An intellectual property primer.

While many may think of it as an "invention" of the modern age, intellectual property ("IP") has existed since at least as early as the 17th Century with the advent of the Statute of Monopolies in the U.K. Intellectual property has evolved significantly since then into an important aspect of modern day society touching all of our lives in some form or another Canadian health care in the 21st Century is no exception. This article attempts to provide health care professionals who may not be familiar with this subject matter with a general overview of what is "intellectual property". Many readers may be aware ofintellectual property on some level but may not understand how the various types of IP function and interrelate, as well as the possible impact on the nature and scope of health care services. The purpose of this article is to attempt to provide the reader with the tools, definition and 'jargon" to understand IP so that they can appreciate the issues discussed in greater detail in the remaining papers of this special edition.

The impact of intellectual property rights on health care in Canada.

Advances in biotechnology can lead to promising disease treatments and medicines. In order for these advances to reach fruition, however; there must be an incentive to incur the significant costs associated with the developments. Intellectual Property ("IP") regimes, particularly patents, are crucial in this regard. The limited monopolies offered by patent rights serve as an incentive to develop technology. The benefits of securing future advancements need, however, to be balanced with the exclusivity of IP protection and any potential "chill" on the use and/or development of health care technology. This article explores the relationship between IP, innovation and public health and examines how all these factors are balanced within a biotechnologically focused economy.

Removing barriers? An overview of the Canadian Access to Medicines Regime.

As a result of significant public health issues in the developing world, there has been a strong desire to increase access to available treatments. In 2005, Canada amended its Patent Act to create the Canadian Access to Medicines Regime ("CAMR") to provide a mechanism whereby a Canadian manufacturer could produce patented pharmaceutical products for export to countries experiencing public health crises. As one of the first countries to enact such a detailed legislative regime, Canada attempted to create a model for addressing the problems created by the intersection of public health and patents. In 2007, Rwanda indicated its intention to import an HIV-drug from the Canadian generic manufacture Apotex. Rwanda's application marked the first time a country had utilized the CAMR in order to obtain essential medicines. This article examines the Canadian CAMR model, its origins, and its effectiveness to date.

Prolonged hypothermia in rat: a safety study using brain-selective and systemic treatments.

Hypothermia is an effective neuroprotectant for cardiac arrest and perinatal ischemic injury. Hypothermia also improves outcome after traumatic brain injury and stroke. Although the ideal treatment parameters (duration, delay, and depth) are not fully delineated, prolonged cooling is usually more effective than shorter periods. There is the concern that extended cooling may be hazardous to brain plasticity and cause damage. In order to evaluate this possibility, we assessed the effects of 3 days of systemic hypothermia (32°C) in rats subjected to a sham stroke surgery. There were no detrimental behavioral effects or signs of brain damage. As even longer cooling may be needed in some patients, we cooled (∼32°C) the right hemisphere of rats for 3 or 21 days. Physiological variables, functional outcome, and measures of cell injury were examined. Focal brain cooling for 21 days modestly decreased heart rate, blood pressure, and core temperature. However, focal hypothermia did not affect subsequent behavior (e.g., spontaneous limb usage), cell morphology (e.g., dendritic arborization, ultrastructure), or cause cell death. In conclusion, prolonged mild hypothermia did not harm the brain of normal animals. Further research is now needed to evaluate whether such treatments affect plasticity after brain injury.

Brief hyperthermia does not worsen outcome after striatal hemorrhage in rats.

Hyperthermia accelerates and increases ischemic brain damage. Owing to overlapping mechanisms of injury, many assume that hyperthermia also worsens outcome after intracerebral hemorrhage (ICH). However, clinical data do not conclusively prove this, and there is only one animal study examining the impact of hyperthermia. In that study (MacLellan and Colbourne, 2005), several hyperthermia protocols were administered after collagenase-induced ICH in rats; none worsened injury. While the collagenase model is widely used, it differs in important ways from another common model - injecting autologous blood directly into the brain. Thus, we evaluated the impact of immediate hyperthermia (HYP, 39 °C for 3 hr) after a 100-µL infusion of blood into the striatum of rats. This treatment, which markedly increases ischemic damage, was compared to control rats kept normothermic (NOR, 37 °C). Three separate experiments were done to measure: 1) edema at 24 hr, 2) edema at 72 hr, and 3) behavioral impairment and lesion size out to 1 month post-ICH. The HYP treatment did not significantly affect edema at 24 hr, but surprisingly, it modestly reduced edema at 72 hr and partly improved behavioral outcome. However, there were no lasting effects of HYP on behavior (e.g., skilled reaching) or the volume of tissue lost (NOR: 14.0 mm(3) vs. HYP: 14.5 mm(3)). In summary, our findings do not support the common belief that hyperthermia worsens outcome after ICH. Additional research is needed to determine whether more severe or prolonged heating or fever and its cause (e.g., infection) affect morbidity and mortality after ICH.

Treatment of intracerebral hemorrhage in rats with 12 h, 3 days and 6 days of selective brain hypothermia.

Intracerebral hemorrhage (ICH) is a devastating stroke with no proven treatment to reduce brain injury. In this study we modeled ICH by injecting 100 microL of autologous blood into the striatum of rats. We then tested whether hypothermia would reduce brain injury and improve recovery as has been repeatedly observed for ischemic and traumatic brain damage. Aside from reducing blood-brain barrier disruption, inflammation and edema, hypothermia has not consistently improved behavioral or histological outcome after ICH in animal studies. As this might relate to the choice of cooling method and the duration of hypothermia, we used a system that selectively cooled the injured hemisphere to approximately 32 degrees C (striatum) while the body remained normothermic. Cooling (vs. normothermia) started 1 h after ICH and lasted for 12 h, 3 days or 6 days followed by slow re-warming (approximately 1 degrees C/h). Functional impairment was evaluated from 2 to 3 weeks post-ICH at which time brain injury was determined. The ICH caused significant impairment on a neurological deficit scale and in tests of walking (horizontal ladder), skilled reaching (tray task) and spontaneous limb usage (cylinder test). Only the limb use asymmetry deficit was significantly mitigated by hypothermia, and then only by the longest treatment. Lesion volume, which averaged 16.9 mm3, was not affected. These results, in conjunction with earlier studies, suggest that prolonged mild hypothermia will not be a profound neuroprotectant for patients with striatal ICH, but it may nonetheless improve functional recovery in addition to its use for treating cerebral edema.

Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.

Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. In comparison to normothermic controls, 12- and 48-h bouts of hypothermia significantly lessened functional impairment, such as skilled reaching ability, and lesion volume out to a 1-month survival. In the second experiment, brain-selective cooling was induced in awake rats via a water-cooled metal strip implanted underneath the temporalis muscle overlying the ischemic territory. Use of a 48-h cooling treatment significantly mitigated injury and behavioral impairment whereas a 12-h treatment did not. These findings show that while systemic and focal techniques are effective when initiated after the onset of pMCAO, they differ in efficacy depending upon the treatment duration. A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method.

Comparison of 12, 24 and 48 h of systemic hypothermia on outcome after permanent focal ischemia in rat.

Mild hypothermia reduces injury in models of global and focal cerebral ischemia even when initiated after the insult. Neuroprotection depends critically upon the duration of hypothermia with longer treatments often being more efficacious. However, the ideal treatment duration is not known for most insults and this knowledge would facilitate clinical studies. Thus, we compared 12, 24 and 48 h of systemic hypothermia (33 degrees C vs. normothermia) initiated 1 h after permanent middle cerebral artery occlusion (pMCAO), which was produced by permanent occlusion of the carotid arteries and cauterization of the distal MCA in rat. Behavioral recovery and lesion volume were determined 7 days after pMCAO. All three treatments significantly and equally attenuated neurological deficits (e.g., forelimb placing response). Conversely, stepping error rate in the horizontal ladder test was significantly reduced only by the 24-h (18.7%) and 48-h treatments (11.7%) compared to normothermic rats (34.4%), and the 48-h treatment was significantly better than the 12-h treatment (28.8%). Similarly, brain injury was significantly reduced by 24-h (78.8 mm(3) lesion volume) and 48-h (66.8 mm(3)) treatments compared to normothermia (142.6 mm(3)), and the 48-h treatment was significantly better than the 12-h duration (114.6 mm(3)). In separate experiments cerebral edema was measured via wet-dry weight measurements and significantly reduced by hypothermia (e.g., from 83.7% water in the injured cortex of normothermic rats to 81.4% in rats cooled for one day), but for this there were no significant duration effects. In summary, prolonged hypothermia treatment provides superior protection overall, but this is not explained by reductions in edema.

A time-motion study of ambulance-to-emergency department radio communications.

OBJECTIVE: A prospective time-motion study of radio communication between inbound ambulances and emergency department (ED) triage personnel was conducted to assess hospital triage staff time utilized, and how often radio reports result in actions taken in the ED to prepare for patient arrival. The study hypothesis was that reports for "priority 2" (P2, nonemergent) patients rarely provide information that is acted upon in the ED prior to the patient's arrival. METHODS: The study was conducted at an academic adult ED receiving 22,000 ambulances per year. An observer in the ED monitored and timed (to the second) all radio reports as well as the activities of triage nurses and arriving emergency medical services (EMS) personnel. RESULTS: A convenience sample of 437 reports was collected: 83 priority 1 (P1, emergent) and 354 P2. Average report times (minutes:seconds) with ranges were 0:53 (0:07-1:57) for P1, and 0:44 (0:04-3:50) for P2. Only 16% of the P2 reports resulted in any preparatory action, and 55% of these were requests to have hospital police officers available to receive intoxicated patients, as per local protocol. An in-person report was given in the ED for 61% of the P2 cases, and in 48% of these, the in-person report was longer than the radio report. CONCLUSIONS: In the system studied, P2 reports rarely provide information that is acted on prior to the patient's arrival. The time spent giving a radio report is frequently duplicated in the ED. Radio reports for low-priority patients may not be an efficient or productive use of providers' or nurses' time.