Limitations of Wright formula estimates of renal function.
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Aged↗
Biomedical subjects
M J Dooley
Publications and source records attributed to M J Dooley.
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.
Adrenal Cortex Hormones↗
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.
Drug-Related Side Effects and Adverse Reactions↗
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), but worsened the effect in those >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 </=100 ml min(-1), then the Scr should be rounded up to 0.06 mmol l(-1) and CrCl recalculated. Further assessment of this approach is warranted in a larger cohort of patients.
Adult↗
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.
Adult↗
Variability in administration of 5-fluorouracil and folinic acid in standard treatment regimens for advanced colorectal cancer.
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Antimetabolites, Antineoplastic↗
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.
Adult↗
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.
Antineoplastic Agents↗
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.
Adult↗
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).
Adenosine↗
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.
Ligands↗
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.
Adenosine↗