An evaluation of continuous subcutaneous infusions across seven NHS acute hospitals: is there potential for 48-hour infusions?

BACKGROUND: Continuous subcutaneous infusions (CSCIs) are commonly used in the United Kingdom as a way of administering medication to patients requiring symptom control when the oral route is compromised. These infusions are typically administered over 24 h due to currently available safety data. The ability to deliver prescribed medication by CSCI over 48 h may have numerous benefits in both patient care and health service resource utilisation. This service evaluation aims to identify the frequency at which CSCI prescriptions are altered at NHS Acute Hospitals. METHODS: Pharmacists or members of palliative care teams at seven acute NHS hospitals recorded anonymised prescription data relating to the drug combination(s), doses, diluent and compatibility of CSCIs containing two or more drugs on a daily basis for a minimum of 2 days, to a maximum of 7 days. RESULTS: A total of 1301 prescriptions from 288 patients were recorded across the seven sites, yielding 584 discrete drug combinations. Of the 584 combinations, 91% (n = 533) included an opioid. The 10 most-common CSCI drug combinations represented 37% of the combinations recorded. Median duration of an unchanged CSCI prescription across all sites was 2 days. CONCLUSION: Data suggests medication delivered by CSCI over 48 h may be a viable option. Before a clinical feasibility study can be undertaken, a pharmacoeconomic assessment and robust chemical and microbiological stability data will be required, as will the assessment of the perceptions from clinical staff, patients and their families on the acceptability of such a change in practice.

Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials.

OBJECTIVES: The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy. METHODS: A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (<50 HIV-1 RNA copies/mL). Rates of virological suppression were analysed using switch-equals-failure and intensification-included endpoints [intent-to-treat (ITT)]. The rate of treatment-emergent resistance mutations, neurocognitive function endpoints, and cerebrospinal fluid (CSF) HIV-1 RNA were also analysed by treatment arm. RESULTS: There were 2303 patients from 13 different randomized clinical trials of darunavir/r monotherapy (n = 784: MONET, MONOI, Monarch and PROTEA), lopinavir/r monotherapy (n = 829: OK pilot, OK-04, KalMo, KALESOLO, KRETA, MOST and DREAM), atazanavir/r monotherapy (n = 103: MODAT), or all three (n = 587: PIVOT). HIV-1 RNA plasma suppression was lower in the PI/r monotherapy arm compared with the triple therapy arm in the switch-equals-failure analysis [difference -8.3%; 95% confidence interval (CI) -11.9 to -4.8%], but not when intensification was included (difference 0.5%; 95% CI -2.5 to 3.6%). Rates of resistance mutations were similar between arms, as was overall neurocognitive function. CONCLUSIONS: PI/r monotherapy showed a higher risk of plasma HIV-1 RNA elevations. However, there was no increased risk of treatment-emergent drug resistance, neurocognitive endpoints did not differ, and HIV-1 RNA suppression rates after intensification were similar between PI/r monotherapy and triple therapy.

Evaluation of free water and water activity measurements as functional alternatives to total moisture content in broiler excreta and litter samples.

Litter moisture contents vary greatly between and within practical poultry barns. The current experiment was designed to measure the effects of 8 different dietary characteristics on litter and excreta moisture content. Additionally, free water content and water activity of the excreta and litter were evaluated as additional quality measures. The dietary treatments consisted of nonstarch polysaccharide content (NSP; corn vs. wheat), particle size of insoluble fiber (coarse vs. finely ground oat hulls), viscosity of a nonfermentable fiber (low- and high-viscosity carboxymethyl cellulose), inclusion of a clay mineral (sepiolite), and inclusion of a laxative electrolyte (MgSO4). The 8 treatments were randomly assigned to cages within blocks, resulting in 12 replicates per treatment with 6 birds per replicate. Limited effects of the dietary treatments were noted on excreta and litter water activity, and indications were observed that this measurement is limited in high-moisture samples. Increasing dietary NSP content by feeding a corn-based diet (low NSP) compared with a wheat-based diet (high NSP) increased water intake, excreta moisture and free water, and litter moisture content. Adding insoluble fibers to the wheat-based diet reduced excreta and litter moisture content, as well as litter water activity. Fine grinding of the oat hulls diminished the effect on litter moisture and water activity. However, excreta moisture and free water content were similar when fed finely or coarsely ground oat hulls. The effects of changing viscosity and adding a clay mineral or laxative deviated from results observed in previous studies. Findings of the current experiment indicate a potential for excreta free water measurement as an additional parameter to assess excreta quality besides total moisture. The exact implication of this parameter warrants further investigation.

Effect of different magnesium sources on digesta and excreta moisture content and production performance in broiler chickens.

Reducing litter moisture is an effective measure to reduce the incidence of footpad dermatitis. Dietary mineral levels affect intestinal conditions with regard to osmolarity and water reabsorption. Magnesium is often used as a laxative, preventing reabsorption of water from the digesta, and as a consequence, more moisture in the excreta. The objective of the current experiment was to evaluate Mg in broiler diets as a model for reduced intestinal water reabsorption. Effects of magnesium source (magnesium sulfate, magnesium oxide, and magnesium chloride), each at 3 levels (0.255, 1.02, and 2.04 g·kg(-1) diet), were studied. Measured effects were digesta moisture levels throughout the gastrointestinal tract and the moisture level of the excreta. The 10 treatments were randomly assigned to cages within 6 blocks, resulting in 6 replicates per treatments with 18 birds per replicate. Adding magnesium to the diet of broilers linearly increased the excreta moisture content, following the pattern MgCl > MgSO(4) = MgO. This rejects the hypothesis that MgO and MgCl are less laxative sources compared with MgSO(4). The magnesium sources most likely changed the water reabsorption in the distal gastrointestinal tract, as confirmed by the increased digesta moisture percentage in the ceca and colon. Increasing dietary MgSO(4) linearly reduced BW gain and feed intake, though absolute differences were minor. The results of this experiment show that Mg addition in the diet may be used as a model to study wet litter caused by reduced intestinal water reabsorption.

Analysis of the role of Mycobacterium tuberculosis kasA gene mutations in isoniazid resistance.

Previous studies have suggested that Mycobacterium tuberculosis kasA G312S and G269S gene mutations may represent sequence polymorphisms of the M. tuberculosis East-African-Indian (EAI) and T families, respectively, rather than relating to isoniazid resistance. The present study examined polymorphisms of these two codons in 98 drug-susceptible M. tuberculosis isolates (68 EAI and 30 T isolates). Twenty-eight isolates belonging to a sub-lineage of the EAI family had the kasA G312S mutation, but none of the 30 T isolates had the G269S mutation. The data suggest that the kasA G312S mutation is not related to isoniazid resistance, but represents a sequence polymorphism in a sub-lineage of the EAI family.

Genotype and phenotype relationships and transmission analysis of drug-resistant tuberculosis in Singapore.

SETTING: The small urban country of Singapore. OBJECTIVES: To investigate the relationships between Mycobacterium tuberculosis genotypes and drug-resistant phenotypes and to analyse the transmission of drug-resistant tuberculosis (DR-TB). DESIGN: A 29-month population-based study comparing drug-resistant and drug-susceptible M. tuberculosis isolates. RESULTS: We found that multidrug-resistant (MDR) isolates (n = 41, OR 2.66, 95%CI 1.28-5.50), rifampicin-resistant isolates (n = 48, OR 2.88, 95%CI 1.44-5.76), and streptomycin (SM) resistant isolates (n = 103, OR 3.35, 95%CI 1.99-5.62) were more common among Beijing genotype strains than among non-Beijing strains, while SM-resistant isolates were less common in East-African-Indian (EAI) genotype strains than in non-EAI strains (OR 0.30, 95%CI 0.14-0.64). Based on clustering analysis and drug-resistant patterns, 22 of 230 drug-resistant isolates were found to have likely resulted from recent transmission. The estimated transmission rate of DR-TB was 9.6% and that of MDR-TB was 7.7%. The transmission rate of DR-TB was significantly higher among Beijing genotype strains than non-Beijing strains (12.9% vs. 4.4%; P = 0.034). CONCLUSIONS: Compared to other genotypes, Beijing genotype strains are associated with a higher frequency of drug resistance, including multidrug resistance, and are more transmissible. However, the overall transmission rate of DR-TB in Singapore is low.

AIDS-defining illness diagnosed within 90 days after starting highly active antiretroviral therapy among patients from the TREAT Asia HIV Observational Database.

Using data from TREAT Asia HIV Observational Database (TAHOD), this paper aims to assess the rate of, and factors associated with the diagnosis of new AIDS-defining illness (ADI) within 90 days after antiretroviral treatment. Patients starting three or more antiretroviral combinations and having subsequent follow-up were included. New ADI cases were checked for evidence of immune reconstitution syndrome (IRS). Among the 1185 patients included, 75 (6.3%) were diagnosed with a new ADI within 90 days, giving a rate of 26.8/100 person-years, compared with a further 3.6% cumulative incidence of new ADI between 90 days to one year (4.2/100 person-years). Of the 75 patients, 21 were judged as definitive or presumptive IRS, giving a rate of 7.3/100 person-years. Patients with new ADI generally had lower CD4 counts before treatment started (median, 43 cells/microL). Lower CD4 count, lower body mass index and starting treatment in the same year as the first HIV-positive test done were associated with developing a new ADI. The higher rate of new ADI within 90 days may be partly explained by IRS occurring shortly after treatment. Although it is difficult to identify IRS from observational data, it appears that in TAHOD setting IRS was relatively uncommon.

Effects of dietary metabolizable energy and protein on early growth responses of broilers to dietary lysine.

Two studies evaluated effects of metabolizable energy (ME), digestible Lys (dLys), and amino acid (AA) balance on broiler performance. In experiment 1 diets contained 3 levels of ME (3,000, 3,100, and 3,200 kcal/kg) in combination with 4 levels of dLys (1.05, 1.13, 1.21, and 1.29%). A fixed proportion of dLys relative to CP and key indispensable AA was maintained in graded increments of CP from 21.9 to 26.9%. There was no interaction of ME and dLys for 21 d BW gain or adjusted feed conversion ratio, which improved linearly with dietary dLys. Increasing the dLys or ME had no effect on feed intake, and the linear improvement in performance was attributed to a step-wise increase in dLys when diets contained a balance of AA and CP. Experiment 2 evaluated broiler response to 20 d of age when diets contained graded increments in dLys while maintaining a fixed proportion of dLys relative to CP and indispensable AA (balanced CP), or when dLys was increased in diets by supplementing synthetic l-Lys to 1 of 2 basal diets with 22.0% CP (low CP) or 27.0% CP (high CP) without adjusting concentrations of other AA or CP. The BW gain of broilers fed the low CP diet series followed a quadratic response, and the dLys requirement was estimated to be 1.19 +/- 0.03% (1.30% total Lys). By contrast, BW gain on both the high CP and balanced CP diet series increased linearly. The higher BW gain and continued response to dLys above 1.19% when CP and AA concentrations were increased confirmed that the dLys requirement of broilers was dependent on the dietary CP. When a fixed ratio of dLys to CP was applied and indispensable and dispensable AA were not limiting, broiler BW gain and adjusted feed conversion ratio responded positively to incremental dLys up to at least 1.32% (27.2% CP) and was independent of the dietary ME over a range from 3,000 to 3,200 kcal/kg.

CADRE: the Central Aspergillus Data REpository.

CADRE is a public resource for housing and analysing genomic data extracted from species of Aspergillus. It arose to enable maintenance of the complete annotated genomic sequence of Aspergillus fumigatus and to provide tools for searching, analysing and visualizing features of fungal genomes. By implementing CADRE using Ensembl, a framework is in place for storing and comparing several genomes: the resource will thus expand by including other Aspergillus genomes (such as Aspergillus nidulans) as they become available. CADRE is accessible at http://www.cadre. man.ac.uk.

A randomised controlled trial of oral zinc on the immune response to tuberculosis in HIV-infected patients.

SETTING: The National HIV Unit, Singapore. OBJECTIVE: To test whether zinc supplementation improves the immune response to tuberculosis in HIV-positive patients. DESIGN: A double-blind, randomised, placebo-controlled trial of 28 days of oral zinc sulphate (50 mg of elemental zinc) or placebo in stable adult HIV-positive patients receiving antiretroviral therapy with a CD4 count <200 cells/microl. METHODS: IFN-gamma response to mycobacterial antigen stimulation, CD4/8 cell count, lymphocyte subsets, T-cell receptor excision circle (TREC) levels and viral load were measured at baseline and day 28. RESULTS: Thirty-two patients received zinc and 34 placebo. There was no significant change in the IFN-gamma response to human PPD stimulation in the zinc or placebo groups (placebo baseline: 0.42 +/- 1.03, day 28: 0.84 +/- 1.21 IU/ml, zinc baseline: 1.26 +/- 2.41, day 28: 1.39 +/- 1.88 IU/ml, P = 0.31 between groups), nor any of the other mycobacterial antigens tested. There were no changes in absolute CD4/8 cell levels or other lymphocyte subsets, TREC or viral load. Baseline zinc levels were normal in 62/66 (93.9%) patients. CONCLUSIONS: We found no evidence for recommending pharmacological supplementation with oral zinc in HIV-positive patients without zinc deficiency.

Short-term growth hormone administration at the time of opportunistic infections in HIV-positive patients.

OBJECTIVES: A 12-week course of recombinant human growth hormone is an effective but expensive therapy for established HIV-related wasting. Wasting in HIV disease is often episodic, coinciding with bouts of acute opportunistic infection. We hypothesized that a short course of growth hormone, targeted at the time of opportunistic infection, might improve protein metabolism thereby reducing lean tissue loss. METHODS: HIV-infected men with acute opportunistic infections, who received standard antimicrobial treatment for their infection as well as intensive nutritional counselling and oral energy supplements, were randomized to receive growth hormone or placebo for 14 days. Principal assessments were protein metabolism (measured by 13C-leucine infusion), body composition (measured by DEXA) and safety. RESULTS: There were no significant changes in outcome parameters in the placebo group (n = 11). In the growth hormone group (n = 9), protein catabolic rate decreased by 60% in the fasted state (P = 0.02 versus placebo), lean body mass increased by 2.2 kg (P = 0.03 versus baseline) and fat mass decreased by 0.7 kg (P = 0.002 versus baseline). There was no increase in adverse or serious adverse events in the growth hormone as compared with the placebo group. CONCLUSIONS: A two-week course of growth hormone at the time of acute opportunistic infection in HIV-infected patients improves protein metabolism and body composition during therapy and appears to be safe. This may represent a rational and economical approach to the use of growth hormone therapy.

Prevalence of and risk factors for nasal colonization with Staphylococcus aureus among human immunodeficiency virus-positive outpatients in Singapore.

We studied the prevalence of and risk factors for Staphylococcus aureus nasal colonization in HIV-positive outpatients in Singapore. Overall prevalence was 23% (45 of 195), with 3% (6 of 195) being MRSA. Recent antibiotic use and hospitalization were independent predictors of MRSA colonization. Isolates were genotypically identical to our hospital's inpatient circulating strain.

Risk factors for infection in Malaysian patients with systemic lupus erythematosus.

To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p < 0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p < 0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.

Bioelectrical impedance analysis in human immunodeficiency virus-infected patients: comparison of single frequency with multifrequency, spectroscopy, and other novel approaches.

Bioelectrical impedance (BIA), a prediction method for estimating body water compartments and body cell mass (BCM), is being increasingly used in studies of human immunodeficiency virus (HIV)-related wasting, but there are few validation studies of the method in this group. The aim of this study is to examine the relationship between impedance measurements and body water compartments in patients with advanced HIV disease, and to investigate whether the newer approaches of multifrequency BIA, BIA spectroscopy, logarithmic transformation using a parallel circuit model, and direct calculation from electrical theory offer any advantage over traditional single-frequency BIA. We measured total body water (TBW) by deuterium dilution and extracellular water by bromide dilution in 33 patients with advanced HIV disease. Intracellular water and BCM were calculated from these results. Impedance was measured over a range of frequencies using a multifrequency analyzer. The relationship between impedance index at various frequencies and body water compartments was assessed by correlation and linear regression. We found that impedance index at higher frequencies had a closer relationship to TBW (r = 0.86, standard error of the estimate [SEE] = 2.96 at 1000 kHz) and at lower frequencies a closer relationship to extracellular water (ECW) (r = 0.47, SEE = 3.13 at 0 kHz) than the traditional 50 kHz measurement (r = 0.84, SE = 3.11 for TBW; r = 0.44 SEE = 3.19 for ECW), but the differences were marginal and not statistically significant. None of the other novel approaches tested were significantly better than traditional single frequency measurement. The 50 kHz equation for BCM developed in this study [BCM (kg) = (0.360331 x Ht2/Z50) + (0.151123 x Wt)-2.95] may be useful to investigators using BIA for hIV-wasting studies.

Multiple frequency bioelectrical impedance analysis: a cross-validation study of the inductor circuit and Cole models.

It has been proposed that multiple frequency bioelectrical impedance models of the human body should include an inductive property for the circulatory system, the inductor circuit model (ICM), and that such a model, when coupled with a new method of data analysis, can improve the predictive power of multiple frequency bioelectrical impedance analysis (MFBIA). This hypothesis was tested using MFBIA measurements and gold standard measures of total body and extracellular water volumes in a cross-validation study in two subject groups (viz. controls and HIV). The MFBIA measurements were analysed using the current, widely accepted Cole model and the alternative ICM model which includes an inductive component. Correlations in the range 0.75 to 0.92 (for TBW) and 0.46 to 0.79 (for ECW) for impedance quotients versus gold standard measures within the subject groups were observed. These decreased, to as low as r = 0.50 for TBW and r = 0.29 for ECW, when the derived algorithms were applied to the alternative subject group. These results suggest that lack of portability of MFBIA algorithms between subject groups is not due to an inadequacy of the analogue circuit model per se but is possibly due more to fundamental flaws in the principles associated with its application. These include assuming a constant proportionality of body segment geometries and tissue fluid resistivities. This study has also demonstrated that this inadequacy cannot be overcome by simply introducing an inductive component into the analogue electrical circuit.

The effect of dietary selenium source and level on the uptake of selenium by developing chick embryos.

We studied the effect of dietary source (organic or inorganic) and level of Se on the Se uptake of chick embryos. After receiving a low-Se diet for 16 wk, 126 Leghorn laying hens were randomly assigned to one of seven dietary treatments. Treatments consisted of feeding a low-Se basal diet alone or with one of three levels of added Se (0.1,0.2, or 0.3 mg/kg Se) supplied by sodium selenite or Se-enriched yeast. Fertile eggs were collected after 33 d of feeding the experimental diets. Eggs were subjected to no incubation or incubation for 5, 10, 15, or 20 d. Non-incubated eggs were separated, and the yolk and albumen were assayed separately for Se. Incubated eggs were separated into the embryo and extra-embryonic portions, which were assayed separately for Se. Se concentrations of the yolk and albumen were significantly different among dietary treatments. Compared with eggs from hens fed sodium selenite, yolk and albumen Se concentrations were higher in eggs from hens fed Se yeast. Embryonic and extra-embryonic Se concentrations were higher in eggs from hens fed Se yeast than eggs from hens fed sodium selenite. The largest increase in embryonic Se concentration was observed during Days 10 to 15 of incubation. It was concluded that Se source and dietary inclusion level influenced the Se concentration of portions of developing embryonated eggs and that embryonic Se concentration changed during incubation.

Importation of seven cases of an unusual helminthic infection into Singapore and assessment of the risk of local transmission.

Singapore remains vulnerable to the introduction of infectious diseases from other countries due to the high traffic of migrant labour and other visitors. We describe seven cases of migrant workers from West Africa who entered Singapore carrying loaisis, a helminthic infection. The clinical presentation, treatment using single dose ivermectin, potential for transmission, and the need for screening of this infection in Singapore are discussed.