A Drug Content, Stability Analysis, and Qualitative Assessment of Pharmacists' Opinions of Two Exemplar Extemporaneous Formulations.

Despite a decline in the number of active pharmaceutical ingredients prepared extemporaneously using proprietary products, there remains a need for such products in the community (for example, liquid medicines for paediatrics which may be otherwise commercially unavailable). A lack of experience and quality assurance systems may have diminished pharmacist's confidence in the extemporaneous preparation process; therefore, pharmacists were asked to prepare two proprietary products, omeprazole and amlodipine. The resulting products were characterised in terms of variability in drug quantity, stability, particle size and antimicrobial properties. Furthermore, a self-administered questionnaire was used to assess 10 pharmacists' opinions on the perceived complexity of the extemporaneous compounding process and their overall confidence in the final extemporaneously compounded products. Drug content studies revealed that 88.5% and 98.0% of the desired drug content was obtained for omeprazole and amlodipine, respectively. Antimicrobial properties were maintained for both drugs, however variability in particle size, particularly for amlodipine, was evident between formulations. While pharmacists who partook in the study had some or high confidence in the final products, they reported difficulty formulating the suspensions. Findings from this study provide insight into pharmacists' views on two extemporaneously prepared products and highlight the variability obtained in preparations prepared by different pharmacists.

Ensuring continuity of patient care across the healthcare interface: Telephone follow-up post-hospitalization.

AIMS: To implement pharmacist-led, postdischarge telephone follow-up (TFU) intervention and to evaluate its impact on rehospitalization parameters in polypharmacy patients, via comparison with a well-matched control group. METHOD: Pragmatic, prospective, quasi-experimental study. Intervention patients were matched by propensity score techniques with a control group. Guided by results from a pilot study, clinical pharmacists implemented TFU intervention, added to routine integrated medicines management service. RESULTS: Using an intention to treat approach, reductions in 30- and 90-day readmission rates for intervention patients compared with controls were 9.9% [odds ratio = 0.57; 95% confidence interval (CI): 0.36-0.90; P < 0.001] and 15.2% (odds ratio = 0.53; 95% CI: 0.36-0.79; P = 0.021) respectively. Marginal mean time to readmission was 70.9 days (95% CI: 66.9-74.9) for intervention group compared with 60.1 days (95% CI: 55.4-64.7) for controls. Mean length of hospital stay compared with control was (8.3 days vs. 6.7 days; P < 0.001). Benefit: cost ratio for 30-day readmissions was 29.62, and 23.58 for 90-day interval. Per protocol analyses gave more marked improvements. In intervention patients, mean concern scale score, using Beliefs about Medicine Questionnaire, was reduced 3.2 (95% CI: -4.22 to -2.27; P < 0.001). Mean difference in Medication Adherence Report Scale was 1.4 (22.7 vs. 24.1; P < 0.001). Most patients (83.8%) reported having better control of their medicines after the intervention. CONCLUSIONS: Pharmacist-led postdischarge structured TFU intervention can reduce 30- and 90-day readmission rates. Positive impacts were noted on time to readmission, length of hospital stay upon readmission, healthcare costs, patient beliefs about medicines, patient self-reported adherence and satisfaction.

A multiple methods approach to determine adherence with prescribed mycophenolate in children with kidney transplant.

AIMS: The aim of this study was, to use a multiple methods approach, including, for the first time, dried blood spot (DBS) sampling with population pharmacokinetic interpretation, to assess adherence to mycophenolate in children with kidney transplant. A second aim was to identify patient/parental factors that influenced adherence and to link adherence behaviour to clinical outcomes. METHODS: A convenience sample of 33 children with kidney transplant (age ≤ 18 years) who had been prescribed mycophenolate for at least 3 months were recruited from participating outpatient clinics in the UK and Jordan. Medication adherence was determined via self-report questionnaires, medication refill data from dispensing records, and via mycophenolic acid concentrations in plasma and DBS samples obtained from children during a clinic visit. RESULTS: Through triangulation of results from the different methodological approaches a total of 12 children (36.4%) were deemed to be nonadherent with their prescribed mycophenolate treatment. Logistic regression analysis indicated that nonadherence was significantly associated with the presence of mycophenolate side effects. Poor adherence was positively linked to measures of poor clinical outcomes (hospitalisation and the need for kidney biopsy). CONCLUSIONS: Despite the imperative regarding medication adherence to help prevent organ rejection, a significant proportion of children are not fully adherent with their therapy. Side-effects appear to be an important factor leading to nonadherence. Measurement of mycophenolate in DBS samples, coupled with the use of population pharmacokinetics modelling, was a convenient direct approach to assessing adherence in children with kidney transplant and has the potential to be introduced into routine practice.

Influence of primary care antibiotic prescribing on incidence rates of multidrug-resistant Gram-negative bacteria in hospitalised patients.

PURPOSE: Use of antibiotics can give rise to the selection of resistant bacteria. It remains unclear whether antibiotic use in primary care can influence bacterial resistance incidence in patients when hospitalised. The aim of this study is to explore the impact of prior community antibiotic usage on hospital-detected multidrug-resistant Gram-negative (MRGN) incidence rate. METHODS: This pharmacoepidemiological study was case-control in design, and was carried out in the Antrim Area Hospital (N. Ireland) in two phases. In phase 1, the controls were matched according to: age, gender, admission ward, date of admission, and age-adjusted Charlson co-morbidity index score. During the second phase, controls were selected randomly from the total population of admissions to the hospital over the 2-year study period. RESULTS: In phase 1, multivariate analysis revealed that prior exposure to the second- and third-generation cephalosporins (p = 0.004) and fluoroquinolones (p = 0.023) in primary care was associated with an increased likelihood of MRGN detection in inpatients. In phase 2, an independent relationship between an increased risk of identification of MRGN, while hospitalised was associated with: prolonged hospitalisation (p < 0.001), being elderly (p < 0.001), being female (p = 0.007), and having genitourinary disease (p < 0.001). CONCLUSION: This study provides clear evidence which supports the need to optimise antibiotic use in primary care to help reduce MRGN incidence in hospitalised patients.

Perceptions and attitudes towards off-label dispensing for pediatric patients, a study of hospital based pharmacists in Jordan.

BACKGROUND: With growing responsibility of the pharmacists in ensuring public health and safe medicine use, an understanding of the issues surrounding off-label prescribing is crucial to allow pharmacists to make informed decisions about such practice. The aim of this study is to assess the perceptions and attitudes of hospital based pharmacists toward off-label medicine dispensing to children. METHODS: After obtaining the required approvals, a validated questionnaire about off-label dispensing to pediatric patients was administered to 250 randomly selected hospital pharmacists. RESULTS: One hundred and fifty (150) completed questionnaires were returned. Less than half of the respondents (44%, n = 66) admitted to being familiar with the concept of off-label dispensing, claiming to have obtained this knowledge basically through their dispensing experience rather than education. A minority of respondents (36%, n = 54) reported dispensing off-label medicines within their practice knowingly. The majority of respondents had concerns regarding the efficacy (82%, n = 123) and safety (98%, n = 147) of off-label medicines. The most common reasons given by respondents for a dispensed prescription being off label were younger age than recommended (88%, n = 132). Most of respondents (94%, n = 141) claimed to double check the calculations of doses of medicines before dispensing off-label medicines and 60% (n = 90) of them felt that parents and guardians should be told when an off-label medicine has been prescribed for their children. CONCLUSION: The majority of respondents were not familiar with the concept of offlabel medicines. While reporting to have gained their knowledge from their professional experience, only a minority of respondents reported knowingly dispensing off-label medicines for pediatric patients. Respondents indicated that manufacturing more appropriate formulations for pediatric patients would reduce such practices in this population. Having concerns regarding the efficacy and safety of off-label medicines used for pediatric patients, respondents felt that the use of off-label medicines would increase the likelihood of adverse drug reactions (ADRs). Finally, respondents felt that such practice of prescribing and dispensing should receive parental consent.

Pharmacogenetics and the print media: what is the public told?

BACKGROUND: Pharmacogenetics is a rapidly growing field that aims to identify the genes that influence drug response. This science can be used as a powerful tool to tailor drug treatment to the genetic makeup of individuals. The present study explores the coverage of the topic of pharmacogenetics and its potential benefit in personalised medicine by the UK newsprint media. METHODS: The LexisNexis database was used to identify and retrieve full text articles from the 10 highest circulation national daily newspapers and their Sunday equivalents in the UK. Content analysis of newspaper articles which referenced pharmacogenetic testing was carried out. A second researcher coded a random sample (21%) of newspaper articles to establish the inter-rater reliability of coding. RESULTS: Of the 256 articles captured by the search terms, 96 articles (with pharmacogenetics as a major component) met the study inclusion criteria. The majority of articles over-stated the benefits of pharmacogenetic testing while paying less attention to the associated risks. Overall beneficial effects were mentioned 5.3 times more frequently than risks (p < 0.001). The most common illnesses for which pharmacogenetically based personalised medicine was discussed were cancer, cardiovascular disease and CNS diseases. Only 13% of newspaper articles that cited a specific scientific study mentioned this link in the article. There was a positive correlation between the size of the article and both the number of benefits and risks stated (P < 0.01). CONCLUSION: More comprehensive coverage of the area of personalised medicine within the print media is needed to inform public debate on the inclusion of pharmacogentic testing in routine practice.

Preferences for a third-trimester ultrasound scan in a low-risk obstetric population: a discrete choice experiment.

OBJECTIVE: Establish maternal preferences for a third-trimester ultrasound scan in a healthy, low-risk pregnant population. DESIGN: Cross-sectional study incorporating a discrete choice experiment. SETTING: A large, urban maternity hospital in Northern Ireland. PARTICIPANTS: One hundred and forty-six women in their second trimester of pregnancy. METHODS: A discrete choice experiment was designed to elicit preferences for four attributes of a third-trimester ultrasound scan: health-care professional conducting the scan, detection rate for abnormal foetal growth, provision of non-medical information, cost. Additional data collected included age, marital status, socio-economic status, obstetric history, pregnancy-specific stress levels, perceived health and whether pregnancy was planned. Analysis was undertaken using a mixed logit model with interaction effects. MAIN OUTCOME MEASURES: Women's preferences for, and trade-offs between, the attributes of a hypothetical scan and indirect willingness-to-pay estimates. RESULTS: Women had significant positive preference for higher rate of detection, lower cost and provision of non-medical information, with no significant value placed on scan operator. Interaction effects revealed subgroups that valued the scan most: women experiencing their first pregnancy, women reporting higher levels of stress, an adverse obstetric history and older women. CONCLUSIONS: Women were able to trade on aspects of care and place relative importance on clinical, non-clinical outcomes and processes of service delivery, thus highlighting the potential of using health utilities in the development of services from a clinical, economic and social perspective. Specifically, maternal preferences exhibited provide valuable information for designing a randomized trial of effectiveness and insight for clinical and policy decision makers to inform woman-centred care.

Adherence to treatment in children and adolescents with cystic fibrosis: a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms.

BACKGROUND: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence. METHODS: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. RESULTS: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence. CONCLUSIONS: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children.

A modified method for measuring antibiotic use in healthcare settings: implications for antibiotic stewardship and benchmarking.

OBJECTIVES: To determine whether adjusting the denominator of the common hospital antibiotic use measurement unit (defined daily doses/100 bed-days) by including age-adjusted comorbidity score (100 bed-days/age-adjusted comorbidity score) would result in more accurate and meaningful assessment of hospital antibiotic use. METHODS: The association between the monthly sum of age-adjusted comorbidity and monthly antibiotic use was measured using time-series analysis (January 2008 to June 2012). For the purposes of conducting internal benchmarking, two antibiotic usage datasets were constructed, i.e. 2004-07 (first study period) and 2008-11 (second study period). Monthly antibiotic use was normalized per 100 bed-days and per 100 bed-days/age-adjusted comorbidity score. RESULTS: Results showed that antibiotic use had significant positive relationships with the sum of age-adjusted comorbidity score (P = 0.0004). The results also showed that there was a negative relationship between antibiotic use and (i) alcohol-based hand rub use (P = 0.0370) and (ii) clinical pharmacist activity (P = 0.0031). Normalizing antibiotic use per 100 bed-days contributed to a comparative usage rate of 1.31, i.e. the average antibiotic use during the second period was 31% higher than during the first period. However, normalizing antibiotic use per 100 bed-days per age-adjusted comorbidity score resulted in a comparative usage rate of 0.98, i.e. the average antibiotic use was 2% lower in the second study period. Importantly, the latter comparative usage rate is independent of differences in patient density and case mix characteristics between the two studied populations. CONCLUSIONS: The proposed modified antibiotic measure provides an innovative approach to compare variations in antibiotic prescribing while taking account of patient case mix effects.

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)(0.75) x EXP(-0.00158 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.

Microneedle-mediated minimally invasive patient monitoring.

BACKGROUND: The emerging field of microneedle-based minimally invasive patient monitoring and diagnosis is reviewed. Microneedle arrays consist of rows of micron-scale projections attached to a solid support. They have been widely investigated for transdermal drug and vaccine delivery applications since the late 1990s. However, researchers and clinicians have recently realized the great potential of microneedles for extraction of skin interstitial fluid and, less commonly, blood, for enhanced monitoring of patient health. METHODS: We reviewed the journal and patent literature, and summarized the findings and provided technical insights and critical analysis. RESULTS: We describe the basic concepts in detail and extensively review the work performed to date. CONCLUSIONS: It is our view that microneedles will have an important role to play in clinical management of patients and will ultimately improve therapeutic outcomes for people worldwide.

Online health information - what the newspapers tell their readers: a systematic content analysis.

BACKGROUND: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers. METHODS: The newspaper database Nexis®UK was searched for articles published from 2003 - 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding. RESULTS: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles. CONCLUSIONS: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership.

Medication Adherence in Children with Asthma.

Asthma is the most common chronic disease in childhood. If untreated, asthma can lead to debilitating daily symptoms which affect quality of life, but more importantly can lead to fatal asthma attacks which unfortunately still occur globally. The most effective treatment strategy for controlling asthma is for the patient to follow a personalised asthma action plan (PAAP) which will invariably include regular use of an inhaled corticosteroid. To examine medication adherence in children with asthma, we collated recent evidence from systematic reviews in this area to address the following 5 key questions; What is adherence? Is there evidence that children are not adhering to preventer medication? Why is adherence poor and what are the barriers to adherence? Does good adherence improve outcomes in asthma? And lastly, how can treatment adherence be improved?

Adherence to antiepileptic medicines in children: a multiple-methods assessment involving dried blood spot sampling.

PURPOSE: To evaluate adherence to prescribed antiepileptic drugs (AEDs) in children with epilepsy using a combination of adherence-assessment methods. METHODS: A total of 100 children with epilepsy (≤17 years old) were recruited. Medication adherence was determined via parental and child self-reporting (≥9 years old), medication refill data from general practitioner (GP) prescribing records, and via AED concentrations in dried blood spot (DBS) samples obtained from children at the clinic and via self- or parental-led sampling in children's own homes. The latter were assessed using population pharmacokinetic modeling. Patients were deemed nonadherent if any of these measures were indicative of nonadherence with the prescribed treatment. In addition, beliefs about medicines, parental confidence in seizure management, and the presence of depressed mood in parents were evaluated to examine their association with nonadherence in the participating children. KEY FINDINGS: The overall rate of nonadherence in children with epilepsy was 33%. Logistic regression analysis indicated that children with generalized epilepsy (vs. focal epilepsy) were more likely (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.37-15.81) to be classified as nonadherent as were children whose parents have depressed mood (OR 3.6, 95% CI 1.16-11.41). SIGNIFICANCE: This is the first study to apply the novel methodology of determining adherence via AED concentrations in clinic and home DBS samples. The present findings show that the latter, with further development, could be a useful approach to adherence assessment when combined with other measures including parent and child self-reporting. Seizure type and parental depressed mood were strongly predictive of nonadherence.

Pharmacokinetics of melatonin in preterm infants.

AIMS: Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials. METHODS: Melatonin was administered to 18 preterm infants in doses ranging from 0.04-0.6 µg kg(-1) over 0.5-6 h. Pharmacokinetic profiles were analyzed individually and by population methods. RESULTS: Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1 µg kg(-1) h(-1) for 2 h showed a median half-life of 15.82 h and median maximum plasma concentration of 203.3 pg ml(-1) . On population pharmacokinetics, clearance was 0.045 l h(-1) , volume of distribution 1.098 l and elimination half-life 16.91 h with gender (P = 0.047) and race (P < 0.0001) as significant covariates. CONCLUSIONS: A 2 h infusion of 0.1 µg kg(-1) h(-1) increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants.

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.

What the newspapers say about medication adherence: a content analysis.

BACKGROUND: This study investigates the coverage of adherence to medicine by the UK and US newsprint media. Adherence to medicine is recognised as an important issue facing healthcare professionals and the newsprint media is a key source of health information, however, little is known about newspaper coverage of medication adherence. METHODS: A search of the newspaper database Nexis®UK from 2004-2011 was performed. Content analysis of newspaper articles which referenced medication adherence from the twelve highest circulating UK and US daily newspapers and their Sunday equivalents was carried out. A second researcher coded a 15% sample of newspaper articles to establish the inter-rater reliability of coding. RESULTS: Searches of newspaper coverage of medication adherence in the UK and US yielded 181 relevant articles for each country. There was a large increase in the number of scientific articles on medication adherence in PubMed® over the study period, however, this was not reflected in the frequency of newspaper articles published on medication adherence. UK newspaper articles were significantly more likely to report the benefits of adherence (p = 0.005), whereas US newspaper articles were significantly more likely to report adherence issues in the elderly population (p = 0.004) and adherence associated with diseases of the central nervous system (p = 0.046). The most commonly reported barriers to adherence were patient factors e.g. poor memory, beliefs and age, whereas, the most commonly reported facilitators to adherence were medication factors including simplified regimens, shorter treatment duration and combination tablets. HIV/AIDS was the single most frequently cited disease (reported in 20% of newspaper articles). Poor quality reporting of medication adherence was identified in 62% of newspaper articles. CONCLUSION: Adherence is not well covered in the newspaper media despite a significant presence in the medical literature. The mass media have the potential to help educate and shape the public's knowledge regarding the importance of medication adherence; this potential is not being realised at present.

Antibiotic dosing in children in Europe: can we grade the evidence from pharmacokinetic/pharmacodynamic studies - and when is enough data enough?

PURPOSE OF REVIEW: Antibiotics are prescribed more frequently to children than any other class of medication. Analysis of the evidence behind antimicrobial dosing regimes is imperative to improve clinical outcomes, minimize antimicrobial resistance development, and to identify priority research areas for the future. This review aims to promote debate amongst paediatricians, pharmacologists, and pharmacists about how to improve antimicrobial prescribing by considering methods to develop and disseminate optimal dosage information. RECENT FINDINGS: There has been increasing use of population analyses to understand pharmacokinetic/pharmacodynamic (PK/PD) parameters in children. Nonlinear mixed effects modelling is widely accepted to be the method of choice for analyses of PK/PD data. However, communicating the quality of PK/PD studies is an equally important factor to allow clinicians to gauge the robustness of the evidence. The possibility of grading PK/PD studies is discussed, along with using systematic reviews and PK/PD meta-analysis for generating high-quality evidence.Many doses in existing formularies (including the British National Formulary for Children) are based on outdated evidence. The need to update formularies to account for new evidence, population changes (e.g. obesity), and changing patterns of resistance requires a more systematic evaluation of antimicrobial PK/PD relationships in children. The possibility of e-formularies with links directly to the evidence should be considered and regulators must also play a role in supporting the re-evaluation of off-patent dosing guidelines. SUMMARY: Advancing our understanding of the evidence behind paediatric antimicrobial therapeutic regimens is essential to improve both clinical outcomes and patient safety. Using a combination of international collaboration, electronic communication, and PK/PD modelling techniques, we can now define the gaps in our knowledge base and develop the techniques to answer them.

An evaluation of the impact of antibiotic stewardship on reducing the use of high-risk antibiotics and its effect on the incidence of Clostridium difficile infection in hospital settings.

OBJECTIVES: To evaluate the impact of a high-risk antibiotic stewardship programme on reducing antibiotic use and on hospital Clostridium difficile infection (CDI) incidence rates. A secondary objective was to present the possible utility of time-series analysis as an antibiotic risk classification tool. METHODS: This was an interventional, retrospective, ecological investigation in a medium-sized hospital over 6.5 years (January 2004 to June 2010). The intervention was the restriction of high-risk antibiotics (second-generation cephalosporins, third-generation cephalosporins, fluoroquinolones and clindamycin). Amoxicillin/clavulanic acid and macrolides were classified as medium-risk antibiotics based on time-series analysis findings and their use was monitored. The intervention was evaluated by segmented regression analysis of interrupted time series. RESULTS: The intervention was associated with a significant change in level of use of high-risk antibiotics (coefficient -17.3, P < 0.0001) and with a borderline significant trend change in their use being reduced by 0.156 defined daily doses/100 bed-days per month (P = 0.0597). The reduction in the use of high-risk antibiotics was associated with a significant change in the incidence trend of CDI (P = 0.0081), i.e. the CDI incidence rate decreased by 0.0047/100 bed-days per month. Analysis showed that variations in the incidence of CDI were affected by the age-adjusted comorbidity index with a lag of 1 month (coefficient 0.137051, P = 0.0182). Significant decreases in slope (coefficient -0.414, P = 0.0309) post-intervention were also observed for the monitored medium-risk antibiotics. CONCLUSIONS: The restriction of the high-risk antibiotics contributed to both a reduction in their use and a reduction in the incidence of CDI in the study site hospital. Time-series analysis can be utilized as a risk classification tool with utility in antibiotic stewardship design and quality improvement programmes.

The impact of antibiotic use on the incidence and resistance pattern of extended-spectrum beta-lactamase-producing bacteria in primary and secondary healthcare settings.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • The emergence and spread of bacteria producing extended-spectrum beta-lactamases (ESBLs) has important therapeutic and epidemiologic implications. • A key target for the establishment of hospital antibiotic stewardship is reducing the occurrence of additional antibiotic resistance. • Further research is needed to accumulate supporting evidence that reducing antibiotic use will result in a parallel reduction in antibiotic resistance. WHAT THIS STUDY ADDS: • Fluoroquinolone restriction reversed ciprofloxacin resistance in primary and secondary healthcare settings. • Fluoroquinolone restriction reduced ESBL-producing bacteria incidence rates in both the primary and secondary healthcare settings. • This study highlights the value of time-series analysis in designing efficient antibiotic stewardship. AIMS: The objective of the present study was to study the relationship between hospital antibiotic use, community antibiotic use and the incidence of extended-spectrum beta-lactamase (ESBL)-producing bacteria in hospitals, while assessing the impact of a fluoroquinolone restriction policy on ESBL-producing bacteria incidence rates. METHODS: The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (ARIMA) model was built to relate antibiotic use to ESB-producing bacteria incidence rates and resistance patterns over a 5 year period (January 2005-December 2009). RESULTS: Analysis showed that the hospital incidence of ESBLs had a positive relationship with the use of fluoroquinolones in the hospital (coefficient = 0.174, P= 0.02), amoxicillin-clavulanic acid in the community (coefficient = 1.03, P= 0.03) and mean co-morbidity scores for hospitalized patients (coefficient = 2.15, P= 0.03) with various time lags. The fluoroquinolone restriction policy was implemented successfully with the mean use of fluoroquinolones (mainly ciprofloxacin) being reduced from 133 to 17 defined daily doses (DDDs)/1000 bed days (P < 0.001) and from 0.65 to 0.54 DDDs/1000 inhabitants/day (P= 0.0007), in both the hospital and its surrounding community, respectively. This was associated with an improved ciprofloxacin susceptibility in both settings [ciprofloxacin susceptibility being improved from 16% to 28% in the community (P < 0.001)] and with a statistically significant reduction in ESBL-producing bacteria incidence rates. DISCUSSION: This study supports the value of restricting the use of certain antimicrobial classes to control ESBL, and demonstrates the feasibility of reversing resistance patterns post successful antibiotic restriction. The study also highlights the potential value of the time-series analysis in designing efficient antibiotic stewardship.