Detection of bacterial DNA in cardiac vegetations by PCR after the completion of antimicrobial treatment for endorcarditis

PCR with broad-range primers for prokaryotic 16S rRNA genes was used to identify bacterial DNA in tissue from patients undergoing valve replacements following a previous episode of infective endocarditis (IF). Of eight valves investigated, bacterial DNA was detected in three from patients for whom IE had been treated by antibiotic therapy 5, 12 and 18 months previously. The demonstration of bacterial DNA within resected heart valves suggests either recurrence of infection, treatment failure or the persistence of bacterial debris within the cardiac vegetation. There may also be implications for routine use of PCR in the diagnosis of infection. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.

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.

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.

The extent and reasons for compliance failure with oral treatment regimens in haematology outpatients

Focal points: Self-completion questionnaires were used to determine issues with compliance surrounding the use of oral chemotherapy in haematology patients Forty-two patients were identified of which 40 responded over a two-month period Twenty-one respondents (52.5 per cent) indicated that they experienced difficulties in taking their medication Difficulties were not apparently related to the time of dosing; the size of dose units (hydroxyurea) and foil packed agents caused particular difficulties

Drug delivery strategies for the treatment of Helicobacter pylori infections

Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. © 2005 Bentham Science Publishers Ltd.

Parental information needs in chronic renal failure and diabetes mellitus

The information needs of parents of children with end stage renal failure (ESRF) or with insulin dependent diabetes mellitus (IDDM) were assessed by questionnaires over a 2-year period. Questionnaires were posted on seven occasions at 4-monthly intervals and were sent to both mothers and fathers. Most information needs were reported to be for detailed test results, for new information about the condition and about the child's future social development. Questions responsible for the three highest scores were concerned with the future: the child's fertility; their social, career and marriage prospects; and the hope for a new improved treatment. For the IDDM mothers, scores were significantly different depending on age of the child (P = 0.02). Change in treatment mode had no significant effect on the information needs of parents of children with ESRF (P = 0.81). Occupation was significantly associated with the mean general information needs scores for parents, with occupations of a lower socioeconomic status associated with higher information needs scores. There were no significant differences between the reported mean general information needs scores of parents of children with ESRF and of parents of children with IDDM (P = 0.69) or between mothers and fathers mean general information needs scores (P = 0.58). CONCLUSION: Multidisciplinary team members need to tailor information to the needs of the individual families and be sensitive to socioeconomic factors and communication issues.

Spillover effects of service failures in coalition loyalty programs:the buffering effect of special treatment benefits

Coalition loyalty programs are on the rise, yet few studies investigate the impact of service failures in such programs. Using data from a retail context, the authors show that a program partner deemed responsible for a service failure suffers negative customer responses. However, customers' perceptions of the benefits of the coalition loyalty program buffer these consequences. Perhaps most importantly, when customers perceive the program's special treatment benefits as low, direct and indirect spillover effects occur, such that a service failure by one program partner has a negative effect on customer loyalty toward the program itself. © 2013 New York University.

Prophylactic ranitidine treatment in critically ill children - a population pharmacokinetic study

Aims - To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. Methods - Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed-effects modelling. Results - A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (−12.618; P < 0.001) compared with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h−1 for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h−1 and 27.5%, respectively. No significant relationship was found between age and weight-corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46. Conclusions - Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary.

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.

How drug metabolism influences treatment outcomes

Recent developments within the National Health Service have led to an increase in personnel 'qualified' to prescribe a wide range of pharmacological agents. A short (38-day) Continuing Professional Development course in prescribing is deemed adequate to fully train individuals for practice. A sound understanding of prescribing medicines has important implications for patient benefit. For example, a prescriber would require some knowledge of drug absorption, distribution, metabolism and excretion, as well as aspects of drug delivery and drug-drug interactions. Drug metabolism in particular exerts a powerful influence on drug action; this can range from complete failure of efficacy through to life-threatening toxicity. Moreover, it is conservatively estimated that there may be several thousand deaths each year in the UK arising from an inadequate knowledge of drug metabolism when prescribing medicines. This one-day course focused on the importance of understanding drug metabolism on treatment strategies and outcomes, and was accessed by a range of healthcare professionals in the West Midlands area of the UK. © 2007 Informa UK Ltd.