From the European Medicines Agency to Project Orbis: new activities and challenges to facilitate UK oncology drug approval following Brexit.

The departure of the UK from the European Union (EU) and affiliated European regulatory bodies, including the European Medicines Agency, on Dec 31, 2020, has resulted in the Medicines and Healthcare products Regulatory Agency becoming an independent national regulator. This change has required a fundamental transformation of the UK drug regulatory landscape, creating both opportunities and challenges for future development of oncology drugs. New UK pharmaceutical policies have sought to make the UK an attractive market for drug development and regulatory review, by offering expedited review pathways coupled to strong collaborative relations with other leading international medicines regulators, outside of Europe. Oncology is a key global therapy area for both drug development and regulatory approval, and the UK Government has been keen to show regulatory innovation and international collaboration through approval of new cancer medicines. In this Policy Review, we examine the new UK regulatory frameworks, policies, and global collaborations affecting new oncology drug approvals after departure from the EU. We explore some of the challenges that might lie ahead as the UK creates new and independent regulatory review and approval processes for the next generation of cancer medicines.

Coping with COVID: Preparing prescribers during the pandemic.

In response to the COVID-19 pandemic, Health Education England (HEE) and the University of Birmingham provided National Health Service (NHS) staff free access to SCRIPT, a national eLearning programme for safer prescribing and therapeutics. The eLearning was particularly for those returning to work or being redeployed. In the year March 2020-21, 3412 users registered to access portfolios and opened an aggregate of 17 198 modules. Each user completed a median of 2 (range 1-50, interquartile range [IQR] 1-7) assessed learning modules. Marks improved from pre-test to post-test by a median of 2 (IQR 0-3) marks out of 10. The most frequently selected modules were Adherence and Concordance (1109 users), Fluids (981 users) and Diabetic Emergencies (818 users). A total of 878 users accessed the unassessed COVID-19 module. The SCRIPT modules provided standardised education in core principles relating to prescribing and therapeutics, and were used by professionals from many healthcare disciplines.

Exploring the barriers and facilitators to non-medical prescribing experienced by pharmacists and physiotherapists, using focus groups.

BACKGROUND: Non-medical prescribing (NMP) was introduced into the United Kingdom to enhance patient care and improve access to medicines. Early research indicated that not all non-medical prescribers utilised their qualification. A systematic review described 15 factors influencing NMP implementation. Findings from a recent linked Delphi study with independent physiotherapist and pharmacist prescribers achieved consensus for 1 barrier and 28 facilitators. However, item ranking differed for pharmacist and physiotherapist groups, suggesting facilitators and barriers to NMP differ depending on profession. The aim of this study was to further explore the lived experiences of NMP by pharmacists and physiotherapists. METHOD: Study design and analytical approach were guided by Interpretative Phenomenology Analysis principles. Focus groups (November and December 2020) used the 'Zoom®ï»¿' virtual platform with pharmacist and physiotherapist prescribers. Each focus group followed a topic guide, developed a priori based on the Delphi study results, and was audio recorded digitally. Transcripts underwent thematic analysis and data were visualised using a concept map and sunburst graph, and a table of illustrative quotes produced. Research trustworthiness was enhanced through critical discussion of the topic guide and study findings by the research group and by author reflexivity. The study is reported in line with COREQ guidelines. RESULTS: Participants comprised three physiotherapists and seven pharmacists. Five themes were identified. The most frequently mentioned theme was 'Staff', and the subtheme 'Clinical team', describing the working relationship between participants and team members. The other themes were 'Self', 'Governance', 'Practical aspects' and 'Patient care'. Important inter-dependencies were described between themes and subthemes, for example between 'Governance' and 'Quality and Safety'. Differences were highlighted between the professions, some relating to the way each profession practises (for example decision making), others to the way the prescribing role had been established (for example administration support). CONCLUSIONS: The key finding of collaborative working with the clinical team emphasises its impact on successful implementation of NMP. Themes may be inter-dependent, and inter-profession differences were identified. Specifically designed prescribing roles were beneficial for participants. For full NMP benefits to be realised all aspects of such roles must be fully scoped, before recruiting or training non-medical prescribers.

A meta-ethnography of adult smokers' exploring the meanings of tobacco dependency medications adherence behaviours during smoking cessation.

AIMS: To synthesize the experiences and adherence of adult smokers' with tobacco dependence medications. DESIGN: Meta-ethnography. DATA SOURCES: Seven bibliographic databases were systematically searched until April 2016. REVIEW METHODS: A standardized appraisal tool evaluated the quality of the selected studies. RESULTS: Seven studies met the eligibility criteria. Three major themes described the experiences and adherence of adult smokers' with tobacco dependence medications; the psychosocial context, predilection for willpower and "natural" methods and a tendency to resist medications. CONCLUSION: The findings of this meta-ethnography are important to future clinical practice guideline development so health professionals contribute effectively to further reduction in smoking prevalence. Further research is needed to understand resistance to tobacco dependence medications and to inform the design of person-tailored interventions to improve tobacco dependence medication adherence that can be incorporated into smoking cessation interventions. IMPACT: Smoking causes more death and disability in the world than any other avoidable factor. Research on smoker perspectives on tobacco dependence medications is sparse. Tobacco dependency is a unique treatment context with specific adherence issues. Smokers are active decision-makers regarding tobacco dependence medications. Inconsistent adherence to tobacco dependency medication regimens was apparent. Implications for health professionals, healthcare policy and clinical practice guidelines regard the structure of consultations with smoking patients. It is critical for all health professionals to assess the person seeking to stop smoking and foresee the possible causes of non-adherence behaviour. Addressing non-adherence will to lead to more effective health communications and positively contribute to quality of smoking cessation care.

A review of prednisolone prescribing for children with acute asthma in the UK.

INTRODUCTION: Worldwide asthma guidelines recommend short courses of oral prednisolone in children with acute exacerbations generating high prescription numbers. There is a paucity of evidence to inform the optimal dose and course duration. This has led to a variation in the recommendations for prednisolone prescribing. Our objective was to assess prednisolone prescribing practise for children with acute asthma in a representative sample of UK prescribers. METHODS: We developed an online questionnaire asking prescribers the prednisolone dosage, course duration and formulation used, whether they discussed oral prednisolone side effects with the family and at what child's age they changed from prescribing soluble to non-soluble formulations. This was sent to 1006 UK prescribers including Paediatric Respiratory Consultants, doctors in training, asthma nurses and General Practitioners. RESULTS: 200 complete responses were received (response rate 20%). The majority of surveyed prescribers follow the British National Formulary for Children recommendations on dosage rather than those included in the British Thoracic Society and the Scottish Intercollegiate Guidelines Network. Despite this, we highlighted a 4-fold variation in prednisolone dosages for acute asthma. The majority of prescribers chose 3 days as the course duration. High use of soluble formulations was highlighted. CONCLUSIONS: There is wide variation in the dose of prednisolone prescribed for children with acute asthma in the UK. This reflects a relative lack of evidence that needs addressing.

An evaluation of UK foundation trainee doctors' learning behaviours in a technology-enhanced learning environment.

BACKGROUND: Technology-Enhanced Learning (TEL) can be used to educate Foundation Programme trainee (F1 and F2) doctors. Despite the advantages of TEL, learning behaviours may be exhibited that are not desired by system developers or educators. The aim of this evaluation was to investigate how learner behaviours (e.g. time spent on task) were affected by temporal (e.g. time of year), module (e.g. word count), and individual (e.g. knowledge) factors for 16 mandatory TEL modules related to prescribing and therapeutics. METHODS: Data were extracted from the SCRIPT e-Learning platform for first year Foundation trainee (F1) doctors in the Health Education England's West Midland region from 1(st) August 2013 to 5(th) August 2014. Generalised Estimating Equation models were used to examine the relationship between time taken to complete modules, date modules were completed, pre- and post-test scores, and module factors. RESULTS: Over the time period examined, 688 F1 doctors interacted with the 16 compulsory modules 10,255 times. The geometric mean time taken to complete a module was 28.9 min (95% Confidence Interval: 28.4-29.5) and 1,075 (10.5%) modules were completed in less than 10 min. In February and June (prior to F1 progression reviews) peaks occurred in the number of modules completed and troughs in the time taken. Most modules were completed, and the greatest amount of time was spent on the learning on a Sunday. More time was taken by those doctors with greater pre-test scores and those with larger improvements in test scores. CONCLUSIONS: Foundation trainees are exhibiting unintended learning behaviours in this TEL environment, which may be attributed to several factors. These findings can help guide future developments of this TEL programme and the integration of other TEL programmes into curricula by raising awareness of potential behavioural issues that may arise.

Paediatric pharmacokinetics: key considerations.

A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials.

Formulations for children: problems and solutions.

Paediatric formulation design is complex as there is a need to understand the developmental physiological changes that occur during childhood and their impact on the absorption of drugs. Paediatric dose adjustments are usually based on achieving pharmacokinetic or pharmacodynamic profiles equivalent to those achieved in adult populations. However, differences in the way in which children handle adult products or the use of bespoke paediatric formulations can result in unexpected pharmacokinetic drug profiles with altered clinical efficacy. Differences in drug formulations need to be understood by healthcare professionals involved in the prescribing, administration or dispensing of drugs to children such that appropriate advice is given to ensure that therapeutic outcomes are achieved. This issue is not confined to oral medicines but is applicable for all routes of administration encountered in paediatric therapy.

Where to start? The Irish Emergency Department Antimicrobial Discharge (EDAD) study: a multicentre, prospective cohort analysis.

Objectives: To determine the percentage of patients across Ireland who are discharged from the Emergency Department (ED) with an antimicrobial prescription, the indication, classification of infections, and guideline compliance. To identify potential areas for antimicrobial stewardship (AMS) interventions in the ED. Patients and methods: A multicentre, prospective cohort analysis study in EDs across eight hospitals in Ireland. At each site, patients aged 1 month and older who presented to the ED and were discharged directly from the ED were included. A random selection of records of patients discharged from the ED were reviewed until a minimum of 30 records with an infection diagnosis resulting in an antibiotic prescription were obtained per hospital. The number of patient discharges with no antibiotic prescriptions were included to calculate the denominator. The indication, infection classification and guideline compliance data were collected on the 30 prescriptions in the participating hospitals. Results: A total of 2619 patient records were reviewed. Of these, 249 (9.5%) patients were discharged with antimicrobial prescriptions from the ED. Most (158; 63%) were classified as probable bacterial infection, 21 (8%) as probable viral, and 18 (7%) had no documented evidence of infection. Three indications accounted for 73% of antimicrobial prescriptions: skin/soft tissue infection; ear, nose and throat infection; and urinary tract infection. Overall guideline compliance was 64%. Conclusions: Several areas for AMS interventions to optimize antimicrobial prescribing in the ED were identified, including targeted local and national guideline reviews, delayed prescribing, improved point-of-care testing and prescriber and patient education.

Influences on the decision to prescribe or administer anticholinergic drugs to treat death rattle: a focus group study.

BACKGROUND: The evidence supporting pharmacological treatment of death rattle is poor; yet, anticholinergic drugs feature in end-of-life care pathways and guidelines worldwide as a treatment option. AIM: This qualitative arm of a wider study aimed to explore important issues which health-care professionals associated with decision-making to prescribe or administer anticholinergics at the end of life. DESIGN: After purposive sampling, five focus groups were conducted. Discussions were audiotaped and transcribed verbatim. SETTING: Thirty medical and nursing personnel working in inpatient and community settings from two specialist palliative care units in the United Kingdom took part in the study. RESULTS: Thematic analysis of transcripts from audiotapes revealed perceived pressures to prescribe and/or administer anticholinergics from colleagues and carers, and drugs were often prescribed or administered in order to be seen to 'do something', although the benefit in terms of therapeutic response was considered minimal. Familiarity with drug regimens and dosing was often based on personal experience. The monitoring of side effects of anticholinergics at the end of life was recognised as problematic and had little influence on prescribing and administration. There was also an indication that patients and carers in the community were more likely to receive timely verbal preparation and explanation around death rattle than those cared for in an inpatient setting. CONCLUSION: The study raises questions about the routine inclusion of anticholinergic treatment in UK end of life care pathways for the treatment of death rattle.

Effect of monitoring adherence to regular inhaled corticosteroid (ICS) alone or in combination with a long-acting ß2-agonist (LABA) using electronic methods on asthma outcomes: a narrative systematic review.

OBJECTIVES: To evaluate through a systematic review the effectiveness of electronic methods in monitoring adherence to regular inhaled corticosteroids (ICS) alone or in combination with long-acting ß2-agonists (LABAs) and their effect on clinical outcomes. DESIGN: A narrative systematic review. DATA SOURCES: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Web of Science were searched through up to 10 July 2022. ELIGIBILITY CRITERIA: We included peer-reviewed studies of qualitative and quantitative outcomes that compared the effect of electronic methods to routine non-electronic monitoring intervention or placebo among children and adults with asthma on medication adherence rates to regular ICS alone or in combination with LABA, asthma control and asthma exacerbations. DATA EXTRACTION AND SYNTHESIS: Data extraction was performed according to a predetermined sheet specific to the review objectives. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomised controlled trials and the Risk of Bias in Systematic Reviews tool for systematic reviews. Meta-analysis was not possible based on the findings of the scoping search; however, a narrative review was performed to allow for the grouping of results based on asthma inhaler adherence rates, asthma control and exacerbations. RESULTS: Six articles comprising 98 studies published from 1998 to 2022 in the USA, Canada and the UK were included. Compared with the control, electronic monitoring devices (EMDs) showed a 23% adherence improvement, mean difference (MD) of 23%, 95% CI 10.84 to 34.16, p=0.0002. Asthmatic children were 1.5 times more likely to be adherent using EMDs compared with non-EMD users (RR=1.5, 95% CI 1.19 to 1.9) (p<0.001). Mobile devices and text message reminders (MHealth) showed a 12% adherence improvement (MD 12%, 95% CI 6.22 to 18.03) (p<0.0001), alongside a small to medium improvement in asthma control (standardised mean difference (SMD) 0.31, 95% CI 0.17 to 0.44), small improvement in asthma-related quality of life (SMD 0.26) (p=0.007) and variable risk reduction in asthma exacerbations for digital health (risk ratio 0.53, 95% CI 0.32 to 0.91) (p=0.02) compared with EMDs, which showed insignificant differences (risk ratio 0.89, 95% CI 0.45 to 1.75) (p=0.72). Technologies combined yielded variable adherence effects, with an SMD for eHealth of 0.41, 95% CI 0.02 to 0.79, and MD for digital health was 14.66% higher than the control, 95% CI 7.74 to 21.57. Heterogeneity between studies was significant (eHealth I2=98%, digital I2=94%). CONCLUSION: Electronic methods improved adherence to inhaled medications in asthma. EMDs appear to be the most effective technology, followed by mHealth. The adherence improvement was associated with a small clinical improvement. There was inconsistent overlapping of terminology describing electronic methods that require standardisation. Data on the cost-effectiveness of electronic devices and their utilisation in severe asthma are lacking and require further research. PROSPERO REGISTRATION NUMBER: CRD42022303069.

Age and the Residual Risk of Cardiovascular Disease following Low Density Lipoprotein-Cholesterol Exposure.

We believe that there is sufficient evidence from basic science, longitudinal cohort studies and randomised controlled trials which validates the low-density lipoprotein cholesterol (LDL-C) or lipid hypothesis. It is important that we can communicate details of the cardiovascular disease (CVD) risk reduction that the average patient could expect depending on the scale of LDL-C decrease following lipid lowering therapy. It is also essential that residual risk (ResR) of CVD be highlighted. To achieve this aim by using existing trial evidence, we developed mathematical models initially for relative risk reduction (RRR) and absolute risk (AR) reduction and then showed that despite optimising LDL-C levels, a considerable degree of ResR remains that is dependent on AR. Age is significantly associated with AR (odds ratio: 1.02, 95% confidence intervals: 1.01-1.04) as was previously demonstrated by analysing the Whickham study cohort using a logistic regression model (age remaining significant even when all the other significant risk factors such as sex, smoking, systolic blood pressure, diabetes and family history were included in the regression model). A discussion of a paper by Ference et al. provided detailed evidence of the relationship between age and AR, based on lifetime LDL-C exposure. Finally, we discussed non-traditional CVD risk factors that may contribute to ResR based on randomised controlled trials investigating drugs improving inflammation, thrombosis, metabolic and endothelial status.

Healthcare Professionals' Perceptions, Barriers, and Facilitators towards Adopting Computerised Clinical Decision Support Systems in Antimicrobial Stewardship in Jordanian Hospitals.

Understanding healthcare professionals' perceptions towards a computerised decision support system (CDSS) may provide a platform for the determinants of the successful adoption and implementation of CDSS. This cross-sectional study examined healthcare professionals' perceptions, barriers, and facilitators to adopting a CDSS for antibiotic prescribing in Jordanian hospitals. This study was conducted among healthcare professionals in Jordan's two tertiary and teaching hospitals over four weeks (June-July 2021). Data were collected in a paper-based format from senior and junior prescribers and non-prescribers (n = 254) who agreed to complete a questionnaire. The majority (n = 184, 72.4%) were aware that electronic prescribing and electronic health record systems could be used specifically to facilitate antibiotic use and prescribing. The essential facilitator made CDSS available in a portable format (n = 224, 88.2%). While insufficient training to use CDSS was the most significant barrier (n = 175, 68.9%). The female providers showed significantly lower awareness (p = 0.006), and the nurses showed significantly higher awareness (p = 0.041) about using electronic prescribing and electronic health record systems. This study examined healthcare professionals' perceptions of adopting CDSS in antimicrobial stewardship (AMS) and shed light on the perceived barriers and facilitators to adopting CDSS in AMS, reducing antibiotic resistance, and improving patient safety. Furthermore, results would provide a framework for other hospital settings concerned with implementing CDSS in AMS and inform policy decision-makers to react by implementing the CDSS system in Jordan and globally. Future studies should concentrate on establishing policies and guidelines and a framework to examine the adoption of the CDSS for AMS.

Bridging the gap between academia and practice: novel organogram at the Pharmacy Council of India.

Harm with inappropriate and irrational use of medications is a global challenge. The need for and patient access to medicines optimisation services is apparent globally and amplified in India due to multiple reasons. Clinical pharmacists are ideally placed to promote patient safety with medicines use optimisation and other pharmaceutical care services through appropriate legislative, policy, and compensation mechanisms to achieve optimal patient outcomes. The need is for a move at a global level, an enabling organisational structure at Pharmacy Councils and in practice regulations, particularly in countries where clinical roles are still in infancy. This narrative describes the current status and future needs for development of medicines optimisation services across sectors through regulatory and organisational reforms at the Pharmacy Council of India with additional registration, continuing professional development, renewal and licensing requirements for clinical pharmacists to respond to patient and societal needs in India.

What is the evidence that a pharmacy team working in an acute or emergency medicine department improves outcomes for patients: A systematic review.

Pharmacy services within hospitals are changing, with more taking on medication reconciliation activities. This systematic review was conducted to determine the measured impacts of Pharmacy teams working in an acute or emergency medicine department. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered on PROSPERO, National Institute for Health and Care Research, UK registration number: CRD42020187487. The systematic review had two co-primary aims: a reduction in the number of incorrect prescriptions on admission by comparing the medication list from primary care to secondary care, and a reduction in the severity of harm caused by these incorrect prescriptions; chosen to determine the impact of pharmacy-led medication reconciliation services in the emergency and acute medicine setting. Seventeen articles were included. Fifteen were non-randomized controlled trials and two were randomized controlled trials. The number of patients combined for all studies was 7630. No studies included were based within the UK. All studies showed benefits in terms of a reduction in medicine errors and patient harm, compared to control arms. Nine articles were included in a statistical analysis comparing the pharmacy intervention arm with the non-pharmacy control arm, with a Chi2 of 101.10 and I2 value = 92%. However, studies were heterogenous with different outcome measures and many showed evidence of bias. The included studies consistently indicated that pharmacy services based within acute or emergency medicine departments in hospitals were associated with fewer medication errors. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings including out-of-hours working.

Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review.

Background: Multiple drug allergy and multiple drug intolerance syndrome (MDAS/MDIS) labels are an impediment to clinical care and knowledge regarding these conditions is limited. This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco-economics of MDAS and MDIS. Methods: Systematic literature search across 11 databases (01 January 2000-06 November 2020) for MDIS, MDAS and related terminology. Studies were reviewed for quality of evidence and risk of bias by employing Critical Appraisal Skills Programme cohort study checklist. A narrative synthesis approach facilitated by systematic textual descriptions, tabulation and thematic analysis was adopted. Results: There was heterogeneity in terminology and methodology. Few studies applied standard drug allergy diagnostic methods. There is some evidence to suggest that multiple drug hypersensitivity syndrome (MDHS; i.e., confirmed allergies in MDAS) is a distinct clinical entity. Prevalence of MDIS and MDAS labels in unselected & selected populations varied between 2.1%-6.4% & 4.9%-90% and 1.2% & 0%-36% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co-morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non-steroidal anti-inflammatory drugs. No studies relating to clinical impact and pharmaco-economics were found. Conclusion: There is considerable burden of MDAS and MDIS labels. Data needs cautious interpretation as majority of studies described involved unverified labels. Despite this limitation and heterogeneity of studies, there is some evidence to suggest that MDHS is a distinct clinical entity. Well-designed multi-centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.

Infant Escherichia coli urinary tract infection: is it associated with meningitis?

OBJECTIVES: Determine the prevalence of coexisting bacterial meningitis (BM) and sterile cerebrospinal fluid (CSF) with raised white cell count relative to age ('pleocytosis') in the presence of Escherichia coli urinary tract infection (UTI), with the addition of CSF E. coli PCR analysis. DESIGN: Single-centre, retrospective cohort study. SETTING: Tertiary paediatric hospital. PARTICIPANTS: Children aged 8 days to 2 years, with a pure growth of E. coli from urine and a CSF sample taken within 48 hours of a positive urine culture between 1 January 2014 and 30 April 2019. MAIN OUTCOME MEASURE: Prevalence of coexisting E. coli BM with UTI, defined as a pure growth E. coli from urine and a CSF culture with pure growth E. coli and/or positive E. coli PCR. RESULTS: 1903 patients had an E. coli UTI, of which 314 (16%) had a CSF sample taken within 48 hours. No cases of coexisting E. coli BM were identified. There were 71 (23%) cases of pleocytosis, 57 (80%) of these had PCR analysis, all of which were E. coli PCR not detected. Patients aged 1-6 months accounted for 72% of all lumbar punctures (LPs). CONCLUSION: The risk of E. coli UTI and coexisting E. coli BM is low. There is potential to reduce the number of routine LPs in infants with a diagnosis of E. coli UTI with the greatest impact in children up to 6 months of age. CSF E. coli PCR can help further reduce post-test probability of BM in the setting of pleocytosis.

Application of a Physiologically Based Pharmacokinetic Model to Predict Cefazolin and Cefuroxime Disposition in Obese Pregnant Women Undergoing Caesarean Section.

Intravenous (IV) cefuroxime and cefazolin are used prophylactically in caesarean sections (CS). Currently, there are concerns regarding sub-optimal dosing in obese pregnant women compared to lean pregnant women prior to CS. The current study used a physiologically based pharmacokinetic (PBPK) approach to predict cefazolin and cefuroxime pharmacokinetics in obese pregnant women at the time of CS as well as the duration that these drug concentrations remain above a target concentration (2, 4 or 8 µg/mL or µg/g) in plasma or adipose tissue. Cefazolin and cefuroxime PBPK models were first built using clinical data in lean and in obese non-pregnant populations. Models were then used to predict cefazolin and cefuroxime pharmacokinetics data in lean and obese pregnant populations. Both cefazolin and cefuroxime models sufficiently described their total and free levels in the plasma and in the adipose interstitial fluid (ISF) in non-pregnant and pregnant populations. The obese pregnant cefazolin model predicted adipose exposure adequately at different reference time points and indicated that an IV dose of 2000 mg can maintain unbound plasma and adipose ISF concentration above 8 µg/mL for 3.5 h post dose. Predictions indicated that an IV 1500 mg cefuroxime dose can achieve unbound plasma and unbound ISF cefuroxime concentration of ≥8 µg/mL up to 2 h post dose in obese pregnant women. Re-dosing should be considered if CS was not completed within 2 h post cefuroxime administration for both lean or obese pregnant if cefuroxime concentrations of ≥8 µg/mL is required. A clinical study to measure cefuroxime adipose concentration in pregnant and obese pregnant women is warranted.

A qualitative study of prescribing errors among multi-professional prescribers within an e-prescribing system.

Background Computerised Physician Order Entry (CPOE) is considered to enhance the safety of prescribing. However, it can have unintended consequences and new forms of prescribing error have been reported. Objective The aim of this study was to explore the causes and contributing factors associated with prescribing errors reported by multidisciplinary prescribers working within a CPOE system. Main Outcome Measure Multidisciplinary prescribers experience of prescribing errors in an CPOE system. Method This qualitative study was conducted in a hospital with a well-established CPOE system. Semi-structured qualitative interviews were conducted with prescribers from the professions of pharmacy, nursing, and medicine. Interviews analysed using a mixed inductive and deductive approach to develop a framework for the causes of error. Results Twenty-three prescribers were interviewed. Six main themes influencing prescribing were found: the system, the prescriber, the patient, the team, the task of prescribing and the work environment. Prominent issues related to CPOE included, incorrect drug name picking, default auto-population of dosages, alert fatigue and remote prescribing. These interacted within a complex prescribing environment. No substantial differences in the experience of CPOE were found between the professions. Conclusion Medical and non-medical prescribers have similar experiences of prescribing errors when using CPOE, aligned with existing published literature about medical prescribing. Causes of electronic prescribing errors are multifactorial in nature and prescribers describe how factors interact to create the conditions errors. While interventions should focus on direct CPOE issues, such as training and design, socio-technical, and environmental aspects of practice remain important.