Although carbohydrate restriction is not a new approach for the management of Type 2 diabetes, interest in its safety and efficacy has increased significantly in recent years. The purpose of the current narrative review is to summarise the key relevant research and practical considerations in this area, as well as to explore some of the common concerns expressed in relation to the use of such approaches. There is a strong physiological rationale supporting the role of carbohydrate restriction for the management of Type 2 diabetes, and available evidence suggests that low carbohydrate dietary approaches (LCDs) are as effective as, or superior to, other dietary approaches for its management. Importantly, LCDs appear to be more effective than other dietary approaches for facilitating a reduction in the requirement for certain medications, which leads to their effects on other health markers being underestimated. LCDs have also been demonstrated to be an effective method for achieving remission of Type 2 diabetes for some people. The available evidence does not support concerns that LCDs increase the risk of cardiovascular disease, that such approaches increase the risk of nutrient deficiencies, or that they are more difficult to adhere to than other dietary approaches. A growing number of organisations support the use of LCDs as a suitable choice for individuals with Type 2 diabetes. The use of low carbohydrate dietary approaches (LCDs) in people with Type 2 diabetes is not new, but standard care around much of the world has focused on the use of a low fat, calorie controlled diet—in line with that usually recommended for the general population—for much of the last few decades. Recently however, LCDs have gained in popularity again. As a result, interest in their safety, efficacy and effectiveness has increased. Despite such diets being used by an increasing number of people with Type 2 diabetes, the use of carbohydrate restriction in this population is still not without controversy. In fact, commentary on this approach has often been hostile, with much of the criticism being inappropriate and failing to objectively consider the available evidence. The purpose of the current narrative review is therefore to consider the existing body of research, and to explore common concerns and practical considerations associated with the use of this approach. The review and its recommendations are aimed at both clinicians, to help guide decision making, and researchers within this area, to summarise the existing evidence and help guide future research directions.Although there is no universally agreed definition of what constitutes a LCD, the most commonly used definitions are those outlined in It can be argued that the definition of any diet is somewhat subjective, and often ambiguous. It is therefore important that, where there is any uncertainty, the definitions used to consider the impact of any given diet is based on those applied by people who work with that approach in the field. This is true of the definitions of LCD used here, which come from specialists in the field and are well-represented within the references used in their review . These dIt is important that the appraisal of available evidence considers these definitions appropriately. It is common for research, both in the form of trials and observational studies, to use terminology such as “low carbohydrate diet scores” or to refer to “low carbohydrate diet patterns” when the carbohydrate intake of individuals within the study far exceeds the thresholds stated here. This is inappropriate and misleading, and such studies should not be used to draw conclusions regarding the safety and efficacy of LCDs.There are a number of routes through which LCDs may be beneficial for people with Type 2 diabetes; the most significant of which are introduced below, and are summarised in Improved blood glucose control (and possible remission of Type 2 diabetes)—Most people with Type 2 diabetes have a reduced ability to remove carbohydrate from their blood efficiently, as a result of insulin resistance  total energy expenditure was reduced in LCDs, in longer studies there was a small but significant increase in total energy expenditure . This fiReduced hunger—As alluded to previously, reduced hunger is often reported in individuals who follow a LCD  that are the primary issue . RegardlReduced hepatic fat storage—Elevated fat storage in the liver is a key driver of Type 2 diabetes  is not as high when an individual adopts a LCD. This period of rest may contribute to the return of beta-cell function .differences in the level of support provided to the intervention and control arms .ad libitum food intake. Further, differing instructions on this front between groups within studies  may further influence the outcomes, independently of the influence of the different eating patterns themselves. The possibility that caloric matching, or lack thereof, may modify outcomes was however assessed in a recent meta-analysis, with the authors concluding that there was no evidence that this was the case  in both the LCD and control groups. This precludes any difference being observed as a result of changes in the case . They dithe methods of tracking and/or assessing the diets of the participants are often flawed, an issue that is largely unavoidable but provides a limitation for much of the body of nutrition research. The limitations of dietary assessment methods such as food frequency questionnaires and 24 h dietary recall are well-known, whilst more robust methods such as weighing foods and completing food diaries are still not without flaws and are often not adhered to.For logistical and financial reasons it is impractical, and often unfeasible, to perform highly controlled long-term studies. There is therefore a reliance on extrapolating surrogate markers from short-term studies to estimate long-term effects, an issue that is particularly problematic in relation to LCDs as some people require an adaptation period when adopting dietary approaches of this nature before any beneficial effects are apparent .a failure to fully consider the influence of the intervention and control arms on medication requirements (particularly on anti-hyperglycaemic medication requirements).n = 12  are outlined in n = 12 , 90–100]The apparently diminishing differences may be as a result of reduced adherence to LCDs over time (and it is the position of many experts in the field that this is the primary explanation in most cases), may be an artefact of limitations of the reviews (or the studies they include), or indeed they may be a true reflection of the effectiveness of such diets. It is however difficult to fully elucidate the cause(s) based on the available information. One of the included meta-analyses did attempt to assess this, finding, for example, that adherence did seem to explain the apparent reduction in efficacy of VLCDs for weight loss at 6 months . The autRegardless of the reasons for any benefits not being maintained (based on the evidence available in these reviews), these outcomes provide clear and consistent evidence that LCDs can be at least as effective as other dietary approaches. The most appropriate manner within which to consider this evidence is on a non-inferiority basis, as the comparison made in the majority of studies assessing the impact of LCDs is against the existing standard of care. As these findings support the non-inferiority of LCDs they therefore support the use of LCDs as a suitable option in people with Type 2 diabetes.Notably, where there are differences between groups they are consistently in favour of LCDs see . DiffereOf the main limitations of research in this area, the failure to consider the varying effect of different dietary approaches on medication requirements is a particularly important one. This is because studies consistently demonstrate greater reductions in diabetes medication requirements in the lower carbohydrate arms see . Where aSnorgaard et al.  found thSainsbury et al.  found thvan Zuuren et al.  reportedKorsmo-Haugen et al.  concludeHuntriss et al.  found thGoldenberg et al.  includedWhen appraising this evidence it should be acknowledged that there is an overlap in the studies included within these reviews. They therefore should not each be considered to provide additional, independent evidence. Nevertheless, the findings are clear and consistent.One final outcome assessed by the most recent of these meta-analyses , but notAs well as considering the conclusions of systematic reviews and meta-analyses it is beneficial to consider the outcomes of individual studies, as this allows the evidence to be appraised in a manner that takes into account some of the limitations identified with existing systematic reviews. For example, it allows a focus on studies where the reported intake of carbohydrate  was consistent with common definitions of LCDs, and it provides an opportunity to further consider the influence of changes in medication requirements.For the purpose of the current review, all studies included within the meta-analyses listed in the previous section were considered. To reduce the risk of bias, no additional studies were sought or included in the appraisal of relevant trials reported here. After excluding studies classified as using “moderate” carbohydrate diets in their intervention arm, 71 studies were included from these meta-analyses. This list was then filtered using the criteria applied by the National Institute of Health and Care Excellence (NICE) in their development of the guidelines for the management of Type 2 diabetes in 2009 (subsequent updates to this guideline did not appraise the relevant evidence pertaining to the effect of different dietary approaches). These criteria, which were simply that studies had to have a minimum of 50 participants and a follow up of at least 3 months, were applied so that the outcomes of this assessment could be used to consider how the existing evidence may affect current guidelines in the UK if they were to be updated now. Of the 71 studies identified, only 31 had a stated target for carbohydrate intake in the low carbohydrate arm that was less than the definitions set out at the start of this review . Of these:15 studies had <50 participants –116. A ntwo studies were not truly studies of LCDs, with one using protein shakes as meal replacements  and anotin one study the reported carbohydrate intake was higher in the LCD arm than in the control group of the study at multiple time points, with the paper also stating that “macronutrient intake did not differ significantly between groups at any point” .one study was only published as a poster abstract .two studies had a reported carbohydrate intake above the threshold to be defined as a LCD, despite the target carbohydrate intake meeting the applied criteria , 121.Of the remaining ten publications , 122–128Although a simple means of outlining the findings of these studies, it is of note that the HbA1c reduction was greater in the low carbohydrate arm of all six of the identified trials , 128; thad libitum consumption in the LCD , whilst weight loss was 12.8 kg more in the LCD group . All patients in the LCD group who were taking insulin at baseline were able to reduce or discontinue this therapy (compared with 23.1% in the control group), and there were no safety issues reported. Adherence to a LCD, defined as <20 g carbohydrate per day, was reported to be high, with detailed food logs used to verify this.A further investigation of the impact of a LCD in a community-based setting in the US provides additional support for its effectiveness, finding significant improvements in HbA1c and body weight in patients with Type 2 diabetes who opted for this approach . PatientArguably above and beyond the quantity and quality of available evidence for a particular approach or intervention, the position of bodies who produce relevant policies and guidelines is highly significant. This is because many healthcare professionals, particularly those who are not specialists within a given area, are not familiar with emerging evidence, and/or do not have the time or skills to fully appraise it. As a result they will defer to the position of relevant organisations to guide their practise, and will often not feel comfortable or confident with promoting and supporting an approach until they perceive it to be supported by such bodies. Importantly, a number of influential organisations now support the use of LCDs for the management of Type 2 diabetes:Diabetes UK (DUK) guidance from 2011  and 2018The British Dietetic Association (BDA) released a position statement in 2018 supporting carbohydrate restriction as a viable option for adults with Type 2 diabetes , with caThe Scottish Intercollegiate Guidelines Network (SIGN) updated their national clinical guidelines for the management of diabetes in 2017 . These gA 2018 joint position statement from the ADA and the European Association for the Study of Diabetes (EASD) reached conclusions similar to DUK, promoting individualised dietary approaches for patients, with LCDs being listed as a suitable option .A 2019 consensus report from the ADA concluded that “a variety of eating patterns are acceptable for the management of diabetes” supporting the need to individualise approaches . In relaHowever, the current guidance provided by the National Institute of Health and Care Excellence (NICE) in the UK is not fully consistent with the organisations referenced above . AlthougAlthough the positions outlined in the previous section acknowledge the potential utility of carbohydrate restriction for people with Type 2 diabetes, there are still caveats regarding the longer-term effects of this approach in many of them. It could be argued however that these qualifying statements, which are generally not applied to other patterns of eating, are not supported by the available evidence.The first argument against the necessity for such caveats, particularly when they are not used for other ways of eating, it that there is an absence of high quality evidence regarding the long-term safety and efficacy of ANY dietary approach. This is perhaps largely due to the limitations of nutritional research, some of which were outlined earlier within this review. These limitations are true in relation to the study of all dietary approaches, including low fat approaches which have been adopted widely by organisations worldwide and Mediterranean-style approaches which are almost universally accepted as healthy. Where longer-term studies have been attempted, the outcomes in relation to low fat dietary approaches, for example, often do not support its superiority over other approaches. For example, in the Women's Health Initiative study glycaemic control was worse in the low fat arm than the control group after 6 years  and in tlowest carbohydrate group of this study was 39.5% energy from carbohydrates; significantly above the standard definitions outlined earlier within this review. Beyond the other limitations of observational research, which would preclude drawing definitive conclusions regardless, this clearly does not provide a valid representation of a LCD. This study is indicative of the methods used in much of the comparable research ..lowest cOne limitation of epidemiological evidence that may be particularly relevant when assessing LCDs is the possibility of healthy/unhealthy user bias, an issue which could influence the results in either direction. Some individuals who ignore existing dietary guidelines and reduce dietary carbohydrate intake may also ignore other guidelines and exhibit behaviours known to have a negative influence on health, such as smoking or being inactive . Conversely, individuals who opt to reduce carbohydrate intake may be doing so as a result of being aware of the potential benefits, and thus may be more health conscious than the general population. This makes them more likely to adopt other behaviours that may be health promoting .The confounding influence of alcohol intake is also potentially significant. Alcohol consumption is poorly recorded through observational data collection methods, with intake commonly being underreported (particularly in people who consume excessive quantities of it) . AttemptA further argument against the use of qualifiers relating to long-term effects when recommending LCDs is that the evidence that does exist does not support the contention that this approach increases cardiovascular disease risk, the issue which is usually the central tenet of such concerns. In the absence of high quality, long-term evidence assessing differences in disease prevalence, cardiovascular mortality and/or total mortality between different dietary approaches, studies considering changes in relevant risk markers provide the best available evidence. Although there are clear limitations with this, changes in cardiovascular markers for the LCD arms of such studies are comparable, or often favourable, to those of the control groups; which are usually based around low fat dietary approaches. In support of this assertion, and as noted previously, the ADA 2019 consensus statement on nutrition therapy for adults with Type 2 diabetes concluded that, based on the available evidence, there was no increase in overall cardiovascular risk in individuals who followed a LCD, and, notably, that this appears to be true even within studies where the intake of saturated fat was increased . FurtherDespite the absence of evidence that LCDs increase the rate of cardiovascular events, and the observation that, on average, LDL cholesterol does not appear to be increased in individuals with Type 2 diabetes who adopt a LCD, this is still an area of concern for many. There is a question mark however over whether an increase in LDL cholesterol alone should be sufficient to justify the cessation of a LCD in individuals who do experience this change . ImportaFurther, it has been posited that changes in LDL in response to dietary changes may not always be pathological. Although further research is required to explore this further, credible hypotheses include that such changes may reflect a necessary adaptation to allow rapid redistribution of cholesterol between specific cells , or thatIf LDL elevation remains a concern despite the mitigating factors set out above, it is often possible to achieve a change in them through making changes to the type of dietary fat that is consumed (by swapping some saturated fat for some monounsaturated or polyunsaturated fat) or by increasing dietary fibre intake . Although there may be some debate over the extent to which this is necessary , such changes may help to provide peace of mind to patients and healthcare professionals alike.Based on these points, caveats in the position of other organisations pertaining to the long-term effects of LCDs can perhaps be challenged; though it is of course essential that this topic continues to be assessed to increase our understanding and to ensure that there are no negative effects in the longer-term.Another common criticism of LCDs is that people are not able to continue to follow them long-term, a term which has no universally agreed definition, but is often defined as >12 months in a research setting. Evidence suggests that the approach which is most likely to result in lasting health improvements is whichever one the individual is able to continue following , so thisIn the Virta Health trial, for example, where participants were highly motivated and self-selected the diet, adherence was 83% at 1 year  and 75% In people's day-to-day lives however, there are still practical barriers to adopting LCDs. These barriers include, in the UK, that reference intakes and traffic light colour coding on food labels are designed to support a low fat dietary approach; that most readily available food in shops and eateries is geared toward a low fat way of eating ; and that many people are not supportive of their friends or family members if they try to follow a LCD, due to misconceptions regarding the safety and efficacy of such approaches. These factors may make it more difficult for someone to adopt a LCD, but that does not mean that it is not possible. Indeed, anecdotal evidence supports that many people are able to sustain a LCD long-term. Furthermore, in a survey of dietitians in the UK the majority responded that they felt a LCD was achievable for the “right individuals” as long as they received appropriate support . Of noteAlthough these barriers may pose challenges to adherence, and may result in some individuals deciding against persisting with a LCD, there is evidence demonstrating that not everybody is put off by such factors. For example, a study reporting findings from interviews with people with Type 1 or Type 2 diabetes who had adopted a VLCD found that participants were sufficiently motivated by the benefits they had seen to persist with this dietary approach despite a perceived lack of support from healthcare professionals . Of noteAs LCDs become more widely accepted some of the existing barriers may dissipate, which will help more people to adhere to such dietary approaches. However, changes in the food environment  are tied more closely to economic priorities than health-related ones; thus are not likely to occur rapidly. It is therefore crucial that people wishing to adopt a LCD are provided with the education and support necessary to help them make informed decisions about their food choices. Practical advice is available through a number of channels, including group based structured education and digital platforms (including mobile phone applications and websites). Support for healthcare professionals, to help them learn about LCDs and how they can support their patients in adopting them, is also available e.g., , 80]..80)].reduced risk of hypoglycaemia in individuals following a LCD, as long as they have a medication review before they begin. Of note, there were no serious adverse events reported in the RCTs identified for inclusion in the current review , key health markers should be tracked to allow consideration of the impact of the specific changes made by the individual.Where relevant, patients should have a medication review before they begin restricting carbohydrate intake, and relevant health markers should be tracked carefully.Individuals with more complex needs, such as the presence of comorbidities and/or with special dietary requirements, should receive additional support from appropriately qualified healthcare professionals when making changes to their diet and lifestyle.Further meta-analyses assessing the impact of LCDs on health should be discouraged, unless they explicitly address the question in a different way (such as stratifying outcomes based on reported carbohydrate intake rather than intended carbohydrate intake).Studies should avoid making claims about the impact of LCDs when there is no evidence that those with data included in the study followed a dietary approach that would meet the generally accepted classification of a LCD.The possible effects of carbohydrate restriction independent of weight loss should be explored further. It should however be acknowledged that such investigations are primarily academic, and that the mechanism through which an intervention is effective is largely redundant from a clinical perspective.The potential impact of differing protein intake and of different types of fat on the safety and efficacy of LCDs, as well as of other potentially influencing factors such as the frequency of eating, should be further explored.Future research should ensure that other important factors, such as changes in medication use and the quality of the diet, are fully considered.As with all nutrition research and dietary approaches, continued attempts to improve the quality of studies, including through the investigation of objective markers of dietary intake, as well as efforts to improve adherence to dietary changes, would be of great value. This would also help to further assess the long-term impact of different dietary approaches, something that is difficult with existing methods.Future reviews should expand on some of the topics that were covered in the current review but, by necessity, were not explored in detail. Consideration of the potential impact of VLCD  approaches should also be explored further, including whether the effects of this are greater than that of more moderate carbohydrate restriction, and an exploration of practical considerations such as adherence and acceptability.Available evidence supports the safety and efficacy of LCDs for the management of Type 2 diabetes, with findings consistently demonstrating such approaches to be at least as effective as other ways of eating for improving blood glucose control and reducing cardiovascular disease risk. Further, LCDs appear to be superior to other dietary approaches for reducing the requirement for diabetic medications and, potentially, for placing Type 2 diabetes into remission. Existing evidence does not appear to support the assertion that LCDs are more difficult to adhere to than other dietary approaches. LCDs should therefore be promoted as a possible option for the management of Type 2 diabetes, and where patients make an informed choice to adopt a LCD they should be supported by their healthcare team to help maximise their chances of achieving their health goals.SW completed the initial draft of the manuscript. All other authors contributed to the development of the manuscript.The authors would like to thank Matthew Whitaker and Nina Evans for providing feedback on an early draft of the current review.Eat Fat! Handbook, which provides additional help and support for people who wish to adopt a low carbohydrate dietary approach. Any income from sales is reinvested into research and development. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.TD is the founder and chief executive of X-PERT Health. SW, PH, and TR are employees of X-PERT Health. X-PERT Health is a registered charity and not-for-profit organisation which provides structured diabetes education. This education includes information on low carbohydrate dietary approaches, introducing them as a potentially suitable option  for people with, or at risk of, Type 2 diabetes. X-PERT Health also produce the


Recommendations in clinical practice guidelines (CPGs) may be reversed when evidence emerges to show they are futile or unsafe. In this study, we identified and characterized recommendation reversals in gastroenterology CPGs.We searched CPGs published by 20 gastroenterology societies from January 1990 to December 2019. We included guidelines which had at least two iterations of the same topic. We defined reversals as when (a) the more recent iteration of a CPG recommends against a specific practice that was previously recommend in an earlier iteration of a CPG from the same body, and (b) the recommendation in the previous iteration of the CPG is not replaced by a new diagnostic or therapeutic recommendation in the more recent iteration of the CPG. The primary outcome was the number of recommendation reversals. Secondary outcomes included the strength of recommendations and quality of evidence cited for reversals.Twenty societies published 1022 CPGs from 1990 to 2019. Our sample for analysis included 129 unique CPGs. There were 11 recommendation reversals from 10 guidelines. New evidence was presented for 10 recommendation reversals. Meta-analyses were cited for two reversals, and randomized controlled trials (RCTs) for seven reversals. Recommendations were stronger after the reversal for three cases, weaker in two cases, and of similar strength in three cases. We were unable to compare recommendation strengths for three reversals.Recommendation reversals in gastroenterology CPGs are uncommon but highlight low value or harmful practices. What is already known about this subject?Recommendations in gastroenterology practice guidelines are often based on low quality evidence. Recommendations may be reversed when new evidence shows they are unsafe or futile.What are the new findings?We identified 11 recommendation reversals among 129 guidelines from 20 subspecialty societies spanning a range of topics in clinical gastroenterology. While rare, recommendation reversals highlight low-value clinical practices that may waste resources and cause harm to patients.How might this impact clinical practice in the foreseeable future?Future trials, and a robust agenda, should assess whether longstanding dogma or recommendations in gastroenterology truly improve patient outcomes. In order to deliver the best medical care to our patients, revising recommendations in CPGs based on new evidence is paramount.Recommendations in clinical practice guidelines (CPGs) should be updated as new evidence emerges . While tAzathioprine for Treatment of Early Crohn’s Disease in Adults (AZTEC) trial  to recommend against early introduction with thiopurines in newly diagnosed Crohn’s disease  trial , however disease .Many recommendations in gastroenterology society guidelines are based on weak evidence . Across We systematically searched all clinical practice guidelines published by select gastroenterology societies from January 1990 to December 2019 and identified recommendation reversals as defined below.We included North American, European, Asian, Australian, and international societies that produced guidelines in English primarily for topics in gastroenterology, including endoscopy, hepatology, inflammatory bowel disease, nutrition, and gastrointestinal surgery. We did not include societies that publish guidelines on topics that include illnesses that affect the gastrointestinal system such as oncology or primary care. Two authors (R.G. and A.R.) hand-searched, independently and in duplicate, all CPGs published by these societies during the period of January 1990 to December 2019. The CPGs were collected from the societies’ respective websites. As we were interested in recommendations that changes over time, we only included guidelines that had two or more iterations on the same topic. We included guidelines that graded the strength of their recommendations and/or evidence. We excluded position statements and clinical pathway documents that were not based on evidence.The two authors used a standardized data collection form to record the following information: name of society producing the guideline, guideline topic, iteration, year of publication, and type of evidence grading system. Explicit recommendations were extracted and categorized based on topic, and strength of recommendation and level of evidence as rated by the guideline authors/committee members. We compared recommendations addressing the same clinical practice in different guideline iterations from the same society. We then identified all instances of recommendation reversals. Evidence cited in both the original and reversed recommendations were recorded. Discrepancies with respect to data collection and recommendation reversal inclusion were resolved by a third author (R.K.).We defined a recommendation reversal using two criteria, both of which were required for inclusion:a. The most recent iteration of a CPG recommended against a specific practice, in contradiction of a previous iteration of the CPG from the same body that recommended the opposite.b. The recommendation in the previous iteration of the CPG is not replaced by a new diagnostic or therapeutic recommendation in the more recent iteration of the CPG.Two other authors  reviewed all identified reversals to ensure that the above two criteria were met. For each reversal that was identified, we also noted both the strength of recommendations and the quality of the underlying evidence for the newer recommendation.The primary outcome was the number of recommendation reversals. Secondary outcomes included new evidence provided in CPGs for recommendation reversals, and changes in recommendation strength after a recommendation was reversed. All data retrieved from the CPGs were managed using Microsoft Excel (2019).Twenty societies published a total of 1022 CPGs from 1990 to 2019. There were 129 unique guideline topics for which there was more than one iteration. Our final sample consisted of 129 final iterations of CPGs, and 292 total CPGs when considering each iteration as an individual guideline . GuideliThere were 11 recommendation reversals  from 10 New evidence presented in guidelines for 10 recommendation reversals, with 1 reversal lacking new data ,21. MetaIn this study of gastroenterology CPGs, we found 11 recommendation reversals from 1990 to 2019. These reversals were from major gastroenterology society guidelines and most commonly related to luminal gastroenterology and liver disease. Most reversals were based on evidence that identified harm or a lack of efficacy for established interventions. To our knowledge, this is the first study to evaluate reversals among gastroenterology CPG recommendations.We propose to categorize the reversals in this study post-hoc into three groups. While we recognize that these categorizations are not mutually exclusive, they can provide a conceptual framework of how reversals can arise. In the first group, initial recommendations based on low quality evidence, such as expert opinion, were reversed in subsequent guidelines after higher quality studies were published. For example, the 2010 ECCO guideline on the management of Crohn’s disease suggested that patients who have poor clinical prognostic factors may be suitable for early thiopurine therapy based on expert opinion and physiological considerations . When a In the second group, recommendations based on high quality studies, such as randomized trials, were reversed after subsequent studies found conflicting results. For example, the 2010 ACG  and 2012In the third group, recommendations were reversed based on changes to practice in other medical specialties. A 2003 ASGE guideline recommended antibiotic prophylaxis before endoscopy for patients at high risk of developing endocarditis or with synthetic vascular grafts less than 1 year old . The 200This study has several limitations. First, we may have missed reversals in guidelines published by societies that we did not include. Second, our small sample size of reversals precluded the ability to perform quantitative analysis. Third, there are not enough data in this study to comment on whether weak recommendations based on lower quality evidence are more likely to be reversed compared to recommendations supported by higher quality evidence. Fourth, while we stated whether recommendation reversals were made based on stronger or weaker evidence compared to the original recommendation, we did not analyze whether the initial recommendation was made prematurely. Fifth, we did not evaluate the quality of independent trials independently, but rather relied on the level and strength of evidence as judged by the guidelines included in this study. Finally, as there is no previously established definition of what constitutes a recommendation reversal, applying different definitions may lead other investigators to identifying other reversals.Our findings reveal that recommendation reversals are infrequent in gastroenterology CPGs, though they may have important clinical consequences. Although prior research has found that 40% of studies in high-impact general medical journals find existing practices to be inferior to a prior standard ,13,74, tIn this large analysis of CPGs in gastroenterology, we identify only 11 recommendations that were subsequently reversed. Guideline reversals are rare, but pertain to important clinical questions and decisions. Future trials should seek to answer longstanding questions in gastroenterology and guideline committees should review post-hoc when new evidence comes to light. In order to deliver the best medical care to our patients, revising recommendations in CPGs based on new evidence is paramount.gwab040_suppl_Supplementary_MaterialClick here for additional data file.


Performance monitoring is a key cognitive function, allowing to detect mistakes and adapt future behavior. Post-decisional neural signals have been identified that are sensitive to decision accuracy, decision confidence and subsequent adaptation. Here, we review recent work that supports an understanding of late error/confidence signals in terms of the computational process of post-decisional evidence accumulation. We argue that the error positivity, a positive-going centro-parietal potential measured through scalp electrophysiology, reflects the post-decisional evidence accumulation process itself, which follows a boundary crossing event corresponding to initial decision commitment. This proposal provides a powerful explanation for both the morphological characteristics of the signal and its relation to various expressions of performance monitoring. Moreover, it suggests that the error positivity –a signal with thus far unique properties in cognitive neuroscience – can be leveraged to furnish key new insights into the inputs to, adaptation, and consequences of the post-decisional accumulation process. Many of the choices that we make every day are based on noisy information, generated in environments that are complex and subject to change. In the face of such sources of uncertainty, it can be of vital importance to evaluate the accuracy of these choices. Estimating confidence in our decisions and detecting mistakes even without external feedback allows us to identify when future behavior should be altered; for example, by taking a more cautious approach to future decisions when we think we have just made an error.detection  that occur following responses on various kinds of choice tasks and were found to be sensitive to whether the executed choice was correct or erroneous . It was vs. error), quantities (e.g. graded confidence judgements) and consequences  relevant to monitoring. While some authors have begun to interpret these phenomena and antecedents in mechanistic and sometimes also computational terms  DV that can be read out from evidence accumulation models by taking the absolute of the accumulated evidence  – is represented in the brain. Indeed, signals that appear to track the evolution of the DV have been observed in rodents , monkeysevidence . Three kAnother salient characteristic of the CPP manifests in paradigms requiring detection of faint sensory stimuli (as opposed to discrimination of features of high-intensity stimuli). Here, the CPP exhibits the properties described above only on trials when the stimulus is judged to be present  evidence to the available choice alternatives (a ‘stimulus/response reference frame’), and it is possible that post-decisional accumulation is simply a continuation of this process. This scenario, which we illustrate schematically in g choice . In thisg choice  and 2 thg choice . Thus, ag choice  and one after the choice is made, thus providing a neural readout of post-decisional accumulation. In the following, we discuss the evidence in favour of this proposal with a focus on how the morphology of the Pe is consistent with that of a post-decisional DV, and how this neural signal relates to error detection and decision confidence.In light of the above insight that post-decisional accumulation accounts for a wide variety of findings related to performance monitoring, an emerging question is whether a neural signature of this process can be identified. As outlined earlier, the CPP has been proposed to reflect the evolution of the DV (i.e. accumulated evidence) during the process of choice formation . Here, wIn the previous section, we described how the CPP exhibits three key dynamical properties of a DV in bounded evidence accumulation models: gradual ramping with a rate proportional to RT (and absolute evidence strength); a stereotyped pre-response amplitude; and a close correspondence between peak latency and RT. Importantly, models that include post-decisional evidence accumulation predict the same three signatures for the post-decisional DV if it too is subject to a decision boundary – as is expected to be the case for tasks requiring self-initiated error signalling see also .Although the apparent similarity between pre-decisional centro-parietal positivities . This changed with the seminal work by As alluded to above, the strong association between the Pe and error detection is naturally accounted for by the proposal that the Pe reflects post-decisional evidence accumulation, coupled with the insight that error detection can be treated analogously to a signal detection problem. Within this framework, error detection is determined by the imposition of a boundary on the post-decisional accumulation process. Thus, detected errors  will be accompanied by larger Pe amplitudes than undetected errors  Pe component. Importantly, there is some evidence in the literature that confidence computations can already be tracked prior to response execution , and it One salient aspect of the findings summarized above is that the Pe is generally large in magnitude when a preceding choice is likely to be incorrect , and diminished or entirely absent when the choice is likely to be correct . This insight is likely informative about the nature of the post-decisional process reflected in the Pe in at least two respects. First, it highlights that the Pe is functionally similar to the CPP/P300 in signal detection contexts , and sugSecond, this key characteristic of the Pe suggests that it reflects a process that deals specifically in the accumulation of evidence that the preceding choice was incorrect, or ‘error evidence’. At a minimum, this upward ramping of the Pe specifically in response to error evidence would seem to necessitate a reconfiguration of the accumulation process, from a stimulus/response reference frame in the pre-decisional period to a choice accuracy reference frame in the post-decisional period  by qualitatively distinct sources of error evidence. Some tentative support for this idea comes from an analysis of the relationship between the Pe and fronto-central theta power – the latter thought to scale with error likelihood, perhaps through encoding of the conflict between competing action plans . Single-motivational salience is a useful concept to link performance monitoring and error detection with adaptive behavior. Notable parallels have been observed between both the neural processing and behavioral consequences of errors and other kinds of salient event  activity in the response-executing effector  is that they fail to reproduce certain behavioral effects – for example, the effects of fine-grained manipulations of speed/accuracy trade-off on the precise shapes of correct and error RT distributions . AnotherAt the onset of this review, we argued that the Pe might track a selective ‘metacognitive’ decision variable reflecting post-decisional evidence accumulation. Although this idea is appealing, it is worthwhile to acknowledge that it can be challenged on at least two grounds. First, some doubt has been cast on whether a selective metacognitive DV is actually represented in the brain. For the initial decision process itself, it seems well accepted that the brain should have some internal representation of a DV . HoweverIn the current review, we have discussed the idea that neural signals of performance monitoring can be understood within the context of post-decisional evidence accumulation. Such an account can explain how error detection and decision confidence arise from the same algorithmic process and relate to adaptive behavior. Moreover, it opens up exciting avenues of research concerning the neural origin of post-decisional performance monitoring signals and how these neural signals integrate different sources of evidence for an error.


Dietary guidelines are important nutrition policy reference standards that should be informed by the best available evidence. The types of evidence that are reviewed and the evidence review methods that are used have implications for evidence translation. The aim of this study was to explore perceived advantages, disadvantages, and practicalities associated with the synthesis and translation of evidence from nutrient-based, food-based, and dietary patterns research in dietary guideline development. A qualitative descriptive study was conducted. Twenty-two semi-structured interviews were conducted with people involved in the development of the 2013 Australian Dietary Guidelines (ADGs). Transcripts were analysed thematically. To inform future ADGs, there was support for reviewing evidence on a range of dietary exposures  and health outcomes, as well as evidence on environmental sustainability and equity. At the evidence synthesis stage, practicalities associated with planning the evidence review and conducting original systematic reviews were discussed. At the evidence translation stage, practicalities associated with integrating the evidence and consulting stakeholders were described. To ensure that the best available evidence is translated into future ADGs, evidence review methods should be selected based on the exposures and outcomes of interest. Dietary guidelines provide recommendations on the foods and dietary patterns that are associated with reduced diet-related chronic disease and obesity risk and provide sufficient amounts of the nutrients required to promote health ,2,3. DieThe FAO provides guidance to member states on the development of dietary guidelines. The dietary guideline development process typically involves the establishment of an expert committee that is responsible for synthesising and translating evidence into dietary guidelines ,2,3. SinAccording to the FAO, dietary guidelines should be informed by a review of the best available evidence on associations between diet and health ,2. SinceIt is now expected that dietary guidelines are underpinned by systematic reviews that are conducted in line with best practice guidelines ,6,8. TheAt the evidence translation stage, the expert committee considers the quality of the evidence that has been reviewed alongside contextual factors including the social, economic, and political environment ,2,3. TheThe Dietary Guidelines for Australians were first published by the Department of Health in 1982 . RevisedA qualitative descriptive study design was used to answer questions about evidence use in dietary guideline development ,38. The Purposive sampling methods were used to recruit participants . The folSemi-structured interviews were conducted online (using Zoom) or over the phone by KW . A semi-structured interview guide was developed and tested in a pilot interview with ML prior to data collection  47]. Pa. Pa47]. Throughout the data collection process, minor adaptations to the interview guide were made based on responses from interviewees  and in response to the release of new information from the NHMRC about the ADG review process. To enhance reflexivity, KW completed a written reflection on the interview process immediately after each interview ,42. The An iterative thematic approach to data analysis was used, which is consistent with the qualitative descriptive research design . An induForty-eight people were eligible to participate in this study . Five peEight themes emerged from the data and were organised under three categories . Four thIn relation to the evidence review that will be conducted to inform the next iteration of the ADGs, participants identified a range of dietary exposures and health outcomes of interest. The importance of reviewing the latest evidence on environmental sustainability and equity was also described. Opinions on the research questions that should be prioritised reflected participants’ views on the public health nutrition issues that future dietary guidelines should aim to address, and their perspectives on the current state of knowledge on relationships between particular exposures and outcomes.The following dietary exposures of interest were identified: dietary patterns, foods and food groups, nutrients and food components, and eating occasions. Conceptually, dietary patterns, foods and food groups, and nutrients and food components are exposures that reflect dietary intake , whereas eating occasions are exposures that reflect eating behaviours  . DietaryIn line with the food synergy theory ,18, diet“… if we’re defining health in terms of maximising functionality and preventing chronic disease, which is a public health goal, then we need to accept that it’s not a single food, it’s not a single nutrient, it’s actually a package, which we are now calling dietary patterns, which influences those outcomes, and it doesn’t happen quickly.”.Food and food groups were described as exposures of interest because although people consume dietary patterns, not every dietary pattern includes every food. For example:“… I guess if you’ve got a dietary pattern, it might not include all the different foods. Whereas if you’ve got food studies, for example, we know that fatty fish is high in omega-3. Those studies are still important, because that’s a strong source of that particular nutrient”.Some participants identified particular food groups of interest , explaining that new evidence has emerged since the current ADGs were developed.Nutrients and food components were described as exposures of interest on the basis that we need to understand the biological mechanisms that underpin associations between particular foods and health outcomes. For example:“… since we’re talking about the biological aspects, we do need to have a good understanding of the molecular basis for how food components influence health, and that’s actually the nutrient side of it. But it’s not just nutrients, it’s the things we don’t call nutrients, like phytocomponents, and it’s also the interaction between nutrients that occur within the food delivery system”.The following nutrients and food components were described as exposures of interest in relation to particular health outcomes: different types of saturated fat in relation to blood lipids, different types of carbohydrate  in relation to body weight, potassium (including the potassium to sodium ratio) in relation to cardiovascular disease risk, flavonoids in relation to vascular health, and food additives (including stabilisers) in relation to inflammation.Eating occasions  were described as exposures of interest by some participants on the basis that there is emerging evidence to suggest that these exposures may be associated with a range of important health outcomes. Other participants were of the opinion that research questions about ‘what’ people should eat should take priority over research questions about ‘how’ people should eat.Cardiovascular disease, type 2 diabetes, cancer, and overweight and obesity were often described as important health outcomes. The following health outcomes of interest were also identified: gut health (including the microbiome), gastrointestinal diseases, food allergies, mental health, immune function, vitamin D deficiency, healthy ageing, sarcopenia, frailty, osteoarthritis, and cognitive outcomes (including dementia and Alzheimer’s disease).There was strong support for an increased focus on environmental sustainability in the development of future dietary guidelines on the basis that it is not possible to promote public health without considering sustainability and in response to increasing environmental threats to food security in Australia. For example:“So the first thing I’d say is that you don’t even have to put those two things together. You don’t even have to say health and environmental sustainability, because anything that degrades environmental sustainability eventually degrades human health, and that’s becoming more and more accepted”.Some participants commented on the broad nature of the term ‘environmental sustainability’ and explained that there are many research questions that could be asked. Reviewing the latest Australian evidence on the environmental impacts associated with food production and consumption was identified as a priority due to an increase in the volume of relevant evidence. For example:“We now have much more evidence than we had back then. And not just of modelling studies of actual observational data. So in terms of environment and food related health, so we’ve got much more data”.Other participants explained that although environmental sustainability was important to consider, the evidence review should focus on dietary exposures and health outcomes, and environmental sustainability should be considered as part of the evidence translation process.There was strong support for an increased focus on equity in the development of future dietary guidelines on the basis that access to food is a social determinant of health and in response to increasing economic threats to food security in Australia. Some participants explained that ‘equity’ is a broad term, and that there are many research questions that could be asked. Reviewing the latest Australian evidence on relationships between socioeconomic status and dietary intake was identified as a priority. For example:“So if there’s anything I think we should be looking at, it’s the relationship between socioeconomic status and dietary intake. I’m not a food security expert by any means, I’ve just been an interested observer during the pandemic, and how people’s food skills, so utilisation has been poor, worse than that, we’ve got people economically doing it tough, not having enough to eat. So I think if there’s any time to be asking questions, that’s an important one to be asking of the literature”.Other participants explained that although equity issues were important to consider, the evidence review should focus on dietary exposures and health outcomes, and equity should be considered as part of the evidence translation process.In relation to the evidence synthesis stage of dietary guideline development, practicalities associated with planning the evidence review and conducting original systematic reviews were described.The importance of having an appropriate methodology in place before the evidence review begins was emphasised by some participants. For example:“So rather than say, ‘go and do some dietary guidelines again’, it’s ‘we thought about how this needs to be done, now here’s the methodology’. And then it’s like the rules of the game have been stipulated before everyone goes on the field; it’s much more functional”.Many participants described the importance of balancing evidence review methods with available resources, including human resources, financial resources, and time. The advantages and disadvantages of conducting original systematic reviews for the purpose of dietary guideline development (rather than using existing systematic reviews that were conducted for other purposes) were discussed. The resource-intensive nature of conducting original systematic reviews was emphasised, and there was support for using a combination of original and existing systematic reviews on this basis. If existing systematic reviews are used, the importance of assessing the quality of those reviews and assessing the applicability of the evidence to the Australian context was described. On this basis, some participants argued that the process of identifying and assessing existing systematic reviews can be less efficient than conducting original systematic reviews.In relation to conducting original systematic reviews, practicalities at the following stages of the systematic review process were described: defining the research question, developing the search strategy and inclusion criteria, assessing the risk of bias associated with individual studies, and assessing the quality of the body of evidence. The importance of managing conflicts of interests and engaging people with expertise in nutrition throughout the systematic review process was also described.To maximise efficiency, the importance of having clearly defined research questions from the outset was often described. Having clear definitions of the exposures of interest was considered particularly important . For example:“… I remember specific points of discussion around, how is [meat] dealt with? You know, what’s red meat? What’s white meat? What’s processed meat? What’s not?”.Some participants described the importance of tailoring the search strategy and the inclusion criteria to the research question so that relevant evidence is not missed or excluded. For example, the inclusion criteria for the date of publication may vary because the evidence that is most suitable for answering a particular research question may have been published during a particular time period. The inclusion criteria for study design may also vary because some study designs are more suitable for addressing particular research questions than others. For example, in relation to evidence on environmental sustainability:“So we have to be prepared to stand back and look at the way in which evidence is constructed in different disciplines, because what you don’t want is to say we’re going to have to have a whole lot of systematic reviews [on environmental sustainability], find there’s two studies, and then find we can’t say anything, because there isn’t any research, but there’s probably a lot of research, it’s just not constructed in that way”.The importance of selecting risk of bias assessment tools that are appropriate for particular research questions and particular study designs was emphasised. Some participants suggested that risk of bias tools should consider unique factors associated with conducting studies with dietary exposures, including the accurate estimation of dietary intake, and difficulties associated with blinding. For example:“I think it’s always useful to have tools that are appropriate for the study designs and the questions being asked. Most of the risk of bias, certainly the Cochrane Risk of Bias tools, downgrade many nutrition studies, because of the problems with blinding, [but] blinding is quite difficult, so that needs to be managed in some way”.The importance of using the most appropriate method for assessing the quality of the body of evidence was emphasised. There were mixed views on the suitability of the GRADE approach. For example, some participants explained that GRADE allows evidence from observational studies to be upgraded when particular criteria are met, which was described as an advantage. Others argued that alternative approaches may be more suitable for assessing the quality of evidence derived from studies with dietary exposures. For example:“I think on reflection, it would be good to have a system which is specific to dietary type studies, because you’re hardly ever going to get RCTs in this kind of field. They’re more likely to be cohort studies or large population studies. And that doesn’t make them bad. But when you rate them in traditional systems, they always look like low quality evidence. So I think whatever system that is used going forward, there needs to be a process for rating the evidence provided by those kinds of studies more appropriately”.Some participants described the importance of having a clear process in place to assess the applicability of evidence. For example, it was noted that most dietary patterns evidence is derived from studies conducted in other countries, which may not be applicable to the Australian context:“… my assumption would be that a lot of the [dietary pattern] studies would not be necessarily conducted in Australia, but they may be European or US studies that could be applied to our Australian context. Again, same thing in reverse, there may be some that may not be relevant at all. And we need to have a process in place where we start to work out, how do we deem them as relevant and what would then be appropriate to be considered for the Australian context”.Practicalities associated with the management of actual, potential, and perceived conflicts of interest throughout the systematic review process were discussed. Some participants described the importance of considering conflicts of interest within the evidence base. For example:“I think something that we’ve recognised is that the scientific literature has conflicts of interest within it. And we did include sources of funding. When we did the literature review, we extracted data on the sources of funding. But I think that this time, we would pay more careful attention to that, and perhaps highlight that”.The importance of managing conflicts of interest within the systematic review team was also highlighted. For example:“So I think it’s really important in the future that there’s a lot of oversight to make sure that we don’t have reviewers who have vested interests, [or] funding for other work”.Some participants described the importance of engaging people with expertise in nutrition throughout the systematic review process on the basis that people without nutrition expertise may misinterpret the evidence. For example:“I think you do need people who understand nutrition to do it. There’s lots of professional, systematic reviewing people, but honestly, if they don’t understand nutrition, it can lead to erroneous conclusions”.In relation to the evidence translation stage of dietary guideline development, practicalities associated with evidence integration and stakeholder consultation were described.Integrating evidence from multiple systematic reviews with different exposures and outcomes, making decisions about the quality of evidence that is required to inform recommendations, and balancing the potential health, economic, social, and environmental consequences associated with particular recommendations were described as important processes that require professional judgement. For example:“So theoretically, we might be getting reasonably close to saying, these are the combinations of foods that we think will give the best outcomes in terms of population health. But then you have to ask yourself, if the population is to consume this way, how good are we at providing it? And what is the impact on the environment of us producing it? What is the economic cost? Is this something that we trade in? How important is it from the point of view of the country’s GDP? And then the social side of it, which groups in our society actually eat like this? And what are the consequences of us saying they have to eat this other way?”.Views on whether dietary guideline statements should focus on dietary patterns or on foods were mixed. Some participants supported the development of dietary guideline statements that describe healthy dietary patterns in broad terms . Others explained that dietary guideline statements should continue to focus on foods because that is what members of the general public are likely to understand.Some participants explained that healthy dietary patterns may include small amounts of unhealthy foods, so, by focusing on dietary patterns, there is a risk that messages about unhealthy foods can get lost or used to the advantage of food industry stakeholders. For example:“I guess one challenge with the dietary patterns approach is that any unhealthy food can be part of a healthy diet pattern, as far as our food industry friends would be concerned. So that’s a bit of a downside, in that we play into this rhetoric of, ‘it’s all about the total diet’ when really we do want to be highlighting some foods, all the discretionary foods basically, and having clear messages about those. I think that’s where it gets a bit difficult”.To address some of these challenges, it was suggested that dietary guidelines should continue to focus on foods but also incorporate clear messages about variety, balance, and moderation.Views on the food classification system that should underpin the dietary guidelines were mixed. Some participants were of the opinion that the current food classification system that includes five core food groups and ‘discretionary foods’ is not well understood by members of the general public. Other participants highlighted the value of consistent messaging and were concerned that the introduction of a new food classification system could lead to confusion about which foods are ‘healthy’ or ‘unhealthy’. For example:“…I do wonder if as nutrition scientists, we actually should just get to the point where we call out what’s not a very healthy food and should be consumed in small amounts. And we all agree on that. If we just keep inventing classification after classification, and spending all our time on that, then it actually may play into the hands of interests that are not so interested in people having a healthy diet”.Some participants supported the development of an Australian-specific version of the NOVA food classification system that classifies foods according to level of processing. Others did not support the use of the NOVA system because they were concerned that consumers may not understand the differences between the four food groups  and, instead, assume that any kind of food processing makes a food ‘unhealthy’.how people should eat might take the focus away from statements about what people should eat; and statements that focus on eating occasions could be used to the advantage of food industry stakeholders. For example:There was limited support for the development of recommendations about eating occasions due to the following risks: statements that promote eating with others might have negative implications for people who live alone; statements that encourage home-prepared meals might have negative implications for people who do not have the capacity to prepare meals at home; concerns that home-prepared meals are not necessarily healthy and that meals eaten away from home are not necessarily unhealthy were expressed; statements about “… the more that we sort of broaden it out with other messages, the more the food industry can say ‘Well, it’s all about enjoyment. We have a dietary guideline about enjoying meals with families and family and friends. And here is our McDonald’s meal on a Friday’…”.Some participants expressed support for recommendations that focus on health promotion rather than disease prevention and messages that focus on short-term rather than long-term benefits on the basis that these messages may be more appealing to members of the general public. For example:“I think we all have a bit of a short-term view of things, and we all feel a little bit invincible. So making it closer in terms of timeframes. So feeling well, not getting sick, being able to do the things that you want to do, so being able to enjoy life, particularly as people get older”.The importance of considering the environmental consequences associated with the production and consumption of the foods and dietary patterns that are recommended was emphasised. However, to avoid unintended health consequences, it was also noted that recommendations that encourage lower consumption of meat and dairy  should be balanced by recommendations that ensure that nutrient reference values for iron and calcium can be met.From an equity perspective, the importance of ensuring that the foods and dietary patterns that are recommended are commonly available, accessible, and able to be utilised was emphasised. For example:“So there’s two layers of evidence, first of all, which foods and which compounds in foods and which combinations of foods are best for health. And there could be a number of different ways you could eat, we know that. But then the second layer is, which of these combinations are achievable in terms of our cuisine, in terms of people’s food preferences, in terms of accessibility and sustainability for ensuring equitable food access?”.Some participants described the importance of involving people with expertise in nutrition in the drafting of dietary guideline statements and the development of food guides. For example:“… the food guide is essential in taking all of those technical reviews and all of the actual guidelines and translating that for the public. So if people with all of that skill and expertise are not involved in that really important next step, it sort of negates the process. Because if you can’t get the message across properly, then there’s no point in having dietary guidelines...”.To inform the wording of dietary guideline statements and the development of food guides and other resources, the need for a comprehensive and well-resourced consultation process was often described. For example:“… we always think that we know best, and we actually don’t know best, we don’t know what the consumer and what the person out there on the street, what message they receive. And we need to just be investing much more time in trying to understand that. But we’re not, we’re going to go through the whole process of doing a million [systematic reviews], synthesising the evidence, which is all good and well, but then we fail at the most important step, which is understanding how consumers understand”.The importance of engaging people from a diverse range of socioeconomic and cultural backgrounds in the consultation process and managing the influence of food industry stakeholders with conflicts of interest was often described. Some participants explained that a robust evidence review process can reduce the influence that submissions from stakeholders with conflicts of interest have on the final version of the dietary guidelines. For example:“When you can say, look, we’re basing it on proper systematic reviews. And that was the good thing about the last one […] we could say, well, this was the evidence that we were using and this was why…”.The aim of this study was to explore perceived advantages, disadvantages, and practicalities associated with the synthesis and translation of evidence from nutrient-based, food-based, and dietary patterns research in dietary guideline development. To inform the next iteration of the ADGs, there was support for reviewing evidence on a range of dietary exposures  and health outcomes. In response to increasing environmental and economic threats to food security in Australia, the importance of reviewing the latest evidence on environmental sustainability and equity was described. At the evidence synthesis stage, practicalities associated with planning the evidence review and conducting original systematic reviews were discussed. At the evidence translation stage, practicalities associated with integrating the evidence and consulting stakeholders were described.The expert committee is typically responsible for identifying and prioritizing the research questions that will be addressed in the evidence review ,2. In thResearch questions about dietary exposures and long-term health outcomes  can be difficult to address using RCTs due to challenges associated with compliance to dietary interventions and the costs associated with delivering interventions over long periods of time ,16,55. PThe importance of using an appropriate tool to assess the quality of evidence from observational studies with dietary exposures was described by study participants. Using the GRADE approach, evidence from RCTs is rated more highly than evidence from non-randomised studies from the outset, regardless of the research question ,23. The At the evidence translation stage, integrating the evidence, making decisions about the quality of evidence that is required to inform recommendations, and balancing the potential consequences of recommendations were described as processes that require professional judgement. Blake et al. analysed dietary guideline development processes in 32 countries . They foBy exploring the ideas and opinions of people with first-hand experience, this study provides insights into the dietary guideline development process in Australia. Although the sample size was not based on the concept of information power, it is likely that a high level of information power was reached because interviews were conducted with a purposive sample of participants, including 6 out of the 12 eligible members of the Working Committee and 16 out of the 36 eligible members of the Review Team, and the quality of the dialogue was strong . HoweverDietary guidelines are important nutrition policy reference standards that should be informed by the best available evidence. This study explored perceived advantages, disadvantages, and practicalities associated with the synthesis and translation of evidence in dietary guideline development. To inform future ADGs, there was support for reviewing evidence on the associations between a range of dietary exposures  and health outcomes along with the latest Australian evidence on environmental sustainability and equity. To ensure that the best available evidence is translated into dietary guidelines, the most appropriate evidence review methods should be selected based on the exposures and outcomes of interest.


The liquid properties of BaS-La2S3 are measured by means of high resolution in-situ visualization coupled with thermal arrest measurements in a thermal imaging furnace. This enables to report the first observation of such melts in a container-less setting. The melting points of BaS and La2S3 are revisited at 2454 K and 2004 K respectively. La2S3 demonstrates a high stability in its liquid state, in strike difference with the sublimation observed for BaS. BaS is however partially stabilized with the addition of few percents of La2S3. The remarkable chemical and thermal stability of La2S3-rich samples contrasts with the partial decomposition and high vapor pressure observed for BaS-rich samples. Observations and analysis of the solidified samples suggest three different solid solutions. Solid and liquid densities are investigated along the different compositions, supporting a first estimate of the volumetric thermal expansion coefficient for La2S3.The high temperature thermodynamic properties of chalcogenides materials based on BaS remain elusive. Herein the pseudo binary BaS-La The high temperature behavior of sulfides, in particular those with promising optical properties, remains a frontier that needs to be explored in the context of materials processing. Often, binary or ternary compounds based on mixtures of sulfides are looked for, offering a tunable but unique set of properties. Unfortunately, the most basic high temperature information such as melting point, evaporation rate or range of miscibility are scarce, hindering the development of manufacturing processes.Sulfides are common compounds on earth and govern society access to a myriad of metals such as copper, nickel, cobalt or even precious metals. As inorganic chemical materials, metal sulfides however have found relatively limited breadth of applications, in part due to their chemical reactivities and the difficulties in their processing. This is in strike difference with the range of properties that they can exhibit, as illustrated by their band-gap which ranges from 1.65 to 3.75 eV2 to the generation of luminescent materials when combined with Indium or Gallium sulfides ln2S3, Ga2S33. The position of Ba in the periodic table makes BaS the most ionic alkaline rare earth sulfide with a band gap of 2.1 eV4 suggesting application in iono-conduction5. The standard melting point of BaS has been reported several times at 2508, 2480, 2475, 2470 and 2430 K (respectively10). Livey et al.9 mentioned an important volatility for BaS at high temperature impeding the obtention of a stable thermal trace or a good optical visualization. BaS is characterized by a face centered cubic structure . In contrast with La2S3, the crystal structure of BaS seems invariant with temperature until its vaporization. The high sensitivity of BaS to air and moisture contamination leads to difficulties in the precise measurements of basic properties such as its melting point as pure BaS. In 1968, Bonnivard described the instability of BaS in ambient air11. As a white salt when pure, it easily oxidizes at ambient temperature and dissolves in water to a maximum of 500 g per liter. A shift of its color toward yellow is indicative of its oxidation. The overall oxidation products of BaS in ambient air remain uncertain, considering the multiple oxidized compounds possible such as oxysulfides, sulfates, oxides, carbonates....Barium (+ 2) sulfide (BaS) has been previously investigated for its possible applications in optics, from the stabilization of host glasseset al.6 investigated the pseudo binary of BaS combined with dicopper (+2) sulfide (Cu2S) using a combination of differential thermal analysis and in-situ thermal imaging furnace. This study indicates a large depression of the melting point of BaS by the addition of as little as 5 mol% Cu2S. A broad liquid miscibility gap is found, the two-liquids being optically distinct: the BaS-rich liquid exhibits optical features of an ionic melt while the Cu2S-rich melt displays optical features closer to Cu2S. The results demonstrate the ability to stabilize a melt with up to 95 mol% BaS, which supported a new electrochemical processing technique using BaS-based sulfides electrolytes with un-precedent solubility and electrical conductivity. Cu2S is a solid and liquid semiconductor, while BaS is an insulating, ionic compound. It is therefore of interest to evaluate if the electronic nature of the second compound added to BaS affects the melting behavior. This requires to investigate a pseudo-binary system with an ionic second compound, and lanthanum (+3) sesquisulfide (La2S3) is a good candidate.Stinn 2S3 is also scarce. Flahaut et al. discovered the remarkable homogeneity of rare-earth ceric sulfides 17 demonstrating commonalities in crystal structures, melting points and oxidation. Andreev et al. experimentally explored the pseudo-binary phase diagrams of metallic (+2) sulfides - rare earth (+3) sulfides, describing similarities and differences in properties25.Unfortunately, knowledge about La2S3 and other ceric (+ 3) sesquisulfides, different solid phases, 26. 2S3, with an orthorhombic structure, is stable until 1173 K. 2S3 has a stability domain from 1173 K to 1573 K and exhibits a tetragonal structure, similar to the oxysulfide 2S3 has a cubic 2S3), where V represents La vacancies. The 2S3 can be stabilized by introducing alkali ions27 or europium28. Furthermore Kumta et al. found a process to generate and stabilize fine 2S3 and 2S3 powder at high temperature29. Two other phases 2S31. Prior studies of La2S3 intended to determine its chemical stability with respect to oxygen and sulfur as a function of temperature. In 1981, Kamarzin et al. studied lanthanum (+3) sesquisulfides from LaS to La2S330. In 1984, Kay et al. proposed a phase stability diagram for lanthanum versus the vapor pressure of 31. Vasilyeva described the thermodynamic of the La2S3-32.For La2S3 has been investigated several times34, reported between 2133 and 2350 K. The potential reactivity with crucibles might have affected the accuracy of the results. In addition, the vaporization of La2S3 before its melting has been reported at around 2000 K. Flahaut and Picon investigated the lanthanum oxide  and rare-earth sulfides (La2S3) are proposed to compare the analyzed phases with the literature. Preliminary results for densities of molten and solidified samples are reported. In closing, an attempt to determine the volumetric isobaric thermal expansion coefficient of La2S3 is presented.Herein, the liquid state properties and solid phases found upon solidification of the pseudo binary BaS-Lax of 10 mol%. The isothermal melt stability over long durations is studied for several temperatures for two specific compositions: The melting behavior is investigated along the pseudo-binary system 2S3 powders come from Alfa Aesar with a respective purity of 99.97 % and 99.99 % . Each sample is prepared in a glove box with atmosphere control using argon, indicating a maximum oxygen content of 10 ppm. Each powder is weighed, mixed and milled into a mortar and pestle. The homogeneous mix is poured into a cleaned rubber balloon. The balloon is stretched and compressed to obtain a rod-like shape of homogeneous density and diameter, then a knot is tight at both ends. With both ends attached to a stainless steel support to maintain a rod-like shape, the balloon is placed into an hydrostatic press and compressed to 30000 psi (2068 bar). After compression, the rod is removed with care by cutting along the rubber balloon with a stainless-steel scalpel in a fume hood. The rod is maintained at the end of a moveable and rotating central shaft of a thermal imaging furnace by means of a tungsten or molybdenum wire. The time required to assemble the rod and set it up in the furnace involves contact with ambient atmosphere for around 1 hour. The compacted rods are slightly friable prior to melting, influencing to a certain extend the repeatability of mass loss measurements.BaS and La2S3 are compounds with melting temperature above 1900 K, requiring special attention with respect to materials compatibility, few refractory materials being compatible. Instead herein a container-less configuration is used in a thermal imaging furnace . It is equipped with four Xenon lamps of 3 kW of power each. The lamps irradiate a center cone of light of around 2S3) is shown in Fig. Both BaS and La45 is used to study the liquidus temperature as illustrated in Fig. Visual access to the samples is possible between the lamps on the 4 sides of the thermal imaging furnace. A camera  equipped with a UV filter is fixed to the front door and used to observe samples live. A second camera  equipped with a zoom lens  is set up on a tripod orthogonal to the front door. Melting and solidification processes are observable, either in live mode or recorded. A feed-through at the bottom of the quartz tube allows to insert a type C thermocouple  for direct temperature measurement of the melt. The thermocouple signal is converted into temperature following the Reference Tables N.I.S.T. Monograph 175- Revised to ITS-90. The reference junction temperature is corrected by 17 K to consider the actual room temperature. The thermocouple signal limits of error is 1 % of the read value in the range 273 K to 2600 K. A frequency acquisition of 3 Hz is typically used, increased to 1000 Hz when monitoring rapid cooling. Simple thermometry−1 is used to reach the melting point and not overheat the sample. When interested in the solid-phases, the power is decreased gradually to 0 % power and samples solidify up to −1. The melting point or liquidus temperature are measured by repeating heating and cooling processes across the phase transition until the thermal trace shows a reproducible profile.When the furnace is turned on at the minimum attainable power (0 % power), the Xenon lamps are already emitting light leading to a minimum temperature of around 1550 K to 1650 K for the samples investigated herein. This value is dependent on the specific sample materials, its geometry, and the furnace configuration. Herein, 1% of power increment leads to 30 to 40 K increase when the sample is solid. A first slow increase at around 1 % power minFor all samples, a gaseous volume is formed inside the liquid droplet during a first melting of a sample. This gaseous volume has several origins, from the initial porosity consequence of the rod processing, to the chemical generation of a sulfuric gaseous phase composed of elemental sulfur S and including traces of metallic elements. The sulfuric gas phase has a yellowish color and is mainly observed for BaS-rich samples. Primary vacuum is applied several times during each experiments to extract this gas phase and ensure a fully liquid composition of the droplet for liquid density measurements. In the case of BaS-rich samples, the formation of a neck is observed at the solid/liquid interface when the sample stay in its liquid state for more than half an hour. The formed neck can be re-melted by slightly lowering the sample into the hot zone, for example for liquid density measurements. The droplet is considered deprived of gaseous phase when no visible effect is observable during the application of primary vacuum.et al.46. Four pictures per sample are analyzed to average the volume and minimize the possible departure from axi-symmetry. After the experiment, the solidified droplet is separated from the rest of the sample with a stainless-steel scalpel, and weighed. The distinction between the melted and non-melted part is clear on the La2S3-rich samples. The neck formation with the BaS-rich samples makes this distinction more tedious. The weighted mass of solidified droplet and the liquid volume from the pictures provide an estimate of the liquid density. Archimedes’ law is used to evaluate the density of the solidified droplet .Pictures from camera recordings along with pixel size determination are used to calculate the equivalent volume of liquid, based on the method detailed by Wu 2S3 samples were polished down to 1 micrometer. Elemental analysis for those samples is conducted with a scanning electron microscope equipped with Wavelength Dispersive Spectroscopy microprobes . Other samples were observed and analyzed on a scanning electron microscope  equipped with a single Energy Dispersive Spectroscopy detector . Several factors are important when considering elemental analysis of the solids phases as reported herein: 2S3 samples have a low electronic conductivity and despite the use of conductive tapes, high definition images proved difficult to obtain at a greater than 20,000x.Solidified BaS-LaBa and La have characteristics X-rays close to each other  using ethanol as a lubricant. BaS and La2S3 samples are unstable in air, leading to potential oxidation after exposure to atmosphere, and some oxygen content was found with EDS or WDS. As found from the literature, oxygen contamination of lanthanum sulfides is mainly due to the formation of BaS-LaA small quantity of powderous material from condensation on the quartz tubes is recovered and analyzed. Its difficult acquisition leads to high uncertainty in its composition. The presence or absence of metallic compound can however be discussed.2S3 generates a small volume of visible gas during the first heating process. A mass loss of 1.5 wt% is observed. S, and La in a minor extent are detected with EDS on the condensate recovered on the quartz tube. After this first melting, La2S3 demonstrates a stunning stability as a liquid phase, never reported before in the literature. Pure BaS generates a non-quantifiable volume of visible gas both as solid upon heating or as liquid. BaS decomposes before melting, producing barium and sulfur vapors that condensate on the quartz tube. No metallic barium is found inside the sample droplet, indicative of a vaporization of both Ba and S, in agreement with the composition of the condensates. As described in the literature, Pure La2S3-rich samples exhibit thermal features that lead to prompt homogenization of the temperature inside the droplet. Analogous melting behavior is found for 50 to 90 mol% La2S3, and results for 2S3 shown in Fig. Lamentclass2pt{minim2S3-rich compositions, regardless of the temperature. This macropore is not found on solidified samples if the droplet is exposed to several cycles of controlled vacuum/atmospheric melting. The small porosity observed at the bottom of the pictures is always present and attributed to the initial solid-rod porosity.Figure 2S3-rich samples. Ba has been rejected on the quartz tube, no La has been found.BaS-rich samples do not exhibit favorable thermal properties and are difficult to melt. A thermal gradient is present and it proved possible to observe a liquid surface while the thermocouple remains mechanically entrapped in the core solid. BaS-rich liquid behavior is complex and cannot be described only through the analysis of Figure 2S3-rich samples. This macropore is not found with repeated application of vacuum.For Three solid phases, named mentclass2pt{minimFor BaS-rich samples, different macrophases are observed as shown on Figs. les Fig. c,d, the Between 10 and 40 mol The average composition over 20 WDS points for the lanthanum sulfide leads to The results are more scattered for BaS, with an atomic concentration between 37 to 51 mol% Ba, 2 to 30 mol% for O, and 31 to 47 mol% for S. The formation of different barium oxides, oxysulfides and oxysulfates support this range of variation. Only the results with a low percentage of oxygen are further considered. The average experimental composition is then ,Table Table From 50 to 100 mol% Figure To the authors’ best knowledge,for the first time this experimental design is used in the study of liquid state properties of high temperature sulfide compounds. Herein is demonstrated the range of possibilities of the thermal imaging furnace in the study of liquid state properties of high temperature compounds hardly attainable with other apparatus.10). The small shift found in the literature can be due to the uncertainty of measurements, the high instability of The melting point of BaS reported here is in good agreement with the range of values reported in the literature: 2508, 2480, 2475, 2470 and 2430 K  sulfides exhibit high stability in their liquid state.Regarding The addition of BaS into 7 make the case for a similar phenomenon for other additions to BaS. The addition of 6. The liquid phase has a longer lifetime than pure BaS, nevertheless the formation of a neck at the solid-liquid frontier is visible over time.The addition of few percent of A strong thermal gradient is observed in the case of BaS-rich samples. Figure A macropore is observed for For BaS-rich samples, a macropore is also observed for short term experiments and has the same origin as for Ideally, experiments should be conducted with slow temperature variations in order to observe only thermodynamic stable phases. In addition, X-Rays Diffraction (XRD) and WDS analysis would bring the complementary information to conclude about the solid state nature, the sulfur concentration and the ratio of metallic elements in the different solid solutions. From the study of the ratio of metallic elements and the literature, assumptions have been made regarding the stoichiometric number of elemental sulfur. The relatively fast cooling processes seen herein may lead to metastable phases, possibly explaining the presence of 21. When combined with SrS or EuS however, 23.24.25.Figure 17. An experiment with another density measurement apparatus and a study of the crystal structure by XRD would be able to confirm or deny the result. A possible explanation to this difference could be the generation of a new crystal structure for The solid density of Except for 48, BaS-No literature discussing the density of rare earth sulfide in temperature has been found. As in the case of metallic sulfideUsing two different samples, the isobaric thermal expansion coefficient was estimated around High temperature liquid sulfide compounds were analyzed using a container-less thermal imaging furnace. Direct visualization of melting and solidification processes allowed to verify the thermal trace obtained from simple thermometry. Liquid properties such as stability, evaporation rate and liquid density were investigated. The melting point of BaS and


Dear Editor,1 As Dabis has noted, this is not consistent with the British Association of SexualHealth and HIV guideline, which recommends that a single dose of intramuscular ceftriaxone begiven in addition to doxycycline/metronidazole.2 Dabis reports a retrospective study that suggests the omission of ceftriaxone did notaffect patient outcomes. However, based on a number of factors, we would question whether thisconclusion is valid.We read with interest the letter from Dabis regarding the decision by Watford Sexual Healthto continue using doxycycline and metronidazole to treat non-gonococcal pelvic inflammatorydisease (PID).Most importantly, clinical practice revolves around the principles of evidence-basedmedicine, where the best available evidence is used to guide clinical decision making. Thereport by Dabis is observational, retrospective, small (131 women) and has a high dropout ratebetween treatment and follow-up (48%), nor were the criteria for PID diagnosis or evaluationof cure standardised. The resultant findings are therefore at high risk of bias and, we wouldsuggest, insufficient to justify a change in recommended practice. It remains possible thatdoxycycline/metronidazole alone may be as good as a cephalosporin-based regimen but, asoutlined below, there are several reasons why this may not be the case.2 A similar level of evidence is not available for doxycycline/metronidazole without acephalosporin. This is reflected not just in the UK PID guidelines but also in those from theUSA, Europe and Australia,5 none of whichrecommends doxycycline plus metronidazole in isolation. The Cochrane review on the treatmentof PID to which Dabis refers6 does not include a comparison of doxycycline/metronidazole regimens with and withoutceftriaxone, and is therefore not helpful in addressing this issue.Large randomised controlled trials have demonstrated that regimens which include acephalosporin have high efficacy in PID.Neisseriagonorrhoeae.8 In contrast,the cover provided by doxycycline/metronidazole is limited.In addition to the empirical evidence from clinical trials, the inclusion of a cephalosporinis also supported by a need to cover the relevant bacteria which cause PID. A wide variety ofaerobic and anaerobic bacteria are associated with pelvic infection and ceftriaxone providesrelevant broad spectrum activity, beyond just 10 However, this is of limited value sinceneither of the comparator regimens are a current standard of care and specifically do notinclude cephalosporin, limiting any conclusions about relative efficacy. A contemporaneousmeta-analysis found the clinical and microbiological cure rate for doxycycline/metronidazoleto be lower than alternative PID treatments.11Finally, Dabis suggests that two previous trials have found doxycycline/metronidazole to benot inferior when compared to other antibiotic regimens used in PID.We agree that further high-quality trials are needed to guide the optimal choice of therapyfor women with PID. However, the current best evidence, based on the microbiology of pelvicinfection and large clinical trials, is that treatment with doxycycline/metronidazole shouldbe combined with ceftriaxone.