Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens.

WHAT IS KNOWN AND OBJECTIVE: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. METHODS: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. RESULTS: Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). WHAT IS NEW AND CONCLUSION: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy.

Integrating smoking cessation into routine care in hospitals--a randomized controlled trial.

AIMS: To evaluate the effectiveness of a pharmacist-led multi-component smoking cessation programme (GIVE UP FOR GOOD) compared with usual care in hospitalized smokers. DESIGN: Randomized, assessor-blinded, parallel-group trial. SETTING: Three tertiary public hospitals in Australia. PARTICIPANTS: A total of 600 adult in-patient smokers [mean ± standard deviation (SD), age 51 ± 14 years; 64% male] available for 12 months follow-up. INTERVENTIONS: Multi-component hospital pharmacist-led behavioural counselling and/or pharmacotherapy provided during hospital stay, on discharge and 1 month post-discharge, with further support involving community health professionals (n = 300). Usual care comprised routine care provided by hospitals (n = 300). MEASUREMENTS: Two primary end-points were tested using intention-to-treat analysis: carbon monoxide (CO)-validated 1-month sustained abstinence at 6-month follow-up and verified 6-month sustained abstinence at 12-month follow-up. Smoking status and pharmacotherapy usage were assessed at baseline, discharge, 1, 6 and 12 months. FINDINGS: Sustained abstinence rates for intervention and control groups were not significantly different at both 6 months [11.6% (34 of 294) versus 12.6% (37 of 294); odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.55-1.50] and 12 months [11.6% (34 of 292) versus 11.2% (33 of 294); OR = 1.04, 95% CI = 0.63-1.73]. Secondary end-points, self-reported continuous abstinence at 6 and 12 months, also agreed with the primary end-points. Use of pharmacotherapy was higher in the intervention group, both during hospital stay [52.3% (157 of 300) versus 42.7% (128 of 300); P = 0.016] and after discharge [59.6% (174 of 292) versus 43.5% (128 of 294); P < 0.001]. CONCLUSIONS: A pharmacist-led multi-component smoking cessation intervention provided during hospital stay did not improve sustained abstinence rates at either 6 or 12 months compared with routine hospital care.

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.

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.

Prevalence of error-prone abbreviations used in medication prescribing for hospitalised patients: multi-hospital evaluation.

The use of error-prone abbreviations in prescribing is a potential cause of misinterpretation that may lead to medication error. This study determined frequency and type of error-prone abbreviations in inpatient medication prescribing across three Australian hospitals. Three hundred and sixty-nine (76.9%) patients had one or more error-prone abbreviations used in prescribing, with 8.4% of orders containing at least one error-prone abbreviation and 29.6% of these considered to be high risk for causing significant harm.

Multiplicity of medication safety terms, definitions and functional meanings: when is enough enough?

OBJECTIVES: To identify the terms and definitions used by organisations involved in medication safety and to examine differences in functional meaning using a novel scenario assignment method. METHODS: Medication safety related terms and definitions were sought from websites of organisations associated with medication safety. The functional meanings of terms and definitions were analysed and compared using a scenario assignment method where each definition found was assessed against four scenarios with a central theme. MAIN OUTCOME MEASURES: Medication safety related terms and definitions currently in use, similarities and differences in their functional meanings, and practical implications of the use of these terms and definitions. RESULTS: Thirty three of 160 websites searched were found to have one or more definitions for medication safety related terms. Twenty five different terms with 119 definitions were found. The most frequently defined groups of terms were "adverse event" (8 different definitions), "error" (n = 9), "near miss" (n = 12), "adverse reaction" (n = 8), and "incident" (n = 4). Substantial diversity of functional meanings of definitions was demonstrated using the scenario-assignment method. Of the five groups of frequently defined terms, definitions within the "adverse event", "near miss", and "incident" groups resulted in three functional meanings each, while two functional meanings resulted for "error" and "adverse reaction". CONCLUSION: The multiplicity of terms, definitions and, most importantly, functional meanings demonstrates the urgent need for agreement on standardisation of nomenclature describing medication related occurrences. This is an essential prerequisite to enable meaningful analysis of incidence data and development of medication safety improvement strategies.

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital.

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (> or =25 mg prednisolone or > or =4 mg dexamethasone daily) for > or =4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis.

Rounding of low serum creatinine levels and consequent impact on accuracy of bedside estimates of renal function in cancer patients.

To compare glomerular filtration rate measured by technetium-99m ([Tc(99m)]) DTPA clearance with estimated creatinine clearance (CrCl) (Cockcroft and Gault (C&G) method) in patients with serum creatinine (Scr) levels <0.06 mmol l(-1), and determine the effect of rounding serum creatinine to 0.06 mmol l(-1). Patients with serum creatinine values <0.06 mmol l(-1) at the time of [Tc(99m)] clearance determination were identified. Creatinine clearance was calculated by the C&G method using both actual and rounded Scr values. A total of 419 adults had GFR measured by technetium-99m diethyl triamine penta-acetic acid ([Tc(99m)] DTPA) clearance. Out of this group, 26 patients had a serum creatinine value <0.06 mmol l(-1). The C&G estimates of renal function using actual serum creatinine resulted in an overall overestimation of 12.9% when compared to [Tc(99m)] DTPA clearance. When the value of serum creatinine was rounded to 0.06 mmol l(-1), the formula underestimated renal function by -7.0%. Analysis of estimated creatinine clearance for different levels of renal function showed significant differences to [Tc(99m)] DTPA clearance. Rounding up of serum creatinine to 0.06 mmol l(-1) improved the predictive ability of the C&G method for the patients with [Tc(99m)] DTPA clearance 100 ml min(-1). This work indicates that when bedside estimates of renal function are calculated using the C&G formula actual Scr should be used first to estimate CrCl. If the resultant CrCl is

A comparison of bedside renal function estimates and measured glomerular filtration rate (Tc99mDTPA clearance) in cancer patients.

BACKGROUND: The aim of this study was to compare measured glomerular filtration rate (GFR) with estimates of GFR derived from the population pharmacokinetic methods of Martin and Wright, and the creatinine clearance (CrCl) estimates of Cockcroft and Gault, and Jelliffe. PATIENTS AND METHODS: GFR was determined by technetium-99m diethyl triamine penta-acetic acid (Tc99DTPA) clearance in adult cancer patients. Height, actual body weight and serum creatinine were measured, and GFR and CrCl estimates calculated. RESULTS: One hundred and twenty-two patients were included. The mean measured GFR was 87 ml/min (range 30-174 ml/min). The mean bias (mean percentage error) was 2, 1, -10 and -17%, and the mean precision (mean absolute percentage error) was 18, 19, 21 and 23% for the Wright, Martin, Cockcroft and Gault, and Jelliffe formulas, respectively. The Martin formula significantly underestimates GFR for females (mean bias -10%) and overestimates GFR for males (mean bias 8%) (P <0.001 for bias of males versus females). The Wright and Martin formulas significantly overestimate GFR <50 ml/min (mean bias 39 and 30%; P = 0.03 and 0.05, respectively) and all formulas underestimate GFR >100 ml/min (mean bias -18, -16, -24 and -32% for Wright, Martin, Cockcroft and Gault, and Jelliffe formulas, respectively; P <0.001). CONCLUSIONS: All the assessed estimates for renal function were found to have significant limitations.

Carboplatin dosing: gender bias and inaccurate estimates of glomerular filtration rate.

The aim was to compare doses of carboplatin calculated using the Calvert formula and Chatelut formula and also to compare doses calculated using Calvert formula, modified with non-isotopic estimation of GFR, using the Cockcroft and Gault formula or the Jelliffe formula. For formulae comparison, doses were calculated to target an AUC of 7 mg/ml x min. When compared with the dose derived from the Calvert formula, the doses calculated in 122 adult cancer patients using the Chatelut formula were significantly higher for males and significantly lower for females. There was a statistically significant difference between the dose per kg calculated for males and females (P<0.0001). The mean percentage difference in dose calculated with substituted measures of renal function with the Cockcroft and Gault formula and Jelliffe formula was -8% (standard deviation (S.D.) 17%) and -14% (S.D. 16%), respectively. Further prospective evaluation of the Chatelut formula is required before it can be recommended for routine clinical application.

Potential for patient harm from intrathecal administration of preserved solutions.

Intrathecal drug administration is an important component of the management of malignancy and symptom control. This route of administration reduces systemic adverse effects, but can increase the risk of local adverse effects such as arachnoiditis. It is accepted practice that any spinal injection should not contain any preservatives (such as benzyl alcohol and parabens-containing compounds). The intrathecal administration of solutions preserved with benzyl alcohol has been shown in case studies to increase the risk of adverse neurological events. Available data do not support the safety of intrathecal injection of products preserved with parabens; rather, they demonstrate a need for further investigation. Steps should be taken to ensure that preservative-free products are used. Staff involved with the preparation and administration of intrathecal preparations need to be educated about the risks associated with preservatives in this setting.

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.

Conformational search for the N6-substituted adenosine analogues and related adenosine A1 receptor antagonists.

The search for 3-D requirements for the adenosine A1 receptor affinity is useful to aid in the design of more potent and/or novel ligands as pharmacological tools and therapeutics for the receptor. To emboss 3-D requirements for adenosine A1 receptor affinity among adenosine receptor antagonists, adenosine and xanthine analogs, conformations for the N6-substituted adenosine analogues and related adenosine A1 receptor antagonists were thoroughly searched by semi-empirical quantum mechanics calculations. Newly established global minima for these compounds (C1'-N6-C6-N1 torsion: 10 degrees) are consistent with retrieved structures from the Cambridge Structural Database and previously published NMR data on the solution conformation of N6-substituted adenosine analogues. However, these newly studied global minima for adenosine analogues are found to be different from those previously reported (C1'-N6-C6-N1 torsion: +/-75 degrees).

Theoretical structure-activity studies of adenosine A1 ligands: requirements for receptor affinity.

The three-dimensional (3-D) requirements for A1 adenosine receptor affinity have been studied based on hydrogen-bonding functionality correlation between a group of twelve A1 adenosine receptor ligands representing ten structurally different classes of compounds. Electrostatic potential similarity indices and shape similarity indices strongly support the proposed receptor-bound orientations of the ligands. We conclude, in areas common to both agonist and antagonist binding at the A1 receptor, that the ligands are recognized by a similar physicochemical 3-D environment. The finding of similar 3-D requirements for agonists and antagonists suggests a fairly static receptor structure in the region common to agonist and antagonist binding. The ribose moiety is remote from antagonist binding site. Such a 3-D environment rationalizes the binding of a number of potent novel antagonists including KW-3902, not previously reported in modeling studies.

The three binding domain model of adenosine receptors: molecular modeling aspects.

Using molecular modeling, adenosine receptor ligands were fitted together to maximize correlations between the three most important factors controlling binding to the receptor, namely steric, hydrophobic, and electrostatic complimentarily. Structure-activity relationships can be explained by three binding domains on the receptors. These are hydrophobic, aromatic, and ribose binding domains. We propose that the N6, C2, and C8 hydrophobic binding domains are not discreet but occupy the same region of the receptor.