Power outages and refrigerated medicines: The need for better guidelines, awareness and planning.

WHAT IS KNOWN AND OBJECTIVE: Vaccines and other pharmaceuticals are essential medical supplies that require continuous storage at specific temperatures to maintain viability. Power outages can lead to a break in the cold chain, resulting in the degradation of essential medicines. COMMENT: After a power outage, the stability of vaccines and other medicines can be difficult to ascertain. Many public health guidelines therefore recommend discarding potentially compromised pharmaceuticals unless the cold chain can be guaranteed-a costly endeavour. There are government guidelines aimed at minimizing exposure to high temperatures in the event of a power outage; however, the usefulness of these guidelines is uncertain. WHAT IS NEW AND CONCLUSION: The actual cost of vaccine and pharmaceutical loss due to a break in the cold chain is poorly studied and requires further research. Additional recommendations regarding the stability of specific medicines would also be a valuable resource.

Quality use of medicines in aged care facilities: A need for new models of care.

WHAT IS KNOWN AND OBJECTIVE: Despite all the advancement in aged care, medication adverse events are still reported to occur frequently in aged care residents and to be a major contributor to hospitalization and reduced quality of life in older adults. Thus, there is an urgent need for interventions and developing new models of care to address medication safety. COMMENT: Interdisciplinary collaboration, as well as accessibility to health professionals, is amongst the factors affecting medication safety in aged care. Increasing access to pharmacists and forming an interdisciplinary team with doctors and nursing staff may improve medication safety in aged care facilities. WHAT IS NEW AND CONCLUSION: To address the medication safety, we suggest a novel model of care in residential aged care facilities, in which an on-site pharmacist integrates with nursing staff to form an interdisciplinary team to prevent medication-related harm and improves the quality use of medicines.

We have had a gutful: The need for deprescribing proton pump inhibitors.

WHAT IS KNOWN AND OBJECTIVE: Proton pump inhibitor (PPI) prescribing may often be inappropriate and expose patients to a risk of adverse effects, while incurring unnecessary healthcare expenditure. Our objective was to determine PPI usage in Australia since 2002 and review international studies investigating inappropriate PPI prescribing, including those that discussed interventions to address this issue. METHODS: Australian Pharmaceutical Benefits Scheme (PBS) and Repatriation Pharmaceutical Benefits Scheme (RPBS) data were analysed. A narrative literature review relevant to the objective was conducted. Time series analysis was also used to examine the trend of reported PPI appropriate use across the international studies included in this review. RESULTS AND DISCUSSION: Proton pump inhibitor use in Australia increased between 2002 and 2010 and then gradually decreased. Estimates of the extent of inappropriate use in the international literature had a wide variation (11-84%). There appeared to be little change in the extent of appropriate PPI use reported through 34 international studies from 2000 to 2016. Interventions to address inappropriate use included patient-centred deprescribing, academic detailing, educational programmes and drug safety notifications. WHAT IS NEW AND CONCLUSION: Proton pump inhibitors continue to be overused worldwide and should be a focus for deprescribing programmes. Ongoing education and awareness campaigns for health professionals and patients, including electronic reminders at the point of prescribing, are strategies that have potential to reduce PPI use in individuals who do not have an evidence-based clinical indication for their long-term use.

A rare cause of hypoactive delirium.

A 90-year-old man was transferred to a geriatric evaluation and management (GEM) unit for management of hypoactive delirium following a pneumonia and acute myocardial infarction complicated by septic shock. He was found to have central hypothyroidism and hypoadrenalism leading to the diagnosis of hypopituitarism. Cerebral imaging confirmed this was secondary to a pituitary haemorrhage. This case illustrates the complexity of assessment of delirium and its aetiologies. Hypoactive forms of delirium in particular can be difficult to detect and therefore remain undiagnosed. While this patient's delirium was likely multifactorial, his hypopituitary state explained much of his hypoactivity. His drowsiness, bradycardia, hypotension and electrolyte imbalance provided clinical clues to the diagnosis.

Operational strategy for nitrogen removal from centrate in a two-stage partial nitrification--anammox process.

This paper presents the operational strategy for nitrogen removal in a two-stage, partial nitrification (PN) process coupled with anaerobic ammonium oxidation (Anammox) process. The process was used to remove ammonium from centrate obtained from a full-scale, wastewater treatment plant in British Columbia, Canada. The PN, which was carried out in a sequencing batch reactor (SBR), successfully converted approximately 49.5 +/- 1.0% of ammonium to nitrite. The operation of SBR under higher dissolved oxygen in combination with slow feeding resulted in significant reduced HRT without nitrate accumulation. Partially nitrified centrate was further treated in Anammox reactors, where the mixture of ammonium and nitrite was converted mainly to nitrogen gas. Anammox treatment was carried out in two different types of Anammox reactors: a moving bed hybrid reactor and an up-flow fixed-bed biofilm reactor. The hybrid Anammox reactor removed an average of 55.8% of NH4-N, versus the 48.3% NH4-N removed in the up-flow fixed-bed reactor. Nitrite removal in the hybrid and up-flow fixed-bed Anammox reactors averaged 80.8% and 62.5%, respectively. This study also illustrated that in both Anammox reactors, better ammonium removal was achieved when the nitrite to ammonium ratio is between 1.35 and 1.45. As such, alkalinity was found to neither control nor limit the Anammox reaction.

The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin.

BACKGROUND: Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action. METHODS: Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin. KEY RESULTS: Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 µg) to the lumbosacral spinal cord. CONCLUSIONS & INFERENCES: Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.

Central resistin enhances renal sympathetic nerve activity via phosphatidylinositol 3-kinase but reduces the activity to brown adipose tissue via extracellular signal-regulated kinase 1/2.

Resistin is an adipokine, originally identified in adipose tissue, and its plasma levels are elevated in obesity. Characteristics of obesity include impaired metabolic regulation and cardiovascular dysfunction, such as increased sympathetic nerve activity (SNA) to the kidney and skeletal muscle vasculature. Resistin can affect energy homeostasis through central mechanisms that include reduced food intake and reduced thermogenesis, and can also increase lumbar SNA via a central action. The present study investigated: (i) the effect of centrally-administered resistin on SNA targeting the kidney and (ii) the intracellular signalling pathways mediating the changes in SNA innervating the kidney and brown adipose tissue (BAT) induced by resistin. Intracerebroventricular resistin (7 µg) injected into overnight fasted, anaesthetised rats induced a significant increase in renal SNA by approximately 40%. This response was prevented when phosphatidylinositol 3-kinase (PI3K) was inhibited by i.c.v. administration of LY294002 (5 µg). Resistin reduced BAT SNA and this response was delayed by 150 min when extracellular-regulated kinase (ERK)1/2 was inhibited by i.c.v. administration of U0126. The findings indicate that resistin increases renal SNA via PI3K and reduces BAT SNA via ERK1/2.

Centrally administered resistin enhances sympathetic nerve activity to the hindlimb but attenuates the activity to brown adipose tissue.

Resistin, an adipokine, is believed to act in the brain to influence energy homeostasis. Plasma resistin levels are elevated in obesity and are associated with metabolic and cardiovascular disease. Increased muscle sympathetic nerve activity (SNA) is a characteristic of obesity, a risk factor for diabetes and cardiovascular disease. We hypothesized that resistin affects SNA, which contributes to metabolic and cardiovascular dysfunction. Here we investigated the effects of centrally administered resistin on SNA to muscle (lumbar) and brown adipose tissue (BAT), outputs that influence cardiovascular and energy homeostasis. Overnight-fasted rats were anesthetized, and resistin (7 µg) was administered into the lateral cerebral ventricle (intracerebroventricular). The lumbar sympathetic nerve trunk or sympathetic nerves supplying BAT were dissected free, and nerve activity was recorded. Arterial blood pressure, heart rate, body core temperature, and BAT temperature were also recorded. Responses to resistin or vehicle were monitored for 4 h after intracerebroventricular administration. Acutely administered resistin increased lumbar SNA but decreased BAT SNA. Mean arterial pressure and heart rate, however, were not significantly affected by resistin. BAT temperature was significantly reduced by resistin, and there was a concomitant fall in body temperature. The findings indicate that resistin has differential effects on SNA to tissues involved in metabolic and cardiovascular regulation. The decreased BAT SNA and the increased lumbar SNA elicited by resistin suggest that it may contribute to the increased muscle SNA and reduced energy expenditure observed in obesity and diabetes.