Susan Poole

A standard weight descriptor for dose adjustment in the obese patient

ObjectiveTo develop a standard weight descriptor that can be used for estimation of patient size for obese patients.Patients and methodsData were available from 3849 patients: 2839 from oncology patients (index data set) and 1010 from general medical patients (validation data set). The patients had a wide range of age (16–100 years), weight (25–165kg) and body mass index (BMI) [12–52 kg/m2] in both data sets. From the normal-weight patients in the oncology data set, an equation for male and female patients was developed to predict their normal weight as the sum of the lean body mass and normal fat body mass. The equations were evaluated by predicting the weight of patients in the general medical data set who had a normal BMI (<25 kg/m2). In addition, the clinical utility of the predicted normal weight (PNWT) descriptor was assessed by (i) comparing body surface area and allometric scaling calculations based on actual weight of obese patients versus PNWT; and (ii) comparing the predictive performance of creatinine clearance using the Cockcroft and Gault equation when using actual weight of obese patients versus PNWT to predict gentamicin clearance.ResultsThe PNWT equations developed from the oncology data set predicted accurately the actual weight of normal weighted (BMI <25 kg/m2) general medical patients (R2 = 0.968 men, R2 = 0.946 women). Using actual weight when computing body surface area and when allometric scaling for obese patients results in significant overestimation of patient size, especially for female patients and those with BMIs >35 kg/m2. The use of PNWT in the Cockcroft and Gault equation provided better predictions of gentamicin clearance than when using actual weight.ConclusionsA standard weight descriptor has been developed that can be used in dosing algorithms for patients who are obese (BMI >30 kg/m2).

Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration

ABSTRACT The purpose of this study was to define the pulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and formed colistin following intravenous (i.v.) and inhaled administration in cystic fibrosis (CF) patients. Six CF subjects were administered nebulized CMS doses of 2 and 4 million IU and an i.v. CMS infusion of 150 mg of colistin base activity. Blood plasma, sputum, and urine samples were collected for 12 to 24 h postdose. To assess the tolerability of the drug, lung function tests, blood serum creatinine concentrations, and adverse effect reports were recorded. All doses were well tolerated in the subjects. The pharmacokinetic parameters for CMS following i.v. delivery were consistent with previously reported values. Sputum concentrations of formed colistin were maintained at <1.0 mg/liter for 12 h postdose. Nebulization of CMS resulted in relatively high sputum concentrations of CMS and formed colistin compared to those resulting from i.v. administration. The systemic availability of CMS was low following nebulization of 2 and 4 million IU (7.93% ± 4.26% and 5.37% ± 1.36%, respectively), and the plasma colistin concentrations were below the limit of quantification. Less than 2 to 3% of the nebulized CMS dose was recovered in the urine samples in 24 h. The therapeutic availability and drug targeting index for CMS and colistin following inhalation compared to i.v. delivery were significantly greater than 1. Inhalation of CMS is an effective means of targeting CMS and formed colistin for delivery to the lungs, as high lung exposure and minimal systemic exposure were achieved in CF subjects.

Off-label prescribing in oncology.

Off-label prescribing occurs when a practitioner prescribes a drug for a use, or in a manner, not listed in the ‘approved product information’ (API) for that drug. The literature suggests that this is a frequent occurrence in many areas of medicine, but data are limited in the hospitalized oncology setting. The aim of this study was to quantify the extent of off-label prescribing in a hospitalized oncology population in Australia. The study was conducted at Peter MacCallum Cancer Centre, Australia. On a single day the medication charts of all hospitalized patients were prospectively reviewed. Drug prescribing was assessed for licensing status by comparison with the API as approved by the Therapeutic Goods Administration of Australia. Prescriptions were classified as licensed, off-label or unlicensed. Medication charts of 130 patients were assessed. There were 1351 prescriptions. In 293 (22%) of the prescriptions the drug was either off-label (242, 18%) or unlicensed (51, 4%). Among the 130 patients, 110 (85%) received at least one drug that was prescribed off-label or that was unlicensed. Off-label dosing was the most frequent reason for a drug being off-label (139, 10% of all prescriptions). Off-label due to use for an unapproved indication was found in 118 prescriptions (9%), and off-label due to an unapproved route of administration was found in 38 prescriptions (3%). Off-label prescribing is widespread in the acute hospitalized oncology population, with approximately 22% of all prescriptions being for off-label or unlicensed medication. Such prescribing affects a significant proportion of patients.

Poor correlation between body surface area and glomerular filtration rate

Purpose: The aim of this study was to determine the correlation between body surface area (BSA) and glomerular filtration rate (GFR) measured by Tc-99m DTPA clearance in adult patients with cancer. Methods: GFR was determined by Tc-99m DTPA clearance in adult patients with cancer. Height and actual body weight were measured. Ideal body weight was calculated. BSA was calculated using the Du Bois and Du Bois linear method using both actual and ideal body weight. Results: Included in the study were 122 patients. The mean GFR measured by Tc-99m DTPA clearance was 87 ml/min (range 30–174 ml/min). The mean BSA (actual weight) was 1.76 m2 (median 1.73 m2, range 1.31–2.58 m2). The mean BSA (ideal body weight) was 1.63 m2 (median 1.63 m2, range 1.20–2.00 m2). The overall correlation between BSA (actual weight) and GFR in this adult population was r=0.24, and the 95% confidence interval was 0.06–0.4. The correlation between BSA (ideal body weight) and GFR was r=0.22. The correlation between BSA and GFR excluding patients with a BSA <1.5 m2 or >2.0 m2 was 0.12. When patients with GFR <50 ml/min or >100 ml/min were excluded, the correlation with BSA was 0.07. The correlations between GFR and height, actual weight and ideal weight were 0.22, 0.21 and 0.22, respectively. Conclusions: This study demonstrated a poor correlation between GFR determined by Tc-99m DTPA clearance and BSA calculated using the Du Bois and Du Bois linear method. The 95% confidence interval for the correlation between BSA and GFR was 0.06–0.4 indicating that a strong applicable clinical correlation is very unlikely.

Vancomycin Dosing: Assessment of Time to Therapeutic Concentration and Predictive Accuracy of Pharmacokinetic Modeling Software

BACKGROUND: Therapeutic drug monitoring is usually required for safe and effective administration of vancomycin. However, dosing recommendations from published guidelines are not suitable in achieving therapeutic vancomycin concentrations in a timely manner in patients with normal renal function. OBJECTIVE: To audit vancomycin dosing and concentrations at our institution and evaluate the predictive accuracy of a pharmacokinetic simulation program, with a view to implementing a pharmacy-based pharmacokinetic service for vancomycin monitoring. METHODS: Patients receiving vancomycin were identified prospectively through the therapeutic drug monitoring archives. Patient information was obtained from medication charts and medical records that were located on wards. Data were entered into the MM-USC*Pack program (Jelliffe R, University of Southern California, 2008, version 12.10). This software was used to predict initial and subsequent concentrations of vancomycin based on patient parameters. The predictive accuracy of this software was evaluated by comparing the predicted concentrations to the observed concentrations. RESULTS: During a 6-week period, 204 concentrations were measured in 77 patients. The most common dosing regimen was 1 g every 12 hours. Overall, initial trough concentrations were subtherapeutic (<10 mg/L) in 58% of patients and trough concentrations did not become therapeutic at any stage throughout therapy in 25% of patients. The pharmacokinetic modeling software demonstrated little systematic bias (−3.1%), but the precision (median prediction error) was 23% (interquartile range, 11-45%). Predictions were poorer in obese patients (body mass index >35 kg/m2) and in patients with unstable renal function. CONCLUSIONS: A delay in attaining target trough concentrations was observed in a significant proportion of patients. Pharmacokinetic modeling software is a potential tool to improve the timeliness of achieving adequate dosing by allowing concentrations to be determined prior to steady-state. The program was able to predict vancomycin concentrations across a heterogeneous patient population with little systematic bias, but only moderate precision.

Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose

BACKGROUND Oncology clinicians are now routinely provided with an estimated glomerular filtration rate on pathology reports whenever serum creatinine is requested. The utility of using this for the dose determination of renally excreted drugs compared with other existing methods is needed to inform practice. PATIENTS AND METHODS Renal function was determined by [Tc(99m)]DTPA clearance in adult patients presenting for chemotherapy. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (4v-MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft and Gault (CG), Wright and Martin formulae. Doses for renal excreted cytotoxic drugs, including carboplatin, were calculated. RESULTS The concordance of the renal function estimates according to the CKD classification with measured Tc(99m)DPTA clearance in 455 adults (median age 64.0 years: range 17-87 years) for the 4v-MDRD, CKD-EPI, CG, Martin and Wright formulae was 47.7%, 56.3%, 46.2%, 56.5% and 60.2%, respectively. Concordance for chemotherapy dose for these formulae was 89.0%, 89.5%, 85.1%, 89.9% and 89.9%, respectively. Concordance for carboplatin dose specifically was 66.4%, 71.4%, 64.0%, 73.8% and 73.2%. CONCLUSION All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function.

Effectiveness of a single fixed dose of rasburicase 3 mg in the management of tumour lysis syndrome

Tumour lysis syndrome (TLS) is a life-threatening oncological emergency characterized by hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia [1, 2] due to the rapid lysis of malignant cells, following the initiation of anticancer therapies [3]. Traditionally, therapy for TLS involved intensive hydration, urinary alkalinization and administration of allopurinol [4–6]. Newer guidelines now include rasburicase, with monitoring of electrolytes, white blood cell counts (WCC) and lactate dehydrogenase (LDH) concentrations [1, 7, 8]. Rasburicase, a recombinant urate oxidase enzyme, effectively decreases existing serum uric acid (UA) by oxidizing it to allantoin which is readily soluble and excretable [3]. Although the recommended dose is 0.2 mg kg−1 day−1 for 5–7 days [9], studies have shown the efficacious use of reduced doses for shorter periods of time and subsequent cost savings [5, 6, 10–17]. Expert guidelines by Coieffer et al. [7] in 2008 and Cairo et al. in 2010 [1] on the management of TLS recommend a rasburicase dose of 0.1–0.2 mg kg−1 on the first day, then repeated for up to 7 days [1] or as necessary [7]. We present an analysis of a fixed 3 mg dose of rasburicase administered to adult patients, treated at a tertiary referral centre. The study was approved by the Alfred Health Human Research Ethics Committee and the Monash University Human Research Ethics Committee. Demographic data were collected. Biochemical parameters (serum creatinine, serum UA, phosphate and LDH concentrations), at baseline, 24 h and 72 h after initial administration of rasburicase were recorded and compared. The institution guideline indicates rasburicase to be given before the first dose of chemotherapy in patients considered high risk for TLS. This includes a diagnosis of Burkitts lymphoma, acute lymhoblastic leukaemia, bulky non-Hodgkins lymphoma, lymphoblastic lymphoma or acute myeloid leukaemia with one or more of the following: serum UA>0.46 mmol l−1, white cell count (WCC) >50 × 109 l−1 or LDH >two times normal. Patients who were at an ongoing risk of TLS (i.e. elevated UA or LDH or multiple days of aggressive cytoreductive chemotherapy) were allowed a repeat dose of rasburicase 3 mg. Adherence to the guideline was measured. Forty-one patients received 42 courses of rasburicase over a 40 month period (Figure 1A). Diagnosis, demographic and baseline biochemical data are presented in Table 1. Figure 1 Summaryof rasburicase courses and uric acid concentrations. A) Summary of rasburicase courses administered. B) Median uric acid concentrations over time stratified by presentation a baseline. ♦, normal; ▪, hyperuricaemic; ▴, all ... Table 1 Patientcharacteristics Rasburicase was administered as per institution guidelines in 40 (95%) of the patients. Median serum UA concentrations were within normal range at 72 h in all groups; in those who presented with hyperuricaemia, in those who presented with normal baseline serum UA concentrations and overall (Figure 1B). The majority of patients received one dose of rasburicase 3 mg (Figure 1A). In 34 patient episodes requiring one dose only, there was a decline in the median (range) UA concentration from 0.44 mmol l−1 (0.13–1.15) at baseline to 0.22 mmol l−1 (0.02–0.66) at 24 h. This decrease was maintained at 72 h (P < 0.0001) with a median of 0.21 mmol l−1 (0.02–0.52). Serum creatinine concentrations were within normal range (60–105 μmol l−1) at baseline in 74% of patients, with 82% having a normal creatinine at 72 h. Hyperphosphataemia was present in 29% of patients at baseline and increased to 44% at 72 h. Eight patient episodes required more than one dose due to the ongoing risk of TLS. In these patients the median (range) baseline UA was 0.50 mmol l−1 (0.02–2.0), 0.33 mmol l−1 (0.02−1.10) at 24 h and 0.24 mmol l−1 (0.02−1.10) at 72 h (P < 0.0001). Of these patients only 52% had a normal creatinine at baseline, increasing to 83% at 72 h. Mean phosphate concentrations decreased over time but all patients remained hyperphosphataemic at 72 h. No hypersensitivity reactions were noted, no patients required haemodialysis and no deaths were related to the administration of rasburicase. Our results demonstrate that a single fixed dose of rasburicase 3 mg, repeated if required, should be the standard regimen in the management of TLS. Recent studies and published guidelines have shown cumulative support for the safe and efficacious use of off-label dosing regimens of rasburicase [1, 5–8, 10, 11, 16, 17]. A quarter of our patients presented with a baseline WCC>100 × 109 l−1 (Table 1), which is considered a high risk for developing TLS [1, 7]. The Product Information recommends rasburicase 0.1–0.2 mg kg−1 day−1 for 1–7 days [9]. We successfully used a fixed 3 mg dose for these patients. Our data support that presented by Trifilio et al. [11] in a recent study of 287 episodes, the largest published series at this time, of raised UA concentrations successfully treated with a single 3 mg dose of rasburicase, repeated if required. In our cohort, which was smaller in size, a single 3 mg dose was equally effective in both patients who had a normal baseline UA and those with hyperuracaemia. This differed from that published by Trifilio et al., where the single dose was more successful in patients with a lower baseline UA concentration. Our patient cohort also had a higher median LDH. Suboptimal management of hyperphosphatemia was identified in our cohort. More stringent monitoring of patient phosphate concentrations may be warranted in the future to minimize the risk of renal impairment. Serum creatinine, showing a gradual decrease with time, was used as a surrogate maker to indicate an improvement in renal function. Rasburicase was used in conjunction with allopurinol, urinary alkalinazation and intravenous hydration. This strategy is also supported by recent studies and recommendations [1, 11, 16], although the benefit of administering alkalinization with rasburicase needs further investigation [1, 7]. A single fixed 3 mg dose of rasburicase, in the setting of an institution guideline, was efficacious in the management of TLS.

A pharmacist-led system-change smoking cessation intervention for smokers admitted to Australian public hospitals (GIVE UP FOR GOOD): study protocol for a randomised controlled trial

BackgroundIntensive smoking cessation interventions initiated during hospitalisation are effective, but currently not widely available. Strategies are needed to integrate smoking cessation treatment into routine inpatient care. Pharmacist-led interventions for smoking cessation are feasible and efficacious in both ambulatory and community pharmacy settings. However, there is a lack of evidence from large scale studies of the effectiveness of pharmacist guided programs initiated during patient hospitalisation in achieving long-term abstinence. This study aims to evaluate the effectiveness of a pharmacist-led system change intervention initiated during hospitalisation in Australian public hospitals.Methods/designA multi-centre, randomised controlled trial will be conducted with 12 months follow-up. Smokers, 18 years or older, will be recruited from the wards of three Victorian public hospitals. Participants will be randomly assigned to a usual care or intervention group using a computer generated randomisation list. The intervention group will receive at least three smoking cessation support sessions by a trained pharmacist: the first during the hospital stay, the second on or immediately after discharge and the third within one month post-discharge. All smoking cessation medications will be provided free of charge during the hospital stay and for at least one week after discharge. Participants randomised to usual care will receive the current care routinely provided by the hospital. All measurements at baseline, discharge, one, six and 12 months will be performed by a blinded Research Assistant. The primary outcome measures are carbon monoxide validated 7-day point prevalence abstinence at six and 12 months.DiscussionThis is the first large scale study to develop and test a pharmacist-led system change intervention program initiated during patient hospitalisation. If successful, the program could be considered for wider implementation across other hospitals.Trial registrationACTRN12612000368831

The prevalence and experience of Australian naturopaths and Western herbalists working within community pharmacies

BackgroundNaturopaths and Western herbal medicine (WHM) practitioners were surveyed to identify their extent, experience and roles within the community pharmacy setting and to explore their attitudes to integration of complementary medicine (CM) practitioners within the pharmacy setting.MethodPractising naturopaths and WHM practitioners were invited to participate in an anonymous, self-administered, on-line survey. Participants were recruited using the mailing lists and websites of CM manufacturers and professional associations.Results479 practitioners participated. 24% of respondents (n = 111) reported they had worked in community pharmacy, three-quarters for less than 5 years. Whilst in this role 74% conducted specialist CMs sales, 62% short customer consultations, 52% long consultations in a private room and 51% staff education. This was generally described as a positive learning experience and many appreciated the opportunity to utilise their specialist knowledge in the service of both customers and pharmacy staff. 14% (n = 15) did not enjoy the experience of working in pharmacy at all and suggested pharmacist attitude largely influenced whether the experience was positive or not. Few practitioners were satisfied with the remuneration received. 44% of the total sample provided comment on the issue of integration into pharmacy, with the main concern being the perceived incommensurate paradigms of practice between pharmacy and naturopathy. Of the total sample, 38% reported that they would consider working as a practitioner in retail pharmacy in future.ConclusionsThe level of integration of CM into pharmacy is extending beyond the mere stocking of supplements. Naturopaths and Western Herbalists are becoming utilised in pharmacies

Estimation of body weight in hospitalized patients

AIM To examine the bias and precision of different methods of estimating body mass and height in hospitalized adult patients. METHODS Patients were enrolled at the Alfred and Caulfield hospitals, Melbourne, Australia following verbal consent. Estimates were made using the Lorenz formula (that utilizes height, waist and hip circumference), the Crandell formula (that utilizes height and arm circumference) and visual estimation of weight based on the average results obtained by two pharmacy interns. Statistical error was calculated as the ratio of estimated to actual weight; bias was assessed as the mean error and precision as the proportion of estimates within 10 and 20% of measured weight and standard deviation of the error. RESULTS In a 5-week period July to August 2010, 198 patients were enrolled. The median age was 64 years (range 19-91) and 52% were female. Thirty-four (17%) patients were obese (BMI >30 kg/m(2)) and 8 (4%) were underweight (BMI <18 kg/m(2)). With the Lorenz formula an estimate within 10% was obtained for 56% of patients; with the Crandell formula prediction was poor. Documentation of body weight in notes and patient self-reporting were both accurate. Seventy-two patients (43%) were prescribed one or more drugs for which dosing potentially should be adjusted for body weight. CONCLUSION In adult hospitalized patients, the estimation of body weight by anthropomorphic measures is not accurate. This supports the need for equipment to be made widely available to accurately weigh patients directly in hospital, including in unconscious and immobile patients.