Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: Null mutations in the PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells

Human pyruvate dehydrogenase complex (PDC) catalyzes a key step in the generation of cellular energy and is composed by three catalytic elements (E1, E2, E3), one structural subunit (E3-binding protein), and specific regulatory elements, phosphatases and kinases (PDKs, PDPs). The E1α subunit exists as two isoforms encoded by different genes: PDHA1 located on Xp22.1 and expressed in somatic tissues, and the intronless PDHA2 located on chromosome 4 and only detected in human spermatocytes and spermatids. We report on a young adult female patient who has PDC deficiency associated with a compound heterozygosity in PDHX encoding the E3-binding protein. Additionally, in the patient and in all members of her immediate family, a full-length testis-specific PDHA2 mRNA and a 5′UTR-truncated PDHA1 mRNA were detected in circulating lymphocytes and cultured fibroblasts, being bothmRNAs translated into full-length PDHA2 and PDHA1 proteins, resulting in the co-existence of both PDHA isoforms in somatic cells.Moreover, we observed that DNA hypomethylation of a CpG island in the coding region of PDHA2 gene is associatedwith the somatic activation of this gene transcription in these individuals. This study represents the first natural model of the de-repression of the testis-specific PDHA2 gene in human somatic cells, and raises some questions related to the somatic activation of this gene as a potential therapeutic approach for most forms of PDC deficiency.

Techniques for needs assessment : state experiences and suggested approaches in response to Title XX of the Social security act /

Companion vol. to the author's State experiences in social services planning.

Cultivating Care: Understanding Intimate Partner Violence Experiences of Undocumented Latinas in Washington State

Thesis (Ph.D.)--University of Washington, 2016-06

Reducing medicines waste in the community

There is increasing concern at the amount and cost of prescribed medicines that are unused or wasted and then have to be disposed of. Previous studies have used health promotion and Dispose Unwanted Medicines Properly campaigns targeted at the patient to describe and quantify the annual cost of waste. The reasons patients return unused drugs to pharmacies have also been explored. The paper focuses on patient explanations for not needing medication; categorized as: over-collection in the past, self-management strategies, changes in medical condition, other changes in patient circumstances, or the repeat medicines policy at the surgery. The aim of the original study was to make a measurable change in prescribed medicines with a reduction in medicines wastage, whilst at the same time achieving improved standards of pharmaceutical care. Information on patient needs and behaviour came from consultation in the pharmacy monitoring forms and interview. The study was based on two medical practices in the West Midlands, UK, comparing an outer city and an inner city population. The participants were general practitioners, pharmacists and 350 repeat prescription patients. Prescriptions were issued for two three-month periods. The outcome was that 23.8% of the prescribed items were not dispensed, at a value of £13.1K, 58% of the medications that would be expected to be regularly supplied were collected. The study suggests that closer professional management at the point of dispensing and an understanding of patient experiences can help reduce the amount of unwanted medication collected by patients.

Quality of life instruments in studies of menorrhagia: a systematic review

BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia. STUDY DESIGN: A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.

Diabetic patient education and motivation. Available in 2 volumes.

Diabetes mellitus is a condition which requires a high degree of patient cooperation in self-management to achieve optimal glycaemic control. The concept of patient education, to enhance the treatment and management of diabetes, is well recognised. Several diabetes education programmes have already been described, but increased knowledge of diabetes did not necessarily result in improved self-mangement or glycaemic control. Other factors, such as attitudes and motivations, may therefore be particuarly important. The aims of the present study were to investigate the influence of patients' attitudes to diabetes, and to develop motivational aspects which enable the application of knowledge to enhance self-management and compliance with treatment. Thirty-one insulin-dependent diabetic (IDD) patients entered into a 12 month educational programme, particularly designed to increase motivation. Patients' attitudes to diabetes, their knowledge and self-management skills were assessed using questionnaires and practical tests, and parameters of glycaemic control were measured. The progress of these patients was compared at intervals with a close matched group of 25 control IFF patients who continued to receive routine clinic care. Patients completing the educational programme achieved better glycaemic control (p< 0.05), greater knowledge (p< 0.001), more favourable attitudes (p< 0.03) and increased competence in management skills (p< 0.02) compared with the control group. Evaluation procedures indicated that the programme was acceptable to the patients, and was successful in terms of increasing patient motivation. Six months after completion of the programme, glycaemic control deteriorated, although knowledge, attitudes and management skills were unchanged. This might reflect the withdrawal of extrinsic motivation, attention and supervision provided during the programme. It is recommended that consideration be given to the development of patients' intrinsic motivation to achieve maximum benefit from diabetes education programmes.

Patients’ and physicians’ experiences of atrial fibrillation and anticoagulation therapy:a qualitative journey

Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF) however it is often underutilized and sometimes refused by patients. This programme of work included a meta-synthesis and two inter-linking studies aiming to explore patients’ and physicians’ experiences of AF and OAC. Methods: A meta-synthesis of qualitative evidence was conducted which informed the empirical work. Semi-structured individual interviews were utilised. Study 1: Three AF patient sub-groups were interviewed; accepted (n=4), refused (n=4), or discontinued (n=3) warfarin. Study 2: Four physician sub-groups (n=4 each group) prescribing OAC to AF patients were interviewed: consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Data was analysed using interpretative phenomenological analysis. Results: Study 1: Three over-arching themes comprised patients’ experiences: (1) the initial consultation, (2) life after the consultation, and (3) patients’ reflections. Patients commented on the relief and reassurance experienced during the consultation but they perceived the decision making process mostly led by the physician. Lack of education and take-home materials distributed during the initial consultation was highlighted. Patients who had experienced stroke themselves or were caregivers, were more receptive to education aimed towards stroke risk reduction rather than bleeding risk. Warfarin monitoring was challenging for patients, however some patients perceived it as beneficial as it served to enhance patient-physician relationship. Study 2: Two over-arching themes emerged from physicians’ experiences: (1) communicating information and (2) challenges with OAC prescription for AF. Physicians’ approach to the consultation style shifted through a continuum of compliance-adherence-concordance during the consultation. They aimed for concordance, however challenges such as time and the perceived patient trust in them as the expert, led to physicians adopting a paternalistic approach. Physicians also pointed out challenges associated with guideline adherence and the need to adopt a multi-disciplinary approach, where other health professionals could provide on-going education. Conclusion: This programme of work has illustrated the benefit of taking an in depth phenomenological approach to understanding the lived experience of the physician-patient consultation. Together with the meta-synthesis, this work has strengthened the evidence base and demonstrated that there is a need to target patients' and physicians' ability to communicate with each other in a comprehensible way.

Experiences of patients with age-related macular degeneration receiving anti-vascular endothelial growth factor therapy:a qualitative study

The societal cost for the average health authority in the United Kingdom for the care of wet age-related macular degeneration (AMD) has been suggested to be around £7.4 million. It is vital that the best possible care based on the best available evidence is provided to reduce the impact of AMD on patients' lives and the financial cost to the health-care system. This study explored the experiences of AMD patients treated with intravitreal ranibizumab injections. Three semistructured interviews were conducted with seven participants over the course of 18 months. Transcripts were analysed using interpretative phenomenological analysis. Analysis identified four themes: preparing for treatment, the treatment process, patient-provider communication, and results of treatment. Patient experiences highlighted the need to move away from the reliance on letters for information provision, and the need for clearer guidelines about when to cease AMD treatment. Interviews highlighted the need for the inclusion of rigorous qualitative evidence with experiential data in future good clinical practice guideline development for AMD. © The Author(s) 2013.

Quality of life instruments in studies of menorrhagia: a systematic review

BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia. STUDY DESIGN: A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.

Benevolent sexism at work:gender differences in the distribution of challenging developmental experiences

The current research draws from ambivalent sexism theory to examine potential gender differences in the quantity and quality of developmental work experiences. In a sample of managers in the energy industry, men and women reported participating in a similar number of developmental experiences (with comparable levels of support), but men rated these experiences as more challenging and received more negative feedback than did women. Similarly, a sample of female managers in the health care industry reported comparable amounts, but less challenging types, of developmental experiences than their male counterparts'. The results of three complementary experiments suggest that benevolent sexism is negatively related to men's assignment of challenging experiences to female targets but that men and women were equally likely to express interest in challenging experiences. Taken together, these results suggest that stereotype-based beliefs that women should be protected may limit women's exposure to challenging assignments, which in turn may partially explain the underrepresentation of women at the highest levels of organizations. © The Author(s) 2012.

Using patient knowledge for better health systems

Purpose – This paper describes a “work in progress” research project being carried out with a public health care provider in the UK, a large NHS hospital Trust. Enhanced engagement with patients is one of the Trust’s core principles, but it is recognised that much more needs to be done to achieve this, and that ICT systems may be able to provide some support. The project is intended to find ways to better capture and evaluate the “voice of the patient” in order to lead to improvements in health care quality, safety and effectiveness. Design/methodology/approach – We propose to investigate the use of a patient-orientated knowledge management system (KMS) in managing knowledge about and from patients. The study is a mixed methods (quantitative and qualitative) investigation based on traditional action research, intended to answer the following three research questions: (1) How can a KMS be used as a mechanism to capture and evaluate patient experiences to provoke patient service change (2) How can the KMS assist in providing a mechanism for systematising patient engagement? (3) How can patient feedback be used to stimulate improvements in care, quality and safety? Originality/value –This methodology aims to involve patients at all phases of the study from its initial design onwards, thus leading to an understanding of the issues associated with using a KMS to manage knowledge about and for patients that is driven by the patients themselves. Practical implications – The outcomes of the project for the collaborating hospital will be firstly, a system for capturing and evaluating knowledge about and from patients, and then as a consequence, improved outcomes for both the patients and the service provider. More generally, it will produce a set of guidelines for managing patient knowledge in an NHS hospital that have been tested in one case example.

"Customer" knowledge management in healthcare

This paper reports on a work-in-progress project on the management of patient knowledge in a UK general hospital. Greater involvement of patients is generally seen as crucial to the effective provision of healthcare in the future. However, this presents many challenges, especially in the light of the ageing population in most developed countries and the consequent increasing demand for healthcare. In the UK, there have been many attempts to increase patient involvement by the systematisation of patient feedback, but typically they have not been open to academic scrutiny or formal evaluation, nor have they used any knowledge management principles. The theoretical foundations for this project come first from service management and thence from customer knowledge management. Service management stresses the importance of the customer perspective. Healthcare clearly meets the definitions of a service even though it may also include some tangible elements such as surgery and provision of medication. Although regarding hospital patients purely as "customers" is a viewpoint that needs to be used with care, application of the theory offers potential benefits in healthcare. The two main elements we propose to use from the theory are the type of customer knowledge and its relationship to attributes of the quality of the service provided. The project is concerned with investigating various knowledge management systems (KMS) that are currently in use (or proposed) to systematise patient feedback in an NHS Trust hospital, to manage knowledge from and to a lesser extent about patients. The study is a mixed methods (quantitative and qualitative) action research investigation intended to answer the following three research questions: • How can a KMS be used as a mechanism to capture and evaluate patient experiences to provoke patient service change • How can the KMS assist in providing a mechanism for systematising patient engagement? • How can patient feedback be used to stimulate improvements in care, quality and safety?

Smartphone-based digital government model:the case of the beyaz masa (white table) app in Turkey

M-Government services are now at the forefront of both user expectations and technology capabilities. Within the current setting, there is growing evidence that interoperability is becoming a key issue towards service sustainability. Thus, the objective of this chapter is to highlight the case of "Beyas Masa" - a Turkish application for infrastructure repair services. This application requires different stakeholders from different cultural background and geographically dispersed regions to work together. The major aim of this chapter to showcase experiences in as far as implementation and adoption of m-Government is concerned in the case of Turkey. The study utilizes the co-creation literature to investigate the factors influencing successful implementation of the Beyas Masa. This study reveals that initiatives are fragmented due to differences in the characteristics of the targeted audience, the marketing strategy, technology supply, distribution, and media utilized to promote its awareness. The chapter posits that in order to have affluent m-Government implementation in Turkey, it is important that many of the standalone applications are integrated to encourage interoperability and that socio-cultural behaviours should be re-shaped to encourage active engagement and interactive government service provisions that unlock the power of ICT.

Psychological influence of the media on patients commencing oral anticoagulation in atrial fibrillation:a qualitative analysis

Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF); however it is still underutilized and sometimes refused by patients. Two inter-related studies were undertaken to understand the experiences and what influences this un- derutilisation of warfarin treatment in AF patients. These studies explored physician and patient experiences of AF and OAC treatment. The paper focuses on specific sub-themes from the study that explored patients’ experiences will be discussed. Aim: The study in question aimed to explore the experiences which influence patients’ decisions to accept, decline or discontinue OAC. Methods: Semi-structured individual interviews with patients were con- ducted. Three sub-groups of patients (n = 11) diagnosed with AF were interviewed; those who accepted, refused, and who discontinued war- farin. Interpretative phenomenological analysis (IPA) was used to examine the data. IPA is a qualitative method that focuses on how participants make sense of an experiences phenomenon Results: Three over-arching themes comprised patients’ experiences: (i)the initial consultation, (ii) life after the consultation, and (iii) patients’reflections. In the last theme, patients reflected on their perceptions ofaspirin and warfarin. Aspirin was perceived as a natural wonder-drugwhile warfarin was perceived as a dangerous drug usually given to peo-ple at the end of their life. Interestingly they perceive both drugs as‘old’. However, for aspirin it had a positive association, old meaningtried and tested. While for warfarin, old meant ‘has been around fortoo long’.Conclusion: Media had an important role in how patients’ perceptionsof these two drugs were influenced. Literature shows that framingtechniques, i.e. using certain words or phrases such as ‘rat poison’, areprocesses adopted by media to alter medical knowledge into lay per-son’s language. Patients in turn form negative cognitive schemas,between the word ‘poison’ and warfarin, leading to the negative per-ception of warfarin which could influence non-adherence to treatment.This qualitative research highlighted the potential influences of themedia on AF patient perceptions commencing OAC treatment. Theassociation between media stimuli and patient perceptions on OACshould be further explored. The influential power of lay-media couldalso be instrumental in disseminating appropriate educational materialto the public