Brain death and brain life: rethinking the connection

The connection between brain life and brain death is neither as simple nor as defensible as it might at first appear. The problem rests with the two dominant competing definitions of death:...the loss of that which is necessary for the organism to continue to function as a whole;....the loss of that which is essentially significant to the nature of the organism... If death is understood as the loss of that which is necessary for the continued functioning of the organism as whole, then the apparent symmetry breaks down. If...death could be understood as the loss of that which is essentially significant to the nature of the organism....consciousness, then the symmetry would hold. However, that definition of death is indefensible. Therefore...statements about the status of anencephalic infants and early human embryos based upon a connection between brain death and brain life are unfounded.     

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.     

The effect of health care reform on academic medicine in Canada. Editorial Committee of the Canadian Institute for Academic Medicine.

Although Canadian health care reform has constrained costs and improved efficiency, it has had a profound and mixed effect on Canadian academic medicine. Teaching hospitals have been reduced in number and size, and in patient programs have shifted to ambulatory and community settings. Specialized care programs are now multi-institutional and multidisciplinary. Furthermore, the influence of regional planning bodies has grown markedly. Although these changes have likely improved clinical service, their impact on the quality of clinical education is uncertain. Within the academic clinical department, recruitment of young faculty has been greatly complicated by constraints on licensing, billing numbers, fee-for-service income and research funding. The departmental practice plan based on university funds and fee-for-service income is being replaced by less favourable funding arrangements. However, emphasis on multidisciplinary programs has rendered these departments more flexible in structure. The future of Canadian academic medicine depends on an effective alliance with government. Academia and government must agree, particularly on human-resource requirements, research objectives and the delivery of clinical and academic programs in regional and community settings. The establishment of focal points for academic health sciences planning within academic health sciences centres and within governments would assist in these developments. Finally, government and the academic health sciences sector must work together to remove the current impediments to the recruitment of highly qualified young faculty.     

Incidence of neurologic death among patients with brain injury: a cohort study in a Canadian health region

Background:

Hospital mortality has decreased over time for critically ill patients with various forms of brain injury. We hypothesized that the proportion of patients who progress to neurologic death may have also decreased.

Methods:

We performed a prospective cohort study involving consecutive adult patients with traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage or anoxic brain injury admitted to regional intensive care units in southern Alberta over a 10.5-year period. We used multivariable logistic regression to adjust for patient age and score on the Glasgow Coma Scale at admission, and to assess whether the proportion of patients who progress to neurologic death has changed over time.

Results:

The cohort consisted of 2788 patients. The proportion of patients who progressed to neurologic death was 8.1% at the start of the study period, and the adjusted odds of progressing to neurologic death decreased over the study period (odds ratio [OR] per yr 0.92, 95% confidence interval [CI] 0.87–0.98, p = 0.006). This change was most pronounced among patients with traumatic brain injury (OR per yr 0.87, 95% CI 0.78–0.96, p = 0.005); there was no change among patients with anoxic injury (OR per yr 0.96, 95% CI 0.85–1.09, p = 0.6). A review of the medical records suggests that missed cases of neurologic death were rare (≤ 0.5% of deaths).

Interpretation:

The proportion of patients with brain injury who progress to neurologic death has decreased over time, especially among those with head trauma. This finding may reflect positive developments in the prevention and care of brain injury. However, organ donation after neurologic death represents the major source of organs for transplantation. Thus, these findings may help explain the relatively stagnant rates of deceased organ donation in some regions of Canada, which in turn has important implications for the care of patients with end-stage organ failure.Mortality has decreased among critically ill patients with various forms of brain injury in Canada and around the world.^1–10 There have also been changes in the incidence of stroke and the rate of admission to hospital for traumatic brain injury, especially among younger people and those whose injuries are related to motor vehicle or bicycle crashes.^5,6,10–13Some countries have noted a possible decline in the total number of patients with neurologic death.^14,15 Neurologic death (“brain death”) may occur when patients with brain injury experience progressive cerebral edema, complicated by transtentorial herniation. It is defined by the irreversible cessation of cerebral and brainstem functions, including respiration.¹⁶ Circulation and gas exchange persist only because of the use of mechanical ventilation. National guidelines exist for the diagnosis of neurologic death.^17,18 We hypothesized that the proportion of patients with acute brain injury who progress to neurologic death may have decreased over time.     

Developing a Canadian prescribing practices network. Network Development Committee of the Canadian Prescribing Practices Network Project.

Expenditure on drug therapy in Canada has been growing at a faster rate than spending on any other aspect of health care. Increasing societal pressure to use scarce resources more efficiently, advances in communication technology and data indicating that there is room for improvement in drug prescribing suggest that the time has come for an organized linkage of the available drug-utilization and health-outcomes data-bases across the country. A national prescribing practices network would assist prescribers, researchers and policymakers to optimize prescribing with respect to both cost effectiveness and health outcomes. The authors outline the main concerns addressed in the 1994 report to the National Pharmaceutical Strategy and present the results of discussions by the Canadian Prescribing Practices Network Project with respect to the potential users and data sources of a national network and the communications technology on which it would rely.     

Group A Streptococcus: a re-emergent pathogen. Infectious Diseases and Immunization Committee,Canadian Paediatric Society.

Rheumatic fever is still rare in North America but must continue to be considered in the appropriate clinical setting. Invasive or severe GABHS disease remains unusual and is unlikely to be missed by the practitioner; however, it is essential that GABHS infection be considered as a possible cause of a severe sepsis-like syndrome. Currently the routine management of GABHS infection is unchanged; however, heightened awareness of the infection''s rare, more serious complications is needed.     

Brain stem death and organ donation.

Organs for donation are in short supply in the United Kingdom, resulting in allegations that relatives of potential donors are not being asked for consent. Legislation on "required request" has been proposed to overcome this. The incidence, causes, complications, and patterns of organ donation in brain stem dead patients in one referral centre were studied over 12 months. Data were collected on all patients fulfilling criteria for brain stem death or considered suitable for donating organs after circulatory arrest. Forty two patients fulfilled the criteria for brain stem death, and in 10 further patients circulatory arrest occurred before formal testing was finished. The major causes of brain stem death were head injury (28) and intracranial haemorrhage (17). Consent to organ donation was obtained for 24 potential donors, and organs were donated by 23 of them. Twenty nine patients did not donate organs. The commonest reasons for failure to donate were medical unsuitability (13) and the coroner not releasing the body (eight). Consent was not sought in three cases, and the relatives refused consent in the remaining five. This study suggests that required request will not considerably increase the supply of donor organs.