Traditional Chinese Medicine (TCM) has been a proposed treatment option for ulcerative colitis (UC), however it has been difficult to understand the breadth and depth of evidence as various Chinese medicine therapies may produce effects differently. The aim of this evidence mapping is to visually understand the available evidence in the use of TCM in the treatment of UC, and to identify gaps in evidence to inform priorities of future research.A systematic electronic literature search of six databases were performed to identify systematic reviews (SRs) on different Chinese medicine therapies in the treatment in UC. Methodological quality of the included SRs was assessed using AMSTAR 2.The mapping was based on 73 SRs, which included nine interventions that met eligibility criteria. The quality of the included SRs was very low. The diseases stages of patients with UC varied greatly, from active to remission, to non-acute outbreak, to not reported. The results mostly favored the method of intervention. Oral administration combined with enema was the most widely used route of administration in secondary research.Based on the current evidence, the treatment of UC with TCM can only be recommended cautiously. A majority of included SRs did not report the location of the disease, the disease classification, and the route of administration of the intervention. Further research is needed on the effectiveness of Chinese medicine alone in the treatment of UC. The effectiveness of combined Chinese and conventional medicine combined with different routes of administration cannot be confirmed. Attention should be paid to the methodological quality of the systematic review. Unifies the outcome indicators used in the evaluation of effectiveness.The online version contains supplementary material available at 10.1186/s12906-021-03387-y. Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) caused by a variety of factors. UC has a tendency of recurrence throughout life , 2. CrohSeveral studies have reported that UC appeared initially in urban areas, where its incidence rose rapidly before decreasing slowly . The cruThis evidence mapping is largely driven by the execution of SRs and meta-analysis. In recent years, evidence-based studies of TCM in the treatment of UC are continuing to increase. At present, there are two overviews of SRs , 12 abouMapping review is used to present evidence in a field using a visual graph or chart after systematic researched. These maps provide assessments of knowledge gaps, knowledge gluts, and patterns across the research literature that promote best practice and direct research resources towards the highest quality research . It can A comprehensive search of databases PubMed, Cochrane Library, CNKI, WanFang, VIP, and SinoMed, was conducted for systematic reviews published from database inception up to and including March 16, 2021. Search terms included “ulcerative colitis”, “Chinese herbal medicine”, “plant”, “systematic review” and “meta”.Search strategy used in PubMed database:#1 Search (((ulcerative colitis[MeSH Terms]) OR ulcerative colitis[Title/Abstract]) OR ulcerative colitis[Text Word]) OR ulcerative colitis[Other Term].#2 Search  OR Traditional Medicine, Chinese[Title/Abstract]) OR Chinese Traditional Medicine[Title/Abstract]) OR Chinese Medicine, Traditional[Title/Abstract]) OR Phytotherapy[Title/Abstract]) OR Medicine, traditional[Title/Abstract]) OR Medicine, Chinese Traditional[Title/Abstract]) OR Plants, Medicinal[Title/Abstract]) OR Herbal Medicine[Title/Abstract]) OR Plant Preparations[Title/Abstract]) OR Drugs, chinese herbal[Title/Abstract].#3 Search ((review[Title/Abstract]) OR systematic review[Title/Abstract]) OR meta[Title/Abstract].#4 #1 AND #2 AND #3.We included systematic reviews with or without meta-analysis.Patients with a confirmed diagnosis of UC, regardless of disease duration and severity, were included.We included SRs where TCM interventions were used, including Chinese herbal medicine, extracts from herb mixtures, individual herbs, Chinese patent medicine, or herb compounds prescribed by Chinese medicine practitioners, regardless of the potential mechanisms of action. Eligible treatments allowed the intervention to be combined with conventional medicine or placebo. No limitation on drug dosage form and route of administration.Systematic reviews were considered where outcome measures included clinical effectiveness, TCM syndromes, inflammatory levels, immunological indicators, blood indicators, electronic endoscopy results, intestinal flora, clinical symptom and incidence of adverse reactions.Studies that involved comorbidity, in particular intestinal diseases, such as CD, schistosomiasis, bacillary dysentery, and intestinal tuberculosis, were excluded. Interventions involving herbal medicines not prescribed according to TCM theory or by Chinese medicine practitioners, were also excluded.Microsoft Excel was used for data extraction and bubble plot creation. Two researchers independently screened the studies, extracted the data, and evaluated the report. A third author was consulted if there were discrepancies. Relevant data extracted included author(s), year of publication, country of origin (based on primary author’s affiliation), total number of patients, diagnostic criteria, severity of illness, medication in intervention group and control group, outcomes, safety evaluation, quality assessment tools, and funding support. We used AMSTAR 2  , “moderate” , “low” , or “critically low”  .Findings for included SRs were summarized in:(a) tables describing the characteristics and outcomes of the included SRs;(b) graphical display of the results of literature quality evaluation, with mapping based on bubble plots. Display information includes: (1) effectiveness trend as ‘no difference’, ‘potentially effective’, and ‘effective’ in x-axis. (2) estimated size of the literature y-axis; and (3) the bubble size as per AMSTAR 2 assessment, representing Chinese herbal therapy intervention type.Our search identified 1892 potential systematic reviews  [n = 12) [Evidence mapping focused on clinical effectiveness outcomes. We evaluated the effectiveness, literature size and confidence level for each intervention identified in the SRs. The most common treatment in randomized controlled trials in the SRs were oral administration and enema interventions with Chinese and conventional medicine n = 18) , 70–76. [n = 12) , 77–79 a , 70–76.[n = 12) , 80–82. [n = 12) , 83–86. There is a constant demand for health care when it comes to chronic disease. Patients with UC tend to have long term effects with increased risk of cancer, which may develop into UC-related colorectal cancer (UC-CRC). UC-CRC is one of the most serious complications in patients with long-term UC . Among an = 18). Oral combined enema was the most widely used route of administration in the trials. TCM only was the most common intervention (n = 34), followed by the combination of TCM and conventional medicine (n = 23). The overall confidence level for each review was limited. So whilst TCM treatments may be effective in UC, more research is needed to determine whether it can be recommended to patients.In accessing the clinical effectiveness of treatment options for UC in the published SRs, we found that a majority of clinical trials used TCM as intervention through a variety of routes of administrations. Our evidence mapping showed that oral administration and enema with both Chinese and conventional medicine was most widely studied  between studies and their findings, depending on the degree of specificity of the coding process . The purIt is noteworthy that the number of SRs on TCM in the treatment of UC has increased since 2012. Prior to this, the number of trials in 2006–2011 was 0–1. Previously UC had a higher incidence in Western countries, but there has been a dramatic increase in the incident rate of UC in Asia in recent years. Because the disease is difficult to cure, easy to relapse, and the risk of cancer lesions is high, it often takes lifelong medication. There are major concerns in diagnosis and treatment of UC worldwide, with research currently being a hot topic in the field of gastroenterology.Various guidelines for the diagnosis and treatment of UC are constantly being revised. In 2004, the American Gastroenterology Association (AGA) revised “Ulcerative colitis practice guidelines in adults” , BritishThe systematic evaluation of relevant topics was searched. We used the PICOS format to organize the available information and describe the results applied to more specific scenarios according to current clinical practice. Our study included 73 SRs, and it is difficult to describe the information involved by general methods. In fields where there are enormous amounts of available information, the bubble plots are a good option. Mapping methodologies describe the quality of included SRs, and we could combine the results of all conducted studies in the field. We assessed the quality of included reviews with AMSTAR 2. This approach allowed results to be displayed on a bubble plot for each systematic review with respect to the other ones with the same comparison, providing a quick view of the existing evidence and their quality.There were several limitations to this research. Firstly, the results of our review need to be interpreted carefully because of the many characteristics in the SRs. Current evidence for interventions used in UC therefore cannot be considered conclusive and show a clear need for further research. Second, our study has some methodologic limitations. When drawing the evidence map, we included domains of estimated overall clinical effectiveness (x-axis), literature size (y-axis), and the confidence of the evidence (size of the bubble). When determining clinical effectiveness, we relied on the results of 58 SRs that potentially included biased information. The clinical effectiveness depends on these outcome indicators, including clinical effectiveness, total effectiveness, cure rate, significant effectiveness, inefficiency rate. Moreover, the AMSTAR 2, used to determine the confidence level, was originally developed to assess the appropriateness of reporting SRs and not to evaluate the confidence level of SRs. We acknowledge that there may be more efficient ways of drawing an evidence map.Since only a few SRs in the included studies showed the stage of the disease, we did not evaluate characteristics on subgroups in acute and non-acute phase of UC. The main reason may be that many RCTs did not clearly define the disease stages of participants, which is a methodological demerit in this field. We hope that more RCTs with definite inclusion and exclusion criteria can be carried out to evaluate the effects on subgroups in the future.In conclusion, oral administration, in combination with enema in both Chinese and conventional medicine, has been the most frequently tested intervention in TCM for UC. But on the basis of current evidence, this therapy can only be recommended cautiously. The low grade methodology quality of the included SRs in our mapping research cannot provide a high level of evidence to recommend in clinical practice. The major issue was that SRs failed to report the location of the disease, the type of the disease, and the route of administration of the intervention. Outcome indicators were also not uniformly reported, and the exact effect of Chinese medicine on UC cannot be derived from available evidence. Further evaluation of the effects of TCM is needed, either alone or in combination with conventional medicine, or via multiple administration routes. Low quality RCTs of TCM in the treatment of UC is of concern. As no valid conclusion can be drawn, it is a waste of energy of authors. Clinicians should carefully execute the trial and report details of the research process. They should also be aware that negative published data do not change the reputation of these authors, whilst do not annoying editors and readers. Before the systematic evaluation, the researchers should register the protocol and list the excluded literatures. In the future, we believe when high quality clinical studies are conducted of various Chinese herbal interventions, superior evidence will be available to confirm the results of these trials. In the meanwhile, evidence mapping is a useful and reliable methodology to identify and present the current evidence about therapeutic interventions. The results can help us accurately locate the focal point and insufficiency of current research in the field.Additional file 1.


On March 11, 2020, as I boarded my flight back to the UK from a conference in Washington, DC, the World Health Organization (WHO) for the first time described the coronavirus situation as a pandemic. At that point, there was already a substantial amount of valuable information about the new virus. The genetic sequence of the virus, first determined by Chinese scientists, had been shared worldwide already on January 12 and data from Wuhan, where the virus first emerged at the end of 2019, had demonstrated the amazingly rapid spread of the virus, but also the remarkable effectiveness of stopping transmission by a severe and well-controlled lockdown. Since then ∼1 million people have died of COVID-19 worldwide and major parts of the world have suffered and continue to suffer from various forms of lockdown with large sections of society now working from home. Video conferencing has replaced physical committee meetings in most organizations and webinars have replaced scientific conferences. The impact has been enormous, global and, at the time of writing this editorial, the crisis is certainly not yet over.Inevitably, in a crisis caused by an infectious agent, society at large expects solutions to come from the biomedical scientific establishment and therefore we have seen much debate in the public domain about scientific advice for policy. In the middle of September, I had the privilege of chairing a webinar, organized by Science Advice for Policy by European Academies (SAPEA), on “Science Advice: What Works in a Crisis,” with some of Europe’s most influential science advisors.Science advise to policymakers should ideally be based on reliable scientific evidence. However, as noted in SAPEA’s MASOS report,Since physical distancing between people can never be perfectly achieved, facemasks could be helpful by limiting transmission of the virus. However, in the early part of the crisis, many national scientific advisors, as well as the WHO, took a narrow view and just emphasized that there was no scientific evidence showing that facemasks would be effective and therefore did not recommend their use. In my opinion, they forgot that “Absence of Evidence is not the same as Evidence of Absence.” In other words, the fact that there was no hard evidence showing that facemasks were effective did not mean that there was evidence that they were ineffective. Furthermore, the important precautionary principle would demand that facemasks should be worn, as it is obvious that they would provide a potential barrier to transmission, while having no significant negative effects. Those warning against the general use of facemasks, including the WHO, also employed the strange argument that they could make people feel overconfident and therefore less careful. However, if we were to accept this kind of argument, we should never introduce any measures that could help solve a problem and wearing safety belts in cars, for example, should not have been recommended and certainly never have been made mandatory. As a member of the German National Academy of Sciences Leopoldina, I was happy that this academy, in its public advice published on April 3, 2020 clearly and unambiguously recommended the use of facemasks.Function, I was happy to be able to publish, in our very first issue, an Evidence Review by the eminent lipid biochemist Valerie O’Donnell that examined the possibility that oral rinses with certain mouthwashes, available without prescription, could provide an effective defense against COVID-19.Function,in vitro, but at least two clinical trials have now been planned to test whether this treatment would work in practice. Unfortunately, it will take time to provide the clinical evidence that may be needed before most scientific advisors would be willing to recommend this cheap and safe procedure. In this case, it is not entirely straightforward to design appropriate clinical trials. Whereas it is relatively easy in test tube experiments to determine precisely the concentration of an agent required to inactivate the virus and the time it takes to accomplish this, it is not so easy to extrapolate from this well-defined situation to the much more complex scenario of treating the human mouth and throat. For how long, and exactly how should one gargle with mouthwash and how many times a day should this be repeated? The question about the required frequency of rinsing is particularly tricky because virus-shedding occurs constantly. “Trial and error” will inevitably be needed and it may well take a considerable amount of time before we know exactly what would be the optimal procedure. However, if information about what is already known were to be shared widely, many individuals might already now decide to gargle a couple of times every day with a mouthwash that has been proven to be able to kill SARS-CoV-2. This might well provide significant protection without doing any harm.There is often a tendency to think that only those measures that cost a lot of money and require development by large teams are likely to be really effective in solving a particular problem. With regard to COVID-19, massive resources have been invested in developing vaccines, and we must of course hope that they will be effective or at least partially effective. In contrast, there has been comparatively little interest in investigating potential effects of simpler and cheaper interventions. As Editor of Throughout this crisis, I have often worried about the low level of relevant and practical information that is transmitted to the general population. Even the so-called quality newspapers, for example, seem more interested in reporting “outrageous” comments and disagreements between different factions, than giving specific information that could help people decide on the best measures to protect themselves. It is worrying that the important issue of how best to deal with a disease caused by a well-defined biological agent, in many places has degenerated into slanging matches between highly polarized political groupings. While certain figures in political leadership positions have played and continue to play destructive roles, it is also the case that the news media have not, on the whole, behaved as responsibly as they could. In both the UK and the USA, for example, the media constantly focus on comments concerning the pandemic made by the President or the Prime Minister, as if the opinion of these individuals, who have no background in medicine or science, should carry special weight. These opinions, that often change very quickly, have mostly served to confuse the public and have therefore provided an unhelpful diversion from more valuable information provided by those who possess insight and common sense, based on real knowledge and experience.As scientists, science advisors, members of academies, and scientific societies, we must all continue to do what we can to counter the infantilizing effect of the news industry, but it will unfortunately continue to be an unequal battle.The author acknowledges funding from the European Commission's Horizon 2020, grant agreement 737432.None declared.


Sub-Saharan Africa is a subcontinent with a proud cultural richness and diversity, yet inexplicably also a region with severe health care challenges and inequity. To challenge this health equity gap and reduce the burden of disease, the patient’s voice in monitoring and evaluation of health and health care interventions is paramount. The aim of this two-phased review is to map the availability of patient-reported outcome measures (PROMs) in a selection of non-English, African Languages, and systematically evaluate the measurement properties of the PROMs that were identified.non-English, African languages . The availability of PROMs will be mapped against the previously reported burden of disease in the respective countries included. Subsequently, in phase 2, we systematically evaluate the measurement properties of these PROMs using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology for systematic reviews on PROMs. To ensure rigour, secondary searches will be developed to specifically locate articles that report on the measurement properties of the PROMs identified during phase 1. The evidence will be graded using the modified GRADE approach.This systematic review will be conducted in two phases. In phase 1, we will scope the literature for patient-reported outcome measures (PROMs), either developed from scratch or through translation and validation in a sub-Saharan African country and a selection of This review will provide a comprehensive overview and quality appraisal of PROMs developed in non-English, African languages. Consequently, this review when concluded may be an important first step in promoting access to these PROMs for use in clinical practice and research, as well as facilitate identification and prioritization of key knowledge gaps.The online version contains supplementary material available at 10.1186/s13063-021-05328-z. The World Health Organization (WHO) defines universal health coverage as “all people having access to the health services they need, when and where they need them, without financial hardship”. It includes the full range of essential health services, from health promotion to prevention, treatment, rehabilitation, and palliative care . FurtherSub-Saharan Africa is a world region characterised by a proud and rich diversity in cultures and languages. However, sub-Saharan Africa is also a world region with rapidly increasing levels of multidimensional poverty , and a sThe average number of living languages per country in sub-Saharan Africa is estimated to be 57, while in some countries (e.g. Nigeria) as many as > 500 recognised languages are spoken . In abouThe objectives of this review are therefore threefold (i) to scope the literature of studies conducted in sub-Saharan Africa on the use and measurement properties of PROMs in commonly spoken sub-Saharan African languages; (ii) indirectly, map the availability of non-English PROMs against the most recent reported burden of disease and International Classification of Functioning (ICF); and (iii) systematically evaluate the measurement properties of the PROMs identified under the first objective.This systematic review will comprise two phases, based on a single yet broad selection of studies see Fig. . The fir(i)All countries in sub-Saharan Africa according to the World Bank ,(ii)the 31 languages (see Table (iii)www.cosmin.nl).a search block for the identification of PROMs  can be found in online supplement Due to the initial scoping nature of our inquiry, the framework provided by Arksey and O’Malley will be followed while cognisant of the refinements suggested by the Joanna Briggs Institute and others –19. AmenStudies will be screened against the following preliminary inclusion and exclusion criteria, however, in line with the scoping nature of this initial phase, these can be revised once the research team gains more familiarity with the body of evidence . Initialwww.cadima.info).In the instance that studies explicitly report on the use of a PROM without reporting on one or more of the measurement properties, a concerted effort will be made to track back to the original work in developing that PROM. No language or time restrictions will be applied during the search, and a concerted effort will be made to obtain assistance in case articles surface in a non-English language that is outside the language skillset of the research team . A first initial screening of study titles will be conducted by a single reviewer (MH). Subsequently, titles and abstracts are assessed for potentially relevant articles and the selection of abstracts for full-text review will be conducted by two independent reviewers (MH and CvZ). If a study seems relevant by at least one reviewer based on the abstract, or in case of doubt, the article will be pushed to full-text review. Inclusion and exclusion of full-text articles are done by two reviewers independently, and a third reviewer will be consulted in case of irreconcilable disagreements between the first two reviewers. The study selection process will be streamlined using the open-access platform CADIMA , and include the following: first author, title, year, article type , journal or article source, country, PROM characteristics , making use of the ICF where possible , languagData extraction is conducted by one reviewer and verified by a second reviewer. The data extraction process will be piloted on a random sample of six articles with percentage agreement needing to be > 80% across reviewers to begin formal extraction , 26, 27.PROM development, content validity  Structural validity, internal consistency, cross-cultural validity, measurement invarianceReliability, measurement error, criterion validity, hypotheses testing for construct validity, and responsiveness.In phase 2, an overview of all evidence of the quality of all available PROMs will be obtained. All studies in which a (version of a) PROM was developed (e.g. translated or developed from scratch), or in which one or more of the measurement properties were evaluated will be included in this review. The COSMIN methodology for systematic reviews of PROMs will be used to conduct the review , and theTheoretically, no judgement can be made on the quality of a PROM when information on the content validity of that PROM is lacking . HoweverThe quality assessment of each study, quality assessment of each PROM (i.e. applying the criteria for good measurement properties against each result), and the grading of the evidence is conducted by two independent reviewers. This phase provides us with an overview of all evidence for the quality (i.e. regarding the nine measurement properties) that is available for each PROM, available in any of the included languages, and will be reported according to set reporting guidelines . It is nThis review will be published in peer-reviewed journals, and when possible, as a multipart series. We foresee that the scope of evidence derived from this review will allow for stratified reporting on the availability (phase 1) of PROMs, as well as the quality of PROMs (phase 2). Furthermore, when the scope of evidence allows it, we can consider stratified reporting based on specific domains of the ICF , disease profiles, or quality aspects . As referred to, the global burden of disease study, in conjunction with the ICF model, will be used as a framework to map the availability of PROMs (see phase 1) . In addieprovide.mapi-trust.org) or meetinstrumentenzorg.nl; yet these are not tailored to the unique African setting. The underlying belief is that this repository may facilitate wider access to the PROMs reviewed, and their evidence-base, for use in clinical practice or academic ventures. Direct access or reference to the instrument may be included, depending on the PROM’s licensing model; where needed we can work with or incentivize stakeholders to unlock the use of specific PROMS more easily and promote access. Once a repository has been established many other parameters of interest may be added, including detailed information on PROM analyses . The research team aims to closely work with a diverse set of stakeholders to help guide both content and ways of dissemination of the repository to cater for all potential users. Second, consensus-based (e.g. through Delphi methods) recommendations can be developed for prioritizing the translation, development, and/or validation of additional or new PROMs. These recommendations could, for instance, be informed by the local burden of disease (e.g. disease-specific gaps), specific populations being excluded from research (e.g. language- or culture-specific gaps), or perceived relevance for specific outcomes in driving health policy (e.g. outcome-specific gaps). Mapping the availability of PROMs against existing frameworks  may provide a starting point for such a consensus procedure. Participatory action research methods can be used to engage patients and stakeholders in the prioritization process, to ensure that outcomes relevant to and valued by the patient are equally considered to those relevant for health policy. Finally, it is the ambition of the research team, through collaboration with stakeholders, that key PROMs will be recorded using voice-overs to ensure that visually impaired or illiterate individuals are not left behind.The team foresees important future perspectives that further aim to disseminate and strengthen the review findings. Firstly, it is the ambition that the PROMs which are identified through this review will be aggregated in an online, open-access repository. The review of measurement properties will provide invaluable evidence to add to this repository that can assist stakeholders in the decision making, use, and appraisal of PROMs specific for their context. Similar platforms exist, for example for clinical assessment outcomes  or some “just spoken” (e.g. not written), it is impossible to include all languages in this review. Besides, as indicated, there is a substantial proportion of the sub-Saharan African population that is illiterate. Hence, while this review is comprehensive, many languages and voices are still excluded. However, to retain its feasibility, we have opted to include those languages that are widely spoken (> 10 million people), supplemented by national languages where applicable. Once an online repository is established, one could add additional languages on a per case basis and potentially use more contemporary methods to include non-written languages. Furthermore, we acknowledge that while having culturally valid and language-appropriate PROMs may assist research specifically, this is merely one aspect within a wider set of transformative aspects that may need to be addressed to further promote inclusivity, including power dynamics, scientific trust, and cultural competencies . A seconThis protocol describes a comprehensive review for the identification of patient-reported outcome measures, and their measurement properties, that are developed, translated, and/or validated in non-English national or widely spoken languages in sub-Saharan Africa. The outcome of this review will provide an invaluable resource for clinicians and academics in the field and aims to promote inclusivity in health care and research.Additional file 1.Additional file 2.


Twenty to thirty percent of psoriasis (Pso) patients will develop psoriatic arthritis (PsA). Detection of Pso patients that are (at risk for) developing PsA is essential to prevent structural damage. We conducted a systematic search of five bibliographic databases, up to May 2020. We searched for studies assessing markers  associated with the development or presence of PsA in Pso patients. Study selection and quality assessment of the included studies was performed, followed by a qualitative best evidence synthesis to determine the level of evidence for a marker and its association with concomitant/developing PsA in Pso. Overall, 259 possible markers were identified in 119 studies that met the inclusion criteria. Laboratory markers related to inflammation and bone metabolism reached a strong level of evidence for the association (not prediction) of PsA in Pso. Only CXCL10 showed strong evidence for a positive predictive value for PsA in Pso. The importance of timely detecting PsA in a Pso population, and finding more (bio)markers contributing to early detection, remains high.The online version contains supplementary material available at 10.1186/s13075-021-02545-4. Psoriatic arthritis (PsA) is an immune-mediated inflammatory disease affecting joints and entheses and is strongly associated with psoriasis (Pso). Twenty to thirty percent of Pso patients will develop PsA, with an average lag time between Pso and PsA of 10 years . This laCurrent screening strategies mostly use questionnaires based on clinical characteristics to detect PsA , 7. BothTherefore, we conducted a systematic review to identify possible markers for the onset of PsA in a Pso population, with the purpose of providing a comprehensive summary of the available markers for PsA in Pso.The protocol was designed according to the Preferred Reporting Items for Systematic review and Meta-Analysis  and regiFive bibliographic databases  were searched for studies from January 1, 1990, up to April 29, 2020. Search terms compromised keywords involving study population, study design, and etiology (supplementary table n = 2), and none for genetic studies. To not miss potential relevant markers in these two categories, we also included genetic and laboratory studies with a cross-sectional design  as a “second best” option. While these might not be useful to identify predictors for development of PsA, they could provide information about possible markers for concomitant PsA.Studies were screened for eligibility based on title and abstract by two independent reviewers . Potentially relevant papers were assessed in full text . Any disagreement was resolved by consensus or by discussion with a third reviewer . Studies were excluded based on the following criteria: (1) < 10 patients per group , (2) age of patients < 18 years, (3) no statistical comparison between Pso and PsA, and (4) languages other than English, German, or Dutch. We primarily focused on studies with a longitudinal design, meaning that the marker was present before the presentation of PsA. A very low number of longitudinal studies was available for laboratory studies .Risk bias was assessed using the Newcastle Ottawa Scale for case-control and cohort studies . This to2 [2) compared to reference level . We then assessed the consistency of the results within and across studies. If within a study, a marker was represented in multiple non-hierarchical conceptually similar constructs, we considered the result consistent if ≥ 75% of the constructs pointed in the same direction. Otherwise, we considered the result for that marker “mixed.” For example, one study looked at fracture, any trauma, and trauma leading to medical care [For the best evidence synthesis (BES), we included markers that either showed a significant difference between Pso and PsA in at least one study or markers that showed no significant results in at least two studies . Markers were grouped into overarching categories  .Conflicting evidence was available for 13 of 51 clinical markers. These markers included several disease characteristics: younger age at Pso onset –25, longStrong evidence was available for nine of 137 investigated laboratory markers. CXCL10 (C-X-C motif ligand 10) was the only laboratory marker which showed a positive association with the development of PsA in Pso patients. It was also the only laboratory marker studied in a longitudinal design.Four markers showed a strong level of evidence for a positive association with the presence of PsA in Pso: a higher level of matrix metalloproteinase 3 (MMP3) , 52, 54,Five markers showed a strong level of evidence for no association with PsA in Pso: vitamin D –45, 130,Moderate evidence was available for 56 of 137 investigated laboratory markers. Fourteen of these 56 have been investigated in more than one study.Of those 14 markers, six showed a positive association with the presence of PsA in Pso: the presence of anti-citrullinated protein antibodies (ACPA) –40, a hiOnly one of the 14 markers which were investigated more than once showed moderate evidence of a negative association with the presence of PsA in Pso: a lower ratio of OPG to receptor activator of nuclear factor kappa-B ligand (RANKL) was associated with the presence of PsA in Pso , 56.There was moderate evidence for no association for seven laboratory markers: serum alkalic phosphate , 47, 48,Conflicting evidence was available for 14 of 137 laboratory markers: markers of bone metabolism (Dickkopf (DKK1) , 53; RANThere were no genetic markers which reached a strong level of evidence for a positive, negative, or no association with the presence of PsA.Moderate evidence was available for 30 of 71 investigated genetic markers. Twenty-two of those 31 have been investigated in more than one study.IL13 gene [Of these 22 markers, six showed a positive association with the presence of PsA in Pso: the presence of haplotype B*27-C*01 , 99, hapL13 gene , 117.IL12B gene [Moderate evidence of a negative association was available for three markers: the presence of haplotype B*57-C*06 , 99, the12B gene , 135.IL1RN [IL12B gene [IL23A [IL23R [TNFAIP3  [TNIP (TNFAIP3-interacting protein) [TSC1 (tuberous sclerosis 1) [There was moderate evidence for no association for 13 genetic markers: the presence of HLA-B*57 , 104, HLIL1RN , 135, thIL1RN , 115 and12B gene , 115, the [IL23A , 135, thA [IL23R , 115, thotein 3) , 135, thprotein) , 135, throsis 1) , 135, anrosis 1) , 122 androsis 1) , 122.IL13 gene [IL23R gene [Conflicting evidence was found for 17 of 71 genetic markers, of which 14 were investigated in more than one study. These were the presence of HLA-B*08 , 103, HLL13 gene , 135, an23R gene , 135.not associated with the development of PsA. Regarding laboratory markers, there was strong evidence for the predictive value of (a change in) CXCL10 serum titers [In this review, we summarized the available evidence for possible markers for the onset or presence of PsA in a Pso patient population in a systematic way. Thereby, we provide an update and addition to a recent narrative review regarding this subject by Scher et al. . When lom titers , 60. Them titers –55 and im titers –75, 130.In line with previous beliefs on possible clinical risk factors , 140, weNotably, we found conflicting evidence for the predictive value of obesity , 33, 34 When looking at BMI at one unspecified timepoint, this marker shows conflicting evidence for a relationship with the development of PsA. In three out of five high/fair quality studies, there was no association , 22, 27,not associated with a higher rate of PsA in Pso patients.The association of trauma and psoriatic arthritis was theorized to be due to a deep Koebner phenomenon . This phThe relationship between smoking and PsA development has been described previously as the “smoking paradox” . This en+ CD4+ and CD8+ T cells [With regard to laboratory markers, only CXCL10 was studied longitudinally. This cytokine was described in two good/fair quality studies; both found an association between CXCL10 and PsA. Pso patients who developed PsA had a higher CXCL10 serum level at baseline . It was  T cells . In the before the start of PsA in Pso. Therefore, it is unknown whether it can be used as a predictive marker. Also, a clear CRP cutoff value for the presence of PsA  is lacking.With regard to cross-sectional studies, and markers that may indicate the presence of PsA in Pso patients, we found strong evidence for a positive association with PsA in Pso for markers of inflammation and bone. CRP is a well-known, widely used inflammatory marker. We found strong evidence that the CRP level in PsA patients was higher than in patients with Pso only , 130. WeOther markers for which strong evidence of a positive association with the development of PsA in Pso exist were IL-6, MMP3, and OPG. IL-6 is widely regarded as a marker for systematic inflammation and an important contributor to the production of CRP by the liver. MMP3 and OPG are associated with bone metabolism; one of the hallmark signs of PsA is new bone formation . Also, uLaboratory markers for cardiovascular disease are studied extensively in psoriatic disease , 77, 130With respect to genetic markers, we focus here on the most important HLA-markers for Pso and PsA, and the IL-12 – IL-23 – IL-17 axis. The most important genetic marker for psoriasis is HLA-C*06, also known as PSOR1 . This maWe found a moderate level of evidence for the presence of concomitant PsA in Pso for HLA-B*27, known for its high prevalence (90%) in ankylosing spondylitis (AS) . In otheIL23 gene for which the presence differs significantly between PsA and Pso patients [IL17 gene was more common in PsA versus Pso patients [IL12 gene [IL12 (rs2082412) was lower in PsA versus Pso patients, while other SNPs in this gene showed no difference [When looking at the IL-17/IL-23 axis from a genetic viewpoint, there was moderate evidence that there are no SNPs in the patients , 147. Wepatients . With reL12 gene . We founfference , 115. WhThe strengths of this study include the extensiveness and systematic way of the search with respect to markers for PsA in patient cohorts with Pso, subsequentially providing a comprehensive overview of the available evidence. Also, the intertwining of clinical, laboratory, and genetic markers in a systematic way is unique. By conducting a best evidence synthesis, taking the study quality into account, we made a qualitative overview of the extensive data.presence of PsA in patients with Pso . The level of evidence was limited by a paucity of high or fair quality studies. Mostly, this was because of a lack of appropriate definition of patient and control groups, in addition to not adjusting for possible confounders.The limitations of this systematic review are mostly due to the limitations of the included studies. Since there were  no prospective/longitudinal studies looking at genetic and laboratory markers, we could only summarize the level of evidence with regard to the relationship between laboratory and genetic markers with the presence of PsA. Promising is CXCL10, which reached a strong level of evidence for predicting development of PsA in a Pso population [This comprehensive systematic review on clinical, laboratory, and genetic markers for PsA in patients with Pso revealed that a useful set of markers is not established yet. There were no clinical or genetic markers with strong evidence which could predict the development of PsA in Pso cohorts. There was strong evidence that laboratory markers related to bone metabolism and inflammation were associated with the pulation , 60. TheAdditional file 1: Supplementary table 1. Search strategy.Additional file 2: Supplementary table 2. Characteristics of included studies (n = 119).Additional file 3: Supplementary table 3. Statistical significance and effect sizes of clinical markers.Additional file 4: Supplementary table 4. Statistical significance and effect sizes of laboratory markers.Additional file 5: Supplementary table 5. Statistical significance and effect sizes of genetic markers.Additional file 6: Supplementary table 6. Quality assessment of cohort studies.Additional file 7: Supplementary table 7. Quality assessment of case control studies.


Over the last 18 months the World Health Organization (WHO) has published over 300 guidelines across a range of clinical, environmental and public health areas to help decision makers around the world respond to the COVID19 pandemic In 2007, WHO established a Guideline Review Committee in response to criticism that WHO guidelines were not based on the best available evidence and relied on expert opinion Guideline development at WHO follows internationally recognized methods and standards to which all approved guidelines must adhere During the COVID19 pandemic these standards have been challenged by the need to rapidly identify and appraise the evidence with frequent updating required across a range of questions in order to formulate recommendations.To have maximum uptake and impact, guidelines need to be trustworthy A central principle that underpins the trustworthiness of any guidelines is transparency. An emphasis on transparency ensures that each of the core steps is publicly available and can be adapted to different settings, but also challenged and ultimately improved. These steps include: what questions of uncertainty are being examined, what evidence was retrieved, who assessed this evidence – their expertise and any conflicts of interest that may exist – the balance of benefits, harms and other judgments for or against recommending a specific intervention, and who peer reviewed the draft guidance. Transparency underpins tools like the RIGHT Statement, a reporting checklist aimed at encouraging transparency to help end users understand the key steps that were followed when developing a guideline Guideline development starts by identifying important questions of uncertainty and implementing a structured appraisal process. The scope of a given guideline, including the formulating of key questions, is set by the technical leaders within WHO. In order to answer the key questions, relevant evidence is systematically appraised by independent researchers and the certainty of the overall body of evidence is assessed using tools such as Grading of Recommendations Assessment, Development, and Evaluation (GRADE) which assesses eight domains: five domains – risk of bias, reporting bias, imprecision, indirectness, and inconsistency – are used to rate down the certainty of the evidence, while the last three – large effects, plausible opposing residual confounding, and dose-effect relations – can be used to increase certainty Guideline development groups are often required to make decisions when evidence is not optimal. This has been a feature of guideline development during the COVID-19 pandemic, and normative bodies need to prepare for any emergent, unconventional future health challenge. Guidelines need to be developed rapidly in response to an emerging disease where there is sparse data, low-quality studies, weak study designs, and an exponential growth in the number of publications, including pre-peer review publications –12. DisaIn the early months of the pandemic response, WHO was criticized for taking too narrow a view of the evidence (modes of transmission), insufficient representation of civil society on guideline panels (community mask wearing), and the lack of broader expertise and perspectives (ventilation and aerobiology). WHO has responded to these concerns by expanding the scope of the evidence assessed and including additional expertise within guideline development groups and peer review groups.When a rapid response to a novel emerging public health concern is needed, it may be a necessary and acceptable trade-off that guideline processes are compressed. This may be understandable given the urgency of responding and the rapidly changing nature of the situation, and reinforces the importance of transparency so that end users are aware of the trade-offs that have been made. Flexible approaches are needed so that recommendations can be updated as new evidence accumulates, including by adopting living approaches to evidence appraisal and guideline development In a period of great uncertainty, when guidance is urgently needed and the evidence is limited and/or in constant evolution, transparency is of upmost importance. If key questions are not addressed, if the evidence assessment is too restrictive, incomplete, or lacking in key areas, if an expert group lacks specific expertise or a particular member has a perceived conflict of interest, end-users of the guideline should be made aware of such limitations to facilitate local decision-making. The recent interrogation of WHOs guideline development process underscores the importance of transparency in ensuring guidance is relevant, credible, and trustworthy, and can be easily adapted and implemented to different settings globally. A valuable area for future research would be to appraise guidelines developed during a period of acute emergency against quality standards WHO remains committed to transparency, and welcomes critical feedback for improving its guideline development and content.All authors contributed to the drafting and revision of this manuscriptThis article was supported by general funds from the Bill & Melinda Gates FoundationViews expressed in this article are those of the authors and do not necessarily represent the views of the World Health Organization.


Previous studies have demonstrated that the rate of evidence integration during perceptual decision making, a specific computationally defined parameter, is negatively correlated with both subclinical symptoms of OCD measured on a continuum and categorically diagnosed patient status. However, the neural mechanisms underlying this deficit are unknown. Separate work has shown that both gamma and beta-band power are related to evidence integration, and differences in beta-band power in particular have been hypothesized to hinder flexible behavioral control. We sought to unify these two disparate literatures, one on OCD-related information processing differences constrained by behavioral data alone, and the other on the neural correlates of evidence integration. Using computational modeling and scalp EEG, we tested (N = 67) the relationships between subclinical symptom scores, drift rate, and gamma/beta-band activity during perceptual decision making. We replicated both prior work showing deficits in evidence integration as a function of OCD symptoms, and work showing a relationship between evidence integration and gamma and beta-band power. As predicted, the slope of beta-band power was correlated with OCD symptoms. However, the relationships between OCD symptoms and drift rate and the slopes of gamma and beta-band power and drift rate remained unchanged when simultaneously accounting for all variables, speaking against the hypothesis that differences in band-band power explain drift rate deficits. A decision is made when the relative amount of evidence reaches one of two decision boundaries, representing the options under consideration. A smaller distance between the boundaries indicates the subject requires less evidence to reach a decision, and vice versa. A pre-existing preference for one of the options, before seeing the stimulus, is represented by a concordant change in the amount of relative evidence at the start of the decision. Finally, a fourth free parameter codes the time taken for non-decision aspects of each trial. The studies noted above showed that OCD symptoms were negatively correlated with drift rate, the average amount of perceptual evidence integrated per unit time, in the dot motion decision task. Furthermore, these impairments were larger for easier (higher coherence) decisions, and were absent for the hardest decisions . Donnerslope of power in each band is a candidate mediator of the previously reported association between OCD symptoms and drift rate. While previous work directly connecting power in each band to OCD symptoms is more limited, beta-band power has been suggested to reflect the maintenance of the current cognitive state or ‘status quo’ , and ouParticipants were recruited based on a dimensional approach to measuring psychopathology, covering a wide range of symptom severity from the low to the high-end . Symptom2Participants. All experimental procedures were approved by the Institutional Review Board at the University of Maryland-College Park. Informed consent was obtained in accordance with the approved procedures. Participants were drawn from the campus and the surrounding community. In all, 67 participants took part in the study. Potential participants were pre-screened in attempt to evenly cover a range of Padua Inventory scores  using Psychtoolbox . For gamma, frequencies of interest were 32–100 in increments of 4 Hz. For beta, frequencies of interest were 12–28, also in increments of 4 Hz. A 250 ms time window and ieldTrip  in MatlaWhole-brain measure of evidence integration. Based on prior work, we derived an aggregate whole-brain neural measure of evidence integration  was also used to fit the drift-diffusion model. We fit the simple form of the model without variance in parameters across trials. Although this version cannot explain differences in reaction time between correct and error trials . We then used the fitted regression coefficients to weigh each electrode and compute an aggregate measure of power for all conditions (including now the medium difficulty conditions) and all time points . Note that because of how it is defined based on logistic regression, the aggregate measure is positive when the magnitude of power at individual electrodes is overall greater for easier decisions, regardless of whether the difference is positive or negative (and the aggregate measure would be negative if the magnitude was greater for harder decisions).To calculate this measure, we computed average power within each respective range and used multi-level Bayesian logistic regression to predict trial difficulty  from power at all electrode sites. This analysis was performed at the median reaction time for hard trials  during perceptual decision making, and the relationship between evidence integration and gamma and beta-band neural activity. Consistent with previous work, we found a negative relationship between OCD symptoms and drift rate, and this effect was larger for easier decisions . We did monitoring does not necessarily translate into the successful use of additional information, and while monitoring may be enhanced, OCD symptoms appear to also be associated with impairments in at least some circumstances. Indeed, these complementary differences are suggestive of a different hypothesis: true  performance impairments may be overgeneralized and result in increased monitoring for errors across a variety of domains and circumstances, in turn also driving “not just right” experiences (A larger impairment for easier decisions in the current context is partly aligned with real-world behavior, where common OCD manifestations include uncertainty about simple perceptual events such as whether a lock is turned the correct way, a stove is off, or the individual caused physical harm to another person. On the surface this appears at odds with work suggesting that OCD is characterized by inflexible enhanced error monitoring . These seriences  and feeleriences . While sWe found that changes in aggregate gamma and beta-band power were steeper for easier decisions, and moreover, the slope of aggregate power in each band was independently associated across subjects with drift rate measured based on behavioral data alone—for all conditions for the gamma band, and for five out of six conditions for the beta band. In line with expectation, the slope of aggregate beta-band power was negatively correlated with OCD score in five out of six conditions, with a trending effect in the remaining condition. However, the relationship between OCD score and drift rate could not be explained by this latter association.Increases in gamma-band power were strongest at posterior and lateral electrode sites, while decreases in beta-band band power were strongest at parieto-occipital electrode sites. We also found smaller effects in the opposite direction in each band at more frontal electrodes. This contrasts with Beta and gamma band power are also not the only candidate EEG-based neural mechanisms for explaining OCD-related evidence integration deficits. For example, multiple studies have shown that the centro-parietal positivity is related to evidence integration, as well as to estimates of drift rate based on behavioral data . It is aIn summary, we replicated the link seen in prior work between OCD symptoms and computationally defined perceptual decision making deficits, and between gamma and beta-band power and perceptual evidence integration. Seeking to unify these disparate literatures, as predicted, we found a relationship between the slope of beta-band power and OCD symptoms. Although this relationship did not explain OCD-related drift rate impairments, our work provides additional constraints on the potential neural mechanisms underlying this deficit.This work was funded by the University of Maryland-College Park.https://osf.io/kx9ry/.Source code for the models is available at: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles.An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data.Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus.Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management. Breast cancer is the most commonly diagnosed malignancy globally, with 2.3 million new cases in 2020 . OutcomeA Canadian national consortium for the neoadjuvant treatment of breast cancer (NABC) has existed since 2010. The most recent meeting of this group of national multidisciplinary experts was in May 2019 . This group assembles national multidisciplinary experts in breast cancer to discuss and disseminate emerging evidence-based guidance across the country, and in particular focus on areas that have incomplete evidence and require expert opinion to help direct practice. Various members of this group have previously published meeting reports and one expert consensus guideline, with a significant focus on the utility of NAC for locally advanced breast cancer (LABC) –6. HowevGuideline type: Evidence Based Consensus.Intended users: Practitioners who treat invasive breast cancer Applicable resource setting: Upper middle to high income nations with access to advanced screening, diagnostic, pathologic, surgical, radiation, and systemic therapy options.An expert guideline steering committee was established at the most recent Canadian National NABC Consortium meeting . The committee was comprised of academic and clinical experts in breast cancer management in the following specialties: medical oncology, surgical oncology, radiation oncology, breast radiology and anatomic pathology. All committee experts practice in academic cancer centres for more than 5 years, treat more than 100 unique breast cancer patients per year, and have demonstrated research and academic impact in NABC  Representation from multiple Canadian provinces was sought.invasive breast cancer, neoadjuvant, limited to phase 3 or 4 studies, meta-analysis, systematic review, or guidelines published in the English language. To focus mainly on new developments in this area, the search was limited to the past 5 years ; the search was then repeated for November 2020 to May 2021 prior to manuscript preparation, to ensure no new relevant evidence had been published  to each statement. Given that multiple oncology specialties were involved, respondents were asked to indicate "no opinion" only if the statement was outside of their area of direct practice and not because they had no opinion about a statement related to their specialty. Reminders were sent twice over an 8-week period. Respondents were required to provide detailed qualitative feedback regarding statements they disagreed with. Specifically, respondents were instructed that if they did not agree with a statement in its entirety, to indicate disagreement, and provide detailed feedback regarding the elements they did not agree with. As per Modified-Delphi process, statements that did not achieve consensus were reviewed by the steering committee and modified based on the qualitative feedback as collected by the survey. These statements were emailed for a second round of survey; this was emailed to the same participants. Participants were instructed to respond only if they had responded to the first survey; one reminder was sent over 6 weeks. A third round was planned if required Fig. .Fig. 2MoN, Agree + Disagree) was calculated as the sum of respondents who agreed and disagreed. Blank responses and those who indicated "no opinion" were excluded from the total number of responses for each question. The numerator  corresponded to the number of respondents who indicated "agree" for each statement. The proportion (n/N) was converted to a percent value (%) to determine the consensus value. A threshold value was determined a priori; consensus was defined as statements with 80% or more of respondents in agreement; statements with consensus > 79.5% were rounded up to 80%. Statements with less than an 80%  agreement level were marked for modification in the next round of survey, as per Modified Delphi methodology. Qualitative feedback was collected from respondents who indicated disagreement with particular statements; this feedback was utilized to modify statements that did not achieve consensus with the initial round.Agreement statistics were calculated for each statement based on the total number of responses. The denominator for each statement  [with consideration of the four domains within the framework for a recommendation’s direction and strength, which include: estimates of effect for desirable and undesirable outcomes of interest, confidence in the estimates of effect, estimates of values and preferences, and resource use [. In considering this framework, recommendations were generally considered strong if they were based on positive data and had level 1 or 2 evidence as per the GRADE framework for ranking evidence [deemed imperative to patient care and received a very high level of consensus (> 89%), it was also rated as strong. Recommendations deemed less impactful to patient care, with level 3 or 4 evidence, with preliminary (short term) level 1 or 2 evidence, high resource implications/lack of public funding, or with no published evidence and consensus < 90%, were marked as conditional. The term conditional was preferred over “weak” to indicate these statements may have evolving data thatmay strengthen the recommendation over time) and/or the statement may still be impactful for patient care, particularly in certain contexts. Available evidence was linked to recommendations in the “Grading” column  , with cource use . In consevidence , and metThe final guideline was reviewed by a pharmacist, breast cancer patient representative, and a neoadjuvant nurse navigator, all affiliated with the Sunnybrook Health Sciences Centre. Their feedback on the premise of the guideline, agreement with recommendations, and on implementation was sought.A total of 47 recommendations were initially created by the steering committee and integrated into a consensus survey. Email invitations to complete the survey were sent to 391 clinicians in October 2020. There were 109 participants who completed the survey, for a response rate of 28%. Surgical oncology represented the largest respondent group , followed by medical oncology  and radiation oncology   achieved 80% or greater consensus (agreement). A summary of all statements with the levels of consensus is presented in Table In the second round, there were 81 respondents . A summary of the modified statements in round 2 is outlined in Table studies that had negative results or did not meet primary efficacy endpoints, or with early phase data only, or therapies that had subsequent or conflicting data demonstrating a lack of meaningful impact on patient care, were excluded. The 78 included citations were fully reviewed and matched with guideline statements. For ease of readability and clarity, detailed descriptions of the evidence were not included in the recommendation table itself. Some recommendations did not have associated citations, as they were based on data published before the systematic review timeframe.There were 389 citations found on systematic review; 311 were excluded based on abstract review; criteria are shown in Fig. Targeted gray literature review did not demonstrate any impact on the accuracy or relevance of existing consensus statements. However, five additional recommendations were created by the expert guideline panel to reflect important areas of practice deemed not to be captured in the initial or revised statements This included statements on sentinel lymph node biopsy for N0 disease , nab-pacThe nursing, patient, and pharmacist feedback sought demonstrated agreement with the recommendations overall, and in particular with the multi-disciplinary approach to NAC care. Suggestions to disseminate the guideline in patient, nursing, and pharmacy forums were made.There was a high level of agreement on 59 final statements encompassing the complex, multidisciplinary care pathway of neoadjuvant breast cancer patients. Five additional statements were not sent for consensus but were integrated to reflect the most up-to-date evidence pertaining to NABC at the time of manuscript preparation. Important highlights of this guideline include the recommendation to use neoadjuvant systemic therapy for early (operable) stage HER-2 positive and triple negative breast cancer, and the subsequent use of additional adjuvant therapies for those patients with residual disease after definitive surgery. In addition, this guideline demonstrates the importance of multi-disciplinary collaboration throughout the patient care journey. Finally, this consensus guideline demonstrates a balance between improving patient outcomes in an evidence-based manner while seeking to minimize toxicities, with a focus on individualized decision making, including clinical trial enrollment, particularly where evidence is less robust or still accumulating. This is particularly relevant for local–regional treatment approaches where evidence continues to accumulate from ongoing studies.High-middle and High income countries. Due to the robust health technology assessment for cancer drug funding recommendations nationally (pan-Canadian Oncology Drug Review through CADTH) [Given the broad scope of this guideline, including many treatment modalities, formal assessment of cost-effectiveness for individual therapies was outside the scope of this guideline. The committee acknowledged that most of the recommendations were applicable to h CADTH) , provincLimitations of this guideline include only a 29% response rate to the consensus survey, and potential sampling and non-response bias. Primarily academic physicians responded to the survey, as such, the opinion of breast cancer clinicians in community practice settings may be under-represented. In addition, medical oncologists and surgeons comprised the largest group of respondents, and the opinion of other specialties may not completely be captured. There were also approximately 25% of initial participants who did not respond to the second round of survey, potentially impacting the results. However, this is unlikely, given the high levels of initial consensus on these statements with the first round (range 66–79%). Patient and other health care professionals were not engaged in the initial development of recommendations; their feedback was only sought on the final guideline and implementation plan. Five additional statements were created but not sent for consensus to prevent delay on the timely dissemination of this guideline; however, they are unlikely to impact on the scope and relevance of the guideline in general.This work represents an updated Canadian National Consensus on the Neoadjuvant treatment of breast cancer, across all parts of the therapeutic patient journey. A systematic review of recent literature and formal grading of recommendations was also achieved. The evidence was reviewed several times during guideline preparation, ensuring the most updated data was incorporated in a meaningful manner. The neoadjuvant treatment of breast cancer is a rapidly evolving area of clinical and academic interest; data can change quickly and uptake in clinical settings can falter based on sub-optimal knowledge dissemination or hesitancy to change practice. We believe our approach demonstrates Canadian consensus on key areas of neoadjuvant care, integrating available evidence, expert opinion, and practice-based consensus. We believe this guideline can help optimize patient outcomes across the country, by synthesizing the evidence into comprehensive recommendations for clinical care. Furthermore, the presence of national practice guidelines may help to foster clinical and policy change within healthcare organizations and health networks, with the hope of achieving uniformity of practice and thus patient outcomes. Given the importance of ensuring patient management is aligned with best practice, and to help optimize the use of resources and expertise in this area, we hope to achieve broad dissemination of this consensus guideline. A particular strength of this work is the inclusion of all elements of the patient treatment journey, formal grading of recommendations, and also achieving high levels of consensus, particularly in areas where evidence is lacking or evolving. This may help implementation and uptake of practice elements that can standardize Canadian breast cancer care as the neoadjuvant landscape continues to rapidly evolve. This guideline will be disseminated at the next Canadian National NABC Consensus meeting (planned for mid-2022), and ideally at national and international academic forums. There is also much interest in this document from national, provincial and hospital-based cancer programs in Canada to help guide local practice and resource allocation. We hope this guideline will be a strong addition to the published literature in this important area.


Medicine is based on knowledge from scientific studies and the validation of clinical experience. Medical knowledge must be well established before it can be considered as the basis for decision making. Journals have a clear responsibility to help readers recognize the level of evidence for the claims published in their manuscripts. Levels of evidence alone do not determine the quality of the article but help readers to understand the significance of the claims.We recognize that our discipline, radiology and medical imaging, also suffers from a certain lack of reproducibility of its results when translated into practice. Although our clinical work is firmly based on years of practice and well-known criteria and characteristics, new proposals and some older standards are not free of errors and biases.Authors are encouraged to specify in the manuscript the appropriate level and recommendation of their claims, following the criteria of this journal. The categorization into only three levels is based on publications in addition to critical approach to technical and clinical studies related to medical imaging [This is the main reason why our journal encourages authors to follow this guideline when analyzing referenced papers and their own work Table . The lev imaging –5. These


If you would like to receive a copy of the approved title registration form, please send an email to the Managing Editor of the relevant Coordinating Group.1School‐based language, math, and reading interventions for executive functions in children and adolescentsMorten Kjær Thomsen, Julie Kaas Seerup, Jens Dietrichson, Martin Williams Strandby, Bjørn Christian Arleth Viinholt30 September 2019Problem solving before Instruction (PS‐I) to promote learning and motivation in child and adult studentsEduardo González‐Cabañes, Trinidad García, Catherine Chase, Jose Carlos Núñez30 September 20192An evidence and gap map of development evaluations conducted in IndiaAshrita Saran, Howard White, Bhumika T V, Divya Sussana Patil, Eti Rajwar30 September 2019An evidence and gap map of development evaluations conducted in Karnataka 2000‐19Bhumika TV, Ashrita Saran, Divya Sussana Patil, Eti Rajwar, Howard White27 September 2019Effectiveness of interventions to reduce environmental air pollution: An evidence and gap map in low‐ and middle‐income countriesJudith A. Noronha, Vijay Shree Dhyani, Prathibha Kamath, Ashrita Saran, Preethy Dsouza, Anil Raj4 November 2019


Aedes aegypti is the main vector of the dengue virus in Colombia. Some factors have been associated with its presence; however, in the local context, it has not been sufficiently evaluated. The present study seeks to identify the socioeconomic, environmental, and behavioral factors associated with the presence and abundance of A. aegypti in urban dwellings in the municipality of Castilla la Nueva. A cross-sectional cohort study was conducted in houses in the urban area of the municipality of Castilla la Nueva, where 307 houses were sampled by systematic random sampling during May 2018. A multifactorial survey was used to measure the socioeconomic, environmental, and behavioral factors as explanatory variables. The infestation and relative abundance were established by the presence of larval stages and ovitraps. The associated factors for the presence and abundance of A. aegypti were identified using negative binomial and logistic regression models. A positive housing infestation of 33.2% was identified by direct inspection and 78.5% with ovitraps. The main factors positively associated with the presence and abundance of A. aegypti were one-story homes , the storage of water for domestic use , and local conditions such as disorganized backyard  and the proportion of shade greater than 50% of the backyard . And, it is negatively associated with residential gas service  and self-administered internal fumigation . The presence and abundance of A. aegypti were explained by interrelated socioeconomic, environmental, and behavioral factors where local conditions and habits such as the organization of the patio, knowledge about vector biology, and cleaning containers are identified as main topics for future prevention strategies for the transmission of dengue in the local and national context. Aedes aegypti is the primary vector of the dengue fever virus (DFV) in Colombia. Its adaptation to the local anthropic conditions and capabilities of transmission of other viruses such as Zika and chikungunya makes the presence and abundance of this vector a significant threat to public health [c health –4. In 20c health . Additioc health .So far, prevention strategies for the transmission of DFV have been based on socioeconomic, environmental, and cultural determinants , 7, 8. SSimilarly, other factors such as traditional cultural dynamics, health education, and behavior have been identified as critical , 15. AlsA. aegypti [The control of vectors in Colombia is conducted following protocols designed for generalized conditions without considering the local particularities. This has hindered the effective execution of programs of vector control and dengue prevention –24. Addi aegypti , 25, 26.A. aegypti in the municipality of Castilla la Nueva. Our findings allow the identification of parameters that can be used to improve the education, control, and surveillance programs of dengue in local communities.In Colombia, the lack of utilities such as water supply, sewage, residual disposal, and nonregulated urbanization have been essential factors related to the vector's presence and dengue outbreaks . HoweverThe study was conducted in the urban center of the municipality of Castilla la Nueva, in the Department of Meta, Colombia . It has an estimated population of 8,787 (2018 projection), distributed as 4,337(49.4%) in urban areas and 4,450 (50.6%) in rural areas. The urban area has 1008 residential properties in 13 neighborhoods, with approximately 60 blocks . The town of 317 houses. At the first building in each block, the sampling was conducted, moving clockwise and maintaining a sampling interval every three houses (N/n), following the national guideline [An observational cross-sectional study was designed and conducted. The study was developed during May 2018 in the urban area, taking households as sampling units. The month of May was selected mainly because of the beginning of the rainy season, which is theoretically related to the increase in the abundance of mosquitoes and the beginning of the peaks of dengue cases. The entomological sampling and the delivery of the multifactorial survey were designed systematically in the urban area of Castilla la Nueva. The systematic sampling was carried out according to what was established for the Stegomyia larval index in Colombia , 30; theInformation bias was controlled with training and standardization of the interviewers, conducting a pilot test, quality control of the survey, and confidentiality of the information, and confounding biases, with binary logistic regression statistical analysis.https://www.cdc.gov/epiinfo/mobile.html). Technicians of the Secretary of Health delivered the survey. The survey was divided into three parts: socioeconomic, environmental, and behavioral.A multidimensional survey collected the information; the instrument was prepared in digital format for mobile phones or tablets using the Epi Info application  positive ovitraps by the presence/absence of positive ovitraps, and (3) the number of eggs per ovitrap. A single sampling was carried out with ovitraps for a month, and eggs collected in the ovitraps were counted using a stereomicroscope at 20 times magnification.The information regarding the presence of immature stages of Colombia , 30. ThrBacillus thuringiensis var. israelensis (Bti) granulated was added, according to Alarcón et al. [The ovitraps were located inside the houses, mainly in the courtyard, in a shady and cool place, on the floor, or at 1.5 meters high in houses where small children or pets lived. The ovitrap was assembled with a 2-liter plastic bottle cut in half and painted black, and then a strip of white cloth was attached inside. The piece bottle is then filled up with 0.95 liters of water, and 1 gram of n et al. .p value >0.05). Similarly, negative binomial regression models were used to assess the association of variables with the egg counts per ovitrap. The stepwise forward selection was used to select the variables for the final model using the Akaike information criterion (AIC). R statistical software (V: 3.6.1) was used, including the following packages epiDisplay and nortest [.Exploratory data analysis was conducted to describe the distribution and frequencies of the variables. After this, the association between independent variables and the outcomes was estimated using bivariate cross-tabulation tests (chi-squared test or Fisher's exact test). The prevalence ratio (PR) was calculated for each variable. The adjusted prevalence ratio was calculated using bivariate logistic regression. A multivariate model was built using the variables with significant associations found in the bivariate analysis  and the department and municipality health branches .A. Aegypti was an average of 74.6; 75% of the traps had a capture of fewer than 238 eggs, and the maximum value of eggs was 1.512.Three hundred and seven residences (96.8%) from the estimated sample (317 houses) participated in the study . The entomological survey allowed determining a general housing infestation proportion of 33.2% in the urban area of the municipality. The presence of concrete washbasins and other forms of in-house water storage for laundry and other housekeeping tasks contributed the most to the infestation index with 22.48% followed by 200-liter metal barrels (6.84%), pet waterers (1.95%), bottles (0.98%), aquatic plants (0.65%), and flower pots (0.33%). A total of 241 (78.5%) positive residences were identified with the ovitrap sampling method—the number of eggs per ovitrap of Most of the participants were women (73.9%). Many participants (76.9%) had at least a high school education, and 1.3% had not received any education. The main occupation identified was housekeeper (44.3%) followed by formal work (22.5%) and self-employed (16.6%). Most of the surveyed population (52.1%) had an income of 2 times the minimum wage in Colombia (approximately US$550). 59.9% of the population owned their house, and all the households in the municipality have access to essential utilities  .76.9% of the residences corresponded to one-story brick and mortar houses, cement roof tiles, tiled floors, and concrete washbasins. 86% of the homes presented good maintenance of painted walls, doors, and windows. However, 24.4% had a disorganized patio, and 35.5% had a partially disorganized patio. In addition, 66.4% of patios had a proportion greater than 50% of shade .As main behavioral factors, it was observed that most of the surveyed population traveled outside the municipality (79.5%), some of them monthly (51.8%). Regarding the habits, it was found that 82.7% of the respondents stated that they wash the reservoirs at least every week. 75.2% of the community stated that the main reason for storing water was domestic activities such as dishwashing, cooking, housekeeping, and laundry.A. aegypti, which shows that a significant proportion of the population is unaware of important aspects of the biology of the vector.A significant proportion of the surveyed population demonstrated some knowledge of the vector (94.5%), the breeding sites of the vector (87%), and the role in the transmission of arboviruses (92.2%). However, 39.7% could not describe the behavior and the place of oviposition for Regarding the practices to prevent reproduction and mosquito bites, it was found that, in a high percentage of households (77.2%), the people in their homes every eight days generally perform self-application of insecticides. Additionally, they used physical barriers  and controlled actions in the tank, which included washing the tank and some lids that could prevent the entry of mosquitoes .A. aegypti. In contrast, the factor having domestic gas showed an opposite effect, with a 1.4 times lower probability of finding infested residences than households that do not have this service . About the environmental factors, it was found that one-story homes are strongly associated with the presence of vector mosquitoes .The bivariate analysis showed that socioeconomic factors such as the number of bedrooms in residence (between 4 and 6 bedrooms), home ownership, and living in an irregular urban development zone were factors significantly associated with positive houses for the presence of immature The most relevant behavioral factors identified were the storage of water for domestic use  and mobility outside the municipality , in which the frequency of monthly mobility showed a lower probability of finding infestation with immature mosquito states compared with households where their inhabitants do travel outside the municipality. In addition, it was observed that the people who identified the vector and practice prevention such as regular home pesticide spraying decreased the probability of home infestation 1.85 and 1.6 times, respectively .An association between positive ovitraps and socioeconomic factors such as Internet service and domestic gas was observed since a home with Internet access and gas was less likely to have positive ovitraps. About the environmental factors, it was observed that rustic cement floors , houses with moderate maintenance , disorganized patios , and a proportion of shade greater than 50% in the patio  increased the probability of finding positive ovitraps  and the proportion of shade greater than 50% of the patio . The model also identified that cleaning the concrete washbasins was positively associated with gravid female mosquitoes in the residences . The same environmental factors were also positively related to the abundance of  ovitrap .A. aegypti. The direct inspection of water containers and the captures of eggs of A. aegypti with ovitraps were adequate for the identification of the presence of the vectors as it has been reported by other studies [This study allowed the identification of socioeconomic, environmental, and behavioral factors associated with the presence and abundance of  studies , 33–37.  studies , 38, 39.A. aegypti . These containers have been identified as the most prolific breeding sites (>60%) for mosquito production in Colombia [The percentage of residences with the presence of the mosquito was 32.2%, which is similar to that reported by other studies , 40, 41.Colombia , 43. TheColombia  in the mColombia , 26.In the present study, the socioeconomic variables associated with the vector's presence were the number of bedrooms in the house, property condition (rent/own), and some services such as gas and Internet. However, the latter two variables are not similar to those used in other studies , 34. A sA. aegypti in the study areas is related to the environmental conditions rather than the socioeconomic level.Other research works in Colombia  have shown that houses in privileged neighborhoods have less density of the vector, thus less risk of exposure to dengue , 45. HowRegarding environmental factors, temperature has been identified as an important factor in the abundance, dispersion, and transmission of arboviruses by the mosquito –48. HoweOther factors related to the presence of the vector were behavioral factors. Habits and monthly frequency of travel out of the municipality showed a low probability of finding the mosquito in the study area. This suggests that people who travel with less frequency could permanently control breeding sites, minimizing the mosquito reproduction. These results are similar to those reported in studies of dengue transmission models by Stoddard et al. , where tThe reasons and motivations for storing water in houses' containers are behavioral factors to consider. In this municipality, all the population has access to tap water with constant supply; however, people decide to store water in the houses for, according to them, its use in “multiple housekeeping chores.” The presence of water containers was associated with a higher probability of the presence of the mosquito. This same association was found in a study in Dhaka, Bangladesh, where they found a threefold risk of the presence of the vector if water was stored compared with those residences where water was not stored . Our resWe also evaluated the potential association of knowledge about the vector and dengue with the presence of the vector. Widespread global recommendations of control and prevention of mosquito populations and dengue transmission always include knowledge access and appropriation as essential . A studyOn the other hand, we found an association between spraying insecticide (by the inhabitants) and the presence of the vector. This effect was also reported in a systematic review by Samuel et al. , where iThe logistic model identified multiple explanatory factors associated with the presence of the vector in the participant households. The main associated factors were the house type, being an owner, and having professional habitants. These findings were surprising since they are characterized by the quality of life and possibly by a better understanding and attitudes toward preventive behaviors for controlling the vector. However, our results were similar to those reported in other studies in Cali , Java 5, and ThaA. aegypti. These factors can also be related to the educational level, the quality of life, and other socioeconomic factors that promote the conditions for reproduction and the presence of the vector [Explanatory models developed with positive ovitraps and the number of eggs per ovitrap found environmental factors associated with the presence of gravid females. The local conditions as poor maintenance, >50% patio shadow, and disorganized patio were associated with the presence and abundance of e vector . These fe vector , 56.The model also identified that washing the concrete washbasins is associated with the presence and abundance of the vector. However, the information of practices obtained may be influenced by participants' answers since this practice is perceived as an accepted norm behavior. Also, we found that participants reporting washing the concrete washbasins weekly in participants' residences reported a higher infestation and abundance of the vector. These findings show that people know the importance of concrete washbasins' cleanliness and frequency of cleaning, but this knowledge does not affect the behavior or the cleaning is not being performed adequately. The results are consistent with those reported in a study conducted in Bucaramanga, where an intervention of information, education, and communication was implemented. This intervention showed a modification of the knowledge about vector control practices, but this did not decrease the number of breeding sites or the incidence of dengue .One limitation of this study is that we determined the presence and abundance of the immature stages of the vector  without using the Stegomyia larval index or density or abundance of pupas or adults, important outcome indexes that might have shown an association with other factors. Second, the study's cross-sectional nature only allowed collecting data at a specific time of the year (rain season). We consider that collecting information in the dry season could have led to different results since the vector's abundance and presence could change in these two seasons.A. aegypti in the study area are explained by socioeconomic, environmental, and behavioral factors such as home ownership status, housing type , service domestic gas, spray the house with insecticides, education level, profession, patio condition, shadow in the patio, and concrete washbasins cleaning, where the conditions of the residences and modes of living of its inhabitants played an important role. Additionally, the study concluded that the main mosquito breeding sites are large water containers larger than 200 liters in which entomological and community control actions should be focused. Likewise, the use of ovitraps as an entomological indicator of the presence of A. aegypti was shown to be more sensitive than direct inspection of water containers, suggesting that this tool could be used routinely for entomological surveillance in Colombia.The present study identified that the presence and abundance of Finally, based on the identified factors, we recommend generating public policies focused on house maintenance, strategies that highlight the importance of patio organization, and adequate water container cleaning as topics in preventive education programs. In addition to these findings, efforts should be made to help the people to go from knowledge to practice. We believe that the implementation of these activities will help decrease the presence and abundance of the vector, thus reducing the risk of exposure to the dengue fever virus.


Acta Orthopaedica. The primary goal was to evaluate “efficacy of individual items of the perioperative treatment pathway to expedite the achievement of discharge criteria”  recently published in While this type of effort is important in order to provide the wider perioperative and anesthesia community with guidance, its publication comes with a great deal of responsibility, as practitioners will use this information to model their practice. Therefore, clinicians need to not only read the conclusions, but be aware of the sources of evidence they are based on. In this context, it must be acknowledged that this consensus document provides an enormous amount of valuable information, however, a number of points should be considered. Specifically, a closer look at the 17 considered recommendations may lead to questions regarding the search methodology as well as the concept of including so many factors, which may be of limited importance in fulfilling the primary aim of the consensus report, namely the earlier achievement of discharge criteria. It must be asked if the inclusion of this large number of interventions is indeed feasible and/or justifiable for such a project. This concern is based on the fact that the information considered was to a large extent not procedure specific nor was it – in many cases – derived from studies conducted during a time that is compatible with documented modern ERAS clinical practice in fast-track THA/TKA. Another factor to consider is that the group’s focus was heavily weighted towards specific clinical studies, thus frequently ignoring information gained from other literature sources, such as population-based investigations, which when considered can provide valuable information.As to the proposed recommendations, preadmission patient optimization regarding smoking and alcohol, although arguably appropriate, is not based on hard scientific, procedure-specific data. Indeed, much of the information is based on transferable evidence from other procedures and not supported from the few fully implemented THA/TKA ERAS data. Preoperative information is obviously to be implemented according to common practice in most countries, but is not a unique procedure-specific item on the specified discharge criteria or documented to enhance discharge in THA/TKA. Preoperative fasting has been emphasized repeatedly in all previous ERAS guidelines. Further, it is a well-established fact that oral intake does not have to be withheld for long. However, there is no procedure-specific evidence from THA/TKA where the patient in modern practice care is admitted on the morning before surgery. The same applies to preoperative carbohydrate treatment, which is not recommended as an essential or routine intervention. To include pre-anesthetic anxiolytic medication is neither procedure-specific nor evidence-based and is obviously not necessary in other types of modern surgery. The recommendations for general vs. neuraxial anesthesia are discussed rather superficially and lead to the conclusion that either technique can be used. Here, the recommendation conflicts with recent (and previous) data suggesting that neuraxial approaches may be preferable . However, the latter conclusion is one that stems from the evaluation of a much broader literature base, including population data that considers complication risk. The topics of spinal opioids and epidurals get to the right conclusion not to be recommended, although the literature basis for this suggestion is superficially presented with regard to side effects. Additionally, the important and large topic of pain management, which is crucial to achieving early mobilization and shortening discharge time (the primary aim for the guideline) is mostly based on old references in which a length of stay (LOS) > 2 days was prevalent in most studies. This fact and the rather limited literature review does therefore not seem to appropriately support the current clinical practice. The same applies to the multimodal analgesia section which also suffers from the surprising lack of discussion of the use of preoperative high-dose steroids  despite the availability of several systematic reviews and RCT’s with rather promising results published before manuscript submission. Further, there is a lack of references to critical systematic reviews on pain management   (Memtsoudis et al. Hopefully, future procedure-specific ERAS guidelines will be divided more specifically into items that constitute transferable evidence/routine perioperative care in modern surgery vs. well-documented interventions to achieve an improved and fully implemented procedure-specific ERAS program to enhance total recovery, shorten LOS, and decrease complications (Kehlet and Joshi