Multiple guidelines are often available to inform practice in complex interventions. Guidance implementation may be facilitated if it is tailored to particular clinical issues and contexts. It should also aim to specify all elements of interventions that may mediate and modify effectiveness, including both their content and delivery. We conducted a focused synthesis of recommendations from stroke practice guidelines to produce a structured and comprehensive account to facilitate the development of community-based exercise programmes after stroke.Published stroke clinical practice guidelines were searched for recommendations relevant to the content and delivery of community-based exercise interventions after stroke. These were synthesised using a framework based on target intervention outcomes, personal and programme proximal objectives, and recommended strategies.STroke Rehabilitation Intervention-Development Evidence Synthesis). Eight target outcomes, 14 proximal objectives, and 94 recommended strategies were identified. The synthesis was structured to present best practice recommendations in a format that could be used by intervention programme developers. It addresses both programme content and context, including personal factors, service standards and delivery issues. Some recommendations relating to content, and many relating to delivery and other contextual issues, were based on low level evidence or expert opinion. Where opinion varied, the synthesis indicates the range of best practice options suggested in guidelines.Nineteen guidelines were included in the synthesis (STRIDES; The synthesis may assist implementation of best practice by providing a structured intervention description that focuses on a particular clinical application, addresses practical issues involved in programme development and provision, and illustrates the range of best-practice options available to users where robust evidence is lacking. The synthesis approach could be applied to other areas of stroke rehabilitation or to other complex interventions. The evidence base for rehabilitation after stroke is expanding rapidly . DrawingA number of strategies have been suggested to reduce barriers to guideline implementation. One is to provide guidelines in multiple formats targeting different professional groups; some stroke practice guidelines do this by providing separate listings of recommendations for nursing and allied health professionals . AnotherThe synthesis of practice guidelines for specific clinical applications is relatively uncommon. A recent example focused on the assessment and management of low back pain . Using aThus, there is a need for application-specific guidelines that address both the content of interventions and the context in which they are delivered. A synthesis of guidelines created for this purpose ,16-22 maThe synthesis used some of the elements described in the ADAPTE approach: defining the health question, searching for and screening guidelines, selecting recommendations, and creating a customised guideline  see Fig. Data exThe question we addressed in this synthesis was: how should community-based exercise programmes for long term stroke survivors be structured, in terms of content and delivery, to maximise their effectiveness?http://www.guideline.gov), and Google Scholar. The search strategy used combinations and variations of the terms 'practice guideline,’ 'stroke,’ 'rehabilitation’ and 'exercise,’ and is described in Additional file We searched for stroke practice guidelines  published between 2000 and July 2012. We consulted the Medline and Cinahl bibliographic databases, the National Guideline Clearinghouse  extracted data from all guidelines, and a second reviewer (SD) verified the process by independent data extraction from four of the guidelines. Any differences were discussed by the reviewers, and additional material was included if agreed to be relevant.Data were analysed thematically, using a form of template analysis in which data are initially. Categorised using predefined themes and then organised iteratively under a hierarchy of emerging sub-themes . In thisOne reviewer (LP) conducted the first iteration of this process using all the extracted data; subsequent iterations were developed through discussion with three other reviewers  with rehabilitation expertise and who were familiar with a sample of the included guidelines, and one reviewer (CA) with expertise in Intervention Mapping methodology. To validate the inference of proximal objectives from the recomendations, two reviewers (LP and SD) independently inspected four guidelines to judge whether the proximal objectives were explicitly or implicitly present in them.The guidelines used a variety of systems to grade the evidence cited to support their recommendations. For the synthesis, the gradings were reclassified under a single simple system that had been employed by one of the guidelines : multiple.g., [The search of bibliographic databases identified 135 potentially relevant publications, which were screened initially by title and abstract, then by full text , othe.g., ,3. The me.g., ,49.e.g., being structured according to the phases of stroke recovery, the concerns of each health professional group, or the types of intervention that could be provided. Terminologies also differed, for example in the naming of forms of exercise or types of health practitioner. Most addressed the continuum of care from acute to chronic phases, but two focused specifically on community-based interventions for longer-term stroke survivors [The guidelines used a variety of formats, urvivors ,42. ThesTables e.g., mental rehearsal of movements and tasks, which received strong support from some guidelines [Seven proximal objectives focusing on the individual participant, along with 38 associated strategies, were identified in the synthesis. The objectives related to both physical outcomes, such as strength, aerobic fitness and functional ability, and to psychological outcomes, such as motivation and exercise self-management skills. The most commonly recommended exercises – with the highest level evidence – focussed on upper and lower limb strengthening, cardiovascular fitness and task-related practice. Treadmill training was frequently recommended both for improving aerobic endurance and to enhance walking performance. Several guidelines recommended and cited high level evidence for balance training, but there was less agreement about other sensorimotor strategies, idelines ,45 but lidelines ,42. StreSeveral guidelines recommended a combination of aerobic endurance, strength, functional practice, and balance exercises for long term stroke survivors ,37,40,43Eight proximal objectives concerned with programme delivery were identified in the synthesis. These ranged from ensuring that activities are delivered in sufficient quantity to achieve a training effect, to providing programme governance. In total, 57 associated strategies were found. The most commonly recommended and highly evidenced were involving family and carers in the programme, and adapting content and delivery to the individual’s circumstances and goals. However, there was inconsistency between guidelines on a number of recommendations. For instance, group classes conducted in fitness clubs or community centres were recommended by some ,42, wherIn total, 6 of the 19 included guidelines were found via free text Google searches rather than bibliographic databases. These included the two guidelines providing most of the recommendations on programme delivery ,42. InteExplicit links between aims and objectives were rarely made in the guidelines, and none were made in the synthesis. However, strategies were linked to particular content-related objectives in many guidelines, and these linkages were incorporated into the synthesis. Delivery-related objectives were formulated on the basis of themes identified during data extraction and analysis, and so delivery strategies were automatically linked to objectives. Some strategies were thought likely to serve more than one objective but, to avoid duplication, each strategy was assigned to a single objective in the synthesis.STroke Rehabilitation Intervention-Development Evidence Synthesis), presents an account of the many components that could be included in community-based exercise programmes for stroke survivors. STRIDES represents an exploratory attempt to develop a method of integrating diverse guidelines into a coherent and clinically applicable synthesis. It is novel in a number of respects: selectively abstracting from the guidelines only those recommendations relevant to a particular clinical application; including recommendations that relate not only to the content of the intervention but also to the way it is delivered and to other contextual factors that may significantly influence outcomes; and presenting recommendations in a format particularly suited to programme development. This combination of specificity, inclusivity and integrative restructuring adds value to the published guidelines by providing an account that is more tailored to particular needs and users, and provides a range of solutions to programme delivery issues, which may be selected according to local contexts and requirements. These characteristics can encourage guideline implementation by presenting relevant recommendations in a usable format, and addressing the range of organisational and service delivery issues that programme commissioners and practitioners must deal with.This synthesis, which we refer to as STRIDES , ande.g., ,62,63. TThe Intervention Mapping approach recommends that intervention descriptions specify theoretical mechanisms by which strategies achieve objectives and target outcomes . These whttp://www.guidelines.gov and found no recommendations additional to those in the synthesis. At least one of the included guidelines has recently been updated [A number of other issues arose during the synthesis process with implications for its future development and use. Several of the included guidelines were found through free text internet searches, rather than bibliographic or guideline databases. This underlines the value of a broad search strategy, including the use of alternative search terms and databases . Our sea updated ; howeverWe did not formally rate the quality of included guidelines, though this was variable. Several provided limited or no descriptions of how the evidence they cited had been selected ,40,42, aThe implementation of practice guidelines may be enhanced by generating accounts that are specific to a particular application and which address not only the content of interventions but also the way they should be delivered, along with other contextual factors that may influence their effectiveness. STRIDES does this by selecting and synthesising relevant best practice recommendations from a range of guidelines, and providing a structured account that can assist those responsible for the development of new programmes and evaluation of existing ones. By including both well-evidenced recommendations and those based on expert consensus, this approach creates a comprehensive description that covers all aspects of programme design. The synthesis also highlights where there is legitimate scope for variation in practice. The methods we have employed require further development, but could be applied to other complex interventions, not only for stroke but for a variety of health conditions.CK is a member of the RCP Intercollegiate Stroke Working Party responsible for development of their 2012 stroke guidelines.An abstract of the early stages of this study has been published .LP was lead author and reviewer; CA advised on Intervention Mapping and the conceptualisation of the review, and contributed to drafts of paper; AF contributed to drafts of the paper; VG and CK were involved in the review synthesis and contributed to drafts of the paper; RT helped conceptualise the review and contributed to drafts of the paper; SD was involved in conceptualising and conducting the synthesis, and contributed to drafts of the paper. All authors read and approved the final manuscript.Guideline search strategies.Click here for fileProgramme proximal objectives and strategies, with guideline page/section references.Click here for fileProximal objectives, strategies and evidence levels cited in guidelines.Click here for file


Martin Gerdin and colleagues argue that disaster health interventions and decision-making can benefit from an evidence-based approachPlease see later in the article for the Editors' Summary As for any type of health care, decisions about interventions in the context of natural disasters, conflict, and other major healthcare emergencies must be guided by the best possible evidence.Disaster health interventions and decision making can benefit from an evidence-based approach.We outline how systematic reviews and methodologically sound research can build a much-needed evidence base.We do this from the standpoint of Evidence Aid, an initiative that aims to improve access to evidence on the effects of interventions, actions, and policies before, during, and after disasters and other humanitarian emergencies, so as to improve health-related outcomes.Natural and man-made disasters are a global concern, with the potential to displace, kill, and injure large numbers of people, disrupt health systems, devastate food, water, and energy supplies, shatter economies, and cause massive destruction of infrastructure Even if it is not possible to predict the specifics of disasters, they happen regularly and can be prepared for. The level of evidence in the disaster health response should be the same as for other health settings. A needs assessment survey by Evidence Aid  gatheredBox 1. Outline of the Evidence Aid initiativewww.evidenceaid.org) is an initiative that tries to improve the quality of evidence and seeks to identify which, if any, systematic reviews from the thousands available in The Cochrane Database of Systematic Reviews and elsewhere are relevant to the disaster context, and which unanswered questions should be tackled in new reviews. The aim of Evidence Aid is to improve access to evidence on how to intervene and the eventual effects before, during, and after natural disasters and other humanitarian emergencies, so as to improve health-related outcomes.Evidence Aid (Box 2. Do electric fans reduce adverse health effects during heat waves?Since 2000, an estimated 150,000 people have died in heat waves across the world. The frequency and severity of heat waves are expected to increase in the future. Electric fans have been available for decades, and are widely used globally. A recent Cochrane Review sought to determine how their use affects important health outcomes during heat waves Box 3. What are the effects of interventions to improve the microbial quality of drinking water for preventing endemic diarrhoea?Diarrhoea causes more than 40% of the deaths in disasters and refugee camp settings. A review identified that interventions to improve water quality at a household level are more effective than those at the source of the water Box 4. Systematic reviews for maternal and child nutrition interventionsThe Lancet series on Maternal and Child Undernutrition in 2008 and 2013 are good examples of how the use of systematic reviews could help the humanitarian aid community to be informed about the effectiveness of health-related interventions. The Maternal and Child Undernutrition Series have included some high-quality systematic reviews to analyse whether the evidence for specific nutrition interventions exists or is unclear. Some Cochrane reviews suggested that vitamin A supplementation reduced allcause mortality by 24% and diarrhoearelated mortality by 28% in children aged 6–59 months For this paper, we use the definition of the United Nations Office for Disaster Risk Reduction: “A [disaster is a] serious disruption of the functioning of a community or a society involving widespread human, material, economic or environmental losses and impacts, which exceeds the ability of the affected community or society to cope using its own resources” PLOS Currents: Disasters series on the human impact of cyclones, floods, earthquakes, tsunamis, and volcanoes Disasters may be the result of a sudden event such as an earthquake or a protracted cause such as malnutrition caused by famine. They may be related to epidemics or armed conflict. Often, disasters are caused by a combination of many factors, both natural and man-made, and take place in challenging political environments Disasters in low-income countries are more likely to cause higher mortality and morbidity than those in middle– and high-income settings, due to a variety of reasons that include higher vulnerabilities of the population, and weaker health systems infrastructure with limited or no surge capacity. However, since the Balkan conflict in the 1990s and with the “Arab Spring,” disasters are more frequent in middle-income countries than in the past. To care for people affected by disasters in resource-limited countries, external assistance from elsewhere in the same country is often not enough and international health assistance may be needed. This “humanitarian assistance” is often guided by voluntary spirit. Whereas domestic assistance for a disaster will usually operate under defined laws and accountabilities, no such framework exists for international assistance Healthcare providers in disasters need readily accessible, reliable, up-to-date information on interventions that might be considered in the context of disasters. The concept of improving health through evidence-based interventions has a strong foundation in the evidence-based healthcare approach Whereas systematic reviews are widely used for improving health in general, their role in improving health in the context of disasters is still in its infancy, but the fundamental principles of systematic reviews still apply. Systematic reviews can be used to highlight which interventions work, which do not work, which need more research, and which, no matter how well intentioned, might be harmful. In the context of systematic reviews for health interventions in disasters, it is important to remember the challenges associated with transferring evidence from one setting to another Currently, research on disaster health interventions is scarce, as shown recently by Blanchet et al. We use management of limb crush injuries in earthquakes as a concrete example of how systematic reviews could inform disaster health decision making. The international health response to the 2010 Haiti earthquake resulted in many calls for an evidence-based approach to limb management after crush injury. Although initial reports are likely to have given too crude a picture of the situation, Haiti was referred to as a “nation of amputees” In this example, we argue that a first step would be a systematic review to identify existing tools to grade the severity and predict outcomes of crush-injured limbs. Such a review could be performed according to the Cochrane methods for a diagnostic test accuracy review Strengthening the evidence base to improve health care in disasters entails work on several fronts. First, a continuous dialogue is needed with the international disaster health community about the role of evidence in disasters and how best to produce and provide it. In health care, systematic reviews of randomised trials are generally considered the highest level of evidence for investigating the effects of interventions In conclusion, there needs to be a paradigm shift in healthcare decision making in disaster preparedness and response, moving towards a reliable and robust evidence base for all interventions being considered in disaster risk reduction, planning, response, and recovery. Evidence Aid presents an opportunity for all those involved in disaster response to collaborate in developing and enacting the best available evidence, so as to ensure that they have the best knowledge needed to decide how to respond in the worst of times.


Fetal alcohol spectrum disorders (FASD) are underdiagnosed in Australia, and health professionals have endorsed the need for national guidelines for diagnosis. The aim of this study was to develop consensus recommendations for the diagnosis of FASD in Australia.A panel of 13 health professionals, researchers, and consumer and community representatives with relevant expertise attended a 2-day consensus development workshop to review evidence on the screening and diagnosis of FASD obtained from a systematic literature review, a national survey of health professionals and community group discussions. The nominal group technique and facilitated discussion were used to review the evidence on screening and diagnosis, and to develop consensus recommendations for the diagnosis of FASD in Australia.The use of population-based screening for FASD was not recommended. However, there was consensus support for the development of standard criteria for referral for specialist diagnostic assessment. Participants developed consensus recommendations for diagnostic categories, criteria and assessment methods, based on the adaption of elements from both the University of Washington 4-Digit Diagnostic Code and the Canadian guidelines for FASD diagnosis. Panel members also recommended the development of resources to: facilitate consistency in referral and diagnostic practices, including comprehensive clinical guidelines and assessment instruments; and to support individuals undergoing assessment and their parents or carers.These consensus recommendations provide a foundation for the development of guidelines and other resources to promote consistency in the diagnosis of FASD in Australia. Guidelines for diagnosis will require review and evaluation in the Australian context prior to national implementation as well as periodic review to incorporate new knowledge. Internationally, five different guidelines have been developed for the diagnosis of fetal alcohol syndrome (FAS) or fetal alcohol spectrum disorders (FASD), three of which were published by national health agencies or proposed for national implementation in North America -3. ExistConsiderable gaps remain in the evidence base for diagnosis , which iThe development of clinical guidelines is most appropriate where the potential impact of this is high . In the The use of systematic and transparent methods in the development of guidelines is important ,19. In aThe purpose of this study was to establish evidence-based consensus recommendations to support the development of guidelines for the diagnosis of FASD in Australia, including assessment methods and diagnostic criteria.Recommendations on the diagnosis of FASD were developed using systematic review and evaluation of the evidence based on the GRADE  approach . Due to The selected panel was small enough to enable exploration of reasons for disagreement or uncertainty, and large enough to produce reliable recommendations . Study cDevelopment of consensus recommendations for the diagnosis of FASD Figure  was condi. evidence collection and preliminary evaluation,ii. a consensus development workshop and critical appraisal of evidence; andiii. post-workshop documentation and review.th September 2010; ii) a national consultation with health professionals using a modified Delphi process to identify their perceptions about adopting existing guidelines for diagnosis and agreement with existing screening and diagnostic criteria as described elsewhere [We conducted: i) a systematic literature review on FASD screening and diagnosis which updated and expanded an existing review  to inclulsewhere ,15,22; aThe nominal group technique, which is an established method for conducting structured group meetings ,24, was All panel members were invited to attend the 2-day workshop in July 2011 and 13 were able to attend. All 13 workshop participants had experience in FASD research and represented the range of expertise of the panel. Panel members who were unable to attend the workshop participated in the subsequent recommendation development and review processes.A diagnostic subgroup, including six medical practitioners (four paediatricians), met by teleconference to review the workshop outcomes and to complete and document recommendations. A three-member consumer subgroup also met by teleconference to review outcomes relating to consumer resources. All panel members then reviewed the consensus recommendations.a priori as agreement by at least 70% of panel members. Recorded outcomes of formal and informal voting processes, flip chart records and field notes taken during open group discussions were used to analyse workshop findings. Qualitative descriptive analysis [Consensus agreement was defined analysis  of partianalysis , was useanalysis .strong recommendation was made when the panel concluded there was clear evidence of balance between the desirable and undesirable effects of the strategy, or when there was little uncertainty about the benefits and harms of the strategy. A conditional recommendation was made where there was less certainty about the balance between desirable and undesirable effects. Strong recommendations were unlikely to be made in the absence of high quality evidence on costs and benefits. Evidence quality was rated high, moderate, low or very low based on its directness, likelihood of bias, consistency of findings, and likelihood that further research would modify confidence in the estimated effect [The GRADE approach , which ad effect . This stThe panel noted the lack of specific, high quality, and locally relevant evidence on which to base recommendations about the diagnosis of FASD in Australia. Two consensus recommendations were developed on screening and referral, and five on diagnosis Table .There are no reliable estimates of the population prevalence of FASD in most countries, including Australia. There is some evidence to suggest that the prevalence of FASD in high income countries may be as high as 2-5% . HoweverThere is some evidence that the benefits of screening may be greater among individuals in foster care, correctional environments and other high risk groups -37. EvalBoth survey  and workOur conditional recommendation reflects the lack of direct high quality evidence of the effectiveness, costs and benefits of specific criteria for referral, and of whether implementation of standard referral criteria can improve awareness among health professionals of the need to assess prenatal alcohol exposure and consider FASD as a potential diagnosis. This recommendation places a high value on early diagnosis  and the There is evidence that making a diagnosis of FASD, in combination with appropriate maternal services and support, can prevent the subsequent birth of affected children ,41, reduThe diagnostic categories recommended for use in Australia are FAS, PFAS and ND-AE. Despite the lack of established agreed diagnostic categories, FAS, PFAS, and alcohol-related neurodevelopmental disorder (ARND) are consistently identified as categories within the FASD spectrum -5,47-52.There was consensus that the diagnostic terminology for ARND should be modified to ensure that it describes the nature of the impairment, is meaningful to clinicians and consumers, and reflects the potentially unknown and multifactorial origins of neurodevelopmental disorders. The diagnostic term ND-AE uses the UW convention of designating a diagnostic category as alcohol exposed, rather than alcohol-related. Consistent with the UW and Canadian Guidelines, and evidence from the systematic review ,54, the There is a growing evidence base for the UW diagnostic criteria ,48,55-60Panel members identified a lack of evidence to compare the performance of criteria for CNS abnormality from the UW and Canadian guidelines, and that the specific criteria for establishing severe CNS damage or dysfunction was the greatest area of uncertainty in diagnosis, particularly in the absence of characteristic facial anomalies. Specifically, there was uncertainty about whether microcephaly alone was sufficient to indicate CNS damage, and whether moderate dysfunction was sufficient to indicate CNS damage. Consistent with the survey findings , use of The requirement for confirmed prenatal alcohol exposure for the diagnosis of ARND or SE-AE in the Canadian and UW guidelines respectively was also recommended for the diagnosis of ND-AE. The panel acknowledged difficulties in the quantification of prenatal alcohol exposure associated with the availability of information on specific levels of exposure; variation in individual susceptibility; and implications for the interpretation of a safe level of exposure. Due to the range of factors that may modify the effect of prenatal alcohol exposure on growth -63, the To facilitate the use of valid and comprehensive assessment methods, workshop participants recommended the development of standard assessment protocols for all required examinations and investigations based on the UW interdisciplinary approach to diagnostic assessment, as also recommended in the Canadian guidelines. The UW diagnostic assessment approach was recommended based on its use of specific, quantifiable assessment methods, the accumulated evidence base resulting from its use ,48,55,56Given the lack of resources for specialised diagnostic services for FASD in Australia, a multidisciplinary approach to diagnosis with coordinated contributions from a range of professionals was considered more feasible for national implementation in the short term than the ideal interdisciplinary assessment model, where professionals from different disciplines work together in a structured and integrated team approach to diagnosis. The panel recommended that diagnostic assessment findings be directly applied to the identification of relevant diagnostic outcomes based on the Australian diagnostic criteria, and that the UW 4-digit code could also be derived if desired.Consistent with nationally endorsed methods for the assessment of alcohol intake during pregnancy , panel mA comprehensive implementation plan was recommended to facilitate national adoption of standard diagnostic practices and development of systems for national surveillance of FASD. The implementation plan should include strategies and resources to: improve health professionals’ awareness of national diagnostic guidelines for FASD; facilitate adoption of standard diagnostic practices; provide training and support for health professionals, and establish national mechanisms for reporting and surveillance. Resources required would include comprehensive guidelines for diagnosis, standard instruments for referral and diagnosis, and training resources for health professionals.Panel members recommended that culturally appropriate information and support services including counselling and advocacy should be available for individuals undergoing diagnostic assessment and their parents or carers. These should inform parents and carers or individuals about the diagnostic and management process and goals prior to the assessment, and provide on-going support. This recommendation recognises the importance of acknowledging the values and preferences of individuals undergoing assessment in clinical decision-making. Informed consent should be obtained and recorded prior to conducting the diagnostic assessment and communicating diagnostic findings to other individuals or external organisations. We recommend that parents and carers are involved in evaluating FASD resources and services as a part of standard quality improvement processes.We propose evidence-based consensus recommendations for the diagnosis of FASD in Australia based on adaption of elements from the UW and Canadian guidelines. These recommendations were based on a review of evidence from published research and input from individuals with relevant expertise, including health professionals and consumer and community representatives. We recommend the three well established diagnostic categories of FAS, PFAS and ND-AE for use in Australia. The construct validity of the endorsed diagnostic categories is supported by the adoption of these categories in all published diagnostic guidelines for FASD internationally -5, despiOur systematic review of the literature demonstrated a lack of agreed diagnostic criteria for FASD and a lack of high quality evidence to enable direct comparison of different diagnostic criteria or evaluate their local applicability. These factors limited the use of the GRADE approach in developing recommendations, and our frequent use of conditional recommendations reflects uncertainty associated with current evidence base for diagnosis. Uncertainty was most notable for the Australian diagnostic criteria for ND-AE, where consensus was to use diagnostic criteria comparable with the UW guidelines for SE-AE and the Canadian guidelines for ARND in the requirement for evidence of severe CNS dysfunction, which is a more conservative approach than recommended in other guidelines ,5. RecomDue to the lack of gold standard criteria for the diagnosis of FASD and categories within the spectrum, guideline development relied on a consensus-based approach. Primary limitations of consensus development panels include the potential for bias in the recruitment of panel members and in the participation of panel members in recommendation development. We attempted to minimise this bias by recruiting panel members from different states and territories and a range of professional backgrounds, use of an experienced facilitator, and use of formal consensus-development methods and structured group interaction to promote the involvement of all panel members.The development of these recommendations was based on an integrated program of evidence collection and evaluation which aimed to facilitate extended engagement in a comprehensive critical evaluation process, used multiple sources of evidence, and consulted with health professionals and consumers to ensure recommendations were acceptable and locally appropriate. These processes allowed identification of uncertainty and reasons for disagreement, and provided a strong foundation for the content validity of these consensus-based recommendations.National guidelines for diagnosis will require review and evaluation to establish their appropriateness and feasibility in the Australian context. This includes review by health professionals, policymakers, consumers and other stakeholders to identify issues that may affect performance, acceptability, cost-effectiveness and implementation . The devNational guidelines are required to promote consistent diagnostic practices for FASD in Australia and improve diagnostic capacity. These workshop recommendations provide a consensus-based foundation for the development of guidelines adapted from the UW and Canadian guidelines. Guidelines for diagnosis will require review and evaluation in the Australian context prior to national implementation as well as periodic review to incorporate new knowledge.The authors declare that they have no competing interests.CB, EJE and JMP designed the study and CB and EJE supervised the study. REW, AM, HJ and CB designed the workshop program, and all authors reviewed the study methods and procedures. HJ organised the workshop, and AM and REW facilitated the workshop. REW analysed the data and drafted the manuscript, and all authors critically reviewed the manuscript and approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2431/13/156/prepub


Current recommendations do not support the use of continuous electronic fetal monitoring (EFM) for low risk women during labour, yet EFM remains widespread in clinical practice. Consideration of the views, perspectives and experiences of individuals directly concerned with EFM application may be beneficial for identifying barriers to and facilitators for implementing evidence-based maternity care. The aim of this paper is to offer insight and understanding, through systematic review and thematic analysis, of research into professionals’ views on fetal heart rate monitoring during labour.Any study whose aim was to explore professional views of fetal monitoring during labour was considered eligible for inclusion. The electronic databases of MEDLINE (1966–2010), CINAHL (1980–2010), EMBASE (1974–2010) and Maternity and Infant Care: MIDIRS (1971–2010) were searched in January 2010 and an updated search was performed in March 2012. Quality appraisal of each included study was performed. Data extraction tables were developed to collect data. Data synthesis was by thematic analysis.Eleven studies, including 1,194 participants, were identified and included in this review. Four themes emerged from the data: 1) reassurance, 2) technology, 3) communication/education and 4) midwife by proxy.This systematic review and thematic analysis offers insight into some of the views of professionals on fetal monitoring during labour. It provides evidence for the continuing use of EFM when caring for low-risk women, contrary to current research evidence. Further research to ascertain how some of these views might be addressed to ensure the provision of evidence-based care for women and their babies is recommended. Current research demonstrates a lack of evidence of benefit for the use of electronic fetal monitoring (EFM) compared to intermittent auscultation (IA) of the fetal heart rate (FHR) during labour ,2. DespiTo offer insight and understanding, through summary, aggregation and interpretation of findings from studies that report on professionals’ views, experiences and/or perspectives, on FHR monitoring during labour .Systematic review is a research method that compares individual research studies on similar topics and summarises their findings in a single report. They are often limited to reports of quantitative studies, such as randomised trials, with pooling and statistical analysis  of study results . Meta-syA framework, used previously by the Evidence for Policy and Practice Information and Coordinating (EPPI) Centre at the Institute of Education in London, in their synthesis of children’s views on healthy eating , was usefetal monitoring’, ‘labour’, ‘pregnancy’ ‘perceptions’, and ‘views’. These were combined using the Boolean operand ‘AND’ . Papers were then discarded, or selected for full text review, based on their relevance as judged by title, or title and abstract. Reference lists of all full text papers were studied to identify potentially relevant studies not captured by the electronic search  haven’t got something to look at they don’t want to know’  at the bedside of a laboring woman’ (p.127)‘Of interest in this review is the finding, in two of the included studies ,32, of aThis review highlights some of the barriers to and facilitators for the use of IA and EFM during labour, and offers some insight and understanding of professionals’ views. These will be useful for clinical decision-makers to consider or target when implementing policy and practice change. The need to educate professionals on the most appropriate, evidence-based means of FHR monitoring for individual women, ensuring availability of FHR monitoring guidelines and policies for staff and by using a collaborative approach to fetal monitoring and CTG interpretation to ensure best practice, have been highlighted in this review. This may be assisted by highlighting that EFM has not, to date, offered any increased evidence of benefit for improved maternal and neonatal outcomes over IA for low risk women ,2.The availability of regular study days on fetal monitoring for all staff would provide an opportunity to discuss some of the barriers, as identified in this review, , to effecting evidence-based practice change.This systematic review and thematic analysis has identified themes related to professionals’ views of FHR monitoring in practice. It has offered some insight as to why EFM has such a strong foothold in professionals’ practice and in their provision of care to women during childbirth, despite the evidence that has accumulated in research studies on the comparative effects of EFM and IA. Careful consideration of professionals’ views is required as part of the process to ensure the implementation of evidence-based care and appropriate practice change in FHR monitoring during labour.This review will be of significant benefit to policy makers, because it is the first systematic review and synthesis of evidence, that we are aware of, that brings together and considers the views, perceptions and experiences of professionals with respect to FHR monitoring during labour. It also has importance and relevance in advancing systematic review methodology, providing an additional example of the synthesis of integrated evidence from qualitative and quantitative enquiry. The views, perceptions and experiences of professionals must be considered when implementing care to effect best practice. Further research is required to establish how some of these views might be addressed to ensure that individual women receive the FHR monitoring method that is most suited to them and their needs, so that optimum care is provided to women and their infants.The authors declare that they have no competing interests.All authors contributed to the rationale for and, the design of, the review. VS participated in the sequence content and drafted the manuscript. CB, MC, and DD read and critically revised the draft manuscript for important intellectual content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/12/166/prepub


Research in 2007 showed that World Health Organization (WHO) recommendations were largely based on expert opinion, rarely used systematic evidence-based methods, and did not follow the organization's own “Guidelines for Guidelines”. In response, the WHO established a “Guidelines Review Committee” (GRC) to implement and oversee internationally recognized standards. We examined the impact of these changes on WHO guideline documents and explored senior staff's perceptions of the new procedures.We used the AGREE II guideline appraisal tool to appraise ten GRC-approved guidelines from nine WHO departments, and ten pre-GRC guidelines matched by department and topic. We interviewed 20 senior staff across 16 departments and analyzed the transcripts using the framework approach. Average AGREE II scores for GRC-approved guidelines were higher across all six AGREE domains compared with pre-GRC guidelines. The biggest changes were noted for “Rigour of Development”  and “Editorial Independence” . Four main themes emerged from the interviews: (1) high standards were widely recognized as essential for WHO credibility, particularly with regard to conflicts of interest; (2) views were mixed on whether WHO needed a single quality assurance mechanism, with some departments purposefully bypassing the procedures; (3) staff expressed some uncertainties in applying the GRADE approach, with departmental staff concentrating on technicalities while the GRC remained concerned the underlying principles were not fully institutionalized; (4) the capacity to implement the new standards varied widely, with many departments looking to an overstretched GRC for technical support.Since 2007, WHO guideline development methods have become more systematic and transparent. However, some departments are bypassing the procedures, and as yet neither the GRC, nor the quality assurance standards they have set, are fully embedded within the organization. The World Health Organization (WHO) is a leading producer of healthcare recommendations, guiding and informing policy worldwide, particularly for low and middle income countries. Research published in 2007 however demonstrated that WHO recommendations were based mainly on expert opinion and rarely used systematic evidence-based methods This public criticism prompted the WHO to establish a ‘Guidelines Review Committee’ (GRC), composed of both internal staff and external advisors, tasked with implementing and overseeing quality assurance The study protocol was discussed with both the Liverpool School of Tropical Medicine Ethics Committee and the WHO Ethics Review Committee and received a formal written waiver. Permission to conduct the study was granted by the Assistant Director General of the WHO. All participants in the study provided written informed consent prior to being interviewed.We sampled WHO guidelines, pre- and post-GRC, from a spread of WHO departments and across a range of broad topic areas , using a ‘matched’ before-and-after study design.To fully evaluate the impact of the changes we chose guidelines published online during 2010 as the initial post-GRC sampling frame . We randomly selected one guideline from each department that published during 2010, and matched this with a pre-GRC guideline from the same department and broad topic area. Where possible this match was with an earlier edition of the same document.We used the AGREE II appraisal tool to assess the methods and presentation of each guideline using 23 criteria across six domains: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability, and editorial independence All four assessors  completed the AGREE II online training modules prior to beginning the study, and to improve standardization, one guideline was appraised and discussed extensively by all four. Each guideline was allocated randomly to two assessors who worked independently but were not blinded to the year of publication. Each assessor initially allocated a score between 1 and 7 for each criterion, and scores were then aggregated across assessors and converted to a percentage for each domain. Wide disagreement in scores was resolved by a third assessor.DS and PG, who have participated in the development of guidelines in malaria, were excluded from appraising guidelines from the Global Malaria Programme.We interviewed senior staff from 18 WHO departments, representing departments experienced with publishing GRC-approved guidelines, others who had not yet been through the process, the GRC chair and members of the secretariat. The GRC secretariat assisted in this selection process to ensure a spread of ‘supporters and opponents’. Following written informed consent, each person was interviewed by two researchers (PG and DS) in April 2012 using a topic guide . InterviSeventeen GRC-approved guidelines were published online in 2010, from nine different WHO departments spread across six departmental clusters. Of note, four were published by the HIV department and five by STOP TB. From these seventeen, ten were selected for formal appraisal: one from each of the nine departments and one additional guideline from the HIV department as it was the only guideline addressing diagnostic questions. Five guidelines addressed questions about treatment, two about safety or illness prevention, and two provided health system guidance.The ten matched guidelines were published between 2003 and 2008 by the same nine WHO departments, all pre-dating the GRC approval process. Of these, five were earlier editions of the same guideline and five were earlier guidelines addressing a similar topic area.Mean scores for all six domains of the AGREE II appraisal were higher in the ten GRC-approved guidelines than in the ten older ‘matched’ guidelines . Seven o‘Rigour of Development’ and ‘Editorial Independence’ were the lowest scoring domains across the pre-GRC guidelines with eight out of ten guidelines scoring less than 40% for both domains. Substantial improvements were seen in seven of the GRC-approved guidelines, with eight of the ten guidelines now scoring greater than 60% for both domains. ‘Stakeholder Involvement’ and ‘Applicability’ were now the lowest scoring domains in GRC-approved guidelines.During the research we identified two additional documents which had bypassed the GRC process, and were informed that one guideline group had a formal ‘waiver’ on the GRC process. An AGREE II appraisal of these three documents gave scores similar to pre-GRC guidelines .The 20 interviews were conducted with ten heads of departments (Directors), seven senior technical staff who had been involved with guideline development , and three others directly involved with the GRC. Through careful analysis of the content of these interviews we identified four main themes .Most directors acknowledged that the criticism levelled at the organization in 2007 was fair and that many WHO guidelines and recommendations published prior to this were of low quality.Some noted that these deficiencies were not universal and gave examples of evidence-based systematic processes in use well before the GRC. These interviewees viewed the recent changes in process as relatively minor for them but essential for raising standards across the organization.Senior staff widely recognized the normative role of the WHO as central to its mission, and guidelines as one of the most visible products on which the organization is judged. High standards were noted as important by interviewees to defend the WHO against criticism (particularly with regard to conflicts of interest); to improve the reliability of recommendations; and to ensure the future credibility and position of the organization.While the interviewees universally advocated high standards, opinions were mixed on the need for a single quality assurance mechanism across the organization, with some questioning the power given to the current GRC.One director expressed strong opinions against the GRC and against a perceived loss of autonomy, describing the process as a “monstrous bureaucracy”; citing negative early experiences with the GRC, and scepticism from external members of guideline panels. Another director questioned whether the GRC should have the power to block documents at either the planning or publication stage, and whether the GRC had the technical capacity to make such a judgement.Others were very positive about the GRC, its influence, and how it had helped them. Some admitted to similar initial concerns – of fear about the ‘guideline police’ delaying and unnecessarily complicating the process – but through positive experiences now viewed the GRC as a valuable resource and essential as one of the few quality assurance mechanisms within the WHO.Representatives of the GRC reported constructive partnerships with many departments but raised examples of groups bypassing the GRC process, either by “game-playing”  or wilfully through disregard for the GRC and the procedures.Several areas of uncertainty relating to the GRADE approach were noted. While departmental staff tended to concentrate on discussing the technicalities and bureaucracy of the process, those from the GRC emphasised the general principles underlying a transparent, systematic, and explicit process, and remained concerned that even these were not yet fully institutionalized.Most interviewees agreed that the GRADE approach to assessing quality of evidence worked well for clinical questions and recommendations, but some were uncertain about whether these methods could be used for health systems or implementation guidance. However, we did hear one example of a group using GRADE for a health systems guideline with enthusiasm. This group felt the additional efforts had increased the clarity and usefulness of their recommendations.Some interviewees discussed uncertainties about how to apply the GRADE approach when the evidence was of very low quality or when the recommendation seemed obviously ‘common sense’. In these instances, some felt forced to search for evidence when it was considered unhelpful or necessarily time-consuming. Some also expressed concerns that if applied wrongly, a formulaic approach to GRADE could mislead or detract people from addressing the right questions with the most appropriate methods, and lead to poorly thought-out documents, or ill-advised recommendations.Many of the interviewees acknowledged that making recommendations that were intended to inform policies in many different settings was not straightforward: disease burden, health infrastructure and financing, and cultural values and preferences are all different and need to be taken into account. There was uncertainty about how to incorporate these considerations into WHO documents or how to provide the necessary contextual guidance within the framework of existing methods.Many who had been through the GRC approval process described it as a steep learning curve, both for them and for the external experts who were often equally unfamiliar with these methods. Several directors and technical staff had attended educational sessions conducted by the GRC and valued these highly.Some senior staff stated that the technical expertise to apply these new methods was not widespread within the organization and others admitted that their progress so far had been reliant on just one or two highly skilled individuals within the department. Some however, appeared fully engaged in the process, were talking with the GRADE working group, and seemed keen to further improve the methods for application to global guidelines.Several directors had hired new staff with the specific skills required to implement the procedures and prepare the documents. Some reported that GRC members had provided useful methodological input to the expert meetings and some had brought in external GRADE methodologists to sit on the expert panels. A few directors did not seem to understand the concept of ‘guideline methodology’ and were content to rely on the statistical understanding of existing expert members who were usually academic researchers or content experts.While some departments seemed to be having difficulty fitting the requirements of the GRC methods around the existing framework of long-established expert groups or committees, others appeared more innovative, readily disbanding such groups and finding new ways to garner expert advice at appropriate stages of the process.Four years after the GRC was formed, our AGREE II evaluation demonstrates that the transparency of WHO guidelines processes has improved and the organization is making wider use of systematic evidence appraisal. However, we found wide differences between groups in their capacity to implement these changes and in their willingness to participate in the GRC procedures; with some groups embracing it enthusiastically, some bypassing it, and some simply rejecting it.The AGREE II appraisal has several limitations. Firstly, the AGREE II tool is unable to fully assess the ‘appropriateness’ of the final recommendations or ‘use-ability’ of the final document – both highly important considerations. Despite this, reporting of funding sources, conflicts of interests, and guideline methodology are considered minimum standards internationally and are essential to the future credibility of the organization From our own experience and understanding of the GRADE approach, the concerns raised during the interviews seem to relate to poor understanding of the process and a lack of embedded institutional capacity, rather than deficiencies in the methods themselves. Effective use of the GRADE approach requires high quality, well-constructed systematic reviews, followed by critical and thoughtful analysis and interpretation of the data by the guideline panels, both of which can prolong and complicate the guideline development process without adequate planning and in-house technical capacity. Difficulties such as ‘common-sense’ recommendations are common across guideline developers and have been addressed elsewhere by the GRADE Working Group At present, the GRC itself appears fragile and the procedures it has put in place could yet be derailed by departments wanting to do things their own way. Indeed, some interviewees recounted the near collapse of the GRC in late 2010/11 through mismanagement, and it is a credit to the organization that it has survived.WHO procedures for developing guidelines have improved considerably since the GRC was established, with wider use of systematic methods, improved transparency and better management of potential conflicts of interest. The interviews with senior WHO staff support the conclusion that a large part of these improvements can be attributed to the GRC.However, as yet neither the GRC, nor the changes implemented by them, are fully embedded within the organization. Political support and greater resourcing are required to institutionalize the principles and procedures, and move forward with further improvements.Appendix S1Draft Interview Guide.(DOCX)Click here for additional data file.Appendix S2Full AGREE II appraisal scores for pre- and post-GRC guidelines.(DOCX)Click here for additional data file.Appendix S3AGREE II appraisal scores for three recent guidelines that did not seek GRC approval.(DOCX)Click here for additional data file.Table S1Theme 1: High standards essential for credibility.(DOCX)Click here for additional data file.Table S2Theme 2: Mixed views on the need for a single quality assurance process.(DOCX)Click here for additional data file.Table S3Theme 3: Uncertainties about applying the GRADE methods.(DOCX)Click here for additional data file.Table S4Theme 4: Variable capacity to implement the new standard.(DOCX)Click here for additional data file.


Low literacy is a significant problem across the developed world. A considerable body of research has reported associations between low literacy and less appropriate access to healthcare services, lower likelihood of self-managing health conditions well, and poorer health outcomes. There is a need to explore the previously neglected perspectives of people with low literacy to help explain how low literacy can lead to poor health, and to consider how to improve the ability of health services to meet their needs.Two stage qualitative study. In-depth individual interviews followed by focus groups to confirm analysis and develop suggestions for service improvements. A purposive sample of 29 adults with English as their first language who had sought help with literacy was recruited from an Adult Learning Centre in the UK.spoken interactions with healthcare professionals.Over and above the well-documented difficulties that people with low literacy can have with the written information and complex explanations and instructions they encounter as they use health services, the stigma of low literacy had significant negative implications for participants’ Participants described various difficulties in consultations, some of which had impacted negatively on their broader healthcare experiences and abilities to self-manage health conditions. Some communication difficulties were apparently perpetuated or exacerbated because participants limited their conversational engagement and used a variety of strategies to cover up their low literacy that could send misleading signals to health professionals.Participants’ biographical narratives revealed that the ways in which they managed their low literacy in healthcare settings, as in other social contexts, stemmed from highly negative experiences with literacy-related stigma, usually from their schooldays onwards. They also suggest that literacy-related stigma can significantly undermine mental wellbeing by prompting self-exclusion from social participation and generating a persistent anxiety about revealing literacy difficulties.Low-literacy-related stigma can seriously impair people’s spoken interactions with health professionals and their potential to benefit from health services. As policies increasingly emphasise the need for patients’ participation, services need to simplify the literacy requirements of service use and health professionals need to offer non-judgemental  literacy-sensitive support to promote positive healthcare experiences and outcomes. Low literacy is a significant problem across the developed world. The OECD International Adult Literacy Survey reported 22% of adults in the USA and 23% of adults in the UK performed at the lowest level of a 5-point scale of functional literacy . A recen“the wide range of skills and competencies that people develop to seek out, comprehend, evaluate and use health information and concepts to make informed choices, reduce health risks and increase quality of life” but I was told by the doctor that they’re checking your stomach, see so I didn’t think they were going the other way, so it was quite ‘bloody hell,’ you know and you don’t realise what you’re gonna feel like after so it was quite an ordeal.” Our findings in relation to written communication are in line with previous research -35.spoken consultations with health professionals and (2) that one key to understanding their difficulties in spoken conversations lies in recognising an often strong reluctance to ‘disclose’ difficulties with reading, writing or understanding in social and healthcare contexts that is rooted in the terrible stigma that can be associated with low literacy.Our two main original findings are (1) that, over and above the well-documented difficulties that people with low literacy can have with the written information and complex explanations and instructions they encounter as they use health services, people with low literacy can have significant difficulties in their Participants’ accounts revealed a range of difficulties that they experienced with spoken communication in health care contexts. These difficulties impacted negatively on participants’ experiences of formal healthcare and abilities to manage their health conditions at home. Some of the difficulties were apparently perpetuated or exacerbated because participants limited their conversational engagements with health professionals and often took care to avoid revealing when they did not understand what was being discussed.gobbledygook;” “big fancy words;” and “twenty four letter words.”Participants frequently reported difficulties in understanding what was said during consultations and they attributed these difficulties in part to the language clinical staff  used. Participants’ descriptions of spoken conversations included terms such as, “Some participants thought some doctors made no effort to help them understand what was being said. For example:“.... and he [hospital consultant] was ‘blah blah blah’ and he knew fine I didn’t have the foggiest idea what he was talking about.” Some participants clearly recognised that their own anxieties could also contribute to their difficulties with understanding what was said in consultations, both because they impaired listening and concentration, and because they deterred them from asking questions. For example, Louise described how she felt every time a healthcare professional produced a piece of paper:“… I’m like that, ‘Oh no, they’re wanting me to write something,’ start panicking and that seems to take over you and sometimes you’re like that, ‘What was they saying there?’ because the anxiety’s took over what’s going on.” It was particularly striking that, in spite of their self-recognised difficulties in grasping potentially important information, a number of participants described feigning understanding to the health professionals they were talking with:“…they never explain anything properly. It’s always their own big words and I just say, ‘Yeah, okay’ and I go home and I’m like, ‘I don’t know what that meant.’” The recurring reason given by participants who said they were reluctant to ask questions or to make it known that they had not understood what was said was that they were concerned to avoid revealing to health professionals that they had literacy difficulties.The concern to keep their literacy problems hidden from health professionals was explicitly shared by most participants in their interviews, and all mentioned some occasions on which they had concealed their low literacy in healthcare settings, for example, by: saying they didn’t have their reading glasses; relying on a trusted person who accompanied them to consultations; saying they would read something later; or making an excuse to leave.Some participants seemed almost wracked with fear that health professionals might discover their low literacy, and regularly limited their conversations with health services as a result. For example, Barbara described what happened when she was asked to complete a form at a first appointment and said she had done this kind of thing many times:“..... I couldn’t spell it. I just went, ‘You know what, I’m going to have to go. I’m not feeling very good. I’ll come back, I will come back’ and I grabbed it [the form] and ran out.” Barbara also described what she felt like and did within consultations, especially if she saw paperwork:“…. you’re nervous and you’re pulling back ...... then you’re just going to finish it as quick as you can, short answers, just get out. ‘I don’t know’, or ‘Yeah’, ‘No’, where you wouldn’t say, ‘Well, actually.....’ and be more explicit, you wouldn’t do that. Well, I wouldn’t. I’d want out.” Not all participants were so strongly concerned to conceal their low literacy, and a minority of our sample told us that they would reveal their low literacy to a healthcare professional if they were asked directly and if they felt comfortable with the person who was asking. However, few were able to recount explicitly having revealed their difficulties to any healthcare staff.would happen if their literacy became apparent to healthcare staff, participants talked primarily in terms of possibly being looked down on, or being suspected of having been somehow irresponsible in respect of their own or their child’s health. For example:When asked what they thought “They [healthcare staff] could treat you differently, and not in a nice way. They could look upon you as if you’re stupid, you don’t understand what I’m telling you.” “… when something bad does happen or there’s an accident or something when you first go to the doctor or the hospital …you’re sitting there thinking like ‘Do I tell them do I not?’ but you’re scared to in case then they twist and they think ‘Well this could have happened because you’ve done wrong.’” might happen, none of our participants could recall any actual experience of having been treated badly in practice as a result of healthcare professionals finding out about their literacy difficulties . Some had, however, experienced poor interactions when they had sought ways around the use of written text. For example, a young mother described the response when she asked a midwife for help with bathing her newborn baby:Despite these fears of what “… you’re saying …‘Could you show me … cos I’m not too sure’ …. and she went ‘Oh (sigh) I just gave you a leaflet.’” Some participants were aware that the behaviours that they used to conceal their low literacy (as well as any literacy-related mistakes they might make) could be misinterpreted:“….if an appointment came…..instead of filing it or writing it down in the diary I’d just put it away and just forget … people were getting a bit like ‘What’s she playing at?’” Participants’ reluctance to reveal their low literacy to health professionals was consistent with their broader reluctance to reveal these difficulties to anyone (other than select family and friends). Overall, participants identified a range of strategies that they used to cover up their literacy difficulties. We heard, for example, of people pretending to read newspapers during work breaks, leaving training sessions at times when there was a possibility of being asked to read or write, avoiding participation in a range of social activities, and even colluding with peers’ expressions of negative attitudes about people with literacy difficulties:“I never told anybody, it was always just something that was hidden away back so nobody could see it. I don’t know why. I think that’s just no confidence, not wanting to tell anybody in case they think I’m an alien.” “I think I’m doing what most people do that can’t read you step back from the crowd. Especially in a group or something because the worst thing that could ever happen is ‘oh (name) could you just read that line for me?’ Boof, your whole world just sinks, you know what I mean. There’s nothing worse and that’s why people always step back near the door just in case that happens.” “… and they were saying … ‘Oh, there was people at [a named group] and they can’t even read and write’ and I’m just sitting there going ‘oooh!’ Things like that. I wouldn’t like my own friends to know” “having to be one step ahead in case you’re handed a form or something.” As one focus group participant summed up, they felt they were always “wears you down.” He quite clearly thought that his literacy problems had contributed to him feeling socially isolated and “weak and depressed.”Some participants thought that both low literacy and its associated stigma had impacted on their health in ways not mediated by their difficulties with healthcare use or the management of health conditions at home. In particular, literacy-related stigma was seen as a negative influence on mental wellbeing. For example, Harry talked extensively about how the stigma of low literacy, the self-imposed exclusion from social activities and the perpetual concern to avoid disclosure Several other participants volunteered that they had been diagnosed with stress and other mental health problems including nervous breakdown, depression, eating disorder and panic attacks. There was nothing in their accounts to suggest that the diagnosing doctors had uncovered or explored low literacy as a possible contributing factor.Our early analyses of participants’ narratives suggested that early experiences of being labelled, stigmatised and discriminated against had been strongly influential in people’s behaviours in healthcare contexts and other social situations. This tentative theory was confirmed in subsequent interviews and during the two focus group discussions.It became evident from participants’ biographical narratives that the literacy-related fears that impaired their social engagement could usually be traced back to childhood experiences. Often without any specific prompting, participants offered information about their schooldays in their interviews. They recounted struggles both with literacy and with being labelled and discriminated against because of these. They reported being humiliated by teachers and picked on and bullied by other children. For example:“… my teacher thought making me read out to the school was one of the best things there was. It wasn’t. It was not. It was so… ..the children, they were the worst cos it was like another notch on… Oh (sighs).. ‘Well, she’s thick, stupid, now she can’t talk.’” These kinds of experiences and subsequent avoidance and cover-up behaviours recurred throughout participants’ life stories. The challenges they faced and the sometimes dysfunctional ways they reported behaving in healthcare contexts, such as limiting conversations with healthcare staff or covering up their lack of understanding to avoid anticipated stigmatisation was explicitly recognised by some as being directly linked to their childhood experiences:“I’m no asking questions cos at school when you ask … kids that ask questions and don’t know what they’re askin’ they get humiliated and humiliated and it goes on and on and on and then it suddenly becomes part of your make up…” think that everyone can read” and suggested a need to educate them about dyslexia and literacy problems. We also heard a variety of other suggestions for service improvement.Some participants clearly believed that healthcare staff “Not surprisingly, participants advocated the simplification of written information, including signage, appointment letters and instructions for medicine-taking, as well as healthcare leaflets. They also suggested that their understanding of clinical information and advice could be much improved if healthcare professionals explained things in lay terms rather than using medical terminology and jargon.would reveal their low literacy to healthcare professionals they felt they could trust, attempts by health services and health professionals to make it easy for people to ask for help with literacy activities without being judged seemed potentially useful–although they still did not like the idea that they might need to tell every health professional they met. Most participants, however, strongly preferred to avoid disclosing literacy difficulties and some suggested that their resolve to conceal their low literacy would be further strengthened if they were asked to identify themselves as needing help. These people favoured what are sometimes called ‘universal’ solutions, for example, simplifying written information, jargon-free simple explanations and advice or providing recordings of key consultations–for everyone, rather than as an option for those who are seen to require it [For the minority of participants who indicated that they quire it . ParticiThis study is among the first to elicit first-hand accounts of experiences with healthcare from people with low literacy living in the UK. We believe it is the first to focus on the ‘hidden population’ whose low literacy may not be obvious to healthcare staff and others. The study has illuminated previously unrecognised sources and implications of the stigma associated with low literacy, and has highlighted the difficulties that people can have with spoken as well as written communication in healthcare contexts. Most notably, we have presented findings that extend understanding of the ways that literacy-related stigma can undermine spoken interactions and relationships between patients and healthcare staff ,  impair phow literacy-related stigma can feature significantly in the causal pathways that link low literacy to poor health, for example, by prompting ‘cover-up’ behaviours that impede engagement with healthcare staff and so threaten the integrity of healthcare consultations, and by limiting information acquisition and help-seeking and so hampering self-management activities. Our study also tends to confirm that the kinds of literacy-related concerns identified by studies conducted in the USA can occur in the UK too. For example, participants highlighted the many aspects of health service use that currently depend on written communication, and the inaccessibility of these to people with low literacy. This has been recognised previously [The stigma associated with low literacy has been acknowledged previously in health-related research: Parikh et al. reported that of 58 patients with low literacy, two thirds (67.2%) indicated in response to structured survey questions that they had not told their spouses and 19% that they had told no one . Our stueviously -33. Theyeviously .One-to-one semi-structured interviewing generated data and insights that would not have been obtained by more structured, closed methods. In particular, by listening to personal biographical narratives we were able to identify explanations for participants’ guarded relationships with healthcare staff and their continued concealment of their low literacy. The focus groups allowed some of those interviewed previously and some new participants to comment on our interpretation of key findings and to discuss proposed service responses in more detail. Data were analysed using a recognised systematic approach.By recruiting participants via adult learning classes, we potentially limited the findings to people who were prepared to be open about their literacy issues–at least in some contexts. It would have been difficult to identify people who had not recognised or sought help for their low literacy in an ethically acceptable manner for research purposes only. Although participants in this study may have been more willing and able than some to acknowledge and address their literacy issues, their willingness and confidence appeared to be restricted to particular contexts such as accessing adult learning. There was no evidence in our data that their having revealed their low literacy in this particular context significantly influenced their disclosure behaviours in other contexts. Consistent with our interest in the ‘hidden population’, few participants had disclosed or sought help with their low literacy within health services.We achieved a diverse sample, although there were more women than men within it. We included some participants whose literacy difficulties had recently lessened to some extent as a result of their participation in adult learning. These people were able to talk about some issues relating to their low literacy that they had not recognised until they started attending the Adult Learning Centre and acquired a new perspective on them.Given the prevalence of low literacy, most frontline clinical staff in many developed countries will encounter people with literacy difficulties every day. This study highlights several implications for both health service policy and health professionals’ practice. In general terms, the study findings  lend support from patients’ perspectives for calls to make changes to healthcare systems and to the health information that is offered by health professionals, in order to make them more engaging for people with low literacy . This wiIn terms of the planning and provision of support for self-management, our study has highlighted a need to review and provide alternatives to peer-support activities, and especially group based training for people living with long-term conditions. Given the concerns about stigma and the avoidance strategies that we heard about from our study participants, group-based education is unlikely to be an attractive or effective option for people who struggle with literacy-related activities. To complement efforts to reduce the literacy demands that health service systems and processes make on health service users, interventions are also needed to raise professional awareness that low literacy is fairly common and potentially has a range of negative consequences for people’s willingness and ability to engage in healthcare and self-care. Training to promote non-discriminatory behaviours towards people who may struggle with literacy tasks would also be welcome. Even short basic interventions might serve to encourage simplified communication and a reduction in the use of ‘on the spot’ literacy activities.The findings of our study caution quite strongly against the use of formal literacy screening, particularly outside the context of an already established and trusted patient-clinician relationship. They reinforce previously expressed concerns about its potential to cause harm in the form of significant anxiety, shame and alienation ,42. AlthMost health literacy research, including the testing and evaluation of initiatives to improve health literacy or improve outcomes for those with low literacy, has been carried out in the US. The findings of this study have highlighted particular issues through first-hand accounts of people with low literacy with reference to the UK health system. While some suggestions for service improvements need not be tested, for example, the colour coding within the hospital environment, or awareness raising among healthcare staff, others would benefit from piloting and robust evaluation. These could include the use of Teach-back and similar techniques in clinical departments. As well as evaluating outcomes, research should focus on the acceptability of interventions to people with low and those with higher literacy levels.both written information and interpersonal communication are acknowledged and addressed, policy ambitions to improve the experiences, effectiveness and safety of healthcare, and to reduce social inequalities in health are unlikely to be realised.When health services and health professionals adopt practices that assume significant literacy skills, their effectiveness for a large but often hidden population of people with low literacy is limited. This study has shown that the stigma associated with low literacy, as well as the consequences of literacy-related mistakes, can impair people’s spoken engagement with healthcare staff, and potential to benefit from health services. Unless problems with The authors declare that they have no competing interests.PE formed the concept of the study, led on the study and topic guide design, carried out all interviews and focus groups, led on the analysis of the data and wrote the first draft of the article. VAE participated in the study and topic guide design, contributed to the analysis of the data and critically reviewed and revised the manuscript. BW participated in the study and topic guide design, contributed to the analysis of the data and contributed to the review and revision of the manuscript. All authors read and approved the final manuscript.VAE and BW were both formerly at the Social Dimensions of Health Institute, Universities of Dundee and St Andrews.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/13/319/prepub


These results demonstrate that the antinociceptive effect of DBV treatment can be significantly enhanced by modulation of adrenal medulla-derived epinephrine and this effect is mediated by peripheral β-adrenoceptors. Thus, DBV acupoint stimulation in combination with inhibition of peripheral β-adrenoceptors could be a potentially novel strategy for the management of inflammatory pain.The injection of diluted bee venom (DBV) into an acupoint has been used traditionally in eastern medicine to treat a variety of inflammatory chronic pain conditions. We have previously shown that DBV had a potent antinociceptive efficacy in several rodent pain models. However, the peripheral mechanisms underlying DBV-induced antinociception remain unclear. The present study was designed to investigate the role of peripheral epinephrine on the DBV-induced antinociceptive effect in the mouse formalin assay. Adrenalectomy significantly enhanced the antinociceptive effect of DBV during the late phase of the formalin test, while chemical sympathectomy had no effect. Intraperitoneal injection of epinephrine blocked this adrenalectomy-induced enhancement of the DBV-induced antinociceptive effect. Moreover, injection of a phenylethanolamine N-methyltransferase (PNMT) inhibitor enhanced the DBV-induced antinociceptive effect. Administration of nonselective  These results indicate that postganglionic sympathetic nerve endings do not play a role in DBV-induced pain reduction during the formalin test.We subsequently investigated whether catecholamines released from postganglionic sympathetic nerve endings alter the antinociceptive effects of DBV. To test this we performed a chemical sympathectomy using 6-OHDA. As illustrated in n = 7) significantly suppressed formalin-induced paw licking behaviors compared to that of vehicle-injected group . However, administration of epinephrine  significantly increased paw licking behavior during the late phase of the formalin test as compared to the vehicle-injected group (#P < 0.05). Coadministration of epinephrine (10 ug/kg) with DBV  significantly decreased the reduction in paw licking time produced by DBV treatment alone during the late phase of the formalin test (&&P < 0.01). Coadministration of epinephrine (10 ug/kg) with DBV  had no effect on licking behaviors during the early phase of the formalin test. These results demonstrated that epinephrine might be closely involved in both peripheral sensitization and DBV's antinociception in late phase but not early phase.In order to investigate whether pure epinephrine might have an influence on DBV-induced antinociceptive effects, we performed adrenalectomy and measured the formalin-induced pain behaviors. As illustrated in n = 7) significantly decreased pain behaviors compared to that of vehicle-injected group . Systemic DCMB injection together with vehicle  rather than DBV did not change formalin-induced pain behaviors as compared to the vehicle-vehicle-injected group in either the early or late phase of the formalin test . This drug combination had no effect on the early phase of the formalin test. Moreover, administration of a low dose of DCMB given prior to DBV treatment  did not change formalin-induced pain responses.Phenylethanolamine N-methyltransferase (PNMT) is an enzyme that converts norepinephrine to epinephrine in the adrenal medulla. We examined whether administration of the PNMT inhibitor, DCMB, alone or in combination with DBV treatment had any effect on formalin-induced nociceptive responses. Administration of DBV  significantly suppressed pain behaviors in comparison to vehicle-vehicle-injected group  + DBV + F, n = 7, resp.] had no significant effect on formalin-induced nociceptive behavior as compared to the control group during either the early or late phase of the formalin test at any of the doses tested. Similarly coadministration of phentolamine with vehicle  did not affect the paw licking time in either phase (n = 7) significantly decreased formalin-evoked paw licking time compared to that of vehicle-injected group , and administration of a β-adrenergic receptor antagonist, propranolol with vehicle , had no effect on this formalin-induced pain behavior during either the early or late phase. On the other hand, coadministration of propranolol with DBV  significantly decreased the paw licking time as compared to the DBV-treated group during the late phase, but not during the early phase of the formalin test (#P < 0.05). Additionally, administration of another β-adrenergic receptor antagonist, nadolol (which cannot cross the blood-brain barrier), with vehicle , did not change formalin-induced pain behaviors as compared to vehicle-treated group in either the early or late phase of the formalin test. Similar to propranolol, injection of nadolol in combination with DBV treatment  produced a significant antinociceptive effect as compared to the vehicle-DBV-treated group during the late phase of the formalin test (##P < 0.01). The group of mice receiving vehicle plus DBV treatment , or the β2-adrenergic receptor antagonist, ICI-118,551 , with DBV, to determine the potential contribution of each β-adrenoceptor subtype to the antinociceptive effect of DBV on formalin-induced nociceptive behaviors. As shown in n = 7) significantly decreased pain behaviors compared to that of vehicle-injected group , and intraperitoneal administration of either atenolol and ICI-118,551 with vehicle  did not change formalin-induced pain behaviors as compared to the vehicle-vehicle-injected group during either the early or late phase of the formalin test. Administration of a low dose of atenolol or ICI-118,551 in combination with administration of DBV  had no effect on formalin-induced nociceptive responses as compared to the vehicle-DBV-treated group, whereas administration of a high dose of atenolol or ICI-118,551 with DBV  significantly decreased the paw licking time as compared to the vehicle-DBV-treated group during the late phase but not during the early phase of the formalin test .We next coadministered either the α2-adrenoceptors [α in a mouse air pouch model of inflammation. Thus, DBV injection can produce both antinociceptive and anti-inflammatory effects. It has also been shown that adrenalectomy significantly reduces this DBV-induced suppression of leucocyte migration and TNF-α expression [DBV injection into an acupoint has been reported to produce a powerful antinociceptive effect in a variety of animal models of acute and chronic pain. Several possible mechanisms have been proposed to explain the biological processes underlying this DBV-induced antinociceptive effect. For example, it has been shown that DBV injection can activate descending bulbospinal noradrenergic pathways, which in turn activate spinal oceptors , 22. On pression . In thispression . While tIn the present study, we demonstrated that injection of a high dose of DBV significantly reduces pain behaviors during the late phase of the formalin test, and this DBV-induced antinociceptive effect can be dramatically enhanced by adrenalectomy. On the other hand, adrenalectomy itself had no influence on formalin-induced pain responses. Recently, several investigators have reported that adrenalectomy increases the antinociceptive effect of several analgesics and decreases the hyperalgesia resulting from vagotomy. In this regard, elimination of HPA axis function through adrenalectomy potentiates the antinociceptive effect of the calcium channel blocker, nifedipine, and attenuates its analgesic tolerance . It has Chemical sympathectomy has been reported to enhance the pain-attenuating effect produced by the alpha(2)-adrenoceptor agonist, MPV-2426 . In thisβ-adrenoceptors mediate epinephrine-induced hypersensitivity, and this β-adrenoceptor-mediated hyperalgesia is associated with both PKC and PKA second-messenger systems [In order to evaluate whether increases in peripheral epinephrine can reverse the potentiation of DBV-induced antinociception in adrenalectomized mice, epinephrine was intraperitoneally injected in adrenalectomized mice. The injection of exogenous epinephrine increased peripheral nociception in late phase and restored the DBV-induced increase in antinociception in adrenalectomized mice. These results demonstrated that epinephrine injection is closely involved in peripheral sensitization in late phase and reversed the adrenalectomy-induced facilitation of DBV's antinociceptive effect in comparison to DBV's effect observed in normal mice. It is well established that increases in peripheral epinephrine can affect peripheral nociception. Khasar et al. determined that mechanical hypersensitivity induced by intraplantar injection of epinephrine in the rat was reduced by propranolol suggesting that peripheral  systems , 20. SinN-methylation of norepinephrine, a reaction catalyzed by PNMT, using a cosubstrate and methyl donor, S-adenosylmethionine (Ado-Met). As a regulator of epinephrine production, PNMT serves as a marker for adrenergic function [Subsequently, we examined whether the suppression of adrenal medulla-derived epinephrine using a PNMT enzyme inhibitor or a peripheral epinephrine receptor antagonist could also potentiate the DBV-induced antinociceptive effect. Epinephrine is synthesized by function . Giordanfunction . These fα- and β-adrenoceptors subtypes. The activation of these receptors via an increase in peripheral epinephrine can lead to peripheral hypersensitivity to noxious stimulus [α-adrenoceptor antagonist, phentolamine, was used to examine the role of α-adrenoceptors in DBV-induced antinociception. Since phentolamine pretreatment did not affect DBV-induced antinociception, it is reasonable to assume that α-adrenoceptors are not associated with DBV-induced antinociception. On the other hand, propranolol, a nonselective β-adrenergic antagonist, significantly potentiated DBV-induced antinociception. In order to examine the role of pure peripheral epinephrine, we also used another β-adrenergic antagonist, nadolol, which does not cross the blood-brain barrier. These results were similar to those in propranolol-treated mice or adrenalectomized mice, indicating that facilitation of DBV-induced antinociception was mediated by inhibition of peripheral β-adrenoceptors, not central nervous system associated β-adrenoceptors. Furthermore, we showed that coadministration of either the β1-selective adrenergic receptor antagonist, atenolol, or the β2-selective adrenergic receptor antagonist, ICI-118,551 with DBV, potentiated the antinociceptive effect of DBV alone. Collectively, these findings demonstrate that DBV treatment results in the release of adrenal medulla-derived epinephrine, which leads to increased peripheral sensitization via activation of β1- and β2-adrenoceptors, and ultimately leads to partial inhibition of the DBV-induced antinociceptive effect in the mouse formalin test. Thus, injection of DBV into an acupoint has an initial antinociceptive effect on the late phase of the formalin test but at the same time affects the adrenal medulla to increase epinephrine secretion leading to a paradoxical reduction in DBV's antinociceptive effect. Finally, we examined which subtype of adrenergic receptor is involved in the negative modulation of this DBV-induced antinociceptive effect. It is well established that peripheral epinephrine serves as an endogenous ligand, which can act on both stimulus , 33. In α-adrenergic antagonists did not alter DBV-induced antinociception, whereas β-adrenergic antagonists significantly increase DBV-induced antinociception. Collectively, these results demonstrate that suppression of adrenal medulla-derived epinephrine, which acts on β-adrenoceptors, can potentiate DBV-induced antinociceptive in the mouse formalin test, suggesting that DBV acupoint stimulation performed in combination with administration of peripheral β-adrenoceptor antagonists would be a potential novel strategy for the pain management. The present study shows that adrenalectomy significantly potentiates DBV-induced antinociception, while chemical sympathectomy has no effect. In addition, administration of exogenous epinephrine reverses the enhanced antinociception produced by DBV in adrenalectomized animals. Pretreatment with