The United States Presidents Council on Bioethics made it clear, for example, in its White Paper of December 2008, that the British concept and clinical criteria are not considered sufficient for the diagnosis of death in the United States. Evolution of diagnostic criteria
The United Kingdom (UK) criteria were first published by the Conference of Medical Royal Colleges (with advice from the Transplant Advisory Panel) in 1976, as prognostic guidelines. They were drafted in response to a perceived need for guidance in the management of deeply comatose patients with severe brain damage who were being kept alive by mechanical ventilators but showing no signs of recovery. The Conference sought "to establish diagnostic criteria of such rigour that on their fulfilment the mechanical ventilator can be switched off, in the secure knowledge that there is no possible chance of recovery". The published criteria – negative responses to bedside tests of some reflexes with pathways through the brainstem and a specified challenge to the brainstem respiratory centre, with caveats about exclusion of endocrine influences, metabolic factors and drug effects – were held to be "sufficient to distinguish between those patients who retain the functional capacity to have a chance of even partial recovery and those where no such possibility exists".
Mechanism of action
Through recombinant DNA technology, the final lysine and proline residues on the C-terminal end of the B-chain are reversed. This modification does not alter receptor binding, but blocks the formation of insulin dimers and hexamers. This allows larger amounts of active monomeric insulin to be immediately available for postprandial injections. Chemistry
It is a manufactured form of human insulin where the amino acids lysine and proline have been switched at the end of the B chain of the insulin molecule. This switch of amino acids mimics Insulin-like growth factor 1 which also has lysine (K) and proline (P) in that order at positions 27 and 28. Cost
In the United States, the price of for a vial of Humalog increased from US$35 in 2001 to US$234 2015, or US$10.06 and US$29.36 per 100 units. In April 2019, Eli Lilly and Company announced they would produce a version selling for US$137.35 per vial, about half the then-current cost. The chief executive said that this was a contribution "to fix the problem of high out-of-pocket costs for Americans living with chronic conditions", but Patients for Affordable Drugs Now said this was just a public relations move, as "other countries pay US$20 for a vial of insulin. "The cost in the United Kingdom was between £1.66 and £1.96 per 100 units, in 2017.