Cost-effectiveness of activated protein C in real-life clinical practice

Background

Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.

Methods

We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.

Results

In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 ± 14.9 years, Simplified Acute Physiology Score II was 56.7 ± 18.5, and the number of organ failures was 3.20 ± 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (€47,870 versus €36,717, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: €20,278 per life-year gained and €33,797 per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay €50,000 per life-year gained. The probability was 64.3% if there were willingness to pay €50,000 per quality-adjusted life-year gained.

Conclusion

This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay €50,000 per life-year gained is 74.5%.     

Combined measurement of procalcitonin and soluble TREM-1 in the diagnosis of nosocomial sepsis

This prospective, non-interventional study was conducted in a medical adult intensive care unit to determine the usefulness of procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determinations in the diagnosis of nosocomial sepsis. Serum PCT and bronchoalveolar lavage fluid sTREM-1 concentrations were measured in 50 critically ill patients suffering from nosocomial sepsis. Ventilator-associated pneumonia (VAP) was diagnosed in 31 patients and extrapulmonary sepsis in 19. Increase serum PCT concentration (>0.15 ng/ml) was found in 44 (88%) patients and was higher in those suffering from a non-pulmonary sepsis. The concomitant BAL sTREM-1 determination correctly classified pulmonary (VAP) versus non-pulmonary origin in 41 out of 44 cases (93%). Even when PCT concentration remained low, sTREM-1 assessment allowed for the detection of the sepsis (VAP) in 50% of cases. Both PCT and sTREM-1 concentrations were low in only 3 patients (6%) in whom sepsis could have been missed if only diagnosed by the measurement of these 2 biomarkers. We therefore concluded that the combined measurement of serum PCT and BAL sTREM-1 concentrations could be of interest in detecting the presence of a nosocomial sepsis and in discriminating VAP versus extrapulmonary infection.     

Bayesian detection of abnormal hematological values to introduce a no-start rule for heterogeneous populations of athletes

Sports authorities exclude athletes with abnormal levels of blood parameters. Here, the consideration of longitudinal blood profiles together with heterogeneous factors such as ethnicity and age produces a model with enhanced sensitivity to detect blood doping. Sports disciplines with heterogeneous populations now have a general method to introduce the no-start rule.     

Subscapular artery Y-shaped flow-through muscle flap: a novel one-stage limb salvage procedure

OBJECTIVES: Major tissue loss caused by the critical limb ischemia requires improvement of distal perfusion and cover of large tissue defects. We propose a new method, the y-shaped subscapular artery flow-through (Y-SCAFT) muscle flap using the subscapular artery that yields an arterial graft and a free muscle flap sustained by a collateral branch of this artery. This prospective study evaluated the feasibility of this technique and analyzed wound healing, graft patency, and limb salvage. METHODS: Between 2002 and 2007, 20 patients, mean age 64 years (range, 55-79 years), were treated with this technique. All presented with critical ischemia and major tissue loss, with exposure of the tendons, bones, or joint, and were candidates for major amputation. Revascularization and cover of tissue loss with the same Y-SCAFT anatomic unit was used for all patients. The distal anastomosis was performed between the distal branch of the Y-SCAFT and the pedal artery in 9, posterior tibial artery in 4, peroneal artery in 1, lateral tarsal artery in 3, and the plantar artery in 3. In four patients, the distal part of the arterial graft, including the anastomosis, was covered with the muscle flap because the tissue loss was nearby. The proximal anastomosis was performed between a leg artery and the arterial graft in 10 patients. A venous graft was necessary in 10 patients to extend the bypass proximally. RESULTS: One patient died during the postoperative period. Duplex control evidenced patency all the Y-SCAFT muscle flaps. Healing was achieved in all patients. Mean follow-up was 31 months (range, 6-58 months). No patients died during follow-up. One patient presented occlusion of the Y-SCAFT muscle flap and underwent amputated. One patient had major amputation despite a patent graft. At 2 years, leg salvage was 85%, patency was 94%, and survival was 94%. At the end of the follow-up, 17 patients (1 death, 2 amputations) had a patent graft, a viable muscle flap, wound healing, and a functional leg. CONCLUSION: We showed the clinical feasibility of the technique of Y-SCAFT muscle flap, which allows for revascularization and cover of major tissue loss with one anatomic unit. This method is particularly useful in selected cases with poor run-off and large ischemic lesions.     

Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients

Introduction

A rational use of antibiotics is of paramount importance in order to prevent the emergence of multidrug resistant bacteria that can lead to therapeutic impasse, especially in intensive care units (ICUs). A de-escalation strategy is therefore naturally advocated as part of better antibiotics usage. However, the clinical impact of such a strategy has not been widely studied. We aimed to assess the feasibility and the clinical impact of a de-escalation strategy in a medical ICU and to identify factors associated when de-escalation was possible.

Methods

We performed a retrospective study of patients hospitalized in a medical ICU over a period of six months. Independent factors associated with de-escalation and its clinical impact were assessed.

Results

Two hundred and twenty-nine patients were included in the study. Antibiotics were de-escalated in 117 patients (51%). The appropriateness of initial antibiotic therapy was the only independent factor associated with the performance of de-escalation (OR = 2.9, 95% CI, 1.5-5.7; P = 0.002). By contrast, inadequacy of initial antibiotic therapy (OR = 0.1, 0.0 to 0.1, P <0.001) and the presence of multidrug resistant bacteria (OR = 0.2, 0.1 to 0.7, P = 0.006) prevented from de-escalation. There were no differences in terms of short (ICU) or long-term (at 1 year) mortality rates or any secondary criteria such as ICU length of stay, duration of antibiotic therapy, mechanical ventilation, incidence of ICU-acquired infection, or multi-drug resistant bacteria emergence.

Conclusions

De-escalation appears feasible in most cases without any obvious negative clinical impact in a medical ICU.     

Isolation of Francisella tularensis by Centrifugation of Shell Vial Cell Culture from an Inoculation Eschar

A 52-year-old man was admitted to the hospital following the development of an inoculation eschar and fever six days after being bitten by a tick. He was clinically diagnosed as suffering from rickettsiosis. Eschar biopsy cultures on standard bacteriological media remained sterile. However, inoculation of cells with the homogenized specimen by the centrifugation-shell vial technique (M. Marrero and D. Raoult, Am. J. Trop. Med. Hyg. 40:197–199, 1989) resulted in the recovery of a bacterium. Determination of the sequence of the 16S rRNA gene amplified from the organism and comparison of the sequence to other sequences identified it as a strain of Francisella tularensis, whereas the specific serology was still negative. Our findings demonstrate that the centrifugation-cell culture, which is a tool for investigation of tick-transmitted diseases, may have the potential to serve as a method for the cultural isolation of F. tularensis.