Healthcare professional experiences and attitudes on unlicensed/off-label paediatric prescribing and paediatric clinical trials

To investigate the knowledge and views of a range of healthcare professionals (consultant paediatricians, general practitioners (GPs), community pharmacists and paediatric nurses) regarding the use of unlicensed/off-label medicines in children and the participation of children in clinical trials.

A tale of two analyses: the use of archived qualitative data

This article provides a unique contribution to the debates about archived qualitative data by drawing on two uses of the same data - British Migrants in Spain: the Extent and Nature of Social Integration, 2003-2005 - by Jones (2009) and Oliver and O'Reilly (2010), both of which utilise Bourdieu's concepts analytically and produce broadly similar findings. We argue that whilst the insights and experiences of those researchers directly involved in data collection are important resources for developing contextual knowledge used in data analysis, other kinds of critical distance can also facilitate credible data use. We therefore challenge the assumption that the idiosyncratic relationship between context, reflexivity and interpretation limits the future use of data. Moreover, regardless of the complex genealogy of the data itself, given the number of contingencies shaping the qualitative research process and thus the potential for partial or inaccurate interpretation, contextual familiarity need not be privileged over other aspects of qualitative praxis such as sustained theoretical insight, sociological imagination and methodological rigour. © Sociological Research Online, 1996-2012.

Exploring the experiences of nurses who care for children who have Acute Life Threatening Events (ALTE) in hospital

This thesis presents a program of work designed to explore and describe what the experience of caring for a child who has an Acute Life Threatening Event (ALTE) is like for the nurses. An ALTE may include a cardiac arrest, respiratory arrest or unplanned admission for a ward to the Paediatric Intensive Care unit. Using the MRC framework for the development of complex interventions, this information was then coupled with theory to develop the PREPARE and SUPPORT interventions. Given the wide-ranging and exploratory nature of this research, a pragmatic, mixed design approach was used to address the aims and objectives of the thesis. The mixed design approach included: a systematic literature review; international survey of practice; interviews with nurses and doctors using Interpretative Phenomenological Analysis; development, refinement and evaluation of interventions during a feasibility study. Two studies were identified through the systematic review which aimed to evaluate the effectiveness of debriefing. The studies did not provide evidence to support the use of these interventions within healthcare. The international survey of practice demonstrated hospitals were using interventions to both prepare and support nurses for these events. The preparatory interventions were clinically focused and the majority of the supportive interventions included a debrief. The interventions were not being evaluated for effectiveness. The interviews conducted with nurses and doctors provided insight into what that experience was like for the participants. Using the MRC framework, this evidence was coupled with theory to develop the PREPARE and SUPPORT interventions. A multidisciplinary working party used an iterative process to refine and evaluate the interventions and study procedures were explored through a feasibility study. The pragmatic, mixed design approach demonstrated how the empirical evidence was coupled with theory and clinical expertise to develop interventions for use within the healthcare environment.

Strategic development and physicochemical analysis of oral preparations for unstable drugs

Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.

Researching experiences of cancer:the importance of methodology

This paper draws on contributions to and discussions at a recent MRC HSRC-sponsored workshop 'Researching users' experiences of health care: the case of cancer'. We focus on the methodological and ethical challenges that currently face researchers who use self-report methods to investigate experiences of cancer and cancer care. These challenges relate to: the theoretical and conceptual underpinnings of research; participation rates and participant profiles; data collection methods (the retrospective nature of accounts, description and measurement, and data collection as intervention); social desirability considerations; relationship considerations; the experiences of contributing to research; and the synthesis and presentation of findings. We suggest that methodological research to tackle these challenges should be integrated into substantive research projects to promote the development of a strong knowledge base about experiences of cancer and cancer care.

New drugs for type 2 diabetes mellitus:what is their place in therapy?

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulforylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women. Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagonlike peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on P cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety. In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.

Disowned recollections:denying true experiences undermines belief in occurrence but not judgments of remembering

Recent research findings have illustrated that false memories induced in the laboratory can be dissociated from the beliefs that the events had in fact occurred. In this study we assessed whether this dissociability is a quality peculiar to false memory, or whether it represents a general characteristic of autobiographical memory. To this end we examined whether people can be induced to stop believing in memories for true experiences. Participants observed and performed simple actions, and were later falsely informed that they had not performed some of them-that false memories for these actions had been implanted through the use of fabricated evidence. Before and after receiving this misinformation, participants rated their belief in and memory of performing those actions, other actions that they had also performed, and actions that they had not performed. Whereas the misinformation substantially undermined participants' beliefs in the specific performed actions about which they had been misinformed, it had little effect on their endorsement of remembering those actions. The misinformation thus boosted the proportion of occasions in which participants rated their memories as stronger than their beliefs, and it weakened the correlation between belief and memory ratings. Thus, this study provides the first experimental demonstration of non-believed memories of true experiences. We discuss our findings with reference to the small literature concerning the use of socially-communicated misinformation to undermine event memories, and with reference to the structure of autobiographical memory. © 2013 Elsevier B.V.

Experiences on dynamic simulation software in chemical engineering education

Commercial process simulators are increasing interest in the chemical engineer education. In this paper, the use of commercial dynamic simulation software, D-SPICE® and K-Spice®, for three different chemical engineering courses is described and discussed. The courses cover the following topics: basic chemical engineering, operability and safety analysis and process control. User experiences from both teachers and students are presented. The benefits of dynamic simulation as an additional teaching tool are discussed and summarized. The experiences confirm that commercial dynamic simulators provide realistic training and can be successfully integrated into undergraduate and graduate teaching, laboratory courses and research. © 2012 The Institution of Chemical Engineers.

The design of contact lens based ocular drug delivery systems for single-day use:part (I) structural factors, surrogate ophthalmic dyes and passive diffusion studies

The poor retention and efficacy of instilled drops as a means of delivering drugs to the ophthalmic environment is well-recognised. The potential value of contact lenses as a means of ophthalmic drug delivery, and consequent improvement of pre-corneal retention is one obvious route to the development of a more effective ocular delivery system. Furthermore, the increasing availability and clinical use of daily disposable contact lenses provides the platform for the development of viable single-day use drug delivery devices based on existing materials and lenses. In order to provide a basis for the effective design of such devices, a systematic understanding of the factors affecting the interaction of individual drugs with the lens matrix is required. Because a large number of potential structural variables are involved, it is necessary to achieve some rationalisation of the parameters and physicochemical properties (such as molecular weight, charge, partition coefficients) that influence drug interactions. Ophthalmic dyes and structurally related compounds based on the same core structure were used to investigate these various factors and the way in which they can be used in concert to design effective release systems for structurally different drugs. Initial studies of passive diffusional release form a necessary precursor to the investigation of the features of the ocular environment that over-ride this simple behaviour. Commercially available contact lenses of differing structural classifications were used to study factors affecting the uptake of the surrogate actives and their release under 'passive' conditions. The interaction between active and lens material shows considerable and complex structure dependence, which is not simply related to equilibrium water content. The structure of the polymer matrix itself was found to have the dominant controlling influence on active uptake; hydrophobic interaction with the ophthalmic dye playing a major role. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Pharmacology and the safe prescribing of drugs

Understanding the pharmacological principles and safe use of drugs is just as important in surgical practice as in any other medical specialty. With an ageing population with often multiple comorbidities and medications, as well as an expanding list of new pharmacological treatments, it is important that surgeons understand the implications of therapeutic drugs on their daily practice. The increasing emphasis on high quality and safe patient care demands that doctors are aware of preventable adverse drug reactions (ADRs) and interactions, try to minimize the potential for medication errors, and consider the benefits and harms of medicines in their patients. This chapter examines these aspects from the view of surgical practice and expands on the implications of some of the most common medical conditions and drug classes in the perioperative period. The therapeutic care of surgical patients is obvious in many circumstances – for example, antibacterial prophylaxis, thromboprophylaxis, and postoperative analgesia. However, the careful examination of other drug therapies is often critical not only to the sustained treatment of the associated medical conditions but to the perioperative outcomes of patients undergoing surgery. The benefit–harm balance of many therapies may be fundamentally altered by the stress of an operation in one direction or the other; this is not a decision that should wait until the anaesthetist arrives for a preoperative assessment or one that should be left to junior medical or nursing staff on the ward.

Civil service reform trends in public personnel management: Experiences from the Commonwealth of the Bahamas

This study has explored the potential for implementing a merit-based public personnel system in The Bahamas, a former British colony in The Commonwealth Caribbean. Specifically, the study evaluated the use of merit-based public personnel management practices in areas of recruitment, selection, promotion, training and employee development and performance evaluation. Driving forces and barriers which impact merit system successes and failures as well as strategies for institutionalizing merit system practices are identified. Finally the study attempted to apply the developmental model created by Klingner (1996) to describe the stage of public personnel management in The Bahamas. The data for the study was collected through in-depth interviews with expert observers. ^

The choice not to use computers: A case study of community college faculty who do not use computers in teaching

The primary purpose of this investigation is to study the motives of community college faculty who decide not to use computers in teaching. In spite of the fact that many of the environmental blocks that would otherwise inhibit the use of the computers have been eliminated at many institutions, many faculty do not use a computer beyond its word-processing function. For the purpose of the study non-adoption of computers in teaching is defined as not using computers for more than word-processing. ^ The issues in the literature focus on resistance and assume a pro-innovation and pro-adoption bias. Previous research on the questions is primarily surveys with narrowly focused assumptions. This qualitative research directly asks the participants about their feelings, beliefs, attitudes, experiences, and behaviors in regard to computers in teaching. Through the interview process a number of other correlated issues emerge. ^ The investigation was conducted at Miami-Dade Community College, a large urban multicampus institution, in Miami-Dade, Florida. It was conducted through a series of in-depth phenomenological interviews. There were nine interviews; eight within the profile; two were pilots; and one was an extreme opposite of the profile. Each participant was interviewed three times for about 45 minutes. ^ The results indicate that the computer conflicts with the participants' values in regard to their teaching and their beliefs in regard to the nature of knowledge, learning, and the relationship that they wish to maintain with students. Computers require significant changes in the values, beliefs, and consequent behaviors. These are changes that the participants are not willing to make without overwhelming evidence that they are worth the sacrifice. For the participants, this worth is only definable as it positively improves learning. For even the experts the evidence is not there. Unlike the innovator, the high end computer user, these participants are not willing to adopt the computer on faith. ^

A case study of the Ellison model's use of mentoring as an approach toward inclusive community building

The Ellison Executive Mentoring Inclusive Community Building (ICB) Model is a paradigm for initiating and implementing projects utilizing executives and professionals from a variety of fields and industries, university students, and pre-college students. The model emphasizes adherence to ethical values and promotes inclusiveness in community development. It is a hierarchical model in which actors in each succeeding level of operation serve as mentors to the next. Through a three-step process—content, process, and product—participants must be trained with this mentoring and apprenticeship paradigm in conflict resolution, and they receive sensitivity and diversity training through an interactive and dramatic exposition. ^ The content phase introduces participants to the model's philosophy, ethics, values and methods of operation. The process used to teach and reinforce its precepts is the mentoring and apprenticeship activities and projects in which the participants engage and whose end product demonstrates their knowledge and understanding of the model's concepts. This study sought to ascertain from the participants' perspectives whether the model's mentoring approach is an effective means of fostering inclusiveness, based upon their own experiences in using it. The research utilized a qualitative approach and included data from field observations, individual and group interviews, and written accounts of participants' attitudes. ^ Participants complete ICB projects utilizing The Ellison Model as a method of development and implementation. They generally perceive that the model is a viable tool for dealing with diversity issues whether at work, at school, or at home. The projects are also instructional in that whether participants are mentored or serve as apprentices, they gain useful skills and knowledge about their careers. Since the model is relatively new, there is ample room for research in a variety of areas including organizational studies to determine its effectiveness in combating problems related to various kinds of discrimination. ^

Alcohol use and sexual victimization among Hispanic college women

Sexual victimization of young women typically occurs within a context of alcohol use, such that women are more likely to be victimized on days on which they consume alcohol compared to days on which no alcohol is consumed. Additionally, most research on sexual victimization of women has focused on forced sexual acts; consequently, little is known about forms sexual victimization that college women typically experience, such as brief (e.g., unwanted touching) or verbally coerced experiences (e.g., doing sexual things to prevent a partner from leaving). Finally, there is a need for more research on the processes underlying college women's drinking and the specific mechanisms through which drinking increases risk for sexual victimization. This dissertation sought to replicate recent findings of a temporal association between alcohol use and sexual victimization, and to investigate whether or not binge use increased risk for victimization, within a sample of young Hispanic college women, using repeated-measures logistic regression. This study also aimed to identify and explore typologies of victimization experiences in order to better understand types of sexual victimization common among young college women. Finally, the validity of a model of alcohol use and sexual victimization was investigated using structural equation modeling techniques. The results confirmed and extended previous research by demonstrating an increase in the conditional probability of sexual victimization on days of alcohol consumption compared with days of no alcohol consumption, and on days of binge alcohol consumption compared with days of moderate alcohol consumption. Sexual victimization experiences reported in this study were diverse, and cluster analysis was used to identify and explore specific typologies of victimization experiences, including intimate relationship victimization, brief victimization with stranger, prolonged victimization with acquaintance, and workplace victimization. The results from structural equation modeling (SEM) analyses were complex and helped to illuminate the relationships between reasons for drinking, alcohol use, childhood sexual abuse, sexual victimization, psychopathology, and acculturation-related factors among Hispanic college women. These findings have implications for the design of university-based prevention and intervention efforts aimed at reducing rates of alcohol-related sexual victimization within Hispanic populations.