trauma care. METHODS: A PubMed/MEDLINE search for articles relating the costs and economics of trauma was performed for the period January 1995 to July 2007. One hundred and seventy-three European publications were identified. Twelve publications were retrieved for complete review that provided original cost data, a breakdown of costs according to the different elements of trauma care, and focused on severe adult polytrauma. The identified publications presented studies from the UK (3), Germany (6), Italy (2), and Switzerland (1). RESULTS: In all publications reviewed, length of stay in the intensive care unit (ICU; 60%) and requirements for surgical interventions (≤ 25%) were the key drivers of hospital costs. The cost of transfusion during the initial rescue therapy can also be substantial, and in fact represented a significant portion of the overall cost of emergency and ICU care. Multiple injuries often require multiple surgical interventions, and prolonged ICU and hospital stay, and across all studies a clear relationship was observed between the severity of polytrauma injuries observed and overall treatment costs. While significant differences existed in the absolute costs of trauma care across countries, the key drivers of costs were remarkably similar. CONCLUSIONS: Irrespective of the idiosyncrasies of the national healthcare systems in Europe, severity of injury, length of stay in ICU, surgical interventions and transfusion requirements represent the key drivers of acute trauma care for severe injury.

Risk of thromboembolic complications after intracerebral hemorrhage according to ethnicity.

INTRODUCTION: Incidence of thromboembolic (TE) disease varies with race and ethnicity yet little is known about whether these differences also apply to the poststroke period. We review the literature and compare published data with observations from two recent global trials on intracerebral hemorrhage (ICH). METHODS: A systematic review of the literature in EMBASE/Medline identified relevant articles. Published data were compared to the TE events--myocardial infarction (MI), cerebral infarction (CI), deep venous thrombosis (DVT), and pulmonary embolism (PE)--observed among placebo patients in two trials investigating the efficacy and safety of recombinant factor VIIa (rFVIIa) (Novo Nordisk A/S, Denmark) in the treatment of spontaneous ICH. The relative risk of TE complications after ICH was estimated for blacks/African Americans and Asians after adjustment for relevant risk factors. RESULTS: Only four relevant studies on TE disease after stroke were identified with data limited to poststroke MI and CI in a mixture of ischemic stroke and ICH patient populations. In the literature, blacks/African Americans appear to have a lower incidence rate of cardiac and cerebro-vascular complications after stroke, and Asians have a higher incidence rate of recurrent strokes, compared with Caucasians. In the two global trials, the overall poststroke incidence rates of MI, CI, DVT, and PE at 3 months after ICH onset were 2.3%, 2.0%, 3.7%, and 1.1%, respectively. After adjustment for differences in baseline risk factors, blacks/African Americans had a significantly higher risk of developing DVT compared with Caucasians (OR=5.64, P=0.0334), while Asians had a strong trend toward a higher risk of DVT (odds ratio=3.22, P=0.0932). The adjusted relative risk of PE, CI, and MI was not significantly different across ethnicities. CONCLUSION: This is the first study to specifically examine the risk of TE complications in the post-ICH period according to ethnicity. In a limited ICH population, we observed a significantly higher risk of DVT in blacks/African Americans compared with Caucasians after adjustment for differences in risk factors. We observed nonsignificant trends toward differences in the relative risk of MI, CI, or PE across ethnicities.

Association between disability measures and short-term health care costs following intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Small improvements in clinical outcomes after intracerebral hemorrhage (ICH) can have a substantial impact on overall health care costs, yet little data exists on the costs associated with the most commonly studied clinical outcomes in this type of stroke. METHODS: The Factor Seven for Acute Hemorrhagic Stroke (FAST) trial was a randomized, multicenter, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries. The resource utilization associated with health care services was prospectively recorded in all patients up to day 90 after stroke onset. Measures of disability included the modified Rankin Scale (mRS), and the Barthel Index (BI), while the National Institutes of Health Stroke Scale (NIHSS) measured neurological impairment. Relationships among resource use, health care costs, and disability/impairment were evaluated using one-way ANOVA with Bonferroni testing. RESULTS: A total of 820 patients had complete data. Length of stay (LOS) and total costs varied significantly by mRS scores at 90 days (P < 0.0001). Mean LOS for mRS scores 0-5 and dead were 16, 29, 40, 61, 80, 79, and 14 days, respectively; all categories of mRS had significantly different total LOS from their adjacent categories except mRS 0-1 and mRS 4-5. Mean total costs were $9,500, $15,500, $18,700, $27,400, $27,300, $27,300, and $8,100, respectively; costs rose incrementally up to mRS 3, but were not significantly different for mRS 3, 4, and 5. Total LOS and total costs varied significantly by the Barthel Index scores (P < 0.0001) and NIHSS scores (P < 0.0001), yet significant incremental differences were only observed for the Barthel Index. CONCLUSION: Health care costs vary significantly by levels of disability as measured by the mRS, but costs do not vary across the full range of mRS outcomes. The mRS is more informative than the Barthel index and NIHSS for discriminating the resource use and costs associated with different levels of disability after ICH.

Valuing lives and life years: anomalies, implications, and an alternative.

Many government interventions seek to reduce the risk of death. The value of preventing a fatality (VPF) is the monetary amount associated with each statistical death that an intervention can be expected to prevent. The VPF has been estimated using a preference-based approach, either by observing market behaviour (revealed preferences) or by asking hypothetical questions that seek to replicate the market (stated preferences). The VPF has been shown to differ across and within these methods. In theory, the VPF should vary according to factors such as baseline and background risk, but, in practice, the estimates vary more by theoretically irrelevant factors, such as the starting point in stated preference studies. This variation makes it difficult to choose one unique VPF. The theoretically irrelevant factors also affect the estimates of the monetary value of a statistical life year and the value of a quality-adjusted life year. In light of such problems, it may be fruitful to focus more research efforts on generating the VPF using an approach based on the subjective well-being associated with different states of the world.

Ischemic stroke and intracerebral hemorrhage: the latest evidence on mortality, readmissions and hospital costs from Scotland.

BACKGROUND AND PURPOSE: Stroke is the third leading cause of death in the UK, yet little information exists on current treatment patterns, outcomes and costs. This study assessed survival, readmissions and total hospital costs over 12 months in patients with first-ever intracerebral hemorrhage (ICH) or ischemic stroke (IS) in Scotland. METHODS: Hospital-based retrospective inception cohort design using data from the Hospital Record Linkage System in the National Health Service in Scotland. Survival, readmissions and total hospital costs were evaluated in all patients admitted to hospital for ICH or IS from April 1, 2004, to March 31, 2005. RESULTS: A total of 1,016 patients with ICH and 4,295 with IS were identified. The average age was 67.6 years (SD 14.5) for ICH and 70.4 years (SD 12.7) for IS at stroke onset. In-hospital mortality was 45.2% (95% confidence interval, CI, 41.0-49.3) for ICH and 15.6% (95% CI, 14.4-16.7) for IS, while 52.5% (95% CI, 48.0-56.9) and 27.2% (95% CI, 25.7-28.8), respectively, were dead at 1 year after stroke onset. The cumulative 1-year risk of rehospitalization for stroke and severe cardiac events was 15.0 and 1.0% in the ICH cohort, respectively, and 10.8 and 1.5% in the IS cohort. The average length of initial hospital stay was 38.4 days for ICH and 39.3 days for IS. The average total hospital costs over 12 months were GBP 13,960 (SD 21,487) for ICH and GBP 14,051 (SD 17,850) for IS. CONCLUSION: Individuals experiencing an ICH continue to exhibit a much worse prognosis than IS, and both forms of stroke continue to imply significant hospital costs to the National Health Service in Scotland.

Outcomes and costs of penetrating trauma injury in England and Wales.

BACKGROUND: Penetrating trauma injury is generally associated with higher short-term mortality than blunt trauma, and results in substantial societal costs given the young age of those typically injured. Little information exists on the patient and treatment characteristics for penetrating trauma in England and Wales, and the acute outcomes and costs of care have not been documented and analysed in detail. METHODS: Using the Trauma Audit Research Network (TARN) database, we examined patient records for persons aged 18+ years hospitalised for penetrating trauma injury between January 2000 and December 2005. Patients were stratified by injury severity score (ISS). RESULTS: 1365 patients were identified; 16% with ISS 1-8, 50% ISS 9-15, 15% ISS 16-24, 16% ISS 25-34, and 4% with ISS 35-75. The median age was 30 years and 91% of patients were men. Over 90% of the injuries occurred in alleged assaults. Stabbings were the most common cause of injury (73%), followed by shootings (19%). Forty-seven percent were admitted to critical care for a median length of stay of 2 days; median total hospital length of stay was 7 days. Sixty-nine percent of patients underwent at least one surgical procedure. Eight percent of the patients died before discharge, with a mean time to death of 1.6 days (S.D. 4.0). Mortality ranged from 0% among patients with ISS 1-8 to 55% in patients with ISS>34. The mean hospital cost per patient was pound 7983, ranging from pound 6035 in patients with ISS 9-15 to pound 16,438 among patients with ISS>34. Costs varied significantly by ISS, hospital mortality, cause and body region of injury. CONCLUSION: The acute treatment costs of penetrating trauma injury in England and Wales vary by patient, injury and treatment characteristics. Measures designed to reduce the incidence and severity of penetrating trauma may result in significant hospital cost savings.

Outcomes and costs of blunt trauma in England and Wales.

BACKGROUND: Trauma represents an important public health concern in the United Kingdom, yet the acute costs of blunt trauma injury have not been documented and analysed in detail. Knowledge of the overall costs of trauma care, and the drivers of these costs, is a prerequisite for a cost-conscious approach to improvement in standards of trauma care, including evaluation of the cost-effectiveness of new healthcare technologies. METHODS: Using the Trauma Audit Research Network database, we examined patient records for persons aged 18 years and older hospitalised for blunt trauma between January 2000 and December 2005. Patients were stratified by the Injury Severity Score (ISS). RESULTS: A total of 35,564 patients were identified; 60% with an ISS of 0 to 9, 17% with an ISS of 10 to 16, 12% with an ISS of 17 to 25, and 11% with an ISS of 26 to 75. The median age was 46 years and 63% of patients were men. Falls were the most common cause of injury (50%), followed by road traffic collisions (33%). Twenty-nine percent of patients were admitted to critical care for a median length of stay of 4 days. The median total hospital length of stay was 9 days, and 69% of patients underwent at least one surgical procedure. Seven percent of the patients died before discharge, with the highest proportion of deaths among those in the ISS 26-75 group (32%). The mean hospital cost per person was 9,530 pounds sterling (+/- 11,872). Costs varied significantly by Glasgow Coma Score, ISS, age, cause of injury, type of injury, hospital mortality, grade and specialty of doctor seen in the accident and emergency department, and year of admission. CONCLUSION: The acute treatment costs of blunt trauma in England and Wales vary significantly by injury severity and survival, and public health initiatives that aim to reduce both the incidence and severity of blunt trauma are likely to produce significant savings in acute trauma care. The largest component of acute hospital cost is determined by the length of stay, and measures designed to reduce length of admissions are likely to be the most effective in reducing the costs of blunt trauma care.