Use of antibiotics in paediatric long-term care facilities.

BACKGROUND: Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. AIM: To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. METHODS: A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. FINDINGS: Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). CONCLUSION: Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical.

Concordance of Mycobacterium tuberculosis fluoroquinolone resistance testing: implications for treatment.

Fluoroquinolone (FQ) drug susceptibility testing (DST) is an important step in the design of effective treatment regimens for multidrug-resistant tuberculosis. Here we compare ciprofloxacin, ofloxacin and moxifloxacin (MFX) resistance results from 226 multidrug-resistant samples. The low level of concordance observed suggests that DST should be performed for the specific FQ planned for clinical use. The results also support the new World Health Organization recommendation for testing MFX at a critical concentration of 2.0 µg/ml.

Panton Valentine leukocidin MSSA leading to multi-organ failure.

We report a case of a 15-year-old boy who developed multiple organ failure secondary to a sport injury leading to infection with a Panton Valentine Leukocidin (PVL) secreting Community-Acquired Methicillin Sensitive Staphylococcus Aureus (CA MSSA). Aggressive antibiotic therapy eventually led to recovery.

Teeth as biomonitors of selenium concentrations in tissues of beluga whales (Delphinapterus leucas).

Selenium (Se) is an essential element which has been shown to play an important role in protecting marine mammals against the toxic effects of mercury (Hg) and other metals. It has been suggested that metal concentration in marine mammal teeth can potentially be used as bioindicators for body burden. The objective of this study was to investigate the relationship between Se concentrations in beluga (Delphinapterus leucas) teeth and those previously measured in soft tissues (liver, kidney, muscle and muktuk). Tooth Hg concentrations are also measured, and the relationships between Se and Hg in teeth and soft tissues are examined. Se in the teeth of beluga was measured using hydride generation atomic fluorescence spectrometry (HG-AFS) and Hg in beluga teeth was measured by cold-vapour atomic absorption. Tooth Se concentrations ranged from 108 ng/g to 245 ng/g dry weight, and tooth Hg concentrations ranged from 10 to 189 ng/g dry weight. In the soft tissues, Se concentrations were highest in the liver, followed by kidney, muktuk, and muscle. There were significant correlations between tooth Se concentrations and animal age, tooth Se and liver and muscle Se, and between liver Se and animal age. The molar ratio of Hg:Se in the liver was found to be 0.70. This study is the first to measure Se in the teeth of a marine mammal species, and HG-AFS is found to be an effective technique for determining Se in beluga teeth. Tooth Se can be used as predictor for liver and muscle Se, although these relationships may be strongly influenced by the association of Se with Hg in marine mammal tissues. This study contributes to an increased understanding of the storage and metabolism of Se in marine mammals.

Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide.

BACKGROUND AND PURPOSE: Patients commonly take complementary medicines in conjunction with conventional drugs without clear evidence of safety or the risk of herb-drug interactions. The aim of this study was to assess potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John's wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) genotypes. EXPERIMENTAL APPROACH: A crossover controlled study was conducted in 21 healthy subjects. Each received gliclazide (80 mg) either alone or during 15 days treatment with St John's wort. The area under the plasma concentration-time curve (AUC(0-infinity)), apparent clearance (CL/F) and elimination half-life (t 1/2) of gliclazide and incremental changes in glucose and insulin AUC(0-4) were compared. CYP2C9*2 and CYP2C9*3 alleles were identified using PCR followed by restriction enzyme digestion analysis. KEY RESULTS: St John's wort significantly altered gliclazide pharmacokinetics in all except for four healthy subjects. The mean ratio and 90% confidence interval (CI) of gliclazide AUC(0-infinity) and CL/F were 0.67 (0.55-0.81) and 1.50 (1.24-1.81), respectively, after St John's wort treatment. St John's wort decreased gliclazide t (1/2), with mean ratio and 90% CI of 0.85 (0.74-0.93). There were no significant changes in glucose or insulin AUC(0-4) after St John's wort treatment and no significant differences according to CYP2C9 genotype. CONCLUSIONS AND IMPLICATIONS: Treatment with St John's wort significantly increases the apparent clearance of gliclazide which is independent of CYP2C9 genotype. People with diabetes receiving this combination should be closely monitored to evaluate possible signs of reduced efficacy.

Supplementary feeding at milking and minimum milking interval effects on cow traffic and milking performance in a pasture-based automatic milking system.

In extensive pastoral dairy farming systems herds graze 12 months of the year with the majority fed a near-100% pasture or conserved pasture diet. The viability of automatic milking in these systems will depend partly upon the amount of supplementary feed necessary to encourage cows to walk from the pasture to the milking unit but also on the efficient use of the automatic milking system (AMS). This paper describes a study to determine the importance of offering concentrate in the milking unit and the effect of minimum milking interval on cow movement and milking performance in a pasture-based AMS. The effects of feeding rate (FR0=0 kg or FR1=1 kg crushed barley/d) and minimum milking interval (MM6=6 h or MM12=12 h) on cow movement and behaviour during milking were studied in a multi-factorial cross-over (feeding level only, 4 weeks per treatment) experiment involving 27 mixed-breed cows milked through a single AMS. Feeding 1 kg barley in the milking unit resulted in a higher visiting frequency to the pre-selection unit (FR0=4.6 visits/d, FR1=5.4 visits/d, sed=0.35, P<0.05) and a higher yield (FR0=22.5 kg/d, FR1=23.6 kg/d, sed=0.385, P<0.01) but had no effect on milking frequency (FR0=1.6 milkings/d, FR1=1.7 milkings/d, sed=0.04, NS). Minimum milking interval was the major factor influencing milking frequency (MM6=1.9, MM12=1.4 milkings/d, sed=0.15, P<0.01). The absence of feeding in the milking unit had no negative effect on behaviour during milking or the number of cows that had to be manually driven from the paddock. The results show that automatic milking can be combined with a near-100% pasture diet and that milking interval is an important determinant for maximizing milk harvested per AMS.

Persistent maternal effects on juvenile survival in North American red squirrels.

Maternal effects can have lasting fitness consequences for offspring, but these effects are often difficult to disentangle from associated responses in offspring traits. We studied persistent maternal effects on offspring survival in North American red squirrels (Tamiasciurus hudsonicus) by manipulating maternal nutrition without altering the post-emergent nutritional environment experienced by offspring. This was accomplished by providing supplemental food to reproductive females over winter and during reproduction, but removing the supplemental food from the system prior to juvenile emergence. We then monitored juvenile dispersal, settlement and survival from birth to 1 year of age. Juveniles from supplemented mothers experienced persistent and magnifying survival advantages over juveniles from control mothers long after supplemental food was removed. These maternal effects on survival persisted, despite no observable effect on traits normally associated with high offspring quality, such as body size, dispersal distance or territory quality. However, supplemented mothers did provide their juveniles an early start by breeding an average of 18 days earlier than control mothers, which may explain the persistent survival advantages their juveniles experienced.

Mycophenolate mofetil therapy for moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that can be refractory to topical and systemic corticosteroids, phototherapy, topical immunomodulators and systemic immunosuppressive drugs. Recent studies have shown promise for the use of mycophenolate mofetil (MMF) to treat recalcitrant AD. AIM: To assess the effectiveness and adverse effects of MMF used for moderate to severe AD in a university outpatient dermatology clinic. METHODS: A retrospective chart review of 20 patient charts was conducted for patient age, gender, duration of disease, prior therapies, concomitant therapy, clinical response and adverse side-effects. RESULTS: Of the 20 patients, 17 improved within 4 weeks of starting MMF therapy. Ten patients had disease remission and were subsequently able to discontinue MMF. Seven attained satisfactory control of their AD using MMF as maintenance therapy. Overall, MMF was well tolerated, with mild headaches, gastrointestinal complaints and fatigue as the commonest side-effects. During therapy, herpes zoster developed in four patients, Staphylococcus aureus cutaneous infections in two, and herpes simplex in one. One patient discontinued MMF because of insufficient control of pruritus. CONCLUSION: MMF can be rapidly effective and well tolerated in patients with moderate to severe AD resistant to conventional therapies. The limitations of this retrospective study include no control group and a lack of a standardized scoring index to assess improvement, and the concomitant use of adjuvant therapies makes the contribution of MMF alone difficult to assess. Larger controlled studies are needed.

The effect of a pectin-lecithin complex on prevention of gastric mucosal lesions induced by feed deprivation in ponies.

This study examined whether a product containing a pectinlecithin complex (Pronutrin) (1) could prevent gastric lesions induced in the equine gastric squamous epithelial mucosa using a protocol of intermittent feed deprivation that resulted in prolonged increased gastric acidity (Murray and Eichorn 1996). Eight ponies were used and served as their own controls in 2 trials in which there were 72 h cumulative deprivation (alternating 24 h with no feed, then 24 h free choice hay), with a 4-week interval between trials. Ponies were assigned randomly to receive either 250 g Pronutrin plus 200 g pelleted feed, or 450 g pelleted feed only. Ponies were conditioned to each treatment for 7 days and received Pronutrin and pellets or only pellets once daily during the feed deprivation protocol. Gastroscopy was performed at the beginning and conclusion of the feed deprivation protocol. The endoscopist (MJ.M.) was blinded as to treatments, and lesion severity was scored on a scale of 0-5. Gastroscopy revealed normal-appearing gastric mucosa at the beginning of feed deprivation, with the exception of 2 ponies which had focal squamous mucosal erosion and 1 pony with focal glandular mucosal erosion. After 72 h cumulative feed deprivation, each pony, except 1 pony in one of the trials, developed erosions or ulcers in the gastric squamous mucosa. There was no difference (P = 0.6) in the presence or severity of gastric lesions between treatments. Lesions did not develop in the gastric glandular mucosa as a result of the intermittent feed deprivation with either treatment. In this study, the pectin-lecithin complex in Pronutrin failed to prevent lesions in the gastric squamous mucosa induced by intermittent feed deprivation.

Attention-dependent suppression of distracter visual input can be cross-modally cued as indexed by anticipatory parieto-occipital alpha-band oscillations.

Recent studies show that in addition to enhancing neural processing for attentionally relevant stimuli, selective attention also operates by suppressing the processing of distracter stimuli. When subjects are pre-cued to selectively deploy attention during voluntary (endogenous) attentional tasks, these mechanisms can be set up in advance of actual stimulus processing. That is, the brain can be placed in a biased attentional state. Two recent cueing studies have provided evidence for the deployment of such biased attentional states [J.J. Foxe, G.V. Simpson, S.P. Ahlfors, Neuroreport 9 (1998) 3929-3933; M.S. Worden, J.J. Foxe, N. Wang, G.V. Simpson, J. Neurosci. 20:RC63 (2000) 1-6]. Specifically, these studies implicated oscillatory activity in the alpha frequency-band (8-14 Hz) as an anticipatory mechanism for suppressing distracter visual stimulation. The current study extends these findings by showing that this alpha-suppressive effect is also invoked by cross-modal cues. Auditory symbolic cues were used in an intermodal attention task, to direct subjects' attention to a subsequent task in either the visual or auditory modality. Cueing attention to the auditory features of the imminent task stimuli resulted in significantly higher parieto-occipital alpha amplitude in the period preceding onset of this stimulus than when attention was cued to the visual features. Topographic mapping suggests that this effect is generated in regions of the inferior parietal cortex, areas that have been repeatedly implicated in the engagement and maintenance of visual attention. Taken together, the results of this series of studies suggest that these parietal regions are capable of integrating sensory cues from multiple sensory modalities in order to program the subsequent deployment of visual attention.

Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide.

OBJECTIVE: Decreased plasma tryptophan in persons infected with human immunodeficiency virus (HIV) was first reported over a decade ago, and this observation has since been confirmed by many groups. Before this study, only zidovudine (an antiviral medication) had been reported to reverse plasma tryptophan depletion in HIV-infected persons. Starting with the hypothesis that HIV induces a pellagra-like state and that plasma tryptophan in HIV-infected patients is decreased as a known biochemical correlate of pellagra, we predicted that niacin therapy would reverse plasma tryptophan depletion as it does in pellagra. METHODS: After receiving approval from the institutional review board, we treated HIV-infected patients for 2 mo with high-dose niacin in the form of oral nicotinamide. RESULTS: There was an average 40% increase in plasma tryptophan (P = 0.01) in the four HIV-infected individuals who completed the 2-mo protocol. This finding was specific in that four other amino acids, which have been shown to have significant plasma concentration alterations during HIV infection (i.e., cystine, methionine, taurine, and lysine), showed no significant change with nicotinamide therapy. CONCLUSIONS: There were no adverse side effects attributable to this treatment. The effects of high-dose nicotinamide treatment on morbidity or mortality in HIV-infected persons are yet to be determined. This report marks the first successful use of a vitamin to reverse this HIV-induced metabolic abnormality.

Outgrowth of chondrocytes from human articular cartilage explants and expression of alpha-smooth muscle actin.

The objectives of this study were to investigate the effect of various enzymatic treatments on the outgrowth of chondrocytes from explants of adult human articular cartilage and the expression of a specific contractile protein isoform, alpha-smooth muscle actin, known to facilitate wound closure in other connective tissues. Explants of articular cartilage were prepared from specimens obtained from patients undergoing total joint arthroplasty. The time to cell outgrowth in vitro was determined and the expression of alpha-smooth muscle actin shown by immunohistochemistry. Treatment of the explants with collagenase for 15 minutes reduced the time to outgrowth from more than 30 days to 3 days. Hyaluronidase, chondroitinase ABC, and trypsin applied for the 15-minute period had no effect on the time to cell outgrowth when compared with untreated controls. Pretreatment with hyaluronidase prior to collagenase reduced the time to outgrowth. A notable finding of this study was that the majority of chondrocytes in the adult human articular cartilage specimens and virtually all of the outgrowing cells contained alpha-smooth muscle actin. We conclude that human articular chondrocytes have the capability to migrate through enzymatically degraded matrix and express a contractile actin isoform. Collagenase treatment reduces the time required for cell outgrowth.

The influence of relative resistance and urea-supplementation on deliberate infection with Teladorsagia circumcincta during winter.

The consequences for lambs of infection over the winter with Teladorsagia circumcincta were quantified by deliberate, trickle infection of selected animals at 7 months of age. Infected and control uninfected animals were each allocated into four groups, relatively resistant animals on a normal diet, relatively resistant animals on an isocaloric diet supplemented with urea, and relatively susceptible animals on the same two diets. Resistance and susceptibility was assessed by faecal egg counts following natural infection during the summer preceding the deliberate infection. During the deliberate infection egg counts remained low and most parasites recovered at necropsy were inhibited larvae. Nonetheless, infection reduced weight gain, decreased albumin and fructosamine concentrations and provoked a noticeable pepsinogen and eosinophil response. As most larvae were inhibited these responses may have been largely a consequence of immuno-inflammatory responses in the host rather than the direct action of parasites themselves. Relatively resistant animals on the supplemented diet allowed fewer larvae to establish and had higher fructosamine concentrations, higher albumin concentrations and decreased pepsinogen responses. Therefore, a combination of relatively resistant sheep and nutritional supplementation appears most efficient at controlling infection.

Multisensory auditory-somatosensory interactions in early cortical processing revealed by high-density electrical mapping.

We investigated the time-course and scalp topography of multisensory interactions between simultaneous auditory and somatosensory stimulation in humans. Event-related potentials (ERPs) were recorded from 64 scalp electrodes while subjects were presented with auditory-alone stimulation (1000-Hz tones), somatosensory-alone stimulation (median nerve electrical pulses), and simultaneous auditory-somatosensory (AS) combined stimulation. Interaction effects were assessed by comparing the responses to combined stimulation with the algebraic sum of responses to the constituent auditory and somatosensory stimuli when they were presented alone. Spatiotemporal analysis of ERPs and scalp current density (SCD) topographies revealed AS interaction over the central/postcentral scalp which onset at approximately 50 ms post-stimulus presentation. Both the topography and timing of these interactions are consistent with multisensory integration early in the cortical processing hierarchy, in brain regions traditionally held to be unisensory.

Effects of eicosapentaenoic and gamma-linolenic acids (dietary lipids) on pulmonary surfactant composition and function during porcine endotoxemia.

STUDY OBJECTIVES: To investigate whether a diet enriched with fish and borage oils, with their high polyunsaturated fatty acid (PUFA) content, alters surfactant composition and function during endotoxemia. DESIGN: Prospective, randomized, blinded, controlled animal study. SETTING: Research laboratory at a medical center. PARTICIPANTS: Thirty-six 15- to 25-kg, disease-free, castrated male pigs. DIETS AND MEASUREMENTS: Three groups of pigs (n = 12 per group) were fed for 8 days diets containing either omega-6 fatty acids (FAs) (corn oil; diet A), or omega-3 FAs (fish oil; diet B), or a combination of omega-6 and omega-3 FAs (borage and fish oils; diet C). Eight of 12 pigs in each group received a 0.1-mg/kg bolus of Escherichia coli endotoxin followed by a continuous infusion (0. 075 mg/kg/h). One lung was subsequently isolated ex vivo, and pressure-volume curves were measured. The contralateral lung was lavaged, and surfactant was analyzed for total and individual phospholipids and FA composition. Minimum and maximum surface tension was measured by bubble surfactometry. RESULTS: Pigs fed either diet B or C had increased oleic acid (C(18:1) omega-9), eicosapentaenoic acid (EPA; C(20:5) omega-3), docosahexaenoic acid (C(22:6) omega-3), and total omega-3 and monounsaturated FAs in their surfactant PUFA pools. The relative percentage of linoleic acid (C(18:2) omega-6) and total omega-6 FAs were significantly lower from pigs fed diets B and C compared with diet A. Palmitic acid (C(16:0)) concentrations, the primary FA in surfactant, had a tendency to be lower in pigs fed diets B and C. There were no demonstrable effects on surfactant function or pulmonary compliance. CONCLUSIONS: Diets containing EPA or EPA and gamma-linolenic acid altered the PUFA composition of pulmonary surfactant, but without demonstrable effects on surfactant function during porcine endotoxemia.

Participation of CYP2C8 in retinoic acid 4-hydroxylation in human hepatic microsomes.

Cytochromes P450 (CYPs) catalyze the 4-hydroxylation of all-trans-retinoic acid (ATRA), an agent used in the treatment of certain malignancies. Literature studies have implicated several CYPs in this reaction, but the relative importance of individual CYPs is unclear. Human microsomal CYPs that contribute to the activity were evaluated by correlation with activities of hepatic drug-metabolizing CYPs, the capacity of cDNA-derived CYPs to catalyze the reaction, and inhibition of the microsomal activity by chemicals. 4-HydroxyATRA formation in microsomes varied 7-fold (8.7 to 61 pmol/mg protein/min) and correlated partially with activities mediated by CYPs 3A, 2C, and 1A (p = 0.53 to 0.66). cDNA-derived CYPs 2C8, 2C9, and 3A4, but not 1A1 or 1A2, catalyzed ATRA 4-hydroxylation (2.53, 4.68, and 1.29 pmol/pmol CYP/hr). The Km for the reaction was 9 +/- 3 microM in hepatic microsomes (N = 3) and 6 microM in microsomes containing cDNA-derived CYP2C8; by comparison, Km values for the activity mediated by CYPs 2C9 and 3A4 were 100 and 74 microM, respectively. Inhibition of microsomal ATRA 4-hydroxylation was elicited by chemicals that interact with CYP2C8 (paclitaxel and diclofenac), but not those that interact with CYP2C9 (sulfaphenazole, tolbutamide, and torasemide). The CYP3A inhibitor troleandomycin and an anti-CYP3A IgG inhibited the activity slightly. Greater inhibition was produced by the less selective CYP3A inhibitors parathion, quinidine, and ketoconazole; CYP1A inhibitors were ineffective. These findings suggest that CYP2C8 is a major contributor to ATRA 4-hydroxylation in human liver and that 3A subfamily CYPs may be minor participants. Individual variation in CYP2C8 and 3A4 expression may influence ATRA pharmacokinetics and drug interactions during therapy.

Audit of the nutritional content of patient meals in Ayrshire and Arran.

Recent studies have indicated an unacceptably high prevalence of malnutrition in hospital patients and inadequacies in the diets offered to patients. In 1995 the Health of the Nation Nutrition Guidelines for Hospital Catering were produced with the aim of raising standards in hospital catering. An audit was conducted to compare the nutritional adequacy of patient meals provided by three NHS Trusts within Ayrshire, with the Health of the Nation Guidelines. Across the three Trusts approximately 45% of days failed to provide the recommended minimum amount of energy. NSP, folate and vitamin C provision was adequate in all three Trusts. However there were some inadequacies in the provision of calcium, iron and zinc. In two of the Trusts approximately, half, and in the other Trust one third, of the main meals failed to provide the recommended 300 kcals. In all three Trusts approximately one third of vegetarian meals failed to provide the recommended amount of protein. It has been recommended that the current menus in the three Trusts are altered to ensure that the nutritional standards in the Guidelines are met. Additionally a menu coding system, which indicates the suitability of dishes for different diets, should be used. The three Trusts have agreed to collaborate to produce a core set of menus that meet the recommendations. These recommendations will be implemented along with those from the National Food and Health Best Practice Guide.

The influence of dietary supplementation with urea on resilience and resistance to infection with Haemonchus contortus.

Previous research has indicated that supplementing an apparently adequate diet with additional protein improves both host resistance and resilience in lambs infected with Haemonchus contortus. The present study tested the influence of supplementation with non-protein nitrogen (urea). Helminth-naive Hampshire Down lambs were given an apparently adequate basal diet or a diet supplemented with urea. The lambs were then infected with Haemonchus contortus for 10 weeks. Supplementation with urea had no discernible effect on resistance to infection; faecal egg counts, worm burdens, worm lengths and mean number of eggs per adult female worm did not differ between the 2 groups. However, lambs on the supplemented diet showed better resilience; they had greater packed red cell volumes, higher plasma albumin concentrations and increased liveweight gain compared to lambs on the basal diet. The loss of appetite following infection was less in lambs fed the urea-supplemented diet. The observed effect of urea supplementation was seemingly due to greater food consumption as well as the better diet.