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 metformin in adults with type 2 diabetes: a combined method approach.

BACKGROUND: Medication adherence, one of the most important aspects in the process of optimal medicines use, is unfortunately still a major challenge in modern healthcare, and further research is required into how adherence can be assessed and optimised. The aim of this study was to use a combined method approach of self-report and dried blood spot (DBS) sampling coupled with population pharmacokinetic (PopPK) modelling, to assess adherence to metformin in adult patients with type 2 diabetes. Further aims were to assess metformin exposure levels in patients, determine factors associated with non-adherence with prescribed metformin, and to explore the relationship between adherence and therapeutic outcomes. METHODS: A combined method approach was used to evaluate metformin adherence in patients with type 2 diabetes who had been prescribed metformin for a minimum period of 6 months. Patients were recruited from consultant-led diabetic outpatient clinics at three hospitals in Northern Ireland, UK. Data collection involved self-reported questionnaires [Medication Adherence Report Scale (MARS), Beliefs about Medicines Questionnaire and Centre for Epidemiologic Studies Depression Scale], direct measurement of metformin concentration in DBS samples, and researcher-led patient interviews. The DBS sampling approach was coupled with population pharmacokinetic (PopPK) modelling, which took account of patient characteristics, metformin dosage and type of formulation prescribed (immediate or sustained release). RESULTS: The proportion of patients considered to be adherent to their prescribed metformin, derived from self-reported MARS scores and metformin concentration in DBS samples, was 61.2% (74 out of 121 patients). The majority (n = 103, 85.1%) of recruited patients had metformin exposure levels that fell within the therapeutic range. However, 17 patients (14.1%) had low exposure to metformin and one patient (0.8%) had undetectable metformin level in their blood sample (non-exposure). Metformin self-administration and use of a purchased adherence pill box significantly increased the probability of a patient being classified as adherent based on logistic regression analysis. Both HbA1c and random glucose levels (representing poor glycaemic control) in the present research were, however, not statistically linked to non-adherence to metformin (P > 0.05). CONCLUSIONS: A significant proportion of participating patients were not fully adherent with their therapy. DBS sampling together with the use of a published PopPK model was a useful, novel, direct, objective approach to estimate levels of adherence in adult patients with type 2 diabetes (61.2%).

Potential of UK and US newspapers for shaping patients' knowledge and perceptions about antidiabetic medicines: a content analysis.

BACKGROUND: Information about how newspapers portray antidiabetic medicines to readers is lacking. This study investigated the reporting on antidiabetic medicines in the most widely circulated newspapers published in the United Kingdom (UK) and the United States (US) over a 10-year period. METHODS: The Nexis UK database was used to identify and select relevant articles. Systematic content analysis of the articles which met the inclusion criteria (articles of any format that contained reference to antidiabetic medicines) within the highest circulated newspapers in the UK and US between 2009 and 2018 was conducted. Inter-rater reliability of coding was established using a 10% sample of the identified articles. RESULTS: A total of 560 (369 UK and 191 US) relevant newspaper articles were retrieved. In the UK, the number of relevant articles showed a slightly increasing trend over the study period, while in the US, article numbers declined over the study period. Safety/risk of antidiabetic medicines was the most frequent theme covered by the articles (34.6%). Over one-third of the newspaper articles were written from a clinical perspective (37.7%). Insulin was the most commonly discussed class of antidiabetic medicine (23.1%). Control of blood sugar levels (53.1%) and side effects/toxicity (92.7%) were the most frequently reported benefit and risk of antidiabetic medicines, respectively. The most frequently reported organ systems harmed by antidiabetic medicines were the cardiovascular, endocrine and gastrointestinal systems. The UK newspapers were more likely to report the benefits of antidiabetic medicines (p = 0.005), while the US articles were more likely to report on harms/risks (p = 0.001). The majority of relevant articles (91.8%) were judged as having a balanced judgement, while 8.2% of the articles were rated as exaggerated. CONCLUSIONS: This study has revealed that antidiabetic medicines are indeed reported on by UK and US newspapers. As media portrayal has the potential to negatively or positively influence patients' views of their medication for diabetes, healthcare professionals should check on patients' beliefs and knowledge about their medication and proactively provide objective and balanced information (including promotion of medication adherence).

General practitioner practice-based pharmacist input to medicines optimisation in the UK: pragmatic, multicenter, randomised, controlled trial.

BACKGROUND: Changing demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs. METHODS: A multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (n = 356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs. RESULTS: Median number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (p < 0.001) in patients who received the full intervention schedule. Medication Appropriateness Index (MAI) scores were reduced (medications more appropriate) for the intervention group, but not for control group patients (8 [4-13] to 5 [0-11] vs 8 [3-13] to 7 [3-12], respectively; p = 0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0-3] to 1 [0-2] vs 1 [0-2] to 1 [0-3], p = 0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from £1041.7 ± 1446.7 to £859.1 ± 1235.2 (p = 0.032). Cost utility analysis showed an incremental cost per patient of - £229.0 (95% CI - 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI - 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017). CONCLUSION: The pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03241498.

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.

Development and characterisation of novel poly (vinyl alcohol)/poly (vinyl pyrrolidone)-based hydrogel-forming microneedle arrays for enhanced and sustained transdermal delivery of methotrexate.

Methotrexate (MTX) is one of the mainstays of treatment for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) and it is mainly administered either orally or by subcutaneous (SC) injection, which are not so satisfactory. While orally administered MTX is associated with variable bioavailability and causes gastrointestinal side effects, including nausea and vomiting, SC injection is painful and produces high peak blood levels of MTX. Transdermal delivery presents an attractive alternative administration route. However, MTX passive permeation through the skin is hindered by the skin barrier and MTX physicochemical properties. To address these issues, hydrogel-forming microneedle arrays (HFMN) and a patch-like reservoir loaded with MTX (MTX-RV) were developed and combined to form a minimally invasive patch to deliver MTX transdermally in a sustained manner. HFMN were prepared from an aqueous blend of poly (vinyl alcohol) (PVA) and poly (vinyl pyrrolidone) (PVP) which was crosslinked chemically with citric acid (CA) at 130˚C. MTX-RV was prepared from hydroxypropyl methylcellulose (HPMC) and glycerol. Both the HFMN and MTX-RV were fully characterised and then combined to form an integrated patch, which was evaluated ex vivo and in preclinical studies. The HFMN demonstrated a satisfactory mechanical strength and insertion capability into excised neonatal porcine skin, as well as moderate swelling properties. The MTX-RV incorporated a high dose of MTX (150.3 ± 5.3 µg/mg) without precipitation. The integrated patch delivered MTX at a steady-state flux of 506.8 ± 136.9 µg.cm2/h in an ex vivo setup. Furthermore, in preclinical studies performed in Sprague Dawley rats, MTX appeared in blood after 1 h from patch application at a concentration of 7.6 ± 2.0 nM. MTX blood level increased gradually to reach its peak, Cmax = 35.1 ± 5.1 nM, at 24 h. Importantly, the HFMN were removed intact from the skin with only mild erythema, despite the cytotoxic nature of MTX. Accordingly, the integrated patch produced in this work represents a promising minimally invasive transdermal drug delivery system that can overcome the skin barrier and deliver MTX in a sustained manner. This may help in minimising or even avoiding the nausea and vomiting, associated with the conventional administration routes.

A novel approach to medicines optimisation post-discharge from hospital: pharmacist-led medicines optimisation clinic.

Background There is a major drive within healthcare to reduce patient readmissions, from patient care and cost perspectives. Pharmacist-led innovations have been demonstrated to enhance patient outcomes. Objective To assess the impact of a post-discharge, pharmacist-led medicines optimisation clinic on readmission parameters. Assessment of the economic, clinical and humanistic outcomes were considered. Setting Respiratory and cardiology wards in a district general hospital in Northern Ireland. Method Randomised, controlled trial. Blinded random sequence generation; a closed envelope-based system, with block randomisation. Adult patients with acute unplanned admission to medical wards subject to inclusion criteria were invited to attend clinic. Analysis was carried out for intention-to-treat and per-protocol perspectives. Main Outcome Measure 30-day readmission rate. Results Readmission rate reduction at 30 days was 9.6% (P = 0.42) and the reduction in multiple readmissions over 180-days was 29.1% (P = 0.003) for the intention-to-treat group (n = 31) compared to the control group (n = 31). Incidence rate ratio for control patients for emergency department visits was 1.65 (95% CI 1.05-2.57, P = 0.029) compared with the intention-to-treat group. For unplanned GP consultations the equivalent incident rate ratio was 2.00 (95% CI 1.18-3.58, P = 0.02). Benefit to cost ratio in the intention-to-treat and per-protocol groups was 20.72 and 21.85 respectively. Patient Health Related Quality of Life was significantly higher at 30-day (P < 0.001), 90-day (P < 0.001) and 180-day (P = 0.036) time points. A positive impact was also demonstrated in relation to patient beliefs about their medicines and medication adherence. Conclusion A pharmacist-led post-discharge medicines optimisation clinic was beneficial from a patient care and cost perspective.

Adherence to Azathioprine/6-Mercaptopurine in Children and Adolescents with Inflammatory Bowel Diseases: A Multimethod Study.

Background: Measurement of the degree of adherence is a key element for the evaluation of treatment efficacy and safety; thus, adherence plays an important role in clinical research and practice. The aim of this study was to investigate medication adherence in children with inflammatory bowel disease (IBD) utilizing a multimethod assessment approach. A further aim was to examine factors that can influence adherence within this population. Methods: Medication adherence in 47 children (age range 3 to 17 years) with IBD in three centers in Northern Ireland and Jordan was assessed via subjective (parent and child versions of the Medication Adherence Report Scale (MARS) specific questionnaire) and objective methods, that is, high-performance liquid chromatography (HPLC) determination of the 6-mercaptopurine (6-MP) and azathioprine (AZA) metabolites in packed red blood cell samples taken during a clinic visit. Beliefs about prescribed medicines were also assessed in parents/guardians using the Beliefs about Medicines Questionnaire (BMQ). Results: An overall nonadherence to AZA/6-MP therapy in children with IBD was found to be 36.17% (17 out of 47 patients were classified as nonadherent using at least one of the assessment methods). A total of 41 patients (91.1%) were classified as adherent to AZA or 6-MP using the blood sampling, while adherence rates using the MARS questionnaire completed by children and parents/guardians were 60.6% and 72.7%, respectively. The latter provides a more longitudinal measure of adherence. Child self-reported nonadherence rates were significantly higher than parent/guardian reported rates (p=0.013). Binary logistic regression analysis identified age to be independently predictive of adherence, with adolescents (children aged ≥ 13 years old) more likely to be classified as nonadherent. Regarding the BMQ, when parental/guardian necessity beliefs outweighed concerns, that is, higher scores in the necessity-concern differential (NCD), adolescents were more likely to be classified as adherent. Conclusion: Results provide evidence for ongoing adherence challenges in the paediatric population with IBD. It is recommended that parents/guardians (particularly of older children) and older children themselves, should receive enhanced counselling and education about their prescribed medicines.

Hematocrit, blood volume, and surface area of dried blood spots - a quantitative model.

The use of the dried blood spot (DBS) sampling technique has extended the scope of clinical research, particularly in children. The effects of different hematocrit levels (25-55%) and different blood volumes (7.5-30 µL) on the surface area of the blood spots were investigated using ImageJ® software. Variation in hematocrit levels between patients and inaccuracies in blood volumes applied to Guthrie cards can have a marked effect on analyte concentrations measured in DBS samples. The current study presents a validated model that links blood volume and hematocrit to the surface area of the blood spot. The final model showed that both factors affect the blood spot surface area, however, the positive effect of blood volume is higher than the negative effect of hematocrit. The measurement of surface area could be added as an additional quality control step in clinical studies that have adopted fixed volume DBS sampling for the quantification of the analytes. This approach can be used in estimating the hematocrit if this is not known for a patient or estimating the volume in spots that are visually different in size from the norm, i.e. technical error.

Determination of azathioprine/6-mercaptopurine metabolites in dried blood spots: Correlation with RBC concentrations.

The analysis of 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-mMP) in biological samples is not straight forward and requires pre-treatment of samples. There are no validated published methods for the analysis of azathioprine/6-mercaptopurine (AZA/6-MP) metabolites in dried blood spot (DBS) samples that study the correlation with red blood cells (RBC) concentrations. DBS was prepared by applying fifteen microliters of blood [spiked with analytes or samples obtained from patients] to a Guthrie card which was then dried at room temperature overnight. The sample treatment procedure used protein precipitation followed by a hydrolysis step in which, 6-mMP was converted into 4-amino-5-(methylthio)carbonyl imidazole (AMTCI) then analytes were transferred to a solid phase extraction cartridge. The extracted sample was chromatographed using a reversed phase system (C18) column preceded by a guard column of matching chemistry. The method gave a linear calibration over the range 0.5-15 µmol/L and 3.75-175 µmol/L for 6-TG and 6-mMP, respectively. The method has been applied successfully to the determination of 6-TG and 6-mMP concentrations in DBS finger-prick samples from 27 paediatric patients with IBD who were receiving (AZA/6-MP). Patient 6-TG and 6-mMP RBC concentrations, calculated from whole blood finger prick DBS samples and those measured in RBCs derived from matched venous samples (analyzed using conventional HPLC-UV technique) showed good agreement using the Bland-Altman test. This is the first published method for determining 6-TG and 6-mMP in DBS that studies their correlation with RBCs concentrations. It is applicable to a range of clinical studies such as adherence and pharmacokinetic studies involving AZA/6-MP.

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.

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.

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.

Mobile direct observation of therapy (MDOT) - A rapid systematic review and pilot study in children with asthma.

We describe, for the first time, the use of a mobile device platform for remote direct observation of inhaler use and technique. The research programme commenced with a rapid systematic review of mobile device (or videophone) use for direct observation of therapy (MDOT). Ten studies (mainly pilots) were identified involving patients with tuberculosis, sickle cell disease and Alzheimer's disease. New studies are ongoing (ClinicalTrials.gov website) in TB, stroke, sickle cell disease, HIV and opioid dependence. Having identified no prior use of MDOT in inhaler monitoring, we implemented a feasibility study in 12 healthy volunteer children (2-12 years; 8 females and 4 males) over a period of 14 days, with twice daily video upload of their 'dummy' inhaler use. Two children uploaded 100% of the requested videos, with only one child having an inhaler upload rate of <75%. The quality of uploaded videos was generally good (only 1.7% of unacceptable quality for evaluation). The final aspect of the research was a pilot study using MDOT (6 weeks) in 22 children with difficult to treat asthma. Healthcare professionals evaluated inhaler technique using uploaded videos and provided telephone instruction on improving inhaler use. The main outcomes were assessed at week 12 post initiation of MDOT. By week 5, all children still engaging in MDOT (n = 18) were judged to have effective inhaler technique. Spirometry values did not vary to a significantly significant degree between baseline and 12 weeks (P>0.05), however, mean fraction of exhaled nitric oxide (FeNO) values normalised (mean 38.7 to 19.3ppm) and mean Asthma Control Test values improved (13.1 to mean 17.8). Feedback from participants was positive. Overall the findings open up a new paradigm in device independent (can be used for any type of inhaler device) monitoring, providing a platform for evaluating / improving inhaler use at home.

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.

Pharmaceutical Care in Children: Self-reported knowledge, attitudes and competency of final-year pharmacy students in Jordan.

OBJECTIVES: Pharmacists require a baseline level of knowledge in paediatric pharmaceutical care in order to be able to adequately care for paediatric patients and counsel their families. This study aimed to explore the self-reported knowledge, attitudes and competency of final-year pharmacy students in Jordan regarding paediatric pharmaceutical care. METHODS: This study took place in Jordan between November 2016 and May 2017. A 28-item questionnaire was designed and administered to 400 students from all pharmacy programmes in Jordan during their final year of training. RESULTS: A total of 354 students agreed to take part in the study (response rate: 88.5%). Most respondents (95.2%) were aware of the term 'paediatrics'. However, almost one-third of the respondents (30.5%) reported never having taken paediatric dose calculation courses and more than half (55.6%) were unfamiliar with the term 'off-label medicines'. Moreover, most respondents (65.1%) had low knowledge scores (≤2 out of 5) when presented with realistic paediatric case scenarios. There were no significant differences in knowledge and attitudes between undergraduate and doctoral students or between those from public or private universities (P >0.05). CONCLUSION: The findings of this study highlight an alarming deficiency in paediatric pharmaceutical knowledge among final-year pharmacy students in Jordan. As such, paediatric-related content should be emphasised in the pharmacy curricula of Jordanian universities so that pharmacy students receive more formalised education and more extensive training in this area.

Quantification of amlodipine in dried blood spot samples by high performance liquid chromatography tandem mass spectrometry.

A sensitive and specific method, utilising high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was developed for the quantitative determination of amlodipine in dried blood spot (DBS) samples. Chromatographic separation was achieved using a Waters XBridge C18 column with gradient elution of a mixture of water and acetonitrile containing 0.1% formic acid (v/v). Amlodipine was quantified using a Waters Quattro Premier mass spectrometer coupled with an electro-spray ionization (ESI) source in positive ion mode. The MRM transitions of 408.9 m/z→238.1m/z and 408.9→294.0 m/z were used to quantify and qualify amlodipine, respectively. The method was validated across the concentration range of 0.5-30ng/mL by assessing specificity, sensitivity, linearity, precision, accuracy, recovery and matrix effect according to the Food and Drug Administration (FDA) guidelines. This method was also validated clinically within a large pharmacoepidemiological study in which amlodipine blood concentration was determined in patients who had been prescribed this medication.

Provision of pharmaceutical care by community pharmacists across Europe: Is it developing and spreading?

RATIONALE, AIMS, AND OBJECTIVES: Pharmaceutical care involves patient-centred pharmacist activity to improve medicines management by patients. The implementation of this service in a comprehensive manner, however, requires considerable organisation and effort, and indeed, it is often not fully implemented in care settings. The main objective was to assess how pharmaceutical care provision within community pharmacy has evolved over time in Europe. METHOD: A cross-sectional questionnaire-based survey of community pharmacies, using a modified version of the Behavioural Pharmaceutical Care Scale (BPCS) was conducted in late 2012/early 2013 within 16 European countries and compared with an earlier assessment conducted in 2006. RESULTS: The provision of comprehensive pharmaceutical care has slightly improved in all European countries that participated in both editions of this survey (n = 8) with progress being made particularly in Denmark and Switzerland. Moreover, there was a wider country uptake, indicating spread of the concept. However, due to a number of limitations, the results should be interpreted with caution. Using combined data from participating countries, the provision of pharmaceutical care was positively correlated with the participation of the community pharmacists in patient-centred activities, routine use of pharmacy software with access to clinical data, participation in multidisciplinary team meetings, and having specialized education. CONCLUSIONS: The present study demonstrated a slight evolution in self-reported provision of pharmaceutical care by community pharmacists across Europe, as measured by the BPCS. The slow progress suggests a range of barriers, which are preventing pharmacists moving beyond traditional roles. Support from professional bodies and more patient-centred community pharmacy contracts, including remuneration for pharmaceutical care services, are likely to be required if quicker progress is to be made in the future.

Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring.

We describe, for the first time, hydrogel-forming microneedle (s) (MN) arrays for minimally-invasive extraction and quantification of lithium in vitro and in vivo. MN arrays, prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) and crosslinked by poly(ethyleneglycol), imbibed interstitial fluid (ISF) upon skin insertion. Such MN were always removed intact. In vitro, mean detected lithium concentrations showed no significant difference following 30min MN application to excised neonatal porcine skin for lithium citrate concentrations of 0.9 and 2mmol/l. However, after 1h application, the mean lithium concentrations extracted were significantly different, being appropriately concentration-dependent. In vivo, rats were orally dosed with lithium citrate equivalent to 15mg/kg and 30mg/kg lithium carbonate, respectively. MN arrays were applied 1h after dosing and removed 1h later. The two groups, having received different doses, showed no significant difference between lithium concentrations in serum or MN. However, the higher dosed rats demonstrated a lithium concentration extracted from MN arrays equivalent to a mean increase of 22.5% compared to rats which received the lower dose. Hydrogel-forming MN clearly have potential as a minimally-invasive tool for lithium monitoring in outpatient settings. We will now focus on correlation between serum and MN lithium concentrations.

Reduction in the incidence of hospital-acquired MRSA following the introduction of a chlorine dioxide 275†ppm based disinfecting agent in a district general hospital.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile are major nosocomial pathogens whose control relies on effective antimicrobial stewardship and infection control practices. This study evaluates the impact of a chlorine dioxide-based disinfectant (275 ppm) on the incidence of hospital-acquired (HA) MRSA and HA-Clostridium difficile infection (CDI) in a district general hospital. METHODS: This study was carried out from November 2009 to September 2013. From November 2009 to October 2011 sodium dichloroisocyanurate was used for routine environmental disinfection. In November 2011, this was changed to a chlorine dioxide 275 ppm based disinfectant. This product was introduced into the hospital in a phased manner with intensive training on its use provided to all nursing, nursing auxiliary and hotel services staff. The effect of this change on the incidence of HA-MRSA and HA-CDI was assessed using segmented regression analysis of interrupted time series. In addition, the potential cost savings as a result of this intervention were assessed. RESULTS: The HA-MRSA trend from November 2009 to October 2011 significantly increased (p=0.006). Following the introduction of the chlorine dioxide-based disinfectant there was significant decrease in the HA-MRSA trend, with the monthly incidence being reduced by 0.003 cases/100 bed days (p=0.001), equating to an average of four cases per month after 12 months of use This resulted in an annual potential cost saving of £276 000. No significant effect on the incidence of HA-CDI was observed (coefficient -0.03; p=0.873). CONCLUSION: This study highlights the importance of effective environmental inanimate surface decontamination in controlling the spread of MRSA and the potential cost savings that can be achieved through decreasing HA-MRSA rates.