Virtual pharmaceutical companies: collaborating flexibly in pharmaceutical development.

Research and development (R&D) collaborations represent one approach chosen by the pharmaceutical industry to tackle current challenges posed by declining internal R&D success rates and fading of the blockbuster model. In recent years, a flexible concept to collaborate in R&D has emerged: virtual pharmaceutical companies (VPCs). These differ from other R&D companies, such as biotech start-ups, collaborating with big pharmaceutical companies, because they solely comprise experienced teams of managers. VPCs have only been described anecdotally in literature. Thus, we present here the characteristics of a VPC and suggest how big pharma can leverage the concept of VPCs by introducing five possible modes of collaboration. We find that one mode, investing, is particularly promising for big pharma.

Is the intraosseous access route fast and efficacious compared to conventional central venous catheterization in adult patients under resuscitation in the emergency department? A prospective observational pilot study.

BACKGROUND: For patients' safety reasons, current American Heart Association and European Resuscitation Council guidelines recommend intraosseous (IO) vascular access as an alternative in cases of emergency, if prompt venous catheterization is impossible. The purpose of this study was to compare the IO access as a bridging procedure versus central venous catheterization (CVC) for in-hospital adult emergency patients under resuscitation with impossible peripheral intravenous (IV) access. We hypothesised, that CVC is faster and more efficacious compared to IO access. METHODS: A prospective observational study comparing success rates and procedure times of IO access (EZ-IO, Vidacare Corporation) versus CVC in adult (>/=18 years of age) patients under trauma and medical resuscitation admitted to our emergency department with impossible peripheral IV catheterization was conducted. Procedure time was defined from preparation and insertion of vascular access type until first drug or infusion solution administration. Success rate on first attempt and procedure time for each access route was evaluated and statistically tested. RESULTS: Ten consecutive adult patients under resuscitation, each receiving IO access and CVC, were analyzed. IO access was performed with 10 tibial or humeral insertions, CVC in 10 internal jugular or subclavian veins. The success rate on first attempt was 90% for IO insertion versus 60% for CVC. Mean procedure time was significantly lower for IO cannulation (2.3 min +/- 0.8) compared to CVC (9.9 min +/- 3.7) (p < 0.001). As for complications, failure of IO access was observed in one patient, while two or more attempts of CVC were necessary in four patients. No other relevant complications, like infection, bleeding or pneumothorax were observed. CONCLUSION: Preliminary data demonstrate that IO access is a reliable bridging method to gain vascular access for in-hospital adult emergency patients under trauma or medical resuscitation with impossible peripheral IV access. Furthermore, IO cannulation requires significantly less time to enable administration of drugs or infusion solutions compared to CVC. Because CVC was slower and less efficacious, IO access may improve the safety of adult patients under resuscitation in the emergency department.

Celiac dissection after blunt abdominal trauma complicated by acute hepatic failure: case report and review of literature.

Injuries of the abdominal visceral vessels are uncommon but devastating entities resulting in extremely high rates of mortality. The most common cause of abdominal vascular injuries is penetrating trauma, accounting for 90% to 95% of these injuries. In contrast, blunt trauma accounts for 5% to 10% of all abdominal vascular lesions. Although traumatic injury to the celiac artery is among the rarest of all vascular injuries, mortality can be as high as 75%. We report a 66-year-old patient who sustained multiple injuries in a motor vehicle crash. The initial whole-body computed tomography (CT) scan revealed a combination of severe brain injury and bilateral thoracic lesions. On day 6 after the accident, the patient's clinical situation deteriorated rapidly. At this time, the abdominal arterial CT scan showed a dissection of the celiac artery. Therapeutic anticoagulation was not feasible because of the intracranial hemorrhage. Also the patient's clinical situation worsened so rapidly that interventional therapy, including surgical and endovascular treatment, could not be performed. Finally, the patient died of fulminant hepatic failure, therefore not surviving a potentially treatable injury. The diagnosis of celiac artery dissection in this patient was significantly delayed because the initial trauma CT protocol did not include an arterial phase of the abdominal vessels.

Trauma surgeons' attitude towards family presence during trauma resuscitation: a nationwide survey.

OBJECTIVE: Trauma is the foremost cause of death in young patients. Not only the patient but also the family experience the consequences of trauma. Interactions of medical staff with family members in the emergency situation may fail psychological and emotional needs. In this context the concept of family presence (FP) during resuscitation is controversial. Therefore, the aim of this study was to analyse the attitude of trauma surgeons towards FP during trauma resuscitation. MATERIALS AND METHODS: A questionnaire concerning beliefs and attitudes towards FP during trauma resuscitation was mailed to level I trauma centres of the Trauma Network of the German Trauma Society (DGU). Statistical difference was determined by Rank-Sum test to analyse ordinal variables, for analysing three groups Kruskal-Wallis and Dunn's testing were used. Data are given in mean+/-S.D. or absolute percentage. RESULTS: The questionnaire was answered by 464 of 545 (85%) trauma surgeons between July 2005 and September 2005. One hundred and sixty seven surgeons (37.9%) already knew about FP, 349 (75.2%) considered it a relevant topic, but 232 (50%) would never allow FP during trauma resuscitation. One hundred and sixty eight surgeons (36.2%) had experience of FP during trauma resuscitation with positive results in 56%. Female respondents tend to be better informed about FP and would promote FP more supportively. Those women with experience with FP reported predominantly positive experiences (87% versus 50%, p<0.001). CONCLUSIONS: Our study investigated the factors affecting physicians' opinions towards FP. Any institutional FP programme will have to address physician objections to be successful, by recommending a well-designed, carefully structured protocol with a designated specially trained staff member to offer the family support and the option of entering the resuscitation room with permission of the staff.

Analysis of NF-kappaB nuclear translocation in PMN-neutrophils of major trauma patients in the early post-traumatic period: a pilot study.

BACKGROUND: Post-traumatic inflammation is connected to polymorphonuclear neutrophil (PMN)-dysfunction characterized by reduced nuclear translocation of NF-kappaB during the post-traumatic period. However, the dynamic of NF-kappaB translocation in PMN of major trauma patients remains unclear. Hence, the aim of this pilot study was to analyze NF-kappaB in PMN from multiply injured patients immediately after trauma. PATIENTS AND METHODS: Blood samples of major trauma patients (ISS > 16) were drawn on admission within 90 minutes after trauma and at 6, 12, 24, 48, and 72 hours after trauma. Neutrophilic NF-kappaB-translocation was analyzed by EMSA and quantified by densitometry as (arbitrary units). In addition, PMN of healthy volunteers were analyzed either in their native state (-control) or after LPS stimulation (+control). RESULTS: Twelve patients (NISS: 34 +/- 10 [mean +/- SEM]) were enrolled. NF-kappaB translocation was significantly increased in trauma patients on admission and after 6 hours. Interestingly, a second activity peak was present after 24 hours. In patients who later died, NF-kappaB activity was significantly elevated initially, to be rapidly diminished after 6 hours, while it increased in the survivors group. After 24 hours NF-kappaB activity increased significantly in the survivors group, to become reduced in both groups at a later time. CONCLUSIONS: Within this pilot study, the dynamic of NF-kappaB translocation in PMN of multiply injured patients immediately after trauma was analyzed for the first time. Enabled by closely matched sequential blood sampling strictly standardized to the traumatic event, an essential biphasic increase of neutrophilic signal transduction could be investigated in the very early post-traumatic period, which preceded the downregulation of the innate immune system.

Intrathecal and systemic concentration of NT-proBNP in patients with severe traumatic brain injury.

Outcome of patients suffering from traumatic brain injury (TBI) depends on the development of secondary brain damage. In this context, recent studies underlined the role of the natriuretic peptides- atrial natriuretic peptide and brain natriuretic peptide (BNP)-in aneurysmatic subarachnoidal hemorrhage (SAH). Especially BNP correlates with intracranial pressure and clinical outcome after SAH. Since its role in TBI remains unclear, the intracranial and systemic concentrations of N-terminal (NT)-proBNP were analyzed in patients suffering from severe TBI. We measured NT-proBNP levels in cerebrospinal fluid (CSF) and serum of 14 patients suffering from severe TBI (GCS15 mm Hg (n=6), the serum (800+/-150 pg/mL) and CSF levels (55+/-9 pg/mL) of NT-proBNP were significantly increased after 24 h, as compared to patients with ICP15 mm Hg. Further studies are currently performed to elucidate the physiologic role of NT-proBNP in TBI.

Initial posttraumatic translocation of NF-kappaB and TNF-alpha mRNA expression in peripheral blood monocytes of trauma patients with multiple injuries: a pilot study.

Post-traumatic inflammation is connected to monocyte dysfunction characterized by reduced NF-kappaB translocation during the first post-traumatic days. Because the exact dynamic of monocytic NF-kappaB translocation in patients directly after trauma remains unclear, the aim of this pilot study was to measure the intranuclear presence of NF-kappaB in monocytes from patients with multiple injuries initially after the trauma and during the early post-traumatic period and to compare these results with downstream-placed mRNA expression alteration of TNF-alpha, as well as with clinical data. Eleven patients were enrolled with an Injury Severity Score of 16 to 66 points, and blood samples were drawn on admission within 90 min and at 6, 12, 24, 48, and 72 h after trauma. NF-kappaB translocation of monocytic nuclear protein was analyzed by electrophoretic mobility shift assay and was quantified by densitometry as arbitrary units. In addition, monocytes of healthy volunteers were analyzed either native (-, control) or after LPS stimulation (+, control). For determination of downstream mRNA encoding for TNF-alpha, quantitative reverse transcriptase-PCR was performed. For both parameters, the negative control values were set as baseline (=1) and results from positive controls and patients were given as a relative alteration ratio without unit. Initial post-traumatic NF-kappaB translocation was significantly increased in trauma patients on admission (88 +/- 37) and 6 h after trauma (59 +/- 28) compared with the baseline level. In contrast, TNF-alpha mRNA was not increased on admission (1.7 +/- 0.9) and decreased even below baseline after 12 h. The substantial information of our study arises from the analysis of the dynamic of NF-kappaB translocation of monocytes. Enabled by closely matched sequential blood sampling strictly standardized to the traumatic event, an essential increase of monocytic signal transduction and transcription could be elucidated in the very early post-traumatic period, which precedes the down-regulation of the innate immune system.