Understanding the barriers to using oral anticoagulants among long-term aspirin users with atrial fibrillation - a qualitative study.

BACKGROUND: Despite international treatment guidelines currently advocating oral anticoagulants (OACs) as the only appropriate stroke prevention therapy for patients with atrial fibrillation (AF) and evidence that OACs can greatly reduce the risk of stroke with similar risk of bleeding compared with aspirin, the underuse of OACs in patients with AF is common globally, especially in Asia. This study aimed to identify the barriers to prescribing and using OACs among long-term aspirin users with AF. METHOD: Face-to-face interviews were conducted with fourteen eligible patients with AF using a semi-structured interview guide. The interview recordings were transcribed verbatim and data was analyzed according to the principles of thematic analysis. RESULTS: Five themes were developed: awareness of AF symptoms and diagnosis; knowledge and understanding of AF and stroke prevention therapy; role of decision-making in prescribing; willingness to switch from aspirin to OACs; and impact of OAC regimen on daily living. The majority of the patients were not aware of the symptoms and diagnosis of AF and only had a vague understanding of the illness and stroke prevention therapy, leading to their minimal involvement in decisions relating to their treatment. Some patients and their caregivers were particularly concerned about the bleeding complications from OACs and perceived aspirin to be a suitable alternative as they find the adverse effects from aspirin manageable and so preferred to remain on aspirin if switching to OACs was not compulsory. Lastly, the lifestyle modifications required when using warfarin, e.g. alternative dosing regimen, diet restriction, were seen as barriers to some patients and caregivers. CONCLUSION: The findings revealed patients' knowledge gap in AF management which may be targeted using educational interventions to improve patients' understanding of AF and its management and hence encourage active participation in the decision-making of their treatment in the future.

Effectiveness of a structured educational intervention using psychological delivery methods in children and adolescents with poorly controlled type 1 diabetes: a cluster-randomized controlled trial of the CASCADE intervention.

INTRODUCTION: Type 1 diabetes (T1D) in children and adolescents is increasing worldwide with a particular increase in children <5 years. Fewer than 1 in 6 children and adolescents achieve recommended glycated hemoglobin (HbA1c) values. METHODS: A pragmatic, cluster-randomized controlled trial assessed the efficacy of a clinic-based structured educational group incorporating psychological approaches to improve long-term glycemic control, quality of life and psychosocial functioning in children and adolescents with T1D. 28 pediatric diabetes services were randomized to deliver the intervention or standard care. 362 children (8-16 years) with HbA1c≥8.5% were recruited. Outcomes were HbA1c at 12 and 24 months, hypoglycemia, admissions, self-management skills, intervention compliance, emotional and behavioral adjustment, and quality of life. A process evaluation collected data from key stakeholder groups in order to evaluate the feasibility of delivering the intervention. RESULTS: 298/362 patients (82.3%) provided HbA1c at 12 months and 284/362 (78.5%) at 24 months. The intervention did not improve HbA1c at 12 months (intervention effect 0.11, 95% CI -0.28 to 0.50, p=0.584), or 24 months (intervention effect 0.03, 95% CI -0.36 to 0.41, p=0.891). There were no significant changes in remaining outcomes. 96/180 (53%) families in the intervention arm attended at least 1 module. The number of modules attended did not affect outcome. Reasons for low uptake included difficulties organizing groups and work and school commitments. Those with highest HbA1cs were less likely to attend. Mean cost of the intervention was £683 per child. CONCLUSIONS: Significant challenges in the delivery of a structured education intervention using psychological techniques to enhance engagement and behavior change delivered by diabetes nurses and dietitians in routine clinical practice were found. The intervention did not improve HbA1c in children and adolescents with poor control. TRIAL REGISTRATION NUMBER: ISRCTN52537669, results.

Effect of the Spiroiminodihydantoin Lesion on Nucleosome Stability and Positioning.

DNA is constantly under attack by oxidants, generating a variety of potentially mutagenic covalently modified species, including oxidized guanine base products. One such product is spiroiminodihydantoin (Sp), a chiral, propeller-shaped lesion that strongly destabilizes the DNA helix in its vicinity. Despite its unusual shape and thermodynamic effect on double-stranded DNA structure, DNA duplexes containing the Sp lesion form stable nucleosomes upon being incubated with histone octamers. Indeed, among six different combinations of lesion location and stereochemistry, only two duplexes display a diminished ability to form nucleosomes, and these only by ∼25%; the other four are statistically indistinguishable from the control. Nonetheless, kinetic factors also play a role: when the histone proteins have less time during assembly of the core particle to sample both lesion-containing and normal DNA strands, they are more likely to bind the Sp lesion DNA than during slower assembly processes that better approximate thermodynamic equilibrium. Using DNase I footprinting and molecular modeling, we discovered that the Sp lesion causes only a small perturbation (±1-2 bp) on the translational position of the DNA within the nucleosome. Each diastereomeric pair of lesions has the same effect on nucleosome positioning, but lesions placed at different locations behave differently, illustrating that the location of the lesion and not its shape serves as the primary determinant of the most stable DNA orientation.

Challenges to optimal medicines use in people living with dementia and their caregivers: A literature review.

Dementia is fast becoming a global concern due to a demographic shift towards an older population. Many studies have shown that caring for a family member or friend has a profound and negative impact on the physical, emotional and psychosocial aspects of the caregivers' life. One significant activity that a family caregiver undertakes is assistance with the management of medicines. This review was undertaken to ascertain what the issues are that affect optimal medicines use from the perspectives of people living with dementia and their caregivers, both in the community and care home settings. A literature search was conducted using electronic databases, employing a combination of search terms. A total of 16 studies met the inclusion criteria. Six broad themes were identified, together with some recommendations to improve medicines use in people with dementia. Challenges to medicines use centred on medicines management and administration, the impact on the caregiver and care recipient, their partnership and interface with formal care. Future research should focus on developing targeted interventions that can overcome these challenges to achieve optimal medicines use.

Effect of Base-Pairing Partner on the Thermodynamic Stability of the Diastereomeric Spiroiminodihydantoin Lesion.

Oxidation of guanine by reactive oxygen species and high valent metals produces damaging DNA base lesions like 8-oxo-7,8-dihydroguanine (8-oxoG). 8-oxoG can be further oxidized to form the spiroiminodihydantoin (Sp) lesion, which is even more mutagenic. DNA polymerases preferentially incorporate purines opposite the Sp lesion, and DNA glycosylases excise the Sp lesion from the duplex, although the rate of repair is different for the two Sp diastereomers. To further understand the biological processing of the Sp lesion, differential scanning calorimetry studies were performed on a series of 15-mer DNA duplexes. The thermal and thermodynamic stabilities of each of the Sp diastereomers paired to the four standard DNA bases were investigated. It was found that, regardless of the base-pairing partner, the Sp lesion was always highly destabilizing in terms of DNA melting temperature, enthalpic stability, and overall duplex free energy. We found no significant differences between the two Sp diastereomers, but changing the base-pairing partner of the Sp lesion produced slight differences in stability. Specifically, duplexes with Sp:C pairings were always the most destabilized, whereas pairing the Sp lesion with a purine base modestly increased stability. Overall, these results suggest that, although the stability of the Sp diastereomers cannot explain the differences in the rates of repair by DNA glycosylases, the most stable base-pairing partners do correspond with the nucleotide preference of DNA polymerases.

Older people's priorities in health and social care research and practice: a public engagement workshop.

PLAIN ENGLISH SUMMARY: A one day public engagement workshop was held to focus on the priorities of older people about research and practice in health and social care. Seventy-five older people from the general public and a variety of backgrounds attended this event to share their views and discuss what should be prioritised. The main aim of this workshop was to identify and prioritise issues that are important to older people that would benefit from further research, as well as create an environment for older people to share ideas and problems related to these important issues. Key priorities brought up by participants included loneliness and isolation, support and training for professional and family carers, post-surgical care, negative perceptions of older people and inequalities related to public services and healthcare. Participants further suggested older people should be actively involved in all stages of the research process. ABSTRACT: As the world's population ages, there is an increasing need for research that addresses the priorities of older people. A public engagement workshop focusing on the priorities of older people for research and practice in health and social care was attended by seventy-five people aged 70 years and above in London, United Kingdom (UK). The workshop aimed to identify and prioritise issues important to older people that would benefit from further research and act as a platform to promote sharing of ideas and problems related to these important issues. Key priorities emerged including loneliness and isolation, support and training for professional and family carers, post-surgical care, negative perceptions of older people and inequalities related to public services and healthcare. Participants further suggested older people should be actively involved in all stages of the research process.

Structured, intensive education maximising engagement, motivation and long-term change for children and young people with diabetes: a cluster randomised controlled trial with integral process and economic evaluation - the CASCADE study.

BACKGROUND: Type 1 diabetes (T1D) in children and young people is increasing worldwide with a particular increase in children under the age of 5 years. Fewer than one in six children and young people achieve glycosylated fraction of haemoglobin (HbA1c) values in the range identified as providing best future outcomes. There is an urgent need for clinic-based pragmatic, feasible and effective interventions that improve both glycaemic control and quality of life (QoL). The intervention offers both structured education, to ensure young people know what they need to know, and a delivery model designed to motivate self-management. OBJECTIVE: To assess the feasibility of providing a clinic-based structured educational group programme incorporating psychological approaches to improve long-term glycaemic control, QoL and psychosocial functioning in a diverse range of young people. DESIGN: The study was a pragmatic, cluster randomised control trial with integral process and economic evaluation. SETTING: Twenty-eight paediatric diabetes services across London, south-east England and the Midlands. RANDOMISATION: Minimised by clinic size, age (paediatric or adolescent) and specialisation (district general hospital clinic or teaching hospital/tertiary clinic). ALLOCATION: Half of the sites were randomised to the intervention arm and half to the control arm. Allocation was concealed until after clinics had consented and the first participant was recruited. Where possible, families were blind to allocation until recruitment finished. PARTICIPANTS: Forty-three health-care practitioners (14 teams) were trained in the intervention. The study recruited 362 children aged 8-16 years, diagnosed with T1D for > 12 months, with a mean 12-month HbA1c level of ≥ 8.5%. INTERVENTION: Two 1-day workshops taught intervention delivery. A detailed manual and resources were provided. The intervention consists of four group education sessions led by a paediatric diabetes specialist nurse with another team member. OUTCOMES: The primary outcome was glycaemic control, assessed at the individual level using venous HbA1c values, measured at baseline, 12 and 24 months. Secondary outcomes were directly and indirectly related to diabetes management, including hypoglycaemic episodes, hospital admissions, diabetes regimen, knowledge, skills and responsibility for diabetes management, intervention compliance, clinic utilisation, emotional and behavioural adjustment, and general and diabetes-specific QoL. PROCESS EVALUATION: Questionnaires, semistructured interviews, informal discussion following observation sessions, fieldwork notes and case note review were used to collect qualitative and quantitative data from key stakeholder groups at specific time points in the trial. STATISTICAL ANALYSES: Primary and secondary analyses were intention-to-treat comparisons of outcomes at 12 and 24 months, using analysis of covariance with a random effect for clinic. Prespecified subgroup analyses based on age, gender, initial HbA1c value and socioeconomic status were estimated from models that included an interaction term. The economic analysis compared long-term costs and predicted quality-adjusted life-years (QALYs). RESULTS: The intervention did not improve HbA1c at 12 months [intervention effect 0.11; 95% confidence interval (CI) -0.28 to 0.50; p = 0.584] or 24 months (intervention effect 0.03; 95% CI -0.36 to 0.41; p = 0.891). A total of 298/362 patients (82.3%) provided blood samples at 12-month follow-up, and 284/362 (78.5%) provided blood samples at 24-month follow-up. Follow-up questionnaires were completed by 307 patients (85.3%) at 12 months and by 295 patients (81.5%) at 24 months. Intervention group parents at 12 months (95% CI 0.74; 0.03 to 1.52) and young people at 24 months (0.85; 95% CI 0.03 to 1.61) had higher scores on the diabetes family responsibility questionnaire. Young people reported reduced happiness with body weight at 12 months (-0.56; 95% CI -1.03 to -0.06). Only 68% of groups were run. Of the 180 families recruited, 96 (53%) attended at least one module. Reasons for low uptake included difficulties organising groups, and work and school commitments. Young people with higher HbA1c levels were less likely to attend. Parents and young people who attended groups described improved family relationships, improved knowledge and understanding, greater confidence and increased motivation to manage diabetes. Twenty-four months after the intervention, nearly half of the young people reported that the groups had made them want to try harder and that they had carried on trying. A high-quality, complex, pragmatic trial of structured education can be delivered alongside standard care in NHS diabetes clinics. Health-care providers benefited from behaviour change skill training and can deliver pragmatic aspects of a National Institute for Health and Care Excellence (NICE)-compliant structured education programme after relatively brief training. The process evaluation provides insight into aspects of the model, and highlights strengths and aspects that may have contributed to the failure to influence primary and secondary outcomes. Current NHS practice dominates CASCADE (Child and Adolescent Structured Competencies Approach to Diabetes Education) in that it achieves the same number of QALYs at a lower cost. The mean cost of providing the intervention was £5098 per site or £683 per child. Members of paediatric diabetes services trained to deliver the CASCADE structured education package using behaviour change techniques did not improve glycaemic control in patients compared with control subjects 1 and 2 years after the intervention. The training workshops for practitioners were well evaluated; however, more intensive training was needed. The intervention cost £683 per patient but was not cost-effective because it did not improve metabolic control. CONCLUSIONS: A high-quality, complex, pragmatic trial of structured education can be successfully conducted alongside standard care in NHS diabetes clinics. Pragmatic components of a NICE-compliant structured education programme can be successfully delivered following a relatively brief 2-day training while paediatric health-care professionals benefit from training in behaviour change skills. The study provides invaluable information on barriers and opportunities regarding future, similar interventions. A low dropout rate and good attendance for the subgroup that attended the intervention suggests there might be improved uptake if offered to young people with lower HbA1c. Testing whether this approach can be more successful with a robust ongoing supervisory element should be a target of further research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52537669. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 20. See the NIHR Journals Library website for further project information.

Public engagement workshop: how to improve medicines for older people?

Public engagement in medication management has become more and more important in promoting population health. A public engagement workshop attended by 78 members of the geriatric community, family carers as well as professionals from academic research, industry and regulatory agencies entitled 'How to improve medicines for older people?' took place on the 2nd July 2013 at the University College London (UCL) School of Pharmacy. The main aim of the event was to provide a dynamic environment for information exchange and to identify ways of improving current and future geriatric drug therapy. The day opened with presentations from UCL School of Pharmacy researchers on the use of medicines at home, formulations, administration devices and multi-component compliance aids (MCAs) whilst a representative from UCL Interaction Centre gave an insightful presentation on human errors and resilience strategies regarding medication use. These opening presentations encouraged participants to share their own experiences as well as initiating a lively debate. Following the plenary presentations, the workshop was divided into 8 groups for parallel discussion session. These opinion sharing sessions witnessed fruitful discussions between patients, carers and researchers. The day closed with a panel session of representatives from the European Medicines Agency (EMA), the Medicines and Healthcare products Regulatory Agency (MHRA), the Geriatric Medicines Society and Guy's and St. Thomas' NHS Foundation Trust (GSTT). Participants were encouraged to voice their questions, concerns and recommendations about medications. The main concern expressed by both patients and carers from the workshop were (but are not limited to) formulation changes, MCA accessibility difficulties, interactions of different medicines, carers' concerns with the administration of medicines and not having enough knowledge of services provided by community pharmacists i.e. medicines use reviews (MURs) or new medicine service (NMS). Overall, this workshop created a useful forum for members of the geriatric community, their carers as well as research and industrial professionals to have an input in the improvement and management of geriatric drug therapy and this event also provided an excellent opportunity for the researchers to share the latest research innovations with attendees.

Inorganic chemistry and IONiC: an online community bringing cutting-edge research into the classroom.

This Viewpoint highlights creative ways that members of the Interactive Online Network of Inorganic Chemists (IONiC) are using journal articles from Inorganic Chemistry to engage undergraduate students in the classroom. We provide information about specific educational materials and networking features available free of charge to the inorganic community on IONiC's web home, the Virtual Inorganic Pedagogical Electronic Resource (VIPEr, www.ionicviper.org ) and describe the benefits of joining this community.

Identifying protein interactions with metal-modified DNA using microarray technology.

Protein microarrays have been used extensively to identify protein-protein interactions; however, this technology has not been widely applied to protein-DNA interactions. In particular, this work demonstrates the utility of this technique for rapidly identifying interactions of proteins with metal-modified DNA. Protein macroarray experiments were carried out with high mobility group protein 1 (HMG-1) and cisplatin- and chromium-modified 50-mer oligonucleotides to demonstrate "proof of principle." Commercially available protein microarrays containing many different classes of human proteins were then employed to search for additional interactions with cisplatin-modified DNA. The results of the microarray experiments confirmed some known interactions and, more importantly, identified many novel protein interactions, demonstrating the utility of this method as a rapid, high-throughput technique to discover proteins that interact with metal-modified DNA.

Impact of the oxidized guanine lesion spiroiminodihydantoin on the conformation and thermodynamic stability of a 15-mer DNA duplex.

Spiroiminodihydantoin (Sp) is a hyperoxidized guanine base produced from oxidation of the mutagenic DNA lesion 7,8-dihydro-8-oxo-2'-deoxguanosine (8-oxoG) by a variety of species including peroxynitrite, singlet oxygen, and the high-valent metals Ir(IV) and Cr(V). In this study, the conformation and thermodynamic stability of a 15-mer DNA duplex containing an Sp lesion are examined using spectroscopic techniques and differential scanning calorimetry (DSC). The Sp lesion does not alter the global B-form conformation of the DNA duplex as determined by circular dichroism spectroscopy. Thermal denaturation experiments find that Sp significantly lowers the thermal stability of the duplex by approximately 20 degrees C. The enthalpies, entropies, and free energies of duplex formation for 15-mers containing guanine, 8-oxoG, and Sp were determined by performing DSC experiments as well as van't Hoff analysis of UV melting spectroscopic data. The thermodynamic stability of the Sp duplex is significantly reduced compared to that of both the 8-oxoG and parent G duplexes, with the thermodynamic destabilization being enthalpic in origin. The thermodynamic impact of the Sp lesion is compared to what is found for other types of DNA base damage and discussed in relation to how the presence of this lesion could affect cellular processes, in particular the recognition and repair of these adducts by the base excision repair enzymes.

Gender differences in reoffending after discharge from medium-secure units. National cohort study in England and Wales.

BACKGROUND: Previous research has shown that there are gender differences in reoffending after discharge from medium-secure units, but these have not been adequately explained. AIMS: To investigate gender differences in reoffending after discharge from medium-secure psychiatric units. METHOD: All people discharged from medium-secure units in England and Wales between April 1997 and March 1998 were followed up for 1 year (n=959; 12% women). Reoffending was estimated by collecting reconviction data from the Home Office's Offenders' Index or from files at the mental health unit up to 2 years after discharge. RESULTS: Women were less likely than men to be reconvicted within 2 years of discharge (9% v. 16%, OR=0.49, 95% CI 0.25-0.98). Adjustments for history of self-harm, drug or alcohol problems and previous offending substantially reduced the gender difference. In the full model the OR was 0.97 (95% CI 0.45-2.12). CONCLUSIONS: Some or all of the gender differences in reoffending between men and women are explained by self-harm, alcohol and drug problems and previous criminal history.

C4' sugar oxidation of deoxyribonucleotide triphosphates by chromium(V) complexes.

The Cr(V) complexes, bis(2-ethyl-2-hydroxybutyrato)oxochromate(V) ([OCr(V)(ehba)(2)](-)) and (2,2-bis(hydroxymethyl)-2-(bis(2-hydroxyethyl)amino)ethanolato)oxochromate(V) ([OCr(V)(BT)](2-)), were reacted with a series of deoxyribonucleotide triphosphates. Oxidation of deoxyribose at C4' was observed by measuring the amount of thiobarbituric acid reactive species (TBARS) produced in these reactions. For both compounds, the TBARS obtained with purine nucleotides was between 2.25 and 3.5 times greater than what was observed with pyrimidine nucleotide. This result suggests that the identity of the nucleic acid base can influence the hydrogen atom abstraction at C4'. Overall, the amount of product obtained with [OCr(V)(BT)](2-) was significantly less than what was observed with [OCr(V)(ehba)(2)](-), indicating that these two Cr(V) model complexes may oxidize DNA differently.

Survey of student nurses and midwives: smoking and alcohol use.

This article presents findings from a survey of 186 first year nursing and midwifery students that relate to their smoking and alcohol consumption. Of the students sampled, 28% were cigarette smokers. This is higher than the smoking rate of 25% for the adult population in the UK. The majority of the students who smoked said that they would like to stop smoking. Most of the students (86.5%) reported having drunk alcohol on at least one occasion during the previous week, with 26.5% having had a drink on three or four days. The amount consumed over the week ranged from no drinks to 90, with the mean being 13.72.Worryingly, 74% had exceeded the daily benchmarks for low-risk drinking on at least one occasion during the week for which consumption was reported, and 55% were drinking at binge levels. The findings raise concerns for the future health of many of our students and for their roles as health promoters.

Follow-up of serious offender patients in the community: multiple methods of tracing.

Longitudinal studies of people with mental disorder are important in understanding outcome and intervention effects but attrition rates can be high. This study aimed to evaluate use of multiple record sources to trace, over 12 years, a one-year discharge cohort of high-security hospital patients. Everyone leaving such a hospital in 1984 was traced until a census date of 31 December 1995. Data were collected from several national databases (Office for National Statistics (ONS), Home Office (HO) Offenders' Index, Police National Computer Records, the Electoral Roll) and by hand-searching responsible agency records (HO, National Health Service). Using all methods, only three of the 204 patients had no follow-up information. Home Office Mental Health Unit data were an excellent source, but only for people still under discharge restrictions (<50% after eight years). Sequential tracing of hospital placements for people never or no longer under such restrictions was laborious and also produced only group-specific yield. The best indicator of community residence was ONS information on general practitioner (GP/primary care) registration. The electoral roll was useful when other sources were exhausted. Follow-up of offenders/offender-patients has generally focused on event data, such as re-offending. People untraced by that method alone, however, are unlikely to be lost to follow-up on casting a wider records net. Using multiple records, attrition at the census was 38%, but, after certain assumptions, reduced further to 5%.

A general synthesis of specifically deuterated nucleotides for studies of DNA and RNA.

An efficient procedure is described for the preparation of ribonucleotides and deoxyribonucleotides with deuterium incorporated at the 1', 4', or 5' position. Three intermediates-[1-2H]-D-ribose, [4-2H]-D-ribose, and [5-2H(2)]-D-ribose-were prepared by chemical synthesis and subsequently converted to ribonucleotides and deoxyribonucleotides via enzymatic reactions. Milligram quantities of the desired products were obtained with an average deuterium content of 96+/-1%.

The use of trial leave for restricted special hospital patients.

INTRODUCTION: For England and Wales, Section 17 of the Mental Health Act 1983 allows for compulsorily detained patients to have trial leave (TL) between hospitals or from hospital to community to allow a period of testing readiness for a change in residency and/or legal status. The aim of this study was to document the use of TL for the largest sub-group of such patients within two discharge cohorts from one high security hospital and to test for correlates. METHOD: Data were collected from the special hospitals' case register for two Broadmoor Hospital discharge cohorts, 1984 and 1990-94, of offender patients with hospital orders under Home Office restrictions on discharge (Section 37/41). RESULTS: In 1984, only two of the 29 people leaving special hospital did so under trial leave arrangements, but by 1990 to 1994, 71% of restricted hospital order departures were under trial leave (92/130), a significant change in practice. Focusing on only the later cohort, women were disproportionately more likely to leave in this way. Trial leave was used more for patients with an index offence of homicide, similarly for violent offences but less so for sex offences. Nature of disorder did not have any bearing on the use of trial leave. Use of trial leave did not significantly shorten length of stay within the special hospital. CONCLUSION: Trial leave has become the most usual route out of special hospital, and is the departure route used almost exclusively for women patients, yet there appears to be no obvious advantage for the patient in shortening length of stay in high security. However, there is no way of knowing how long patients would have stayed had the option of trial leave not been available to them. Furthermore, no advantage for the public was found in the preferential use of TL for discharges to the community.

La enfermería en iberoamerica / Nursing in Iberoamerica

Apresenta a história da enfermagem na América Latina e nos demais países. Destaca o surgimento das escolas de enfermagem e faz um balanço da situaçäo da enfermagem no século XX, destacando o papel da enfermeira nos períodos de guerra.(JGC)