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.

The effect of incremental levels of dietary nitrate on methane emissions in Holstein steers and performance in Nelore bulls.

Two experiments were conducted to study effects of dietary nitrate on enteric methane production, blood methemoglobin concentration, and growth rate in cattle. In Exp. 1, 36 Holstein steers (288 ± 25 kg BW) were fed increasing levels of dietary nitrate (6 levels; 0 to 3.0% of feed DM) in corn silage-based total mixed rations. Nitrate was introduced gradually in a 25-d adaptation period before methane production was determined in environmentally controlled rooms. In the rooms, feed intake was restricted and similar among all treatments. Methane production (g/d) decreased linearly as dietary nitrate concentration increased (P < 0.01). The apparent efficiency (measured methane reduction divided by potential methane reduction) with which enteric methane was mitigated was 49%. Blood methemoglobin levels increased with increasing nitrate dose. In Exp. 2, 300 Nelore bulls (392 ± 28 kg) were fed increasing levels of nitrate (6 levels; 0 to 2.4% of feed DM) in high-concentrate total mixed rations offered ad libitum. Feed intake decreased linearly with increasing level of dietary nitrate (P < 0.01). However, ADG was not affected by nitrate dose (P = 0.54), resulting in a linear improvement in G:F (P = 0.03) as dietary nitrate level increased. Carcass dressing percentage showed a quadratic response to incremental dietary nitrate, reaching the highest value at 0.96% of NO3/kg DM (P = 0.04).

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.

Moisture content in broiler excreta is influenced by excreta nutrient contents.

High litter moisture content, often referred to as wet litter, is a major problem in poultry production. Wet litter is often related to poor management, diseases, and digestive problems. In this experiment, the objective was to study the relationship between nutrient content and the moisture content of the excreta of broilers. A dataset containing 351 observations was built and contained the nutrient contents data including moisture content of excreta samples collected in 8 different broiler feeding trials. A biological based model approach was used to create a model with 10 and another one with 14 variables that may explain the excreta moisture level response. Subsequently, these models were compared with a statistical model that was built automatically and adjusted only if this improved the biological model. The R(2) of the 10 variable model was 0.54, in which Zn content and the interaction of NDF × K and Ca × P content were negatively associated with excreta moisture. Sodium, P, and Ca content and the interaction between content of NDF × Na were positively associated with excreta moisture. The R(2) of the 14 variable model was 0.58, in which Zn and K content and the interaction of NDF × protein and Ca × P content were negatively associated with excreta moisture, and Na, protein, P, and Ca content and the interactions in contents of NDF × Na, NDF × Zn, and K × Cu were positively associated with excreta moisture content. In conclusion, the models confirmed the effect of Na, protein, P, and Ca on excreta moisture content. Furthermore, hitherto unknown nutrient interactions that contribute to excreta moisture level were identified. As excreta levels of most nutrients can be manipulated by adjusting dietary nutrient levels, dietary formulation can be adjusted with the findings of this analysis to change levels of excreted nutrients and, consequently, also moisture output.

Is a 4-month regimen adequate to cure patients with non-cavitary tuberculosis and negative cultures at 2 months?

A recent trial evaluating a 4-month regimen of standard drugs in adults with non-cavitary tuberculosis (TB) and negative cultures at 2 months failed to demonstrate equivalence compared to the same regimen given for 6 months. To contribute further evidence, data from two trials conducted by the British Medical Research Council (BMRC) comparing 4 and 6 month regimens were re-analysed. The results from the BMRC trials in patients with non-cavitary TB and negative cultures at 2 months were consistent with those from the recent trial. However, given that there was no acquired drug resistance, the estimated 6.6% relapse rate (95%CI 4.3-10.1) across all three trials might be considered acceptable for a 4-month regimen in patients with non-cavitary pulmonary TB.

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.

Verotoxin-2 activates mitogen-activated protein kinases in bovine adherent peripheral blood mononuclear cells.

The effects of verotoxin (VT) on the mitogen-activated protein (MAP) kinase signalling pathways were investigated in bovine adherent peripheral blood mononuclear cells (PBMCs). VT2 stimulated a transient activation of both p38 MAP kinase and extracellular-regulated kinase (ERK) and stimulated an increase in tumour necrosis factor-α release from PBMCs. Bovine PBMCs react with very similar kinetics to human peripheral blood monocytes, despite the gross differences in disease outcome of the two species on infection with verotoxigenic Escherichia coli.

Una experiencia con grupos multifamiliares en pacientes con esquizofrenia / An experience with multi-family groups in patients with schizophrenia

Se expone la experiencia de la aplicación de los grupos multifamiliares de Mc Farlane a siete pacientes y sus ocho cuidadores en una unidad de media estancia para mejorar el conocimiento sobre la esquizofrenia, la carga y el apoyo social de los cuidadores y para optimizar el funcionamiento de los pacientes. Se realiza una evaluación basal y otra post intervención, observándose una mejoría del conocimiento de la enfermedad y de la carga de los familiares. El apoyo social familiar y el funcionamiento general del paciente no se modifica tras la intervención familiar (AU)

The experience of the application of McFarlane’s multiple family group intervention in seven schizophrenic patients and their eigth caregivers in a middle-stay unit in order to improve burden and social support for the caregivers and to improve patient functioning is reported. A baseline evaluation and another post-intervention evaluation were made. Improvement in the knowledge about the disease and in the family burden was observed. Social support for the family and general functioning of the patient was not changed after family intervention (AU)

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.

Validation of three-dimensional laser scanning for the assessment of facial fat changes.

OBJECTIVE: We aimed to evaluate the accuracy of three-dimensional laser scanning as an objective method for detecting facial changes. METHODS: Facial laser scanning was performed at baseline and repeated after a median of 10 months in 24 HIV-infected patients, 12 with ongoing lipodystrophy, five with >10% weight loss and seven with >10% weight gain. Surface volume change was estimated using a standardized technique, and compared with change in cheek fat measured by magnetic resonance imaging (MRI). RESULTS: The median laser scanning surface volume changes were -2.1 (range -4.6 to -0.8) mL in the lipoatrophy group, -1.5 (range -6.8 to -1.3) mL in the weight loss group and +3.1 (range -0.2 to +5.4) mL in the weight gain group (the median MRI cheek fat changes were -4.6, -3.7 and +7.0 mL in the three groups, respectively). Laser scanning and MRI measurements were not significantly associated in lipoatrophy patients (r=0.34, P=0.28), but there was a good association in patients who changed weight (r=0.71, P=0.01). CONCLUSIONS: Laser scanning detects changes in the appropriate direction, although it underestimates MRI-measured cheek fat changes. Laser scanning may be useful as an objective measure of cheek surface volume changes, but needs further validation in larger clinical cohorts.

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.

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.

Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database.

BACKGROUND: The antiretroviral treatment (ART) combination of stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the most frequently used initial regimen in many Asian countries. There are few data on the outcome of this treatment in clinic cohorts in this region. METHODS: We selected patients from the TREAT Asia HIV Observational Database (TAHOD) who started their first ART regimen with d4T/3TC/NVP. Treatment change was defined as cessation of therapy or the addition or change of one or more drugs. Clinical failure was defined as diagnosis with an AIDS-defining illness, or death while on d4T/3TC/NVP treatment. RESULTS: The rate of treatment change among TAHOD patients starting d4T/3TC/NVP as their first antiretroviral treatment was 22.3 per 100 person-years, with lower baseline haemoglobin (i.e. anaemia) associated with slower rate of treatment change. The rate of clinical failure while on d4T/3TC/NVP treatment was 7.3 per 100 person-years, with baseline CD4 cell count significantly associated with clinical failure. After d4T/3TC/NVP was stopped, nearly 40% of patients did not restart any treatment and, of those who changed to other treatment, the majority changed to zidovudine (ZDV)/3TC/NVP and less than 3% of patients changed to a protease inhibitor (PI)-containing regimen. The rates of disease progression on the second-line regimen were similar to those on the first-line regimen. CONCLUSION: These real-life data provide an insight into clinical practice in Asia and the Pacific region. d4T/3TC/NVP is maintained longer than other first-line regimens and change is mainly as a result of adverse effects rather than clinical failure. There is a need to develop affordable second-line antiretroviral treatment options for patients with HIV infection in developing countries.

The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy.

BACKGROUND: The impact that malnutrition at the time of starting antiretroviral therapy (ART) has on survival and the CD4 count response is not known. METHODS: A retrospective cohort study of patients attending the national HIV referral centre in Singapore who had a CD4 count less than 250 cells/microL and a measurement of body weight performed at the time of starting ART was carried out. Demographic and clinical variables were extracted from an existing database. Body mass index (BMI) was calculated from the weight in kilograms divided by the square of the height in metres. Moderate to severe malnutrition was defined as BMI less than 17 kg/m(2). Intent-to-treat Cox models were used to determine the predictors of survival. RESULTS: A total of 394 patients were included in the analysis, of whom 79 died during a median study follow-up of 2.4 years. Moderate to severe malnutrition was present in 16% of patients at the time of starting ART, and was found to be a significant independent predictor of death [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.29-3.73, P=0.004 for those with BMI<17 compared with those with BMI>18.5] as were stage of disease (HR 2.47, 95% CI 1.20-5.07, P=0.014 for those who were at stage C compared with those at stage A) and the type of ART [HR 0.50, 95% CI 0.27-0.93, P=0.03 for highly active antiretroviral therapy (HAART) compared with non-HAART treatment]. Malnutrition did not impair the magnitude of the increase in CD4 count at 6 or 12 months. CONCLUSIONS: Malnutrition at the time of starting ART was significantly associated with decreased survival, but the effect appeared not to be mediated by impaired immune reconstitution. Given the increasing access to ART in developing countries and the high frequency of HIV-associated wasting, studies of nutritional therapy as an adjunct to the initiation of HAART are urgently needed.