Five Easy Pieces. The Total Synthesis of Phosphoiodyn A (and Placotylene A).

The convergent total synthesis of the marine natural product phosphoiodyn A, a nanomolar agonist of human peroxisome proliferator-activated receptor delta (hPPARδ), was achieved in five steps total from commercially available and inexpensive starting materials. The synthesis relies on the unprecedented regioselective hydrozirconation of a terminal acetylene in the presence of a conjugated 1,3-diyne and on ammonolysis of a ß-chlorophosphonic acid monoester. The scheme also provides the newly isolated placotylene A, an inhibitor of bone marrow-derived macrophage (BMM) differentiation.

The Health Quality and Safety Commission: making good health care better.

New Zealand has one of the best value health care systems in the world, but as a proportion of GDP our spending on health care has increased every year since 1999. Further, there are issues of quality and safety in our system we must address, including rates of adverse events. The Health Quality and Safety Commission was formed in 2010 as a crown agent to influence, encourage, guide and support improvement in health care practice in New Zealand. The New Zealand Triple Aim has been defined as: improved quality, safety and experience of care; improved health and equity for all populations; and best value for public health system resources. The Commission is pursuing the Triple Aim via two fundamental objectives: doing the right thing by providing care supported by the best evidence available, focused on what matters to each individual patient, and doing the right thing right, first time, by making sure health care is safe and of the highest quality possible. Improvement efforts must be supported by robust but economical measurements. New Zealand has a strong culture of quality, so the Commission's role is to work with our colleagues to make good health care better.

A multi-disciplinary approach to congenitally missing anterior teeth.

Congenitally missing teeth are not an unusual occurrence. What makes this case study unique is the combination of restorative challenges offered. The patient presented with the permanent upper right cuspid and lower anterior right and left central incisors congenitally missing, and with an underdeveloped upper right lateral incisor. Distinctive existing occlusion and tooth alignment difficulties precluded a simple approach of merely extracting the residual primary teeth and replacing the missing teeth prosthetically. Using orthodontics to create ideal interocclusal and interarch space was critical in preparing this case for prosthetic restoration.

Colchicine overdose: the devil is in the detail.

Colchicine, a highly poisonous alkaloid, is a commonly used treatment for gout, Bechet's disease, and familial Mediterranean fever. Despite the knowledge of its side effects, the near universally fatal consequence of a significant overdose is commonly under-appreciated. In this report, we present a case series of 9 patients over the past 15 years (from within the Auckland region of New Zealand) that have presented with a colchicine overdose. Surprisingly, a significant number were accidental overdoses and all cases, apart from one, resulted in death. We question the current knowledge base about the toxicity of this drug amongst prescribers, patients, and their families and its use in the treatment of acute gout. Given its extremely narrow therapeutic index, should the manner in which medical practitioners prescribe this drug be reassessed?

Networks: a key to the future of health services.

Health service reforms and structures have, in general, emphasised hierarchical systems to enable control and accountability. In doing so, policies have substantially sidelined networks and their potential for contributing to health service performance. Networks play a number of roles, such as in supporting expertise development, arranging referrals, coordinating programs, undertaking projects, sharing common interests and providing mutual support in managing common conditions. They handle knowledge, support expertise and deal with complexity in ways that hierarchies are unable to, and are fundamental to supporting professionalism. Until networks are used to a greater extent, the development of health services will be substantially impeded. This will require enhancing the role and contribution that networks play, which is dependent on resources, leadership and skills.

Caring for patients and families at the end of life: withdrawal of intensive care in the patient's home.

AIM: To describe our experience of transporting 17 intensive care patients home to die. DESIGN: A brief report. SETTING: Mixed medical/surgical intensive care unit (ICU). RESULTS: After discussions with their families, 17 adult patients in whom ongoing care was deemed either inappropriate or futile were transported home. Once there, intensive care modalities of ventilation and vasopressor therapy were withdrawn. The patients were sedated initially with intravenous morphine and if death was not immediately imminent, subcutaneous morphine was administered. In these cases where death took longer than 2 hours, the patients were managed with the assistance of district nurses, the family general practitioner, or staff from the South Auckland Hospice. CONCLUSIONS: All the patients in this report were Maori or Polynesian and all families reported this as a positive experience. Since completion of this report, we have taken our first European patient home to die.

Sustained low-efficiency daily diafiltration (SLEDD-f) for critically ill patients requiring renal replacement therapy: towards an adequate therapy.

BACKGROUND: Sustained low-efficiency daily dialysis (SLEDD) is an increasingly popular renal replacement therapy for intensive care unit (ICU) patients. SLEDD has been previously reported to provide good solute control and haemodynamic stability. However, continuous renal replacement therapy (CRRT) is considered superior by many ICU practitioners, due first to the large amounts of convective clearance achieved and second to the ability to deliver treatment independently of nephrology services. We report on a program of sustained low-efficiency daily diafiltration (SLEDD-f) delivered autonomously by ICU nursing personnel, and benchmark solute clearance data with recently published reports that have provided dose-outcome relationships for renal replacement therapy in this population. METHODS: SLEDD-f treatments were delivered using countercurrent dialysate flow at 200 ml/min and on-line haemofiltration at 100 ml/min for 8 h on a daily or at least alternate day basis. All aspects of SLEDD-f were managed by ICU nursing personnel. Clinical parameters, patient outcomes and solute levels were monitored. Kt/V, corrected equivalent renal urea clearance (EKRc) and theoretical Kt/V(B12) were calculated. RESULTS: Fifty-six SLEDD-f treatments in 24 critically ill acute renal failure patients were studied. There were no episodes of intradialytic hypotension or other complications. Observed hospital mortality was 46%, not significantly different from the expected mortality as determined from the APACHE II illness severity scoring system. Electrolyte control was excellent. Kt/V per completed treatment was 1.43+/-0.28 (0.96-2.0). Kt/V(B12) per completed treatment was 1.02+/-0.21 (0.6-1.38). EKRc for patients was 35.7+/-6.4 ml/min (25.0-48.2). CONCLUSION: SLEDD-f provides stable renal replacement therapy and good clinical outcomes. Logistic elements of SLEDD-f delivery by ICU nursing personnel are satisfactory. Small solute clearance is adequate by available standards for CRRT and intermittent haemodialysis, and larger solute clearance considerable. SLEDD-f is a viable alternative to CRRT in this setting.