The Impact of an Electronic Prescribing Template with Decision Support upon the Prescribing of Subcutaneous Infusions at the End of Life in a Community Setting: A Future Vision for Community Palliative Care.

Objectives: To assess the impact of an electronic prescribing template with decision support upon the frequency of prescription errors, guideline adherence (relating to dose ranges), and prescription legality when prescribing continuous subcutaneous infusions (CSCI) in a palliative demographic. Design, setting, and participants: Before-and-after study across a large UK city utilizing local prescribing data taken from patients receiving end-of-life care. Intervention: An electronic prescribing template with decision support. Main outcome measures: The following were assessed: (1) the rate of prescription errors; (2) the proportion of prescriptions specifying a dose range and if the specified range complied with local recommendations; and (3) the proportion of prescriptions specifying legal mixing directions. Results: The intervention was associated with a significant reduction in errors of omission, with all prescriptions clearly stating drug indication, route of administration, drug dose, and infusion duration. The numbers of continuous subcutaneous infusion prescriptions that specified dose ranges were similar at baseline and post-intervention, at 71% (n = 122) and 72% (n = 179), respectively. At baseline, 69% (n = 84) of CSCI prescriptions specifying a dose range were deemed safe, and post-intervention, 97% (n = 173) were determined to be safe. At baseline, mixing directions were not specified correctly on any continuous subcutaneous infusion prescriptions, while post-intervention, such directions were correct on 75% (n = 157; p < 0.05) of the prescriptions. Conclusions: The intervention eliminated errors of omission, ensured the safety of prescribed dose ranges, and improved compliance with legislation surrounding the mixing of multicomponent infusions. Overall, the intervention has the potential to improve patient safety at the end of life and to increase the efficiency of community services.

Experimental evidence for previously unclassified calcium phosphate structures in the casein micelle.

1H-31P Cross-polarization magic angle spinning (CP-MAS) measurements of 40-d-old Mozzarella cheese and 20 mM EDTA-treated casein micelles revealed that each sample had immobile phosphorus with the same spectral pattern, which did not match that of native casein micelles. To identify the immobile phosphorus bodies, 1H-31P CP-MAS spectra and cross-polarization kinetics measurements were undertaken on native casein micelles, EDTA-chelated casein micelles, and reference samples of ß-casein and hydroxyapatite. The results showed that the immobile phosphorus bodies in the mature Mozzarella cheese had the following characteristics: they are immobile phosphoserine residues (not colloidal calcium phosphate); they are not the product of phosphoserine to colloidal calcium phosphate bridging; the phosphate is complexed to calcium; their rigidity is localized to a phosphorus site; their rigidity and bond coupling is unaffected by protein hydration; and the immobile bodies share a narrow range of bond orientations. Combining these observations, the best explanation of the immobile phosphorus bodies is that bonding structures of phosphorus-containing groups and calcium exist within the casein micelle that are not yet clearly classified in the literature. The best candidate is a calcium-bridged phosphoserine-to-phosphoserine linkage, either intra- or inter-protein.

Acute irritant reaction to an antiseptic bath emollient.

Antiseptic bath emollients are commonly prescribed for treatment of eczema and are generally safe for frequent application. Although acute irritant reactions are uncommon it is nevertheless recognised and could have significant morbidity. This case describes a young male patient who developed an acute irritant reaction localised to the external genitalia, mimicking Fournier's gangrene, after overnight application of Oilatum Plus antiseptic bath emollients.

An NMR study of the freezing of emulsion-containing drops.

Various nuclear magnetic resonance (NMR) techniques were used to monitor the freezing behaviour of suspended 2-mm-diameter drops. The drops were composed of hydrocarbon oils emulsified in either water or water/sucrose mixtures. As such they were good model systems for the study of spray freezing, sharing structural similarities with potential products such as ice cream. In particular, simple 1H NMR spectroscopy was used to monitor and individually quantify the freezing or solidification behaviour of the various constituent species of the drops. In addition, the effect of freezing on the emulsion droplet size distribution (and hence emulsion stability) was also measured based on NMR self-diffusion measurements. The effect of freeze/thaw cycling was also similarly studied. The nucleation temperature of the emulsion droplets was found to depend on the emulsion droplet size distribution: the smaller the droplets, the lower the nucleation temperature. Emulsion droplet sizing indicated that oil-in-sucrose-solution emulsions were more stable, showing minimal coalescence, whereas oil-in-water emulsions showed significant coalescence during freezing and freeze/thaw cycling.

The porphyrias, appropriate test selection.

BACKGROUND: Clinical and biochemical diagnosis of the porphyrias is a difficult task and is currently based upon review of the clinical features and measurement of the various porphyrin metabolites in body fluids. MATERIALS: Different techniques are available for the diagnosis of the porphyrias and the identification of the eventual defect(s), ranging from simple biochemical measurement of aminolevulinic acid (ALA) and porphobilinogen (PBG) through enzymatic assays to the investigation of genetic abnormalities. RESULTS: Except for erythrocyte porphobilinogen deaminase, the use of porphyrin enzyme measurement is beyond the scope of most laboratories. Genetic studies are progressing apace in all the porphyrias and are rapidly becoming the 'gold standard' for difficult diagnoses, but actually, these techniques are confined to highly specialized research laboratories. CONCLUSION: At present time, most clinical chemists must rely on the measurement of porphyrin metabolites for diagnosis and a proposed algorithm for this purpose is presented.

Inhibition of neuronal nitric oxide synthase increases dopamine efflux from rat striatum.

The physiological role of nitric oxide in the control of striatal dopamine release has not been fully established, therefore, the effect of neuronally produced nitric oxide (NO) on striatal dopamine (DA) efflux were investigated using in vivo microdialysis in anaesthetised and conscious rats. In the anaesthetised rat, the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) produced concentration-dependent increases in DA efflux. The L-NAME (1 mM)- and 7-NINA (1 mM)-induced increase was reduced by co-administration with the NO precursor, L-arginine (L-ARG; 1 mM) by 37% and 54% respectively, and was prevented by tetrodotoxin (TTX, 1 microM). Similarly, in conscious rats, L-NAME (1 mM) and 7-NINA (1 mM) increased DA efflux to 161% and 166% of basal efflux respectively. These data suggest that neuronally produced NO inhibits striatal DA efflux through an indirect mechanism.

Single-strand conformational polymorphism and denaturing gradient gel electrophoresis in screening for variegate porphyria: identification of two new mutations.

Single-strand conformational polymorphism and denaturing gel electrophoresis were used to screen for mutations in the protoporphyrinogen oxidase gene (PPOX) of three patients with clinically and biochemically proven variegate porphyria in order to select genomic regions for specific DNA sequence analysis. Two previously undescribed mutations were identified: PPOX1423-1426-delATCT and PPOX2272insG. Denaturing gel electrophoresis was able to discern the point mutation in exon 5 (PPOX2272insG) of the PPOX gene. Once an index individual has been identified, single-strand conformational polymorphism and denaturing gel electrophoresis techniques are useful to identify family members who may be unaffected carriers. Such identification can help potential cases to avoid medications and other triggers that could precipitate acute porphyric attacks.

Caveats in hair analysis in chronic arsenic poisoning.

The diagnosis and evaluation of chronic arsenic poisoning remains a difficult task. Clinical indicators are crude measures, and electromyography adds little to the picture. Blood arsenic levels are transitory, however urine levels are useful for monitoring ongoing exposure. Hair arsenic is useful as a confirmatory feature in chronic arsenic poisoning provided external contamination by arsenic can be excluded. The distribution of arsenic in cross sections or along the length of a shaft of hair cannot distinguish external contamination from arsenic derived from ingestion.

Neuronal nitric oxide synthase inhibition reduces MPP+-evoked hydroxyl radical formation but not dopamine efflux in rat striatum.

Nigral cell degeneration induced by 1-methyl-4-phenyl-1,2,3,6-tertrahydropyridine (MPTP) or its metabolite 1-methyl-4-phenyl pyridinium (MMP+) may involve toxicity induced by nitric oxide. In the present study a microdialysis procedure incorporating salicylate hydroxylation was used to measure striatal hydroxyl radical production through the formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). MPP+ (5-20mM for 20 min) increased 2,3-DHBA formation in the rat striatum in a concentration-dependent manner with a concomitant increase in dopamine release and decrease in 3,4-dihydroxyphenyl acetic acid (DOPAC) formation. Inhibition of NO synthesis following N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mM) and 7-nitroindazole monosodium salt (7-NINA; 1 mM), but not N(G)-nitro-D-arginine methyl ester (D-NAME; 1 mM) attenuated the MPP+-induced increase in hydroxyl radical formation. However, neither L-NAME nor 7-NINA had any effect on the MPP+-induced increase in dopamine efflux measured in vivo by microdialysis or in vitro using superfused striatal slices, although nomifensine (10 microM) abolished the MPP+-evoked dopamine efflux in vitro. These data suggest that NO formation is necessary for the production of hydroxyl radical following MPP+ treatment, but is not involved in the MPP+-evoked dopamine release.

Plasma porphyrins in the porphyrias.

BACKGROUND: As an aid in the diagnosis and management of porphyria we have developed a method to fractionate and quantify plasma porphyrins and have evaluated its use in various porphyrias. METHODS: We used HPLC with fluorometric detection to measure plasma concentrations of uroporphyrin I and III, heptacarboxyl III, hexacarboxyl III, pentacarboxyl III, and coproporphyrin I and III. We studied 245 healthy subjects, 32 patients with classical porphyria cutanea tarda (PCT), 12 patients with PCT of renal failure, 13 patients with renal failure, 8 patients with pseudoporphyria of renal failure, 3 patients with acute intermittent porphyria, 5 patients with variegate porphyria, 5 patients with hereditary coproporphyria, and 4 patients with erythropoietic protoporphyria. RESULTS: Between-run CVs were 5.4-13%. The recoveries of porphyrins added to plasma were 71-114% except for protoporphyrin, which could not be reliably measured with this technique. Plasma porphyrin patterns clearly identified PCT, and its clinical sensitivity equaled that of urine porphyrin fractionation. The patterns also allowed differentiation of PCT of renal failure from pseudoporphyria of renal failure. CONCLUSIONS: The assay of plasma porphyrins identifies patients with PCT and appears particularly useful for differentiating PCT of renal failure from pseudoporphyria of renal failure.

Effect of an educational multimedia prostate program on the International Prostate Symptom Score.

OBJECTIVE: To determine the effect of an interactive multimedia prostate education program (MMP) on self assessment of symptom scores due to benign prostatic hyperplasia (BPH). METHODS: The interactive MMP was developed including a computer-administered version of the International Prostate Symptom Score (IPSS) questionnaire. Eighty-eight men referred to the Urology Out-patients with prostatic symptoms entered the study. They first completed the IPSS on paper and secondly used the MMP before completing the computer-administered IPSS. A final feedback questionnaire enquiring into their experience including previous exposure to computers, ease of use, and value of the program content was completed. RESULTS: The use of the MMP resulted in a significant decrease in mean IPSS score from 16.6 to 13.9 (t = 7.456, d.f. = 87, p < 0.01), but no change in quality of life. Patients felt that their knowledge had increased (chi2(1) = 21.253, p < 0.01) and that they had completed the IPSS more accurately (chi2(1) = 10.227, p < 0.01) with the MMP IPSS module compared to the IPSS on paper. Previous use of patient education, patient characteristics and MMP use beyond the information required for the IPSS did not affect IPSS difference (IPSS before versus after MMP use). CONCLUSION: The use of the MMP enhanced patients' knowledge of their condition and reduced patients' IPSS score. The results were independent of previous exposure to information, previous IPSS completion, computer use and age.

Biochemical differentiation of the porphyrias.

OBJECTIVES: To differentiate the porphyrias by clinical and biochemical methods. DESIGN AND METHODS: We describe levels of blood, urine, and fecal porphyrins and their precursors in the porphyrias and present an algorithm for their biochemical differentiation. Diagnoses were established using clinical and biochemical data. Porphyrin analyses were performed by high performance liquid chromatography. RESULTS AND CONCLUSIONS: Plasma and urine porphyrin patterns were useful for diagnosis of porphyria cutanea tarda, but not the acute porphyrias. Erythropoietic protoporphyria was confirmed by erythrocyte protoporphyrin assay and erythrocyte fluorescence. Acute intermittent porphyria was diagnosed by increases in urine delta-aminolevulinic acid and porphobilinogen and confirmed by reduced erythrocyte porphobilinogen deaminase activity and normal or near-normal stool porphyrins. Variegate porphyria and hereditary coproporphyria were diagnosed by their characteristic stool porphyrin patterns. This appears to be the most convenient diagnostic approach until molecular abnormalities become more extensively defined and more widely available.

Are vocationally trained general practitioners better GPs? A review of research designs and outcomes.

Implicit and explicit in reviews of and changes to vocational education for general practitioners in the 1990s is the challenge to defend the assumption that vocationally trained GPs are better GPs. This paper provides a review of the international literature which has reported on outcomes of general practice vocational training programmes. Through the review we identify both the types of research methodologies used (including a brief discussion of their strengths and limitations) and the outcomes reported of vocational training. Twenty-five studies on the outcomes of vocational training are reviewed. These studies used multiple data sources and one of four methodologies: pre- and post-training comparisons, analysis of learners' or teachers' accounts, audits of general practice or analysis of examination pass rates. When collated, the following range of outcomes from vocational training were identified: improved quality of patient care, increased knowledge, improved general practice skills, increased confidence and desirable GP attitudes and personality traits, increased adherence to practice guidelines and higher examination pass rates. The paper concludes with a summary of research and education issues which arise when we examine the question posed at the outset: are trained GPs better GPs?

L-arginine produces NO-independent increases in dopamine efflux in rat striatum.

The effect of L-arginine (L-ARG; 10-100 mM) on dopamine efflux from rat striatum was investigated using in vivo microdialysis. L-ARG (50 mM-100 mM), but not D-arginine (100 mM) nor L-citrulline (100 mM), produced a biphasic effect on dopamine efflux with an initial small reduction, followed by a large sustained increase. The effect of L-ARG was not prevented by nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester or 7-nitroindazole monosodium salt. Efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by L-ARG (10-100 mM), D-arginine (100 mM) and L-citrulline (100 mM). These data suggest that changes in dopamine, DOPAC and HVA efflux produced by high concentrations of L-ARG occur independently of NO, and that the use of high L-ARG concentrations are inappropriate when investigating the role of NO in striatum.

The effect of fenfluramine dosage regimen and reduced food intake on levels of 5-HT in rat brain.

Male Wistar rats received fenfluramine in subacute (5 mg/kg b.i.d. i.p. for 4 days) or escalating (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg b.i.d. i.p., each dose given for 4 days) doses. Saline-treated controls received food ad libitum, or were pair-fed with the fenfluramine-treated animals. Rats were killed 1, 15 and 30 days after drug withdrawal. On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered. Both treatment regimes, and pair-feeding reduced food intake and body weight. Subacute fenfluramine reduced brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels for up to 30 days. Brain 5-HT and 5-HIAA levels were unaltered following escalating-doses of fenfluramine. Additionally, pair-feeding transiently decreased hippocampal 5-HT levels. These data suggest that escalating-doses of fenfluramine prevent the 5-HT-depleting effect of a sub-cute challenge without altering the anorexic action of the drug.