Continuous subcutaneous infusion: is community anticipatory prescribing and administration safe?

OBJECTIVE: The anticipatory prescribing of pro re nata medications and continuous subcutaneous infusion (CSCI) medication is essential for the timely management of symptomatic patients at the end of life. There is no evidence to support the safety or appropriateness of anticipatory CSCIs. In 2013, in response to safety concerns about end of life prescribing in the community, we designed an educational intervention to improve prescribing practices among non-specialist prescribers in this area. METHODS HOW THE STUDY WAS PERFORMED: We performed a safety-focussed retrospective cohort analysis of end of life community prescriptions of anticipatory CSCIs over a 12-month period, 5 years after creating clinical guidelines and embedding a multiprofessional rolling education programme. Medications prescribed and administered for symptom control at the end of life are compared between specialist and non-specialist prescribers in terms of their adherence to best practice guidance. RESULTS: Medications prescribed were not universally administered and more commonly not administered without specialist input. Prescriptions of higher doses of opioids and benzodiazepines beyond those recommended by guidance were significantly greater within the cohort of patients receiving specialist oversight. The prescription of a dose range did not result in excessive dose escalation. For patients not receiving specialist palliative care, median morphine and midazolam doses did not escalate at all once a CSCI was commenced. All midazolam administrations were safe. CONCLUSIONS: The practice of anticipatory CSCI prescribing and administration can be safe in the community non-specialist setting when supported by clinical guidelines, specialist advice and ongoing multiprofessional education.

Analysis of biogenic amine variability among individual fly heads with micellar electrokinetic capillary chromatography-electrochemical detection.

Neurochemical variability among individual Drosophila heads has been examined with the sensitivity of electrochemical detection and the selectivity of micellar electrokinetic capillary chromatography. Homogenization of single Drosophila heads in volumes as small as 100 nL has been accomplished. Here we demonstrate reproducible separations for single fly heads in 250-nL volumes providing a 4-fold increase in sensitivity without overloading the electrochemical detector. This increase in sensitivity allows detection of previously undetected analytes, such as N-acetyltyramine (naTA) and octopamine (OA). Analytes including L-3,4-dihydroxyphenylalanine, N-acetyl octopamine, N-acetyldopamine, naTA, N-acetylserotonin, OA, dopamine, tyramine, and serotonin also have been consistently identified in single-head homogenates and observed with homogenates representing populations of Drosophila. Neurochemical variation between individual flies as well as the consistency within a population indicates varying amounts of neurotransmitter turnover. The inception, design, and fabrication of a miniature tissue homogenizer has enabled the separation of biogenic amines and metabolites from these severely volume-limited single Drosophila head homogenates.

Microcolumn separation of amine metabolites in the fruit fly.

Electrophoretic resolution of 14 biogenic amines and metabolites with similar mobilities is addressed by employing micellar electrokinetic capillary chromatography coupled to amperometric electrochemical detection. The present study describes the optimization of separation conditions to achieve resolution of analytes of biological significance within 20 min in a single separation. They include dopamine, epinephrine, norepinephrine, octopamine (OA), L-3, 4-dihydroxyphenylalanine, tyramine (TA), and serotonin as well as metabolites 5-hydroxyindolacetic acid, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxytyramine in addition to N-acetylated metabolites including N-acetyldopamine, N-acetyloctopamine (naOA), and N-acetylserotonin. The optimized conditions used result in excellent reproducibility and predictable peak shifting, thus enabling identification of several metabolites along with their biogenic amine precursors in biological samples, specifically from the fruit fly Drosophila melanogaster. The separation method is sensitive, selective, and quantitative as demonstrated by its capacity to detect changes in TA, OA, and naOA present in the head homogenates of the Canton-S and mutant inactive(1) Drosophila lines. Quantitative analysis of metabolites in conjunction with their biogenic amine precursors in a single separation offers tremendous potential to understand the physiological processes and underlying mechanisms mediated by various biogenic amines in Drosophila and other animals.

Recent advances in the application of capillary electrophoresis to neuroscience.

With fast separation times (seconds to minutes), minimal sample requirements (nanoliters to femtoliters), and excellent mass detection limits (femtomole to zeptomole), capillary electrophoresis (CE) is ideally suited for in vitro and in vivo sampling of neurological samples with a high degree of spatial resolution. Advances in extracellular fluid analysis employing improved microdialysis and push-pull perfusion sampling methodologies has enabled the resolution of neurotransmitters present in limited amounts using CE. Great progress has been made to resolve complex neuropeptides, amino acids, and biogenic amines in tissue and cell cultures. Finally, owing largely to the small volume sampling abilities of CE, investigations of single nerve cells, both invertebrate and mammalian, have been accomplished. These applications of CE to the advancement of neuroscience are presented.

Analysis of Mammalian Cell Cytoplasm with Electrophoresis in Nanometer Inner Diameter Capillaries.

Capillary electrophoresis in 770 nanometer inner diameter capillaries coupled to electrochemical detection with an etched electrode matching an etched capillary (etched electrochemical detection) has been used with ultrasmall sampling to inject subcellular samples from intact single mammalian cells. Separations of cytoplasmic samples taken from rat pheochromocytoma cells have been achieved. As little as 8% of the total volume of a single cell has been sampled and analyzed. Dopamine has been identified and quantified in these PC12 cells using this technique. The average cytoplasmic level of dopamine in rat pheochromocytoma cells has been determined to be 240 ± 60 µM. The use of electrophoresis in 770 nanometer inner diameter capillaries with electrochemical detection to monitor cytoplasmic neurotransmitters at the single cell level can provide information about complex cellular functions such as neurotransmitter storage and synthesis.

Characterization of etched electrochemical detection for electrophoresis in micron inner diameter capillaries.

An enhanced etched electrochemical (EC) detection technique has been developed for CE in micron inner diameter capillaries. The design improvements allow for better alignment between the capillary bore and the electrode. This new method involves utilizing a carbon fiber microelectrode and etching both the carbon fiber and the detection end of a micrometer-sized inner diameter capillary to limit dead volume and analyte diffusion at the amperometric EC detector. To understand the factors affecting enhanced detector efficiency, a detailed examination of the relationship between detector design and performance has been completed by exploring the effects of varying electrode diameter, tip shape, and size, in addition to the etch length of the capillary outlet. The enhanced detection provides peak efficiencies as high as 75000 theoretical plates and estimated detection limits as low as 40 nM for dopamine. This etched detection method should further facilitate volume-limited sample analysis by CE.

Review and update of insulin dependent diabetes mellitus.

The purpose of this article is to provide the health care practitioner with a comprehensive review of the pathophysiology and treatment of Type 1 Diabetes Mellitus. Traditionally, insulin has been administered via an insulin syringe. In the recent past, diabetes research has focused on developing more convenient insulin delivery devices and longer acting insulin's in hopes of increasing compliance with insulin therapy and improving the management of Type 1 diabetes in both children and adults. Rapidly developing approaches to insulin delivery for Type 1 diabetes continue to be developed at a rapid rate, including administration via continuous subcutaneous insulin infusion in addition to other new approaches. With these advances in therapy, pediatric patients with Type 1 diabetes have been able to achieve strict glycemic control, although the treatment of hypoglycemia remains a burden. The objectives of this article are to the following: to review the epidemiology, risk factors, pathophysiology, clinical manifestations, and diagnostic criteria of Type 1 diabetes mellitus in children,; to discuss the management of these patients, including, insulin therapy, monitoring, diet and exercise, carbohydrate counting and treatment of hypoglycemia,; and to review insulin administration devices, including insulin pens, insulin jet injectors, insulin pumps, and novel insulin delivery systems.