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Context: Treatment burden, the burden associated with the treatment and management of chronic illness, has not yet been well articulated., Objective: Using Rodgers' (1989, Journal of Advanced Nursing, 14, 330-335) method of concept analysis, this review describes the ways in which treatment burden has been conceptualized to define the concept and to develop a framework for understanding its attributes, antecedents and consequences., Methods: Leading databases were searched electronically between the years 2002 and 2011. To ensure the review focused on actual observations of the concept of interest, articles that did not measure treatment burden (either qualitatively or quantitatively) were excluded. An inductive approach was used to identify themes related to the concept of treatment burden., Main Results: Thirty articles, identified from 1557 abstracts, were included in the review. The attributes of treatment burden include burden as a dynamic process, as a multidimensional concept, and comprising of both subjective and objective elements. Prominent predisposing factors (antecedents) include the person's age and gender, their family circumstances, possible comorbidity, high use of medications, characteristics of treatment and their relationship with their health-care provider. The most dominant consequences are poor health and well-being, non-adherence to treatment, ineffective resource use and burden on significant others. Furthermore, many of these consequences can also become antecedents, reflecting the cyclic and dynamic nature of treatment burden., Conclusion: The findings underscore the need for researchers and health-care professionals to engage in collaborative discussions and make cooperative efforts to help alleviate treatment burden and tailor treatment regimens to the realities of people's daily lives., (© 2013 Blackwell Publishing Ltd.)

In successful community pharmacy business enterprises suitably responsive actions to meet ever-increasing change require capable pharmacy managers who readily learn and adapt. Capability as a concept is generally understood to be the ability of a manager to identify and act to solve unfamiliar problems in unfamiliar situations. Capability is characterized by adaptability and flexibility. However, different understandings of the concept 'capability' and what it means to be 'capable' are indirect and incomplete. This paper aims to clarify current theories regarding the concept of 'capability' at the level of the individual, and through this to make more explicit what is known about the phenomenon, but more particularly, how we know what we know. The analysis includes the concept of 'competence' because explanations of capability include competence, and the two concepts are not clearly separated in the literature. By probing the epistemological origins of current theory concerning both concepts, the limiting taken for granted assumptions are revealed. Assumptions about context and time, and the psychological theory through which individuals are assumed to perceive, know and learn, are illuminated. The analysis, in connection with the literature, shows how the interpretive philosophic research approach may reveal a different and useful theoretical perspective for explaining capability as a dynamic performance. It is suggested that such a perspective may narrow the gap between the theory of capability and its practice. The interpretive perspective holds potential to reveal how capability, as performed by successful community pharmacy managers, might be further researched and strengthened. This paper supports the challenging suggestion that pharmacy social research needs to rebalance the dominance of purely empirical research by exploring interpretive methodologies to better understand human actions and relations in the context of pharmacy., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Background: Pregabalin is a treatment option for patients with persistent neuropathic pain. Its use has been associated with changes in mood and the development of depression and/or suicidal ideation., Objective: Case presentations were reviewed of five patients reporting changes in mood, depression and suicidal ideation from the first 50 (approximately) patients commenced on pregabalin at the clinic., Discussion: Although these patients had a history of depression, their mood had been stable before commencing pregabalin. Soon after commencement they reported changes in mood, and development of depression and/or suicidal ideation, which improved with dose reduction or cessation of pregabalin. Ultimately, all five patients ceased pregabalin treatment. Suicidal ideation is a recognised adverse effect of pregabalin. Patients should be warned of and monitored for deterioration in mood.

Objective: To explore the attributes of pharmacy choice for people with chronic conditions., Methods: Semi-structured interviews were conducted between May and October 2012, across four regions in three Australian states. Purposive sampling was used to recruit participants with chronic conditions and unpaid carers. Interviews were analysed via the constant comparison method., Key Findings: Ninety-seven interviews were conducted. The majority of participants were regular patrons of one pharmacy and five attributes influenced this choice: patient-centred care, convenience, price, personal trait or preference and service/medication need. Patient-centred care, such as providing individualised medication counselling, continuity of care, development of relationships and respectful advice, emerged as an important attribute. There was minimal discussion as to choosing a pharmacy based on the provision of professional services, underscoring the limited consumer knowledge of such services and related standards of care., Conclusion: Patient-centred care is an important attribute of quality care as perceived by people who are regular community pharmacy users. These findings highlight the need for pharmacy staff to implement a patient-centred approach to care, thus meeting the perceived needs of their customers. A greater effort is also necessary to raise the profile of pharmacy as a healthcare destination., (© 2013 Royal Pharmaceutical Society.)

Objectives: To explore pharmacy students' ethical behaviour and care towards patients in relation to the provision of emergency hormonal contraception (EHC)., Methods: Three hundred and forty-seven pharmacy students were presented a hypothetical scenario involving refusal of EHC, based on religious or moral grounds, and asked to write responses as to how the patient should be managed; 270 (77.8%) responded., Key Findings: Of all respondents, 90.4% referred the patient to another health professional to facilitate continuity of care, with referrals increasing as students progressed through the programme. Religion had no influence on referral, while female gender was related to increased referral., Conclusions: Gender difference, if continued into practice, has the potential to negatively impact on patient care., (© 2013 Royal Pharmaceutical Society.)

Objective: To investigate community pharmacists' proposed actions in hypothetical medical emergency situations in South-East Queensland, Australia., Method: A survey was posted to 151 Gold Coast and Toowoomba community pharmacies in October 2009. Pharmacists were asked to document their opinions regarding the pharmacist's role in medical emergencies and to respond to statements associated with two hypothetical medical emergency situations: an anaphylaxis and an asthma attack., Key Findings: Forty-five pharmacists responded to the survey (29.8%). In response to a hypothetical situation involving an asthma attack, 41 pharmacists (91.1%) agreed that they would assist the asthmatic person to administer salbutamol through a spacer, with 28 pharmacists (62.2%) confident in treating an asthma attack in the pharmacy. In comparison, only 21 pharmacists (21/38; 55.3%) agreed to administer an adrenaline auto-injector (Epi-Pen) for a child experiencing an anaphylaxis, with nine respondents (9/38; 23.7%) indicating that they would ask the mother for directions in a situation where they were unsure how to administer it. There were comments questioning whether indemnity insurance covers pharmacists for medicine administration, and 12 pharmacists (12/38; 31.6%) indicated that if they were unsure about insurance cover they would ask the mother to administer the adrenaline., Conclusion: Pharmacists' responses to administering medications in hypothetical medical emergencies were variable. The cause of this variation is multi-factorial and likely to include familiarity with the medication, its safety profile and uncertainty about the pharmacist's role and responsibilities in these situations. Further clarification, training and guidelines are needed in order to address this., (© 2012 The Authors. IJPP © 2012 Royal Pharmaceutical Society.)

Transient myeloproliferative disorder (TMD) can be found in well or ill newborns with Down syndrome. Although it is a relatively harmless process for most, in some children, TMD can present as a life-threatening state requiring critical care. As the disease is seemingly uncommon, some providers may lack a sense of urgency in the dissemination of TMD awareness; however, one can never know on whose door this patient may knock tomorrow. Advanced practice professionals should be prepared for the TMD patient that may present without warning. The goals of this article are to discuss common presentations, diagnosis, and management; and to bring attention to this often de-emphasized disease.

Objectives: To provide preliminary evidence regarding the presence, identity and level of microbial contamination of metered-dose inhalers sourced from the community. To correlate the level of microbial colonisation to the visible presence of debris on the interior and exterior surface of the device mouthpiece., Methods: In this exploratory study, 45 post-use de-identified pressurised metered-dose inhalers were collected from the South-East Queensland Australian community. Prior to swabbing, the presence of visible debris on the internal and external surfaces of the mouthpiece was recorded for each device. Swabs taken from external and inner surfaces of the mouthpiece of each device were streaked onto standard growth media for colony counts. Individual colonies were selected and enriched then streaked onto a range of differential and chromogenic media for differential identification., Key Findings: A total of 36 post-use pressurised metered dose inhalers (80%) were shown to be colonised by microbes relative to unused devices (P=0.01). Devices were primarily colonised by common respiratory flora, including Staphylococcus, Streptococcus and Haemophilus species. Of greatest concern was the positive identification of methicillin-resistant Staphylococcus aureus (18%) and extended-spectrum β-lactamase-producing Enterobacteriaceae (7%), Pseudomonas aerugonisa (2%) and Candida species (9%). The level of internal microbial contamination appeared to correlate to the presence of visible debris on the inside of the inhaler mouthpiece (P=0.06) but not external debris (P=0.59) while external contamination was not associated with internal (P=0.99) or external debris (P=0.63)., Conclusions: These preliminary data suggest that pressurised metered dose inhalers are potential reservoirs for bacteria. While this study was not aimed at determining the impact that contaminated pressurised metered-dose inhalers may have on the user, future research is being conducted to address the implications of these findings and the consequences they may have for the population of users., (© 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.)

Objective: To obtain community pharmacists' opinions of their role in administering Pharmacy (S2) and Pharmacist Only (S3) Medicines in a medical emergency. These medicines can only be sold in a pharmacy and are not available for self-selection by patients. Whilst qualified pharmacy assistants can supply S2 medicines, pharmacists must be directly involved in the supply of S3 medicines., Setting: Community pharmacies in South East Queensland, Australia., Method: A survey of 151 Gold Coast and Toowoomba community pharmacists was conducted during October 2009., Main Outcome Measures: Pharmacists were asked their opinions as to whether the administration of S2 and S3 medicines should fall within their scope of practice, whether they had administered S2 and S3 medicines in a medical emergency in the past and if clarification of this role was required., Results: The study achieved a 30% (n = 45) response rate and demonstrated similar results regarding whether pharmacists should administer salbutamol (22/44), adrenaline (23/42), glyceryl trinitrate (22/43) and aspirin (18/36) in a medical emergency. The majority (36/43) believed that role clarification was required. Pharmacists were more likely to administer an S3 medicine in a medical emergency when they considered potential outcomes first, had no easy access to a doctor and the patient could not administer the medicine they carried with them themselves (40/45)., Conclusion: Community pharmacists have direct access to S2 and S3 medicines that could be required in the management of a variety of medical emergencies. This study demonstrates that some pharmacists have administered S2 and S3 medicines in an emergency situation. However, there are currently no clear guidelines for pharmacists when faced with a medical emergency other than to act within their professional competence. To promote patient safety through the appropriate use of S2 and S3 medicines in the event of a medical emergency, additional training of pharmacists on the administration of these readily accessible medicines is needed. Clarification of the role of pharmacists in an emergency situation is required.

Cardiac fibroblasts play a key role in fibrosis development in response to stress and injury. Angiotensin II (ANG II) is a major profibrotic activator whose downstream effects (such as phospholipase Cβ activation, cell proliferation, and extracellular matrix secretion) are mainly mediated via G(q)-coupled AT(1) receptors. Regulators of G protein signaling (RGS), which accelerate termination of G protein signaling, are expressed in the myocardium. Among them, RGS2 has emerged as an important player in modulating G(q)-mediated hypertrophic remodeling in cardiac myocytes. To date, no information is available on RGS in cardiac fibroblasts. We tested the hypothesis that RGS2 is an important regulator of ANG II-induced signaling and function in ventricular fibroblasts. Using an in vitro model of fibroblast activation, we have demonstrated expression of several RGS isoforms, among which only RGS2 was transiently upregulated after short-term ANG II stimulation. Similar results were obtained in fibroblasts isolated from rat hearts after in vivo ANG II infusion via minipumps for 1 day. In contrast, prolonged ANG II stimulation (3-14 days) markedly downregulated RGS2 in vivo. To delineate the functional effects of RGS expression changes, we used gain- and loss-of-function approaches. Adenovirally infected RGS2 had a negative regulatory effect on ANG II-induced phospholipase Cβ activity, cell proliferation, and total collagen production, whereas RNA interference of endogenous RGS2 had opposite effects, despite the presence of several other RGS. Together, these data suggest that RGS2 is a functionally important negative regulator of ANG II-induced cardiac fibroblast responses that may play a role in ANG II-induced fibrosis development.

The Australian generic medicine substitution landscape has changed over recent years. The latest changes include the introduction of incentive payments by the government to community pharmacists to dispense generic medicines instead of more expensive brand equivalents. Generic dispensing imposes additional time constraints on pharmacists in terms of patient counselling requirements. Substitution also involves an increased need for professional judgment as pharmacists need to ensure the substitution is appropriate for the patient. It is therefore important that pharmacists develop processes and procedures that enable staff to follow good practice standards and guidelines during the dispensing of generic medicines in order to minimise patient risk.

Objective: To explore the usefulness and implementation of practice standards in community pharmacy practice regarding contemporary core services., Setting: Community pharmacies in South East Queensland, Australia., Method: During August and September 2006 semi-structured interviews with community pharmacists explored practice processes and procedures and the utilisation of endorsed standards and guidelines. Thematic content analysis of the interviews, inductive analysis and continual comparison of categories and concepts enabled common and distinct themes to be clarified., Main Outcome Measure: Usefulness and integration of practice standards in the provision of core pharmacy services, utilisation of support staff, record keeping and overall risk management processes in community pharmacy., Results: Seventeen community pharmacists participated, representing a wide range of demographics, experience and pharmacy types. Staff utilisation and record keeping practices were analysed as well as two core services, namely: (1) the supply of over-the-counter medicines, and (2) the dispensing of prescriptions. The procedures followed concerning the supply of over-the-counter medicines varied. The majority of participants did not regard this as a pharmacist's immediate role, but rather relied on support staff to identify when the supply required a pharmacist's intervention. Whilst all participants involved dispensary assistants in the dispensing process, the delegation of procedures differed. Most participants did not clearly differentiate between pharmacists' and dispensary assistants' activities. Dispensing processes and the involvement of pharmacists in the provision of patient advice varied. Pharmacist intervention record keeping was uncommon and records of 'near misses' were not routinely kept by any of the participants., Conclusion: A lack of integration of practice standards indicated a need to review the standards for relevance. Additionally, pharmacists need to re-evaluate workflow models and the delegation of tasks in the light of new roles and responsibilities.

Objectives: To determine the prevalence of inappropriate prescribing, defined by applying modified Beers' criteria, and to examine the influence of the Pharmaceutical Benefits Scheme (PBS), Australia's national scheme for subsidising medicines, on inappropriate prescribing., Methods: Cross-sectional survey of nursing home records, including 7-days data from medication charts., Setting: Fiveteen randomly selected nursing homes (998 residents) in Southeast Queensland and Northern New South Wales, Australia., Main Outcome Measures: The prevalence of inappropriate prescribing as defined by modified Beers' criteria and its correlation with PBS restrictions., Results: 18.5% of residents were ordered one or more inappropriate medications, and 1.5% of residents were ordered two or more. The level of PBS restriction and the percentage of residents ordered a medication were highly correlated (p = -0.87, P < 0.001). Medications in Beers' criteria that were not listed (subsidised) on the PBS were not ordered for any resident. PBS medicines with subsidies restricted to certain populations or indications were ordered for 0% to 0.1% of residents. Dextropropoxyphene, diazepam, amitriptyline and methyldopa were the only medications in Beers' criteria prescribed to more than 0.5% of residents. Dextropropoxyphene was only subsidised for war veterans, with a caution warning of its potential to cause drug dependence, while diazepam, amitriptyline and methyldopa were listed on the PBS without any subsidy restrictions., Conclusion: Increases in the level of PBS restriction were associated with decreases in the prevalence of inappropriate prescribing, The targeting of drug subsidies to reduce inappropriate prescribing warrants further investigation.

Alzheimer's Disease (AD) is defined histopathologically by extracellular beta-amyloid (Abeta) fibrils plus intraneuronal tau filaments. Studies of transgenic mice and cultured cells indicate that AD is caused by a pathological cascade in which Abeta lies upstream of tau, but the steps that connect Abeta to tau have remained undefined. We demonstrate that tau confers acute hypersensitivity of microtubules to prefibrillar, extracellular Abeta in nonneuronal cells that express transfected tau and in cultured neurons that express endogenous tau. Prefibrillar Abeta42 was active at submicromolar concentrations, several-fold below those required for equivalent effects of prefibrillar Abeta40, and microtubules were insensitive to fibrillar Abeta. The active region of tau was localized to an N-terminal domain that does not bind microtubules and is not part of the region of tau that assembles into filaments. These results suggest that a seminal cell biological event in AD pathogenesis is acute, tau-dependent loss of microtubule integrity caused by exposure of neurons to readily diffusible Abeta.

Background: Previous work from our center has suggested a correlation between increased donor-derived Vdelta1+ gammadelta T cells and long-term relapse-free survival following bone marrow transplantation for leukemia. Questions remain, however, as to whether this observation can be explained by a gammadelta T cell-based immune response against primary leukemia., Methods: We examined gammadelta T cell receptor (TCR) phenotype, cell proliferation, and cytolytic activity following culture with irradiated primary leukemia blasts from a haploidentical first-degree relative. Subsequently, we also studied the gammadelta TCR phenotype and complimentarity determining region 3 (CDR3) cDNA sequences from 17 newly diagnosed leukemia patients., Results: In 17/28 (61%) of in vitro cultures, gammadelta T cells proliferated in culture with primary blasts. Vdelta1+ T cells were proportionally increased in all cultures and were the predominant cell population in 6/17. In the 7 cultures where cytotoxicity could be assessed, 6 (86%) showed some degree of cytotoxicity to the primary leukemia. Vdelta1+ T cells were also the predominant gammadelta T cell subtype in pre-treatment leukemia patients principally due to loss of Vdelta2+ T cells rather than expansion of Vdelta1+ cells. The Vdelta1 CDR3-region cDNA sequence from these patients revealed exclusive use of the Jdelta1 constant region and sequence conservation in 4/11 patients., Conclusions: gammadelta T cells exhibit an in vitro response to primary leukemia blasts that is manifested by proliferation, an increased proportion of Vdelta1+ T cells, and cytotoxicity to the primary leukemia blasts. The Vdelta1+ T cell population is also predominant in newly diagnosed leukemia patients likely due to a loss of circulating Vdelta2+ T cells. A small proportion of newly diagnosed patients showed Vdelta1 CDR3 region similarity. These findings suggest a role for gammadelta T cells in the immune response to leukemia.

Alzheimer's disease (AD) is a progressive disease of aging primarily characterized at the behavioral level by symptoms of memory loss. The pathological hallmarks of AD are extracellular plaques and intracellular neurofibrillary tangles that are composed of filamentous polymers of beta-amyloid (Abeta) and tau, respectively. Aggregates of filaments are not unique to AD--fibrous polymers are the pathological signatures of many diseases of aging such as Huntington's disease and Parkinson's disease. Whether Abeta or tau filaments cause AD is still an open question, as a wide variety of proteins and pathways have been implicated in the initiation and advancement of the disease--processes such as apoptosis, oxidative stress, and protein degradation. That polymers are the prevalent species observed in aging disorders suggests that this morphology of aggregation represents a significant physiological role. As a consequence of an independent insult or aging itself, the filament shifts from a physiological role to one with pathological implications. The relative importance of Abeta filaments versus tau filaments has also been a focus of significant debate within the research community. Although genetic evidence indicates that Abeta filaments are an integral component in AD, only tau pathology has been found to correlate with symptom presentation in patients. Not only do tau filaments greatly contribute to the systematic loss of neurons and the pathological presentation of memory loss, but they may represent a physiological process whose regulation may be controlled.