Clinical and cost implications of amyloid beta detection with amyloid beta positron emission tomography imaging in early Alzheimer's disease - the case of florbetapir.

OBJECTIVE: Amyloid beta (Aß) positron emission tomography (PET) imaging helps estimate Aß neuritic plaque density in patients with cognitive impairment who are under evaluation for Alzheimer's disease (AD). This study aims to evaluate the cost-effectiveness of the Aß-PET scan as an adjunct to standard diagnostic assessment for diagnosis of AD in France, using florbetapir as an example. METHODS: A state-transition probability analysis was developed adopting the French Health Technology Assessment (HTA) perspective per guidance. Parameters included test characteristics, rate of cognitive decline, treatment effect, costs, and quality of life. Additional scenarios assessed the validity of the analytical framework, including: (1) earlier evaluation/treatment; (2) cerebrospinal fluid (CSF) as a comparator; and (3) use of other diagnostic procedures. Outputs included differences in quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). All benefits and costs were discounted for time preferences. Sensitivity analyses were performed to assess the robustness of findings and key influencers of outcomes. RESULTS: Aß-PET used as an adjunct to standard diagnostic assessment increased QALYs by 0.021 years and 10 year costs by €470 per patient. The ICER was €21,888 per QALY gained compared to standard diagnostic assessment alone. When compared with CSF, Aß-PET costs €24,084 per QALY gained. In other scenarios, Aß-PET was consistently cost-effective relative to the commonly used affordability threshold (€40,000 per QALY). Over 95% of simulations in the sensitivity analysis were cost-effective. CONCLUSION: Aß-PET is projected to affordably increase QALYs from the French HTA perspective per guidance over a range of clinical scenarios, comparators, and input parameters.

Investigation of a bio-inspired lift-enhancing effector on a 2D airfoil.

A flap mounted on the upper surface of an airfoil, called a 'lift-enhancing effector', has been shown in wind tunnel tests to have a similar function to a bird's covert feathers, which rise off the wing's surface in response to separated flows. The effector, fabricated from a thin Mylar sheet, is allowed to rotate freely about its leading edge. The tests were performed in the NCSU subsonic wind tunnel at a chord Reynolds number of 4 × 10(5). The maximum lift coefficient with the effector was the same as that for the clean airfoil, but was maintained over an angle-of-attack range from 12° to almost 20°, resulting in a very gentle stall behavior. To better understand the aerodynamics and to estimate the deployment angle of the free-moving effector, fixed-angle effectors fabricated out of stiff wood were also tested. A progressive increase in the stall angle of attack with increasing effector angle was observed, with diminishing returns beyond the effector angle of 60°. Drag tests on both the free-moving and fixed effectors showed a marked improvement in drag at high angles of attack. Oil flow visualization on the airfoil with and without the fixed-angle effectors proved that the effector causes the separation point to move aft on the airfoil, as compared to the clean airfoil. This is thought to be the main mechanism by which an effector improves both lift and drag. A comparison of the fixed-effector results with those from the free-effector tests shows that the free effector's deployment angle is between 30° and 45°. When operating at and beyond the clean airfoil's stall angle, the free effector automatically deploys to progressively higher angles with increasing angles of attack. This slows down the rapid upstream movement of the separation point and avoids the severe reduction in the lift coefficient and an increase in the drag coefficient that are seen on the clean airfoil at the onset of stall. Thus, the effector postpones the stall by 4-8° and makes the stall behavior more gentle. The benefits of using the effector could include care-free operations at high angles of attack during perching and maneuvering flight, especially in gusty conditions.

Treatment patterns and resource use among patients with comorbid diabetes mellitus and major depressive disorder.

OBJECTIVE: To descriptively analyze patient characteristics, treatment patterns, and medical resource use of individuals with diabetes mellitus (DM) with and without comorbid major depressive disorder (MDD). RESEARCH DESIGN AND METHODS: Using an administrative claims database, commercially insured adults diagnosed with DM were studied over the calendar years 2005 and 2006. Demographic characteristics, comorbid illnesses, medication use, resource utilization, and costs were examined descriptively among patients with DM both with and without comorbid MDD. RESULTS: Patients with DM and MDD were found to have a high resource burden, compared to patients with DM without MDD. Specifically, these patients were found to be more likely to be diagnosed with other comorbid medical conditions, to use multiple medications, and to use more healthcare services such as inpatient visits, emergency admissions, and outpatient visits. Consistent with these findings, costs for these patients were found to be $19,707 per year, compared to $11,237 for patients with DM without comorbid MDD. LIMITATIONS: The study utilizes data from an administrative claims database of insured individuals and hence, results may not be generalizable. Furthermore, the analysis is unable to examine clinical severity or indirect costs. CONCLUSION: Compared to patients with DM and no comorbid MDD, patients with DM and MDD tend to have a larger burden of disease and to use more healthcare resources.

Transparent and open discussion of errors does not increase malpractice risk in trauma patients.

OBJECTIVE: We set out to determine if there is an increased medical malpractice lawsuit rate when trauma patient cases are presented at an open, multidisciplinary morbidity and mortality conference (M&M). INTRODUCTION: Patient safety proponents emphasize the importance of transparency with respect to medical errors. In contrast, the tort system focuses on blame and punishment, which encourages secrecy. Our question: Can the goals of the patient safety movement be met without placing care providers and healthcare institutions at unacceptably high malpractice risk? METHODS: The trauma registry, a risk management database, along with the written minutes of the trauma morbidity and mortality conference (M&M) were used to determine the number and incidence of malpractice suits filed following full discussion at an open M&M conference at an academic level I trauma center. RESULTS: A total of 20,749 trauma patients were admitted. A total of 412 patients were discussed at M&M conference and a total of seven lawsuits were filed. Six of the patients were not discussed at M&M prior to the lawsuit being filed. One patient was discussed at M&M prior to the lawsuit being filed. The incidence of lawsuit was calculated in three groups: all trauma patients, all trauma patients with complications, and all patients presented at trauma M&M conference. The ratio of lawsuits filed to patients admitted and incidence in the three groups is as follows: All Patients, 7 lawsuits/20,479 patients (4.25 lawsuits/100,000 patients/year); M&M Presentation, 1 lawsuit/421 patients (29.6 lawsuits/100,000 patients/year); All Trauma Complications, 7 lawsuits/6,225 patients (14 lawsuits/100,000 patients/year). Patients with a complication were more likely to sue (P < 0.01); otherwise, there were no statistical differences between groups. CONCLUSIONS: A transparent discussion of errors, complications, and deaths does not appear to lead to an increased risk of lawsuit.

Percutaneous tracheostomy: one center's experience with a new modality.

BACKGROUND: A retrospective review of our experience with percutaneous tracheostomy was performed to determine our complication rate and pattern of use since this modality was introduced at our institution. METHODS: A retrospective chart review captured all patients in whom tracheostomy was performed or supervised by a trauma/critical care faculty member. Dates of hospital admission, ICU admission, intubation, discontinuation of mechanical ventilation, type and location of procedure, procedural complications, Injury Severity Score, charges, and patient demographics were collected. Percutaneous tracheostomy (PT) and open tracheostomy (OT) experiences were compared. RESULTS: Three hundred sixty-eight tracheostomies were performed (190 OT and 178 PT). The average time to tracheostomy (TTT) for PT patients decreased from 12.7 to 7.4 days. The average TTT for OT patients remained stable at 14.0 days. The complication rate was 3.5%, with 4 complications (1.5%) associated with OT and 9 complications (5.1%) associated with PT. All complications in the PT group occurred before using a single dilator system. The 9 complications in the PT group occurred among 5 surgeons, all before their 11th attempt. PT saves 444 dollars in charges per procedure. CONCLUSION: OT continues to be a safe method of performing tracheostomies. PT has a steep learning curve but can be mastered quickly. Benefits include a shorter time to tracheostomy, elimination of patient transport, and saving in charges. Initial PT attempts should be supervised by an experienced surgeon.

Trauma surgery malpractice risk: perception versus reality.

OBJECTIVE: We set out to compare the malpractice lawsuit risk and incidence in trauma surgery, emergency surgery, and elective surgery at a single academic medical center. SUMMARY AND BACKGROUND DATA: The perceived increased malpractice risk attributed to trauma patients discourages participation in trauma call panels and may influence career choice of surgeons. When questioned, surgeons cite malpractice risk as a rationale for not providing trauma care. Little data substantiate or refute the perceived high trauma malpractice risk. We hypothesized that the malpractice risk was equivalent between an elective surgical practice and a trauma/emergency practice. METHODS: Three prospectively maintained institutional databases were used to calculate and characterize malpractice incidence and risk: a surgical operation database, a trauma registry, and a risk management/malpractice database. Risk groups were divided into elective general surgery (ELECTIVE), urgent/emergent, nontrauma general surgery (URGENT), and trauma surgery (TRAUMA). Malpractice claims incidence was calculated by dividing the total number of filed lawsuits by the total number of operative procedures over a 12-year period. RESULTS: Over the study period, 62,350 operations were performed. A total of 21 lawsuits were served. Seven were dismissed. Three were granted summary judgments to the defendants. Ten were settled with payments to the plaintiffs. One went to trial and resulted in a jury verdict in favor of the defendants. Total paid liability was 4.7 million dollars(391,667 dollars/year). Total legal defense costs were 1.3 million dollars(108,333 dollars/year). The ratio of lawsuits filed/operations performed and incidence in the 3 groups is as follows: ELECTIVE 14/39,080 (3.0 lawsuits/100,000 procedures/year), URGENT 5/17,958, (2.3 lawsuits/100,000 procedures/year), and TRAUMA 2/5312 (3.1/100,000 procedures/year). During the study period, there were an estimated 49,435 trauma patients evaluated. The incidence of malpractice lawsuits using this denominator is 0.34 lawsuits/100,000 patients/year. CONCLUSIONS: These data demonstrate no increased risk of lawsuit when caring for trauma patients, and the actual risk of a malpractice lawsuit was low.

Antisense oligonucleotide inhibition of Bcl-xL and Bid expression in liver regulates responses in a mouse model of Fas-induced fulminant hepatitis.

Activation of the cell-surface receptor Fas can lead to apoptosis in parenchymal cells in the liver, and if severe enough, result in fulminant hepatic failure and animal death. In the present study, we have examined the roles played by the Bcl-2 family members Bcl-xL and Bid in regulating this response. To do this, we have developed chemically modified 2'-O-(2-methoxy) ethyl antisense inhibitors of both Bid and Bcl-xL expression. In Balb/c mice, dosing with these antisense oligonucleotides reduced expression of the targeted mRNA by greater than 80% in the liver. This reduction was highly dependent upon oligonucleotide sequence and oligonucleotide dose. Reduction of Bcl-xL expression resulted in a potentiation of Fas-mediated apoptosis in liver and significant increase of the lethality of Fas-mediated fulminant hepatitis (p < 0.0001). In contrast, reduction of Bid expression protected the animals against Fas-mediated fulminant hepatitis and death (p < 0.0001). Simultaneous dosing of mice with Bcl-xL and Bid-targeting antisense oligonucleotides resulted in an inhibition of expression of both targeted proteins and protection of the animals from Fas-mediated apoptosis. These results demonstrate, for the first time, the role of Bcl-xL in regulating responses to proapoptotic Fas signaling in mouse liver. In addition, this is the first reported example demonstrating the ability of antisense inhibitors to reduce expression of multiple proteins in animals by simultaneous dosing.