Many initiatives have been taken in the Islamic Republic of Iran to promote evidence-informed health policy-making (EIHP). However, these initiatives are not systematic. Since the implementation of EIHP is not consistent and the interventions in this regard are complex, a comprehensive plan could be a useful tool for employing initiatives to achieve and promote EIHP. Hence, this study aims to develop a roadmap for strengthening EIHP over a 3-year period in Iran.Nine projects will be conducted to define the roadmap for strengthening EIHP. These projects include two reviews and a stakeholder analysis to identify the factors that facilitate or hinder achieving EIHP. The next study will be a qualitative study to prioritise the challenges and outline the main causes. The following steps will be a review of reviews to extract global experiences on interventions used for strengthening EIHP and two qualitative studies to examine the adoption of these interventions and develop an operational plan for strengthening EIHP in Iran. The research will be completed through conducting two qualitative-quantitative studies to design a tool for measuring EIHP and assessing EIHP in Iran at baseline.This national EIHP roadmap will surely be able to identify the gaps and bumps that might exist in the implementation plan for establishing EIHP and eliminate them as needed in the future. This roadmap can be a step in moving towards transparency and accountability in the health system and as thus towards good governance and improvement of the health system’s performance. Although the plan can be a good model for developing countries and may promote the use of evidence in health policy-making, we should assume that there are some critical contextual factors that could potentially hinder the complete and successful implementation of EIHP. Thus, to enhance EIHP in these countries with a policy-making context that does not fully support the use of evidence, it is crucial to think about not only those interventions that directly address the EIHP barriers, but also some long-term strategies to make required changes in the context, both beyond and within the health system. Iran has undertaken a number of important initiatives, particularly during the recent health sector reform  that began in 2014, to achieve healthcare for everyone by expanding universal health coverage (UHC) by 2025 . To tackThe importance and consequences of EIHP are widely acknowledged in the literature –12. The Many initiatives have been conducted to increase and institutionalise the EIHP and to identify its determinants –27. MoreThe increasing growth of global attention to the use of evidence in health policies motivated Iran’s health system to introduce some initiatives toward promoting EIHP –43. As aTo develop the roadmap for strengthening EIHP in Iran, nine research projects will be conducted. These projects will be conducted simultaneously in some areas and consecutively in others. The whole project will last approximately 2 years Fig. . What foThis project is being undertaken to identify the probable barriers and facilitators of EIHP in the health sector through a qualitative approach. The data will be collected in three stages. In the first phase, the research team will define the study questions. These questions must be described as such so that they can cover the topic under study, i.e. identifying the barriers and influential factors that may affect EIHP in the future in Iran. Subsequently, by using the available documents , the list of issues and trends that may affect the health system in the future will be extracted. These trends and issues will be classified using the STEEP  model. With the help of this model, information regarding the important future causes of change will be identified in various components, including the social, technological, economic, ecologic and political components, and their outcomes will be classified as opportunities or threats. In the second phase, a focus group discussion (FGD) will be held with relevant experts to outline the main important trends. In the FGD session, in which experts familiar with health policy-making, trends and mega-trends analysis will be attending, the participants will be asked to discuss and exchange ideas on the trends affecting EIHP in Iran. These participants will be informed of the meeting’s objectives beforehand by phone or email. After the initial agreement, invitations will be sent along with a list of trends extracted from the first phase. Two facilitators will be responsible for steering the communications. With the participants’ consent, their conversations will be audio-recorded with a digital voice-recorder. Notes will also be taken during the discussion. After listening to the audio files, they will be transcribed verbatim. A summary of emerging trends and issues identified at the meeting will then be emailed to the participants for their revision and completion if needed. The identified trends will be finalised according to the participants’ comments. In the second FGD session, the participants will be asked to discuss the impact of identified trends and the opportunities and threats faced by EIHP in Iran. At this stage, the same FGD participants will be invited. The summary of the meeting will be compiled in the form of a list of influential trends. The most important future opportunities and trends of EIHP in Iran that were recognised from the identified trends will also be compiled and finalised in a meeting held by the research team. In the third phase, the research team will determine the scenario’s components and share them in group discussions to identify relevant scenarios.Several studies have been conducted to identify the factors influencing the improvement of EIHP. Therefore, we decided to conduct a systematic review to summarise the results of the available studies. This review will include investigations that have examined the facilitators and barriers to EIHP. The inclusion criteria for the articles will be all research that has identified factors enabling or hindering the use of evidence in health policy at a macro level in Iran. The studies on clinical decision-making and/or service-providing organisations  will be excluded. The articles will be in both Persian and English. The search will be conducted using appropriate Persian and English keywords in PubMed, Medline, Scopus, Embase, Health Systems Evidence and Scientific Information Database. To increase the sensitivity of the search, hand-searching will be done in relevant national and international journals, reference lists and related documents from various organisations , and citation tracking will be performed. Endnote software will be used to manage the references. The primary screening (based on the article title and abstract), the secondary screening (based on the article full texts) and data extraction will be independently conducted by two individuals and, in the case of disagreement, and it will be examined by the research team. The data extracted from each article will be as follows: title, year of publication, year in which the study has been conducted, study objective, methods, population under study, sampling frame and procedure, sample size, data collection tool, analysis method, barriers, facilitators, interventions and outcomes relevant to EIHP, stakeholders mentioned in the study, and the method of evaluating EIHP status. The systematic review will be a mixed research synthesis of the integrated design types , and allA stakeholder is an individual or a group that may affect the organisation and in turn be affected by the organisation’s actions, policies, practices and decisions . Any polThe second stakeholder analysis will be conducted to determine whose interests should be taken into account when implementing interventions of the plan. To do this, the key stakeholders of each proposed intervention will be identified through a brainstorming session with the research team’s members. To analyse the stakeholders’ power, position and interest, a list of interviewees will be prepared through purposive and respondent-driven sampling and they will be interviewed. The selection criteria will be based on their knowledge, experience, impact and involvement in EIHP in Iran. We will explore influence and power by questions focusing on the alliances and resources of the stakeholders . Interviews will be continued until the point of data saturation is reached. An interview consent form will be completed by each interviewee before starting. The qualitative data will be analysed through a thematic analysis (inductive and deductive) approach. Based on interpretation of the interview, stakeholders’ power and influence will be categorised, according to whether they had high or low influence on the intervention, and specifically the degree to which they were able to place the issue on the public or political agenda, influence legislation, or actively participate in implementing and mobilising the intervention. At this stage, the stakeholders’ matrix will be drawn based on their characteristics. Finally, given the position of each stakeholder, appropriate strategies will be designed and presented for better engagement and interaction through a brainstorming session. The output of this stage of the study will be a list of EIHP stakeholders and actors, along with their characteristics and strategies for encouraging their participation.To assess EIHP status at baseline and post interventions, a tool is needed to properly measure it. There are limited tools for measuring EIHP, most of which subjectively measure policy-maker knowledge, individual and organisational capacity, and the factors affecting EIHP. For example, Lavis et al.  and ImanGiven the outputs of the first and second projects, and upon extracting EIHP’s challenges, this phase will be conducted to identify the major challenges faced by EIHP in Iran using the root cause analysis approach and ‘the 5 Whys technique’. Data collection will take place through FGDs. The participants will be selected purposively from among EIHP stakeholders in Iran, including health policy-makers, directors of various health organisations and faculty members. The participants will be chosen in accordance with the challenges selected for that session. During the session, a list of relevant challenges will be selected and handed out to the participants. First, they will be asked why this issue has arisen. All the responses will be noted down in a flip chart. Gradually, and step by step, other ‘whys’ will be asked and the responses will be written in the flip chart. The method of analysis will be in the form of a tree diagram based on the nature of the identified barriers and challenges. The outcome of this study will be a list of prioritised challenges faced by EIHP in Iran.Selecting the appropriate interventions to strengthen EIHP should be informed by scientific evidence. Thus, the best option is to review global experiences to choose these interventions instead of simply using expert opinions. Therefore, to prepare a list of previously tested interventions to confront highly prioritised EIHP challenges, a review of current reviews –53 will A good programme should propose context-specific solutions in order to achieve a successful outcome. Thus, this project will aim to provide tailored solutions extracted from previous settings to overcome the identified and prioritised challenges of EIHP. The interventions will be contextualised according to two variables, namely general political and health system characteristics. In the general political environment, political institutions , interests of active political groups, alignment of interventions with beliefs and values, and the effect of external factors  will be considered . In healBased on reports and expert opinion, the status of EIHP in Iran remains far from desirable ; furtherThe context of the study is Iran’s health sector. Since the tool applied has not yet been finalised, we cannot determine the details of the size and characteristics of the sample. However, it seems that the respondents will be selected from the MOHME’s senior managers , health policy-makers in law-making bodies  and health policy-makers in resource allocation organisations . The method of analysis will be selected based on the type of tool employed.The development of a plan of action can effectively steer interventions towards targeted relevant efforts for strengthening the status quo and abstaining from wasting of resources. We expect that the development and utilisation of this plan will help bring about effective results for the health system and improve its governance. To conduct this project, first the programme development framework will be finalised by examining the existing frameworks and relevant elements by the research team, including the activities, timeframe, person responsible and the budget. Given the outputs of earlier projects, each of which covers an important section of the main elements of the programme, an operational plan for strengthening EIHP will be developed for Iran’s health sector. Finally, a skill-based capacity-building programme will be tailored to the needs of each stakeholder.While Iran’s government has committed to achieve UHC , its heaAlthough the proposed roadmap may improve the use of evidence in health policy-making, we presume that there are some critical factors that hinder the full and successful implementation of EIHP. Contextual factors are an example of the barriers that can affect the use of evidence in health policy-making. With a shortage of overarching transparency and accountability, it is hard to expect that we can make sustainable changes to improve the use of evidence in decision-making and to institutionalise this approach. Because of this, the changes in these factors are out of the scope of the present project and cannot be achieved in the short term. On the other hand, they largely determine the ways in which the evidence is used in the policy process, as well as being a criterion for what should be considered to be good evidence. Of course, political instability can affect the situation. Therefore, conflicts with other countries and geo political challenges can change EIHP in a significant way.We also assume that our plan will be at risk of a conflict of interest and the process employed to achieve an impact in policy-making. There are many different stakeholders with varied and incompatible interests and aims. The conflict that they have in their interests can impact both what constitutes evidence and how the evidence is interpreted and applied. They can also bring personal issues or relationships to the table that might not be addressed, altering the purpose and context for decision-making. In conclusion, to enhance EIHP in countries with policy-making contexts that do not fully support the use of evidence, it is crucial to think about not only those interventions that directly address EIHP barriers, but also long-term strategies necessary to implement the required changes both beyond and within the health system.


What is a normative reason for acting? In this paper, I introduce and defend a novel answer to this question. The starting-point is the view that reasons are right-makers. By exploring difficulties facing it, I arrive at an alternative, according to which reasons are evidence of respects in which it is right to perform an act, for example, that it keeps a promise. This is similar to the proposal that reasons for a person to act are evidence that she ought to do so; however, as I explain, it differs from that proposal in two significant ways. As a result, I argue, the evidence-based account of reasons I advance shares the advantages of its predecessor while avoiding many of the difficulties facing it. Paris, Texas is showing is a reason for Miyuki to go to the cinema. The reason in each case is a normative reason, a consideration which, to use Scanlon’s , irrespective of a person’s epistemic relationship to the facts.2O seems a satisfactory and informative account of the nature of water, even if there is more to be said about the natures of hydrogen and oxygen. Be that as it may, even if R = MR falls short of a final analysis, it remains a non-trivial and substantive claim about the nature of reasons.One might worry that R = MR not be fully adequate as an account of reasons unless the notion of rightness is basic or fundamental.Third, which facts make it right to act? I take it that it is the job of first-order normative theory to answer that question. Perhaps there is a plurality of right-makers—that acting keeps a promise, that it benefits others, that it avoids harm, that it is fair, and so on. Perhaps there is one fundamental right-maker—that acting causes pleasure, say. The proponent of R = MR does not need to take a stand on these issues, and nor do I. Along the way, I will make some remarks about when it is right to act, but for illustrative purposes only.morally right to act, its being prudentially right to act, its being aesthetically right to act, and so on. On that basis, a proponent of R = MR might distinguish moral reasons, prudential reasons, aesthetic reasons, and so on  is an overall notion.A respect in which doing something has a certain property is a fact, one in virtue of which doing that thing possesses or exemplifies that property in some way or regard. For example, that cereal is high in fibre is a fact, one which makes eating cereal healthy in a way. So, it is a respect in which eating cereal is healthy, even if eating cereal is unhealthy in other respects or overall. Likewise, that the race is a marathon is a fact, one which makes her running it impressive in one regard. So, it is a respect in which her running the race is impressive, even if it is not impressive in every regard or overall.To return to the example, that Miyuki promised to go the pub is a fact, one which makes it right for her to go to the pub in a way. So, it is a respect in which her going to the pub is right, even if it is wrong in another respect or overall. So, according to R = MRR, that Miyuki promised to go to the pub is a reason for her to go to the pub.evidence of some such respect, for instance, that by staying in the building she will suffer harm.R = MRR is a step in the right direction. But there is a further problem facing the proposal—it seems not to accord with our ordinary habits of treating certain considerations as reasons in thought, talk, and action. Many considerations which we treat as reasons are not respects in which it is right to act, or facts which make it right to act in some respect. Suppose, for example, that a fire alarm is sounding. Ananya might say or think that that is a reason for her to leave the building. When deciding what to do, she might take into account the fact that the alarm is sounding; it might figure as a premise in her practical reasoning. As a result of this deliberation, or via some other route, Ananya might leave the building for the reason that the alarm is sounding. When challenged, she might cite the fact that the alarm is sounding in justifying her behaviour. She might also appeal to that fact in trying to convince her colleagues to leave. In all these ways, Ananya treats the fact that the alarm is sounding as a reason for leaving. However, that fact is not plausibly a respect in which it is right for Ananya to leave the building or a fact which makes it right in some respect for her to do so; instead, it is To dwell on this, suppose that a first-order normative theorist arrives at a list of the fundamental respects in which it is right to act: that it avoids harm, that it keeps a promise, that it benefits others, that it is fair, and so on. That an alarm is sounding is not going to appear on this list.because consuming poison causes pain, where the fact that some act causes pain is a fundamental reason not to perform it. However, the fact that the alarm is sounding does not stand in an explanatory relation to any of the items on the list; it does not explain why leaving the building keeps a promise, or benefits others, or avoids harm, or is fair, and so on. Rather, it stands in an evidential relation to certain items on the list; that the fire alarm is sounding indicates that leaving the building avoids harm, for example. To put the same point differently, it is not the case that leaving the building avoids harm  because the alarm is sounding; leaving the building does not avoid harm in virtue of the fact that the alarm is sounding. Rather, that the alarm is sounding is evidence that leaving the building avoids harm.Perhaps there are derivative right-makers—facts that stand in a suitable explanatory relationship to the fundamental right-makers. For example, that the food contains poison might be a derivative reason not to eat it The point is not that, if reasons are facts which make it right in some respect to act, they cannot play the roles which reasons play in our ethical lives; rather, it is that many of the considerations which do play the relevant roles are not facts which make it right in some respect to act. R = MRR undergenerates reasons.Perhaps there is no requirement that an account of reasons respect all aspects of our ethical lives, or that it take our everyday habits of treating considerations as reasons at face value. However, if an account does accord with, or even vindicate, such things, that is a positive feature of it. In the next section, I will introduce such an account.R = ERRThe fact that p is a reason for a person to φ if and only if:R is a respect in which it is right for her to φ;and the fact that p is evidence of R.The above leads naturally to the view that a reason is evidence of a respect in which it is right to act. More fully:To illustrate, that an alarm is sounding is evidence that Ananya will avoid harm if she leaves. That she will avoid harm is a respect in which it is right for Ananya to leave. So, given R = ERR, that the alarm is sounding is a reason for her to leave. To return to an earlier example, that it is Stanley’s birthday is evidence of a respect in which it is right for Elliot to give him a present—that it will bring Stanley pleasure, say, or that it treats him fairly. So, given R = ERR, that it is Stanley’s birthday is a reason for Elliot to give him a present.R = ERR is, of course, similar to R = MRR insofar as it appeals to the notion of rightness in a respect but there is an important difference. Whereas R = MRR involves the notion of making something the case, R = ERR involves the notion of being evidence that something is the case.Like the proponent of R = MRR, a proponent of R = ERR might distinguish moral, prudential, aesthetic, etc., reasons for action by distinguishing respects in which it is morally, prudentially, aesthetically, etc., right to act, she might distinguish justifying and requiring reasons by distinguishing evidence of respects in which it is (merely) right to act from evidence of respects in which it is also wrong not to act, and she might distinguish objective and subjective reasons, or possessed and unpossessed reasons, by appeal to familiar distinctions between objective and subjective evidence, or between possessed and unpossessed evidence. Also, like the proponent of R = MRR, a proponent of R = ERR need not take a stand on what the respects are in which it is right to act, which is a question for first-order normative theory.One might ask what it is for a fact to provide evidence for some proposition. I am not going to offer here an account of the evidential relation. Instead, I will rely on the intuitive idea that evidence to some degree makes it likely, renders it probable, indicates, etc., that a proposition is true. I do not think that anything will turn on the details of what evidence is.Note that evidence can be decisive. When there is decisive evidence that p, it follows that p. In this way, the fact that p is itself decisive evidence that p. So, R = ERR is consistent with the claim that a respect in which φing is right is itself a reason for φing, insofar as it is decisive evidence of a respect in which φing is right.To say that a reason for acting is evidence is not to say that the conclusion of practical reasoning is the belief or judgement the evidence supports. While R = ERR is silent on such matters, it is consistent with the view to hold that the conclusion of practical reasoning is the action or decision which the evidence, or the reasons it provides, supports. So, R = ERR does not turn practical reasoning into a species of theoretical reasoning.R = EOThe fact that p is a reason for a person to φ if and only if it is evidence that she ought to φR = ERR is similar to a recent and influential proposal which Thomson  and, indParis, Texas is showing is evidence that Miyuki ought to go to the cinema. Hence, given R = EO, it is a reason for her to do so.To illustrate, that R = ERR is like R = EO insofar as it appeals to a normative notion and the notion of evidence. But R = ERR differs from R = EO in two important ways. The significance of these differences will become clear in what follows.First, while R = EO appeals to an overall notion, specifically, that of what a person ought to do, R = ERR appeals to a contributory notion, specifically, that of a respect in which acting is right.Second, according to R = EO, what makes something a reason is that it is evidence for a normative proposition, specifically, the proposition that a person ought to φ. According to R = ERR, in contrast, what makes something a reason is that it is evidence for a non-normative proposition. An example of evidence of a respect in which it is right to φ might be evidence that φing causes pleasure. That φing causes pleasure is a non-normative proposition. Of course, evidence of a respect in which it is right to φ can be evidence that φing is right . I do not deny this. The claim is only that the relevant consideration is not a reason in virtue of being evidence for such a normative proposition.Kearns and Star argue that R = EO enjoys several virtues. I will list some of those virtues and suggest that R = ERR enjoys them too.First, Kearns and Star : §2.1 clSecond, Kearns and Star : §2.3 suThird, Kearns and Star : §2.4 clFourth, R = EO allows ‘many of the mundane considerations crucial to ordinary ethical thinking’ to count as reasons Star : 37. R =Paris, Texas is showing is a reason of some weight for Miyuki to go the cinema, while that she promised to go to the pub is a weightier reason for her not go to the cinema, and to go to the pub instead. R = EO lends itself to a straightforward account of the weights of reasons. According to Kearns and Star  of a respect in which not φing is very wrong (0.9), while that q is moderate evidence (0.5) of a respect in which φing is a bit wrong (0.2) the account predicts that that p is a weightier reason to φ than that q (0.18 > 0.1).Of course, this is a crude sketch.I have suggested that R = ERR shares the positive features of R = EO. R = EO also faces a number of objections that, individually or cumulatively, present a serious challenge to the view. Given the similarity between R = ERR and R = EO, one might wonder if my account faces versions of those objections. In this section, I will explore some difficulties facing R = EO and show that my account of reasons avoids them from the outset.against this proposition . According to RIC, if there is a reason for a person to do something, she can do that thing. R = EO seems to clash with RIC . According to OIC, if a person ought to do something, she can do that thing. Since ‘ought’ is a requiring notion, I take ‘reason’ as it figures in RIC to concern requiring reasons, rather than merely justifying reasons.Note first that RIC is the contributory counterpart to and that Nishi will be there is evidence of that fact. But, if Miyuki cannot go to the pub, it is not in any way wrong for her not to go. So, given E = ERR, that Nishi will be there is not a reason for Miyuki to go the pub.According to the proponent of R = ERR, that Nishi will be there is a (requiring) reason for Miyuki to go to the pub only if there is a fact which makes it wrong in some way for her not to go to the pub wrong in a respect not to act implies can act, which I take to be as plausible as RIC. From this principle, plus R = ERR, it follows that there is a (requiring) reason for a person to act only if she can act.The principle in play here is I have argued that R = ERR is able to avoid a number of objections which appear to undermine R = EO. There are, however, further challenges which any account of reasons as evidence faces. In this section, I will explore some of those challenges and suggest that they are unsuccessful or, at least, far from decisive.enabling conditions . According to R = ERR, evidence for a proposition is a reason for believing it because it is evidence of a respect in which so believing is right (cf. fn14 above). Here, rightness is the normative notion, not evidence.All of that said, I do not accept that the concept of evidence is normative in the relevant sense. Settling this issue is beyond the scope of this paper but I will offer some preliminary remarks. Kelly, an influential proponent of the view, writes:Second, suppose that it is absurd or confused to judge: I have overwhelming evidence that p but no reason for believing that p. A proponent of R = ERR can explain this without appeal to the idea that evidence is normative. This judgement reveals a failure to grasp the concept of a reason, not of evidence.Third, it is not obviously confused or absurd to judge: I have overwhelming evidence that p but no reason for believing that p. Suppose that the person who judges this is a pragmatist and maintains that it is right to believe a proposition just in case doing so promotes wellbeing. On this view, evidence of the truth of a proposition is not evidence of a respect in which believing it is right. One might think that the pragmatist is mistaken but one need not think that she fails to grasp the concept of evidence, or that she employs it a way which fails to accord with its content. The pragmatist’s position is a substantive, first-order view, not a meta-normative one. It is comparable to the position of a hedonist who thinks that it is right to perform some act just in case doing so is pleasurable.In summary, if the concept of evidence is normative, the account of reasons I advance here might be circular, but that need not be a problem. However, the concept evidence is not normative, at least, not for the reasons Kelly gives.In view of difficulties facing the idea that reasons are right-makers, I suggested that a reason for acting is evidence of a respect in which acting is right. This account differs from the view that a reason for acting is evidence that a person ought to act in two ways. First, it appeals to a contributory notion, not an overall notion. Second, it holds that the relevant evidence is evidence for a non-normative proposition, not a normative proposition. As a result, my proposal avoids the more serious difficulties facing its predecessor while enjoying its advantages, chief among them that it respects the wide-ranging roles that reasons play in our ethical lives.


Tokyo 2020 Summer Olympics are projected to experience environmental heat stress that surpasses the environmental conditions observed in the Atlanta (1996), Athens (2004), Beijing (2008), and Rio (2016) Summer Olympics. This raises particular concerns for athletes who will likely to be exposed to extreme heat during the competitions. Therefore, in mass-participation event during warm season, it is vital for the hosting organization to build preparedness and resilience against heat, including appropriate treatment, and management strategies for exertional heat stroke (EHS). However, despite the existing literature regarding the evidence-based management of EHS, rectal thermometry and whole-body cold-water immersion are not readily accepted by medical professionals outside of the sports, and military medicine professionals. Current Japanese medical standard is no exception in falling behind on evidence-based management of EHS. Therefore, the first aim of this paper is to elucidate the inconsistency between the standard of care provided in Japan for EHS and what has been accepted as the gold standard by the scientific literature. The second aim of this paper is to provide optimal EHS management strategies that should be implemented at the Tokyo 2020 Summer Olympics from organizational level to maximize the safety of athletes and to improve organizational resilience to heat. The risk of extreme heat is often neglected until a catastrophic incidence occurs. It is vital for the Japanese medical leadership and athletic communities to re-examine the current EHS management strategies and implement evidence-based countermeasure for EHS to expand the application of scientific knowledge. Tokyo 2020 Summer Olympics are projected to experience environmental heat stress that surpasses the environmental conditions observed in the Atlanta (1996), Athens (2004), Beijing (2008), and Rio (2016) Summer Olympics . This racool first transport second  the EHS patient before sending to a hospital, unless an EHS-specific protocol is pre-established  and fanning (≈0.05°C min−1) have very limited ability to cool exercise-induced hyperthermia in a timely manner. Since the severity of organ damage and chance of survival are dictated by the duration of sustained internal body temperature above 40°C  . Since eIn conclusion, an evidence-based countermeasure for EHS has not been implemented in Japan and strong leaderships from medical and athletic communities are warranted to reduce the risk of EHS at the Tokyo 2020 Summer Olympics. The need to implement evidence-based management of EHS has long been overlooked due to the unfamiliarity of the condition by most healthcare providers. It is critical that medical community recognize the shortcoming of their current practice and implement what is proven to be best in the current literature.YH created the main conceptual ideas for the paper. All authors conducted a thorough review of the existing literature and contributed to the manuscript writing and review process.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


K replicas of the same packet to combat such collisions. Previous studies have shown that grant-free scheduling with K replicas and shared resources increases the packet delivery. However, relying upon the transmission of K replicas to achieve a target reliability level can result in additional delays, and it is yet unknown whether grant-free scheduling with K replicas and shared resources can guarantee very high reliability levels with very low latency. This is the objective of this study, that identifies the reliability and latency levels that can be achieved by 5G grant-free scheduling with K replicas and shared resources in the presence of aperiodic traffic, and as a function of the number of UEs, reserved radio resources and replicas K. The study demonstrates that current Fifth Generation New Radio (5G NR) grant-free scheduling has limitations to sustain stringent reliability and latency levels for aperiodic traffic.5G and beyond networks are being designed to support the future digital society, where numerous sensors, machinery, vehicles and humans will be connected in the so-called Internet of Things (IoT). The support of time-critical verticals such as Industry 4.0 will be especially challenging, due to the demanding communication requirements of manufacturing applications such as motion control, control-to-control applications and factory automation, which will require the exchange of critical sensing and control information among the factory nodes. To this aim, important changes have been introduced in 5G for Ultra-Reliable and Low-Latency Communications (URLLC). One of these changes is the introduction of grant-free scheduling for uplink transmissions. The objective is to reduce latency by eliminating the need for User Equipments  to request resources and wait until the network grants them. Grant-free scheduling can reserve radio resources for dedicated UEs or for groups of UEs. The latter option is particularly relevant to support applications with aperiodic or sporadic traffic and deterministic low latency requirements. In this case, when a UE has information to transmit, it must contend for the usage of radio resources. This can lead to potential packet collisions between UEs. 5G introduces the possibility of transmitting  As shown in (22), i equal to cero. To simplify the notation, The process illustrated for The parameters p1 that was generated before t0. Let us then suppose then that a second packet p2 is generated before the K replicas of the previous packet p1 have been transmitted. This is a self-collision. If a self-collision happens, p2 can be stored, and its transmission will start after the UE has transmitted the Kth replica of p1 . If p2 is generated before t2 − L, it is not possible to complete the transmission of the K replicas of p2 before the latency deadline L. t], where ∆t represents the time difference between t2 − L and the time p1 is generated (see (26)). The transmission of the K, since K influences the time a packet might be stored until the transmission of the previous packet is finished. However, increasing the number K of replicas transmitted for each packet is preferred, in order to combat possible collisions with other UEs sharing the same pool of radio resources. The next section will analyze both the effect of collisions from other UEs and the effect of self-collisions to analyze the reliability achievable with the grant-free scheduling with K-repetitions and shared radio resources.As shown in (25) and (26), the negative effect of self-collisions increases with the value of This section validates the analytical expressions derived in K-repetitions and shared resources. The simulator emulates a single cell with N UEs that generate aperiodic traffic. Each UE models the packet traffic arrival, using a Poisson distribution with exponential inter-arrival time. The average packet inter-arrival time is equal to 1/λ, where λ is the average number of packets generated per second. The simulator implements the time/frequency resource grid map of 5G NR. The time and frequency duration of RBs is configurable based on the considered 5G NR numerology µ. It is possible to also configure the number U of RBs available per time slot. The number K of replicas can also be configured in the simulation platform.We have implemented a system level simulator in Matlab™ that accurately models the 5G NR grant-free scheduling process with K equal to 2, 4 and 8, λ equal to 0.1 packets, µ equal to 3, and U equal to 6 RBs per slot. UEs transmit small packets with a size of 32 bytes , where ∆t represents the time difference between t2 − L and the time p1 is generated (see (25) and (26)).All previous results have been derived without considering the effect of self-collisions. Self-collisions were illustrated in t is homogeneously distributed between ∆t1 and ∆t2. For K = 4 in t1 is equal to 0 and ∆t2 is equal to p1 can be homogeneously generated between t0 and t0 − K = 6, ∆t1 is equal to 4 t2 is equal to (4+1) p1 can be homogeneously generated between t0 and t0 − t1 and ∆t2 are equal to 8 K = 8. t is equal to ∆t1 or ∆t2 considering L = 1 ms and K = 4, 6 and 8. ∆t = ∆t1 corresponds to the scenario where self-collisions are less probable, while ∆t = ∆t2 corresponds to the case in which they are more probable.We consider that packets are generated following a Poisson process with exponential inter-arrival time. As a result, ∆−4 and 9.99 × 10−4 when K is equal to 4 and 8, respectively, and λ = 1 packet. It is also important to highlight that a comparison of results in K = 8: −7 and 10−5 for λ equal to 0.1 and 1 packet(s), respectively (−4 and 10−3 (K increases. It is then important that the reliability (or probability that a packet is correctly received before the latency deadline) of grant-free scheduling with K-repetitions and shared radio resources is computed considering both the effect of collisions from other UEs and the effect of self-collisions following (1).The results in ectively , while Pand 10−3 . Grant-fK and L when considering both t = ∆t1 for computing t = ∆t1 corresponds to the case where self-collisions are less probable. K within L to combat collisions from other UEs and correctly receive a packet at the BS. For example, K must be equal to 8 in order to achieve −9 when λ is equal to 1 packet. However, K even to the point that self-collisions limit the reliability that can be achieved. This is actually shown in L = 1 ms. In principle, it could be possible to satisfy a 1 ms latency requirement if we transmit 4, 6 or 8 replicas of a packet. K = 4 and ∆t = ∆t1 , respectively; these results are in line with those observed in K = 4. However, when K is equal to 6 or 8, the effect of self-collisions becomes more relevant  that can be achieved is 1–10−3 when the latency requirement L is equal to 1 ms. It should be noted that reliability levels even higher than 1 − −9 were achieved when the effect of self-collisions was not considered /2, since ∆t is homogeneously distributed between ∆t1 and ∆t2. −5 and 1–6.3 × 10−4 when λ is equal to 0.1 and 1 packet(s). t = ∆t1 to ∆t = ∆avgt is again due to a major relevance of the effect of self-collisions when we compute the reliability.relevant , and Fignsidered . The resL. The effect of self-collisions is more relevant when the latency requirement is stricter. For example, K = 4 if the latency requirement is equal to 0.5 ms. Latency requirements significantly influence the reliability levels that can be satisfied. This is the case because latency requirements limit the number K of replicas that can be sent for each packet. Expressions in (25) and (26) show that K-repetitions and shared resources cannot guarantee some of the more demanding reliability and latency levels. However, it is important emphasizing that other proposals cannot meet such requirements either, and these actually perform worse than the implementation analyzed in this study. This is actually the case for the proposals that transmit the first copy of a packet in dedicated resources for the UEs. These resources can be reserved using grant-based scheduling , procT is the processing latency (this latency represents the latency between the reception of the SR and the transmission of the grant message), and txT is the time required to transmit the SR and grant messages. Following [LT/L21 = alignT = txT = 1 TTI, and procT = 2.33 TTI. These values are a best-case scenario, since they represent reduced processing times that can be achieved with 3GPP Release 15 compared to Release 14. Equation (27) shows that the total latency (2.3 ms) introduced by the grant-based scheduling process to assign dedicated resources to UEs is higher than the latency achieved with the 5G NR grant-free scheduling implementation analyzed in this study. For example, −5 when K = 4, λ = 0.1 packets, U = 6, and ∆t = ∆avgt).The results in ch as in ) or semich as in ). Grant-ollowing , we consN = 300 users that generate aperiodic traffic (λ = 0.1 packets). We shall then suppose that users request a maximum latency of 1 ms and a reliability level equal to 1–10−5. Satisfying this demand requires reserving 300 RBs (one per UE) in a 1 ms time windowA lower number of resources would be necessary if traffic was periodic and we could estimate when each UE would require resources for their transmission. In this case, several UEs could share the same RB if they generate their packets at different time instants. This would reduce the total number of RBs necessary to serve all users. This is not possible in the case of aperiodic traffic, since we cannot predict when a UE would need radio resources. The alternative to grant-based scheduling is Semi-Persistent Scheduling (SPS). In this case, UEs are assigned dedicated resources for a period of time. During this period, UEs can utilize the resources without requesting permission from the BS. This avoids the latency introduced by grant-based scheduling. However, semi-persistent scheduling inefficiently utilizes the radio resources when the traffic is aperiodic. This is the case, because it is not possible to predict when UEs will need resources. To illustrate this effect, let us consider a scenario with K-repetitions and shared radio resources. This implementation has been chosen, since sharing radio resources is an attractive option for aperiodic traffic. In addition, the K-repetitions scheme can combat possible packet collisions between UEs that share radio resources. This study has analyzed the reliability and latency levels that can be achieved with existing 5G NR grant-free scheduling with shared radio resources as a function of the number of UEs, the number of reserved radio resources, and the number of replicas K. To this aim, this study has derived analytical expressions that quantify the exact probability of collision with packets transmitted by other UEs, and the impact of self-collisions. It is important to emphasize that this study is the first one that has evaluated the impact of self-collisions. Packet collisions and self-collisions have then been taken into account to derive analytically the reliability that can be achieved by existing 5G NR grant-free scheduling with shared resources. The derived analytical expressions have been validated against simulations. These expressions are a valuable contribution to the community, since they can be easily utilized to evaluate 5G NR grant-free scheduling.This paper has analyzed the capacity of 5G NR grant-free scheduling to support URLLC services with strict reliability and latency levels such as those demanded by Industry 4.0. The study has focused on aperiodic or sporadic traffic and an implementation of 5G NR grant-free scheduling with K that can be transmitted. In addition, self-collisions have a non-negligible impact that even limits the reliability that can be achieved when K increases. The impact of self-collisions also increases with the latency requirements. The obtained results demonstrate that new solutions are necessary for 5G NR grant-free scheduling to be able to support applications with stringent URLLC latency and reliability requirements under the presence of aperiodic traffic. In particular, the transmission of K replicas per packet might be inadequate to support aperiodic traffic with very low latency levels due to the impact of self-collisions. Consequently, other approaches should be designed to minimize collisions between UEs sharing radio resources. This study has shown that these new solutions cannot be based either on grant-based or semi-persistent scheduling. Grant-based scheduling introduces additional latency due to the exchange of messages between the UEs and the BS for assigning the radio resources. Semi-persistent scheduling with dedicated resources inefficiently utilizes the available resources when considering dedicated resources and aperiodic traffic. Innovative grant-free scheduling solutions are hence necessary to meet the URLLC requirements identified for 3GPP Release 16 and beyond. This could include, for example, the use of sensing mechanisms or full duplex techniques that can reduce packet collisions.This study has demonstrated that current 5G NR grant-free scheduling solutions cannot guarantee high reliability levels with strong latency requirements. This is partly due to the fact that strong latency requirements limit the number of replicas


There is a widespread belief that information technologies will improve diagnosis, treatment and care. Evidence about their effectiveness in health care is, however, mixed. It is not clear why this is the case, given the remarkable advances in hardware and software over the last 20 years. This review focuses on interoperable information technologies, which governments are currently advocating and funding. These link organisations across a health economy, with a view to enabling health and care professionals to coordinate their work with one another and to access patient data wherever it is stored. Given the mixed evidence about information technologies in general, and current policies and funding, there is a need to establish the value of investments in this class of system. The aim of this review is to establish how, why and in what circumstances interoperable systems affect patient safety.A realist synthesis will be undertaken, to understand how and why inter-organisational systems reduce patients’ clinical risks, or fail to do so. The review will follow the steps in most published realist syntheses, including (1) clarifying the scope of the review and identifying candidate programme and mid-range theories to evaluate, (2) searching for evidence, (3) appraising primary studies in terms of their rigour and relevance and extracting evidence, (4) synthesising evidence, (5) identifying recommendations, based on assessment of the extent to which findings can be generalised to other settings.The findings of this realist synthesis will shed light on how and why an important class of systems, that span organisations in a health economy, will contribute to changes in patients’ clinical risks. We anticipate that the findings will be generalizable, in two ways. First, a refined mid-range theory will contribute to our understanding of the underlying mechanisms that, for a range of information technologies, lead to changes in clinical practices and hence patients’ risks (or not). Second, many governments are funding and implementing cross-organisational IT networks. The findings can inform policies on their design and implementation.PROSPERO CRD42017073004 There is a widespread belief, particularly among policy makers, that information technologies will improve diagnosis, treatment and care . Evidencwhy the evidence has, to date, fallen short of expectations. We seek to shed light on the question in this systematic review. It focuses on the effects of a particular class of IT systems, interoperable systems, on patient safety. The term ‘system’ here refers to the combination of technologies and the people who used them. In a well-designed system, technologies are seamlessly integrated into users’ working practices. In poorly designed systems, in contrast, the technologies do not fit easily into users’ working practices, and in the worst cases can make it more difficult to deliver safe treatment and care. The term ‘interoperable’ refers to the ability of any two or more IT systems to exchange data, and for the receiving system to make use of the data. The IT systems of interest in this protocol allow professionals to access patients’ records held in other organisations.There is, therefore, a need to understand Many people who live in their own homes, and who are frail or have chronic health problems, need support from a range of professionals. These include general (or family) practitioners, community nurses, therapists, social workers, and planned and emergency hospital services. There is good evidence that treatment and care is often fragmented –10. Linkintended effects of an intervention, and the underlying logic that links them together. A number of initial theories are typically identified.This protocol describes a realist synthesis, which seeks to understand how and why inter-organisational IT systems reduce patients’ clinical risks, or fail to do so. The realist synthesis method involves opening up the ‘black box’ of events that lie between an intervention and its effects , 14. It actual steps in the sequences. The evidence can, in addition, lead teams to realise that a programme is effective, but not in the way originally envisaged. A programme theory therefore needs to be reformulated. More searches may then be needed, to evaluate elements of the revised theory. That is, the cycle of programme theory formulation and evaluation can be iterative and—resources permitting—pursued until a settled, evidence-based account has been identified [Literature searches are then designed. It is not usually feasible to identify evidence about all of the sequences in all of the theories. Searches therefore focus on two or three theories, or on key sequences within those theories. Empirical evidence is then identified, assessed and synthesised, in order to evaluate the entified .There are literatures that will enable us to develop and evaluate programme theories . For exaThis protocol has been written in accordance with PRISMA-P guidelines .Identify initial programme theories and prioritise theories to review;Search systematically for evidence to test and refine the theories;Undertake quality appraisal and use included texts to support, refine or reject programme theories;Synthesise the findings;Disseminate the findings to a range of audiences.We will undertake a realist synthesis. The aim of the study is to establish how, why and in what circumstances networked, inter-organisational IT systems affect patient safety. The objectives of the study are to:The following sections focus on the first four objectives.This stage is essentially developmental in nature. The first step in this review will be to construct one or more programme theories, concerning the use of networked IT systems and their effects on patient safety. Mid-range theories, which are usefully thought of as a broader class of theory than programme theories, and which will be used to generalise findings at the end of the review, will also be identified. We will supplement our existing knowledge of candidate theories with literature searches to define and develop them. The programme theories will determine the scope (inclusion and exclusion criteria) for the searches and synthesis in the following stages, which will be used to support, refine or reject each theory examined.Theories can be explicitly mentioned in research articles and policy documents, or they can be implied in the introductory or discussion sections of documents. They can also be found in commentaries and opinion pieces. We will use conventional literature searching using free text words, synonyms and subject index terms, and some CLUSTER searching techniques  . Using tBackground search of systematic reviews. We will search for systematic reviews that link IT systems and patient safety. This will identify any reviews on this topic that have been published since our scoping review, undertaken before the start of the project. The reviews may describe programme theories or fragments in their introduction or discussion sections, providing insights into the sequences of events linking the intervention and outcomes. We will search the core databases plus the Cochrane Database of Systematic Reviews, the Epistemonikos database and Health Systems Evidence (McMaster University). An example MEDLINE search strategy containing a full set of search terms is available in the Additional file Policies, opinion pieces and research reports. We will search the core databases plus Health Management Information Consortium (1983–present) and Web of Science - Science Citation Index (1990–present) for policy documents, opinion pieces  and reports describing leading theories about the relationships between IT systems and patient safety , Web of Science - Science Citation Index (1990–present), Google Scholar and Scopus (1823–present). Literature by David Bates, the most cited author in the health informatics literature, and Robert Wachter, the author of an influential report on IT in the NHS in England, will be searched  and EMBASE (1947–present) will be searched as a core set of databases for all of the theory generating searches.IT networks that link two or more organisations outside (but possibly including) hospitals;IT networks that support direct treatment and care;Arguments that identify relationships between IT networks and patient safety;Published in the English language between 2000 and 2018.The records identified in the searches will be saved and managed in an EndNote library. Details of all search activities  will be recorded in a timeline spreadsheet. The inclusion criteria for the three searches will be:Non-English language articles will not be included. The project does not have sufficient resources to translate the full text of articles that may be relevant. In conventional systematic reviews, it is not necessary to translate whole papers, as it is only necessary to identify defined data. In this review, however, we will be looking for data that might occur anywhere in a paper, and a full translation would be needed.Describe hospital-only IT systems;Describe systems that do not link two or more distinct services;Focus on IT systems that support secondary uses of data, e.g for service planning, research;are published before 2000;are published in languages other than English.The exclusion criteria will be for studies that:Two reviewers (MA and JK) will first independently screen the titles and abstracts of the records for relevance and then assess full-text reports. Any discrepancies will be solved by discussion, and if needed consultation with a third author (JG or RR). Data extraction forms will be developed to capture basic details of studies—authors, publication year, etc.—and passages on theories and theory fragments.The selected studies will be used to develop visual representations of programme theories, with accompanying text that explains the reasoning that underpins those theories. Experience gained in earlier reviews suggests that there are likely to be several programme theories at this point, and that some of them will be partial, in the sense that the chains of reasoning are ‘high level’ and not fully articulated, or only cover some of the steps linking networked information technologies and patient safety. Where available, claims about the reasons why programmes succeed or fail in practice will be used to annotate the representations.The programme theories will be used as the basis for consultation with three groups of stakeholders—policy makers, senior IT managers and frontline clinicians. We will use the nominal group technique, which has been used in a previous realist study . At the The outputs of the three groups will be further reviewed by a patient and public involvement (PPI) group, and discussed with our project steering group. Following these meetings, we will decide on the programme theories, and key elements of those theories, that we will explore in depth in stages 2–4.The next stage of the review is a search for empirical studies to test and refine the leading programme theories identified in stage 1. The initial searches will be designed to identify evidence about the steps in the chains of reasoning in each theory. Literatures often focus on one or other section in a chain of reasoning, and as a result, individual searches will often focus on sections rather than a whole programme theory . We willWe anticipate hand searching papers from leading conferences which are not indexed, for example Software Engineering in Healthcare workshops papers, from the International Conference on Software Engineering. The search strategies for identifying empirical evidence for programme theories can only be fully developed once the programme theories are agreed. However, we anticipate they will contain search concepts for an aspect of patient safety such as medication reconciliation, inter-organisational IT networks and evaluative studies.The search results will be reviewed in stage 3  and further searches will develop iteratively to follow lines of enquiry. Initial searches may not identify empirical evidence that supports or rejects a programme theory. If that happens, the search will be re-designed to capture empirical evidence that may be found in a different discipline or information resource. For example, we could extend the scope of our searches to look for evidence about other IT applications, including hospital-based systems, and/or extend the scope of the populations of interest. As in stage 1, these searches may use CLUSTER search techniques as an efficient method for finding relevant papers .The results of the electronic searches and all references that are retrieved for stage 2 will be kept in the same EndNote library as those found during stage 1. Details of all search activities during stage 2 will be recorded in the timeline spreadsheet.An appraisal of the contribution of any section of data (within a document) should be made on two criteria:Relevance – whether it can contribute to theory building and/or testing; and• Rigour – whether the method used to generate that particular piece of data is credible and trustworthy [• stworthy .Titles and abstracts of records identified, and the full-text papers selected in stage 2, will be independently screened by two reviewers (MA and JK) to identify those which contain evidence that sheds light on one or more elements of the programme theories identified in stage 1. The RAMESES I guidance states that:within type, whether that is a process evaluation, an ethnography or other type of study [We will follow Rycroft-Malone and colleagues in developing criteria for judging relevance . We willof study .The empirical data for supporting and/or refuting programme theories will be extracted from the included studies. It is anticipated that a significant proportion of the evidence will be in the form of narrative data and will accordingly be copied into Word files. To maximise accuracy and transparency, a proportion of data extraction will be performed independently by two members of the research team.Synthesis involves two distinct, but linked, activities. In the first, the empirical evidence identified in stages 2 and 3 will be used to evaluate the programme theories developed in stage 1. In the most straightforward case, the evidence will support the chains of reasoning in one programme theory and serve to reject alternative or competing theories. Less straightforwardly, the evidence might provide support for one part of a programme theory and adverse evidence for another part of the same theory. Or, it might not ‘fit’ a programme theory, neither supporting nor undermining it. Both instances suggest that there may be a problem with the programme theory itself and will lead us to refine it, to achieve a better fit between evidence and theory. On the basis of experience of earlier realist syntheses, we expect that at least one of the selected theories—or theory fragments—will be reasonably well supported by empirical evidence, and at least one will not be not supported.Second, when a settled programme theory or theories have been produced, they will be interpreted in the broader context of the mid-range theory. This involves abduction, where inferences that lead to the best available explanation are identified. The details of the abductive reasoning processes vary from review to review, but a key point is that it involves inter-play between situation-specific programme theories and broader mid-range theory . In the The nominal groups will be re-convened for email consultation. We will summarise our findings to this point, including our provisional syntheses, and present them to the groups. They will be asked to comment on the findings, including whether any of the theories can be rejected, and whether any further searches are merited. The PPI group will also meet at the end of this stage and review the findings and interpretations of the three nominal groups. We will refine our interpretations on the basis of the comments of all four groups.Policy makers in many countries believe that IT systems can contribute to safer patient care. Interoperable systems are currently being promoted by governments, and funding made available for their development, in many countries. As noted above, though, the empirical evidence about this belief is mixed, and it is not clear why this is the case. We are using the realist synthesis method because we believe that it will shed light on how and why interoperable systems contribute to reductions in patients’ clinical risks, and hence help to explain why the evidence is so mixed.As with any evidence synthesis, there are risks and limitations associated with the method. The most obvious risk, in common with other review methods that focus on effectiveness, is that we are not able to identify high-quality effectiveness evidence. This will necessarily limit the extent to which we are able to explain ‘what works’ when interoperable systems are deployed. Another significant risk is the flip side of a potential strength. The explicit inclusion of theory in the method means that the basis for interpreting the available evidence is clear. But, there must be a risk that—however much care is taken—a sub-optimal theoretical framework will be used, and valuable insights foregone. If we are able to mitigate these risks in the course of the review, though, it should produce two main outcomes. First, the refined mid-range theory will contribute to our understanding of the underlying mechanisms that lead to changes in clinical practices and hence patients’ risks (or not). Second, many governments are funding and implementing cross-organisational IT networks. The findings can be used to inform policies on their design and implementation.Additional file 1. Search strategies to identify reports for generating theory.


Several societies and associations have produced and disseminated clinical practice guidelines (CPGs) for gestational diabetes mellitus (GDM). However, the quality of such guidelines has not been appraised so far. This study aims to evaluate the quality of CPGs for GDM published in the last decade using the AGREE II instrument.A systematic search of the National Institute for Health and Care Excellence, New Zealand Guidelines Group, Scottish Intercollegiate Guidelines Network, Medlive, American Diabetes Association, Canadian Diabetes Association, International Diabetes Federation, as well as PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Chinese Periodical Database, and VIP Chinese Periodical Database was conducted from inception to June 2018. The quality was assessed by four trained researchers independently, using the AGREE IIinstrument.p = 0.028). Overall score of 10 guidelines were 5 points and above, and four guidelines were 7 points. Among six domains, two domains: Scope and Purpose, and Clarity of Presentation, had high scores; however, the domains of Rigor of Development, Stakeholder Involvement and Editorial Independence received lower scores.A total of 13 guidelines, published from 2009 to 2018, were finally included. Among them, 11 guidelines were evidence-based guidelines, and 2 were expert consensus. Scores for each of the six AGREE II domains(Median ± IQR) were 94 ± 11, 89 ± 53, 58 ± 37, 100 ± 6, 79 ± 48, 100 ± 71 and 67% ± 42%, and guidelines based on expert consensus generally scored lower than evidence-based guidelines (Z = -2.201, In general, the methodological quality of GDM guidelines is high, and evidence-based guidelines are superior to expert consensus. However, the domains of Rigor of Development, Stakeholder Involvement and Editorial Independence still need improvement. A systematic approach in the development of these guidelines and updating timely is needed. In some regions, more attention for guideline adaptation is recommended. Gestational diabetes mellitus (GDM) is defined as “any degree of glucose intolerance with onset or first recognition during pregnancy” . The preIt is acknowledged that GDM is associated with a higher incidence of maternal and fetal morbidity, and may have long-term sequelae in offspring, leading to a higher social burden –8. In 20However, maternal and fetal adverse outcomes can be significantly reduced if GDM women are properly managed , 14. As Two reviewers independently reviewed the guidelines yielded by the search, based on these inclusion criteria: 1) full guideline is available in English or Chinese; 2) CPG is systematically developed under the auspices of medical specialty associations, government agencies at the federal, state or local level or health care organizations; 3) CPG contains recommendations regarding GDM interventions; 4) the guideline has been developed, reviewed or revised within the last 10 years.The following literature was excluded: 1) translations of guidelines; 2) short summaries, abstracts, brief versions or only sections of guidelines; 3) guidelines for patients and editorials.One reviewer performed a search of the following electronic databases from inception to June 2018: Guideline websites of the National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Scottish Intercollegiate Guidelines Network (SIGN) and China Medlive; websites of medical specialty associations, such as American Diabetes Association (ADA), Canadian Diabetes Association (CDA) and International Diabetes Federation (IDF); and PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database and, VIP Chinese Periodical Database.The search strategy used keywords “pregnancy”, “gravida*”, “conception”, “maternity”, “diabetes”, “hyperglycemia”, “insulin resistance”, “glucose intolerance”, “guideline”, “criteria”, “recommendation” and “standard”. For example, the PubMed search strategy is presented in Table Quality appraisal for included guidelines was conducted by four reviewers. Four trained appraisers  independently evaluated GDM CPGs using the AGREE II instrument . AccordiAfter quality appraisal, data extraction and analysis was performed by one reviewer and checked by another one. Any discrepancies were resolved by discussion between them or with a third party. The main characteristics of these publications were extracted, including development organization, publication year, development method, and the number of references. In addition, the results of the AGREE II appraisals  were extracted from the publications included and a descriptive statistics analysis undertaken.p values of 0.05 or less were considered significant. In order to measure agreement among reviewers, intra-class correlation coefficients (ICC) were also calculated. ICC values above 0.75 were considered to represent good reliability.The IBM SPSS Version 25.0  was used for all statistical analyses. Descriptive analysis values included median and inter-quartile range (IQR). Differences between CPG and expert consensus scores were calculated based on the Wilcoxon Signed Rank Test Z-score, and The systematic search retrieved a total of 107 publications, including 48 searched in relevant websites and 59 searched in electronic databases. Two reviewers independently selected guidelines according to the inclusion criteria. After excluding 48 duplicated records, 59 publications were considered to be potentially relevant. Then, the publications were screened by title and abstract as well as full text. Eventually, 13 guidelines fulfilled the inclusion criteria  Stakeholder InvolvementThe overall objectives of all the evidence-based guidelines were specifically described to some degree (item 1). Seven guidelines , 26, 27 3)Rigor of DevelopmentSix guidelines , 23, 27 4)Clarity of PresentationThe process of evidence retrieval and recommendation formation varied considerably in different guidelines. Four guidelines , 22, 23 5)ApplicabilityThe recommendations of 10 guidelines , 26, 29 6)Editorial IndependenceSeven guidelines , 26, 29 Nine guidelines , 25–27 cClinical Practice Guidelines are “statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options” . TherefoIn addition, views and preferences of the target population, competing interests of guideline development group members and procedures for updating the guideline were also influential factors in guideline quality, with only four guidelines , 22, 23 With evidence-based medicine being a critical scientific methodology in the development of CPGs, there is a growing international tendency to develop guidelines based on evidence. In this study, we included 13 guidelines, of which 11 –27, 29 wThe search for relevant publications was limited to Chinese and English language publications, and potentially relevant publications in other languages were not considered, which might lead to bias and scope limitations. Besides, the management recommendations for GDM could be presented not only in GDM CPGs, but also any other guidelines related to diabetes, so the search strategy in this research may be not comprehensive to include all relevant guidelines. Also, we may have missed guidelines published in other forms such as books and internal reports.In terms of the appraisal instrument, the AGREE II instrument can only assess the methodological quality of the guideline but not the quality of the content of the guideline , 26, 30.In general, the methodological quality of GDM guidelines is high, and evidence-based guidelines are superior to expert consensus. Although the development methodology of these guidelines was credible, the domains of Rigor of Development, Stakeholder Involvement and Editorial Independence still need improvement. A systematic approach in the development of these guidelines and updating guidelines in a timely manner is recommended.However, in some countries and regions, there were only GDM guidelines developed through expert consensus, and the process of the guideline development was far from being rigorous. Given the thought of using high quality evidence and reducing duplication of efforts, guideline adaptation could be an alternative. In additional, it is crucial that clinical staffs should use guidelines on the basis of local contextual factors.


At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner. Structural support for data collection and follow-up tests seems essential for improvement of monitoring practices in psychiatric outpatients. The implementation of a structured somatic monitoring program as part of routine clinical practice, as we describe in this study protocol, may be a solution.In order to address these issues, we developed the innovative program ‘Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR)’. MOPHAR is an infrastructure for implementation of standardized routine outcome monitoring , monitoring of adverse psychotropic medication effects in psychiatric outpatients, encompassing both somatic adverse effects (e.g. metabolic disturbances) and subjective adverse effects  and medication reconciliation.In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program is feasible and beneficial for patients in any MHS organisation. This paper describes the objectives, target population, setting and the composition and roles of the treatment team. It also indicates what measurements are performed at which time points during outpatient treatment in the MOPHAR monitoring program, as well as the research aspects of this project.NL4779).MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014. (The online version of this article (10.1186/s12913-019-3951-2) contains supplementary material, which is available to authorized users. Severe mental illness patients are expected to live a 13–30 year shorter life compared to the general population . Somaticn = 218,940) investigating metabolic syndrome in patients with mostly schizophrenia or related disorders and that were using antipsychotics, showed that baseline metabolic screening before commencement of pharmacotherapy was suboptimal and in more than 50% of patients only blood pressure and triglycerides blood concentrations were checked [Worldwide, at many specialized outpatient clinics for psychiatric disorders, systematic monitoring of the safety of prescribed drugs is not routinely performed in daily clinical practice. Previous research from our group has indicated that medication reconciliation and monitoring of somatic parameters are not routine clinical practice at outpatient departments for mood and anxiety disorders in the north of The Netherlands , 13. Lik checked . Researc checked . Further checked . In concImproving monitoring practices may ensure that somatic co-morbidities and adverse drug reactions are detected and treated in a timely manner. Unfortunately, the introduction of new guidelines, education materials,  quality improvement programs or consensus statements alone have shown only minimal improvement in monitoring practices , 17–20. Taken together, structural support of mental health care professionals for data collection and follow-up testing at a local or regional level seems essential for improvement of monitoring practices in psychiatric outpatients. Implementing a structured somatic monitoring program that is incorporated in routine clinical practice may be a solution . In ordeAlthough it seems logical to monitor and treat known complications of psychiatric disease and psychotropic medication, the evidence for benefits of monitoring specific (sets of) parameters (and subsequent treatment if indicated) in terms of for example less somatic complications, better quality of life or shorter treatment duration is lacking. The (cost)effectiveness of monitoring of specific (sets of) parameters needs to be established to provide an evidence base for investing in implementation of systematic monitoring programs and reimbursement by health care insurance companies. This paper describes the research aspects of the MOPHAR study as well as the process and measurements of the MOPHAR monitoring program.Apart from a somatic monitoring care path for routine clinical practice, the MOPHAR monitoring program also provides the opportunity for long-term  prospective and retrospective observational cohort studies. The large amount of information collected in the patient registry of MOPHAR can be used for research: many questions may be answered in retrospective studies, including association studies and prediction models on the effect and side effects of psychotropic drugs. Because apart from all current patients, also all new patients are asked for informed consent to be included in MOPHAR, the sample size will increase in time. The sample sizes for analyses will be pre-specified per individual research question.Next to retrospective studies, MOPHAR also gives the perspective for future prospective studies. After implementation of MOPHAR there is a structured program in place with uniform moments for evaluation by a MOPHAR nurse. These moments can be used for future prospective interventions as well. Furthermore, patient and treatment characteristics are gathered systematically thereby allowing selection of patients suited for specific prospective studies.To investigate the association between patient characteristics and outcomes (e.g. (cost)effectiveness, adverse effects) of psychiatric pharmacotherapy. Amongst others the association between pharmacogenetic determinants/biomarkers and the prevalence of adverse effects of antidepressants will be investigated.To investigate the association between the use of specific psychotropic drugs and adverse effects like metabolic abnormalities in selected samples and the unselected population (population-based research). In addition we will be able to set up intervention studies targeting such adverse effects.The general research objectives are:Our research objectives reflect both the aim to investigate how we can most efficiently detect the relevant signals for somatic complications and the aim to investigate how we can predict which patients will probably benefit from specific psychotropic drugs and/or are vulnerable for specific side effects. Results of these studies can be used to prevent, monitor and treat adverse effects in the near future. More specific research questions will be formulated per individual study within MOPHAR, along with theoretical frameworks and specific definitions, if applicable. In addition, the statistical analyses plans will be described per individual research question. We expect to use for example regression analysis techniques and longitudinal data analysis techniques (for clustered data), including mixed effects models.https://www.trialregister.nl/trial/4779). The research aspects of MOPHAR were approved by the independent medical ethics committee , and all participants provide written informed consent. We ask general informed consent to conduct research on the data collected in the MOPHAR monitoring program including the linkage of the clinical data with an extra blood sample obtained for MOPHAR research (see below under ‘extra blood sample’). Subjects can withdraw from further participation in the MOPHAR research cohort at any time for any reason without any consequences regarding their treatment and MOPHAR monitoring care.MOPHAR research has been registered with the Netherlands Trial Register  are eligible for inclusion in MOPHAR).There are no general exclusion criteria for inclusion in the MOPHAR patient registry.For research purposes, an extra blood sample (20 ml) will be taken from each subject. This blood sample will be taken at the same time as one of the blood sample withdrawals for routine clinical practice. Therefore, no additional venepuncture is necessary and no additional risks are associated with this single study procedure. This blood sample can be used for future research  to investigate associations between drug or patient characteristics and treatment success and/or the prevalence of somatic side effects concerning scientific questions related to psychiatric health issues for which the patient visited the outpatient department.The primary objective of the MOPHAR monitoring program is to systematically provide mental health care providers with more and better information for treatment decisions and to facilitate monitoring of the treatment effect and adverse effects of psychiatric pharmacotherapy in psychiatric outpatients.Secondary objective is to enable routine collection of longitudinal monitoring data of daily psychiatric practice for research purposes. The general research objectives have been discussed above.The MOPHAR monitoring program targets adult patients (≥ 18 years) referred to mental health care outpatient clinics for any psychiatric diagnosis. Patients can be referred by their general practitioner or by a mental health care treatment officer from another department or institution. Any information on the psychiatric symptoms, co-morbidities and medication use that has been noted in the referral letter is incorporated in the available information for the initial visit for MOPHAR. After referral and initial visit at the outpatient clinic, regular mental health care at the general practitioner’s practice stops. MOPHAR accommodates patients either at initial visit or already in treatment at the outpatient clinic at the time of implementation.The MOPHAR monitoring program is currently implemented at a large secondary community mental health care outpatient department. However, in its current form, it can be implemented at any mental health care outpatient clinic serving a broad population of persons with a (severe) mental illness. While a core set of elements and monitoring measurements is provided in MOPHAR, the current program as described in this paper does not preclude access to other somatic services or program amendments fitted to specific populations (e.g. disease-specific measurements or questionnaires or paper-based instead of online questionnaires for elderly patients).The MOPHAR treatment team is multidisciplinary. The MOPHAR team comprises the regular treatment team with at least one psychiatrist, at least one psychiatric nurse trained in the somatic screening of MOPHAR and a secretary. However, usually more than one person per discipline is involved, as well as a psychologist and a nursing specialist. There is a flexibility in the size and composition of the team.The roles of the different team members can be described as follows. The secretary plans the appointments and invites the patient, which marks the start of the MOPHAR monitoring program for individual patients. The psychiatric nurse performs the MOPHAR screenings. To this end, in a one-day session the psychiatric nurses are trained by the MOPHAR pharmacist in the logistics of the MOPHAR monitoring program and how to perform medication reconciliation, how to enter the medication use in the electronic prescribing system and how to register the MOPHAR screening results. The medication prescriber  is responsible for decisions on and execution of interventions and follow-up based on the results of the MOPHAR screenings along with the psychiatric treatment. The team must identify a clear workflow regarding the communication of results with other relevant health care professionals . At MHS Drenthe, the primary treatment officer sends a summary of the findings from the MOPHAR screenings to the general practitioner. The prescriptions are sent to the community pharmacy.Members of the MOPHAR treatment team may have collateral responsibilities to MOPHAR patients or other non-MOPHAR (inpatient) teams. In addition, the nurses can be scheduled interchangeably for different outpatient teams to perform MOPHAR screenings if necessary. This flexibility may be a major appeal of the MOPHAR model of somatic monitoring for mental health care institutions. Since somatic monitoring is in part recommended in Dutch guidelines, MOPHAR is meant to be fitted into the usual workflow of the team. However, extra resources are needed for training, supervision, implementation and support. Implementation and project support are provided by a project manager and a pharmacist to ensure project progress and resolve practical issues. The pharmacist is responsible for training the MOPHAR nurses (e.g. medication reconciliation) and the quality assurance of the established (psychotropic drug-specific) monitoring protocols. In addition, the pharmacist can be consulted by the treatment team with medication-related questions.Figure A general somatic screening is performed at the first appointment, irrespective of  diagnosis or medication use. This general somatic screening (±45 min) serves to screen for existing somatic co-morbidities, side effects of drugs already in use (e.g. metabolic disturbances), and potential  causes of the mental illness (e.g. thyroid dysfunction for depression). In addition, it may serve as a baseline screening before start of psychotropic drug treatment if applicable.In the invitation letter for the first appointment, patients are asked to fill in questionnaires about their demographics, family history of psychiatric disease, smoking, alcohol and illicit substance use and previous psychiatric (pharmacotherapeutic) treatments. These questionnaires have been developed by the department of Psychiatry of the University Medical Centre Groningen, The Netherlands (HGR) . In addiDuring the MOPHAR screening visit, roughly four types of monitoring information are collected by the trained nurse Fig. . First, Second, laboratory measurements. A nursing specialist or doctor orders the laboratory tests on a paper-based laboratory order form. The laboratory associated with MOPHAR has developed a dedicated laboratory order form for MOPHAR, on which the applicant can order all test from one measurement moment with one check. The nurse can perform the venepuncture, but patients from most teams are asked in the invitation for the appointment to go to the laboratory for blood withdrawal in the week before the screening with the laboratory order form sent along with the invitation. The total set of physical and laboratory measurements collected is shown in Supplemental Table 1 [see Additional file Third, two structured interviews: one regarding somatic disease history of the patient and first-degree family members and the other regarding the patient’s lifestyle, including physical exercise and diet. The nurse completes these with the patient through the online portal in the electronic medical records.Last, medication reconciliation. This is performed by the nurse through a combination of the pharmacy records and patient counselling. In preparation of the screening appointment, the nurse requests a medication overview  from the community pharmacy of the patient by fax. At the screening appointment, the nurse reconciles this overview with the actual medication use by interviewing the patient. Medication reconciliation provides an up-to-date and complete medication overview including all drugs currently in use and all medication allergies or intolerances that the nurse enters in the electronic prescribing system. In case of relevant medication discrepancies (compared to the pharmacy records), the MOPHAR nurse will notify the psychiatrist/nursing specialist.The information collected via questionnaires beforehand and during the MOPHAR screening is immediately available to the mental health care provider via the patient portal and serves as a starting point for the anamnesis, psychiatric examination and a (semi-)structured interview for diagnostic purposes. The patient portal generates a summary of all information collected at the MOPHAR appointment. This summary selects a set of pre-specified most relevant parameters for a quick assessment of the clinical status of the patient, together with the information on medication use and laboratory tests.The general somatic screening at the first appointment is repeated yearly in all patients (±30 min), irrespective of psychiatric diagnosis or medication use. However, with respect to the patient-filled online questionnaires, only the smoking/alcohol/illicit substance use questionnaire, the WHO-DAS 2.0, the DSM-5 screener, and the SMS are repeated at the yearly screening as well as the disorder-specific questionnaire and OQ45 (if applicable).In addition to the general somatic screenings at the first appointment and yearly thereafter, the MOPHAR nurse conducts additional screenings according to drug-specific monitoring protocols if a patient starts with or already uses one or more psychotropic drugs (±30 min per appointment). To this end, the abovementioned multidisciplinary working group has additionally written MOPHAR monitoring protocols per psychotropic drug (class). The monitoring protocols are shown in Additional files In order to monitor subjective side effects, the SMS questionnaire is repeated three monthly when psychotropic medication is used. The physical exercise and lifestyle questionnaire (filled in by the nurse during a MOPHAR appointment) may also be repeated in the course of monitoring of psychotropic medication use.Medication reconciliation is performed by the nurse at MOPHAR appointments or by the medication prescriber  if medication is prescribed, stopped or changed.The summary generated from the patient portal, the medication overview from the electronic prescribing system and the laboratory test results together provide a full picture of the patient for the weekly to monthly multidisciplinary meeting where interventions and follow-up are planned . A recenApart from the abovementioned adjustments to fit specific populations, the core set of monitoring program elements will be adjusted over time. There is on ongoing debate regarding the necessity and appropriate frequency of monitoring of parameters such as the ECG , 41, livThe MOPHAR monitoring program is currently incorporated in routine psychiatric care at the outpatient departments of MHS Drenthe after the assignment and approval for the implementation from the general board of MHS Drenthe. Eventually, all approximately 5700 adult patients with a  diagnosis of a psychiatric disorder who are annually referred to a psychiatrist or psychologist at the MHS Drenthe outpatient departments will be asked to participate in MOPHAR. After that, we aim to implement MOPHAR at other mental health care institutions and also include patients from these other centres in MOPHAR research.To the best of our knowledge, we are the first to describe a comprehensive monitoring program that actively supports mental health care professionals to implement guideline-concordant general somatic and psychotropic-specific monitoring of psychiatric patients in daily clinical practice, that is flexible to accommodate patients with any psychiatric diagnosis. Two monitoring programs have been described in the literature which, although with a similar level of active support, focused on psychotic patients only and/or on metabolic syndrome screening and monitoring , 46.Implementation of MOPHAR started at the outpatient department for bipolar disorders. First appointment somatic screenings took place from January 2016 onward and yearly somatic screenings from November 2016 to synchronize MOPHAR with the individual yearly treatment evaluation schemes for patients that were already in treatment. Results of the first appointment somatic screenings for the outpatient department for bipolar disorders have been reported separately .At this moment a general practitioner is not part of the treatment team. In the near future we would like to add this professional in order to ensure patient-centred care, including the treatment of detected somatic complications and adverse drug effects. Other potential future innovations of the program are a digital assurance system to ascertain protocol adherence and standardized interventions on aberrant test results where possible. In addition, the monitoring program may be adjusted for implementation in first-line health care-organizations, thereby serving the target population throughout the continuum of relevant  health care providers for psychiatric outpatients.Psychiatric patients are vulnerable for somatic co-morbidities and side effects of psychotropic medication. However, current monitoring frequencies of somatic health of these patients may be low. There is a need for structural support for improvement of somatic monitoring practices in psychiatric outpatients in line with available monitoring guidelines. The active implementation of a structured monitoring program in which somatic monitoring is ensured as part of routine clinical will provide be a possible solution. In addition, it provides the opportunity to establish a patient registry for research purposes. In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program including the research aspects is feasible and beneficial for patients in any MHS organisation.Additional file 1:Table S1. MOPHAR protocol for baseline/yearly screening (DOCX 19 kb)Additional file 2:Table S2. MOPHAR monitoring protocol tricyclic antidepressants (TCAs) (DOCX 19 kb)Additional file 3:Table S3. MOPHAR monitoring protocol selective serotonin reuptake inhibitors (SSRIs) (DOCX 18 kb)Additional file 4:Table S4. MOPHAR monitoring protocol selective serotonin and noradrenaline reuptake inhibitors (SNRIs) (DOCX 18 kb)Additional file 5:Table S5. MOPHAR monitoring protocol Monoamide oxidase inhibitors (MAOIs) (DOCX 18 kb)Additional file 6:Table S3. MOPHAR monitoring protocol other antidepressants  (DOCX 18 kb)Additional file 7:Table S7. MOPHAR monitoring protocol antipsychotics other than clozapine (DOCX 18 kb)Additional file 8:Table S8. MOPHAR monitoring protocol clozapine (DOCX 18 kb)Additional file 9:Table S9. MOPHAR monitoring protocol lithium (DOCX 29 kb)Additional file 10:Table S10. MOPHAR monitoring protocol carbamazepine (DOCX 19 kb)Additional file 11:Table S11. MOPHAR monitoring protocol valproic acid (DOCX 17 kb)Additional file 12:Table S12. MOPHAR monitoring protocol lamotrigine (DOCX 17 kb)


Falls are the leading cause of injury among older adults, resulting in 3 million emergency department visits and 800,000 hospitalizations each year in the United States alone. In the hospital setting, falls are among the most common adverse events, causing longer stays and higher costs of care. Substantial efforts have been made to reduce falls in the past decade but with limited sustained effect. This may in part be due to limitations of existing tools for fall-risk assessment and evidence-based fall prevention. Therefore, there is a need to strengthen the evidence on risk factors for hospital-acquired falls and address barriers to translating the best available evidence into practice. To this end, we undertook the development of an innovative dissemination tool to implement fall-related evidence generated through state-of-the-art data science and information visualization approaches. Through a multidisciplinary academic-clinical partnership, we have developed an infographic to disseminate empirical evidence to nurses and administrators in the hospital setting. The infographic was developed based on principles of user-centered design and persuasive communication, and focuses on providing clear and accessible information about factors contributing to a patients’ risk of falling in the hospital. This innovative dissemination approach is intended to foster dialogue between administrators, mid-level nursing management and staff nurses as well as evidence-based practice at the bedside. Future use and evaluation of this fall prevention tool will focus on adapting the infographic as an interactive digital tool for education and engagement of patients and families in the hospital setting.