How to create innovation by building the translation bridge from basic research into medicinal drugs: an industrial perspective.

The global healthcare industry is undergoing substantial changes and adaptations to the constant decline of approved new medical entities. This decrease in internal research productivity is resulting in a major decline of patent-protected sales (patent cliff) of most of the pharmaceutical companies. Three major global adaptive trends as driving forces to cope with these challenges are evident: cut backs of internal research and development jobs in the western hemisphere (Europe and USA), following the market growth potential of Asia by building up internal or external research and development capabilities there and finally, 'early innovation hunting' with an increased focus on identifying and investing in very early innovation sources within academia and small start-up companies. Early innovation hunting can be done by different approaches: increased corporate funding, establishment of translational institutions to bridge innovation, increasing sponsored collaborations and formation of technology hunting groups for capturing very early scientific ideas and concepts. This emerging trend towards early innovation hunting demands special adaptations from both the pharmaceutical industry and basic researchers in academia to bridge the translation into new medicines which deliver innovative medicines that matters to the patient. This opinion article describes the different modalities of cross-fertilisation between basic university or publicly funded institutional research and the applied research and development activities within the pharmaceutical industry. Two key factors in this important translational bridge can be identified: preparation of both partnering organisations to open up for new and sometime disruptive ideas and creation of truly trust-based relationships between the different groups allowing long-term scientific collaborations while acknowledging that value-creating differences are an essential factor for successful collaboration building.

Death from cardiac failure in a child with ruptured cerebral arteriovenous malformation.

We present the case of a 13-year-old boy with a ruptured cerebral arteriovenous malformation who had rapidly progressive cardiac failure leading to death. Serial electrocardiograms, cardiac enzymes, echocardiograms, and pulmonary artery catheter data confirmed severe ventricular dysfunction related to myocardial ischemia and infarction. Cardiac dysfunction after cerebral insult is commonly described in adults with aneurysmal subarachnoid hemorrhage and has been termed "neurogenic stunned myocardium" because of its transient nature in most of patients. In children, cardiovascular dysfunction has been described in a few reports and only after traumatic brain injury. No deaths have been reported. This case report illustrates the potentially lethal consequences of cardiovascular dysfunction in children after ruptured cerebral arteriovenous malformation with subarachnoid hemorrhage. Compromised cardiac function should be considered during the early evaluation and management of these patients and supportive care instituted to limit secondary brain injury from poor perfusion.

Olfactory dysfunction: a sequela of pediatric blunt head trauma.

OBJECTIVE: To evaluate olfactory function in children with blunt head trauma. METHODS: Eligible subjects were consecutive children presenting at San Diego Children's Hospital Emergency Department or Trauma Service with blunt head trauma. Thirty-seven head injured children mean age 10.11+/-2.74 were evaluated; 36 healthy age and gender matched community children, mean age 10.08+/-2.99, served as controls. The medical record was reviewed for clinical measures related to head injury (HI). All children underwent olfactory assessment with the San Diego Children's Odor Identification Test (SDOIT). Olfactory event-related potentials were recorded on a subset of head injured and control children. RESULTS: Three of 37 head injured children had olfactory dysfunction. The head injured hyposmics had signs of more severe head injury represented by lower Glasgow Coma Scores (GCS), 10.33+/-5.51, when compared to their normosmic counterparts with mean GCS of 14.06+/-2.82. When stratifying the head injured children by clinical measures, lower Glasgow Coma Score, and abnormalities on head CT scan were associated with poorer olfactory performance. CONCLUSION: Children with blunt head injury may suffer post-traumatic olfactory impairment. More severe head injuries are more likely to produce olfactory deficits. In cases of significant head injury, cranial nerve I evaluation is imperative.