Antimicrobial Susceptibility of Escherichia coli and Salmonella spp. Isolates From Healthy Pigs in Australia: Results of a Pilot National Survey.

This study investigated the frequency of antimicrobial non-susceptibility (defined as the frequency of isolates with minimum inhibitory concentrations above the CLSI susceptible clinical breakpoint) among E. coli and Salmonella spp. isolated from healthy Australian finisher pigs. E. coli (n = 201) and Salmonella spp. (n = 69) were isolated from cecal contents of slaughter-age pigs, originating from 19 farms distributed throughout Australia during July-December 2015. Isolates underwent minimum inhibitory concentration (MIC) susceptibility testing to 11 antimicrobials. The highest frequencies of non-susceptibility among respective isolates of E. coli and Salmonella spp. were to ampicillin (60.2 and 20.3%), tetracycline (68.2 and 26.1%), chloramphenicol (47.8 and 7.3%), and trimethoprim/sulfamethoxazole (33.8 and 11.6%). Four E. coli isolates had MICs above the wild-type epidemiological cut-off value for ciprofloxacin, with two isolates from the same farm classified as clinically resistant (MICs of > 4 µg/ml), a noteworthy finding given that fluoroquinolones (FQs) are not legally available for use in Australian food-producing animals. Three of these four E. coli isolates belonged to the sequence type (ST) 10, which has been isolated from both humans and production animals, whilst one isolate belonged to a new ST (7573) and possessed qnrS1. This study shows that non-susceptibility to first line antimicrobials is common among E. coli and Salmonella spp. isolates from healthy slaughter age pigs in Australia. However, very low levels of non-susceptibility to critically important antimicrobials (CIAs), namely third generation cephalosporins and fluoroquinolones were observed. Nevertheless, the isolation of two ciprofloxacin-resistant E. coli isolates from Australian pigs demonstrates that even in the absence of local antimicrobial selection pressure, fluoroquinolone-resistant E. coli clonal lineages may enter livestock production facilities despite strict biosecurity.

Decision-making in early clinical drug development.

This paper illustrates an approach to setting the decision framework for a study in early clinical drug development. It shows how the criteria for a go and a stop decision are calculated based on pre-specified target and lower reference values. The framework can lead to a three-outcome approach by including a consider zone; this could enable smaller studies to be performed in early development, with other information either external to or within the study used to reach a go or stop decision. In this way, Phase I/II trials can be geared towards providing actionable decision-making rather than the traditional focus on statistical significance. The example provided illustrates how the decision criteria were calculated for a Phase II study, including an interim analysis, and how the operating characteristics were assessed to ensure the decision criteria were robust. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetic and pharmacodynamic profile of rosuvastatin in patients with end-stage renal disease on chronic haemodialysis.

BACKGROUND: Rosuvastatin has been shown to provide effective treatment of dyslipidaemia in patients with end-stage renal disease (ESRD) undergoing haemodialysis, but data from controlled trials are very limited on the pharmacokinetics and pharmacodynamics of rosuvastatin in this population. OBJECTIVE: The aim of the present study was to better define the pharmacokinetic and pharmacodynamic profiles of repeated doses of rosuvastatin at a starting dose of 10 mg/day in a group of patients with ESRD. STUDY DESIGN: This was a single-centre, open-label study of rosuvastatin 10 mg daily, given over a 16-day treatment period in patients with ESRD undergoing chronic haemodialysis. SETTING: The study was carried out at a single site in the USA. PATIENTS: Patients aged 18-65 years with ESRD who had been on dialysis for ≥ 3 months were eligible for inclusion. Of 12 patients enrolled, 11 were included in the pharmacokinetic and pharmacodynamic analysis and all were included in the safety evaluation. The mean age of patients was 43.9 years (range 24-60 years). Five patients were Caucasian, six were black and one was Hispanic. INTERVENTION: Patients received an oral dose of rosuvastatin 10 mg once daily in the morning for 16 consecutive days. MAIN OUTCOME MEASURE: The primary objective was to estimate the degree of rosuvastatin accumulation in plasma by measuring the area under the plasma concentration time curve (AUC) from time zero to 24 h following a single dose of rosuvastatin 10 mg on day 1, and the AUC at steady state on day 15. RESULTS: Following administration of single and multiple doses, plasma concentrations of rosuvastatin declined in an apparent bi-exponential manner and remained above the limit of assay detection throughout the entire sampling periods on both day 1 and day 15. Steady-state plasma concentrations of rosuvastatin were achieved by day 11. Little accumulation of rosuvastatin after repeated, once-daily dosing was observed; the geometric mean accumulation ratio for rosuvastatin was 1.37 (coefficient of variation = 36.4 %). Clearance of rosuvastatin and its metabolites via dialysis was minimal. Following rosuvastatin 10 mg daily for 16 days, total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B were reduced from baseline by 30.6 %, 38.9 % and 30.6 %, respectively. Rosuvastatin was well tolerated. CONCLUSION: The degree of rosuvastatin accumulation observed in patients receiving dialysis is similar to that in healthy individuals. The results of the current study suggest that rosuvastatin 10 mg may be administered to patients with ESRD on chronic haemodialysis without need for dose reduction.

Cultural barriers to exclusive breastfeeding by mothers in a rural area of Cameroon, Africa.

Because of the known nutritional and health benefits to the infant, the World Health Organization recommends that women in resource-poor countries exclusively breastfeed until their babies reach 6 months of age. In the primarily rural geographical region of the North West Province of Cameroon, previous studies identified the prevalence of breastfeeding to be 90%. It is common knowledge that women are culturally encouraged to mix-feed their infants, but the extent of these feeding practices is not known. The objective of this study was to identify the extent of mixed feeding/supplementation and the cultural/social barriers to exclusive breastfeeding. All women surveyed introduced water and food supplementation prior to 6 months of age, with more than 38% giving water in the first month of life. Mothers identified cultural factors influencing their decision to mix-feed their babies, which included 1) pressures by village elders and families to supplement because it is a traditional practice, 2) belief that breast milk is an incomplete food that does not increase the infants weight, 3) belief that all family members should receive the benefit of food grown in the family farm, and 4) the taboo of prohibiting sexual contact during breastfeeding.

Joint replacement and case management in indigent hospitalized patients.

More than 260,000 total joint replacements are performed every year in the United States. The University of New Mexico Hospital is a publicly held hospital that provides healthcare to many patients who are uninsured and indigent. More than 200 joint replacement surgeries are performed every year at University Hospital, Albuquerque, NM, resulting in an average length of stay of 5.7 days and other patient outcomes. The average cost ranges from $18,000 to $22,000 per procedure, with a reimbursement rate of 61%. Nursing care of these patients can be a challenge and an orthopaedic nurse case manager can effect positive patient outcomes.

Procedure for the assessment of lung function with spirometry.

Spirometry records breath movements, inhalation and exhalation, and is integral to the management of lung disease, alongside good history taking and careful documentation. Tests can indicate a patient's optimal response to treatment or triggers, and the rate of decline in lung function. It is useful to detect the presence of lung disease, those susceptible to developing lung disease and to classify patients into severity classifications to optimise management.