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.

Effects of Antibiotic Cycling Policy on Incidence of Healthcare-Associated MRSA and Clostridioides difficile Infection in Secondary Healthcare Settings.

This quasi-experimental study investigated the effect of an antibiotic cycling policy based on time-series analysis of epidemiologic data, which identified antimicrobial drugs and time periods for restriction. Cyclical restrictions of amoxicillin/clavulanic acid, piperacillin/tazobactam, and clarithromycin were undertaken over a 2-year period in the intervention hospital. We used segmented regression analysis to compare the effect on the incidence of healthcare-associated Clostridioides difficile infection (HA-CDI), healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA), and new extended-spectrum ß-lactamase (ESBL) isolates and on changes in resistance patterns of the HA-MRSA and ESBL organisms between the intervention and control hospitals. HA-CDI incidence did not change. HA-MRSA incidence increased significantly in the intervention hospital. The resistance of new ESBL isolates to amoxicillin/clavulanic acid and piperacillin/tazobactam decreased significantly in the intervention hospital; however, resistance to piperacillin/tazobactam increased after a return to the standard policy. The results question the value of antibiotic cycling to antibiotic stewardship.

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.

Predictors of nonadherence in children and adolescents with epilepsy: A multimethod assessment approach.

BACKGROUND: There is a lack of a standardized tool for adherence measurement in patients with epilepsy. Studies in children with epilepsy have reported adherence in 50-96.5%. The primary objective of this study was to identify predictors of nonadherence to antiepileptic drugs (AEDs) using two different methods in Jordanian children and adolescents with epilepsy. METHODS: Participants included 63 children and adolescents with epilepsy and their primary caregivers. Adherence measures included a subjective approach (using parent and child self-reports via Medication Adherence Report Scale (MARS)) and an objective method (measuring plasma levels of AEDs coupled with the application of population pharmacokinetic models to predict AED concentrations in the children). The Beliefs about Medicines Questionnaire (BMQ) was used to examine the association beliefs about medicines with nonadherence in the participating patients. RESULTS: Measuring AEDs in plasma samples captured the highest percentage of nonadherence (36.2%). No significant agreement was found between the AED plasma level method and both the MARS (parent) and MARS (child). The overall nonadherence (combined methods) to AED therapy in children with epilepsy was 44.4%. Logistic regression analysis indicated that children with longer duration of disease were more likely (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16-2.04) to be classified as nonadherent as were children whose parents have lower AED Necessity scores (OR: 0.68, 95% CI: 0.53-0.87) and higher AED Concerns (OR: 1.6, 95% CI: 1.26-2.04) as measured by the BMQ. CONCLUSION: The use of a multimethod approach for assessing adherence increases sensitivity for detection of nonadherence to AEDs. Disease duration and parental necessity beliefs and concerns assessed by the BMQ-specific questionnaire were significant predictors of nonadherence to the AED therapy. The need for the development and implementation of interventions that can be employed to improve adherence within this pediatric population has been highlighted by the high levels of nonadherence identified.

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.

High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination.

BACKGROUND: Antibiotic dosing in neonates varies between countries and centres, suggesting suboptimal exposures for some neonates. We aimed to describe variations and factors influencing the variability in the dosing of frequently used antibiotics in European NICUs to help define strategies for improvement. METHODS: A sub-analysis of the European Study of Neonatal Exposure to Excipients point prevalence study was undertaken. Demographic data of neonates receiving any antibiotic on the study day within one of three two-week periods from January to June 2012, the dose, dosing interval and route of administration of each prescription were recorded. The British National Formulary for Children (BNFC) and Neofax were used as reference sources. Risk factors for deviations exceeding ±25% of the relevant BNFC dosage recommendation were identified by multivariate logistic regression analysis. RESULTS: In 89 NICUs from 21 countries, 586 antibiotic prescriptions for 342 infants were reported. The twelve most frequently used antibiotics - gentamicin, penicillin G, ampicillin, vancomycin, amikacin, cefotaxime, ceftazidime, meropenem, amoxicillin, metronidazole, teicoplanin and flucloxacillin - covered 92% of systemic prescriptions. Glycopeptide class, GA <32 weeks, 5(th) minute Apgar score <5 and geographical region were associated with deviation from the BNFC dosage recommendation. While the doses of penicillins exceeded recommendations, antibiotics with safety concerns followed (gentamicin) or were dosed below (vancomycin) recommendations. CONCLUSIONS: The current lack of compliance with existing dosing recommendations for neonates needs to be overcome through the conduct of well-designed clinical trials with a limited number of antibiotics to define pharmacokinetics/pharmacodynamics, efficacy and safety in this population and by efficient dissemination of the results.

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?

Service development project to pilot a digital technology innovation for video direct observation of therapy in adult patients with asthma.

BACKGROUND: Adherence to pharmacotherapy and use of the correct inhaler technique are important basic principles of asthma management. Video- or remote-direct observation of therapy (v-DOT) could be a feasible approach to facilitate monitoring and supervising therapy, supporting the delivery of standard care. OBJECTIVE: To explore the utility and the feasibility of v-DOT to monitor inhaler technique and adherence to treatment in adults attending the asthma outpatient service in a tertiary hospital in Northern Ireland. METHOD: The project evaluated use of the technology with 10 asthma patients. Patient and clinician feedback was obtained, in addition to measures of patient engagement and disease-specific clinical markers to assess the feasibility and utility of v-DOT technology in this group of patients. RESULTS: The engagement rate with v-DOT for participating patients averaged 78% (actual video uploads vs expected video uploads) over a median 7 week usage period. Although 50% of patients reported a technical issue at some stage during the usage period, all patients and clinicians reported that the technology was easy to use and that they were satisfied with the outcomes. A range of positive impacts were observed, including optimised inhaler technique and an observed improvement in lung function. An increase in asthma control test scores aligned with clinical aims to promote adherence and alleviate symptoms. CONCLUSION: The v-DOT technology was shown to be a feasible method of assessing inhaler technique and monitoring adherence in this small group of adult asthma patients. A range of positive impacts for participating patients and clinicians were observed. Not all patients invited to join the project agreed to participate or engage with using the technology, highlighting that in this setting, digital modes of delivering care provide only one of the approaches in the necessary "tool kit" for clinicians and patients.

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.