A critical synthesis of the role of the pharmacist in oral healthcare and management of medication-related osteonecrosis of the jaw.

OBJECTIVE: To consolidate extant published evidence in relation to the potential of integrating oral healthcare for patients at risk of developing medication-related osteonecrosis of the jaw (MRONJ). METHODS: A critical synthesis and consolidation of five publications was undertaken. As a mechanism of situating the extant work within the context of primary healthcare provision, the Rainbow Model of Integrated Care was applied as a theoretical lens through which the conceptual findings could be collectively applied to practice. RESULTS: The critical synthesis revealed a thematic emergence relating to both formative and normative integration. The most salient of these were the identification of limited shared clinical records, and disconnection of oral healthcare provision from patients' general medical care. The three levels of the Rainbow Model of Integrated Care reflected a series of issues for address. CONCLUSION: In the context of collaborative, multi-disciplinary working for patients at risk of development of MRONJ, pharmacists are a professional group which this research reveals to be an underutilised resource. Reduction of oral health inequality at all levels of patient care is a key priority and this research highlights areas for address in relation to requirements for interprofessional education, optimal communication and policies reflective and facilitative of these.

Materials library collections as tools for interdisciplinary research.

This paper examines how materials libraries are used as tools for interdisciplinary collaboration in 3 research projects that inhabit a disciplinary triangle between materials research, design and user needs: PhysFeel, which explores how materials collections can be used in psychological therapies; Light.Touch.Matters, a design-led project to develop new smart materials; and Hands of X, which uses materials collections to develop a bespoke prosthetics service. The paper analyses and contrasts these case studies to better understand the affordances and limitations of materials collections when used as research, translational and design tools. We conclude that in collaborations between materials researchers, designers and end users, tensions arise as a result of the primacy that each partner gives to creativity, the development of new knowledge and to solving societal problems. The use of a materials library addresses many of these issues but is not a panacea for all the problems associated with interdisciplinary working.

A qualitative synthesis of pharmacist, other health professional and lay perspectives on the role of community pharmacy in facilitating care for people with long-term conditions.

BACKGROUND: There is increasing interest in an enhanced role for community pharmacy (CP) in facilitating care for people with long-term conditions (LTCs). It is important to understand the perspectives of stakeholders in order to identify key issues that may impact on future development of the role and related services. OBJECTIVES: Explore pharmacist, other health professional and lay perspectives on the role of CP in facilitating care for people with LTCs. METHODS: Synthesis of qualitative research from UK based studies published between 2007 and January 2017 using a meta-ethnographic interpretative approach. RESULTS: Variation in the conceptualisation of the role of CP in facilitating the care of people with LTCs was apparent across and within lay and health professional accounts. Despite evidence of positive attitudes and a culture amenable to change, there remains a lack of clarity about the existing and potential role of the pharmacist in this area. A theoretical framework is proposed that highlights the dynamic nature of the process involved in the development of lay and health professionals' understanding of the role and engagement with services. Influences on this process include experience and perceived need, service operationalisation, and ongoing developments within wider healthcare policy and commercial environments. Perceived integration with existing professional and peer support structures, views about traditional medical hierarchies and concerns about potential duplication are important influences on the value attributed to the role of CP and the services provided. CONCLUSIONS: There is acknowledged potential for an extended role in CP to support the care of people with LTCs. To ensure the likelihood of successful engagement with patients and positive health outcomes, developments should acknowledge influences within and beyond the CP setting. Potential overlap with other healthcare services should be explicitly addressed, ensuring this is framed and delivered as valued reinforcement with clearly defined boundaries of responsibility.

Stakeholders' views of recurrent sore throat, tonsillitis and their management: a qualitative interview study for the NAtional Trial of Tonsillectomy IN Adults (NATTINA Part 1).

OBJECTIVES: To determine the impact of recurrent sore throats and tonsillitis in adults and stakeholder views of treatment pathways. DESIGN: Qualitative semistructured interview design reporting novel data from a feasibility study for a UK national trial of tonsillectomy in adults. SETTING: Nine study sites linked to ear, nose and throat departments in National Health Service hospitals located across the United Kingdom. PARTICIPANTS: Fifteen patients, 11 general practitioners and 22 ear, nose and throat staff consented to in-depth interviews, which were analysed using a framework analysis approach. MAIN OUTCOME MEASURES: Views of stakeholder groups. RESULTS: Recurrent sore throats were reported to severely impact patients' family, work and social life. Ear, nose and throat staff stated that patients faced increasing barriers to secondary care service access. General practitioners were under pressure to reduce 'limited clinical value' surgical procedures. CONCLUSIONS: The findings from this study suggest that there is a disconnect between the attitudes of the stakeholders and the reality of recurrent sore throat, tonsillectomy procedures and service provision. More evidence for the role of tonsillectomy is needed from randomised controlled trials to determine whether it should continue to be ranked as a procedure of limited clinical effectiveness.

'Thinking that somebody's going to delay [a tonsillectomy] for one to two years is quite horrifying really': a qualitative feasibility study for the NAtional Trial of Tonsillectomy IN Adults (NATTINA Part 2).

OBJECTIVES: Level one evidence on the value of adult tonsillectomy versus non-surgical management remains scarce. Before embarking on a costly national randomised controlled trial, it is essential to establish its feasibility. DESIGN: Feasibility study with in-depth qualitative and cognitive interviews. SETTING: ENT staff and patients were recruited from nine hospital centres across England and Scotland. PARTICIPANTS: Patients who were referred for tonsillectomy (n = 15), a convenience sample of general practitioners (n = 11) and ear, nose and throat staff (n = 22). MAIN OUTCOME MEASURES: To ascertain whether ear, nose and throat staff would be willing to randomise patients to the treatment arms. To assess general practitioners' willingness to refer patients to the NAtional Trial of Tonsillectomy IN Adults (NATTINA) centres. To assess patients' willingness to be randomised and the acceptability of the deferred surgery treatment arm. To ascertain whether the study could progress to the pilot trial stage. RESULTS: Ear, nose and throat staff and general practitioners were willing to randomise patients to the proposed NATTINA. Not all ENT staff were in equipoise concerning the treatment pathways. Patients were reluctant to be randomised into the deferred surgery group if they had already waited a substantial time before being referred. CONCLUSIONS: Findings suggest that the NATTINA may not be feasible. Proposed methods could not be realistically assessed without a pilot trial. Due to the importance of the question, as evidenced by NATTINA clinicians, and strong support from ENT staff, the pilot trial proceeded, with modifications.

Report from the kick-off meeting of the Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN).

A major obstacle of evidence-based clinical decision making is the use of nonstandardized, partly untested outcome measurement instruments. Core Outcome Sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcomes and outcome measurement instruments in clinical trials, in order to pool results of trials or to allow indirect comparison between interventions. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The international, multidisciplinary Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN) aims to develop and implement COSs in dermatology, thus making trial evidence comparable and, herewith, more useful for clinical decision making. The inaugural meeting of CSG-COUSIN was held on 17-18 March 2015 in Dresden, Germany, as the exclusive theme of the Annual Cochrane Skin Group Meeting. In total, 29 individuals representing a broad mix of different stakeholder groups, professions, skills and perspectives attended. This report provides a description of existing COS initiatives in dermatology, highlights current methodological challenges in COS development, and presents the concept, aims and structure of CSG-COUSIN.

The epidemiology of hospitalised acute kidney injury not requiring dialysis in England from 1998 to 2013: retrospective analysis of hospital episode statistics.

AIMS: Epidemiology studies of acute kidney injury (AKI) have focused on cases requiring dialysis but those not requiring dialysis represent the majority. To address this gap, we interrogated hospital episode statistics (HES) to investigate population trends in temporal epidemiology of AKI not requiring dialysis between 1998 and 2013. METHODOLOGY: In this retrospective observational study of HES data covering the entire English National Health Service, we identified 1,136,167 AKI events, not requiring dialysis, diagnosed between 1998 and 2013. We explored the effect of age, gender, ethnicity, Charlson's comorbidity score (CCS), method of admission, diagnosis period and AKI in diagnosis codes on temporal changes in the incidence and case-fatality of AKI with specific examination of its predictors. RESULT: The incidence of AKI increased from 15,463 cases (317 pmp) in 1998-1999 to 213,700 cases (3995 pmp) in 2012-2013. There was increase in proportion of people over 75 years from 51.1% in 1998-1999 to 63.4% in 2012-2013. Overall unadjusted case-fatality decreased from 42.3% in 1998-2003 to 27.1% in 2008-2013, p < 0.001. Compared with 1998-2003, the multivariable adjusted odds ratio for death was 0.64 in 2003-2008 (95% CI 0.63-0.65) and 0.35 in 2008-2013 (95% CI 0.34-0.35). Odds for death were higher for patients over 85 years (2.93; 95% CI 2.89-2.97), CCS of more than five (2.75; 95% CI 2.71-2.79), emergency admissions (2.14; 95% CI 2.09-2.18) and AKI in the secondary diagnosis code (1.35; 95% CI 1.33-1.36) and AKI in other diagnoses codes (2.17; 95% CI 2.15-2.20). CONCLUSIONS: In England, the incidence of AKI not requiring dialysis has increased and case-fatality has decreased over last 15 years. Efforts to reduce the incidence of AKI and improve survival should focus on elderly people, emergency admissions and those with multi-morbidity.

Pragmatic, observational study of bupropion treatment for smoking cessation in general practice.

BACKGROUND: Cigarette smoking remains the single largest cause of premature death in the United Kingdom. As part of the government's national service framework for coronary heart disease, smoking cessation forms a key part of the strategy. OBJECTIVES: To determine the effectiveness of bupropion treatment for smoking cessation in a general practice setting, measuring continuous abstinence from smoking, from 8 weeks to 52 weeks. DESIGN: Prospective observational study. SETTING: One general practice (six whole time equivalent doctors, 11,070 patients) in rural Northumberland. SUBJECTS: Of the 243 patients who presented to the practice over a one year period for smoking cessation, a total of 227 motivated people, who were appropriate for bupropion treatment as a pharmacological aid for smoking cessation, entered the study. Continuous smoking cessation at one year was validated by an exhaled carbon monoxide level of 10 ppm or less. RESULTS: Fifty patients successfully gave up smoking, giving a one year smoking cessation prevalence with bupropion of 22% (95% confidence intervals (CI) 17% to 28%). There was no difference in success rate for sex, number of cigarettes smoked, the number of years smoking, or whether there were other smokers in the household or not. CONCLUSION: Bupropion treatment in this general practice helped 22% of motivated people to quit and remain stopped smoking at one year. Mainly nurses, whose prescribing rights are restricted and currently exclude bupropion, deliver smoking cessation services in primary care.

Isolation, characterization, and systematic significance of 2-pyrone-4,6-dicarboxylic acid in Rosaceae.

2-Pyrone-4,6-dicarboxylic acid was isolated from Potentilla anserina. Until now this substance was only found in bacteria and not in higher plants. By sterile cultivation it was verified that this compound is genuine also in plants. In addition the systematic relevance of 2-pyrone-4,6-dicarboxylic acid within the Rosaceae was tested. The compound seems to be a chemotaxonomic marker for the Rosoideae sensu stricto proposed by Morgan et al. (Morgan, D.R., Soltis, D.E., Robertson, K.R., 1994. Systematic and evolutionary implications of rbcL sequence variation in Rosaceae. American Journal of Botany 81, 890-903).

Benign monoclonal expansion of CD8+ lymphocytes in HIV infection.

BACKGROUND: A transient expansion of the CD8+ T cell pool normally occurs in the early phase of HIV infection. Persistent expansion of this pool is observed in two related settings: diffuse infiltrative lymphocytosis syndrome (DILS) and HIV associated CD8+ lymphocytosis syndrome. AIM: To investigate a group of HIV infected patients with CD8+ lymphocytosis syndrome with particular emphasis on whether monoclonality was present. METHODS: A group of 18 patients with HIV-1 infection and persistent circulating CD8+ lymphocytosis was compared with 21 HIV positive controls. Serum samples were tested for antinuclear antibodies, antibodies to extractable nuclear antigens, immunoglobulin levels, paraproteins, human T lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus, and cytomegalovirus serology. Lymphocyte phenotyping and HLA-DR typing was performed, and T cell receptor (TCR) gene rearrangement studies used to identify monoclonal populations of T cells. CD4+ and CD8+ subsets of peripheral blood lymphocytes were purified to determine whether CD8+ populations inhibited HIV replication in autologous CD4+ cells. RESULTS: A subgroup of patients with HIV-1 infection was found to have expanded populations of CD8+ T cell large granular lymphocytes persisting for 6 to 30 months. The consensus immunophenotype was CD4- CD8+ DRhigh CD11a+ CD11c+ CD16- CD28+/- CD56- CD57+, consistent with typical T cell large granular lymphocytes expressing cellular activation markers. Despite the finding of monoclonal TCR gene usage in five of 18 patients, there is evidence that the CD8+ expansions are reactive populations capable of mediating non-cytotoxic inhibition of HIV replication. CONCLUSIONS: A subgroup of HIV positive patients has CD8+ lymphocytosis, but despite the frequent occurrence of monoclonal TCR gene usage there is evidence that this represents an immune response to viral infection rather than a malignant disorder.

Monoclonal Epstein-Barr virus-related lymphoproliferative disorder following adult acute lymphoblastic leukaemia.

A 31-year-old patient in remission of acute lymphoblastic leukaemia (ALL), receiving oral maintenance chemotherapy (6-mercaptopurine, methotrexate (MTX), cyclophosphamide), developed a monoclonal, Epstein-Barr virus (EBV)-related lymphoproliferative disorder (LPD). Treatment consisted of excisional biopsy and the discontinuation of maintenance chemotherapy. To our knowledge, this is the first such report in an adult. The histological similarity to previous reports of 'lymphomatoid granulomatosis' following paediatric ALL suggests that they are the same disease. MTX may play a central role in the development of LPD in this setting. Although it is a rare complication of ALL, EBV-related LPD should be considered in patients who develop lymphadenopathy.

Fluorescein kinetics in interstitial fluid harvested from diabetic skin during fluorescein angiography: implications for glucose monitoring.

BACKGROUND: Glucose monitoring based on sampling skin interstitial fluid (ISF) is being developed as an alternative to fingerstick blood glucose monitoring. Time delays between rapidly changing levels of glucose in blood and interstitial fluid have been reported in the literature to be between 5 and 20 minutes. This study investigated the time delay between the injection of a small molecular weight fluorescent tracer into the circulation and interstitial fluid. METHODS: Diabetic subjects undergoing fluorescein angiography were studied. Skin ISF was sampled using a proprietary microporation and harvesting process. ISF was drawn through micropores created in the stratum corneum. After intravenous injection of sodium fluorescein, samples of ISF were drawn from 2 sites for 30 seconds over a period of 20 minutes. Fluorescence levels in ISF were measured with a fluorometer and used to create ISF fluorescein concentration versus time profiles. RESULTS: The ISF fluorescein versus time profiles were characterized by a rapid rise followed by a slow decay. The time to peak of the ISF fluorescein concentration ranged from 2-4 minutes for the patients studied. CONCLUSIONS: Intravenous injection of a bolus of low molecular weight fluorescent tracer was used to estimate the time delay between changing glucose levels in blood and ISF. The results indicate that the ISF sampling technology utilized here is capable of tracking rapidly rising levels of blood glucose.

A cross-sectional study comparing the motivation for smoking cessation in apparently healthy patients who smoke to those who smoke and have ischaemic heart disease, hypertension or diabetes.

BACKGROUND: Smoking remains the largest preventable cause of morbidity and mortality in the UK. OBJECTIVES: We aim to compare the motivation to stop smoking of patients with either ischaemic heart disease, hypertension or diabetes (diseased smokers) with apparently healthy smokers (controls), and comment on smoking cessation rates at 18 months following nurse-led active intervention in those who are motivated to stop smoking. METHODS: Questionnaires were sent out to 220 patients in each group. Those patients who had expressed a desire to stop smoking were invited to attend one to one or within a group. RESULTS: In total, 328 questionnaires were returned. Significantly more patients in the diseased group were ex-smokers, 29% versus 18% (P = 0.04), expressed a desire to stop smoking, 45% versus 30% (P = 0.02), and stated that they would like to receive individual support, 38% versus 23% (P = 0.05). Thirty-four patients attended for professional help to stop smoking. At 18 months follow-up, four patients remained not smoking. CONCLUSIONS: The findings in this study suggest that individuals who smoke and have either ischaemic heart disease, hypertension or diabetes may be more motivated to give up smoking and were more receptive to individual support. However smoking cessation rates at 18 months were disappointing.

Use of the polymerase chain reaction and direct sequencing analysis to detect cells with the t(14;18) in autologous bone marrow from patients with follicular lymphoma, before and after in vitro treatment.

Between August 1993 and February 1994, 25 patients with follicular or transformed follicular lymphoma had bone marrow harvested at St Bartholomew's Hospital (SBH) with a view to proceeding to high-dose treatment comprising: cyclophosphamide 60 mg/kg x 2 and total body irradiation, 200 cGy x 6, supported by autologous bone marrow transplantation (ABMT). The marrow mononuclear cell fraction was treated in vitro with four anti-B cell antibodies and baby rabbit complement. The aim of this study was to determine whether in vitro treatment of the marrow could remove morphologically undetectable lymphoma cells. PCR analysis for the t(14;18) was used to determine the presence or absence of lymphoma. At the time of the bone marrow harvest, 21/25 bone marrow samples were positive for the t(14;18), in 15/22 patients, the rearrangement could also be demonstrated in peripheral blood. After in vitro treatment, 18/21 samples (86%) remained 'PCR positive'. Sequence analysis of the t(14;18) PCR products was performed on the latter and on lymph node biopsy material taken at diagnosis from 12 patients. The same t(14;18) sequences were found in the bone marrow harvest samples as in the patients' original biopsies. These results suggest that this form of in vitro treatment does not completely eradicate the t(14;18) bearing clone. New and better methods need to be developed.