Care of dying adults in the last days of life .

Care of people in their last days of life should be based on compassion, respect and, wherever possible, on research evidence. Previously the Liverpool Care Pathway attempted to facilitate this but it was withdrawn after an independent government report found that its uncritical implementation could lead to poor care. This Concise Guideline overviews NICE Clinical Guideline (NG31), which addresses: recognising dying; communication and shared decision making; maintaining hydration; and pharmacological symptom control, including anticipatory prescribing. Doctors may need to change their attitudes to care of dying people and those important to them. Specific areas where practices will need to reflect the individualised approach to care are highlighted. Limitations of the guideline are discussed. Potential barriers to implementation include need for further training and 24/7 availability of specialist support to front-line clinicians.

Bortezomib (Velcadetrade mark) in the Treatment of Multiple Myeloma.

The introduction of bortezomib, a novel first-in-class proteasome inhibitor, has been a major break through in the treatment of multiple myeloma. It is currently approved for the treatment of myeloma in the relapsed setting post transplant or as a second line treatment in patients unsuitable for transplantation. In pre-clinical studies bortezomib showed a number of different anti-myeloma effects including disruption of the cell cycle and induction of apoptosis, alteration of the bone marrow microenvironment and inhibition of nuclear factor kappa B (NFkappaB). Due to its novel mechanism of action, bortezomib has been shown to induce responses in previously refractory patients (including those with poor risk cytogenetics), and results in an increased progression free and overall survival in relapsed patients when compared with dexamethasone treatment alone. It is well tolerated and can be administered in the outpatient setting with manageable toxicities. Peripheral neuropathy is the most common dose limiting toxicity and thrombocytopenia can generally be managed with platelet transfusions without reducing or omitting doses. Bortezomib shows a synergistic effect in combination with dexamethasone and also sensitises myeloma cells to the effects of other chemotherapeutic agents with major response rates of over 50% being shown in the relapsed setting. Initial data from ongoing trials in front line therapy are encouraging with response rates of 80%-90% when bortezomib is given in combination with other agents and importantly, the ability to mobilize peripheral blood stem cells is not impaired.