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Aim: To investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow-up study and to investigate its potential mechanisms. Methods: A total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population-based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin-like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time-varying effect of incident PPI use on T2DM during follow-up. Results: Baseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment-insulin resistance (0.100, 95% CI 0.056, 0.145) and C-reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (−0.009 mmol/L, 95% CI −0.014, −0.004) and IGF-1 (−0.805 nmoL/L, 95% CI −1.015, −0.595). After adjustment for risk factors such as physical activity and body mass index/waist-to-hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36-2.10). The effect was dose-dependent with the highest risk (HR 1.88, 95% CI 1.29-2.75) in those on more than one defined daily dose. Conclusion: New users of PPIs during follow-up had a significantly higher dose-dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.

Purpose: To evaluate the stability of meropenem trihydrate in elastomeric infusion devices at a range of selected concentrations (6, 12, 20 and 25 mg/mL) at ambient, refrigeration and freezing temperatures. Methods: Meropenem Ranbaxy® (meropenem trihydrate equivalent to anhydrous meropenem 1 g) vials for injection were reconstituted with 0.9% sodium chloride and adjusted to pH 6.5 using 1 M hydrochloric acid. Following preparation, solutions were stored for 7 days at either 6.7°C in elastomeric infusion devices or at −19°C in glass vials; samples of each concentration were removed from the infusion devices at specific time-points and stored for 24 hrs at 22.5°C. All solutions were assayed at specific time-points using high-performance liquid chromatography. Forced degradation in hydrochloric acid, sodium hydroxide and hydrogen peroxide was carried out at 40°C. Results: The lowest concentration of meropenem (6 mg/mL) displayed the highest stability. It maintained >90% of its initial concentration for up to 144 hrs when stored at 6.7°C and 72 hrs following 24 hrs storage at 22.5°C, having been initially refrigerated for 48 hrs. Meropenem 20 mg/mL required immediate administration following preparation under ambient temperatures, whilst meropenem 25 mg/mL did not remain stable following 24 hrs storage at ambient temperatures. Frozen meropenem solutions displayed good stability in all concentrations but were physically unstable due to the formation of a precipitate. Conclusion: At lower concentrations, meropenem showed suitable stability for storage and administration in elastomeric infusion devices, at refrigerated temperatures. To enhance the stability of lower concentration solutions when exposed to ambient temperatures by ambulatory patients, a more adept method of maintaining lower temperatures that reflect refrigerated conditions for elastomeric infusion devices should be devised.

Objectives: To evaluate the prevalence of off-label and unlicensed prescribing in inpatients at a major paediatric teaching hospital in Western Australia and to identify which drugs are commonly prescribed off-label or unlicensed, including factors influencing such prescribing. Methods: A retrospective cross-sectional study was conducted in June, 2013. Patient and prescribing data were collected from 190 inpatient medication chart records which had been randomly selected from all admissions during the second week of February 2013. Drugs were catego-rised as licensed, off-label or unlicensed, according to their approved Australian registration product information (PI). All drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. Results There were 120 male and 70 female inpatients. The average age was 6.0 years (± 4.7). The study included 1160 prescribed drugs suitable for analysis. The number of drugs prescribed per patient ranged from 1 to 25 with an average of 6.1 (± 4.3). More than half (54%) were prescribed off-label. Oxycodone, clonidine, parecoxib and midazolam were always prescribed off-label. The most common off-label drugs were ondansetron (18.5%), fentanyl (12.9%), oxycodone (8.8%) and paracetamol (6.1%). Many ATC classifications included high off-label proportions especially the genitourinary system and sex hormones, respiratory system drugs, systemic hormonal preparations and alimentary tract and metabolism drugs. Conclusions: This study highlights that prescribing of paediatric drugs needs to be better supported by existing and new evidence. Incentives should be established to foster the conduct of evidence-based studies in the paediatric population. The current level of off-label prescribing raises issues of unexpected toxicity and adverse drug effects in children that are in some cases severely ill.

Objective: The primary objective was to determine if initial empirical intravenous dosing of gentamicin improved patient’s outcomes in pyelonephritis/urosepsis compared with alternative IV antibiotic management. Design Retrospective cross-sectional descriptive study. Setting: Public TertiaryTeaching Hospital serving adults in an urban centre. Participants: All adult patient records with a recorded diagnosis of any of pyelonephritis/urosepsis, urinary tract infection, UTI, complicated urinary tract infection, bacteriuria, symptomatic bacteriuria and asymptomatic bacteriuria from 2nd February 2012 to 10th May 2014 were reviewed. Only patients treated with an empirical regimen of one or more IV antibiotics were included in the study. Main outcomes The primary outcomes were: duration of IV antibiotic treatment, time to resolution of symptoms and length of hospital stay (LOS). Secondary end points were: compliance with Therapeutic Guidelines: Antibiotic (electronic version) (eTG) for severe pyelonephritis/urosepsis and appropriateness of gentamicin use. Data analysis Univariate and multivariable associations between baseline and demographic variables and the main outcomes were performed using Chi-square tests and a General Linear Model using the SAS version 9.2 software. Results: Of 295 patients reviewed 152 were prescribed one or more IV antibiotics and included in the study. Approximately half of the patients (n = 73, 48%) were prescribed IV piperacillin/tazobactam (Tazocin), while gentamicin was prescribed for 66 patients (43.4%). Of the 152 patients evaluated, 49 (32%) were given gentamicin first. Multivariable regression analysis showed that duration of IV treatment was shorter for those aged over 70 (40.2 hours vs 85.5 hours for those aged up to 70; p = 0.0074), and those who received gentamicin as first line treatment (41.3 hours vs 89.8 hours for those not receiving any gentamicin; p = 0.0312). After adjustment for age and gentamicin administration, there appeare

Background: Pharmacist-administered vaccination services have been available in various countries for several years. In 2014, Western Australian (WA) legislation was introduced to allow pharmacist immunisers to administer the influenza vaccine to consumers 18 years and older. Objective: To determine consumer satisfaction with pharmacist-administered influenza vaccination services in WA and identify factors associated with opinions to extend the service to include other vaccines. Setting: Thirteen WA community pharmacies. Method: In 2015, 133 pharmacies in WA offered pharmacist-administered influenza vaccinations. Of the 133 pharmacies, a purposive sample of 10% (13) were invited to participate in this 2016 study. Following vaccination, consumers were given a questionnaire and asked to evaluate the service and if they would support expansion of the service to include other vaccinations. Main outcome measure Consumer satisfaction with aspects of the service using a 5-point Likert scale. Results: A total of 434 (66.8%) questionnaires were completed at the 13 pharmacies and returned. The majority of consumers (99.5%) were satisfied with the service overall, and 97.2% advised they would receive a vaccination from a community pharmacist in the future. Over 60% would like vaccinations to expand to other conditions. Women and those who would again have their influenza vaccine from the pharmacist were particularly supportive of this expansion. Conclusion: Consumer satisfaction with pharmacist-administered vaccinations was high. Consumers found the service convenient, comfortable and professional. The majority of respondents supported expansion of pharmacist-administered vaccination services to a wider range of vaccines.

Copyright 2018 Lavers et al. Background. Surgical site infections (SSIs) are a common complication following breast surgery procedures, despite being considered a clean surgery. The prevalence of SSIs can be minimised with the appropriate use of antibiotic prophylaxis as outlined in the Australian Therapeutic Guidelines (eTG). The aims of this study were to evaluate adherence to the eTG for antibiotic prophylaxis in breast surgery procedures at a Western Australian teaching hospital following an update of the guidelines in 2014 and examine the impact of prophylactic antibiotics on SSI incidence and length of hospital stay. Method. A retrospective cross-sectional study which reviewed medical records from a random sample of 250 patients selected from 973 patients who underwent breast surgical procedures between February 2015 and March 2017. Results. Overall adherence to current eTG occurred in 49.2% (123/250) of operations. Pre-operative and post-operative antibiotics were prescribed in 98.4% (246/250) and 11.2% (28/250) operations respectively. Adherence rates to three specific elements of the eTG (drug prescribed, drug dosage and timing of administration) were 91.6% (229/250), 53.6% (134/250) and 86.4% (216/250) respectively. For the 14.4% (36/250) patients with relevant drug allergies, there was zero adherence to the eTG. Overall recorded SSI prevalence was low at 5.2% (13/250). The mean length of stay in patients (2.3 ± 1.7 days) was not influenced by level of eTG adherence (p = 0.131) or SSIs (p = 0.306). Conclusion.These data demonstrate a significant improvement in overall adherence to the eTG from 13.3% to 49.2% (p = < 0.001). The level of detected SSIs in this study was low. Further improvement is necessary with respect to prescribing appropriate antibiotic dosages and for those with allergies.

© 2018 Sinkala et al. Background. Antibiotic misuse in the community contributes to antimicrobial resistance. One way to address this may be by better utilizing community pharmacists' skills in antibiotic prescribing. The aims of this study were to examine the level of support for "down-scheduling" selected antibiotics and to evaluate factors determining the appropriateness of community pharmacist prescribing for a limited range of infections, including their decision to refer to a doctor. Methods. Self-administered questionnaires, including graded case vignette scenarios simulating real practice, were sent to Western Australian community pharmacists. In addition to descriptive statistics and chi-square testing, a General Estimating Equation (GEE) was used to identify factors associated with appropriateness of therapy and the decision to refer, for each of the seven vignettes. Results. Of the 240 pharmacists surveyed, 90 (37.5%) responded, yielding 630 responses to seven different case vignettes. There was more than 60% respondent support for expanded prescribing (rescheduling) of commonly prescribed antibiotics. Overall 426/630 (67.6%) chose to treat the patient while the remaining 204/630 (32.4%) referred the patient to a doctor. Of those electing to treat, 380/426 (89.2%) opted to use oral antibiotics, with 293/380 (77.2%) treating with an appropriate selection and regimen. The GEE model indicated that pharmacists were more likely to prescribe inappropriately for conditions such as otitis media (p = 0.0060) and urinary tract infection in pregnancy (p < 0:0001) compared to more complex conditions. Over 80% of all pharmacists would refer the patient to a doctor following no improvement within 3 days, or within 24 h in the case of community acquired pneumonia. It was more common for younger pharmacists to refer the patient to a doctor (p=0:0165). Discussion. This study adds further insight into community pharmacy/pharmacist characteristics associated with appropr

Rachel Taylor, Bruce Sunderland, Giuseppe Luna, Petra Czarniak School of Pharmacy, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia Purpose: The aim was to evaluate the stability of linezolid in commonly used intravenous fluids and in aqueous solution to determine the kinetics of degradation and shelf-life values at alkaline pH values. Methods: Forced degradation studies were performed on linezolid in solution to develop a validated high-performance liquid chromatography analysis. Sodium chloride 0.9%, sodium lactate, and glucose 5% and glucose 10% solution containing 2.0 mg/mL linezolid were stored at 25.0°C (±0.1°C) for 34 days. The effect of temperature on the stability of linezolid in 0.1 M sodium hydroxide solution was investigated to determine the activation energy. The degradation rates of linezolid at selected pH values at 70.0°C and the influence of ionic strength were also examined. Activation energy data were applied to determine the shelf-life values at selected pH values, and a pH rate profile was constructed over the pH range of 8.7–11.4. The stability of intravenous linezolid (Zyvox®) solution was evaluated by storing at 70.0°C for 72 hours. Results: Linezolid was found to maintain >95.0% of its initial concentration after storage at 25.0°C for 34 days in sodium lactate, 0.9% in sodium chloride, and 5% and 10% in glucose solutions. Linezolid was degraded at alkaline pH values by first-order kinetics. Activation energy data showed that temperature, but not ionic strength, influenced the degradation rate significantly. An activation energy of 58.22 kJ/mol was determined for linezolid in 0.1 M sodium hydroxide solution. Linezolid was least stable at high pH values and at elevated temperatures. It was determined that linezolid has adequate stability for the preparation of intravenous fluids for clinical administration. Conclusion: Linezolid was found to have a

© 2017, Springer International Publishing.Background Guidelines for the appropriate use of antibiotic prophylaxis are provided in the Therapeutic Guidelines: Antibiotics (eTG) in Australia. Inappropriate use of antibiotics is problematic. Objective To examine adherence with therapeutic guidelines (eTG) in breast surgery and trends in non-adherence dependent on the type of breast surgery performed. Setting Major Western Australian teaching hospital. Method A retrospective cross-sectional study reviewed a random sample of 150 from 1049 eligible medical records of patients who underwent a breast surgical procedure in 2013 or 2014. Main outcome measure Adherence to the eTG. Results Antibiotic prophylaxis was prescribed for 139 (92.7%) operations. Adherence to the eTG occurred in 20 (13.3%) operations, whilst 11 (7.3%) did not adhere to any element of the eTG. Appropriate timing was the main factor not adhered to. Postoperative antibiotics were prescribed following 35 (23.3%) operations, with 32 (91.4%) administered beyond 24 h. Length of stay was significantly different (p = 0.0036) between surgical groups. There was a tendency for risk of an infection to be decreased with adherence (odds ratio: 0.23; 95% CI: 0.05, 1.07; p = 0.06). Conclusion Adherence to the eTG was low (13.3%), despite a decreased risk of SSI when guidelines were followed.

Purpose: The aim was to evaluate the stability of linezolid in commonly used intravenous fluids and in aqueous solution to determine the kinetics of degradation and shelf-life values at alkaline pH values. Methods: Forced degradation studies were performed on linezolid in solution to develop a validated high-performance liquid chromatography analysis. Sodium chloride 0.9%, sodium lactate, and glucose 5% and glucose 10% solution containing 2.0 mg/mL linezolid were stored at 25.0°C (±0.1°C) for 34 days. The effect of temperature on the stability of linezolid in 0.1 M sodium hydroxide solution was investigated to determine the activation energy. The degradation rates of linezolid at selected pH values at 70.0°C and the influence of ionic strength were also examined. Activation energy data were applied to determine the shelf-life values at selected pH values, and a pH rate profile was constructed over the pH range of 8.7–11.4. The stability of intravenous linezolid (Zyvox®) solution was evaluated by storing at 70.0°C for 72 hours. Results: Linezolid was found to maintain > 95.0% of its initial concentration after storage at 25.0°C for 34 days in sodium lactate, 0.9% in sodium chloride, and 5% and 10% in glucose solutions. Linezolid was degraded at alkaline pH values by first-order kinetics. Activation energy data showed that temperature, but not ionic strength, influenced the degradation rate significantly. An activation energy of 58.22 kJ/mol was determined for linezolid in 0.1 M sodium hydroxide solution. Linezolid was least stable at high pH values and at elevated temperatures. It was determined that linezolid has adequate stability for the preparation of intravenous fluids for clinical administration. Conclusion: Linezolid was found to have a shelf life of 34 days at 25°C when added to sodium lactate, 0.9% sodium chloride, and 5% and 10% glucose solutions. It was least stable at high pH values and at elevated temperatures.

Purpose: The purpose of this study was to evaluate the chemical stability of Lincocin® (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. Materials and methods: The stability of Lincocin® injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann’s), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin® in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Results: Lincomycin hydrochloride was found to maintain its shelf life at 25°C in sodium lactate (Hartmann’s) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Conclusion: Lincocin® injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann’s) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability.