Exploring the correlation between lipid packaging in lipoplexes and their transfection efficacy

Whilst there is a large body of evidence looking at the design of cationic liposomes as transfection agents, correlates of formulation to function remain elusive. In this research, we investigate if lipid packaging can give further insights into transfection efficacy. DNA lipoplexes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in combination with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) were prepared by the lipid hydration method. Each of the formulations was prepared by hydration in dH2O or phosphate buffer saline (PBS) to investigate the effect of buffer salts on lipoplex physicochemical characteristics and in vitro transfection. In addition, Langmuir monolayer studies were performed to investigate any possible correlation between lipid packaging and liposome attributes. Using PBS, rather than dH2O, to prepare the lipoplexes increased the size of vesicles in most of formulations and resulted in variation in transfection efficacies. However, one combination of lipids (DSPE:DOTAP) could not form liposomes in PBS, whilst the DSPE:DSTAP combination could not form liposomes in either aqueous media. Monolayer studies demonstrated saturated lipid combinations offered dramatically closer molecular packing compared to the other combinations which could suggest why this lipid combination could not form vesicles. Of the lipoplexes prepared, those formulated with DSTAP showed higher transfection efficacy, however, the effect of buffer on transfection efficiency was formulation dependent. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Reinforcing the security of corporate information resources:a critical review of the role of the acceptable use policy

Increasingly users are seen as the weak link in the chain, when it comes to the security of corporate information. Should the users of computer systems act in any inappropriate or insecure manner, then they may put their employers in danger of financial losses, information degradation or litigation, and themselves in danger of dismissal or prosecution. This is a particularly important concern for knowledge-intensive organisations, such as universities, as the effective conduct of their core teaching and research activities is becoming ever more reliant on the availability, integrity and accuracy of computer-based information resources. One increasingly important mechanism for reducing the occurrence of inappropriate behaviours, and in so doing, protecting corporate information, is through the formulation and application of a formal ‘acceptable use policy (AUP). Whilst the AUP has attracted some academic interest, it has tended to be prescriptive and overly focussed on the role of the Internet, and there is relatively little empirical material that explicitly addresses the purpose, positioning or content of real acceptable use policies. The broad aim of the study, reported in this paper, is to fill this gap in the literature by critically examining the structure and composition of a sample of authentic policies – taken from the higher education sector – rather than simply making general prescriptions about what they ought to contain. There are two important conclusions to be drawn from this study: (1) the primary role of the AUP appears to be as a mechanism for dealing with unacceptable behaviour, rather than proactively promoting desirable and effective security behaviours, and (2) the wide variation found in the coverage and positioning of the reviewed policies is unlikely to be fostering a coherent approach to security management, across the higher education sector.

The information security policy unpacked:a critical study of the content of university policies

Ensuring the security of corporate information, that is increasingly stored, processed and disseminated using information and communications technologies [ICTs], has become an extremely complex and challenging activity. This is a particularly important concern for knowledge-intensive organisations, such as universities, as the effective conduct of their core teaching and research activities is becoming ever more reliant on the availability, integrity and accuracy of computer-based information resources. One increasingly important mechanism for reducing the occurrence of security breaches, and in so doing, protecting corporate information, is through the formulation and application of a formal information security policy (InSPy). Whilst a great deal has now been written about the importance and role of the information security policy, and approaches to its formulation and dissemination, there is relatively little empirical material that explicitly addresses the structure or content of security policies. The broad aim of the study, reported in this paper, is to fill this gap in the literature by critically examining the structure and content of authentic information security policies, rather than simply making general prescriptions about what they ought to contain. Having established the structure and key features of the reviewed policies, the paper critically explores the underlying conceptualisation of information security embedded in the policies. There are two important conclusions to be drawn from this study: (1) the wide diversity of disparate policies and standards in use is unlikely to foster a coherent approach to security management; and (2) the range of specific issues explicitly covered in university policies is surprisingly low, and reflects a highly techno-centric view of information security management.

Estimating the scope for savings in referrals and drug prescription costs in the general Practice units of a UK primary care trust

This paper explores the potential for cost savings in the general Practice units of a Primary Care Trust (PCT) in the UK. We have used Data Envelopment Analysis (DEA) to identify benchmark Practices, which offer the lowest aggregate referral and drugs costs controlling for the number, age, gender, and deprivation level of the patients registered with each Practice. For the remaining, non-benchmark Practices, estimates of the potential for savings on referral and drug costs were obtained. Such savings could be delivered through a combination of the following actions: (i) reducing the levels of referrals and prescriptions without affecting their mix (£15.74 m savings were identified, representing 6.4% of total expenditure); (ii) switching between inpatient and outpatient referrals and/or drug treatment to exploit differences in their unit costs (£10.61 m savings were identified, representing 4.3% of total expenditure); (iii) seeking a different profile of referral and drug unit costs (£11.81 m savings were identified, representing 4.8% of total expenditure). © 2012 Elsevier B.V. All rights reserved.

Extent and nature of unlicensed and off-label medicine use in hospitalised children in Palestine

Objective of the study To determine the extent and nature of unlicensed/off-label prescribing patterns in hospitalised children in Palestine. Setting Four paediatric wards in two public health system hospitals in Palestine [Caritas children’s hospital (Medical and neonatal intensive care units) and Rafidia general hospital (Medical and surgical units)]. Method A prospective survey of drugs administered to infants and children <18 years old was carried out over a five-week period in the four paediatric wards. Main outcome measure Drug-licensing status of all prescriptions was determined according to the Palestinian Registered Product List and the Physician’s Desk Reference. Results Overall, 917 drug prescriptions were administered to 387children. Of all drug prescriptions, 528 (57.5%) were licensed for use in children; 65 (7.1%) were unlicensed; and 324 (35.3%) were used off-label. Of all children, 49.6% received off-label prescriptions, 10.1% received unlicensed medications and 8.2% received both. Seventy-two percent of off-label drugs and 66% of unlicensed drugs were prescribed for children <2 years. Multivariate analysis showed that patients who were admitted to the neonatal intensive care unit and infants aged 0–1 years were most likely to receive a greater number of off-label or unlicensed medications (OR 1.80; 95% CI 1.03–3.59 and OR 1.99; 95% CI 0.88–3.73, respectively). Conclusion The present findings confirmed the elevated prevalence of unlicensed and off-label paediatric drugs use in Palestine and strongly support the need to perform well designed clinical studies in children.

Provision of pharmaceutical care by community pharmacists:a comparison across Europe

Objective To investigate the provision of pharmaceutical care by community pharmacists across Europe and to examine the various factors that could affect its implementation. Methods A questionnaire-based survey of community pharmacies was conducted within 13 European countries. The questionnaire consisted of two sections. The first section focussed on demographic data and services provided in the pharmacy. The second section was a slightly adapted version of the Behavioral Pharmaceutical Care Scale (BPCS) which consists of three main dimensions (direct patient care activities, referral and consultation activities and instrumental activities). Results Response rates ranged from 10–71% between countries. The mean total score achieved by community pharmacists, expressed as a percentage of the total score achievable, ranged from 31.6 (Denmark) to 52.2% (Ireland). Even though different aspects of pharmaceutical care were implemented to different extents across Europe, it was noted that the lowest scores were consistently achieved in the direct patient care dimension (particularly those related to documentation, patient assessment and implementation of therapeutic objectives and monitoring plans) followed by performance evaluation and evaluation of patient satisfaction. Pharmacists who dispensed higher daily numbers of prescriptions in Ireland, Germany and Switzerland had significantly higher total BPCS scores. In addition, pharmacists in England and Ireland who were supported in their place of work by other pharmacists scored significantly higher on referral and consultation and had a higher overall provision of pharmaceutical care. Conclusion The present findings suggest that the provision of pharmaceutical care in community pharmacy is still limited within Europe. Pharmacists were routinely engaged in general activities such as patient record screening but were infrequently involved in patient centred professional activities such as the implementation of therapeutic objectives and monitoring plans, or in self-evaluation of performance.

Medication errors in mental healthcare:a systematic review

Methods: It has been estimated that medication error harms 1-2% of patients admitted to general hospitals. There has been no previous systematic review of the incidence, cause or type of medication error in mental healthcare services. Methods: A systematic literature search for studies that examined the incidence or cause of medication error in one or more stage(s) of the medication-management process in the setting of a community or hospital-based mental healthcare service was undertaken. The results in the context of the design of the study and the denominator used were examined. Results: All studies examined medication management processes, as opposed to outcomes. The reported rate of error was highest in studies that retrospectively examined drug charts, intermediate in those that relied on reporting by pharmacists to identify error and lowest in those that relied on organisational incident reporting systems. Only a few of the errors identified by the studies caused actual harm, mostly because they were detected and remedial action was taken before the patient received the drug. The focus of the research was on inpatients and prescriptions dispensed by mental health pharmacists. Conclusion: Research about medication error in mental healthcare is limited. In particular, very little is known about the incidence of error in non-hospital settings or about the harm caused by it. Evidence is available from other sources that a substantial number of adverse drug events are caused by psychotropic drugs. Some of these are preventable and might probably, therefore, be due to medication error. On the basis of this and features of the organisation of mental healthcare that might predispose to medication error, priorities for future research are suggested.

CP-036 evaluation of outpatient clinic letters for medication errors

Background - It is well recognised that errors are more likely to occur during transitions of care, especially medicines errors. Clinic letters are used as a communication tool during a transition from hospital (outpatient clinics) to primary care (general practitioners). Little is known about medicines errors in clinic letters, as previous studies in this area have focused on medicines errors in inpatient or outpatient prescriptions. Published studies concerning clinic letters largely focus on perceptions of patients or general practitioners in respect to overall quality. Purpose - To investigate medicines errors contained in outpatient clinic letters generated by prescribers within the Neurology Department of a specialist paediatric hospital in the UK.Materials and methods - Single site, retrospective, cross-sectional review of 100 clinic letters generated during March–July 2013 in response to an outpatient consultation. Clinic letters were conveniently selected from the most recent visit of each patient. An evaluation tool with a 10-point scale, where 10 was no error and 0 was significant error, was developed and refined throughout the study to facilitate identification and characterisation of medicines errors. The tool was tested for a relationship between scores and number of medicines errors using a regression analysis.Results - Of 315 items related to neurology mentioned within the letters, 212 items were associated with 602 errors. Common missing information was allergy (97%, n = 97), formulation (60.3%, n = 190), strength/concentration (59%, n = 186) and weight (53%, n = 53). Ninety-nine letters were associated with at least one error. Scores were in range of 4–10 with 42% of letters scored as 7. Statistically significant relationships were observed between scores and number of medicines errors (R2 = 0.4168, p < 0.05) as well as between number of medicines and number of drug-related errors (R2 = 0.9719, p < 0.05). Conclusions - Nearly all clinic letters were associated with medicines errors. The 10-point evaluation tool may be a useful device to categorise clinic letter errors.

Synergistic synthesis of quasi-monocrystal CdS nanoboxes with high-energy facets

Hollow nanostructures with a highly oriented lattice structure and active facets are promising for catalytic applications, while their preparation via traditional approaches contains multiple steps and is time and energy consuming. Here, we demonstrate a new one-step strategy involving two complementary reactions which promote each other; it is capable of producing unique hollow nanoparticles. Specifically, we apply synergic cooperation of cation exchange and chemical etching to attack PbS nanosized cubes (NCs) and produce CdS quasi-monocrystal nanoboxes (QMNBs) which possess the smallest dimensions reported so far, a metastable zinc-blende phase, a large specific surface area, and particularly high-energy {100} facets directly visualized by aberration-corrected scanning transmission electron microscopy. These properties in combination allow the nanoboxes to acquire exceptional photocatalytic activities. As an extension of the approach, we use the same strategy to prepare Co9S8 and Cu7.2S4 single-crystal hollow nanooctahedrons (SCHNOs) successfully. Hence, the synergic reaction synthesis strategy exhibits great potential in engineering unique nanostructures with superior properties.

Medicines optimisation for young people with juvenile arthritis and other long-term conditions:system-level barriers to engagement

To explore the views of pharmacy and rheumatology stakeholders about system-related barriers to medicines optimisation activities with young people with long-term conditions. A three-phase consensus-building study comprising (1) focus groups with community and hospital pharmacists; (2) semi-structured telephone interviews with lay and professional adolescent rheumatology stakeholders and pharmacy policymakers, and (3) multidisciplinary discussion groups with community and hospital pharmacists and rheumatology staff. Qualitative verbatim transcripts from phases 1 and 2 were subjected to framework analysis. Themes from phase 1 underpinned a briefing for phase 2 interviewees. Themes from phases 1 and 2 generated elements of good pharmacy practice and current/future pharmacy roles for ranking in phase 3. Results from phase 3 prioritisation and ranking exercises were captured on self-completion data collection forms, entered into an Excel spreadsheet and subjected to descriptive statistical analysis. Institutional ethical approval was given by Aston University Health and Life Sciences Research Ethics Committee. Four focus groups were conducted with 18 pharmacists across England, Scotland and Wales (7 hospital, 10 community and 1 community/public health). Fifteen stakeholders took part in telephone interviews (3 pharmacist commissioners; 2 pharmacist policymakers; 2 pharmacy staff members (1 community and 1 hospital); 4 rheumatologists; 1 specialist nurse, and 3 lay juvenile arthritis advocates). Twenty-five participants took part in three discussion groups in adolescent rheumatology centres across England and Scotland (9 community pharmacists; 4 hospital pharmacists; 6 rheumatologists; 5 specialist nurses, and 1 physiotherapist). In all phases of the study, system-level issues were acknowledged as barriers to more engagement with young people and families. Community pharmacists in the focus groups reported that opportunities for engaging with young people were low if parents collected prescriptions alone, which was agreed by other stakeholders. Moreover, institutional/company prescription collection policies – an activity largely disallowed for a young person under 16 without an accompanying parent - were identified by hospital and community pharmacists as barriers to open discussion and engagement. Few community pharmacists reported using Medicines Use Review (England/Wales) or Chronic Medication Service (Scotland) as a medicines optimisation activity with young people; many were unsure about consent procedures. Despite these limitations, rheumatology stakeholders ranked highly the potential of pharmacists empowering young people with general health care skills, such as repeat prescription ordering. The pharmacy profession lacks vision for its role in the care of young people with long-term conditions. Pharmacists and rheumatology stakeholders identified system-level barriers to more engagement with young people who take medicines regularly. We acknowledge that the modest number of participants may have had a specific interest and thus bias for the topic, but this underscores their frank admission of the challenges. Professional guidance and policy, practice frameworks and institutional/company policies must promote flexibility for pharmacy staff to recognise and empower young people who are able to give consent and take responsibility for medicines activities. This will increase mutual confidence and trust, and foster pharmacy’s role in teaching general health care skills. In this way, pharmacists will be able to build long-term relationships with young people and families.

Microporous polycaprolactone matrices for drug delivery and tissue engineering:the release behaviour of bioactives having extremes of aqueous solubility

Microporous polycaprolactone (PCL) matrices loaded with hydrophobic steroidal drugs or a hydrophilic drug - pilocarpine hydrochloride - were produced by precipitation casting using solutions of PCL in acetone. The efficiency of steroid incorporation in the final matrix (progesterone (56 %) testosterone (46 %) dexamethasone (80 %)) depended on the nature of the drug initially co-dissolved in the PCL solution. Approximately 90 % w/w of the initial load of progesterone, 85 % testosterone and 50 % dexamethasone was released from the matrices in PBS at 37°C over 8 days. Pilocarpine hydrochloride (PH)-loaded PCL matrices, prepared by dispersion of powder in PCL solution, released 70-90 % of the PH content over 12 days in PBS. Application of the Higuchi model revealed that the kinetics of steroid and PH release were consistent with a Fickian diffusion mechanism with corresponding diffusion coefficients of 5.8 × 10-9 (progesterone), 3.9 × 10 -9 (testosterone), 7.1 × 10-10 (dexamethasone) and 22 × 10-8 cm2/s (pilocarpine hydrochloride). The formulation techniques described are expected to be useful for production of implantable, insertable and topical devices for sustained delivery of a range of bioactive molecules of interest in drug delivery and tissue engineering.

Epidemiology of medication discrepancies upon hospital admission in children - a systematic review

Objectives: NICE/NPSA excluded children under 16 from their guidance concerning medicines reconciliation (MR) upon admission.1 Our aims and objectives of conducting the literature review was to identify the epidemiology of medication discrepancies upon admission, transfer and discharge in children, and if they require MR. Method: Six bibliographical databases (Medline, Embase, CINAHL, International Pharmaceutical Abstracts, Web of Science and Biosis Previews) and selected key words were used to find epidemiological studies on medication discrepancies in children upon hospital admission, transfer and discharge (key words included ‘medication discrepancy’; ‘medication reconciliation’; ‘hospital admission’; ‘hospital discharge’; ‘hospital transfer’); studies where the data for children could be extracted were included. Results: From the 1239 articles found (in May 2011), eight of the articles had extractable paediatric information, (five from Canada, two from USA, one from UK). Five of the studies involved discrepancies on admission, one involved discrepancies on admission and transfer, one involved discrepancies at transfer and one considered discharge. The reference point used to compare against the admission, transfer and the discharge order differed in each of the studies. Four studies used a rating scale to assess the clinical significance of the discrepancies to demonstrate the potential adverse clinical outcome of patients in the absence of clinical intervention. Two studies2 3 used a rating scale that was used in adults.4 A study of paediatric neurosurgical patients found that initial hospital prescriptions for children differed from the preadmission prescriptions in 39% of occasions and 50% of all prescribing variations had the potential to cause moderate or severe discomfort or clinical deterioration.2 A study by Coffey et al in general paediatric admissions in Canada showed 22% of patients experienced at least one discrepancy and 29% of the discrepancies had the potential to cause moderate or severe discomfort or clinical deterioration.3 By comparison an epidemiological study in discrepancies in adults on admission had 38.6% of the discrepancies identified with a potential to cause moderate or severe discomfort or clinical deterioration.4 All the studies involved small samples or specific patient groups such as medically complex patients. However all of the studies demonstrated that discrepancies occurred among paediatric populations during transitions in care settings and mentioned MR as an intervention. Conclusion: The results have shown that discrepancies of medication upon hospital admission, transfer and discharge occur regularly in children. With only one published study in the UK looking at hospital admission in children, and no published articles on the incidence and epidemiology of medication discrepancies upon hospital transfer or discharge further research is required in a wider paediatric population. Further work is also required to define the required interventions to improve practice.