Structure of a phosphoglycerate mutase:3-phosphoglyceric acid complex at 1.7 A.

Journal ArticleResearch Support, Non-U.S. Gov'tThe crystal structure of the tetrameric glycolytic enzyme phosphoglycerate mutase from the yeast Saccharomyces cerevisiae has been determined to 1.7 A resolution in complex with the sugar substrate. The difference map indicates that 3-phosphoglycerate is bound at the base of a 12 A cleft, positioning C2 of the substrate within 3.5 A of the primary catalytic residue, histidine 8.BBSR

Drivers of overall satisfaction with primary care: Evidence from the English General Practice Patient Survey

This is the final version. Available from Wiley via the DOI in this record.Background/objectives: To determine which aspects of primary care matter most to patients, we aim to identify those aspects of patient experience that show the strongest relationship with overall satisfaction and examine the extent to which these relationships vary by socio-demographic and health characteristics. Design/setting: Data from the 2009/10 English General Practice Patient Survey including 2 169 718 respondents registered with 8362 primary care practices. Measures/analyses: Linear mixed-effects regression models (fixed effects adjusting for age, gender, ethnicity, deprivation, self-reported health, self-reported mental health condition and random practice effect) predicting overall satisfaction from six items covering four domains of care: access, helpfulness of receptionists, doctor communication and nurse communication. Additional models using interactions tested whether associations between patient experience and satisfaction varied by socio-demographic group. Results: Doctor communication showed the strongest relationship with overall satisfaction (standardized coefficient 0.48, 95% CI = 0.48, 0.48), followed by the helpfulness of reception staff (standardized coefficient 0.22, 95% CI = 0.22, 0.22). Among six measures of patient experience, obtaining appointments in advance showed the weakest relationship with overall satisfaction (standardized coefficient 0.06, 95% CI = 0.05, 0.06). Interactions showed statistically significant but small variation in the importance of drivers across different patient groups. Conclusions: For all patient groups, communication with the doctor is the most important driver of overall satisfaction with primary care in England, along with the helpfulness of receptionists. In contrast, and despite being a policy priority for government, measures of access, including the ability to obtain appointments, were poorly related to overall satisfaction.UK Department of HealthNational Institute for Health Research (NIHR

Web-based textual analysis of free-text patient experience comments from a survey in primary care.

BACKGROUND: Open-ended questions eliciting free-text comments have been widely adopted in surveys of patient experience. Analysis of free text comments can provide deeper or new insight, identify areas for action, and initiate further investigation. Also, they may be a promising way to progress from documentation of patient experience to achieving quality improvement. The usual methods of analyzing free-text comments are known to be time and resource intensive. To efficiently deal with a large amount of free-text, new methods of rapidly summarizing and characterizing the text are being explored. OBJECTIVE: The aim of this study was to investigate the feasibility of using freely available Web-based text processing tools (text clouds, distinctive word extraction, key words in context) for extracting useful information from large amounts of free-text commentary about patient experience, as an alternative to more resource intensive analytic methods. METHODS: We collected free-text responses to a broad, open-ended question on patients' experience of primary care in a cross-sectional postal survey of patients recently consulting doctors in 25 English general practices. We encoded the responses to text files which were then uploaded to three Web-based textual processing tools. The tools we used were two text cloud creators: TagCrowd for unigrams, and Many Eyes for bigrams; and Voyant Tools, a Web-based reading tool that can extract distinctive words and perform Keyword in Context (KWIC) analysis. The association of patients' experience scores with the occurrence of certain words was tested with logistic regression analysis. KWIC analysis was also performed to gain insight into the use of a significant word. RESULTS: In total, 3426 free-text responses were received from 7721 patients (comment rate: 44.4%). The five most frequent words in the patients' comments were "doctor", "appointment", "surgery", "practice", and "time". The three most frequent two-word combinations were "reception staff", "excellent service", and "two weeks". The regression analysis showed that the occurrence of the word "excellent" in the comments was significantly associated with a better patient experience (OR=1.96, 95%CI=1.63-2.34), while "rude" was significantly associated with a worse experience (OR=0.53, 95%CI=0.46-0.60). The KWIC results revealed that 49 of the 78 (63%) occurrences of the word "rude" in the comments were related to receptionists and 17(22%) were related to doctors. CONCLUSIONS: Web-based text processing tools can extract useful information from free-text comments and the output may serve as a springboard for further investigation. Text clouds, distinctive words extraction and KWIC analysis show promise in quick evaluation of unstructured patient feedback. The results are easily understandable, but may require further probing such as KWIC analysis to establish the context. Future research should explore whether more sophisticated methods of textual analysis (eg, sentiment analysis, natural language processing) could add additional levels of understanding

Investigating the meaning of 'good' or 'very good' patient evaluations of care in English general practice: A mixed methods study

This is the final version. Available from the publisher via the DOI in this record.The data set is available on request from the authors: please email Jenni Burt ( [email protected]) for details.Objective: To examine concordance between responses to patient experience survey items evaluating doctors' interpersonal skills, and subsequent patient interview accounts of their experiences of care. Design: Mixed methods study integrating data from patient questionnaires completed immediately after a video-recorded face-to-face consultation with a general practitioner (GP) and subsequent interviews with the same patients which included playback of the recording. Setting: 12 general practices in rural, urban and inner city locations in six areas in England. Participants: 50 patients (66% female, aged 19-96 years) consulting face-to-face with 32 participating GPs. Main outcome measures: Positive responses to interpersonal skills items in a postconsultation questionnaire ('good' and 'very good') were compared with experiences reported during subsequent video elicitation interview (categorised as positive, negative or neutral by independent clinical raters) when reviewing that aspect of care. Results: We extracted 230 textual statements from 50 interview transcripts which related to the evaluation of GPs' interpersonal skills. Raters classified 70.9% (n=163) of these statements as positive, 19.6% (n=45) neutral and 9.6% (n=22) negative. Comments made by individual patients during interviews did not always express the same sentiment as their responses to the questionnaire. Where questionnaire responses indicated that interpersonal skills were 'very good', 84.6% of interview statements concerning that item were classified as positive. However, where patients rated interpersonal skills as 'good', only 41.9% of interview statements were classified as positive, and 18.9% as negative. Conclusions: Positive responses on patient experience questionnaires can mask important negative experiences which patients describe in subsequent interviews. The interpretation of absolute patient experience scores in feedback and public reporting should be done with caution, and clinicians should not be complacent following receipt of 'good' feedback. Relative scores are more easily interpretable when used to compare the performance of providers.NHS Cambridgeshire and Peterborough CCGNational Institute for Health Researc

Framework and indicator testing protocol for developing and piloting quality indicators for the UK quality and outcomes framework

Contains fulltext : 96936.pdf (publisher's version ) (Open Access)BACKGROUND: Quality measures should be subjected to a testing protocol before being used in practice using key attributes such as acceptability, feasibility and reliability, as well as identifying issues derived from actual implementation and unintended consequences. We describe the methodologies and results of an indicator testing protocol (ITP) using data from proposed quality indicators for the United Kingdom Quality and Outcomes Framework (QOF). METHODS: The indicator testing protocol involved a multi-step and methodological process: 1) The RAND/UCLA Appropriateness Method, to test clarity and necessity, 2) data extraction from patients' medical records, to test technical feasibility and reliability, 3) diaries, to test workload, 4) cost-effectiveness modelling, and 5) semi-structured interviews, to test acceptability, implementation issues and unintended consequences. Testing was conducted in a sample of representative family practices in England. These methods were combined into an overall recommendation for each tested indicator. RESULTS: Using an indicator testing protocol as part of piloting was seen as a valuable way of testing potential indicators in 'real world' settings. Pilot 1 (October 2009-March 2010) involved thirteen indicators across six clinical domains and twelve indicators passed the indicator testing protocol. However, the indicator testing protocol identified a number of implementation issues and unintended consequences that can be rectified or removed prior to national roll out. A palliative care indicator is used as an exemplar of the value of piloting using a multiple attribute indicator testing protocol - while technically feasible and reliable, it was unacceptable to practice staff and raised concerns about potentially causing actual patient harm. CONCLUSIONS: This indicator testing protocol is one example of a protocol that may be useful in assessing potential quality indicators when adapted to specific country health care settings and may be of use to policy-makers and researchers worldwide to test the likely effect of implementing indicators prior to roll out. It builds on and codifies existing literature and other testing protocols to create a field testing methodology that can be used to produce country specific quality indicators for pay-for-performance or quality improvement schemes

Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice

Cell death by apoptosis has a critical role during embryonic development and in maintaining tissue homeostasis. In mammals, there are two converging apoptosis pathways: the ‘extrinsic’ pathway, which is triggered by engagement of cell surface ‘death receptors’ such as Fas/APO-1; and the ‘intrinsic’ pathway, which is triggered by diverse cellular stresses, and is regulated by prosurvival and pro-apoptotic members of the Bcl-2 family of proteins. Pro-survival Mcl-1, which can block activation of the proapoptotic proteins, Bax and Bak, appears critical for the survival and maintenance of multiple haemopoietic cell types. To investigate the impact on haemopoiesis of simultaneously inhibiting both apoptosis pathways, we introduced the vavP-Mcl-1 transgene, which causes overexpression of Mcl-1 protein in all haemopoietic lineages, into Faslpr/lpr mice, which lack functional Fas and are prone to autoimmunity. The combined mutations had a modest impact on myelopoiesis, primarily an increase in the macrophage/monocyte population in Mcl-1tg/lpr mice compared with lpr or Mcl-1tg mice. The impact on lymphopoiesis was striking, with a marked elevation in all major lymphoid subsets, including the non-conventional double-negative (DN) T cells (TCRβ+ CD4– CD8– B220+ ) characteristic of Faslpr/lpr mice. Of note, the onset of autoimmunity was markedly accelerated in Mcl-1tg/lpr mice compared with lpr mice, and this was preceded by an increase in immunoglobulin (Ig)-producing cells and circulating autoantibodies. This degree of impact was surprising, given the relatively mild phenotype conferred by the vavP-Mcl-1 transgene by itself: a two- to threefold elevation of peripheral B and T cells, no significant increase in the non-conventional DN T-cell population and no autoimmune disease. Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types

Measuring access to primary care appointments: a review of methods

BACKGROUND: Patient access to primary care appointments is not routinely measured despite the increasing interest in this aspect of practice activity. The generation of standardised data (or benchmarks) for access could inform developments within primary care organisations and act as a quality marker for clinical governance. Logically the setting of targets should be based on a sound system of measurement. The practicalities of developing appropriate measures need debate. Therefore we aimed to search for and compare methods that have been published or are being developed to measure patient access to primary care appointments, with particular focus on finding methods using appointment system data. METHOD: A search and review was made of the primary care literature from 1990 to 2001, which included an assessment of online resources (websites) and communication with recognised experts. The identified methods were assessed. RESULTS: The published literature in this specific area was not extensive but revealed emerging interest in the late 1990s. Two broad approaches to the measurement of waiting times to GP appointments were identified. Firstly, appointment systems in primary care organisations were analysed in differing ways to provide numerical data and, secondly, patient perceptions (reports) of access were evaluated using survey techniques. Six different methods were found which were based on appointment systems data. CONCLUSION: The two approaches of either using patient questionnaires or appointment system data are methods that represent entirely different aims. The latter method when used to represent patient waiting times for 'routine' elective appointments seems to hold promise as a useful tool and this avoids the definitional problems that surround 'urgent' appointments. The purpose for which the data is being collected needs to be borne in mind and will determine the chosen methods of data retrieval and representation

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

An assessment of opportunities and challenges for public sector involvement in the maternal health voucher program in Uganda

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Continued inequities in coverage, low quality of care, and high out-of-pocket expenses for health services threaten attainment of Millennium Development Goals 4 and 5 in many sub-Saharan African countries. Existing health systems largely rely on input-based supply mechanisms that have a poor track record meeting the reproductive health needs of low-income and underserved segments of national populations. As a result, there is increased interest in and experimentation with results-based mechanisms like supply-side performance incentives to providers and demand-side vouchers that place purchasing power in the hands of low-income consumers to improve uptake of facility services and reduce the burden of out-of-pocket expenditures. This paper describes a reproductive health voucher program that contracts private facilities in Uganda and explores the policy and implementation issues associated with expansion of the program to include public sector facilities. Methods: Data presented here describes the results of interviews of six district health officers and four health facility managers purposefully selected from seven districts with the voucher program in southwestern Uganda. Interviews were transcribed and organized thematically, barriers to seeking RH care were identified, and how to address the barriers in a context where voucher coverage is incomplete as well as opportunities and challenges for expanding the program by involving public sector facilities were investigated. Results: The findings show that access to sexual and reproductive health services in southwestern Uganda is constrained by both facility and individual level factors which can be addressed by inclusion of the public facilities in the program. This will widen the geographical reach of facilities for potential clients, effectively addressing distance related barriers to access of health care services. Further, intensifying ongoing health education, continuous monitoring and evaluation, and integrating the voucher program with other services is likely to address some of the barriers. The public sector facilities were also seen as being well positioned to provide voucher services because of their countrywide reach, enhanced infrastructure, and referral networks. The voucher program also has the potential to address public sector constraints such as understaffing and supply shortages.Conclusions: Accrediting public facilities has the potential to increase voucher program coverage by reaching a wider pool of poor mothers, shortening distance to service, strengthening linkages between public and private sectors through public-private partnerships and referral systems as well as ensuring the awareness and buy-in of policy makers, which is crucial for mobilization of resources to support the sustainability of the programs. Specifically, identifying policy champions and consulting with key policy sectors is key to the successful inclusion of the public sector into the voucher program

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

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