Reasons for poor guideline adherence in acute gastroenteritis (AGE) in children in high-income countries are unclear, but may be due to inconsistency between guideline recommendations, lack of evidence, and lack of generalizability of the recommendations to general practice. The aim of this study was to assess the quality of international guidelines on AGE in children and investigate the generalizability of the recommendations to general practice.Guidelines were retrieved from websites of professional medical organisations and websites of institutes involved in guideline development. In addition, a systematic search of the literature was performed. Articles were selected if they were a guideline, consensus statement or care protocol.Eight guidelines met the inclusion criteria, the quality of the guidelines varied. 242 recommendations on diagnosis and management were found, of which 138 (57%) were based on evidence.There is a large variety in the classification of symptoms to different categories of dehydration. No signs are generalizable to general practice.It is consistently recommended to use hypo-osmolar ORS, however, the recommendations on ORS-dosage are not evidence based and are inconsistent. One of 14 evidence based recommendations on therapy of AGE is based on outpatient research and is therefore generalizable to general practice.The present study shows considerable variation in the quality of guidelines on AGE in children, as well as inconsistencies between the recommendations. It remains unclear how to asses the extent of dehydration and determine the preferred treatment or referral of a young child with AGE presenting in general practice. In acute gastroenteritis (AGE), a common childhood illness occurring worldwide, the most threatening complication is dehydration. In high-income countries, implementation of oral rehydration therapy (ORT) has not been as successful as in low-income countries,2. In DuImplementation of a guideline on AGE management in children can lead to a reduction in invasive procedures and hospital admissions, and shorter hospital stays ,8,9. BecHowever, although physicians consider guidelines to be helpful, negative attitudes about the goal of the guideline, the producers of the guideline, the practicality of the guideline, as well as controversies and/or inconsistencies between guidelines regarding recommendations, can reduce adherence -16. The The aim of the present study is to assess the quality of international practice guidelines for the management of acute diarrhea in children in high income countries with the Appraisal of Guidelines, Research and Evaluation (AGREE) instrument. We aim to investigate the consistency of the recommendations, evaluate the quality of evidence and the practicability of these recommendations to general practice, where most children with AGE initially present.To identify guidelines on acute diarrhea in children, searches were made in websites of professional societies in the clinical fields of paediatrics, gastroenterology and general practice, and websites of institutes involved in guideline development. On each website we used the available search technique, searching for diarrhea and/or gastroenteritis. In addition, a systematic search of the literature was performed using Medline, Embase, Cinahl and the Cochrane Library database. The search term combination captured the concept diarrhea, practice guidelines and children, using a variety of index terms, text words and word variants. No limitations were used (see Appendix 1).Clinical practice guidelines were defined to be "systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances" ,18. SeleSelection of articles was performed by two independent researchers. Disagreements about inclusion or exclusion were resolved by consensus.The quality of a guideline was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument . The AGRData were extracted using a predefined form, covering the following items: 1) general information: guideline developers; GP in the development team (yes/no); method used for assessing the level of evidence, i.e. the ranking system used to stratify evidence by quality, for which multiple systems have been developed -24, 2) rAll recommendations were grouped by subject and the number of guidelines making a recommendation on a subject was summed. If more than 50% of these guidelines made an identical recommendation, the recommendation was considered consistent.For recommendations based on published evidence, an appraisal about the generalizability to general practice was made. Recommendations were defined as applicable to general practice if the evidence came from studies in general practice or an outpatient non-referred population. A recommendation was not applicable to general practice if it was based on evidence emerging from studies in a hospital setting or a referred population. If evidence came from a mixed population (outpatient as well as inpatient), it was assessed if a separate analysis was performed to evaluate differences in outcome between in- and outpatient populations, if this was not the case, generalizability was considered inconclusive.For recommendations based on consensus, recommendations were said to be applicable to general practice if a GP was involved in guideline development. The assumption was that the GP would have controlled for feasibility and applicability of the recommendation in general practice.Without predefined definition most guidelines classified the extent of dehydration differently. Therefore, we defined three subgroups based on the WHO definition : no  and screening of titles and abstracts, 62 citations were suitable for full-text evaluation. After the initial appraisal, 21 citations were evaluated in detail; one additional duplicate was found . Nine doTable The quality of the guidelines was heterogeneous, ranging from poor to excellent quality Table . The NICIn total, 242 recommendations on diagnosis and management were found, of which 138 (57%) were based on evidence (Table Five guidelines stated the LofE of a recommendation. Four ranking systems for the classification of the LofE were used. Two ranking systems (CPS and Muir Gray) combined quality of evidence and strength of the recommendation in one score containing a number and a letter. Two ranking systems classified quality of evidence only. Quality of evidence could be classified on a range of 5 to 12 levels. The best score for quality of evidence was appointed to a systematic review of multiple well designed RCTs ; a systematic review (CCHMC) or at least one properly randomized controlled trial (CPS). Because of the heterogeneity of the definition of the classes, we refrained from comparing the outcome of the ranking systems.Categories of dehydration were defined differently. The NHG guideline only described the categories 'no' and 'severe' dehydration. The ESPGHAN guideline encouraged the use of categories, but did not define how to categorize dehydration. It did mention, however, the signs for 5% dehydration, and these signs were placed in our mild-moderate group. The remaining guidelines used categories, with  or without (WGO and NICE) percentages, for the extent of dehydration; the signs and symptoms were placed in our categories accordingly.Table There were no recommendations for the diagnosis of dehydration based on consensus only. All guidelines provide diagnostic signs/symptoms and relate them to different categories of dehydration. However, there is a large variety in the classification of symptoms to the different categories. ''Altered mental status'; 'normal to increased heart rate'; 'normal to decreased pulses'; 'normal to fast or deep (acidotic) breathing'; 'sunken eyes'; 'decreased or absent tears'; 'dry mucous membranes'; 'decreased skin pinch'; 'normal to prolonged capillary refill' and 'warm to cool extremities' were consistently related to one of the categories of dehydration. But only 'decreased skin pinch' was consistently related to mild-moderate dehydration in all guidelines. Inconsistent recommendations were 'thirst'; 'decreased urine output'; 'blood pressure' and 'sunken fontanel'. The sign 'normal to slight increased thirst' was the only sign consistently mentioned (in > 50% of guidelines) for the subgroup 'no dehydration'. Nine signs were consistently mentioned for the subgroup 'mild to moderate dehydration' and four signs were consistently mentioned for the subgroup 'severe dehydration' Table .In two guidelines , the evidence for the assigned symptoms for assessing dehydration status is not stated. Four guidelines  use the study of Steiner et al. , a meta-In total, 22 recommendations on the management of AGE were made: 14 recommendations were based on evidence and 8 on consensus. Seven recommendations based on evidence and 5 based on consensus are consistent. All guidelines, except one (CCH) recommend that hypo-osmolar rehydration solution should be used to prevent or treat dehydration (evidence based). Table All guidelines state that breastfeeding should be continued throughout rehydration; an age-appropriate diet should be started during or after initial rehydration (4-6 hours) and dilution of the formula or the use of a milk-free formula is unnecessary (evidence based). These recommendations are based on a review of Brown et al.  and a laFor the use of probiotics, the recommendations are inconsistent. The recommendations are based on 19 different studies and 5 of these studies, all meta-analyses -58, wereOne recommendation was based on an outpatient population and is therefore generalizable to general practice. For all recommendations based on a mixed population, no separate analysis correcting for study setting was performed, therefore applicability remains inconclusive.Table For all consistent recommendations based on consensus, a GP was present in guideline development. They are therefore applicable to patients in general practice.Eight guidelines on the management of AGE in children were evaluated. Based on quality criteria as defined by the AGREE instrument, the reviewers recommended 4 guidelines for use in daily practice. There is a large variety in the classification of symptoms to different categories of dehydration. Of 14 signs and symptoms for assessing dehydration, 'decreased skin pinch' was the only sign mentioned in all guidelines. None of the signs were studied in general practice.It is consistently recommended to use hypo-osmolar ORS to treat or prevent dehydration. This recommendation was based on evidence of good quality. The recommendations regarding ORS dosage, however, are inconsistent.Except for probiotics, all recommendations on therapy are consistent.Recommendation for use in daily practice was mostly influenced by the items 'rigour of development', 'clarity and presentation', and 'editorial independence'. Guidelines receiving the highest scores on these items  received a 'recommend' or 'strongly recommend' rating.Lowest scores were obtained for the items 'stakeholder involvement' and 'applicability'. This is in accordance with the findings of Alonso-Coello et al , who perThree guidelines did not state the ranking system for the classification of the LofE of a recommendation. In addition, it was an intriguing finding that the evidence for a comparable recommendation could differ between guidelines, and vice versa that the recommendations could vary despite the same evidence. Quality of the evidence is an important indication for the strength of a recommendation, and should be consistently measured. We assume that non-adherence might be explained by the lack of consensus about quality of evidence, one of the most important indicators for the strength of a recommendation.But obviously quality of evidence is not the only determinant of the strength of a recommendation. According to the GRADE Working Group,61, fourA uniform ranking system for the classification of the strength of recommendations is needed to make guideline-use more comprehensible and therewith increases adherence.The recommendations on signs related to dehydration are consistent, whereas the classification of signs in categories of dehydration is not. Even though hospital based evidence might, to some degree, be used for general practice, the generalizability of the recommendations for general practice is suboptimal. As a consequence, it remains unclear which signs are most important for classifying the extent of dehydration in a child with AGE, and to decide which child should be referred or admitted to a hospital.The recommended ORS regimen for each category of dehydration differed between guidelines. Possible reasons for this heterogeneity are the differences in cut-off points defining categories of dehydration, and the fact that expert opinions rather then evidence was used to formulate recommendations. As for now the optimal ORS regimen remains unclear.The recommendations on prescribing probiotics are inconsistent and are evidently subject to interpretation by the guideline team. Only two guidelines  provide arguments for their interpretation of the available evidence, and conclude that there is insufficient evidence for recommendations on probiotics.For none of the recommendations based on a mixed population it could be assessed if the study setting influenced the outcome, nor was this difference discussed in any guideline. For the guideline user, generalizability to general practice remains unknown.Appraisal of quality was performed by two reviewers, where preferably four appraisers are needed. Because we specifically wanted to review the guidelines from the perspective of the GP and both appraisers were GPs, ánd because the ranges of scores were small, we feel another two GPs would not give more precise or valid estimates of quality. Even though a thorough search of possible guidelines was performed, the possibility remains that we missed a guideline. We assumed that if a recommendation was based on consensus, because evidence was lacking, the presence of a GP gave the best available indication that applicability, and balance between benefit and harm had been evaluated from the perspective of the GP. We realise that this assumption is disputable.The present systematic review shows considerable variation in the quality of guidelines on AGE in children, as well as considerable inconsistencies between the recommendations. In 43% the quality of the evidence could not be interpreted because no level of evidence was stated and most recommendations are not generalizable to general practice. Although we know that ORT should be given, it remains unclear 'how' or to 'whom'; this may explain why adherence to treatment is currently suboptimal.This study reveals implications for further research. Future studies, particularly in general practice, need to determine the value of clinical signs and symptoms in assessing dehydration. Second, the optimal ORS dosage for each grade of dehydration should be established, so that consistent recommendations can be made. Third, we need to investigate the considerations of clinicians to prescribe medication to children with AGE, and assess whether these considerations are valid. Finally, a uniform grading system, such as the GRADE system, should be used to grade the strength of guideline recommendations.AGE: Acute Gastroenteritis; AGREE: Appraisal of Guidelines for Research and Evaluation; ARM: Guideline by Armon et al; CCH: Guideline by Cincinnati Children's Hospital Medical Center; CDC: Centers for Disease Control and Prevention; CPS: Guideline by the Canadian Paediatric Society; ESP: Guideline by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and European Society for Paediatric Infectious Diseases; GP: General Practitioner; LofE- Level of Evidence; NHG: Guideline by the Nederlands Huisartsen Genootschap; NICE: Guideline by the National Institute for Health and Clinical Excellence; ORS: Oral Rehydration Solution; ORT: Oral Rehydration Therapy; WHO: World Health Organisation; WGO: Guideline by the World Gastroenterology Organisation.The authors declare that they have no competing interests.JB and MB contributed equally to this work. Both authors read and approved the final manuscript.Search strings databases and researched websitesPubmed((child OR infant) OR ("Child"[Mesh]) OR ("Infant"[Mesh])) AND ((((guideline) OR (practice guideline) OR (consensus development) OR (recommendations)) OR ("Guideline "[Publication Type])) AND ((diarrhea OR diarr*) OR (("Diarrhea"[Mesh]) OR ("Gastroenteritis"[Mesh]))))Embase('diarrhea'/exp OR 'gastroenteritis'/exp OR gastroenteritis OR diarrhea) AND (guideline OR 'practice guideline'/exp OR consensus OR 'consensus'/exp OR recommendations) AND (child or 'child'/exp)Cochrane("Diarrhea"[Mesh]) OR ("Gastroenteritis"[Mesh]) AND guidelineCinahl((MH "Practice Guidelines") or guideline or practice guideline or recommendation or consensus) AND ((MH "Diarrhea") or (MH "Gastroenteritis") or diarrhea or gastroenteritis or diarr*) AND ((MH "Child") or child)Websites: (diarrhea and/or gastroenteritis)http://www.guideline.gov • http://www.tripdatabase.com (TRIP database)• http://www.cma.ca • http://www.worldgastroenterology.org (World Gastroenterology Organisation)• • http://nhg.artsennet.nl/home.htm (Nederlands Huisartsen Genootschap)http://www.aap.org (American Academy of Pediatrics)• http://www.who.int • http://www.cdc.gov (Centers for Disease Control and Prevention)• http://www.pediatriconcall.com• http://www.library.nhs.uk • http://www.emedicine.medscape.com• http://www.childhealthfoundation.org • http://www.racgp.org.au • http://www.rcgp.org.uk • http://www.nice.org.uk • http://www.sign.ac.uk (Scottish Intercollegiate Guidelines Network (SIGN)• http://clinicalevidence.bmj.com • • www.gfmer.ch http://www.acponline.org (American College of Physicians)• http://www.nzgg.org.nz/ • • www.cbo.nl • www.nvk.pedianet.nl (Nederlandse Vereniging voor kindergeneeskunde)http://www.espghan.org  to 4 (strongly agree) is given by each appraiser after which a standardised domain score is calculated by summing all the scores of the individual items in a domain, and by standardising the total as a percentage of the maximum possible score for that domain. An overall assessment leads to recommendations for use of the appraised guideline.http://www.agreetrust.orgFor further information, see The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/12/134/prepub


Tens of thousands of healthcare workers worldwide can only wear a plain wedding ring at work, if any at all. This arose from policies citing early laboratory evidence that rings can carry clinically relevant bacteria, but with little supporting clinical data. Policies that are both invasive and perceived as lacking evidence create a broader scepticism of infection control guidelines: it is therefore important to regularly review the evidence for such guidance.A systematic literature review was performed of studies investigating the infection risk of ring wearing by healthcare workers. PubMed, Cochrane Library and clinical trials registries were searched. Data was extracted on study design and quality, and the following outcomes: hospital acquired infection (HAI) rates, bacterial transmission, and bacterial contamination of healthcare workers’ hands.Two interventional randomised controlled trials (RCTs) and ten observational studies were identified. No study investigated an association between ring wearing and HAI rates. The RCTs were very small and used hand colonization as the primary outcome. One RCT found higher colonization of hands of healthcare wokers randomised to wear rings than those not wearing rings, whereas the other RCT found no difference. One observational study assessed bacterial transmission through handshaking and found the presence of a ring did not result in higher transmission. Three observational studies found higher bacterial contamination of hands with rings, and five studies found no difference. The presence of rings did not result in higher contamination after handwashing in most studies. No study identified a significant increase in hand contamination with multiple rings compared with one ring, nor between different types of ring.No direct evidence was found that healthcare workers wearing rings results in higher HAI or bacterial transmission rates. Most studies did not identify higher contamination associated with ring wearing; furthermore, the clinical significance of a statistical difference in the number of colony forming units is unclear. Guidelines could benefit from reconsidering ring wearing guidance, and focussing on interventions with a more defined evidence base; fewer intrusions into healthcare workers’ personal autonomy may increase willingness to participate in other important interventions.None declared


Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans.The simian malaria parasite, After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment. Plasmodium knowlesi is a malaria parasite found in monkeys which can infect humans via mosquito bites. People infected with the P. knowlesi parasite can suffer severe disease and death yet this disease has often been misdiagnosed as a different malaria type and its geographical distribution is largely unknown. The lack of data on human infections in much of Southeast Asia means a simple map of reported cases would likely misrepresent the extent of the disease. Instead we evaluated and ranked a range of evidence types according to how informative they are about the presence of an infection risk to humans and we mapped this ranked information. This highlighted those geographical areas where new data on the monkey and mosquito species involved in the infection of humans would add most to our knowledge of the full range of factors involved in disease risk. The resulting map highlights known locations of the parasite, and areas where presence of the disease in humans is unknown but possible. Plasmodium knowlesi parasite, found in wild monkey populations, is a serious public health concern yet almost nothing is known about its geographical extent. It is known to cause severe and fatal disease in humans P. falciparumP. knowlesi-specific molecular diagnostic techniques are only used to confirm diagnosis by microscopy in one area, Malaysian Borneo, whereas human cases have been reported from Brunei The P. knowlesi is a truly neglected tropical disease and there are substantial obstacles to defining the geographical extent and risk of this disease. The symptoms of the disease in humans overlap with those caused by other malaria parasites P. knowlesi from P. malariae (a more benign infection) and P. falciparum  and in routine practice P. knowlesi is also misdiagnosed as P. vivaxP. knowlesiP. falciparum or P. vivax . These two factors provide an opportunity to map the potential reservoir of the parasite in the absence of human case data. Defining areas of risk, however, is further complicated by the fact that much of the potential parasite range is spread over a large archipelago of many thousands of islands separated by substantial distances; a biogeographical factor often neglected in global disease mapping exercises and of particular relevance to a zoonotic vector-borne disease with a reservoir in wild mammal populations.P. knowlesi malaria, however, there is insufficient direct evidence of disease presence/absence to replicate this approach. In this study, instead of assessing the consensus of evidence for disease presence/absence, evidence on locations of host and vector species, as well as human case data, were combined to obtain ranked scores for the capacity to support an infectious reservoir. We first reviewed the evidence on non-human primate hosts and transmission by different anopheline vector species and then gathered data on the ranges of these two groups, as well as the locations of known human cases of the disease. This information was used to assess the potential of each province or island to support an infectious reservoir. The final output is a comprehensive summary of the current state of evidence for a P. knowlesi reservoir. Importantly, it is not a map of the likelihood of a reservoir occurring within an area but it does highlight areas where evidence is lacking. The results of this study allow us to propose priorities for the new data that are urgently needed in order to understand the spatial variation in risk to humans from this disease.Previous studies have defined a range for neglected diseases such as dengue by reviewing the consensus of evidence for the presence/absence of the disease at each location 2 in area were defined as separate geographical units. Within the archipelago, islands within 10 km of each other were grouped together and islands less than 100 km2 and more than 10 km away from any other island were disregarded. Following these approximate guidelines we were able to divide this region of 19 countries spread over approximately 25,000 islands into 475 geographical units.Maps of human disease often use administrative divisions to subdivide countries. This is the structure in which much national health data are provided and is a useful format to feed results back to public health agencies. For zoonotic diseases, however, the distributions of wild host species will not necessarily map closely to administrative divisions. In this instance, the majority of cases reported to-date are located within a huge archipelago where administrative divisions can encompass multiple islands separated by large distances. For this study we took a mixed approach using administrative divisions to subdivide the mainland and the largest islands in the archipelago . The largest administrative division in the area of study, Xizang Zizhiqu (the Tibet Autonomous Region) in China, was further divided into level two divisions. Additionally, islands greater than 25 km from the mainland and greater than 200 kmP. knowlesi parasite  have only been available for the last decade so this dictated the period reviewed (2004 to 2013). All data on wild animals tested for P. knowlesi infection were extracted and used to determine which alternative host and vector species would contribute to the next stage of the work.We conducted a literature survey in Web of Knowledge using the terms ‘knowlesi’, ‘zoono* and malaria’, ‘monkey and malaria’ to collate journal articles on the parasite and then excluded studies conducted solely in the laboratory (e.g. immunity studies using a rhesus-knowlesi model). The bibliography of each article was then searched for further published sources of information and authors working in locations of particular interest were contacted. The search was completed on 30 September 2013. Molecular techniques that can distinguish the Each subnational area was assigned a score based on three classes of evidence: the presence of the parasite; the presence of a monkey host species, and; the presence of a malaria vector species known to bite humans . Each arThe scores assigned provide a simple ranking. In summary, confirmation of a human infection ranked highest with +9 overriding all other evidence, then confirmation of sporozoites in a human-biting vector scored +8. Confirmation of a monkey infection was combined with the score for presence of a human malaria vector (see below) to give a maximum score of +7. In the absence of the parasite itself, presence of both a known host species and a known vector species scored +6. Combinations of known/putative host species presence and known/putative vector species presence (see below) scored from +2 to +5. Combinations of host species absence, vectors species absence and absence of any malaria in humans (see below) scored values ranging from −1 to −9. In locations where both presence and absence indicators were found, the respective scores were added together.P. knowlesi-specific molecular identification methods or 2) a combination of microscopy and molecular techniques that distinguish P. knowlesi from P. falciparum and P. malariae, were extracted from the library of published literature described above. The location of occurrence was defined as the location of infection, not the location of symptom onset or diagnosis, and studies that could not identify the location of infection (to state/island level) were excluded. For each occurrence, the date of study, diagnostic technique(s) and subnational location of infection were extracted. Only the most recent infection from each area/island was retained. In two studies we could not distinguish between adjacent administrative divisions so these areas were combined (at the Myanmar/China border and at the Myanmar/Thailand border). Two reports of human cases from Brunei did not meet the inclusion criteria because one used microscopy only for diagnosis All occurrences of the parasite, identified using either 1) P. knowlesi cases and, conversely, divisions within these countries that report no malaria cases are less likely to have undetected P. knowlesi cases. Areas within malaria endemic countries reporting no malaria cases were defined using the 2012 World Malaria Report P. falciparum and P. vivax defined by the Malaria Atlas Project to classify each area There were no survey results that provided clear evidence for absence of the parasite in an area. In countries that routinely report cases of the four human malarias, occurrence of these other species may mask Macaca fascicularis  and M. nemestrina (the pig-tailed or Southern pig-tailed macaque). Two other species have been identified as hosts, Trachypithecus obscuras and Presbytis melalophus, however the ranges of these species fall entirely within the range of M. fascicularis, therefore, these areas already receive the maximum score for presence of a known non-human host species.The ranges for M. fascicularis and M. nemestrina were initially defined using the International Union for Conservation of Nature (IUCN) ranges P. knowlesi infections in M. nemestrina monkeys, this monkey species was divided by taxonomists into M. nemestrina and M. leonina (the Northern pig-tailed macaque). We made the decision to include both species because, although it is likely that the monkeys tested were M. nemestrina (as currently classified), human cases have been found outside the ranges of M. nemestrina and M. fascicularis but within the range of M. leonina. A lower score of +2 was assigned to areas within the M. leonina range.Based on the data collected from published studies see , we madeP. knowlesi parasites in the wild, and laboratory studies have shown that other species can be infected by this parasite The IUCN ranges were combined for all three macaque species and a score of −1 was assigned to areas outside the combined host species range (excluding locations with introduced populations) and −2 for those areas more than 100 km outside this range. The maximum possible negative score was not assigned because we do not have a definitive list of primate species that can host a reservoir of Anopheles species are capable of transmitting P. knowlesi  known to transmit malaria to humans but of unknown P. knowlesi vector status was assigned a lower score of +2. The species in this category were the Fluviatilis Complex, the Minimus Complex, An. koliensis, An. aconitus, An. annularis, the Culicifacies Complex and An. flavirostris. Finally, where no vector species from either of the above two classes were present, presence of any of the other human malaria vectors was assigned a lower score of +1 to reflect the fact that these species are known to have the capacity to transmit malaria parasites to humans P. knowlesi. To assess the presence of all three vector classes, we used the predicted distributions generated by the Malaria Atlas Project Based on evidence from the published literature on which lesi see  and evidP. knowlesi but much stronger evidence for the definitive list of vectors that transmit malaria to humans.A score of −4 was assigned to areas outside the combined range of the vector species and −6 to areas 100 km outside this range. This score  reflected the fact that there is a lack of evidence for the definitive list of vectors transmitting The scores were combined as shown in To test the scores generated, the scores that would have been obtained if evidence for presence of the parasite itself was excluded were compared between areas with confirmed parasite presence and those of unknown parasite status. A jackknife approach was then used to assess the dependence of the final scores on each individual factor. Each individual factor was excluded and the scores were re-calculated. The results were compared between areas with confirmed parasite presence and those of unknown parasite status, and the relative ranking of all areas before and after each factor was removed were compared. To assess the predictive power of the scores, the area under the receiver operating characteristic curve (AUC) was calculated for each version of the scoring system created when single factors were removed in turn (with parasite presence excluded) P. knowlesi infection in wild monkey populations is summarised in M. fascicularis and M. nemestrina populations in Sarawak in Malaysian Borneo and lower prevalences in Singapore, Kuala Lumpur and Pahang States in Malaysia, Narathiwat and Ranong Provinces in Thailand, and North Sulawesi Province in Indonesia. Older studies (pre-2004) have also found infected M. fascicularis monkeys in Cebu, Philippines The review of published studies of P. knowlesi in wild mosquito populations is summarised in P. knowlesi transmission is unknown. In the areas studied, there is evidence that Anopheles latens from the Leucosphyrus Complex and members of the Dirus Complex transmit P. knowlesi. Members of both Complexes are known to transmit human malarias. Earlier studies (pre-2004) have implicated members of the Hackeri Subgroup in transmission of P. knowlesi within monkey populations in Peninsular Malaysia P. knowlesi, however, these studies also confirmed that the most effective vectors, of those tested, were members of the Leucosphyrus Group The review of published studies of The information from the reviews of monkey hosts and of vectors was used to generate parasite, host and vector evidence scores for each geographical area and these were combined with the evidence for parasite presence to give an overall score representing the evidence for potential presence of a parasite reservoir that is infectious to humans shown in . The indP. knowlesi and no factors indicating absence of a reservoir (presence of the parasite itself is unknown); areas of weak evidence for the presence of a full set of reservoir prerequisites; and areas where there is evidence for an absence of reservoir prerequisites. It is important to note that M. fascicularis and M. nemestrina) have not been found in this area but M. leonina is present. Studies that have investigated malaria parasites in the monkey populations in this area have not yet found evidence of P. knowlesi infection in any of the species present .M. fascicularis but there is no evidence of any known or putative monkey host species populations on the northern islands, including Smith Island and Car Nicobar P. knowlesi infections in these locations  comes from a single study of human malaria cases in the Andaman and Nicobar Islands P. knowlesi reservoir existing on the northern islands of the Andaman and Nicobar Islands, including the possibility of human-to-human transmission and the possibility of a parasite reservoir in the captive long-tailed macaques at Port Blair's zoo Two neighbouring areas with confirmed parasite presence scored only +1 when the evidence for parasite presence itself was excluded. These were two islands in the north of the Andaman and Nicobar Islands; Smith Island and Car Nicobar. The southern islands fall within the range of P. knowlesi reservoir. If this study had covered a broader geographic area, the number of these areas would be much higher.Finally, P. knowlesi reservoir capable of infecting humans has been confirmed and those that support known hosts and vectors. In the absence of routine confirmation of P. knowlesi in human cases, and of definitive lists of host and vector species, it is harder to map areas of known disease absence. We have, however, been able to classify the rest of the region into areas that range in the evidence for their capacity to sustain a parasite reservoir that is infectious to humans, based on the current state of knowledge. Both the review of species shown to host and transmit P. knowlesi, and the ranking of the evidence for a parasite reservoir, highlight the urgent need for more evidence in large parts of the region of study and provide information on the types of data that are needed. The results of this study highlight priority geographical areas for future study that would enable us to build a more precise map. Areas of Indonesia , parts of the Philippines, Cambodia, S. Thailand, S. Myanmar and S. Vietnam support both the known hosts and the known vectors, and are obvious targets for studies investigating new locations of parasite infections and disease prevalence. Locations with high disease potential could be targetted further by identifying areas that report cases of P. malariae malaria when using microscopy for routine species confirmation. The blank cells in By assessing the evidence in a systematic way based on the current state of knowledge, we have been able to map subnational areas where a P. knowlesi studies conducted outside of Malaysia used the same assumptions about host and vector species as this study, when choosing their study locations, leading to a bias in locations where the parasite has been found. Evidence from human cases in returning travellers, however, may not be subject to the same biases for presence of presumed host and vector species. All of the published cases of P. knowlesi infection in returning travellers, diagnosed outside the region, involve patients that had spent time in one or more subnational areas where both the known monkey hosts and the known vectors are present P. knowlesi  while surveys of macaque populations in Nepal (average score −1 = weak evidence/absence of reservoir prerequisites) and Bangladesh (average score 1.67 = weak evidence) also found no evidence of P. knowlesi infection .When parasite presence was excluded from the scoring system, the predictive power of the scores generated from the evidence on hosts, vectors and human malarias was very good (AUC = 0.8146). It is important, though, not to assume that the factors used in this scoring system give the full picture. It is likely that the researchers who designed the P. knowlesi incidence has increased at this location over the last decade The sensitivity analysis presented here suggests that some of the factors included in this study could be removed and the scores would still perform as well, however, the areas with confirmed parasite presence are a potentially biased sample and so it would be unwise to remove any potential factors until we are closer to a definitive list of vectors and alternative hosts. This would help to refine the map presented here, enabling us to assign higher positive or negative scores for either presence or absence, and therefore to delineate more accurately the outer limits of the disease reservoir. This is necessary in order to provide precise information to public health agencies, and to provide a contemporary baseline to monitor future changes in the disease distribution. Longitudinal studies in Sabah, Malaysia have shown that M. fascicularis and M. nemestrina are absent but M. leonina, M. assamensis and T. phayrei are present P. knowlesi malaria on Smith Island and Car Nicobar P. knowlesi transmission are a complex and dynamic mix of subspecies and sibling species In the past a lack of diagnostics meant that data on human cases was lacking and high population movement further complicated the picture. We are now in a better position to obtain human case data and this study has highlighted the regions to target. Further studies of the monkey species able to host this parasite would also be particularly informative, particularly in Northern Myanmar where P. knowlesi, the social organisation of these primates differs, in terms of ranging patterns, relationships to humans and time spent on the ground versus the canopy. These factors may have an important influence on their relevance as a reservoir for transmission of P. knowlesi to humans. These factors also differ between populations; for example, in areas with extensive primate hunting, primate reservoir populations may be pushed far from humans reducing the probability that humans will intersect with primate-vector cycles.As well as their susceptibility to Plasmodium knowlesi has been found on Sulawesi M. fascicularis and M. nemestrina are kept as pets and have escaped into the wild This work also highlights the importance of understanding the role of introduced populations when the ultimate goal is to map a disease reservoir. M. fasciularis or M. nemestrina. Hybrids are likely to occur in the narrow contact zone between M. fascicularis and M. mulatta in Thailand, Vietnam, Laos and Myanmar P. knowlesi host species will not impact the geographical limits of the disease, but if hybrids are found beyond the range of the known hosts this could affect the disease risk in these locations.When monkey host species have been introduced to areas where other macaque species are endemic P. knowlesi infection prevalences, and rhesus monkeys, that may not be able to survive in the presence of P. knowlesi, is particularly interesting and currently unknown. The impact on P. knowlesi host status following introgression of genes from one species into populations of another is also unknown; we simply do not know whether introgression (contemporary or ancient) of M. fascicularis genes into M. mulatta populations at the southern end of their range M. mulatta into M. fascicularis populations north of peninsular Thailand reduces their ability to act as a reservoir for this parasite, or whether more complex genetic interactions occur. Which genes are important in P. knowlesi infection and their status in any of these species or populations is unknown. Taking a pragmatic approach for the purpose of producing a map of disease risk for public health use, however, the most important questions are 1) what is the prevalence of human infection at precise locations and 2) what is the prevalence of infection in species/hybrids of monkeys and mosquitoes at precise locations across the region? A recent preliminary finding reports a P. knowlesi infection in either a M. mulatta monkey or a M. mulatta/M. fascicularis hybrid in Vietnam close to the location of known human and vector infections of P. knowlesi in wild M. mulatta populations, and in populations of hybrids, is needed to provide evidence for their role in hosting a parasite reservoir.The disease status of hybrids between known hosts, whose populations can sustain high P. knowlesi readily infects and is usually fatal to M. mulatta  but the surviving animals have the ability to pass the parasite on to mosquito vectors M. mulatta populations cannot co-exist with the parasite M. mulatta could be a natural host for the parasite M. mulatta in different locations may differ in their level of immunity to P. knowlesi, which would mean both hypotheses could be true depending on location. The overlap of the P. knowlesi parasite and the rhesus monkey found in two subnational areas (N Myanmar and NW Thailand) suggests the parasite and the rhesus macaque may co-exist, however, within these two areas the precise locations of the parasite and of the macaque may still differ. A finer scale approach will help to resolve the question of whether M. mulatta can co-exist with P. knowlesi. In addition, a second monkey species, Presbytis (Semnopithecus) entellus, which is also known to have a high fatality rate when infected in the laboratory P. knowlesi absence or alternatively this species could also provide a parasite reservoir. Inclusion of P. entellus as a negative indicator would reduce the scores for areas of Southern India and Sri Lanka on the edges of the area of this study. More data on the naturally-occurring malaria infections found in the full range of species in the region is needed and further data to back up the finding of a P. knowlesi infection in either a M. mulatta monkey or a M. mulatta/M. fascicularis hybrid in Vietnam M. mulatta presence is a useful indicator for a potential disease reservoir.Large numbers of laboratory experiments have shown that 2 which is not endemic for any of the known or potential host species but which supports a single isolated population of M. fascicularis near Jayapura P. knowlesi-free can be used to exclude the population from the scoring system. A surveyed population that is found to be infected will still affect the score for the whole state/island, as will an isolated human case or infected vectors at a single discrete location, and a finer resolution mapping approach is needed to address this limitation of the current map.The approach used in this paper has the limitation that presence of a single isolated host population in one part of a state/island increases the score assigned to the whole state/island. One example of this is Papua, a Province of 320,000 kmThe map presented here has divided the region into 475 areas and provides good subnational resolution, but it is not a fine resolution map and cannot distinguish the large variation that may exist within a province or island. Specifically, there will be areas within most provinces/islands that are less likely to support a reservoir. Point-located data for the parasite, hosts and vectors is available, which opens up the possibility of using ecological niche modelling techniques to produce a finer resolution map. Niche models will identify areas suitable for disease transmission that fall outside the actual disease range, unless constrained by information on the geographical extent of the disease. The study published here has used an evidence-based approach to examine the putative range of the disease reservoir and can be used to delineate outputs from studies that use a niche modelling approach to map this disease on a fine scale. Furthermore, the methods developed in this study are broadly applicable and could usefully be extended to other severely neglected vector-borne and/or zoonotic diseases such as scrub typhus or chikungunya.P. knowlesi reservoir. It is not a map of the likelihood of a reservoir occurring within each area and an area may receive a zero score because the evidence available is lacking or it may in fact be less likely to support an infectious reservoir. This issue is particularly apparent within the Malay Archipelago. Smaller islands are less likely to have evidence for parasite and/or host and/or vector presence, but they may also differ in their underlying ability to support a parasite reservoir. The map shows where evidence is strong and is inherently biased to areas where studies have been conducted. When considering methods to model the probability of occurrence of a reservoir, on a fine-scale, it will be essential to address the issue of sample bias. In order to produce such fine scale maps, more data is needed and the current study has highlighted the types of data and the geographical areas of study that would be most informative, based on our current state of knowledge.The goal of the map presented here is to provide a comprehensive summary of the current state of evidence for a Figure S1Leucosphyrus vectors excluded; C) other sylvatic vectors excluded; D) other human vectors excluded; E) combined vector range excluded; F) other human malarias excluded; G) the natural range of M. fasciularis excluded; H) the natural range of M. nemestrina excluded; I) introduced M. fascicularis and M. nemestrina populations excluded; J) M. leonina excluded; K) combined monkey range excluded.A figure showing histograms of the scores generated each time the scoring system was adjusted. Subnational areas with confirmed cases of knowlesi malaria in either humans or macaques are marked in black and all other areas are light grey. Panel A shows the scores when evidence of parasite presence is excluded. Panels B–L show the scores generated when a second individual evidence class is excluded: B) (TIF)Click here for additional data file.Figure S2Leucosphyrus vectors excluded; C) other sylvatic vectors excluded; D) other human vectors excluded; E) combined vector range excluded; F) other human malarias excluded; G) the natural range of M. fasciularis excluded; H) the natural range of M. nemestrina excluded; I) introduced M. fascicularis and M. nemestrina populations excluded; J) M. leonina excluded; K) combined monkey range excluded.A figure showing ranked scores generated when individual factors were excluded. Each graph shows the ranked scores when evidence of parasite presence is excluded (the x axis) against the ranked scores when the score is adjusted as follows: A) the mean score obtained across all exclusions (B–L); B) (TIF)Click here for additional data file.Table S1An Excel file containing the full set of individual scores for each evidence class and the overall evidence score as displayed in (XLSX)Click here for additional data file.Table S2An Excel file containing the scores assigned to each subnational area when parasite evidence was excluded and the scores generated when each individual evidence class was removed.(XLSX)Click here for additional data file.


Stijn Van de Velde and colleagues describe the African First Aid Materials project, which developed evidence-based guidelines on administering first aid in the African context as well as training materials to support the implementation of the guidelines. In sub-Saharan Africa, much disease and injury can be addressed by emergency care. First aid training has been promoted as an inexpensive way to save lives. However, first aid training in sub-Saharan Africa is often based on handbooks prepared outside of the continent that are not adapted to the African context.We formulated evidence-based guidelines that comprehensively address how basic first responders should be trained to manage emergency situations in an African context. The guidelines focussed on first aid interventions requiring minimal or no equipment.Two assessors reviewed the evidence, giving special attention to studies on African cultural remedies and preferences. A multidisciplinary panel of 11 African experts discussed each recommendation until they reached agreement. GRADE was used to grade the quality of evidence and strength of recommendations. Peer reviewers gave feedback on the guidelines.These new guidelines formed the basis of a flexible didactic materials kit that is available to those involved in first aid training programmes in Africa. An implementation guide is also available to help tailor the training materials to the local context and target group.http://www.afam.redcross.be/). This project developed evidence-based guidelines on how basic first responders should be trained to manage emergency situations in an African context. The project also includes the development of training materials to support the implementation. The objective of this manuscript is to inform educators and health care professionals about these guidelines and training materials and to promote their use when developing first aid training programmes for sub-Saharan Africa.This Health in Action report describes the African First Aid Materials project  identified studies assessing the effects and feasibility of first aid procedures for the selected emergency situations. To identify evidence-based guidelines, they searched the Guidelines International Network (GIN) database, the WHO Library Database, and African Index Medicus using the search terms detailed in the technical appendix . MEDLINEBased on pre-defined selection criteria , which takes into account limitations in design, inconsistency, indirectness, imprecision, and likelihood of publication bias. The quality of evidence could either be high, moderate, low, or very low The expert panel included four African specialists with expertise in evidence-based medicine and primary care or emergency medicine, five representatives of African Red Cross societies (managers and first aid trainers), and an expert in medical anthropology. The co-director of the South-African Cochrane Centre (JV), part of the international Cochrane Collaboration, served as the chairperson.The expert panel met for the first time in September 2009. The aims of this meeting were to identify any potential conflict of interest, to explain the guidelines development methods, and to present the draft evidence synthesis and recommendations. The recommendations were accompanied with photos and drawings that illustrated the conditions and actions. In the next few weeks, the experts revised the draft documents and sent their feedback by email. A checklist based on items from the AGREE A follow-up two-day consensus meeting was held in October 2009. This meeting aimed to reformulate the recommendations until agreement was reached among the full expert panel and to decide on the strength of each recommendation (strong or weak) according to GRADE In February 2010, four reviewers who specialised in emergency medicine, traumatology, paediatrics, and obstetrics were invited to give feedback on the guidelines and on the draft of the didactical material. The chair of the guidelines development panel then considered the responses and improvements were made.The final version of the guidelines was approved electronically by the expert panel.Overall, we screened 24,000 references and selected 143 publications to provide the evidence base for the guidelines. The systematic reviews allowed us to learn about practices that try to make the best use of the limited resources available. Examples of such practices that were considered by the panel include ash for hand washing The complete guidelines  include In sub-Saharan Africa, snakebites are a neglected health problem with an important burden of disease for which many victims never receive formal medical care Based on these findings, the panel recommended immobilisation of the bitten limb without application of an elastic bandage. The level of evidence is low to very low with a weak grade of recommendation. Additional recommendations are to stop the bitten person from moving, calming the person, taking off any rings, watches, or tight clothing that may cut off blood flow because of swelling, and taking actions to obtain medical help.Writing guidelines is only the beginning and should be followed by measures to support implementation in practice. Therefore, these new guidelines formed the basis of a flexible training materials kit that comes on a DVD. This DVD will be available to those responsible for first aid training programmes in Africa. The training materials include an electronic version of the manual illustrated with hundreds of quality illustrations including youths, adults, and elderly people from multiple ethnic and religious backgrounds. The manual is available in English, French, and Portuguese and describes for every condition the most important signs to look for and actions to take. Currently, didactical posters and videos are being developed to demonstrate the different procedures. Providers of first aid courses can pick what they need from the DVD to compose their first aid courses for their specific target audience.Although the guidelines attempted to be generic for sub-Saharan Africa, there are local specificities that need to be addressed in order to apply the training materials. For example, misunderstandings and mistrust regarding health information may arise when the biomedical approach is at odds with local perceptions and management. Advice that incorporates local terms, perceptions, and preferences is considered to be more convincing Between June and December 2010 we piloted the training materials and implementation guide in Uganda and Swaziland. These pilots include focus group discussions on whether the illustrations are understood to evaluate clarity, and field-testing the feasibility of more complex instructions. For this purpose, individuals with different levels of experience in first aid (from novice to trainer) were asked to perform specific first aid tasks under different test conditions. The test conditions included performing the task when being provided with drawings only, with drawings and written instructions only, or after the demonstration by a trainer. An observer recorded if the participants completed the task correctly or incorrectly.Implementation of AFAM in the Red Cross national societies from Namibia, Mozambique, South Africa, Malawi, Uganda, Swaziland, the Comoros, and Kenya is planned. We are also developing a strategy to formulate a similar set of guidelines and training materials for South Asia. Furthermore, because first aid training is often used as an entry point for primary prevention, we have commenced a project to formulate evidence-based preventive measures that can be used in addition to the first aid guidelines described in AFAM.Text S1Further details of methods.(DOCX)Click here for additional data file.Text S2African First Aid Materials: Guidelines (Belgian Red Cross-Flanders).(PDF)Click here for additional data file.


Enhancing CPG acceptance and implementation can play a major role in the development and establishment of emergency medicine as a specialty in many parts of the world. A Guideline International Network special interest group established to support collaboration to improve uptake of clinical practice guidelines (CPGs) across the emergency care sector conducted an international survey to identify attributes of guideline likely to enhance their use.A Web-based survey was undertaken to determine how CPGs were accessed, the preferred formats and attributes of guidelines, and familiarity with GRADE. The criteria used to identify preferred attributes of guidelines were adapted from the AGREE II Tool.Two hundred six responses were received from 31 countries, 74/206 (36%) from the US, 28/206 (16%) from Canada, 17/206 (8%) from Australia and 15/206 (7%) from the UK. The majority of responses were from physicians  with 15/206 (7%) of responses from nurses and 9/206 (4%) from pre-hospital emergency services personnel. The preferred format for guidelines was clinical protocols that incorporated recommendations into workflow, and the most preferred attribute of guidelines was the clear identification of key recommendations. The results also identified that within the group that responded to the question related to GRADE, 66% were unfamiliar with this system for summarizing evidence in relationship to recommendations.The findings provide the basis for further research to explore the most appropriate formats for guidelines or guidelines resources tailored to the needs of the emergency care providers. In 2007 the Guidelines International Network (G-I-N) established the Emergency Care (EC) Community as a special interest group of G-I-N to support collaboration to improve both the awareness and uptake of clinical practice guidelines across the emergency care sector internationally. One of the first initiatives of this group was to seek to identify the attributes of guidelines and guideline resources to improve the usability and implementation of guideline recommendations.The 2006 IOM report “Future of Emergency Care Series, Hospital Emergency Care at the Breaking Point” called for the standardization and implementation of guidelines . This reThe gap in general awareness and implementation of guidelines has been well documented over the last 2 decades with specific reference to emergency medicine by Schriger et al. in 1993 . EnhanciA Web-based survey (Attachment A) was undertaken from 14 November 2010 to 15 December 2010. The survey was developed by a working group of the G-I-N EC Community with questions focusing on:1) how CPGs are accessed,2) which guideline formats and attributes are preferred, and3) the degree of respondent familiarity with GRADE .http://www.ilcor.org), the premier organization for developing evidence-based guidance on emergency care, is transitioning to GRADE in 2015.The criteria used to identify preferred attributes of guidelines were adapted from the AGREE II Tool  . The worThe survey (Appendix A) was piloted widely through the EC Community membership. Further feedback was also sought from G-I-N board members. Changes made to the survey included revising the Likert rating to remove a neutral response and ensure that all professional groups were considered in the demographic information. The Australasian College for Emergency Medicine framework was used to classify practice settings based on the Emergency Departments’ level of service available .A snowballing technique was used to distribute the survey; this method relies on referrals from initially sampled respondents to others who are believed to have the same interest . The surFrequency tables were used to determine the results of from the survey questions. A SPSS package was used to analyze the data. The chi-square test was used to analyze several associations: (1) length of practice and use of guidelines in daily practice, (2) practice setting and preferred guideline formats and (3) practice setting and methods of accessing of guidelines.Aggregation of the practice setting into community level care and tertiary level care that included the major referral and major regional emergency departments was done to increase the sample size. The responses were aggregated to provide more meaningful interpretation  . AssociaTwo hundred six responses were received from 31 countries with representation from the US, UK, Canada and Australia. The majority of responses were from physicians  with 15/206 (7%) of responses from nurses and 9/206 (4%) from pre-hospital emergency services personnel.Practice experience of responding emergency practitioners ranged from less than 2 years to greater than 20 years. Of the respondents, 144/206 (16%) were from tertiary-level health facilities, 14/206 (16%) from community- or urban-based healthcare facilities settings and 30/206 (15%) from rural or maritime settings.The responses identified that the most common sources for guidelines are from professional societies and peer review journals as shown in Figure Table This study has provided data from the emergency care practice environment related to the behaviors, attitudes, preferences and knowledge about CPGs. Barriers to the uptake of CPGs across these domains were first reported by Cabana in 1999 ; many ofP < 0.001) [The results of this study support previous research that identified that guideline formats and content are important determinants of usability of guidelines in busy clinical environments such as the emergency care sector -13. A su< 0.001) -14. The The most preferred guideline attribute identified through this survey was the clear identification of key recommendations. The preferences support information related to ‘what to do, why and to whom.’ Knowledge of the CPG development process was also listed as important; the systematic approach taken to review the evidence provides a level of confidence and authority in the recommendations made.Professional societies and peer review journals were the most frequently used sources to access CPGs. G-I-N and the National Guideline Clearinghouse (NGC) are large web-based repositories of guidelines, which were almost never used to source guidelines among the respondents; some of the reasons for this could be a lack of knowledge of these repositories or that health providers have a higher level of assurance of the quality of guidelines that are published in the peer review literature.There was no evidence of an association between the level of service provided, e.g., tertiary care or community-based care, preferred formats or where the CPGs were accessed. However, there was a positive association between more years of practice within the setting and use of CPGs. The value of guidelines as a means of establishing standards of care and reducing variation in practice may be better appreciated as more experience is gained working within the health systems.As the guideline development process continues to evolve, there has been an emergence of grading systems such as GRADE, which is gaining some prominence. This study revealed that 66% of the respondents were unfamiliar with the GRADE system for rating the quality of evidence and recommendations. This is supported by Kotzeva et al. -15, who This study is the first to explore the preferred attributes of guidelines of those emergency care practitioners who work in an environment that is unique in the diversity of presentations often requiring time-critical decisions on management needing access to relevant high-quality information. The findings suggest the need for further research to explore the most appropriate formats for guidelines or guideline resources tailored to both the needs of the specific setting and healthcare providers within that setting. They also support the usefulness of educational efforts to increase awareness and literacy in emergency systems of grading evidence and recommendations such as GRADE.Although the results of this survey largely reflect the attitudes of health professionals in well-resourced countries, the following concepts, illustrated in Figure Guideline developers need to engage with end-users to ensure that guideline formats and information are relevant for specific settings and tailored to needs of EMS providersPublishers of guidelines need to be aware of EMS provider behaviors for accessing guidelines, andPromotion of guidelines to EMS providers at point of care is central to their practice to support enduring evidence-based behaviors.There are a number of limitations of this study. The distribution of respondents was very heavily biased toward physicians practicing in a tertiary care setting. The sample was predominantly from the US, UK, Australia and Canada with minimal representation from developing countries. The process used was nonrandom selection of participants and relied on the subjective judgments of respondents.We would like to know a little information about you.Please select your professional status from the following list:❒ Physician❒ Physician assistant❒ Nurse❒ Nurse assistant❒ Emergency services personnel ❒ OtherIf other, please specify:Please select which timeframe best describes the period you have been working in or have worked in the emergency care sector.❒ Up to 2 years❒ From 2 to 5 years❒ From 5 to 10 years❒ From 10 to 15 years❒ From 15 to 20 years❒ Greater than 20 yearsPlease state in which country you predominantly practice.Please select which best describes the practice environment that you predominantly work in:❒ Major referral emergency department (tertiary care)❒ Urban district emergency department (community care)❒ Major regional/rural base emergency department (tertiary care)❒ Rural emergency service (community care)❒ Primary care/remote rural emergency service❒ OtherIf other, please describe.The following questions relate to your preferred formats of guidelines or other documents that incorporate evidence-based recommendations drawn from guidelines that have been developed from the best available evidence/research.Is the use of clinical practice guidelines a part of your daily practice?What are your preferred formats of guidelines or guideline resources to support uptake of best practice at point of care?- Full systematic review with evidence tables and associated recommendations- Clinical protocols that translate evidence-based recommendations into a desired workflow or process.- Plain language ‘Evidence into Practice’ resources that summarize the evidence and implications for practice.- Clinical algorithms or flow charts that provide a step-by-step decision-support tool- Educational materials to promote the use of evidence-based recommendations in practicePlease select the answer that best describes where you access guidelines to inform your practice:- Government-based agencies, e.g., NICS, NHMRC, SIGN, New Zealand Guideline Group, Singapore Ministry of Health, etc.- From professional specialties or specialty organizations, e.g., the American College of Emergency Physicians (ACEP), International Resuscitation Council, British Thoracic Society, etc.- From the Guideline International Network (G-I-N) Library- From the National Guideline Clearing House (NGC)- Use of the Internet search function, e.g., Google, Yahoo, etc.- Peer review journals- Locally developed guidelines- Other (please specify)http://www.agreetrust.org/.For the following questions, please consider what information within a guideline is important for you at point of care. These questions are adapted from the criteria used by AGREE II . AGREE II is an internationally validated tool for the assessment of clinical practice guidelines; Scope and purpose- The overall objective(s) of the guideline is (are) specifically described.- The health question(s) covered by the guideline is (are) specifically described.- The population  to whom the guideline is meant to apply is specifically described.Stakeholder involvementThe guideline development group includes individuals from all the relevant professional groups.- The views and preferences of the target population  have been sought.- The target users of the guideline are clearly defined.Rigor of development- Systematic methods were used to search for evidence.- The criteria for selecting the evidence are clearly described.- The strengths and limitations of the body of evidence are clearly described.- The methods for formulating the recommendations are clearly described.- The health benefits, side effects and risks have been considered in formulating the recommendations.- There is an explicit link between the recommendations and the supporting evidence.- The guideline has been externally reviewed by experts prior to its publication.- A procedure for updating the guideline is provided.Clarity and presentation- The recommendations are specific and unambiguous- The different options for management of the condition or health issue are clearly presented.- Key recommendations are easily identifiable.Applicability (implementability of the guideline or guideline product)- The guideline describes facilitators and barriers to its application.- The guideline provides advice and/or tools on how the recommendations can be put into practice.The potential resource implications of applying the recommendations have been considered.The guideline presents (includes) monitoring and/or auditing criteria.Editorial independence.The views of the funding body have not influenced the content of the guideline.Competing interests of guideline development group members have been recorded and addressed.Are you familiar with the GRADE system to assess guideline recommendations?❒ Yes❒ NoIf your answer is yes to the above question, how useful do you find the GRADE assessment❒ Very useful❒ Useful❒ Neutral❒ Useful sometimes❒ Not useful at allThe authors declare that they have no competing interests.SA is lead author and provided statistical analysis. SH was co-author and reviewed the manuscript. PW reviewed and contributed editorial advice to the article. EL reviewed and contributed editorial advice. All authors read and approved the final manuscript.http://www.g-i-n.net) is a Scottish Charity recognized under Scottish Charity No. SC034047.This article reports on the work of the EC Community and does not reflect the views of G-I-N. The EC Community supported G-I-N through the provision of secretarial support and a small grant. The Guidelines International Network (G-I-N;


China is experiencing increased health care use and expenditures, without sufficient controls to ensure quality and value. Transparent, cost-conscious and patient-centered guidelines based on the best available evidence could help establishing these quality and practice measures.We examined how guidelines could support the Chinese health reform. Specifically, we summarized the current state of the art and related challenges in guideline development and explored possible solutions in the context of the Chinese health reform.assisting practitioners as opposed to providing rules requiring adherence, and a perception that traditional Chinese medicine (TCM) cannot be appropriately incorporated in guidelines are present.China currently lacks capacity for evidence-based guideline development and coordination by a central agency. Most Chinese guideline users rely on recommendations developed by professional groups that lack demonstration of transparency (including conflict of interest management and evidence synthesis) and quality. These deficiencies appear larger than in other regions of the world. In addition, misperceptions about the role of guidelines in China’s capacity could be strengthened by a central guideline agency to provide or coordinate evidence synthesis for guideline development and to oversee the work of guideline developers. China can build on what is known and work with the international community to develop methods to meet the challenges of evidence-based guideline development. In his opening remarks to an international symposium on guideline development, Prof. YinDakui, former Chinese Vice Minister of Health and now president of the Chinese Association of Medical Doctors, stated that “all medical practitioners in China should learn about and apply high-quality evidence-based guidelines to practice in order to make contributions to the health of people in China as well as the world”. But how can this vision become reality? The authors of this article organized an international conference and brought together leading scientists in evidence synthesis and Chinese health policy to examine how guidelines could support the Chinese health reform. In this article, together with the conference speakers, we summarize the current state of the art and related challenges in guideline development and explored possible solutions in Lanzhou, China, on May 28 and 29, 2012, specifically in the context of the Chinese health reform.China is experiencing increased health care use and expenditures, without sufficient controls to ensure quality and value. For example, between 2003 and 2011, the insurance coverage increased from 30% to 96% and the average share of inpatient costs reimbursed from insurance increased from 14 to 47. There has been concern about rising of cost and the Ministry of Health of China called for a control of medical expenses in 2012 may relate to clinical interventions, public health activities, or government policies . Internahttp://www.g-i-n.net/library) and the National Guideline Clearinghouse (NGC) contains about 2300 (http://www.guideline.gov). However, no guideline from mainland of China is documented in either of these databases. There is no specific organizational structure that supports clinical trials, systematic reviews and guideline development. In addition, conference attendees witnessed misperceptions about the role of guidelines in assisting practitioners as opposed to providing rules requiring adherence, and a perception that traditional Chinese medicine (TCM) cannot be appropriately incorporated in guidelines. These concerns stem from the belief that TCM is based on centuries of observations and the holistic concept of TCM that cannot be reevaluated or appropriately assessed in research studies that reduce bias. Proper research designs could however be employed to either summarize what is known or plan studies that avoid bias.China currently lacks capacity for evidence-based guideline development and coordination by a central agency. Most Chinese guideline users rely on recommendations developed by professional groups that lack demonstration of transparency (including conflict of interest management and evidence synthesis) and quality. These deficiencies appear larger than in other regions of the world ,9. As ofChina’s capacity could be strengthened by a central guideline agency to provide or coordinate evidence synthesis for guideline development and to oversee the work of guideline developers. A central health technology assessment unit, a China NICE, the Chinese Cochrane Center or the Chinese GRADE center could support or fulfill such a role . If progChina has an excellent opportunity to build on experience of international guideline development efforts, avoid the mistakes they made and set an example for other emerging countries. We advocate that for all guidelines, the development process should be transparent leading to actionable recommendations and advocate for patients’ interests by acknowledging their preferences and values. It could mean the beginning of a new era for health care in China.Members of the Lanzhou International Guideline Symposium:Sarah L Barber, World Health Organization, Beijing, ChinaJan Brozek, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, CanadaFrançoise Cluzeau, National Institute for Health & Clinical Excellence International, London, UKMarina Davoli, Dipartimento Epidemiologia del S.S.R. - ASL RME Regione Lazio, Rome, ItalyRoman Dong Xu, Beijing Office of China Medical Board, Beijing, ChinaYngve Falck-Ytter, Case Western Reserve University, Case and VA Medical Center, Cleveland, Ohio, USASigne Flottorp, Norwegian Knowledge Centre for the Health Services, University of Bergen, Bergen, NorwayLaragh Gollogly, World Health Organization, Geneva, SwitzerlandAnne Lethaby, Research Consultant, Auckland, New ZealandSusan L. Norris, Oregon Health & Science University, Portland, OR, USANancy Santesso, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, CanadaRob J.P.M. Scholten, Deparment of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The NetherlandsKun Zhao, China National Health Development and Research Center, Division of Health Policy Evaluation and Technology Assessment, Beijing, China


We have developed a framework for translating existing sources of synthesized and quality-assessed evidence, primarily systematic reviews, into actionable messages in the form of short accessible briefings. The service aims to address real-life problems in response to requests from decision-makers.Development of the framework was based on a scoping review of existing resources and our initial experience with two briefing topics, including models of service provision for young people with eating disorders. We also drew on previous experience in dissemination research and practice. Where appropriate, we made use of the SUPporting POlicy relevant Reviews and Trials (SUPPORT) tools for evidence-informed policymaking.To produce a product that it is fit for this purpose it has been necessary to go beyond a traditional summary of the available evidence relating to effectiveness. Briefings have, therefore, included consideration of cost effectiveness, local applicability, implications relating to local service delivery, budgets, implementation and equity. Our first evidence briefings produced under this framework cover diagnostic endoscopy by specialist nurses and integrated care pathways in mental healthcare settings.The framework will enable researchers to present and contextualize evidence from systematic reviews and other sources of synthesized and quality-assessed evidence. The approach is designed to address the wide range of questions of interest to decision-makers, especially those commissioning services or managing service delivery and organization in primary or secondary care. Evaluation of the use and usefulness of the evidence briefings we produce is an integral part of the framework and will help to fill a gap in the literature. Producers of systematic reviews use various methods to make their findings more accessible to decision-makers, including plain language summaries, structured critical abstracts, overviews of reviews on a particular topic, and briefings that combine systematic reviews with other evidence sources ,2. The pad hoc process. While they were generally well received, it became apparent that we needed to develop a standardized process to clarify and confirm the question(s) to be considered and the methods used to address them. In this paper we present the framework that we have developed and are currently testing.In order to produce a product that it is fit for this purpose, it has been necessary to go beyond a traditional summary of the available evidence relating to effectiveness ,5. BriefEffective Health Care bulletin series [Development of the framework was based on a scoping review of existing resources  and our n series , and expn series . The metBriefings are produced in response to requests from NHS decision-makers who require an independent assessment of evidence to inform a decision. The rationale for this was based on our experience that a briefing produced in response to a real-life problem (service reconfiguration for eating disorders) had an impact that other pilot briefings lacked. The service was initially aimed at commissioners of healthcare services but in principle the framework could also cover a wide range of other decisions in the areas of clinical effectiveness and service delivery and organization.On receiving a request, the first step is to arrange a meeting to clarify the question(s) to be addressed. Wherever possible this will be a face to face meeting with those involved in the decision from different perspectives . This is important because direct contact between decision-makers and researchers has been identified as a facilitator of use of research evidence ,8.The objectives of the meeting are to:· clarify the issues to be addressed in terms of population, intervention, comparator and outcomes (PICO). If the research question as originally framed appears to be excessively broad, it may be necessary to modify the scope or break the question down into a number of more specific questions;· discuss the background to the decision and obtain as much relevant contextual information as possible;· agree a timescale for production and review of the evidence briefing.Our checklist of information to clarify the research question and establish the local context is presented in Figure At this meeting we also make clear our intent to make the final evidence briefing publicly available and aim to agree with the ‘customer’ on an appropriate timeframe for making a final version available to the wider NHS community. Evidence briefings are treated as confidential during the process of production and review. The research question will normally involve a comparison of the evidence base for two or more interventions (including models of delivery and/or organization of care). Our working assumption is that the decision-makers have framed the problem and identified appropriate options before approaching us and it is not our primary role to address any other alternatives that may exist. However, the possibility that the question may be modified as a result of our research should not be ruled out. If at any point it appears that the question cannot be appropriately answered using existing evidence sources  we will inform the ‘customer’ of this and stop work on the evidence briefing.Searches for relevant evidence are performed by the researcher responsible for the briefing, with the involvement of an information specialist for more complex topics. The primary sources of evidence about effectiveness are systematic reviews. Reviews are identified by searching the following sources:· Database of Abstracts of Reviews of Effects (DARE) for quality-assessed systematic reviews of interventions;· Cochrane Database of Systematic Reviews;· NHS Health Technology Assessment (HTA) programme reports;· Centre for Reviews and Dissemination (CRD) HTA database;· National Institute for Health and Clinical Excellence (NICE) guidelines (for systematic reviews performed to support guideline recommendations).DARE focuses on systematic reviews that evaluate the effects of health and social care interventions and the delivery and organization of care. The DARE process involves extensively searching for, identifying, and critically appraising the global stock of systematic reviews. DARE currently provides access to over 25,000 systematic reviews and this content is also supplied to The Cochrane Library, PubMed Health, NHS Evidence and Health Systems Evidence. Other sources of systematic reviews and HTA reports ;· NICE guidelines (for economic modeling studies performed to support guideline recommendations and other economic evidence):· NHS HTA program reports and CRD HTA database .For systematic reviews and economic evaluations derived from DARE and NHS EED, we are able to make use of an existing critical appraisal (structured abstract) in most cases. If a critical abstract has not been written, we critically appraise the study using standard DARE and NHS EED methods. Cochrane Reviews and NHS HTA program reports are considered high-quality evidence sources and are not formally appraised as part of the DARE production process. We will, however, assess the quality and reliability of such reviews where they are included in an evidence briefing.If systematic review evidence is limited and the best evidence clearly comes from one or two primary studies, we will critically appraise this evidence using the approach of the Cochrane Effective Practice and Organization of Care (EPOC) Group .Our briefings relate the evidence to the local setting. As a minimum, we assess generalizability of the evidence to the UK NHS  at the local as well as the national level; potential impact on outcomes locally ; and state any implications for local service delivery and budgets. We use items 7 to 10 of our checklist to work with the customer to identify any evidence related to the local context. These are supplemented by interrogation of any national/local policy and guidance documents, prevalence data or episode statistics that are relevant to the question under consideration. Any variations in the availability, quality or results of local evidence are assessed and described using an approach based on previous experience of producing national guidance on commissioning cancer services but one that is also similar to the approach of the SUPPORT Collaboration .It is important to assess any implications of changes to practice or service delivery for health equity. Our preferred approach follows that developed by the SUPPORT Collaboration  and invo· Which groups or settings are likely to be disadvantaged in relation to the option being considered?· Are there plausible reasons for anticipating differences in the relative effectiveness of the option for disadvantaged groups or settings?· Are there likely to be different baseline conditions across groups or settings such that the absolute effectiveness of the option would be different, and the problem more or less important, for disadvantaged groups or settings?· Are there important considerations that should be made when implementing the option to ensure that inequities are reduced, if possible, and that they are not increased?However, we recognize that this information may not always be available from systematic reviews and is likely to need to be supplemented or replaced by information gathered locally, using documents produced by or relevant to the NHS, such as Joint Strategic Needs Assessments and equity audits.We also attempt to assess the likely ease of implementation of any changes to practice or service delivery. This involves consideration of issues such as the time and resources required to implement change, the numbers of services and staff affected, and the likely attitudes of relevant stakeholders. To date we have used this informal approach rather than the more comprehensive approach, including consideration of implementation strategies, developed by the SUPPORT Collaboration . InitialIn addition, as health care resources are finite there may also be a need to consider the costs and benefits of investment in implementation itself. Implementation efforts compete with other health-care programs for limited health-care resources, so it is, therefore, important that we determine whether implementation is actually worthwhile. We have been exploring the feasibility of applying a framework for assessing the cost-effectiveness of quality improvement efforts , but recThe precise format depends on the topic but will normally include:· Front page bullet point summary of main messages Figure .· Background section describing local context and topic to be addressed.· Methods section.· Evidence base for effectiveness. Summary of existing systematic reviews and their findings; critical appraisal of the strength of the evidence and methodological rigor of the review(s); assessment of generalizability. Critical appraisal based as far as possible on information contained in the reviews themselves and existing appraisals, such as DARE abstracts.· Evidence base for cost-effectiveness. Summary of existing economic evaluations/models and their findings; critical appraisal of strength of the evidence and methodological rigor of the studies. Critical appraisal based as far as possible on information contained in the studies themselves and existing appraisals such as NHS EED abstracts.· Potential implications. Based on the evidence presented, what are the possible implications of any decision to change practice or service delivery in the local NHS setting in terms of quality of care; patient and process outcomes; cost savings or better use of resources; and health equity? Implementation issues will also be considered.· References.Additional information, such as search strategies and data extraction tables/evidence profiles, is made available as appendices or on request from the authors.As a minimum, briefings are reviewed and edited by a second researcher and representative(s) of the customer organization. To date, peer review has been undertaken by researchers independent of the project team.Evaluation of use, usefulness and impact is an important part of the process of evidence briefing production and interaction with decision-makers. The briefing on models of service provision for adolescents with eating disorders (produced before we developed this framework) was evaluated using a brief questionnaire Figure  that wenOur first evidence briefings produced under this framework cover diagnostic endoscopy by specialist nurses, integrated care pathways in mental healthcare settings and drug treatments for patients with functional class II pulmonary hypertension. For full details of all evidence briefings, see the project web page . At the The framework presented in this paper is intended to enable researchers to present and contextualize evidence from systematic reviews and other sources of synthesized and quality-assessed evidence. The approach is designed to address the wide range of questions of interest to decision-makers, especially those commissioning services or managing service delivery and organization in primary or secondary care. As such, the framework attempts to go beyond the types of questions normally addressed in systematic reviews of effectiveness. We aim to build relations with decision-makers through initial face to face meetings, followed by continued contact (face-to-face or email) to clarify the issue or question to be addressed. The use of the checklist Figure  enables While the approach appears promising, our experience with producing briefings using this framework has been limited to date. Collection of feedback from decision-makers is an important part of the process and will help us to refine our approach further over time. We are aware of the need to develop the peer review system and possibly to involve a wider range of experts, particularly for assessing aspects other than clinical and cost-effectiveness.As a matter of policy, we are currently limiting production of evidence briefings to questions brought to us by decision-makers, rather than proactively seeking to identify topical and important issues. This could be seen as either a strength or a weakness in our approach. Analyzing real problems in collaboration with those directly affected should mean that research evidence is more likely to be used and have an impact on decision-making. Systematic reviews suggest that the interaction of decision-makers and researchers promotes uptake of research evidence . On the Services that synthesize systematic reviews with other research evidence and context-specific information to answer a specific question are defined as ‘policy briefs’ in the taxonomy developed by Lavis . These sSome new services of this type have started since we did the searches for our scoping review, demonstrating a wide current interest in optimizing the use of systematic reviews by decision-makers. This may be related to the increasing pressure to make the best use of limited resources for healthcare in both developed and developing countries. The closest parallel to our service has been developed by the Ottawa Hospital Research Institute, Canada, working with the Champlain Local Health Integration Network, a commissioner of healthcare services . This seAs noted previously , there hFurther developments could include incorporation of local data supplied to us by the organization requesting the briefing and extraction of data from the wide range of resources available through, for example, the NHS Information Centre. If we were to attempt the latter, systematic and transparent methods for searching and using the data would need to be developed.Effective Health Care), we will be able to recruit a core group of responsive peer reviewers. Post-publication peer review is also possible, with readers invited to submit comments for response.Peer review is another area that we are seeking to develop further and is especially important in relation to adapting the briefings for wider audiences. As we decide how best to balance the need for rapid information to support decision-making against the time required for rigorous peer review, it may be that , University of York, UK. PW manages the CRD knowledge translation service and is a co-applicant of the TRiP-LaB (Translating Research into Practice in Leeds and Bradford) research theme which supported much of the work described in this paper. DC is a TRiP-LaB Research Fellow based at CRD.