Data envelopment analysis model for the appraisal and relative performance evaluation of nurses at an intensive care unit

The appraisal and relative performance evaluation of nurses are very important and beneficial for both nurses and employers in an era of clinical governance, increased accountability and high standards of health care services. They enhance and consolidate the knowledge and practical skills of nurses by identification of training and career development plans as well as improvement in health care quality services, increase in job satisfaction and use of cost-effective resources. In this paper, a data envelopment analysis (DEA) model is proposed for the appraisal and relative performance evaluation of nurses. The model is validated on thirty-two nurses working at an Intensive Care Unit (ICU) at one of the most recognized hospitals in Lebanon. The DEA was able to classify nurses into efficient and inefficient ones. The set of efficient nurses was used to establish an internal best practice benchmark to project career development plans for improving the performance of other inefficient nurses. The DEA result confirmed the ranking of some nurses and highlighted injustice in other cases that were produced by the currently practiced appraisal system. Further, the DEA model is shown to be an effective talent management and motivational tool as it can provide clear managerial plans related to promoting, training and development activities from the perspective of nurses, hence increasing their satisfaction, motivation and acceptance of appraisal results. Due to such features, the model is currently being considered for implementation at ICU. Finally, the ratio of the number DEA units to the number of input/output measures is revisited with new suggested values on its upper and lower limits depending on the type of DEA models and the desired number of efficient units from a managerial perspective.

Health care professionals' views of paediatric outpatient non-attendance:implications for general practice

Background. Non-attendance at paediatric hospital outpatient appointments poses potential risks to children's health and welfare. Prevention and management of missed appointments depends on the perceptions of clinicians and decision makers from both primary and secondary care, including general practitioners (GPs) who are integral to non-attendance follow-up. Objectives. To examine the views of clinical, managerial and executive health care staff regarding occurrence and management of non-attendance at general paediatric outpatient clinics. Methods. A qualitative study using individual semi-structured interviews was carried out at three English Primary Care Trusts and a nearby children's hospital. Interviews were conducted with 37 staff, including GPs, hospital doctors, other health care professionals, managers, executives and commissioners. Participants were recruited through purposive and 'snowball' sampling methods. Data were analysed following a thematic framework approach. Results. GPs focused on situational difficulties for families, while hospital-based staff emphasized the influence of parents' beliefs on attendance. Managers, executives and commissioners presented a broad overview of both factors, but with less detailed views. All groups discussed sociodemographic factors, with non-attendance thought to be more likely in 'chaotic families'. Hospital interviewees emphasized child protection issues and the need for thorough follow-up of missed appointments. However, GPs were reluctant to interfere with parental responsibilities. Conclusion. Parental motivation and practical and social barriers should be considered. Responsibilities regarding missed appointments are not clear across health care sectors, but GPs are uniquely placed to address non-attendance issues and are central to child safeguarding. Primary care policies and strategies could be introduced to reduce non-attendance and ensure children receive the care they require. © The Author 2013.

The cost of paediatric obesity

There has been a great deal of media attention given to the rising levels of obesity and overweight in children and adolescents, but what is the real cost of pediatric obesity? This article reviews information about the recent rise in pediatric obesity and discusses the cost of this condition from medical, financial and psychological perspectives.

Ethanol intake of paediatric intensive care patients

Background - Limiting the amount of alcohol in children's medicines is advisable but as alcohol is the second most common solvent used in liquid preparations, paediatric patients with increased medication intake may be exposed to a considerable alcohol intake. Few medicines are specifically designed for children in Paediatric Intensive Care (PICU), and therefore adult formulations are frequently administered, with high medication use further exposing a PICU patient to undesired alcohol intake. Aims - This small pilot study aimed to examiine the intake of a sample of PICU patients, highlight common medicines used on PICU containing alcohol, provide alternatives where possible and where alternatives are not possible, provide the prescriber with a list of the higher alcohol containing medicines. Method - A retrospective medication chart review was undertaken as a two point snap shot. Data collected included age, weight, medications prescribed and the formulations used at time of the study. The patients' sedation score was recorded. The electronic medicine compendium (EMC) was consulted for any ethanol content for the commercially available products. The manufacturer was contacted for ethanol content of all ‘specials’ and any commercial products found to contain ethanol from the EMC. The PICU patient's daily intake of ethanol was calculated. The calculation was converted to an adult equivalent alcohol unit intake and although this method of conversion is crude and does not take physiological differences of adult and children into account, it was done in order to provide the clinician with commonly used terminology in deciding the risk to the patient. Results - Twenty-eight patients were prescribed a range of 69 different medications. Of the 69 medicines, 12 products were found to contain ethanol. Patient ages ranged from a 26 week premature infant to 15 years old, weights ranges from 0.7 kg to 45 kg. Only 2 out of the 28 patients did not receive ethanol containing medications, and most patients were prescribed at least two medicines containing ethanol. Daily ethanol intake uncorrected for weight ranged from 0.006 ml to 2.18 ml (median 0.26 ml). Converting this to adult units per week, alcohol intake ranged from 0.07 to 15.2 units (median 1.4 units). The two patients receiving above 15 units/week adult equivalent were prescribed an oral morphine weaning regimen, therefore the high alcohol exposure was short term. The most common drugs prescribed containing alcohol were found to be nystatin, ranitidine, furosemide and morphine. No commercially available alcohol-free oral liquid preparations were found for ranitidine, furosemide or morphine at the time of the study. Correlation of the sedation score against ethanol intake was difficult to analyse as most patients were actively sedated. Conclusions - Polypharmacy in PICU patients increases the exposure to alcohol. Some commercially available medicines provide excessive ethanol intake, providing the clinician with ethical, potentially economical dilemmas of prescribing an unlicensed medicine to minimise ethanol exposure. Further research is required to evaluate the scope of the problem, effects of exposure and provision of alcohol free formulations.

Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

Aims - To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation. Methods - The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates. Results - The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: TVCL = 12.9 x (Weight/13.2)0.35 x EXP (-0.0058 x TPT) x EXP (0.428 x CYP3A5) where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%. Conclusion Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself. • Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDS • The first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed. • The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates. • The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS - To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS - Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS - The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS - The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

Population pharmacokinetic model of canrenone after intravenous administration of potassium canrenoate to paediatric patients

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about the pharmacokinetics of potassium canrenoate/canrenone in paediatric patients WHAT THIS STUDY ADDS • A population pharmacokinetic model has been developed to evaluate the pharmacokinetics of canrenone in paediatric patients who received potassium canrenoate as part of their therapy in the intensive care unit. AIMS To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate to paediatric patients. METHODS Data were collected prospectively from 23 paediatric patients (2 days to 10 years of age; median weight 4 kg, range 2.16–28.0 kg) who received intravenous potassium canrenoate (K-canrenoate) as part of their intensive care therapy for removal of retained fluids, e.g. in pulmonary oedema due to chronic lung disease and for the management of congestive heart failure. Plasma samples were analyzed by HPLC for determination of canrenone (the major metabolite and pharmacologically active moiety) and the data subjected to pharmacokinetic analysis using NONMEM. RESULTS A one compartment model best described the data. The only significant covariate was weight (WT). The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) were CL/F (l h−1) = 11.4 × (WT/70.0)0.75 and V/F (l) = 374.2 × (WT/70) where WT is in kg. The values of CL/F and V/F in a 4 kg child would be 1.33 l h−1 and 21.4 l, respectively, resulting in an elimination half-life of 11.2 h. CONCLUSIONS The range of estimated CL/F in the study population was 0.67–7.38 l h−1. The data suggest that adjustment of K-canrenoate dosage according to body weight is appropriate in paediatric patients.

Development of an enantiomer selective microsampling assay for the quantification of ketorolac suitable for paediatric pharmacokinetic studies

Background: Ketorolac, a potent nonsteroidal anti-inflammatory drug used for pain control in children, exists as a racemate of inactive R (+) and active S (-) enantiomers. Aim: To develop a microsampling assay for the enantioselective analysis of ketorolac in children. Methods: Ketorolac enantiomers were extracted from 50 µl of plasma by liquid–liquid extraction and separated on a ChiralPak AD-RH. Detection was by a TSQ quantum triple quadrupole mass spectrometer with an electrospray ionisation source operating in a positive ion mode. Five children (age 13.8 (1.6) years, weight 52.7 (7.2) kg), were administered intravenous ketorolac 0.5 mg/kg (maximum 10 mg) and blood samples were taken at 0, 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h post administration. CL, VD and t1/2 were calculated based on non-compartmental methods. Results: The standard curves for R (+) and S (-) ketorolac were linear in the range 0–2000 ng/ml. The LLOQs of the method were 0.15 ng on column and 0.31 ng on column for R (+) and S (-) ketorolac, respectively. The median (range) VD and CL of R (+) and S (-) ketorolac were 0.12 l/kg (0.07–0.17), 0.017 l/h/kg (0.12–0.29) and 0.17 (0.09–0.31) l/kg, 0.049 (0.02–0.1) l/h/kg, p = 0.043), respectively. The median (range) elimination half-life (t1/2) of the R (+) and S (-) ketorolac was 5.0 h (2.5–5.8) and 3.1 h (1.8–4.4), p = 0.043), respectively. Conclusion: The development of a simple, rapid and reliable ketorolac assay suitable for paediatric PK studies is reported. Copyright © 2013 John Wiley & Sons, Ltd.

Potassium canrenoate treatment in paediatric patients:a population pharmacokinetic study using novel dried blood spot sampling

Objective: To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients. Methods: Data were collected prospectively from 37 paediatric patients (median weight 2.9 kg, age range 2 days–0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n = 213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n = 16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices. Results: A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h) = 12.86 ×  (WT/70.0)0.75 × e [0.066 ×  (PMA - 40]) and V/F (l) = 603.30 ×  (WT/70) × (GA/40)1.89 where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9 kg are 1.11 l/h and 20.48 l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37 h, respectively, in 70 kg patient). Conclusion: The range of estimated CL/F in DBS for the study population was 0.12–9.62 l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.

Children's views on unlicensed/off-label paediatric prescribing and paediatric clinical trials

Objectives - To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. Methods - Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A purposeful sample was chosen to facilitate representation of various socioeconomic groupings. Results - A total of 123 pupils, aged from 10 to 16 years, from six schools, participated in 16 focus groups. In general, pupils viewed the unlicensed/off-label use of medicines in children as unsafe and unethical and felt it is necessary to test medicines in children to improve the availability of licensed products. The majority felt that older children should be told, and that parents should be told, about the unlicensed/off-label use of medicines in children, yet they recognised some implications of this, such as potential medication non-adherence. Conclusions - This is the first study to explore the views of healthy children on unlicensed medicine use in children. Children were able to recognise potential risks associated with the unlicensed use of medicines and felt it is necessary to test and license more medicines in children. Practice implications - Health care professionals should consider the views of children in decisions that affect their health.

Perceptions and attitudes of Jordanian paediatricians towards off-label paediatric prescribing

Objective To assess current experiences and attitudes of hospital based paediatricians towards off-label medicine prescribing. Setting Paediatric hospital wards and out-patient clinics. Design A prospective, questionnaire based study. Results A 30 item questionnaire was sent to 300 hospital based paediatricians and 250 (83%) were returned completed. Over 69% of responders were familiar with the term off-label medicines. However, only 28% were knowingly prescribing off-label medicines to children. The majority of respondents (90%) expressed concerns about the safety and efficacy of off-label medicines. Only 15% had observed Adverse Drug Reactions, and 31% a treatment failure. The vast majority of respondents (83%) did not obtain informed consent or tell parents they were prescribing off label medicines to their children. Conclusions Off-label prescribing of medicines to children is a familiar concept to the majority of paediatricians in Jordan although only a smaller number are aware that it is common in their practice. Respondents showed concern about off label prescribing, although the majority do not consider it necessary to inform parents. More comprehensive research is needed in this area in Jordan and other Middle Eastern countries.

The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia - an exploratory study

Aims - To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP). Methods - A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire. Results - Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing “carelessness at times about taking medication” as the primary reason for non-adherence followed by “forgetting to take the medication” (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored ≥ 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P < 0.05). Conclusions - The present study explored various ways to assess adherence rates to thiopurine medication in ALL patients and highlighted the importance of combining both objective and subjective measures as a better way to assess adherence to oral thiopurines.

Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Importance of the field: Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining interindividual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children. Areas covered in this review: This review explores pharmacogenetic knowledge developed over the last decade regarding the impact of ABCB1 polymorphisms on tacrolimus toxicity and dosage requirements in children. What the reader will gain: A better understanding of the role of ABCB1 genetic polymorphisms (and corresponding haplotypes) and ABCB1 expression levels in various tissues and organs on tacrolimus outcomes in children with liver transplant. Take home message: Pharmacogenetics offers significant potential for optimising tacrolimus use. ABCB1 donor genotypes and ABCB1 expression level in the intestine and leukocytes may be useful in dosage selection. Large prospective studies are, however, required to further explore the potential of genetic testing in identifying children who are at risk of toxicity and to better individualise tacrolimus therapy.

Automated prediction of deterioration of infants in paediatric intensive care using SpO2

Acute life-threatening events are mostly predictable in adults and children. Despite real-time monitoring these events still occur at a rate of 4%. This paper describes an automated prediction system based on the feature space embedding and time series forecasting methods of the SpO2 signal; a pulsatile signal synchronised with heart beat. We develop an age-independent index of abnormality that distinguishes patient-specific normal to abnormal physiology transitions. Two different methods were used to distinguish between normal and abnormal physiological trends based on SpO2 behaviour. The abnormality index derived by each method is compared against the current gold standard of clinical prediction of critical deterioration. Copyright © 2013 Inderscience Enterprises Ltd.

Proplyene glycol intake from medications used on paediatric intensive care

here is an increasing number of reports of propylene glycol (PG) toxicity in the literature, regardless of its inclusion on the Generally Recognized as Safe List (GRAS).1 PG is an excipient used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Method A snapshot of 50 PICU patients oral or intravenous medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists' opinions on PG intake was sought via e-survey. Results The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52%) were parenteral formulations. Median weight of the patients was 5.5 kg (range 2–50 kg), ages ranged from 1 day to 13 years of age. Eleven of the patients were classed as renally impaired (defined as 1.5 times the baseline creatinine). Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations. Thirty-eight patients received at least one prescription containing PG and 29/38 of these patients were receiving formulations that contained excipients that may have competed with the metabolic pathways of PG. PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day. Total intake was inconclusive for 2 patients due to a of lack of availability of information from the manufacturer; these formulations were licensed but used in for off-label indications. Five commonly used formulations contributed to higher intakes of PG, namely co-trimoxazole, dexamethasone, potassium chloride, dipyridamole and phenobarbitone. Lactate levels were difficult to interpret due to the underlying conditions of the patients. One of the sixteen intensivist was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions Certain formulations used on PICU can considerably increase PG exposure to patients. Due to a lack of awareness of PG content, these should be highlighted to the clinician to assist with making informed decisions regarding risks versus benefits in continuing that drug, route of administration or formulation.